bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative study of the causes and circumstances of drowning in Uganda
Authors: Buyinza Mugeere Anthony , Oporia Frederick , Kobusingye Olive
Published: November 2022

Background

Drowning is a serious worldwide and preventable injury problem, especially in low- and middle-income countries (LMICs). The aim of this paper is to draw on the results of semi-structured interviews with witnesses, family members and friends of persons involved in fatal and nonfatal drowning incidents to describe the circumstances of drowning in both lakeside and non-lakeside districts and to identify potential contextually appropriate interventions for drowning prevention and surveillance in Uganda.

Methods

The findings presented in this study were based on data collected from study participants selected through purposive sampling comprising 324 individual face-to-face interviews with drowning witnesses, family members, friends of and survivors of drowning and ten (10) focus group discussions held with community members in 14 districts in Uganda. Data analysis was done using the Framework Analysis Approach with the aid of the Microsoft Atlas ti software (version 8) program.

Results

The study results reveal a range of circumstances under which drowning occurs in Uganda, poor record keeping of drowning incidents, fear of reporting drowning incidences to the authorities, challenges in preventing drowning and proposed strategies for mitigating the problem.

Conclusions

This study found that there is no specialized record keeping system for drowning cases in Uganda and where such records are kept, the system is entirely manual (in hard copy form) with no electronic storage of data. Secondly, the drowning cases reported to police posts and stations in various parts of the country are not transmitted to the district headquarters and national database. These and other conclusions not only provide valuable insights into understanding of drowning circumstances but also the key policy and programme interventions for water-based economic activities such as fishing and public water transportation in Uganda and other LMICs.
Modeling and optimizing in vitro percentage and speed callus induction of carrot via Multilayer Perceptron-Single point discrete GA and radial basis function
Authors: Fallah Ziarani Masoumeh , Tohidfar Masoud , Navvabi Mohammad
Published: November 2022

Background

Callus induction is the first step in optimizing plant regeneration. Fit embryogenesis and shooting rely on callus induction. In addition, using artificial intelligence models in combination with an algorithm can be helpful in the optimization of in vitro culture. The present study aimed to evaluate the percentage and speed of callus induction optimization in carrot with a Multilayer Perceptron-Single point discrete genetic algorithm (GA).

Materials and methods

In this study, the outputs included callus induction percentage and speed, while inputs were different types and concentrations of plant growth regulator (0. 5, 0.2 mg/l 2,4-D, 0.3, 0.2, 0.5 mg/l BAP, 1, 0.2 mg/l Kin, and 2 mg/l NAA), different explants (shoot, root, leaf, and nodal), a different concentration compound of MS medium (1 × MS, 4× MS, and 8× MS) and time of sampling. The data were obtained in the laboratory, and multilayer perceptron (MLP) and radial basis function (RBF), two well-known ANNs, were employed to model. Then, GA was used for optimization, and sensitivity analysis was performed to indicate the inputs’ importance.

Results

The results showed that MLP had better prediction efficiency than RBF. Based on the results, R2 in training and testing data was 95 and 95% for the percentage of callus induction, while it was 94 and 95% for the speed of callus induction, respectively. In addition, a concentration compound of MS had high sensitivity, while times of sampling had low sensitivity. Based on the MLP-Single point discrete GA, the best results were obtained for shoot explants, 1× MS media, and 0.5 mg/l 2, 4-D + 0.5 mg/l BAP. Further, a non-significant difference was observed between the test result and predicted MLP.

Conclusions

Generally, MLP-Single point discrete GA is considered a potent tool for predicting treatment and fit model results used in plant tissue culture and selecting the best medium for callus induction.
Effect of roughness and acidic medium on wear behavior of dental resin composite
Authors: Guo Jiawen , Bing Zhaoxia , Yang Jiajun , Tsoi James K. H. , Wang Yan
Published: November 2022

Background

The aim of the study was to investigate whether the citric acid and rough surface have a synergistic effect leading to severe wear behavior of resin composite.

Materials and methods

Disk-shaped (Ø15 × 1.5 mm) specimens of resin composite (n = 12) with different initial roughness were prepared. Reciprocating ball-on-flat wear tests were performed under distilled water and citric acid (pH = 5.5) respectively. The coefficient of friction (COF), wear volume loss, and duration of the running-in period were quantified to assess the wear performance. And the values were analyzed with one-way ANOVA (α = 0.05). Regression analysis was applied to examine the influence of Ra values and mediums on the wear data. The wear morphology was analyzed by scanning electron microscopy and a 3D profilometer.

Results

The average COF was higher in distilled water than in citric acid but was independent of the surface roughness. For the composite, the volume loss of worn area and running-in period increased with surface roughness when tested under distilled water. However, these increasing trends were not found in citric acid. All specimens exhibited mild wear behavior with low COF and less superficial abrasion in acidic medium.

Conclusions

The effect of initial roughness on wear behavior depends on the medium. In distilled water, resin composites with high initial roughness exhibit a longer running-in time, which eventually leads to a significant increase in material loss. The adverse effects of high roughness can be alleviated by the lubrication of citric acid, which can maintain a mild wear behavior regardless of initial surface roughness.
Biomechanical analysis of stress around the tilted implants with different cantilever lengths in all-on-4 concept
Authors: Wang Qi , Zhang Zhen-zhen , Bai Shi-zhu , Zhang Shao-feng
Published: November 2022

Background

Many clinical studies have reported the high success rate of the All-on-4 concept. In the present study, we aimed to compare the stress distribution with different tilted distal implants and cantilever lengths in an All-on-4 system using the two-dimensional photoelastic method and to establish the All-on-4 implant photoelastic model by computer-aided design (CAD) and rapid prototyping (RP). 

Methods

The data of the human edentulous mandible were acquired by computed tomography (CT). Three human edentulous mandible All-on-4 implant models with different distally inclined implant holes were fabricated using Mimic, Geomagic Studio software, and a light solidifying fast shaping machine. Then the final photoelastic models were established through the traditional method. Each of the three models had four NobelSpeedy Replace implants between the interforaminal regions. The two posterior implants were placed 0, 15, and 45 degrees distally before the mental foramen. The four implants were splinted by wrought cobalt-chromium alloy frameworks. Each of the three photoelastic models was submitted to a 150 N vertical load at five points on the framework: the central fossa of the mandibular first molar, and 0 mm, 5 mm, 10 mm, and 15 mm of the cantilever length. The stress produced in the models was photographed with a digital camera, and the highest value of the stressed fringe pattern was recorded.

Results

The All-on-4 implant photoelastic model established by CAD and RP was highly controllable and easy to modify. The position and inclination of implants were accurate, and the frameworks could be passively emplaced. The stress values were higher around a single tilted implant compared with the distal implant in All-on-4 with the same inclination. The 0-degree distal implant and 45-degree distal implant demonstrated the highest and lowest stress when loading at the central fossa of the mandibular first molar, respectively. With the same inclination of distal implant, the peri-implant bone stress increased as the length of cantilever increased.

Conclusion

The method of establishing the All-on-4 implant photoelastic model by CAD and RP was highly controllable, convenient, fast, and accurate. The tilted implants splinted in the fully fixed prosthesis with reduced cantilever lengths did not increase the stress level compared with the vertical distal implants.And this illustrated that the influence of cantilever on stress distribution was greater than the influence of implant inlination.
Association between dental agenesis and delay in dental development: a preliminary study in a Spanish paediatric population in relation with Dental Anomaly Pattern (DAP)
Authors: León-Rubio Carmen , Martín-Vacas Andrea , Saavedra-Marbán Gloria , Paz-Cortés Marta Macarena
Published: November 2022

Background

The association between dental anomalies has been studied, giving rise to the concept of Dental Anomaly Pattern (DAP). Tooth agenesis has been associated with alterations such as molar infracclusion, taurodontism and delayed dental development. The aim of this study was to evaluate the dental development pattern in patients with non-syndromic dental agenesis, in comparison with a control group.

Methods

Dental and chronological age was analysed in a sample size of 204 orthopantomographs divided into a study group (n = 104) and a control group (n = 100) with the Demirjian Method. Intra and intergroup differences in chronological and dental age, and the correlation between them were calculated by statistical analysis with a 95% confidence level (p < 0.05).

Results

Dental age exceeded chronological age both in the control group and in the study group. Statistically significant differences (p = 0.004) were found when comparing the difference between chronological and dental age in the study (-0.16 ± 1.12) and control group (-0.58 ± 0.90). Regarding sex and age intergroup differences, the results were only statistically significant in the girls’ group (p = 0.017), and the age over 8 years old (p < 0.05). There were no significant differences in tooth development depending on the number of missing teeth or the affected tooth group, but there was a delay in the development of the homologous tooth contralateral to the absent one in 14.9% of patients.

Conclusions

The difference between chronological and dental age in permanent dentition is significantly lower in Spanish children with non-syndromic agenesis compared to a control group, presenting a lower dental age than chronological age than children without non-syndromic agenesis.
Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study
Authors: Liu Yue , Yu Xin , Huang Jing , Du Chengchao , Zhou Honggui , Yang Yamei , Qu Dacheng
Published: November 2022

Background

To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs).

Methods

Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed.

Results

The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment.

Conclusion

Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment.
Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes
Authors: Lee CH , Wu MZ , Lui DTW , Fong CHY , Ren QW , Yu SY , Yuen MMA , Chow WS , Huang JY , Xu A , Yiu KH , Lam KSL
Published: November 2022

Background

Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes.

Methods

Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year.

Results

Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06–1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e’ and left atrial volume index (p = 0.04 and < 0.01, respectively).

Conclusion

Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes.

Trial registration

Not Applicable
The presence of Plasmodium malariae and Plasmodium knowlesi in near malaria elimination setting in western Indonesia
Authors: Nainggolan Irbah Rea Alvieda , Syafutri Rycha Dwi , Sinambela Monica Nadya , Devina Clara , Handayani  , Hasibuan Beby Syofiani , Chuangchaiya Sriwipa , Divis Paul C. S. , Idris Zulkarnain Md , Permatasari Ranti , Lubis Inke Nadia Diniyanti
Published: November 2022

Background

Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia.

Methods

A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction.

Results

A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100–500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%).

Conclusion

Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination.
The philosophical foundations of ‘health for all’ and Universal Health Coverage
Authors: Allen Luke N.
Published: November 2022

The WHO constitution calls for ‘health for all’ and Universal Health Coverage has been called “the ultimate expression of fairness”, however it is not always clear how health systems can move towards equity. Should we prioritise the needs of the worst off? And if so, should we direct resources to these marginalised groups or marginalised individuals? This article provides an overview of the philosophical underpinnings of health equity and proportionate universalism, highlighting the trade-offs involved in operationalising a core tenant of global health practice.
Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metal–organic framework nanoparticles
Authors: Li Yue , Li Fang , Pan Hui , Huang Xiaolin , Yu Jie , Liu Xueru , Zhang Qinghao , Xiao Caiwen , Zhang He , Zhang Leilei
Published: November 2022

Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metal–organic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability.

Graphical Abstract
Establishment of early diagnosis models for cervical precancerous lesions using large-scale cervical cancer screening datasets
Authors: Meng Bo , Li Guibin , Zeng Zhengyu , Zheng Baowen , Xia Yuyue , Li Chen , Li Minyu , Wang Hairong , Song Yuelong , Yu Shihui
Published: November 2022

Background

Human papilloma virus (HPV) DNA test was applied in cervical cancer screening as an effective cancer prevention strategy. The viral load of HPV generated by different assays attracted increasing attention on its potential value in disease diagnosis and progression discovery.

Methods

In this study, three HPV testing datasets were assessed and compared, including Hybrid Capture 2 (n = 31,954), Aptima HPV E6E7 (n = 3269) and HPV Cobas 4800 (n = 13,342). Logistic regression models for diagnosing early cervical lesions of the three datasets were established and compared. The best variable factor combination (VL + BV) and dataset (HC2) were used for the establishment of six machine learning models. Models were evaluated and compared, and the best-performed model was validated.

Results

Our results show that viral load value was significantly correlated with cervical lesion stages in all three data sets. Viral Load and Bacterial Vaginosis were the best variable factor combination for logistic regression model establishment, and models based on the HC2 dataset performed best compared with the other two datasets. Machine learning method Xgboost generated the highest AUC value of models, which were 0.915, 0.9529, 0.9557, 0.9614 for diagnosing ASCUS higher, ASC-H higher, LSIL higher, and HSIL higher staged cervical lesions, indicating the acceptable accuracy of the selected diagnostic model.

Conclusions

Our study demonstrates that HPV viral load and BV status were significantly associated with the early stages of cervical lesions. The best-performed models can serve as a useful tool to help diagnose cervical lesions early.
Occupational disease predictors in the nickel pyrometallurgical production: a prospective cohort observation
Authors: Syurin Sergei , Vinnikov Denis
Published: November 2022

Background

Pyrometallurgical nickel production exposes workers to a wide range of occupational risk factors, including nickel aerosol, occupational noise and heat, but occupational (compensation) claims do not get enough attention in the literature. We, therefore, aimed to identify and analyze new occupational disease predictors in order to tailor prevention measures in the nickel pyrometallurgical production workers.

Methods

In a prospective observational study, a cohort of workers grouped in 16 occupations (N = 1424, 88% males, median age 39 (interquartile range (IQR) 31–47 years)), was fixed in 2007 at a large nickel production plant in the Russian High North. We then followed the cohort until 2021 and analyzed the association of selected predictors, including exposure to nickel and occupational group, with the risk of an occupational (compensation) claim in a Cox regression analysis.

Results

With 18,843 person-years of observation, occupational disease claims were confirmed in 129 workers (9% of the initial cohort, N = 108 men (84%)). Top three diagnoses were chronic bronchitis (3.81 cases/1000 workers/year), sensorineural deafness (2.36 cases/1000 workers /year) and musculoskeletal disorders (1.90 cases/1000 workers/year). Smoking was significantly associated with each diagnosis (adjusted hazard ratio (HR) ranged from 2.56 (95% confidence interval (CI) 1.17–5.57) for bronchitis to 6.69 (95% CI 1.46–30.64) for chronic obstructive pulmonary disease (COPD)). High nickel exposure was associated with occupational bronchitis and occupational asthma, whereas associations of occupational groups were also identified for COPD, asthma and musculoskeletal disorders.

Conclusion

Smoking, high exposure to nickel and specific exposure in the occupational groups increase the risk of occupational disease claims and should be prioritized directions for targeted intervention.
Chemoinformatics-driven classification of Angiosperms using sulfur-containing compounds and machine learning algorithm
Authors: Abdullah-Zawawi Muhammad-Redha , Govender Nisha , Karim Mohammad Bozlul , Altaf-Ul-Amin Md. , Kanaya Shigehiko , Mohamed-Hussein Zeti-Azura
Published: November 2022

Background

Phytochemicals or secondary metabolites are low molecular weight organic compounds with little function in plant growth and development. Nevertheless, the metabolite diversity govern not only the phenetics of an organism but may also inform the evolutionary pattern and adaptation of green plants to the changing environment. Plant chemoinformatics analyzes the chemical system of natural products using computational tools and robust mathematical algorithms. It has been a powerful approach for species-level differentiation and is widely employed for species classifications and reinforcement of previous classifications.

Results

This study attempts to classify Angiosperms using plant sulfur-containing compound (SCC) or sulphated compound information. The SCC dataset of 692 plant species were collected from the comprehensive species-metabolite relationship family (KNApSAck) database. The structural similarity score of metabolite pairs under all possible combinations (plant species-metabolite) were determined and metabolite pairs with a Tanimoto coefficient value > 0.85 were selected for clustering using machine learning algorithm. Metabolite clustering showed association between the similar structural metabolite clusters and metabolite content among the plant species. Phylogenetic tree construction of Angiosperms displayed three major clades, of which, clade 1 and clade 2 represented the eudicots only, and clade 3, a mixture of both eudicots and monocots. The SCC-based construction of Angiosperm phylogeny is a subset of the existing monocot-dicot classification. The majority of eudicots present in clade 1 and 2 were represented by glucosinolate compounds. These clades with SCC may have been a mixture of ancestral species whilst the combinatorial presence of monocot-dicot in clade 3 suggests sulphated-chemical structure diversification in the event of adaptation during evolutionary change.

Conclusions

Sulphated chemoinformatics informs classification of Angiosperms via machine learning technique.
Comparison of surgical efficacy of locking plates and interlocking intramedullary nails in the treatment of proximal humerus fractures
Authors: Guo Zheming , Sang Linchao , Meng Qingting , Tian Lijun , Yin Yingchao
Published: November 2022

Background

The objective of this study was to evaluate the efficacy of locking plates versus interlocking intramedullary nails in the treatment of proximal humerus fractures to provide clinical data support and theoretical guidance.

Methods

Patients with proximal humerus fracture from the Third hospital of Shijiazhuang city and Third hospital of Hebei medical university and from January 2017 to June 2019 were selected, included and divided into the locking plate group and the interlocking intramedullary nail group according to the intervention received. Information pertaining to the perioperative period (operation time, hospital stay, blood loss, etc.) of patients in both groups was collected. VAS pain scores, shoulder activity Constant-Murley scores and postoperative complications were documented. The perioperative data of the two groups were compared, and P < 0.05 was considered statistically significant.

Results

A total of 64 patients were enrolled, including 36 patients in the locking plate group, with a mean age of 61.3 ± 13.9 years, while the mean age of the interlocking intramedullary nail group was 65.6 ± 11.2 years. There was no statistical difference in gender, affected side, injury mechanism and Neer classification between the two groups (P > 0.05). However, the average operation time of the locking plate group was shorter than that of the interlocking nail group (84.9 ± 11.7 vs. 102.6 ± 22.1 min, P = 0.00), and the intraoperative blood loss of the locking plate group (137.4 ± 16.8 ml) was higher than that of the interlocking nail group (72.5 ± 10.5 ml, P = 0.00). There was no significant difference in the VAS score and Constant-Murley score between these two groups at the final follow-up.

Conclusion

Interlocking intramedullary nails are more minimally invasive than locking plates, but fracture reduction and fixation take longer. There was no significant difference in pain and shoulder function scores between the two internal fixation strategies for the treatment of proximal humerus fracture.
Detailed statistical analysis plan for a randomised controlled trial of the effects of a modified muscle sparing posterior technique (SPAIRE) in hip hemiarthroplasty for displaced intracapsular fractures on post-operative function compared to a standard lateral approach: HemiSPAIRE
Authors: Ball Susan , McAndrew Amy , Aylward Alex , Cockcroft Emma , Gordon Elizabeth , Kerridge Alison , Morgan-Trimmer Sarah , Powell Roy , Price Anna , Rhodes Shelley , Timperley Andrew J. , van Horik Jayden , Wickins Robert , Charity John
Published: November 2022

Background

The HemiSPAIRE trial is being conducted to determine whether a modified muscle sparing technique (SPAIRE-“Save Piriformis and Internus, Repairing Externus”) in hip hemiarthroplasty brings clinical benefits compared to the standard lateral technique in adults aged 60 years or older, with a displaced intracapsular hip fracture. This article describes the detailed statistical analysis plan for the trial. 

Methods and design

HemiSPAIRE is a definitive, pragmatic, superiority, multicentre, randomised controlled trial (with internal pilot) with two parallel groups. Participants, ward staff and all research staff involved in post-operative assessments are blinded to allocation. This article describes in detail (1) the primary and secondary outcomes; (2) the statistical analysis principles, including a survivor average causal effect (SACE) method chosen specifically to address the issue of potential bias from differential survival between trial arms, which was seen from data review by the Trial Steering Committee, the participants that will be included in each analysis, the covariates that will be included in each analysis, and how the results will be presented; (3) planned main analysis of the primary outcome; (4) planned analyses of the secondary outcomes; and (5) planned additional analyses of the primary and secondary outcomes.

Trial registration

ClinicalTrials.gov NCT04095611. Registered on 19 September 2019.
Overexpression of PtoMYB115 improves lignocellulose recalcitrance to enhance biomass digestibility and bioethanol yield by specifically regulating lignin biosynthesis in transgenic poplar
Authors: Fan Chunfen , Zhang Wenyi , Guo YuHao , Sun Kuan , Wang Lijun , Luo Keming
Published: November 2022

Background

Woody plants provide the most abundant biomass resource that is convertible for biofuels. Since lignin is a crucial recalcitrant factor against lignocellulose hydrolysis, genetic engineering of lignin biosynthesis is considered as a promising solution. Many MYB transcription factors have been identified to involve in the regulation of cell wall formation or phenylpropanoid pathway. In a previous study, we identified that PtoMYB115 contributes to the regulation of proanthocyanidin pathway, however, little is known about its role in lignocellulose biosynthesis and biomass saccharification in poplar.

Results

Here, we detected the changes of cell wall features and examined biomass enzymatic saccharification for bioethanol production under various chemical pretreatments in PtoMYB115 transgenic plants. We reported that PtoMYB115 might specifically regulate lignin biosynthesis to affect xylem development. Overexpression of PtoMYB115 altered lignin biosynthetic gene expression, resulting in reduced lignin deposition, raised S/G and beta-O-4 linkage, resulting in a significant reduction in cellulase adsorption with lignin and an increment in cellulose accessibility. These alterations consequently improved lignocellulose recalcitrance for significantly enhanced biomass saccharification and bioethanol yield in the PtoMYB115-OE transgenic lines. In contrast, the knockout of PtoMYB115 by CRISPR/Cas9 showed reduced woody utilization under various chemical pretreatments.

Conclusions

This study shows that PtoMYB115 plays an important role in specifically regulating lignin biosynthesis and improving lignocellulose features. The enhanced biomass saccharification and bioethanol yield in the PtoMYB115-OE lines suggests that PtoMYB115 is a candidate gene for genetic modification to facilitate the utilization of biomass.
Shaping a research agenda to ensure a successful European health technology assessment: insights generated during the inaugural convention of the European Access Academy
Authors: Julian Elaine , Pavlovic Mira , Sola-Morales Oriol , Gianfrate Fabrizio , Toumi Mondher , Bucher Heiner C. , Dierks Christian , Greiner Wolfgang , Mol Peter , Bergmann Jean-François , Salmonson Tomas , Hebborn Ansgar , Grande Mathilde , Cardone Antonella , Ruof Jörg
Published: November 2022

Objectives

Key challenges for a joint European Health Technology Assessment (HTA) include consolidated approaches towards the choice of adequate comparator(s), selection of endpoints that are relevant to patients with a given disease, dealing with remaining uncertainties as well as transparent and consistent management of related processes. We aimed to further crystallize related core domains within these four areas that warrant further research and scrutiny.

Methods

Building on the outcomes of a previously conducted questionnaire survey, four key areas, processes, uncertainty, comparator choice and endpoint selection, were identified. At the inaugural convention of the European Access Academy dedicated working groups were established defining and prioritizing core domains for each of the four areas. The working groups consisted of ~ 10 participants each, representing all relevant stakeholder groups (patients/ clinicians/ regulators/ HTA & payers/ academia/ industry). Story books identifying the work assignments were shared in advance. Two leads and one note taker per working group facilitated the process. All rankings were conducted on an ordinal Likert Response Scale scoring from 1 (low priority) to 7 (high priority).

Results

Identified key domains include for processes: i) address (resource-) challenge of multiple PICOs (Patient/ Intervention/ Comparator/ Outcomes), ii) time and capacity challenges, iii) integrating all involved stakeholders, iv) conflicts and aligning between different multi-national stakeholders, v) interaction with health technology developer; for uncertainty: i) early and inclusive collaboration, ii) agreement on feasibility of RCT and acceptance of uncertainty, iii) alignment on closing evidence gaps, iv) capacity gaps; for comparator choice: i) criteria for the choice of comparator in an increasingly fragmented treatment landscape, ii) reasonable number of comparators in PICOs, iii) shape Early Advice so that comparator fulfils both regulatory and HTA needs, iv) acceptability of Indirect Treatment Comparisons (ITC), v) ensure broad stakeholder involvement in comparator selection; for endpoint selection: i) approaching new endpoints; ii) patient preferences on endpoints; iii) position of HTA and other stakeholders; iv) long-term generation and secondary use of data; v) endpoint challenges in RCTs.

Conclusions

The implementation of a joint European HTA assessment is a unique opportunity for a stronger European Health Union. We identified 19 domains related to the four key areas, processes, uncertainty, comparator choice and endpoint selection that urgently need to be addressed for this regulation to become a success.
Suitability of lectin binding studies for the characterization of redox-active microbial environmental biofilms
Authors: Ingino Pablo , Tiew Kai Hao , Obst Martin
Published: November 2022

Aquatic environmental microbial biofilms grow in a broad range of redox environments from oxic to methanogenic, and they often also establish internal redox gradients. In technical applications, biofilms are also subjected to controlled redox conditions. Studies on biofilms often make use of fluorescence microscopic imaging techniques together with lectin binding analysis to gain insights into structure, composition, and functions of the biofilms. Here we studied the direct influence of redox potentials on fluorescence lectin binding analyses (FLBA) for two commonly used lectin-fluorophore conjugates. An effect of the electrical potential on signal intensity was observed and found to be statistically significant. The signal intensity changes however, remained within the range of a few percent total. A significant drop in intensity was only observed for extremely oxidizing potentials, typically not found under environmental conditions. Our results showed that the fluorophore itself and not the lectin binding to the respective glycoconjugate causes fluorescence changes. The two tested lectin-fluorophores are shown to be suitable for studying the distribution and composition of EPS in environmental biofilms or technical applications and under varying redox conditions.
Characterisation of marine bacterium Microbulbifer sp. ALW1 with Laminaria japonica degradation capability
Authors: Li Zhipeng , Du Zeping , Li Hebin , Chen Yanhong , Zheng Mingjing , Jiang Zedong , Du Xiping , Ni Hui , Zhu Yanbing
Published: November 2022

Marine bacterium Microbulbifer sp. ALW1 was revealed to be able to effectively degrade Laminaria japonica thallus fragments into fine particles. Polysaccharide substrate specificity analysis indicated that ALW1 could produce extracellular alginate lyase, laminarinase, fucoidanase and cellulase. Based on alignment of the 16 S rRNA sequence with other reference relatives, ALW1 showed the closest relationship with Microbulbifer aggregans CCB-MM1T. The cell morphology and some basic physiological and biochemical parameters of ALW1 cells were characterised. ALW1 is a Gram-negative, rod- or oval-shaped, non-spore-forming and non-motile bacterium. The DNA–DNA relatedness values of ALW1 with type strains of M. gwangyangensis (JCM 17,800), M. aggregans (JCM 31,875), M. maritimus (JCM 12,187), M. okinawensis (JCM 16,147) and M. rhizosphaerae (DSM 28,920) were 28.9%, 43.3%, 41.2%, 35.4% and 45.6%, respectively. The major cell wall sugars of ALW1 were determined to be ribose and galactose, which differed from other closely related species. These characteristics indicated that ALW1 could be assigned to a separate species of the genus Microbulbifer. The complete genome of ALW1 contained one circular chromosome with 4,682,287 bp and a GC content of 56.86%. The putative encoded proteins were categorised based on their functional annotations. Phenotypic, physiological, biochemical and genomic characterisation will provide insights into the many potential industrial applications of Microbulbifer sp. ALW1.

Key points.
Optimizing tobacco treatment delivery for people with HIV: trial protocol for a randomized controlled trial
Authors: Sanford Brandon T. , Toll Benjamin A. , Eckard Allison Ross , Sterba Katherine R. , Cummings K. Michael , Baker Nathaniel L. , Rojewski Alana M.
Published: November 2022

Background

With advances in antiretroviral therapy, people with HIV (PWH) are living longer and are less likely to die from AIDS-related complications. Yet, prior research has shown that smoking is often not addressed in the context of HIV care, and few individuals are offered cessation treatment. Optimizing tobacco treatment delivery for PWH may increase engagement with evidence-based treatments and successful quit attempts.

Methods

The current study is a type 1 hybrid effectiveness-implementation trial to evaluate the impact of a proactive, opt-out tobacco treatment intervention on cessation outcomes and advance understanding of key barriers and facilitators of implementation processes. A total of 230 PWH who smoke will be recruited from an infectious diseases clinic at an academic medical center and will be randomized to receive (1) treatment as usual (TAU) or (2) Proactive Outreach with Medication Opt-out for Tobacco Treatment Engagement (PrOMOTE). Primary outcomes include: biochemically verified 7-day point prevalence abstinence (PPA) rates, continuous abstinence (Weeks 9–12), and the number of 24-hour quit attempts at the end of study treatment (Week 12). Secondary outcomes include: participant reach (proportion reached out of contact attempts), implementation fidelity (including number of prescriptions written), participant adherence to prescribed pharmacotherapy, acceptability (participant and provider satisfaction with intervention delivery and content), and perceived barriers.

Discussion

This study will examine a novel approach to optimizing tobacco treatment delivery for PWH. Integrating effectiveness and implementation results will help define best practices for engaging PWH with evidence-based tobacco treatment interventions. The intervention is low-cost, has the potential to be highly scalable, and could be translatable to other ambulatory HIV clinic settings.

Trial Registration

ClinicalTrials.gov: NCT05019495 (August 24, 2021).
Low barrier medication for opioid use disorder at a federally qualified health center: a retrospective cohort study
Authors: Carter Jamie , Li Zhen , Chen Hillary , Greiner Melissa , Bush Christopher , Bhattacharya Debanjan , Poley Stephanie , Sachdeva Nidhi , Crowder Jane Carolyn , Feigal Jacob
Published: November 2022

Background

Medication for opioid use disorder (MOUD) reduces mortality, but few patients access MOUD. At a Federally Qualified Health Center (FQHC), we implemented a low barrier model of MOUD, including same-day MOUD initiation and a harm reduction philosophy.

Objective

To investigate whether low barrier MOUD improved retention in care compared to traditional treatment.

Design and participants

Retrospective cohort study of patients with at least one visit seeking MOUD at the FQHC during a historical control period (3/1/2018—3/31/2019) and a low barrier intervention period (11/1/2019—7/31/2020).

Main measures

Primary outcomes were any MOUD prescription within 6 months of the index visit and 3- and 6-month retention in treatment without care gap, with care gap defined as 60 consecutive days without a visit or prescription. Secondary outcomes were all-cause hospitalization and emergency department visit within 6 months of the index visit.

Key results

Baseline characteristics were similar between the intervention (n = 113) and control (n = 90) groups, except the intervention group had higher rates of uninsured, public insurance and diabetes. Any MOUD prescription within 6 months of index visit was higher in the intervention group (97.3% vs 70%), with higher adjusted odds of MOUD prescription (OR = 4.01, 95% CI 2.08–7.71). Retention in care was similar between groups at 3 months (61.9% vs 60%, aOR = 1.06, 95% CI 0.78–1.44). At 6 months, a higher proportion of the intervention group was retained in care, but the difference was not statistically significant (53.1% vs 45.6%, aOR 1.27, 95% CI 0.93–1.73). There was no significant difference in adjusted odds of 6-month hospitalization or ED visit between groups.

Conclusions

Low barrier MOUD engaged a higher risk population and did not result in any statistically significant difference in retention in care compared with a historical control. Future research should determine what interventions improve retention of patients engaged through low barrier care. Primary care clinics can implement low barrier treatment to make MOUD accessible to a broader population.
Plant sex affects plant-microbiome assemblies of dioecious Populus cathayana trees under different soil nitrogen conditions
Authors: Guo Qingxue , Liu Lin , Liu Jiantong , Korpelainen Helena , Li Chunyang
Published: November 2022

Background

Dioecious plants have coevolved with diverse plant microbiomes, which are crucial for the fitness and productivity of their host. Sexual dimorphism in morphology, physiology, or gene expression may relate to different microbial compositions that affect male and female fitness in different environments. However, sex-specific impacts on ecological processes that control the microbiome assembly are not well known. In this study, Populus cathayana males and females were planted in different nitrogen conditions. It was hypothesized that males and females differently affect bacterial and fungal communities in the rhizosphere soil, roots, old leaves, and young leaves. Physiological traits and transcriptome profiles of male and female plants were investigated to reveal potential mechanisms that control the microbiome assembly.

Results

Our results showed strong niche differentiation that shapes microbial communities leading to a rapid loss of diversity along a decreasing pH gradient from the rhizosphere soil to leaves. Sex had different impacts on the microbial assembly in each niche. Especially fungal endophytes showed great differences in the community structure, keystone species, and community complexity between P. cathayana males and females. For example, the fungal co-occurrence network was more complex and the alpha diversity was significantly higher in young female leaves compared to young male leaves. Transcriptome profiles revealed substantial differences in plant-pathogen interactions and physiological traits that clearly demonstrated divergent internal environments for endophytes inhabiting males and females. Starch and pH of young leaves significantly affected the abundance of Proteobacteria, while tannin and pH of roots showed significant effects on the abundance of Chloroflexi, Actinobacteria, and Proteobacteria, and on the bacterial Shannon diversity.

Conclusion

Our results provided important knowledge for understanding sexual dimorphism that affects microbial assemblies, thus advancing our understanding of plant-microbiome interactions.
Association between sleep habits and behavioral problems in early adolescence: a descriptive study
Authors: Hosokawa Rikuya , Tomozawa Riho , Fujimoto Megumi , Anzai Sumire , Sato Mai , Tazoe Haruko , Katsura Toshiki
Published: November 2022

Background

Sleep habits are related to children's behavior, emotions, and cognitive functioning. A strong relationship exists between sleep habits and behavioral problems. However, precisely which sleep habits are associated with behavioral problems remains unclear. Therefore, the purpose of this study is to clarify the relationship between sleep habits and behavioral problems in early adolescence.

Methods

This study used data from a larger longitudinal research, specifically, data from the year 2021. First-year junior high school students (12–14 years) in Japan were surveyed; their parents (N = 1288) completed a parent-report questionnaire. The main survey items were subject attributes, the Pittsburgh Sleep Quality Index (PSQI), and the Strength and Difficulties Questionnaire (SDQ).

Results

Of the 652 valid responses received, 604 individuals who met the eligibility criteria (no developmental disability in the child and completion of all survey items) were included in the analysis. To examine the relationship between sleep habits and behavioral problems, logistic regression analysis using the inverse weighted method with propensity score was conducted with sleep habits (sleep quality, time to fall asleep, sleep duration, sleep efficiency, sleep difficulty, use of sleeping pills, difficulty waking during the day, and sleep disturbances) as explanatory variables and behavioral problems (overall difficulty in SDQ) as objective variables. The propensity score was calculated by employing the logistic regression using the inverse weighted method based on propensity scores. Propensity scores were calculated based on gender, family structure, household income, and parental educational background. The results showed that behavioral problems tended to be significantly higher in the group at risk for sleep quality, sleep difficulties, daytime arousal difficulties, and sleep disturbances than in the group with no risk.

Conclusion

The results suggest that deterioration in sleep quality, sleep difficulties, daytime arousal difficulties, and sleep disturbances may increase the risk of behavioral problems in adolescents.