bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenomenological Research Needs to be Renewed: Time to Integrate Enactivism as a Flexible Resource
Authors: Stilwell Peter , Harman Katherine
Published: February 2021

Qualitative research approaches under the umbrella of phenomenology are becoming overly prescriptive and dogmatic (e.g., excessive and unnecessary focus on the epoché and reduction). There is a need for phenomenology (as a qualitative research approach) to be renewed and refreshed with opportunities for methodological flexibility. In this process paper, we offer one way this could be achieved. We provide an overview of the emerging paradigm of post-cognitivism and the aligned movement of enactivism which has roots in phenomenology and embodied cognition. We argue that enactivism can be used as a flexible resource by qualitative researchers exploring the unfolding of first-person (subjective) experience and its meanings (i.e., the enactive concept of sense-making). Enactive approaches are commonly tethered to “E-based” theory, such as the idea that sense-making is a 5E process (Embodied, Embedded, Enacted, Emotive, and Extended). We suggest that enactivism and E-based theory can inform phenomenological research in eclectic and non-prescriptive ways, including integration with existing methods such as observation/interviews and thematic analysis with hybrid deductive-inductive coding. Enactivism-informed phenomenological research moves beyond methodological individualism and can inform novel qualitative research exploring the complex, dynamic, and context-sensitive nature of sense-making. We draw from our enactive study that explored the co-construction of pain-related meanings between clinicians and patients, while also offering other ways that enactive theory could be applied. We provide a sample interview guide and codebook, as well as key components of rigor to consider when designing, conducting, and reporting a trustworthy phenomenological study using enactive theory.
A four-level test system for evaluating pavement compaction performance of autonomous articulated vehicles
Authors: Xu Tong , Wang Dong , Xiao Zuodong , Chu Cancan , Zhang Weigong
Published: February 2021

This article develops a four-level test system for accurately evaluating pavement compaction performance of autonomous articulated vehicles. In the evaluation layer, various performance indicators are evaluated, including the stability, rapidity and accuracy of trajectory tracking, and the ratio of required compaction to actual compaction once and twice and compaction repeatability index when pavement compaction. The guidance and control layer can be described in terms of theory and application. At the theoretical level, the line of sight guidance algorithm and incremental proportional integral control algorithm are introduced to eliminate system control lag. Among them, the best line of sight guidance and incremental proportional integral control parameters are selected by the Elitist strategies genetic algorithm, and the initial parameters are set according to human driving experience initial control parameters. At the application level, the BECKHOFF controller, a kind of programmable logic controller, acts as the main guidance and control unit in the four-level control system, fixed speed is given to the autonomous articulated vehicle by setting the engine speed and transmission gear, and steering wheel angle is adjusted in real time by the BECKHOFF controller. In the sensor level, a simplified sensor configuration is used to reduce overall cost. The comparative simulation results of no controller, the incremental proportional integral controller, line of sight guidance-incremental proportional integral controller with human driving experience initial control parameters, line of sight guidance-incremental proportional integral controller with random initial control parameters, and elitist strategies genetic algorithm-line of sight guidance-incremental proportional integral controller with human driving experience initial control parameters manifest evidently that the proposed elitist strategies genetic algorithm-line of sight guidance-incremental proportional integral controller with human driving experience initial control parameters has almost no steady-state error, no overshoot, and short settling time. Field results show that ratio of required compaction to actual compaction once achieves 100%, ratio of required compaction to actual compaction twice achieves 94.6%, and compaction repeatability index achieves 35%.
Soft tissue sarcoma of the upper extremity: oncological and functional results after surgery
Authors: Baysal Özgür , Toprak Canan Şanal , Günar Berkin , Erol Bülent
Published: February 2021

This retrospective study evaluates outcomes after treatment of upper-extremity soft tissue sarcoma in 44 patients. We re-resected 19 tumours that had been resected elsewhere without adequate preoperative planning, and we made 25 well-planned primary resections. Four patients in the unplanned group and five in the planned group eventually received amputations. Thirty-three patients were alive at a median follow-up time of 33 months (IQR 18 to 57). Tumour size > 7 cm, tumour Grade 3 and the presence of distant organ metastases were the main factors affecting the oncological outcomes. We found no statistical differences between the planning groups. Functional outcomes and quality of life were significantly worse after amputation or major nerve resections. We conclude with this sized sample that the lack of planning in itself did not influence the final results, but there were differences in tumour size, grade and localization between the groups that may play a role.

Level of evidence: IV
The ageing population
Authors: Walton Jenny , Kaye Angus
Published: February 2021

As we all age, the demographic of the world changes. Looking after older people well can bring a huge amount of pleasure and satisfaction, not just to the individual, but also to their family, friends and indeed healthcare professionals. How we care for our elderly now is likely to set a precedent for our own care in the future. This article highlights some of the features of ageing and discusses the role of primary care in the management of the older population, within the context of the general practice curriculum.
Management of breast infections in primary care
Authors: Rose Strickland Serena , Sharma Rishabha Deva
Published: February 2021

Breast infections are a common presentation globally. Symptoms can range from mild discomfort and erythema of the skin to systemic sepsis and abscess formation with associated long-term physical and psychological morbidity. Although more common in the puerperium, non-lactating women, in particular, those between the ages of 18 and 50 years can be affected by the condition. Prompt recognition and treatment in primary care can reduce the incidence of abscess formation. Delayed or inappropriate treatment can lead to chronic infection with associated tissue destruction. In a minority of cases an inflammatory mass and skin changes can be a presenting feature of breast cancer.
Supraretinacular endoscopic carpal tunnel release: A safe alternative method for treatment of carpal tunnel syndrome
Authors: Sato Kotaro , Murakami Kenya , Mimata Yoshikuni , Takahashi Gaku , Doita Minoru
Published: February 2021

Purpose:

Supraretinacular endoscopic carpal tunnel release (SRECTR) is a technique in which an endoscope is inserted superficial to the flexor retinaculum through a subcutaneous tunnel. The benefits of this method include a clear view for the surgeon and absence of median nerve compression. Surgeons can operate with a familiar view of the flexor retinaculum and median nerve downward, similar to open surgery. This study aimed to investigate the learning curve for SRECTR, an alternate method for carpal tunnel release, and evaluate its complications and the functional outcomes using a disposable commercial kit.

Methods:

We examined the open conversion rates and complications associated with SRECTR in 200 consecutive patients performed by two surgeons. We compared the operative time operated by a single surgeon. We evaluated outcomes in 191 patients according to Kelly’s grading system. Patients’ mean follow-up period was 12.7 months.

Results:

Nine patients required conversion to open surgery. There were no injuries to the nerves and tendons and no hematoma or incomplete dissection of the flexor retinaculum. The operative times varied between 11 and 34 minutes. We obtained the following results based on Kelly’s grading of outcomes: excellent in 116, good in 59, fair in 13, and poor in 3 patients.

Conclusions:

We found no patients with neurapraxia, major nerve injury, flexor tendon injury, superficial palmar arch injury, and hematoma. Although there was a learning curve associated with SRECTR, we performed 200 consecutive cases without neurovascular complications. This method may be a safe alternative to minimally invasive carpal tunnel surgery.
Usefulness of the obturator hook technique for guiding the initial trajectory control in infra-acetabular screw placement
Authors: Lim Eic Ju , Sakong Seungyeob , Son Whee Sung , Kim HanJu , Cho Jae-Woo , Oh Jong-Keon
Published: February 2021

Purpose:

Proper placement of infra-acetabular screws is technically demanding; there is a limited safe zone for screw fixation because of the complexity of the bone anatomy around the hip joint and the vulnerability of the major neurovascular bundles in the pelvic cavity. We aimed to present the obturator hook technique as a surgical technique for infra-acetabular screw placement in acetabular and pelvic fractures and report its radiological outcomes.

Methods:

Patients treated with infra-acetabular screw placement using the obturator hook technique between January 2015 and August 2020 were enrolled in this study. We collected data on demographics, surgical approach, reduction status, complications, and outcomes. The radiological outcomes of infra-acetabular screw placement based on computed tomography findings were evaluated as follows: success, articular penetration, or out of the bone.

Results:

Thirty-five patients underwent infra-acetabular screw placement (26 men, 9 women; mean age, 55 years; range, 27–90 years). One patient underwent bilateral infra-acetabular screw placement; therefore, 36 infra-acetabular screws were inserted in all patients. An ideal placement was achieved with 27 infra-acetabular screws (27/36, 75%). Seven infra-acetabular screws (7/36, 19%) showed articular penetration, and two infra-acetabular screws (2/36, 6%) were placed outside the bone. One patient with articular penetration and mechanical symptoms of the hip joint required screw replacement. No other complications, including obturator nerve and vascular injuries, were observed.

Conclusion:

The obturator hook technique could be a favorable and individualized method for infra-acetabular screw placement in patients with acetabular and pelvic fractures.

Level of Evidence:

IV, retrospective descriptive study.
Percutaneous posteroanterior screw fixation for Haraguchi type 1 posterior malleolar fracture in tri-malleolar fracture: Operative technique and randomized clinical results
Authors: Yu Tianming , Ying Jichong , Liu Jianlei , Huang Dichao , Yan Hailin , Xiao Baiping , Zhuang Yunqiang
Published: February 2021

Purpose:

The study described a novel surgical treatment of Haraguchi type 1 posterior malleolar fracture in tri-malleolar fracture and patient outcomes at intermediate period follow-up.

Methods:

All patients from January 2015 to December 2017 with tri-malleolar fracture of which posterior malleolar fractures were Haraguchi type 1, were surgically treated in this prospective study. Lateral and medial malleolar fractures were managed by open reduction and internal fixation through dual incision approaches. 36 cases of Haraguchi type 1 posterior malleolar fractures were randomly performed by percutaneous posteroanterior screw fixation with the aid of medial exposure (group 1). And 40 cases were performed by percutaneous anteroposterior screw fixation (group 2). Clinical outcomes, radiographic outcomes and patient-reported outcomes were recorded.

Results:

Seventy-six patients with mean follow-up of 30 months were included. There were no significant differences in the mean operation time (81.0 ± 11.3 vs. 77.2 ± 12.4), ankle function at different periods of follow-up, range of motions and visual analog scale (VAS) at 24 months between the two groups ( p > 0.05). However, the rate of severe post-traumatic arthritis (Grade 2 and 3) and the rate of step-off rather than gap in radiological evaluation were lower in group 1 than that in group 2 ( p < 0.05).

Conclusion:

Using our surgical technique, more patients had good outcome with a lower rate of severe post-traumatic arthritis, compared with the group of percutaneous anteroposterior screw fixation. Percutaneous posteroanterior screw fixation can be a convenient and reliable alternative in treating Haraguchi type 1 posterior malleolar fracture.
Multi-dimensional Measurements of Crowding for Pediatric Emergency Departments: A Systematic Review
Authors: Abudan Areej , Merchant Roland C.
Published: February 2021

The absence of accepted crowding measurement tools that encompass the unique characteristics of pediatric emergency departments (EDs) creates a deficit in advancing efforts to identify and evaluate solutions for this growing problem. In this systematic review, we examined 4 studies that reported on the development and testing of multidimensional pediatric ED crowding measurements. Two investigations involved models (PEDOCS, SOTU-PED) that measured factors indicative or contributory to crowding. A third investigation developed a model mapping the flow of patients through the pediatric ED. The final study modeled the magnitude of physician’s work load, particularly when this load is high when crowding is likely present, based on patient arrivals, presenting complaints and conditions, and tests ordered. These works from 4 studies on measuring crowding in pediatric EDs show promise, but this field is at an early stage. Future work should concentrate on comparing the utility of crowding measurements across multiple pediatric ED settings.
Microstructure and wear resistance of red mud iron alloy with chromium and titanium
Authors: Zhou Jiachang , Kang Heyi , Wei Haiping , Tang Hongqun , Ou Xingcheng , Luo Chaoqin
Published: February 2021

Red mud is a solid waste in the production of alumina from bauxite. Red mud iron alloy (RMIA) is prepared from the red mud and laterite nickel ore via the high-temperature carbothermal reduction smelting and refining. Herein, by adjusting the contents of chromium (Cr) and titanium (Ti) in RMIA, low alloy cast iron with high hardness and wear resistance was obtained. Optical emission spectrometer, optical microscope, scanning electron microscopy, and hardness and two-body wear test were used for characterization. The results show that the addition of either Cr or Ti element can lead to carbide formation and refining of graphite. With an increase in the content of Cr or Ti, the hardness and the wear resistance of the alloy were enhanced, and the effect of Cr element was better than that of Ti element. The optimal microstructure and properties of the alloy were obtained at 4.8%Cr0.36%Ti, at which stage, the network eutectic carbide structure disappeared and evenly distributed in the matrix, and meanwhile, the graphite morphology was refined. The hardness of the alloy was higher than high chromium cast iron (HCCI), and the wear resistance of the modified alloy was better than HCCI under low load. The aim of this work is to provide a reference for the preparation of wear-resistant ferroalloys from the red mud directly via high-temperature carbothermal reduction.
Evaluation of image partitioning strategies for preserving spatial information of cross-sectional micrographs in automated wood recognition of Fagaceae
Authors: Hwang Sung-Wook , Sugiyama Junji
Published: February 2021

Although wood cross sections contain spatiotemporal information regarding tree growth, computer vision-based wood identification studies have traditionally favored disordered image representations that do not take such information into account. This paper describes image partitioning strategies that preserve the spatial information of wood cross-sectional images. Three partitioning strategies are designed, namely grid partitioning based on spatial pyramid matching and its variants, radial and tangential partitioning, and their recognition performance is evaluated for the Fagaceae micrograph dataset. The grid and radial partitioning strategies achieve better recognition performance than the bag-of-features model that constitutes their underlying framework. Radial partitioning, which is a strategy for preserving spatial information from pith to bark, further improves the performance, especially for radial-porous species. The Pearson correlation and autocorrelation coefficients produced from radially partitioned sub-images have the potential to be used as auxiliaries in the construction of multi-feature datasets. The contribution of image partitioning strategies is found to be limited to species recognition and is unremarkable at the genus level.
Headspace analyses using multi-capillary column-ion mobility spectrometry allow rapid pathogen differentiation in hospital-acquired pneumonia relevant bacteria
Authors: Kunze-Szikszay Nils , Euler Maximilian , Kuhns Martin , Thieß Melanie , Groß Uwe , Quintel Michael , Perl Thorsten
Published: February 2021

Background

Hospital-acquired pneumonia (HAP) is a common problem in intensive care medicine and the patient outcome depends on the fast beginning of adequate antibiotic therapy. Until today pathogen identification is performed using conventional microbiological methods with turnaround times of at least 24 h for the first results. It was the aim of this study to investigate the potential of headspace analyses detecting bacterial species-specific patterns of volatile organic compounds (VOCs) for the rapid differentiation of HAP-relevant bacteria.

Methods

Eleven HAP-relevant bacteria (Acinetobacter baumanii, Acinetobacter pittii, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Serratia marcescens) were each grown for 6 hours in Lysogeny Broth and the headspace over the grown cultures was investigated using multi-capillary column-ion mobility spectrometry (MCC-IMS) to detect differences in the VOC composition between the bacteria in the panel. Peak areas with changing signal intensities were statistically analysed, including significance testing using one-way ANOVA or Kruskal-Wallis test (p < 0.05).

Results

30 VOC signals (23 in the positive ion mode and 7 in the negative ion mode of the MCC-IMS) showed statistically significant differences in at least one of the investigated bacteria. The VOC patterns of the bacteria within the HAP panel differed substantially and allowed species differentiation.

Conclusions

MCC-IMS headspace analyses allow differentiation of bacteria within HAP-relevant panel after 6 h of incubation in a complex fluid growth medium. The method has the potential to be developed towards a feasible point-of-care diagnostic tool for pathogen differentiation on HAP.
Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China
Authors: Du Ruofei , Wang Xin , Ma Lixia , Larcher Leon M. , Tang Han , Zhou Huiyue , Chen Changying , Wang Tao
Published: February 2021

Background

The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data.

Methods

A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups.

Results

A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group.

Conclusion

The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.
Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial
Authors: Andersen Asger , Waziri Farhad , Schultz Jacob Gammelgaard , Holmboe Sarah , Becker Søren Warberg , Jensen Tage , Søndergaard Hanne Maare , Dodt Karen Kaae , May Ole , Mortensen Ulrik Markus , Kim Won Yong , Mellemkjær Søren , Nielsen-Kudsk Jens Erik
Published: February 2021

Background

To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).

Methods

Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5–1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR.

Results

Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (− 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97).

Conclusion

A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results.

Trial Registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1.
Advancing frontiers in rheumatic and musculoskeletal imaging
Authors: Albano Domenico , Carubbi Francesco
Published: February 2021

In recent years, technological improvements allowed imaging modalities to become increasingly essential in achieving early and precise diagnoses in the field of rheumatic and musculoskeletal diseases (RMDs). To date, imaging examinations are routinely used in all steps of diagnostic and therapeutic care pathways of patients affected by RMDs. The articles published in this Article Collection clearly show the efforts of researchers to find innovative applications of musculoskeletal imaging in clinical practice and to face the crucial challenges that remain in the interpretation and quality control of images. Highly performing diagnostic technologies are currently available to early diagnose and accurately monitor several musculoskeletal disorders, but also to guide personalized interventional therapeutic procedures tailored to the individual patients in the emerging process of precision medicine. Among these new modalities, some are particularly promising and thereby subject to several lines of research in RMDs, including SPECT-CT and dual-energy CT, MRI sequences, high and ultra-high frequency ultrasound with effective tools like shear wave elastography.
The impact of smoking on annual healthcare cost: an econometric model analysis in China, 2015
Authors: Huang Shiyao , Wei Han , Yao Tingting , Mao Zhengzhong , Sun Qun , Yang Lian
Published: February 2021

Background

Smoking exerts substantial medical burdens on society. Precise estimation of the smoking-attributable medical expenditures (SAME) helps to inform tobacco control policy makers. Based on the epidemiological approach, prior studies in China only focused on a few smoking-related diseases to estimate SAME. In contrast, this study used the econometric approach, which is capable of capturing all of the potential costs.

Methods

Three waves of panel data from the 2011–2015 national China Health and Retirement Longitudinal Study (CHARLS) were used. A total of 34,503 observations aged 45 and above were identified. Estimates from econometric models were combined to predict the smoking-attributable fraction (SAF) and medical expenditures attributable to smoking by sex, registered residency and healthcare service categories. All monetary amounts were adjusted to 2015 dollars.

Results

In 2015, the overall smoking-attributable fraction (SAF) of China was 10.97%, ranging from 5.77% for self-medication to 16.87% for inpatient visits. The smoking-attributable medical expenditure (SAME) was about $45.28 billion, accounting for 7.24% of the total health expenditure. The SAME was $226.77 per smoker aged 45 and above. The regression results suggest that being a former smoker has the greatest impact, which decreases over time after quitting however, on the value of medical expenditures.

Conclusions

Smoking-attributable medical expenditures was substantial and placed a heavy burden on Chinese society. Comprehensive tobacco control policies and regulations are still needed to promote progress toward curbing the tobacco related losses.
Primary characterization of the immune responses in Tibetan pigs infected with Chinese Tibet isolate of Trichinella spiralis
Authors: Tingting Li , Wenhui Li , Nianzhang Zhang , Zigang Qu , Ohiolei John A , Li Li , Hongbin Yan , Wanzhong Jia , Baoquan Fu
Published: February 2021

Background

Trichinellosis, caused by Trichinella spiralis, is a serious foodborne parasitic zoonosis. Tibetan pig is an infrequent, endemic plateau pig species, mainly distributed in Tibet Plateau, China. Because of the free-range system, Tibetan pigs are at risk of infection with Trichinella. The present study aimed to primarily profile the characteristics of T. spiralis infection in Tibetan pigs, including IgG levels, larvae burdens, and cytokines.

Results

The immune responses to Chinese Tibet T. spiralis isolate infection in Tibetan pigs with different doses were investigated in a tracking duration of 49 days. The muscle larvae per gram (lpg) were evaluated at 105 days post-infection (dpi). The results showed that the mean larval number of T. spiralis in Tibetan pigs increased with infective dose, with average lpg values of 3.5, 50.4 and 115.6 for Tibetan pigs infected with 200, 2,000, and 20,000 muscle larvae (ML) of T. spiralis. The anti-Trichinella IgG increased with inoculum dose and dpi, and peaked at 49 dpi. The kinetics of cytokines in the sera was detected by microarray, including interferon-γ (IFN-γ), interleukin (IL)-1β, IL-8, IL-12, IL-4, IL-6, IL-10, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1. The Th1/Th2 mixed cytokines were detectable in all samples. Interleukin-12 demonstrated the highest concentration compared to other cytokines and peaked at 42 dpi. Almost all cytokines were maintained at a high level at 42 dpi. Additionally, we also report a Trichinella seropositive rate of 43.9 % (18 out of 41) from field samples of Tibetan pigs.

Conclusions

The present study showed an increased Th1/Th2 mixed cytokines in Tibetan pigs elicited by T. spiralis. The high seroprevalence of Trichinella infection in field samples of Tibetan pigs further raises serious concern for the prevention and control of trichinellosis in this host for public health safety.
Measurement of gene amplifications related to drug resistance in Plasmodium falciparum using droplet digital PCR
Authors: Srisutham Suttipat , Suwannasin Kanokon , Sugaram Rungniran , Dondorp Arjen M. , Imwong Mallika
Published: February 2021

Background

Copy number variations (CNVs) of the Plasmodium falciparum multidrug resistance 1 (pfmdr1), P. falciparum plasmepsin2 (pfplasmepsin2) and P. falciparum GTP cyclohydrolase 1 (pfgch1) genes are associated with anti-malarial drug resistance in P. falciparum malaria. Droplet digital PCR (ddPCR) assays have been developed for accurate assessment of CNVs in several human genes. The aim of the present study was to develop and validate ddPCR assays for detection of the CNVs of P. falciparum genes associated with resistance to anti-malarial drugs.

Methods

A multiplex ddPCR assay was developed to detect the CNVs in the pfmdr1 and pfplasmepsin2 genes, while a duplex ddPCR assay was developed to detect CNV in the pfgch1 gene. The gene copy number (GCN) quantification limit, as well as the accuracy and precision of the ddPCR assays were determined and compared to conventional quantitative PCR (qPCR). In order to reduce the cost of testing, a multiplex ddPCR assay of two target genes, pfmdr1 and pfplasmepsin2, was validated. In addition, the CNVs of genes of field samples collected from Thailand from 2015 to 2019 (n = 84) were assessed by ddPCR and results were compared to qPCR as the reference assay.

Results

There were no significant differences between the GCN results obtained from uniplex and multiplex ddPCR assays for detection of CNVs in the pfmdr1 and pfplasmepsin2 genes (p = 0.363 and 0.330, respectively). Based on the obtained gene copy number quantification limit, the accuracy and percent relative standard deviation (%RSD) value of the multiplex ddPCR assay were 95% and 5%, respectively, for detection of the CNV of the pfmdr1 gene, and 91% and 5% for detection of the CNV of the pfplasmepsin2 gene. There was no significant difference in gene copy numbers assessed by uniplex or duplex ddPCR assays regarding CNV in the pfgch1 gene (p = 0.276). The accuracy and %RSD value of the duplex ddPCR assay were 95% and 4%, respectively, regarding pfgch1 GCN. In the P. falciparum field samples, pfmdr1 and pfplasmepsin2 GCNs were amplified in 15% and 27% of samples from Ubon Ratchathani, Thailand, while pfgch1 GCN was amplified in 50% of samples from Yala, Thailand. There was 100% agreement between the GCN results obtained from the ddPCR and qPCR assays (κ = 1.00). The results suggested that multiplex ddPCR assay is the optional assay for the accurate detection of gene copy number without requiring calibration standards, while the cost and required time are reduced. Based on the results of this study, criteria for GCN detection by ddPCR analysis were generated.

Conclusions

The developed ddPCR assays are simple, accurate, precise and cost-effective tools for detection of the CNVs in the pfmdr1, pfplasmepsin2 and pfgch1 genes of P. falciparum. The ddPCR assay is a useful additional tool for the surveillance of anti-malarial drug resistance.
In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus
Authors: Patil Poonam , Agrawal Megha , Almelkar Shahdab , Jeengar Manish Kumar , More Ashwini , Alagarasu Kalichamy , Kumar Naveen V. , Mainkar Prathama S. , Parashar Deepti , Cherian Sarah
Published: February 2021

Background

Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection.

Methods

The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies.

Results

In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2–E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain.

Conclusions

The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell
Authors: Zhang Xialin , Dou Linqin , Zhang Ming , Wang Yu , Jiang Xin , Li Xinqiong , Wei Long , Chen Yuejia , Zhou Cuisong , Geng Jia
Published: February 2021

Interface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity and excellent selectivity for real-time monitoring neurotransmitters transport through single live cell. Sensing techniques including electrode-based methods, optogenetics, and nanowire cell penetration systems have been developed to monitor the neuron activities. However, their biocompatibilities remain a challenge. Protein nanopores with membrane compatibility and lumen tunability provide real-time, single-molecule sensitivities for biosensing of DNA, RNA, peptides and small molecules. In this study, an engineered protein nanopore MspA (Mycobacterium smegmatis porin A) through site-directed mutation with histidine selectively bind with Cu2+ in its internal lumen. Chelation of neurotransmitters such as L-glutamate (L-Glu), dopamine (DA) and norepinephrine (NE) with the Cu2+ creates specific current signals, showing different transient current blockade and dwell time in single channel electrophysiological recording. Furthermore, the functionalized M2MspA-N91H nanopores have been embedded in live HEK293T cell membrane for real-time, in situ monitoring of extracellular L-glutamate translocating through the nanopore. This biomimetic neurotransmitter nanopore has provided a new platform for future development of neuron sensors, drug carrier and artificial synapse.
Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion
Authors: Petry Clive J , Burling Keith A , Barker Peter , Hughes Ieuan A , Ong Ken K , Dunger David B
Published: February 2021

Context

Delta like noncanonical notch ligand 1 (DLK1) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.

Objective

We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.

Patients, design, and setting

We measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.

Results

Maternal DLK1 concentrations were associated with the paternally transmitted fetal DLK1 rs12147008 allele (P = 7.8 × 10-3) but not with maternal rs12147008 genotype (P = 0.4). Maternal DLK1 concentrations were positively associated with maternal prepregnancy body mass index (P = 3.5 × 10-6), and (after adjustment for maternal body mass index) with both maternal fasting insulin resistance (Homeostatic Model Assessment of Insulin Resistance: P = 0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: P = 1.2 × 10-3; insulin disposition index: P = 0.049). Further positive associations were found with offspring weight (P = 0.02) and head circumference at birth (P = 0.04).

Conclusion

These results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.
An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone
Authors: Walker Joanne M , Yao Gang-Qing , Siu Edwin , Zhu Meiling , Sun Ben-hua , Simpson Christine , Insogna Karl L
Published: February 2021

Sphingosine-1-phosphate (S1P) is an anabolic clastokine. Sphingosine kinase (SPHK) is the rate-limiting enzyme in S1P production and has 2 isoforms. To evaluate the roles of SPHK1 and SPHK2 in bone, we examined the skeletal phenotype of mice with selective deletion of SPHK1 in osteoclasts (SPHK1-Oc−/−) and mice in which the SPHK2 gene was deleted in all tissues (SPHK2−/−). SPHK1-Oc−/− had normal bone mass. By contrast, SPHK2−/− female mice had a 14% lower spinal bone mineral density (BMD; P < 0.01) and males a 22% lower BMD at the same site (P < 0.001). SPHK2−/− and control mice were subsequently treated either with daily parathyroid hormone [PTH](1-34) or vehicle for 29 days. The response to PTH was significantly attenuated in the SPHK2−/−mice. The mean femoral bone volume to total volume fraction (BV/TV) increased by 24.8% in the PTH-treated female control animals vs 10.6% in the vehicle-treated female controls (P < 0.01). In contrast, in the SPHK2−/− female mice the difference in femoral trabecular BV/TV at the end of treatment was not significant (20.5 vs13.3%, PTH vs vehicle, P = NS). The anabolic response to PTH was significantly attenuated in the spine of male SPHK2−/− mice (29.7% vs 23.1%, PTH vs vehicle, in controls, P < 0.05; 26.9% vs 19.5% PTH vs vehicle in SPHK2−/− mice, P = NS). The spine responded normally in the SPHK2−/− female mice. Interestingly, suppression of sclerostin was blunted in the SPHK2−/− mice when those animals were treated with an anabolic PTH regimen. We conclude that SPHK2 has an important role in mediating both normal bone remodeling and the anabolic response to PTH.
Parathyroid Hormone Induces Transition of Myofibroblasts in Arteriovenous Fistula and Increases Maturation Failure
Authors: Liu Chung-Te , Hsu Shih-Chang , Hsieh Hui-Ling , Chen Cheng-Hsien , Chen Chun-You , Sue Yuh-Mou , Lin Feng-Yen , Shih Chun-Ming , Shiu Yan-Ting , Huang Po-Hsun
Published: February 2021

Context

Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown.

Objective

This work aimed to investigate the association between plasma PTH and AVF maturation.

Methods

Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion.

Results

In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin β6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast.

Conclusion

Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.
Surgical management of symptomatic osteonecrosis and utility of core decompression of the femoral head in young people with acute lymphoblastic leukaemia recruited into UKALL 2003
Authors: Amin Nadia , Kraft Jeannette , Fishlock Adelle , White Alan , Holton Colin , Kinsey Sally , Feltbower Richard , James Beki
Published: February 2021

Aims

Osteonecrosis (ON) can cause considerable morbidity in young people who undergo treatment for acute lymphoblastic leukaemia (ALL). The aims of this study were to determine the operations undertaken for ON in this population in the UK, along with the timing of these operations and any sequential procedures that are used in different joints. We also explored the outcomes of those patients treated by core decompression (CD), and compared this with conservative management, in both the pre- or post-collapse stages of ON.

Methods

UK treatment centres were contacted to obtain details regarding surgical interventions and long-term outcomes for patients who were treated for ALL and who developed ON in UKALL 2003 (the national leukaemia study which recruited patients aged 1 to 24 years at diagnosis of ALL between 2003 and 2011). Imaging of patients with ON affecting the femoral head was requested and was used to score all lesions, with subsequent imaging used to determine the final grade. Kaplan-Meier failure time plots were used to compare the use of CD with non surgical management.

Results

Detailed information was received for 85 patients who had developed ON during the course of their ALL treatment. A total of 206 joints were affected by ON. Of all joints affected by ON, 21% required arthroplasty, and 43% of all hips affected went on to be replaced. CD was performed in 30% of hips affected by ON. The majority of the hips were grade 4 or 5 at initial diagnosis of ON. There was no significant difference in time to joint collapse between those joints in which CD was performed, compared with no joint-preserving surgical intervention.

Conclusion

There is a high incidence of surgery in young people who have received treatment for ALL and who have developed ON. Our results suggest that CD of the femoral head in this group of patients does not delay or improve the rates of femoral head survival. Cite this article: Bone Joint J 2021;103-B(3):589–596.
Does total hip arthroplasty have a higher risk of failure in patients who undergo lumbar spinal fusion?
Authors: Di Martino Alberto , Bordini Barbara , Ancarani Cristina , Viceconti Marco , Faldini Cesare
Published: February 2021

Aims

Total hip arthroplasty (THA) patients undergoing or having a prior lumbar spine fusion (LSF) have an increased risk of mechanical complications. The aim of this registry-based, retrospective comparative cohort study is to assess the longer term survival of THA in patients who have undergone a LSF during a 17-year period (2000 to 2017).

Methods

A registry-based population study was conducted on 679 patients who underwent both THA and LSF surgeries. Patients were identified from the regional arthroplasty data base and cross linked to patients with LSF from the regional hospital discharge database between 2000 and 2017. Demographic data, diagnosis leading to primary THA, primary implant survival, perioperative complications, number and causes of failure, and patients requiring revision arthroplasty were collated and compared. For comparison, data from 67,919 primary THAs performed during the same time time period were also retrieved and analyzed.

Results

Patients undergoing THA and LSF showed homogeneous demographic data compared to those undergoing THA alone, but a significantly lower eight-year THA implant survival (96.7 vs 96.0, p = 0.024) was observed. Moreover, THA plus LSF patients showed increased incidence of mechanical complications in the first two years after THA surgery compared to THA alone patients.

Conclusion

This registry-based population study shows that approximately 679 (1%) THA patients were subjected to LSF. Patients undergoing THA and LSF have an increased risk of mechanical complications with their THA and a slightly increased risk of revision arthroplasty. Cite this article: Bone Joint J 2021;103-B(3):486–491.