bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between exposure to perfluoroalkyl substances and body fat evaluated by DXA and MRI in 109 adolescent boys
Authors: Thomsen Mathilde Lolk , Henriksen Louise Scheutz , Tinggaard Jeanette , Nielsen Flemming , Jensen Tina Kold , Main Katharina M.
Published: June 2021

Background

Exposure to perfluoroalkyl substances (PFASs) has been associated with changes in body mass index and adiposity, but evidence is inconsistent as study design, population age, follow-up periods and exposure levels vary between studies. We investigated associations between PFAS exposure and body fat in a cross-sectional study of healthy boys.

Methods

In 109 boys (10–14 years old), magnetic resonance imaging and dual-energy X-ray absorptiometry were performed to evaluate abdominal, visceral fat, total body, android, gynoid, android/gynoid ratio, and total fat percentage standard deviation score. Serum was analysed for perfluorooctanoic acid, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid, and perfluorodecanoic acid using liquid chromatography and triple quadrupole mass spectrometry. Data were analysed by multivariate linear regression.

Results

Serum concentrations of PFASs were low. Generally, no clear associations between PFAS exposure and body fat measures were found; however, PFOS was negatively associated with abdominal fat (β = -0.18, P = 0.046), android fat (β = -0.34, P = 0.022), android/gynoid ratio (β = -0.21, P = 0.004), as well as total body fat (β = -0.21, P = 0.079) when adjusting for Tanner stage.

Conclusions

Overall, we found no consistent associations between PFAS exposure and body fat. This could be due to our cross-sectional study design. Furthermore, we assessed PFAS exposure in adolescence and not in utero, which is considered a more vulnerable time window of exposure.
Increased levels of S100A8/A9, IL-1ß and IL-18 as a novel biomarker for recurrent tonsillitis
Authors: Spiekermann Christoph , Seethaler Alicia , McNally Annika , Stenner Markus , Rudack Claudia , Roth Johannes , Vogl Thomas
Published: June 2021

Background

Acute tonsillitis represents one of the most frequent reasons patients seek primary medical care and otorhinolaryngology consultation. Therefore, recurrent episodes of acute tonsillitis (RAT), also called chronic tonsillitis, exhaust a substantial amount of medical and financial resources. Diagnosis of tonsillitis depends on a physical examination, which therefore does not allow for a reliable differentiation between viral and bacterial infection. However, the frequency of bacterial infections during the previous three years is currently being used as the major deciding factor in patient selection for tonsillectomy. The aim of the present study was to determine an objective biomarker to help in the identification of patients suffering from recurrent tonsillitis.

Results

By analyzing a panel of cytokines and chemokines in serum and saliva of patients with RAT compared to healthy controls, increased levels of IL-1ß (153.7 ± 48.5 pg/ml vs 23.3 ± 6.6 pg/ml, p = 0.021), IL-18 (120.2 ± 16.5 vs 50.6 ± 9.3 pg/ml, p = 0.007) and/or S100A8/A9 (996 ± 102 ng/ml vs 546 ± 86 ng/ml, p = 0.042) could be observed in patients suffering from RAT. Cut-off values of these parameters were determined and combined to a new RAT-score allowing for reliable identification of patients suffering from recurrent tonsillitis with a sensitivity of 95% and a specificity of 88%.

Conclusion

The RAT-score represents the first objective criterion as a tool for the diagnosis of recurrent tonsillitis and it also improves patient selection for tonsillectomy.
Public availability of information from WFME-recognized accreditation agencies
Authors: Baniadam Kahlo , Arfeen Zakia , Rashid Mohammed Ahmed , Ho Ming-Jung , Tackett Sean
Published: June 2021

The World Federation for Medical Education (WFME) Recognition Programme was created to ensure the comparability of medical school accrediting agencies, so that the schools accredited by those agencies would have similar educational quality. WFME explicitly values transparency and has recognition criteria that relate to agencies making information publicly available. Our study examined 20 WFME-recognized agencies’ transparency by reviewing agency websites for 27 information elements related to accreditation standards, procedures, and processes. We contacted agencies as needed for information that we could not find on their websites. We were only able to retrieve additional information from 3 of the 12 agencies that we attempted to contact. We found that while 12 agencies had over 90% of expected information elements available, 6 agencies had less than 50%. Our findings illustrate barriers for those who wish to better understand medical school accreditation in some regions and raise questions about how comparable WFME-recognized agencies are.
Lack of impact of radiation on blood physiology biomarkers of Chernobyl tree frogs
Authors: Burraco Pablo , Bonzom Jean-Marc , Car Clément , Beaugelin-Seiller Karine , Gashchak Sergey , Orizaola Germán
Published: June 2021

Background

Human actions have altered natural ecosystems worldwide. Among the many pollutants released to the environment, ionizing radiation can cause severe damage at different molecular and functional levels. The accident in the Chernobyl Nuclear Power Plant (1986) caused the largest release of ionizing radiation to the environment in human history. Here, we examined the impact of the current exposure to ionizing radiation on blood physiology biomarkers of adult males of the Eastern tree frog (Hyla orientalis) inhabiting within and outside the Chernobyl Exclusion Zone. We measured the levels of eight blood parameters (sodium, potassium, chloride, ionized calcium, total carbon dioxide, glucose, urea nitrogen, and anion gap), physiological markers of homeostasis, as well as of liver and kidney function.

Results

Levels of blood physiology biomarkers did not vary in function of the current exposure of tree frogs to ionizing radiation within the Chernobyl Exclusion Zone. Physiological blood levels were similar in frogs inhabiting Chernobyl (both in areas with medium-high or low radiation) than in tree frogs living outside Chernobyl exposed only to background radiation levels.

Conclusions

The observed lack of effects of current radiation levels on blood biomarkers can be a consequence of the low levels of radiation currently experienced by Chernobyl tree frogs, but also to the fact that our sampling was restricted to active breeding males, i.e. potentially healthy adult individuals. Despite the clear absence of effects of current radiation levels on physiological blood parameters in tree frogs, more research covering different life stages and ecological scenarios is still needed to clarify the impact of ionizing radiation on the physiology, ecology, and dynamics of wildlife inhabiting radioactive-contaminated areas.
The use of solvent-preserved human and bovine cancellous bone blocks for lateral defect augmentation - an experimental controlled study in vivo
Authors: Schorn Lara , Fienitz Tim , Berndsen Kathrin , Kübler Norbert R. , Holtmann Henrik , Rothamel Daniel
Published: June 2021

Background

The aim of this study was to compare new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material in laterally augmented alveolar bone defects using allogeneic, pre-treated and cleaned human bone blocks (tested in dogs, therefore considered to be xenogeneic), and pre-treated and cleaned bovine cancellous bone blocks, both with and without a collagen membrane in order to evaluate their augmentative potential.

Methods

Thirty-two critical size horizontal defects were prepared in the mandible of 4 adult foxhound dogs (8 per dog, 4 on each side). After 3 months of healing, the defects were laterally augmented in a split-mouth-design with either human (HXB) or bovine solvent-preserved bone blocks (BXB). Afterwards, defects were randomly covered with a bovine collagenous membrane (HXB + M, BXB + M). After a healing interval of 6 months, percentages of new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material were compared.

Results

Results showed little new bone formation of up to 3.7 % in human bone blocks (HXB 3.7 % ± 10.2, HXB + M 0.3 %± 0.4, BXB, 0.1 % ± 0.8, BXB + M 2.6 % ± 3.2,p = > 0.05). Percentages of fibrous encapsulation were higher in human bone blocks than in bovine bone blocks (HXB 71.2 % ± 8.6, HXB + M 73.71 % ± 10.6, BXB, 60.5 % ± 27.4, BXB + M 52.5 % ± 28.4,p = > 0.05). Resorption rates differed from 44.8 % in bovine bone blocks covered with a membrane to 17.4 % in human bone blocks (HXB 17.4 % ± 7.4, HXB + M 25.9 % ± 10.7, BXB, 38.4 % ± 27.2, BXB + M 44.8 % ± 29.6,p = > 0.05). The use of additional membranes did not significantly affect results.

Conclusions

Within its limitations, results of this study suggest that solvent-preserved xenogenic human and bovine bone blocks are not suitable for lateral bone augmentation in dogs. Furthermore, defect coverage with a membrane does not positively affect the outcome.
Circular RNA circRHOBTB3 is downregulated in hepatocellular carcinoma and suppresses cell proliferation by inhibiting miR-18a maturation
Authors: Hu Gang , Zhai Shusen , Yu Sheng , Huang Zhen , Gao Ran
Published: June 2021

Background

Circular RNA circRHOBTB3 has been characterized as a tumor suppressor in gastric cancer, while its role in hepatocellular carcinoma (HCC) is unknown. This study was carried out to analyze the role of circRHOBTB3 in HCC.

Methods

In this study, circRHOBTB3, mature miR-18a, and miR-18a precursor in HCC and paired non-cancer tissues were detected by RT-qPCR. The role of circRHOBTB3 in the production of mature miR-18a was explored by transfecting circRHOBTB3 expression vector into HCC cells, followed by RT-qPCR to determine the expression of mature miR-18a and miR-18a precursor. The role of circRHOBTB3 and miR-18a in HCC cell proliferation was studied using CCK-8 assay.

Results

CircRHOBTB3 was under-expressed in HCC compared to normal tissues. In HCC cells, circRHOBTB3 overexpression decreased mature miR-18a level but not miR-18a precursor. Cell proliferation analysis showed that circRHOBTB3 overexpression decreased cell proliferation while miR-18a overexpression increased cell proliferation. Moreover, circRHOBTB3 suppressed the role of miR-18a in cell proliferation.

Conclusions

CircRHOBTB3 is downregulated in HCC and may suppress cell proliferation by reducing miR-18a production.
Advanced thyroid carcinomas: neural network analysis of ultrasonographic characteristics
Authors: Cordes Michael , Götz Theresa Ida , Lang Elmar Wolfgang , Coerper Stephan , Kuwert Torsten , Schmidkonz Christian
Published: June 2021

Background

Ultrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain characteristics observable by ultrasound have recently been identified that may indicate malignancy. This retrospective cohort study was conducted to test the hypothesis that advanced thyroid carcinomas show distinctive clinical and sonographic characteristics. Using a neural network model as proof of concept, nine clinical/sonographic features served as input.

Methods

All 96 study enrollees had histologically confirmed thyroid carcinomas, categorized (n = 32, each) as follows: group 1, advanced carcinoma (ADV) marked by local invasion or distant metastasis; group 2, non-advanced papillary carcinoma (PTC); or group 3, non-advanced follicular carcinoma (FTC). Preoperative ultrasound profiles were obtained via standardized protocols. The neural network had nine input neurons and one hidden layer.

Results

Mean age and the number of male patients in group 1 were significantly higher compared with groups 2 (p = 0.005) or 3 (p <  0.001). On ultrasound, tumors of larger volume and irregular shape were observed significantly more often in group 1 compared with groups 2 (p <  0.001) or 3 (p ≤ 0.01). Network accuracy in discriminating advanced vs. non-advanced tumors was 84.4% (95% confidence interval [CI]: 75.5–91), with positive and negative predictive values of 87.1% (95% CI: 70.2–96.4) and 92.3% (95% CI: 83.0–97.5), respectively.

Conclusions

Our study has shown some evidence that advanced thyroid tumors demonstrate distinctive clinical and sonographic characteristics. Further prospective investigations with larger numbers of patients and multicenter design should be carried out to show whether a neural network incorporating these features may be an asset, helping to classify malignancies of the thyroid gland.
Characterization of a novel mutation V136L in bone morphogenetic protein 15 identified in a woman affected by POI
Authors: Ferrarini Eleonora , De Marco Giuseppina , Orsolini Francesca , Gianetti Elena , Benelli Elena , Fruzzetti Franca , Simoncini Tommaso , Agretti Patrizia , Tonacchera Massimo
Published: June 2021

Background

Premature ovarian insufficiency (POI) is an ovarian defect characterized by primary or secondary amenorrhea, hypergonadotropism and hypoestrogenism which occurs before the age of 40 years with a major genetic component. In this study we performed clinical evaluation and genetic analysis of a group of 18 patients with POI.

The study involved 18 consecutive women with POI. Karyotiping and genetic analysis for research of mutations in GDF9 (Growth Differentation Factor 9) and BMP15 (Bone morphogentic protein 15) genes and FMR1 (Fragile X Mental Retardation 1) premutation were carried out. In vitro functional study of the novel BMP15 mutation was performed using COV434 (Human ovarian granulosa tumour cells 434) cells of ovarian granulosa, which consistently express BMP responsive element, and luciferase reporter assay.

Results

Three patients (17%) had a family history of POI. Ten patients (56%) had a family history of autoimmune diseases and nine patients (50%) showed a personal history of one or more autoimmune diseases. Of patients for whom morphological assessment was available, almost half (44%) had poor follicle assets or small ovaries’s size at pelvic US. Two patients (13%) showed reduced bone density at DEXA (Dual Energy X-ray Absorptiometry). All the women had normal female kariotype and no mutations in the GDF-9 gene or FMR1 premutations were found. A novel heterozygous mutation c.406G > C (V136L) of BMP15 gene was identified in one patient. After transfection in COV434 cells, BMP15 variant showed a significantly reduced luciferase activity compared to wild type.

Conclusions

POI is a multifactorial disease with several health implications. Autoimmunity and genetics represent the most common aetiology. We identified and characterized a novel BMP15 mutation, providing an additional elucidation of molecular basis of this complex disorder.
Management of respiratory distress following prehospital implementation of noninvasive ventilation in a physician-staffed emergency medical service: a single-center retrospective study
Authors: Dunand Adeline , Beysard Nicolas , Maudet Ludovic , Carron Pierre-Nicolas , Dami Fabrice , Piquilloud Lise , Caillet-Bois David , Pasquier Mathieu
Published: June 2021

Background

Noninvasive ventilation (NIV) is recognized as first line ventilatory support for the management of acute pulmonary edema (APE) and chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to study the prehospital management of patients in acute respiratory distress with an indication for NIV and whether they received it or not.

Methods

This retrospective study included patients ≥18 years old who were cared for acute respiratory distress in a prehospital setting. Indications for NIV were oxygen saturation (SpO2) <90% and/or respiratory rate (RR) >25/min with a presumptive diagnosis of APE or COPD exacerbation. Study population characteristics, initial and at hospital vital signs, presumptive and definitive diagnosis were analyzed. For patients who received NIV, dyspnea level was evaluated with a dyspnea verbal ordinal scale (D-VOS, 0-10) and arterial blood gas (ABG) values were obtained at hospital arrival.

Results

Among the 187 consecutive patients included in the study, most (n = 105, 56%) had experienced APE or COPD exacerbation, and 56 (30%) received NIV. In comparison with patients without NIV, those treated with NIV had a higher initial RR (35 ± 8/min vs 29 ± 10/min, p < 0.0001) and a lower SpO2 (79 ± 10 vs 88 ± 11, p < 0.0001). The level of dyspnea was significantly reduced for patients treated with NIV (on-scene D-VOS 8.4 ± 1.7 vs 4.4 ± 1.8 at admission, p < 0.0001). Among the 131 patients not treated with NIV, 41 (31%) had an indication. In the latter group, initial SpO2 was 80 ± 10% in the NIV group versus 86 ± 11% in the non-NIV group (p = 0.0006). NIV was interrupted in 9 (16%) patients due to either discomfort (n = 5), technical problem (n = 2), persistent desaturation (n = 1), or vomiting (n = 1).

Conclusions

The results of this study contribute to a better understanding of the prehospital management of patients who present with acute respiratory distress and an indication for NIV. NIV was started on clinically more severe patients, even if predefined criteria to start NIV were present. NIV allows to improve vital signs and D-VOS in those patients. A prospective study could further elucidate why patients with a suspected diagnosis of APE and COPD are not treated with NIV, as well as the clinical impact of the different strategies.

Trial registration

The study was approved by our institutional ethical committee (CER-VD 2020-01363).
Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?
Authors: Liao Chun-Kai , Lin Yueh-Chen , Hsu Yu-Jen , Chern Yih-Jong , You Jeng-Fu , Chiang Jy-Ming
Published: June 2021

Background

Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients.

Patients and methods

Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses.

Results

Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup.

Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257–0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172–.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219–1.150, p = 0.103) for EC subgroup compared with SC subgroup.

Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346–9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788–7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found.

Conclusions

Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.
Neurally adjusted ventilatory assist as a weaning mode for adults with invasive mechanical ventilation: a systematic review and meta-analysis
Authors: Yuan Xueyan , Lu Xinxing , Chao Yali , Beck Jennifer , Sinderby Christer , Xie Jianfeng , Yang Yi , Qiu Haibo , Liu Ling
Published: June 2021

Background

Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient–ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient–ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear.

Methods

We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed.

Results

Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = − 2.63; 95% CI − 4.22 to − 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes.

Conclusions

Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.
Management of allergic rhinitis with leukotriene receptor antagonists versus selective H1-antihistamines: a meta-analysis of current evidence
Authors: Feng Yan , Meng Ya-Ping , Dong Ying-Ying , Qiu Chang-Yu , Cheng Lei
Published: June 2021

Background

Inconsistencies remain regarding the effectiveness and safety of leukotriene receptor antagonists (LTRAs) and selective H1-antihistamines (SAHs) for allergic rhinitis (AR). A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the medications.

Methods

Relevant head-to-head comparative RCTs were retrieved by searching the PubMed, Embase, and Cochrane’s Library databases from inception to April 20, 2020. A random-effects model was applied to pool the results. Subgroup analyses were performed for seasonal and perennial AR.

Results

Fourteen RCTs comprising 4458 patients were included. LTRAs were inferior to SAHs in terms of the daytime nasal symptoms score (mean difference [MD]: 0.05, 95% confidence interval [CI] 0.02 to 0.08, p = 0.003, I2 = 89%) and daytime eye symptoms score (MD: 0.05, 95% CI 0.01 to 0.08, p = 0.009, I2 = 89%), but were superior in terms of the nighttime symptoms score (MD: − 0.04, 95% CI − 0.06 to − 0.02, p < 0.001, I2 = 85%). The effects of the two treatments on the composite symptom score (MD: 0.02, 95% CI − 0.02 to 0.05, p = 0.30, I2 = 91%) and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) (MD: 0.01, 95% CI − 0.05 to 0.07, p = 0.71, I2 = 99%) were similar. Incidences of adverse events were comparable (odds ratio [OR]: 0.97, 95% CI 0.75 to 1.25, p = 0.98, I2 = 0%). These results were mainly obtained from studies on seasonal AR. No significant publication bias was detected.

Conclusions

Although both treatments are safe and effective in improving the quality of life (QoL) in AR patients, LTRAs are more effective in improving nighttime symptoms but less effective in improving daytime nasal symptoms compared to SAHs.
Cell-specific expression and individual function of prohormone convertase PC1/3 in Tribolium larval growth highlights major evolutionary changes between beetle and fly neuroendocrine systems
Authors: Fritzsche Sonja , Hunnekuhl Vera S.
Published: June 2021

Background

The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates, ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome.

Results

In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient yolk to the developing oocytes. Larval RNAi against PC2 produced moulting defects where the larvae were not able to shed their old cuticle. This ecdysis phenotype was also observed in a small subset of PC1/3 knockdown larvae and was strongest in a double knockdown. Unexpectedly, most PC1/3-RNAi larvae showed strongly reduced growth, but went through larval moults despite minimal to zero weight gain.

Conclusions

The cell type-specific expression of PC1/3 and its essential requirement for larval growth highlight the important role of this gene within the insect neuroendocrine system. Genomic conservation in most insect groups suggests that it has a comparable individual function in other insects as well, which has been replaced by alternative mechanisms in flies.
Workload of diagnostic radiologists in the foreseeable future based on recent scientific advances: growth expectations and role of artificial intelligence
Authors: Kwee Thomas C. , Kwee Robert M.
Published: June 2021

Objective

To determine the anticipated contribution of recently published medical imaging literature, including artificial intelligence (AI), on the workload of diagnostic radiologists.

Methods

This study included a random sample of 440 medical imaging studies published in 2019. The direct contribution of each study to patient care and its effect on the workload of diagnostic radiologists (i.e., number of examinations performed per time unit) was assessed. Separate analyses were done for an academic tertiary care center and a non-academic general teaching hospital.

Results

In the academic tertiary care center setting, 65.0% (286/440) of studies could directly contribute to patient care, of which 48.3% (138/286) would increase workload, 46.2% (132/286) would not change workload, 4.5% (13/286) would decrease workload, and 1.0% (3/286) had an unclear effect on workload. In the non-academic general teaching hospital setting, 63.0% (277/240) of studies could directly contribute to patient care, of which 48.7% (135/277) would increase workload, 46.2% (128/277) would not change workload, 4.3% (12/277) would decrease workload, and 0.7% (2/277) had an unclear effect on workload. Studies with AI as primary research area were significantly associated with an increased workload (p < 0.001), with an odds ratio (OR) of 10.64 (95% confidence interval (CI) 3.25–34.80) in the academic tertiary care center setting and an OR of 10.45 (95% CI 3.19–34.21) in the non-academic general teaching hospital setting.

Conclusions

Recently published medical imaging studies often add value to radiological patient care. However, they likely increase the overall workload of diagnostic radiologists, and this particularly applies to AI studies.
A team-based competition for undergraduate medical students to learn radiology within the virtual world Second Life
Authors: Rudolphi-Solero Teodoro , Jimenez-Zayas Alberto , Lorenzo-Alvarez Rocio , Domínguez-Pinos Dolores , Ruiz-Gomez Miguel Jose , Sendra-Portero Francisco
Published: June 2021

Background

A multi-user competitive game within the virtual world Second Life for undergraduate radiology learning was adapted for team participation. This study aimed to assess student perception, impact on learning, and eventual correlation of game results with post-exposure tests and course grades.

Methods

The game consisted of six weekly stages, dedicated to thoracic, abdominal, and musculoskeletal radiological anatomy and semiology. Participants had several days a week to review self-guided radiology educational content and then complete individual multiple-choice tests and solve team tasks to progress through the game's ranking. Additionally, they completed a cognitive load test, a questionnaire about the experience and a post-exposure knowledge test.

Results

Fifty-two students organised into 13 teams participated in the game and assessed different aspects of the experience with a mean score ≥ 7.8 on a 10-point scale, highlighting the participation of the teacher (9.3 ± 1.1), the educational contents (8.8 ± 1.4) and the usefulness for their education (8.7 ± 1.4). Participants obtained better post-exposure test results (p < 0.007) and better course grades (p < 0.021) than non-participants did.

Conclusion

A multi-user game adapted to team competition to learn radiology in Second Life was very positively perceived by third-year medical students, who highly valued its content, organisation, and usefulness for their training. Most of the participants agreed that they had collaborated as a team and that playing in competitive environments helps them learn better. The best post-exposure and academic results compared to non-participating students indicate the potential impact of the game on learning.
hPMSCs inhibit the expression of PD-1 in CD4+IL-10+ T cells and mitigate liver damage in a GVHD mouse model by regulating the crosstalk between Nrf2 and NF-κB signaling pathway
Authors: Zhang Aiping , Zhang Jiashen , Li Xiaohua , Zhang Hengchao , Xiong Yanlian , Wang Zhuoya , Zhao Nannan , Wang Feifei , Luan Xiying
Published: June 2021

Background

The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4+IL-10+ T cells and liver tissue and alleviate GVHD remains unclear. This study aimed to investigate the effect of hPMSC-mediated treatment of GVHD associated with CD4+IL-10+ T cell generation via control of redox metabolism and PD-1 expression and whether the Nrf2 and NF-κB signaling pathways were both involved in the process.

Methods

A GVHD mouse model was induced using 6–8-week-old C57BL/6 and Balb/c mice, which were treated with hPMSCs. In order to observe whether hPMSCs affect the generation of CD4+IL-10+ T cells via control of redox metabolism and PD-1 expression, a CD4+IL-10+ T cell culture system was induced using human naive CD4+ T cells. The percentage of CD4+IL-10+ T cells and their PD-1 expression levels were determined in vivo and in vitro using flow cytometry, and Nrf2, HO-1, NQO1, GCLC, GCLM, and NF-κB levels were determined by western blotting, qRT-PCR, and immunofluorescence, respectively. Hematoxylin-eosin, Masson’s trichrome, and periodic acid-Schiff staining methods were employed to analyze the changes in hepatic tissue.

Results

A decreased activity of superoxide dismutase (SOD) and a proportion of CD4+IL-10+ T cells with increased PD-1 expression were observed in GVHD patients and the mouse model. Treatment with hPMSCs increased SOD activity and GCL and GSH levels in the GVHD mouse model. The percentage of CD4+IL-10+ T cells with decreased PD-1 expression, as well as Nrf2, HO-1, NQO1, GCLC, and GCLM levels, both in the GVHD mouse model and in the process of CD4+IL-10+ T cell generation, were also increased, but NF-κB phosphorylation and nuclear translocation were inhibited after treatment with hPMSCs, which was accompanied by improvement of hepatic histopathological changes.

Conclusions

The findings suggested that hPMSC-mediated redox metabolism balance and decreased PD-1 expression in CD4+IL-10+ T cells were achieved by controlling the crosstalk between Nrf2 and NF-κB, which further provided evidence for the application of hPMSC-mediated treatment of GVHD.
Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury
Authors: Chen Yen-Ta , Chuang Fei-Chi , Yang Chih-Chao , Chiang John Y. , Sung Pei-Hsun , Chu Yi-Ching , Huang Chi-Ruei , Huang Kuan-Hui , Yip Hon-Kan
Published: June 2021

Background

This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.

Methods and results

Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001).

Conclusion

Mel-ADMSCs effectively protected the testis against TTIR injury.
LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels
Authors: Zhao Chen-Guang , Qin Jie , Li Jia , Jiang Shan , Ju Fen , Sun Wei , Ren Zhen , Ji Yu-Qiang , Wang Rui , Sun Xiao-Long , Mou Xiang , Yuan Hua
Published: June 2021

Background

Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells.

Methods

sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and β-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0–35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test.

Results

We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery.

Conclusions

LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.
MicroRNAs: emerging driver of cancer perineural invasion
Authors: Zhang Mei , Xian Hong-chun , Dai Li , Tang Ya-ling , Liang Xin-hua
Published: June 2021

The perineural invasion (PNI), which refers to tumor cells encroaching on nerve, is a clinical feature frequently occurred in various malignant tumors, and responsible for postoperative recurrence, metastasis and decreased survival. The pathogenesis of PNI switches from ‘low-resistance channel’ hypothesis to ‘mutual attraction’ theory between peripheral nerves and tumor cells in perineural niche. Among various molecules in perineural niche, microRNA (miRNA) as an emerging modulator of PNI through generating RNA-induced silencing complex (RISC) to orchestrate oncogene and anti-oncogene has aroused a wide attention. This article systematically reviewed the role of microRNA in PNI, promising to identify new biomarkers and offer cancer therapeutic targets.
An effective localization algorithm for moving sources
Authors: Wang Hao , Li Liping
Published: June 2021

By utilizing the time difference of arrival (TDOA), the frequency difference of arrival (FDOA), and the differential Doppler rate (DDR) measurements from sensors, this paper proposes an effective moving source localization algorithm with closed solutions. Instead of employing the traditional two-step weighted least squares (WLS) process, the Lagrange multiplier technique is employed in the first step to obtain the initial solution. This initial solution yields a better solution than the existing solution because the dependence among the variables are taken into account. The initial solution is further refined in the second step. The simulation results verify the effectiveness of the proposed algorithm when compared with the relevant existing algorithms.
Event-triggered H-infinity finite-time consensus control for nonlinear second-order multi-agent systems with disturbances
Authors: Luo Yiping , Zhu Wanling
Published: June 2021

The study considers the problem of finite-time event-triggered H-infinity consensus for second-order multi-agent systems (MASs) with intrinsic nonlinear dynamics and external bounded disturbances. Based on the designed triggering function, a distributed event-triggered control strategy is presented on the basis of the designed triggering function to ensure consensus in the system, which effectively reduces the data transmission. Then, sufficient conditions for the finite-time consensus with H-infinity performance level of the resulting event-triggered MAS are derived by utilizing the Lyapunov function and finite-time stability theory. Furthermore, Zeno behavior is proven to be excluded under the proposed event-triggered scheme. Finally, the validity of the proposed results is verified by numerical simulation.
Reimagining brief interventions for alcohol: towards a paradigm fit for the twenty first century?
Authors: McCambridge Jim
Published: June 2021

Background

There is no longer support for the idea that brief intervention programmes alone can contribute meaningfully to the improvement of population health relating to alcohol. As a result, calls for major innovations and paradigm shifts grow, notably among research leaders.

Main text

This paper briefly examines the history of the development of the evidence-base from the landmark World Health Organisation projects on Screening and Brief Intervention (SBI) in the 1980s onwards. Particular attention is given to weaknesses in the theorisation of social influence and interventions design, and declining effect sizes over time. Although the old SBI paradigm may be exhausted where it has been applied, it has not been replaced by a new paradigm. Alcohol marketing encourages heavy drinking and today may have more powerful effects on thinking about alcohol, and about alcohol problems, than previously. The nature of the societal challenge being faced in an alcogenic environment in which alcohol is widely promoted and weakly regulated underpins consideration of the possibilities for contemporary evidence-informed public health responses. Evidence-informed perspectives in discourses on alcohol problems need to be strengthened in redeveloping rationales for brief interventions. This process needs to move away from sole reliance on a model based on a two-person discussion of alcohol, which is divorced from wider concerns the person may have. Reimagining the nature of brief interventions involves incorporating digital content, emphasising meso-level social processes based on material that people want to share, and seeking synergies with macro-level population and media issues, including alcohol policy measures.

Conclusions

Current versions of brief interventions may be simply too weak to contend with the pressures of an alcogenic environment. A new generation of brief interventions could have a key role to play in developing multi-level responses to the problems caused by alcohol.
Plausibility of patient-centred care in high-intensity methadone treatment: reflections of providers and patients
Authors: Marshall Kerry , Maina Geoffrey , Sherstobitoff Jordan
Published: June 2021

Background

Patients with opioid use disorder (OUD) often have complex health care needs. Methadone is one of the medications for opioid use disorder (MOUD) used in the management of OUDs. Highly restrictive methadone treatment—which requires patient compliance with many rules of care—often results in low retention, especially if there is inadequate support from healthcare providers (HCPs). Nevertheless, HCPs should strive to offer patient-centred care (PCC) as it is deemed the gold standard to care. Such an approach can encourage patients to be actively involved in their care, ultimately increasing retention and yielding positive treatment outcomes.

Methods

In this secondary analysis, we aimed to explore how HCPs were applying the principles of PCC when caring for patients with OUD in a highly restrictive, biomedical and paternalistic setting. We applied Mead and Bower’s PCC framework in the secondary analysis of 40 in-depth, semi-structured interviews with both HCPs and patients.

Results

We present how PCC's concepts of; (a) biopsychosocial perspective; (b) patient as a person; (c) sharing power and responsibility; (d) therapeutic alliance and (e) doctor as a person—are applied in a methadone treatment program. We identified both opportunities and barriers to providing PCC in these settings.

Conclusion

In a highly restrictive methadone treatment program, full implementation of PCC is not possible. However, implementation of some aspects of PCC are possible to improve patient empowerment and engagement with care, possibly leading to increase in retention and better treatment outcomes.
Characterisation of mobile colistin resistance genes (mcr-3 and mcr-5) in river and storm water in regions of the Western Cape of South Africa
Authors: Snyman Yolandi , Whitelaw Andrew C. , Barnes Jo M. , Maloba Motlatji R. B. , Newton-Foot Mae
Published: June 2021

Background

Colistin is regarded as a last-resort antimicrobial against multi-drug resistant Gram-negative bacteria (GNB), therefore the dissemination of colistin resistance in the environment is of great concern. Horizontal transfer of mobile colistin resistance (mcr) genes to potential pathogens poses a serious problem. This study aimed to describe the presence of colistin resistant GNB and mcr genes in river and storm water in regions of the Western Cape.

Methods

Water samples were collected from three rivers during May 2019 and January 2020 and two storm water samples were collected in November 2019. Colistin resistant GNB were cultured on MacConkey agar containing colistin and identified by MALDI-TOF. Colistin resistance was confirmed using broth microdilution (BMD). mcr-1-5 genes were detected by PCR performed directly on the water samples and on the colistin resistant isolates. mcr functionality was assessed by BMD after cloning the mcr genes into pET-48b(+) and expression in SHuffle T7 E. coli.

Results

mcr-5.1 and various mcr-3 gene variants were detected in the Plankenburg-, Eerste- and Berg rivers and in storm water from Muizenberg, and only mcr-5.1 was detected in storm water from Fish Hoek. Colistin resistant GNB were isolated from all of the water sources. Aeromonas spp. were the most common colistin resistant organisms detected in the water sources; 25% (6/24) of colistin resistant Aeromonas spp. isolated from the Berg river contained novel mcr-3 variants; mcr-3.33 (n = 1), mcr-3.34 (n = 1) mcr-3.35 (n = 1) mcr-3.36 (n = 2) and mcr-3.37 (n = 1), which were confirmed to confer colistin resistance.

Conclusions

The mcr-5.1 and mcr-3 colistin resistance gene variants were present in widely dispersed water sources in regions of the Western Cape. The mcr genes were only detected in water sampled downstream of and alongside communities, suggesting that their presence is driven by human influence/contamination. This is the first documentation of mcr-3 and mcr-5 gene variants in any setting in South Africa. Spill-over of these genes to communities could result in horizontal gene transfer to pathogenic bacteria, exacerbating the challenge of controlling multidrug resistant GNB infections.
The effects of transcranial direct current stimulation on gait in patients with Parkinson’s disease: a systematic review
Authors: Pol Fateme , Salehinejad Mohammad Ali , Baharlouei Hamzeh , Nitsche Michael A.
Published: June 2021

Background

Gait problems are an important symptom in Parkinson’s disease (PD), a progressive neurodegenerative disease. Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions. Despite an increasing number of gait-related tDCS studies in PD, the efficacy of this technique for improving gait has not been systematically investigated yet. Here, we aimed to systematically explore the effects of tDCS on gait in PD, based on available experimental studies.

Methods

Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, PubMed, Web of Science, Scopus, and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD.

Results

Eighteen studies were included in this systematic review. Overall, tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD. Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results. More studies are needed to systematically compare the efficacy of different tDCS protocols, including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD.

Conclusions

tDCS is a promising intervention approach to improving gait in PD. Anodal tDCS over the motor areas has shown a positive effect on gait, but stimulation of other areas is less promising. However, the heterogeneities of methods and results have made it difficult to draw firm conclusions. Therefore, systematic explorations of tDCS protocols are required to optimize the efficacy.