bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome and enzymatic analyses of an androstenedione-producing Mycobacterium strain with residual phytosterol-degrading pathways
Authors: Wang Hongwei , Song Shikui , Peng Fei , Yang Fei , Chen Tian , Li Xin , Cheng Xiyao , He Yijun , Huang Yongqi , Su Zhengding
Published: October 2020

Mycobacterium neoaurum strains can transform phytosterols to 4-androstene-3,17-dione (4-AD), a key intermediate for the synthesis of advanced steroidal medicines. In this work, we presented the complete genome sequence of the M. neoaurum strain HGMS2, which transforms β-sitosterol to 4-AD. Through genome annotation, a phytosterol-degrading pathway in HGMS2 was predicted and further shown to form a 9,10-secosteroid intermediate by five groups of enzymes. These five groups of enzymes included three cholesterol oxidases (ChoM; group 1: ChoM1, ChoM2 and Hsd), two monooxygenases (Mon; group 2: Mon164 and Mon197), a set of enzymes for side-chain degradation (group 3), one 3-ketosteroid-1,2-dehydrogenase (KstD; group 4: KstD211) and three 3-ketosteroid-9a-hydroxylases (Ksh; group 5: KshA226, KshA395 and KshB122). A gene cluster encoding Mon164, KstD211, KshA226, KshB122 and fatty acid β-oxidoreductases constituted one integrated metabolic pathway, while genes encoding other key enzymes were sporadically distributed. All key enzymes except those from group 3 were prepared as recombinant proteins and their activities were evaluated, and the proteins exhibited distinct activities compared with enzymes identified from other bacterial species. Importantly, we found that the KstD211 and KshA395 enzymes in the HGMS2 strain retained weak activities and caused the occurrence of two major impurities, i.e., 1,4-androstene-3,17-dione (ADD) and 9-hydroxyl-4-androstene-3,17-dione (9OH-AD) during β-sitosterol fermentation. The concurrence of these two 4-AD analogs not only lowered 4-AD production yield but also hampered 4-AD purification. HGMS2 has the least number of genes encoding KstD and Ksh enzymes compared with current industrial strains. Therefore, HGMS2 could be a potent strain by which the 4-AD production yield could be enhanced by disabling the KstD211 and KshA395 enzymes. Our work also provides new insight into the engineering of the HGMS2 strain to produce ADD and 9OH-AD for industrial application.
Catabolism of l-rhamnose in A. nidulans proceeds via the non-phosphorylated pathway and is glucose repressed by a CreA-independent mechanism
Authors: MacCabe Andrew P. , Ninou Elpinickie I. , Pardo Ester , Orejas Margarita
Published: October 2020

l-rhamnose (6-deoxy-mannose) occurs in nature mainly as a component of certain plant structural polysaccharides and bioactive metabolites but has also been found in some microorganisms and animals. The release of l-rhamnose from these substrates is catalysed by extracellular enzymes including α-l-rhamnosidases, the production of which is induced in its presence. The free sugar enters cells via specific uptake systems where it can be metabolized. Of two l-rhamnose catabolic pathways currently known in microorganisms a non-phosphorylated pathway has been identified in fungi and some bacteria but little is known of the regulatory mechanisms governing it in fungi. In this study two genes (lraA and lraB) are predicted to be involved in the catabolism of l-rhamnose, along with lraC, in the filamentous fungus Aspergillus nidulans. Transcription of all three is co-regulated with that of the genes encoding α-l-rhamnosidases, i.e. induction mediated by the l-rhamnose-responsive transcription factor RhaR and repression of induction in the presence of glucose via a CreA-independent mechanism. The participation of lraA/AN4186 (encoding l-rhamnose dehydrogenase) in l-rhamnose catabolism was revealed by the phenotypes of knock-out mutants and their complemented strains. lraA deletion negatively affects both growth on l-rhamnose and the synthesis of α-l-rhamnosidases, indicating not only the indispensability of this pathway for l-rhamnose utilization but also that a metabolite derived from this sugar is the true physiological inducer.
Integrated analysis of immune-related genes in endometrial carcinoma
Authors: Wang Yiru , Liu Yunduo , Guan Yue , Li Hao , Liu Yuan , Zhang Mengjun , Cui Ping , Kong Dan , Chen Xiuwei , Yin Hang
Published: October 2020

Background

Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis.

Methods

Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan–Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results.

Results

A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan–Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells.

Conclusions

Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.
Infection of highly insecticide-resistant malaria vector Anopheles coluzzii with entomopathogenic bacteria Chromobacterium violaceum reduces its survival, blood feeding propensity and fecundity
Authors: Gnambani Edounou Jacques , Bilgo Etienne , Sanou Adama , Dabiré Roch K. , Diabaté Abdoulaye
Published: October 2020

Background

This is now a concern that malaria eradication will not be achieved without the introduction of novel control tools. Microbiological control might be able to make a greater contribution to vector control in the future. The interactions between bacteria and mosquito make mosquito microbiota really promising from a disease control perspective. Here, the impact of Chromobacterium violaceum infections, isolated from both larvae and adult of wild-caught Anopheles gambiae sensu lato mosquitoes in Burkina Faso, was evaluated on mosquito survival, blood feeding and fecundity.

Methods

To assess entomopathogenic effects of C. violaceum infection on mosquitoes, three different types of bioassays were performed in laboratory. These bioassays aimed to evaluate the impact of C. violaceum infection on mosquito survival, blood feeding and fecundity, respectively. During bioassays mosquitoes were infected through the well-established system of cotton ball soaked with 6% glucose containing C. violaceum.

Results

Chromobacterium violaceum kills pyrethroid resistant Anopheles coluzzii (LT80 of 8.78 days ± 0.18 at 108 bacteria cell/ml of sugar meal). Interestingly, this bacterium had other negative effects on mosquito lifespan by significantly reducing (~ 59%, P < 0.001) the mosquito feeding willingness from day 4-post infection (~ 81% would seek a host to blood feed) to 9- day post infection (22 ± 4.62% would seek a host to blood feed). Moreover, C. violaceum considerably jeopardized the egg laying (~ 16 eggs laid/mosquito with C. violaceum infected mosquitoes vs ~ 129 eggs laid/mosquito with control mosquitoes) and hatching of mosquitoes (a reduction of ~ 22% of hatching rate with C. violaceum infected mosquitoes). Compared to the bacterial uninfected mosquitoes, mosquitoes infected with C. violaceum showed significantly higher retention rates of immature eggs and follicles.

Conclusion

These data showed important properties of Burkina Faso C. violaceum strains, which are highly virulent against insecticide-resistant An. coluzzii, and reduce both mosquito blood feeding and fecundity propensities. However, additional studies as the sequencing of C. violaceum genome and the potential toxins secreted will provide useful information render it a potential candidate for the biological control strategies of malaria and other disease vectors.
Risks of emergency use authorizations for medical products during outbreak situations: a COVID-19 case study
Authors: Badnjević Almir , Pokvić Lejla Gurbeta , Džemić Zijad , Bečić Fahir
Published: October 2020

Background

The world is facing an unprecedented outbreak affecting all aspects of human lives which is caused by the COVID-19 pandemic. Due to the virus novelty, healthcare systems are challenged by a high rate of patients and the shortage of medical products. To address an increased need for essential medical products, national authorities, worldwide, made various legislative concessions. This has led to essential medical products being produced by automotive, textile and other companies from various industries and approved under the emergency use authorizations or legal concessions of national regulatory bodies. This paper presents a narrative commentary of the available documentation on emergency use authorizations and legal concessions for medical products during COVID-19 pandemic.

Methodology

The basis for narrative commentary includes scientific articles published in Web of Science, Scopus, PubMed and Embase databases, official publications of international organizations: Food and Drug Agency (FDA), World Health Organisation (WHO), World Bank and United Nations (UN), and national regulatory agency reports in native languages (English, German, Bosnian, and Croatian) published from November 1, 2019 to May 1, 2020. This paper focuses on three types of essential medical products: mechanical ventilators, personal protective equipment (PPE) and diagnostic tests. Evidence-informed commentary of available data and potential identified risks of emergency use authorizations and legal concessions is presented.

Discussion

It is recognized that now more than ever, raising global awareness and knowledge about the importance of respecting the essential requirements is needed to guarantee the appropriate quality, performance and safety of medical products, especially during outbreak situation, such as the COVID-19 pandemic. Emergency use authorizations for production, import and approval of medical products should be strictly specified and clearly targeted from case to case and should not be general or universal for all medical products, because all of them are associated with different risk level.

Conclusion

Presented considerations and experiences should be taken as a guide for all possible future outbreak situations to prevent improvised reactions of national regulatory bodies.
Translation and validation of the Short HIV Stigma scale in Brazilian Portuguese
Authors: Luz Paula M. , Torres Thiago S. , Almeida-Brasil Celline C. , Marins Luana M. S. , Bezerra Daniel R. B. , Veloso Valdilea G. , Grinsztejn Beatriz , Harel Daphna , Thombs Brett D.
Published: October 2020

Background

HIV-related stigma, or the degree to which people living with HIV endorse negative stereotypes associated with HIV, is associated with poor continuum of care outcomes. We translated the 12-item Short HIV Stigma scale and evaluated its psychometric properties in a Brazilian context with regard to construct validity and reliability.

Methods

The first step included translation, back-translation, evaluation, peer review, and pre-testing of the Short HIV Sigma scale developed by Reinius et al. (Health Qual Life Outcomes 15(1):115, 2017).
The second step involved piloting the scale in three convenience samples of adults recruited online through advertisements on different platforms: Grindr (October/2019) and Hornet (February–March/2020), geospatial network apps for sexual encounters for gay, bisexuals and other men who have sex with men, and social media apps (Facebook and WhatsApp, October/2019). The psychometric evaluation included confirmatory factor analysis, differential item functioning using the Multiple-Indicator Multiple-Cause model, and correlations between subscale scores and antiretroviral treatment use and adherence. Reliability was assessed using Cronbach’s alpha, and ordinal alpha and omega from the polychoric correlation matrix.

Results

In total, 114, 164, and 1824 participants completed the measure items through Grindr, social media, and Hornet, respectively. We confirmed a 4-factor structure with factors for personalized stigma (3 items), disclosure concerns (3 items), concerns with public attitudes (3 items), and negative self-image (3 items). Small differential item functioning with respect to sample was found for one item (“I feel guilty because I have HIV”), which did not substantively influence estimates of latent factor scores. Grindr and Hornet’s participants scored significantly higher than social media participants on all factors except personalized stigma. Higher subscale scores correlated with antiretroviral treatment use among participants from Hornet and with lower treatment adherence in participants from Grindr and Hornet. Reliability as measured by Cronbach’s alpha, ordinal alpha and omega were 0.83, 0.88 and 0.93 for the entire scale.

Discussion

The Brazilian Portuguese version of the Short HIV Stigma scale had satisfactory psychometric properties with present results suggesting that scores from different samples may be compared without concern that measurement differences substantively influence results though further studies with greater representation of women and heterosexual men are warranted.
Coding transcriptome analyses reveal altered functions underlying immunotolerance of PEG-fused rat sciatic nerve allografts
Authors: Smith Tyler A. , Ghergherehchi Cameron L. , Tucker Haley O. , Bittner George D.
Published: October 2020

Background

Current methods to repair ablation-type peripheral nerve injuries (PNIs) using peripheral nerve allografts (PNAs) often result in poor functional recovery due to immunological rejection as well as to slow and inaccurate outgrowth of regenerating axonal sprouts. In contrast, ablation-type PNIs repaired by PNAs, using a multistep protocol in which one step employs the membrane fusogen polyethylene glycol (PEG), permanently restore sciatic-mediated behaviors within weeks. Axons and cells within PEG-fused PNAs remain viable, even though outbred host and donor tissues are neither immunosuppressed nor tissue matched. PEG-fused PNAs exhibit significantly reduced T cell and macrophage infiltration, expression of major histocompatibility complex I/II and consistently low apoptosis. In this study, we analyzed the coding transcriptome of PEG-fused PNAs to examine possible mechanisms underlying immunosuppression.

Methods

Ablation-type sciatic PNIs in adult Sprague-Dawley rats were repaired using PNAs and a PEG-fusion protocol combined with neurorrhaphy. Electrophysiological and behavioral tests confirmed successful PEG-fusion of PNAs. RNA sequencing analyzed differential expression profiles of protein-coding genes between PEG-fused PNAs and negative control PNAs (not treated with PEG) at 14 days PO, along with unoperated control nerves. Sequencing results were validated by quantitative reverse transcription PCR (RT-qPCR), and in some cases, immunohistochemistry.

Results

PEG-fused PNAs display significant downregulation of many gene transcripts associated with innate and adaptive allorejection responses. Schwann cell-associated transcripts are often upregulated, and cellular processes such as extracellular matrix remodeling and cell/tissue development are particularly enriched. Transcripts encoding several potentially immunosuppressive proteins (e.g., thrombospondins 1 and 2) also are upregulated in PEG-fused PNAs.

Conclusions

This study is the first to characterize the coding transcriptome of PEG-fused PNAs and to identify possible links between alterations of the extracellular matrix and suppression of the allorejection response. The results establish an initial molecular basis to understand mechanisms underlying PEG-mediated immunosuppression.
COVID-19 pandemic: current knowledge about the role of pets and other animals in disease transmission
Authors: Kiros Mulugeta , Andualem Henok , Kiros Teklehaimanot , Hailemichael Wasihun , Getu Sisay , Geteneh Alene , Alemu Derbie , Abegaz Woldaregay Erku
Published: October 2020

On 11 March 2020, the World Health Organization (WHO) announced Corona Virus Disease (COVID-19), a disease caused by a pathogen called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pandemic. This ongoing pandemic has now been reported in 215 countries with more than 23 million confirmed cases and more than 803 thousand deaths worldwide as of August 22, 2020. Although efforts are undergoing, there is no approved vaccine or any specific antiretroviral drug to treat COVID-19 so far. It is now known that SARS-CoV-2 can affect not only humans but also pets and other domestic and wild animals, making it a one health global problem. Several published scientific evidence has shown that bats are the initial reservoir hosts of SARS-CoV-2, and pangolins are suggested as an intermediate hosts. So far, little is known concerning the role of pets and other animals in the transmission of COVID-19. Therefore, updated knowledge about the potential role of pets in the current outbreak will be of paramount importance for effective prevention and control of the disease. This review summarized the current evidence about the role of pets and other animals in the transmission of COVID-19.
A CRISPR/dCas9 toolkit for functional analysis of maize genes
Authors: Gentzel Irene N. , Park Chan Ho , Bellizzi Maria , Xiao Guiqing , Gadhave Kiran R. , Murphree Colin , Yang Qin , LaMantia Jonathan , Redinbaugh Margaret G. , Balint-Kurti Peter , Sit Tim L. , Wang Guo-Liang
Published: October 2020

Background

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system has become a powerful tool for functional genomics in plants. The RNA-guided nuclease can be used to not only generate precise genomic mutations, but also to manipulate gene expression when present as a deactivated protein (dCas9).

Results

In this study, we describe a vector toolkit for analyzing dCas9-mediated activation (CRISPRa) or inactivation (CRISPRi) of gene expression in maize protoplasts. An improved maize protoplast isolation and transfection method is presented, as well as a description of dCas9 vectors to enhance or repress maize gene expression.

Conclusions

We anticipate that this maize protoplast toolkit will streamline the analysis of gRNA candidates and facilitate genetic studies of important trait genes in this transformation-recalcitrant plant.
Proton pencil beam scanning reduces secondary cancer risk in breast cancer patients with internal mammary chain involvement compared to photon radiotherapy
Authors: Cartechini Giorgio , Fracchiolla Francesco , Menegotti Loris , Scifoni Emanuele , La Tessa Chiara , Schwarz Marco , Farace Paolo , Tommasino Francesco
Published: October 2020

Purpose

Proton pencil beam scanning (PBS) represents an interesting option for the treatment of breast cancer (BC) patients with nodal involvement. Here we compare tangential 3D-CRT and VMAT to PBS proton therapy (PT) in terms of secondary cancer risk (SCR) for the lungs and for contralateral breast.

Methods

Five BC patients including supraclavicular (SVC) nodes in the target (Group 1) and five including SVC plus internal-mammary-nodes (IMNs, Group 2) were considered. The Group 1 patients were planned by PT versus tangential 3D-CRT in free-breathing (FB). The Group 2 patients were planned by PT versus VMAT considering both FB and deep-inspiration breath hold (DIBH) irradiation. The prescription dose to the target volume was 50 Gy (2 Gy/fraction). A constant RBE = 1.1 was assumed for PT. The SCR was evaluated with the excess absolute risk (EAR) formalism, considering also the age dependence. A cumulative EAR was finally computed.

Results

According to the linear, linear-exponential and linear-plateau dose response model, the cumulative EAR for Group 1 patients after PT was equal to 45 ± 10, 17 ± 3 and 15 ± 3, respectively. The corresponding relative increase for tangential 3D-CRT was equal to a factor 2.1 ± 0.5, 2.1 ± 0.4 and 2.3 ± 0.4. Group 2 patients showed a cumulative EAR after PT in FB equal to 65 ± 3, 21 ± 1 and 20 ± 1, according to the different models; the relative risk obtained with VMAT increased by a factor 3.5 ± 0.2, 5.2 ± 0.3 and 5.1 ± 0.3. Similar values emerge from DIBH plans. Contrary to photon radiotherapy, PT appears to be not sensitive to the age dependence due to the very low delivered dose.

Conclusions

PBS PT is associated to significant SCR reduction in BC patients compared to photon radiotherapy. The benefits are maximized for young patients with both SVC and IMNs involvement. When combined with the improved sparing of the heart, this might contribute to the establishment of effective patient-selection criteria for proton BC treatments.
OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial
Authors: Algara López Manuel , Rodríguez García Elvira , Beato Tortajada Inmaculada , Martínez Arcelus Francisco José , Salinas Ramos Juan , Rodríguez garrido José Reyes , Sanz Latiesas Xavier , Soler Rodríguez Ana , Juan Rijo Germán , Flaquer García Amanda
Published: October 2020

Background

Conservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes. However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the One-Step Nucleic Acid Amplification (OSNA) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN.

Methods

BC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250–15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates.

Discussion

Standardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy.

Trial registration

ClinicalTrial.gov, NCT02335957; https://clinicaltrials.gov/ct2/show/NCT02335957
Long-term outcomes of moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions) for prostate cancer confined to the pelvis: a single center retrospective analysis
Authors: Yao Lihong , Shou Jianzhong , Wang Shulian , Song Yongwen , Fang Hui , Lu Ningning , Tang Yuan , Chen Bo , Qi Shunan , Yang Yong , Jing Hao , Jin Jing , Yu Zihao , Li Yexiong , Liu Yueping
Published: October 2020

Background

There is an increasing application of moderately hypofractionated radiotherapy for prostate cancer. We presented our outcomes and treatment-related toxicities with moderately hypofractionated (67.5 Gy in 25 fractions) radiotherapy for a group of advanced prostate cancer patients from China.

Methods

From November 2006 to December 2018, 246 consecutive patients with prostate cancer confined to the pelvis were treated with moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions). 97.6% of the patients received a different duration of androgen deprivation therapy. Failure-free survival (FFS), prostate cancer-specific survival (PCSS), overall survival (OS), and cumulative grade ≥ 2 late toxicity were evaluated using the Kaplan–Meier actuarial method. Prognostic factors for FFS, PCSS, and OS were analyzed.

Results

The median follow-up time was 74 months (range: 6–150 months). For all patients, the 5- and 10-year FFS rates were 80.0% (95% CI: 74.7–85.7%) and 63.5% (95% CI 55.4–72.8%). The failure rates for the intermediate, high-risk, locally advanced, and N1 groups were 6.1%, 13.0%, 18.4%, and 35.7%, respectively (P = 0.003). Overall, 5- and 10-year PCSS rates were 95.7% (95% CI 93.0–98.5%) and 88.2% (95% CI 82.8–93.8%). Prostate cancer-specific mortality rates for the high-risk, locally advanced, and N1 groups were 4.0%, 8.2%, and 23.8%, respectively (P < 0.001). Overall, 5- and 10-year actuarial OS rates were 92.4% (95% CI 88.8–96.1%) and 72.7% (95% CI 64.8–81.5%). High level prostate-specific antigen and positive N stage were significantly associated with worse FFS (P < 0.05). Advanced T stage and positive N stage emerged as worse predictors of PCSS (P < 0.05). Advanced age, T stage, and positive N stage were the only factors that were significantly associated with worse OS (P < 0.05). The 5-year cumulative incidence rate of grade ≥ 2 late GU and GI toxicity was 17.8% (95% CI 12.5–22.7%) and 23.4% (95% CI 17.7–28.7%), respectively.

Conclusions

Moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions) for this predominantly high-risk, locally advanced, or N1 in Chinese patients demonstrates encouraging long-term outcomes and acceptable toxicity. This fractionation schedule deserves further evaluation in similar populations.
Home-based motor imagery intervention improves functional performance following total knee arthroplasty in the short term: a randomized controlled trial
Authors: Paravlic Armin H. , Maffulli Nicola , Kovač Simon , Pisot Rado
Published: October 2020

Background

Motor imagery (MI) is effective in improving motor performance in the healthy asymptomatic adult population. However, its possible effects among older orthopaedic patients are still poorly investigated. Therefore, this study explored whether the addition of motor imagery to routine physical therapy reduces the deterioration of quadriceps muscle strength and voluntary activation (VA) as well as other variables related to motor performance in patients after total knee arthroplasty (TKA).

Methods

Twenty-six patients scheduled for TKA were randomized to either MI practice combined with routine physical therapy group (MIp) or to a control group receiving physical therapy alone (CON). MIp consisted of maximal voluntary isometric contraction (MViC) task: 15 min/day in the hospital, then 5 times/week in their homes for 4 weeks. MViC and VA of quadriceps muscle, knee flexion and extension range of motion, pain level, along with a Timed Up-and-Go Test (TUG) and self-reported measure of physical function (assessed using the Oxford Knee Score questionnaire [OKS]) were evaluated before (PRE) and 1 month after surgery (POST).

Results

Significantly better rehabilitation outcomes were evident on the operated leg for the MIp group compared to CON: at POST, the MIp showed lower strength decrease (p= 0.012,η2=0.237) and unaltered VA, significantly greater than CON (p= 0.014,η2=0.227). There were no significant differences in knee flexion and extension range of motion and pain level (p> 0.05). Further, MIp patients performed better in TUG (p< 0.001,η2=0.471) and reported better OKS scores (p= 0.005,η2=0.280). The non-operated leg showed no significant differences in any outcomes at POST (allp> 0.05). In addition, multiple linear regression analysis showed that failure of voluntary activation explained 47% of the quadriceps muscle strength loss, with no significant difference in perceived level of pain.

Conclusion

MI practice, when added to physical therapy, improves both objective and subjective measures of patients’ physical function after TKA, and facilitates transfer of MI strength task on functional mobility.

Trial registration

Retrospectively registered onClinicalTrials.govNCT03684148
Application of a novel shape-memory alloy concentrator in displaced olecranon fractures: a report of the technique and mid-term clinical results
Authors: Xia Demeng , Zhou Panyu , Li Lei , Xia Yan , Hao Zichen , Zhang Yuntong , Xu Shuogui
Published: October 2020

Purpose

Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture.

Methods

Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit.

Results

The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1).

Conclusion

The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.
Efficacy, safety, and long-term survival of concomitant valve replacement and bipolar radiofrequency ablation in patients aged 70 years and older: a comparative study with propensity score matching from a single-Centre
Authors: Lin Zhi-qin , Luo Zeng-rong , Li Qian-zhen , Chen Liang-wan , Lin Feng
Published: October 2020

Abstracts

Background

Concomitant bipolar radiofrequency ablation and valve replacement in the elderly remains controversial. In the current study, we aimed to compare the outcomes of concomitant valve replacement and bipolar radiofrequency ablation with valve replacement alone in elderly patients with atrial fibrillation (AF).

Methods

This was a retrospective study of patients aged ≥70 years who underwent valve replacement with or without bipolar radiofrequency ablation in a single-centre between January 2006 and March 2015. The early postoperative results and long-term clinical outcomes were compared after propensity score matching.

Results

A total of 34 pairs of patients (73.94 ± 2.64 years old; 34 in the AF with ablation group and 34 in the AF without ablation group) were enrolled in the propensity score matching analysis. There were no significant differences between the two matched groups in terms of surgical mortality (5.88% vs. 2.94%, P = 0.555) and major postoperative morbidity. Kaplan–Meier analysis revealed a significantly better overall survival in the AF with ablation group compared to the AF without ablation group (P = 0.009). Cumulative incidence curves showed a lower incidence of cardiovascular death in the AF with ablation group (P = 0.025, Gray’s test). Patients in the AF with ablation group had a reduced incidence of stroke compared to patients in the AF with ablation group (P = 0.009, Gray’s test). The freedom from AF after 5 years was 58.0% in the AF with ablation group and 3.0% in the AF without ablation group.

Conclusions

The addition of bipolar radiofrequency ablation is a safe and feasible procedure, even in patients aged ≥70 years, with a better long-term survival and a reduced incidence of stroke compared to valve replacement alone. These findings suggest that bipolar radiofrequency ablation should always be considered as a concomitant procedure for elderly patients with AF who require cardiac surgery. However, a large-scale, prospective, multi-centre, randomized study should be performed in the future to fully validate our findings.
An interventricular membranous septal aneurysm obstructing the right ventricle outflow tract in a five-year-old boy: a case report
Authors: Bakr Lubna , Al-Jadaan Mohammad , Younes Mohammad
Published: October 2020

Background

While the aneurysms of the membranous septum (AVS) are rare, the possibility that they lead to obstruction is even rarer. To the best of our knowledge, 11 similar cases have been reported since 1982.

Case presentation

Initially, the five-year-old boy was evaluated for dyspnoea that had been present since birth. He did not receive any medical treatment until the previous year. At the age of four, the transthoracic echocardiography showed a large aneurysm extending to the right ventricular outflow tract (RVOT) and causing RVOT stenosis. Complete surgical resection of the aneurysmal tissue was performed, and the boy was discharged home in satisfactory condition.

Conclusions

As the occurrence of RVOT obstruction by a membranous ventricular septal aneurysm is very rare, we are reporting the second case in which an aneurysm of the membranous septum dynamically obstructed the RVOT in a child. We are also reviewing all the previously reported similar cases in the literature. Further studies are needed to obtain a more comprehensive understanding of aneurysms of the membranous septum (AVS).
Conflict and COVID-19: a double burden for Afghanistan’s healthcare system
Authors: Lucero-Prisno Don Eliseo , Essar Mohammad Yasir , Ahmadi Attaullah , Lin Xu , Adebisi Yusuff Adebayo
Published: October 2020

The novel coronavirus disease (COVID-19) has put an additional strain on Afghanistan’s weak healthcare system. Prior to the pandemic, the government and its allies had already problems in providing high quality health services for the people in Afghanistan because of inadequate facilities, insecurities, and ongoing conflicts. This year, COVID-19 exacerbated the situation and overwhelmed the healthcare system even further. As predicted, an influx of migrants suspected of having COVID-19 contributed to community transmission and led to an increase of cases across the country. A series of deadly attacks on civilians and healthcare workers in the country poses an additional burden, and severely weakens healthcare structures in times where health services are indispensable. These circumstances make evident that the international community needs to provide more support for Afghanistan’s healthcare system and pass the United Nations resolution for a ceasefire in the country.
Peptidome analysis of cerebrospinal fluid in neonates with hypoxic-ischemic brain damage
Authors: Hou Xuewen , Yuan Zijun , Wang Xuan , Cheng Rui , Zhou Xiaoguang , Qiu Jie
Published: October 2020

Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal HIBD. CSF samples were collected from neonates with HIBD (n = 4) or controls (n = 4). ITRAQ LC–MS/MS was used to identify differentially expressed peptides between two groups. A total of 35 differentially expressed peptides from 25 precursor proteins were identified. The 2671.5 Da peptide (HSQFIGYPITLFVEKER), one of the down-regulated peptides in neonatal HIBD, is a fragment of heat shock protein 90-alpha (HSP90α/HSP90AA1). Results of bioinformatics analysis showed that HSP90α/HSP90AA1 was located in the protein–protein interaction (PPI) network hub and was involved in the NOD-LIKE receptor (NLR) signaling pathway. This peptide, we named it Hypoxic-Ischemic Brain Damage Associated Peptide (HIBDAP), is a hydrophilic peptide with high stability and has a long half-life of 3.5 h in mammalian reticulocytes. It was demonstrated that TAT-HIBDAP could successfully enter PC12 cells and further into the nucleus. After HIBDAP pretreatment and 6 h of OGD treatment, low concentrations of HIBDAP increased the survival rate of cells, except 40 μM had a toxic effect. Safe concentrations of HIBDAP reduced pyroptosis of PC12 cells under OGD, except 20 μM had no effect, by suppressing expressions of NLRP3, ASC and Caspase-1 except NLRP1. The results of our study identified the characterization and expression profiles of peptides in CSF of neonatal HIBD. Several meaningful peptides such as HIBDAP may play significant roles in neonatal HIBD and provide new therapeutic targets for neonatal HIBD.
Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma
Authors: Qian Yunzhen , Gong Yitao , Fan Zhiyao , Luo Guopei , Huang Qiuyi , Deng Shengming , Cheng He , Jin Kaizhou , Ni Quanxing , Yu Xianjun , Liu Chen
Published: October 2020

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. The realization of targeted therapies in patients with PDAC may be summarized by three approaches. First, because oncogenes play a pivotal role in tumorigenesis, inhibition of dysregulated oncogenes is a promising method (Table 3). Numerous researchers are developing strategies to target oncogenes, such as KRAS, NRG1, and NTRK and related molecules, although most of the results are unsatisfactory. Accordingly, emerging strategies are being developed to target these oncogenes, including simultaneously inhibiting multiple molecules or pathways, modification of mutant residues by small molecules, and RNA interference. Second, researchers have attempted to reactivate inactivated tumour suppressors or modulate related molecules. TP53, CDKN2A and SMAD4 are three major tumour suppressors involved in PDAC. Advances have been achieved in clinical and preclinical trials of therapies targeting these three genes, and further investigations are warranted. The TGF-β-SMAD4 signalling pathway plays a dual role in PDAC tumorigenesis and participates in mediating tumour-stroma crosstalk and modulating the tumour microenvironment (TME); thus, molecular subtyping of pancreatic cancer according to the SMAD4 mutation status may be a promising precision oncology technique. Finally, genes such as KDM6A and BRCA have vital roles in maintaining the structural stability and physiological functions of normal chromosomes and are deficient in some patients with PDAC, thus serving as potential targets for correcting these deficiencies and precisely killing these aberrant tumour cells. Recent clinical trials, such as the POLO (Pancreas Cancer Olaparib Ongoing) trial, have reported encouraging outcomes. In addition to genetic event-guided treatment, immunotherapies such as chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates, and immune checkpoint inhibitors also exhibit the potential to target tumours precisely, although the clinical value of immunotherapies as treatments for PDAC is still limited. In this review, we focus on recent preclinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for PDAC.
Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: what has changed and future prospects for restarting
Authors: Lubrano Riccardo , Villani Alberto , Berrettini Stefano , Caione Paolo , Chiara Alberto , Costantino Antonella , Formigari Roberto , Franzoni Emilio , Gattinara Guido Castelli , Giustardi Arturo , La Marca Giancarlo , Lionetti Paolo , Lima Mario , Maffei Claudio , Malamisura Monica , Manzoni Giantonio , Marseglia Gian Luigi , Memeo Antonio , Mosca Fabio , Perricone Giovanna , Peruzzi Licia , Piacentini Giorgio , Pozzobon Gabriella , Riva Enrica , Tesoro Simonetta , Zampino Giuseppe , Zanetto Federica , Zecca Marco , Bloise Silvia
Published: October 2020

Background

The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting.

Methods

We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment.

Results

The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians.

Conclusions

Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.
A spatial database of colorectal cancer patients and potential nutritional risk factors in an urban area in the Middle East
Authors: Firouraghi Neda , Bagheri Nasser , Kiani Fatemeh , Goshayeshi Ladan , Ghayour-Mobarhan Majid , Kimiafar Khalil , Eslami Saeid , Kiani Behzad
Published: October 2020

Objectives

Colorectal cancer (CRC) is the third most common cancer across the world that multiple risk factors together contribute to CRC development. There is a limited research report on impact of nutritional risk factors and spatial variation of CRC risk. Geographical information system (GIS) can help researchers and policy makers to link the CRC incidence data with environmental risk factor and further spatial analysis generates new knowledge on spatial variation of CRC risk and explore the potential clusters in the pattern of incidence. This spatial analysis enables policymakers to develop tailored interventions. This study aims to release the datasets, which we have used to conduct a spatial analysis of CRC patients in the city of Mashhad, Iran between 2016 and 2017.

Data description

These data include five data files. The file CRCcases_Mashhad contains the geographical locations of 695 CRC cancer patients diagnosed between March 2016 and March 2017 in the city of Mashhad. The Mashhad_Neighborhoods file is the digital map of neighborhoods division of the city and their population by age groups. Furthermore, these files include contributor risk factors including average of daily red meat consumption, average of daily fiber intake, and average of body mass index for every of 142 neighborhoods of the city.
Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer’s disease mouse model with suppression of glymphatic clearance
Authors: Feng Weixi , Zhang Yanli , Wang Ze , Xu Hanrong , Wu Ting , Marshall Charles , Gao Junying , Xiao Ming
Published: October 2020

Background

Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer’s disease (AD) are currently unknown.

Methods

Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice.

Results

AQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance.

Conclusion

The above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD.