bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review
Authors: Wang Ping , Xu Zuojun
Published: September 2021

Background

Dyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported.

Case presentation

A 23-year-old student presented with a four-year history of progressive cough and exertional dyspnea. Physical examination was remarkable for typical mucocutaneous abnormalities. Chest computerized tomography scan revealed interstitial fibrosis. Testing of peripheral blood leukocytes confirmed that his telomeres were 30th percentile of age-matched controls. A heterozygous missense mutation located in exon 22 of PARN gene was identified in the patient by whole exome sequencing. The patient refused danazol therapy and lung transplantation, and died of respiratory failure 2 years later. In addition, this case and 26 reported cases of DC-related PF identified through the comprehensive search of PubMed, Web of Science, WANFANG and CNKI were reviewed. Later-onset PF was observed in 11 patients (40.7%). Radiological usual interstitial pneumonia (UIP) pattern or possible UIP pattern was noted only in half of patients. However, histopathological UIP or probable UIP patterns were found in 63.6% of patients. Age at bone marrow failure (BMF) and the frequency of normal to mild thrombocytopenia in later-onset patients was significantly higher than in early-onset patients (p = 0.017 and p = 0.021, respectively). Age at PF and age at BMF in DC patients with TERC/TERT variants was significantly higher than in those with TINF2 variants or DKC1/NHP2 variants (p = 0.004 and p = 0.003, respectively). The patients with TERT/TERC/RTEL1/PARN variants had a significantly better transplant-free survival than those with TINF2 variants or DKC1/NHP2 variants (p < 0.05). Patients who underwent surgical lung biopsy had significantly worse transplant-free survival than those without lung biopsy (p = 0.042). Worse survival was found in patients with immunosuppression therapy than in those without (p = 0.012).

Conclusions

It is common for DC-associated PF to occur later in life without significant hematological manifestations. Mutations in the genes encoding different components of the telomere maintenance pathway were associated with clinical phenotypes and prognosis. PF caused by DC should be kept in mind by clinicians in the differential diagnosis of patients with unexplained PF and should be excluded before diagnostic surgical lung biopsy is undertaken or empirical immunosuppression therapy is prescribed.
Perceptions, beliefs, and needs of Japanese people with knee osteoarthritis during conservative care: a qualitative study
Authors: Uritani Daisuke , Ikeda Akane , Shironoki Toru , Matsubata Kentaro , Mutsura Yuto , Fujii Tadashi , Ikeda Koji
Published: September 2021

Background

Patients’ perceptions and beliefs of disease could be influenced by their lifestyle and culture. Although it is important to understand their perceptions and beliefs toward disease to prevent and manage osteoarthritis (OA) through conservative care, this topic has not been investigated in Japanese people with knee OA. Therefore, this qualitative study aims to clarify how Japanese patients with knee OA experience and perceive their symptoms and disabilities, and how they face them during conservative care.

Methods

Participants were recruited by purposive sampling. Face-to-face, semi-structured interviews were conducted with nine patients (2 men and 7 women; mean age, 74.3 ± 5.5 years) with knee OA until data saturation was reached. Interview data comprised participants’ accounts of particular personal experiences of living with knee OA, including their perceptions and attitudes toward knee OA-related symptoms and disabilities. Two physiotherapists (one with extensive experience conducting qualitative studies) and four physiotherapy students conducted the interviews. Recorded interview data were transcribed verbatim in Japanese. Data analysis, including developing a coding scheme, was conducted based on a grounded theory approach.

Results

Two core categories were extracted from the data: ‘Negative experiences’ and ‘Coping with difficulties’. ‘Negative experiences’ included three main categories: ‘Self-analysis on the cause of knee OA’, ‘Difficulties in daily life due to knee symptoms’, and ‘Psychological barrier’. ‘Coping with difficulties’ included three main categories: ‘How to deal with knee pain and difficulty in moving’, ‘Information considered useful to cope with knee OA’ and ‘Importance of connecting with others’. Japanese patients with knee OA desired evidence-based information and to connect with other people in the same situation to solve problems related to their condition.

Conclusions

To address patients’ concerns, medical professionals should conduct careful interviews and obtain information regarding patients’ past experiences, and understand their experiences related to knee OA. Symptoms and difficulties experienced by patients with knee OA should be managed by evidence-based information integrating their perceptions and beliefs toward knee OA.
Evaluating the specialist palliative care clinical nurse specialist role in an acute hospital setting: a mixed methods sequential explanatory study
Authors: Connolly Michael , Ryder Mary , Frazer Kate , Furlong Eileen , Escribano Teresa Plazo , Larkin Philip , Carruthers Eileen , McGuigan Eileen
Published: September 2021

Background

Special palliative care is provided in a range of settings including a patient’s home (their primary place of dwelling), a hospice in-patient unit, or an acute hospital. The aim of the study was to evaluate the role of the specialist in palliative care clinical nurse specialist (SPC CNS) role in an acute hospital setting.

Methods

This study was conducted using a mixed methods sequential explanatory approach in two phases; phase 1 involved completion of a study questionnaire (n = 121) and phase 2 involved part-taking in a focus group (n = 6) or individual interview (n = 4).

Results

Phase 1 results indicated that respondents held positive attitudes towards the Specialist Palliative Care Clinical Nurses Specialist (SPC CNS) in relation to clinical care, education and patient advocacy. Phase 2 qualitative findings identified the importance of the role in terms of symptom management, education and support.

Conclusions

This study provides an evaluation of a SPC CNS role since it was established in an acute hospital setting. The evidence indicates that there is a varied understanding of the role of the SPC CNS. The role was seen as an important one particularly in terms of referrals to and support provided by the SPC CNS, as well as recognition of the importance of the role is providing ongoing education to staff.
Molecular mechanism of Epicedium treatment for depression based on network pharmacology and molecular docking technology
Authors: Dong Yankai , Tao Bo , Xue Xing , Feng Caixia , Ren Yating , Ma Hengyu , Zhang Junli , Si Yufang , Zhang Sisi , Liu Si , Li Hui , Zhou Jiahao , Li Ge , Wang Zhifei , Xie Juanping , Zhu Zhongliang
Published: September 2021

Background

Increasing attention has been paid to the effect of Epimedium on the nervous system, particularly anti-depression function. In the present study, we applied network pharmacology to introduce a testable hypothesis on the multi-target mechanisms of Epicedium against depression.

Methods

By reconstructing the network of protein–protein interaction and drug–component–target, we predicted the key protein targets of Epicedium for the treatment of depression. Then, through molecular docking, the interaction of the main active components of Epicedium and predicted candidate targets were verified.

Results

Nineteen active compounds were selected from Epicedium. There were 200 targets associated with Epicedium and 537 targets related to depression. The key targets of Epicedium for treating depression were IL6, VEGFA, AKT1, and EGF. According to gene ontology functional enrichment analysis, 22 items of biological process (BP), 13 items of cell composition (CC) and 9 items of molecular function (MF) were obtained. A total of 56 signaling pathways (P < 0.05) were identified by Kyoto Encyclopedia of Genes and Genomes analysis, mainly involving depression-related pathways such as dopaminergic synapse, TNF signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the most important activity components, including luteoklin, quercetin and kaempferol, were well combined with the key targets.

Conclusions

Luteoklin, quercetin, kaempferol and other active compounds in Epicedium can regulate multiple signaling pathways and targets such as IL6, AKT1, and EGF, therefore playing therapeutic roles in depression.
Teaching patient-centred communication skills during clinical procedural skill training - a preliminary pre-post study comparing international and local medical students
Authors: Nagy Ede , Luta Gloria Matondo Miguel , Huhn Daniel , Cranz Anna , Schultz Jobst-Hendrik , Herrmann-Werner Anne , Bugaj Till Johannes , Friederich Hans-Christoph , Nikendei Christoph
Published: September 2021

Background

International medical students are frequently confronted with intercultural, psychosocial, and language barriers and often receive lower marks in written, oral, and clinical-practical examinations than fellow local students. Training communication competence in procedural skills, such as blood sampling, is further challenge in this particular group of medical students. This pre-post comparative intervention study aimed to investigate the effects of training communication skills during the performance of procedural skills (taking blood samples from a silicone model) in international and local students as part of their clinical practical medical training.

Methods

Study participants performed blood sampling on an arm prosthesis model (part-task trainer) before and after the communication skills training, focusing on accompanying communication with a simulation patient sitting next to the arm model. The pre- and post-evaluation video was assessed by two independent evaluators using a binary checklist, the Integrated Procedural Performance Instrument (IPPI) and global assessments of clinical professionalism in terms of procedural and communication performance. Linear models with mixed effects were used. Group differences regarding global competence levels were analysed with χ2-tests.

Results

International medical students did not perform as well as their local counterparts in the pre- and post-examinations. Both groups improved their performance significantly, whereby the international students improved more than their local counterparts in terms of their communication performance, assessed via binary checklist. Clinical professionalism evaluated via global assessments of procedural and communication performance highlights the intervention’s impact insofar as no international student was assessed as clinically not competent after the training.

Conclusions

Our results suggest that already a low-dose intervention can lead to improved communication skills in medical students performing procedural tasks and significantly increase their confidence in patient interaction.
Dietary patterns and cardiometabolic diseases in 0.5 million Chinese adults: a 10-year cohort study
Authors: Qin Chenxi , Lv Jun , Yu Canqing , Guo Yu , Bian Zheng , Gao Meng , Du Huaidong , Yang Ling , Chen Yiping , Shen Leijia , Zhou Songgen , Chen Junshi , Chen Zhengming , Li Liming
Published: September 2021

Background

The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases.

Methods

A prospective cohort recruited around 0.5 million Chinese residents aged 30–79 years from 10 diverse survey sites during 2004–08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression.

Results

Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5–11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11–32%) for haemorrhagic stroke (HS), 14% (8–19%) for ischaemic stroke (IS), and 15% (6–24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59–0.77). Corresponding HRs were 0.89 (0.86–0.92) for CVD, 0.88 (0.77–0.99) for MCE, 0.85 (0.80–0.89) for IS, and 0.89 (0.81, 0.97) for diabetes.

Conclusion

Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors.
Primary extraskeletal osteosarcoma of sigmoid mesocolon: a case report and a review of the literature
Authors: Nie Xinyang , Fu Weihua , Li Chuan , Lu Li , Li Weidong
Published: September 2021

Background

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy, which produces osteoid, bone, or chondroid material and is located in the soft tissue without attachment to skeletal bones and periosteum. One of the things that ESOS originated from mesentery is much rarer.

Case presentation

A 75-year female had a history of pain in the left lower abdomen for more than 4 months. Abdominal computerized tomography (CT) and magnetic resonance imaging revealed a large, irregular, and solid-cystic mass (largest diameter was 11.5 cm). The tumor was radically removed during an open operation. It was composed of abundant osteoid and polyhedral-shaped tumor cells with high atypia and high mitotic activity microscopically. The final pathological diagnosis was osteoblastic osteosarcoma, arising from the sigmoid mesocolon with negative margins. A 9-month follow-up by CT exhibited signs of peritoneal metastasis.

Conclusions

Given the rarity of cases of mesenteric ESOS, diagnosis mainly depended on pathology findings or should be taken into consideration when the mesenteric mass was found. Its most effective treatment had not been determined, with surgical excision being generally accepted. Ensuring negative surgical margins may be an important factor affecting prognosis.
Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy
Authors: Oner Gizem , Önder Semen , Karatay Hüseyin , Ak Naziye , Tükenmez Mustafa , Müslümanoğlu Mahmut , İğci Abdullah , Dincçağ Ahmet , Özmen Vahit , Aydiner Adnan , Yavuz Ekrem , Cabioğlu Neslihan
Published: September 2021

Background

Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival.

Methods

PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC).

Results

Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by “MD Anderson Cancer Center Residual Cancer Burden Index” (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS.

Conclusions

Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.
Importance of Circ0009910 in colorectal cancer pathogenesis as a possible regulator of miR-145 and PEAK1
Authors: Kadkhoda Sepideh , Taslimi Reza , Noorbakhsh Farshid , Darbeheshti Farzaneh , Bazzaz Javad Tavakkoly , Ghafouri-Fard Soudeh , Shakoori Abbas
Published: September 2021

Introduction

Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer.

Methods

After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients.

Results

Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC.

Conclusion

For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients.
Prognostic and clinicopathological importance of microRNA-140 expression in cancer patients: a meta-analysis
Authors: Zheng Mengxia , Liu Jingting , Meng Chunyan , Tang Kaifeng , Liao Jianhua
Published: September 2021

Background

MicroRNA-140 (miR-140) is one of the most widely investigated miRNAs in cell carcinogenesis and cancer development. Despite present proposals of employing miR-140 as a candidate biomarker for cancer prognosis, its effectiveness in predicting patient survival and clinicopathological outcome is still under debate.

Methods

A systematic search for English literature using online databases was performed with pre-established criteria. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to delineate the correlation between miR-140 levels and cancer patient prognosis.

Results

For this meta-analysis, we selected 12 papers for analysis, involving 1386 participants. Based on our analysis, high levels of miR-140 were strongly correlated with enhanced patient overall survival (OS) (HR = 0.728, 95% CI = 0.601-0.882, P = 0.001). In addition, we also observed that elevated miR-140 levels significantly led to better OS in patients with cancers in different parts of the body like digestive system (HR = 0.675, 95% CI = 0.538-0.848, P = 0.001), digestive tract (HR = 0.709, 95% CI = 0.565-0.889, P = 0.003), and head and neck (HR = 0.603, 95% CI = 0.456-0.797, P < 0.001). Additionally, we verified that the low miR-140 levels was related to advanced TNM stage (OR = 0.420, 95% CI = 0.299-0.590, P < 0.001), worse histologic grade (OR = 0.410, 95% CI = 0.261-0.643, P < 0.001), and positive lymph node metastasis status (OR = 0.341, 95% CI = 0.144-0.807, P = 0.014).

Conclusions

Taken together, our results suggest that elevated miR-140 levels can be employed as a favorable biomarker for cancer patient prognosis. This information can greatly benefit in the formation of an individualized therapeutic plan for the treatment of cancer patients.
Confirmatory factor analysis of the Children's Eating Behaviour Questionnaire in a Chinese urban preschooler sample
Authors: Zhou Nan , Sun Luning
Published: September 2021

Background

Understanding young children's eating behaviours is vital to childhood obesity prevention. However, the widely used Children's Eating Behaviour Questionnaire (CEBQ) has not been validated in Chinese young children. Thus, the present study aimed to assess the validity of the CEBQ in a Chinese urban sample of preschool children.

Methods

Participants included 389 mothers with preschool children residing in Beijing, China. Confirmatory factor analysis was conducted, and measurement invariance between child genders was evaluated.

Results

The modified 8-factor structure of the CEBQ exhibited acceptable model fit in our sample, and no measurement bias against any gender was observed. The associations between the CEBQ factors and child age showed that desire to drink, emotional overeating, and emotional undereating significantly decreased with age, but food responsiveness increased with age. The relation between child BMI and the CEBQ factors provided convergent validity for the CEBQ.

Conclusions

Our study supported the validity of the CEBQ as a measurement tool for examining preschool children's eating behaviours in a Chinese urban sample.
Silica encapsulation of ZnO nanoparticles reduces their toxicity for cumulus cell-oocyte-complex expansion
Authors: Camaioni Antonella , Massimiani Micol , Lacconi Valentina , Magrini Andrea , Salustri Antonietta , Sotiriou Georgios A. , Singh Dilpreet , Bitounis Dimitrios , Bocca Beatrice , Pino Anna , Barone Flavia , Prota Valentina , Iavicoli Ivo , Scimeca Manuel , Bonanno Elena , Cassee Flemming R. , Demokritou Philip , Pietroiusti Antonio , Campagnolo Luisa
Published: September 2021

Background

Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion.

Methods

Mouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated.

Results

We show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low.

Conclusions

Altogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity.
Global health classroom: mixed methods evaluation of an interinstitutional model for reciprocal global health learning among Samoan and New Zealand medical students
Authors: Bothara Roshit K. , Tafuna’i Malama , Wilkinson Tim J. , Desrosiers Jen , Jack Susan , Pattemore Philip K. , Walls Tony , Sopoaga Faafetai , Murdoch David R. , Miller Andrew P.
Published: September 2021

Background

Global health education partnerships should be collaborative and reciprocal to ensure mutual benefit. Utilisation of digital technologies can overcome geographic boundaries and facilitate collaborative global health learning.

Global Health Classroom (GHCR) is a collaborative global health learning model involving medical students from different countries learning about each other’s health systems, cultures, and determinants of health via videoconference. Principles of reciprocity and interinstitutional partnership informed the development of the GHCR. This study explores learning outcomes and experiences in the GHCR between students from New Zealand and Samoa.

Methods

This study used a mixed methods approach employing post-GHCR questionnaires and semi-structured face-to-face interviews to explore self-reported learning and experiences among medical students in the GHCR. The GHCR collaboration studied was between the medical schools at the University of Otago, New Zealand and the National University of Samoa, Samoa.

Results

Questionnaire response rate was 85% (74/87). Nineteen interviews were conducted among New Zealand and Samoan students. Students reported acquiring the intended learning outcomes relating to patient care, health systems, culture, and determinants of health with regards to their partner country. Interview data was indicative of attitudinal changes in relation to cultural humility and curiosity. Some reported a vision for progress regarding their own health system. Students in the GHCR reported that learning with their international peers in the virtual classroom made learning about global health more real and tangible. The benefits to students from both countries indicated reciprocity.

Conclusions

This study demonstrates GHCR to be a promising model for collaborative and reciprocal global health learning using a student-led format and employing digital technology to create a virtual classroom. The self-reported learning outcomes align favourably with those recommended in the literature. In view of our positive findings, we present GHCR as an adaptable model for equitable, collaborative global health learning between students in internationally partnered institutions.
Genotyping of polyploid plants using quantitative PCR: application in the breeding of white-fleshed triploid loquats (Eriobotrya japonica)
Authors: Wang Haiyan , Dang Jiangbo , Wu Di , Xie Zhongyi , Yan Shuang , Luo Jingnan , Guo Qigao , Liang Guolu
Published: September 2021

Background

Ploidy manipulation is effective in seedless loquat breeding, in which flesh color is a key agronomic and economic trait. Few techniques are currently available for detecting the genotypes of polyploids in plants, but this ability is essential for most genetic research and molecular breeding.

Results

We developed a system for genotyping by quantitative PCR (qPCR) that allowed flesh color genotyping in multiple tetraploid and triploid loquat varieties (lines). The analysis of 13 different ratios of DNA mixtures between two homozygous diploids (AA and aa) showed that the proportion of allele A has a high correlation (R2 = 0.9992) with parameter b [b = a1/(a1 + a2)], which is derived from the two normalized allele signals (a1 and a2) provided by qPCR. Cluster analysis and variance analysis from simulating triploid and tetraploid hybrids provided completely correct allelic configurations. Four genotypes (AAA, AAa, Aaa, aaa) were found in triploid loquats, and four (AAAA, AAAa, AAaa, Aaaa; absence of aaaa homozygotes) were found in tetraploid loquats. DNA markers analysis showed that the segregation of flesh color in all F1 hybrids conformed to Mendel's law. When tetraploid B431 was the female parent, more white-fleshed triploids occurred among the progeny.

Conclusions

qPCR can detect the flesh color genotypes of loquat polyploids and provides an alternative method for analyzing polyploid genotype and breeding, dose effects and allele-specific expression.
The use of a novel deer antler decellularized cartilage-derived matrix scaffold for repair of osteochondral defects
Authors: Chu Wenhui , Hu Gaowei , Peng Lin , Zhang Wei , Ma Zhe
Published: September 2021

Background

The physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair.

Methods

Antler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects.

Results

AdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen.

Conclusions

We concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.
Astrocyte metabolism of the medium-chain fatty acids octanoic acid and decanoic acid promotes GABA synthesis in neurons via elevated glutamine supply
Authors: Andersen Jens V. , Westi Emil W. , Jakobsen Emil , Urruticoechea Nerea , Borges Karin , Aldana Blanca I.
Published: September 2021

The medium-chain fatty acids octanoic acid (C8) and decanoic acid (C10) are gaining attention as beneficial brain fuels in several neurological disorders. The protective effects of C8 and C10 have been proposed to be driven by hepatic production of ketone bodies. However, plasma ketone levels correlates poorly with the cerebral effects of C8 and C10, suggesting that additional mechanism are in place. Here we investigated cellular C8 and C10 metabolism in the brain and explored how the protective effects of C8 and C10 may be linked to cellular metabolism. Using dynamic isotope labeling, with [U-13C]C8 and [U-13C]C10 as metabolic substrates, we show that both C8 and C10 are oxidatively metabolized in mouse brain slices. The 13C enrichment from metabolism of [U-13C]C8 and [U-13C]C10 was particularly prominent in glutamine, suggesting that C8 and C10 metabolism primarily occurs in astrocytes. This finding was corroborated in cultured astrocytes in which C8 increased the respiration linked to ATP production, whereas C10 elevated the mitochondrial proton leak. When C8 and C10 were provided together as metabolic substrates in brain slices, metabolism of C10 was predominant over that of C8. Furthermore, metabolism of both [U-13C]C8 and [U-13C]C10 was unaffected by etomoxir indicating that it is independent of carnitine palmitoyltransferase I (CPT-1). Finally, we show that inhibition of glutamine synthesis selectively reduced 13C accumulation in GABA from [U-13C]C8 and [U-13C]C10 metabolism in brain slices, demonstrating that the glutamine generated from astrocyte C8 and C10 metabolism is utilized for neuronal GABA synthesis. Collectively, the results show that cerebral C8 and C10 metabolism is linked to the metabolic coupling of neurons and astrocytes, which may serve as a protective metabolic mechanism of C8 and C10 supplementation in neurological disorders.
Prognostic and therapeutic implications of measurable residual disease in acute myeloid leukemia
Authors: Aitken Marisa J. L. , Ravandi Farhad , Patel Keyur P. , Short Nicholas J.
Published: September 2021

Quantification of measurable residual disease (MRD) provides critical prognostic information in acute myeloid leukemia (AML). A variety of platforms exist for MRD detection, varying in their sensitivity and applicability to individual patients. MRD detected by quantitative polymerase chain reaction, multiparameter flow cytometry, or next-generation sequencing has prognostic implications in various subsets of AML and at various times throughout treatment. While it is overwhelmingly evident that minute levels of remnant disease confer increased risk of relapse and shortened survival, the therapeutic implications of MRD remain less clear. The use of MRD as a guide to selecting the most optimal post-remission therapy, including hematopoietic stem cell transplant or maintenance therapy with hypomethylating agents, small molecule inhibitors, or immunotherapy is an area of active investigation. In addition, whether there are sufficient data to use MRD negativity as a surrogate endpoint in clinical trial development is controversial. In this review, we will critically examine the methods used to detect MRD, its role as a prognostic biomarker, MRD-directed therapeutics, and its potential role as a study endpoint.
Histidine buffered media maintains pH stabile during cooled transportation of human ovarian tissue
Authors: Pors Susanne Elisabeth , Kristensen Stine Gry , Nikiforov Dmitry , Mamsen Linn Salto , Cadenas Jesus , Greve Vinnie Hornshøj , Dueholm Margit , Andersen Claus Yding
Published: September 2021

The aim of this study was to investigate whether pH is stable when transporting ovarian tissue in media buffered with either HEPES or histidine. Furthermore, if the choice of transport media impacts the in vitro maturation rate of oocytes collected in connection with ovarian tissue cryopreservation. Human ovaries (n = 34) collected for ovarian tissue cryopreservation were transported immersed in either 30 ml of HEPES buffered (follicle flushing media (Origio; Denmark)) or histidine buffered media (Custodiol®-HTK, Koehler-Chemie, Germany). Tissue was transported on ice for 4–5 h. At arrival, the ovary was weighed, and the pH of the media was measured at 0 °C. From 15 patients, immature oocytes were collected for in vitro maturation, oocytes that matured to metaphase II were evaluated. The pH measured in the HEPES buffered media (pH = 7.5 ± 0.13, n = 18) was significantly higher (p < 0.001) than the pH measured in the histidine buffered media (pH = 7.2 ± 0.05, n = 16). The standard deviation of pH measurements for the histidine buffered media was significantly lower than for the HEPES buffered media measurements (p < 0.0001). A total of 170 and 247 immature oocytes were collected and in vitro matured from ovaries transported in HEPES and histidine buffered media, respectively. The maturation rate of immature oocytes after IVM was similar in the two groups. The results show that pH in the histidine buffered media is closer to the physiological level and more stable than in HEPES buffered medium and support the use of histidine buffered media for cooled transportation of human ovaries.
Exploring the inclusion of under-served groups in trials methodology research: an example from ethnic minority populations’ views on deferred consent
Authors: Raven-Gregg Timia , Shepherd Victoria
Published: September 2021

Background

Deferred consent is used to recruit patients in emergency research, when informed consent cannot be obtained prior to enrolment. This model of consent allows studies to recruit larger numbers of participants, especially where a surrogate-decision maker may be unavailable to provide consent. Whilst deferred consent offers the potential to promote trial diversity by including under-served groups, it is ethically complex and views about its use amongst these populations require further exploration. The aim of this article is to build upon recent initiatives to improve inclusivity in trials, such as the NIHR INCLUDE project, and consider whether trials methodology research is inclusive, focusing on ethnic minority populations’ attitudes towards the use of deferred consent.

Main text

Findings from the literature suggest that research regarding attitudes toward recruitment methods like deferred consent largely fail to adequately represent ethnic minorities. Many studies fail to report the composition of patient samples or conduct analyses on any differences between specific patient groups. In those that do, the categorisation of ethnic groups is ambiguous. Frequently diversely different groups are considered as more homogenous than they are. Whilst deferred consent is deemed generally acceptable, analysis of patient sub-groups shows that this attitude is not universal. Those from racial and ethnic minority backgrounds reported higher levels of unacceptability, which was impacted by previous first or second-hand experience of its use and historical mistrust in research. However, whilst deferred consent was found to increase the numbers of black participants enrolled in some trials, their over-enrolment in other trials may raise further concerns.

Conclusions

Inclusivity in clinical trials is important, as highlighted by the COVID-19 pandemic. To improve this, we must ensure that methodological studies such as those exploring attitudes to research are inclusive. More effort is needed to understand the views of under-served groups, such as ethnic minorities, toward research in order to improve participation in clinical trials. Our findings echo those from the INCLUDE project, in that better reporting is needed and increasing the confidence of ethnic minority groups in research requires improving representation throughout the research process. This will involve diversifying research teams and ethics committees.
Virucidal and antiviral activities of pomegranate (Punica granatum) extract against the mosquito-borne Mayaro virus
Authors: Salles Tiago Souza , Meneses Marcelo Damião Ferreira , Caldas Lucio Ayres , Sá-Guimarães Thayane Encarnação , de Oliveira Danielle M. , Ventura José A. , Azevedo Renata Campos , Kuster Ricardo M. , Soares Márcia Regina , Ferreira Davis Fernandes
Published: September 2021

Background

The arthropod-borne Mayaro virus (MAYV) causes “Mayaro fever,” a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. There are currently no licensed drugs against most mosquito-transmitted viruses. Punica granatum (pomegranate) fruits cultivated in Brazil have been subjected to phytochemical investigation for the identification and isolation of antiviral compounds. In the present study, we explored the antiviral activity of pomegranate extracts in Vero cells infected with Mayaro virus.

Methods

The ethanol extract and punicalagin of pomegranate were extracted solely from the shell and purified by chromatographic fractionation, and were chemically identified using spectroscopic techniques. The cytotoxicity of the purified compounds was measured by the dye uptake assay, while their antiviral activity was evaluated by a virus yield inhibition assay.

Results

Pomegranate ethanol extract (CC50 = 588.9, IC50 = 12.3) and a fraction containing punicalagin as major compound (CC50 = 441.5, IC50 = 28.2) were shown to have antiviral activity (SI 49 and 16, respectively) against Mayaro virus, an alphavirus. Immunofluorescence analysis showed the virucidal effect of pomegranate extract, and transmission electron microscopy (TEM) revealed damage in viral particles treated with this extract.

Conclusions

The P. granatum extract is a promising source of antiviral compounds against the alphavirus MAYV and represents an excellent candidate for future studies with other enveloped RNA viruses.

Graphical abstract
Molecular detection of Strongyloides sp. in Australian Thoroughbred foals
Authors: Abbas Ghazanfar , Ghafar Abdul , Koehler Anson V. , Bauquier Jenni , Wilkes Edwina J. A. , Jacobson Caroline , Beasley Anne , Hurley John , Cudmore Lucy , Carrigan Peter , Tennent-Brown Brett , El-Hage Charles , Nielsen Martin K. , Gauci Charles G. , Hughes Kristopher J. , Beveridge Ian , Jabbar Abdul
Published: September 2021

Background

Strongyloides westeri is found in the small intestine of young horses, mainly in foals up to about 16 weeks of age. The main source of infection for foals is through transmammary transmission, and foals can develop acute diarrhoea, weakness, dermatitis and respiratory signs. The epidemiology of S. westeri in Australia is largely unknown. Further, molecular techniques have never been employed for detection of S. westeri in horses. This pilot study aimed to assess the utility of a molecular phylogenetic method for the detection of S. westeri in the faeces of foals.

Methods

Faecal samples were collected from a foal of less than 2 months of age, and eggs of Strongyloides sp. were detected using the modified McMaster technique. DNA was extracted from purified eggs, and a partial fragment of the small subunit of the nuclear ribosomal DNA (18S) was characterised using polymerase chain reaction, DNA sequencing and phylogenetic methods.

Results

Microscopic examination of faeces revealed small ellipsoidal eggs typical of Strongyloides sp. The 18S sequence generated by PCR in this study revealed 98.4% identity with that of a reference sequence of S. westeri available from GenBank. Phylogenetic analyses revealed a polyphyletic clustering of S. westeri sequences.

Conclusion

This is the first study reporting the detection of DNA of Strongyloides sp. in faeces of a foal using a molecular phylogenetic approach targeting the variable region of 18S rDNA. It is anticipated that this study will allow future molecular epidemiological studies on S. westeri in horses.

Graphical abstract
Ten-year longitudinal molecular epidemiology study of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire, UK
Authors: Lipworth Samuel , Vihta Karina-Doris , Chau Kevin , Barker Leanne , George Sophie , Kavanagh James , Davies Timothy , Vaughan Alison , Andersson Monique , Jeffery Katie , Oakley Sarah , Morgan Marcus , Hopkins Susan , Peto Timothy E. A. , Crook Derrick W. , Walker Ann Sarah , Stoesser Nicole
Published: September 2021

Background

The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however, the causes of this are unclear and effective interventions are therefore hard to design.

Methods

In this study, we sequenced 3468 unselected isolates over a decade in Oxfordshire (UK) and linked this data to routinely collected electronic healthcare records and mandatory surveillance reports. We annotated genomes for clinically relevant genes, contrasting the distribution of these within and between species, and compared incidence trends over time using stacked negative binomial regression.

Results

We demonstrate that the observed increases in E. coli incidence were not driven by the success of one or more sequence types (STs); instead, four STs continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp., most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs have no known acquired virulence loci. Finally, we demonstrate a diverse but largely genus-restricted mobilome with close associations between antimicrobial resistance (AMR) genes and insertion sequences but not typically specific plasmid replicon types, consistent with the dissemination of AMR genes being highly contingent on smaller mobile genetic elements (MGEs).

Conclusions

Our large genomic study highlights distinct differences in the molecular epidemiology of E. coli and Klebsiella BSIs and suggests that no single specific pathogen genetic factors (e.g. AMR/virulence genes/sequence type) are likely contributing to the increasing incidence of BSI overall, that association with AMR genes in E. coli is a contributor to the increasing number of E. coli BSIs, and that more attention should be given to AMR gene associations with non-plasmid MGEs to try and understand horizontal gene transfer networks.
The prevalence of oral mucosal lesions and related factors in systemic lupus erythematosus patients
Authors: Kudsi Mayssoun , Nahas Louei Darjazini , Alsawah Rama , Hamsho Ahmad , Omar Abdullah
Published: September 2021

Background

Systemic lupus erythematosus (SLE) is a chronic inflammatory multi systematic disease of unknown aetiology. SLE has a wide range of symptoms. The most common symptoms are joint pain, skin rash and fever. Oral lesions in SLE manifest in a variety of forms, such as oral mucosal ulceration, mouth burns, xerostomia and salivary gland diseases, temporomandibular joint disease, periodontal disease, dysgeusia, white lesions, oedema, bleeding and petechiae.

Objective

This study was conducted to evaluate the prevalence of oral mucosal lesions and their related factors in patients with SLE, giving the lack of comprehensive statistical data in Syria and the differences between reported prevalence.

Patients and methods

A cross-sectional study was performed in the Al-Mouassat University Hospital in Damascus. Patients were evaluated appropriating observation, clinical examination, completing questionnaires, studying patient’s medical records and paraclinical laboratory tests if required. Four types of oral lesions were evaluated: ulcer, erythema, white plaque and spots. The diagnosis of these lesions was made according to observation and clinical examination, and the location of each lesion was also recorded. Data were analysed using SPSS version 16.0.

Result

In this study, 42 (70% %) out of 60 patients (38 women and 4 men) had oral lesions, while 18 (30%) had none. The most common areas for the lesions were the buccal mucosa (26.1%) and the lips (14.2%). Of the 42 patients with oral lesions, 12 (27.6%) showed ulcers. There was a significant relationship between the following factors and oral lesions: oral hygiene status, the duration of the disease involvement, frequency of pregnancies, the amount of daily use of corticosteroids without significant difference between dosage groups, and medications used for SLE treatment other than corticosteroids (p < 0.008) without mentioned names or dosages. Conversely, age, sex, cigarette smoking and medications other than those used for SLE treatment were not significantly related to the presence of oral lesions (p value was greater than 0.05 in all subjects).