bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for and localization of proposed causative variants in cattle and pig genomes
Authors: Johnsson Martin , Jungnickel Melissa K.
Published: August 2021

Background

This paper reviews the localization of published potential causative variants in contemporary pig and cattle reference genomes, and the evidence for their causality. In spite of the difficulties inherent to the identification of causative variants from genetic mapping and genome-wide association studies, researchers in animal genetics have proposed putative causative variants for several traits relevant to livestock breeding.

Results

For this review, we read the literature that supports potential causative variants in 13 genes (ABCG2, DGAT1, GHR, IGF2, MC4R, MSTN, NR6A1, PHGK1, PRKAG3, PLRL, RYR1, SYNGR2 and VRTN) in cattle and pigs, and localized them in contemporary reference genomes. We review the evidence for their causality, by aiming to separate the evidence for the locus, the proposed causative gene and the proposed causative variant, and report the bioinformatic searches and tactics needed to localize the sequence variants in the cattle or pig genome.

Conclusions

Taken together, there is usually good evidence for the association at the locus level, some evidence for a specific causative gene at eight of the loci, and some experimental evidence for a specific causative variant at six of the loci. We recommend that researchers who report new potential causative variants use referenced coordinate systems, show local sequence context, and submit variants to repositories.
The expression of kappa-opioid receptor promotes the migration of breast cancer cells in vitro
Authors: Li Huiqing , Ma Zhenzhen , Lei Yunlong
Published: August 2021

Background

Opioid receptors are implicated in cell proliferation and cancer migration. However, the effects and underlying mechanisms of opioid receptor κ (OPRK1) in breast cancer remain unknown.

Methods

Small interfering RNA (siRNAs) was used to knockdown the expression of OPRK1. Western blot was used to determine the protein expression and reverse transcription-quantitative PCR (RT-qPCR) determined the genes transcription. Cell viability was detected by MTT assay and cell death rates were determined by Annexin V/PI and flow cytometry. Cell migration and invasion were detected by wound healing analysis and transwell assay, respectively.

Results

Our research demonstrated that OPRK1 was overexpressed in breast cancer cells compared with the normal human mammary epithelial cells. OPRK1 knockdown could inhibited cell viability and migration in cancer cells, accompanied with the decreased proteins and genes expression of N-cadherin, Snail, MMP2 and Vimentin, while the E-cadherin expression was increased. Additionally, OPRK1 knockdown also promoted PI3K/AKT signaling inactivation. Activation of AKT reversed the OPRK1 knockdown-induced cell viability inhibition and migration suppression, while inhibition of AKT reduced cell viability and promoted cell death.

Conclusions

Our findings illustrated the role of OPRK1 played on promoting migration in vitro, and we also provided the therapeutic research of OPRK1 knockdown combined with AKT inhibition.
Bronchial rupture following endobronchial blocker placement: a case report of a rare, unfortunate complication
Authors: Oo Shuwen , Chia Rachel Hui Xuan , Li Yue , Sampath Hari Kumar , Ang Sophia Bee Leng , Paranjothy Suresh , Tam John Kit Chung , Lee Chang Chuan Melvin
Published: August 2021

Background

Lung separation may be achieved through the use of double lumen tubes or endobronchial blockers. The use of lung separation techniques carries the risk of airway injuries which range from minor complications like postoperative hoarseness and sore throat to rare and potentially devastating tracheobronchial mucosal injuries like bronchus perforation or rupture. With few case reports to date, bronchial rupture with the use of endobronchial blockers is indeed an overlooked complication.

Case presentation

A 78-year-old male patient with a left upper lobe lung adenocarcinoma underwent a left upper lobectomy with a Fuji Uniblocker® as the lung separation device. Despite an atraumatic insertion and endobronchial blocker balloon volume within manufacturer specifications, an intraoperative air leak developed, and the patient was found to have sustained a left mainstem bronchus rupture which was successfully repaired and the patient extubated uneventfully. Unfortunately, the patient passed on in-hospital from sepsis and other complications.

Conclusion

Bronchial rupture is a serious complication of endobronchial blocker use that can carry significant morbidity, and due care should be exercised in its use and placement. Bronchoscopy should be used during insertion, and the volume and pressure of the balloon kept to the minimum required to prevent air leak. Bronchial injury should be considered as a differential in the presence of an unexplained air leak.
Impact of social and mobility restrictions in Parkinson’s disease during COVID-19 lockdown
Authors: Luis-Martínez Raquel , Di Marco Roberto , Weis Luca , Cianci Valeria , Pistonesi Francesca , Baba Alfonc , Carecchio Miryam , Biundo Roberta , Tedesco Chiara , Masiero Stefano , Antonini Angelo
Published: August 2021

Background

The consequences of strict COVID-19 mobility restrictions on motor/non-motor features in Parkinson’s disease (PD) have not been systematically studied but worse mobility and quality of life have been reported. To elucidate this question, 12 mild to moderate PD patients were assessed in March 2020 before and after two months of isolation as part of a clinical study that had to be interrupted due to the pandemic and the implementation of COVID19 mobility restrictions.

Methods

Twelve patients were systematically evaluated before and after the lockdown period as part of a larger cohort that previously underwent thermal water rehabilitation. Clinical outcomes were the Body Mass index, the Mini-Balance Evaluation Systems Test, the MDS-Unified Parkinson’s Disease Rating Scale part III, the 6 Minute Walking Test and the New Freezing of Gait Questionnaire. Global cognition was evaluated with the Montreal Cognitive Assessment scale. The impact of COVID-19 restrictions on quality of life and functional independence was evaluated with The Parkinson’s disease Quality of life (PDQ-39), the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living questionnaires (IADL) and the Parkinson’s disease cognitive functional rating scales (PD-CFRS).

Results

After two months of isolation the Mini-BESTest score worsened (p=0.005), and four patients reported one or more falls during the lockdown. BMI increased (p=0.031) while the remaining clinical variables including quality of life did not change.

Conclusion

We observed moderate worsening at Mini-BESTest, greater risk of falls and increased body weight as consequence of prolonged immobility. We believe negative effects were partially softened since patients were in contact with our multidisciplinary team during the lockdown and had previously received training to respond to the needs of this emergency isolation. These findings highligh the importnace of patient-centered interventions in PD management.
Infiltration of CD1a-positive dendritic cells in advanced laryngeal cancer correlates with unfavorable outcomes post-laryngectomy
Authors: Minesaki Akimichi , Kai Keita , Kuratomi Yuichiro , Aishima Shinichi
Published: August 2021

Background

The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established.

Methods

We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters.

Results

Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013).

Conclusions

Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.
Customized treatment protocols for patients with closed fracture in hospitals at varying coronavirus disease 2019 (COVID-19) risk
Authors: He Yu , Guo Zhong-Hua , Wu Yong-Guang , Li Rui , Xie Xie , Fu De-Hao
Published: August 2021

Background

To determine an optimized treatment protocol during the COVID-19 epidemic for patients with closed fracture and delayed surgery.

Methods

The epidemic data of three hospitals, randomly selected from different administrative regions of Wuhan, were analyzed retrospectively from 23 January to 31 March 2020. Changes in the number of confirmed cases per day (cumulative and new) of each region were tracked as a reflection of changing epidemic risk levels. The risk level map was drawn. The epidemic status, treatment protocols, and treatment efficiencies for patients with closed fracture in the three hospitals were compared.

Results

Overall, 138 patients with closed fracture were admitted. Each hospital had established its own protocol, according to the initial perceived risk. Based on the risk level map, over the study period, the risk levels of the three regions changed independently and were not in sync. All patients recovered and were timely discharged. No staff member was detected with COVID-19.

Conclusions

The COVID-19 risk level of each area is dynamic. To optimize medical resources, avoid cross-infection, and improve efficiency, changes in epidemic risk should be monitored. For patients with closed fracture, treatment protocols should be adjusted according to changes in epidemic risk.
Associations between the spiritual well-being (EORTC QLQ-SWB32) and quality of life (EORTC QLQ-C30) of patients receiving palliative care for cancer in Cyprus
Authors: Kyranou Maria , Nicolaou Marianna
Published: August 2021

Background

Spiritual well-being is increasingly investigated in relation to patients’ perceived quality of life and is generally thought as having the potential to support patients with cancer who receive palliative care. Until recently, questionnaires used to assess spiritual well-being were developed mainly in the US. The purpose of this study was to translate and use the EORTC- SWB32, a newly developed tool, validated recently in 4 continents, 14 countries, and in 10 languages, to explore relationships of spiritual well-being with quality of life in patients with cancer.

Methods

One hundred four patients participated in this study with an average age of 59 years. Of those, 79% were dealing with metastatic cancer. Data collection took place in three oncology centers from two large cities in Cyprus. The acceptability of the translated items was tested. Two questionnaires were employed for the assessment of quality of life and spiritual well-being, developed by the same organization: the EORTC QLQ-C30 and the EORTC QLQ-SWB32. The scores for each tool were analyzed separately and correlations between the two measures were explored.

Results

Patients found the items of the SWB32 tool easy to understand and answer. They attested that filling the questionnaire prompted thoughts about their own spirituality. The mean score for Global Spiritual Well-Being was 60.4 (SD = 23.7) and it was associated with the mean scores in the scales “Emotional functioning” and “Cognitive functioning” of the EORTC-QOL-C30 (0.42 and 0.40 respectively, p < 0.01). The mean score for the “Relationship with God” scale (74.9, SD = 29.7) reported by the Cypriot patients is high and compatible with the homogenous spiritual orientation of the island’s population.

Conclusions

All subscales of the SWB32 tool demonstrated good internal consistency in this study. Significant associations were observed between dimensions of quality of life and spiritual well-being. Additionally, the participants found the items easy to answer consistent with the tool’s suggested clinical utility which lays the ground for the application of targeted interventions to enhance spiritual well-being.
Comparison of empathy with patients between first-year and last-year medical students of Tehran University of Medical Sciences
Authors: Hizomi Arani Reyhane , Naji Zohrehsadat , Moradi Ali , Shariat Seyed Vahid , Mirzamohamadi Sara , Salamati Payman
Published: August 2021

Purpose

This study was conducted to assess the developmental factors of empathy among medical students of Tehran University of Medical Sciences (TUMS).

Methods

To assess the empathy levels, 42 first-year and an equal number of last-year medical students were randomly selected. They answered a questionnaire including the medical student version of the Jefferson Scale, demographic, and some related variables. Statistical analyses were performed using the Chi-square test, T-test, univariate, and multivariate regressions.

Result

The study population consisted of 51 (60.7 %) men and 33 (39.3 %) women with a mean (SD) age of 22.24 (4.10) years. The Jefferson score was 110.19 ± 13.61 and 103.52 ± 20.00 in first- and last-year medical students, respectively. Moreover, medical students who completely passed at least one of the considered empathy courses of the TUMS curriculum had higher empathy scores compared to their counterparts (109.83 ± 15.54 vs. 103.68 ± 19.02). There was no significant association between empathy and gender, self-experience of illness, marital status, family history of chronic disease, and parents’ education (all P-values > 0.05). After adjusting for the effects of confounders, the empathy scores were significantly associated with the academic year level (p = 0.04), level of interest in medicine (p = 0.001), and passing the empathy courses (p = 0.04).

Conclusions

The data provided from a top Iranian medical school indicated that the academic year level, level of interest in medicine, and passing the empathy courses were significantly associated with the empathy level. Further studies are recommended.
The lived experiences of intensive care nursing students exposed to a new model of high-fidelity simulation training: a phenomenological study
Authors: Dante Angelo , Masotta Vittorio , Marcotullio Alessia , Bertocchi Luca , Caponnetto Valeria , La Cerra Carmen , Petrucci Cristina , Alfes Celeste Marie , Lancia Loreto
Published: August 2021

Background

In postgraduate intensive care nursing courses, high-fidelity simulation is useful to prepare students to guarantee safe and quality care of critically ill patients. Surprisingly, this issue has not attracted sufficient attention in the literature, and it is not clear whether the linear application of the traditional high-fidelity simulation method based on prebriefing, the simulation session and debriefing, can serve as empirical reference in postgraduate students’ education. The aim of this study was to investigate the lived experiences of postgraduate students receiving multiple exposures to an innovative high-fidelity simulation design based on Kolb’s Experiential Learning Theory.

Methods

A phenomenological study was conducted at an Italian University involving a purposive sample of 15 nursing students attending the postgraduate intensive care course. Audio-recorded face-to-face in-depth interviews were held by a researcher in a dedicated room complemented with non-verbal communication outlined in the field notes. Thematic analysis was used to analyse the transcribed data.

Results

Three themes and ten categories were derived from the data analysis. The themes included pragmatic learning experience, the emotional path, and confidence.

Conclusions

Multiple exposure to high-fidelity simulation was lived as a pragmatic learning experience enhancing the students’ ability to apply theory into practice. This novel approach also contributed to the transition from negative to positive feelings and improved students’ confidence about technical and non-technical skills when caring for a critically ill patient.
Health and resource burden of a cancer diagnosis on the caregiver: an analysis of administrative claims data
Authors: Hess Lisa M , Wong-Jacobson Siew Hoong , Peterson Patrick M
Published: August 2021

Purpose

Cancer diagnosis is known to affect the family; however, administrative claims data are not commonly used to evaluate the broader impact of cancer diagnosis. This study was designed to evaluate the feasibility of using claims data to explore the impact of cancer diagnosis on the caregiver.

Methods

IBM Marketscan data were used to identify eligible cancer patients, who were required to have a second adult over the age of 18 (defined as “caregiver” for this study) covered by the same the healthcare policy. Eligible control pairs included any two adults in the same policy with no evidence of cancer; for each pair one adult was randomly assigned to be the “patient control” while their partner was assigned as “caregiver control”. Probabilistic stratified sampling was used select control pairs for analysis by matching the relative frequencies within sex and age group strata to those of patient/caregiver pairs. Eligible control pairs were probabilistically sampled without replacement until the stratum with at least 0.5 % relative frequency had been completely sampled. Caregiver and caregiver control healthcare resource utilization (HCRU), new diagnoses, and healthcare costs were compared during the 12-month post-diagnosis period. Subgroup analyses were conducted by cancer subtypes (breast, colorectal, lung, gastric, sarcoma) and by sex of the patient and caregiver.

Results

A total of 62,893 patient/caregiver pairs and 449,177 control pairs were included. Overall, caregivers used slightly fewer healthcare resources and expended less costs during the 12-month period after the cancer diagnosis than controls (physician visits; 85.8 % vs. 95.7 %; hospitalizations 5.4 % vs. 7.0 %; emergency room visits 15.7 % versus 16.2 %, all p ≤ 0.001). This finding was consistent in all subgroup analyses. New diagnoses were lower in the caregiver cohort, except for mental disorders, which were higher than controls (14.3 % vs. 9.9 %, p < 0.0001). Psychotherapeutic/antidepressant utilization occurred among 21.0 % of caregivers versus 17.2 % of caregiver controls during this period.

Conclusions

It is feasible to use administrative claims data to evaluate the impact of a cancer diagnosis on the caregiver to evaluate outcomes such as HCRU, diagnoses and costs. These findings raise hypotheses about deferment of health care and increased mental distress during the caregiving period.
The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer
Authors: Xiong Kangping , Wang Gang , Peng Tianchen , Zhou Fenfang , Chen Siming , Liu Wei , Ju Lingao , Xiao Yu , Qian Kaiyu , Wang Xinghuan
Published: August 2021

Background

New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer.

Methods

In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model.

Results

The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, β-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group.

Conclusions

Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.
Quantifying malaria acquired during travel and its role in malaria elimination on Bioko Island
Authors: Citron Daniel T. , Guerra Carlos A. , García Guillermo A. , Wu Sean L. , Battle Katherine E. , Gibson Harry S. , Smith David L.
Published: August 2021

Background

Malaria elimination is the goal for Bioko Island, Equatorial Guinea. Intensive interventions implemented since 2004 have reduced prevalence, but progress has stalled in recent years. A challenge for elimination has been malaria infections in residents acquired during travel to mainland Equatorial Guinea. The present article quantifies how off-island contributes to remaining malaria prevalence on Bioko Island, and investigates the potential role of a pre-erythrocytic vaccine in making further progress towards elimination.

Methods

Malaria transmission on Bioko Island was simulated using a model calibrated based on data from the Malaria Indicator Surveys (MIS) from 2015 to 2018, including detailed travel histories and malaria positivity by rapid-diagnostic tests (RDTs), as well as geospatial estimates of malaria prevalence. Mosquito population density was adjusted to fit local transmission, conditional on importation rates under current levels of control and within-island mobility. The simulations were then used to evaluate the impact of two pre-erythrocytic vaccine distribution strategies: mass treat and vaccinate, and prophylactic vaccination for off-island travellers. Lastly, a sensitivity analysis was performed through an ensemble of simulations fit to the Bayesian joint posterior probability distribution of the geospatial prevalence estimates.

Results

The simulations suggest that in Malabo, an urban city containing 80% of the population, there are some pockets of residual transmission, but a large proportion of infections are acquired off-island by travellers to the mainland. Outside of Malabo, prevalence was mainly attributable to local transmission. The uncertainty in the local transmission vs. importation is lowest within Malabo and highest outside. Using a pre-erythrocytic vaccine to protect travellers would have larger benefits than using the vaccine to protect residents of Bioko Island from local transmission. In simulations, mass treatment and vaccination had short-lived benefits, as malaria prevalence returned to current levels as the vaccine’s efficacy waned. Prophylactic vaccination of travellers resulted in longer-lasting reductions in prevalence. These projections were robust to underlying uncertainty in prevalence estimates.

Conclusions

The modelled outcomes suggest that the volume of malaria cases imported from the mainland is a partial driver of continued endemic malaria on Bioko Island, and that continued elimination efforts on must account for human travel activity.
General Spanish population normative data analysis for the EORTC QLQ-C30 by sex, age, and health condition
Authors: Arraras Juan Ignacio , Nolte Sandra , Liegl Gregor , Rose Matthias , Manterola Ana , Illarramendi Jose Juan , Zarandona Uxue , Rico Mikel , Teiejria Lucia , Asin Gemma , Hernandez Irene , Barrado Marta , Vera Ruth , Efficace Fabio , Giesinger Johannes M. ,   the EORTC Quality of Life Group
Published: August 2021

Purpose

General population normative data for the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire facilitates interpretation of data assessed from cancer patients. This study aims to present normative data of the general Spanish population.

Methods/patients

Data were obtained from a prior larger study collecting EORTC QLQ-C30 norm data across 15 countries. Data were stratified by sex and age groups (18–39, 40–49, 50–59, 60–69 and > 70 years). Sex and age distribution were weighted according to population distribution statistics. Sex- and age-specific normative values were analysed separately, as were participants with versus those without health conditions. Multiple linear regression was used to estimate the association of each of the EORTC QLQ-C30 scales with the determinants age, sex, sex-by-age interaction term, and health condition.

Results

In total, 1,165 Spanish individuals participated in the study. Differences were found by sex and age. The largest sex-related differences were seen in fatigue, emotional functioning, and global QOL (Quality of Life), favouring men. The largest age differences were seen in emotional functioning, insomnia, and pain, with middle-aged groups having the worst scores. Those > 60 years old scored better than those < 60 years old on all scales except for physical functioning. Participants with no health conditions scored better in all QLQ-C30 domains.

Conclusions

The present study highlights differences in HRQOL between specific sex/age strata and especially between people with and without a health condition in the general Spanish population. These factors must be considered when comparing general population HRQOL data with that of cancer patients.
Health-related quality of life profiles and their dimension-specific associated factors among Malaysian stroke survivors: a cross sectional study
Authors: Wong Hui Jie , Lua Pei Lin , Harith Sakinah , Ibrahim Khairul Azmi
Published: August 2021

Background

Apart from maximizing functional abilities and independence after stroke, improving overall health-related quality of life (HRQoL) should also become part of the stroke treatment and rehabilitation process goals. This study aimed to assess the HRQoL profiles and explore the dimension-specific associated factors of HRQoL among stroke survivors.

Methods

This was a cross-sectional study of stroke survivors attending post-stroke care clinics in three public hospitals in the states of Pahang and Terengganu, Malaysia. The HRQoL was assessed by EuroQol-5 dimension-5 levels. Data on socio-demographic, clinical profiles, malnutrition risk, and physical activity level were collected through an interviewer-administered survey. Descriptive analyses for HRQoL profiles and multiple logistic regression analyses for its associated factors were performed. Crude and adjusted odds ratios were reported.

Results

A total of 366 stroke survivors were recruited with a mean age of 59 ± 11 years. The most -commonly reported health problems were mobility (85%), followed by usual activities (82%), pain/discomfort (63%), anxiety/depression (51%) and self-care (41%). The mean of the EQ visual analogue scale and the median of the EQ5D summary index was reported at 60.3 ± 14.2 and 0.67 ± 0.37, respectively. Malnutrition risk (mobility, usual activities, and self-care), wheelchair users (self-care and usual activities), speech impairment (usual activities and pain/discomfort), number of stroke episodes (self-care and pain/discomfort), body mass index, physical activity level and types of strokes (usual activities), age and use of a proxy (anxiety/depression), working and smoking status (mobility), were factors associated with either single or multiple dimensions of HRQoL.

Conclusion

Routine malnutrition screening, tailored program for speech therapy, prevention of recurrent stroke, and physical activity promotion should be addressed and further reinforced in current rehabilitation interventions to improve the HRQoL among stroke survivors in Malaysia.
Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients
Authors: Zhao Hua-fu , Zhou Xiu-ming , Wang Jing , Chen Fan-fan , Wu Chang-peng , Diao Peng-yu , Cai Lin-rong , Chen Lei , Xu Yan-wen , Liu Jing , Li Zong-yang , Liu Wen-lan , Chen Zhong-ping , Huang Guo-dong , Li Wei-ping
Published: August 2021

Background

Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet.

Methods

This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People’s Hospital and the Sun Yat-sen University Cancer Center.

Results

The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas.

Conclusions

Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.
Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE
Authors: Gilbert Mileka , Goilav Beatrice , Hsu Joyce J. , Nietert Paul J. , Meidan Esra , Chua Annabelle , Ardoin Stacy P. , Wenderfer Scott E. , von Scheven Emily , Ruth Natasha M. ,   for the Pediatric Nephrology and Rheumatology Collaborative Group, the Childhood Arthritis and Rheumatology Research Alliance, and the American Society for Pediatric Nephrology
Published: August 2021

Background

Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.

Methods

Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination.

Results

Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05).

Conclusions

Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.
A qualitative exploration of pharmacovigilance policy implementation in Jordan, Oman, and Kuwait using Matland’s ambiguity-conflict model
Authors: Garashi Hamza Y. , Steinke Douglas T. , Schafheutle Ellen I.
Published: August 2021

Background

As Arab countries seek to implement the ‘Guideline on Good Pharmacovigilance Practice (GVP) for Arab countries’, understanding policy implementation mechanisms and the factors impacting it can inform best implementation practice. This study aimed to explore the mechanisms of and factors influencing pharmacovigilance policy implementation in Arab countries with more established pharmacovigilance systems (Jordan, Oman), to inform policy implementation in a country with a nascent pharmacovigilance system (Kuwait).

Results

Matland’s ambiguity-conflict model served to frame data analysis from 56 face-to-face interviews, which showed that policy ambiguity and conflict were low in Jordan and Oman, suggesting an “administrative implementation” pathway. In Kuwait, policy ambiguity was high while sentiments about policy conflict were varied, suggesting a mixture between “experimental implementation” and “symbolic implementation”. Factors reducing policy ambiguity in Jordan and Oman included: decision-makers’ guidance to implementors, stakeholder involvement in the policy’s development and implementation, training of policy implementors throughout the implementation process, clearly outlined policy goals and means, and presence of a strategic implementation plan with appropriate timelines as well as a monitoring mechanism. In contrast, policy ambiguity in Kuwait stemmed from the absence or lack of attention to these factors. Factors reducing policy conflict included: the policy’s compliance with internationally recognised standards and the policy’s fit with local capabilities (all three countries), decision-makers’ cooperation with and support of the national centre as well as stakeholders’ agreement on policy goals and means (Jordan and Oman) and adopting a stepwise approach to implementation (Jordan).

Conclusions

Using Matland’s model, both the mechanism of and factors impacting successful pharmacovigilance policy implementation were identified. This informed recommendations for best implementation practice in Arab as well as other countries with nascent pharmacovigilance systems, including increased managerial engagement and support, greater stakeholder involvement in policy development and implementation, and undertaking more detailed implementation planning.
Changes in peripheral lymphocyte populations in patients with advanced/recurrent ovarian cancer undergoing splenectomy during cytoreductive surgery
Authors: Chen Wei , Ye Shuang , Wu Yutuan , Pei Xuan , Xiang Libing , Ping Bo , Shan Boer , Yang Huijuan
Published: August 2021

Background

To investigate changes in peripheral lymphocyte subsets after splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancers.

Methods

We enrolled 83 patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery. Twenty patients who also underwent splenectomy were assigned to the splenectomy cohort and the rest were assigned to the non-splenectomy cohort. Flow cytometry was used to measure peripheral lymphocyte subsets consisting of T cells, regulatory T cells, natural killer cells, B cells, and activation antigens before and after surgery.

Results

There was no difference in the number and distribution of peripheral lymphocyte subsets between the two cohorts before surgery. After surgery, we observed elevated levels of T cells (CD3+, CD3+CD8+) in the splenectomy cohort compared to those in the non-splenectomy cohort, and the difference was statistically significant. CD8+CD28+ T cells had a significant decreasing tendency (P = 0.011) while CD3+/HLA-DR+ T cells showed the opposite trend (P = 0.001) in the splenectomy cohort. The proportion of Tregs (P = 0.005) and B cells (P < 0.001) including CD3−/HLA-DR+ B cells (P = 0.007) increased after surgery, and the absolute number of T cells and NK cells decreased to different extents (P < 0.001) in the non-splenectomy cohort. The post-operative percentage of CD8+CD28+ T cells was less than the pre-operative percentage (P = 0.022), which was similar to the splenectomy cohort. There was no significant difference in progression-free survival or overall survival between the groups after a median follow-up time of 41 months.

Conclusions

The changes in peripheral lymphocyte populations were different between patients with and those without splenectomy during cytoreductive surgery for ovarian cancers. T cells were increased and activated in the splenectomy cohort, whereas, B cells were increased and activated in the non-splenectomy cohort.
DArT-based evaluation of soybean germplasm from Polish Gene Bank
Authors: Czembor Elzbieta , Czembor Jerzy H. , Suchecki Radoslaw , Watson-Haigh Nathan S.
Published: August 2021

Objective

Soybean is an important plant used for food, feed and many industrial purposes. Interest in soybean breeding is growing in Central Europe, including Poland. A very large number of soybean accessions are stored in gene banks, but less than 1% of them have been used for breeding. Here, we present genotypic data as well as phenotypic data on plant and seed performance, including seed chlorophyll fluorescence traits, and on yield components within a collection of soybean accessions that are conserved in the Polish Gene Bank at the Plant Breeding and Acclimatization Institute-National Research Institute.

Results

The materials used consisted of sub-collections: 79 Polish genotypes, including old traditional cultivars, 24 Canadian, 21 American, 21 Swedish and 31 from Central and Eastern European Countries, 9 from France and 6 from Japan. In total, 9602 high quality SNPs were derived from DArTseq, a method utilising GBS technology. GWAS, performed with the BLINK model, revealed that a total of 41 significant SNPs were mapped for days to flowering, flower colour, plant height, days to pod formation, 100 seed weight, pod colour, seeds and hilum colour and steady-state chlorophyll fluorescence under light (Ft_Lss). This is the first report about the diversity of traditional old Polish soybean cultivars.
Intratracheal transplantation of trophoblast stem cells attenuates acute lung injury in mice
Authors: Han Junwen , Li Gu , Hou Minmin , Ng Julie , Kwon Min-Young , Xiong Kevin , Liang Xiaoliang , Taglauer Elizabeth , Shi Yuanyuan , Mitsialis S. Alex , Kourembanas Stella , El-Chemaly Souheil , Lederer James A. , Rosas Ivan O. , Perrella Mark A. , Liu Xiaoli
Published: August 2021

Background

Acute lung injury (ALI) is a common lung disorder that affects millions of people every year. The infiltration of inflammatory cells into the lungs and death of the alveolar epithelial cells are key factors to trigger a pathological cascade. Trophoblast stem cells (TSCs) are immune privileged, and demonstrate the capability of self-renewal and multipotency with differentiation into three germ layers. We hypothesized that intratracheal transplantation of TSCs may alleviate ALI.

Methods

ALI was induced by intratracheal delivery of bleomycin (BLM) in mice. After exposure to BLM, pre-labeled TSCs or fibroblasts (FBs) were intratracheally administered into the lungs. Analyses of the lungs were performed for inflammatory infiltrates, cell apoptosis, and engraftment of TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar lavage fluid (BALF) were also assessed.

Results

The lungs displayed a reduction in cellularity, with decreased CD45+ cells, and less thickening of the alveolar walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. TSCs decreased infiltration of neutrophils and macrophages, and the expression of interleukin (IL) 6, monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived chemokine (KC) in the injured lungs. The levels of inflammatory cytokines in BALF, particularly IL-6, were decreased in ALI mice receiving TSCs, compared to ALI mice that received PBS or FBs. TSCs also significantly reduced BLM-induced apoptosis of alveolar epithelial cells in vitro and in vivo. Transplanted TSCs integrated into the alveolar walls and expressed aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I and II cells, respectively.

Conclusion

Intratracheal transplantation of TSCs into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation and cell death. Furthermore, TSCs engrafted into the alveolar walls to form alveolar epithelial type I and II cells. These data support the use of TSCs for the treatment of ALI.
Primary recovery of hyaluronic acid produced in Streptococcus equi subsp. zooepidemicus using PEG–citrate aqueous two-phase systems
Authors: Flores-Gatica Miguel , Castañeda-Aponte Héctor , Gil-Garzon Mónica Rebeca , Mora-Galvez Liliana Monserrath , Banda-Magaña Martin Paul , Jáuregui-Jáuregui Jesús Antonio , Torres-Acosta Mario A. , Mayolo-Deloisa Karla , Licona-Cassani Cuauhtemoc
Published: August 2021

Given its biocompatibility, rheological, and physiological properties, hyaluronic acid (HA) has become a biomaterial of increasing interest with multiple applications in medicine and cosmetics. In recent decades, microbial fermentations have become an important source for the industrial production of HA. However, due to its final applications, microbial HA must undergo critical and long purification processes to ensure clinical and cosmetic grade purity. Aqueous two-phase systems (ATPS) have proven to be an efficient technique for the primary recovery of high-value biomolecules. Nevertheless, their implementation in HA downstream processing has been practically unexplored. In this work, polyethylene glycol (PEG)–citrate ATPS were used for the first time for the primary recovery of HA produced with an engineered strain of Streptococcus equi subsp. zooepidemicus. The effects of PEG molecular weight (MW), tie-line length (TLL), volume ratio (VR), and sample load on HA recovery and purity were studied with a clarified fermentation broth as feed material. HA was recovered in the salt-rich bottom phase, and its recovery increased when a PEG MW of 8000 g mol−1 was used. Lower VR values (0.38) favoured HA recovery, whereas purity was enhanced by a high VR (3.50). Meanwhile, sample load had a negative impact on both recovery and purity. The ATPS with the best performance was PEG 8000 g mol−1, TLL 43% (w/w), and VR 3.50, showing 79.4% HA recovery and 74.5% purity. This study demonstrated for the first time the potential of PEG–citrate ATPS as an effective primary recovery strategy for the downstream process of microbial HA.
Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor
Authors: Liu Jinbiao , Bodnar Brittany H. , Meng Fengzhen , Khan Adil I. , Wang Xu , Saribas Sami , Wang Tao , Lohani Saroj Chandra , Wang Peng , Wei Zhengyu , Luo Jinjun , Zhou Lina , Wu Jianguo , Luo Guangxiang , Li Qingsheng , Hu Wenhui , Ho Wenzhe
Published: August 2021

Background

As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection.

Results

We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells.

Conclusions

These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.