bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive symptoms and their determinants in patients who are on antiretroviral therapy in the case of a low-income country, Ethiopia: a systematic review and meta-analysis
Authors: Necho Mogesie , Belete Asmare , Tsehay Mekonnen
Published: January 2021

Background

The presence of depression in people living with HIV/AIDS could lead to non-adherence to antiretroviral medications. It also leads to further comorbid and opportunistic illness and then lowering the patient's quality of life. The objective of this study was therefore to determine the pooled prevalence of depression and its related factors in HIV patients.

Methods

Relevant articles in PubMed, Scopus, and EMBASE were investigated. The Meta-XL version 5.3 was used to extract data and STATA-11 Meta-prop packages with the Random effect model was used to quantify depression and its related factors. Sensitivity and subgroup analysis were performed to explore sources of heterogeneity. The Cochran’s Q-statistic and the Higgs I2 test were also done. Besides, the Eggers test and symmetry in the funnel plot were used to detect the presence/absence of publication bias.

Result

In this meta-analysis, we included 21 articles that assessed 10,090 participants. The average prevalence of depression among people with HIV/AIDS was 35.8% (95% CI 28.29, 43.25). The average estimated prevalence of depressive symptoms was 59.4% in the Oromia region and 29.25% in southern Ethiopia. Besides, the average prevalence of depression was 45.6% and 26.2% as measured with Beck’s depression inventory and Hospital anxiety and depression scale respectively. Moreover, the prevalence of depression was 47.7% in studies that used a sample size ≤ of 400 participants and 28.5% in studies that used a sample size of > 400 participants. The pooled adjusted odds ratio (AOR) of perceived HIV stigma was 3.75 (95% CI 2.34, 5.16) and that of poor social support was 6.22 (95% CI 2.96, 9.47). Moreover, the average odds ratio of poor medication adherence, opportunistic infection, and advanced stages of AIDS were 3.03 (95% CI 1.00, 5.05), 5.5 (95% CI 1.97, 10.03), and 5.43 (95% CI 1.60, 9.28) respectively.

Conclusion

The pooled prevalence of depression among individuals living with HIV/AIDS was high. Factors such as perceived HIV stigma, poor social support, opportunistic infection, advanced AIDS stage, and poor medication adherence were related to it. Routine screening and management of depression and its related factors should be given due consideration.
Attitudes and compliance with the WHO surgical safety checklist: a survey among surgeons and operating room staff in 138 hospitals in China
Authors: Tan Jie , Ngwayi James Reeves Mbori , Ding Zhaohan , Zhou Yufa , Li Ming , Chen Yujie , Hu Bingtao , Liu Jinping , Porter Daniel Edward
Published: January 2021

Background

Ten years after the introduction of the Chinese Ministry of Health (MoH) version of Surgical Safety Checklist (SSC) we wished to assess the ongoing influence of the World Health Organisation (WHO) SSC by observing all three checklist components during elective surgical procedures in China, as well as survey operating room staff and surgeons more widely about the WHO SSC.

Methods

A questionnaire was designed to gain authentic views on the WHO SSC. We also conducted a prospective cross-sectional study at five level 3 hospitals. Local data collectors were trained to document specific item performance. Adverse events which delayed the operation were recorded as well as the individuals leading or participating in the three SSC components.

Results

A total of 846 operating room staff and surgeons from 138 hospitals representing every mainland province responded to the survey. There was widespread acceptance of the checklist and its value in improving patient safety.

860 operations were observed for SSC compliance. Overall compliance was 79.8%. Compliance in surgeon-dependent items of the ‘time-out’ component reduced when it was nurse-led (p < 0.0001). WHO SSC interventions which are omitted from the MoH SSC continued to be discussed over half the time. Overall adverse events rate was 2.7%. One site had near 100% compliance in association with a circulating inspection team which had power of sanction.

Conclusion

The WHO SSC remains a powerful tool for surgical patient safety in China. Cultural changes in nursing assertiveness and surgeon-led teamwork and checklist ownership are the key elements for improving compliance. Standardised audits are required to monitor and ensure checklist compliance.
HOMER3 facilitates growth factor-mediated β-Catenin tyrosine phosphorylation and activation to promote metastasis in triple negative breast cancer
Authors: Liu Qinghua , He Lixin , Li Siqi , Li Fengyan , Deng Guangzheng , Huang Xinjian , Yang Muwen , Xiao Yunyun , Chen Xiangfu , Ouyang Ying , Chen Jinxin , Wu Xuxia , Wang Xi , Song Libing , Lin Chuyong
Published: January 2021

Background

HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear.

Methods

HOMER3 expression was examined by immunohistochemistry in breast cancer patient specimens, and its significance in prognosis was assessed by Kaplan–Meier survival analysis. The effects of HOMER3 in growth factor-induced β-Catenin activation were analyzed by assays such as TOP/FOP flash reporter, tyrosine phosphorylation assay and reciprocal immunoprecipitation (IP) assay. Role of HOMER3 in breast cancer metastasis was determined by cell function assays and mice tumor models.

Results

Herein, we find that, among the three HOMER proteins, HOMER3 is selectively overexpressed in the most aggressive triple negative breast cancer (TNBC) subtype, and significantly correlates with earlier tumor metastasis and shorter patient survival. Mechanismly, HOMER3 interacts with both c-Src and β-Catenin, thus providing a scaffolding platform to facilitate c-Src-induced β-Catenin tyrosine phosphorylation under growth factor stimulation. HOMER3 promotes β-Catenin nuclear translocation and activation, and this axis is clinically relevant. HOMER3 promotes and is essential for EGF-induced aggressiveness and metastasis of TNBC cells both in vitro and in vivo.

Conclusion

These findings identify a novel role of HOMER3 in the transduction of growth factor-mediated β-Catenin activation and suggest that HOMER3 might be a targetable vulnerability of TNBC.
Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer
Authors: Wang Rui-Qi , Long Xiao-Ran , Zhou Ning-Ning , Chen Dong-Ni , Zhang Mei-Yin , Wen Zhe-Sheng , Zhang Lan-Jun , He Fa-Zhong , Zhou Zhi-Lin , Mai Shi-Juan , Wang Hui-Yun
Published: January 2021

Background

Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of non-small-cell lung cancer (NSCLC); however, the role of most lncRNAs in NSCLC remains unknown. This study explored the clinical significance, biological function and underlying mechanism of lnc-GAN1 in NSCLC.

Methods

With a custom lncRNA microarray we found that lnc-GAN1 is markedly downregulated in NSCLC tissues. Then lnc-GAN1 expression level was measured using qRT-PCR in NSCLC tissues and cell lines. Survival was assessed using the Kaplan-Meier method. The biological functions of lnc-GAN1 in lung cancer cells were evaluated in vitro and in vivo. RNA fluorescence in situ hybridization and subcellular localization assays revealed the subcellular distribution of lnc-GAN1 in cells. Bioinformatic analysis was adopted to predict miRNAs and signaling pathways regulated by lnc-GAN1. RNA immunoprecipitation and Dual-luciferase reporter assays were used to assess the interaction between lnc-GAN1 and miR-26a-5p in lung cancer cells.

Results

lnc-GAN1 is downregulated in HCC tissues and associated with larger tumor size and poor overall survival and disease-free survival; its ectopic expression suppresses cell proliferation, colony formation, and cell cycle progression and induces apoptosis in NSCLC cells; it also inhibits tumor growth in the NSCLC xenograft model. We further proved that lnc-GAN1 is localized in cytoplasm and transcribed independently from its parental gene GAN. Mechanistically, lnc-GAN1 acts as a sponge for miR-26a-5p by two seed sequences, and the two non-coding RNAs have a negative relationship in NSCLC tissues; we further prove that PTEN is a direct target of miR-26a-5p and lnc-GAN1 inhibits cell cycle signaling pathway by activating PTEN, whose expression level correlated negatively with miR-26a-5p level but positively with lnc-GAN1 level in NSCLC samples.

Conclusions

Lnc-GAN1 is downregulated and associated with poor survival of NSCLC patients, and mechanistically acts as a tumor suppressor via sponging and inhibiting miR-26a-5p to upregulate PTEN. This study provides a potential prognostic biomarker and treatment target for NSCLC.
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): update and insights into current practices and future directions for research and implementation
Authors: Thrailkill Marianne A. , Gladin Kevin H. , Thorpe Catherine R. , Roberts Teryn R. , Choi Jae H. , Chung Kevin K. , Necsoiu Corina N. , Rasmussen Todd E. , Cancio Leopoldo C. , Batchinsky Andriy I.
Published: January 2021

Background

In this review, we assess the state of Resuscitative Endovascular Occlusion of the Aorta (REBOA) today with respect to out-of-hospital (OOH) vs. inhospital (H) use in blunt and penetrating trauma, as well as discuss areas of promising research that may be key in further advancement of REBOA applications.

Methods

To analyze the trends in REBOA use, we conducted a review of the literature and identified articles with human or animal data that fit the respective inclusion and exclusion criteria. In separate tables, we compiled data extracted from selected articles in categories including injury type, zone and duration of REBOA, setting in which REBOA was performed, sample size, age, sex and outcome. Based on these tables as well as more detailed review of some key cases of REBOA usage, we assessed the current state of REBOA as well as coagulation and histological disturbances associated with its usage. All statistical tests were 2-sided using an alpha=0.05 for significance. Analysis was done using SAS 9.5 (Cary, NC). Tests for significance was done with a t-test for continuous data and a Chi Square Test for categorical data.

Results

In a total of 44 cases performed outside of a hospital in both military and civilian settings, the overall survival was found to be 88.6%, significantly higher than the 50.4% survival calculated from 1,807 cases of REBOA performed within a hospital (p<.0001). We observe from human data a propensity to use Zone I in penetrating trauma and Zone III in blunt injuries. We observe lower final metabolic markers in animal studies with shorter REBOA time and longer follow-up times.

Conclusions

Further research related to human use of REBOA must be focused on earlier initiation of REBOA after injury which may depend on development of rapid vascular access devices and techniques more so than on any new improvements in REBOA. Future animal studies should provide detailed multisystem organ assessment to accurately define organ injury and metabolic burden associated with REBOA application. Overall, animal studies must involve realistic models of injury with severe clinical scenarios approximating human trauma and exsanguination, especially with long-term follow-up after injury.
Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: usefulness for tranexamic acid treatment criteria
Authors: Ageron Francois-Xavier , Coats Timothy J. , Darioli Vincent , Roberts Ian
Published: January 2021

Background

Tranexamic acid reduces surgical blood loss and reduces deaths from bleeding in trauma patients. Tranexamic acid must be given urgently, preferably by paramedics at the scene of the injury or in the ambulance. We developed a simple score (Bleeding Audit Triage Trauma score) to predict death from bleeding.

Methods

We conducted an external validation of the BATT score using data from the UK Trauma Audit Research Network (TARN) from 1st January 2017 to 31st December 2018. We evaluated the impact of tranexamic acid treatment thresholds in trauma patients.

Results

We included 104,862 trauma patients with an injury severity score of 9 or above. Tranexamic acid was administered to 9915 (9%) patients. Of these 5185 (52%) received prehospital tranexamic acid. The BATT score had good accuracy (Brier score = 6%) and good discrimination (C-statistic 0.90; 95% CI 0.89–0.91). Calibration in the large showed no substantial difference between predicted and observed death due to bleeding (1.15% versus 1.16%, P = 0.81). Pre-hospital tranexamic acid treatment of trauma patients with a BATT score of 2 or more would avoid 210 bleeding deaths by treating 61,598 patients instead of avoiding 55 deaths by treating 9915 as currently.

Conclusion

The BATT score identifies trauma patient at risk of significant haemorrhage. A score of 2 or more would be an appropriate threshold for pre-hospital tranexamic acid treatment.
The child with medical complexity
Authors: Gallo Manuela , Agostiniani Rino , Pintus Roberta , Fanos Vassilios
Published: January 2021

Children with medical complexity represent a big challenge for the physicians, their families and the society as well. Although there is no clear definition of this type of patients, they are affected by a chronic, often very severe condition for their whole life. They also represent a huge cost for the health care system due to their needs of continuous assistance.

In this review we summarized the definitions of child with medical complexity. Then we illustrated the strategies to treat and take care of these children in order to look at them not as a burden or a cost but as an opportunity to growth and improve as clinicians and to improve the society, to give them the best life they can live.

We also wanted to give voice to the physicians, the parents and the children themselves to really show and understand what are their experiences and their feelings in dealing with their conditions. We concluded with the description of one example of children with medical complexity: prematurity. We discussed the progresses in their treatment so far in order to illustrate what is the future of pediatrics. Since it has been more and more acknowledged that every child with medical complexity is unique, the future of pediatric is to organize an individualized approach and to “see things with the eye of a child”.
Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review
Authors: Yamashita Michiko , Kamei Yoshiaki , Murakami Akari , Ozaki Erina , Okujima Kumiko , Takemoto Kana , Takaoka Megumi , Tsukamoto Daiki , Kusakabe Erina , Shidahara Tomoyuki , Noda Haruna , Aoki Reina , Taguchi Kana , Nishiyama Kanako , Eguchi Mariko , Takada Yasutsugu
Published: January 2021

Background

Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia.

Case presentation

A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery.

Conclusions

There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.
Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates
Authors: Kurul Şerife , Simons Sinno H. P. , Ramakers Christian R. B. , De Rijke Yolanda B. , Kornelisse René F. , Reiss Irwin K. M. , Taal H. Rob
Published: January 2021

Background

Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis.

Methods

The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia).

Results

A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support.

Conclusions

Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy.
Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”
Authors: Godoy Daniel Agustin , Badenes Rafael , Pelosi Paolo , Robba Chiara
Published: January 2021

Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.
Acupuncture for chronic persistent asthma based on the theory of Meridian-viscera Association: study protocol for a multi-center randomized controlled trial in China
Authors: Cheng Shirui , Dong Xiaohui , Lan Lei , He Zhaoxuan , Yu Siyi , Yang Yi , Zhang Chuantao , Chen Mei , Yang Jun , Chu Haoran , Liu Yalan , Wang Menglin , Huang Qingsong , Zeng Fang
Published: January 2021

Background

Acupuncture is effective in symptom and quality of life improvement of chronic asthma, but the efficacy differences between different acupoints are uncertain. In terms of the theory of Meridian-viscera Association, the study aims to investigate the different effectiveness between acupoints in Lung meridian and the acupoints in Heart meridian, so as to provide the evidence to develop a better prescription of the acupuncture treatment of chronic persistent asthma.

Methods

This study is a multicentral randomized controlled trial. A total of 68 chronic persistent asthma patients will be randomly allocated into two groups: the Lung meridian group and the Heart meridian group. This trial will include a 2-week baseline period, a 4-week treatment period with 12 sessions’ acupuncture, and an 8-week follow-up period. The primary outcome is the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes are the Asthma Control Test (ACT), Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1). The AQLQ and ACT will be collected at baseline, week 4, week 8, and week 12 after randomization. PEF, FEV1, the Self-rating Anxiety Scale (SAS), and the Self-rating Depression Scale (SDS) will be assessed at baseline and week 4.

Discussion

The results will provide evidence for acupuncture prescription selection and the clinical efficacy improvement. The results of this trial will also be used to determine whether or not a full definitive trial will go ahead, which will further confirm the theory of Meridian-viscera Association.

Trial registration

Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=43803) ChiCTR1900027284. Registered on 7 November 2019
Pulmonary rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism (the PeRehab study): study protocol for a two-center randomized controlled trial
Authors: Haukeland-Parker Stacey , Jervan Øyvind , Johannessen Hege Hølmo , Gleditsch Jostein , Stavem Knut , Steine Kjetil , Spruit Martijn A. , Holst René , Tavoly Mazdak , Klok Frederikus A. , Ghanima Waleed
Published: January 2021

Background

Recently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name “post pulmonary embolism syndrome” (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients.

Methods

A two-center randomized controlled trial (RCT) is being performed at Østfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1 h) for 8 weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise.

Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12 weeks, and 36 weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL).

Recruitment of 190 patients is currently ongoing.

Discussion

Results from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE.

Trial registration

Clinical Trials NCT03405480. Registered prospectively on September 2017.

Protocol version 1 (from original protocol September 2017).

The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).
Partnering with general practitioners to optimize survivorship for patients with lymphoma: a phase II randomized controlled trial (the GOSPEL I trial)
Authors: Chan Raymond Javan , Buhagiar Stephanie , Teleni Laisa , Simonsen Camilla , Turner Jane , Rawson Courtney , Hart Nicolas H. , Jones Lee , Gordon Louisa , Joseph Ria , Agbejule Oluwaseyifunmi Andi , Henderson Fiona , Rhee Joel , Ryan Marissa , Carrington Christine , Mapp Sally
Published: January 2021

Background

Survival rates for lymphoma are highest amongst hematological malignancies. In 2019, it was estimated that over 6400 Australians were diagnosed with lymphoma, a group of hematological malignancies with a high 5-year survival rate of ~ 76%. There is an increased focus on the promotion of wellness in survivorship and active approaches to reducing morbidity related to treatment; however, current models of follow-up care heavily rely on hospital-based specialist-led care.

Maximizing the potential of general practitioners (GPs) in the ongoing management of cancer is consistent with the national health reform principles and the Cancer Council Australia’s Optimal Care Pathways. GPs are well positioned to provide guideline-based follow-up care and are more likely to address comorbidities and psychosocial issues and promote healthy lifestyle behaviors. This study aims to test the feasibility of the GOSPEL I intervention for implementing an integrated, shared care model in which cancer center specialists and community-based GPs collaborate to provide survivorship care for patients with lymphoma.

Methods

We describe a protocol for a phase II, randomized controlled trial with two parallel arms and a 1:1 allocation. Sixty patients with Hodgkin’s and non-Hodgkin’s lymphoma will be randomized to usual specialist-led follow-up care (as determined by the treating hematologists) or a shared follow-up care intervention (i.e., GOSPEL I). GOSPEL I is a nurse-enabled, pre-specified shared care pathway with follow-up responsibilities shared between cancer center specialists (i.e., hematologists and specialist cancer nurses) and GPs. Outcome measures assess feasibility as well as a range of patient-reported outcomes including health-related quality of life as measured by the Functional Assessment of Cancer Therapy—Lymphoma, patient experience of care, symptom distress, comorbidity burden, dietary intake, physical activity behaviors, financial distress/interference, and satisfaction of care. Safety indicators including hospital admission and unscheduled lymphoma clinic visits as well as process outcomes such as intervention fidelity and economic indicators will be analyzed.

Discussion

This trial is designed to explore the feasibility and acceptability of a new model of shared care for lymphoma survivors. Patient-reported outcomes as well as potential barriers to implementation will be analyzed to inform a larger definitive clinical trial testing the effects and implementation of a shared care model on health-related quality of life of lymphoma survivors.

Trial registration

Australia and New Zealand Clinical Trials Registry ACTRN12620000594921. Registered on 22 May 2020.
Effects of different acupuncture treatment methods on post-stroke cognitive impairment: study protocol for a multicenter randomized controlled trial
Authors: Su Kai-Qi , Liu Su-Tong , Li Jie-Ying , Li Rui-Qing , Feng Hui-Li , Xue Yang , Feng Xiao-Dong
Published: January 2021

Background

Cognitive impairment is a common dysfunction after stroke that seriously affects the overall recovery of patients. Cognitive rehabilitation training is currently the main treatment to improve cognitive function, but its curative effect is limited. Acupuncture is a core component of traditional Chinese medicine (TCM), and some previous clinical studies have shown that it might be effective in treating post-stroke cognitive impairment (PSCI), but further evidence from large-sample studies is needed. The overall objective of this trial is to obtain further data to develop an optimized acupuncture treatment for PSCI by comparing the effects of different acupuncture treatment methods on cognitive function in PSCI patients.

Methods/design

In this multicenter, prospective, randomized controlled trial, 206 eligible stroke inpatients who meet the trial criteria will be randomly assigned to 2 groups: an electroacupuncture (EA) plus needle retention (NR) group and an EA group. Both groups of patients will undergo the same routine cognitive rehabilitation treatments. All treatments will be given 5 times per week for 8 weeks. The primary outcomes will be assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment scale (MOCA). The secondary outcome will be measured by the Barthel Index (BI). All outcomes will be evaluated at baseline, week 4, week 8, and the third and sixth month after the end of treatment.

Discussion

Our aim is to evaluate the effects of two different acupuncture treatment methods for treating PSCI patients. This study is expected to provide data to be used in developing an optimized acupuncture treatment method for PSCI treatment.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900027849. Registered on 30 November 2019, http://www.chictr.org.cn/showproj.aspx?proj=46316
Genome-scale metabolic modeling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory for biofuel production
Authors: Pham Nhung , Reijnders Maarten , Suarez-Diez Maria , Nijsse Bart , Springer Jan , Eggink Gerrit , Schaap Peter J.
Published: January 2021

Background

Cutaneotrichosporon oleaginosus ATCC 20509 is a fast-growing oleaginous basidiomycete yeast that is able to grow in a wide range of low-cost carbon sources including crude glycerol, a byproduct of biodiesel production. When glycerol is used as a carbon source, this yeast can accumulate more than 50% lipids (w/w) with high concentrations of mono-unsaturated fatty acids.

Results

To increase our understanding of this yeast and to provide a knowledge base for further industrial use, a FAIR re-annotated genome was used to build a genome-scale, constraint-based metabolic model containing 1553 reactions involving 1373 metabolites in 11 compartments. A new description of the biomass synthesis reaction was introduced to account for massive lipid accumulation in conditions with high carbon-to-nitrogen (C/N) ratio in the media. This condition-specific biomass objective function is shown to better predict conditions with high lipid accumulation using glucose, fructose, sucrose, xylose, and glycerol as sole carbon source.

Conclusion

Contributing to the economic viability of biodiesel as renewable fuel, C. oleaginosus ATCC 20509 can effectively convert crude glycerol waste streams in lipids as a potential bioenergy source. Performance simulations are essential to identify optimal production conditions and to develop and fine tune a cost-effective production process. Our model suggests ATP-citrate lyase as a possible target to further improve lipid production.
CRISPR-mediated multigene integration enables Shikimate pathway refactoring for enhanced 2-phenylethanol biosynthesis in Kluyveromyces marxianus
Authors: Li Mengwan , Lang Xuye , Moran Cabrera Marcos , De Keyser Sawyer , Sun Xiyan , Da Silva Nancy , Wheeldon Ian
Published: January 2021

Background

2-phenylethanol (2-PE) is a rose-scented flavor and fragrance compound that is used in food, beverages, and personal care products. Compatibility with gasoline also makes it a potential biofuel or fuel additive. A biochemical process converting glucose or other fermentable sugars to 2-PE can potentially provide a more sustainable and economical production route than current methods that use chemical synthesis and/or isolation from plant material.

Results

We work toward this goal by engineering the Shikimate and Ehrlich pathways in the stress-tolerant yeast Kluyveromyces marxianus. First, we develop a multigene integration tool that uses CRISPR-Cas9 induced breaks on the genome as a selection for the one-step integration of an insert that encodes one, two, or three gene expression cassettes. Integration of a 5-kbp insert containing three overexpression cassettes successfully occurs with an efficiency of 51 ± 9% at the ABZ1 locus and was used to create a library of K. marxianus CBS 6556 strains with refactored Shikimate pathway genes. The 33-factorial library includes all combinations of KmARO4, KmARO7, and KmPHA2, each driven by three different promoters that span a wide expression range. Analysis of the refactored pathway library reveals that high expression of the tyrosine-deregulated KmARO4K221L and native KmPHA2, with the medium expression of feedback insensitive KmARO7G141S, results in the highest increase in 2-PE biosynthesis, producing 684 ± 73 mg/L. Ehrlich pathway engineering by overexpression of KmARO10 and disruption of KmEAT1 further increases 2-PE production to 766 ± 6 mg/L. The best strain achieves 1943 ± 63 mg/L 2-PE after 120 h fed-batch operation in shake flask cultures.

Conclusions

The CRISPR-mediated multigene integration system expands the genome-editing toolset for K. marxianus, a promising multi-stress tolerant host for the biosynthesis of 2-PE and other aromatic compounds derived from the Shikimate pathway.
The influence of different sources of blood meals on the physiology of Aedes aegypti harboring Wolbachia wMel: mouse blood as an alternative for mosquito rearing
Authors: Farnesi Luana Cristina , Carvalho Fabiano Duarte , Lacerda Anna Paula Canuto , Moreira Luciano Andrade , Bruno Rafaela Vieira
Published: January 2021

Background

Aedes aegypticontrol programs have failed to restrain mosquito population expansion and, consequently, the spread of diseases such as dengue, Zika, and Chikungunya.Wolbachiainfection of mosquitoes is a new and promising complementary tool for the control of arbovirus transmission. The use ofWolbachia-infected mosquitoes, mass reared using human blood, is currently being tested in several countries. However, the use of human blood for mass rearing mosquitoes, and thus expansion of this strategy, is problematic. With the aim of overcoming this problem, we tested the effect of different types of blood source on the fitness parameters of femaleAe. aegyptiand theWolbachiatiter over generations to be able to guarantee the suitability of an alternative source to human blood for mass rearingWolbachia-infected mosquitoes.

Methods

We investigated and compared essential parameters of the vector capacity of laboratory strains ofAe. aegyptiwith and withoutWolbachiathat fed on blood of different types of host (human, guinea pig, and mouse). The parameters analyzed were fecundity, fertility, pupation dynamics, and adult survival. Also, we tested whether it is possible to maintain mosquitoes withWolbachiaon mouse blood over generations without losing the bacterium titer.

Results

The average number of eggs per female, egg viability and pupation dynamics in theWolbachia-infected mosquito (wMelBr) strain were similar, regardless of the blood source. The F1 progenies of females that fed on mouse blood or human blood were analyzed. The longevity of males was lower than that of females. F1 female survival differed depending on the presence ofWolbachiain the mother. In subsequent generations analyzed up until F35, the relativeWolbachiadensity was even higher when mosquitoes fed on mouse blood in comparison to human blood.

Conclusions

Taken together, our results provide no evidence that the different types of blood influenced the fitness of theWolbachia-infected mosquitoes. The presence of the bacterium in the colonies ofWolbachia-infectedAe. aegyptiafter 35 generations under the conditions evaluated indicates that they can be maintained on mouse blood. Based on these results, we show that it is possible to use mouse blood to feed female mosquitoes when using human blood for this purpose is problematic.

Graphical Abstract
A first report of Thelazia callipaeda infection in Phortica okadai and wildlife in national nature reserves in China
Authors: Jin Yipeng , Liu Zichen , Wei Jiaqi , Wen Yifan , He Nianjun , Tang Liubin , Lin Degui , Lin Jiahao
Published: January 2021

Background

Thelazia callipaedais a zoonotic parasitic nematode of the family Thelaziidae, withPhortica okadaias its intermediate host and only confirmed vector in China. China has the largest number of human cases of thelaziosis in the world. It is generally believed that infected domestic animals (dogs and cats) are the most important reservoir hosts ofT. callipaeda, and thus pose a direct threat to humans. At present, there is little research or attention focused on the role of wildlife in the transmission cycle of thelaziosis in nature reserves.

Methods

We selected locations in four national nature reserves across China to monitorP. okadaiand wildlife. We used a fly-trap method to monitorP. okadaidensity. Morphological analysis of the parasites collected from the conjunctival sac of the infected wildlife was undertaken as the first step in species identification, and polymerase chain reaction (PCR) was used for species confirmation.

Results

In 2019, the density ofP. okadaiin Foping National Nature Reserve in China increased sharply, and infectedP. okadaiwere newly found in the reserve. Giant panda, wild boar, leopard cat, and black bear were found to be newly infected withT. callipaeda(one individual of each species). A total of four worms were collected, one from each species of wildlife. The four worms were identified asT. callipaedaby their morphological characteristics; species identification was confirmed by PCR amplification.

Conclusions

To the best of our knowledge, this is the first report ofT. callipaedainfection inP. okadaias well as in a variety of wildlife, including giant panda, in nature reserves in China. These results indicate that there is a transmission cycle ofT. callipaedaamong wildlife in these nature reserves. The increasing number of case reports of thelaziosis in wildlife suggest a likely risk ofT. callipaedainfection for the inhabitants of villages situated around nature reserves.
Ectoparasitic community of the Mahali mole-rat, Cryptomys hottentotus mahali: potential host for vectors of medical importance in South Africa
Authors: Fagir Dina M. , Bennett Nigel C. , Ueckermann Eddie A. , Howard Alexandra , Hart Daniel W.
Published: January 2021

Background

The endemic rodent family of Bathyergidae in Africa, particularly South Africa, are understudied as reservoirs of diseases of significant medical importance. Considering the diversity and wide distribution of African mole-rats in South Africa, many of these bathyergids could act as carriers of zoonoses.

Methods

The present study assessed the ectoparasite community of the Mahali mole-rat (Cryptomys hottentotus mahali). We aimed to identify possible parasitic arthropods that may infest this mole-rat species and explore host preference, contributions of seasonality, host sex and body mass as well as social class and colony size on ectoparasite assemblage prevalence and abundance.

Results

A limited number of ectoparasite species were found on C. h. mahali belonging to two significant taxa: mites (Acari) and fleas, with mites being the most prevalent and abundant. We recorded the presence of X. philoxera, a flea well known as the principal reservoir of plague in the southern African region on the Mahali mole-rats. Only three mite species were collected: Androlaelaps scapularis, Androlaelaps capensis and Laelaps liberiensis. Seasonal peaks in prevalence and abundance of X. philoxera and A. scapularis were observed during summer. Xenopsylla philoxera abundance and A. scapularis loads significantly increased on reproductive mole-rat individuals in comparison to non-reproductive individuals.

Conclusion

Despite the wide distribution of the subterranean African mole-rats, studies investigating their parasitic fauna remain limited and scarce. This dearth in knowledge raises the concern regarding their potential role as an endemic reservoir for zoonotic diseases. Consequently, additional sampling of their ectoparasitic community throughout their distributional range and research addressing their role as a reservoir for zoonotic diseases in southern Africa are urgently needed.
The presence of erosive joints is a strong predictor of radiological progression in hand osteoarthritis: results of a 2-year prospective follow-up of the Liège Hand Osteoarthritis Cohort (LIHOC)
Authors: Neuprez Audrey , Kaux Jean-François , Locquet Médéa , Beaudart Charlotte , Reginster Jean-Yves
Published: January 2021

Background

This study measured the magnitude and determinants of clinical and radiological progression in patients with hand osteoarthritis (HOA) over a 2-year prospective follow-up to gain a greater understanding of the disease time course.

Methods

Two hundred three consecutive outpatients diagnosed with HOA were followed for 2 years (183 women, median age 69 years). Pain and function were evaluated using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), and clinical examination recorded the number of painful/swollen joints and nodes. X-rays were scored using Kellgren-Lawrence (KL) and Verbruggen-Veys scales. Clinical progression was defined as deterioration in AUSCAN ≥ the minimal clinically important difference. Radiographic progression was defined as (a) one new erosive/remodeled joint, (b) progression of ≥ one anatomical stage in one joint, or (c) change in KL total score above the smallest detectable difference. Logistic regression was performed to determine whether patient characteristics influenced clinical and radiological progression.

Results

After 2 years, all radiographic scores deteriorated significantly in the study population (p <  0.05), and the number of proximal and distal interphalangeal nodes was significantly higher (p <  0.01). The AUSCAN, number of painful joints at rest or at pressure, number of swollen joints, and pain measure on a visual analog scale remained unchanged. At the individual level, the number of patients with clinically meaningful progression ranged from 25 to 42% (clinical progression) and from 22 to 76% (radiological progression). The only significant predictor of worsening of total AUSCAN was AUSCAN pain subscale < 74.5 (odds ratio [OR] 1.02 [1.01, 1.03]; p <  0.01). The presence of ≥ four swollen joints (OR 2.78 [1.21, 6.39]; p = 0.02) and erosive osteoarthritis (OR 13.23 [5.07, 34.56]; p <  0.01) at baseline predicted a new erosive joint. A meaningful change in KL was more frequent with painful joints at baseline (OR 3.43 [1.68, 7.01]; p <  0.01).

Conclusions

Evidence of radiological progression over 2 years was observed in patients with HOA in the LIHOC population even without clinical worsening of disease. For individual patients, baseline pain level is predictive for clinical progression and the presence of erosive or swollen joints are significant predictors of radiological progression.
Improving justification of medical exposures using ionising radiation: considerations and approaches from the European Society of Radiology
Authors:   European Society of Radiology, Ebdon-Jackson Steve , Frija Guy
Published: January 2021

This discussion paper has been produced within the context of the European Society of Radiology EuroSafe Imaging initiative and considers primarily the issues and challenges associated with justification of medical exposures using ionising radiation for individual patient diagnostic imaging procedures. It addresses both regulatory requirements and practical considerations and discusses approaches that are intended to improve justification.
The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson’s disease
Authors: Xiao Zhuangzhuang , Lei Tong , Liu Yanyan , Yang Yanjie , Bi Wangyu , Du Hongwu
Published: January 2021

Parkinson’s disease (PD), the second most common neurodegenerative disease worldwide, is caused by the loss of dopaminergic (DAergic) neurons in the substantia nigra resulting in a series of motor or non-motor disorders. Current treatment methods are unable to stop the progression of PD and may bring certain side effects. Cell replacement therapy has brought new hope for the treatment of PD. Recently, human dental tissue-derived mesenchymal stem cells have received extensive attention. Currently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are considered to have strong potential for the treatment of these neurodegenerative diseases. These cells are considered to be ideal cell sources for the treatment of PD on account of their unique characteristics, such as neural crest origin, immune rejection, and lack of ethical issues. In this review, we briefly describe the research investigating cell therapy for PD and discuss the application and progress of DPSCs and SHED in the treatment of PD. This review offers significant and comprehensive guidance for further clinical research on PD.
A passenger risk assessment method based on 5G-IoT
Authors: Chen Weishi , Huang Yifeng , Yang Hao , Li Jing , Lu Xianfeng
Published: January 2021

For the airports worldwide, it is important to establish a "passenger integrity system" based on the basic information of passengers and their related credit system. Correspondingly, this paper develops a new risk assessment model for the passenger graded security check by introducing several new technologies to obtain the passengers’ real-time status information as well as historical data. We first propose to deploy a variety of 5G-IoT devices to monitor the passengers in real time, including high-definition cameras, millimeter-wave security detectors, etc. We then rely on machine learning to analyze the passenger risk level and integrate improved analytic hierarchy process (AHP) with group decision theory, namely GD-AHP. According to the risk level, the passengers can be classified into known, ordinary and dangerous targets. The differentiated handling of different targets could significantly save the time of security check and improve the passenger experience.
Some basic properties and fundamental relations for discrete Muckenhoupt and Gehring classes
Authors: Saker S. H. , Rabie S. S. , Alzabut Jehad , O’Regan D. , Agarwal R. P.
Published: January 2021

In this paper, we prove some basic properties of the discrete Muckenhoupt class $\mathcal{A}^{p}$

A
p

and the discrete Gehring class $\mathcal{G}^{q}$

G
q

. These properties involve the self-improving properties and the fundamental transitions and inclusions relations between the two classes.
Novel finite point approach for solving time-fractional convection-dominated diffusion equations
Authors: Liu Xiaomin , Abbas Muhammad , Yang Honghong , Qin Xinqiang , Nazir Tahir
Published: January 2021

In this paper, a stabilized numerical method with high accuracy is proposed to solve time-fractional singularly perturbed convection-diffusion equation with variable coefficients. The tailored finite point method (TFPM) is adopted to discrete equation in the spatial direction, while the time direction is discreted by the G-L approximation and the L1 approximation. It can effectively eliminate non-physical oscillation or excessive numerical dispersion caused by convection dominant. The stability of the scheme is verified by theoretical analysis. Finally, one-dimensional and two-dimensional numerical examples are presented to verify the efficiency of the method.