bluuebunny/crossref_metadata_2025 huggingface dataset:
Duodenal major papilla morphology can affect biliary cannulation and complications during ERCP, an observational study
Authors: Chen Po-Han , Tung Chun-Fang , Peng Yen-Chung , Yeh Hong-Zen , Chang Chi-Sen , Chen Chia-Chang
Published: September 2020

Background

We investigated whether duodenal major papilla morphology could be a risk factor for failure of selective biliary cannulation (SBC) and post endoscopic retrograde cholangiography and pancreatography (ERCP) complications.

Methods

A prospectively recorded database was reviewed retrospectively. Patients were included if they received therapeutic ERCP and had naïve major duodenal papilla. We used Haraldsson’s classification for papilla morphology, as follows: Regular (Type 1), Small (Type 2), Protruding or Pendulous (Type 3) and Creased or Ridged (Type 4). Risk factors for failing SBC and post-ERCP complications were analyzed by multivariate analysis.

Results

A total of 286 cases were included. Age, gender, indications and therapeutic procedures were not different among the four types of papillae. The failure rates of SBC with Type 3 papilla and Type 4 papilla were 11.11% and 6.25%, respectively. In the multivariate analysis, Type 2 papilla (odd ratio 7.18, p = 0.045) and Type 3 papilla (odd ratio 7.44, p = 0.016) were associated with greater SBC failure compared with Type 1 papilla. Malignant obstruction compared to stone (odds ratio 4.45, p = 0.014) and age (odd ratio = 1.06, p = 0.010) were also risk factors for cannulation failure. Type 2 papilla was correlated with a higher rate of post-ERCP pancreatitis (20%, p = 0.020) compared to the other types of papilla However, papilla morphology was not a significant risk factor for any complications in the multivariate analysis.

Conclusion

Small papilla and protruding or pendulous papilla are more difficult to cannulate compared to regular papilla. Small papilla is associated with a higher rate of post-ERCP pancreatitis.
“Screening for small-for-gestational age neonates at early third trimester in a high-risk population for preeclampsia”
Authors: Mula Raquel , Meler Eva , García Sandra , Albaigés Gerard , Serra Bernat , Scazzocchio Elena , Prats Pilar
Published: September 2020

Background

Strategies to improve prenatal detection of small-for-gestational age (SGA) neonates are necessary because its association with poorer perinatal outcome. This study evaluated, in pregnancies with first trimester high risk of early preeclampsia, the performance of a third trimester screening for SGA combining biophysical and biochemical markers.

Methods

This is a prospective longitudinal study on 378 singleton pregnancies identified at high risk of early preeclampsia according to a first trimester multiparametric algorithm with the cutoff corresponding to 15% false positive rate. This cohort included 50 cases that delivered SGA neonates with birthweight < 10th centile (13.2%) and 328 cases with normal birthweight (86.8%). At 27–30 weeks’ gestation, maternal weight, blood pressure, estimated fetal weight, mean uterine artery pulsatility index and maternal biochemical markers (placental growth factor and soluble FMS-Like Tyrosine Kinase-1) were assessed. Different predictive models were created to evaluate their performance to predict SGA neonates.

Results

For a 15% FPR, a model that combines maternal characteristics, estimated fetal weight, mean uterine artery pulsatility index and placental growth factor achieved a detection rate (DR) of 56% with a negative predictive value of 92.2%. The area under receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval (CI), 0.72–0.86). The DR of a model including maternal characteristics, estimated fetal weight and mean uterine artery pulsatility index was 54% (AUC, 0.77 (95% CI, 0.70–0.84)). The DR of a model that includes maternal characteristics and placental growth factor achieved a similar performance (DR 56%, AUC 0.75, 95% CI (0.67–0.83)).

Conclusions

The performance of screening for SGA neonates at early third trimester combining biophysical and biochemical markers in a high-risk population is poor. However, a high negative predictive value could help in reducing maternal anxiety, avoid iatrogenic interventions and propose a specific plan for higher risk patients.
Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy regimens: a subgroup analysis from a randomized clinical trial of response in subjects by cancer type
Authors: Weinstein Cindy , Jordan Karin , Green Stuart , Khanani Saleem , Beckford-Brathwaite Elizabeth , Vallejos Waldimir , Pong Annpey , Noga Stephen J. , Rapoport Bernardo L.
Published: September 2020

Background

Results from a phase III, randomized, double-blind, active comparator-controlled, parallel-group trial evaluating fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) found that a single-day, triple-antiemetic fosaprepitant regimen resulted in a significantly higher proportion of patients achieving a complete response (CR; no vomiting or rescue medication use) in the delayed phase (25–120 h after chemotherapy initiation), compared with a 3-day control regimen (ClinicalTrials.gov, NCT01594749). As the risk for CINV is dependent on chemotherapy regimen and generally guided by tumor type, this post hoc analysis evaluated the efficacy and safety of this regimen by cancer subpopulations (gastrointestinal [GI] or colorectal, lung, breast, and gynecologic cancers).

Methods

Subjects with confirmed cancer who were naive to highly and moderately emetogenic chemotherapy (HEC and MEC) and were scheduled to receive intravenous (IV) anthracycline-cyclophosphamide (AC)–based MEC on the first day of chemotherapy were randomly assigned to receive oral ondansetron and oral dexamethasone plus either a single IV dose of fosaprepitant 150 mg (fosaprepitant regimen) or placebo (control regimen). The primary efficacy end point was the proportion of subjects achieving CR in the delayed phase. CR rates in the overall and acute phases (0–120 h and 0–24 h after MEC initiation, respectively) were assessed as secondary end points. Safety and tolerability were also assessed.

Results

CR rates in the delayed phase favored the fosaprepitant regimen over the control regimen across the GI/colorectal, lung, breast, and gynecologic cancer subgroups (range, 6.2–22%); similar findings were observed for CR in the overall phase. CR in the acute phase was high for all groups (≥87%). The fosaprepitant regimen was well tolerated in all cancer subgroups.

Conclusions

This post hoc analysis indicated that a single-day fosaprepitant regimen was effective in preventing CINV in patients receiving MEC, regardless of cancer type.

Trial registration

ClinicalTrials.govNCT01594749, registered May 9, 2012.
Impact of congenital heart disease on outcomes among pediatric patients hospitalized for influenza infection
Authors: Ghimire Laxmi V. , Chou Fu-Sheng , Moon-Grady Anita J.
Published: September 2020

Background

Young children and those with chronic medical conditions are at risk for complications of influenza including cardiopulmonary compromise. Here we aim to examine risks of mortality, clinical complications in children with congenital heart disease (CHD) hospitalized for influenza.

Methods

We analyzed data from in-hospital pediatric patients from 2003, 2006, 2009, 2012 and 2016 using the nationally representative Kids Inpatient Database (KID). We included children 1 year and older and used weighted data to compare the incidence of in-hospital mortality and rates of complications such as respiratory failure, acute kidney injury, need for mechanical ventilation, arrhythmias and myocarditis.

Results

Data from the KID estimated 125,470 children who were admitted with a diagnosis of influenza infection. Out of those, 2174(1.73%) patients had discharge diagnosis of CHD. Children with CHD who required hospitalization for influenza had higher in-hospital mortality (2.0% vs 0.5%), with an adjusted OR (aOR) of 2.8 (95% CI: 1.7–4.5). Additionally, acute respiratory failure and acute kidney failure were more likely among patients with CHD, with aOR of 1.8 (95% CI: 1.5–2.2) and aOR of 2.2 (95% CI: 1.5–3.1), respectively. Similarly, the rate of mechanical ventilatory support was higher in patients with CHD compared to those without, 14.1% vs 5.6%, aOR of 1.9 (95% CI: 1.6–2.3). Median length of hospital stay in children with CHD was longer than those without CHD [4 (IQR: 2–8) days vs. 2 (IQR: 2–4) days]. Outcomes were similar between those with severe vs non-severe CHD.

Conclusions

Children with CHD who require hospital admission for influenza are at significantly increased risk for in-hospital mortality, morbidities, emphasizing the need to reinforce preventative measures (e.g. vaccination, personal hygiene) in this particularly vulnerable population.
Modified mini-open SRS-Schwab grade 4 osteotomy combined with percutaneous pedicle screws fixation in post-traumatic thoracolumbar kyphosis
Authors: Liu Wubo , Zhao Yiwei , Yuan Suomao , Tian Yonghao , Liu Xinyu
Published: September 2020

Background

We aimed to analyze the clinical results of Schwab grade 4 osteotomy combined with percutaneous pedicle screws (PPS) fixation for treatment of post-traumatic thoracolumbar kyphosis (PTK).

Methods

Thirty four patients with PTK (group A) were included in our study. The average age was 54.9 ± 3.3 years. All patients had severe back pain with 8.6 ± 1.3 VAS scores. The affected level was T12 in 16 patients and L1 in 18 patients. The average preoperative regional kyphosis angle (RKA) was 30.7 ± 6.00. Three patients had neurological dysfunction with ASIA grade D. All patients underwent Schwab grade 4 osteotomy combined with PPS fixation. The control group (Group B) were 26 PTK patients treated with Schwab grade 4 osteotomy and open pedicle screws fixation in our institution.

Results

Operation time in groups A and B was 280 ± 50 min and 210 ± 30 min, respectively (P < 0.05). Estimated blood loss in groups A and B was 310 ± 70 ml and 630 ± 40 ml, respectively (P < 0.05). No cerebral spinal fluid leakage, segmental nerve function damage, and other complications observed during and after the operations in both groups. RKA, SVA, and LL improved significantly after surgery in both groups (P < 0.05). The average correction rate in groups A and B was 64.5 and 66.3% (P > 0.05). CT showed that the misplacement rate in groups A and B was 5.5 and 6.6% (P > 0.05). The average follow-up in groups A and B was 25.2 ± 7.6 months and 30.6 ± 2.7 months. No fracture and other complications were observed in both groups. Solid bone fusion was showed in all cases at 6 months follow-up. In groups A and B, all patients with preoperative neurological dysfunction recovered to ASIA grade E at the last follow-up. The VAS score of back pain improved significantly from 8.6 ± 1.3 to 1.6 ± 1.0 at the last follow-up in group A (P < 0.05), while it improved significantly from 8.3 ± 1.2 to 3.0 ± 1.1 at the last follow-up in group B (P < 0.05). VAS of back pain was better in group A than that in group B.

Conclusion

Schwab grade 4 osteotomy combined with percutaneous pedicle screws fixation is a minimally invasive, safe and effective method for PTK treatment.
Effectiveness of circular hexapod external fixation with soft tissue reconstruction in treating severe knee dislocation due to burn scarring: a case report
Authors: Nozaka Koji , Miyakoshi Naohisa , Saito Hidetomo , Kijima Hiroaki , Mita Motoki , Shimada Yoichi
Published: September 2020

Background

Severe varus deformity and soft tissue injury caused by a burn around a complex knee dislocation is a rare injury. Soft tissue reconstruction and deformity correction with circular hexapod external fixation of the knee and hinged total knee arthroplasty (TKA) are challenging and can lead to major complications if not performed appropriately. We present a case in which a combination of soft tissue reconstruction, circular hexapod external fixation, and TKA was used treat severe knee dislocation due to burn scarring.

Case presentation

We report the case of a 58-year-old woman who presented for knee surgery with soft tissue reconstruction, deformity correction with circular hexapod external fixation, and hinged TKA for a severe complex deformity and soft tissue injury caused by a burn injury at 6 months of age. The left leg was shorter by 35 mm in terms of functional leg length discrepancy. She walked with a limp, with a marked varus deformity of the left knee during the stance phase of walking. After a 3-stage repair, the patient was able to walk without assistance, confirming improvement of mobility.

Conclusion

The treatment method was an effective use of a combination of soft tissue reconstruction, circular hexapod external fixation, and rehearsal surgery using a 3D printed bone model of the modular rotating hinge component of TKA, which was successfully used to treat a severe knee dislocation due to burn scarring. This staged surgery maintained the leg length and ultimately achieved a satisfactory alignment.
Evaluation of continuous quality improvement in accreditation for medical education
Authors: Akdemir Nesibe , Peterson Linda N. , Campbell Craig M. , Scheele Fedde
Published: September 2020

Background

Accreditation systems are based on a number of principles and purposes that vary across jurisdictions. Decision making about accreditation governance suffers from a paucity of evidence. This paper evaluates the pros and cons of continuous quality improvement (CQI) within educational institutions that have traditionally been accredited based on episodic evaluation by external reviewers.

Methods

A naturalistic utility-focused evaluation was performed. Seven criteria, each relevant to government oversight, were used to evaluate the pros and cons of the use of CQI in three medical school accreditation systems across the continuum of medical education. The authors, all involved in the governance of accreditation, iteratively discussed CQI in their medical education contexts in light of the seven criteria until consensus was reached about general patterns.

Results

Because institutional CQI makes use of early warning systems, it may enhance the reflective function of accreditation. In the three medical accreditation systems examined, external accreditors lacked the ability to respond quickly to local events or societal developments. There is a potential role for CQI in safeguarding the public interest. Moreover, the central governance structure of accreditation may benefit from decentralized CQI. However, CQI has weaknesses with respect to impartiality, independence, and public accountability, as well as with the ability to balance expectations with capacity.

Conclusion

CQI, as evaluated with the seven criteria of oversight, has pros and cons. Its use still depends on the balance between the expected positive effects—especially increased reflection and faster response to important issues—versus the potential impediments. A toxic culture that affects impartiality and independence, as well as the need to invest in bureaucratic systems may make in impractical for some institutions to undertake CQI.
Responsiveness to societal needs in postgraduate medical education: the role of accreditation
Authors: Philibert Ingrid , Blouin Danielle
Published: September 2020

Background

Social accountability in medical education has been defined as an obligation to direct education, research, and service activities toward the most important health concerns of communities, regions, and nations. Drawing from the results of a summit of international experts on postgraduate medical education and accreditation, we highlight the importance of local contexts in meeting societal aims and present different approaches to ensuring societal input into medical education systems around the globe.

Main text

We describe four priorities for social responsiveness that postgraduate medical education needs to address in local and regional contexts: (1) optimizing the size, specialty mix, and geographic distribution of the physician workforce; (2) ensuring graduates’ competence in meeting societal goals for health care, population health, and sustainability; (3) promoting a diverse physician workforce and equitable access to graduate medical education; and (4) ensuring a safe and supportive learning environment that promotes the professional development of physicians along with safe and effective patient care in settings where trainees participate in care. We relate these priorities to the values proposed by the World Health Organization for social accountability: relevance, quality, cost-effectiveness, and equity; discuss accreditation as a lever for change; and describe existing and evolving efforts to make postgraduate medical education socially responsive.

Conclusion

Achieving social responsiveness in a competency-based postgraduate medical education system requires accrediting organizations to ensure that learning emphasizes relevant competencies in postgraduate curricula and educational experiences, and that graduates possess desired attributes. At the same time, institutions sponsoring graduate medical education need to provide safe and effective patient care, along with a supportive learning and working environment.
Grading reflective essays: the reliability of a newly developed tool- GRE-9
Authors: Makarem Nisrine N. , Saab Basem R. , Maalouf Grace , Musharafieh Umayya , Naji Fadila , Rahme Diana , Brome Dayana
Published: September 2020

Background

The main objective of this study is the development of a short reliable easy-to-use assessment tool in the aim of providing feedback to the reflective writings of medical students and residents.

Methods

This study took place in a major tertiary academic medical center in Beirut, Lebanon. Seventy-seven reflective essays written by 18 residents in the department of Family Medicine at the American University of Beirut Medical Center (AUBMC) were graded by 3 raters using the newly developed scale to assess the scale reliability. Following a comprehensive search and analysis of the literature, and based on their experience in reflective grading, the authors developed a concise 9-item scale to grade reflective essays through repeated cycles of development and analysis as well as the determination of the inter-rater reliability (IRR) using intra-class correlation coefficients (ICC) and Krippendorff’s Alpha.

Results

The inter-rater reliability of the new scale ranges from moderate to substantial with ICC of 0.78, 95% CI 0.64–0.86, p < 0.01 and Krippendorff’s Alpha was 0.49.

Conclusions

The newly developed scale, GRE-9, is a short, concise, easy-to-use reliable grading tool for reflective essays that has demonstrated moderate to substantial inter-rater reliability. This will enable raters to objectively grade reflective essays and provide informed feedback to residents and students.
Which factors are related to Finnish home care workers’ job satisfaction, stress, psychological distress and perceived quality of care? - a mixed method study
Authors: Ruotsalainen Salla , Jantunen Sami , Sinervo Timo
Published: September 2020

Background

The desire to increase the role of home care in Finland has created problems in home care work. Working conditions have deteriorated, the quality of care experienced is low, and staff members suffer from time pressure and stress, amongst other things. The aim of this article is to explore the challenges, stressors, teamwork and management factors that are associated with home care staff members’ well-being, job satisfaction and experienced care quality, and further, how staff members experience their work.

Methods

A survey was sent to home care workers in two case organizations that participated in the study. In addition, semi-structured theme interviews with home care workers were conducted. The data from the survey was analysed using analysis of covariance, and interview data was analysed using the Grounded Theory-based method from Gioia et al.

Results

Respondents of the survey and the interview participants were mainly female practical nurses. The results from the survey showed, for example, that time pressure was associated with higher stress and psychological distress, and interruptions were associated with lower job satisfaction and higher stress. In addition, variables related to teamwork, such as participative safety, were shown to explain the variation in quality of care. The analysis of the interview data further brought up dissatisfaction with management practices, which seems to have led to a decrease in job satisfaction. Exhaustion and strain were present among staff members, which originated from an insufficient number of carers.

Conclusions

Current working conditions and work practices in Finnish home care are experienced stressful. The results from this study indicate that having more autonomy at work was associated with job satisfaction, according to both analyses. Team climate and idea implementation were related to quality of care. Therefore, increasing self-organizing team practices might be a possible development method for improving working conditions and staff members’ well-being. Implementing self-organizing team practices could possibly also attract employees to work in home care and prevent turnover.
Functional signatures of evolutionarily young CTCF binding sites
Authors: Azazi Dhoyazan , Mudge Jonathan M. , Odom Duncan T. , Flicek Paul
Published: September 2020

Background

The introduction of novel CTCF binding sites in gene regulatory regions in the rodent lineage is partly the effect of transposable element expansion, particularly in the murine lineage. The exact mechanism and functional impact of evolutionarily novel CTCF binding sites are not yet fully understood. We investigated the impact of novel subspecies-specific CTCF binding sites in two Mus genus subspecies, Mus musculus domesticus and Mus musculus castaneus, that diverged 0.5 million years ago.

Results

CTCF binding site evolution is influenced by the action of the B2-B4 family of transposable elements independently in both lineages, leading to the proliferation of novel CTCF binding sites. A subset of evolutionarily young sites may harbour transcriptional functionality as evidenced by the stability of their binding across multiple tissues in M. musculus domesticus (BL6), while overall the distance of subspecies-specific CTCF binding to the nearest transcription start sites and/or topologically associated domains (TADs) is largely similar to musculus-common CTCF sites. Remarkably, we discovered a recurrent regulatory architecture consisting of a CTCF binding site and an interferon gene that appears to have been tandemly duplicated to create a 15-gene cluster on chromosome 4, thus forming a novel BL6 specific immune locus in which CTCF may play a regulatory role.

Conclusions

Our results demonstrate that thousands of CTCF binding sites show multiple functional signatures rapidly after incorporation into the genome.
Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles
Authors: Altei Wanessa F. , Pachane Bianca C. , dos Santos Patty K. , Ribeiro Lígia N. M. , Sung Bong Hwan , Weaver Alissa M. , Selistre-de-Araújo Heloisa S.
Published: September 2020

Background

Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.

Methods

To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.

Results

We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.

Conclusion

In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs.

Graphical abstract
The Implementation Research Logic Model: a method for planning, executing, reporting, and synthesizing implementation projects
Authors: Smith Justin D. , Li Dennis H. , Rafferty Miriam R.
Published: September 2020

Background

Numerous models, frameworks, and theories exist for specific aspects of implementation research, including for determinants, strategies, and outcomes. However, implementation research projects often fail to provide a coherent rationale or justification for how these aspects are selected and tested in relation to one another. Despite this need to better specify the conceptual linkages between the core elements involved in projects, few tools or methods have been developed to aid in this task. The Implementation Research Logic Model (IRLM) was created for this purpose and to enhance the rigor and transparency of describing the often-complex processes of improving the adoption of evidence-based interventions in healthcare delivery systems.

Methods

The IRLM structure and guiding principles were developed through a series of preliminary activities with multiple investigators representing diverse implementation research projects in terms of contexts, research designs, and implementation strategies being evaluated. The utility of the IRLM was evaluated in the course of a 2-day training to over 130 implementation researchers and healthcare delivery system partners.

Results

Preliminary work with the IRLM produced a core structure and multiple variations for common implementation research designs and situations, as well as guiding principles and suggestions for use. Results of the survey indicated a high utility of the IRLM for multiple purposes, such as improving rigor and reproducibility of projects; serving as a “roadmap” for how the project is to be carried out; clearly reporting and specifying how the project is to be conducted; and understanding the connections between determinants, strategies, mechanisms, and outcomes for their project.

Conclusions

The IRLM is a semi-structured, principle-guided tool designed to improve the specification, rigor, reproducibility, and testable causal pathways involved in implementation research projects. The IRLM can also aid implementation researchers and implementation partners in the planning and execution of practice change initiatives. Adaptation and refinement of the IRLM are ongoing, as is the development of resources for use and applications to diverse projects, to address the challenges of this complex scientific field.
Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: a population-based retrospective cohort study (1995–2018)
Authors: Chu William Ching-Yuen , Chiang Lorraine Lok-Wing , Chan Dorothy Chi-Ching , Wong Wilfred Hing-Sang , Chan Godfrey Chi-Fung
Published: September 2020

Background

We aim to elucidate the disease impact by accounting the prevalence, survival rate, genetics, mTOR inhibitor use and direct costs of tuberous sclerosis complex (TSC) in our local setting. TSC patients with documented visits to our local public hospitals in 1995–2018 were identified. The public hospitals captured most if not all local TSC patients. Demographics such as age, sex, death, genetic profiles were retrieved from the central electronic database. Data including prevalence, age distribution and survival rate were analysed. Direct cost was calculated with reference to the drug use and number of visits to various public hospital facilities.

Results

We identified 284 surviving TSC patients (55.3% male) in Hong Kong. The age range was from 4.5 months to 89.9 years, with a median age of 27.2 years. Paediatrics (< 18 years) to adult (≥18 years) ratio was 1:2.84. The overall prevalence of TSC patients was 3.87 in 100,000 (i.e. 1 in 25,833). Genetically, TSC1:TSC2 ratio is 1:2.7.

Thirty seven patients died within the study period. The age of death ranged from 7.6 years to 77.8 years, with a median age of death at 36.6 years (IQR: 24.7–51.1 years). Most patients survived till adulthood. Survival rate at 20 and 50 years follow-up was 98.6 and 79.5% respectively.

Two hundred and twenty nine TSC patients (71.3%) had neurological manifestations, sixteen patients (5.0%) had chronic kidney diseases and five patients (1.6%) had pulmonary lymphangioleiomyomatosis. Forty seven (16.5%) TSC patients were prescribed with mTOR inhibitors within the study period. Healthcare facility utilization was further analysed in the 2008–2018 cohort. In particular, the mean number of specialist out-patient clinic visits per patient-year was 9.23 per patient-year, which was 4.91 times more than that of local general population.

Conclusions

Prevalence of local TSC patients is within the range of that reported in the literature. Local TSC patients have fair long term survival, but they require disproportionally high healthcare cost when compared with the general population, particularly in terms of outpatient (OP) visits. Although effective disease-modifying agent (i.e. mTOR inhibitor) is available, it was not widely used yet in Hong Kong despite the fact that Government approved and supported its use recently. Further research on quality of life and setting up a comprehensive patient registry are necessary for more accurate assessment of cost and benefit.
Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1
Authors: Ye Youqiong , Kuang Xinwei , Xie Zuozhong , Liang Long , Zhang Zhao , Zhang Yongchang , Ma Fangyu , Gao Qian , Chang Ruimin , Lee Heng-Huan , Zhao Shuang , Su Juan , Li Hui , Peng Jingbo , Chen Huifang , Yin Minzhu , Peng Cong , Yang Nong , Wang Jing , Liu Jing , Liu Hong , Han Leng , Chen Xiang
Published: September 2020

Background

Immune checkpoint blockade (ICB) therapy has demonstrated considerable clinical benefit in several malignancies, but has shown favorable response in only a small proportion of cancer patients. Recent studies have shown that matrix metalloproteinases (MMPs) are highly associated with the microenvironment of tumors and immune cells. However, it is unknown whether MMPs are involved in immunotherapy.

Methods

Here, we used integrative analysis to explore the expression landscape of the MMP family and its association with immune features across multiple cancer types. We used T cell cytotoxicity-mediated tumor killing assay to determine the co-cultured T cell activity of SB-3CT, an MMP2/9 inhibitor. We then used in vitro assays to examine the regulating roles of SB-3CT on PD-L1. We further characterized the efficacy of SB-3CT, in combination with anti-PD-1 and/or anti-CTLA4 treatment in mouse models with melanoma and lung cancer.

Results

Our computational analysis demonstrated a strong association between MMP2/9 and immune features. We demonstrated that inhibition of MMP2/9 by SB-3CT significantly reduced the tumor burden and improved survival time by promoting anti-tumor immunity. Mechanistically, we showed that SB-3CT treatment significantly diminished both mRNA and protein levels of PD-L1 in cancer cells. Pre-clinically, SB-3CT treatment enhanced the therapeutic efficacy of PD-1 or CTLA-4 blockade in the treatment of both primary and metastatic tumors.

Conclusions

Our study unraveled novel molecular mechanisms regarding the regulation of tumor PD-L1 and provided a novel combination therapeutic strategy of SB-3CT and ICB therapy to enhance the efficacy of immunotherapy.
Evaluation of bacterial diversity during fermentation process: a comparison between handmade and machine-made high-temperature Daqu of Maotai-flavor liquor
Authors: Zuo Qiancheng , Huang Yongguang , MinGuo
Published: September 2020

Purpose

High-temperature Daqu is a traditional fermentation starter that is used for Chinese Maotai-flavor Baijiu production. Although the bacteria in high-temperature Daqu are known to be responsible for developing the quality and flavor of Baijiu during the fermentation process, there is little information on the properties of the bacteria during the fermentation of high-temperature Daqu, especially machine-made high-temperature Daqu. This has limited the development of the Maotai-flavor Baijiu industry, particularly with regard to the mechanized production of Maotai-flavor Baijiu.

Methods

Illumina MiSeq high-throughput sequencing was applied to study bacterial compositions during the fermentation of handmade and machine-made high temperatures.

Results

The results show that bacterial diversity in machine-made Daqu was similar but higher than that in handmade Daqu at the end of fermentation, and there was no significant difference between the methods with regard to the dominant genera and their dynamic changes during fermentation. Rhizobium, Bacillus, Thermoactinomyces, Weissella, Lactobacillus, and Saccharopolyspora were the dominant genera during the fermentation of both Daqus, although the relative abundance of these dominant genera differed between the two methods. Interestingly, the machine-made Daqu contained a higher relative abundance of Bacillus than handmade Daqu at all fermentation times. Bacillus is the most important functional bacteria in the fermentation of Maotai-flavor Baijiu, suggesting that mechanical-molding methods could be applied to industrial Maotai-flavor Daqu production.

Conclusion

These results suggest that mechanical-molding methods could be applied to industrial Maotai-flavor Daqu production, which could be helpful for industrial Maotai-flavor Baijiu production and the development of fermentation technology.
Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts
Authors: Filice Dominic , Dhahri Wahiba , Solan Joell L. , Lampe Paul D. , Steele Erin , Milani Nikita , Van Biber Benjamin , Zhu Wei-Zhong , Valdman Tamilla Sadikov , Romagnuolo Rocco , Otero-Cruz José David , Hauch Kip D. , Kay Matthew W. , Sarvazyan Narine , Laflamme Michael A.
Published: September 2020

Background

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show tremendous promise for cardiac regeneration, but the successful development of hESC-CM-based therapies requires improved tools to investigate their electrical behavior in recipient hearts. While optical voltage mapping is a powerful technique for studying myocardial electrical activity ex vivo, we have previously shown that intra-cardiac hESC-CM grafts are not labeled by conventional voltage-sensitive fluorescent dyes. We hypothesized that the water-soluble voltage-sensitive dye di-2-ANEPEQ would label engrafted hESC-CMs and thereby facilitate characterization of graft electrical function and integration.

Methods

We developed and validated a novel optical voltage mapping strategy based on the simultaneous imaging of the calcium-sensitive fluorescent protein GCaMP3, a graft-autonomous reporter of graft activation, and optical action potentials (oAPs) derived from di-2-ANEPEQ, which labels both graft and host myocardium. Cardiomyocytes from three different GCaMP3+ hESC lines (H7, RUES2, or ESI-17) were transplanted into guinea pig models of subacute and chronic infarction, followed by optical mapping at 2 weeks post-transplantation.

Results

Use of a water-soluble voltage-sensitive dye revealed pro-arrhythmic properties of GCaMP3+ hESC-CM grafts from all three lines including slow conduction velocity, incomplete host-graft coupling, and spatially heterogeneous patterns of activation that varied beat-to-beat. GCaMP3+ hESC-CMs from the RUES2 and ESI-17 lines both showed prolonged oAP durations both in vitro and in vivo. Although hESC-CMs partially remuscularize the injured hearts, histological evaluation revealed immature graft structure and impaired gap junction expression at this early timepoint.

Conclusion

Simultaneous imaging of GCaMP3 and di-2-ANEPEQ allowed us to acquire the first unambiguously graft-derived oAPs from hESC-CM-engrafted hearts and yielded critical insights into their arrhythmogenic potential and line-to-line variation.
Correction to: The chemfp project
Authors: Dalke Andrew
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Comparison of terrestrial and Martian TEC at dawn and dusk during solstices
Authors: Burrell Angeline G. , Sánchez-Cano Beatriz , Witasse Olivier , Lester Mark , Cartacci Marco
Published: September 2020

This paper used the similarities between the ionospheres on Mars and Earth, the most similar of the terrestrial planets, to examine the relative importance of photochemical and transport processes at dawn and dusk. The amount of plasma present in the ionosphere, as measured by the total electron content (TEC), was examined at different locations for both solstice seasons over a solar cycle. Using the rate of change of TEC as a function of solar zenith angle made it possible to compare the plasma production via photoionisation and loss via recombination in the main layer of each planetary ionosphere despite the extreme differences in the total quantity of plasma. This study finds that, at least to first order, the dawn and dusk TEC slopes at Mars are symmetric. This symmetry is interpreted as an indicator of photochemical equilibrium. Deviations from photochemical equilibrium in different geographic and aerographic regions were used to explore the underlying processes responsible for plasma transport. Seasonal and solar cycle variations were also examined at dusk. These variations found that differing interactions with solar forcing mechanisms resulted in a Martian ionosphere with regions that showed evidence of significant transport processes at solar maximum, while at Earth transport processes were most important at solar minimum. In general, the photochemical processes in both ionospheres behave similarly when no magnetic field is considered. The presence or absence of a magnetic field shape the production via photoionisation and loss via recombination processes in both ionospheres, especially when considering plasma transport. This study has notable implications for comparative aeronomy, as a good understanding of how the ionosphere of magnetised and un-magnetised bodies compares is important for characterising planetary environments and atmospheric evolution over long time scales.
Kinematics and center of axial rotation during walking after medial pivot type total knee arthroplasty
Authors: Miura Kota , Ohkoshi Yasumitsu , Ino Takumi , Ukishiro Kengo , Kawakami Kensaku , Suzuki Sho’ji , Suzuki Ko , Maeda Tatsunori
Published: September 2020

Purpose

In recent years, the medial pivot (MP) type total knee arthroplasty (TKA) implant has been developed and marketed for achieving more natural kinematics with MP. However, little is known about the pivot pattern during walking after MP type TKA. This study aimed to determine the kinematics and center of axial rotation during walking after MP type TKA.

Methods

This randomized prospective study enrolled 40 patients with MP type TKA, 20 with cruciate-substituting TKA (MP-CS group), 20 with posterior-stabilized TKA (MP-PS group), and 10 healthy volunteers (control group). The kinematics and center of axial rotation during overground walking were measured by a three-dimensional motion analysis system. The six-degrees-of-freedom kinematics of the knee were calculated by the point cluster method.

Results

The amount of change in knee flexion in early stance phase was significantly lower in the MP-CS and MP-PS groups than in the control group. The femur showed anterior translation during early stance phase in all three groups. The median center of axial rotation in the transverse plane was predominantly on the lateral side of the knee during stance in all groups.

Conclusions

Kinematics during gait are thought to be determined by physical posture, the kinetic chain during weight-bearing, and the kinematic features of adjacent structures, such as the behavior of the biarticular muscles. MP-CS and MP-PS did not necessarily induce rotational motion centered on the medial ball-in-socket component during walking; translational and lateral pivoting movements were also observed. Long-term follow-up is needed to monitor for polyethylene wear and implant loosening.
Salt and potassium intake among adult Ghanaians: WHO-SAGE Ghana Wave 3
Authors: Menyanu Elias K. , Corso Barbara , Minicuci Nadia , Rocco Ilaria , Russell Joanna , Ware Lisa J. , Biritwum Richard , Kowal Paul , Schutte Aletta E. , Charlton Karen E.
Published: September 2020

Though Ghana has high hypertension prevalence, the country lacks current national salt consumption data required to build and enhance advocacy for salt reduction. We explored the characteristics of a randomly selected sub sample that had valid urine collection, along with matched survey, anthropometric and BP data (n = 839, mean age = 60y), from the World Health Organization’s Study on global AGEing and adult health (WHO-SAGE), Ghana Wave 3, n = 3053). We also investigated the relationship between salt intake and blood pressure (BP) among the cohort. BP was measured in triplicate and 24 h urine was collected for the determination of urinary sodium (Na), potassium (K), creatinine (Cr) and iodine levels. Hypertension prevalence was 44.3%. Median salt intake was 8.3 g/day, higher in women compared to men (8.6, interquartile range (IQR) 7.5 g/day vs 7.5, IQR 7.4 g/day, p <  0.01), younger participants (18–49 y) compared to older ones (50+ y) (9.7, IQR 7.9 g/day vs 8.1, IQR 7.1 g/day, p <  0.01) and those with higher Body Mass Index (BMI) (> 30 kg/m2) compared to a healthy BMI (18.5–24.9 kg/m2) (10.04, IQR 5.1 g/day vs 6.2, IQR 5.6 g/day, p <  0.01). More than three quarters (77%, n = 647) of participants had salt intakes above the WHO maximum recommendation of 5 g/d, and nearly two thirds (65%, n = 548) had daily K intakes below the recommended level of 90 mmol. Dietary sodium to potassium (Na: K) ratios above 2 mmol/mmol were positively associated with increasing BP with age. Population-based interventions to reduce salt intake and increase K consumption are needed.
Two effective cases of additional pedal artery angioplasty for severe lower limb ischemia following acute thrombotic artery occlusion with hypercoagulable state diseases
Authors: Shoji Keisuke , Zen Kan , Yanishi Kenji , Wakana Noriyuki , Nakanishi Naohiko , Nakamura Takeshi , Matoba Satoaki
Published: September 2020

Background

Acute limb ischemia (ALI) and critical limb ischemia (CLI) following ALI are life-threatening diseases. The rare potential causes of ALI include hypercoagulable state diseases, such as antiphospholipid syndrome (APS) and essential thrombocythemia (ET). Hypercoagulability often make revascularization for arterial occlusion, especially associated with infrapopliteal lesions, difficult. This is because the vessels have poor run-off, and elevated peripheral vascular resistance associated with microcirculation failure, due to a high thrombus burden. There is no established treatment for this issue.

Case presentation

A 45 years-old and a 56 years-old male suffered from thrombotic arterial occlusion as a first manifestation of APS and ET, respectively. Combination therapy with aggressive anti-thrombotic therapy and revascularization, such as endovascular therapy and surgical thrombectomy based on the angiosome concept, was performed. However, the high thrombus burden caused a poor pedal outflow, and significant limb ischemia remained. Additional pedal artery angioplasty was performed to improve residual limb ischemia in each case and provided sufficient blood flow to the foot.

Conclusion

The pedal artery angioplasty for thrombotic pedal artery occlusion cases, associated with hypercoagulable state diseases, seems to be a treatment option for relieving residual limb ischemia.
Sofosbuvir and daclatasvir are safe and effective in treatment of recurrent hepatitis C virus in Egyptian patients underwent living donor liver transplantation
Authors: Aly Osama Aboelfotoh , Yousry Wael Ahmed , Teama Nahla Mohamed , Shona Eman Mohammed , ElGhandour Ahmed Mohamed
Published: September 2020

Background

Liver transplant population has been considered as a special population in the treatment of hepatitis C virus infection, not only because of lower sustained virological response (SVR) rates in comparison with pretransplant setting, but also for other aspects (i.e., immunosuppressive therapy, renal function, drug–drug interactions). We aimed to evaluate the efficacy and safety of the combined treatment with sofosbuvir and daclatasvir with or without ribavirin in liver transplant recipients with recurrent hepatitis C following transplantation and screening for the development of hepatocellular carcinoma during treatment, after the end of treatment, or during follow-up. This multicenteric prospective study was conducted in Egypt. This study included 40 patients who underwent living donor liver transplantation that started treatment at least 3 months following transplantation. All participants received 400 mg sofosbuvir once daily plus daclatasvir 60 mg daily ± ribavirin. Treatment lasted for up to 24 weeks, and participants were followed up as outpatients monthly for 12 and 24 weeks and 36 weeks post-treatment to determine sustained virological response (SVR12 and SVR24), considered to be a cure and detection of any changes in tumor markers or radiological imaging during follow-up.

Results

In the current study, 40 patients (100%) have good response to treatment during treatment and during follow-up (SVR 12 was 100%). No abnormal side effects to treatment were detected; also, no drug–drug interactions were noted during the treatment.

Conclusions

Treatment of HCV after living donor liver transplantation with combined sofosbuvir and daclatasvir is safe and well-tolerated and provides high rates of SVR.
Validity and reliability of the Arabic dyscalculia test in diagnosing Egyptian dyscalculic school-age children
Authors: Abdou R. M. , Hamouda N. H. , Fawzy A. M.
Published: September 2020

Background

Mathematical skills have an important role in progress of the educational level of nations. Unfortunately, there are still some pupils in school with normal intellectual function, but they have different degrees of mathematical disabilities that really can fall apart their whole life.

Dyscalculia is called number blindness. It is the name given to the condition that affects our ability to acquire arithmetical skills. In the Arabic language, there is a deficiency in tools for diagnosis of dyscalculia, so we conducted this study to formulate a test suitable for diagnosis of dyscalculia in Egyptian children via translation and modification of an American test (TOMA 3 test).

Results

The modified test was highly significant in discriminating dyscalculic from non-dyscalculic Egyptian pupils regarding all items of the test.

Conclusion

The Arabic version of TOMA-3 is valid and reliable for diagnosis of dyscalculia in Egyptian school-age children.