bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward more efficient ergothioneine production using the fungal ergothioneine biosynthetic pathway
Authors: Chen Zhihui , He Yongzhi , Wu Xinyu , Wang Li , Dong Zhiyang , Chen Xiuzhen
Published: May 2022

Background

Ergothioneine (ERG) is a potent histidine-derived antioxidant that confers health-promoting effects. Only certain bacteria and fungi can biosynthesize ERG, but the ERG productivity in natural producers is low. ERG overproduction through genetic engineering represents an efficient and cost-effective manufacturing strategy.

Results

Here, we showed that Trichoderma reesei can synthesize ERG during conidiogenesis and hyphal growth. Co-expression of two ERG biosynthesis genes (tregt1 and tregt2) from T. reesei enabled E. coli to generate 70.59 mg/L ERG at the shaking flask level after 48 h of whole-cell biocatalysis, whereas minor amounts of ERG were synthesized by the recombinant E. coli strain bearing only the tregt1 gene. By fed-batch fermentation, the extracellular ERG production reached 4.34 g/L after 143 h of cultivation in a 2-L jar fermenter, which is the highest level of ERG production reported thus far. Similarly, ERG synthesis also occurred in the E. coli strain engineered with the two well-characterized genes from N. crassa and the ERG productivity was up to 4.22 g/L after 143 h of cultivation under the above-mentioned conditions.

Conclusions

Our results showed that the overproduction of ERG in E. coli could be achieved through two-enzymatic steps, demonstrating high efficiency of the fungal ERG biosynthetic pathway. Meanwhile, this work offers a more promising approach for the industrial production of ERG.
Long-term exposure to residential greenness and neurodegenerative disease mortality among older adults: a 13-year follow-up cohort study
Authors: Rodriguez-Loureiro Lucía , Gadeyne Sylvie , Bauwelinck Mariska , Lefebvre Wouter , Vanpoucke Charlotte , Casas Lidia
Published: May 2022

Background

Living in greener areas is associated with slower cognitive decline and reduced dementia risk among older adults, but the evidence with neurodegenerative disease mortality is scarce. We studied the association between residential surrounding greenness and neurodegenerative disease mortality in older adults.

Methods

We used data from the 2001 Belgian census linked to mortality register data during 2001–2014. We included individuals aged 60 years or older and residing in the five largest Belgian urban areas at baseline (2001). Exposure to residential surrounding greenness was assessed using the 2006 Normalized Difference Vegetation Index (NDVI) within 500-m from residence. We considered all neurodegenerative diseases and four specific outcomes: Alzheimer’s disease, vascular dementia, unspecified dementia, and Parkinson’s disease. We fitted Cox proportional hazard models to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the associations between one interquartile range (IQR) increment in surrounding greenness and neurodegenerative disease mortality outcomes, adjusted for census-based covariates. Furthermore, we evaluated the potential role of 2010 air pollution (PM2.5 and NO2) concentrations, and we explored effect modification by sociodemographic characteristics.

Results

From 1,134,502 individuals included at baseline, 6.1% died from neurodegenerative diseases during follow-up. After full adjustment, one IQR (0.22) increment of surrounding greenness was associated with a 4–5% reduction in premature mortality from all neurodegenerative diseases, Alzheimer’s disease, vascular and unspecified dementia [e.g., for Alzheimer’s disease mortality: HR 0.95 (95%CI: 0.93, 0.98)]. No association was found with Parkinson’s disease mortality. Main associations remained for all neurodegenerative disease mortality when accounting for air pollution, but not for the majority of specific mortality outcomes. Associations were strongest in the lower educated and residents from most deprived neighbourhoods.

Conclusions

Living near greener spaces may reduce the risk of neurodegenerative disease mortality among older adults, potentially independent from air pollution. Socioeconomically disadvantaged groups may experience the greatest beneficial effect.
Construction and application of star polycation nanocarrier-based microRNA delivery system in Arabidopsis and maize
Authors: Yang Jia , Yan Shuo , Xie Shipeng , Yin Meizhen , Shen Jie , Li Zhaohu , Zhou Yuyi , Duan Liusheng
Published: May 2022

Background

MicroRNA (miRNA) plays vital roles in the regulation of both plant architecture and stress resistance through cleavage or translation inhibition of the target messenger RNAs (mRNAs). However, miRNA-induced gene silencing remains a major challenge in vivo due to the low delivery efficiency and instability of miRNA, thus an efficient and simple method is urgently needed for miRNA transformation. Previous researches have constructed a star polycation (SPc)-mediated transdermal double-stranded RNA (dsRNA) delivery system, achieving efficient dsRNA delivery and gene silencing in insect pests.

Results

Here, we tested SPc-based platform for direct delivery of double-stranded precursor miRNA (ds-MIRNA) into protoplasts and plants. The results showed that SPc could assemble with ds-MIRNA through electrostatic interaction to form nano-sized ds-MIRNA/SPc complex. The complex could penetrate the root cortex and be systematically transported through the vascular tissue in seedlings of Arabidopsis and maize. Meanwhile, the complex could up-regulate the expression of endocytosis-related genes in both protoplasts and plants to promote the cellular uptake. Furthermore, the SPc-delivered ds-MIRNA could efficiently increase mature miRNA amount to suppress the target gene expression, and the similar phenotypes of Arabidopsis and maize were observed compared to the transgenic plants overexpressing miRNA.

Conclusion

To our knowledge, we report the first construction and application of star polycation nanocarrier-based platform for miRNA delivery in plants, which explores a new enable approach of plant biotechnology with efficient transformation for agricultural application.

Graphical Abstract
Development and content validation of patient-reported outcomes tools for ulcerative colitis and Crohn’s disease in adults with moderate-to-severe disease
Authors: Nag Arpita , Romero Beverly
Published: May 2022

Background

Ulcerative colitis (UC) and Crohn’s disease (CD) are associated with a range of symptoms that adversely affect health-related quality of life. This research aimed to develop and validate two patient-reported outcome (PRO) tools to assess signs and symptoms in patients with moderate-to-severe UC or CD.

Methods

PRO-UC and PRO-CD Diaries were developed in accordance with US Food and Drug Administration (FDA) recommendations. Data were collected from concept elicitation interviews (in which patients described their symptoms and experience of the disease) and further refined through cognitive interviews (in which patients assessed the relevance and clarity of questions in the tools).

Results

Interviews were conducted with 12 patients for each indication. Five symptoms (urgent bowel movements, abdominal pain, frequent bowel movements, bloody stools, diarrhea/watery stools) were reported by 83–100% of participants with UC and were included in the final 6-item PRO-UC Diary: stool frequency, rectal bleeding (2 items), diarrhea, rectal urgency, and abdominal pain. For CD, seven symptoms (abdominal pain, diarrhea/loose stools, urgent bowel movements, fatigue/tiredness/weakness, frequent bowel movements, bloody stools, nausea) were reported by 50–100% of participants. These, together with vomiting and incontinence (reported by 42% and 33% of participants, respectively), were included in the final 10-item PRO-CD Diary, covering abdominal pain (2 items), stool frequency, liquid/very soft stool frequency, rectal bleeding, rectal urgency, nausea, vomiting, bowel incontinence, and general well-being. Symptoms were consistently cited across both indications to have an impact on quality of life, with frequent complaints being the need to always be near a toilet and inability to leave home, as well as general pain, discomfort, and nausea. For both tools, questions were accurately interpreted, with at least 67% of participants in both indications stating that items were easy to answer/relevant to their condition and symptoms were easy to recall over the last 24 h.

Conclusions

Both the PRO-UC and PRO-CD Diaries were developed and validated in accordance with FDA recommendations, providing two new tools for use in clinical trials to assess response to treatment in patients with UC or CD. Psychometric analyses are warranted to fully evaluate their properties and value for use in clinical trials.
WHO competency framework for health authorities and institutions to manage infodemics: its development and features
Authors: Rubinelli Sara , Purnat Tina D. , Wilhelm Elisabeth , Traicoff Denise , Namageyo-Funa Apophia , Thomson Angus , Wardle Claire , Lamichhane Jaya , Briand Sylvie , Nguyen Tim
Published: May 2022

Background

In April 2020, the World Health Organization (WHO) Information Network for Epidemics produced an agenda for managing the COVID-19 infodemic. “Infodemic” refers to the overabundance of information—including mis- and disinformation. In this agenda it was pointed out the need to create a competency framework for infodemic management (IM). This framework was released by WHO on 20th September 2021. This paper presents the WHO framework for IM by highlighting the different investigative steps behind its development.

Methods

The framework was built through three steps. Step 1 included the preparatory work following the guidelines in the Guide to writing Competency Framework for WHO Academy courses. Step 2 was based on a qualitative study with participants (N = 25), identified worldwide on the basis of their academic background in relevant fields of IM or of their professional experience in IM activities at the institutional level. The interviews were conducted online between December 2020 and January 2021, they were video-recorded and analyzed using thematic analysis. In Step 3, two stakeholder panels were conducted to revise the framework.

Results

The competency framework contains four primary domains, each of which comprised main activities, related tasks, and knowledge and skills. It identifies competencies to manage and monitor infodemics, to design, conduct and evaluate appropriate interventions, as well as to strengthen health systems. Its main purpose is to assist institutions in reinforcing their IM capacities and implementing effective IM processes and actions according to their individual contexts and resources.

Conclusion

The competency framework is not intended to be a regulatory document nor a training curriculum. As a WHO initiative, it serves as a reference tool to be applied according to local priorities and needs within the different countries. This framework can assist institutions in strengthening IM capacity by hiring, staff development, and human resources planning.
How to work with intangible software in public health systems: some experiences from India
Authors: Ramani Sudha , Parashar Rakesh , Roy Nobhojit , Kullu Arpana , Gaitonde Rakhal , Ananthakrishnan Ramya , Arora Sanjida , Mishra Shantanu , Pitre Amita , Saluja Deepika , Srinivasan Anupama , Uppal Anju , Bose Prabir , Yellappa Vijayshree , Kumar Sanjeev
Published: May 2022

This commentary focuses on “intangible software”, defined as the range of ideas, norms, values and issues of power or trust that affect the performance of health systems. While the need to work with intangible software within health systems is increasingly being recognized, the practicalhowsof doing so have been given less attention. In this commentary, we, a team of researchers and implementers from India, have tried to deliberate on these hows through a practice lens. We engage with four questions of current relevance to intangible software in the field of health policy and systems research (HPSR): (1) Is it possible to rewire intangible software in health systems? (2) What approaches have been attempted in the Indian public health system to rewire intangibles? (3) Have such approaches been evaluated? (4) What practical lessons can we offer from our experience on rewiring intangibles? From our perspective, approaches to rewiring intangible software recognize that people in health systems are capable of visioning, thinking, adapting to and leading change. These approaches attempt to challenge the often-unchallenged power hierarchies in health systems by allowing people to engage deeply with widely accepted norms and routinized actions. In this commentary, we have reported on such approaches from India under six categories: approaches intended to enable visioning and leading; approaches targeted at engaging with evidence better; approaches intended to help health workers navigate contextual complexities; approaches intended to build the cultural competence; approaches that recognize and reward performance; and approaches targeted at enabling collaborative work and breaking power hierarchies. Our collective experiences suggest that intangible software interventions work best when they are codesigned with various stakeholders, are contextually adapted in an iterative manner and are implemented in conjunction with structural improvements. Also, such interventions require long-term investments. Based on our experiences, we highlight the need for the following: (1) fostering more dialogue on this category of interventions among all stakeholders for cross-learning; (2) evaluating and publishing evidence on such interventions in nonconventional ways, with a focus on participatory learning; and (3) building ecosystems that allow experiential learnings on such interventions to be shared.
An evaluation of the evidence brief for policy development process in WHO EVIPNet Europe countries
Authors: Murphy Adrianna , Šubelj Maja , Babarczy Balázs , Köhler Kristina , Chapman Evelina , Truden-Dobrin Polonca , Oliver Kathryn , Nahrgang Saskia , Reinap Marge , Kuchenmüller Tanja
Published: May 2022

Background

Evidence briefs for policy (EBPs) represent a potentially powerful tool for supporting evidence-informed policy-making. Since 2012, WHO Evidence-Informed Policy Network (EVIPNet) Europe has been supporting Member States in developing EBPs. The aim of this study was to evaluate the process of developing EBPs in Estonia, Hungary and Slovenia.

Methods

We used a rapid appraisal approach, combining semi-structured interviews and document review, guided by the Medical Research Council (MRC) process evaluation framework. Interviews were conducted with a total of 20 individuals familiar with the EBP process in the three study countries. Data were analysed thematically, and emerging themes were related back to the MRC framework components (implementation, mechanisms of impact, and context). We also reflected on the appropriateness of this evaluation approach for EVIPNet teams without evaluation research expertise to conduct themselves.

Results

The following themes emerged as important to the EBP development process: how the focus problem is prioritized, who initiates this process, EBP team composition, EBP team leadership, availability of external support in the process, and the culture of policy-making in a country. In particular, the EBP process seemed to be supported by early engagement of the Ministry of Health and other stakeholders as initiators, clear EBP team roles and expectations, including a strong leader, external support to strengthen EBP team capacity and cultural acceptance of the necessity of evidence-informed policy-making. Overall, the evaluation approach was considered feasible by the EBP teams and captured rich qualitative data, but may be limited by the absence of external reviewers and long lag times between the EBP process and the evaluation.

Conclusions

This process occurs in a complex system and must be conceptualized in each country and each EBP project in a way that fits local policy-making culture, priorities, leadership and team styles, roles and available resources. The use of a rapid appraisal approach, combining qualitative interviews and document review, is a feasible method of process evaluation for EVIPNet member countries.
Late career participation of late retirees in the age of the silver tsunami: understanding the influencing mechanism of health status and employment-based health insurance participation
Authors: Yuan Bocong , Li Jiannan , Liang Wenqi , Lan Junbang
Published: May 2022

Background

The delayed retirement initiative and population aging have led to a growing group of late retirees. However, it remains unclear whether the existing employment-based health insurance system can effectively match the recently proposed initiative and support late retirees, especially those with pre-existing function limitations. Thus, this study aims to investigate the influencing mechanism of China’s Urban Employee Basic Medical Insurance (UEBMI), physical functioning limitation (PFL) and difficulty in instrumental activities of daily living (IADLs) on labour participation of late retirees in China.

Methods

This study uses data from the China Health and Retirement Longitudinal Study (CHARLS) survey, which tracks the quality of life among older adults in China (valid sample size = 5560).

Results

Empirical results show that China’s employment-based health insurance (i.e. UEBMI) and health conditions (i.e. PFL and difficulty in IADLs) are positively associated with late retirees’ withdrawal from late career participation. In addition, a higher level of difficulty in IADLs could strengthen the effect of PFL on late retirees’ withdrawal from late career participation, which could be further buffered by UEBMI beneficiary status.

Conclusion

In the formulation of delayed retirement policies, it is necessary to consider the influencing mechanism of the social health insurance system and health conditions on late career participation of older workers to ensure policy effectiveness.
Mitochondrial apolipoprotein A-I binding protein alleviates atherosclerosis by regulating mitophagy and macrophage polarization
Authors: Duan Meng , Chen Hainan , Yin Linjie , Zhu Xiao , Novák Petr , Lv Yuncheng , Zhao Guojun , Yin Kai
Published: May 2022

Apolipoprotein A-I binding protein (AIBP), a secreted protein, has been shown to play a pivotal role in the development of atherosclerosis. The function of intracellular AIBP, however, is not yet well characterized. Here, we found that AIBP is abundantly expressed within human and mouse atherosclerotic lesions and exhibits a distinct localization in the inner membrane of mitochondria in macrophages. Bone marrow-specific AIBP deficiency promotes the progression of atherosclerosis and increases macrophage infiltration and inflammation in low-density lipoprotein receptor-deficient (LDLR−/−) mice. Specifically, the lack of mitochondrial AIBP leads to mitochondrial metabolic disorders, thereby reducing the formation of mitophagy by promoting the cleavage of PTEN-induced putative kinase 1 (PINK1). With the reduction in mitochondrial autophagy, macrophages polarize to the M1 proinflammatory phenotype, which further promotes the development of atherosclerosis. Based on these results, mitochondrial AIBP in macrophages performs an antiatherosclerotic role by regulating of PINK1-dependent mitophagy and M1/M2 polarization.
SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration
Authors: Ardizzone Alessio , Bova Valentina , Casili Giovanna , Filippone Alessia , Campolo Michela , Lanza Marika , Esposito Emanuela , Paterniti Irene
Published: May 2022

Background

Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration.

Methods

Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction.

Results

The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+-binding proteins while inhibiting the apoptotic cascade.

Conclusion

Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.
Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid
Authors: Ainiwan Yilamujiang , Chen Yiguang , Mao Chaofu , Peng Junxiang , Chen Siyuan , Wei Songtao , Qi Songtao , Pan Jun
Published: May 2022

Introduction

The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors.

Objective

The objective of this study was to construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid.

Methods

An animal model was established by injecting human ACP cyst fluid into the bilateral hypothalamus of mice. ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means.

Results

ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp–Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74–APP is significantly strengthened between inflammatory activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid.

Conclusion

In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74–APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.
Developing a novel treatment for patients with chronic pain and Opioid User Disorder
Authors: Wachholtz Amy , Robinson Dallas , Epstein Elizabeth
Published: May 2022

Background

It is critical to develop empirically based, community-treatment friendly, psychotherapy interventions to improve treatment for patients with comorbid chronic pain and Opioid Use Disorder. Understanding factors that increase patient adherence and attendance is important, along with strategies targeted to address those issues.

Methods

Based on initial psychophysiology research on adults with OUD and chronic pain, we created an integrated cognitive-behavioral, 12-week outpatient group therapy called STOP (Self-regulation Therapy for Opioid addiction and Pain). In this study, we pilot tested STOP in a Stage 1a feasibility and acceptability study to identify unique treatment needs and factors that increased session attendance, adherence to treatment, and improved outcomes. Fourteen individuals on medication for OUD with co-occurring chronic pain participated.

Results

STOP had high attendance rates (80%; and active patient engagement). Urine toxicology showed no illicit drug use after week 8. Data analysis from pre-intervention to a 3-month follow-up showed significant functional improvement (F(1,12) = 45.82;p < 0.001) and decreased pain severity levels (F(1,12) = 37.62;p < 0.01). Participants reported appreciation of the unique tools to counteract physiological activation during a pain flare or craving. Participants also reported benefit from in-session visual aids, applicable pain psychology information, take-home worksheets, tools for relaxation practice, learning to apply the therapy tools.

Discussion

STOP is a 90-min 12-week rolling-entry group therapy based on previous research identifying psychophysiological needs of pain and OUD patients that can be seamlessly incorporated into community addiction treatment clinics.

Conclusion

Preliminary results of STOP are promising with high patient engagement and adherence and significant reductions in drug use and pain.

Trial registration

ClinicalTrials.Gov NCT03363243, Registered Dec 6, 2017.
A qualitative exploration of daily path and daily routine among people in Ukraine who inject drugs to understand associated harms
Authors: Owczarzak Jill , Chien Jessie , Tobin Karin , Mazhnaya Alyona , Chernova Olena , Kiriazova Tetiana
Published: May 2022

Background

Patterns of movement, heterogeneity of context, and individual space-time patterns affect health, and individuals’ movement throughout the landscape is shaped by addiction, meeting basic needs, and maintaining relationships. Place and social context enable or constrain behavior and individuals use social networks and daily routines to accomplish individual goals and access resources.

Methods

This article explores drug use as part of daily routines and daily paths among people who inject drugs in Dnipro City, Ukraine. Between March and August 2018, we interviewed 30 people who inject drugs living in Dnipro City, Ukraine. Study participants completed a single interview that lasted between 1 and 2 hours. During the interview, participants described their daily routine and daily path using a printed map of Dnipro as a prompt. Participants were asked to draw important sites; give time estimates of arrival and departure; and annotate on the map the points, paths, and areas most prominent or important to them. Participants also described to what extent their daily routines were planned or spontaneous, how much their daily path varied over time, and how drug use shaped their daily routine.

Results

We identified 3 major types of daily routine: unpredictable, predictable, and somewhat predictable. Participants with unpredictable daily routines had unreliable sources of income, inconsistent drug suppliers and drug use site, and dynamic groups of people with whom they socialized and used drugs. Participants with predictable daily routines had reliable sources of income, a regular drug dealer or stash source, and a stable group of friends or acquaintances with whom they bought and/or used drugs. Participants with somewhat predictable daily routines had some stable aspects of their daily lives, such as a steady source of income or a small group of friends with whom they used drugs, but also experienced circumstances that undermined their ability to have a routinized daily life, such as changing drug use sites or inconsistent income sources.

Conclusions

Greater attention needs to be paid to the daily routines of people who use drugs to develop and tailor interventions that address the place-based and social contexts that contribute to drug-use related risks.
Application of piecewise VMAT technique to whole-brain radiotherapy with simultaneous integrated boost for multiple metastases
Authors: Xu Yuan , Xu Yingjie , Men Kuo , Xiao Jianping , Dai Jianrong
Published: May 2022

Purpose

This study implemented a piecewise volumetric modulated arc therapy (P-VMAT) for realizing whole-brain radiation therapy (WBRT) with simultaneous integrated boost (SIB) for multiple brain metastases (> 40 metastases) with a conventional C-arm linear accelerator.

Materials and methods

This study retrospectively analyzed 10 patients with multiple brain metastases (40–120 metastases, median 76), who underwent WBRT and SIB using helical tomotherapy (HT). The prescribed doses were 40 Gy/20 f and 60 Gy/20 f for WBRT and SIB, respectively. Corresponding new HT plans were designed with P-VMAT using 7 arcs. For each arc, the collimator was rotated to 45°, and the field width was limited to 2.5 cm with 0.5 cm overlap with adjacent arcs. Thus, each arc covered only one section of the brain target volume. A conventional dual arc VMAT (DA-VMAT) plan was also designed. HT, P-VMAT, and DA-VMAT plans were compared using dose distribution reviews and dosimetric parameters. ArcCHECK phantom measurements were performed for verification of P-VMAT plans.

Results

No significant differences in the mean coverage of the whole-brain target and metastases were observed between HT and P-VMAT (p > 0.05). The conformity index for the whole-brain target improved with P-VMAT compared with HT (p < 0.05). Furthermore, the volume of 44 Gy V44 (110% of prescribed dose for WBRT) received for whole-brain significantly reduced with P-VMAT from 38.2 ± 12.9% to 23.3 ± 9.4% (p < 0.05), and the maximum dose for organs at risks such as the hippocampus, optical nerve, optical chiasm, and spinal cord declined with P-VMAT (p < 0.05). Unlike HT and P-VMAT, DA-VMAT was clinically unacceptable because V44 in the whole-brain was too high (54.7 ± 8.2%). The mean absolute dose gamma passing rate for P-VMAT plans was 97.6 ± 1.1% (3%/3 mm criterion, 10%).

Conclusions

P-VMAT is favorable for WBRT and SIB for multiple brain metastases. It provides comparable coverage of whole-brain target and SIB, with better conformity, lower V44, and better dose sparing of organs at risk compared with HT. Furthermore, results show that DA-VMAT fails clinical practice even for a relatively large number of brain metastases with a high degree of plan complexity. The patient specific verification demonstrates the feasibility of P-VMAT for clinical application.
Application of POSSUM and P-POSSUM scores in the risk assessment of elderly hip fracture surgery: systematic review and meta-analysis
Authors: Wanjiang Feng , Xiaobo Zhang , Xin Wu , Ye Meng , Lihua Huang , Jianlong Wang
Published: May 2022

Background

Since Mohamed et al. analyzed 2326 orthopedic cases in 2002 and believed that the POSSUM formula can be directly used to predict postoperative morbidity and mortality in orthopedic patients, applications of POSSUM and P-POSSUM scores in the hip fracture surgery have been mostly reported in the field of orthopedics, but there are still some inconsistencies in the related reports.

Methods

The electronic library was searched for all literature that met the purpose from its inception to 2021. Relative risk (RR) was selected to evaluate whether the model could be used to assess the risk of surgery in patients with elderly hip fractures. Finally, sensitivity analyses and subgroup analyses were performed.

Results

Thirteen studies were finally included, including 9 retrospective and 4 prospective studies.The morbidity analysis includes 11 studies, and the result was RR = 1.07 (95% CI 0.93–1.24), The mortality analysis includes 11 studies on POSSUM and 5 studies on P-POSSUM. The results of mortality by POSSUM and by P-POSSUM were RR = 1.93 (95% CI 1.21–3.08) and RR = 1.15 (95% CI 0.89–1.50), respectively. POSSUM had more accuracy to predict mortality for sample < 200 subgroup(RR = 2.45; 95% CI 0.71–8.42) than sample > 200 subgroup(RR = 1.59; 95% CI 1.06–2.40), and in the subgroup of hip fractures that did not distinguish between specific fracture types(RR = 1.69, 95% CI 0.87–3.32) than intertrochanteric neck fracture subgroup(RR = 5.04, 95% CI 1.07–23.75) and femoral femoral fracture subgroup(RR = 1.43,95% CI 1.10–1.84).

Conclusion

POSSUM can be used to predict morbidity in elderly hip fractures. The P-POSSUM was more accurate in predicting mortality in elderly hip fracture patients compared to the POSSUM, whose predictive value for mortality was influenced by the sample size and type of fracture studied. In addition, we believe that appropriate improvements to the POSSUM system are needed to address the characteristics of orthopedic surgery.
The effects of total knee arthroplasty on knee proprioception of patients with knee osteoarthritis: a meta-analysis
Authors: Xue Ya-Yue , Shi Jing-Nan , Zhang Kuan , Zhang Hao-Hua , Yan Song-Hua
Published: May 2022

Background

Studies have given some pieces of evidence for the effect of total knee arthroplasty (TKA) on knee proprioception of patients with knee osteoarthritis (KOA), but their results were conflicting. This review was performed to provide an updated evidence-based meta-analysis investigating the influence of TKA on knee proprioception.

Methods

The electronic databases including PubMed, Google Scholar, and the Cochrane Library were accessed from their inception to March 2020. Two reviewers identified the studies that met the selection criteria for this review. Information on study type, participants, follow-up time, and outcome measures was extracted. Methodological quality was independently assessed by two reviewers using the Cochrane Handbook 5.1.0. Eleven studies with 475 participants were included in the meta-analysis.

Results

The I2 index assessed the heterogeneity between studies. The results showed that the pooled standard mean difference of mean angle of error was − 0.58° (95% CI − 1 to – 0.16; P = 0.007; I2 = 69%), and the joint position sense of KOA patients was better after TKA surgery than that before surgery. Pooled standard mean difference of displacement of center of pressure (COP) was − 0.39 (95% CI − 0.72 to − 0.06; P = 0.02; I2 = 51%), and KOA patients had better static balance after TKA surgery than before surgery.

Conclusions

To conclude, no standardized comprehensive evaluation protocol presently exists though different assessment tools are available to measure proprioception. Contrasting results were found in the literature since some studies found that TKA improves proprioception in KOA patients, while others found no difference in proprioception. These differences are seen whether the proprioception was assessed by joint position sense (JPS), or it was indirectly assessed by static balance. However, the lack of sufficient data on the threshold to detect passive movement (TTDPM) and dynamic balance made it difficult to draw a conclusion about whether or not the sense of motion improved after surgery. The method for measuring and evaluating knee joint force sense is worth paying attention, which will make progress with knee proprioception on TKA patients.
Five-year outcomes of trauma-specific function in patients after acute blunt popliteal artery injury: a matched cohort analysis
Authors: Liu Gang , Chen Jialei , Xiang Zhou
Published: May 2022

Background

Few studies focus on the trauma-specific functional outcomes after surgical revascularization and risk factors contributing to poor outcomes in patients with acute blunt popliteal artery injury (PAI). The objective of this study was to investigate the long-term trauma-specific functional outcomes in patients with acute blunt PAI and identify the associated risk factors.

Methods

There were 36 patients with acute blunt PAI who require surgical revascularization at a national trauma center of West China Hospital of Sichuan University between March 2010 and April 2019. After propensity matching, each patient was matched to one patient who did not have a concomitant vascular injury in control cohort. Functional outcomes were assessed with trauma-specific functional scores, physical examination of range of motion, nerve functional status and knee stability. A logistics regression model was established to determine the independent risk factors.

Results

The 5-year (range 2–10 years) follow-up showed that 22 patients (22/36, 61.1%) had functional deficit due to limited activity or chronic neurological symptoms. Patients in vascular cohort had significantly decreased FIM score and AHFS score compared with matched patients without vascular involvement (P = 0.003 andP < 0.001), whereas there was no statistically significant difference in KSS (P = 0.136). Spearman correlation analysis of functional scores in vascular cohort showed that the FIM score was positively correlated with AHFS score (r = 0.926,P < 0.001), but not correlated with the KSS (r =  − 0.007,P = 0.967). Additionally, there was significant difference in the range of motion of ankle between two groups (P < 0.001 andP = 0.034). Logistic regression analysis further demonstrated nerve injuries and compartment syndrome were risk factors for poor ankle function after surgery (OR 22.580,P = 0.036 and OR 12.674,P = 0.041).

Conclusion

Most patients who sustained blunt PAI had significant functional deficit associated with limited activity and chronic neurological symptoms of ankle and foot, and poor functional outcomes were related to nerve injury and compartment syndrome. Therefore, early and effective decompression for compartment syndrome remains the only potentially modifiable risk factor for improving functional outcomes following PAI.
Pulmonary tumour embolism and lymphangitis carcinomatosa: a case report and review of the literature
Authors: Engel Jan , Auer Johann
Published: May 2022

Background

Pulmonary tumour embolism and lymphangitis carcinomatosa are complications of malignancy that may mimic the clinical presentation of pulmonary embolism.

Case presentation

We present the case of a 52-year-old male patient with acute-onset right ventricular strain and dyspnoea with elevated D-dimer and without signs of pulmonary embolism on computed tomography pulmonary angiogram (CTPA) and ventilation/perfusion scintigraphy. The patient died eleven days after initial presentation. The diagnosis of pulmonary tumour embolism and lymphangitis carcinomatosa due to carcinoma of unknown origin was made post-mortem by immunohistochemical examination.

Conclusion

Pulmonary tumour embolism and lymphangitis carcinomaosa are complications of malignancy and potential causes of acute right ventricular strain. Radiological signs are unspecific and the clinical course usually fatal. These differential diagnoses should be considered in patients with acute right ventricular strain, dyspnoea and positive D-dimer if there are no signs of pulmonary embolism on CTPA.
The impact of segmentectomy versus lobectomy on pulmonary function in patients with non-small-cell lung cancer: a meta-analysis
Authors: Xu Yuan , Qin Yingzhi , Ma Dongjie , Liu Hongsheng
Published: May 2022

Objective

Segmentectomy has been reported as an alternative to lobectomy for small-sized NSCLC without detriment to survival. The long-term benefits of segmentectomy over lobectomy on pulmonary function have not been firmly established. This meta-analysis aims to compare postoperative changes in pulmonary function in NSCLC patients undergoing segmentectomy or lobectomy.

Methods

Medline, Embase, Web of Science and Scopus were searched through March 2021. Statistical comparisons were made when appropriate.

Results

Fourteen studies (2412 participants) out of 324 citations were included in this study. All selected studies were high quality, as indicated by the Newcastle–Ottawa scale for assessing the risk of bias. Clinical outcomes were compared between segmentectomy and lobectomy. ΔFEV1 [10 studies, P < 0.01, WMD = 0.40 (0.29, 0.51)], ΔFVC [4 studies, P < 0.01, WMD = 0.16 (0.07, 0.24)], ΔFVC% [4 studies, P < 0.01, WMD = 4.05 (2.32, 5.79)], ΔFEV1/FVC [2 studies, P < 0.01, WMD = 1.99 (0.90, 3.08)], and ΔDLCO [3 studies, P < 0.01, WMD = 1.30 (0.69, 1.90)] were significantly lower in the segmentectomy group than in the lobectomy group. Subgroup analysis showed that in stage IA patients, the ΔFEV1% [3 studies, P < 0.01, WMD = 0.26 (0.07, 0.46)] was significantly lower in the segmentectomy group. The ΔDLCO% and ΔMVV% were incomparable.

Conclusion

Segmentectomy preserves more lung function than lobectomy. There were significantly smaller decreases in FEV1, FVC, FVC%, FEV1/FVC and DLCO in the segmentectomy group than in the lobectomy group.
Surgical repair for left coronary artery-right atrium fistula with giant coronary aneurysm
Authors: Jin Yan , Zhang Mengfei , He Juan
Published: May 2022

Background

Coronary artery fistula is a rare coronary anomaly which is defined as a communication between coronary artery and other heart chambers or vascular structures. The coronary artery which supply the fistula with blood can dilated, as a consequence, coronary aneurysm developed.

Case introduction

Coronary artery fistula is frequently asymptomatic in its early stage, here we report a 26-year-old woman with left coronary artery fistula and left coronary artery aneurysm who presented in our hospital with dyspnea, fatigue and palpitation. The orifice of fistula was closed by continuous suture via right atriotomy. The wall of the aneurysm and enlarged LCA were partially resected along its longitudinal axis so that we can reduce the diameter of LCA to approximately normal.

Conclusion

This technique provides a safe method for surgical repair of the giant coronary artery aneurysm with CAF.
Application of Bayesian methods to accelerate rare disease drug development: scopes and hurdles
Authors: Kidwell Kelley M. , Roychoudhury Satrajit , Wendelberger Barbara , Scott John , Moroz Tara , Yin Shaoming , Majumder Madhurima , Zhong John , Huml Raymond A. , Miller Veronica
Published: May 2022

Background

Design and analysis of clinical trials for rare and ultra-rare disease pose unique challenges to the practitioners. Meeting conventional power requirements is infeasible for diseases where sample sizes are inherently very small. Moreover, rare disease populations are generally heterogeneous and widely dispersed, which complicates study enrollment and design. Leveraging all available information in rare and ultra-rare disease trials can improve both drug development and informed decision-making processes.

Main text

Bayesian statistics provides a formal framework for combining all relevant information at all stages of the clinical trial, including trial design, execution, and analysis. This manuscript provides an overview of different Bayesian methods applicable to clinical trials in rare disease. We present real or hypothetical case studies that address the key needs of rare disease drug development highlighting several specific Bayesian examples of clinical trials. Advantages and hurdles of these approaches are discussed in detail. In addition, we emphasize the practical and regulatory aspects in the context of real-life applications.

Conclusion

The use of innovative trial designs such as master protocols and complex adaptive designs in conjunction with a Bayesian approach may help to reduce sample size, select the correct treatment and population, and accurately and reliably assess the treatment effect in the rare disease setting.
Do patients with Prader–Willi syndrome have favorable glucose metabolism?
Authors: Qian Yanjie , Xia Fangling , Zuo Yiming , Zhong Mianling , Yang Lili , Jiang Yonghui , Zou Chaochun
Published: May 2022

Background

In recent years, more studies have observed that patients with Prader–Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism.

Method

The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms “Prader–Willi syndrome” with “glucose”, “insulin”, “diabetes mellitus”, “fat”, “adipo*”, “ghrelin”, “oxytocin”, “irisin” or “autonomic nervous system”.

Results

The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader–Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader–Willi syndrome.

Conclusion

Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.
Rare and potential pathogenic mutations of LMNA and LAMA4 associated with familial arrhythmogenic right ventricular cardiomyopathy/dysplasia with right ventricular heart failure, cerebral thromboembolism and hereditary electrocardiogram abnormality
Authors: Chen Jia , Ma Yuting , Li Hong , Lin Zhuo , Yang Zhe , Zhang Qin , Wang Feng , Lin Yanping , Ye Zebing , Lin Yubi
Published: May 2022

Background

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with ventricular arrhythmia, heart failure (HF), and sudden death. Thromboembolism is also an important and serious complication of ARVC/D. However, the etiology of ARVC/D and thromboembolism and their association with genetic mutations are unclear.

Methods

Genomic DNA samples of peripheral blood were conducted for whole-exome sequencing (WES) and Sanger sequencing in the ARVC/D family. Then, we performed bioinformatics analysis for genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations were affecting the hydrophobicity and phosphorylation of amino acids and their joint pathogenicity by ProtScale, NetPhos and ORVAL algorisms.

Results

We discovered a Chinese Han family of ARVC/D with right ventricular HF (RVHF), cerebral thromboembolism, arrhythmias (atrial fibrillation, atrial standstill, multifocal ventricular premature, complete right bundle block and third-degree atrioventricular block) and sudden death. Based on the WES data, the variants ofLMNAp.A242V,LAMA4p.A225P andRYR2p.T858M are highly conserved and predicated as “deleterious” by SIFT and MetaSVM algorithms. Their CADD predicting scores are 33, 27.4 and 25.8, respectively. These variants increase the hydrophobicity of their corresponding amino acid residues and their nearby sequences by 0.378, 0.266 and 0.289, respectively. TheLAMA4andRYR2variants lead to changes in protein phosphorylation at or near their corresponding amino acid sites. There were high risks of joint pathogenicity for cardiomyopathy among these three variants. Cosegregation analysis indicated thatLMNAp.A242V might be an important risk factor for ARVC/D, electrocardiogram abnormality and cerebral thromboembolism, whileLAMA4p.A225P may be a pathogenic etiology of ARVC/D and hereditary electrocardiogram abnormality.

Conclusions

TheLMNAp.A242V may participate in the pathogenesis of familial ARVC/D with RVHF and cerebral thromboembolism, whileLAMA4p.A225P may be associated with ARVC/D and hereditary electrocardiogram abnormality.