bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Serum Eicosapentaenoic Acid to Arachidonic Acid Ratio and Atherosclerotic Risk Factors in Patients With Peripheral Artery Disease
Authors: Nishibe Toshiya , Dardik Alan , Nishibe Masayasu , Kano Masaki , Matsumoto Ryumon , Nakano Yu , Maekawa Koki , Irikata Yuki , Ogino Hitoshi , Ono Shun , Koizumi Jun
Published: October 2020

Background:

The eicosapentaenoic acid to arachidonic acid ratio (EPA/AA) is attracting attention as a risk factor for peripheral artery disease (PAD). However, there have been few studies investigating the relationship between the EPA/AA ratio and atherosclerotic risk factors in patients with PAD. The purpose of the present study was to analyze atherosclerotic risk factors in patients with PAD to identify those factors associated with a low EPA/AA ratio.

Methods.

The data of patients treated for symptomatic PAD at Tokyo Medical University Hospital and Eniwa Midorino Clinic between April 2014 and March 2018 were retrospectively analyzed.

Results.

A total of 149 patients were tested for blood levels of n-3 and n-6 polyunsaturated fatty acids, including EPA and AA. 73 patients had a low EPA/AA ratio (<0.4) and 76 patients had a high EPA/AA ratio (≥ 0.4). Univariate analysis showed that older age (≥ 75 years), female sex, smoking history, body mass index (BMI), and hemoglobin A1C (HbA1C) were associated with the low EPA/AA ratio. Multivariable analysis showed that older age (odds ratio [OR], 0.34; 95% confidential interval [CI], 0.15-0.76; p = 0.008), BMI (OR, 0.87; 95% CI, 0.77-0.98; p = 0.027), smoking history (OR, 2.67; 95% CI, 1.09-6.55; p = 0.007), and HbA1C (OR, 0.46; 95% CI, 0.29-0.72; p = 0.020) were independently associated with the low EPA/AA ratio.

Conclusions.

The EPA/AA ratio was related to existing arteriosclerotic risk factors in patients with PAD; it was positively correlated with older age, increasing BMI, and higher HbA1C, whereas it was negatively correlated with smoking history. These results suggest that the EPA/AA ratio may be closely intertwined with other atherosclerotic risk factors and have an influence on cardiovascular health.
A Case Series of Long-Term Surgical Outcomes of Primary Pulmonary Artery Sarcomas With Opportunities for 3D-Printed Models in Surgical Planning
Authors: Mahajan Nandita N. , Cicek Sertac M. , McGregor Christopher G.A. , Boland Jennifer M. , Morris Jonathan M. , Okuno Scott H. , Robinson Steven I. , White Darin B. , Yi Eunhee S. , Blackmon Shanda H.
Published: October 2020

There are limited data regarding the surgical management of primary pulmonary artery sarcomas (PPAS) because of their rarity and complicated diagnostic history. The objective of this study was to analyze our institution’s long-term surgical management outcomes for PPAS in the absence of a care pathway. From May 1997 to June 2013, 8 patients (mean age 60.6 ± 11.8 years; range, 40-73 years; 5 women and 3 men) underwent surgical intervention for PPAS at our institution. The most common computed tomography finding was a luminal filling defect obstructing the pulmonary artery (PA), without evidence of extraluminal extension. Three patients underwent debulking/pulmonary endarterectomy alone and 5 patients underwent a more radical resection with PA patch angioplasty, PA resection and reconstruction, pulmonary valve replacement, and unilateral pneumonectomy. The mean postoperative survival in this series was 3.8 ± 3.6 years (range, 1-11.9 years), with 2 radical surgical resection patients alive at 4.9 and 11.9 years, respectively. For those patients with incomplete resection, 3-dimensional (3D) models were created to demonstrate the advantage of a preoperative guide for a more complete resection and what it would entail. Six patients had local recurrences with mean disease-free interval of 14 ± 10.9 months (range, 2 months-2.5 years), and 2 patients with re-resections had an overall postoperative survival of 2.8 and 11.9 years, respectively. In our small cohort of PPAS, patients treated with radical surgical resection had better survival. The small number of PPAS cases in this series makes proving this association unlikely but warrants consideration.
Outcome Metrics in the Treatment of Carpal Tunnel Syndrome: A Systematic Review
Authors: Mertz Kevin , Lindsay Sarah E. , Morris Arden , Kamal Robin N.
Published: October 2020

Background:

The purpose of this systematic review was to determine the metrics used to assess outcomes after treatment for carpal tunnel syndrome.

Methods:

We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of level I and II randomized controlled trials of treatment for carpal tunnel syndrome. We searched the PubMed/MEDLINE electronic database for studies on treatment of carpal tunnel syndrome from January 2008 to January 2018. A total of 105 studies were included in the final analysis. The metrics used to assess outcomes in each studies were collected, compared, and described.

Results:

Nearly all the studies used a patient-reported outcome measure (PROM) to assess outcomes (94%). The most common PROMs used were the Boston Carpal Tunnel Questionnaire (60%) and the Visual Analog Scale for pain (51%). Electrophysiological testing and physical examination were also commonly used to assess outcomes (50% and 46%, respectively). Cost, sleep, and return to activities of daily living were assessed in a minority of studies (1%, 1%, and 5%, respectively).

Conclusions:

Successful treatment of carpal tunnel syndrome is commonly defined based on a PROM, highlighting recent efforts to measure outcomes from the patient’s perspective. Other patient-centered metrics such as return to work and sleep quality, however, were rarely reported, whereas objective measures such as nerve conduction studies were prevalent. Further work is needed to determine patients’ preferred method of measuring outcomes after treatment for carpal tunnel syndrome to inform goal-directed decision-making and treatment.
What affects the magnitude of age-related dual-task costs in working memory? The role of stimulus domain and access to semantic representations
Authors: Jaroslawska Agnieszka J , Rhodes Stephen , Belletier Clément , Doherty Jason M , Cowan Nelson , Neveh-Benjamin Moshe , Barrouillet Pierre , Camos Valerie , Logie Robert H
Published: October 2020

Although there is evidence that the effect of including a concurrent processing demand on the storage of information in working memory is disproportionately larger for older than younger adults, not all studies show this age-related impairment, and the critical factors responsible for any such impairment remain elusive. Here we assess whether domain overlap between storage and processing activities, and access to semantic representations, are important determinants of performance in a sample of younger and older adults ( N = 119). We developed four versions of a processing task by manipulating the type of stimuli involved (either verbal or non-verbal) and the decision that participants had to make about the stimuli presented on the screen. Participants either had to perform a spatial judgement, in deciding whether the verbal or non-verbal item was presented above or below the centre of the screen, or a semantic judgement, in deciding whether the stimulus refers to something living or not living. The memory task was serial-ordered recall of visually presented letters. The study revealed a large increase in age-related memory differences when concurrent processing was required. These differences were smaller when storage and processing activities both used verbal materials. Dual-task effects on processing were also disproportionate for older adults. Age differences in processing performance appeared larger for tasks requiring spatial decisions rather than semantic decisions. We discuss these findings in relation to three competing frameworks of working memory and the extant literature on cognitive ageing.
Oxygen therapy via high flow nasal cannula in severe respiratory failure caused by Sars-Cov-2 infection: a real-life observational study
Authors: Procopio Giada , Cancelliere Anna , Trecarichi Enrico Maria , Mazzitelli Maria , Arrighi Eugenio , Perri Graziella , Serapide Francesca , Pelaia Corrado , Lio Elena , Busceti Maria Teresa , Pelle Maria Chiara , Ricchio Marco , Scaglione Vincenzo , Davoli Chiara , Fusco Paolo , La Gamba Valentina , Torti Carlo , Pelaia Girolamo
Published: October 2020

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death.

In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man–machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS.

The reviews of this paper are available via the supplemental material section.
Diagnosis and treatment of hemophagocytic histiocytic sarcoma in a cat
Authors: Huber Brian , Leleonnec Marc
Published: October 2020

Case summary

A 7-year-old spayed female domestic shorthair cat was presented for persistent anemia of unknown origin. Splenomegaly was diagnosed through physical examination and abdominal radiographs, and an abdominal ultrasound was performed. The ultrasound showed splenomegaly, as well as one discrete mass in the body of the spleen. A splenectomy was performed and histopathology along with immunohistochemistry for CD18 and CD204 confirmed a diagnosis of hemophagocytic histiocytic sarcoma (HS). Two courses of lomustine (CCNU) chemotherapy were used in this cat along with adjuvant oral prednisolone and iron dextran injections, but the cat eventually succumbed to hepatic failure, presumed to be secondary to metastatic disease.

Relevance and novel information

The clinical pathology results and ultrasonographic studies performed before and after treatment in this cat provide useful preliminary information about the biologic behavior and response to treatment for this rare cancer. This is also the first reported case where both CD18 and CD204 were strongly positive, confirming hemophagocytic HS in a cat.
A Jack of All Trades Is a Master of None: The Nexus of Firm-specific Human Capital, Ambidexterity, Productivity and Firm Performance
Authors: Kengatharan Navaneethakrishnan
Published: October 2020

Drawing on the knowledge-based theory of the firm and organisational learning theory, the present study chiefly examines the impact of firm-specific human capital on organisational ambidexterity and the subsequent effect of organisational ambidexterity on productivity by integrating human capital theory with the theory of transaction cost. The data were garnered from 197 managers in Sri Lanka with self-reported questionnaires in a time-lagged approach. The results disclose strong significant relationships between the variables investigated: a chain of positive relationships between firm-specific human capital and organisational ambidexterity, organisational ambidexterity and productivity, and productivity and firm performance; and mediated relationships between firm-specific human capital and productivity through organisational ambidexterity, and between organisational ambidexterity and firm performance via productivity. The findings of the study push back the frontiers of human resource management literature in many ways. Notably, managers should be cognizant of the effects of firm-specific human capital, organisational ambidexterity, and productivity on firm performance.
Social Justice and Inclusion Within the Right-based Universal Workfare Programme with Self-selection: Lessons and Ways Forward from the Participation of SCs and STs in MGNREGA in Karnataka
Authors: Kumar Sanjiv , Madheswaran S. , Vani B. P.
Published: October 2020

MGNREGA is a right-based universal, demand-driven workforce programme with self-selection, providing 100 days of guaranteed employment and productive asset to the poor households (HHs). Its universalism assured unlimited resources to satisfy any demand and hard manual labour ensured that only poor would like to access it by design. The programme earmarked 33 per cent share for women but did not as a right or policy incorporate any definite share or affirmative action for the Scheduled Castes/Scheduled Tribes (SCs/STs) like other flagship programmes of Pradhan Mantri Awas Yojana (PMAY) or Deen Dayal Upadhyaya Grameen Kaushalya Yojana (DDU-GKY). In the light of the above paradigm, this study explores as to how far this programme had accommodated the interests and requirements of the SCs/STs in Karnataka, providing equitable wage work and productive sustainable assets by building their awareness, providing them equitable space in participatory planning and grassroots monitoring, augmenting their capability to demand work and enabling them to self-select, and in case of breach of their rights approaching accountability through social audit or Ombudsman. The study finds low awareness, low grassroots participation in planning and monitoring, and inequitable participation of SCs/STs in both wage employment and assets. The study finds exclusion of SCs/STs from the assets sharper and more pronounced than their exclusion in wage employment. The study finds evidence that a right-based workfare programme with self-selection alone was incapable of being a substitute for earmarking (reservation, affirmative action) and protecting the interests of SC/ST HHs. The study finds that promotional goals included in the guidelines do not by themselves translate into formal actions, monitorable outputs and outcomes. Our primary data also show that the socio-economic and political predicament of SC/ST HHs justified a case for definite affirmative action for them. The study gathers primary and secondary evidences to show that in Karnataka, the programme failed the test of social justice and inclusion proportionate to the disabilities and need of SCs/STs and required immediate attention and policy responses.
The “Munich School” as a Corrective in World Christianity
Authors: Daughrity Dyron B.
Published: October 2020

Klaus Koschorke and others from the so-called Munich School have added an important corrective to the study of World Christianity. With an emphasis on “South to South” connections, an insistence on “polycentric” origins, and an ever-present awareness of transcontinental cooperation in Christian missions, this school of thought is an extremely helpful and thought-provoking approach to World Christian studies that many in the English-speaking West are only recently learning about. Koschorke’s latest two books break new ground in the field and should be on the radar of all scholars of World Christianity.
Submental Artery Island Flap for Soft Tissue Coverage of a Mandibular Reconstruction Plate in a High-Risk Patient With Medication-Related Osteonecrosis of the Jaw
Authors: Shanti Rabie M. , Choi James G. , Okasha Mohammad , Stanton David C.
Published: October 2020

We present a case of a 69-year-old woman with multiple complicating comorbidities who developed medication-related osteonecrosis of the jaw secondary to extraction of multiple teeth with a history of intravenous bisphosphonate therapy for metastatic breast cancer requiring staged management with segmental mandibulectomy with placement of external pin fixator with subsequent exchange of this device for a titanium reconstruction plate and a submental island pedicled flap for soft tissue coverage of the bridging reconstruction plate. Once the surgical sites were well-healed that patient would immediately return to a satisfactory functional outcome with ability to tolerate a soft diet. Furthermore, the patient did not have complications (ie, cardiac, pulmonary, venous thromboembolism, sepsis, surgical site infection, reoperation) during her hospitalization and has done well with her long-term recovery.
Parenting stress and risk of child maltreatment during the COVID-19 pandemic: A family stress theory-informed perspective
Authors: Wu Qi , Xu Yanfeng
Published: October 2020

The risk of child maltreatment is heightened during the pandemic due to multiple COVID-19 related stressors, such as physical and mental health concerns, economic stress, challenges in homeschooling, marital conflicts and intimate personal violence, and intensified child–parent relationships. Both parental internal (e.g., parenting styles) and external resources (e.g., social support), and parental perceptions toward stressors will affect how parents cope with these stressors, which may exacerbate or mitigate the risk of child maltreatment. Guided by family stress theory, this article identifies COVID-19 related stressors at the family level, and further elaborates on how these stressors are associated with child maltreatment via parents’ resources, perceptions, and coping strategies. Implications for future practice and research are discussed.
Entrepreneurship responding to adversity: Equilibrating Adverse Events and Disequilibrating Persistent Adversity
Authors: Shepherd Dean A. , Williams Trenton
Published: October 2020

Entrepreneurship and organization theory can both benefit from a mutual exchange to theorize on a number of topics. One such topic is organizational responses to adversity. In this paper, we theorize by abstracting across highly contextualized papers on entrepreneurship’s role in responding to adversity and propose that entrepreneurial action, such as the creation of new ventures, performs a different function depending on whether the adversity is an event or a persistent state. Specifically, we theorize that entrepreneurial action performs the role of an equilibrating mechanism when adversity is an event, such as an earthquake that kills thousands of people and injures many more, business failure, and perhaps the Covid-19 pandemic, and performs the role of a disequilibrating mechanism when adversity is a persistent state, such as for poor farmers in rural India, women in patriarchal communities in Bangladesh, and perhaps the Covid-19 pandemic. We then explore the possibilities of entrepreneurship for both equilibrating and disequilibrating adversity and offer some future research opportunities that we believe can make important contributions to organization theory and the entrepreneurship literature.
A robust multiplex immunoaffinity mass spectrometry assay (PromarkerD) for clinical prediction of diabetic kidney disease
Authors: Bringans Scott , Ito Jason , Casey Tammy , Thomas Sarah , Peters Kirsten , Crossett Ben , Coleman Orla , Ebhardt Holger A. , Pennington Stephen R. , Lipscombe Richard
Published: October 2020

Background

PromarkerD is a novel proteomics derived blood test for predicting diabetic kidney disease (DKD). The test is based on an algorithm that combines the measurement of three plasma protein biomarkers (CD5L, APOA4, and IBP3) with three clinical variables (age, HDL-cholesterol, and eGFR). The initial format of the assay used immunodepletion of plasma samples followed by targeted mass spectrometry (MRM-LCMS). The aim of this study was to convert the existing assay into an immunoaffinity approach compatible with higher throughput and robust clinical application.

Methods

A newly optimised immunoaffinity-based assay was developed in a 96 well format with MRM measurements made using a low-flow LCMS method. The stability, reproducibility and precision of the assay was evaluated. A direct comparison between the immunoaffinity method and the original immunodepletion method was conducted on a 100-person cohort. Subsequently, an inter-lab study was performed of the optimised immunoaffinity method in two independent laboratories.

Results

Processing of plasma samples was greatly simplified by switching to an immunoaffinity bead capture method, coupled to a faster and more robust microflow LCMS system. Processing time was reduced from seven to two days and the chromatography reduced from 90 to 8 min. Biomarker stability by temperature and time difference treatments passed acceptance criteria. Intra/Inter-day test reproducibility and precision were within 11% CV for all biomarkers. PromarkerD test results from the new immunoaffinity method demonstrated excellent correlation (R = 0.96) to the original immunodepletion method. The immunoaffinity assay was successfully transferred to a second laboratory (R = 0.98) demonstrating the robustness of the methodology and ease of method transfer.

Conclusions

An immunoaffinity capture targeted mass spectrometry assay was developed and optimised. It showed statistically comparable results to those obtained from the original immunodepletion method and was also able to provide comparable results when deployed to an independent laboratory. Taking a research grade assay and optimising to a clinical grade workflow provides insights into the future of multiplex biomarker measurement with an immunoaffinity mass spectrometry foundation. In the current format the PromarkerD immunoaffinity assay has the potential to make a significant impact on prediction of diabetic kidney disease with consequent benefit to patients.
Development and validation of a fourteen- innate immunity-related gene pairs signature for predicting prognosis head and neck squamous cell carcinoma
Authors: Zhang Fujun , Liu Yu , Yang Yixin , Yang Kai
Published: October 2020

Background

Immune-related genes is closely related to the occurrence and prognosis of head and neck squamous cell carcinoma (HNSCC). At the same time, immune-related genes have great potential as prognostic markers in many types of cancer. The prognosis of HNSCC is still poor currently, and it may be effective to predict the clinical outcome of HNSCC by immunogenic analysis.

Methods

RNASeq and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), the MINiML format GSE65858 chip expression data was downloaded from NCBI, and immune-related genes was downloaded from the InnateDB database. Immune-related genes in 519 HNSC patients were integrated from TCGA dataset. By using multivariate COX analysis and Lasso regression, robust immune-related gene pairs (IRGPs) that predict clinical outcomes of HNSCC were identified. Finally, a risk prognostic model related to immune gene pair was established and verified by clinical features, test sets and GEO external validation set.

Results

A total of 699 IRGPs were significantly correlated with the prognosis of HNSCC patients. Fourteen robust IRGPs were finally obtained by Lasso regression and a prognostic risk prediction model was constructed. Risk score of each sample were calculated based on Risk models and divided into the high-risk group (Risk-H) and low Risk group (Risk-L). Risk models were able to stratify the risk in patients with TNM Stage, Age, gender, and smoking history, and the AUC > 0.65 in training set and test set, shows that 14-IRGPs signature in patients with HNSCC has excellent classification performance. In addition, 14-IRGPs had the highest average C index compared with the prognostic characteristics and T, N, and Age of the 3 previously reported HNSCC.

Conclusion

This study constructed 14-IRGPs as a novel prognostic marker for predicting survival in HNSCC patients.
The impact of hypothetical PErsonalised Risk Information on informed choice and intention to undergo Colorectal Cancer screening colonoscopy in Scotland (PERICCS)—a randomised controlled trial
Authors: Digby Jayne , O’Carroll Ronan E. , Chambers Julie A. , Steele Robert J. C.
Published: October 2020

Background

There is currently no existing evidence on the effects of personalised risk information on uptake of colonoscopy following first line screening for colorectal cancer. This study aimed to measure the impact of providing risk information based on faecal haemoglobin concentration to allow a fully informed choice around whether or not to undergo colonoscopy.

Methods

Two thousand seven hundred sixty-seven participants from the Scottish Bowel Screening Programme (SBoSP) database, who had not recently been invited for screening, were randomised to receive one of three types of hypothetical risk information materials: (1) numerical risk information (risk categories of one in 40, one in 1600 and one in 3500), (2) categorical risk information (highest, moderate and lowest risk), or (3) positive screening result letter (control group). The primary outcome was the impact of the risk materials on intention to undergo colonoscopy, to allow comparison with the current colonoscopy uptake of 77% for those with a positive screening result in the SBoSP. Secondary outcomes were knowledge, attitudes and emotional responses to the materials.

Results

Four hundred thirty-four (15.7%) agreed to participate with 100 from the numerical risk group (69.0%), 104 from the categorical risk group (72.2%) and 104 from the control group (71.7%) returning completed materials. Intention to undergo colonoscopy was highest in the highest risk groups for the numerical and categorical study arms (96.8% and 95.3%, respectively), but even in the lowest risk groups was > 50% (58.1% and 60.7%, respectively). Adequate knowledge of colorectal screening and the risks and benefits of colonoscopy was found in ≥ 98% of participants in all three arms. All participants reported that they found the information easy-to-understand. 19.1%, 24.0% and 29.6% of those in the numerical, categorical and control group, respectively, reported that they found the information distressing (p > 0.05).

Conclusions

Applying the risk categories to existing SBoSP data shows that if all participants were offered an informed choice to have colonoscopy, over two thirds of participants would intend to have the test. Equating to an increase in the number of screening colonoscopies from approx. 14,000 to 400,000 per annum, this would place an unmanageable demand on colonoscopy services, with a very small proportion of cancers and pre-cancers detected. However, the response to the materials were very positive, suggesting that providing risk information to those in lowest and moderate risk groups along with advice that colonoscopy is not currently recommended may be an option. Future research would be required to examine actual uptake.

Trial registration

Date applied 1 December 2017 ISRCTN number 14254582.
Automated computed tomography quantification of fibrosis predicts prognosis in combined pulmonary fibrosis and emphysema in a real-world setting: a single-centre, retrospective study
Authors: Nemoto Masahiro , Nei Yuichiro , Bartholmai Brian , Yoshida Kazuki , Matsui Hiroki , Nakashita Tamao , Motojima Shinji , Aoshima Masahiro , Ryu Jay H.
Published: October 2020

Background

Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.

Methods

We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE.

Results

Among 228 patients with CPFE, 89 had fibrosis affecting < 5% of their lungs, 54 had 5 to < 10% fibrosis, and 85 had ≥ 10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p < 0.001). In particular, among those with < 5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥ 10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥ 10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to < 10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.

Conclusions

Less severe (< 5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed.

Trial Registration Retrospectively registered.
Improved methods for mass production of magnetosomes and applications: a review
Authors: Basit Abdul , Wang Jiaojiao , Guo Fangfang , Niu Wei , Jiang Wei
Published: October 2020

Magnetotactic bacteria have the unique ability to synthesize magnetosomes (nano-sized magnetite or greigite crystals arranged in chain-like structures) in a variety of shapes and sizes. The chain alignment of magnetosomes enables magnetotactic bacteria to sense and orient themselves along geomagnetic fields. There is steadily increasing demand for magnetosomes in the areas of biotechnology, biomedicine, and environmental protection. Practical difficulties in cultivating magnetotactic bacteria and achieving consistent, high-yield magnetosome production under artificial environmental conditions have presented an obstacle to successful development of magnetosome applications in commercial areas. Here, we review information on magnetosome biosynthesis and strategies for enhancement of bacterial cell growth and magnetosome formation, and implications for improvement of magnetosome yield on a laboratory scale and mass-production (commercial or industrial) scale.
A qualitative analysis of vaccine decision makers’ conceptualization and fostering of ‘community engagement’ in India
Authors: Dutta Tapati , Meyerson Beth E. , Agley Jon , Barnes Priscilla A. , Sherwood-Laughlin Catherine , Nicholson-Crotty Jill
Published: October 2020

Background

Globally, and in India, research has highlighted the importance of community engagement in achieving national vaccination goals and in promoting health equity. However, community engagement is not well-defined and remains an underutilized approach. There is also paucity of literature on community engagement’s effectiveness in achieving vaccination outcomes. To address that gap, this study interviewed Indian vaccination decision makers to derive a shared understanding of the evolving conceptualization of community engagement, and how it has been fostered during India’s Decade of Vaccines (2010-2020).

Methods

Semi-structured interviews were conducted with 25 purposefully sampled national-level vaccine decision makers in India, including policymakers, immunization program heads, and vaccine technical committee leads. Participants were identified by their ‘elite’ status among decisionmakers in the Indian vaccination space. Schutz’ Social Phenomenological Theory guided development of an a priori framework derived from the Social Ecological Model. The framework helped organize participants’ conceptualizations of communities, community engagement, and related themes. Inter-rater reliability was computed for a subsample of coded interviews, and findings were validated in a one-day member check-in meeting with study participants and teams.

Results

The interviews successfully elucidated participants’ understanding of key terminology (“community”) and approaches to community engagement propagated by the vaccine decision makers. Participants conceptualized ‘communities’ as vaccine-eligible children, their parents, frontline healthcare workers, and vaccination influencers. Engagement with those communities was understood to mean vaccine outreach, capacity-building of healthcare workers, and information dissemination. However, participants indicated that there were neither explicit policy guidelines defining community engagement nor pertinent evaluation metrics, despite awareness that community engagement is complex and under-researched. Examples of different approaches to community engagement ranged from vaccine imposition to empowered community vaccination decision-making. Finally, participants proposed an operational definition of community engagement and discussed concerns related to implementing it.

Conclusions

Although decision makers had different perceptions about what constitutes a community, and how community engagement should optimally function, the combined group articulated its importance to ensure vaccination equity and reiterated the need for concerted political will to build trust with communities. At the same time, work remains to be done both in terms of research on community engagement as well as development of appropriate implementation and outcome metrics.
Continuum of hepatitis C care cascade in prison and following release in the direct-acting antivirals era
Authors: Hariri Sanam , Sharafi Heidar , Sheikh Mahdi , Merat Shahin , Hashemi Farnaz , Azimian Fatemeh , Tamadoni Babak , Ramazani Rashid , Gouya Mohammad Mehdi , Abbasi Behzad , Tashakorian Mehrzad , Alasvand Ramin , Alavian Seyed Moayed , Poustchi Hossein , Malekzadeh Reza
Published: October 2020

Background

People with criminal justice involvement contribute remarkably to the rising hepatitis C virus (HCV) burden; however, the continuum of care is a major barrier to prison-based programs. We aimed to evaluate a comprehensive HCV care model in an Iranian provincial prison.

Methods

Between 2017–2018, in the Karaj Central Prison, newly admitted male inmates received HCV antibody testing and venipuncture for RNA testing (antibody-positive only). Participants with positive RNA underwent direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir). Sustained virological response was evaluated at 12 weeks post-treatment (SVR12).

Results

Overall, from 3485 participants, 182 (5.2%) and 117 (3.4%) tested positive for HCV antibody and RNA, respectively. Among 116 patients who were eligible for treatment, 24% (n = 28) were released before treatment and 72% (n = 83) initiated DAA therapy, of whom 81% (n = 67/83) completed treatment in prison, and the rest were released. Of total released patients, 68% (n = 30/44) were linked to care in community, and 70% (n = 21/30) completed treatment, including 60% (n = 12/20) and 90% (n = 9/10) among those who were released before and during treatment, respectively. The overall HCV treatment uptake and completion were 89% (n = 103/116) and 85% (n = 88/103), respectively. From people who completed treatment, 43% (n = 38/88) attended for response assessment and all were cured (SVR12 = 100%).

Conclusions

Integrated HCV care models are highly effective and can be significantly strengthened by post-release interventions. The close collaboration of community and prison healthcare systems is crucial to promote high levels of treatment adherence. Future studies should investigate the predictors of engagement with HCV care following release.
The modifying role of physical activity in the cross-sectional and longitudinal association of health-related quality of life with physiological functioning-based latent classes and metabolic syndrome
Authors: Cerletti Paco , Keidel Dirk , Imboden Medea , Schindler Christian , Probst-Hensch Nicole
Published: October 2020

Background

Single cardio-metabolic risk factors are each known modifiable risk factors for adverse health and quality of life outcomes. Yet, evidence on the clustered effect of these parameters and the metabolic syndrome (MetS) on health-related quality of life (HRQoL) is still limited and mostly cross-sectional. The objectives of this study were to identify clusters of cardio-metabolic physiological functioning, to assess their associations with HRQoL in comparison with the MetS, to elucidate the modifying role of physical activity, and to assess differences in health service utilization.

Methods

This study is based on longitudinal data from two time points (2010/11 & 2017/18) of the Swiss Study on Air Pollution and Lung and Heart Diseases (SAPALDIA). Latent class analysis (LCA) grouped participants based on a priori selected cardio-metabolic and MetS related physiological functioning variables(Body mass index, body fat, glycated hemoglobin, blood triglycerides, blood pressure). The 36-item Short-Form Health Survey (SF-36) was used to assess HRQoL. Quantile regressions were performed with and without adjustment for physical activity, to detect independent associations of the latent classes, MetS and physical activity with HRQoL. To assess the modifying role of physical activity, we additionally grouped participants based on the combination of physical activity and latent classes or MetS, respectively. Logistic regressions were used to investigate health service utilization as outcome.

Results

The LCA resulted in three classes labeled “Healthy” (30% of participants in 2017/18), “At risk” and “Unhealthy” (29%). The Unhealthy class scored lowest in all physical component scores of HRQoL. Compared to healthy and active participants, inactive participants in the “Unhealthy” class showed lower scores in the physical functioning domain both cross-sectionally (− 9.10 (− 12.02; − 6.18)) and longitudinally. This group had an odds ratio of 2.69 (1.52; 4.74) for being hospitalized in the previous 12 months.

Conclusions

These results point to subjects with adverse cardio-metabolic physiological functioning and low activity levels as an important target group for health promotion and maintenance of well-being. The promotion of physical activity at the early stages of aging seems pivotal to mitigate the impact of the MetS on HRQoL at higher age.
Medial humeral epicondylar lesions and discreet calcified structures in the canine elbow: radiographic description of 183 cases
Authors: Rørvik Arne Magnus , Trangerud Cathrine , Grondalen Jorunn
Published: October 2020

Background

In this 4-year prospective observational study, all elbows in a dysplasia screening program including 14,073 dogs were studied using radiographs in two projections. Elbows were evaluated for the presence of medial humeral epicondylar lesions or discreet calcified structures and were described as they appeared. The age, breed, and sex of affected dogs were recorded. The prevalence for each lesion was calculated exclusively on breeds where the number of radiographed dogs exceeded 500.

Results

Medial humeral epicondylar lesions or medial discreet calcified structures were diagnosed in 183 dogs and 211 elbows. The prevalence of true Flexor enthesopathy (FE) in this Norwegian population of mainly young, large breed dogs was calculated to be approximately 1.4 per 1000 dogs and varied by breed. Also, the prevalence of the other lesions varied considerably by breed. The most common finding was discreet calcified structures, termed medial ossified structures (MOS) (0.7%).

In elbows affected with fragmented medial epicondyles (FME) (0.07%) and especially FE (0.14%), the degree of periarticular new bone formation (PNBF) was increased when compared to unaffected elbows. In joints affected with MOSs or medial lucent lesions MLLs (0.25%), there was no difference in the presence or degree of PNBF compared to unaffected joints, even in older dogs.

Conclusions

The prevalence of medial humeral epicondylar lesions and MOSs differs considerably among dog breeds. Elbow joints with FMEs and particularly FE had a highly increased presence and degree of PNBF compared to joints without these lesions. Elbow joints with MOSs or MLLs did not have an increased presence or degree of PNBF compared to joints without these lesions.
The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury
Authors: Murugan Madhuvika , Zheng Jiaying , Wu Gongxiong , Mogilevsky Rochelle , Zheng Xin , Hu Peiwen , Wu Junfang , Wu Long-Jun
Published: October 2020

Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1−/−) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1−/− mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1−/− mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.
MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1
Authors: Vescarelli Enrica , Gerini Giulia , Megiorni Francesca , Anastasiadou Eleni , Pontecorvi Paola , Solito Luciana , De Vitis Claudia , Camero Simona , Marchetti Claudia , Mancini Rita , Benedetti Panici Pierluigi , Dominici Carlo , Romano Ferdinando , Angeloni Antonio , Marchese Cinzia , Ceccarelli Simona
Published: October 2020

Background

Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance.

Methods

Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons’ correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells.

Results

We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells.

Conclusions

These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.
Metabolic engineering of Yarrowia lipolytica for thermoresistance and enhanced erythritol productivity
Authors: Wang Nan , Chi Ping , Zou Yawen , Xu Yirong , Xu Shuo , Bilal Muhammad , Fickers Patrick , Cheng Hairong
Published: October 2020

Background

Functional sugar alcohols have been widely used in the food, medicine, and pharmaceutical industries for their unique properties. Among these, erythritol is a zero calories sweetener produced by the yeast Yarrowia lipolytica. However, in wild-type strains, erythritol is produced with low productivity and yield and only under high osmotic pressure together with other undesired polyols, such as mannitol or d-arabitol. The yeast is also able to catabolize erythritol in non-stressing conditions.

Results

Herein, Y. lipolytica has been metabolically engineered to increase erythritol production titer, yield, and productivity from glucose. This consisted of the disruption of anabolic pathways for mannitol and d-arabitol together with the erythritol catabolic pathway. Genes ZWF1 and GND encoding, respectively, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also constitutively expressed in regenerating the NADPH2 consumed during erythritol synthesis. Finally, the gene RSP5 gene from Saccharomyces cerevisiae encoding ubiquitin ligase was overexpressed to improve cell thermoresistance. The resulting strain HCY118 is impaired in mannitol or d-arabitol production and erythritol consumption. It can grow well up to 35 °C and retain an efficient erythritol production capacity at 33 °C. The yield, production, and productivity reached 0.63 g/g, 190 g/L, and 1.97 g/L·h in 2-L flasks, and increased to 0.65 g/g, 196 g/L, and 2.51 g/L·h in 30-m3 fermentor, respectively, which has economical practical importance.

Conclusion

The strategy developed herein yielded an engineered Y. lipolytica strain with enhanced thermoresistance and NADPH supply, resulting in a higher ability to produce erythritol, but not mannitol or d-arabitol from glucose. This is of interest for process development since it will reduce the cost of bioreactor cooling and erythritol purification.