bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic behavior of metabolic syndrome progression: a comprehensive systematic review on recent discoveries
Authors: Bagheri Pezhman , Khalili Davood , Seif Mozhgan , Rezaianzadeh Abbas
Published: March 2021

Background

The assessment of the natural history of metabolic syndrome (MetS) has an important role in clarifying the pathways of this disorder.

Objective

This study purposed to provide a rational statistical view of MetS progression pathway.

Methods

We performed a systematic review in accordance with the PRISMA Statement until September 2019 in the Medline/PubMed, Scopus, Embase, Web of Science and Google Scholar databases. From the 68 found studies, 12 studies were eligible for review finally.

Results

The selected studies were divided in 2 groups with Markovian and non-Markovian approach. With the Markov approach, the most important trigger for the MetS chain was dyslipidemia with overweight/obesity in the under-50 and with hypertension in the over-50 age group, where overweight/obesity was more important in women and hypertension in men. In non-Markov approach, the most common trigger was hypertension. Transition probability (TP) from no component to MetS were higher in all Markovian studies in men than in women. In the Markovians the combination of dyslipidemia with overweight/obesity and in non-Markovians, hyperglycemia with overweight/obesity were the most common combinations. Finally, the most important components, which predict the MetS, were 2-component states and hyperglycemia in Markovian approach and overweight/obesity in non-Markovians.

Conclusions

Among the components of the MetS, dyslipidemia and hypertension seems to be the main developer components in natural history of the MetS. Also, in this chain, the most likely combination over time that determines the future status of people seems to be the combination of dyslipidemia with obesity or hyperglycemia. However, more research is needed.
Complete root coverage in the treatment of Miller class III or RT2 gingival recessions: a systematic review and meta-analysis
Authors: Fernández-Jiménez Aitziber , García-De-La-Fuente Ana-María , Estefanía-Fresco Ruth , Marichalar-Mendia Xabier , Aguirre-Urizar José-Manuel , Aguirre-Zorzano Luis-Antonio
Published: March 2021

Background

The primary objective of this systematic review and meta-analysis was to assess the evidence on complete root coverage (CRC) achieved by periodontal plastic techniques in the treatment of Miller class III/RT2 gingival recessions, comparing techniques developed along the twentieth century (pre-twenty-first) versus surgical approaches of the twenty-first century (21st).

Methods

An electronic bibliographic search was carried out in four databases up to December 2019, focusing on studies that reported CRC results in Miller class III or RT2 recessions treatment with at least a six-month follow-up. In addition, a random-effects models’ meta-analysis was performed for the CRC, comparing pre-twenty-first versus twenty-first century techniques at 6 months, 12 months and more than 12 months.

Results

Thirty-seven publications were included. A total of 933 gingival recessions were treated, 298 with pre-twenty-first century surgical techniques and 635 with techniques from the twenty-first century. CRC was achieved at 6 months on half of the recessions (pre-twenty-first: 57.60% vs. 21st: 51.11%), but decreased markedly for twenty-first century techniques at 12 months (pre-twenty-first: 63.82% vs. 21st: 32.87%). Thereafter, this difference was the other way around (> 12 months: pre-twenty-first: 5.26% vs. 21st: 19.65%). The meta-analysis showed a high heterogeneity, with no significant differences amongst the techniques.

Conclusions

Although CRC might be achievable by treating Miller class III or RT2 recessions with any of the described techniques, its long-term stability is not predictable. More randomized clinical trials with longer follow-ups and several visits, are needed. In addition, the patient’s satisfaction should also be assessed.
Exploring the pedagogical design features of the flipped classroom in undergraduate nursing education: a systematic review
Authors: Youhasan Punithalingam , Chen Yan , Lyndon Mataroria , Henning Marcus A.
Published: March 2021

Background

In recent years, technological advancement has enabled the use of blended learning approaches, including flipped classrooms. Flipped classrooms promote higher-order knowledge application – a key component of nursing education. This systematic review aims to evaluate the empirical evidence and refereed literature pertaining to the development, application and effectiveness of flipped classrooms in reference to undergraduate nursing education.

Methods

A PRISMA systematic review protocol was implemented to investigate the literature pertaining to the development, implementation and effectiveness of flipped classroom pedagogy in undergraduate nursing education. Seven databases (Scopus, PsycINFO, CINAHL, ERIC, MEDLINE, Cochrane, Web of Science) were utilised to survey the salient literature. Articles were appraised with respect to their level of evidence, the origin of study, study design, the aims/s of the study, and the key outcomes of the study. A qualitative synthesis was then conducted to summarise the study findings.

Results

The initial search identified 1263 potentially relevant articles. After comprehensively reviewing the initial catchment using several analytical phases, 27 articles were considered for the final review, most of which were conducted in the USA and South Korea. A range of research designs were applied to measure or discuss the outcomes and design features of the flipped classroom pedagogy when applied to undergraduate nursing education. The review indicated that a common operational flipped classroom model involves three key components, namely pre-classroom activities, in-classroom activities and post-classroom activities, guided by two instructional system design principles. The review predominantly identified positive learning outcomes among undergraduate nursing students, after experiencing the flipped classroom, in terms of skills, knowledge and attitudes. However, a few studies reported contrasting findings, possibly due to the incompatibility of the flipped classroom pedagogy with the traditional learning culture.

Conclusions

Current evidence in this systematic review suggests that incorporating the flipped classroom pedagogy could yield positive educational outcomes in undergraduate nursing education. There are promising pedagogical models available for adapting or developing the flipped classroom pedagogy in undergraduate nursing education.
Healthcare professionals’ perceptions about interprofessional teamwork: a national survey within Swedish child healthcare services
Authors: Nygren Ulrika Svea , Tindberg Ylva , Eriksson Leif , Larsson Ulf , Sandberg Håkan , Nordgren Lena
Published: March 2021

Background

Globally, interprofessional teamwork is described as a key method to promote health and prevent illness in children, namely, to achieve the goals of Child Healthcare Services (CHS). However, how teamwork should be designed within CHS to achieve the goals is unclear. This study aimed to investigate healthcare professionals’ perceptions about 1) taking part in interprofessional teamwork, 2) team characteristics, and 3) whether the perceptions were related to professional affiliation or workplace.

Methods

A national cross-sectional survey was conducted using a web-based study-specific questionnaire sent to all accessible nurses, physicians, and psychologists in Swedish CHS (n = 3552). The response rate was 31.5%. To identify possible associations, logistic regressions were conducted.

Results

Almost all respondents, 1096/1119 (97.9%), reported taking part in some type of interprofessional teamwork within the Swedish CHS. Among those, the most common was team-based visits (82.2%). It was perceived that performing team-based visits resulted in fulfilled goals, expertise exceeding individual team members’ competences, provision of high-quality care, and meeting children’s and families’ needs, to a greater extent, than if not performing team-based visits. Correspondingly, working as a team in parental groups was perceived as resulting in fulfilled goals, meeting the needs of children and their families, and continuity within the team to a greater extent than if not working together in a team. Professional affiliation was associated with different perceptions and types of teamwork. Family Centers were positively associated with all types of teamwork as well as continuity within the team.

Conclusions

Healthcare professionals’ perceptions about team characteristics were associated with professional affiliation, workplace, and type of teamwork (defined as team activities) within the CHS. Professionals within Swedish CHS, taking part in team-based visits and in interprofessional teamwork in parental groups, perceived that the team fulfilled its goals and met the needs of children and families to a greater extent than professionals not taking part in these types of teamwork. Professionals at Family Centers were more likely to work in teams in different ways.

Knowledge about interprofessional teamwork for individuals and groups in Swedish CHS might also be valuable in other healthcare settings, dealing with complex needs.
The prediction of Metabolic Syndrome alterations is improved by combining waist circumference and handgrip strength measurements compared to either alone
Authors: Lopez-Lopez Jose P. , Cohen Daniel D. , Ney-Salazar Daniela , Martinez Daniel , Otero Johanna , Gomez-Arbelaez Diego , Camacho Paul A. , Sanchez-Vallejo Gregorio , Arcos Edgar , Narvaez Claudia , Garcia Henry , Perez Maritza , Molina Dora I. , Cure Carlos , Sotomayor Aristides , Rico Álvaro , Hernandez-Triana Eric , Duran Myriam , Cotes Fresia , Leong Darryl P. , Rangarajan Sumathy , Yusuf Salim , Lopez-Jaramillo Patricio
Published: March 2021

Background

Adiposity is a major component of the metabolic syndrome (MetS), low muscle strength has also been identified as a risk factor for MetS and for cardiovascular disease. We describe the prevalence of MetS and evaluate the relationship between muscle strength, anthropometric measures of adiposity, and associations with the cluster of the components of MetS, in a middle-income country.

Methods

MetS was defined by the International Diabetes Federation criteria. To assess the association between anthropometric variables (waist circumference (WC), waist-to-hip ratio (W/H), body mass index (BMI)), strength (handgrip/kg bodyweight (HGS/BW)) and the cluster of MetS, we created a MetS score. For each alteration (high triglycerides, low HDLc, dysglycemia, or high blood pressure) one point was conferred. To evaluate the association an index of fat:muscle and MetS score, participants were divided into 9 groups based on combinations of sex-specific tertiles of WC and HGS/BW.

Results

The overall prevalence of MetS in the 5,026 participants (64% women; mean age 51.2 years) was 42%. Lower HGS/BW, and higher WC, BMI, and W/H were associated with a higher MetS score. Amongst the 9 HGS/BW:WC groups, participants in the lowest tertile of HGS/BW and the highest tertile of WC had a higher MetS score (OR = 4.69 in women and OR = 8.25 in men;p < 0.01) compared to those in the highest tertile of HGS/BW and in the lowest tertile of WC.

Conclusion

WC was the principal risk factor for a high MetS score and an inverse association between HGS/BW and MetS score was found. Combining these anthropometric measures improved the prediction of metabolic alterations over either alone.
Correction to: Optimizing the contributions of nursing and midwifery workforces: #Protect, #Invest, #Together
Authors: Buchan James , Campbell James , McCarthy Carey
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Circadian clock: a regulator of the immunity in cancer
Authors: Zhang Zhen , Zeng Puhua , Gao Wenhui , Zhou Qing , Feng Ting , Tian Xuefei
Published: March 2021

The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer.
Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate- data of the German BIKER registry
Authors: Raab A. , Kallinich T. , Huscher D. , Foeldvari I. , Weller-Heinemann F. , Dressler F. , Kuemmerle-Deschner J. B. , Klein A. , Horneff G.
Published: March 2021

Background

Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate.

Methods

Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events.

Results

From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate.

Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years.

Conclusions

Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.
Tibial cutting guide (resector) holding pins position and subsequent risks of periprosthetic fracture in unicompartmental knee arthroplasty: a finite element analysis study
Authors: Chui Elvis Chun-sing , Lau Lawrence Chun-man , Kwok Carson Ka-bon , Ng Jonathan Patrick , Hung Yuk-wah , Yung Patrick Shu-hang , Fan Jason Chi-ho
Published: March 2021

Background

Periprosthetic fracture of the tibia after unicompartmental knee arthroplasty has been reported to be associated with excessive pin holes created for stabilization of the cutting guide. However, fractures have also been reported in cases using two pins as in the method suggested by the manufacturer. It is currently unclear whether variations in pinhole positions make a difference in proximal tibial fracture risk.

Methods

Finite element models were constructed using Chinese female bone computed tomography images, with bone cuts made according to the surgical steps of implanting a fixed bearing unicompartmental arthroplasty. Four combinations of pinholes (pins placed more closely to the medial tibial cortex or centrally along the mechanical axis as allowed by the tibial cutting guide) created for tibial cutting guide placement were tested by finite element analyses. Testing loads were applied for simulating standing postures. The maximum von Mises stress on the tibial plateau was evaluated.

Results

Pinhole placed close to the medial edge of the proximal tibial plateau is associated with the highest stress (27.67 Mpa) and is more likely to result in medial tibial fracture. On the contrary, pinhole placed along the central axis near the tibial tuberosity has the lowest stress (1.71 Mpa) and reflects lower risk of fracture.

Conclusion

The present study revealed that placing tibial cutting guide holding pins centrally would lower the risks of periprosthetic fracture of the medial tibial plateau by analyzing the associated stress in various pin hole positions using finite element analysis.
A modified oblique incision in hamstring tendon graft harvesting during ACL reconstruction
Authors: Zhu Biao , Li Xuelei , Lou Tengteng
Published: March 2021

Background

During anterior cruciate ligament (ACL) reconstruction, different methods of harvesting hamstring tendon may lead to different degrees of injury to the inferior patellar branch of the saphenous nerve (IPBSN). Most of recent studies in the literature suggest that the classic oblique incision (COI) can reduce the incidence of IPBSN injury. We proposed a modified oblique incision (MOI) and compared it with the COI in terms of the resulting levels of injury and sensory loss and the clinical outcome.

Methods

Patients with ACL injury admitted to our hospital from April 2015 to July 2019 were randomly selected and included in our study. Thirty patients underwent the COI to harvest hamstring tendons, and the other 32 patients underwent the MOI. The pin prick test was performed to detect the sensation loss at 2 weeks, 6 months, and 1 year after the operation. Digital photos of the region of hypoesthesia area were taken, and then, a computer software (Adobe Photoshop CS6, 13.0.1) was used to calculate the area of the hypoesthesia. The length of the incision and knee joint functional score were also recorded.

Results

At the final follow-up, the incidence of IPBSN injury in COI and MOI were 33.3% and 9.4%, and the areas of paresthesia were 26.4±2.4 cm2 and 9.8±3.4 cm2 respectively. There was no significant difference in the incision length or knee functional score between the two groups.

Conclusion

The MOI can significantly reduce the risk of injury to the IPBSN, reduce the area of hypoesthesia, and lead to high subjective satisfaction. Therefore, compared with the COI, the MOI is a better method of harvesting hamstring tendons in ACL reconstruction.
Deer antler extract potentially facilitates xiphoid cartilage growth and regeneration and prevents inflammatory susceptibility by regulating multiple functional genes
Authors: Guan Mengqi , Pan Daian , Zhang Mei , Leng Xiangyang , Yao Baojin
Published: March 2021

Background

Deer antler is a zoological exception due to its fantastic characteristics, including amazing growth rate and repeatable regeneration. Deer antler has been used as a key ingredient in traditional Chinese medicine relating to kidney and bone health for centuries. The aim of this study was to dissect the molecular regulation of deer antler extract (DAE) on xiphoid cartilage (XC).

Methods

The DAE used in this experiment was same as the one that was prepared as previously described. The specific pathogen-free (SPF) grade Sprague-Dawley (SD) rats were randomly divided into blank group (n =10) and DAE group (n =10) after 1-week adaptive feeding. The DAE used in this experiment was same as the one that was prepared as previously described. The rats in DAE group were fed with DAE for 3 weeks at a dose of 0.2 g/kg per day according to the body surface area normalization method, and the rats in blank group were fed with drinking water. Total RNA was extracted from XC located in the most distal edge of the sternum. Illumina RNA sequencing (RNA-seq) in combination with quantitative real-time polymerase chain reaction (qRT-PCR) validation assay was carried out to dissect the molecular regulation of DAE on XC.

Results

We demonstrated that DAE significantly increased the expression levels of DEGs involved in cartilage growth and regeneration, but decreased the expression levels of DEGs involved in inflammation, and mildly increased the expression levels of DEGs involved in chondrogenesis and chondrocyte proliferation.

Conclusions

Our findings suggest that DAE might serve as a complementary therapeutic regent for cartilage growth and regeneration to treat cartilage degenerative disease, such as osteoarthritis.
Association between thyroid autoimmunity and ovarian reserve in women with hypothyroidism
Authors: Morales-Martínez Felipe A. , Sordia-Hernández Luis H. , Ruiz Martha Merino , Garcia-Luna Selene , Valdés-Martínez Otto H. , Vidal-Gutierez Oscar
Published: March 2021

Background

The ovarian function and therefore the ovarian reserve may be compromised by the pathogenesis of autoimmune diseases of which, Hashimoto’s thyroiditis (HT) is the most common in women of reproductive age. Furthermore, a prolonged reduction in thyroid hormone concentration results in a broad spectrum of reproductive alteration. Previous reports in the literature have been controversial regarding the impact of hypothyroidism and alterations in the ovarian reserve. Thus, this prospective and comparative study aimed to evaluate the association of hypothyroidism with low ovarian reserve.

Materials and Methods

A subset of 27 patients with primary autoimmune hypothyroidism were compared to healthy women. The ovarian reserve was assessed through the anti-Mullerian hormone (AMH) and the antral follicle count (AFC).

Results

Overall, the two groups did not display significant differences in length of their menstrual cycles neither in the AMH serum levels nor the AFC.

Conclusions

No significant alteration was found in the ovarian reserve of women with HT.
Impact of the SARS-COV-2 outbreak on epidemiology and management of major traumain France: a registry-based study (the COVITRAUMA study)
Authors:   and the Traumabase Group, Moyer Jean-Denis , James Arthur , Gakuba Clément , Boutonnet Mathieu , Angles Emeline , Rozenberg Emmanuel , Bardon Jean , Clavier Thomas , Legros Vincent , Werner Marie , Mathais Quentin , Ramonda Véronique , Le Minh Pierre , Berthelot Yann , Colas Clélia , Pottecher Julien , Gauss Tobias
Published: March 2021

Background

Emerging evidence suggests that the reallocation of health care resources during the COVID-19 pandemic negatively impacts health care system. This study describes the epidemiology and the outcome of major trauma patients admitted to centers in France during the first wave of the COVID-19 outbreak.

Methods

This retrospective observational study included all consecutive trauma patients aged 15 years and older admitted into 15 centers contributing to the TraumaBase® registry during the first wave of the SARS-CoV-2 pandemic in France. This COVID-19 trauma cohort was compared to historical cohorts (2017–2019).

Results

Over a 4 years-study period, 5762 patients were admitted between the first week of February and mid-June. This cohort was split between patients admitted during the first 2020 pandemic wave in France (pandemic period, 1314 patients) and those admitted during the corresponding period in the three previous years (2017–2019, 4448 patients). Trauma patient demographics changed substantially during the pandemic especially during the lockdown period, with an observed reduction in both the absolute numbers and proportion exposed to road traffic accidents and subsequently admitted to traumacenters (348 annually 2017–2019 [55.4% of trauma admissions] vs 143 [36.8%] in 2020 p < 0.005). The in-hospital observed mortality and predicted mortality during the pandemic period were not different compared to the non-pandemic years.

Conclusions

During this first wave of COVID-19 in France, and more specifically during lockdown there was a significant reduction of patients admitted to designated trauma centers. Despite the reallocation and reorganization of medical resources this reduction prevented the saturation of the trauma rescue chain and has allowed maintaining a high quality of care for trauma patients.
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing
Authors: Gu Xi , Wang Daqi , Xu Zhijiao , Wang Jinghan , Guo Luo , Chai Renjie , Li Genglin , Shu Yilai , Li Huawei
Published: March 2021

Background

Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection.

Results

The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz.

Conclusions

These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.
Correction to: IMMPACT-recommended outcome measures and tools of assessment in burning mouth syndrome RCTs: an international Delphi survey protocol
Authors: Carey Barbara , Farag Arwa M. , Nasri-Heir Cibele , Klasser Gary D. , Ariyawardana Anura , Chmieliauskaite Milda , Sardella Andrea , Carlson Charles R. , Miller Craig S. , Mejia Lina , O’Neill Francis E. , Albuquerque Ruy
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases
Authors: Yao Chen , Joehanes Roby , Wilson Rory , Tanaka Toshiko , Ferrucci Luigi , Kretschmer Anja , Prokisch Holger , Schramm Katharina , Gieger Christian , Peters Annette , Waldenberger Melanie , Marzi Carola , Herder Christian , Levy Daniel
Published: March 2021

Background

DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases.

Results

We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data.

Conclusions

Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.
Renaissance of armored immune effector cells, CAR-NK cells, brings the higher hope for successful cancer therapy
Authors: Marofi Faroogh , Rahman Heshu Sulaiman , Thangavelu Lakshmi , Dorofeev Aleksey , Bayas-Morejón Favian , Shirafkan Naghmeh , Shomali Navid , Chartrand Max Stanley , Jarahian Mostafa , Vahedi Ghasem , Mohammed Rebar N. , Shahrokh Somayeh , Akbari Morteza , Khiavi Farhad Motavalli
Published: March 2021

In recent decades, a new method of cellular immunotherapy was introduced based on engineering and empowering the immune effector cells. In this type of immunotherapy, the immune effector cells are equipped with chimeric antigen receptor (CAR) to specifically target cancer cells. In much of the trials and experiments, CAR-modified T cell immunotherapy has achieved very promising therapeutic results in the treatment of some types of cancers and infectious diseases. However, there are also some considerable drawbacks in the clinical application of CAR-T cells although much effort is in progress to rectify the issues. In some conditions, CAR-T cells initiate over-activated and strong immune responses, therefore, causing unexpected side-effects such as systemic cytokine toxicity (i.e., cytokine release syndrome), neurotoxicity, on-target, off-tumor toxicity, and graft-versus-host disease (GvHD). To overcome these limitations in CAR-T cell immunotherapy, NK cells as an alternative source of immune effector cells have been utilized for CAR-engineering. Natural killer cells are key players of the innate immune system that can destroy virus-infected cells, tumor cells, or other aberrant cells with their efficient recognizing capability. Compared to T cells, CAR-transduced NK cells (CAR-NK) have several advantages, such as safety in clinical use, non-MHC-restricted recognition of tumor cells, and renewable and easy cell sources for their preparation. In this review, we will discuss the recent preclinical and clinical studies, different sources of NK cells, transduction methods, possible limitations and challenges, and clinical considerations.
The impact of sleep disorders on microvascular complications in patients with type 2 diabetes (SLEEP T2D): the protocol of a cohort study and feasibility randomised control trial
Authors: Antza Christina , Ottridge Ryan , Patel Smitaa , Slinn Gemma , Tearne Sarah , Nicholls Matthew , Cooper Brendan , Ali Asad , Tahrani Abd A.
Published: March 2021

Background

Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D). We and others have shown that OSA was associated with diabetes-related microvascular complications in patients with T2D in cross-sectional and longitudinal studies and that compliance with continuous positive airway pressure (CPAP) reduced the progression of microvascular complications. Hence, we hypothesised that adequate CPAP reduces the development of microvascular complication in patients with T2D.

Methods

SLEEP T2D is a cohort study with embedded feasibility, open-label, parallel-arm, randomised control trial (RCT) over 2 years. The primary aim is the feasibility of conducting a definitive RCT assessing the impact of CPAP on chronic kidney disease and other microvascular complications in patients with T2D. The main parameters are to assess willingness of participants to be randomised, follow-up rates, CPAP adherence/compliance, to optimise the choice of outcome measures for a substantive trial, and to identify the parameters for sample size calculations. The secondary aims of the study are related to the impact of CPAP, sleep-related disorders, and sleep chronotype on a variety of diabetes-related end points. The study participants were recruited from the T2D services in multiple NHS trusts across England. The main exclusion criteria for the cohort study are as follows: T1D, eGFR < 15 mL/min/1.73 m2, known OSA, active malignancy or chronic kidney disease from reasons other than diabetes, pregnancy, professional drivers, and a history of falling asleep whilst driving within last 2 years. The main exclusion criteria from the RCT were as follows: Apnoea-Hypopnoea Index < 10 and Epworth Sleepiness Score ≥ 11. Study participants were extensively phenotyped clinically and biochemically. The OSA diagnosis was based on multichannel portable device (ApneaLink AirTM, Resmed).

Discussion

The feasibility RCT will help us design the future RCT to assess the impact of CPAP on diabetes-related microvascular complications. The cohort study will generate preliminary data regarding the impact of sleep quality, duration, and chronotype on diabetes-related outcomes which could lead to further mechanistic and interventional studies.

Trial registration

ISRCTN, ISRCTN12361838. Registered 04 April 2018, Protocol version: v5.0 02.12.19.
Light a lamp and look at the stock market
Authors: Chundakkadan Radeef
Published: March 2021

In this study, we investigate the impact of the light-a-lamp event that occurred in India during the COVID-19 lockdown. This event happened across the country, and millions of people participated in it. We link this event to the stock market through investor sentiment and misattribution bias. We find a 9% hike in the market return on the post-event day. The effect is heterogeneous in terms of beta, downside risk, volatility, and financial distress. We also find an increase (decrease) in long-term bond yields (price), which together suggests that market participants demanded risky assets in the post-event day.
A guideline for 3D printing terminology in biomedical research utilizing ISO/ASTM standards
Authors: Alexander Amy E. , Wake Nicole , Chepelev Leonid , Brantner Philipp , Ryan Justin , Wang Kenneth C.
Published: March 2021

First patented in 1986, three-dimensional (3D) printing, also known as additive manufacturing or rapid prototyping, now encompasses a variety of distinct technology types where material is deposited, joined, or solidified layer by layer to create a physical object from a digital file. As 3D printing technologies continue to evolve, and as more manuscripts describing these technologies are published in the medical literature, it is imperative that standardized terminology for 3D printing is utilized. The purpose of this manuscript is to provide recommendations for standardized lexicons for 3D printing technologies described in the medical literature. For all 3D printing methods, standard general ISO/ASTM terms for 3D printing should be utilized. Additional, non-standard terms should be included to facilitate communication and reproducibility when the ISO/ASTM terms are insufficient in describing expository details. By aligning to these guidelines, the use of uniform terms for 3D printing and the associated technologies will lead to improved clarity and reproducibility of published work which will ultimately increase the impact of publications, facilitate quality improvement, and promote the dissemination and adoption of 3D printing in the medical community.
Ultrasonic welding of magnetic hybrid material systems –316L stainless steel to Ni/Cu/Ni-coated Nd2Fe14B magnets
Authors: Liesegang Moritz , Beck Tilmann
Published: March 2021

The performance of electric sensors is continuously improving due to the demands of modern vehicles and electronic devices. Magnetic sensors are used in a wide field of applications. However, handling and mounting the typical high-performance rare earth permanent magnets are challenging due to their brittleness. A constant magnetic flux is a key property of the magnetic setup in many devices. State-of-the-art adhesive bonding of magnets in devices can cause problems due to the low durability and viscous behaviour of adhesive polymers, as the magnet may change its position and hence, the magnetic flux distribution in the magnetic setup changes.

Ultrasonic welding is a powerful technique to join hybrid material systems quickly and reliably, providing high joint strength, even for brittle materials such as glasses, ceramics and rare earth permanent magnets. The latter is being investigated in this work for the first time. The ultrasonic welding process was adapted to join 316L stainless steel, representing potential components of magnetic devices, to Ni/Cu/Ni-coated Nd2Fe14B. In addition to directly joined steel/magnet-hybrids, ductile aluminium and nickel interlayers were used in order to enhance the joint strength.

Process parameters were developed and evaluated considering the resulting shear strength of the joints. The highest shear strength of 35 MPa was achieved for 316L/Nd2Fe14B and 316L/Al/Nd2Fe14B, which is more than twice the shear strength of adhesively bonded joints of up to 20 MPa, according to the literature. The functional performance of the hybrid material systems, evaluated by the magnetic flux density of the hybrid material systems was the highest for directly bonded joints, and those with a nickel interlayer, which did not show any losses in comparison to the single magnet in its initial state. Joints with an aluminium interlayer showed losses of 3% and adhesively bonded joints showed losses of 7% of the magnetic flux density.

In summary, the results of this work indicate that ultrasonic welding is a suitable technique to improve the production process and performance of magnetic devices.
Correction to: Characterization, antioxidant, and cytotoxic effects of some Egyptian wild plant extracts
Authors: Diab Thoria A. , Donia Thoria , Saad-Allah Khalil M.
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Tipifarnib in Head and Neck Squamous Cell Carcinoma WithHRASMutations
Authors: Ho Alan L. , Brana Irene , Haddad Robert , Bauman Jessica , Bible Keith , Oosting Sjoukje , Wong Deborah J. , Ahn Myung-Ju , Boni Valentina , Even Caroline , Fayette Jerome , Flor Maria José , Harrington Kevin , Hong David S. , Kim Sung-Bae , Licitra Lisa , Nixon Ioanna , Saba Nabil F. , Hackenberg Stephan , Specenier Pol , Worden Francis , Balsara Binaifer , Leoni Mollie , Martell Bridget , Scholz Catherine , Gualberto Antonio
Published: March 2021

PURPOSE

Mutations in the HRAS (m HRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC.

METHODS

We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.

RESULTS

Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).

CONCLUSION

Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist ( NCT02383927 ).
Extended UV detection bandwidth: h-BN/Al powder nanocomposites photodetectors sensitive in a middle UV region due to localized surface plasmon resonance effect
Authors: Volkov Ilia N. , Yermekova Zhanna S. , Khabibrakhmanov Almaz I. , Kovalskii Andrey M. , Corthey Shakty , Tameev Alexey R. , Aleksandrov Alexey E. , Sorokin Pavel B. , Shtansky Dmitry V. , Matveev Andrei T.
Published: March 2021

The development of high-effective photodetectors operating in a wide spectral range is an important technological task. In this work we have demonstrated that the detection bandwidth ofh-BN photodetectors in the UV range can be extended due to the surface plasmon resonance (SPR) effect. Theoretical calculations showed that, among Al, Au, Ag, and Cu, Al is the most suitable metal for theh-BN UV sensible detectors due to the SPR effect in the middle UV range. Based on the theoretical predictions, a simple and highly efficient method for obtainingh-BN/Al nanocomposites for localized SPR-based UV detectors was developed. It was demonstrated that theh-BN/Al material is sensitive to UV radiation with a wavelength of 266 nm that is far away of the detection limit of 240 nm inherent for pureh-BN.
Taxonomic relationships and population differentiation of the south-western Eurasian Zelkova species inferred in leaf morphology
Authors: Jasińska Anna K. , Rucińska Beata , Kozlowski Gregor , Fazan Laurence , Garfì Giuseppe , Pasta Salvatore , Bétrisey Sébastien , Gerber Emanuel , Boratyńska Krystyna , Boratyński Adam
Published: March 2021

The relict tree species Zelkova abelicea and Z. sicula (Ulmaceae) occur in Crete and Sicily, respectively. Zelkova abelicea grows in approximately 40 localities in the mountains of Crete, while Z. sicula has been found in only two stands in Sicily. We compared 25 morphological characters of the leaves of both species and used statistical methods (Tukey’stest, discrimination analysis, principal component analysis, agglomeration) to reveal the differences between these two species, their relation to Z. carpinifolia (the third Zelkova south-west Eurasian species), and between the leaves from different shoot types. Our study represents the first comparative biometric analysis of the three Zelkova species localized in the western edge of the current geographic range of the genus. We found that the species differed from each other both, in terms of leaf form characters and level of leaf variation. Zelkova carpinifolia was clearly different from Z. abelicea, while the two populations of Z. sicula, SIB and SIA, were more similar to Z. carpinifolia and Z. abelicea, respectively. The latter finding supports the results of recent molecular studies suggestingt he hybrid origin of Z. sicula. Zelkova abelicea, Z. sicula and Z. carpinifolia differ each other in the leaf characteristics and level of phenotypic variation.
Experimental investigation of isothermal and reacting flow characteristics downstream of axisymmetric bluff body stabilizers under stratified or fully premixed inlet mixture conditions
Authors: Πατεράκης Γεώργιος
Published: March 2021

The current work describes an experimental investigation of isothermal and turbulent reacting flow field characteristics downstream of axisymmetric bluff body stabilizers under a variety of inlet mixture conditions. Fully premixed and stratified flames established downstream of this double cavity premixer/burner configuration were measured and assessed under lean and ultra-lean operating conditions. The aim of this thesis was to further comprehend the impact of stratifying the inlet fuelair mixture on the reacting wake characteristics for a range of practical stabilizers under a variety of inlet fuel-air settings. In the first part of this thesis, the isothermal mean and turbulent flow features downstream of a variety of axisymmetric baffles was initially examined. The effect of different shapes, (cone or disk), blockage ratios, (0.23 and 0.48), and rim thicknesses of these baffles was assessed. The variations of the recirculation zones, back flow velocity magnitude, annular jet ejection angles, wake development, entrainment efficiency, as well as several turbulent flow features were obtained, evaluated and appraised. Next, a comparative examination of the counterpart turbulent cold fuel-air mixing performance and characteristics of stratified against fully-premixed operation was performed for a wide range of baffle geometries and inlet mixture conditions. Scalar mixing and entrainment properties were investigated at the exit plane, at the bluff body annular shear layer, at the reattachment region and along the developing wake were investigated. These isothermal studies provided the necessary background information for clarifying the combustion properties and interpreting the trends in the counterpart turbulent reacting fields. Subsequently, for selected bluff bodies, flame structures and behavior for operation with a variety of reacting conditions were demonstrated. The effect of inlet fuel-air mixture settings, fuel type and bluff body geometry on wake development, flame shape, anchoring and structure, temperatures and combustion efficiencies, over lean and close to blow-off conditions, was presented and analyzed. For the obtained measurements infrared radiation, particle image velocimetry, laser doppler velocimetry, chemiluminescence imaging set-ups, together with Fouriertransform infrared spectroscopy, thermocouples and global emission analyzer instrumentation was employed. This helped to delineate a number of factors that affectcold flow fuel-air mixing, flame anchoring topologies, wake structure development and overall burner performance. The presented data will also significantly assist the validation of computational methodologies for combusting flows and the development of turbulence-chemistry interaction models.