bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the causal relationship between physical activity and chronic back pain: a bidirectional two-sample Mendelian randomization study
Authors: Gao Shaowei , Zhou Huaqiang , Luo Siyu , Cai Xiaoying , Ye Fang , He Qiulan , Huang Chanyan , Zheng Xiaoyang , Li Ying , Du Zhanxin , Wang Yaqing , Qi Zhihui , Wang Zhongxing
Published: July 2021

Background

Recent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP.

Methods

The two-sample MR was used with independent genetic variants associated with physical activity phenotypes and CBP as genetic instruments from large genome-wide association studies (GWASs) on individuals of European ancestry. The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results.

Results

For primary analysis, instrumental variables were extracted from 337,234 participants for physical activity (the same as the outcome cohort) and 158,025 participants (29,531 cases) for CBP, while the outcome cohort for CBP included 117,404 participants (80,588 cases). No evidence of a causal relationship was found in the direction of physical activity to CBP (odds ratio [OR], 0.98; 95% CI, 0.85-1.13; P = 0.81). In contrast, a negative causal relationship in the direction of CBP to physical activity was detected (β = -0.07; 95% CI, -0.12 to -0.01; P = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls.

Conclusions

The negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.

Highlights

➢ Previous studies found a negative relationship between physical activity and chronic back pain, but the causal inference behind the relationship is lacking in evidences.

➢ We applied Mendelian randomization and revealed that the negative relationship probably derived from the fact that patients experiencing CBP tend to reduce their physical activities.

➢ If the negative relationship between physical activity and CBP is truly a reverse causality, the concept that patients with CBP should be engaging in activity, which is recommended by current guidelines, may need to be reconsidered.
Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status
Authors: Klinger Jörn E. , Ravarani Charles N. J. , Baukmann Hannes A. , Cope Justin L. , Böttinger Erwin P. , Konigorski Stefan , Schmidt Marco F.
Published: July 2021

Polygenic risk scores (PRS) aggregating results from genome-wide association studies are state of the art to predict the susceptibility to complex traits or diseases. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson’s Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson’s Disease. For instance, the model revealed an interaction of previously described drug target candidate genesTMEM175andGAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.
Australia’s worsening mental health – what’s next?
Authors: Enticott Joanne , Dawadi Shrinkhala , Shawyer Frances , Inder Brett , Fossey Ellie , Teede Helena , Rosenberg Seb , Ozol Ingrid , Meadows Graham
Published: July 2021

Objectives

To examine trends in psychological distress in Australia between 2001 to 2017-18, including analysis by age, sex, and location.

Design, setting and participants

Secondary analysis of six successive national health surveys of representative samples of the working age population (18-64 years).

Main outcome measures

Prevalence of psychological distress at very-high symptom level (defined by a Kessler Psychological Distress Scale [K10] score of 30 or more) and combined high/very-high level (K10 score of 22 or more).

Results

The latest survey showed 5.1% of Australians reporting very-high level distress and 14.8% combined high/very-high level - both the largest rates recorded this century. The greatest increase from 2001 to 2017-18 was in women aged 55-64 with very-high distress significantly increasing from 3.5% (95% CI: 2.5-4.5%) to 7.2% (5.9-8.5%), and; high/very-high distress from 12.4% (10.5-14.2%) to 18.7% (16.7-20.7%). Men aged 25-34 had very-high distress increase from 2.1% (1.4-2.8) to 4.0% (2.9-5.1%); and combined high/very-high distress remained stable at 10.6% (9.1-12.1%) to 11.5% (9.7-13.3%). In 2017-18, greatest distress was in women aged 18-24 years (very-high 8.0% (5.9-10.2%); high/very-high 22.1% (18.8-25.3%)). Overall, distress was significantly more prevalent in inner regional Australia than elsewhere (very-high level 4.8% (4.4-5.1%); high/very-high 14.4% (13.8-15%)).

Conclusions

Australia’s annual mental health expenditure over this period has doubled, yet population level psychological distress has increased. A whole of government approach and targeted strategies focusing on groups with the poorest mental health such as older working aged women, younger people, particularly women, and those outside of major cities are indicated.

Box

“The known” Previous examinations of national health surveys had suggested that population mental health was stable as measured by psychological distress.

“The new” Examining six consecutive national surveys we provide evidence that mental health has significantly deteriorated between 2001 and 2018. The latest survey showed 5.1% of Australians reporting very-high distress and 14.8% combined high/very-high distress, which are the largest rates reported this century.

“The implications” Whole of government approach and targeted strategies focusing on groups with the poorest mental health such as older working aged women, younger people particularly women, and those outside of major cities are indicated.
Low CD4/CD8 ratio predicts cancer risk among adults with HIV
Authors: Castilho Jessica L. , Bian Aihua , Jenkins Cathy A. , Shepherd Bryan E. , Sigel Keith , Gill M. John , Kitahata Mari M. , Silverberg Michael J. , Mayor Angel M. , Coburn Sally B. , Wiley Dorothy , Achenbach Chad J. , Marconi Vincent C. , Bosch Ronald J. , Horberg Michael A. , Rabkin Charles , Napravnik Sonia , Novak Richard M. , Mathews W. Christopher , Thorne Jennifer E. , Sun Jing , Althoff Keri N. , Moore Richard D. , Sterling Timothy R. , Sudenga Staci L. ,   the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA)
Published: July 2021

Background

Independent of CD4 cell count, low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the USA and Canada.

Methods

We examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines.

Models were adjusted for age, sex, race/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.

Results

Among 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all p<0.05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values.

Conclusions

Low CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study
Authors: Gajbhiye Rahul K , Mahajan Niraj N , Waghmare Rakesh , Surve Suchitra , Howal Prashant , Bhurke Aishwarya , Pious Merlin , Modi Deepak N , Mahale Smita D
Published: July 2021

Introduction

Pregnant women are at increased risk of contracting coronavirus disease 2019 (COVID-19) due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, post-partum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India.

Methods and analysis

PregCovid is a hospital-based registry for capturing information of pregnant, post-partum women with COVID-19 and their newborns in India. Medical case records of pregnant and post-partum women with laboratory-confirmed diagnoses of COVID-19 will be captured in real-time using an online electronic patient record (EPR) software. The frequency of each symptom will be calculated. The laboratory data will be analyzed for calculating the frequency of laboratory parameters consistently higher in women with COVID- The adverse pregnancy and neonatal outcomes will be analyzed and their frequency will be calculated. Response to treatment will be analyzed for frequency calculation (number of women treated with different treatment regimens). The mother-to-child transmission data will be analyzed from the RT-PCR and/ antibody data of neonatal and maternal samples tested wherever the information is available. The registry data will be crucial for developing strategies for reducing the adverse impact of COVID-19 on pregnant women and their new-born.

Ethics and dissemination

The study is approved by the Institutional Ethics Committee of ICMR-National Institute for Research in Reproductive Health (#55/2020), BYL Nair Hospital, Mumbai, India (# 63/2020); and all the 18 participating study sites under Medical Education and Drugs Department of Government of Maharashtra. The Institutional Ethics Committees granted a waiver of consent as the data is collected from the medical case records.

Trial registration number

CTRI/2020/05/025423

Article summary

Strengths and limitations of this study

The PregCovid registry is a hospital-based registry at dedicated COVID-19 hospitals in India. The registry will help to identify new epidemiological, clinical characteristics, obstetrics outcomes associated with pregnant women and/post-partum women with COVID-19 in India. The study will also generate information on clinical presentations and outcomes of neonatal born to mothers with COVID-19 in India.

PregCovid registry will provide evidence of mother to child transmission of SARS-CoV-2 infection in Indian women

The evidence on unusual presentations of COVID-19 in pregnant and post-partum women will be generated.

The follow-up of participants is only till the discharge from the hospital. Long-term follow-up is not included in the study.
Patients treated with anti-CD20 therapy can mount robust T cell responses to mRNA-based COVID-19 vaccines
Authors: Madelon Natacha , Lauper Kim , Breville Gautier , Royo Irène Sabater , Goldstein Rachel , Andrey Diego O. , Grifoni Alba , Sette Alessandro , Siegrist Claire-Anne , Finckh Axel , Lalive Patrice H. , Didierlaurent Arnaud M. , Eberhardt Christiane S.
Published: July 2021

Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8+T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4+and CD8+T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.
The COVID-19 pandemic and child malnutrition in sub-Saharan Africa: A scoping review
Authors: Sestito Paolo , Velásquez Sabina Rodriguez , Orel Erol , Keiser Olivia
Published: July 2021

Background

Although the COVID-19 pandemic has resulted in lower reported number of cases and deaths within the paediatric population, indirect impacts on the health of children in Sub-Saharan Africa such as malnutrition are evident. Data on the socioeconomic factors affecting malnutrition in the under-age population of Sub-Saharan Africa brought by the COVID-19 pandemic remain limited. This paper assesses socioeconomic factors of malnutrition in relation with COVID-19 and potential mitigating measures.

Methods

A scoping review of PubMed, Embase, and Web of Science from March 11, 2020, to May 1, 2021, was conducted. The included studies focused on COVID-19, children malnutrition, and Sub-Saharan Africa and adhered to the PRISMA guideline.

Results

Among 73 total screened articles, 15 studies filled the inclusion criteria. The identified socioeconomic factors leading to malnutrition in children were reduction in average income or increase in unemployment rate, access to healthcare and food supplements, disrupted food supply chains and increased prices of food products, pauses in humanitarian responses, and reduced access to school-based meals. Potential mitigation measures were food subsidies, food price control measures, the identification of new vulnerable groups and the implementation of financial interventions.

Conclusion

Malnutrition amongst Sub-Saharan African children due to COVID-19 is a result of a combination of multiple socioeconomic factors. To stabilize household purchasing power and eventually malnutrition in children in SSA, a combined strategy of initial detection of newly developing vulnerable groups and efficient, rapid financial assistance through mobile phone transfers was suggested. These strategies were proposed in combination with other economical models.
Association of Sleep-Disordered Breathing With Cardiovascular Events and Death in patients With Ischemic Heart Disease: A systematic review and meta-analysis
Authors: Zhang Yaodan , Tan Jin , Miao Yuyang , Zhang Qiang
Published: July 2021

Objective

Previous studies have identified that sleep-disordered breathing is associated with the increased risk of cardiovascular disease. However, CPAP, the preferred treatment of sleep apnea, does not appear to reduce the risk of adverse cardiovascular events and deaths in ischemic heart disease. Our aim was to determine whether OSA can be a prognostic factor for cardiovascular adverse events and deaths in patients with ischemia heart disease.

Methods

We searched Medline via PubMed, Embase, and the Cochrane Library database for clinical studies reporting the major adverse cardiac outcomes of SDB in patients with myocardial ischemia. Sleep apnea tests is mainly performed with cardiorespiratory polygraphy or portable diagnostic device. Summary hazard ratio(HR) and 95% CIs were conducted using random-effects meta-analysis.

Results

Eighteen literatures were included, with total participants of 9,138. Sixteen studies reported MACCEs, there was significant association of SDB with MACCES (HR, 1.66[95% CI, 1.41 to 1.94]; P< 0.0001), all-cause mortality (HR, 1.39[95% CI 1.12 to 1.73], P=0.0027) and cardiovascular mortality (HR, 2.12[95% CI 1.23 to 3.65], P=0.007). Subgroup analysis showed that one study was the cause of heterogeneity, while no correlation between SDB and outcomes for sleep apnea severity, follow-up time or whether surgery was performed.

Conclusion

SDB is associated with adverse cardiac outcomes in patients with ischemic heart disease, suggesting that sleep apnea can be screened for patients with ischemic heart disease, which can be used as a clinically relevant strategy of secondary prevention to reduce the risk of adverse outcomes.
Health Related Quality of Life and Hospitalizations In Chronic Thromboembolic Pulmonary Hypertension Versus Idiopathic Pulmonary Arterial Hypertension: An Analysis from the Pulmonary Hypertension Association (PHAR)
Authors: Minhas Jasleen , Narasimmal Sai Prasanna , Bull Todd , De Marco Teresa , McConnell John Wesley , Lammi Matthew R. , Thenappan Thenappan , Feldman Jeremy , Sager Jeffrey , Badesch David , Ryan John J. , Grinnan Daniel , Zwicke Dianne , Horn Evelyn , Elwing Jean M. , Moss John E. , Eggert Michael , Shlobin Oksana A. , Frantz Robert , Bartolome Sonja , Mathai Stephen C. , Mazimba Sula , Pugliese Steven , Al-Naamani Nadine
Published: July 2021

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH and 169 CTEPH patients. 21% of CTEPH patients underwent pulmonary thrombendarterectomy (PTE) before the end of follow-up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p=0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH after adjusting for age, sex, body mass index, WHO functional class and six-minute walk distance (IRR 1.66, 95%CI 1.04 – 2.65, p=0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those that were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six-minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL.
Regulation of DNA damage response by trimeric G-protein Signaling
Authors: Abd El-Hafeez Amer Ali , Sun Nina , Chakraborty Anirban , Ear Jason , Roy Suchismita , Chamarthi Pranavi , Rajapakse Navin , Das Soumita , Luker Kathryn E. , Hazra Tapas K. , Luker Gary D. , Ghosh Pradipta
Published: July 2021

Upon sensing DNA double-strand breaks (DSBs), eukaryotic cells either die or repair DSBs via one of two competing pathways, i.e., non-homologous end-joining (NHEJ) or homologous recombination (HR). We show that cell fate after DNA damage hinges on the guanine nucleotide-exchange modulator of heterotrimeric G-protein, Giα•βγ, GIV/Girdin. GIV suppresses HR by binding and sequestering BRCA1, a key coordinator of multiple steps within the HR pathway, away from DSBs; it does so using a C-terminal motif that binds BRCA1’s BRCT-modules via both phospho-dependent and -independent mechanisms. GIV promotes NHEJ, and binds and activates Gi and enhances the ‘free’ Gβγ→PI-3-kinase→Akt pathway, thus revealing the enigmatic origin of prosurvival Akt signals during dsDNA repair. Absence of GIV, or the loss of either of its two functions impaired DNA repair, and induced cell death when challenged with numerous cytotoxic agents. That GIV selectively binds few other BRCT-containing proteins suggests convergent signaling such that heterotrimeric G-proteins may finetune sensing, repair, and outcome after DNA damage.

GRAPHIC ABSTRACT

HIGHLIGHTS

Non-receptor G protein modulator, GIV/Girdin binds BRCA1

Binding occurs in both canonical and non-canonical modes

GIV sequesters BRCA1 away from dsDNA breaks, suppresses HR

Activation of Gi by GIV enhances Akt signals, favors NHEJ

IN BRIEF

In this work, the authors show that heterotrimeric G protein signaling that is triggered by non-receptor GEF, GIV/Girdin, in response to double-stranded DNA breaks is critical for decisive signaling events which favor non-homologous end-joining (NHEJ) and inhibit homologous recombination (HR).
NetSolP: predicting protein solubility in E. coli using language models
Authors: Thumuluri Vineet , Martiny Hannah-Marie , Armenteros Jose J. Almagro , Salomon Jesper , Nielsen Henrik , Johansen Alexander R.
Published: July 2021

Solubility and expression levels of proteins can be a limiting factor for large-scale studies and industrial production. By determining the solubility and expression directly from the protein sequence, the success rate of wet-lab experiments can be increased.

In this study, we focus on predicting the solubility and usability for purification of proteins expressed in Escherichia coli directly from the sequence. Our model NetSolP is based on deep learning protein language models called transformers and we show that it achieves state-of-the-art performance and improves extrapolation across datasets. As we find current methods are built on biased datasets, we curate existing datasets by using strict sequence-identity partitioning and ensure that there is minimal bias in the sequences.

The predictor is available at https://services.healthtech.dtu.dk/service.php?NetSolP-1.0
Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats
Authors: Partain Brittany D. , Bracho-Sanchez Evelyn , Farhadi Shaheen A. , Yarmola Elena G. , Keselowsky Benjamin G. , Hudalla Gregory A. , Allen Kyle D.
Published: July 2021

Objective

Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO’s joint residence time. In this study, we evaluated IDO-Gal3’s ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA.

Methods

Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3’s ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed.

Results

The Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p≤0.033), and improved vertical ground reaction forces (p≤0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025).

Conclusion

Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.
Unitary Structure of Palindromes in DNA
Authors: Tibatan Mehmet Ali , Sarisaman Mustafa
Published: July 2021

We investigate the quantum behavior encountered in palindromes within DNA structure. In particular, we reveal the unitary structure of usual palindromic sequences found in genomic DNAs of all living organisms, using the Schwinger’s approach. We clearly demonstrate the role played by palindromic configurations with special emphasis on physical symmetries, in particular subsymmetries of unitary structure. We unveil the prominence of unitary structure in palindromic sequences in the sense that vitally significant information endowed within DNA could be transformed unchangeably in the process of transcription. We introduce a new symmetry relation, namely purine-purine or pyrimidine-pyrimidine symmetries (p-symmetry) in addition to the already known symmetry relation of purine-pyrimidine symmetries (pp-symmetry) given by Chargaff’s rule. Therefore, important vital functions of a living organisms are protected by means of these symmetric features. It is understood that higher order palindromic sequences could be generated in terms of the basis of the highest prime numbers that make up the palindrome sequence number. We propose that violation of this unitary structure of palindromic sequences by means of our proposed symmetries leads to a mutation in DNA, which could offer a new perspective in the scientific studies on the origin and cause of mutation.
Genome-wide association study identifies susceptibility loci for acute myeloid leukemia
Authors: Lin Wei-Yu , Fordham Sarah E , Hungate Eric , Sunter Nicola J , Elstob Claire , Xu Yaobo , Park Catherine , Quante Anne , Strauch Konstantin , Gieger Christian , Skol Andrew , Rahman Thahira , Sucheston-Campbell Lara , Wang Junke , Hahn Theresa , Clay-Gilmour Alyssa I , Jones Gail L , Marr Helen J , Jackson Graham H , Menne Tobias , Collin Mathew , Ivey Adam , Hills Robert K , Burnett Alan K , Russell Nigel H , Fitzgibbon Jude , Larson Richard A , Le Beau Michelle M , Stock Wendy , Heidenreich Olaf , Alharbi Abrar , Allsup David J , Houlston Richard S , Norden Jean , Dickinson Anne M , Douglas Elisabeth , Lendrem Clare , Daly Ann K , Palm Louise , Piechocki Kim , Jeffries Sally , Bornhäuser Martin , Röllig Christoph , Altmann Heidi , Ruhnke Leo , Kunadt Desiree , Wagenführ Lisa , Cordell Heather J , Darlay Rebecca , Andersen Mette K , Fontana Maria C , Martinelli Giovanni , Marconi Giovani , Sanz Miguel A , Cervera José , Gómez-Seguí Inés , Cluzeau Thomas , Moreilhon Chimène , Raynaud Sophie , Sill Heinz , Voso Maria Teresa , Lo-Coco Francesco , Dombret Hervé , Cheok Meyling , Preudhomme Claude , Gale Rosemary E , Linch David , Gaal-Wesinger Julia , Masszi Andras , Nowak Daniel , Hofmann Wolf-Karsten , Gilkes Amanda , Porkka Kimmo , Milosevic Feenstra Jelena D , Kralovics Robert , Grimwade David , Meggendorfer Manja , Haferlach Torsten , Krizsán Szilvia , Bödör Csaba , Stölzel Friedrich , Onel Kenan , Allan James M
Published: July 2021

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we performed a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identified a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identified a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N=1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology by identifying putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).
The role of mouthwash sampling in SARS-CoV-2 diagnosis
Authors: Biber Asaf , Lev Dana , Mandelboim Michal , Lustig Yaniv , Harmelin Geva , Shaham Amit , Erster Oran , Schwartz Eli
Published: July 2021

Background

The current practice of COVID-19 diagnosis worldwide is the use of oro-nasopharyngeal (ONP) swabs. Our study aim was to explore mouthwash (MW) as an alternative diagnostic method, in light of the disadvantages of ONP swabs.

Methods

Covid-19 outpatients molecular-confirmed by ONP-swab were repeatedly examined with ONP-swab and MW with normal-saline (0.9%). Other types of fluids were compared to normal-saline. The Cq values obtained with each method were compared.

Results

Among 137 pairs of ONP-swabs and MW samples, 84.6% (116/137) of ONP-swabs were positive by at least one of the genes (N, E, R). However MW detected 70.8% (97/137) of samples as positive, which means 83.6% (97/116) out of positive ONP-swabs, missing mainly Cq value>30. In both methods, the N gene was the most sensitive one. Therefore MW samples targeting N-gene, which was positive in 95/137 (69.3%), is comparable to ONP-swabs targeting E and R genes which gave equal results – 95/137 (69.3%) and 90/137 (65.7%) respectively.

Comparing saline MW to distilled-water gave equal results, while commercial mouth-rinsing solutions were less sensitive.

Conclusions

MW with normal-saline, especially when tested by N gene, can effectively detect COVID-19 patients. Furthermore, this method was not inferior when compared to R and E genes of ONP-swabs, which are common targets in many laboratories around the world.
A collaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia
Authors: Hui Lisa , Marzan Melvin Barrientos , Potenza Stephanie , Rolnik Daniel L. , Said Joanne M. , Palmer Kirsten R , Whitehead Clare L. , Sheehan Penelope M. , Ford Jolyon , Pritchard Natasha , Mol Ben W. , Walker Susan P.
Published: July 2021

Background

The COVID-19 pandemic has resulted in a range of unprecedented disruptions to the delivery of maternity care globally and has been associated with regional changes in perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne endured one of the longest and most stringent lockdowns in 2020. This paper presents the protocol for a collaborative maternity dashboard project to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic.

Methods

De-identified maternal and newborn outcomes will be collected monthly from all public maternity services in Melbourne, allowing rapid analysis of a multitude of perinatal indicators. Weekly outcomes will be displayed as run charts according to established methods for detecting non-random ‘signals’ in health care. A pre-pandemic median for all indicators will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≤ six consecutive weeks, all above or below the pre-pandemic median. Additional statistical analyses such as regression, time-series, and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests.

Ethics and Dissemination

This study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).

Strengths and weaknesses of this study

⍰ This project is the first clinician-led, multi-centre perinatal data collection system for metropolitan Melbourne.

⍰ It complements the state government data collection, with the significant benefits of more timely and flexible reporting of outcomes, and granular detail on emerging areas of concern.

⍰ The study relies on primary source coding of exposure and outcomes from each hospital that have not been internally validated during the study period.

⍰ Data from private maternity hospitals, containing 25% of Melbourne births, are not available.

⍰ This resource will support data-informed hospital pandemic responses through to the end of 2022.
Matrix elasticity gradients guide neuronal polarity by controlling microtubule network mobility
Authors: Burute Mithila , Jansen Klara I. , Mihajlovic Marko , Vermonden Tina , Kapitein Lukas C.
Published: July 2021

Neuronal polarization and axon specification depend on extracellular cues, intracellular signaling, cytoskeletal rearrangements and polarized transport, but the interplay between these processes has remained unresolved. The polarized transport of kinesin-1 into a specific neurite is an early marker for axon identity, but the mechanisms that govern neurite selection and polarized transport are unknown. We show that extracellular elasticity gradients control polarized transport and axon specification, mediated by Rho-GTPases whose local activation is necessary and sufficient for polarized transport. Selective Kinesin-1 accumulation furthermore depends on differences in microtubule network mobility between neurites and local control over this mobility is necessary and sufficient for proper polarization, as shown using optogenetic anchoring of microtubules. Together, these results explain how mechanical cues can instruct polarized transport and axon specification.
ADAR mediated A-to-I RNA editing affects SARS-CoV-2 characteristics and fuels its evolution
Authors: Song Yulong , He Xiuju , Yang Wenbing , Tang Tian , Zhang Rui
Published: July 2021

Upon SARS-CoV-2 infection, viral intermediates activate the Type I interferon (IFN) response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, and on average, approximately 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans. Collectively, our data suggest that SARS-CoV-2 hijacks components of the host antiviral machinery to edit its genome and fuel its evolution.
Origin and evolutionary landscape of Nr2f transcription factors across Metazoa
Authors: Coppola Ugo , Waxman Joshua S.
Published: July 2021

Background

Nuclear Receptor Subfamily 2 Group F (Nr2f) orphan nuclear hormone transcription factors (TFs) are fundamental regulators of many developmental processes in invertebrates and vertebrates. Despite the importance of these TFs throughout metazoan development, previous work has not clearly outlined their evolutionary history.

Results

We integrated molecular phylogeny with comparisons of intron/exon structure, domain architecture, and syntenic conservation to define critical evolutionary events that distinguish the Nr2f gene family in Metazoa. Our data indicate that a single ancestral pre-metazoan Nr2f gene, we have termed Nr2f1/2/5/6, predated six main Bilateria subfamilies, which include a single Nr2f1/2/5 homolog that is present throughout protostomes and invertebrate deuterostomes, Nr2f1/2 homologs in agnathans, and Nr2f1, Nr2f2, Nr2f5, Nr2f6 orthologs that are found in gnathostomes. The three Nr2f1/2 members in agnathans are due to independent expansions not found in gnathostomes, while the vertebrate Nr2f1, Nr2f2, Nr2f5 members arose from whole-genome duplications (WGDs). However, Nr2f6 members are the most divergent subfamily, likely originating from an ancient duplication, and are only retained by gnathostomes. Interestingly, Nr2f5 TFs have been independently lost in both cartilaginous fish and amniotes, such as humans. Furthermore, our analysis shows there are differential expansions and losses of Nr2f genes in teleosts following their additional rounds of WGDs.

Conclusion

Overall, our evolutionary genomic analysis of Nr2f proteins helps to reveal the origins and previously unrecognized relationships of this ancient transcription factor family, which may allow for greater insights into the conservation of Nr2f functions that shape Metazoan body plans.
Review and selection of commercially available IMU for a short time inertial navigation
Authors: Borodacz Krystian , Szczepański Cezary , Popowski Stanisław
Published: July 2021

Purpose

The selection of a suitable inertial measurement unit (IMU) is a critical step in an inertial navigation system (INS) design. Nevertheless, inertial sensors manufacturers are unwilling to publish their products’ accurate performance parameters along with a price. This paper aims to summarise the current IMU market review and point out parameters important for short-term inertial navigation.

Design/methodology/approach

The market review is based on the information published by manufacturers in brochures, datasheets and websites. Some information, including price, was also collected from sensors distributors. The entire collection of data includes data of over 150 sensors from 32 manufacturers and is valid for the first half of the year 2020.

Findings

This paper answers the following questions: •Why and where use inertial navigation? •Which parameters should one emphasise during IMU selection?•What is currently available on the IMU market? •Which parameters have a significant influence on price? •What are the advantages of specific sensor technology?

Originality/value

This paper gathers data published by IMU manufacturers, allowing for a quick overview of the current market. Based on real data, different sensor technologies are compared. The performed analysis presents the statistical basis for the IMU selection. By theoretical considerations a significance of sensor parameters is drawn and an approach to an IMU selection based on limited number of parameters is proposed. Although the considerations have been carried out regarding inertial navigation, the results from an extensive analysis of commercially available sensors may also be useful for other applications.
Identification of potential biomechanical risk factors for low back disorders during repetitive rebar lifting
Authors: Antwi-Afari Maxwell Fordjour , Li Heng , Edwards David John , Pärn Erika Anneli , Owusu-Manu De-Graft , Seo Joonoh , Wong Arnold Yu Lok
Published: July 2021

Purpose

Work-related low back disorders (LBDs) are prevalent among rebar workers although their causes remain uncertain. The purpose of this study is to examine the self-reported discomfort and spinal biomechanics (muscle activity and spinal kinematics) experienced by rebar workers.

Design/methodology/approach

In all, 20 healthy male participants performed simulated repetitive rebar lifting tasks with three different lifting weights, using either a stoop (n = 10) or a squat (n = 10) lifting posture, until subjective fatigue was reached. During these tasks, trunk muscle activity and spinal kinematics were recorded using surface electromyography and motion sensors, respectively.

Findings

A mixed-model, repeated measures analysis of variance revealed that an increase in lifting weight significantly increased lower back muscle activity at L3 level but decreased fatigue and time to fatigue (endurance time) (p < 0.05). Lifting postures had no significant effect on spinal biomechanics (p < 0.05). Test results revealed that lifting different weights causes disproportional loading upon muscles, which shortens the time to reach working endurance and increases the risk of developing LBDs among rebar workers.

Research limitations/implications

Future research is required to: broaden the research scope to include other trades; investigate the effects of using assistive lifting devices to reduce manual handling risks posed; and develop automated human condition-based solutions to monitor trunk muscle activity and spinal kinematics.

Originality/value

This study fulfils an identified need to study laboratory-based simulated task conducted to investigate the risk of developing LBDs among rebar workers primarily caused by repetitive rebar lifting.
Creativity-related traits and the scientific production of professors from the Autonomous University of Chihuahua
Authors: Delgado-Carreón Claudia C. , Machin-Mastromatteo Juan D. , Romo-González José Refugio , Pacheco-Mendoza Josmel
Published: July 2021

Purpose

This work studied the influence of creativity-related traits in university professors’ scientific productivity.

Design/methodology/approach

A survey, applied to 120 university professors, included closed-ended questions for participants to rate 33 items derived from the specialized literature and classified into five dimensions (novelty; flexibility-fluidity; achievements-dedication; confidence; and problem-solving). After the survey was applied, data were merged with three other data sets: bibliometric data (Scopus), Altmetrics (Dimensions) and peer-reviews and editorial management (Publons) for the period from 2013 to 2018. Descriptive, correlational and inferential statistical analyzes were conducted on the data collected.

Findings

There was little relationship between professors’ creativity scores and their bibliometric and Altmetric indicators. The highest-rated creativity dimension was flexibility-fluidity and the most prominent creativity-related trait was “I perform my activities with dedication” (belonging to the achievements-dedication dimension). During the period studied, professors published 379 documents, but there were large gaps among their indicators; for instance, only 61 professors published in journals indexed in Scopus during the period. The inferential analysis implied that the professors with the best indicators did not present substantial differences in their creativity scores when compared to their colleagues with fewer or no indicators. However, descriptive and correlational insights may aid in fostering the aspects that can positively influence creativity and the indicators studied.

Originality/value

Although there is a wealth of literature about the study of creativity and part of it tackles creativity and scientific research at a theoretical level, this paper did not find other empirical studies that analyzed the relationship between creativity and scientific production. It might be important for librarians to be familiar with user studies such as the present, as they may consider studying these kinds of aspects in their users. Moreover, this study can be interesting because librarians have increasingly been involved in the evaluation of scientific production and in training processes for enhancing it within their institutions. Here, information professionals have found opportunities to improve users’ knowledge, performance and experiences on digital scientific ecosystems and their indicators.
An evidence-based framework validation for building code improvement in New Zealand
Authors: Nwadike Amarachukwu Nnadozie , Wilkinson Suzanne
Published: July 2021

Purpose

New Zealand building code may be serving its purpose to an extent, there is still a need to develop a framework to improve the use and application of building code for better building performance and services. This study aims to validate the identified parameters in the developed framework to improve building code practice in New Zealand.

Design/methodology/approach

Subject matter experts interview was conducted with key stakeholders that use building code, standards and other associated compliance documents.

Findings

The findings from this study establish the importance of improving the building code, and the efficacy of validated framework helps to identify the areas with the most pressing needs within the building regulatory system. All the subject matter experts unanimously agreed on educating and training the building code users. Besides, the validated framework will enable the policy decision-makers in the building regulatory system to promote the use of building code and the utilisation of its potentials in reducing disaster while increasing the built environment resilience. The study concludes that the designed framework will create more robust strategy implementations to enhance innovative solutions embedded in performance-based building code.

Originality/value

This study originality centres on the practical application of an evidence-based framework for performance-based building code, standards and other related compliance documents.
Group behaviour process and learning: a review and assessment of emerging online technologies in executive education
Authors: Kearney Arthur , Harrington Denis , Rajwani Tazeeb
Published: July 2021

Purpose

This paper aims to investigate the interaction of the relationships between group behaviour, group process and learning outcomes in online executive education.

Design/methodology/approach

A systematic review of literature in the relevant conceptual domains is performed.

Findings

A framework is proposed from the systematic review and proposes a dynamic classroom environment where instructor capability interacts with group process and behaviour to generate new learning outcomes. The impact of institutional context and technology infrastructure are highlighted as drivers of both the classroom and instructor effectiveness.

Research limitations/implications

The systematic review highlights several future research trajectories posing the questions: How disruptive innovation impacts on instructor capability development? How alternative theories explain the routines underpinning instructor capability? What is the role of external partners in the development of learning in context? What is the nature of instructor innovation capability? and How does instructor technology capability impact on learning outcomes?

Practical implications

Human resource development practitioners are presented with insights as to their existing and potential future roles in enhancing group behaviour, process and learning outcomes in executive classrooms impacted by technological change. The subsequent potential for practitioner enabled learning innovation is highlighted.

Originality/value

This paper contributes to contemporary debates regarding the interaction of emerging technologies and the executive online classroom, specifically focusing on the area of group behaviour process and learning.