bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental and individual factors associated with gestational weight gain
Authors: Silva Thales Philipe Rodrigues da , Viana Thamara Gabriela Fernandes , Pessoa Milene Cristine , Felisbino-Mendes Mariana Santos , Inácio Monique Louise Cassimiro , Mendes Larissa Loures , Velasquez-Melendez Gustavo , Martins Eunice Francisca , Matozinhos Fernanda Penido
Published: March 2022

Background

Environmental factors have an impact on inappropriate food choices and sedentary lifestyle, and both individually and in combination these factors favour improper gestational weight gain (GWG) and consequent maternal and neonatal health problems. The objective of this study was to analyze the environmental and individual factors associated with GWG.

Methods

Data were from “Born in Belo Horizonte: Survey on childbirth and birth”, a hospital-based retrospective cohort of 506 pregnant women with deliveries in public and private maternity hospitals in Belo Horizonte, Minas Gerais. Data were collected via face-to-face interviews from November 2011 to March 2013. The outcome variable of this study was the GWG categorized based on the Institute of Medicine Guidelines. Explanatory environmental variables included the availability and access to food environment and places available for physical activity in the neighborhood. Explanatory individual variables included socioeconomic and demographic, obstetric and childbirth variables. Generalized estimating equations examined the association of environmental and individual factors with insufficient or excessive GWG.

Results

The final sample consisted of 506 mothers. There was 36.4% pregnant women showing excessive GWG and 22.7% showing GWG below the recommended interval. Regarding excessive GWG, there was a positive association with the number of mixed food purchasing establishments close to the place of residence, pre-pregnancy body mass index in the categories of overweight and obesity, arterial hypertension and the private sector as the predominant place for prenatal consultations.

Conclusion

GWG outside of the recommended interval was associated with individual and environmental factors, and most pregnant women had insufficient or excessive gestational weight gain. Such results can complement previously published evidence, important for creating more effective strategies for the prevention of excessive and inadequate GWG and the consequent problems related to it during pregnancy.
Tibial internal rotation in combined anterior cruciate ligament and high-grade anterolateral ligament injury and its influence on ACL length
Authors: Hodel Sandro , Torrez Carlos , Flury Andreas , Fritz Benjamin , Steinwachs Matthias R. , Vlachopoulos Lazaros , Fucentese Sandro F.
Published: March 2022

Background

Assessment of combined anterolateral ligament (ALL) and anterior cruciate ligament (ACL) injury remains challenging but of high importance as the ALL is a contributing stabilizer of tibial internal rotation. The effect of preoperative static tibial internal rotation on ACL -length remains unknown. The aim of the study was analyze the effect of tibial internal rotation on ACL length in single-bundle ACL reconstructions and to quantify tibial internal rotation in combined ACL and ALL injuries.

Methods

The effect of tibial internal rotation on ACL length was computed in a three-dimensional (3D) model of 10 healthy knees with 5° increments of tibial internal rotation from 0 to 30° resulting in 70 simulations. For each step ACL length was measured. ALL injury severity was graded by a blinded musculoskeletal radiologist in a retrospective analysis of 61 patients who underwent single-bundle ACL reconstruction. Preoperative tibial internal rotation was measured in magnetic resonance imaging (MRI) and its diagnostic performance was analyzed.

Results

ACL length linearly increased 0.7 ± 0.1 mm (2.1 ± 0.5% of initial length) per 5° of tibial internal rotation from 0 to 30° in each patient.

Seventeen patients (27.9%) had an intact ALL (grade 0), 10 (16.4%) a grade 1, 21 (34.4%) a grade 2 and 13 (21.3%) a grade 3 injury of the ALL. Patients with a combined ACL and ALL injury grade 3 had a median static tibial internal rotation of 8.8° (interquartile range (IQR): 8.3) compared to 5.6° (IQR: 6.6) in patients with an ALL injury (grade 0–2) (p = 0.03). A cut-off > 13.3° of tibial internal rotation predicted a high-grade ALL injury with a specificity of 92%, a sensitivity of 30%; area under the curve (AUC) 0.70 (95% CI: 0.54–0.85) (p = 0.03) and an accuracy of 79%.

Conclusion

ACL length linearly increases with tibial internal rotation from 0 to 30°. A combined ACL and high-grade ALL injury was associated with greater preoperative tibial internal rotation. This potentially contributes to unintentional graft laxity in ACL reconstructed patients, in particular with concomitant high-grade ALL tears.

Study design

Cohort study; Level of evidence, 3.
Hemoptysis due to progressive scoliosis associated with congenital heart disease: a case report
Authors: Yamaguchi Kohei , Uehara Masashi , Oba Hiroki , Hatakenaka Terue , Kuraishi Shugo , Ikegami Shota , Takizawa Takashi , Munakata Ryo , Kamanaka Takayuki , Miyaoka Yoshinari , Takigiku Kiyohiro , Takahashi Jun
Published: March 2022

Background

Patients with congenital heart disease (CHD) are associated with an increased incidence of scoliosis, often with severe progression. We report a case of hemoptysis caused by rapid scoliosis progression subsequent to surgery for CHD that was successfully managed by surgical curve correction following coil embolization.

Case presentation

A 14-year-old girl with scoliosis had undergone open heart surgery for CHD at the age of 1 year. She was first noted to have scoliosis at 12 years of age, which began to progress rapidly. At age 13, her main thoracic curve Cobb angle was 46°, and hemoptysis with high pulmonary vein pressure due to vertebral rotation was detected. Nine months after coil embolization, she received posterior spinal fusion from T5 to L2 for scoliosis correction. Postoperatively, her pulmonary vein diameter was enlarged, with no detectable signs of hemoptysis.

Conclusions

We encountered a case of hemoptysis caused by advanced scoliosis after cardiac surgery that was successfully treated by correction of the scoliotic curve following coil embolization. Patients with secondary scoliosis after surgery for CHD should be carefully monitored for the possibility of cardiovascular system deterioration.
Participatory methods in a digital setting: experiences from the co-creation of an eHealth tool for people with chronic obstructive pulmonary disease
Authors: Lundell Sara , Toots Annika , Sönnerfors Pernilla , Halvarsson Alexandra , Wadell Karin
Published: March 2022

Background

Using participatory methods to engage end-users in the development and design of eHealth is important to understand and incorporate their needs and context. Within participatory research, recent social distancing practice has forced a transition to digital communication platforms, a setting that warrants deeper understanding. The aim of this study was to describe the experiences of, and evaluate a digital co-creation process for developing an eHealth tool for people with chronic obstructive pulmonary disease (COPD).

Methods

The co-creation was guided by Participatory appreciative action and reflection, where a convenience sample (n = 17), including persons with COPD, health care professionals, relatives and a patient organization representative participated in six digital workshops. User instructions, technical equipment, and skilled support were provided if necessary. Workshops centred around different topics, with pre-recorded films, digital lectures and home assignments to up-skill participants. Process validity, experiences and ownership in the co-creation process were evaluated by repeated respondent validation, member checking, questionnaires and by assessing attendance. Data was analysed quantitatively or qualitatively as appropriate.

Results

The co-creators were in general satisfied with the digital format of the workshops. Mean attendance and perceived engagement in workshops was high and the experience described as enjoyable. Engagement was facilitated by up-skilling activities and discussions in small groups. Few had used digital communication previously, and feelings ranging from excitement to concern were expressed initially. Technical issues, mainly audio related, were resolved with support. At completion, skills using equipment and digital platform surpassed expectations. Few disadvantages with the digital format were identified, and advantages included reduced travel, time efficiency and reduced infection risk.

Conclusions

Experiences of digital co-creation were overwhelmingly positive, despite initial barriers related to computer naivety and use of digital equipment and platforms. The high level of satisfaction, engagement, attendance rates, and agreement between individual and group views suggests that a digital co-creation process is a feasible method. Several important success factors were identified, such as the provision of information and education on discussion topics in advance of workshops, as well as the smaller group discussions during workshops. The knowledge gained herein will be useful for future digital co-creation processes.
Detection performance of PCR for Legionella pneumophila in environmental samples: a systematic review and meta-analysis
Authors: Yin Xin , Chen Ying-Zhou , Ye Qi-Qing , Liao Li-Juan , Cai Zhuo-Rui , Lin Min , Li Jia-Na , Zhang Geng-Biao , Peng Xiao-Li , Shi Wen-Fang , Guo Xu-Guang
Published: March 2022

Background

Legionellosis remains a public health problem. The most common diagnostic method to detect Legionella pneumophila (L. pneumophila) is culture. Polymerase chain reaction (PCR) is a fast and accurate method for this detection in environmental samples.

Methods

Four databases were searched for studies that evaluated the detection efficiency of PCR in L. pneumophila. The quality evaluation was conducted using Review Manager 5.3. We used Meta-DiSc 1.4 software and the Stata 15.0 software to create forest plots, a meta-regression, a bivariate boxplot and a Deeks’ funnel plot.

Results

A total of 18 four-fold tables from 16 studies were analysed. The overall pooled sensitivity and specificity of PCR was 94% and 72%, respectively. The positive likelihood ratio (RLR) and negative likelihood ratio (NLR) was 2.73 and 0.12, respectively. The result of the diagnostic odds ratio (DOR) was 22.85 and the area under the curve (AUC) was 0.7884.

Conclusion

Establishing a laboratory diagnostic tool for L. pneumophila detection is important for epidemiological studies. In this work, PCR demonstrated a promising diagnostic accuracy for L. pneumophila.
Doxorubicin and CpG loaded liposomal spherical nucleic acid for enhanced Cancer treatment
Authors: Deng Bo , Ma Bing , Ma Yingying , Cao Pei , Leng Xigang , Huang Pengyu , Zhao Yuanyuan , Ji Tianjiao , Lu Xueguang , Liu Lanxia
Published: March 2022

Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8+ and CD4+ T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect.

Graphical Abstract
Role of store-operated Ca2+ entry in cardiovascular disease
Authors: Lu Ting , Zhang Yihua , Su Yong , Zhou Dayan , Xu Qiang
Published: March 2022

Store-operated channels (SOCs) are highly selective Ca2+ channels that mediate Ca2+ influx in non-excitable and excitable (i.e., skeletal and cardiac muscle) cells. These channels are triggered by Ca2+ depletion of the endoplasmic reticulum and sarcoplasmic reticulum, independently of inositol 1,4,5-trisphosphate (InsP3), which is involved in cell growth, differentiation, and gene transcription. When the Ca2+ store is depleted, stromal interaction molecule1 (STIM1) as Ca2+ sensor redistributes into discrete puncta near the plasma membrane and activates the protein Ca2+ release activated Ca2+ channel protein 1 (Orai1). Accumulating evidence suggests that SOC is associated with several physiological roles in endothelial dysfunction and vascular smooth muscle proliferation that contribute to the progression of cardiovascular disease. This review mainly elaborates on the contribution of SOC in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in cardiovascular disease.

Graphical Abstract
A machine learning-based risk stratification tool for in-hospital mortality of intensive care unit patients with heart failure
Authors: Luo Cida , Zhu Yi , Zhu Zhou , Li Ranxi , Chen Guoqin , Wang Zhang
Published: March 2022

Background

Predicting hospital mortality risk is essential for the care of heart failure patients, especially for those in intensive care units.

Methods

Using a novel machine learning algorithm, we constructed a risk stratification tool that correlated patients’ clinical features and in-hospital mortality. We used the extreme gradient boosting algorithm to generate a model predicting the mortality risk of heart failure patients in the intensive care unit in the derivation dataset of 5676 patients from the Medical Information Mart for Intensive Care III database. The logistic regression model and a common risk score for mortality were used for comparison. The eICU Collaborative Research Database dataset was used for external validation.

Results

The performance of the machine learning model was superior to that of conventional risk predictive methods, with the area under curve 0.831 (95% CI 0.820–0.843) and acceptable calibration. In external validation, the model had an area under the curve of 0.809 (95% CI 0.805–0.814). Risk stratification through the model was specific when the hospital mortality was very low, low, moderate, high, and very high (2.0%, 10.2%, 11.5%, 21.2% and 56.2%, respectively). The decision curve analysis verified that the machine learning model is the best clinically valuable in predicting mortality risk.

Conclusion

Using readily available clinical data in the intensive care unit, we built a machine learning-based mortality risk tool with prediction accuracy superior to that of linear regression model and common risk scores. The risk tool may support clinicians in assessing individual patients and making individualized treatment.
Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab
Authors: Sims Jonathan T. , Poorbaugh Josh , Chang Ching-Yun , Holzer Timothy R. , Zhang Lin , Engle Sarah M. , Beasley Stephanie , Doman Thompson N. , Naughton Lynn , Higgs Richard E. , Kallewaard Nicole , Benschop Robert J.
Published: March 2022

Background

A thorough understanding of a patient’s inflammatory response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial to discerning the associated, underlying immunological processes and to the selection and implementation of treatment strategies. Defining peripheral blood biomarkers relevant to SARS-CoV-2 infection is fundamental to detecting and monitoring this systemic disease. This safety-focused study aims to monitor and characterize the immune response to SARS-CoV-2 infection via analysis of peripheral blood and nasopharyngeal swab samples obtained from patients hospitalized with Coronavirus disease 2019 (COVID-19), in the presence or absence of bamlanivimab treatment.

Methods

23 patients hospitalized with COVID-19 were randomized to receive a single dose of the neutralizing monoclonal antibody, bamlanivimab (700 mg, 2800 mg or 7000 mg) or placebo, at study initiation (Clinical Trial; NCT04411628). Serum samples and nasopharyngeal swabs were collected at multiple time points over 1 month. A Proximity Extension Array was used to detect inflammatory profiles from protein biomarkers in the serum of hospitalized COVID-19 patients relative to age/sex-matched healthy controls. RNA sequencing was performed on nasopharyngeal swabs. A Luminex serology assay and Elecsys® Anti-SARS-CoV-2 immunoassay were used to detect endogenous antibody formation and to monitor seroconversion in each cohort over time. A mixed model for repeated measures approach was used to analyze changes in serology and serum proteins over time.

Results

Levels of IL-6, CXCL10, CXCL11, IFNγ and MCP-3 were > fourfold higher in the serum of patients with COVID-19 versus healthy controls and linked with observations of inflammatory and viral-induced interferon response genes detected in nasopharyngeal swab samples from the same patients. While IgA and IgM titers peaked around 7 days post-dose, IgG titers remained high, even after 28 days. Changes in biomarkers over time were not significantly different between the bamlanivimab and placebo groups.

Conclusions

Similarities observed between nasopharyngeal gene expression patterns and peripheral blood biomarker profiles reveal a connection between the circulation and processes in the nasopharyngeal cavity, reinforcing the potential utility of systemic blood biomarker profiling for therapeutic monitoring of patient response. Serological antibody responses in patients correlated closely with reductions in the COVID-19 inflammatory protein biomarker signature. Bamlanivimab did not affect the biomarker dynamics in this hospitalized patient population.
Is there a trade-off between economy and task goal variability in transfemoral amputee gait?
Authors: Lee I-Chieh , Fylstra Bretta L. , Liu Ming , Lenzi Tommaso , Huang He
Published: March 2022

Background

Energy cost minimization has been widely accepted to regulate gait. Optimization principles have been frequently used to explain how individuals adapt their gait pattern. However, there have been rare attempts to account for the role of variability in this optimization process. Motor redundancy can enable individuals to perform tasks reliably while achieving energy optimization. However, we do not know how the non-goal-equivalent and goal-equivalent variability is regulated. In this study, we investigated how unilateral transfemoral amputees regulate step and stride variability based on the task to achieve energy economy.

Methods

Nine individuals with unilateral transfemoral amputation walked on a treadmill at speeds of 0.6, 0.8, 1.0, 1.2 and 1.4 m/s using their prescribed passive prostheses. We calculated the step-to-step and stride-to-stride variability and applied goal equivalent manifold (GEM) based control to decompose goal-equivalent and non-goal-equivalent manifold. To quantify the energy economy, the energy recovery rate (R) was calculated based on potential energy and kinetic energy. Comparisons were made between GEM variabilities and commonly used standard deviation measurements. A linear regression model was used to investigate the trade-off between R and GEM variabilities.

Results

Our analysis shows greater variability along the goal-equivalent manifold compared to the non-goal-equivalent manifold (p < 0.001). Moreover, our analysis shows lower energy recovery rate for amputee gait compared to nonamputee gait (at least 20% less at faster walking speed). We found a negative relationship between energy recovery rate and non-goal-equivalent variability. Compared to the standard deviation measurements, the variability decomposed using GEM reflected the preferred walking speed and the limitation of the passive prosthetic device.

Conclusion

Individuals with amputation cleverly leverage task redundancy, regulating step and stride variability to the GEM. This result suggests that task redundancy enables unilateral amputees to benefit from motor variability in terms of energy economy. The differences observed between prosthetic step and intact step support the development of prosthetic limbs capable of enhancing positive work during the double support phase and of powered prosthesis controllers that allow for variability along the task space while minimizing variability that interferes with the task goal. This study provides a different perspective on amputee gait analysis and challenges the field to think differently about the role of variability.
Circulation of genotypes of dengue virus serotype 2 in Guangzhou over a period of 20 years
Authors: Jiang Liyun , Liu Yuan , Su Wenzhe , Cao Yimin , Jing Qinlong , Wu Xinwei , Yang Zhicong
Published: March 2022

Background

The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here, we present the genotype data for dengue virus serotype 2 (DENV-2) to improve understanding of this dengue epidemic.

Methods

We sequenced the envelope gene of DENV-2 obtained from patient serum samples and subsequently performed maximum-likelihood phylogenetic analysis using PhyMLv3.1, maximum clade credibility analysis using BEAST v.1.10.4, and selection pressure analysis using Datamonkey 2.0.

Results

The prevalent DENV-2 strains identified in Guangzhou region are related to those in Southeast Asian countries. In particular, the Malaysia/Indian subcontinent genotype is prevailing in Guangzhou with no apparent genotype shift having occurred over the past 20 years. However, episodic positive selection was detected at one site.

Conclusions

Local control of the DENV-2 epidemic in Guangzhou requires effective measures to prevent and monitor imported cases. Moreover, the shift between the Malaysia/Indian subcontinent genotype lineages, which originated at different time points, may account for the rise in DENV-2 cases in Guangzhou. Meanwhile, the low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.
Association of serum methionine metabolites with non-alcoholic fatty liver disease: a cross-sectional study
Authors: Tang Yi , Chen Xu , Chen Qian , Xiao Jinghe , Mi Jiaxin , Liu Qiannan , You Yiran , Chen Yuming , Ling Wenhua
Published: March 2022

Background and project

Non-alcoholic fatty liver disease (NAFLD) is viewed as the hepatic manifestation of metabolic syndrome. Methionine metabolites have been linked to metabolic syndrome and its related diseases. Whether serum methionine metabolites levels are associated with NAFLD remains unclear. The study aimed to assess the association between methionine metabolites and NAFLD.

Methods

This cross-sectional study included a total of 2814 individuals aged 40–75 years old. All participants underwent anthropometric measurements, laboratory tests, dietary assessment and abdominal ultrasonography. Multivariable logistic regression analysis was performed to estimate the association of methionine metabolites with NAFLD.

Results

Overall, 1446 with and 1368 without NAFLD were enrolled in this study. Participants with NAFLD had significantly higher serum S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine (Hcy) levels, and a lower S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio than those without NAFLD (all P < 0.001). After adjusting multiple confounders, odds ratios (95% confidence interval) for quartile 4 versus quartile 1 of SAH, Hcy and SAM/SAH ratio were 1.65 (1.27–2.14), 1.63 (1.26–2.12) and 0.63 (0.49–0.83), respectively (all P for trend < 0.01). In addition, serum SAH, Hcy levels and SAM/SAH ratio were significantly correlated with the degree of hepatic steatosis (all P for trend < 0.001).

Conclusion

Elevated serum SAH, Hcy levels and lower SAM/SAH ratio may be independently associated with the presence of NAFLD in middle-aged and elder Chinese.
Validation of an MRI-only planning workflow for definitive pelvic radiotherapy
Authors: O’Connor Laura M. , Dowling Jason A. , Choi Jae Hyuk , Martin Jarad , Warren-Forward Helen , Richardson Haylea , Best Leah , Skehan Kate , Kumar Mahesh , Govindarajulu Geetha , Sridharan Swetha , Greer Peter B.
Published: March 2022

Purpose

Previous work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies.

Patients and methods

Forty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation.

Results

The median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was − 0.4% (IQR of 0 to − 0.6), and − 0.3% (IQR of 0 to − 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively.

Conclusions

A multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites.

Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.anzctr.org.au) on 04/10/2017. Trial identifier ACTRN12617001406392.
Fast characterization of segmental duplication structure in multiple genome assemblies
Authors: Išerić Hamza , Alkan Can , Hach Faraz , Numanagić Ibrahim
Published: March 2022

Motivation

The increasing availability of high-quality genome assemblies raised interest in the characterization of genomic architecture. Major architectural elements, such as common repeats and segmental duplications (SDs), increase genome plasticity that stimulates further evolution by changing the genomic structure and inventing new genes. Optimal computation of SDs within a genome requires quadratic-time local alignment algorithms that are impractical due to the size of most genomes. Additionally, to perform evolutionary analysis, one needs to characterize SDs in multiple genomes and find relations between those SDs and unique (non-duplicated) segments in other genomes. A naïve approach consisting of multiple sequence alignment would make the optimal solution to this problem even more impractical. Thus there is a need for fast and accurate algorithms to characterize SD structure in multiple genome assemblies to better understand the evolutionary forces that shaped the genomes of today.

Results

Here we introduce a new approach, BISER, to quickly detect SDs in multiple genomes and identify elementary SDs and core duplicons that drive the formation of such SDs. BISER improves earlier tools by (i) scaling the detection of SDs with low homology to multiple genomes while introducing further 7–33$$\times$$
×
speed-ups over the existing tools, and by (ii) characterizing elementary SDs and detecting core duplicons to help trace the evolutionary history of duplications to as far as 300 million years.

Availability and implementation

BISER is implemented in Seq programming language and is publicly available at https://github.com/0xTCG/biser.
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Authors: Liu Jian , Fu Minyang , Wang Manni , Wan Dandan , Wei Yuquan , Wei Xiawei
Published: March 2022

Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc.Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.
Determinants of SARS-CoV-2 waning immunity in allogeneic hematopoietic stem cell transplant recipients
Authors: Leclerc Mathieu , Redjoul Rabah , Le Bouter Anne , Beckerich Florence , Robin Christine , Parinet Vincent , Pautas Cécile , Menouche Dehbia , Bouledroua Selwa , Roy Lydia , Cabanne Ludovic , Nait-Sidenas Yakout , Fourati Slim , Maury Sébastien
Published: March 2022

Hematopoietic stem cell transplant (HSCT) recipients are at high-risk for severe COVID-19 and have altered immune responses to vaccination. We sought to evaluate the dynamics of immune response to BNT162b2 mRNA vaccine in HSCT recipients. We systematically proposed vaccination with BNT162b2 to HSCT recipients and gave a third vaccine dose to those showing titers of IgG(S-RBD) below 4160 AU/mL 1 month following the second dose. We then quantified anti-SARS-CoV-2 antibodies dynamics in 133 of these HSCT recipients (88 after two and 45 after three vaccine doses) 6 months after the first vaccine dose. Mean IgG(S-RBD) titer at 6 months was significantly lower than the peak value measured 1 month after a second (p < 0.001) or third (p < 0.01) vaccine dose. IgG(S-RBD) titers at 6 months were strongly correlated to peak values (p < 0.001) and a peak titer above 10,370 AU/mL predicted persistent protection at 6 months. Seventy-two percent (96/133) of patients retained protective antibody levels at 6 months. Immunosuppressive drugs and low lymphocyte counts in peripheral blood correlated with lower IgG(S-RBD) titers at 6 months. Four patients (3%) developed PCR-documented SARS-CoV-2 infection and one died.
Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness
Authors: Tu Cheng-Fen , Li Fu-An , Li Ling-Hui , Yang Ruey-Bing
Published: March 2022

Background

We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown.

Method

We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis.

Results

Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis.

Conclusions

Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.
Self-reported symptoms and health complaints associated with exposure to Ixodes ricinus-borne pathogens
Authors: Azagi Tal , Harms Margriet , Swart Arno , Fonville Manoj , Hoornstra Dieuwertje , Mughini-Gras Lapo , Hovius Joppe W. , Sprong Hein , van den Wijngaard Cees
Published: March 2022

Background

The impact of infections with tick-borne pathogens (TBPs) other than Borrelia burgdorferi (s.l.) and tick-borne encephalitis virus (TBEV) on public health in Europe remains unclear. Our goal is to evaluate whether the presence of these TBPs in ticks can be associated with self-reported health complaints.

Methods

We enrolled individuals who were bitten by I. ricinus between 2012 and 2015 and collected their relevant demographic and clinical information using a self-administered online questionnaire. A total of 4163 I. ricinus ticks sent by the participants were subject to molecular analyses for detection of specific TBPs. Associations between the presence of TBPs in ticks and self-reported complaints and symptoms were evaluated by means of a stepwise approach using a generalized linear model (GLM).

Results

Of 17 self-reported complaints and symptoms significant in the univariate analyses, 3 had a highly significant association (P < 0.01) with at least one TBP in the multivariate analysis. Self-reported Lyme borreliosis was significantly associated (P < 0.001) with B. burgdorferi (s.l.) infection. Facial paralysis was associated (P < 0.01) with infection with B. miyamotoi, N. mikurensis and R. helvetica. Finally, a significant association (P < 0.001) was found between nocturnal sweating and A. phagocytophilum.

Conclusions

We found associations between the presence of TBPs in ticks feeding on humans and self-reported symptoms. Due to the subjective nature of such reports and the fact that infection was determined in the ticks and not in the patient samples, further prospective studies utilizing diagnostic modalities should be performed before any clinical outcome can be causally linked to infection with TBPs.

Graphical Abstract
Innovative and conventional “conservative” technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment
Authors: Ferrario L. , Garagiola E. , Gerardi C. , Bellavia G. , Colombo S. , Ticca C. , Rossetti C. , Ciboldi M. , Meroni M. , Vanzulli A. , Rampoldi A. , Bignardi T. , Arrigoni F. , Porazzi E. , Foglia E.
Published: March 2022

Background

To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard “conservative” procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE).

Methods

A Health Technology Assessment was conducted, assuming the payer’s perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients’ clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids’ experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy).

Results

Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients’ perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients’ productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of − 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs.

Conclusions

Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.
Duck plague virus UL41 protein inhibits RIG-I/MDA5-mediated duck IFN-β production via mRNA degradation activity
Authors: He Tianqiong , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Jia Renyong , Chen Shun , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Tian Bin , Ou Xumin , Mao Sai , Sun Di , Gao Qun , Yu Yanling , Zhang Ling , Liu Yunya
Published: March 2022

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors that initiate innate antiviral immunity. Recent reports found that duck RLRs significantly restrict duck plague virus (DPV) infection. However, the molecular mechanism by which DPV evades immune responses is unknown. In this study, we first found that the DPV UL41 protein inhibited duck interferon-β (IFN-β) production mediated by RIG-I and melanoma differentiation-associated gene 5 (MDA5) by broadly downregulating the mRNA levels of important adaptor molecules, such as RIG-I, MDA5, mitochondrial antiviral signalling protein (MAVS), stimulator of interferon gene (STING), TANK-binding kinase 1 (TBK1), and interferon regulatory factor (IRF) 7. The conserved sites of the UL41 protein, E229, D231, and D232, were responsible for this activity. Furthermore, the DPV CHv-BAC-ΔUL41 mutant virus induced more duck IFN-β and IFN-stimulated genes (Mx, OASL) production in duck embryo fibroblasts (DEFs) than DPV CHv-BAC parent virus. Our findings provide insights into the molecular mechanism underlying DPV immune evasion.
Non-melanoma skin cancer among ethnic German immigrants (resettler) from the former Soviet Union: a cohort study from 1990 to 2007
Authors: Markeeva-Ilisevic Evgenia , Holleczek Bernd , Becher Heiko , Winkler Volker
Published: March 2022

Background

UV radiation is a significant risk factor for non-melanoma skin cancer (NMSC). Ethnic Germans (resettlers) who immigrated to Germany from the former Soviet Union may have had a relatively high UV light exposure and thus a higher risk of developing NMSC. We compared the incidence of NMSC in a resettler cohort with the general population of the Saarland (Federal state of Germany) in relation to tumour location.

Methods

All new NMSC cases (resettler cohort and total population) between 1990 and 2007 were retrieved from the Saarland cancer registry and classified according to sex, histology, and location. The classification used for tumour location approximated the previous UV exposure. Age-standardized incidence rates (ASR) for the general population and standardized incidence ratios (SIR) for resettlers compared to the general population were calculated and modelled using Poisson regression.

Results

Sex-specific overall SIR indicated a significant increase in female resettlers (SIR 1.31 (95% CI 1.02–1.67)) which can mostly be attributed to an increased incidence of squamous cell carcinoma. The regression analysis showed that among resettlers the risk of developing tumours in UV-exposed skin areas was 2.16 (95% CI 1.35–3.45) higher compared to the general population.

Conclusions

Female resettlers have a higher risk to be diagnosed with NMSC than the general German population. Based on the observed distribution of tumour location, it is suspected that UV exposure contributed significantly to this risk.
Interaction between historical earthquakes and the 2021 Mw7.4 Maduo event and their impacts on the seismic gap areas along the East Kunlun fault
Authors: Dong Peiyu , Zhao Bin , Qiao Xuejun
Published: March 2022

On May 21, 2021 (UTC time), an Mw7.4 earthquake struck Maduo County, Qinghai Province, China. The rupture of this typical strike-slip event and its aftershocks along the Kunlun-Jiangcuo fault (JCF) propagated approximately 170 km from the epicenter. In this study, we calculated the coseismic and postseismic Coulomb stress changes induced by 14 historical earthquakes and investigated their impacts on the 2021 Maduo source area. We found that the JCF is in the stress shadow of these historical events with a combined ΔCFS range of approximately − 400 to − 200 kPa. Since the seismogenic fault of the 1937 event is nearly parallel and close to the JCF, the rupture of the 1937 event had the greatest inhibitory effect on Maduo source area. We hypothesize that the actual loading rate at the depth of the seismogenic layer in the Maduo source area is much higher than the simulated value (0.3 kPa/a). Consequently, the Maduo earthquake still occurred despite the considerable delaying effect of these historical earthquakes (especially the 1937 event). Our findings also indicate that the tectonic stress in the eastern Bayanhar block is still rapidly accumulating and adjusting. Our investigation further reveals the enhanced stress induced by the historical and Maduo events with ΔCFS values of approximately 30–300 kPa and 50–300 kPa on the Xidatan-Dongdatan segment (XDS) and the eastern end of the East Kunlun Fault (EKF), respectively, not only on the Maqin-Maqu segment (MMS) but also at the eastern end of each branch segment of the EKF. Hence, considering the accumulation of tectonic stress, we suggest that the seismic hazard in these two regions has been promoted.

Graphic Abstract
Posterior reversible encephalopathy syndrome in a known case of sickle-beta-thalassemia: a case presentation
Authors: Kausha Mumbaikar , Vishal Sawant , Kondekar Alpana S.
Published: March 2022

Background

Posterior reversible encephalopathy syndrome is a reversible condition, which occurs in response to acute changes in blood pressure due to failure of posterior circulatory autoregulation. Posterior reversible encephalopathy syndrome in sickle cell patients has been rarely reported previously in the setting of severe crisis or uncontrolled hypertension.

Case presentation

We report a very rare case of posterior reversible encephalopathy syndrome that occurred in a 10-year-old male child with sickle-beta-thalassemia which was detected at 4 years of age and required 2 units of packed red blood cells transfusion in last 6 years. At the time of the presentation, he was hypertensive with blood pressure 140/100 mm of Hg (> 99th percentile) and had focal seizures with magnetic resonance imaging findings suggestive of posterior reversible encephalopathy syndrome. Patient was treated with anticonvulsant and antihypertensives and had complete recovery of symptoms.

Conclusions

Posterior reversible encephalopathy syndrome is a rare neurological presentation in a sickle-beta thalassemia; this case guides in differentiating it from other common neurological manifestations in sickel-beta thalassemia and emphasis on early management as it is completely reversible.
On gravity and quantum interactions
Authors: Trinhammer Ole L.
Published: March 2022

We introduce the metric of general relativity into a description of baryon mass spectra which otherwise has been founded entirely on the concept of an intrinsic configuration space, the Lie group U(3). We find that the general relativistic metric influences the mass eigenstates in gravitational fields. We discuss parts per million effects that may be observed in space missions close to the Sun or the planet Jupiter, for instance by accurate Cavendish experiments or energy shifts in gamma decays of metastable nuclei like Ba-137m. We review how the particle and gauge fields are generated by momentum forms on the intrinsic wave functions to form the quantum field bases for instance of quantum chromodynamics. Our strategy to combine quantum interactions and general relativity is that of geometrising quantum mechanics rather than quantising gravity.
The epsilon-mu-near-zero (EMNZ) device realized by a novel structure of air gap ring at microwave frequency
Authors: Zhao Lin , Wang Ning , Xie Hui
Published: March 2022

The epsilon-and-mu-near-zero (EMNZ) medium, as a kind of zero-refractive-index material, has broad application perspectives. In general, there are three main methods to realize the EMNZ phenomenon based on conventional metamaterials such as fishnet metamaterials, Dirac-like cone-based metamaterials, and doped ENZ mediums in the full frequency range. However, the above EMNZ metamaterials have complex structures and stringent process requirements, and the development of mature engineering applications outside the laboratory is still a long way off. Herein, a novel, simple and stable air gap ring compatible with the EMNZ medium based on the doping method has been proposed to mitigate the above constraints. The proposed structure is composed of a set of nested metal boxes and an air gap ring formed between the nested metal boxes. By changing the size of the cross-sectional area of the perfect electric conductor (PEC) doped into an ENZ medium to manipulate the air gap ring in the nested metal boxes, the effective magnetic permeability of the whole structure can be adjusted. Finally, the equivalent EMNZ medium characterized by a simple structure can be realized in the microwave band. Thus, the proposed novel air gap ring device exhibits promising potential for broad applications such as frequency selection, impedance regulation, super-coupling, and power splitting.