bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Modic Changes on Cervical Fusion After Single-level Anterior Cervical Discectomy and Fusion.
Authors: Zhang Mengxin , Zhang Shangpu , Shen Yong , Wu Zhanyong
Published: February 2021

Objective: The purpose of this study was to investigate the relationship between cervical Modic changes and cervical fusion. Methods: This study enrolled 222 patients who underwent single-level anterior cervical discectomy and fusion(ACDF) surgical treatment between April 2014 and July 2019 at our institution, xingtai mining group general. All patients were followed up for more than 1 year after surgery. According to the presence or absence of Modic changes, 66 cases were divided into group A with Modic changes and 156 cases in group B without Modic changes. The pathological changes of cervical spine Modic were divided into 3 stages: Type 1 (inflammation or edema), manifested as endplate and subendplate The tissue is replaced by fibrovascular tissue, accompanied by granulation tissue ingrowth, bone marrow and trabecular edema; type 2 (fatty stage or yellow bone marrow stage), showing the corresponding histopathological changes as red bone marrow transition between trabecular bone It is yellow bone marrow with a large amount of adipose tissue deposition; Type 3 (osteosclerosis stage), which manifests as the endplate and the sub-endplate tissue hyperplasia and hardening into bone tissue. The bone healing process is roughly divided into the organizing period of hematoma formation; the original callus formation period; and the plastic period of callus transformation. According to Modic I, II, and III classifications, sub-groups are carried out in sequence: A1, A2, A3, and the differences in fusion between the groups during follow-up are compared. Results: There was a statistically significant difference between the two groups at the 3 months (p=0.004) and 6 months (p=0.044) follow-up of group A and group B, and there was no statistical difference between the two groups at the last follow-up (p=0.43) Significance; the three groups of A1, A2, and A3 were followed up for 3 months (p=0.007) and 6 months (p=0.002). The difference between the three groups was statistically significant, and the difference between the three groups at the last follow-up (p=0.092) No statistical significance. Conclusion: The fusion rate of patients with cervical Modic changes in the early and middle postoperative period is lower than that of normal cervical patients, and the fusion effect of Modic type I patients is better than that of Moidc II and III. However, the last follow-up showed that all patients have achieved fusion, that is, cervical Modic changes have a positive effect. The patient's fusion rate has no effect.
Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study
Authors: Maindal Helle Terkildsen , Timm Anne , Dahl-Petersen Inger Katrine , Davidsen Emma , Hillersdal Line , Jensen Nanna Husted , Thøgersen Maja , Jensen Dorte Møller , Ovesen Per , Damm Peter , Kampmann Ulla , Vinter Christina Anne , Mathiesen Elisabeth Reinhardt , Nielsen Karoline Kragelund
Published: February 2021

Background: Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks.Methods: The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. We iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites. Results: During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes. Conclusions: This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders. Trial registration: ClinicalTrials.gov NCT03997773, registered retrospectively on 25 June 2019. https://clinicaltrials.gov/ct2/show/NCT03997773
Dynamics of anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 in a Brazilian Amazon Population
Authors: Bichara Carlos David Araújo , Amoras Ednelza da Silva Graça , Vaz Gergiane Lopes , Torres Maria Karoliny da Silva , Queiroz Maria Alice Freitas , Amaral Isabella Pinheiro Costa do , Vallinoto Izaura Maria Vieira Cayres , Bichara Cléa Nazaré Carneiro , Vallinoto Antonio Carlos Rosário
Published: February 2021

Background: In this study, the prevalence and persistence of anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) IgG was evaluated in volunteers 90 days after COVID-19 (coronavirus disease 2019) diagnosis by correlating response dynamics with clinical conditions, IL-1β and IL-6 cytokine levels, epidemiological characteristics, and disease severity. Methods: The study recruited 200 volunteers aged 18 years or older of both sexes diagnosed with COVID-19. ELISA testing was performed to detect IgG persistence and cytokine levels in 135 individuals with a previous serological test at the time of COVID-19 diagnosis.Results: Among the 135 individuals who underwent a previous serological test for anti-SARS-CoV-2 antibody and provided a new blood sample 90 days after the first examination, 125 showed reactivity to IgG (92.6%). Of the 125 individuals with detectable IgG in the first test, 69.6% showed persistence of this antibody after 90 days; however, in 10 (30.4%) individuals, IgG was nonreactive in the second evaluation. The frequency of all reported symptoms was higher in individuals who maintained IgG persistence after 90 days of symptoms, and no relationship with cytokine levels was observed. Conclusions: The results of the present study show a high frequency of loss of anti-SARS-CoV-2 IgG antibodies within three months after COVID-19 diagnosis in the Brazilian Amazon.
Association Between Maternal Dietary Pattern and Infant Birth Weight: a Structural Equation Modelling Analysis
Authors: Santana Jerusa Mota , Queiroz Valterlinda Alves Oliveira , Pereira Marcos , Paixao Enny S. , Brito Sheila Monteiro , Santos Djanilson Barbosa dos , Oliveira Ana Marlucia
Published: February 2021

Background: The mother’s diet during pregnancy is associated with maternal and child health. However, there are few studies with moderation analysis on maternal dietary patterns and infant birth weight. We aim to analyse the association between dietary patterns during pregnancy and birth weight. Methods: A cohort study was performed with pregnant women in Bahia, Brazil. A food frequency questionnaire was used to evaluate dietary intake. Birth weight was measured by a prenatal service team. Statistical analyses were performed using factor analysis with a principal component extraction technique and structural equation modelling. Results: Four patterns of dietary consumption were identified for each trimester of the pregnancy evaluated. Adherence to the "Meat, Eggs, Fried Snacks and Processed foods” dietary pattern (pattern 1) and the "Sugars and Sweets" dietary pattern (pattern 4) in the third trimester directly reduced birth weight, by 98.42 g (Confidence interval (CI) 95%: 24.26, 172.59) and 92,03g (CI 95%: 39.88, 165.30), respectively. Insufficient dietary consumption in the third trimester increases maternal complications during pregnancy, indirectly reducing birth weight by 145 g (CI 95%: -21.39, -211.45). Conclusion: Inadequate dietary intake in the third trimester appears to have negative results on birth weight, directly and indirectly.
Effects of Potassium Deficiency on Growth of Pakchoi in Cold and Dry Areas
Authors: LI Shi-Heng , LI Wei-Ming , BU Ling-Hao
Published: February 2021

[Background] To reveal the effect of potassium deficiency on the growth and development of pakchoi in cold and dry areas.[Results] The effect of potassium deficiency on the growth status of P. pakchoi in cold and dry areas was significant. P. pakchoi treated with potassium-free nutrient solution had the best growth, the largest number of leaves, leaf length, leaf width, leaf area, root length and weight; P. pakchoi treated with 100% potassium deficiency had the smallest plant, leaf length, leaf width, leaf area, root length and weight; P. pakchoi treated with potassium deficiency 50% had the middle growth and development status, and the root ratio was the smallest in d 21.[Conclusion] Potassium can effectively promote the growth and development of pakchoi in cold and dry areas, increase its root length, leaf width, leaf area, weight, etc. The quality of the upper part and the underground part of d,21 of pakchoi treated with deficiency is the most different.
Modified Ileal Conduit for Urinary Diversion After Radical Cystectomy: Perioperative and Oncological Outcomes
Authors: Zhang Yimu , Li Jing , Bai Jiyan , Zhou Zhengyu , Tian Pei , Yang Dong , Ma Yan , Zhao Pengcheng , He Chaohong
Published: February 2021

Background: To evaluate the surgical effects and oncological outcomes of modified ileal conduit (IC) after radical cystectomy (RC) for bladder cancer.Methods: A single-centre cohort of 211 consecutive bladder cancer patients who underwent RC + modified IC from September 2012 to August 2019 were retrospectively studied. Demographic data, perioperative results, complications 30 and 90 days after surgery and oncological outcomes were recorded. Kaplan–Meier method was used to plot the stage-specific survival results. The 5-year recurrence-free survival (RFS）and overall survival (OS) rate was calculated. Univariate and multivariate Cox regression analyses assessed the predictive risk factors on survival rate.Results: Overall, 211 patients received modified IC after RC. The median operative time (OT) was 315 minutes (IQR, 260–375 minutes), and the median estimated blood loss (EBL) was 500 ml (IQR, 300–900 ml). There were a total of 103 (48.8%) complications. There were 35, 54, 11, and 2 cases of grade I, II, III, and IV complications, respectively; of which 89 cases were grade I and II, accounting for 87.3% of total cases. There were 38 cases of preoperative hydronephrosis and 22 cases of postoperative hydronephrosis. There were 19, 24, 108, 40, and 20 cases of PT0, T1, T2, T3, and T4, respectively, in postoperative pathological stages. The median lymphadenectomy was 14 (IQR, 6–18), and lymph node was found positive in 18 patients. The median follow-up time was 26 months (IQR, 13–43), with a total survival of 177 (83.9%), an RFS of 171 (81%), and 34 deaths. The estimated 5-year OS and RFS rates were 76.80% and 79.10%. Preoperative comorbidities, pathological stage, grade, and lymph node involvement were important influencing factors for OS, while preoperative comorbidities and high pathological grade were important influencing factors for RFS.Conclusions: Modified IC after RC not only can achieve lower postoperative complications, especially the lower incidence of uretero-ileal anastomosis and stoma-related complications but can also achieve the established oncological outcomes of critical radical surgery.
Factors Associated With the People Preferences for the Breast Cancer Genetic Tests: a Systematic Review
Authors: Meshkani Zahra , Aboutorabi Ali , Moradi Najmeh , Langarizadeh Mostafa , Motlagh Ali Ghanbari
Published: February 2021

Background: Despite the genetic test’s benefits in early detection of disease, many people do not have the test performed. This study aimed to systematically review the associated factors with a preference for the gene tests regarding breast cancer. Methods: It was a systematic review study. Data were collected from Scopus, PubMed, Web of Science (WOS), ProQuest, and Embase databases. All full-text English language studies up to 2020 that addressed the preference for the gene screening tests for early detection of breast cancer were included. Data extracted and assessed for quality by two independent reviewers. Disagreements were resolved by a consensus meeting with a third reviewer. The vote counting was determined for identifying the associated factors with the preference.Results: From 1269 initially retrieved citations, 25 studies were included. According to vote counting analysis, age was identified as strongly negative factor while being married, income, family history of breast cancer, personal history or presence of breast cancer, BRCA-related knowledge were identified as strongly positive factors with preference of genetic tests for breast cancer. About 96% of articles were in high quality.Conclusion: There was low evidence in associated factors with a preference on gene tests, especially for psychological factors. So, further research is needed to help policymakers to develop early detection strategies and increase people's participation that leads to the success of the strategies and avoiding the high cost of treatment as well.Systematic review registration: PROSPERO 2020 (ID: CRD42020190811).
Kirschner Wire as a Reference Marker for the Positioning of a Syndesmotic Screw: a Radiological Study and Clinical Application
Authors: Zhang Congming , Wang Qian , Duan Ning , Ma Teng , Zhang Kun , Xue Hanzhong , Li Zhong
Published: February 2021

Background: Without a reliable and static reference, the rate of eccentrically positioned distal syndesmotic screw is very high. This article describes an additional method to improve surgeons’ ability to ideally place this screw. The purposes of our study were (1) to determine if an ideal space at 2.5 cm proximal to the plafond existed between the tibia and fibula for the placement of a Kirschner (K) wire and (2) to detect if it could act as a reliable and static fibular incisura plane reference. Methods: Computed tomography (CT) scans of 42 uninjured adult ankles with foot fractures were analysed to measure the tibiofibular vertical distance (TFVD) at 2.5 cm proximal to the plafond on transverse images. TFVD was defined as the distance between two lines: Line 1 was tangent to the fibular incisura, and Line 2 was parallel to Line 1 along the medial fibula. Patients were divided into four groups according to our TFVD data: 0–1, 1–2, 2–3, and 3–4 mm, and the number of patients in each group was counted. We assessed 23 patients who underwent syndesmotic screw fixation for ankle fractures. Comparison of the angle between the anatomic axis of the syndesmosis and screw axis (AAS) was performed between patients using conventional method (11 patients) and with K-wire marker (12 patients). Results: TFVD measured 2.23 ± 1.01 mm at 2.5 cm proximal to the plafond. TFVD occurred at 25% of the distance from 2 to 3 mm in 47.6% of patients. This new technique decreased the deformation of AAS by 75%, from 13.06 ± 2.55° to 4.28 ± 1.72°, in the conventional group.Conclusions: Placing a 1.6-mm K-wire in the syndesmosis at 2.5 cm proximal to the tibial plafond is easy because of emerging TFVDs. Compared to the conventional method, this new technique increased the accuracy of syndesmotic screw placement by up to 75 percent. Therefore, K-wire could be used as a reliable and static intraoperative reference of the fibular incisura plane through which surgeons can accurately place a screw trajectory.
Design Plasmonic Optical 4×2 Encoder based on 2D Photonic Crystal Ring Resonator
Authors: hamedi samaneh , Negahdari Roozbeh , Ansari Hamid Reza
Published: February 2021

Digital encoders are one of the key devices required in optical communication and digital signal processing systems. In this paper, a new photonic crystal structure is used to design all optical 4x2 encoder constructed from GaAs rods with square lattice in the pentane bachground based on plasmonic effect. Gold rods have also been used at the interface of dielectric rods and lines defect, which create plasmonic properties into the photonic crystal structure. The designed optical device is composed of four input waveguides and two output waveguides with two ring resonators at the resonant wavelength of 1.4mm with TM polarization. The presented encoder platform has the small size of 19 mm ×33 mm, that makes it to integration into all optical communication systems. The encoder operation is simulated and analyzed with numerical Finite Difference Time Domain (FDTD) method hand Plane Wave Expansion (PWE) method. In the proposed structure, we have shown that by selecting the appropriate radius size for the resonant cavities, the desirable wavelength can be obtained. The maximum values of transmission efficiency for the first and second outputs are 82% and 96%, respectively. Resonant cavities are also located in the crystal lattice in such a way that by activating third input, 50% and 48% of the input signal will be obtained in each output ports indicating (1,1) logic state. So the new plasmonic photonic crystal encoder could be future applicable in the field of optical computing.
Experience of patients with Asthma from the role of social support in self-care: A qualitative study
Authors: Haghighi mohammadAli , vali leila , goudarzi reza , samare mitra , GhorbaniNia Rahil
Published: February 2021

BackgroundAsthma is one of the biggest challenges of health systems. One of the most effective ways to control this chronic disease is self-care. Self-care can be affected by social support. This study aimed to explain the experience of patients with Asthma from the role of social support in their self-care.MethodsThis study was qualitative and phenomenological and conducted in 2019. Data collected through semi-structured interviews with 40 patients using purposive sampling. It is noteworthy that the implemented interviews were analyzed using the seven-step Colaizzi method.ResultsFindings presented two main themes (patient communication network, self-care of asthmatics) and ten sub-themes. Some of the sub-themes included motivating peers as a reason for self-care, lifestyle and self-care advice, add exercise to the life plan, and therapeutic recommendations are a factor in following a treatment regimen.ConclusionsIt seems that self-care with social support and establishing a communication network between people with Asthma to transfer information and experiences and identify their needs in the management and control of this disease at the community level can be very serious.Trial registration: IR.KMU.REC.1399.357 date: 1399/6/17 (7september2020)
Transcriptomic and histological analysis of exposed facial skin areas wrinkled or not and unexposed skin
Authors: Martin Renan Paulo , Varela Patricia , Gomes Caio Peres , Marins Maryana Mara , Filippelli-Silva Rafael , Yarak Samira , Soares Juliana L.M. , Sanudo Adriana , Idkowiak-Baldys Jolanta , Chen Siming , Hwang Cheng , Zhuang Yong , Lyga John , Pesquero João Bosco , Bagatin Edileia
Published: February 2021

Skin aging involves genetic, environmental and hormonal factors. Facial wrinkles also depend on muscular activity. Gene expression investigation may be useful for new anti-aging products. To evaluate structure and gene expression differences among exposed and unexposed skin in menopausal women. Cross-sectional study, including 15 menopausal women, 55-65yo, phototype III; photo-exposed, periorbital wrinkles (A1), preauricular, not wrinkled (A2), and unexposed gluteal (A3) areas were described and compared by non-invasive measures, histology, immunohistochemistry and gene expression (RNASeq); participants mean age was 61yo, presenting moderate periorbital wrinkles and light facial photodamage. Higher roughness, wrinkles number and echogenicity were observed in A1 and A2 versus A3. Decreased epidermal thickness and dermal collagen IV were demonstrated in A1 versus A2 and A3. Exposed areas impacted different pathways compared to unexposed. Exposed wrinkled skin (A1) showed impact on cell movement with decreased inflammatory activation state. Pathways related to lipid and aminoacids metabolism were modulated in non-wrinkled exposed (A2) compared to unexposed (A3) skin. Expected histological findings and gene expression differences among areas were observed. Photoaging in menopausal women may modulate lipid and aminoacids metabolism and decrease inflammatory and keratinization pathways, cellular homeostasis, immune response, fibrogenesis and filament formation. These findings may help development of new therapies for skin health and aging control.
Tocilizumab-induced unexpected increase of several inflammatory cytokines in critically ill COVID-19 patients
Authors: Ponthieux Fanny , Dauby Nicolas , Maillart Evelyne , Fils Jean-François , Smet Julie , Claus Marc , Besse-Hammer Tatiana , Bels David De , Corazza Francis , Nagant Carole
Published: February 2021

Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 and may explain why TCZ has failed to improve survival in critically ill COVID-19 patients when given alone.
Clinical Significance of COL11A1 and Its Effect on Immune Infiltration in Colorectal Cancer
Authors: Wu Yibin , Cai Yuankun , Chen Wenjie , Ye Tao , Xu Ye , Wang Huipeng
Published: February 2021

Background

Collagen type XI alpha 1 chain (COL11A1) is an extracellular matrix (ECM) protein and plays a crucial role in tumors. However, the correlations of COL11A1 to prognosis and tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain unclear.
Methods

Here, we used bioinformatics methods with experimental exploration to evaluate the prognostic value of COL11A1 in CRC, while the alteration of the gene and its function in CRC was explored by using cBioPortal and DAVID. Furthermore, the correlations between COL11A1 expression and cancer immune infiltrates, gene marker sets of immune infiltrates were analyzed by TIMER, GEPIA and human samples.
Results

Increased COL11A1 expression was found in CRC and positive correlated with tumor stage, node metastasis and histological type. Patients with higher COL11A1 expression had shorter survival data. Function network revealed that COL11A1 mainly regulated pathways involving in focal adhesion, PI3K-AKT signaling pathways and ECM-receptor interaction. Furthermore, COL11A1 expression was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD). COL11A1 expression showed strong correlations with diverse immune marker sets in COAD. In addition, COL11A1 expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in COAD.
Conclusions

Our data identify COL11A1 as a novel prognostic biomarker for determining prognosis and immune infiltration in COAD, which might optimize therapeutic strategies for CRC patients.
Using Historical Data to Facilitate Clinical Prevention Trials in Alzheimer Disease?
Authors: Berres Manfred , Monsch Andreas U. , Spiegel René
Published: February 2021

BackgroundThe Placebo Group Simulation Approach (PGSA) aims at partially replacing Randomized Placebo-Controlled Trials (RPCTs) using data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms were originally derived from Mild Cognitive Impairment (MCI) data of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in an heuristic manner to create a ‘standard control algorithm’ for use in future clinical trials.MethodsWe compared data from two North American cohort studies (n= 395 and 4,328, respectively) one international clinical drug trial (n= 831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1,558).ResultsDespite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30 percent.ConclusionConventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published MCI criteria are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.
HP1 oligomerization compensates for low-affinity H3K9me recognition and provides a tunable mechanism for heterochromatin-specific localization
Authors: Biswas Saikat , Karslake Joshua , Chen Ziyuan , Farhat Ali , Freddolino Peter , Biteen Julie , Ragunathan Kaushik
Published: February 2021

HP1 proteins bind with low affinity but high specificity to histone H3 lysine 9 methylation (H3K9me), forming transcriptionally inactive genomic compartments referred to as heterochromatin. How HP1 proteins traverse a complex and crowded chromatin landscape on the millisecond timescale to bind H3K9me chromatin remains paradoxical. Here, we apply single-molecule imaging to visualize an HP1 homolog, the fission yeast Swi6, in its native chromatin environment. By analyzing Swi6 motions, we identify individual mobility states that map to discrete biochemical intermediates. Using mutants that perturb Swi6 H3K9me recognition, oligomerization, or nucleic acid binding, we mechanistically parse how each biochemical property affects protein dynamics. While nucleic acid binding titrates Swi6 away from heterochromatin, as few as four tandem chromodomains are sufficient to restore H3K9me-dependent localization. Our studies propose a new paradigm where HP1 oligomerization stabilizes higher-order complexes to outcompete inhibitory nucleic acid and non-specific chromatin interactions, enabling high specificity H3K9me recognition in cells.
Hopping conduction mechanism and impedance spectroscopy analyses of La0.70Sr0.25Na0.05Mn0.70Ti0.30O3 ceramic
Authors: raddaoui zeineb , safwen elkossi , Trukhanov alex , Kozlovskiy alex , Zdorovets M , dhahri jemai
Published: February 2021

The perovskite sample La0.7Sr0.25Na0.05Mn0.7Ti0.3O3 (LSNM0.70T0.30) was produced via a solid-state route process. Impedance spectra of LSNM0.70T0.30 in the frequency interval [40Hz -1MHz] were studied at several temperatures [80K to 440 K]. The ac conductivity (σac) established that according to the Jonscher law. σac is described by Non-overlapping Small Polaron Tunneling model at low temperatures and Correlated Barrier Hopping model at high temperatures. From dc conductance analysis, conduction seems to be thermally activated, suggesting the existence of semiconductor process. Detailed investigation of impedance data revealed the non-Debye nature of the relaxation processes in the sample. In addition, Dielectric constant curves were applied to examine the relaxation dynamics of charge carriers. In fact, the Debye-like relaxation was performed on the basis of the polarization of spatial charges following Maxwell-Wagner model and Koop’s phenomenological theory.
Estimating High Mobility Group Box Protein 1 (HMGB1) Single Nucleotide Polymorphisms Among Hepatitis B Virus Infected Patients of Pakistan Origin
Authors: Tabassum Sobia , Khalid Zanib , Piracha Zahra Zahid , Saeed Umar , Ashraf Muhammad , Aziz Hafsa
Published: February 2021

HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which inducesfibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our resultsshowedsignificant correlationof HMGB1 polymorphism with HBV infection in the selected Pakistani population.
Gastrointestinal and Genitourinary Toxicity Profiles of Metformin Versus Placebo in Men With Prostate Cancer Receiving Pelvic Radiotherapy: Interim Toxicity Results of a Double-blinded, Multicenter, Phase II Randomized Controlled Trial
Authors: Usmani Nawaid , McDonald Megan O. , Ong Aldrich , Koul Rashmi , Dubey Arbind , Hunter William , Ahmed Shahida , Quon Harvey , Yee Don , Parliament Matthew , Sivananthan Gokulan , Danielson Brita , Rowe Lindsay , Ghosh Sunita , Kim Julian O.
Published: February 2021

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p=0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p=0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p=0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.
Genomic and phenotypic description of Streptococcus resistens sp. nov., Streptococcus buccae sp. nov. and Streptococcus mediterraneus sp. nov., three new members of the Streptococcus genus isolated from the human oral cavity
Authors: Naud Sabrina , Hasni Issam , Bellali Sara , Kieu Hoang Thong , Lo Cheikh Ibrahima , Anani Hussein , Bonnet Marion , Armstrong Nicholas , Richez Magali , Robinne Simon , Raoult Didier , Lagier Jean-Christophe , Alou Maryam Tidjani
Published: February 2021

Phenotypic, phylogenetic and genomic studies were carried out on three unidentified Gram-stain positive, facultative anaerobic, and cocci-shaped bacteria isolated from the human oral cavity. The 16S rRNA gene of strains Marseille-P5794 T , Marseille-P6264 T and Marseille-P7376 T exhibited a sequence identity of 99,41%, 99.67% and 97.88%, respectively with Streptococcus cristatus, their closest phylogenetic relative with standing in nomenclature. Moreover, the rpoB gene sequence of strains Marseille-P5794 T and Marseille-P6264 T shared a similarity level with 96.1%, and 95.9% with Streptococcus cristatus whereas strain Marseille-P7376 T shared a 93.98% identity with Streptococcus sanguinis. Whole genome comparison of strains Marseille-P5794 T , Marseille-P6264 T and Marseille-P7376 T with their phylogenetic neighbours were under the threshold values set to define new species using digital DNA-DNA hybridization and Orthologous Average Nucleotide Identity. The taxonogenomics analysis thus allowed the classification of these strains as new species within the Streptococcus genus named Streptoccocus resistens sp. nov. Strain Marseille-P5794 T (=CSUR P5794 = CECT9902), Streptococcus buccae sp. nov. Strain Marseille-P6264 T (=CSUR P6264 = CECT9910) and Streptococcus mediterraneus sp. nov. Strain Marseille-P7376 (=CSUR P7376 = CECT30035).
Follower Link Prediction using the XGBoostClassification Model with Multiple Graph Features
Authors: Behera Dayal Kumar , Dash Madhabananda , Swetanisha Subhra , Nayak Janmenjoy , Vimal S , Naik Bighnaraj
Published: February 2021

The Follower Link Prediction is an emerging application preferred by social networking sites to increase their user network. It helps in finding potential unseen individual and can be used for identifying relationship between nodes in social network. With the rapid growth of many users in social media, which users to follow leads to information overload problems. Previous works on link prediction problem are generally based on local and global features of a graph and limited to a smaller dataset. The number of users in social media is increasing in an extraordinary rate. Generating features for supervised learning from a large user network is challenging. In this paper, a supervised learning model (LPXGB) using XGBoost is proposed to consider the link prediction problem as a binary classification problem. Many hybrid graph feature techniques are used to represent the dataset suitable for machine learning. The efficiency of the LPXGB model is tested with three real world datasets Karate, Polblogs and Facebook. The proposed model is compared with various machine learning classifiers and also with traditional link prediction models. Experimental results are evident that the proposed model achieves higher classification accuracy and AUC value.
Controlling COVID-19 via test-trace-quarantine
Authors: Kerr Cliff , Mistry Dina , Stuart Robyn , Rosenfeld Katherine , Hart Gregory , Núñez Rafael , Cohen Jamie , Selvaraj Prashanth , Abeysuriya Romesh , Jastrzębski Michał , George Lauren , Hagedorn Brittany , Panovska-Griffiths Jasmina , Fagalde Meaghan , Duchin Jeffrey , Famulare Mike , Klein Daniel
Published: February 2021

Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine. We performed this analysis using Covasim, an open-source agent-based model, which was calibrated to detailed demographic, mobility, and epidemiological data for the Seattle region from January through June 2020. With current levels of mask use and schools remaining closed, we found that high but achievable levels of testing and tracing are sufficient to maintain epidemic control even under a return to full workplace and community mobility and with low vaccine coverage. The easing of mobility restrictions in June 2020 and subsequent scale-up of testing and tracing programs through September provided real-world validation of our predictions. Although we show that test-trace-quarantine can control the epidemic in both theory and practice, its success is contingent on high testing and tracing rates, high quarantine compliance, relatively short testing and tracing delays, and moderate to high mask use. Thus, in order for test-trace-quarantine to control transmission with a return to high mobility, strong performance in all aspects of the program is required.
Plasticity in thermal hardening of the invasive Asian house gecko
Authors: Lapwong Yingyod , Dejtaradol Ariya , Webb Jonathan K.
Published: February 2021

The Asian house gecko (Hemidactylus frenatus) is a tropical invasive species that has established and spread throughout several temperate regions around the world. In some invasive species, rapid thermal acclimation (thermal hardening) may contribute to their success in occupying a wide range of climates. In this study, we investigated whether invasive house geckos from southeastern Australia show differing thermal hardening responses than individuals from the native range in Thailand. In the laboratory, we measured the basal heat tolerance (CTmax) of the geckos and their heat hardening response after being subjected to the second thermal stress after 1, 3, 5, 7, 9, or 11 hours. When geckos had recovered, we measured their basal cold tolerance (CTmin) and cold hardening response over the same time intervals. We then explored whether hardening responses differed between populations or among time intervals. We found that basal heat tolerances did not differ between populations, but geckos from Australia had lower cold tolerance than geckos from Thailand. The magnitude of the heat hardening was similar between populations, but the introduced geckos had a higher magnitude of cold hardening. The native geckos could maximize their cold tolerance capacity for only 0.6 °C, comparing to 0.9 °C of the introduced geckos. Also, geckos from Australia exhibited faster responses to thermal stress than did geckos from Thailand. Maximum thermal tolerances as a result of hardening responses peaked within three hours after thermal stress in Australian geckos (adjusted means = 44.0 °C for CTmax and 9.9 °C for CTmin) and at five hours after thermal stress in Thai geckos (adjusted means = 44.2 °C and 10.2 °C, respectively). The plasticity in the thermal hardening of the invasive gecko should enable it to survive rapid temperature fluctuations, especially cold snap, that occasionally occur in temperate regions.
Rapid sequence evolution driven by transposable elements at a virulence locus in a fungal wheat pathogen
Authors: Singh Nikhil Kumar , Badet Thomas , Abraham Leen , Croll Daniel
Published: February 2021

Background: Plant pathogens cause substantial crop losses in agriculture production and threaten food security. Plants evolved the ability to recognize virulence factors and pathogens have repeatedly escaped recognition due rapid evolutionary change at pathogen virulence loci (i.e. effector genes). The presence of transposable elements (TEs) in close physical proximity of effector genes can have important consequences for gene regulation and sequence evolution. Species-wide investigations of effector gene loci remain rare hindering our ability to predict pathogen evolvability.Results: Here, we performed genome-wide association studies (GWAS) on a highly polymorphic mapping population of 120 isolates of Zymoseptoria tritici, the most damaging pathogen of wheat in Europe. We identified a major locus underlying significant variation in reproductive success of the pathogen and damage caused on the wheat cultivar Claro. The most strongly associated locus is intergenic and flanked by genes encoding a predicted effector and a serine type protease, respectively. The center of the locus contained a highly dynamic region consisting of multiple families of TEs. Based on a large global collection of assembled genomes, we show that the virulence locus has undergone substantial recent sequence evolution. Large insertion and deletion events generated length variation between the flanking genes by a factor of seven (5–35 kb). The locus showed also strong signatures of genomic defenses against TEs (i.e. RIP) contributing to the rapid diversification of the locus.Conclusions: In conjunction, our work highlights the power of combining GWAS and population-scale genome analyses to investigate major effect loci in pathogens.
Generalized Mixed Modeling in Massive Electronic Health Record Databases: What is a Healthy Serum Potassium?
Authors: Bologa Cristian G. , Pankratz Vernon Shane , Unruh Mark L , Roumelioti Maria Eleni , Shah Vallabh , Shaffi Saeed Kamran , Arzhan Soraya , Cook John , Argyropoulos Christos
Published: February 2021

Background: Converting electronic health record (EHR) entries to useful clinical inferences requires one to address the poor scalability of existing implementations of Generalized Linear Mixed Models (GLMM) for repeated measures. The major computational bottleneck concerns the numerical evaluation of multivariable integrals, which even for the simplest EHR analyses may involve millions of dimensions (one for each patient). The hierarchical likelihood (h-lik) approach to GLMMs is a methodologically rigorous framework for the estimation of GLMMs that is based on the Laplace Approximation (LA), which replaces integration with numerical optimization, and thus scales very well with dimensionality. Methods: We present a high-performance implementation of the h-lik for GLMMs in the R package TMB. Using this approach, we examined the relation of repeated serum potassium measurements and survival in the Cerner Real World Data (CRWD) EHR database. Analyzing this data requires the evaluation of an integral in over 3 million dimensions, putting this problem beyond the reach of conventional approaches. We also assessed the scalability and accuracy of LA in smaller samples of 1 and 10% size of the full dataset that were analyzed via the a) original, interconnected Generalized Linear Models (iGLM), approach to h-lik, b) Adaptive Gaussian Hermite (AGH) and c) the gold standard of Markov Chain Monte Carlo (MCMC) for multivariate integration. Results: Random effects estimates generated by the LA were within 10% of the values obtained by the iGLMs, AGH and MCMC techniques. The H-lik approach was 4-30 times faster than AGH and nearly 800 times faster than MCMC. The major clinical inferences in this problem are the establishment of the non-linear relationship between the potassium level and the risk of mortality, as well as estimates of the individual and health care facility sources of variations for mortality risk in CRWD. Conclusions: We found that the combination of the LA and AD offers a computationally efficient, numerically accurate approach for the analysis of extremely large, real world repeated measures data via the h-lik approach to GLMMs. The clinical inference from our analysis may guide choices of threatment thresholds for treating potassium disorders in the clinic.
Investigating mechanical properties of 3D printed parts manufactured in different orientations on Multijet printer
Authors: Chand Ramesh , Sharma Vishal S , Rajeev Trehan
Published: February 2021

Polymer material based products in the engineering field are most widely produced by the multi jet printing (MJP). These products impart inherent benefits in manufacturing intricate contours and shapes at less additional expenses. This emphasizes the importance of studying the mechanical behavior of the manufactured parts, using polymeric materials in different orientations. In this investigation density, tensile behavior & hardness were studied for 3D-printed parts produced in four different orientations (A, B, C and D). It is found that for the best mechanical properties part should be fabricated using orientation ‘A’. Furthermore, for density and tensile strength part should not be fabricated using orientation ‘C’. Also in case of hardness part should not be fabricated in orientation ‘B’.
ERK Inhibitor ASN007 Effectively Overcomes Acquired Resistance to EGFR Inhibitor in Non-small Cell Lung Cancer
Authors: Ku Bo Mi , Heo Jae Yeong , Kim Jinchul , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju
Published: February 2021

The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Thus, development of effective strategies to overcome resistance to EGFR-TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR-TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR-TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR-TKIs synergistically decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR-TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR-TKIs by overcoming acquired resistance.