bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated TCGA and GEO analysis showed that SMAD7 is an independent prognostic factor for lung adenocarcinoma
Authors: Dai Zhou-Tong , Wang Jun , Zhao Kai , Xiang Yuan , Li Jia Peng , Zhang Hui-Min , Peng Zi-Tan , Liao Xing Hua
Published: October 2020

The lack of effective markers leads to missed optimal treatment times, resulting in poorer prognosis in most cancers. Drosophila mothers against decapentaplegic protein (SMAD) family members are important cytokines in the transforming growth factor-beta family. They jointly regulate the processes of cell growth, differentiation, and apoptosis. However, the expression of SMAD family genes in pan-cancers and their impact on prognosis have not been elucidated. Perl software and R software were used to perform expression analysis and survival curve analysis on the data collected by TCGA, GTEx, and GEO, and the potential regulatory pathways were determined through gene ontology enrichment and kyoto encyclopedia of genes and genomes enrichment analysis. It was found that SMAD7 and SMAD9 expression decreased in lung adenocarcinoma (LUAD), and their expression was positively correlated with survival time. Additionally, SMAD7 could be used as an independent prognostic factor for LUAD. In general, SMAD7 and SMAD9 can be used as prognostic markers of LUAD. Further, SMAD7 is expected to become a therapeutic target for LUAD.
The acupuncture-related therapy for post-stroke urinary incontinence
Authors: Cheng Pan , Chi Zhenhai , Xiao Yuanyi , Xie Wenping , Zhu Daocheng , Yu Ting , Li Haiyan , Qin Siyu , Jiao Lin
Published: October 2020

Background:

With the rising incidences stroke, the Post-Stroke Urinary Incontinence (PSUI) has become one of the common clinical sequelae. PSUI not only lowers the quality of life of patients, but also impacts tremendously to mental health. As a treasure of Chinese medicine, acupuncture and its related therapies have been widely accepted in clinical treatment of PSUI. Recently, there have been many clinical studies on the treatment of PSUI with acupuncture and related therapies, but the best way to treat PSUI is controversial. Therefore, the purpose of this paper is to provide an optimal ranking regarding acupuncture and its related therapies for PSUI.

Methods:

The five domestic and foreign databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database will be systematically searched. The time range of the literature search is from the date of establishment to August 31, 2020. The main evaluation outcome was the number of patients after treatment, and the frequency of urinary incontinence. The secondary evaluation outcome was International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Barthel Activities of Daily Living Index (Barthel ADL Index) and the incidence rate of adverse events. The methodological quality of the article will evaluated by Cochrane Collaboration's Tool and the quality of evidence will evaluated through Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. The Network Meta-Analysis (NMA) will be completed using Stata statistical software.

Results:

The final results of this study will be published in a peer-reviewed journal.

Conclusion:

This network meta-analysis will compare the efficacy and safety of different acupuncture therapies in the treatment of PSUI and summarize the best treatment options, which will help patients and doctors to choose effective acupuncture methods in time.
The effectiveness and cost-effectiveness of motion style acupuncture treatment (MSAT) for acute neck pain
Authors: Kim Doori , Lee Yoon Jae , Park Kyoung Sun , Kim Suna , Seo Ji-Yeon , Cho Hyun Woo , Ha In-Hyuk
Published: October 2020

Background:

Neck pain is a common complaint in the general population. Despite the consistent ongoing pain and the resulting economic burden on affected individuals, there have only been a few studies investigating the treatment of acute neck pain. This study aims to evaluate the effectiveness, safety, and cost-effectiveness of the motion style acupuncture treatment (MSAT) and acupuncture treatment for acute neck pain.

Methods:

This 2-armed, parallel, multi-centered randomized controlled trial will be conducted at 4 community-based hospitals in Korea. A total of 128 subjects will be randomly assigned, at a 1:1 ratio, to the MSAT and the acupuncture treatment groups. Treatment will be administered 2 to 3 times a week for 2 weeks. The primary outcome will be the visual analog scale of neck pain on movement. The secondary outcomes will be the numeric rating scale of the neck, neck disability index, Northwick Park questionnaire, patient global impression of change, range of motion of the neck, 5-level EuroQol-5 dimension, 12-item Short-Form Health Survey, and EuroQol visual analogue scale. This protocol has been registered at the Clinicaltrials.gov (NCT04539184).

Discussion:

To our knowledge, this study is the first well-designed multi-centered randomized controlled trial to evaluate the effectiveness, safety, and cost-effectiveness of MSAT on acute neck pain. The results of this study will be useful for clinicians in primary medical institutions that frequently treat acute neck pain patients and for policymakers working with national health insurance.
Anemia and iron deficiency in primigent parturients in a municipality of Brazilian west Amazon
Authors: Santos Maria Tamires Lucas dos , Costa Kleynianne Medeiros de Mendonça , Bezerra Italla Maria Pinheiro , Santos Edigê Felipe De Sousa , Szarfarc Sophia Cornbluth , Rocha Pereira Maria José Francalino da , Abreu Luiz Carlos de , Venancio Daniel Paulino
Published: October 2020

To analyze the prevalence of anemia and associated factors in primiparous parturient.

Cross-sectional study conducted in a municipality of the Brazilian Western Amazon from July 2014 to December 2015. A convenience sample of 461 first-time pregnant women were interviewed. Data on their sociodemographic, clinical, obstetric, personal habits and nutritional status were collected. Anemia and iron depletion were measured by peripheral blood collection with hemoglobin, hematocrit, serum ferritin and transferrin saturation index. To test the association between the variables, the χ2 tests were applied and Poisson regression analysis with a 95% confidence interval was performed, and P < .05 values were considered significant. The Forward stepwise strategy was used to construct the adjusted model. These analyzes were performed using the STATA 14.0 program (College Station, TX, 2013).

A higher risk of anemia was identified among adolescent; white; who had a partner; with unpaid occupation, with less than eight years of formal education. Residents in the countryside; smokers; who had more than six prenatal consultations and were overweight.

Anemia was reported in 28.20% and iron depletion in 60.52% of parturient women. The variables studied did not have association with the anemia outcome, except alcohol consumption.
Effect of trimetazidine on incidence of major adverse cardiac events in coronary artery disease patients undergoing percutaneous coronary intervention
Authors: Zhu Kun , Zheng Yu-shui , Fang Yong
Published: October 2020

Background:

Percutaneous coronary intervention (PCI) is a common treatment method for coronary artery disease (CAD). PCI can cause myocardial ischemia or injury, and lead to major adverse cardiac events (MACEs). Trimetazidine has significant cardioprotective effects and improves endothelial dysfunction and myocardial injury. We will conduct a comprehensive systematic review and meta-analysis to evaluate effect of trimetazidine on incidence of MACE in CAD patients undergoing PCI.

Methods:

PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database will be searched to collect randomized controlled trials (RCTs) of trimetazidine for CAD patients undergoing PCI. The range of publication time will be from the inception of the database to October 2020 without language limitation. Two reviewers will independently conduct study selection, data extraction and management, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Review Manager Software 5.3 will be used for meta-analysis. The Cochrane risk of bias tool will be used to assess the risk of bias.

Results:

This study will provide a systematic synthesis of current published data to summarize the effect of trimetazidine on incidence of MACE such as stent restenosis, stent thrombosis, new significant coronary stenosis, myocardial infarction, heart failure, and cardiac arrest in CAD patients undergoing PCI.

Conclusions:

This meta-analysis will provide evidence as to whether trimetazidine can reduce incidence of MACE in CAD patients undergoing PCI.

Study registration number:

INPLASY202090083.
Impact of neurological diseases on family planning
Authors: Alanazy Mohammed H. , Asiri Alanood , Edrees Maha F. , Abuzinadah Ahmad R.
Published: October 2020

This cross-sectional study aimed to assess the impact of epilepsy, myasthenia gravis (MG), and multiple sclerosis (MS) on pregnancy and family planning decision-making in a cohort of Saudi women. Women with epilepsy, MG, and MS were recruited consecutively at the time of their follow-up visits at a neurology clinic. Data were collected using 3 standardized questionnaires, and presented using descriptive statistics. A logistic regression was performed to determine variables associated with decisions regarding abstaining from pregnancy and encouraging other women to conceive. A total of 272 (83 epilepsy, 69 MG, and 120 MS) women with a mean age of 29.9 ± 8.0 years participated. The proportion of women who abstained from or postponed pregnancy was 41.2% and 31.4%, respectively. The concerns mentioned most often were disease worsening during pregnancy, peripartum and postpartum, side effects of medications on the unborn child, and inability to care for the child. Older age was independently associated with the decision to abstain from pregnancy (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 - 1.25). Higher knowledge levels were independently associated with encouraging other women to have children (OR 1.3, 95% CI 1.11–1.53). Over 50% of women reported that they were not counseled on issues related to pregnancy and childbirth. In conclusion, we identified a major influence of epilepsy, MG, and MS on pregnancy and family planning. Comprehensive counseling programs are needed to help women with these neurological diseases make informed family-planning decisions.
Evaluation of life quality, anxiety, and depression in patients with skin diseases
Authors: Guo Fei , Yu Qin , Liu Zhaoxia , Zhang Chenghui , Li Pengying , Xu Youlu , Zuo Yongjie , Zhang Guirong , Li Yuanyuan , Liu Hongxia
Published: October 2020

To investigate the incidence of skin diseases, the factors affecting the life quality, anxiety, and depression of patients with skin diseases and the correlation among the 3.

A total of 1127 patients with skin diseases were selected online from March 2018 to June 2018. Logistic regression was used to analyze the factors influencing life quality, anxiety, and depression. Spearman rank correlation was used to analyze the correction among the life quality, anxiety, and depression.

There was no significant difference in ethnicity, education, and time of question among patients (P > .05). Sex ratio, age, marital status, and occupation were statistically significant difference among patients with different skin diseases (P < .05). The life quality index of patients with psoriasis, atopic dermatitis, acne, steroid-dependent dermatitis, and alopecia were 11.96 ± 6.74, 9.84 ± 6.99, 11.57 ± 6.85, 13.86 ± 6.31, 7.86 ± 6.82, respectively. The differences were statistically significant (P < .05). The main factors affecting quality of life included age, family history, and types of skin diseases. The age, ethnicity, education, and family history of skin diseases were the main factors affecting anxiety of patients with different skin diseases. Additionally, sex, marital status, education, and family history of skin diseases were the main factors influencing depression. Spearman rank correlation analysis showed that the life quality, anxiety, and depression were positively correlated.

Psoriasis, atopic dermatitis, acne, steroid-dependent dermatitis, and alopecia have a certain impact on the life quality of most patients, and may cause different degrees of anxiety and depression.
Comparison anterior minimally invasive oblique retroperitoneal approach and posterior transpedicular approach for debridement fusion in patients with lumbar vertebral osteomyelitis
Authors: Gao Xiang , Wan Shu , Lv Jie , Cheng Wei , Zhang Yangbin
Published: October 2020

Background:

Pyogenic osteomyelitis of the spine usually occurs in patients over 55 years old with acute osteomyelitis. Surgical treatment and fixation can relieve pain, enhance spinal balance and nerve function, so that patients can walk as soon as possible. Different outcomes of surgical methods include anterior minimally invasive oblique retroperitoneal approach (ORA) and posterior transpedicular approach (PTA). While, there is no consensus on the best treatment for PVO. The goal of the protocol is to compare the clinical consequences between PTA and ORA for treating PVO.

Method:

The experiment is a single-center randomized clinical research. This experiment was admitted by the Ethics Committee of the People's Hospital of Dayi County (Approval number: 1002-084). In all, 50 patients with lumbar vertebral osteomyelitis (LVO) who prepares surgical treatment will be included in the study. We contain adult patients (aged over 18 years) who accept debridement and spinal stabilization with LVO. Cases are removed if there is previous hardware placement, cases who are not confirmed by microbiology, or severe renal and liver dysfunction. The primary outcomes are intraoperative blood loss, operative time, hospital stay, primary failure and recurrence, and bone fusion. The secondary outcomes are postoperative pain score and physical recovery. SPSS Sample Power version 3.0 (IBM, Armonk, NY, USA) is used for data analysis.

Results:

Table 1 will show the outcomes in both groups.

Conclusion:

This protocol may offer a reliable basis for the effectiveness of the two approaches in the treatment of PVO.

Trial registration number:

researchregistry6046
Impact of cancer on mortality and severity of corona virus disease 2019
Authors: Zhang Yi , Han Hao , Tian Yunling , Dong Jing , Yu Yage , Kang Yingying , Xing Lina , Lian Rongna , Zhang Ruinian , Xie Dairong
Published: October 2020

Background:

Cancer patients are in a state of systemic immunosuppression and are considered a highly vulnerable population in the Corona Virus Disease 2019 (COVID-19) epidemic. However, the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aims to evaluate whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality.

Methods:

We will perform comprehensive searches in PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials to identify studies providing prevalence of cancer between patients with severe and non-severe illness or between non-survivors and survivors. We will use the Newcastle-Ottawa quality assessment scale to assess the quality of included studies. We will conduct pairwise meta-analyses to compute the odds ratio and 95% confidence interval using the Mantel Haenszel method with the random-effects model. The statistical heterogeneity will be assessed using the I2 statistic. Subgroup analyses, sensitivity analyses, and meta-regression analyses will be performed to explore the sources of heterogeneity.

Results:

The results of this study will be published in a peer-reviewed journal.

Conclusion:

Our meta-analysis will systematically evaluate the association between cancer and the severity and mortality of patients with COVID-19. This study will provide evidence to help determine whether cancer patients should be provided with special precautions and advised to use stronger personal protection.

INPLASY registration number:

INPLASY202090093.
The single nucleotide polymorphisms of interleukin-10 are associated with the risk of leukaemia
Authors: Gao Shupei , Tang Kun , Chen Jinqing , Wang Jianmiao
Published: October 2020

Interleukin-10(IL-10) is an immunosuppressive cytokine and plays an important role in inflammation and cancers. Numerous studies have explored the association between single nucleotide polymorphisms of IL-10 and leukemia, but their results were conflicting, so we performed this meta-analysis to elucidate the association between 3 common single nucleotide polymorphisms of IL-10 (rs1800896, rs1800871 and rs1800872) and risk of leukemia.

We conducted a comprehensive research in Pubmed, Chinese Biomedical Literature Database disc and Embase using related terms. After strict selection, 18 studies with 2264 cases and 3846 controls were included into this meta-analysis. Odds ratio and 95% confidence interval were used to evaluate the strength of the association.

We found that polymorphism of IL-10 -1082A/G was associated with decreased risk of leukemia both in overall analysis and in stratified analysis according to ethnicity and cancer type. A strong relationship was also uncovered between polymorphism of IL-10 -592C/A and increased risk of leukemia in non-Chinese.

GG genotype of IL-10 -1082A/G is associated with decreased risk of leukemia, especially chronic lymphocytic leukemia. CC genotype of -592C/A is associated with decreased risk of leukemia in non-Chinese.
Oncologic Impact of Local Recurrence in Resected Pancreatic Cancer and Topographic Preference in Local Recurrence Patterns According to Tumor Location
Authors: Choi Sung Hoon , Kim Ha Yan , Hwang Ho Kyoung , Kang Chang Moo , Lee Woo Jung
Published: October 2020

Objectives

The objective of this study was to investigate the pattern and the oncologic impact of local recurrence after surgical resection of pancreatic cancer.

Methods

From July 1992 to December 2016, 388 patients who underwent curative-intent surgery for pancreatic ductal adenocarcinoma were retrospectively reviewed.

Results

At a median follow-up of 29.0 months, 286 (73.7%) of the 367 patients experienced recurrence, and the 5-year overall survival rate was 31.3%. The first recurrence pattern was local in 83 patients (22.0%), systemic in 152 patients (40.2%), and locosystemic in 51 patients (13.5%). There was no difference in overall survival between the patients who had either local or systemic recurrence (P > 0.05). Remnant pancreas, common hepatic artery, celiac trunk, and para-aortic area were the common local recurrence sites in both head and body/tail cancer. However, the superior mesenteric artery (P = 0.050) and portal vein (P = 0.001) were more frequent local recurrence sites for a head tumor, and the surgical bed was a common recurrence site for body/tail tumor (P < 0.001).

Conclusions

Our study shows the importance of local recurrence on overall survival and that preferred sites of local recurrence according to tumor location are predictable.
Concordance Between the Ki-67 Index Cutoff Value of 55% and Differentiation in Neuroendocrine Tumor and Neuroendocrine Carcinoma in Grade 3 Pancreatic Neuroendocrine Neoplasms
Authors: Shi Huiying , Chen Luohai , Zhang Qin , Lin Yuan , Jiang Chen , Yao Hailing , Hou Xiaohua , Chen Minhu , Lin Rong , Chen Jie
Published: October 2020

Objective

In 2017 and 2019, the World Health Organization defined grade 3 neuroendocrine tumors (G3 NETs) and neuroendocrine carcinoma (G3 NEC) in the pancreas. The validity of this classification remains to be verified.

Methods

Clinical data were collected and analyzed for 39 G3 pancreatic neuroendocrine neoplasms (PanNENs) patients between 2009 and 2018.

Results

The tumor-node-metastasis stage (P = 0.0260), differentiation (P = 0.0115), and Ki-67 index (P = 0.0371) are prognostic factors for G3 PanNENs by Kaplan-Meier survival analysis. Among 39 patients, 18 had a Ki-67 index of less than 55% and well-differentiated morphology (G3 NET) and 16 had a Ki-67 index of 55% or greater and poorly differentiated morphology (G3 NEC). Grade 3 neuroendocrine tumor had a significant better prognosis than G3 NEC (median overall survival time, 25 months [95% confidence interval, 10.854–39.146 months] vs 12 months [95% confidence interval, 6.316–17.684 months], P = 0.0164). Based on Cox regression analyses, tumor-node-metastasis stage (P = 0.016) was identified as the independent prognostic factor for G3 PanNENs.

Conclusions

The upper Ki-67 index cutoff of 55% might be the best cutoff value to define G3 NETs and G3 NECs for G3 PanNENs. The World Health Organization 2017 and 2019 classification system for G3 PanNENs can identify high-risk patients with G3 PanNENs.
TRIGGERED: could refocused cell signaling be key to natural killer cell-based HIV immunotherapeutics?
Authors: Sugawara Sho , Manickam Cordelia , Reeves R. Keith
Published: October 2020

Natural killer (NK) cells are one of the critical innate immune effector cells that directly kill tumors and virus-infected cells, and modulate other immune cells including dendritic cells, CD4+ and CD8+ T cells. Signals from activating and inhibitory surface receptors orchestrate the regulatory and cytotoxic functions of NK cells. Although a number of surface receptors are involved, multiple signaling molecules are shared so that NK cell responses are synergistically regulated. Many pathogens and tumors evade NK cell responses by targeting NK cell signaling. Particularly in HIV/simian immunodeficiency virus (SIV) infection, the NK cell repertoire is diminished by changes in subsets of NK cells, expression of activating and inhibitory receptors, and intracellular signaling molecules. However, in-depth studies on intracellular signaling in NK cells in HIV/SIV infections remain limited. Checkpoint blockade and chimeric antigen receptor (CAR)-NK cells have demonstrated enhanced NK cell activities against tumors and viral infections. In addition, targeting intracellular signaling molecules by small molecules could also improve NK cell responses towards HIV/SIV infection in vivo. Therefore, further understanding of NK cell signaling including identification of key signaling molecules is crucial to maximize the efficacy of NK cell-based treatments. Herein, we review the current state of the literature and outline potential future avenues where optimized NK cells could be utilized in HIV-1 cure strategies and other immunotherapeutics in PLWH.
A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances
Authors: Cappelletti Daniele , Gupta Ankit , Khammash Mustafa
Published: October 2020

Biochemical systems that express certain chemical species of interest at the same level at any positive steady state are called ‘absolute concentration robust’ (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, provided that the system reaches a (potentially new) positive steady state. Such a property has been proven to be of importance in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness than was previously known. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables the design of insulator devices that are able to buffer the loading effect from downstream systems—a crucial requirement for modular circuit design in synthetic biology. We further note that while the best performance of the insulators are achieved when these act at a faster timescale than the upstream module (as typically required), it is not necessary for them to act on a faster timescale than the downstream module in our construction.
Hybrid sideways/longitudinal swimming in the monoflagellateShewanella oneidensis: from aerotactic band to biofilm
Authors: Stricker Laura , Guido Isabella , Breithaupt Thomas , Mazza Marco G. , Vollmer Jürgen
Published: October 2020

Shewanella oneidensisMR-1 are facultative aerobic electroactive bacteria with an appealing potential for sustainable energy production and bioremediation. They gather around air sources, forming aerotactic bands and biofilms. Here, we experimentally follow the evolution of the band around an air bubble, and we find good agreement with the numerical solutions of the pertinent transport equations. Video microscopy reveals a transition between motile and non-motile MR-1 upon oxygen depletion, preventing further development of the biofilm. We discover that MR-1 can alternate between longitudinal fast and sideways slow swimming. The resulting bimodal velocity distributions change in response to different oxygen concentrations and gradients, supporting the biological functions of aerotaxis and confinement.
AMPA receptor auxiliary subunits emerged during early vertebrate evolution by neo/subfunctionalization of unrelated proteins
Authors: Ramos-Vicente David , Bayés Àlex
Published: October 2020

In mammalian synapses, the function of ionotropic glutamate receptors is critically modulated by auxiliary subunits. Most of these specifically regulate the synaptic localization and electrophysiological properties of AMPA-type glutamate receptors (AMPARs). Here, we comprehensively investigated the animal evolution of the protein families that contain AMPAR auxiliary subunits (ARASs). We observed that, on average, vertebrates have four times more ARASs than other animal species. We also demonstrated that ARASs belong to four unrelated protein families: CACNG-GSG1, cornichon, shisa and Dispanin C. Our study demonstrates that, despite the ancient origin of these four protein families, the majority of ARASs emerged during vertebrate evolution by independent but convergent processes of neo/subfunctionalization that resulted in the multiple ARASs found in present vertebrate genomes. Importantly, although AMPARs appeared and diversified in the ancestor of bilateral animals, the ARAS expansion did not occur until much later, in early vertebrate evolution. We propose that the surge in ARASs and consequent increase in AMPAR functionalities, contributed to the increased complexity of vertebrate brains and cognitive functions.
Synthesis, structure and physical properties of the new layered oxyselenides Bi
2
LnO
4
Cu
2
Se
2
(Ln = rare earth)
Authors: Tan Shugang , Gao Chenhao , Wang Cao , Jing Qiang , Zhou Tong , Yin Guangchao , Sun Meiling , Xing Fei , Cao Rui , Sun Yuping
Published: October 2020

We have synthesized a new series of layered oxyselenides Bi
2
LnO
4
Cu
2
Se
2
(Ln=Nd, Sm, Eu, Dy, Er, Yb). Their crystal structures and physical properties were studied through X-ray diffraction, electric transport measurements, bulk magnetization and first-principle calculation. All these compounds have a tetragonal structure with space group I4/mmm. They exhibit hole-type metallic behaviours which is also verified by the DFT calculation. The new Bi
2
LnO
4
-type block in these compounds may give people some enlightenment in synthesizing new iron-based superconductors or other layered compounds.
Model reduction by mean-field homogenization in viscoelastic composites. I. Primal theory
Authors: Idiart Martín I. , Lahellec Noel , Suquet Pierre
Published: October 2020

A homogenization scheme for viscoelastic composites proposed by Lahellec & Suquet (2007
Int. J. Solids Struct.
44
, 507–529 (
doi:10.1016/j.ijsolstr.2006.04.038
)) is revisited. The scheme relies upon an incremental variational formulation providing the inelastic strain field at a given time step in terms of the inelastic strain field from the previous time step, along with a judicious use of Legendre transforms to approximate the relevant functional by an alternative functional depending on the inelastic strain fields only through their first and second moments over each constituent phase. As a result, the approximation generates a reduced description of the microscopic state of the composite in terms of a finite set of internal variables that incorporates information on the intraphase fluctuations of the inelastic strain and that can be evaluated by mean-field homogenization techniques. In this work we provide an alternative derivation of the scheme, relying on the Cauchy–Schwarz inequality rather than the Legendre transform, and in so doing we expose the mathematical structure of the resulting approximation and generalize the exposition to fully anisotropic material systems.
The sensory basis of schooling by intermittent swimming in the rummy-nose tetra (Hemigrammus rhodostomus)
Authors: McKee Amberle , Soto Alberto P. , Chen Phoebe , McHenry Matthew J.
Published: October 2020

Schooling is a collective behaviour that enhances the ability of a fish to sense and respond to its environment. Although schooling is essential to the biology of a diversity of fishes, it is generally unclear how this behaviour is coordinated by different sensory modalities. We used experimental manipulation and kinematic measurements to test the role of vision and flow sensing in the rummy-nose tetra (Hemigrammus rhodostomus), which swims with intermittent phases of bursts and coasts. Groups of five fish required a minimum level of illuminance (greater than 1.5 lx) to achieve the necessary close nearest-neighbour distance and high polarization for schooling. Compromising the lateral line system with an antibiotic treatment caused tetras to swim with greater nearest-neighbour distance and lower polarization. Therefore, vision is both necessary and sufficient for schooling inH. rhodostomus, and both sensory modalities aid in attraction. These results can serve as a basis for understanding the individual roles of sensory modalities in schooling for some fish species.
Motor constraints influence cultural evolution of rhythm
Authors: Miton Helena , Wolf Thomas , Vesper Cordula , Knoblich Günther , Sperber Dan
Published: October 2020

While widely acknowledged in the cultural evolution literature, ecological factors—aspects of the physical environment that affect the way in which cultural productions evolve—have not been investigated experimentally. Here, we present an experimental investigation of this type of factor by using a transmission chain (iterated learning) experiment. We predicted that differences in the distance between identical tools (drums) and in the order in which they are to be used would cause the evolution of different rhythms. The evidence confirms our predictions and thus provides a proof of concept that ecological factors—here a motor constraint—can influence cultural productions and that their effects can be experimentally isolated and measured. One noteworthy finding is that ecological factors can on their own lead to more complex rhythms.
Sarcomere length non-uniformities dictate force production along the descending limb of the force–length relation
Authors: Haeger Ricarda , de Souza Leite Felipe , Rassier Dilson E.
Published: October 2020

The force–length relation is one of the most defining features of muscle contraction, and yet a topic of debate in the literature. The sliding filament theory predicts that the force produced by muscle fibres is proportional to the degree of overlap between myosin and actin filaments, producing a linear descending limb of the active force–length relation. However, several studies have shown forces that are larger than predicted, especially at long sarcomere lengths (SLs). Studies have been conducted with muscle fibres, preparations containing thousands of sarcomeres that make measurements of individual SL challenging. The aim of this study was to evaluate force production and sarcomere dynamics in isolated myofibrils and single sarcomeres from the rabbit psoas muscle to enhance our understanding of the theoretically predicted force–length relation. Contractions at varying SLs along the plateau (SL = 2.25–2.39 µm) and the descending limb (SL > 2.39 µm) of the force–length relation were induced in sarcomeres and myofibrils, and different modes of force measurements were used. Our results show that when forces are measured in single sarcomeres, the experimental force–length relation follows theoretical predictions. When forces are measured in myofibrils with large SL dispersions, there is an extension of the plateau and forces elevated above the predicted levels along the descending limb. We also found an increase in SL non-uniformity and slowed rates of force production at long lengths in myofibrils but not in single sarcomere preparations. We conclude that the deviation of the descending limb of the force–length relation is correlated with the degree of SL non-uniformity and slowed force development.
The evolution of insect metallothioneins
Authors: Luo Mei , Finet Cédric , Cong Haosu , Wei Hong-yi , Chung Henry
Published: October 2020

Metallothioneins (MTs) are a family of cysteine-rich metal-binding proteins that are important in the chelating and detoxification of toxic heavy metals. Until now, the short length and the low sequence complexity of MTs have hindered the inference of robust phylogenies, hampering the study of their evolution. To address this longstanding question, we applied an iterative BLAST search pipeline that allowed us to build a unique dataset of more than 300 MT sequences in insects. By combining phylogenetics and synteny analysis, we reconstructed the evolutionary history of MTs in insects. We show that the MT content in insects has been shaped by lineage-specific tandem duplications from a single ancestral MT. Strikingly, we also uncovered a sixth MT, MtnF, in the model organism
Drosophila melanogaster
. MtnF evolves faster than other MTs and is characterized by a non-canonical length and higher cysteine content. Our methodological framework not only paves the way for future studies on heavy metal detoxification but can also allow us to identify other previously unidentified genes and other low complexity genomic features.
Tabrizicola oligotrophica sp. nov. and Rhodobacter tardus sp. nov., two new species of bacteria belonging to the family Rhodobacteraceae
Authors: Sheu Ceshing , Li Zhi-Hao , Sheu Shih-Yi , Yang Che-Chia , Chen Wen-Ming
Published: October 2020

Two Gram-stain-negative, aerobic, non-motile bacteria, designated KMS-5T and CYK-10T, were isolated from freshwater environments. 16S rRNA gene sequence similarity results indicated that these two novel strains belong to the family

Rhodobacteraceae

. Strain KMS-5T is closely related to species within the genus

Tabrizicola

(96.1–96.8 % sequence similarity) and

Cypionkella

(96.5–97.0 %). Strain CYK-10T is closest to

Rhodobacter thermarum

YIM 73036T with 96.6 % sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set showed that strain KMS-5T is affiliated with species in the genus

Tabrizicola

and strain CYK-10T is placed in a distinct clade with

Rhodobacter blasticus

ATCC 33485T,

Rhodobacter thermarum

YIM 73036T and

Rhodobacter flagellatus

SYSU G03088T. These two strains shared common chemotaxonomic features comprising Q-10 as the major quinone, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as the principal polar lipids, and C18 : 1
 ω7c as the main fatty acid. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between these two novel isolates and their closest relatives were below the cut-off values of 95–96, 90 and 70 %, respectively, used for species demarcation. The obtained polyphasic taxonomic data suggested that strain KMS-5T represents a novel species within the genus

Tabrizicola

, for which the name Tabrizicola oligotrophica sp. nov. is proposed with KMS-5T (=BCRC 81196T=LMG 31337T) as the type strain, and strain CYK-10T should represent a novel species of the genus

Rhodobacter

, for which the name Rhodobacter tardus sp. nov. is proposed with CYK-10T (=BCRC 81191T=LMG 31336T) as the type strain.
Whole-genome epidemiology links phage-mediated acquisition of a virulence gene to the clonal expansion of a pandemic Salmonella enterica serovar Typhimurium clone
Authors: Tassinari Eleonora , Bawn Matt , Thilliez Gaetan , Charity Oliver , Acton Luke , Kirkwood Mark , Petrovska Liljana , Dallman Timothy , Burgess Catherine M. , Hall Neil , Duffy Geraldine , Kingsley Robert A.
Published: October 2020

Epidemic and pandemic clones of bacterial pathogens with distinct characteristics continually emerge, replacing those previously dominant through mechanisms that remain poorly characterized. Here, whole-genome-sequencing-powered epidemiology linked horizontal transfer of a virulence gene, sopE, to the emergence and clonal expansion of a new epidemic

Salmonella enterica

serovar Typhimurium (S. Typhimurium) clone. The sopE gene is sporadically distributed within the genus

Salmonella

and rare in

S

.

enterica

Typhimurium lineages, but was acquired multiple times during clonal expansion of the currently dominant pandemic monophasic S. Typhimurium sequence type (ST) 34 clone. Ancestral state reconstruction and time-scaled phylogenetic analysis indicated that sopE was not present in the common ancestor of the epidemic clade, but later acquisition resulted in increased clonal expansion of sopE-containing clones that was temporally associated with emergence of the epidemic, consistent with increased fitness. The sopE gene was mainly associated with a temperate bacteriophage mTmV, but recombination with other bacteriophage and apparent horizontal gene transfer of the sopE gene cassette resulted in distribution among at least four mobile genetic elements within the monophasic

S

.

enterica

Typhimurium ST34 epidemic clade. The mTmV prophage lysogenic transfer to other

S. enterica

serovars in vitro was limited, but included the common pig-associated

S

.

enterica

Derby (S. Derby). This may explain mTmV in S. Derby co-circulating on farms with monophasic S. Typhimurium ST34, highlighting the potential for further transfer of the sopE virulence gene in nature. We conclude that whole-genome epidemiology pinpoints potential drivers of evolutionary and epidemiological dynamics during pathogen emergence, and identifies targets for subsequent research in epidemiology and bacterial pathogenesis.
CO2 measurements in instrumental and vocal closed room settings as a risk reducing measure for a Coronavirus infection
Authors: Nusseck Manfred , Richter Bernhard , Holtmeier Ludwig , Skala Dominik , Spahn Claudia
Published: October 2020

Contaminated aerosols in room air are one of the transmission routes of the coronavirus. The amount of contaminated aerosols in the room seems to play an important role for the infection risk. In rooms without technical air refreshing systems, the aerosol concentration can be reduced with simple natural ventilation activity. Instrumental and vocal lessons and rehearsals take place in closed indoor rooms. Therefore it is important to optimize the necessary ventilation activity in order to keep the infection risk for musicians low. Therefore, knowledge about the maximum duration of the lesson or rehearsal for ventilation intervals are necessary. In this study, carbon dioxide concentration (CO2) as an indicator of the indoor air quality (IAQ) was measured during 47 music lessons and rehearsals at a university of music including 141 persons. From these measurements, the air exchange rates of the rooms and the CO2 emission rates per person were extracted. The results show that the CO2 emission in musical activities can be assigned to light and moderate activities between 28 l/h and 39 l/h. Wind instruments had the highest CO2 emissions. Singers showed low CO2 emission rates comparable to the control group which only spoke and listened. Recommendations for the frequency of ventilation breaks were derived from empirical data and allow for an individual risk assessment of instrumental and vocal lessons and rehearsals depending on room size and number of musicians.
Pandemic impacts on healthcare utilisation: a systematic review
Authors: Moynihan Ray , Sanders Sharon , Michaleff Zoe A , Scott Anna , Clark Justin , To Emma J , Jones Mark , Kitchener Eliza , Fox Melissa , Johansson Minna , Lang Eddy , Duggan Anne , Scott Ian , Albarqouni Loai
Published: October 2020

Objectives

To determine the extent and nature of changes in utilisation of healthcare services during COVID-19 pandemic.

Design

Systematic review

Eligibility

Eligible studies compared utilisation of services during COVID-19 pandemic to at least one comparable period in prior years. Services included visits, admissions, diagnostics, and therapeutics. Studies were excluded if from single-centres or studied only COVID-19 patients.

Data sources

PubMed, Embase, Cochrane COVID-19 Study Register, and pre-prints were searched, without language restrictions, until August 10, using detailed searches with key concepts including COVID-19, health services and impact.

Data analysis

Risk of bias was assessed by adapting ROBINS-I and Cochrane Effective Practice and Organization of Care tool. Results were analysed using descriptive statistics, graphical figures, and narrative synthesis.

Outcome measures

Primary outcome was change in service utilisation between pre-pandemic and pandemic periods. Secondary outcome was the change in proportions of users of healthcare services with milder or more severe illness (e.g. triage scores).

Results

3097 unique references were identified, and 81 studies across 20 countries included, reporting on >11 million services pre-pandemic and 6.9 million during pandemic. For the primary outcome, there were 143 estimates of changes, with a median 37% reduction in services overall (interquartile range −51% to −20%), comprising median reductions for visits of 42%(−53% to −32%), admissions, 28%(−40% to −17%), diagnostics, 31%(−53% to −24%), and for therapeutics, 30%(−57% to −19%). Among 35 studies reporting secondary outcomes, there were 60 estimates, with 27(45%) reporting larger reductions in utilisation among people with a milder spectrum of illness, and 33 (55%) reporting no change.

Conclusions

Healthcare utilisation decreased by about a third during the pandemic, with considerable variation, and with greater reductions among people with less severe illness. While addressing unmet need remains a priority, studies of health impacts of reductions may help health-systems prioritise higher-value care in the post-pandemic recovery.

Funding, Study registration

No funding was required. PROSPERO: CRD42020203729

Strengths and limitations of this study

–

The review is the first broad synthesis of global studies of pandemic related changes in utilisation across all categories of healthcare services.

–

The review provides novel findings informing design of future studies of pandemic-related changes in utilisation and its impacts.

–

Limitations include the possibility of publication bias and the potential of our eligibility criteria to exclude important data sources such as studies in single-centres and unpublished datasets from health systems.

–

Heterogenous designs and settings precluding meta-analysis.
Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models
Authors: Li Yingjun , Cao Liu , Li Ge , Cong Feng , Li Yunfeng , Sun Jing , Luo Yinzhu , Chen Guijiang , Li Guanguan , Wang Ping , Xing Fan , Ji Yanxi , Zhao Jincun , Zhang Yu , Guo Deyin , Zhang Xumu
Published: October 2020

The outbreak of coronavirus disease 2019 (COVID-19) rapidly spreads across worldwide and becomes a global pandemic. Remdesivir is the only COVID-19 treatment approved by U.S. Food and Drug Administration (FDA); however, its effectiveness is still under questioning as raised by the results of a large WHO Solidarity Trial. Herein, we report that the parent nucleotide of remdesivir, GS-441524, potently inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero E6 and other cells. It exhibits good plasma distribution and longer half-life (t1/2=4.8h) in rat PK study. GS-441524 is highly efficacious against SARS-CoV-2 in AAV-hACE2 transduced mice and murine hepatitis virus (MHV) in mice, reducing the viral titers in CoV-attacked organs, without noticeable toxicity. Given that GS-441524 was the predominant metabolite of remdesivir in the plasma, the anti-COVID-19 effect of remdesivir may partly come from the effect of GS-441524. Our results also supported that GS-441524 as a promising and inexpensive drug candidate in the treatment of COVID-19 and future emerging CoVs diseases.
Gamete simulation improves polygenic transmission disequilibrium analysis
Authors: Chen Jiawen , You Jing , Zhao Zijie , Ni Zheng , Huang Kunling , Wu Yuchang , Fletcher Jason M. , Lu Qiongshi
Published: October 2020

Polygenic risk scores (PRS) derived from summary statistics of genome-wide association studies (GWAS) have enjoyed great popularity in human genetics research. Applied to population cohorts, PRS can effectively stratify individuals by risk group and has promising applications in early diagnosis and clinical intervention. However, our understanding of within-family polygenic risk is incomplete, in part because the small samples per family significantly limits power. Here, to address this challenge, we introduce ORIGAMI, a computational framework that uses parental genotype data to simulate offspring genomes. ORIGAMI uses state-of-the-art genetic maps to simulate realistic recombination events on phased parental genomes and allows quantifying the prospective PRS variability within each family. We quantify and showcase the substantially reduced yet highly heterogeneous PRS variation within families for numerous complex traits. Further, we incorporate within-family PRS variability to improve polygenic transmission disequilibrium test (pTDT). Through simulations, we demonstrate that modeling within-family risk substantially improves the statistical power of pTDT. Applied to 7,805 trios of autism spectrum disorder (ASD) probands and healthy parents, we successfully replicated previously reported over-transmission of ASD, educational attainment, and schizophrenia risk, and identified multiple novel traits with significant transmission disequilibrium. These results provided novel etiologic insights into the shared genetic basis of various complex traits and ASD.