bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating age-specific COVID-19 fatality risk and time to death by comparing population diagnosis and death patterns: Australian data
Authors: Marschner Ian C.
Published: June 2021

Background

Mortality is a key component of the natural history of COVID-19 infection. Surveillance data on COVID-19 deaths and case diagnoses are widely available in the public domain, but they are not used to model time to death because they typically do not link diagnosis and death at an individual level. This paper demonstrates that by comparing the unlinked patterns of new diagnoses and deaths over age and time, age-specific mortality and time to death may be estimated using a statistical method called deconvolution.

Methods

Age-specific data were analysed on 816 deaths among 6235 cases over age 50 years in Victoria, Australia, from the period January through December 2020. Deconvolution was applied assuming logistic dependence of case fatality risk (CFR) on age and a gamma time to death distribution. Non-parametric deconvolution analyses stratified into separate age groups were used to assess the model assumptions.

Results

It was found that age-specific CFR rose from 2.9% at age 65 years (95% CI:2.2 – 3.5) to 40.0% at age 95 years (CI: 36.6 – 43.6). The estimated mean time between diagnosis and death was 18.1 days (CI: 16.9 – 19.3) and showed no evidence of varying by age (heterogeneity P = 0.97). The estimated 90% percentile of time to death was 33.3 days (CI: 30.4 – 36.3; heterogeneity P = 0.85). The final age-specific model provided a good fit to the observed age-stratified mortality patterns.

Conclusions

Deconvolution was demonstrated to be a powerful analysis method that could be applied to extensive data sources worldwide. Such analyses can inform transmission dynamics models and CFR assessment in emerging outbreaks. Based on these Australian data it is concluded that death from COVID-19 occurs within three weeks of diagnosis on average but takes five weeks in 10% of fatal cases. Fatality risk is negligible in the young but rises above 40% in the elderly, while time to death does not seem to vary by age.
A steep increase in healthcare seeking behaviour in the last months before colorectal cancer diagnosis
Authors: Kuiper Josephina G. , van Herk-Sukel Myrthe P. P. , Lemmens Valery E. P. P. , Kuipers Ernst J. , Herings Ron M. C.
Published: June 2021

Background

Timely recognition of colorectal cancer related symptoms is essential to reduce time to diagnosis. This study aims to investigate the primary healthcare use preceding a colorectal cancer diagnosis.

Methods

From a cohort of linked cancer and primary care data, patients diagnosed with primary colorectal cancer in the period 2007–2014 were selected and matched to cancer-free controls on gender, birth year, GP practice and follow-up period. Primary healthcare use among colorectal cancer cases before diagnosis was compared with matched cancer-free controls. Mean monthly number of GP consultations and newly prescribed medication was assessed in the year before index date (diagnosis date for cases). Results were stratified by colorectal cancer site: proximal colon cancer, distal colon cancer and rectal cancer.

Results

A total of 6,087 colorectal cancer cases could be matched to four cancer-free controls (N = 24,348). While mean monthly number of GP consultation were stable through the year among cancer-free controls, a statistical significant increase was seen among colorectal cancer cases in the last 4–8 months before diagnosis. Proximal colon cancer cases showed the longest time interval of increased mean monthly number of GP consultations. This increase was largely driven by a consultation for malignant neoplasm colon/rectum. The number patients receiving a newly prescribed medication was stable around 120 per 1,000 persons per month until 8 months before index date for proximal colon cancer cases, 4 months before index date for distal colon cancer cases and 3 months for rectal cancer cases. This increase was mainly driven by the prescription of laxatives drugs.

Conclusion

An increase in the healthcare seeking behaviour of colorectal cancer patients prior to diagnosis was seen. The longest period of increased GP consultations and newly prescribed medication was seen among patients diagnosed with proximal colon cancer. This can be explained by the difficultly to diagnose proximal colon cancer given the more subtle signs compared to distal colon cancer and rectal cancer. Therefore, faster diagnosis for this specific tumour subtype may only be possible when clear clinical signs and symptoms are present.
The association between nutritional status and functional limitations among centenarians: a cross-sectional study
Authors: Song Yang , Liu Miao , Jia Wang-ping , Han Ke , Wang Sheng-shu , He Yao
Published: June 2021

Background

Although there have been studies on the association between nutritional status and functional limitations, there were few studies on Asian centenarians in community. Therefore, this study aims to identify associations between nutritional status and functional limitations among centenarians in China.

Methods

This cross-sectional study was conducted with the data from the China Hainan Centenarian Cohort Study. These data ultimately included basic characteristics, hematologic indicators, and chronic disease status for 1,002 centenarians. The nutritional status was evaluated using the Mini Nutritional Assessment Short-Form scale. The functional limitations were assessed using the activities of daily living (ADL) scale, namely Barthel Index and Lawton Scale. The association between nutritional status and ADL was assessed using multivariate logistic regression models.

Results

In this study, the prevalence of malnutrition was 20.8 % among centenarians, basic ADL (BADL) limitation was 28.6 %, and instrumental ADL (IADL) limitation was 64.7 %. As the nutritional status deteriorated, the risk of ADL limitations increased in total population (BADL limitation: OR = 17.060, 95 % CI: 8.093-35.964; IADL limitation: OR = 11.221, 95 % CI: 5.853-21.511; p for trend < 0.001). Similar results were found in both men and women after stratifying sex but were more prominent in women.

Conclusions

Malnutrition is associated with functional limitations among centenarians in China and more pronounced among women.
Feasibility of and barriers to thalassemia screening in migrant populations: a cross-sectional study of Myanmar and Cambodian migrants in Thailand
Authors: Xu Julia Z. , Tanongsaksakul Wilaslak , Suksangpleng Thidarat , Ekwattanakit Supachai , Riolueang Suchada , Telen Marilyn J. , Viprakasit Vip
Published: June 2021

Background

Thalassemia, an inherited hemoglobin disorder, has become a global public health problem due to population migration. Evidence-based strategies for thalassemia prevention in migrants are lacking. We characterized barriers to thalassemia screening and the burden of thalassemia in migrant workers in Thailand.

Methods

Multilingual demographic and KAP surveys were completed by 197 Thai, 119 Myanmar, and 176 Cambodian adults residing in Thailand. Thalassemia awareness, socio-demographic predictors, and knowledge and attitude scores were compared between migrant and Thai subjects. Comprehensive thalassemia testing was performed for migrants.

Results

Migrants had extremely poor thalassemia awareness (4.1%) compared to Thai subjects (79.6%) and had lower thalassemia knowledge scores but similar attitude scores. Surveys identified differing sociodemographic factors predicting awareness in Thai and migrant subjects, as well as key misconceptions likely to hinder thalassemia screening uptake. Nearly all migrants consented to thalassemia testing. We identified abnormal hemoglobin profiles in 52.7% of migrants and a higher projected rate of severe thalassemia births in migrants.

Conclusions

The high burden of thalassemia and tremendous knowledge gap in migrants needs urgent attention. Thalassemia screening was feasible and acceptable in our migrant population. Sociocultural and structural barriers merit further attention when designing thalassemia screening and prevention policies for migrants in Thailand and globally.
Use of magnetic nanotrap particles in capturing Yersinia pestis virulence factors, nucleic acids and bacteria
Authors: Ii Alexandra N. , Lin Shih-Chao , Lepene Benjamin , Zhou Weidong , Kehn-Hall Kylene , van Hoek Monique L.
Published: June 2021

Background

Many pathogens, including Yersinia pestis, cannot be consistently and reliably cultured from blood. New approaches are needed to facilitate the detection of proteins, nucleic acid and microorganisms in whole blood samples to improve downstream assay performance. Detection of biomarkers in whole blood is difficult due to the presence of host proteins that obscure standard detection mechanisms. Nanotrap® particles are micron-sized hydrogel structures containing a dye molecule as the affinity bait and used to detect host biomarkers, viral nucleic acids and proteins as well as some bacterial markers. Nanotraps have been shown to bind and enrich a wide variety of biomarkers and viruses in clinically relevant matrices such as urine and plasma. Our objective was to characterize the binding ability of Nanotrap particle type CN3080 to Y. pestis bacteria, bacterial proteins and nucleic acids from whole human blood in order to potentially improve detection and diagnosis.

Results

CN3080 Nanotraps bind tightly to Yersinia bacteria, even after washing, and we were able to visualize the co-localized Nanotraps and bacteria by electron microscopy. These magnetic hydrogel Nanotraps were able to bind Yersinia DNA, supporting the utility of Nanotraps for enhancing nucleic acid-based detection methods. Nanotraps were capable of increasing Y. pestis nucleic acid yield by fourfold from whole human blood compared to standard nucleic acid extraction. Interestingly, we found CN3080 Nanotraps to have a high affinity for multiple components of the Yersinia type III secretion system (T3SS), including chaperone proteins, Yop effector proteins and virulence factor protein LcrV (V). Using Nanotraps as a rapid upstream sample-prep tool, we were able to detect LcrV in human blood by western blotting with minimal blood interference in contrast to direct western blotting of blood samples in which LcrV was obscured. We were able to computationally model the interaction of LcrV with the CN3080 Nanotrap dye and found that it had a low delta-G, suggesting high affinity. Importantly, Nanotraps were also able to enhance detection of secreted Yersinia proteins by mass spectrometry.

Conclusion

Upstream use of magnetic CN3080 Nanotrap particles may improve the downstream workflow though binding and enrichment of biomarkers and speed of processing. Utilization of Nanotrap particles can improve detection of Yersinia pestis proteins and nucleic acid from whole human blood and contribute to downstream assays and diagnostics including molecular methods such as sequencing and PCR and protein-based methods.

Graphic Abstract
Disk compression of k-mer sets
Authors: Rahman Amatur , Chikhi Rayan , Medvedev Paul
Published: June 2021

K-mer based methods have become prevalent in many areas of bioinformatics. In applications such as database search, they often work with large multi-terabyte-sized datasets. Storing such large datasets is a detriment to tool developers, tool users, and reproducibility efforts. General purpose compressors like gzip, or those designed for read data, are sub-optimal because they do not take into account the specific redundancy pattern in k-mer sets. In our earlier work (Rahman and Medvedev, RECOMB 2020), we presented an algorithm UST-Compress that uses a spectrum-preserving string set representation to compress a set of k-mers to disk. In this paper, we present two improved methods for disk compression of k-mer sets, called ESS-Compress and ESS-Tip-Compress. They use a more relaxed notion of string set representation to further remove redundancy from the representation of UST-Compress. We explore their behavior both theoretically and on real data. We show that they improve the compression sizes achieved by UST-Compress by up to 27 percent, across a breadth of datasets. We also derive lower bounds on how well this type of compression strategy can hope to do.
ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis
Authors: Zhang Yuqiang , Cao Sufen , Zhuang Chunyu , Chen Jiacheng , Chen Xiaojing , Sun Hong , Lin Shengying , Lin Bailang
Published: June 2021

Objective

To explore the relationship between ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in ovarian cancer by the method of meta-analysis.

Methods

Pubmed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were comprehensively searched up to September 2020, to identify the relationship between ERCC1 rs11615 polymorphism and chemosensitivity of ovarian cancer. The data was analyzed by Stata 15.0 statistic software.

Results

A total of 10 published papers were included, including 1866 patients with ovarian cancer. The results showed that compared allele C at ERCC1 rs11615 locus with allele T, the pooled OR was 0.92 (95%CI:0.68 ~ 1.24,P > 0.05). There were no significant differences in recessive, dominant, homozygous, and heterozygous models. In accordance with a subgroup analysis of Ethnicity, all genotypes were statistically significant in the Asian population. In the allelic, dominant, recessive, homozygous and heterozygous models, the OR was 0.70 (95%CI:0.51 ~ 0.95), 0.20 (95%CI:0.07 ~ 0.56), 0.79 (95%CI:0.63 ~ 1.00), 0.21 (95%CI:0.07 ~ 0.59), 0.19 (95%CI:0.07 ~ 0.54), respectively, while in the Caucasian population, no statistically significant genotype was found.

Conclusion

The ERCC1 rs11615 polymorphism is associated with chemosensitivity in patients with ovarian cancer, especially in the Asian population, but not in the Caucasian population.
Effectiveness of a psychological online training to promote physical activity among students: protocol of a randomized-controlled trial
Authors: Krämer Lena Violetta , Eschrig Nadine , Keinhorst Lena , Schöchlin Luisa , Stephan Lisa , Stiene Malin , Bengel Jürgen
Published: June 2021

Background

Many students in Germany do not meet recommended amounts of physical activity. In order to promote physical activity in students, web-based interventions are increasingly implemented. Yet, data on effectiveness of web-based interventions in university students is low. Our study aims at investigating a web-based intervention for students. The intervention is based on the Health Action Process Approach (HAPA), which discriminates between processes of intention formation (motivational processes) and processes of intention implementation (volitional processes). Primary outcome is change in physical activity; secondary outcomes are motivational and volitional variables as proposed by the HAPA as well as quality of life and depressive symptoms.

Methods

A two-armed randomized controlled trial (RCT) of parallel design is conducted. Participants are recruited via the internet platform StudiCare (www.studicare.com). After the baseline assessment (t1), participants are randomized to either intervention group (immediate access to web-based intervention) or control group (access only after follow-up assessment). Four weeks later, post-assessment (t2) is performed in both groups followed by a follow-up assessment (t3) 3 months later. Assessments take place online. Main outcome analyses will follow an intention-to-treat principle by including all randomized participants into the analyses. Outcomes will be analysed using a linear mixed model, assuming data are missing at random. The mixed model will include group, time, and the interaction of group and time as fixed effects and participant and university as random effect.

Discussion

This study is a high-quality RCT with three assessment points and intention-to-treat analysis meeting the state-of-the-art of effectiveness studies. Recruitment covers almost 20 universities in three countries, leading to high external validity. The results of this study will be of great relevance for student health campaigns, as they reflect the effectiveness of self-help interventions for young adults with regard to behaviour change as well as motivational and volitional determinants. From a lifespan perspective, it is important to help students find their way into regular physical activity.

Trial registration

The German clinical trials register (DRKS) DRKS00016889. Registered on 28 February 2019
Correction to: Schistosoma haematobium infection morbidity, praziquantel effectiveness and reinfection rate among children and young adults in Gabon
Authors: Dejon-Agobé Jean Claude , Edoa Jean Ronald , Honkpehedji Yabo Josiane , Zinsou Jeannot Fréjus , Adégbitè Bayodé Roméo , Ngwese Mirabeau Mbong , Mangaboula Ance , Lell Bertrand , Woldearegai Tamirat Gebru , Grobusch Martin Peter , Mordmüller Benjamin , Adegnika Ayôla Akim
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
The effect of a 24-week training focused on activities of daily living, muscle strengthening, and stability in idiopathic inflammatory myopathies: a monocentric controlled study with follow-up
Authors: Špiritović Maja , Heřmánková Barbora , Oreská Sabína , Štorkánová Hana , Růžičková Olga , Vernerová Lucia , Klein Martin , Kubínová Kateřina , Šmucrová Hana , Rathouská Adéla , Česák Petr , Komarc Martin , Bunc Václav , Pavelka Karel , Šenolt Ladislav , Mann Heřman , Vencovský Jiří , Tomčík Michal
Published: June 2021

Background

The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care.

Methods

Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG,n= 30) or control (CG,n= 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck’s Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention.

Results

Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention.

Conclusions

This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients.

Trial registration

ISRCTN35925199(retrospectively registered on 22 May 2020).
Pulmonary artery thrombosis as the first presentation of Behçet’s syndrome: a case report and review of the literature
Authors: Alakkas Ziyad , Kazi Waad , Mattar Mohamed , Salem Eman Abdul Wahhab , Seleem Naglaa Fawzy
Published: June 2021

Background

Behçet’s syndrome is a type of systemic chronic vasculitis of unknown etiology, frequently characterized by recurrent oral and genital ulcers and uveitis. It is less commonly characterized by arthritis and skin, vascular, and gastrointestinal involvements. Behçet’s syndrome affects various sizes of vessels by perivascular infiltration and vasculitis. Unlike other classic types of vasculitis, Behçet’s syndrome patients can present with both arterial and venous involvement. Although vascular Behçet’s syndrome is found in only around 15% of Behçet’s syndrome patients, it is the major cause of morbidity and mortality among them. Furthermore, although deep venous thrombosis has high incidence in Behçet’s syndrome patients, pulmonary artery thrombosis is an uncommon complication. Combining the findings of this and previous case reports of pulmonary artery thrombosis in Behçet’s syndrome patients, we sought to determine the best treatment options for pulmonary artery thrombosis in Behçet’s syndrome patients.

Case presentation

We present the case of a 22-year-old Arabian male who was admitted to an emergency department with acute chest pain, dyspnea, and hemoptysis for 2 weeks. He gave a long history of recurrent oral and genital ulcers for the last 4 months but without seeking medical advice. Spiral computed tomography showed arterial filling defects with a pulmonary nodule for which the presence of a pulmonary artery aneurysm ruled out. The lung perfusion scan showed multiple pulmonary perfusion defects. After excluding common infectious diseases such as tuberculosis and brucellosis, a diagnosis of Behçet’s syndrome with pulmonary artery thrombosis was made. Steroids with enoxaparin were initiated. The patient was discharged later on prednisolone (tapering dose) with adalimumab and apixaban. He was on regular follow-up for the next 9 months.

Conclusions

Vascular involvement in Behçet’s syndrome is a major contributor to morbidity and mortality of Behçet’s syndrome patients. Consequently, early detection of vascular involvement has a major impact on the prognosis of patients with Behçet’s syndrome.
Stress distribution and displacement of three different types of micro-implant assisted rapid maxillary expansion (MARME): a three-dimensional finite element study
Authors: André C. B. , Rino-Neto J. , Iared W. , Pasqua B. P. M. , Nascimento F. D.
Published: June 2021

Background/objective

Until 2010, adults underwent surgical treatment for maxillary expansion; however, with the advent of micro-implant-assisted rapid maxillary expansion (MARME), the availability of less invasive treatment options has increased. Nevertheless, individuals with severe transverse maxillary deficiency do not benefit from this therapy. This has aroused interest in creating a new device that allows the benefit of maxillary expansion for these individuals. The aim of this study was to evaluate the efficacy of three MARME models according to tension points, force distribution, and areas of concentration in the craniofacial complex when transverse forces are applied using finite element analysis.

Materials and methods

Digital modeling of the three MARME models was performed. Model A comprised five components: one body screw expander and four adjustable arms with rings for mini-implant insertion. These arms have an individualized height adjustment that allows MARME positioning according to the patient’s palatal anatomy, thereby preventing body screw expander collision with the lateral mucosa in severe cases of maxillary deficiency. Model B was a maxillary expander with screw rings joined to the body, and model C was similar to model B, except that model C had open rings for the insertion of the mini-implants. Through the MEF (Ansys software), the stresses, distribution, and area of concentration of the stresses were evaluated when transverse forces of 7.85 N were applied.

Results

The three models maintained the following pattern: model C presented weak stress peaks with limited distribution and lower concentration area, model B obtained median stress peaks with better distribution when compared to that of model C, and model A showed better stress distribution and larger concentration area. In model A, tensions were located in the lateral lamina of the pterygoid process, which is an important site for maxillary expansion. The limitation of the present study was that it did not include the periodontal tissues and muscles in the finite element method evaluation.

Conclusions

Model A showed the best stress distribution conditions. In cases of severe atresia, model A seems to be an excellent option.
RTP4 is a novel prognosis-related hub gene in cutaneous melanoma
Authors: Li Yiqi , Qi Jue , Yang Jiankang
Published: June 2021

Objective

Melanoma accounts for 80% of skin cancer deaths. The pathogenesis of melanoma is regulated by gene networks. Thus, we aimed here to identify gene networks and hub genes associated with melanoma and to further identify their underlying mechanisms.

Methods

GTEx (normal skin) and TCGA (melanoma tumor) RNA-seq datasets were employed for this purpose. We conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes associated with melanoma. Log-rank analysis and multivariate Cox model analysis were performed to identify prognosis genes, which were validated using two independent melanoma datasets. We also evaluated the correlation between prognostic gene and immune cell infiltration.

Results

The blue module was the most relevant for melanoma and was thus considered the key module. Intersecting genes were identified between this module and differentially expressed genes (DEGs). Finally, 72 genes were identified and verified as hub genes using the Oncomine database. Log-rank analysis and multivariate Cox model analysis identified 13 genes that were associated with the prognosis of the metastatic melanoma group, and RTP4 was validated as a prognostic gene using two independent melanoma datasets. RTP4 was not previously associated with melanoma. When we evaluated the correlation between prognostic gene and immune cell infiltration, we discovered that RTP4 was associated with immune cell infiltration. Further, RTP4 was significantly associated with genes encoding components of immune checkpoints (PDCD1, TIM-3, and LAG3).

Conclusions

RTP4 is a novel prognosis-related hub gene in cutaneous melanoma. The novel gene RTP4 identified here will facilitate the exploration of the molecular mechanism of the pathogenesis and progression of melanoma and the discovery of potential new target for drug therapy.
Attempts by Avicenna and Ibn alNafīs to Expand the Field of the Transference of Demonstration in the Context of the Relationship Between Geometry and Medicine
Authors: Musametov Bakhadir
Published: June 2021

This paper aims to deal with the disputes on transferring demonstration between the various sciences in the context of the medicine-geometry relationship. According to Aristotle’s metabasis-prohibition, these two sciences should be located in separate compartments due to the characteristics of their subject-matter. However, a thorough analysis of the critical passage in Aristotle’s Posterior Analytics on circular wounds forces a revision of the boundaries of the interactions between sciences, since subsequently Avicenna, on the grounds of this passage, would widen the area of the transference of demonstration. Furthermore, the fact that Avicenna and Ibn al-Nafīs continued to use geometrical demonstrations in their anatomical investigations shows the need to understand kind-crossing prohibition as a reminder to take into account the present scientific infrastructure and logical rules before proceeding onto a scientific investigation instead of accepting it as a mere nominal doctrine. Therefore, whether kind-crossing was possible or not depended on the extent to which the conclusion derived at the end of the scientific investigation, using a different method after taking into account all these reminders, had contributed to the solution of a particular proposition or the achievement of an approximate truth.
Toxicity and Anti-Oxidation Capacity of The Extracts from Caulerpa lentillifera
Authors: Osotprasit Supawadee , Samrit Tepparit , Chaiwichien Athit , Changklungmoa Narin , Meemon Krai , Niamnont Nakorn , Manohong Preeyanuch , Noonong Kunwadee , Tamtin Montakan , Sobhon Prasert , Kueakhai Pornanan
Published: June 2021

Caulerpa lentillifera (sea grape) has been widely used in pharmaceutical industry and health-care products in Thailand. In this study, we attempted to evaluate the toxicity and antioxidant capacity of sea grape extracts in five fractions (ethanol- CLET, hexane- CLHE, ethyl acetate- CLEA, butanol-CLBU, and aqueous-CLAQ). The extracts were evaluated for cytotoxicity by MTT and LDH assays on four cell lines, fibroblast (L929), macrophages (RAW 264.7), hepatocytes (FL83B), and keratinocytes (HaCaT). Genotoxicity was tested by comet assay and micronucleus assay on human lymphoblast cells (TK6). The antioxidant capacity was measured by DPPH and ABTS scavenging assays. Our results demonstrated low cytotoxicity and genotoxicity of CLET, CLBU and CLAQ. When tested by DPPH and ABTS assays, CLET, CLEA, and CLHE showed high antioxidant activity. In conclusion, CLET, CLBU, and CLAQ demonstrated no toxic effects, and CLET, CLEA, and CLHE exhibited high antioxidant capacity. Therefore, our results indicated that CLET, CLEA, and CLHE could be consumed safely at doses lower than 500 and 200 μg/ml for CLHE and CLEA, respectively.

Keywords: Anti-oxidation, Caulerpa lentillifera, Cytotoxicity, Genotoxicity
Efficient plasmonic functional lens constructed via a nano-dichroic element
Authors: Qin Yulu , Ji Boyu , Song Xiaowei , Lin Jingquan
Published: June 2021

The plasmonic functional lens can realize an efficient and functional focusing of surface plasmon polaritons (SPPs), making it have great potential in applications including nano-electron point sources, smart pixels, and particle manipulation. Here, we report for the first time a novel plasmonic functional lens constructed via a nano-dichroic element. The results show that the wavelength-selective nano-focusing of SPPs in the plasmonic functional lens can be achieved. Different from the conventional plasmonic lens that equally splits SPP power to propagate inward and outward from the boundaries, the plasmonic functional lens directs all of the SPP power of the matched wavelength inward for the focusing, resulting in higher collecting efficiency and SPP focusing intensity. Furthermore, we have demonstrated that a much higher focal spot intensity can be obtained even under the condition of a smaller inner radius. These findings provide a new way for the design of plasmonic functional lenses and can be facilitated to develop high-efficiency miniaturized focusing devices.
Wideband and wide-angle radar cross section reduction using a hybrid mechanism metasurface
Authors: Xi Yan , Jiang Wen , Hong Tao , Wei Kun , Gong Shuxi
Published: June 2021

In this paper, a hybrid mechanism metasurface (HMM) that incorporates absorption, polarization conversion and phase cancellation mechanisms is proposed for wideband and wide-angle radar cross section (RCS) reduction. The polarization conversion absorber (PCA) is proposed by embedding the lumped resistors into the polarization conversion structure, which integrates the absorption and polarization conversion mechanisms. Then, the phase cancellation mechanism is employed to redirect the scattering energy to the non-incident directions through the chessboard configuration, which exploits the opposite phase between the PCA and its mirror structure. Unlike previous HMMs that depended on nested or cascaded structures, the proposed strategy integrates the absorption and polarization conversion mechanisms in the same structure, and the two mechanisms are complementary to each other. Through the integration of multiple mechanisms, the HMM can achieve more than a 10 dB monostatic and bistatic RCS reduction in 8.7–32.5 GHz and 8.6–31.2 GHz, respectively. Furthermore, the specular and bistatic RCS reduction performances under oblique incident waves are also studied, and the stable scattering suppression performances are determined. The proposed hybrid mechanism strategy exhibits significant scattering suppression capability through the incorporation of multiple mechanisms, which have potential applications in the multifunctional metasurface.
Unusual parallel laser irradiation for suppressing self-absorption in single pulse laser-induced breakdown spectroscopy
Authors: Pardede Marincan , Karnadi Indra , Lie Zener Sukra , Jobiliong Eric , Tanra Ivan , Hedwig Rinda , Marpaung Alion Mangasi , Suyanto Hery , Suliyanti Maria Margaretha , Kwaria Dennis , Lie Tjung Jie , Kurniawan Koo Hendrik , Kagawa Kiichiro
Published: June 2021

This study demonstrates a new approach for suppressing the self-absorption effect in single-pulse laser-induced breakdown spectroscopy (LIBS) using unusual parallel laser irradiation. A nanosecond Nd:YAG laser with a wavelength of 1064 nm was fired parallel to and focused at a very close distance of 1 mm to the sample surface. The experiment was carried out in air at atmospheric pressure. In this configuration, the sample was ablated by a shockwave generated from the air breakdown plasma formed near the sample surface. Under this condition, we successfully obtained spectra of the resonance emission line for high concentration K (K I 766.4 nm and K I 769.9 nm) that are free from self-reversal and weakly affected by the self-absorption. Furthermore, the quantitative analysis results for the element K showed that a linear calibration curve over a wide concentration range could be achieved, which indicates the effectiveness of this technique in reducing the self-absorption effect and improving the analytical performance of ordinary single-pulse LIBS.
High-speed hyperspectral four-wave-mixing microscopy with frequency combs
Authors: Smith Brad C. , Lomsadze Bachana , Cundiff Steven T.
Published: June 2021

A four-wave-mixing, frequency-comb-based, hyperspectral imaging technique that is spectrally precise and potentially rapid, and can in principle be applied to any material, is demonstrated in a near-diffraction-limited microscopy application.
High-entropy chaos generation using semiconductor lasers subject to intensity-modulated optical injection for certified physical random number generation
Authors: Tseng Chin-Hao , Funabashi Ryo , Kanno Kazutaka , Uchida Atsushi , Wei Chia-Chien , Hwang Sheng-Kwang
Published: June 2021

This study investigates high-entropy chaos generation using a semiconductor laser subject to intensity-modulated optical injection for certified physical random number generation. Chaos with a continuous spectral profile that is not only widely distributed but also broadly flattened over a bandwidth of 33 GHz is generated. The former suggests that the chaos can be sampled at a high rate while keeping sufficient un-correlation between data samples, and the latter indicates that the chaos possesses high entropy, both of which enhance the generation rate of physical random numbers with guaranteed unpredictability. A minimum entropy value of 2.19 bits/sample is obtained without any post-processing and by excluding the contribution from measurement noise, suggesting that, to the least extent, the chaotic source can be used as a 2-bit physical random number generator at a rate of 160 Gbits/s.
pyTFM: A tool for traction force and monolayer stress microscopy
Authors: Bauer Andreas , Prechová Magdalena , Fischer Lena , Thievessen Ingo , Gregor Martin , Fabry Ben
Published: June 2021

Cellular force generation and force transmission are of fundamental importance for numerous biological processes and can be studied with the methods of Traction Force Microscopy (TFM) and Monolayer Stress Microscopy. Traction Force Microscopy and Monolayer Stress Microscopy solve the inverse problem of reconstructing cell-matrix tractions and inter- and intra-cellular stresses from the measured cell force-induced deformations of an adhesive substrate with known elasticity. Although several laboratories have developed software for Traction Force Microscopy and Monolayer Stress Microscopy computations, there is currently no software package available that allows non-expert users to perform a full evaluation of such experiments. Here we present pyTFM, a tool to perform Traction Force Microscopy and Monolayer Stress Microscopy on cell patches and cell layers grown in a 2-dimensional environment. pyTFM was optimized for ease-of-use; it is open-source and well documented (hosted at https://pytfm.readthedocs.io/) including usage examples and explanations of the theoretical background. pyTFM can be used as a standalone Python package or as an add-on to the image annotation tool ClickPoints. In combination with the ClickPoints environment, pyTFM allows the user to set all necessary analysis parameters, select regions of interest, examine the input data and intermediary results, and calculate a wide range of parameters describing forces, stresses, and their distribution. In this work, we also thoroughly analyze the accuracy and performance of the Traction Force Microscopy and Monolayer Stress Microscopy algorithms of pyTFM using synthetic and experimental data from epithelial cell patches.
Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity
Authors: Quillien Aurélie , Gilbert Guerric , Boulet Manon , Ethuin Séverine , Waltzer Lucas , Vandel Laurence
Published: June 2021

During development, the vertebrate vasculature undergoes major growth and remodeling. While the transcriptional cascade underlying blood vessel formation starts to be better characterized, little is known concerning the role and mode of action of epigenetic enzymes during this process. Here, we explored the role of the Protein Arginine Methyl Transferase Prmt5 in blood vessel formation as well as hematopoiesis using zebrafish as a model system. Through the combination of differentprmt5loss-of-function approaches we highlighted a key role of Prmt5 in both processes. Notably, we showed that Prmt5 promotes vascular morphogenesis through the transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Interestingly, using a catalytic dead mutant of Prmt5 and a specific drug inhibitor, we found that while Prmt5 methyltransferase activity was required for blood cell formation, it was dispensable for vessel formation. Analyses of chromatin architecture impact on reporter genes expression and chromatin immunoprecipitation experiments led us to propose that Prmt5 regulates transcription by acting as a scaffold protein that facilitates chromatin looping to promote vascular morphogenesis.
The Mexico SimSmoke tobacco control policy model: Development of a simulation model of daily and nondaily cigarette smoking
Authors: Sánchez-Romero Luz María , Zavala-Arciniega Luis , Reynales-Shigematsu Luz Myriam , de Miera-Juárez Belén Sáenz , Yuan Zhe , Li Yameng , Lau Yan Kwan , Fleischer Nancy L. , Meza Rafael , Thrasher James F. , Levy David T.
Published: June 2021

Background

Nondaily smoking has been on the rise, especially in Mexico. While Mexico has strengthened its tobacco control policies, their effects on nondaily smokers have gone largely unexamined. We developed a simulation model to estimate the impact of tobacco control policies on daily and nondaily smoking in Mexico.

Methods

A previously validated Mexico SimSmoke model that estimated overall trends in smoking prevalence from 2002 through 2013 was extended to 2018 and adapted to distinguish daily and nondaily smoking prevalence. The model was then validated using data from Mexican surveys through 2016. To gauge the potential effects of policies, we compared the trends in smoking under current policies with trends from policies kept at their 2002 levels.

Results

Between 2002 and 2016, Mexico SimSmoke underestimated the reduction in male and female daily smoking rates. For nondaily smoking, SimSmoke predicted a decline among both males and females, while survey rates showed increasing rates in both genders, primarily among ages 15–44. Of the total reduction in smoking rates predicted by the model by 2018, tax policies account for more than 55%, followed by health warnings, cessation treatment, smoke-free air laws, and tobacco control spending.

Conclusions

Although Mexico SimSmoke did not successfully explain trends in daily and nondaily smoking, it helps to identify gaps in surveillance and policy evaluation for nondaily smokers. Future research should consider appropriate measures of nondaily smoking prevalence, trajectories between daily and nondaily smoking, and the separate impact of tobacco control policies on each group.
A network pharmacology approach to determine the underlying mechanisms of action of Yishen Tongluo formula for the treatment of oligoasthenozoospermia
Authors: Chen Yangdi , Bi Fanggang , Sun Zixue
Published: June 2021

Oligoasthenozoospermia is a complex disease caused by a variety of factors, and its incidence is increasing yearly worldwide. Yishen Tongluo formula (YSTLF), created by Professor Sun Zixue, has been used to treat oligoasthenozoospermia in clinical practice for several decades with a good therapeutic effect. However, the chemical and pharmacological profiles of YSTLF remain unclear and need to be elucidated. In this study, a network pharmacology approach was applied to explore the potential mechanisms of YSTLF in oligoasthenozoospermia treatment. All of the compounds in YSTLF were retrieved from the corresponding databases, and the bioactive ingredients were screened according to their oral bioavailability (OB) and drug-likeness (DL). The potential proteins of YSTLF were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, while the potential genes of oligoasthenozoospermia were obtained from the GeneCards database and the DisGeNET database. The STRING database was used to construct an interaction network according to the common targets identified by the online tool Venny for YSTLF and oligoasthenozoospermia. The topological characteristics of nodes were visualized and analyzed through Cytoscape. Biological functions and significant pathways were determined and analyzed using the Gene Ontology (GO) knowledgebase, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Metascape. Finally, the disease-formula-compound-target-pathway network was constructed by Cytoscape. A total of 106 bioactive ingredients and 134 potential targets from YSTLF were associated with oligoasthenozoospermia or considered to be therapeutically relevant. Pathway analysis indicated that the PI3K/Akt, MAPK and apoptosis signaling pathways were significant pathways involved in oligoasthenozoospermia. In conclusion, the current study expounded the pharmacological actions and molecular mechanisms of YSTLF in treating oligoasthenozoospermia from a holistic viewpoint. The potential molecular mechanisms were closely related to antioxidative stress, antiapoptosis and anti-inflammation, with TNF, CCND1, ESR1, NFKBIA, NR3C1, MAPK8, and IL6 being possible targets. This network pharmacology prediction may offer a helpful tool to illustrate the molecular mechanisms of the Chinese herbal compound YSTLF in oligoasthenozoospermia treatment.
Nucleophosmin1 and isocitrate dehydrogenase 1 and 2 as measurable residual disease markers in acute myeloid leukemia
Authors: Kövy Petra , Őrfi Zoltán , Bors András , Kozma András , Gopcsa László , Dolgos János , Lovas Nóra , Harasztdombi József , Lakatos Viktor , Király Ágnes , Mikala Gábor , Vályi-Nagy István , Reményi Péter , Andrikovics Hajnalka
Published: June 2021

Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25–3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09–7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers.
An evolution-based high-fidelity method of epistasis measurement: Theory and application to influenza
Authors: Pedruzzi Gabriele , Rouzine Igor M.
Published: June 2021

Linkage effects in a multi-locus population strongly influence its evolution. The models based on the traveling wave approach enable us to predict the average speed of evolution and the statistics of phylogeny. However, predicting statistically the evolution of specific sites and pairs of sites in the multi-locus context remains a mathematical challenge. In particular, the effects of epistasis, the interaction of gene regions contributing to phenotype, is difficult to predict theoretically and detect experimentally in sequence data. A large number of false-positive interactions arises from stochastic linkage effects and indirect interactions, which mask true epistatic interactions. Here we develop a proof-of-principle method to filter out false-positive interactions. We start by demonstrating that the averaging of haplotype frequencies over multiple independent populations is necessary but not sufficient for epistatic detection, because it still leaves high numbers of false-positive interactions. To compensate for the residual stochastic noise, we develop a three-way haplotype method isolating true interactions. The fidelity of the method is confirmed analytically and on simulated genetic sequences evolved with a known epistatic network. The method is then applied to a large sequence database of neurominidase protein of influenza A H1N1 obtained from various geographic locations to infer the epistatic network responsible for the difference between the pre-pandemic virus and the pandemic strain of 2009. These results present a simple and reliable technique to measure epistatic interactions of any sign from sequence data.