bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Acute Insulin Resistance on Myocardial Blush in Non-Diabetic Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Kasem Soheir M. , Saied Ghada Mohamed , Hegazy Abdel Nasser MA , Abdelsabour Mahmoud
Published: May 2021

Background: Myocardial blush grading is considered to be a novel tool for assessment of coronary microvasculature and myocardial perfusion in patients undergoing coronary angiography and angioplasty, and its reduction identifies patients at high risk. Our study aimed to evaluate the association between acute insulin resistance and myocardial blush in non-diabetic patients with ST-segment elevation myocardial infarction (STEMI).

Methods: Two hundred forty non-diabetic patients with STEMI who underwent primary percutaneous coronary intervention were consecutively recruited. The relationship of homeostasis model assessment—estimated insulin resistance (HOMA-IR) to myocardial blush and in-hospital outcome was investigated.

Results: Higher HOMA-IR tertile was observed in obese patients, with hyperinsulinemia, had Killip class >1, with higher CPK-MB level and was correlated to impaired myocardial blush after adjusting for the other confounding risk factors. It was also concluded that higher HOMA-IR was independently associated with no/minimal myocardial blush after STEMI. Moreover, it was founded to be an independent predictor of pulmonary edema and impaired left ventricular systolic function.

Conclusion: This study revealed that acute insulin resistance was prevalent in non-diabetic patients with STEMI and was an independent predictor for post-infarction myocardial and microvascular injury and poor in-hospital outcome.

Trial Registration: The trial was registered at the registry of Clinicaltrials.gov, ClinicalTrials.gov Identifier: NCT04651842, Date of registration: 2nd December 2020 Registry URL, https://clinicaltrials.gov/ct2/show/NCT04385589?cond=Dapagliflozin+in+diabetic+patients&cntry=EG&draw=2&rank=1.
Feasibility and Safety of Chronic Total Occlusion Percutaneous Coronary Intervention via Distal Transradial Access
Authors: Lin Cheng-Jui , Lee Wei-Chieh , Lee Chieh-Ho , Chung Wen-Jung , Hsueh Shu-Kai , Chen Chien-Jen , Yang Cheng-Hsu , Fang Hsiu-Yu , Cheng Cheng-I , Wu Chiung-Jen
Published: May 2021

Aims: The current study aims to verify the feasibility and safety of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) via the distal transradial access (dTRA).

Methods: Between April 2017 and December 2019, 298 patients who underwent CTO PCI via dTRA were enrolled in this study. The baseline demographic and procedural characteristics were listed and compared between groups. The incidences of access-site vascular complications and procedural complications and mortality were recorded.

Results: The mean J-CTO (Japanese chronic total occlusion) score was 2.6 ± 0.9 points. The mean access time was 4.6 ± 2.9 min, and the mean procedure time was 115.9 ± 55.6 min. Left radial snuffbox access was performed successfully in 286 patients (96.5%), and right radial snuffbox access was performed successfully in 133 patients (97.7%). Bilateral radial snuffbox access was performed in 107 patients (35.9%). 400 dTRA (95.5%) received glidesheath for CTO intervention. Two patients (0.7%) developed severe access-site vascular complications. None of the patients experienced severe radial artery spasm and only 2 patients (0.5%) developed radial artery occlusion during the follow-up period. The overall procedural success rate was 93.5%. The procedural success rate was 96.5% in patients with antegrade approach and 87.7% in patients with retrograde approach.

Conclusions: It is both safe and feasible to use dTRA plus Glidesheath for complex CTO intervention. The incidences of procedure-related complications and severe access-site vascular complications, and distal radial artery occlusion were low.
Spatial Distribution and Provenance of Detrital Minerals of Surface Sediment in the Okhotsk Sea
Authors: Wang Kunshan , Shi Xuefa , Zou Jianjun , Liu Yanguang , Yao Zhengquan , Gorbarenko Sergey Alexandrovich
Published: May 2021

The Okhotsk Sea is a distinctive marginal sea in the northwestern Pacific Ocean, which is characterized by the prevalence of seasonal sea ice in winter. Sediment is sourced from the around region through sea ice transportation, rivers input, and volcanic eruptions. Surface sediments of the Okhotsk Sea shelf vary greatly in grain size, and the sand content is generally high, which is conducive to source-to-sink studies using ice-rafted detritus (IRD),detrital minerals and single mineral geochemistry methods. In this paper, the 63–125 μm grain size fraction was selected for the detrital minerals analysis of surface sediments (top 0–10 cm) from 58 sediment stations and 15 stations samples has been chosen for garnet chemistry. These stations are mainly located in the south central Okhotsk Sea. The distribution and composition of the heavy minerals are influenced by material derived from the Amur River, the north shelf (Okhotsk-Chukotka volcanic belt), Sakhalin Island, the Kamchatka Peninsula, and the Kuril Islands. The detrital mineral results show that hornblende, epidote and garnet are terrigenous material indicators. High contents of fresh hypersthene can be used as an indicator of volcanic eruption materials. And high content of abraded hypersthene can be used as an indicator of Okhotsk-Chukotka volcanic materials. In the northern Okhotsk Sea, the southward moving sea ice produced in Sakhalin Bay collides with the sea ice produced off the east coast of Sakhalin Island, which causes the sea ice to accumulate to the southeast. This results in the deposited ice-rafted debris having a southeastward facing fan shape, and the geochemical analysis of the garnet supports this conclusion. From west to east, the amount of material from Sakhalin Island gradually decreases, while the amount of material from the Amur River and Chukchi-Kamchatka increases.
The Assessment of the Osteoporosis Self-Assessment Tool for Asians and Calcaneal Quantitative Ultrasound in Identifying Osteoporotic Fractures and Falls Among Chinese People
Authors: Gao Chao , Song Huijiang , Chen Bihua , Zhang Zhenlin , Yue Hua
Published: May 2021

The lack of DXA has made the diagnosis and treatment of osteoporosis extremely difficult in the vast rural areas of China, which has the largest population with high risks of osteoporosis. The aims of this cross-sectional study were to evaluate the association between the osteoporosis self-assessment tool for Asians (OSTA) and calcaneus quantitative ultrasound (QUS) in populations residing in Shanghai, China, and their assessment in predicting osteoporotic fractures and falls. A population of 12,033 participants, including 1272 males (average age 68.3 ± 9.8 years, range 28–100 years) and 10,761 females (average 56.8 ± 11.4 years, range 23–99 years), was gathered. OSTA and calcaneus QUS (Sonost 2000, OsteoSys) values were measured. Spearman’s correlation and Cohen’s kappa were used to determine the association and agreement between the OSTA and QUS. Receiver operating characteristic (ROC) curves were adapted to assess the performance and optimal cutoff values for the OSTA and QUS in osteoporotic fracture and fall screening. In total, the prevalence of osteoporotic fractures (low-trauma fractures including fractures of the spine, hip, forearm, humerus and ribs) was 15.2% in women, and 17.7% reported a history of falls (falling from standing height more than once in the past year). The percentages of men with the same history were 8.4% and 11.7%, respectively. The association between the OSTA and QUS was found to be rs = 0.393, κ = 0.137, p < 0.001. The OSTA (cutoff < −1) revealed an area under ROC curve (AUC) of 0.590 in identifying female individuals with moderate or high risk of osteoporosis defined by QUS (T-score < −1). The QUS T-score lower than −1.55 or −1.40 in postmenopausal women may lead to an increased risk of falls or osteoporotic fractures, respectively. The agreement between QUS and the OSTA seemed to be limited in determining individuals at risk of osteoporosis. Measuring bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) may still be necessary in the clinical diagnosis of osteoporosis. OSTA and QUS T-scores less than the respective cutoff values may indicate an increased risk of osteoporotic fractures and falls that individual should be further treated and screened by DXA.
Effects of Film Thickness and Coating Techniques on the Photoelectrochemical Behaviour of Hematite Thin Films
Authors: Kyesmen Pannan I. , Nombona Nolwazi , Diale Mmantsae
Published: May 2021

In this research, three different sets of hematite (α-Fe2O3) films of various thicknesses were prepared using dip, spin, and combined dip/spin coating methods. α-Fe2O3films of 450–500, 740–800 and 920–980 ± 30 nm thicknesses were prepared using each of the coating methods, and their photoelectrochemical (PEC) behaviour was investigated. Dip coated films produced the best photoresponse while the films prepared using the spin coating method yielded the least photocurrent values across films of different thicknesses. Maximum photocurrent densities of 34.6, 7.8, and 13.5 μA/cm2V vs reversible hydrogen electrode (RHE) were obtained for the dip, spin and combined dip/spin coated films with a thickness of 740–800 ± 30 nm respectively. Improved crystallization, low charge transfer resistance at the α-Fe2O3/electrolyte interface, high surface states capacitance and the more negative flat band potential values obtained for dip coated films have been associated with the enhanced photocurrent response recorded for the films. The preferential crystal growth of spin coated films in the (104) plane associated with low electron mobility and the high resistance to charge transfer at the α-Fe2O3/electrolyte interface of the films is largely responsible for their low photoresponse. This study underscores the significance of simultaneously optimizing both coating techniques for film deposition and the film’s thickness in preparing nanostructured α-Fe2O3films for PEC applications.
An Evaluation of Habitat Uses and Their Implications for the Conservation of the Chinese Bumblebee Bombus pyrosoma (Hymenoptera: Apidae)
Authors: Hu Xiao , Liu Jiyao , Ding Guiling , Naeem Muhammad , Li Jilian , Ma Fangzhou , Huang Jiaxing , An Jiandong
Published: May 2021

Bumblebees are important pollinators for many wild plants and crops. However, the bumblebee populations are seriously declining in many parts of the world. Hence, the bumblebee conservation strategy should be urgently addressed, and the species distribution modeling approach can effectively evaluate the potentially suitable areas for their conservation. Here, one of the most abundant and endemic species of bumblebee in China, Bombus pyrosoma, was selected to assess current and future climates’ influence on its distribution with MaxEnt. Nine high-resolution bioclimatic/environmental variables with high contribution rates and low correlations were used. Four of the nine bioclimatic/environmental variables, min temperature of the coldest month (bio_06), annual mean temperature (bio_01), precipitation of wettest month (bio_13) and radiation of warmest quarter (bio_26), were found to be the most critical factors influencing the distribution of B. pyrosoma. The modeling results showed that the areas with high and moderate suitability for B. pyrosoma covered 141,858 and 186,198 km2 under the current climate conditions. More than 85% of the sampling sites in 2019 were found to be suitable under the current scenario. Under the future A1B and A2 scenarios in 2050 and 2100, the areas with low and moderate suitability for B. pyrosoma increased. However, alarmingly, the high suitability areas decreased under the future A1B and A2 scenarios in 2050 and 2100. Furthermore, regions covering seven provinces of northern China were the most crucial for developing nature reserves for B. pyrosoma, with the following order of suitable areas: Gansu, Shanxi, Ningxia, Qinghai, Shaanxi, Hebei and Beijing. Our study highlights the impact of future climate changes on the distribution of B. pyrosoma, and conservation strategies should mitigate the threats posed by environmental changes, particularly in the current high suitability areas.
A PIK3R2 Mutation in Familial Temporal Lobe Epilepsy as a Possible Pathogenic Variant
Authors: Wang Yishu , Peng Jing , Bai Shuwei , Yu Haojun , He Hong , Fan Chunxiang , Hao Yong , Guan Yangtai
Published: May 2021

Temporal lobe epilepsy (TLE), the most common form of medically refractory focal epilepsy in adults, often requires surgery to alleviate seizures. By using next-generation sequencing, we identified a PIK3R2 mutation (NM_005027.4: c.265C > T; NP_005018.2: p.Arg89Cys) in a family with mesial temporal lobe epilepsy. PIK3R2 encodes p85β, the regulatory subunit of Class IA phosphoinositide 3-kinase (PI3K) and the mutation we identified in PIK3R2 seems to function unexpectedly as a possible pathogenic variant. The mutation is predicted to be potentially pathogenic by multiple bioinformatics tools. Through a functional assay, we verified that the mutation enhances the function of PI3K in induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of the proband. Finally, pathological testing of the resected temporal lobe cortex showed that the expression of PIK3R2 was significantly higher in patients with refractory temporal lobe epilepsy than in those of non-epileptic diseases as a control group. It can be inferred that PIK3R2 might play an important role in the development of TLE.
A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing
Authors: Andreu-Sánchez Sergio , Chen Lianmin , Wang Daoming , Augustijn Hannah E. , Zhernakova Alexandra , Fu Jingyuan
Published: May 2021

Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK’s tools as reliable variant callers for metagenomic samples.
Reproductive Isolation Between Taxonomically Controversial Forms of the Gray Voles (Microtus, Rodentia; Arvicolinae): Cytological Mechanisms and Taxonomical Implications
Authors: Bikchurina Tatiana I. , Golenishchev Fedor N. , Kizilova Elena A. , Mahmoudi Ahmad , Borodin Pavel M.
Published: May 2021

The formation of hybrid sterility is an important stage of speciation. The voles of the genus Microtus, which is the most speciose genus of rodents, provide a good model for studying the cytological mechanisms of hybrid sterility. The voles of the “mystacinus” group of the subgenus Microtus (2n = 54) comprising several recently diverged forms with unclear taxonomic status are especially interesting. To resolve the taxonomic status of Microtus mystacinus and Microtus kermanensis, we crossed both with Microtus rossiaemeridionalis, and M. kermanensis alone with Microtus arvalis “obscurus” and M. transcaspicus and examined the reproductive performance of their F1 hybrids. All interspecies male hybrids were sterile. Female M. kermanensis × M. arvalis and M. kermanensis × M. transcaspicus hybrids were sterile as well. Therefore, M. mystacinus, M. kermanensis, and M. rossiaemeridionalis could be considered valid species. To gain an insight into the cytological mechanisms of male hybrid sterility, we carried out a histological analysis of spermatogenesis and a cytological analysis of chromosome synapsis, recombination, and epigenetic chromatin modifications in the germ cells of the hybrids using immunolocalization of key meiotic proteins. The hybrids showed wide variation in the onset of spermatogenesis arrest stage, from mature (although abnormal) spermatozoa to spermatogonia only. Chromosome asynapsis was apparently the main cause of meiotic arrest. The degree of asynapsis varied widely across cells, individuals, and the crosses—from partial asynapsis of several small bivalents to complete asynapsis of all chromosomes. The asynapsis was accompanied by a delayed repair of DNA double-strand breaks marked by RAD51 antibodies and silencing of unpaired chromatin marked by γH2A.X antibodies. Overall, the severity of disturbances in spermatogenesis in general and in chromosome synapsis in particular increased in the hybrids with an increase in the phylogenetic distance between their parental species.
Case Report: THSD7A-Positive Membranous Nephropathy Caused by Tislelizumab in a Lung Cancer Patient
Authors: Chen Minjiang , Zhang Lei , Zhong Wei , Zheng Ke , Ye Wei , Wang Mengzhao
Published: May 2021

Immune checkpoint inhibitors (ICIs) became the standard treatment for many different kinds of cancers and can result in a variety of immune-related adverse events (irAEs). IrAEs of kidney are uncommon and consists of different pathology types. Among the different types, membranous nephropathy (MN) is rare and have not been well-described. Since MN can also be associated with malignancies, differential diagnosis in patients receiving ICIs who develop MN can be very difficult. We present the case of a 74-year-old man with metastatic non-small cell lung cancer who developed MN after ICIs therapy. The patient tested positive for thrombospondin type-1 domain-containing 7A antibodies (THSD7A) when diagnosed with MN. Supplementary examinations revealed the predisposing antigen in the primary tumor and present of the antibody after immunotherapy, which corresponded to the patient’s clinical course of nephropathy. Treatment consisting of systemic glucocorticoids and rituximab resulted in a good clinical response, and the THSD7A antibodies were no longer detected. In this case, we first discuss the potential mechanism of immunotherapy related MN, in which the activation of humoral immunity may play an important role.
Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome
Authors: Gougeon Marie-Lise , Poirier-Beaudouin Béatrice , Ausseil Jérome , Zérah Michel , Artaud Cécile , Heard Jean-Michel , Deiva Kumaran , Tardieu Marc
Published: May 2021

Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. It was reported that AAV-mediated gene therapies might elicit a strong host immune response resulting in decreased transgene expression. To address this issue, we performed a comprehensive analysis of cellular immunity and cytokine patterns generated against the therapeutic enzyme in the four treated children over 5.5 years of follow-up. We report the emergence of memory and polyfunctional CD4+ and CD8+ T lymphocytes sensitized to the transgene soon after the start of therapy, and appearing in peripheral blood in waves throughout the follow-up. However, this response had no apparent impact on CNS transgene expression, which remained stable 66 months after surgery, possibly a consequence of the long-term immunosuppressive treatment. We also report that gene therapy did not trigger neuroinflammation, evaluated through the expression of cytokines and chemokines in patients’ CSF. Milder disease progression in the youngest patient was found associated with low level and less differentiated circulating NAGLU-specific T cells, together with the lack of proinflammatory cytokines in the CSF. Findings in this study support a systematic and comprehensive immunomonitoring approach for understanding the impact immune reactions might have on treatment safety and efficacy of gene therapies.
Characterization of DNA G-Quadruplex Structures in Human Immunoglobulin Heavy Variable (IGHV) Genes
Authors: Tang Catherine , MacCarthy Thomas
Published: May 2021

Activation-induced deaminase (AID) is a key enzyme involved in antibody diversification by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) of the Immunoglobulin (Ig) loci. AID preferentially targets WRC (W=A/T, R=A/G) hotspot motifs and avoids SYC (S=C/G, Y=C/T) coldspots. G-quadruplex (G4) structures are four-stranded DNA secondary structures with key functions in transcription, translation and replication. In vitro studies have shown G4s to form and bind AID in Ig switch (S) regions. Alterations in the gene encoding AID can further disrupt AID-G4 binding and reduce CSR in vivo. However, it is still unclear whether G4s form in the variable (V) region, or how they may affect SHM. To assess the possibility of G4 formation in human V regions, we analyzed germline human Ig heavy chain V (IGHV) sequences, using a pre-trained deep learning model that predicts G4 potential. This revealed that many genes from the IGHV3 and IGHV4 families are predicted to have high G4 potential in the top and bottom strand, respectively. Different IGHV alleles also showed variability in G4 potential. Using a high-resolution (G4-seq) dataset of biochemically confirmed potential G4s in IGHV genes, we validated our computational predictions. G4-seq also revealed variation between S and V regions in the distribution of potential G4s, with the V region having overall reduced G4 abundance compared to the S region. The density of AGCT motifs, where two AGC hotspots overlap on both strands, was roughly 2.6-fold greater in the V region than the Constant (C) region, which does not mutate despite having predicted G4s at similar levels. However, AGCT motifs in both V and C regions were less abundant than in S regions. In silico mutagenesis experiments showed that G4 potentials were generally robust to mutation, although large deviations from germline states were found, mostly in framework regions. G4 potential is also associated with higher mutability of certain WRC hotspots on the same strand. In addition, CCC coldspots opposite a predicted G4 were shown to be targeted significantly more for mutation. Our overall assessment reveals plausible evidence of functional G4s forming in the Ig V region.
Revisiting Integrated Coastal and Marine Management in Canada: Opportunities in the Bay of Fundy
Authors: Eger Sondra L. , Stephenson Robert L. , Armitage Derek , Flannery Wesley , Courtenay Simon C.
Published: May 2021

Limited progress has been made in implementing integrated coastal and marine management (ICM) policies globally. A renewed commitment to ICM in Canada offers an opportunity to implement lessons from previous efforts over the past 20 years. This study applies three core ICM characteristics identified from the literature (formal structures; meaningful inclusion; and, innovative mechanisms) to identify opportunities for operationalizing ICM from participants’ lived experiences in Atlantic Canada. These characteristics are employed to assess and compare ICM initiatives across two case studies in the Upper Bay and the Lower Bay of Fundy. The assessments are based on semi-structured interviews conducted with key participants and a supplementary document analysis. The following insights for future ICM policies were identified: adaptive formal structures are required for avoiding previous mistakes; a spectrum of approaches will support meaningful engagement in ICM; local capacity is needed for effective innovative mechanisms; and, policy recommendations should be implemented in parallel. Although these insights are relevant to each of the two sub-regional case studies, the paths taken to incorporating and realizing them appear to be location-specific. To account for these site-specific differences, we suggest more attention be given to strategies that incorporate local history, unique capacity of actor groups and location-specific social-ecological systems objectives. We provide the following recommendations on policy instruments to assist in moving toward enhanced regional ICM in the Bay of Fundy, and that may also be transferable to international ICM efforts: update policy statements to incorporate lessons from previous experiences; strengthen commitment to ICM in Federal law; create a regional engagement strategy to enhance involvement of local actor groups; and, enhance the role of municipal governments to support local capacity building and appropriate engagement of local actors in ICM processes.
Chemometrics-Assisted Raman Spectroscopy Characterization of Tunable Polymer-Peptide Hybrids for Dental Tissue Repair
Authors: Spencer Paulette , Ye Qiang , Kamathewatta Nilan J. B. , Woolfolk Sarah K. , Bohaty Brenda S. , Misra Anil , Tamerler Candan
Published: May 2021

The interfaces that biological tissues form with biomaterials are invariably defective and frequently the location where failure initiates. Characterizing the phenomena that lead to failure is confounded by several factors including heterogeneous material/tissue interfaces. To seamlessly analyze across these diverse structures presents a wealth of analytical challenges. This study aims to develop a molecular-level understanding of a peptide-functionalized adhesive/collagen hybrid biomaterial using Raman spectroscopy combined with chemometrics approach. An engineered hydroxyapatite-binding peptide (HABP) was copolymerized in dentin adhesive and dentin was demineralized to provide collagen matrices that were partially infiltrated with the peptide-functionalized adhesive. Partial infiltration led to pockets of exposed collagen—a condition that simulates defects in adhesive/dentin interfaces. The spectroscopic results indicate that co-polymerizable HABP tethered to the adhesive promoted remineralization of the defects. The spatial distribution of collagen, adhesive, and mineral as well as crystallinity of the mineral across this heterogeneous material/tissue interface was determined using micro-Raman spectroscopy combined with chemometrics approach. The success of this combined approach in the characterization of material/tissue interfaces stems from its ability to extract quality parameters that are related to the essential and relevant portions of the spectral data, after filtering out noise and non-relevant information. This ability is critical when it is not possible to separate components for analysis such as investigations focused on, in situ chemical characterization of interfaces. Extracting essential information from complex bio/material interfaces using data driven approaches will improve our understanding of heterogeneous material/tissue interfaces. This understanding will allow us to identify key parameters within the interfacial micro-environment that should be harnessed to develop durable biomaterials.
Evaluation of Prognostic Factors for Clinical Pregnancy Rate Following Artificial Insemination by Husband in the Chinese Population
Authors: Luo Yumei , Wu Shunhong , Yuan Jingru , Zhou Hua , Zhong Yufang , Zhang Mimi , Li Qing , Xu Xia , Sun Xiaofang , Zhu Detu
Published: May 2021

Background: To determine the independent prognostic factors and develop a multivariate logistic regression model for predicting successful pregnancy following artificial insemination by husband (AIH) in infertile Chinese couples.

Methods: A total of 3,015 AIH cycles with superovulation from 1,853 infertile Chinese couples were retrospectively analyzed. The clinical characteristics and sperm parameters were compared between the pregnant and non-pregnant groups. Multivariate logistic regression analysis was performed to remove the confounding factors and create an equation to predict the successful pregnancy. Receiver operating characteristic (ROC) curves were constructed for evaluating the abilities for prognostic classification of the independent predictors and the equation.

Results: The overall pregnancy rate was 13.0%. The pregnancy rate of double intrauterine insemination (IUI) (18.9%) was significantly higher than that of single IUI (11.4%). The pregnancy rate of the stimulated cycle (14.4%) was significantly higher than that of the natural cycle (9.0%). The pregnancy rates of the age groups <40 years are ~3 times higher than that of the ≥40 years age group. Among sperm parameters, the influencing factors included straight-line velocity (VSL), sperm deformity index (SDI), and normal form rate (all P < 0.05). A multivariate logistic regression equation was created based on the above influencing factors. ROC analysis showed that the prognostic power of the equation is better than those of individual predictors.

Conclusion: Cycle treatment options, single/double IUI, female age, sperm VSL, SDI, and normal form rate could predict successful pregnancy following AIH in China. The multivariate logistic regression equation exhibited a greater value for prognostic classification than single predictors.
The Relationship Between Food-Based Pro-inflammatory Diet and Sarcopenia: Findings From a Cross-Sectional Study in Iranian Elderly People
Authors: Bagheri Amir , Hashemi Rezvan , Soltani Sanaz , Heshmat Ramin , Dorosty Motlagh Ahmadreza , Larijani Bagher , Esmaillzadeh Ahmad
Published: May 2021

Background: Sarcopenia has rarely been linked to Food-based Inflammatory Potential of the Diet (FIPD) in earlier studies. This study was performed to examine the association of FIPD and sarcopenia and its components.

Method: In the cross-sectional research, dietary intakes of 300 randomly-selected elderly adults aged 55 years or older were collected through a validated food frequency questionnaire. We constructed FIPD score based on average consumptions of 28 food items. According to The European Working Group on Sarcopenia definition, sarcopenia and its components such as muscle strength, muscle mass, and gait speed were defined.

Result: No significant difference was found between the prevalence of sarcopenia (P = 0.05), low muscle mass (P = 0.27), low handgrip strength (P = 0.72), and lower gait speed (P = 0.14) across tertiles of FIPD score. Moreover, we did not find significant differences among means of handgrip strength (P = 0.65), muscle mass (P = 0.33), and walking speed (P = 0.89) across FIPD categories. However, binary logistic regression analysis indicated a significant positive relationship between FIPD score and odds of sarcopenia; such that subjects in the top vs. those in the bottom FIPD tertile had 155% greater chance of having sarcopenia (OR: 2.55; 95% CI: 1.17–5.55). After controlling for all confounding factors, this association strengthened (OR: 2.67; 95% CI: 1.18–6.01).

Conclusion: We found that greater FIPD score, which means a more pro-inflammatory diet, was positively linked with sarcopenia.
False Negative Mitigation in Group Testing for COVID-19 Screening
Authors: Alizad-Rahvar Amir Reza , Vafadar Safar , Totonchi Mehdi , Sadeghi Mehdi
Published: May 2021

After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.
Spatial Distribution of Arctic Bacterioplankton Abundance Is Linked to Distinct Water Masses and Summertime Phytoplankton Bloom Dynamics (Fram Strait, 79°N)
Authors: Cardozo-Mino Magda G. , Fadeev Eduard , Salman-Carvalho Verena , Boetius Antje
Published: May 2021

The Arctic is impacted by climate warming faster than any other oceanic region on Earth. Assessing the baseline of microbial communities in this rapidly changing ecosystem is vital for understanding the implications of ocean warming and sea ice retreat on ecosystem functioning. Using CARD-FISH and semi-automated counting, we quantified 14 ecologically relevant taxonomic groups of bacterioplankton (Bacteria and Archaea) from surface (0–30 m) down to deep waters (2,500 m) in summer ice-covered and ice-free regions of the Fram Strait, the main gateway for Atlantic inflow into the Arctic Ocean. Cell abundances of the bacterioplankton communities in surface waters varied from 105 cells mL–1 in ice-covered regions to 106 cells mL–1 in the ice-free regions. Observations suggest that these were overall driven by variations in phytoplankton bloom conditions across the Strait. The bacterial groups Bacteroidetes and Gammaproteobacteria showed several-fold higher cell abundances under late phytoplankton bloom conditions of the ice-free regions. Other taxonomic groups, such as the Rhodobacteraceae, revealed a distinct association of cell abundances with the surface Atlantic waters. With increasing depth (>500 m), the total cell abundances of the bacterioplankton communities decreased by up to two orders of magnitude, while largely unknown taxonomic groups (e.g., SAR324 and SAR202 clades) maintained constant cell abundances throughout the entire water column (ca. 103 cells mL–1). This suggests that these enigmatic groups may occupy a specific ecological niche in the entire water column. Our results provide the first quantitative spatial variations assessment of bacterioplankton in the summer ice-covered and ice-free Arctic water column, and suggest that further shift toward ice-free Arctic summers with longer phytoplankton blooms can lead to major changes in the associated standing stock of the bacterioplankton communities.
The Good and the Bad: Ecological Interaction Measurements Between the Urinary Microbiota and Uropathogens
Authors: Zandbergen Laurens E. , Halverson Thomas , Brons Jolanda K. , Wolfe Alan J. , de Vos Marjon G. J.
Published: May 2021

The human body harbors numerous populations of microorganisms in various ecological niches. Some of these microbial niches, such as the human gut and the respiratory system, are well studied. One system that has been understudied is the urinary tract, primarily because it has been considered sterile in the absence of infection. Thanks to modern sequencing and enhanced culture techniques, it is now known that a urinary microbiota exists. The implication is that these species live as communities in the urinary tract, forming microbial ecosystems. However, the interactions between species in such an ecosystem remains unknown. Various studies in different parts of the human body have highlighted the ability of the pre-existing microbiota to alter the course of infection by impacting the pathogenicity of bacteria either directly or indirectly. For the urinary tract, the effect of the resident microbiota on uropathogens and the phenotypic microbial interactions is largely unknown. No studies have yet measured the response of uropathogens to the resident urinary bacteria. In this study, we investigate the interactions between uropathogens, isolated from elderly individuals suffering from UTIs, and bacteria isolated from the urinary tract of asymptomatic individuals using growth measurements in conditioned media. We observed that bacteria isolated from individuals with UTI-like symptoms and bacteria isolated from asymptomatic individuals can affect each other’s growth; for example, bacteria isolated from symptomatic individuals affect the growth of bacteria isolated from asymptomatic individuals more negatively than vice versa. Additionally, we show that Gram-positive bacteria alter the growth characteristics differently compared to Gram-negative bacteria. Our results are an early step in elucidating the role of microbial interactions in urinary microbial ecosystems that harbor both uropathogens and pre-existing microbiota.
Prospective Role of Peptide-Based Antiviral Therapy Against the Main Protease of SARS-CoV-2
Authors: Mahmud Shafi , Paul Gobindo Kumar , Biswas Suvro , Afrose Shamima , Mita Mohasana Akter , Hasan Md. Robiul , Shimu Mst. Sharmin Sultana , Hossain Alomgir , Promi Maria Meha , Ema Fahmida Khan , Chidambaram Kumarappan , Chandrasekaran Balakumar , Alqahtani Ali M. , Emran Talha Bin , Saleh Md. Abu
Published: May 2021

The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex’s stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2.
Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology
Authors: Fasnacht Michel , Polacek Norbert
Published: May 2021

Ever since the “great oxidation event,” Earth’s cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell’s capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.
Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens
Authors: Gadila Shiva Kumar Goud , Rosoklija Gorazd , Dwork Andrew J. , Fallon Brian A. , Embers Monica E.
Published: May 2021

The complex etiology of neurodegenerative disease has prompted studies on multiple mechanisms including genetic predisposition, brain biochemistry, immunological responses, and microbial insult. In particular, Lyme disease is often associated with neurocognitive impairment with variable manifestations between patients. We sought to develop methods to reliably detect Borrelia burgdorferi, the spirochete bacteria responsible for Lyme disease, in autopsy specimens of patients with a history of neurocognitive disease. In this report, we describe the use of multiple molecular detection techniques for this pathogen and its application to a case study of a Lyme disease patient. The patient had a history of Lyme disease, was treated with antibiotics, and years later developed chronic symptoms including dementia. The patient's pathology and clinical case description was consistent with Lewy body dementia. B. burgdorferi was identified by PCR in several CNS tissues and by immunofluorescent staining in the spinal cord. These studies offer proof of the principle that persistent infection with the Lyme disease spirochete may have lingering consequences on the CNS.
Differences in Characteristics and Ambulance Pathway Adherence Between Strokes and Mimics Presenting to a Large UK Centralized Hyper Acute Stroke Unit (HASU)
Authors: Sammut-Powell Camilla , Ashton Christopher , Paroutoglou Kyriaki , Parry-Jones Adrian
Published: May 2021

Background: In Greater Manchester (GM), prehospital clinicians use the Face Arm Speech Test (FAST) to identify suspected stroke patients alongside pathway exclusions. Within the centralized stroke service, patients with a suspected stroke are taken directly to a Hyper Acute Stroke Unit (HASU), often bypassing their local emergency department (ED). However, many of these patients are experiencing an illness that looks like a stroke but is not a stroke. The data collected in the prehospital setting is rarely used in research yet could give valuable insights into the performance of the pathway.

Aim: To evaluate the presenting symptoms and final diagnoses of prehospital suspected strokes and to evaluate the adherence of prehospital stroke pathway exclusions.

Methods: We analyzed data from all patients brought in by ambulance and admitted on the stroke pathway between 01/09/15 and 28/02/17. Patient demographics and all data recorded in the prehospital setting were evaluated to identify differences in stroke, TIA, and mimic patients. Pathway adherence was assessed according to whether the patient was local or out-of-area (OOA) and bypassed their local ED.

Results: A total of 4,216 suspected strokes were identified: 2,213 (52.5%) had a final diagnosis of stroke, 492 (11.7%) experienced a transient ischemic attack (TIA), and 1,511 (35.8%) were stroke mimics. There were 714 (16.9%) patients that were identified as having at least one pathway exclusion or were FAST negative, of which 270 (37.8%) experienced a stroke. The proportion of strokes was significantly lower in those with a pathway exclusion (41.8 vs. 53.5%; p < 0.001) and the proportion of breaches tended to be comparable or higher in the local population.

Discussion: There are high volumes of stroke mimics but identified differences indicate there is an opportunity to better utilize prehospital data. Ambulance clinicians were able to correctly overrule FAST negative results and the volume of these suggest that FAST alone may be too restrictive.
Stochasticity, Nonlinear Value Functions, and Update Rules in Learning Aesthetic Biases
Authors: Grzywacz Norberto M.
Published: May 2021

A theoretical framework for the reinforcement learning of aesthetic biases was recently proposed based on brain circuitries revealed by neuroimaging. A model grounded on that framework accounted for interesting features of human aesthetic biases. These features included individuality, cultural predispositions, stochastic dynamics of learning and aesthetic biases, and the peak-shift effect. However, despite the success in explaining these features, a potential weakness was the linearity of the value function used to predict reward. This linearity meant that the learning process employed a value function that assumed a linear relationship between reward and sensory stimuli. Linearity is common in reinforcement learning in neuroscience. However, linearity can be problematic because neural mechanisms and the dependence of reward on sensory stimuli were typically nonlinear. Here, we analyze the learning performance with models including optimal nonlinear value functions. We also compare updating the free parameters of the value functions with the delta rule, which neuroscience models use frequently, vs. updating with a new Phi rule that considers the structure of the nonlinearities. Our computer simulations showed that optimal nonlinear value functions resulted in improvements of learning errors when the reward models were nonlinear. Similarly, the new Phi rule led to improvements in these errors. These improvements were accompanied by the straightening of the trajectories of the vector of free parameters in its phase space. This straightening meant that the process became more efficient in learning the prediction of reward. Surprisingly, however, this improved efficiency had a complex relationship with the rate of learning. Finally, the stochasticity arising from the probabilistic sampling of sensory stimuli, rewards, and motivations helped the learning process narrow the range of free parameters to nearly optimal outcomes. Therefore, we suggest that value functions and update rules optimized for social and ecological constraints are ideal for learning aesthetic biases.