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Non-noble metal catalyst with high catalytic activity and stability towards oxygen reduction reaction (ORR) is critical for durable bioelectricity generation in air-cathode microbial fuel cells (MFCs). Herein, nitrogen-doped (iron-cobalt alloy)/cobalt/cobalt phosphide/partly-graphitized carbon ((FeCo)/Co/Co 2 P/NPGC) catalysts are prepared by using cornstalks via a facile method. Carbonization temperature exerts a great effect on catalyst structure and ORR activity. FeCo alloys are in-situ formed in the catalysts above 900 °C, which are considered as the highly-active component in catalyzing ORR. AC-MFC with FeCo/Co/Co 2 P/NPGC (950 °C) cathode shows the highest power density of 997.74 ± 5 mW m−2, which only declines 8.65% after 90 d operation. The highest Coulombic efficiency (23.3%) and the lowest charge transfer resistance (22.89 Ω) are obtained by FeCo/Co/Co 2 P/NPGC (950 °C) cathode, indicating that it has a high bio-electrons recycling rate. Highly porous structure (539.50 m2 g−1) can provide the interconnected channels to facilitate the transport of O 2. FeCo alloys promote charge transfer and catalytic decomposition of H 2 O 2 to •OH and •O 2 −, which inhibits cathodic biofilm growth to improve ORR durability. Synergies between metallic components (FeCo/Co/Co 2 P) and N-doped carbon energetically improve the ORR catalytic activity of (FeCo)/Co/Co 2 P/NPGC catalysts, which have the potential to be widely used as catalysts in MFCs. [Display omitted] • Residual cornstalks as the recycling carbon source are environmental-friendly. • FeCo alloy anchored in N-doped carbon improves ORR catalytic activity in AC-MFCs. • Porous carbon structure with doped N-species facilitates the O 2 transport for ORR. • AC-MFC with FeCo/Co/Co 2 P/NPGC (950 °C) cathode has higher power output than Pt/C. • FeCo/Co/Co 2 P/NPGC catalyst shows a good durability for long-time AC-MFCs operation. [ABSTRACT FROM AUTHOR]

A consensus regarding subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer is lacking. These patients typically receive non-platinum-based chemotherapy; however, survival outcomes remain poor. Compared with chemotherapy alone, combination therapy with novel target agents can provide additional benefits to these patients. Oregovomab, an investigational murine monoclonal antibody against CA-125, has shown promising efficacy in a phase II study in patients with recurrent ovarian cancer. Herein, we described the rationale and design of OPERA/KGOG 3065/APGOT-OV6, a multicenter, investigator-initiated, two-cohort, single-arm phase II trial, aimed at examining the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with PARPi/platinum-resistant ovarian cancer. The primary end point was the objective response rate, according to RECIST 1.1. Clinical Trial Registration:NCT05407584 (ClinicalTrials.gov) Plain Language Summary OPERA/KGOG 3065/APGOT-OV6 is a promising phase II studies that test new drug (oregovomab) on the patients with poly (ADP-ribose) polymerase inhibitor (PARPi)/platinum-resistant epithelial ovarian cancer. PARPis have changed the treatment landscape of ovarian cancer in a relatively short time. PARPi/platinum-resistant epithelial ovarian cancer refer to a subtype of recurrent epithelial cancer of ovarian, tubal or peritoneal origin who experienced disease progression despite treatment with a PARPi or platinum-based chemotherapy drugs. Although various new drugs have been tested to improve the treatment response in resistant patients, a consensus regarding the international standard of treatment is yet to be established, despite the poor survival outcomes of these patients. OPERA/KGOG 3065/APGOT-OV6 has been designed to add oregovomab, a murine monoclonal antibody to cancer antigen-125 (CA-125), to non-platinum chemotherapy (pegylated liposomal doxorubicin or paclitaxel) for patients with ovarian cancer determined as PARPi/platinum-resistant and ineligible for bevacizumab treatment. The results of this study will aid in developing effective treatment strategies for patients with PARPi/platinum-resistant ovarian cancer. Tweetable Abstract OPERA/KGOG 3065/APGOT-OV6: a multicenter, investigator-initiated, two-cohort, single-arm phase II trial, aimed at examining the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with poly (ADP-ribose) polymerase inhibitor/platinum-resistant ovarian cancer. Article highlights Subsequent therapeutic strategies for patients with platinum- and poly (ADP-ribose) polymerase inhibitor (PARPi)-resistant ovarian cancer are to be established. Oregovomab, a murine monoclonal antibody specifically targeting cancer antigen (CA)-125, has shown promising efficacy in patients with recurrent ovarian cancer, achieving a median progression-free interval of 11 weeks and median overall survival of 70.4 weeks. The efficacy of oregovomab in combination with non-platinum chemotherapy for patients with PARPi/platinum-resistant epithelial ovarian cancer (EOC) remains unexplored. The OPERA/KGOG 3065/APGOT-OV6 is designed to investigate the efficacy of oregovomab plus non-platinum-based chemotherapy in patients with PARPi-resistant EOC unsuitable for platinum-based therapy. The findings of this trial will afford novel insights into the antitumor efficacy and safety profile of oregovomab plus non-platinum chemotherapy in patients with PARPi-resistant EOC. [ABSTRACT FROM AUTHOR]

Background: Drugs targeting disease causal genes are more likely to succeed for that disease. However, complex disease causal genes are not always clear. In contrast, Mendelian disease causal genes are well-known and druggable. Here, we seek an approach to exploit the well characterized biology of Mendelian diseases for complex disease drug discovery, by exploiting evidence of pathogenic processes shared between monogenic and complex disease. One way to find shared disease etiology is clinical association: some Mendelian diseases are known to predispose patients to specific complex diseases (comorbidity). Previous studies link this comorbidity to pleiotropic effects of the Mendelian disease causal genes on the complex disease. Methods: In previous work studying incidence of 90 Mendelian and 65 complex diseases, we found 2,908 pairs of clinically associated (comorbid) diseases. Using this clinical signal, we can match each complex disease to a set of Mendelian disease causal genes. We hypothesize that the drugs targeting these genes are potential candidate drugs for the complex disease. We evaluate our candidate drugs using information of current drug indications or investigations. Results: Our analysis shows that the candidate drugs are enriched among currently investigated or indicated drugs for the relevant complex diseases (odds ratio = 1.84, p = 5.98e-22). Additionally, the candidate drugs are more likely to be in advanced stages of the drug development pipeline. We also present an approach to prioritize Mendelian diseases with particular promise for drug repurposing. Finally, we find that the combination of comorbidity and genetic similarity for a Mendelian disease and cancer pair leads to recommendation of candidate drugs that are enriched for those investigated or indicated. Conclusions: Our findings suggest a novel way to take advantage of the rich knowledge about Mendelian disease biology to improve treatment of complex diseases. [ABSTRACT FROM AUTHOR]

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The substantial investments in human genetics and genomics made over the past three decades were anticipated to result in many innovative therapies. Here we investigate the extent to which these expectations have been met, excluding cancer treatments. In our search, we identified 40 germline genetic observations that led directly to new targets and subsequently to novel approved therapies for 36 rare and 4 common conditions. The median time between genetic target discovery and drug approval was 25 years. Most of the genetically driven therapies for rare diseases compensate for disease-causing loss-of-function mutations. The therapies approved for common conditions are all inhibitors designed to pharmacologically mimic the natural, disease-protective effects of rare loss-of-function variants. Large biobank-based genetic studies have the power to identify and validate a large number of new drug targets. Genetics can also assist in the clinical development phase of drugs—for example, by selecting individuals who are most likely to respond to investigational therapies. This approach to drug development requires investments into large, diverse cohorts of deeply phenotyped individuals with appropriate consent for genetically assisted trials. A robust framework that facilitates responsible, sustainable benefit sharing will be required to capture the full potential of human genetics and genomics and bring effective and safe innovative therapies to patients quickly.This Review provides a perspective on the development of non-cancer therapies based on human genetics studies and suggests measures that can be taken to streamline the pipeline from initial genetic discovery to approved therapy. [ABSTRACT FROM AUTHOR]

Myopia is a refractive disorder arising from a mismatch between refractive power and relatively long axial length of the eye. With its dramatically increasing prevalence, myopia has become a pervasive social problem. It is commonly accepted that abnormal visual input acts as an initiating factor of myopia. As the first station to perceive visual signals, the retina plays an important role in myopia etiology. The retina is a fine-layered structure with multitudinous cells, processing intricate visual signals via numerous molecular pathways. Accordingly, dopaminergic mechanisms, contributions of rod and cone photoreceptors, myopic structural changes of retinal pigment epithelium (RPE) and neuro-retinal layers have all suggested a vital role of retinal dysfunction in myopia development. Herein, we separately discuss myopia-related retinal dysfunction and current dilemmas by different levels, from molecules to cells, with the hope that the comprehensive delineation could contribute to a better understanding of myopia etiology, indicate novel therapeutic targets, and inspire future studies. [ABSTRACT FROM AUTHOR]

An alphaherpesvirus carries dozens of viral proteins in the envelope, tegument and capsid structure, and each protein plays an indispensable role in virus adsorption, invasion, uncoating and release. After infecting the host, a virus eliminates unfavourable factors via multiple mechanisms to escape or suppress the attack of the host immune system. Post-translational modification of proteins, especially phosphorylation, regulates changes in protein conformation and biological activity through a series of complex mechanisms. Many viruses have evolved mechanisms to leverage host phosphorylation systems to regulate viral protein activity and establish a suitable cellular environment for efficient viral replication and virulence. In this paper, viral protein kinases and the regulation of viral protein function mediated via the phosphorylation of alphaherpesvirus proteins are described. In addition, this paper provides new ideas for further research into the role played by the post-translational modification of viral proteins in the virus life cycle, which will be helpful for understanding the mechanisms of viral infection of a host and may lead to new directions of antiviral treatment. [ABSTRACT FROM AUTHOR]

The aim of this paper is to compare the classical continuum mechanics and the peridynamic models in the structural analysis of a monolithic glass plate subjected to ball drop. Governing equations are recalled in order to highlight the differences and basic features of both approaches. In this study the behavior of glass is assumed to be linear-elastic and damage processes are ignored. The generalized Hooke's law is assumed within the classical theory, while the linear peridynamic solid constitutive model is applied within the peridynamic analysis. Mechanical models for the ball drop simulation are discussed in detail. An emphasis is placed on the discretization including finite element mesh, peridynamic node lattice and time stepping, as well as appropriate constraints and contact conditions in both finite element and non-local peridynamics models. Deflections of the plate after the ball drop are presented as functions of time and the results based on the finite element and peridynamic analysis are compared. Good agreements between the deflection values in selected points of the plate as well as deflection fields at several time points indicate, that the model assumptions for the non-local peridynamic analysis including the horizon size, the short-range force contact settings and the support conditions are well suited. The developed peridynamics models can be applied in the future to analyze damage patterns in glass plates. [ABSTRACT FROM AUTHOR]

Specific learning disorders (SLD) persist into adulthood. Persons with SLD frequently experience emotional and social difficulties. Following qualitative descriptions of individuals with SLD who experienced learning, as traumatic, we hypothesized that individuals reporting SLD would report higher levels of learning-based post-traumatic-stress-disorder (PTSD) symptoms. In Study 1 (N = 216), participants responded to questionnaires concerning SLD and learning-based PTSD. A separate sample (N = 43) was queried about adjustment disorder symptoms. Study 2 (N = 176) examined if current psychological distress was predicted by levels of learning-based PTSD at each developmental stage (elementary/high-school/post-high-school) and whether SLD links to current psychological distress. Finally, we assessed if SLD-psychological distress associations are mediated by cumulative levels of learning-based PTSD across these school periods. In Study 1 individuals reporting SLD displayed higher learning-based PTSD levels than those without SLD. SLD-PTSD associations held beyond adjustment disorder symptom levels. In Study 2, SLD was linked with psychological distress, mediated by accumulated learning-based PTSD symptom levels across school periods. These results suggest that in individuals with SLD, learning experiences may be associated with learning-based PTSD symptoms. Further, persons with SLD may be scarred by their traumatic learning experiences linking with current psychological distress, a link mediated by cumulative difficulties experienced over school years. [ABSTRACT FROM AUTHOR]

Identifying and understanding the role of key molecular factors involved in the orientation/discrimination phenomena of analytes in polymer-based chiral liquid crystals (CLCs) are essential tasks for optimizing computational predictions (molecular dynamics simulation) of the existing orienting systems, as well as designing novel helically chiral polymers as new enantiodiscriminating aligning media. From this perspective, we propose to quantify and compare the enantiodiscrimination power of four homochiral polymer-based lyotropic liquid crystals (LLCs) toward a given chiral solute using their 2H residual quadrupolar couplings (2H-RQCs) measured by anisotropic natural abundance deuterium 2D-NMR (ANAD 2D-NMR). Two families of chiral polymers are investigated in this study: (i) poly-peptide polymers (PBLG and PCBLL), and (ii) polyacetylene polymers (PDA and L -MSP, a new system never published so far). As model solute, we investigate the case of camphor, an interesting rigid bicyclic chiral molecule possessing ten 2H-RQCs (10 inequivalent monodeurated isotopomers per enantiomer). In order to analyse the orientational behaviour of each enantiomer in a single oriented sample, while simplifying the identification of the (D / L)-isomer signals on spectra, a D -isomer enriched scalemic mixture (ee(D) = 30%) was used. Orientational data of camphor in each mesophase were calculated for the first time using the computer program ConArch+, modified to accept 2H-RQCs as anisotropic data input. Differences in enantiodiscriminations provided by the four aligning systems are examined and discussed in terms of structural and chemical features between polymers. The new L -MSP mesophase described in this work exhibits very promising enantiodiscrimination capacities. [ABSTRACT FROM AUTHOR]

The world is rapidly changing, the resources are getting depleted, and the demand for newer technologies and products is increasing. To keep up with these new advances, highly efficient catalytic routes need to be taken to be sustainable and ensure a drawn-out existence of resources for future generations. Catalysis turns out to be a significantly important field of application when it comes to the era of nanoscience, where all devices and technologies are becoming smaller and smaller in size with improved properties. When deeming the usability of a catalyst, it is of paramount importance to have a good understanding of their properties and their synergistic effect on the other reagents in the reaction. Over the last decade, the field of nanocatalysis has grown rapidly, both in homogeneous and heterogeneous catalysis. Given that nanoparticles have a high surface-to-volume ratio when compared to bulk materials, they are appealing as catalysts. Catalysts accelerate and boost thousands of different chemical reactions on a daily basis, forming the foundation of the multibillion-dollar chemical industry worldwide, a pathway leading to green chemistry, and a novel, yet crucial, environmental protection technology. As a result, in this review, the use of nanocatalysts and the application of their special features in the renewable energy, hydrocarbon processing, and fine chemical synthesis sector was explored. A detailed explanation of the working mechanism of these nanocatalysts, starting from how they are synthesized to the effect of modification of their surface, has been put together. We have tried to collect all the current progresses in these three sectors to the best of our abilities. Furthermore, it is anticipated that this paper would be useful for future researchers and academicians wishing to contribute toward this subject of interest. [ABSTRACT FROM AUTHOR]

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders' perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants. [ABSTRACT FROM AUTHOR]

Background: Clinical genomic professionals are increasingly facing decisions about returning incidental findings (IFs) from genetic research. Although previous studies have shown that research participants are interested in receiving IFs, yet there has been an argument about the extent of researcher obligation to return IFs. We aimed in this study to explore the perspectives of clinical genomics professionals toward returning incidental findings from genomic research.Methods: We conducted a national survey of a sample (n = 113) of clinical genomic professionals using a convenient sampling. A self-administered questionnaire was used to explore their attitudes toward disclosure of IFs, their perception of the duties to return IFs and identifying the barriers for disclosure of IFs. A descriptive analysis was employed to describe participants' responses.Results: Sixty-five (57.5%) respondents had faced IFs in their practice and 31 (27.4%) were not comfortable in discussing IFs with their research subjects. Less than one-third of the respondents reported the availability of guidelines governing IFs. The majority 84 (80%) and 69 (62.7%) of the study participants indicated they would return the IFs if the risk of disease threat ≥ 50% and 6-49%, respectively and 36 (31.9%) reported they have no obligation to return IFs.Conclusion: Clinical genomics professionals have positive attitudes and perceptions toward the returning IFs from genomic research, yet some revealed no duty to do so. Detailed guidelines must be established to provide insights into how genomics professionals should be handled IFs. [ABSTRACT FROM AUTHOR]

The United States has adopted the targeted killing of high-ranking members of terrorist organizations to disrupt terrorist networks and exert general deterrence. The most salient of these killings occurred on 2 May 2011, when US Navy Seals killed Osama bin Laden in Pakistan. Although general deterrence suggests this should result in decreased subsequent terrorism, high-profile targeted killings can also result in increased terrorist violence through backlash. This study uses dual trajectory analysis to examine the divergent influence that the killing of bin Laden had on global terrorism trends between November 2007 and May 2014. These analyses reveal that killing bin Laden did not have the desired deterrent impact on global terrorism or on terrorism committed by Al Qaeda. [ABSTRACT FROM AUTHOR]

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness.Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function.Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome.Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function.Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses.Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome.Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (GvHD) has become a leading cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT) and can burden patients with devastating and lifelong health effects. Our understanding of the pathogenic mechanisms underlying chronic GvHD remains incomplete and this lack of understanding is reflected by lack of clear therapeutic approaches to steroid refractory disease. Observations predominantly from mouse models and human correlative studies currently support a three phase model for the initiation and development of chronic GvHD: 1) early inflammation and tissue damage triggers the innate immune system. This leads to inflammatory cytokine/chemokine patterns that recruit effector immune cell populations; 2) chronic inflammation causes the loss of central and peripheral tolerance mechanisms leading to emergence of pathogenic B and T cell populations that promote autoimmune and alloimmune reactions; 3) the dysregulated immunity causes altered macrophage polarization, aberrant tissue repair leading to scarring and end organ fibrosis. This model has led to the evaluation of many new therapies aimed at limiting inflammation, targeting dysregulated signaling pathways and restoring tolerance mechanisms. However, chronic GvHD is a multisystem disease with complex clinical phenotypes and it remains unclear as to which cluster of patients will respond best to specific therapeutic strategies. However, it is possible to gain novel insights from immune-related monogenic diseases. These diseases either share common clinical manifestations, replicate steps from the three phase chronic GvHD model or serve as surrogates for perfectly targeted drugs being investigated in chronic GvHD therapy. In this review, we will summarize the evidence from these monogenic immune related diseases that provide insight into pathogenic pathways in chronic GvHD, rationales for current therapies and novel directions for future drug discovery. [ABSTRACT FROM AUTHOR]

The lack of data on perspectives of racial and ethnic minority populations regarding family disclosure of individual research results (IRR) hinders the development of return of IRR policies and practices that are meaningful and culturally appropriate in diverse populations. This research aims to uncover preferences regarding family disclosure of IRR and identify factors that may shape the preferences in three minority populations. Nine focus groups with 68 adult African American, Hispanic/Latinx, and American Indian/Alaska Native individuals were conducted. Data were analyzed using thematic analysis. Participants were willing to share IRR with relatives who elected to know and preferred a participant-driven (vs. researcher-driven) decision-making process. Privacy of personal information was deemed important, as were anticipated familial benefits from genetic information, except when improper use of the information was suspected. Factors influencing family disclosure decisions included the family's biological and emotional closeness, and participants' perceived mental preparedness of the relative. Family disclosure of IRR among racial and ethnic minority individuals is a complex decision-making process wherein issues of individual privacy are entangled with family dynamic and familial benefit considerations. These data suggest that policies surrounding family disclosure of IRR should carefully consider participant preferences and adopt a participant-driven approach. [ABSTRACT FROM AUTHOR]

This study examines how parents of pediatric patients might differ in their views and attitudes towards genetic technology and information when compared to adult patients. There is surprisingly little evidence on how parents compare to other parts of population in their attitudes. Previous empirical studies often relate health-related preferences and attitudes to factors such as age, education, and income instead of parental status, thus evading comparison of parents to others as health-related decision makers. Findings related to the parental status can be useful when implementing genetic technology in clinical practice. We conducted a survey of views on genetic technology and information for groups of adult neurology patients (n = 68) and parents of pediatric neurology patients (n = 31) to shed some light on this issue. In addition to our own survey instrument, we conducted other surveys to gain insight on psychosocial factors that might affect these attitudes. The results suggest that parents are more concerned about their children's genetic risk factors when compared to the attitudes of adult patients about their own risk. For both groups, negative emotional state was associated with more concerns towards genetic information. Our study provides insights on how parental views might affect the acceptance of genetic technology and information. [ABSTRACT FROM AUTHOR]

Interfacial nanostructured materials have stimulated extensive interests in the research areas of green energy production and conversion due to their unique structures and performance. These interfacial crystalline structures with rich intrinsic defects, such as oxygen vacancies, adatoms, grain boundaries, and substitutional impurities, have led to unique activities in a variety of catalytic reactions. The rational design and engineering development of the interfaces provide an attractive way to optimize the catalytic performance and finally improve the efficiency of energy conversion and storage. Herein, a comprehensive overview of interfacial inorganic nanostructures and their electrocatalytic applications are summarized, and some future challenge and opportunity have also been proposed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate rs2107856 single-nucleotide polymorphism (SNP) of CNTNAP2 gene in Turkish population with pseudoexfoliation and to correlate clinical characteristics with the genotypic profile.Materials and methods: Forty-three patients with pseudoexfoliation syndrome (PXS), 46 patients with pseudoexfoliation glaucoma (PXG) and 99 healthy controls were enrolled. Comprehensive ophthalmological examination, central corneal thickness measurement and retinal nerve fiber layer thickness analysis of the peripapillary area were performed. Blood samples of 2 mL with EDTA were obtained and sent for genetic analysis. The role of the detected polymorphism on disease tendency along with the genotype and allele frequencies in each group was evaluated.Results: The mean age of the groups was 70.0 ± 8.0 (range 51-86) in PXS, 71.2 ± 8.8 (range 51-93) in PXG and 64.6 ± 8.3 (range 51-91) in controls. The percentages of homozygote individuals were 11.6, 10.9, 21.2%, and heterozygote individuals were 41.9, 45.7, 42.4% in patients with PXS, PXG and controls, respectively. There was no statistically significant difference between groups in terms of both genotype and allele frequencies of rs2107856 (p = 0.429 and p = 0.178, respectively). Retinal nerve fiber layer thickness did not differ between SNP-positive and SNP-negative individuals in PXG, and there was no significant difference between genotype and age, sex, best corrected visual acuity, intraocular pressure, central corneal thickness, cup/disk ratio and retinal nerve fiber layer thickness in any of the groups (p > 0.05).Conclusion: rs2107856 SNP of CNTNAP2 gene has no association with PXS and PXG in the evaluated Turkish population. [ABSTRACT FROM AUTHOR]

Abstract: In the modern drug discovery pipeline, identification of novel drug targets is a critical step. Despite rapid progress in developing biomedical techniques, it is still a great challenge to find promising new targets from the ample space of human genes. This fact is partially responsible for the situation of “more investments, fewer drugs” in the pharmaceutical industry. A series of recent researches revealed that successfully targeted genes share some common evolutionary and genetic features, which means that the knowledge accumulated in modern evolutionary biology and genetics is very helpful to identify potential drug targets and to find new drugs as well. In this article, we comprehensively summarize the links between human drug targets and genetic diseases and their evolutionary origins, with an attempt to introduce these novel concepts and their medical implications to the biomedical community. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate whole lysyl oxidase like 1 (LOXL1) gene by sequence analysis in Turkish patients with exfoliation glaucoma (XFG). A total of 48 (35 male, 13 female) patients with XFG were enrolled. Besides routine ophthalmological examination, peripapillary retinal nerve fibre layer (RNFL) analysis with optic coherence tomography was performed. Blood samples of 2 ml with EDTA were obtained and sent to Medical Genetics Department, Molecular Genetics Laboratory for LOXL1 polymorphism (PCR and agarose gel imaging) analysis. The role of the detected changes on disease severity was evaluated. No LOXL1 gene mutations in any of the patients were detected. Three types of single-nucleotide polymorphisms (SNPs) including R141L(rs1048661), A320A(rs41435250), and F184F were detected in 17 (35.3 %) patients. When compared, SNP-positive patients had thinner RNFL than SNP-negative patients (64.5 ± 17.6 and 66.1 ± 20.4 µ, respectively), and SNP-positive patients had higher cupping/disc ratio than SNP-negative patients (0.76 ± 0.2 and 0.70 ± 0.3, respectively). However, both values were not statistically significant ( p = 0.966 and p = 0.539, respectively). When compared, R141L-positive patients had significantly thinner cornea thickness (516.11 ± 30.3 µ) than R141L-negative patients (556.69 ± 27.2 µ) ( p = 0.004). There was not any statistical significant difference in the means of age, gender, BCVA, MD, PSD, IOP, number of hypotensive agents, and percent of glaucoma surgery ( p > 0.05). In this study group of Turkish population, no LOXL1 mutations were found. No associations between the defined SNPs (A320A, R141L and F184F) and the severity of the disease were detected. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. RA affects up to 1 % of the population worldwide. Currently, there are no drugs that can cure RA or achieve sustained remission. The unknown cause of the disease represents a significant challenge in the drug development. In this study, we address this challenge by proposing an alternative drug discovery approach that integrates and reasons over genetic interrelationships between RA and other genetic diseases as well as a large amount of higher-level drug treatment data. We first constructed a genetic disease network using disease genetics data from Genome-Wide Association Studies (GWAS). We developed a network-based ranking algorithm to prioritize diseases genetically-related to RA (RA-related diseases). We then developed a drug prioritization algorithm to reposition drugs from RA-related diseases to treat RA. Results: Our algorithm found 74 of the 80 FDA-approved RA drugs and ranked them highly (recall: 0.925, median ranking: 8.93 %), demonstrating the validity of our strategy. When compared to a study that used GWAS data to directly connect RA-associated genes to drug targets ("direct genetics-based" approach), our algorithm ("indirect genetics-based") achieved a comparable overall performance, but complementary precision and recall in retrospective validation (precision: 0.22, recall: 0.36; F1: 0.27 vs. precision: 0.74, recall: 0.16; F1: 0.28). Our approach performed significantly better in novel predictions when evaluated using 165 not-yet-FDA-approved RA drugs (precision: 0.46, recall: 0.50; F1: 0.47 vs. precision: 0.40, recall: 0.006; F1: 0.01). Conclusions: In summary, although the fundamental pathophysiological mechanisms remain uncharacterized, our proposed computation-based drug discovery approach to analyzing genetic and treatment interrelationships among thousands of diseases and drugs can facilitate the discovery of innovative drugs for treating RA. [ABSTRACT FROM AUTHOR]

Next-generation sequencing has challenged the consensus that predictive testing should not be performed on asymptomatic minors for conditions that are not medically actionable in childhood. While the available literature suggests that most parents want access to incidental findings discovered in genomic sequencing, there is little information regarding adolescents' views. This study's goal is to determine adolescent views regarding the disclosure of incidental findings for adult onset conditions that are not medically actionable in childhood. We conducted a cross-sectional survey of students enrolled in 7-12th grade science classes in three Cincinnati public schools. Most (235 of 282, 83%) students wanted access to non-actionable incidental findings. These participants most frequently (38%) endorsed future planning as the reason for disclosure. Seventy-two percent of students believed they should participate in the decision making process. Seventy-three percent of students believed that parents of children less than 12 years old should have access to this information. Adolescents want to have access to and participate in decisions about incidental findings. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Mendelian mutations are the most medically actionable variants in the human genome and have always played a central role in its functional annotation. Despite the relative ease with which Mendelian mutations are identified compared to other classes of variants, the pace of their discovery has until recently been slow. However, recent technological advances in genomic sequencing have made the prospect of identifying all genes that can harbor Mendelian mutations an achievable near-term goal. The many lessons learned from previous discoveries of Mendelian mutations should inform future studies as I will discuss in this review. Also discussed are some of the challenges that will gain more prominence as we approach the last phase of the effort to map all Mendelian genes. [ABSTRACT FROM AUTHOR]

Purpose:To evaluate the association of the lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) in a Spanish population with pseudoexfoliation syndrome (XFS) and pseudoexfoliation glaucoma (XFG). Materials and methods:The present case-control study included 100 Spanish patients (60 patients with XFS and 40 patients with XFG) and 90 control subjects. Genotypes of the three single nucleotide polymorphisms of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed with direct sequencing. Results:The G allele and the GG genotype of SNP rs3825942 were detected at a statistically higher frequency in pseudoexfoliation patients than in control subjects (p = 3.36 × 10−5, OR = 5.71, 95% CI: 2.30–14.18;p = 3.38 × 10−5, OR = 6.91, 95% CI: 2.51–19.03 respectively). The T allele and the TT genotype of SNP rs2165241 presented at significantly higher frequencies in pseudoexfoliation patients than in controls (p = 2.50 × 10−4, OR = 2.18, 95% CI: 1.43–3.33;p = 1.21 × 10−2, OR = 2.13, 95% CI: 1.75–3.85 respectively). No significant association between XFS/XFG and the rs1048661 was observed. The GGT haplotype composed of all three risk alleles was determined to be significantly associated with pseudoexfoliation. The genotypic and allelic distributions of the three SNPs were similar between XFS and XFG. Conclusions:This is the first study associating two SNPs of LOXL1 (rs3825942 and rs2165241) and XFS/XFG in a Spanish population, confirming findings in patients from Europe. However rs1048661 SNP did not show an association with XFS. [ABSTRACT FROM PUBLISHER]

Students choose to go to university for many reasons. They include those with disabilities and those without. The reasons why students with disabilities go to university and how these reasons impact university experience, including coping (academic resourcefulness), adapting, academic ability beliefs (academic self-efficacy), and grades, are investigated. Results show that unlike non-disabled peers, first-year students with disabilities who go to university for internal reasons (e.g. for the challenge, because they like learning) show higher academic resourcefulness and self-efficacy, and that those disabled students who choose to go to university in order to get a better job show higher academic self-efficacy. Upper-year students with disabilities less often choose to go to university for others and in order to get a better job than counterparts without disabilities. Upper-year students with disabilities less often choose to go to university for the university features (e.g. student services) than first-year students with disabilities. Upper-year students with disabilities choosing to go to university in order to delay responsibilities are less adapted, and those choosing to go for the reason of getting a better job have lower grades. Recommendations on strategies to increase student coping and self-efficacy and the need for qualitative research are made. [ABSTRACT FROM AUTHOR]

Background: Targeted next-generation sequencing (NGS) is a cost-effective approach for rapid and accurate detection of genetic mutations in patients with suspected genetic disorders, which can facilitate effective diagnosis. Methodology/Principal Findings: We designed a capture array to mainly capture all the coding sequence (CDS) of 2,181 genes associated with 561 Mendelian diseases and conducted NGS to detect mutations. The accuracy of NGS was 99.95%, which was obtained by comparing the genotypes of selected loci between our method and SNP Array in four samples from normal human adults. We also tested the stability of the method using a sample from normal human adults. The results showed that an average of 97.79% and 96.72% of single-nucleotide variants (SNVs) in the sample could be detected stably in a batch and different batches respectively. In addition, the method could detect various types of mutations. Some disease-causing mutations were detected in 69 clinical cases, including 62 SNVs, 14 insertions and deletions (Indels), 1 copy number variant (CNV), 1 microdeletion and 2 microduplications of chromosomes, of which 35 mutations were novel. Mutations were confirmed by Sanger sequencing or real-time polymerase chain reaction (PCR). Conclusions/Significance: Results of the evaluation showed that targeted NGS enabled to detect disease-causing mutations with high accuracy, stability, speed and throughput. Thus, the technology can be used for the clinical diagnosis of 561 Mendelian diseases. [ABSTRACT FROM AUTHOR]

Background: Disease genes cause or contribute genetically to the development of the most complex diseases. Drugs are the major approaches to treat the complex disease through interacting with their targets. Thus, drug targets are critical for treatment efficacy. However, the interrelationship between the disease genes and drug targets is not clear. Results: In this study, we comprehensively compared the network properties of disease genes and drug targets for five major disease categories (cancer, cardiovascular disease, immune system disease, metabolic disease, and nervous system disease). We first collected disease genes from genome-wide association studies (GWAS) for five disease categories and collected their corresponding drugs based on drugs' Anatomical Therapeutic Chemical (ATC) classification. Then, we obtained the drug targets for these five different disease categories. We found that, though the intersections between disease genes and drug targets were small, disease genes were significantly enriched in targets compared to their enrichment in human protein-coding genes. We further compared network properties of the proteins encoded by disease genes and drug targets in human protein-protein interaction networks (interactome). The results showed that the drug targets tended to have higher degree, higher betweenness, and lower clustering coefficient in cancer Furthermore, we observed a clear fraction increase of disease proteins or drug targets in the near neighborhood compared with the randomized genes. Conclusions: The study presents the first comprehensive comparison of the disease genes and drug targets in the context of interactome. The results provide some foundational network characteristics for further designing computational strategies to predict novel drug targets and drug repurposing. [ABSTRACT FROM AUTHOR]

Reaching the right destination is of vital importance for molecules, proteins, organelles, and cargoes. Thus, intracellular traffic is continuously controlled and regulated by several proteins taking part in the process. Viruses exploit this machinery, and viral proteins regulating intracellular transport have been identified as they represent valuable tools to understand and possibly direct molecules targeting and delivery. Deciphering the molecular features of viral proteins contributing to (or determining) this dynamic phenotype can eventually lead to a virus-independent approach to control cellular transport and delivery. From this virus-independent perspective we looked at US9, a virion component of Herpes Simplex Virus involved in anterograde transport of the virus inside neurons of the infected host. As the natural cargo of US9-related vesicles is the virus (or its parts), defining its autonomous, virus-independent role in vesicles transport represents a prerequisite to make US9 a valuable molecular tool to study and possibly direct cellular transport. To assess the extent of this autonomous role in vesicles transport, we analyzed US9 behavior in the absence of viral infection. Based on our studies, Us9 behavior appears similar in different cell types; however, as expected, the data we obtained in neurons best represent the virus-independent properties of US9. In these primary cells, transfected US9 mostly recapitulates the behavior of US9 expressed from the viral genome. Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and S34ES36) have no effect on protein incorporation on vesicles and on its localization on both proximal and distal regions of the cells. These results support the idea that, while US9 post-translational modification may be important to regulate cargo loading and, consequently, virion export and delivery, no additional viral functions are required for US9 role in intracellular transport. [ABSTRACT FROM AUTHOR]

Previous investigations conducted on post-secondary adult students with learning disabilities (LD) suggest that deficits in visual-motor skills contribute to difficulties in written expression which impact academic achievement. Intervention strategies for individuals with LD include assistive computer-based technologies (ATs) to compensate for or maximize performance. However, research fails to assess the impact of ATs on performance, learning, and motivation of students with LD. Also, one of the limitations of ATs is that they cannot be used for assessment and training and there are very few methods to assess or train visual-motor skills in this population. The present study explores the usefulness of a hapto-visual virtual reality motor skills assessment (MSA) device for visual-motor functioning in adults with and without LD. This is a preliminary step of developing an intervention to improve impaired visual-motor skills in adults with LD. A sample of 22 male and female university students with and without LD had their visual-motor skills pretested using a standard paper-and-pencil Bender-Gestalt (BG) test and were compared according to their performance on the MSA tool. We hypothesized that our LD participants' performance would be significantly lower than our control participants on the VR task in terms of number of errors and speed. Results showed that participants without LD performed better and more rapidly on the VR task than participants with LD. There were no correlations between the BG and MSA performance. We did not find significant differences between the groups on the Bender-Gestalt scores, previous experience with video game, arousal, and mood. Our results suggest that a novel 3D virtual reality tool such as the MSA can potentially discriminate motor function of people with and without LD; however, the difference between both may also be due to a lack of problem-solving ability in LD. [ABSTRACT FROM AUTHOR]

A series of non-precious metal electrocatalysts, namely pyrolyzed carbon-supported cobalt-polypyrrole, Co-PPy-TsOH/C, are synthesized with various cobalt precursors, including cobalt acetate, cobalt nitrate, cobalt oxalate, and cobalt chloride. The catalytic performance towards oxygen reduction reaction (ORR) is comparatively investigated with electrochemical techniques of cyclic voltammogram, rotating disk electrode and rotating ring-disk electrode. The results are analyzed and discussed employing physiochemical techniques of X-ray diffraction, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, elemental analysis, and extended X-ray absorption fine structure. It shows that the cobalt precursor plays an essential role on the synthesis process as well as microstructure and performance of the Co-PPy-TsOH/C catalysts towards ORR. Among the studied Co-PPy-TsOH/C catalysts, that prepared with cobalt acetate exhibits the best ORR performance. The crystallite/particle size of cobalt and its distribution as well as the graphitization degree of carbon in the catalyst greatly affects the catalytic performance of Co-PPy-TsOH/C towards ORR. Metallic cobalt is the main component in the active site in Co-PPy-TsOH/C for catalyzing ORR, but some other elements such as nitrogen are probably involved, too. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the 'infection-inflammation-exacerbation' axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

There are long-standing concerns over low fertility levels in Europe and an increasingly important debate on the extent to which migration can compensate for below-replacement fertility. To inform this debate, a wide array of indicators have been developed to assess the joint influence of fertility, mortality, and migration on birth replacement and intergenerational replacement. These indicators are based on various models and assumptions and some are particularly data demanding. In this article we propose a simple method to assess how far migration alters the extent of replacement for a birth cohort as it ages. We term the measure the overall replacement ratio (ORR). It is calculated by taking the size of a female birth cohort at selected ages divided by the average size of the cohorts of mothers in the year of birth. We present estimates of the ORR for a range of European countries representing different replacement regimes. We demonstrate that for many countries net migration has become a key factor in their population trends during the last few decades. [ABSTRACT FROM AUTHOR]

A theoretical model, based on linear stability analysis, is proposed to predict the onset of natural convection in lakes and reservoirs due to night time cooling. To such purpose, the system was modelled as a initially quiescent deep Boussinesq fluid reservoir, whose upper boundary temperature changes sinusoidally. From scaling analysis, it is found that critical onset times for convection are proportional to R, where R is a Rayleigh number including fluid properties and forcing frequency. The proportionality constant was found, from the solution of an eigenvalue problem, as a function of the Prandtl number. The onset time for convection was easily observed from experiments and quantitatively detected as a rapid increase of the RMS of the computed velocity field obtained using PIV. In this controlled conditions, differences close to 10% between predicted and observed times for the start of the convective flow was found. It is apparent from the present set of results that predictions are reasonable. [ABSTRACT FROM AUTHOR]