bluuebunny/crossref_metadata_2025 huggingface dataset:
Localised MPF regulation in eggs
Authors: Beckhelling Clare , Pérez‐Mongiovi Daniel , Houliston Evelyn
Published: July 2002

In this review we discuss the evidence that activation and inactivation of M‐phase promoting factor (MPF), the universal mitotic activator, are regulated locally within the cell, and consider the mechanisms that might be responsible. Localised initiation of MPF activation has been demonstrated in Xenopus eggs and egg fragments by examination of the timing of surface contraction waves (SCWs), indicators of MPF activity, and confirmed by direct measurement of MPF in such fragments. Both the timing and the site of SCW initiation relate to the presence of nuclei and of associated centriole‐nucleated microtubules. Localised MPF activation is likely to occur in the perinuclear cytoplasm as well as within the nucleus. Studies in a number of cell types show that the perinuclear/centrosomal region is the site of accumulation of MPF itself (the cyclin B‐Cdc2 kinase complex) and of many of its molecular regulators. It also harbours calcium‐regulating machinery, and in sea urchin eggs is the site of transient calcium release at the onset of mitosis. During mitosis MPF, regulatory molecules and calcium signalling components associate with spindle structures. Inactivation of MPF to end mitosis has been shown to be initiated locally at the mitoic spindle in Drosophila embryos. In sea urchin and frog eggs, calcium transients are required for both mitotic entry and exit and in mouse eggs, MPF inactivation requires both a calcium signal and an intact spindle. It thus appears that calcium signals coinciding with localised accumulation of MPF regulators are required first to set off and/or amplify the MPF activation process around the nucleus, and later to promote MPF inactivation via cyclin B destruction. Calcium release from sequestering machinery organised around nuclear and astral structures may act co‐operatively with localised MPF regulatory molecules to trigger both mitotic entry and exit.
Essential fatty acids and the brain: possible health implications
Authors: Youdim Kuresh A. , Martin Antonio , Joseph James A.
Published: July 2002

Linoleic andα‐linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions affecting membrane fluidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs reflect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n‐6 and n‐3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit.
The wealth effects of shareholder‐sponsored proposals
Authors: Forjan James M.
Published: July 2002

Shareholder‐sponsored proposals represent direct attempts to improve the operating and governance performance of publicly held corporations. This study examines the different types of shareholder proposals to determine their impact on value. While some recent studies show positive wealth effects for small or specific samples associated with shareholder proposal announcements or no wealth effects at all, this study documents significant negative abnormal returns for a large sample of firms. The results of previous studies suggest that shareholder proposals are beneficial to shareholders, and this study shows that to be true for only a fraction of them. Although management opposes the overwhelming majority of shareholder proposals, there are rare instances in which they either support the proposal and negotiate a settlement or in which the proposal receives enough support at the annual meeting to pass. This study documents positive abnormal returns for these cases.
New evidence on the impact of size and taxation on the seasonality of UK equity returns
Authors: Menyah Kojo
Published: July 2002

The paper investigates the extent to which capital gains taxation and the portfolio rebalancing hypothesis may account for the seasonality of UK equity returns. The empirical results show that in small firm portfolios during the period of capital gains taxation, April but not January seasonality is consistent with the tax‐loss selling hypothesis. The January seasonality, which is detected even before the introduction of capital gains taxation, is also consistent with the portfolio rebalancing hypothesis until the 1980s, when such seasonality becomes increasingly insignificant.
Is the prognosis of heart failure improving?
Authors: Cleland John G.F. , Gemmell Islay , Khand Aleem , Boddy Andrew
Published: July 2002

Background and Methods.

Heart failure is common and effective therapy exists but as yet there is little evidence that the overall prognosis is improving in clinical practice. We sought to determine if mortality, re‐admission with heart failure and re‐admission for any cause, had changed between cohorts of first‐time admissions for heart failure identified in 1984, 1988 and 1992 using linked hospital discharge and mortality data from Scotland (population approximately 5 million).

Findings.

The number of first‐time admissions for heart failure increased by 30% between 1984 and 1992, from 9716 to 12640. Their mean age was 74 years and 54% were women. Over the same period 3‐year mortality declined in patients < 65 years from 53 to 41% (reduction in risk 12% (95% confidence interval 9–15%. Log‐rank 70.0;P< 0.001) and for patients ≥ 65 years from 71% to 66% (reduction in risk 5% (95% confidence interval 3–6%. Log‐rank 74.5;P< 0.0001). Time to death or first re‐admission with heart failure also improved but not time to death or first re‐admission for any cause. The total number of re‐admissions increased between 1984 and 1992 but bed‐days occupancy for heart failure and for any cause, adjusted for days alive, declined due to a reduction in length of stay.

Interpretation.

These data suggest that the prognosis of patients with a first admission for heart failure is improving. The timing of improvement coincides with the gradual increase in the use of angiotensin converting enzyme inhibitors for heart failure although a causal link cannot be proved from these data.
Being a modern pharmaceutical company: New paradigms for the pharmaceutical industry*
Authors: Hassan Fred
Published: July 2002

Clinical Pharmacology & Therapeutics (2001) 69, 281–285; doi: 10.1067/mcp.2001.115450
The high‐resolution X‐ray structure of vinca‐domain inhibitors of microtubules provides a rational approach for drug design
Authors: Chengyong Wu , Jinghong Xian , Yanyan Wang , Qing‐Jie Xiao , Lingling Ma , Yuyan Li , Hai Chen , Qian Lei , Quan Zhang , Bo Sun , Yuxi Wang
Published: November 2020

Tubulin vinca‐domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance and toxicities, development of novel vinca‐domain ligands is still needed. In this study, we determined the high‐resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5 Å. Additionally, we recapitulated all previously published high‐resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca‐domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt‐bridge and H‐bond interactions with Asp179β1 and Asn329α2. Our studies provided the structural basis for designing novel tubulin vinca‐domain ligands.
How to make better use of scientific knowledge for cancer prevention
Authors: Puska Pekka
Published: November 2020

Cancer prevention research has produced profound scientific knowledge that has led to the development of several evidence‐based prevention strategies. But do these research outcomes lead to preventive action in real life? Many factors contribute to the so‐called ‘implementation gap’ between prevention recommendations and their application and adherence, including individual actions and behaviour, health service structures and political actions. This article discusses factors underlying the implementation gap in both clinical‐ and population‐based prevention. Understanding how these factors contribute to the implementation gap is important for planning successful cancer prevention strategies, as well as generally achieving disease prevention.
Circulating platelets as liquid biopsy sources for cancer detection
Authors: Antunes‐Ferreira Mafalda , Koppers‐Lalic Danijela , Würdinger Thomas
Published: November 2020

Nucleic acids and proteins are shed into the bloodstream by tumor cells and can be exploited as biomarkers for the detection of cancer. In addition, cancer detection biomarkers can also be nontumor‐derived, having their origin in other organs and cell types. Hence, liquid biopsies provide a source of direct tumor cell‐derived biomolecules and indirect nontumor‐derived surrogate markers that circulate in body fluids or are taken up by circulating peripheral blood cells. The capacity of platelets to take up proteins and nucleic acids and alter their megakaryocyte‐derived transcripts and proteins in response to external signals makes them one of the richest liquid biopsy biosources. Platelets are the second most abundant cell type in peripheral blood and are routinely isolated through well‐established and fast methods in clinical diagnostics but their value as a source of cancer biomarkers is relatively recent. Platelets do not have a nucleus but have a functional spliceosome and protein translation machinery, to process RNA transcripts. Platelets emerge as important repositories of potential cancer biomarkers, including several types of RNAs (mRNA, miRNA, circRNA, lncRNA, and mitochondrial RNA) and proteins, and several preclinical studies have highlighted their potential as a liquid biopsy source for detecting various types and stages of cancer. Here, we address the usability of platelets as a liquid biopsy for the detection of cancer. We describe several studies that support the use of platelet biomarkers in cancer diagnostics and discuss what is still lacking for their implementation into the clinic.
Research finds new evidence of benefit from reduced drinking in AUD patients
Authors: Enos Gary
Published: November 2020

Mounting research evidence is suggesting that a considerable number of individuals with an alcohol use disorder (AUD) can achieve improved health and functioning with drinking reductions that fall short of total abstinence.
NY Medicaid IG is shutting down OTPs for paperwork problems
Authors: Knopf Alison
Published: November 2020

In the midst of an opioid epidemic, opioid treatment programs (OTPs) are being hit with a pre‐COVID‐19 audit by the New York State Office of the Medicaid Inspector General (OMIG). The first victim was Mount Sinai Beth Israel on New York City's Lower East Side. This program, incidentally, was run by the late methadone champion Bob Newman. After being hit with more than $7 million in fines, the Beth Israel OTP shut down, and its 1,500 patients are being placed in OTPs around the city.
Interfacial Potassium‐Guided Grain Growth for Efficient Deep‐Blue Perovskite Light‐Emitting Diodes
Authors: Shen Yang , Shen Kong‐Chao , Li Yan‐Qing , Guo Minglei , Wang Jingkun , Ye Yongchun , Xie Feng‐Ming , Ren Hao , Gao Xingyu , Song Fei , Tang Jian‐Xin
Published: November 2020

Perovskite light‐emitting diodes (PeLEDs) are emerging candidates for the applications of solution‐processed full‐color displays. However, the device performance of deep‐blue PeLED still lags far behind that of their red and green counterparts, which is largely limited by low external quantum efficiency (EQE) and poor operational stability. Here, a facile and reliable crystallization strategy for perovskite grains is proposed, with improved deep‐blue emission through rational interfacial engineering. By modifying the substrate with potassium cation (K+) as the supplier of heterogeneous nucleation seeds, the interfacial K+‐guided grain growth is realized for well‐packed perovskite assemblies with high surface coverage and the controlled crystal orientation, leading to the enhanced radiative recombination and hole‐transport capabilities. Synergistical boost in device performance is achieved for deep‐blue PeLEDs emitting at 469 nm with a peak EQE of 4.14%, a maximum luminance of 451 cd m–2, and spectrally stable color coordinates of (0.125, 0.076) that matches well with the National Television System Committee (NTSC) standard blue.
Revealing the Double‐Edged Behaviors of Heteroatom Sulfur in Carbonaceous Materials for Balancing K‐Storage Capacity and Stability
Authors: Qian Yong , Li Yang , Yi Zheng , Zhou Jie , Pan Zhen , Tian Jie , Wang Yusong , Sun Shanshan , Lin Ning , Qian Yitai
Published: November 2020

Heteroatoms in the carbon matrix are generally considered as active sites to enhance potassium storage capacity, while their adverse effects on ion batteries remain unclear. Herein, a series of sulfur doped carbon (SCDPx) with adjustable S content and crystallinity are accurately synthesized in the closed autoclave by controlling the ratios of precursors. Electrochemical measurements exhibit that heteroatom sulfur displays double‐edged electrochemical activities with a high initial potassium storage capacity but poor cycling stability for carbon anode. Combined with solid‐state nuclear magnetic resonance (NMR), catalytic tests, and various ex‐situ characterizations, it is demonstrated that abundant S in the carbon would not only form CSC bonds, acting as active sites to reversibly adsorb/desorb potassium ions for high capacity, but also significantly catalyze the reduction and decomposition of the electrolyte including KPF6 and ethylene carbonate/diethyl carbonate (EC/DEC) to form thicker solid electrolyte interface (SEI) and degrade electrolyte, resulting in rapid capacity decay. As a result, the optimized sample (SCDP2) with the appropriate sulfur doping content exhibits the best electrochemical performance with high capacity (688.4 mA h g−1 at 100 mA g−1), long‐term cycling stability (198.4 mA h g−1 at 2000 mA g−1 after 10 000 cycles), and excellent rate capability (238.8 mA h g−1 at 5000 mA g−1).
3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks
Authors: Hull Sarah M. , Lindsay Christopher D. , Brunel Lucia G. , Shiwarski Daniel J. , Tashman Joshua W. , Roth Julien G. , Myung David , Feinberg Adam W. , Heilshorn Sarah C.
Published: November 2020

Three‐dimensional (3D) bioprinting is a promising technology to produce tissue‐like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, a versatile bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers is developed. This family of materials is termed UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin‐like protein (ELP), and polyethylene glycol (PEG) are each used as backbone polymers to create inks with storage moduli spanning from 200 to 10 000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix‐adherent human corneal mesenchymal stromal cells and non‐matrix‐adherent human induced pluripotent stem cell‐derived neural progenitor spheroids are printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.
Bio‐Inspired Ionic Skin for Theranostics
Authors: Lei Zhouyue , Zhu Wencheng , Zhang Xingcai , Wang Xiongjun , Wu Peiyi
Published: November 2020

The first‐generation ionic skins demonstrate great advantages in the tunable mechanical properties, high transparency, ionic conductivities, and multiple sensory capacities. However, little attention is paid to the interfacial interactions among the ambient environment, natural organisms, and the artificial skins. In particularly, current ionic skins based on traditional synthetic hydrogels suffer from dehydration in vitro and lack of substance communication channels with biological tissues. Herein, this work develops a bio‐inspired hydrogel to address these key challenges. The hydrogel is designed with natural moisturizing factors to lock water, biomineral ions to transmit signals, and biomimetic gradient channels to transport substances from non‐living to living interfaces. It is stable in ambient condition, adhesive and hydrated on mammal skins, and capable of non‐invasive point‐to‐point theranostics. This theranostic ionic skin realizes sensitive detection, enhanced treatment efficacy, and reduced side effects toward major diseases in vitro. It will shed light on the hydrogel bioelectronics with excellent biocompatibility, bio‐protection, and bio‐integration for human–machine interfaces and intelligent theranostics.
Recent Advances in the Design and Sensing Applications of Hemin/Coordination Polymer‐Based Nanocomposites
Authors: Alsharabasy Amir M. , Pandit Abhay , Farràs Pau
Published: November 2020

The fabrication of biomimetic catalysts as substituents for enzymes is of critical interest in the field due to the problems associated with the extraction, purification, and storage of enzymes in sensing applications. Of these mimetics, hemin/coordination polymer‐based nanocomposites, mainly hemin/metal–organic frameworks (MOF), have been developed for various biosensing applications because of the unique properties of each component, while trying to mimic the normal biological functions of heme within the protein milieu of enzymes. This critical review first discusses the different catalytic functions of heme in the body in the form of enzyme/protein structures. The properties of hemin dimerization are then elucidated with the supposed models of hemin oxidation. After that, the progress in the fabrication of hemin/MOF nanocomposites for the sensing of diverse biological molecules is discussed. Finally, the challenges in developing this type of composites are examined as well as possible proposals for future directions to enhance the sensing performance in this field further.
MXenes for Rechargeable Batteries Beyond the Lithium‐Ion
Authors: Ming Fangwang , Liang Hanfeng , Huang Gang , Bayhan Zahra , Alshareef Husam N.
Published: November 2020

Research on next‐generation battery technologies (beyond Li‐ion batteries, or LIBs) has been accelerating over the past few years. A key challenge for these emerging batteries has been the lack of suitable electrode materials, which severely limits their further developments. MXenes, a new class of 2D transition metal carbides, carbonitrides, and nitrides, are proposed as electrode materials for these emerging batteries due to several desirable attributes. These attributes include large and tunable interlayer spaces, excellent hydrophilicity, extraordinary conductivity, compositional diversity, and abundant surface chemistries, making MXenes promising not only as electrode materials but also as other components in the cells of emerging batteries. Herein, an overview and assessment of the utilization of MXenes in rechargeable batteries beyond LIBs, including alkali‐ion (e.g., Na+, K+) storage, multivalent‐ion (e.g., Mg2+, Zn2+, and Al3+) storage, and metal batteries are presented. In particular, the synthetic strategies and properties of MXenes that enable MXenes to play various roles as electrodes, metal anode protective layers, sulfur hosts, separator modification layers, and conductive additives in these emerging batteries are discussed. Moreover, a perspective on promising future research directions on MXenes and MXene‐based materials, ranging from material design and processing, fundamental understanding of the reaction mechanisms, to device performance optimization strategies is provided.
Polarized Stimulated Emission of 2D Ensembles of Plasmonic Nanolasers
Authors: Toropov Nikita , Kamalieva Aisylu , Starovoytov Anton , Zaki Sajid , Vartanyan Tigran
Published: November 2020

Plasmonic nanolasers produce coherent light with wavelengths on a scale similar to their own or larger. In the past decade they have attracted intense interest, particularly from the emerging areas of integrated photonic circuits and biomedicine. Despite these capabilities, plasmonic nanolasers are still not completely understood, and this lack of understanding leads to confusing them with spasers and random lasers. Herein, the operation of pure spaser‐based plasmonic nanolaser arrays is presented. For this, a monolayer of silver nanoparticles (NPs) affixed to a dielectric surface and covered with a fluorescent polymethyl methacrylate (PMMA)–coumarin solid composite is investigated. The input–output characteristic measured for the composites on a bare substrate (without Ag NPs) reveals that the emission at pump pulse energies above 2.4 mJ (at 355 nm excitation wavelength) stops growing, and instead is inhibited by saturation. In contrast, in such structures with Ag NPs an additional emission band pops up over a fluorescence background. It has a spectral width order of units of nanometers and its intensity grows faster than at lower pump pulse energies, revealing a nonlinear dependence of the input–output characteristic. The spaser‐based lasing observed is completely linearly polarized and clearly directed as 45° from the substrate.
Phosphine Oxides Manipulate Aggregation‐Induced Delayed Fluorescence for Time‐Resolved Bioimaging
Authors: Zhao Bingjie , Wang Huiqin , Xie Mingjuan , Han Chunmiao , Yang Huiran , Zhao Weili , Zhao Qiang , Xu Hui
Published: November 2020

Delayed fluorescence (DF) materials have shown great potential in time‐resolved luminescence imaging (TRLI), due to the relatively elongated emission lifetimes. However, the sensitivity of DF to environmental quenching leads to a challenge to realize TRLI directly using pure thermally‐activated DF (TADF) molecules. Herein, two TADF molecules, namely CzPOTCF and tBCzPOTCF, are designed and synthesized, featuring a diphenylphosphine oxide (DPPO) group substituted at the ortho‐position of the carbazole group. Compared with DPPO‐free CzTCF, the steric hindrance of DPPO groups enlarges dihedral angles between TCF and the carbazole groups in CzPOTCF and tBCzPOTCF; meanwhile, PO provides other channels for forming intermolecular hydrogen bonds. The optimized intermolecular interactions facilitate the dimer formation of CzPOTCF and tBCzPOTCF, which simultaneously enhance aggregation‐induced DF and mitigate disordered packing‐induced quenching. As a consequence, CzPOTCF and tBCzPOTCF show the enhanced aggregation‐induced DF with largely increased lifetimes. Without any additional assistance, the long‐lived fluorescence of CzPOTCF and tBCzPOTCF is successfully observed for cell TRLI, with 1–1.7 μs elongated average lifetimes of 6.69 and 7.41 μs, respectively.
Roles of Organic Molecules in Inorganic CsPbX3 Perovskite Solar Cells
Authors: Wang Hailiang , Dong Zijing , Liu Huicong , Li Weiping , Zhu Liqun , Chen Haining
Published: November 2020

Over 25% efficiencies have been achieved by organic–inorganic hybrid perovskite solar cells (PSCs). However, their practical applications are limited by the instability of the hybrid perovskite materials. Replacing hybrid perovskites with inorganic CsPbX3 perovskites shows great promise to address the above issue and much progress has been made. To achieve high efficiency and stable inorganic CsPbX3 PSCs, organic molecular engineering has been playing a vital role. Herein, the progress of the organic molecular engineering in inorganic CsPbX3 PSCs is systematically reviewed. First, structure evolution induced by organic molecular engineering for inorganic CsPbX3 perovskites is demonstrated. Then, organic molecular engineering in CsPbX3 PSCs is categorized and reviewed (alloying in perovskite structures, as sacrificial agents, forming 2D structures, and modifying surfaces and interfaces). Finally, future research directions are suggested to further improve the performance of inorganic PSCs.
Faculty Sim: Implementation of an Innovative, Simulation‐based Continuing Professional Development Curriculum for Academic Emergency Physicians
Authors: Mastoras George N. , Cheung Warren J. , Krywenky Ashley , Addleman Sarah , Weitzman Brian , Frank Jason R.
Published: November 2020

Background

Maintaining and enhancing competence in the breadth of emergency medicine (EM) is an ongoing challenge. In particular, resuscitative care in EM involves high‐risk clinical encounters that demand strong procedural skills, effective team leadership, and up‐to‐date clinical knowledge. Simulation‐based medical education is an effective modality for enhancing technical and nontechnical skills in crisis situations and has been effectively embedded in undergraduate and postgraduate medical curricula worldwide. To our knowledge, there are few existing systematic department‐wide simulation programs to address continuing professional development (CPD) for practicing academic EM faculty.

Development Process

We developed our novel, simulation‐based CPD program following Kern’s six‐step model. Based on the results of a multimodal needs assessment, a longitudinal curriculum was mapped and tailored to the available resources. Institutional support was provided in the form of a departmental grant to fund a physician program lead, monthly session instructors, and operating costs.

Outcomes

CPD simulation sessions commenced in January 2017. Our needs assessment identified two key types of educational needs: 1) crisis resource management skills and 2) frequent practice of high‐stakes critical care procedures (e.g., surgical airways). Simulation sessions involve two high‐fidelity simulated resuscitations and one skills lab per day. To date, 21 sessions have been delivered, reaching 161 practicing EPs. Feedback from our faculty has been positive.

Reflective Discussion

We have successfully introduced a curriculum of monthly simulation‐based CPD based on the educational needs of our EPs. Future work will include more detailed program evaluation linked to clinical outcomes and program expansion to support nearby institutions.
COFS type 3 in an Indian family with antenatally detected arthrogryposis
Authors: Panigrahi Inusha , Shankar Prasad Bangalore Anantharamu , Kaur Harleen , Kalra Jasvinder
Published: November 2020

Fetal akinesia and contractures can be caused by mutations in various genes that lead to overlapping phenotypes with contractures, rocker bottom feet, cerebellar hypoplasia, ventriculomegaly, growth retardation, pulmonary hypoplasia, cystic hygroma and cleft palate in various combinations. Cerebro‐oculo‐facio‐skeletal (COFS) syndrome is a condition resulting from defects in DNA repair pathway, and genes involved include ERCC1 (COFS), ERCC2 (XPD), ERCC5(XPG), and ERCC6 (CSB). It is a severe disorder presenting in fetal or neonatal period with microcephaly, arthrogryposis, prominent nose, and kyphoscoliosis, and leads to early death in childhood. We report a baby with antenatally identified arthrogryposis in which the homozygous pathogenic variant in exon 8 was identified in ERCC5 gene, by targeted next generation sequencing. This was predicted to cause premature chain termination in the protein. ERCC5 gene is mainly implicated in xeroderma pigmentosum, sometimes in COFS syndrome.
An international telemedicine program for diagnosis of genetic disorders: Partnership of pediatrician and geneticist
Authors: Mena Rafael , Mendoza Esperanza , Gomez Peña Maria , Valencia C. Alexander , Ullah Ehsan , Hufnagel Robert B. , Prada Carlos E.
Published: November 2020

There is a shortage of genetics providers worldwide and access is limited to large academic centers. Telemedicine programs can facilitate access to genetic services to patients living in remote locations. The goal of this study was to improve access to genetic services in the Dominican Republic by creating a partnership model between a pediatrician and geneticist. This approach has been used within the United States but not in the setting of two different countries, healthcare system, and cultures. Patients were referred to the Centro de Obstetricia y Ginecologia program if a syndromic or genetic etiology was suspected by their local provider. Pediatrician first evaluated all patients prior to telemedicine appointment to review family and medical history. All genetic visits were scheduled within 2 weeks of referral in collaboration with telehealth program at Cincinnati Children's Hospital Medical Center. A total of 66 individuals were evaluated during a period of 5 years. Fifty‐seven individuals underwent genetic studies, and a molecular diagnosis was made in 39 individuals. Exome sequencing was the most common first line test when differential diagnosis was broad (n = 40). The most common inheritance was autosomal recessive in 15 individuals, followed by 13 individuals with autosomal dominant disorders, 7 individuals X‐linked disorders, and 4 individuals with chromosomal abnormalities. This study provides data to support utility of geneticist and pediatrician partnership to provide outreach telemedicine diagnostics and management services for rare diseases in an international setting.
Skeletal dysplasias in Latin America
Authors: Cavalcanti Denise P. , Fano Virginia , Mellado Cecilia , Lacarrubba‐Flores Maria Dora J. , Silveira Cynthia , Silveira Karina C. , del Pino Mariana , Moresco Angelica , Caino Silvia , Ramos Mejía Rosario , García Cristián J. , Lay‐Son Guillermo , Ferreira Carlos R.
Published: November 2020

Skeletal dysplasias (SD) are disturbances in growth due to defects intrinsic to the bone and/or cartilage, usually affecting multiple bones and having a progressive character. In this article, we review the state of clinical and research SD resources available in Latin America, including three specific countries (Brazil, Argentina, and Chile), that have established multidisciplinary clinics for the care of these patients. From the epidemiological point of view, the SD prevalence of 3.2 per 10,000 births from nine South American countries included in the ECLAMC network represents the most accurate estimate not just in Latin America, but worldwide. In Brazil, there are currently five groups focused on SD. The data from one of these groups including the website www.ocd.med.br, created to assist in the diagnosis of SD, are highlighted showing that telemedicine for this purpose represents a good strategy for the region. The experience of more than 30 years of the SD multidisciplinary clinic in an Argentinian Hospital is presented, evidencing a solid experience mainly in the follow‐up of the most frequent SD, especially those belonging the FGFR3 group and OI. In Chile, a group with 20 years of experience presents its work with geneticists and pediatricians, focusing on diagnostic purposes and clinical management. Altogether, although SD health‐care and research activities in Latin America are in their early stages, the experience in these three countries seems promising and stimulating for the region as a whole.
Sexual assault law and community education: A case study of New South Wales, Australia
Authors: Mason Gail
Published: November 2020

The offence of sexual assault has been reformed significantly since the 1980s. These reforms have been designed to create a fairer criminal justice system and contribute to primary prevention through community education. Yet, how exactly does this education happen? This article draws on a qualitative interview study with government and non‐government stakeholders in the Australian State of NSW to consider how members of the public are equipped with the information they need to understand the laws that govern their sexual lives. Despite multiple educational pathways on key legal concepts such as consent, the study found a knowledge gap between the legal meaning of sexual assault and effective public access to that meaning. The article concludes with recommendations for addressing the barriers that undergird this gap. It argues that law’s educative promise depends on the state’s preparedness to create policy that fosters the public’s appreciation of the sexual standards embedded in legal rules.
Perfusion‐Dependent Cerebral Autoregulation Impairment in Hemispheric Stroke
Authors: Hecht Nils , Schrammel Max , Neumann Konrad , Müller Marc‐Michael , Dreier Jens P. , Vajkoczy Peter , Woitzik Johannes
Published: November 2020

Objective

Loss of cerebral autoregulation (CA) plays a key role in secondary neurologic injury. However, the regional distribution of CA impairment after acute cerebral injury remains unclear because, in clinical practice, CA is only assessed within a limited compartment. Here, we performed large‐scale regional mapping of cortical perfusion and CA in patients undergoing decompressive surgery for malignant hemispheric stroke.

Methods

In 24 patients, autoregulation over the affected hemisphere was calculated based on direct, 15 to 20‐minute cortical perfusion measurement with intraoperative laser speckle imaging and mean arterial blood pressure (MAP) recording. Cortical perfusion was normalized against noninfarcted tissue and 6 perfusion categories from 0% to >100% were defined. The interaction between cortical perfusion and MAP was estimated using a linear random slope model and Pearson correlation.

Results

Cortical perfusion and CA impairment were heterogeneously distributed across the entire hemisphere. The degree of CA impairment was significantly greater in areas with critical hypoperfusion (40–60%: 0.42% per mmHg and 60–80%: 0.46% per mmHg) than in noninfarcted (> 100%: 0.22% per mmHg) or infarcted (0–20%: 0.29% per mmHg) areas (*p< 0.001). Pearson correlation confirmed greater CA impairment at critically reduced perfusion (20–40%: r = 0.67; 40–60%: r = 0.68; and 60–80%: r = 0.68) compared to perfusion > 100% (r = 0.36; *p< 0.05). Tissue integrity had no impact on the degree of CA impairment.

Interpretation

In hemispheric stroke, CA is impaired across the entire hemisphere to a variable extent. Autoregulation impairment was greatest in hypoperfused and potentially viable tissue, suggesting that precise localization of such regions is essential for effective tailoring of perfusion pressure‐based treatment strategies. ANN NEUROL 2021;89:358–368
Short‐Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State
Authors: Kim Jiwon , Jang Hee Jeong , Schellingerhout Dawid , Lee Su‐Kyoung , Kim Ha , Kim Young Dae , Lee Kyung‐Yul , Choi Hye‐Yeon , Cho Han‐Jin , Jang Seong‐Soo , Jeon Sangmin , Kwon Ick Chan , Kim Kwangmeyung , Ryu Wi‐Sun , Nahrendorf Matthias , Choi Seungbum , Kim Dong‐Eog
Published: November 2020

Objective

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short‐term (1–3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.

Methods

Ten‐week‐old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate‐buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single‐dose aspirin. Thereafter, we induced FeCl3‐mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation‐related cerebral infarction in a large acute stroke cohort.

Results

We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single‐dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single‐dose aspirin pretreatment. In patients, short‐term (≤ 3 days) cessation of NOAC therapy, compared with longer‐term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity.

Interpretation

We provide the first preclinical evidence that a rebound prothrombotic state follows short‐term cessation of dabigatran therapy. ANN NEUROL 2021;89:444–458
Diagnostic Accuracy of Amyloid versus18F‐Fluorodeoxyglucose Positron Emission Tomography inAutopsy‐ConfirmedDementia
Authors: Lesman‐Segev Orit H. , La Joie Renaud , Iaccarino Leonardo , Lobach Iryna , Rosen Howard J. , Seo Sang Won , Janabi Mustafa , Baker Suzanne L. , Edwards Lauren , Pham Julie , Olichney John , Boxer Adam , Huang Eric , Gorno‐Tempini Marilu , DeCarli Charles , Hepker Mackenzie , Hwang Ji‐Hye L. , Miller Bruce L. , Spina Salvatore , Grinberg Lea T. , Seeley William W. , Jagust William J. , Rabinovici Gil D.
Published: November 2020

Objective

The purpose of this study was to compare the diagnostic accuracy of antemortem11C‐Pittsburgh compound B (PIB) and18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients.

Methods

One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information. PIB PET was rated as positive or negative for cortical retention, whereas FDG scans were read as showing an Alzheimer disease (AD) or non‐AD pattern. Neuropathological diagnoses were assigned using research criteria. Majority visual reads were compared to intermediate–high AD neuropathological change (ADNC).

Results

One hundred one participants were included (mean age = 67.2 years, 41 females, Mini‐Mental State Examination = 21.9, PET‐to‐autopsy interval = 4.4 years). At autopsy, 32 patients showed primary AD, 56 showed non‐AD neuropathology (primarily frontotemporal lobar degeneration [FTLD]), and 13 showed mixed AD/FTLD pathology. PIB showed higher sensitivity than FDG for detecting intermediate–high ADNC (96%, 95% confidence interval [CI] = 89–100% vs 80%, 95% CI = 68–92%,p= 0.02), but equivalent specificity (86%, 95% CI = 76–95% vs 84%, 95% CI = 74–93%,p= 0.80). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% (95% CI = 92–100%) and specificity was 98% (95% CI = 93–100%). Nine of 24 patients with incongruent reads were found to have co‐occurrence of AD and non‐AD pathologies.

Interpretation

In our sample enriched for younger onset cognitive impairment, PIB‐PET had higher sensitivity than FDG‐PET for intermediate–high ADNC, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, whereas mixed pathology should be considered when PIB and FDG are incongruent. ANN NEUROL 2021;89:389–401
Glucose Binding Drives Reconfiguration of a Dynamic Library of Urea‐Containing Metal–Organic Assemblies
Authors: Yang Dong , von Krbek Larissa K. S. , Yu Le , Ronson Tanya K. , Thoburn John D. , Carpenter John P. , Greenfield Jake L. , Howe Duncan J. , Wu Biao , Nitschke Jonathan R.
Published: November 2020

A bis‐urea‐functionalized ditopic subcomponent assembled with 2‐formylpyridine and FeII, resulting in a dynamic library of metal–organic assemblies: an irregular FeII4L6structure and three FeII2L3stereoisomers: left‐ and right‐handed helicates and ameso‐structure. This library reconfigured in response to the addition of monosaccharide derivatives, which served as guests for specific library members, and the rate of saccharide mutarotation was also enhanced by the library. The (P) enantiomer of the FeII2L3helical structure bound β‐D‐glucose selectively over α‐D‐glucose. As a consequence, the library collapsed into the (P)‐FeII2L3helicate following glucose addition. The α‐D‐glucose was likewise transformed into the β‐D‐anomer during equilibration and binding. Thus, β‐D‐glucose and (P)‐3amplified each other in the product mixture, as metal–organic and saccharide libraries geared together into a single equilibrating system.
Ternary Cobalt(II), Nickel(II), and Copper(II) complexes containing metformin and ethylenediamine: Synthesis, characterization, thermal, in vitro DNA binding, in silico molecular docking, and in vivo antihyperglycemic studies
Authors: Rajeshwari K. , Anantha Lakshmi P.V. , Archana J. , Sumakanth M.
Published: November 2020

Three new water soluble ternary metal complexes, [Co(metf)(en)2]Cl2(1), [Ni(metf)(en)2]Cl2(2), and [Cu(metf)(en)2]Cl2(3), (Metf = metformin, en = ethylenediamine), were synthesized and characterized, and pharmacodynamic evaluation was reported. From the spectral analysis, octahedral geometry was proposed to all the three metal complexes. The Kinetic parameters have been determined by thermogravimetric data using Coats‐Redfern method. The stability of the complexes was obtained from their molecular orbital structures from which the quantum chemical parameters were calculated using the highest occupied molecular orbital (HOMO)‐lowest unoccupied molecular orbital (LUMO) energies. The DNA binding studies of these complexes were explored by absorption, emission, and viscosity. Groove mode of surface binding of these complexes with DNA was explained by viscosity studies. Nuclease activity exhibited by these complexes on pUC19 DNA was experimented by agarose gel electrophoresis. Discovery Studio 2.1 software was used for docking studies of these complexes into B‐DNA sequence, 5′(D*AP*CP*CP*GP*AP*CP*GP*TP*CP*GP*GP*T)‐3′ retrieved from protein data bank (PDB ID: 423D). The maximum score is seen for complex 1. The antihyperglycemic activity of these complexes was studied in streptozotocin (STZ)‐diabetic rats. The substantial increase in the antihyperglycemic activity of the complexes is seen when compared with pure drug. The maximum antihyperglycemic activity is recorded for complex 1.
Optimization of the Mass Yield in the Biodiesel Production from Chicken Viscera Oil
Authors: Mazatto Amanda Caroline Fernandes , da Silva Geovane Aparecido Ramos , dos Santos Patricia Daniele Silva , Senes Carlos Eduardo Rubio , Visentainer Jesui Vergilio , Oliveira Santos Oscar
Published: November 2020

This work proposes the conversion of chicken viscera oil into biodiesel through the transesterification reaction using basic catalysis. For this, the properties of the raw material and the interferences of the variables on the mass yield of the chemical procedure were evaluated, such as reaction temperature (50–90 °C), catalyst concentration (0.5–2.5% m/m), oil: alcohol molar ratio (1:3 to 1:15) and reaction time (15–75 min).Through the execution of an experimental design procedure and subsequent application of the response surface methodology it was possible to maximize the yield of the transesterification reaction to 87.41% w/w, using the following experimental conditions: reaction temperature 70 °C, catalyst concentration 1% m/m, molar ratio 1:9, and reaction time 30 min. This result provides a reduction of 200% in the percentage of the catalyst used, 67% in the volume of alcohol, and 700% in the reaction time when compared to works using similar raw material published in the literature. Besides, the quality of the biodiesel produced was verified and is following the standards required by ASTM D6751 and EN 14214.
Camouflaging in Autism: Examining Sex‐Based and Compensatory Models in Social Cognition and Communication
Authors: Corbett Blythe A. , Schwartzman Jessica M. , Libsack Erin J. , Muscatello Rachael A. , Lerner Matthew D. , Simmons Grace L. , White Susan W.
Published: November 2020

Camouflaging refers to behavioral adaptations that individuals with autism spectrum disorder (ASD), especially females, use to mask symptoms during social situations. Compensation is a component of camouflaging in which an individual's observed behavior is considerably better than actual ability. The study explored diagnostic, sex‐based, and compensatory differences using the Contextual Assessment of Social Skills (CASS). The sample included 161 youth 10:0‐to‐16:11 years (115 males, 46 females). T‐tests were performed based on sex (female, male) or High (good ADOS + poor Theory of Mind (TOM)) compared to Low (poor ADOS + poor TOM) Compensation groups. Comparisons were examined for Social Affect (SA), Restricted Repetitive Behavior, (RRB), IQ, social behavior (Positive Affect, Overall Involvement) and communication (Vocal Expression, Gestures). Females exhibited fewer RRB t(158) = 3.05, P = 0.003, d = 0.54. For the CASS, females evidenced more Vocal Expressiveness t(157) = −2.03, P = 0.05, d = 0.35, which corroborates sex‐based differences in the literature. Compensation group differences indicated the High compared to Low group showed stronger Social and Communication behaviors on the CASS for Vocal Expression t(72) = 2.56, P = 0.01, d = 0.62, and overall rapport t(72) = 2.36, P = 0.02, d = 0.56. Several differences were observed when the groups were stratified based on level of compensation, with the High compensation participants showing stronger social engagement and communication behaviors. Findings may inform efforts to understand camouflaging, compensation, and clinical practices for male and female adolescents with ASD. A more nuanced consideration of camouflaging alongside compensation models reveals subtle differences in cognition, behavior, and affect that may reflect underlying profiles of challenge and strength in youth with ASD.

Lay Summary

Camouflaging refers to ways individuals with autism spectrum disorder (ASD), especially females, mask symptoms. Compensation occurs when a person's observed behavior appears more typical than what would be expected based on underlying ability and symptoms. The study explored camouflaging and compensation differences in 161 youth with ASD. Findings suggest sex‐based differences with females showing better vocal expression. However, several compensation differences were observed with the High compensators showing stronger social communication and rapport. A more nuanced consideration of camouflaging using compensation models reveal subtle differences in underlying challenge and strength.