bluuebunny/crossref_metadata_2025 huggingface dataset:
Further delineation of HIDEA syndrome
Authors: Maddirevula Sateesh , Ben‐Omran Tawfeg , AlMureikhi Mariam , Eyaid Wafa , Arabi Hisham , Alkuraya Hisham , Alfaifi Abdullah , Alfalah Abdullah Hamed , Alsaif Hessa S. , Abdulwahab Firdous , Alfadhel Majid , Alkuraya Fowzan S.
Published: September 2020

Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in P4HTM, which encodes an atypical member of the prolyl 4‐hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole‐exome sequencing (WES) revealed novel disease‐causing variants in P4HTM. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment/developmental delay, and hypotonia, which seem to be consistent findings. One patient only presented with hypotonia, developmental delay, and abnormal eye movements, which highlights the challenge in diagnosing milder cases with this new syndrome. Other notable features include mild facial dysmorphism, obesity, and brain dysmyelination and atrophy. We conclude that HIDEA is a highly variable syndrome and suspect that a large fraction of patients will be diagnosed via reverse phenotyping after recessive P4HTM variants are identified by agnostic genomic sequencing assays.
Roadmap to recovery: Reporting on a research taskforce supporting Indigenous responses to COVID‐19 in Australia
Authors: Moodie Nikki , Ward James , Dudgeon Patricia , Adams Karen , Altman Jon , Casey Dawn , Cripps Kyllie , Davis Megan , Derry Kate , Eades Sandra , Faulkner Samantha , Hunt Janet , Klein Elise , McDonnell Siobhan , Ring Ian , Sutherland Stewart , Yap Mandy
Published: September 2020

In April 2020 a Group of Eight Taskforce was convened, consisting of over 100 researchers, to provide independent, research‐based recommendations to the Commonwealth Government on a “Roadmap to Recovery” from COVID‐19. The report covered issues ranging from pandemic control and relaxation of social distancing measures, to well‐being and special considerations for vulnerable populations. Our work focused on the critical needs of Aboriginal and Torres Strait Islander communities; this paper presents an overview of our recommendations to the Roadmap report. In addressing the global challenges posed by pandemics for citizens around the world, Indigenous people are recognised as highly vulnerable. At the time of writing Australia's First Nations Peoples have been largely spared from COVID‐19 in comparison to other Indigenous populations globally. Our recommendations emphasise self‐determination and equitable needs‐based funding to support Indigenous communities to recover from COVID‐19, addressing persistent overcrowded housing, and a focus on workforce, especially for regional and remote communities. These latter two issues have been highlighted as major issues of risk for Indigenous communities in Australia It remains to be seen how governments across Australia take up these recommendations to support Indigenous peoples' health and healing journey through yet another, potentially catastrophic, health crisis.
Synchronous reversible cerebral vasoconstriction syndrome following thyrotoxicosis in a postpartum woman
Authors: Arakaki Daichi , Terasawa Teruhiko , Iwata Mitsunaga , Uenishi Norimichi
Published: September 2020

Background

Reversible cerebral vasoconstriction syndrome (RCVS) typically manifests with acute‐onset, recursive, severe headache that continues for a month; it rarely manifests as seizures. Development of RCVS following thyrotoxicosis has not been previously reported in detail.

Case Presentation

A 30‐year‐old postpartum woman with thyrotoxicosis developed a generalized seizure refractory to anticonvulsants. Magnetic resonance angiography demonstrated cerebral artery stenosis in the right anterior cerebral artery and the right middle cerebral artery. These findings were compatible with RCVS. Reversible cerebral vasoconstriction syndrome was treated successfully with i.v. nicardipine and conventional management was undertaken for thyrotoxicosis.

Conclusion

This is the first well‐documented case of a postpartum woman with synchronous RCVS following thyrotoxicosis. Reversible cerebral vasoconstriction syndrome and thyrotoxicosis can coincidentally occur in postpartum women and manifest with postpartum seizures.
Location and Size of Preterm Cerebellar Hemorrhage and Childhood Development
Authors: Garfinkle Jarred , Guo Ting , Synnes Anne , Chau Vann , Branson Helen M. , Ufkes Steven , Tam Emily W. Y. , Grunau Ruth E. , Miller Steven P.
Published: September 2020

Objective

To examine the association between cerebellar hemorrhage (CBH) size and location and preschool‐age neurodevelopment in very preterm neonates.

Methods

Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC‐2]), visuomotor integration (Beery‐Buktenica Developmental Test of Visual‐Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5‐year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome.

Results

Thirty‐six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC‐2 motor scores at 4.5 years (β = −0.095, 95% confidence interval = −0.184 to −0.005), with a standardized β coefficient (−0.16) that was similar to that of white matter injury volume (standardized β = −0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion‐symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes.

Interpretation

CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose‐dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095–1108
An Active‐Site Sulfonate Group Creates a Fast Water Oxidation Electrocatalyst That Exhibits High Activity in Acid
Authors: Nash Aaron G. , Breyer Colton J. , Vincenzini Brett D. , Elliott Gregory I. , Niklas Jens , Poluektov Oleg G. , Rheingold Arnold L. , Smith Diane K. , Musaev Djamaladdin G. , Grotjahn Douglas B.
Published: September 2020

The storage of solar energy in chemical bonds will depend on pH‐universal catalysts that are not only impervious to acid, but actually thrive in it. Whereas other homogeneous water oxidation catalysts are less active in acid, we report a catalyst that maintained high electrocatalytic turnover frequency at pH values as low as 1.1 and 0.43 (kcat=1501±608 s−1 and 831±254 s−1, respectively). Moreover, current densities, related to catalytic reaction rates, ranged from 15 to 50 mA cm−2 mM−1 comparable to those reported for state‐of‐the‐art heterogeneous catalysts and 30 to 100 times greater than those measured for two prominent literature homogeneous catalysts at pH 1.1 and 0.43. The catalyst also exhibited excellent durability when a chemical oxidant was used (CeIV, 7400 turnovers, TOF 0.88 s−1). Preliminary computational studies suggest that the unusual active‐site sulfonate group acts a proton relay even in strong acid, as intended.
Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s
Authors: Launay Kévin , Amalian Jean‐Arthur , Laurent Eline , Oswald Laurence , Al Ouahabi Abdelaziz , Burel Alexandre , Dufour Florent , Carapito Christine , Clément Jean‐Louis , Lutz Jean‐François , Charles Laurence , Gigmes Didier
Published: September 2020

A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub‐segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side‐products from the amide‐based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side‐reactions and enable automated MS/MS sequencing. Different styryl‐TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in‐chain benzyl ring, with no side‐reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS‐DECODER software, which interprets fragmentation data recorded for each sub‐segment and re‐align them in their original order based on location tags.
A Surface‐Strained and Geometry‐Tailored Nanoreactor that Promotes Ammonia Electrosynthesis
Authors: Li Panpan , Jin Zhaoyu , Fang Zhiwei , Yu Guihua
Published: September 2020

A surface‐strained and geometry‐optimized TiO2 nanoreactor enhances the performance of electrocatalytic nitrogen fixation. The nanotubular confinement allows spatial regulation of the mass transport of nitrogen during the NRR process and offers an enlarged surface area, thus boosting the ammonia production with high selectivity. Both experimental and theoretical evidence support strained Ti3+ sites, demonstrating a more favorable pathway for the N2 activation and selective NH3 production with a faster kinetic rate than the pristine TiO2. The TiO2‐based nanoreactor with surface and bulk structure tailoring delivered an NH3 yield rate up to 5.50 μg h−1 cm−2 (16.67 μg h−1 mgcat−1) and high faradaic efficiency of 26 % under ambient aqueous conditions. Our findings highlight the concept of lattice strain and geometry modified nanoreactors, which will have broad implications in the renewable energy catalysis and electrosynthesis of valuable products.
Direct Writing Large‐Area Multi‐Layer Ultrasmooth Films by an All‐Solution Process: Toward High‐Performance QLEDs
Authors: Zhang Min , Deng Huanhuan , Meng Lili , Wang Hongqin , Wang Yunjun , Liu Huan
Published: September 2020

With increasing the film area/layer, deteriorating in both smoothness and uniformity of thin‐films frequently happen, which remains a barrier for making large‐area quantum dot light‐emitting diodes (QLEDs) by solution processes. Here, we demonstrated a facile all‐solution process guided by the conical fiber array to write multi‐layer ultrasmooth thin‐films directly in centimeter scale. The side‐by‐side fibrous array helps to align surface tensions at the tri‐phase contact line to facilitate large‐area homogeneous deposition, which was verified by theoretical simulation. The Laplace pressure along individual conical fiber contributes to the steady liquid transfer. Thin‐films with small roughness (<2.03 nm) and large‐area (2×2 cm2) uniformity were prepared sequentially on the target substrate, leading to large‐area high‐performance QLEDs. The result offers new insights for fabricating large‐area high‐performance thin‐film devices.
Shear Stress‐Responsive Polymersome Nanoreactors Inspired by the Marine Bioluminescence of Dinoflagellates
Authors: Rifaie‐Graham Omar , Galensowske Nikolas F. B. , Dean Charlie , Pollard Jonas , Balog Sandor , Gouveia Micael G. , Chami Mohamed , Vian Antoine , Amstad Esther , Lattuada Marco , Bruns Nico
Published: September 2020

Some marine plankton called dinoflagellates emit light in response to the movement of surrounding water, resulting in a phenomenon called milky seas or sea sparkle. The underlying concept, a shear‐stress induced permeabilisation of biocatalytic reaction compartments, is transferred to polymer‐based nanoreactors. Amphiphilic block copolymers that carry nucleobases in their hydrophobic block are self‐assembled into polymersomes. The membrane of the vesicles can be transiently switched between an impermeable and a semipermeable state by shear forces occurring in flow or during turbulent mixing of polymersome dispersions. Nucleobase pairs in the hydrophobic leaflet separate when mechanical force is applied, exposing their hydrogen bonding motifs and therefore making the membrane less hydrophobic and more permeable for water soluble compounds. This polarity switch is used to release payload of the polymersomes on demand, and to activate biocatalytic reactions in the interior of the polymersomes.
NIR‐Sensitized Cationic and Hybrid Radical/Cationic Polymerization and Crosslinking
Authors: Pang Yulian , Shiraishi Atsushi , Keil Dietmar , Popov Sergey , Strehmel Veronika , Jiao Hongjun , Gutmann Jochen S. , Zou Yingquan , Strehmel Bernd
Published: September 2020

NIR‐sensitized cationic polymerization proceeded with good efficiency, as was demonstrated with epoxides, vinyl ether, and oxetane. A heptacyanine functioned as sensitizer while iodonium salt served as coinitiator. The anion adopts a special function in a series selected from fluorinated phosphates (a: [PF6]−, b: [PF3(C2F5)3]−, c: [PF3(n‐C4F9)3]−), aluminates (d: [Al(O‐t‐C4F9)4]−, e: [Al(O(C3F6)CH3)4]−), and methide [C(O‐SO2CF3)3]− (f). Vinyl ether showed the best cationic polymerization efficiency followed by oxetanes and oxiranes. DFT calculations provided a rough pattern regarding the electrostatic potential of each anion where d showed a better reactivity than e and b. Formation of interpenetrating polymer networks (IPNs) using trimethylpropane triacrylate and epoxides proceeded in the case of NIR‐sensitized polymerization where anion d served as counter ion in the initiator system. No IPN was formed by UV‐LED initiation using the same monomers but thioxanthone/iodonium salt as photoinitiator. Exposure was carried out with new NIR‐LED devices emitting at either 805 or 870 nm.
Development of a multiclass method to quantify phthalates, pharmaceuticals, and personal care products in river water using ultra‐high performance liquid chromatography coupled with quadrupole hybrid Orbitrap mass spectrometry
Authors: Rendedula Deviprasad , Satyanarayana Gubbala Naga Venkata , Asati Ankita , Kaliyaperumal Muralidharan , Mudiam Mohana Krishna Reddy
Published: September 2020

Rationale

The organic micropollutants such as phthalates, pharmaceuticals, and personal care products (PPPCPs) enter the surface water through various routes. The aim of this study is to develop a sensitive and efficient method to identify and quantify 26 PPPCPs found in river water with acceptable accuracy and precision using a liquid chromatograph hyphenated with quadrupole hybrid Orbitrap mass spectrometry (Q‐Orbitrap‐MS) in a single chromatographic run.

Method

The organic micropollutants were extracted from river water by solid‐phase extraction (SPE) using hydrophilic‐lipophilic balance sorbent and analyzed using an ultra‐high performance liquid chromatograph (UHPLC) equipped with C18 stationary phase for chromatographic separation. The targeted mass experiments were conducted in a Q‐Orbitrap‐MS system in positive and negative electrospray ionization mode.

Results

The method was found to be linear in the concentration range of 1‐125 ng/L with coefficient of determination lying in the range of 0.995‐0.999. The method achieved limit of quantification in the range of 0.41‐1.72 ng/L, and method recovery measured at three different concentrations was found to be in the range of 75‐115%. Intra‐ and interday precision expressed as percent relative standard deviation was found to be <15%. Matrix effect was found to be in the range of 83.5‐109.79%. The matrix match calibration was used for quantification of PPPCPs in river water sample. The method performance was evaluated by analyzing real samples collected from Ganga River, and the concentrations of 21 analytes were found to be in the range of 0.76‐9.49 ng/L for pharmaceuticals, 1.49–8.67 ng/L for phthalates, and 0.9‐7.58 ng/L for personal care products.

Conclusions

The present method was found to be precise, sensitive, and rapid to determine 26 PPPCPs including phthalates in river water samples using SPE‐UHPLC‐Q‐Orbitrap‐MS.
The investigation of relaxation mechanism and model of polystyrene in high‐elastic state
Authors: Zeng Guangsheng , Sun Zexun , Huang Xinping , Jiang Taijun , Hu Can
Published: September 2020

The relaxation behavior of polymer in its high elastic state is a key factor which determines the molding process and accuracy of its products. Polystyrene with different molecular weights are selected as research object and its relaxation time at different temperatures was tested by torque rheometer. Combining the relationship of “temperature‐relaxation time”, to deeply analyze its relaxation mechanism, a physical model of high elastic relaxation time of polystyrene based on the movement of molecular chains was established, and the change of the physical model at different temperatures was explained. The corresponding mathematical model was obtained by analyzing the influence of the weight average molecular weight Mw, dispersion D, and temperature T parameters of polystyrene on its relaxation time. The results of experiments and model calculations reveal that the relaxation time of polystyrene under high elasticity does not continue to decrease with the increase of temperature, but it changes in an M‐shape with the increase of temperature, that is, the relaxation time shows an upward trend at 155°C – 160°C and a downward trend at 160°C – 165°C. It has an increasing trend at 165°C – 170°C, and a decreasing trend at 170°C – 175°C. Polystyrenes with different molecular weights and dispersion degrees have different M forms. The research results have theoretical guiding significance for polymer processing.
Thermal insulation behaviour of Ethylene propylene diene monomer rubber/kevlar fiber based hybrid composites containing Nanosilica for solid rocket motor insulation
Authors: George Kesiya , Mohanty Smita , Biswal Manoranjan , Nayak Sanjay K.
Published: September 2020

The current research discusses the properties of an elastomeric heat‐shielding material, based on nano‐silica (NS) filled ethylene propylene diene monomer (EPDM) rubber/Kevlar fiber (KF) hybrid composites. The developed elastomeric insulating material consists of an aromatic polyamide fiber (KF) and silica nanoparticles. An in‐depth analysis of mechanical properties, density, coefficient of thermal expansion, thermal conductivity, thermogravimetric analysis, and heat release rate of the insulating materials ‐was performed. TEM micrograph represents an excellent distribution of nanoparticles in the EPDM matrix. The improvement in the mechanical and the flame retardancy of the NS filled EPDM/KF hybrid composite insulations is based on the fiber/matrix adhesion. Maleic anhydride grafting confers polarity to the nonpolar rubber matrix. The char residues of the insulations inspected by scanning electron microscopy and energy dispersive spectroscopy are depicting a rigid and rough surface by the optimal composites, which can aid in better insulation. The optimal formulation of the hybrid composites exhibited a 220% enhancement in char residue with improved thermal stability and mechanical properties.
Changes in free volume and gas permeation properties of poly(vinyl alcohol) nanocomposite membranes modified using cage‐structured polyhedral oligomeric silsesquioxane
Authors: Swapna Valiya Parambath , Kaliyathan Abitha Vayyaprontavida , Abhisha Vakkoottil Sivadasan , Maria Hanna Joseph , Nambissan Padinharu Madathil Gopalakrishnan , Thomas Sabu , Stephen Ranimol
Published: September 2020

The present work reports the effect of various organically functionalized polyhedral oligomeric silsesquioxane (POSS) particles on the gas transport properties (N2, O2, and CO2 molecules) in poly(vinyl alcohol) (PVA) membranes. The incorporation of polyethylene glycol‐POSS (PEG‐POSS), octa‐tetramethylammonium‐POSS (Octa‐TMA‐POSS) and m‐POSS (Octa‐TMA‐POSS molecule was modified using cetyltrimethyl ammonium bromide) led to the enhancement in CO2 separation performance of PVA, among which, PEG‐POSS exhibited highest CO2 separation due to the dipole‐quadrupolar interaction of CO2 with ethylene oxide group in POSS. Octa‐TMA‐POSS and m‐POSS reduced the O2 and N2 permeability of the PVA membrane due to the reduction in the number of permeating pathways as compared to pure PVA. Free volume of the membranes was evaluated by positron annihilation lifetime spectroscopic (PALS) and coincidence Doppler broadening measurements. PALS confirms the increase in polymer free volume in PVA/POSS system due to the presence of rigid and spherical POSS molecule, which could enter in the polymer chain and provide viable pathway for molecular transport. Maxwel–Wagner–Sillar and Higuchi models were applied for the theoretical prediction of permeability of the fabricated membranes.
Battered mothers and children in the courts: A lawyer's view
Authors: Fischel‐Wolovick Lisa
Published: September 2020

The prevention of harm to battered mothers and children during custody and divorce litigation requires a trauma‐informed judicial approach. The existence of competing definitions of domestic violence, gender‐biased theories of parental alienation, and requirements that battered mothers co‐parent have undermined legislation intended to protect victims of domestic violence and their children. An informed judicial response to domestic violence requires mental health professionals who are able to identify the multiple patterns of abuse including physical, emotional, economic, and sexual coercively controlling behaviors, as well as the risks of post‐separation violence. The family courts' lack of transparency and limited public access has further contributed to its reliance on empirically weak gender‐biased parental alienation theories. Mental health professionals who provide interdisciplinary support to these courts must have graduate clinical education in domestic violence, child maltreatment, development, and trauma. Additional systemic changes should include neutral court watch observers to promote accountability and transparency, as well as appropriate services, to these vulnerable families.
Citizen science sheds light on the cryptic ornate eagle ray Aetomylaeus vespertilio
Authors: Araujo Gonzalo , Legaspi Christine , Matthews Kinsey , Ponzo Alessandro , Chin Andrew , Manjaji‐Matsumoto B. Mabel
Published: September 2020

The ornate eagle ray Aetomylaeus vespertilio (Bleeker, 1852) is a rare and Endangered species of eagle ray, with a patchy distribution across the Indo‐West Pacific region, for which data are scarce.

Citizen science‐sourced data from online social media platforms were used to shed light on the distribution and ecology of the ornate eagle ray.

A total of 53 reports of A. vespertilio were found on Facebook, Instagram, Twitter, and YouTube, including four reports of dead specimens. All live reports occurred in shallow reef or lagoon ecosystems. Two individual A. vespertilio specimens were re‐sighted in the same general area following initial identification within 9 and 13 months at Ningaloo Reef and at Lady Elliot Island, Australia, respectively, as confirmed through their dorsal spot patterns. One report was at Richard's Bay in South Africa, the southernmost known location for this species in the Indian Ocean (28°S). Live reports were also reported from the Maldives, the Seychelles, Egypt (Red Sea), Philippines, Palau, and elsewhere on the Great Barrier Reef, Australia.

Results indicate that citizen‐collected data can shed light on the occurrence and distribution of cryptic species, as well as complement monitoring programmes.
Research data management policy and practice in Chinese university libraries
Authors: Huang Yingshen , Cox Andrew M. , Sbaffi Laura
Published: September 2020

On April 2, 2018, the State Council of China formally released a national Research Data Management (RDM) policy “Measures for Managing Scientific Data”. In this context and given that university libraries have played an important role in supporting RDM at an institutional level in North America, Europe, and Australasia, the aim of this article is to explore the current status of RDM in Chinese universities, in particular how university libraries have been involved in taking the agenda forward. This article uses a mixed‐methods data collection approach and draws on a website analysis of university policies and services; a questionnaire for university librarians; and semi‐structured interviews. Findings indicate that Research Data Service at a local level in Chinese Universities are in their infancy. There is more evidence of activity in developing data repositories than support services. There is little development of local policy. Among the explanations of this may be the existence of a national‐level infrastructure for some subject disciplines, the lack of professionalization of librarianship, and the relatively weak resonance of openness as an idea in the Chinese context.
Oxygen doped g‐C3N4 with nitrogen vacancy for enhanced photocatalytic hydrogen evolution
Authors: Tang Hua , Xia Zhihua , Chen Ran , Liu Qinqin , Zhou Tianhua
Published: September 2020

Generally, bulk graphic carbon nitride (g‐C3N4) suffers from fast photogenerated charge carrier combination, inferior light absorption and insufficient active sites. Herein, we developed a defect engineering approach which can simultaneously realize O dopant and N defects in the g‐C3N4 framework via an acid‐assisted thermal treatment route. The modified g‐C3N4 demonstrated greatly enhanced photocatalytic H2 activity with a H2 evolution rate of 2.20 mmol ⋅ g−1 ⋅ h−1, which is more than three times higher than that of bulk g‐C3N4. The mechanism of the enhanced activity was investigated and proposed that the introduction of O dopants and N defects in the g‐C3N4 could optimize the electron structure, up‐shift the conduction band, increase the surface area, and thus achieve more efficient separation of photogenerated carriers, stronger reduction ability and abundant active sites for photocatalytic H2 evolution. Thus, defect engineering has been demonstrated to be a prospective strategy to modify the performance of g‐C3N4 for future photocatalytic energy generation.
Inferential aspects for the optimal selection of the control parameters in Taguchi method
Authors: Facchinetti Silvia , Osmetti Silvia Angela , Magagnoli Umberto
Published: September 2020

This article focuses on the estimation of dispersion effects in off‐line quality control techniques. In this context, the Taguchi design for the optimal choice of process parameters is one of the most commonly used statistical methods. Starting from Taguchi methodology, we consider that an additive or a multiplicative model defines the relationship between the deterministic component and the variability of the process. We apply a hypothesis testing in order to find the optimal factor combination that minimizes the variability indicator of product quality, using ranking and selection methods of the Bechhofer kind. Moreover, an extensive simulation study shows how the probability of finding the optimal set of factors changes according to the main sampling parameters, in order to provide guidance for practitioners.
Extremely Low‐Frequency Magnetic Fields and the Risk of Childhood B‐Lineage Acute Lymphoblastic Leukemia in a City With High Incidence of Leukemia and Elevated Exposure to ELF Magnetic Fields
Authors: Núñez‐Enríquez Juan C. , Correa‐Correa Víctor , Flores‐Lujano Janet , Pérez‐Saldivar María L. , Jiménez‐Hernández Elva , Martín‐Trejo Jorge A. , Espinoza‐Hernández Laura E. , Medina‐Sanson Aurora , Cárdenas‐Cardos Rocío , Flores‐Villegas Luz V. , Peñaloza‐González José G. , Torres‐Nava José R. , Espinosa‐Elizondo Rosa M. , Amador‐Sánchez Raquel , Rivera‐Luna Roberto , Dosta‐Herrera Juan J. , Mondragón‐García Javier A. , González‐Ulibarri Juana E. , Martínez‐Silva Sofía I. , Espinoza‐Anrubio Gilberto , Duarte‐Rodríguez David A. , García‐Cortés Luis R. , Gil‐Hernández Ana E. , Mejía‐Aranguré Juan M.
Published: September 2020

It is important to study the relationship between extremely low‐frequency magnetic fields (ELF‐MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF‐MF, such as Mexico City. The aim was to investigate the association between ELF‐MF exposure and the risk of B‐lineage acute lymphoblastic leukemia (B‐ALL). A case–control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24‐h ELF‐MF measurements were obtained for 290 incident B‐ALL patients and 407 controls, aged less than 16 years. Controls were frequency‐matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF‐MF exposure at <0.2 μT was used to define the reference group. ELF‐MF exposure at ≥0.3 μT was observed in 11.3% of the controls. Different ELF‐MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B‐ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 μT = 1.26 (95% CI: 0.84–1.89); ≥0.3 μT = 1.53 (95% CI: 0.95–2.48); ≥0.4 μT = 1.87 (95% CI: 1.04–3.35); ≥0.5 μT = 1.80 (95% CI 0.95–3.44); ≥0.6 μT = 2.32 (95% CI: 1.10–4.93). ELF‐MF exposure as a continuous variable (per 0.2 μT intervals) was associated with B‐ALL risk (aOR = 1.06; 95% CI: 1.01–1.12). In the present study, the proportion of children exposed to ≥0.3 μT is among the highest reported worldwide. Additionally, an ELF‐MF exposure ≥0.4 μT may be associated with the risk of B‐ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society
Testing inflated zeros in binomial regression models
Authors: Ye Peng , Tang Yi , Sun Liuquan , Tang Wan , He Hua
Published: September 2020

Binomial regression models are commonly applied to proportion data such as those relating to the mortality and infection rates of diseases. However, it is often the case that the responses may exhibit excessive zeros; in such cases a zero‐inflated binomial (ZIB) regression model can be applied instead. In practice, it is essential to test if there are excessive zeros in the outcome to help choose an appropriate model. The binomial models can yield biased inference if there are excessive zeros, while ZIB models may be unnecessarily complex and hard to interpret, and even face convergence issues, if there are no excessive zeros. In this paper, we develop a new test for testing zero inflation in binomial regression models by directly comparing the amount of observed zeros with what would be expected under the binomial regression model. A closed form of the test statistic, as well as the asymptotic properties of the test, is derived based on estimating equations. Our systematic simulation studies show that the new test performs very well in most cases, and outperforms the classical Wald, likelihood ratio, and score tests, especially in controlling type I errors. Two real data examples are also included for illustrative purpose.
Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model
Authors: Seeliger B , Alesina P F , Walz M K , Pop R , Charles A-L , Geny B , Messaddeq N , Kontogeorgos G , Mascagni P , Seyller E , Marescaux J , Agnus V , Diana M
Published: September 2020

Background

A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function.

Methods

Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy.

Results

Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments.

Conclusion

In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevancePreservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown.New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion.Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.
Assessing differential effects of single and accelerated low‐frequency rTMS to the visual cortex on GABA and glutamate concentrations
Authors: Rafique Sara A. , Steeves Jennifer K. E.
Published: September 2020

Background

The application of repetitive transcranial magnetic stimulation (rTMS) for therapeutic use in visual‐related disorders and its underlying mechanisms in the visual cortex is under‐investigated. Additionally, there is little examination of rTMS adverse effects particularly with regards to visual and cognitive function. Neural plasticity is key in rehabilitation and recovery of function; thus, effective therapeutic strategies must be capable of modulating plasticity. Glutamate and γ‐aminobutyric acid (GABA)‐mediated changes in the balance between excitation and inhibition are prominent features in visual cortical plasticity.

Objectives and method

We investigated the effects of low‐frequency (1 Hz) rTMS to the visual cortex on levels of neurotransmitters GABA and glutamate to determine the therapeutic potential of 1 Hz rTMS for visual‐related disorders. Two rTMS regimes commonly used in clinical applications were investigated: participants received rTMS to the visual cortex either in a single 20‐min session or five accelerated 20‐min sessions (not previously investigated at the visual cortex). Proton (1H) magnetic resonance spectroscopy for in vivo quantification of GABA (assessed via GABA+) and glutamate (assessed via Glx) concentrations was performed pre‐ and post‐rTMS.

Results

GABA+ and Glx concentrations were unaltered following a single session of rTMS to the visual cortex. One day of accelerated rTMS significantly reduced GABA+ concentration for up to 24 hr, with levels returning to baseline by 1‐week post‐rTMS. Basic visual and cognitive function remained largely unchanged.

Conclusion

Accelerated 1 Hz rTMS to the visual cortex has greater potential for approaches targeting plasticity or in cases with altered GABAergic responses in visual disorders. Notably, these results provide preliminary insight into a critical window of plasticity with accelerated rTMS (e.g., 24 hr) in which adjunct therapies may offer better functional outcome. We describe detailed procedures to enable further exploration of these protocols.
Self‐assembled, Programmable DNA Nanodevices for Biological and Biomedical Applications
Authors: Bhatia Dhiraj , Wunder Christian , Johannes Ludger
Published: September 2020

The broad field of structural DNA nanotechnology has diverged into various areas of applications ranging from computing, photonics, synthetic biology, and biosensing to in‐vivo bioimaging and therapeutic delivery, to name but a few. Though the field began to exploit DNA to build various nanoscale architectures, it has now taken a new path to diverge from structural DNA nanotechnology to functional or applied DNA nanotechnology. More recently a third sub‐branch has emerged‐biologically oriented DNA nanotechnology, which seeks to explore the functionalities of combinatorial DNA devices in various biological systems. In this review, we summarize the key developments in DNA nanotechnology revealing a current trend that merges the functionality of DNA devices with the specificity of biomolecules to access a range of functions in biological systems. This review seeks to provide a perspective on the evolution and biological applications of DNA nanotechnology, where the integration of DNA structures with biomolecules can now uncover phenomena of interest to biologists and biomedical scientists. Finally, we conclude with the challenges, limitations, and perspectives of DNA nanodevices in fundamental and applied research.
Synthetic Antibody Mimics Based on Cancer‐Targeting Immunostimulatory Peptides
Authors: Descalzi‐Montoya Dante , Montel Rachel A. , Smith Keith , Dziopa Eugenia , Darwich Andrieh , Yang Zheng , Bitsaktsis Constantine , Korngold Robert , Sabatino David
Published: September 2020

De novo cancer‐targeting immunostimulatory peptides have been designed and developed as synthetic antibody mimics. A series of bifunctional peptides incorporating NKp30‐binding and NK‐cell‐activating domains were synthesized as linear dimers and then extended into branching trimeric peptides by the incorporation of GRP78‐targeting and tumor‐cell‐binding sequences. A selected trimeric peptide from this small set of peptides displayed binding capabilities on GRP78+ HepG2 and A549 target cells. Cell binding diminished in the presence of an anti‐GRP78 peptide blocker, thus suggesting GRP78‐binding dependence. Similarly, the selected trimeric peptide was also found to exhibit NK cell binding in an NKp30‐dependent manner, which translated into NK cell activation as indicated by cytokine secretion. In co‐culture, fluorescence microscopy revealed that the target GFP‐expressing A549 cells were visibly associated with the effector NK cells when pre‐activated with lead trimeric peptide. Accordingly, A549 cells were found to be compromised, as evidenced by the loss of GFP signal and notable detection of early‐/late‐stage apoptosis. Investigation of the immunological markers related to toxicity revealed detectable secretion of pro‐inflammatory cytokines and chemokines, including IFN‐γ, TNF‐α, and IL‐8. Furthermore, administration of peptide‐activated NK cells into A549‐tumor‐bearing mice resulted in a consistent decrease in tumor growth when compared to the untreated control group. Taken together, the identification of a lead trimeric peptide capable of targeting and activating NK cells’ immunotoxicity directly towards GRP78+/B7H6‐ tumors provides a novel proof‐of‐concept for the development of cancer‐targeting immunostimulatory peptide ligands that mimic antibody‐targeting and ‐activating functions related to cancer immunotherapy applications.
Photo‐biocatalytic Cascades: Combining Chemical and Enzymatic Transformations Fueled by Light
Authors: Özgen Fatma Feyza , Runda Michael E. , Schmidt Sandy
Published: September 2020

In the field of green chemistry, light – an attractive natural agent – has received particular attention for driving biocatalytic reactions. Moreover, the implementation of light to drive (chemo)enzymatic cascade reactions opens up a golden window of opportunities. However, there are limitations to many current examples, mostly associated with incompatibility between the enzyme and the photocatalyst. Additionally, the formation of reactive radicals upon illumination and the loss of catalytic activities in the presence of required additives are common observations. As outlined in this review, the main question is how to overcome current challenges to the exploitation of light to drive (chemo)enzymatic transformations. First, we highlight general concepts in photo‐biocatalysis, then give various examples of photo‐chemoenzymatic (PCE) cascades, further summarize current synthetic examples of PCE cascades and discuss strategies to address the limitations.
The Peculiar Structure of Acetobacter pasteurianus CIP103108 LPS Core Oligosaccharide
Authors: Marchetti Roberta , Nieto Fabregat Ferran , Pallach Mateusz , Gully Djamel , Giraud Eric , Molinaro Antonio , Duda Katarzyna A. , Silipo Alba
Published: September 2020

Acetobacter pasteurianus, a member of the Alphaproteobacteria, is an acetic acid‐producing bacterium present on sugar‐rich substrates such as such as fruits, flowers and vegetables and traditionally used in the production of fermented food. The preferred living habitat associated with acid conditions makes the structure of the bacterial cell wall interesting to study, due to expected uncommon features. We have used a combination of chemical, analytical and NMR spectroscopy approaches to define the complete structure of the core oligosaccharide from A. pasteurianus CIP103108 LPS. Interestingly, the core oligosaccharide displays a high concentration of negatively charged groups, structural features that might contribute to reinforcing the bacterial membrane.
Site‐Specific Incorporation of a Photoactivatable Fluorescent Amino Acid
Authors: Tang Juan , Yu Chenfei , Loredo Axel , Chen Yuda , Xiao Han
Published: September 2020

Photoactivatable fluorophores are emerging optical probes for biological applications. Most photoactivatable fluorophores are relatively large in size and need to be activated by ultraviolet light; this dramatically limits their applications. To introduce photoactivatable fluorophores into proteins, recent investigations have explored several protein‐labeling technologies, including fluorescein arsenical hairpin (FlAsH) Tag, HaloTag labeling, SNAPTag labeling, and other bioorthogonal chemistry‐based methods. However, these technologies require a multistep labeling process. Here, by using genetic code expansion and a single sulfur‐for‐oxygen atom replacement within an existing fluorescent amino acid, we have site‐specifically incorporated the photoactivatable fluorescent amino acid thioacridonylalanine (SAcd) into proteins in a single step. Moreover, upon exposure to visible light, SAcd can be efficiently desulfurized to its oxo derivatives, thus restoring the strong fluorescence of labeled proteins.
Semaphorin3A released from human dental pulp cells inhibits the increase in interleukin‐6 and CXC chemokine ligand 10 production induced by tumor necrosis factor‐α through suppression of nuclear factor‐κB activation
Authors: Shindo Satoru , Kumagai Tomoki , Shirawachi Satomi , Takeda Katsuhiro , Shiba Hideki
Published: September 2020

Human dental pulp cells (HDPCs) play an important role in pulpitis. Semaphorin3A (Sema3A), which is an axon guidance molecule, is a member of the secretory semaphorin family. Recently, Sema3A has been reported to be an osteoprotective factor and to be involved in the immune response. However, the role of Sema3A in dental pulp inflammation remains unknown. The aim of this study was to reveal the existence of Sema3A in human dental pulp tissue and the effect of Sema3A which is released from tumor necrosis factor (TNF)‐α‐stimulated HDPCs on production of proinflammatory cytokines, such as interleukin (IL)‐6 and CXC chemokine ligand 10 (CXCL10), from HDPCs stimulated with TNF‐α. Sema3A was detected in inflamed pulp as compared to normal pulp. HDPCs expressed Neuropilin‐1(Nrp1) which is Sema3A receptor. TNF‐α increased the levels of IL‐6 and CXCL10 in HDPCs in time‐dependent manner. Sema3A inhibited production of these two cytokines from TNF‐α‐stimulated HDPCs. TNF‐α induced soluble Sema3A production from HDPCs. Moreover, antibody‐based neutralization of Sema3A further promoted production of IL‐6 and CXCL10 from TNF‐α‐stimulated HDPCs. Sema3A inhibited nuclear factor (NF)‐κB P65 phosphorylation and inhibitor κBα degradation in TNF‐α‐stimulated HDPCs. These results indicated that Sema3A is induced in human dental pulp, and TNF‐α acts on HDPCs to produce Sema3A, which partially inhibits the increase in IL‐6 and CXCL10 production induced by TNF‐α, and that the inhibition leads to suppression of NF‐κB activation. Therefore, it is suggested that Sema3A may regulate inflammation in dental pulp and be novel antiinflammatory target molecule for pulpitis.
Chemoenzymatic Stereoselective Synthesis of Substituted γ‐ or δ‐lactams with Two Chiral Centers via Transaminase‐catalysed Dynamic Kinetic Resolution
Authors: Dong Wenyue , Yao Peiyuan , Wang Yingang , Wu Qiaqing , Zhu Dunming
Published: September 2020

The biocatalytic stereoselective synthesis of lactams with two chiral centers by a dynamic kinetic resolution strategy is demonstrated. Five transaminases were examined for the transamination of chemically synthesized substituted γ‐ or δ‐keto esters. The application of (R)‐ and (S)‐selective enzymes led to the corresponding chiral amines with moderate to high diastereomeric ratios and excellent enantiomeric excess, followed by the formation of γ‐ or δ‐lactams in some cases. Reaction conditions including pH, co‐solvent and ratio of amine donor vs. acceptor were optimised. The stereoselective biotransaminations were performed at semi‐preparative scale, successfully generating the corresponding lactams or amine in 46–70 % isolated yields, up to 99 : 1 diastereomeric ratios and >99 % ee values. This study represents a promising approach to the biocatalytic synthesis of important γ‐ and δ‐lactams with two chiral centers.