bluuebunny/crossref_metadata_2025_split huggingface dataset:
Returning negative results from large‐scale genomic screening: Experiences from the eMERGE III network
Authors: Finn Kelsey Stuttgen , Lynch John , Aufox Sharon , Bland Harris T. , Chung Wendy , Halverson Colin , Hebbring Scott , Hoell Christin , Holm Ingrid , Jarvik Gail , Kullo Iftikhar , Leppig Kathleen , Myers Melanie , Prows Cynthia , Rasouly Hila Milo , Singh Rajbir , Weisner Georgia , Williams Janet , Wynn Julia , Smith Maureen , Sharp Richard 
Published: December 2020

AbstractPopulation‐based genomic screening has the potential to improve health outcomes by identifying genetic causes of disease before they occur. While much attention has been paid to supporting the needs of the small percentage of patients who will receive a life‐altering positive genomic screening result that requires medical attention, little attention has been given to the communication of negative screening results. As there are currently no best practices for returning negative genomic screening results, we drew on experiences across the electronic medical records and genomics (eMERGE) III Network to highlight the diversity of reporting methods employed, challenges encountered in reporting negative test results, and “lessons learned” across institutions. A 60‐item survey that consisted of both multiple choice and open‐ended questions was created to gather data across institutions. Even though institutions independently developed procedures for reporting negative results, and had very different study populations, we identified several similarities of approach, including but not limited to: returning results by mail, placing results in the electronic health record via an automated process, reporting results to participants' primary care provider, and providing genetic counseling to interested patients at no cost. Differences in procedures for reporting negative results included: differences in terminology used to describe negative results, definitions of negative results, guidance regarding the meaning of negative results for participants and their family members, and recommendations for clinical follow up. Our findings highlight emerging practices for reporting negative genomic screening results and highlight the need to create patient education and clinical support tools for reporting negative screening results.
Intraperitoneal bladder rupture in a young child with vascular Ehlers‐Danlos syndrome
Authors: Nanduri Rahul , Jones Eric , Miller‐Hance Wanda , Lewis Andrea M. , Morris Shaine A. 
Published: December 2020

AbstractIn this report, we present the case of a 3‐year‐old child with vascular Ehlers‐Danlos syndrome (vEDS) previously known as Ehlers‐Danlos syndrome type IV. After experiencing a minor traumatic injury to the abdomen, consisting of falling over a bathroom stool on the way to the restroom with a full bladder, the child developed acute abdominal pain. He was found to have an intraperitoneal bladder rupture that was successfully repaired with management techniques tailored to his known diagnosis of vEDS. While tissue fragility and internal organ rupture occurring with minor trauma are known complications of vEDS, this is the first case in the literature of a bladder rupture in a child with vEDS with a confirmed variant in the COL3A1 gene, to our knowledge. This case broadens the clinical presentation of vEDS, demonstrates that children can have life‐threatening organ rupture at a young age, and may alert providers to consider this diagnosis when a child presents with bladder rupture.
PIGO variants in a boy with features of Mabry syndrome who also exhibits Fryns syndrome with peripheral neuropathy
Authors: Okuda Taro , Yonekawa Takahiro , Murakami Yoshiko , Kinoshita Taroh , Ito Takahiro , Matsushita Kohei , Koike Yuhki , Inoue Mikihiro , Uchida Keiichi , Yodoya Noriko , Ohashi Hiroyuki , Sawada Hirofumi , Iwamoto Shotaro , Mitani Yoshihide , Hirayama Masahiro 
Published: December 2020

AbstractWe report a 2‐year‐old boy with left congenital diaphragmatic defect (CDH), pulmonary hypoplasia, and polyhydramnios who harbors compound heterozygous mutations, c.1109A>G and c.2497_2498del, in the PIGO gene. The facial appearance was characterized by cloudy cornea, broad and flat nasal bridge, long philtrum, low‐set ears, and micrognathia. Serum alkaline phosphatase level was consistently elevated, suggesting that he meets the criteria for Mabry syndrome. However, the observation of other anomalies including micropenis, cryptorchidism, and Hirschsprung disease suggests clinical features compatible with Fryns syndrome (FS). Left CDH and Hirschsprung disease were surgically repaired at 1 week and 3 months of age, respectively. He also exhibited multiple joint contractures and markedly decreased voluntary movement. Craw hands were seen but pes cavus was absent. Electrophysiology studies showed diffuse axonal demyelinating neuropathy. The cell surface expression of CD16, CD24, and CD59 on blood granulocytes was significantly reduced. The PIGO gene encodes ethanolamine phosphate transferase 3 in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. Mutations in the gene are known to cause Mabry syndrome, an inherited GPI deficiency (IGD) characterized by hyperphosphatasia. IGDs show clinical heterogeneity and overlap with other syndromes and diseases. A severe end of the phenotypic spectrum can be recognized as FS. This is the first report of PIGO gene mutations in a Mabry syndrome patient who also meets the criteria for FS.
Free‐Electron Qubits
Authors: Reinhardt Ori , Mechel Chen , Lynch Morgan , Kaminer Ido 
Published: December 2020

AbstractFree‐electron interactions with laser‐driven nearfields can quantize the electrons’ energy spectrum and provide control over this quantized degree of freedom. The study proposes to use such interactions to promote free electrons as carriers of quantum information and show how to create a qubit on a free electron, which holds promise for applications in electron microscopy and spectroscopy. A method to implement the qubit's noncommutative spin algebra, and to control and measure the qubit state with a universal set of 1‐qubit gates is shown. These gates are within the current capabilities of ultrafast transmission electron microscopes. Laser‐driven free‐electron qubits promise configurability by the laser intensity, frequency, and polarizability, simultaneously with high‐resolution temporal control on femtosecond timescales.
Triazenyl Alkynes as Versatile Building Blocks in Multicomponent Reactions: Diastereoselective Synthesis of β‐Amino Amides
Authors: Wang Chaorong , Lai Zhencheng , Xie Hujun , Cui Sunliang 
Published: December 2020

AbstractMulticomponent reactions (MCRs) are powerful tool for the construction of polyfunctional molecules in an operationally simple and atom‐economic manner, and the discovery of novel MCRs requests various building blocks. Herein, triazenyl alkynes were disclosed as versatile building blocks in a multicomponent reaction with carboxylic acids, aldehydes and anilines to furnish β‐amino amides with the achievement of high diastereoselectivity and structural diversity. In this process, triazenyl alkynes were bifunctional so that the alkyne moiety acts as C2 fragment and triazene serves as directing group to modulate the transition state thus achieving high diastereoselectivity, in consistence with DFT calculations. Furthermore, the triazenyl group also enables diverse late‐stage transformation. This protocol opens a new vision for the discovery of building block and rational design of MCRs.
The Logic Behind Markovnikov's Rule: Was It an Inspired Guess? …No!
Authors: Lewis David E. 
Published: December 2020

AbstractVladimir Vasil′evich Markovnikov (1837–1904) was a Russian chemist whose graduate research at Kazan Imperial University from 1860–1869 gave us, among other things, one of the most enduring empirical rules in organic chemistry. Markovnikov's Rule for electrophilic addition was first published in the inaugural volume of the Journal of the Russian Chemical Society (Zh. Russ. Khim. O‐va.), but it was not until a year later when it was published in German that it received attention internationally. The rule itself was worded differently from the most common modern versions, in that it is expressed in terms of the electronegative part of the adding reagent. It has been suggested that this rule was the result of an inspired guess, but a careful examination of Markovnikov's graduate dissertations reveals a very different picture. In the dissertations, there is a careful build‐up of logic from which the rule itself, as defined by Markovnikov, emerges naturally. Markovnikov's Rule was most decidedly not an inspired guess.
Drug‐Sponge Lipid Nanocarrier for in Situ Cargo Loading and Release Using Dynamic Covalent Chemistry
Authors: Liu Fei , Niko Yosuke , Bouchaala Redouane , Mercier Luc , Lefebvre Olivier , Andreiuk Bohdan , Vandamme Thierry , Goetz Jacky G. , Anton Nicolas , Klymchenko Andrey 
Published: December 2020

AbstractCurrently, drug‐delivery strategies using nanocarriers (NCs) deal with encapsulation of cargo or its covalently modified prodrug. Herein, we propose a concept of reversible pH‐controlled capture and delivery of active cargo based on dynamic covalent chemistry inside lipid nano‐droplets (nanoemulsions), coined as “drug sponge”. We designed a highly lipophilic hydrazide (LipoHD) capable of reacting with a free cargo‐ketone (fluorescent dye and doxorubicin drug) directly inside lipid NCs, yielding a lipophilic hydrazone prodrug efficiently captured in the oil core. LipoHD‐loaded NCs spontaneously accumulated cargo‐ketones, yielding formulations stable against cargo leakage at pH 7.4, and further released their dye/drug cargo at low pH range (5.0–6.8) in solution and live cells. Doxorubicin‐loaded drug‐sponge NCs showed cytotoxicity in four cancer cell lines and capacity to inhibit tumor growth in subcutaneous xenografts of mice. Finally, unprecedented extraction of dye/drug cargos directly from cells and tissues (i.e. detoxification) was realized by the drug‐sponge NCs.
Skeletal development of Kinosternon scorpioides limbs (Chelonia: Kinosternidae)
Authors: dos Santos Braga Brenda Stefany , Fernandes‐Neto Dário Lisboa , Teixeira Leonardo Conceição , da Silva Costa Juliane , Ferreira Maria Auxiliadora Pantoja , Oliveira‐Bahia Verônica Regina , Marques José Ribamar Felipe , de Araújo Guimarães Diva Anelie 
Published: December 2020

AbstractThe morphological study of limbs is important for the understanding of tetrapod biology, where it can be applied to taxonomy and phylogeny, as well ecology and behavior. In this study area, osteogenesis is a subject in Kinosternidae, which has been little researched. The main aim of this study was to characterize the skeletogenesis of Kinosternon scorpioides limbs. Samples were histologically processed, and the embryos were cleared with potassium hydroxide and stained with alcian blue and alizarin red. It was observed that the limbs arose in embryonic Stage 10 as mesenchymal condensate cells. The first stylopodium chondrification centers were noted at Stage 14. Zeugopodium chondrification centers appeared at Stage 15; carpal, metacarpal, tarsal, and metatarsal regions were observed at Stage 16, and the cartilage molds of all bones limbs were present at Stage 18. Ossification began in the humerus and femur at Stage 20, and continued into the radius, ulna, tibia, and fibula bones. By Stage 23, it was already effectively directed toward the bone epiphyses in both limbs. At Stage 26 and hatching, only articular cartilages remained, and in the majority of samples the carpal region showed no affinity for alcian blue or alizarin red staining. This study acts as an indicative parameter of the taxon's normal development and can contribute to the phylogenetic understanding of this group.
Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation
Authors: Weber Brittany , He Zeling , Yang Nicole , Playford Martin P. , Weisenfeld Dana , Iannaccone Christine , Coblyn Jonathan , Weinblatt Michael , Shadick Nancy , Di Carli Marcelo , Mehta Nehal N. , Plutzky Jorge , Liao Katherine P. 
Published: December 2020

ObjectivePatients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low‐density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury.MethodsA total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high‐sensitivity C‐reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin‐6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high‐sensitivity cardiac troponin T [hs‐cTnT], N‐terminal pro–brain natriuretic peptide) were measured.ResultsAmong the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A‐I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs‐cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs‐cTnT levels remained stable despite a reduction in inflammation over follow‐up. In both cohorts, hs‐cTnT levels were associated with the overall estimated risk of CVD.ConclusionAmong RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs‐cTnT for CVD risk stratification in RA.
Thermoelectric Converters Based on Ionic Conductors
Authors: Wu Xun , Gao Naiwei , Jia Hanyu , Wang Yapei 
Published: December 2020

AbstractThermoelectric materials represent a new paradigm for harvesting low‐grade heat, which would otherwise be dissipated to the environment uselessly. Relative to conventional thermoelectric materials generally composed of semiconductors or semi‐metals, ionic thermoelectric materials are rising as an alternative choice which exhibit higher Seebeck coefficient and lower thermal conductivity. The ionic thermoelectric materials own a completely different thermoelectric conversion mechanism, in which the ions do not enter the electrode but rearrange on the electrode surface to generate a voltage difference between the hot and cold electrodes. This unique character has inspired worldwide interests on the design of ionic‐type thermoelectric converters with attractive advantages of high flexibility, low cost, limited environmental pollution, and self‐healing capability. Referring to the categories of ionic thermoelectric conversion, some representative ionic thermoelectric materials with their respective characteristics are summarized in this minireview. In addition, examples of applying ionic thermoelectric materials in supercapacitors, wearable devices, and fire warning system are also discussed. Insight into the challenges for the further development of ionic thermoelectric materials is finally provided.
A novel GTPBP2 splicing mutation in two siblings affected with microcephaly, generalized muscular atrophy, and hypotrichosis
Authors: Abdi Rad Isa , Vahabi Ali , Akbariazar Elinaz 
Published: December 2020

AbstractA novel splice site mutation in the GTPBP2 gene was identified by whole‐exome sequencing in two siblings with microcephaly and progressive generalized muscular atrophy associated with hypotrichosis.
Understanding the Hydrogen Evolution Reaction Kinetics of Electrodeposited Nickel‐Molybdenum in Acidic, Near‐Neutral, and Alkaline Conditions
Authors: Bao Fuxi , Kemppainen Erno , Dorbandt Iris , Bors Radu , Xi Fanxing , Schlatmann Rutger , van de Krol Roel , Calnan Sonya 
Published: December 2020

AbstractNickel‐molybdenum (NiMo) alloys can be a possible alternative to platinum as hydrogen evolution reaction (HER) catalysts because of the superior HER activity. However, the superior HER activity and the pH‐dependent kinetics are not currently fully understood. Herein, we present a study of HER kinetics and mechanisms of NiMo in alkaline, near‐neutral and acidic media by combining voltammetry measurements with electrochemical impedance spectroscopy and a microkinetic model. The results indicate that, compared to Ni, NiMo has significantly higher active surface area and intrinsic HER activity. In the subsequent measurements, we demonstrated that different from the existing explanations to the HER mechanisms for NiMo, the HER process in acidic, near‐neutral, and alkaline media is controlled by the Heyrovsky step. Our results show that increasing pH increases the hydrogen coverage, which increases the Tafel‐slope at low overpotentials, eventually resulting in only a single Tafel slope, which would commonly be interpreted as a Volmer‐limited reaction. Furthermore, the studies of thickness effect on HER kinetics show that the HER kinetics of NiMo are thickness‐dependent. In phosphate buffer, the increase in thickness did not significantly increase the double‐layer capacitance, but simulations with the microkinetic model indicate that the active surface area still increased similarly to other electrolytes, which is likely related to the type of electrolyte used.
In Situ Corrosion Fabrication of NaNbO3/Nb3O7F Heterojunctions with Optimized Band Realignment for Enhanced Photocatalytic Hydrogen Evolution
Authors: Li Zhen , Huang Fei , Xiong Xin , Yan Aihua , Dong Haiming , Xu Yifeng , Gao Qingyu 
Published: December 2020

AbstractHeterostructured photocatalysis is a significant issue owing to the unique band alignment, improved spectrum absorption, and enhanced photocatalytic activity. However, the construction of uniform, controllable, and effective heterojunctions is still a huge challenge. Herein, NaNbO3/Nb3O7F heterojunctions are fabricated through an in situ corrosion technique for the first time. The influence of phase transformation on the hydrogen evolution reaction (HER) activity is investigated systematically in terms of photocatalytic water splitting for H2 production. Interestingly, the band realignment and good interfacial contact endow the NaNbO3/Nb3O7F heterojunctions with a high HER activity (43.3 mmol g−1 h−1), which is about 2.4 times that of pure Nb3O7F and 1.36 times that of pure NaNbO3. The results may provide some new insights into the corrosion technique and HER activity of novel heterostructured catalysts.
Experimental and Computational Study on the Anti‐Markovnikov Hydrofunctionalization of Olefins Using Glycine‐Extended AQ‐Auxiliaries
Authors: Nnamdi Fred U. , Diner Colin , Champagne Pier Alexandre , Organ Michael G. 
Published: December 2020

AbstractTwo similar tridentate directing groups derived from glycine and 8‐aminoquinoline were shown to enable the palladium‐catalyzed anti‐Markovnikov hydrofunctionalization of 4‐pentenylamine with drastically different efficiencies. A computational investigation into the origin of the reactivity difference between these isomeric, carbonyl‐transposed auxiliaries suggests that protonation state, thus charge of the substrate‐metal complex prior to nucleopalladation is key. These investigations have culminated in a directing group design that can undergo Pd‐catalyzed hydrofunctionalization under relatively mild conditions, as low as room temperature.
Structural basis for noradrenergic regulation of neural circuits in the mouse olfactory bulb
Authors: Horie Sawa , Kiyokage Emi , Hayashi Shuichi , Inoue Kanako , Sohn Jaerin , Hioki Hiroyuki , Furuta Takahiro , Toida Kazunori 
Published: December 2020

AbstractOlfactory input is processed in the glomerulus of the main olfactory bulb (OB) and relayed to higher centers in the brain by projection neurons. Conversely, centrifugal inputs from other brain regions project to the OB. We have previously analyzed centrifugal inputs into the OB from several brain regions using single‐neuron labeling. In this study, we analyzed the centrifugal noradrenergic (NA) fibers derived from the locus coeruleus (LC), because their projection pathways and synaptic connections in the OB have not been clarified in detail. We analyzed the NA centrifugal projections by single‐neuron labeling and immunoelectron microscopy. Individual NA neurons labeled by viral infection were three‐dimensionally traced using Neurolucida software to visualize the projection pathway from the LC to the OB. Also, centrifugal NA fibers were visualized using an antibody for noradrenaline transporter (NET). NET immunoreactive (‐ir) fibers contained many varicosities and synaptic vesicles. Furthermore, electron tomography demonstrated that NET‐ir fibers formed asymmetrical synapses of varied morphology. Although these synapses were present at varicosities, the density of synapses was relatively low throughout the OB. The maximal density of synapses was found in the external plexiform layer; about 17% of all observed varicosities contained synapses. These results strongly suggest that NA‐containing fibers in the OB release NA from both varicosities and synapses to influence the activities of OB neurons. The present study provides a morphological basis for olfactory modulation by centrifugal NA fibers derived from the LC.
A Reversible Photoacid Switched by Different Wavelengths of Light
Authors: Alghazwat Osamah , Elgattar Adnan , Alharithy Hajar , Liao Yi 
Published: December 2020

AbstractReversible photoacids have been widely used in different areas for control of proton‐driven processes with light. Previously reported reversible photoacids rely on thermal relaxation to return to the low‐acidity ground state. Herein we report a photoacid that can be switched between low‐acidity and high‐acidity states by different wavelengths of light. The photoacid can be converted into a high‐acidity metastable state by 470 nm irradiation. The thermal relaxation of the metastable state is very slow and its half‐life in DMSO is 55 h. Irradiation with 365 nm light quickly induced the reverse reaction and reached a photostationary state. UV/Vis absorption spectra of the forward and reverse processes induced by 470 nm and 365 nm irradiation, respectively, have well‐matched isosbestic points. No decomposition was observed after the photoacid was switched by the two wavelengths of light for many cycles. Reversible patterning with both writing and erasing steps performed with light was demonstrated using a polymer thin film containing the photoacid and chlorophenol red as the proton acceptor.