bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics in Acromegaly
Authors: Xekouki Paraskevi , Stratakis Constantine A 
Published: February 2016

Abstract

Pituitary tumours are the most frequent intracranial neoplasms, affecting 1/1000 of the worldwide population. Growth hormone (GH)‐secreting adenomas, also known as somatotropinomas, comprise about 20% of all pituitary tumours. Acromegaly is the clinical syndrome that results from high levels of GH in patients after the end of their growing years, whereas gigantism occurs when high GH acts on a skeleton that is still growing. Most cases of acromegaly/gigantism occur as a result of sporadic GH‐secreting pituitary adenomas. However, in 5% of cases (and significantly more frequently in the young ages), they can occur as a result of a genetic defect, most of the time in association with other endocrine abnormalities or as an isolated disorder. These familial syndromes include multiple endocrine neoplasia (MEN) type 1 (MEN1), Carney complex (CNC), MEN type 4 (MEN4). McCune–Albright syndrome (MAS), familial isolated pituitary adenoma (FIPA), the 3Ps association (pheochromocytoma/paraganglioma and pituitary adenoma syndrome or 3PAs) and X‐linked acrogigantism (X‐LAG).

Key Concepts

About 5% of acromegaly may be caused by a genetic mutation; this may be significantly higher in the young ages.

The frequency of GH‐producing pituitary tumours in MEN1 syndrome is only about 10%, with a mean age at diagnosis comparable to the sporadic GH‐secreting adenomas (40–45 years) but with a more aggressive behaviour.

The incidence of GH‐producing pituitary tumours in Carney complex (CNC) has been estimated to be less than 15%; however, insulin‐like growth factor 1 (IGF‐1) elevation may be present in up to 80% of affected patients who have no detectable tumours due to somatomammotrophic hyperplasia, which may precede clinically evident acromegaly.

GH excess is found in up to 20% of patients with McCune–Albright syndrome mainly due to GH‐producing cell hyperplasia rather than due to pituitary tumours, which are identified in only a few patients.

Somatotropinomas are the most common tumour type in both
AIP
mutation‐positive and ‐negative familial isolated pituitary adenoma (FIPA) families.
AIP
mutation‐positive FIPA patients are more likely to have larger tumours, more likely to invade the extrasellar region and more resistant to medication treatment

GH‐secreting pituitary adenomas in 3PAs due to SDHx mutations display more aggressive phenotype, are more resistant to somatostatin analogues, and most often require surgery

X‐linked acrogigantism (X‐LAG) caused by an Xq26.3 genomic duplication is a paediatric disorder characterised by early onset gigantism resulting from an excess of growth hormone as early as in infancy. The
GPR101
gene duplication most likely causes X‐LAG.
Molecular Genetics of
S
tüve–
W
iedemann Syndrome
Authors: Oxford Julia T 
Published: February 2016

Abstract

Stüve–Wiedemann syndrome (STWS; OMIM #610559) is a rare bent‐bone dysplasia that includes radiologic bone anomalies, respiratory distress, feeding difficulties and hyperthermic episodes. STWS usually results in infant mortality, yet some STWS patients survive at least into early adolescence. STWS is caused by a mutation in the leukaemia inhibitory factor receptor (
LIFR
) gene, which is inherited in an autosomally recessive pattern. Most
LIFR
mutations resulting in STWS are null mutations which cause instability of the mRNA (messenger ribonucleic acid), preventing the formation of LIFR and impairing the signalling pathway. LIFR signalling usually follows the JAK/STAT3 pathway, and is initiated by several interleukin‐6‐type cytokines. STWS is managed on a symptomatic basis, because there is no treatment currently available.

Key Concepts

STWS comprises multiple symptoms affecting multiple physiological systems.

Mutations in LIFR cause mRNA instability, preventing the formation of LIFR protein.

LIFR is important for many IL‐6 cytokine family members; and in the case of LIFR mutations, activities of several cytokines are impaired.

The JAK/STAT3 pathway plays a critical role in STWS.
Pharmacologic treatment for postviral olfactory dysfunction: a systematic review
Authors: Harless Lucas , Liang Jonathan 
Published: February 2016

BackgroundPostviral olfactory dysfunction (PVOD) is the most common cause of olfactory dysfunction. Several treatments have been presented in the literature. The objective of this study is to systematically review the existing literature on the effectiveness of pharmacologic treatments for PVOD.MethodsWe performed a literature search of PubMed, Ovid, and ScienceDirect from 1966 to 2014. Inclusion criteria included English‐language articles containing original data on pharmacologic treatment of PVOD with ≥5 subjects, measurable outcomes, and readily available treatments. Data was collected regarding study design, subject demographic information, clinical outcomes, and level of evidence. Two investigators reviewed all articles independently.ResultsOf 445 abstracts identified, 8 articles were included, yielding 563 patients. Treatments investigated included oral corticosteroids, local injections of corticosteroids, zinc sulfate, alpha lipoic acid, caroverine, vitamin A, Ginkgo biloba, and minocycline. Outcome measures were determined by symptom scores and objective olfactory test methods—the most common being Sniffin’ Sticks. Improvement was noted in subjects receiving oral corticosteroid therapy, local injections of corticosteroid, alpha lipoic acid, and caroverine, whereas vitamin A, zinc sulfate, Ginkgo biloba, and minocycline groups did not show significant improvement.ConclusionThe majority of therapies investigated that show benefit in treating PVOD are of poor quality. Although caroverine therapy showed benefit and is a level 1b study, etiologies of olfactory dysfunction other than PVOD were included as well, which clouds the results. Overall, there is no strong evidence for any pharmacologic treatment of PVOD in the literature.
The effect of blood pressure and cardiac output on the quality of the surgical field and middle cerebral artery blood flow during endoscopic sinus surgery
Authors: Ha Thanh Ngoc , van Renen Robert Graham , Ludbrook Guy L. , Wormald Peter‐John 
Published: February 2016

BackgroundA clear surgical field is critical during endoscopic sinus surgery (ESS). Hypotensive anesthesia and cardiac output (CO) may optimize the surgical field; however, evidence of their effect on bleeding and cerebral blood flow is conflicting. The aim of this study was to evaluate the effect of blood pressure (BP) and CO on intraoperative bleeding and middle cerebral artery blood flow velocity (Vmca) during ESS.MethodsThis was a prospective randomized controlled trial. Patients undergoing ESS for chronic rhinosinusitis at a tertiary institution in 2013 were randomized to receive BP manipulation using target‐controlled noradrenaline infusion during surgery to either their left or right sinuses. The contralateral side in each patient served as control. Bleeding was scored using a 0 to 10 point bleeding assessment scale (BAS, 0–10) and Vmca was measured using transcranial Doppler ultrasonography every 10 minutes or when surgically opportune, and time‐matched with BP and CO. Data was analyzed using Bland–Altman methods.ResultsA total of 105 time points were collected across a mean arterial pressure (MAP) range of 32 to 118 mmHg. Significant correlations were demonstrated between MAP and Vmca (r = 0.7, p < 0.0001), MAP and BAS (r = 0.50, p < 0.0001), CO and Vmca (r = 0.57, p < 0.0001), and CO and BAS (r = 0.42, p < 0.0001). The best surgical fields were seen at 40 to 59 mmHg MAP. However, MAP below 60 mmHg produced >50% reduction in Vmca in more than 10% of time points.ConclusionBalancing surgical visibility with organ perfusion remains a challenge. The results of this study show that moderate hypotension significantly improves the surgical field; however reducing BP below 60 mmHg may risk cerebral hypoperfusion.
Palladium‐Catalyzed, tert‐Butyllithium‐Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene A
Authors: Buter Jeffrey , Heijnen Dorus , Vila Carlos , Hornillos Valentín , Otten Edwin , Giannerini Massimo , Minnaard Adriaan J. , Feringa Ben L. 
Published: February 2016

AbstractA palladium‐catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium–halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst‐induced remote point‐to‐axial chirality transfer.
Metastable Nitric Acid Trihydrate in Ice Clouds
Authors: Weiss Fabian , Kubel Frank , Gálvez Óscar , Hoelzel Markus , Parker Stewart F. , Baloh Philipp , Iannarelli Riccardo , Rossi Michel J. , Grothe Hinrich 
Published: February 2016

AbstractThe composition of high‐altitude ice clouds is still a matter of intense discussion. The constituents in question are ice and nitric acid hydrates, but the exact phase composition of clouds and its formation mechanisms are still unknown. In this work, conclusive evidence for a long‐predicted phase, alpha‐nitric acid trihydrate (alpha‐NAT), is presented. This phase was characterized by a combination of X‐ray and neutron diffraction experiments, allowing a convincing structure solution. Furthermore, vibrational spectra (infrared and inelastic neutron scattering) were recorded and compared with theoretical calculations. A strong interaction between water ice and alpha‐NAT was found, which explains the experimental spectra and the phase‐transition kinetics. On the basis of these results, we propose a new three‐step mechanism for NAT formation in high‐altitude ice clouds.
Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation
Authors: Park Dae‐Hwan , Cho Jaeyong , Kwon Oh‐Joon , Yun Chae‐Ok , Choy Jin‐Ho 
Published: February 2016

AbstractThe biodegradable inorganic nanovector based on a layered double hydroxide (LDH) holds great promise for gene and drug delivery systems. However, in vivo targeted delivery of genes through LDH still remains a key challenge in the development of RNA interference therapeutics. Here, we describe in vivo and in vitro delivery system for Survivin siRNA (siSurvivin) assembled with passive LDH with a particle size of 100 nm or active LDH conjugated with a cancer overexpressing receptor targeting ligand, folic acid (LDHFA), conferring them an ability to target the tumor by either EPR‐based clathrin‐mediated or folate receptor‐mediated endocytosis. When not only transfected into KB cells but also injected into xenograft mice, LDHFA/siSurvivin induced potent gene silencing at mRNA and protein levels in vitro, and consequently achieved a 3.0‐fold higher suppression of tumor volume than LDH/siSurvivin in vivo. This anti‐tumor effect was attributed to a selectively 1.2‐fold higher accumulation of siSurvivin in tumor tissue compared with other organs. Targeting to the tumor with inorganic nanovector can guide and accelerate an evolution of next‐generation theranosis system.
Phenyl‐Modified Carbon Nitride Quantum Dots with Distinct Photoluminescence Behavior
Authors: Cui Qianling , Xu Jingsan , Wang Xiaoyu , Li Lidong , Antonietti Markus , Shalom Menny 
Published: February 2016

AbstractA novel type of quantum dot (Ph‐CN) is manufactured from graphitic carbon nitride by “lining” the carbon nitride structure with phenyl groups through supramolecular preorganization. This approach requires no chemical etching or hydrothermal treatments like other competing nanoparticle syntheses and is easy and safe to use. The Ph‐CN nanoparticles exhibit bright, tunable fluorescence, with a high quantum yield of 48.4 % in aqueous colloidal suspensions. Interestingly, the observed Stokes shift of approximately 200 nm is higher than the maximum values reported for carbon nitride based fluorophores. The high quantum yield and the large Stokes shift are related to the structural surface organization of the phenyl groups, which affects the π‐electron delocalization in the conjugated carbon nitride networks and induces colloidal stability. The remarkable performance of the Ph‐CN nanoparticles in imaging is demonstrated by a simple incubation study with HeLa cells.
A Rhodium–Pentane Sigma‐Alkane Complex: Characterization in the Solid State by Experimental and Computational Techniques
Authors: Chadwick F. Mark , Rees Nicholas H. , Weller Andrew S. , Krämer Tobias , Iannuzzi Marcella , Macgregor Stuart A. 
Published: February 2016

AbstractThe pentane σ‐complex [Rh{Cy2P(CH2CH2)PCy2}(η2:η2‐C5H12)][BArF4] is synthesized by a solid/gas single‐crystal to single‐crystal transformation by addition of H2 to a precursor 1,3‐pentadiene complex. Characterization by low temperature single‐crystal X‐ray diffraction (150 K) and SSNMR spectroscopy (158 K) reveals coordination through two Rh⋅⋅⋅H−C interactions in the 2,4‐positions of the linear alkane. Periodic DFT calculations and molecular dynamics on the structure in the solid state provide insight into the experimentally observed Rh⋅⋅⋅H−C interaction, the extended environment in the crystal lattice and a temperature‐dependent pentane rearrangement implicated by the SSNMR data.
Synthesis of Highly Functionalized 4‐Aminoquinolines
Authors: Wezeman Tim , Zhong Sabilla , Nieger Martin , Bräse Stefan 
Published: February 2016

AbstractA diverse set of highly substituted 4‐aminoquinolines was synthesized from ynamides, triflic anhydride, 2‐chloropyridine, and readily accessible amides in a mild one‐step procedure.
Highly Unsaturated Platinum and Palladium Carbenes PtC3 and PdC3 Isolated and Characterized in the Gas Phase
Authors: Bittner Dror M. , Zaleski Daniel P. , Tew David P. , Walker Nicholas R. , Legon Anthony C. 
Published: February 2016

AbstractCarbenes of platinum and palladium, PtC3 and PdC3, were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and ab initio calculations confirm that both molecules are linear. The geometry of PtC3 was accurately determined by fitting to the experimental moments of inertia of twenty‐six isotopologues. The results are consistent with the proposal of an autogenic isolobal relationship between O, Au+, and Pt atoms.
Mechanochemical Iridium(III)‐Catalyzed C−H Bond Amidation of Benzamides with Sulfonyl Azides under Solvent‐Free Conditions in a Ball Mill
Authors: Hermann Gary N. , Becker Peter , Bolm Carsten 
Published: February 2016

AbstractMechanochemical conditions have been applied to an iridium(III)‐catalyzed C−H bond amidation process for the first time. In the absence of solvent, the mechanochemical activation enables the formation of an iridium species that catalyzes the ortho‐selective amidation of benzamides with sulfonyl azides as the nitrogen source. As the reaction proceeds in the absence of organic solvents without external heating and yields the desired products in excellent yields within short reaction times, this method constitutes a powerful, fast, and environmentally benign alternative to the common solvent‐based standard approaches.
Direct Spectroscopic Evidence for an n→π* Interaction
Authors: Singh Santosh K. , Mishra Kamal K. , Sharma Neha , Das Aloke 
Published: February 2016

AbstractThe n→π* interaction is an extremely weak but very important noncovalent interaction. Although this interaction is widely present in biomolecules and materials, its existence is counterintuitive and so has been debated extensively. Herein, we have reported direct spectroscopic evidence for an n→π* interaction for the first time by probing the carbonyl stretching frequency in phenyl formate using isolated gas‐phase IR spectroscopy. This result also demonstrates that the conformational preference for the cis conformer of phenyl formate compared to the trans conformer arises due to the presence of the n→π* interaction in the former. The direct proof reported herein for this controversial but important noncovalent interaction should stimulate further experimental and theoretical investigation on this intriguing research topic.
Effect of Electrolyte Concentration on the Stern Layer Thickness at a Charged Interface
Authors: Brown Matthew A. , Goel Alok , Abbas Zareen 
Published: February 2016

AbstractThe chemistry and physics of charged interfaces is regulated by the structure of the electrical double layer (EDL). Herein we quantify the average thickness of the Stern layer at the silica (SiO2) nanoparticle/aqueous electrolyte interface as a function of NaCl concentration following direct measurement of the nanoparticles’ surface potential by X‐ray photoelectron spectroscopy (XPS). We find the Stern layer compresses (becomes thinner) as the electrolyte concentration is increased. This finding provides a simple and intuitive picture of the EDL that explains the concurrent increase in surface charge density, but decrease in surface and zeta potentials, as the electrolyte concentration is increased.
Catalytic Asymmetric Tandem Reaction of Tertiary Enamides: Expeditious Synthesis of Pyrrolo[2,1‐a]isoquinoline Alkaloid Derivatives
Authors: Xu Xin‐Ming , Zhao Liang , Zhu Jieping , Wang Mei‐Xiang 
Published: February 2016

AbstractReported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1‐a]isoquinolin‐3(2H)‐one structure from unique tertiary enamide synthons. A Cu(OTf)2/chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron‐rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1‐a]isoquinolin‐3(2H)‐one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1‐a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids.
Development of lightweight high‐performance polymeric composites with functionalized nanotubes
Authors: Vijayan Vigil Jasmin , Arun A. , Bhowmik Shantanu , Abraham Mathew , Ajeesh G. , Pitchan Mohan Kumar 
Published: February 2016

ABSTRACTIn this article, we highlight the various properties of an ultralightweight poly(ether ketone) (PEK) composite. In this study, special emphases were laid on the preparation of low‐density, high‐performance polymeric foams with foaming agents and activators. PEK, foamed PEK, and carbon nanotube (CNT)–reinforced foamed PEK composites were considered for this study. The density of the polymer decreased with the reinforcement of the foaming agent. We also noted that with the reinforcement of the modified CNT in the foamed PEK, there were marginal increases in the density and hardness of the composites. We also noted that the mechanical properties of the CNT‐reinforced foamed PEK was on par with those of basic PEK. Thermogravimetric analysis gave us a clear indication that the thermal stability of the composites was not affected by the reinforcing foaming agent and nanoparticles. Scanning electron microscopy and transmission electron microscopy clearly indicated the formation of foams and also the dispersion of nanoparticles in the composite structure. We also observed that because of the reinforcement of multiwalled CNTs in the composite, there was an improvement in the hardness of the composite. An increase in the specific strength was observed in the foamed PEK composites. The CNT‐reinforced foamed PEK showed a marginal decrease in the specific strength without a compromise in the impact strength. The impact strength of the CNT‐reinforced foamed PEK composite was found to be similar to that of the basic PEK. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43471.
Changes in Body Mass Related to the Initiation of Disease‐Modifying Therapies in Rheumatoid Arthritis
Authors: Baker Joshua F. , Sauer Brian C. , Cannon Grant W. , Teng Chia‐Chen , Michaud Kaleb , Ibrahim Said , Jorgenson Erik , Davis Lisa , Caplan Liron , Cannella Amy , Mikuls Ted R. 
Published: February 2016

ObjectiveUnintentional weight loss is important and can be predictive of long‐term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database.MethodsUnique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C‐reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow‐up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m2. Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched‐weighting techniques.ResultsIn total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate‐treated patients, prednisone‐treated patients had significantly more weight gain, while leflunomide‐treated patients demonstrated weight loss. In multivariable models, more weight loss (β = −0.41 kg/m2, 95% confidence interval [95% CI] −0.46, −0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (β = 0.072 kg/m2, 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses.ConclusionLeflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA.
Synthesis and Applications of (ONO Pincer)Ruthenium‐Complex‐Bound Norvalines
Authors: Isozaki Katsuhiro , Yokoi Tomoya , Yoshida Ryota , Ogata Kazuki , Hashizume Daisuke , Yasuda Nobuhiro , Sadakane Koichiro , Takaya Hikaru , Nakamura Masaharu 
Published: February 2016

AbstractTwo (ONO pincer)ruthenium‐complex‐bound norvalines, Boc−[Ru(pydc)(terpy)]Nva−OMe (1; Boc=tert‐butyloxycarbonyl, terpy=terpyridyl, Nva=norvaline) and Boc−[Ru(pydc)(tBu‐terpy)]Nva−OMe (5), were successfully synthesized and their molecular structures and absolute configurations were unequivocally determined by single‐crystal X‐ray diffraction. The robustness of the pincer Ru complexes and norvaline scaffolds against acidic/basic, oxidizing, and high‐temperature conditions enabled us to perform selective transformations of the N‐Boc and C−OMe termini into various functional groups, such as alkyl amide, alkyl urea, and polyether groups, without the loss of the Ru center or enantiomeric purity. The resulting dialkylated Ru‐bound norvaline, n‐C11H23CO−l‐[Ru(pydc)(terpy)]Nva−NH‐n‐C11H23 (l‐4) was found to have excellent self‐assembly properties in organic solvents, thereby affording the corresponding supramolecular gels. Ru‐bound norvaline l‐1 exhibited a higher catalytic activity for the oxidation of alcohols by H2O2 than parent complex [Ru(pydc)(terpy)] (11 a).