bluuebunny/crossref_metadata_2025 huggingface dataset:
Triplet‐State Position and Crystal‐Field Tuning in Opto‐Magnetic Lanthanide Complexes: Two Sides of the Same Coin
Authors: Gálico Diogo A. , Marin Riccardo , Brunet Gabriel , Errulat Dylan , Hemmer Eva , Sigoli Fernando A. , Moilanen Jani O. , Murugesu Muralee
Published: August 2019

Lanthanide‐complex‐based luminescence thermometry and single‐molecule magnetism are two effervescent fields of research, owing to the great promise they hold from an application standpoint. The high thermal sensitivity achievable, their contactless nature, along with sub‐micrometric spatial resolution make these luminescent thermometers appealing for accurate temperature probing in miniaturised electronics. To that end, single‐molecule magnets (SMMs) are expected to revolutionise the field of spintronics, thanks to the improvements made in terms of their working temperature—now surpassing that of liquid nitrogen—and manipulation of their spin state. Hence, the combination of such opto‐magnetic properties in a single molecule is desirable in the aim of overcoming, among others, addressability issues. Yet, improvements must be made through design strategies for the realisation of the aforementioned goal. Moving forward from these considerations, we present a thorough investigation of the effect that changes in the ligand scaffold of a family of terbium complexes have on their performance as luminescent thermometers and SMMs. In particular, an increased number of electron‐withdrawing groups yields modifications of the metal coordination environment and a lowering of the triplet state of the ligands. These effects are tightly intertwined, thus, resulting in concomitant variations of the SMM and the luminescence thermometry behaviour of the complexes. Supported by ab initio calculations, we can rationally interpret the observed trends and provide solid foundations for the development of opto‐magnetic lanthanide complexes.
Asymmetric Synthesis of α‐Amino Phosphonic Acids using Stable Imino Phosphonate as a Universal Precursor
Authors: Inokuma Tsubasa , Sakakibara Takuya , Someno Takatoshi , Masui Kana , Shigenaga Akira , Otaka Akira , Yamada Ken‐ichi
Published: August 2019

A practical method for synthesizing chiral α‐amino phosphonic acid derivatives was developed. Readily available and stable N‐o‐nitrophenylsulfenyl (Nps) imino phosphonate was utilized as a substrate for a highly enantioselective Friedel–Crafts‐type addition of indole or pyrrole nucleophiles catalyzed by chiral phosphoric acid. The resulting adduct was easily converted into N‐9‐fluorenylmethyloxycarbonyl (Fmoc) amino phosphonic acid, which is useful for synthesizing peptides containing an amino phosphonic acid.
Die Chemikalien‐verordnung REACH
Authors: Herrmann Andrea , Maeß Christian
Published: August 2019

Die europäische Chemikalienverordnung REACH führt derzeit zu einem Umbruch in der chemischen Industrie. Das Ziel von REACH ist es, ein hohes Schutzniveau für die menschliche Gesundheit und für die Umwelt sicherzustellen. Die Hersteller müssen daher neue Chemikalien, die in der EU hergestellt oder gehandelt werden sollen, bei der Europäischen Chemikalienbehörde registrieren, dazu müssen sie umfassende Daten zur Umweltverträglichkeit liefern. Zusätzlich müssen für alle Substanzen, die vor 1981 in Verkehr gebracht wurden, die Daten nachgereicht werden. Die letzte Frist für die Registrierung dieser Altstoffe endete im Mai 2018. Als besonders gefährlich eingestufte Stoffe können in ihrer Verwendung beschränkt oder verboten werden.
Physicians' perspectives on medication adherence and health promotion among cancer survivors
Authors: Stump Tammy K. , Robinson June K. , Yanez Betina , Penedo Frank , Ezeofor Adaeze , Kircher Sheetal , Spring Bonnie
Published: August 2019

Background

Cancer survivors face an increased risk of cardiovascular events compared with the general population. Adopting a healthy lifestyle may reduce these risks, and guidelines encourage health‐promotion counseling for cancer survivors, but the extent of physician adherence is unclear.

Methods

This mixed‐method study surveyed 91 physicians, including 30 primary care physicians (PCPs), 30 oncologists, and 31 specialists (urologists, dermatologists, and gynecologists). Interviews also were conducted with 12 oncologists.

Results

Most PCPs (90%) reported recommending health promotion (eg, weight loss, smoking cessation) to at least some cancer survivors, whereas few oncologists (26.7%) and specialists (9.7%) said they ever did so (P < .001). Although most physicians believed that at least 50% of cancer survivors would be adherent to medication regimens to prevent cancer recurrence, they also believed that, if patients were trying to lose weight, they would not remain medication‐adherent. In interviews, oncologists expressed fear that providing health‐promotion advice would distress or overwhelm patients. Additional health‐promotion barriers identified by thematic analysis included: identifying cancer as oncologists' focal concern, time pressure, insufficient behavior change training, and care coordination challenges. Facilitators included perceiving a patient benefit and having health‐promotion resources integrated into the cancer care system.

Conclusions

Physicians often do not have the time, expertise, or resources to address health promotion with cancer survivors. Research is needed to evaluate whether health‐promotion efforts compromise medical regimen adherence, as physicians' responses suggest.
Standardized activities for lay patient navigators in breast cancer care: Recommendations from a citywide implementation study
Authors: Freund Karen M. , Haas Jennifer S. , Lemon Stephenie C. , Burns White Karen , Casanova Nicole , Dominici Laura S. , Erban John K. , Freedman Rachel A. , James Ted A. , Ko Naomi Y. , LeClair Amy M. , Moy Beverly , Parsons Susan K. , Battaglia Tracy A.
Published: August 2019

Background

There is a need for guidelines on patient navigation activities to promote both the quality of patient navigation and the standards of reimbursement for these services because a lack of reimbursement is a major barrier to the implementation, maintenance, and sustainability of these programs.

Methods

A broad community‐based participatory research process was used to identify the needs of patients for navigation. A panel of stakeholders of clinical providers was convened to identify specific activities for navigators to address the needs of patients and providers with the explicit goal of reducing delays in the initiation of cancer treatment and improving adherence to the care plan.

Results

Specific activities were identified that could be generalized to all patient navigation programs for care during active cancer management to address the needs of vulnerable communities.

Conclusions

Oncology programs that seek to implement lay patient navigation may benefit from the adoption of these activities for quality monitoring. Such activities are necessary as we consider reimbursement strategies for navigators without clinical training or licensure.
Opposing Electronic and Nuclear Quantum Effects on Hydrogen Bonds in H2O and D2O
Authors: Clark Timothy , Heske Julian , Kühne Thomas D.
Published: August 2019

The effect of extending the O−H bond length(s) in water on the hydrogen‐bonding strength has been investigated using static ab initio molecular orbital calculations. The “polar flattening” effect that causes a slight σ‐hole to form on hydrogen atoms is strengthened when the bond is stretched, so that the σ‐hole becomes more positive and hydrogen bonding stronger. In opposition to this electronic effect, path‐integral ab initio molecular‐dynamics simulations show that the nuclear quantum effect weakens the hydrogen bond in the water dimer. Thus, static electronic effects strengthen the hydrogen bond in H2O relative to D2O, whereas nuclear quantum effects weaken it. These quantum fluctuations are stronger for the water dimer than in bulk water.
Natural Products as a Foundation for Drug Discovery
Authors: Beutler John A.
Published: August 2019

Many natural products have been used as drugs for the treatment of diverse indications. Although most U.S. pharmaceutical companies have reduced or eliminated their in‐house natural‐product research over the years, new approaches for compound screening and chemical synthesis are resurrecting interest in exploring the therapeutic value of natural products. The aim of this commentary is to review emerging strategies and techniques that have made natural products a viable strategic choice for inclusion in drug discovery programs. Published 2019. U.S. Government.
In Situ Self‐Assembly of Core–Shell Multimetal Prussian Blue Analogues for High‐Performance Sodium‐Ion Batteries
Authors: Yin Jinwen , Shen Yi , Li Chang , Fan Chenyang , Sun Shixiong , Liu Yi , Peng Jian , Qing Li , Han Jiantao
Published: August 2019

Metal–organic frameworks (MOFs), such as Prussian blue and its analogues (PB and PBAs) with open frameworks have attracted tremendous attentions as cathode materials for sodium‐ion batteries, owing to their simple method of synthesis and high theoretical specific capacity. In this study, core–shell‐structured PBAs are prepared by an in situ self‐assembly method. Owing to the advantages of both constituents, the as‐prepared core–shell PBAs show excellent rate and cycling electrochemical properties through a dual‐level‐controlled charge–discharge depth mechanism. It delivers a specific capacity of 104.3 mAh g−1 at 0.1 C, as well as a remarkably enhanced cycle performance, giving 88.3 % of its initial capacity over 1000 cycles at 300 mA g−1. In particular, the coating strategy described herein could be extended to other MOF materials, leading to wider application in energy storage.
Correlation of MLCTs of Group 7 fac‐[M(CO)3]+ Complexes (M = Mn, Re) with Bipyridine, Pyridinylpyrazine, Azopyridine, and Pyridin‐2‐ylmethanimine Type Ligands for Rational photoCORM Design
Authors: Kottelat Emmanuel , Lucarini Fiorella , Crochet Aurelien , Ruggi Albert , Zobi Fabio
Published: August 2019

A mathematical correlation of the MLCT absorption maxima of structurally related fac‐[M(CO)3L2Br] complexes (M = Mn, Re; L2 = bidentate ligand) is obtained by the comparison of a total of 50 species bearing bipyridine, pyridinylpyrazine, azopyridine and pyridin‐2‐ylmethanimine L2 type ligands. The empirical relationship is first derived by the initial comparison of the MLCT absorption maxima of 26 previously published complexes and subsequently used to predict the same absorption value of 24 other species. In order to check the validity of the prediction, several new complexes were prepared. These were spectroscopically characterized and, where possible, their X‐ray solid‐state structure elucidated. The initial mathematical correlation allowed to predict MLCT absorption maxima of the unknown species with an average discrepancy of 12 nm. The relationship was subsequently refined to an average error of 6 nm with following derived formula CalcMnmLCT = (ObsReMLCT/0.88) – 15.1 (where CalcMnmLCT = predicted values of Mn complexes MLCT and ObsReMLCT = experimentally observed MLCT transitions of Re complexes). The correlation and the formula, the significance of which are discussed, may prove useful in the long run for the rational design of Mn‐based photoCORMs starting from known data of widely investigated fac‐[Re(CO)3L2Br] complexes.
Biotransformations in Pure Organic Medium: Organic Solvent‐Labile Enzymes in the Batch and Flow Synthesis of Nitriles
Authors: Hinzmann Alessa , Adebar Niklas , Betke Tobias , Leppin Monja , Gröger Harald
Published: August 2019

In recent years, there has been an increasing tendency to use biocatalysts in industrial chemistry, especially in the pharma and fine chemical sector. Preferably, enzymes or whole cells, applied as catalysts for a specific biotransformation, are utilized in aqueous reaction media since water is the natural medium for enzymes. In numerous examples of biocatalytic systems, however, a major problem is the insolubility of hydrophobic substrates in such aqueous reaction media. Apart from lipases, many enzymes are highly sensitive to organic solvents and are inactivated by an organic medium. Therefore, a change of solvent for biotransformations from water to organic solvents is usually challenging. In this study, we investigated the synthesis of nitriles by an organic solvent‐labile aldoxime dehydratase in pure organic solvents, exemplified for the dehydration of n‐octanaloxime to n‐octanenitrile. We present a method for applications in batch as well as flow mode based on an “immobilized aqueous phase” bearing the whole cells in a superabsorber as solid phase, thus enabling the use of a purely organic solvent as “mobile phase” and reaction medium.
Genetics of adaptation: Experimental test of a biotic mechanism driving divergence in traits and genes
Authors: Rennison Diana J. , Rudman Seth M. , Schluter Dolph
Published: August 2019

The genes underlying adaptations are becoming known, yet the causes of selection on genes—a key step in the study of the genetics of adaptation—remains uncertain. We address this issue experimentally in a threespine stickleback species pair showing exaggerated divergence in bony defensive armor in association with competition-driven character displacement. We used semi-natural ponds to test the role of a native predator in causing divergent evolution of armor and two known underlying genes. Predator presence/absence altered selection on dorsal spines and allele frequencies at the Msx2a gene across a generation. Evolutionary trajectories of alleles at a second gene, Pitx1, and the pelvic spine trait it controls, were more variable. Our experiment demonstrates how manipulation of putative selective agents helps to identify causes of evolutionary divergence at key genes, rule out phenotypic plasticity as a sole determinant of phenotypic differences, and eliminate reliance on fitness surrogates. Divergence of predation regimes in sympatric stickleback is associated with coevolution in response to resource competition, implying a cascade of biotic interactions driving species divergence. We suggest that as divergence proceeds, an increasing number of biotic interactions generate divergent selection, causing more evolution in turn. In this way, biotic adaptation perpetuates species divergence through time during adaptive radiation in an expanding number of traits and genes.
Hourly weather observations from the Scottish Highlands (1883–1904) rescued by volunteer citizen scientists
Authors: Hawkins Ed , Burt Stephen , Brohan Philip , Lockwood Michael , Richardson Harriett , Roy Marjory , Thomas Simon
Published: August 2019

Weather observations taken every hour during the years 1883–1904 on the summit of Ben Nevis (1345 m above sea level) and in the town of Fort William in the Scottish Highlands have been transcribed from the original publications into digital form. More than 3,500 citizen scientist volunteers completed the digitization in less than 3 months using the WeatherRescue.org website. Over 1.5 million observations of atmospheric pressure, wet‐ and dry‐bulb temperatures, precipitation and wind speed were recovered. These data have been quality controlled and are now made openly available, including hourly values of relative humidity derived from the digitized dry‐ and wet‐bulb temperatures using modern hygrometric algorithms. These observations are one of the most detailed weather data collections available for anywhere in the UK in the Victorian era. In addition, 374 observations of aurora borealis seen by the meteorologists from the summit of Ben Nevis have been catalogued and this has improved the auroral record for studies of space weather.
The Prevalence of Wilson’s Disease: An Update
Authors: Sandahl Thomas Damgaard , Laursen Tea Lund , Munk Ditte Emilie , Vilstrup Hendrik , Weiss Karl Heinz , Ott Peter
Published: August 2019

Background and Aims

In 1984, Scheinberg and Sternlieb estimated the prevalence of Wilson’s disease to be 1:30,000 based on the limited available data. This suggested a large number of overlooked cases with potentially fatal consequences. The “Scheinberg‐Sternlieb Estimate” is still widely used, although more recent clinical and genetic studies of higher quality are now available. In the present study, we included these data to update the prevalence estimate.

Approach and Results

A MEDLINE Ovid, Science Citation Index Expanded, and PubMed systematic search for all relevant studies on the prevalence of Wilson’s disease was conducted. In total, 59 studies (50 clinical and 9 population‐based genetic) were included in the final analysis. We identified 4 recent clinical studies based on nationwide databases of high quality, providing prevalence estimates from 1:29,000 to 1:40,000. Higher frequency populations do exist because of frequent first‐cousin marriages and/or a higher mutation frequency. When calculating prevalence from the incidence related to number of births, estimates were 1:40,000‐1:50,000. Clinical screening studies, including examination for Kayser‐Fleischer rings or ceruloplasmin, did not improve these estimates because of insufficient sample size or selection biases. Population‐based genetic studies in US and UK populations were not in disagreement with the clinically based estimates. At the same time, studies from France and Sardinia suggested that the genetic prevalence may be 3‐4 times higher than the clinical disease prevalence. This raises the question whether the penetrance is indeed 100% as generally assumed.

Conclusions

The original prevalence estimate from 1984 of 1:30,000‐1:50,000 still appears valid, at least for the United States, Europe, and Asia. In some population‐based studies, the genetic prevalence was 3‐4 times higher than clinically based estimates. The question of penetrance needs further evaluation.
LncRNA HULC promotes lung squamous cell carcinoma by regulating PTPRO via NF‐κB
Authors: Xu Yang , Li Jingyun , Wang Pingping , Zhang Zhenliang , Wang Xuetao
Published: August 2019

Accumulating studies have implicated that long noncoding RNA (lncRNA) plays a vital role in lung cancer. However, little is known of the role of lncRNA highly upregulated in liver cancer (HULC) in the pathogenesis of lung squamous cell carcinoma (LSCC). In this study, we investigated the modifying effects and underlying mechanisms of lncRNA HULC in LSCC. Significantly decreased level of lncRNA HULC was observed in LSCC samples compared with adjacent tissues. Besides, the expression of lncRNA HULC was negatively associated with protein tyrosine phosphatase receptor type O (PTPRO) in LSCC. Moreover, lncRNA HULC could promote the proliferation of LSCC cells by downregulating the expression PTPRO dependent on the phosphorylation and activation of nuclear factor‐κB (NF‐κB). The present study firstly shows strong evidence supporting a critical role of lncRNA HULC in promoting LSCC by regulating PTPRO/NF‐κB signaling pathway, which provides new promising biomarkers for LSCC.
How residents in multifamily housing cope with neighbour noise: The role of attitude towards the neighbours
Authors: Park Sang Hee , Lee Pyoung Jik
Published: August 2019

Aims

Residents in multifamily housing are considerably exposed to neighbour noise, which can lead to neighbour disputes and even criminal violence. This study investigated how residents’ attitudes towards noisy neighbours develop and the role of such attitudes in their reactions to neighbour noise.

Methods

In‐depth interviews were carried out with 57 South Korean residents. The data were collected and analyzed using grounded theory methods. Concepts and categories were identified through open coding and axial coding, respectively.

Results

Residents’ attitudes towards the neighbours (i.e., noise source) were grouped into friends, enemies, and strangers/acquaintances. Each attitude formation was influenced by the individual's past experience/history, the attitude shown by the neighbours, and the predictability/certainty of noise exposure. Different attitudes towards the neighbours resulted in different cognitive and behavioural copings.

Conclusion

Given that the neighbour noise issue involves the interpersonal relationship between neighbours, the findings extend the scope of existing understanding. The paper suggests that further investigation into coping strategies would have practical implementations for reducing conflict arising from neighbour disputes.
Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants
Authors: Hammer Gregory B. , Maxwell Lynne G. , Taicher Brad M. , Visoiu Mihaela , Cooper David S. , Szmuk Peter , Pheng Leng Hong , Gosselin Nathalie H. , Lu Jia , Devarakonda Krishna
Published: August 2019

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo‐controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24 hours were enrolled. Subjects were randomly assigned to receive intravenous acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of intravenous acetaminophen was updated by combining 581 samples from the current study of 158 neonate and infant subjects with results from a previously developed model. The individual predicted‐versus‐observed concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen concentration‐versus‐time profiles in the active and placebo groups. Terminal elimination half‐life was prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults. When compared with placebo, total rescue opioid consumption was similar and significantly fewer intravenous acetaminophen patients prematurely discontinued because of treatment‐emergent adverse events (P < .01). For intravenous acetaminophen, neonates receiving 12.5 mg/kg every 6 hours had PK profiles similar to younger, intermediate, and older infants, adolescents, and adults weighing <50 kg receiving 15 mg/kg every 6 hours and adults ≥ 50 kg receiving 1000 mg every 6 hours.
Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure‐Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib
Authors: Mohamed Mohamed‐Eslam F. , Beck Denise , Camp Heidi S. , Othman Ahmed A.
Published: August 2019

Upadacitinib is a selective Janus kinase (JAK) 1 inhibitor being developed for treatment of rheumatoid arthritis. This study characterizes the relationships between upadacitinib exposure and interleukin (IL)‐6–induced signal transducer and activator of transcription proteins 3 (STAT3) phosphorylation (pSTAT3) and IL‐7–induced STAT5 phosphorylation (pSTAT5) in the ex vivo setting as measures for JAK1 and JAK1/JAK3 inhibition, respectively, with comparison to tofacitinib. Drug plasma concentrations and ex vivo IL‐6–induced pSTAT3 and IL‐7–induced pSTAT5 in blood from subjects evaluated in 2 phase 1 studies who received immediate‐release 1 mg to 48 mg upadacitinib, 5 mg twice daily (BID) tofacitinib, or placebo were determined. Exposure‐response models were developed, and the effects of different upadacitinib doses on ex vivo biomarker responses were simulated and compared to tofacitinib. Upadacitinib (and tofacitinib) reversibly inhibited IL‐6–induced pSTAT3 and IL‐7–induced pSTAT5 in a concentration‐dependent manner. Model‐estimated values of 50% of the maximum effect were 60.7 nM for upadacitinib and 119 nM for tofacitinib for IL‐6–induced pSTAT3 inhibition, and 125 nM for upadacitinib and 79.1 nM for tofacitinib for IL‐7–induced pSTAT5 inhibition. Tofacitinib 5 mg BID is estimated to have a similar magnitude of effect on IL‐6–induced pSTAT3 to ∼3 mg BID of upadacitinib (immediate‐release formulation), whereas a 4‐fold higher dose of upadacitinib (∼12 mg BID), is estimated to show a similar magnitude of inhibition on IL‐7–induced pSTAT5 as tofacitinb 5 mg BID. This study confirms that in humans, upadacitinib has greater selectivity for JAK1 vs JAK3 relative to the rheumatoid arthritis approved dose of tofacitinib, and results from these analyses informed the selection of upadacitinib IR doses evaluated in phase 2.
New Thiophene Derivatives as Antimicrobial Agents
Authors: Mabkhot Yahia Nasser , Kaal Nahed Ahmed , Alterary Seham , Mubarak Mohammad S. , Alsayari Abdulrhman , Bin Muhsinah Abdullatif
Published: August 2019

Phenacylbromide derivatives constitute a multilateral group of precursors for the synthesis of numerous heterocycles of organic compounds. Briefly, 5‐(2‐bromo‐acetyl)‐substituted‐thiophene derivative has been used as a synthon for synthesis of new thiophene‐containing compounds through the reaction with nucleophilic nitrogen compounds and thioamides. The suggested structures of the newly synthesized thiophene compounds were confirmed and assured with different spectroscopic tools and with CHN elemental analysis. Additionally, the antimicrobial activity of these thiophene compounds was recorded to investigate their potency against various types of bacteria and fungi. Results showed that these compounds exhibit significant inhibitory activity against the growth of tested bacterial and fungal strains and that some derivatives were more potent than the employed reference drugs.
An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure–Associated Liver Disease in Infants With Intestinal Failure
Authors: Belza Christina , Wales John C. , Courtney‐Martin Glenda , de Silva Nicole , Avitzur Yaron , Wales Paul W.
Published: August 2019

Background

SMOFlipid has a more diverse lipid profile than traditional Intralipid and has become the standard lipid for patients in our intestinal rehabilitation program. Our objective was to compare outcomes in neonates with intestinal failure (IF) who received SMOFlipid against those receiving Intralipid.

Methods

This was a retrospective cohort study of infants with IF with a minimum follow‐up of 12 months in 2008–2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels. Statistical analysis included the Mann‐Whitney U and χ2 tests, with an α value < 0.05 considered significant. Approval was obtained from our institutional review board.

Results

Thirty‐seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z‐scores were improved for patients receiving SMOFlipid at 3 months (−0.932 vs −2.092; P = 0.028) and 6 months (−0.633 vs −1.614; P = 0.018). There were no differences in PN‐supported patients or demographics between the groups.

Conclusion

Use of SMOFlipid resulted in decreased development of IF‐associated liver disease in patients with IF when assessed using biochemical tests.
A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique
Authors: Gamboa Adriana C. , Liu Yuan , Lee Rachel M. , Zaidi Mohammad Y. , Staley Charles A. , Russell Maria C. , Cardona Kenneth , Sullivan Patrick S. , Maithel Shishir K.
Published: August 2019

Background/Objective

Staging and type of resection for rectal neuroendocrine tumors (R‐NETS) relies on preoperative identification of lymph node (LN) involvement. Study objective was to develop a Preoperative Rectal Stratification Score (PReSS) for LN‐positivity and to assess the association of PReSS with overall survival (OS).

Methods

All patients in the National Cancer Database (2004‐2014) with non‐metastatic/nonfunctional R‐NETS were included. Tumor size was divided into three categories (<1, 1‐2, and ≥2 cm).

Results

Among 383 patients, median age was 57 years, 52% were male (n = 200), median tumor size was 1.4 cm, 43% had positive LNs (n = 163). On univariate analysis, age  > 60, poorly differentiated grade, depth of invasion past submucosa, and size >1 cm were associated with LN positivity. On multivariable analysis, depth of invasion past submucosa, and increasing tumor size >1 cm remained associated with LN positivity. As these can be determined preoperatively, incidence of LN positivity was determined for each combination of tumor size and depth of invasion. Each variable was assigned a score to create a PReSS of four groups (0‐3) associated with an increasing rate of LN‐positivity (PReSS group 0: 11%, 1: 38%, 2: 50%, 3: 78%, P < .01). PReSS correlated with 10‐year OS (PReSS 0: 90%; 1: 81%; 2: 59%; 3: 41%).

Conclusion

For R‐NETS, depth of invasion and tumor size predict LN positivity and both can be obtained preoperatively. PReSS incorporates both variables and stratifies tumors into four risk groups of progressively increasing LN positivity and should be used to guide surgical approach.
Risk factors for unplanned readmission in total laryngectomy patients
Authors: Vimawala Swar , Topf Michael C. , Savard Corey , Zhan Tingting , Keane William , Luginbuhl Adam , Goldman Richard , Cognetti David M. , Curry Joseph M.
Published: August 2019

Objective

To determine which patient or surgical factors affect the likelihood of unplanned readmission (within 30 days) after total laryngectomy (TL).

Methods

Retrospective chart review of all patients who underwent TL at a single institution from April 2007 through August 2016. Primary outcome was unplanned readmission to the hospital within 30 days of discharge. Univariable and multivariable logistic regression were performed to identify risk factors for unplanned readmission.

Results

Two hundred seventy‐eight patients met inclusion criteria. Twenty‐nine patients (10.4%) had unplanned readmissions within 30 days. The most common reasons for readmission were pharyngocutaneous fistula (n = 15), neck abscess (n = 3), and wound breakdown (n = 4). Average time to unplanned readmission was 11.2 days (range 0–27 days). Fistula (OR 30.259; 95% CI, 9.186, 118.147; P ≤ .001), postoperative pneumonia (OR 9.491; 95% CI, 1.783, 53.015; P = .008), and history of cardiac disease (OR 7.074; 95% CI, 2.324, 25.088, P = .001) were independently associated with an increased risk of 30‐day unplanned readmission on multivariate analysis. However, return to OR on initial admission was associated with a lower risk of unplanned readmission (OR 0.075; 95% CI, 0.009, 0.402; P = .007). Unplanned readmission was associated with a delay in initiation of adjuvant radiation (OR 1.494; 95% CI, 1.397, 1.599; P < .001).

Conclusion

Unplanned readmission occurs in a small but significant number of TL patients. Patients who have a 30‐day unplanned readmission may be at risk for a delay in initiation of adjuvant therapy.

Level of Evidence

4 Laryngoscope, 130:1725–1732, 2020
Static endoscopic swallow evaluation in children
Authors: Meister Kara D. , Okland Tyler , Johnson April , Galera Rhona , Ayoub Noel , Sidell Douglas R.
Published: August 2019

Objectives

Static Endoscopic Evaluation of Swallowing (SEES) has been demonstrated to have a strong correlation with the Videofluoroscopic Swallow Study (VFSS) in adults. In children, Fiberoptic Endoscopic Evaluations of Swallow (FEES) are frequently performed to avoid repeated VFSS; however, a subset of the population does not tolerate FEES. The purpose of this study was to evaluate the utility of a modified SEES in children.

Methods

Charts of 50 consecutive patients who underwent FEES evaluations were reviewed. Patients age 3 months to 12 years undergoing SEES, FEES, and VFSS were extracted. We compared a binary assessment of outcome on SEES versus VFSS as the diagnostic standard to report characteristics, including sensitivity, specificity, and positive and negative predicted value.

Results

A total of 36 patients met all inclusion criteria (mean age 2.8 years). Using the VFSS as the diagnostic standard, residue seen on SEES had a sensitivity of 80.0%, specificity of 85.7%, a positive predictive value of 88.9%, and a negative predictive value of 75.0% for predicting deep penetration or aspiration.

Conclusion

SEES may be helpful for developing an initial diagnostic impression and may serve as a platform for patient and caregiver counseling. In children who are unable to cooperate with FEES, SEES may provide clinical insight in predicting an abnormal swallow study; however, a normal SEES was less reliable in predicting a safe swallow on subsequent VFSS in this patient population.

Level of Evidence

4 Laryngoscope, 130:1590–1594, 2020
Effects of intragenomic polymorphism in the SSU rRNA gene on estimating marine microeukaryotic diversity: A test for ciliates using single‐cell high‐throughput DNA sequencing
Authors: Zhao Feng , Filker Sabine , Xu Kuidong , Li Ju , Zhou Tong , Huang Pingping
Published: August 2019

Diversity assessments using the small subunit (SSU) rRNA gene allow for rapid assessments of microeukaryotic communities. Yet, for microeukaryotes, only limited information is available on the extent to which sequence variations within individual genomes exist at this locus. We investigated 14 marine species belonging to four major ciliate groups by single‐cell high‐throughput DNA sequencing to estimate the extent of intragenomic polymorphism in the V4 region of the SSU rRNA gene. Based on these results, we evaluated the potential effect of polymorphism on metabarcoding studies. The intragenomic variability was generally below 3% among about 1000 unique sequences obtained from each studied cell, except of Protocruzia sp., whose intragenomic variability was as high as 15.6% among about 2000 unique sequences. Intragenomic variations significantly correlated with the number of macronuclei, but not with the biovolume of cell or macronuclei, indicating the occurrence of nonuniform evolution within the macronuclei. The removal of rare unique sequences greatly decreased the number of variations. For diversity studies, we therefore propose to conservatively discard rare amplicons. Considering the intragenomic variation within the V4 region, a sequence similarity cutoff of 3% to delimit marine ciliate operational taxonomic units could be substantiated, as at least this threshold could exclude most effect of intragenomic polymorphisms, although it may be too strict for some particular groups.
Spectral Difference Interferometry for the Characterization of Optical Media
Authors: Bottrill Kyle R. H. , Ettabib Mohamed A. , Demirtzioglou Iosif , Marchetti Riccardo , Lacava Cosimo , Parmigiani Francesca , Richardson David J. , Petropoulos Periklis
Published: August 2019

A new form of interferometry combining high phase sensitivity and excellent mechanical isolation is proposed and demonstrated. These features arise from maintaining a probe and reference tone in the same medium under test at all times, their ultimate homodyne detection, as well as a novel method employing an optical programmable filter which is used to extract their relative phase difference. A compilation of studies performed to illustrate the applicability of the scheme to a range of measurements of optical propagation characteristics is presented. Measurements include the chromatic dispersion of SMF‐28 of lengths ranging from 1 m to 1 km, the nonlinear coefficient of highly nonlinear fiber and the phase transfer profile of an integrated optical ring resonator.
In Situ Viscosity‐Controlled Electrospinning with a Low Threshold Voltage
Authors: He Haijun , Kara Yahya , Molnár Kolos
Published: August 2019

In the present study, a novel electrospinning method is proposed,where jet formation is aided by shearing the solution in situ. With a generalpolymer solution, viscosity decreases by shearing, that is, the solution isshear‐thinning. Poly(ethylene‐oxide) is used as a model polymer andthe effects of rotation speed, solution concentration, and gap size (the widthof the annular orifice) on the process and the morphology of the obtainedfibers are investigated. It is found that the threshold voltage for generatingmultiple jets decreased from 35 to 12 kV when rotation speed is higher than60 rpm (or shear rate more than 310 s−1). Additionally, the results show thatfiber diameter increases as the concentration of the solution increases. Thechi‐square two‐sample test is used to compare the distribution of fibersproduced by the capillary method and the novel electrospinning process. Inthe authors' method, the viscosity of the solution can be changed by applyingmechanical forces on it during the electrospinning process, which results inthe initiation of the electrospinning jet at a low threshold voltage. It is alsofound that gap size has a similar effect on fiber diameter as needle diameter in classical electrospinning.
The Influence of Pre‐Electrospinning Plasma Treatment on Physicochemical Characteristics of PLA Nanofibers
Authors: Rezaei Fatemeh , Planckaert Tom , Vercruysse Chris , Verjans Jente , Van Der Voort Pascal , Declercq Heidi , Hoogenboom Richard , Morent Rino , De Geyter Nathalie
Published: August 2019

Morphology, crystallinity, thermal, and mechanical properties of nanofibrous mats are known to highly affect the behavior of these materials in desired applications. In this study, multiple characteristics of poly(lactic acid) (PLA) nanofibrous mats prepared from plasma‐treated pre‐electrospinning solutions are studied as a function of various plasma operational parameters. X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, X‐ray photoelectron spectroscopy, scanning electron microscopy, and tensile tests are performed. In addition, the pristine and plasma‐treated PLA solutions are examined with size exclusion chromatography to study the effect of the conducted pre‐electrospinning plasma treatments (PEPT) on the molecular weight of PLA. Aging analysis of the pristine and plasma‐treated solutions is also performed by evaluating the viscosity, conductivity, surface tension, and pH during an aging period of 10 days. To investigate if the results are only affected by the plasma treatment or also affected by the electrospinning, pristine and plasma‐treated PLA cast layers are also analyzed. The results reveal that PEPT preserved the surface chemical composition of the nanofibers and the molecular weight distribution of PLA, while morphology and mechanical properties of the nanofibers are considerably enhanced. Moreover, plasma‐treated polymer solutions resulted in the formation of nicely elongated nanofibers up to 4 days after plasma treatment.
Three‐reaction high‐resolution melting assay for rapid differentiation of Mycobacterium tuberculosis complex members
Authors: Landolt Patricia , Stephan Roger , Stevens Marc J. A. , Scherrer Simone
Published: August 2019

The possibility of introducing a reliable assay for a quick identification and differentiation of the main species of Mycobacterium tuberculosis complex (MTBC) supports the improvement of efficient tuberculosis combating strategies worldwide. Commercially available assays are often based on cultured samples; however, due to the long cultivation time of mycobacteria, results are delayed. Developed PCR approaches have been published previously, though, when testing intricate veterinary samples, the complex composition of multiplex qPCRs frequently leads to assay failure. In order to overcome those limits, a paradigm of a three‐reaction high‐resolution melting (HRM) assay for the simultaneous identification and differentiation of the main members of MTBC was established. The assay is based on single nucleotide polymorphisms within gyrB and gyrA, which have been used as target for the establishment of two highly specific HRM assays (HRM assays 1 and 2) discriminating M. tuberculosis/ Mycobacterium canetti, Mycobacterium bovis/M. bovis BCG, Mycobacterium caprae/rare M. caprae/M. bovis ecotypes, Mycobacterium africanum/Mycobacterium orygis/ Mycobacterium pinnipedii/Clade A1, Mycobacterium microti, and a rare subtype of M. canettii followed by a third HRM assay (HRM assay 3) allowing a further differentiation of M. bovis, M. bovis BCG, and a rare subtype of M. caprae/M. bovis, which is considered to be a novel ecotype. High‐resolution melting assay 1 is described in a previously published report. High‐resolution melting assay 2 showed 100% correlation of all 39 examined isolates with the results of a commercial identification kit. 96% of the clinical samples tested demonstrated concordant results. High‐resolution melting assay 3 showed an accordance of 100% with the results of the commercially available identification kit of all 22 samples analyzed. The proposed strategy of the three‐reaction HRM assay can be used for an accurate differentiation of up to seven groups of MTBC and potentially to identify a rare subtype of M. canettii either on isolates or on clinical samples.
YY1 cooperates with TFEB to regulate autophagy and lysosomal biogenesis in melanoma
Authors: Du Jing , Ren Wenyan , Yao Fengping , Wang Hong , Zhang Kexin , Luo Meiying , Shang Yuxue , O'Connell Douglas , Bei Zhuchun , Wang Hongquan , Xiong Ran , Yang Yongfei
Published: August 2019

Autophagy is a self‐proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are rarely identified. Here, we found that Yin Yang 1 (YY1) regulated autophagy and lysosome biogenesis in melanoma cells. YY1 cooperates with TFEB to regulate autophagy through controlling the transcription of autophagy and lysosome biogenesis related genes. Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment.
Seeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy
Authors: Espa Elena , Clemensson Erik K.H. , Luk Kelvin C. , Heuer Andreas , Björklund Tomas , Cenci M. Angela
Published: August 2019

Background

Cortical α‐synuclein pathology plays a role in the development of cognitive dysfunction in both Parkinson's disease and dementia with Lewy bodies, although the causative cellular lesions have remained unclear. We aimed to address causal links between α‐synuclein‐driven pathology in the cerebral cortex and the development of cognitive impairments using new experimental models.

Methods

Neuronal overexpression of human α‐synuclein was induced in the rat medial prefrontal cortex using viral vectors. This was combined with inoculations of preformed fibrils of human α‐synuclein in some animals. Rats were evaluated with tests probing prefrontal cognitive functions (delayed matching/nonmatching to position and 5‐choice serial reaction time task). Patterns of neuropathology were characterized immunohistochemically.

Results

Neither α‐synuclein overexpression nor the fibril seeds alone yielded any behavioral phenotype. In contrast, combining the 2 approaches produced significant impairments in working memory, attention, and inhibitory control. All animals injected with α‐synuclein vectors exhibited high immunoreactivity for human α‐synuclein in the medial prefrontal cortex and its primary projection targets. However, only when this overexpression was combined with fibril inoculations did animals exhibit large, proteinase K‐resistant and Ser129‐phosphorylated α‐synuclein intraneuronal inclusions in the medial prefrontal cortex and its closely interconnected brain regions. The inclusions were associated with distorted dendritic morphologies and partial neuronal loss in the targeted cortical areas.

Conclusions

Cortical overexpression of human α‐synuclein is not sufficient to produce cognitive dysfunction, whereas combining this overexpression with fibril seeds yields both cognitive and histopathological phenotypes that are relevant to human Lewy body disease. © 2019 International Parkinson and Movement Disorder Society
Twenty years on: Myoclonus‐dystonia and ε‐sarcoglycan — neurodevelopment, channel, and signaling dysfunction
Authors: Menozzi Elisa , Balint Bettina , Latorre Anna , Valente Enza Maria , Rothwell John C. , Bhatia Kailash P.
Published: August 2019

Myoclonus‐dystonia is a clinical syndrome characterized by a typical childhood onset of myoclonic jerks and dystonia involving the neck, trunk, and upper limbs. Psychiatric symptomatology, namely, alcohol dependence and phobic and obsessive‐compulsive disorder, is also part of the clinical picture. Zonisamide has demonstrated effectiveness at reducing both myoclonus and dystonia, and deep brain stimulation seems to be an effective and long‐lasting therapeutic option for medication‐refractory cases. In a subset of patients, myoclonus‐dystonia is associated with pathogenic variants in the epsilon‐sarcoglycan gene, located on chromosome 7q21, and up to now, more than 100 different pathogenic variants of the epsilon‐sarcoglycan gene have been described. In a few families with a clinical phenotype resembling myoclonus‐dystonia associated with distinct clinical features, variants have been identified in genes involved in novel pathways such as calcium channel regulation and neurodevelopment. Because of phenotypic similarities with epsilon‐sarcoglycan gene–related myoclonus‐dystonia, these conditions can be collectively classified as “myoclonus‐dystonia syndromes.” In the present article, we present myoclonus‐dystonia caused by epsilon‐sarcoglycan gene mutations, with a focus on genetics and underlying disease mechanisms. Second, we review those conditions falling within the spectrum of myoclonus‐dystonia syndromes, highlighting their genetic background and involved pathways. Finally, we critically discuss the normal and pathological function of the epsilon‐sarcoglycan gene and its product, suggesting a role in the stabilization of the dopaminergic membrane via regulation of calcium homeostasis and in the neurodevelopmental process involving the cerebello‐thalamo‐pallido‐cortical network. © 2019 International Parkinson and Movement Disorder Society
Targeting B7‐1 in immunotherapy
Authors: Chen Rui , Ganesan Aravindhan , Okoye Isobel , Arutyunova Elena , Elahi Shokrollah , Lemieux M. Joanne , Barakat Khaled
Published: August 2019

Modulation of T‐cell immune functions by blocking key immune checkpoint protein interactions using monoclonal antibodies (mAbs) has been an innovative immunotherapeutic strategy. T‐cells are regulated by different checkpoint proteins at the immunological synapse including the B7 ligands (B7‐1 or CD80 and B7‐2 or CD86), which is discussed in this review. These ligands are typically expressed on antigen presenting cells and interact with CD28 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4) receptors on T‐cells. Their interactions with CD28 trigger a costimulatory signal that potentiates T‐cell activation, function and survival in response to cognate antigen. In addition, their interactions with CTLA‐4 can also inhibit certain effector T‐cell responses, particularly in response to sustained antigen stimulation. Through these mechanisms, the balance between T‐cell activation and suppression is maintained, preventing the occurrence of immunopathology. Given their crucial roles in immune regulation, targeting B7 ligands has been an attractive strategy in cancer and autoimmunity. This review presents an overview of the essential roles of B7‐1, highlighting the therapeutic benefits of modulating this protein in immunotherapy, and reviewing earlier and state‐of‐the‐art efforts in developing anti‐B7‐1 inhibitors. Finally, we discuss the challenges facing the design of selective B7‐1 inhibitors and present our perspectives for future developments.