bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistent adenoma and serrated polyps on index colonoscopy and the risk of metachronous advanced colorectal neoplasia
Authors: Park Soo-Kyung , Kim Hak-Soo , Yang Hyo-Joon , Jung Yoon Suk , Park Jung Ho , Sohn Chong Il , Park Sang Hyun , Sohn Jin Hee , Lee Mi Yeon , Park Dong Il
Published: December 2019

Background and aims The family of serrated polyps (SP) includes hyperplastic polyps (HP), sessile serrated adenomas/polyps, and traditional serrated adenoma. We investigated whether SP synchronous with adenoma at index colonoscopy is associated with metachronous advanced colorectal neoplasia (CRN).

Methods Patients with ≥ 1 adenoma on index colonoscopy and who had undergone a follow-up colonoscopy were included. The patients were divided into four groups according to the presence of SP and advanced adenoma (AA) on index colonoscopy (non-AA, non-AA + SP, AA, AA + SP). The cumulative incidence of metachronous advanced CRN at surveillance colonoscopy was compared between groups.

Results Among a total of 2209 patients, the numbers of patients in the non-AA, non-AA + SP, AA, and AA + SP groups were 922, 441, 625, and 221, respectively. The cumulative incidence of metachronous advanced CRN was higher in patients in the AA + SP group than that in the AA group (P<0.001), and there was no significant difference between the non-AA + SP group and the non-AA group (P = 0.06). The cumulative incidence of metachronous advanced CRN at 3 years was 17.9 % [95 % confidence interval (CI) 8.0–27.6], 10.7 % [95 %CI 7.7–3.6], 3.5 % [95 %CI 1.3–5.6], and 3.4 % [95 %CI 2.0–4.7] in the AA + SP, AA, non-AA + SP, and non-AA group, respectively. In a multivariate analysis, overall SP [hazard ratio (HR) 2.24; 95 %CI 1.38–3.64, P = 0.001], proximal SP (HR 2.31; 95 %CI 1.32–4.08), and HP (HR 2.19; 95 %CI 1.35–3.57) were risk factors for metachronous advanced CRN in patients with AA on index colonoscopy.

Conclusions Coexistent AA and SP on index colonoscopy significantly increased the risk of metachronous advanced CRN compared with AA alone. Further large prospective studies are needed to confirm whether more intensive follow-up improves outcomes in these high risk patients.
Needle-knife fistulotomy vs. standard biliary sphincterotomy for choledocholithiasis: common bile duct stone recurrence and complication rate
Authors: Archibugi Livia , Mariani Alberto , Capurso Gabriele , Traini Mariaemilia , Petrone Maria Chiara , Rossi Gemma , Testoni Sabrina Gloria Giulia , Testoni Pier Alberto , Arcidiacono Paolo Giorgio
Published: December 2019

Background and study aims With common bile duct (CBD) stones, access to the CBD can be achieved through the papilla orifice followed by standard biliary sphincterotomy (SBS), or through precut fistulotomy (PF) in case of difficult cannulation. The two methods alter papilla anatomy differently, potentially leading to a different rate of stone recurrence. No data have been published on stone recurrence after PF in patients with CBD stones. The aim of this study was to evaluate CBD stone recurrence, reintervention rate after PF versus SBS, and complications.

Patients and methods This was a retrospective single-center cohort study including patients undergoing for the first time endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones with PF in case of failed repeated cannulation attempts, matched for sex/age to patients with SBS randomly extracted from our database. T-test and Fisher’s tests were used for continuous and categorical variable comparison. Recurrence probability was calculated with Kaplan–Meier curve. Factors associated with ERCP repetition were evaluated with logistic regression through a Cox’s proportional hazards model.

Results Eighty-five patients with PF were included, with 85 matched controls (mean age 68.7 years, 45.9 % males). Overall, patients with PF had the same reintervention rate as those with SBS (14.1 % vs. 12.9 %) with a hazard ratio (HR) of 1.11 (95 % CI 0.49 – 2.50; P = 0.81), but mean time to reintervention was significantly lower (74.9 ± 74.6 vs. 765.6 ± 961.3 days; P < 0.0001), with 100 % of stones recurring within the first year in the PF group vs. 54.5 % in the SBS group (P = 0.01). The only factor associated with ERCP repetition risk was incomplete CBD clearing. Complications, including pancreatitis, did not differ significantly.

Conclusions The reintervention rate was significantly higher in the short term after PF. Therefore, closer follow-up in the first 6 to 12 months after ERCP might be appropriate for patients underoing PF.
Leistungs- und Abrechnungsdatum in GKV-Routinedaten: Umgang mit
zeitlichen Abweichungen
Authors: Ditscheid Bianka , Storch Josephine , Krause Markus , Meyer Ingo , Freytag Antje
Published: December 2019

Ziel Ziel dieser Untersuchung ist es, das aus dem Auseinanderfallen von
Leistungs- und Abrechnungsdatum in Krankenkassenroutinedaten resultierende
Risiko von Fehleinschätzungen der Inanspruchnahme in verschiedenen
Leistungsbereichen (ambulante ärztliche Behandlung, Arzneimittel, Heil-
und Hilfsmittel, Krankenhaus) in Bezug zum Tod als Indexereignis sowie in Bezug
zum Jahreswechsel zu quantifizieren, Erklärungsansätze
darzulegen und mögliche Lösungsstrategien aufzuzeigen.

Methodik In einem Wissenschaftlichen Data Warehouse einer großen
deutschen Krankenkasse standen vorstrukturierte Daten von in 2016 verstorbenen
Versicherten zur Verfügung. Die Darstellung zeitlicher Abweichungen von
Leistungs- und Abrechnungsdaten erfolgte für verschiedene ambulante und
stationäre Versorgungsbereiche unter Heranziehung von Daten der Jahre
2015 bis 2017. Ein exaktes Abrechnungsdatum (TT/MM/JJJJ) war
lediglich bei Heil- und Hilfsmittelverordnungen verfügbar. Bei
Arzneimittel-Verordnungen war das Abrechnungsdatum lediglich monatsgenau
(MM/JJJJ). Bei ambulanten ärztlichen Leistungen lag nur das
Abrechnungsquartal vor (Q/JJJJ).

Ergebnisse Die Analysen zeigen, dass im Leistungsbereich der ambulanten
ärztlichen Behandlung und der Krankenhausbehandlung <1%
der Fälle/Gebührenordnungspositionen (GOP)/OPS
nach dem Tod abgerechnet wurden, im Bereich der Heil- und Hilfsmittel jedoch
28–31% der Verordnungen (VO). Ein Großteil der
Leistungsabrechnungen nach dem Tod erfolgte innerhalb von 3 Monaten (93%
der Heil- und Hilfsmittel, 67% der ambulanten ärztlichen
Behandlungsfälle). Über den Jahreswechsel 2015/2016
zeigte sich eine zeitliche Differenz bei <1% der ambulanten GOP
bis hin zu 18% bei den Heilmittel-VO. Auch hier wurde die Mehrzahl der
Leistungen innerhalb der ersten 3 Monate nach dem Jahreswechsel abgerechnet
(100% der Heil- und Hilfsmittel, 65% der ambulanten GOP).

Schlussfolgerung Der zeitliche Verzug zwischen Leistungs- und
Abrechnungsdaten stellt bei Analysen der GKV-Leistungsinanspruchnahme bis zum
Tod eines Versicherten sowie beim Jahreswechsel eine Herausforderung dar und ist
eine Quelle für Unter-/Überschätzungsfehler. So
ist bei Datenanforderung, -aufbereitung und -auswertung explizit darauf zu
achten, dass auch noch nach dem zu betrachtenden Zeitraum abgerechnete
Leistungen berücksichtigt werden.
Management of Patients Symptomatically Unresponsive to Levothyroxine:
Natural Desiccated Thyroid Extract or the Combination of Levothyroxine and
Liothyronine? A Research Priority
Authors: Heald Adrian , Livingston Mark , Hughes Dyfrig
Published: December 2019

Around 5–10% of hypothyroid patients continue to experience
profound and sometimes disabling symptoms, including fatigue, depression and
impaired cognition, in spite of being adequately replaced biochemically. The use
of the combination of levothyroxine and liothyronine and natural desiccated
thyroid extract is controversial for reasons of costs, a lack of evidence of
additional benefit over levothyroxine alone, and potential safety concerns.
Clinical guidelines caution against the use of both, and advise that only in
exceptional cases may a short trial be considered. Natural desiccated thyroid
extract is not licensed for use in the UK. However, key deficiencies in the
existing evidence-base together with improved understanding of the pharmacology
of levothyroxine resistance, indicates that now is the right time for a
definitive clinical trial to address this important area of uncertainty.
Langwirksame Buprenorphinpräparate als neue pharmakologische
Option bei Opiatabhängigkeit
Authors: Soyka Michael
Published: December 2019

Die Opioidsubstitution mit Methadon (oral) oder Buprenorphin (sublingual) ist
eine etablierte weltweit praktizierte First-Line-Behandlung der
Opiatabhängigkeit. Beide Substanzen müssen täglich oder
zumindest alle 2 Tage (Buprenorphin) gegeben werden. Langwirksame Opioide
standen zur Substitution nicht zur Verfügung. Das ändert sich
jetzt mit dem bereits zugelassenen, wöchentlich oder monatlich subkutan
injizierbaren Buprenorphin Depot CAM 2038 (Buvidal®), dem
monatlich zu applizierenden Depotpräparat RBP-6000 (Sublocade™)
und dem 6-Monate wirkenden Buprenorphin Depot-Implantat (Probuphine™).
Klinische Befunde und mögliche Indikationen dieser Medikamente werden
diskutiert.
Transition-Metal-Free Aerobic Oxidative Cross-Coupling of Indoles with Arylidenemalononitriles
Authors: Yang Aizhen , Li Zheng
Published: December 2019

An efficient method for the direct construction of C(sp2)–C(sp2) bonds by aerobic oxidative cross-coupling of indoles with arylidenemalononitriles is described. Various [aryl(1H-indol-3-yl)methylene]malononitriles were efficiently synthesized by using air as an oxidant under mild conditions. The salient features for this protocol are no transition-metal catalysts, no organometallic reagents, high atom economy, high yield, mild conditions, and simple workup procedures.
Pineal Parenchymal Tumor with Intermediate Differentiation—A Case Report and Review of Literature from Rural India
Authors: Kumar Raj , Dayal Seema , Krishna Mani
Published: December 2019

Pineal gland tumors are rare tumors. According to World Health Organization (WHO) classification (2016) of the central nervous system, pineal parenchymal tumors of intermediate differentiation (PPTID) occupied their position between pineocytoma and pineoblastoma. It is either grade II or III. There are small numbers of reported cases, so its classification is still a matter of controversy. Here, we report a case of a 35-year-old man who presented with complaints of headache, nausea, vomiting, and focal weakness for 1 year. Computed tomography revealed an enhancing mass lesion in the region of pineal gland along with hydrocephalus. Following operation, histopathology of excised specimen was done, and it showed cellular tumor. Cells were having larger nuclei, vesicular chromatin pattern, ample cytoplasm, focal neuropil-like stroma along with moderate atypia, 3 to 5 mitotic figures per 10 hpf (high-power field), marked vascular proliferation, and pseudo rosette. Immunohistochemistry was found strongly positive for glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), variable for synaptophysin, and negative for neurofilament and epithelial membrane antigen (EMA). These findings confirmed the diagnosis. As this tumor is rare with uncertain behavior following available treatment, the case report of PPTID grade III large cell type may enrich the existing data and is being presented because of its rarity.
Left Atrial to Femoral Artery Full Cardiopulmonary Bypass: A Novel Technique for Descending and Thoracoabdominal Aortic Surgery
Authors: Papanikolaou Dimitra , Savio Chris , Zafar Mohammad A. , Freudzon Leon , Wu Jinlin , Abdelbaky Mohamed , Pelletier Keith J. , Buntin Joelle , Faggion Vinholo Thais , Ziganshin Bulat A. , Schwartz Brian , Elefteriades John A.
Published: December 2019

Left atrial-femoral artery (LA-FA) bypass with a centrifugal pump and no oxygenator is commonly used for descending and thoracoabdominal aortic (DTAA) operations, mitigating the deleterious effects of cross-clamping. We present our initial experience performing DTAA replacement under LA-FA (left-to-left) cardiopulmonary bypass (CPB) with an oxygenator. DTAA replacement under LA-FA bypass with an oxygenator was performed in 14 consecutive patients (CPB group). The pulmonary vein and femoral artery (or distal aorta) were cannulated and the full CPB machine were used, including oxygenator, roller pump, pump suckers, and kinetically enhanced drainage. The CPB group was compared with 50 consecutive patients who underwent DTAA replacement utilizing traditional LA-FA bypass without an oxygenator (LA-FA group). Perioperative data were collected and statistical analyses were performed. All CPB patients maintained superb cardiopulmonary stability. The pump sucker permitted immediate salvage and return of shed blood. Superb oxygenation was maintained at all times. High-dose full CPB heparin was reversed without difficulty. The CPB group required markedly fewer blood transfusions than the LA-FA group (2.21 vs. 5.88 units, p < 0.004). The 30-day mortality rate was 7.1% (n = 1) and there were no paraplegia cases in the CPB group versus 7 (14%) deaths and 3 (6%) paraplegia cases in the LA-FA group. Traditional LA-FA bypass without an oxygenator avoids high-dose heparin. In the present era, heparin reversal is more secure. Our experience finds that the novel application of LA-FA CPB with an oxygenator is safe and suggests improved hemodynamics (immediate return of shed blood) and a hemostatic advantage (avoidance of loss of coagulation factors in the cell saver).
AGE–RAGE Stress in the Pathophysiology of Atrial Fibrillation and Its Treatment
Authors: Prasad Kailash
Published: December 2019

Atrial fibrillation (AF) is the most common of cardiac arrhythmias. Mechanisms such as atrial structural remodeling and electrical remodeling have been implicated in the pathogenesis of AF. The data to date suggest that advanced glycation end products (AGEs) and its cell receptor RAGE (receptor for AGE) and soluble receptor (sRAGE) are involved in the pathogenesis of AF. This review focuses on the role of AGE–RAGE axis in the pathogenesis of AF. Interaction of AGE with RAGE generates reactive oxygen species, cytokines, and vascular cell adhesion molecules. sRAGE is a cytoprotective agent. The data show that serum levels of AGE and sRAGE, and expression of RAGE, are elevated in AF patients. Elevated levels of sRAGE did not protect the development of AF. This might be due to greater elevation of AGE than sRAGE. Measurement of AGE–RAGE stress (AGE/sRAGE) would be appropriate as compared with measurement of AGE or RAGE or sRAGE alone in AF patients. AGE and its interaction with RAGE can induce AF through alteration in cellular protein and extracellular matrix. AGE and its interaction with RAGE induce atrial structural and electrical remodeling. The treatment strategy should be directed toward reduction in AGE levels, suppression of RAGE expression, blocking of binding of AGE to RAGE, and elevation of sRAGE and antioxidants. In conclusion, AGE–RAGE axis is involved in the development of AF through atrial structural and electrical remodeling. The treatment modalities for AF should include lowering of AGE, suppression of RAGE, elevation of sRAGE, and use of antioxidants.
The psychology of guns: risk, fear, and motivated reasoning
Authors: Pierre Joseph M.
Published: December 2019

The gun debate in America is often framed as a stand-off between two immutable positions with little potential to move ahead with meaningful legislative reform. Attempts to resolve this impasse have been thwarted by thinking about gun ownership attitudes as based on rational choice economics instead of considering the broader socio-cultural meanings of guns. In this essay, an additional psychological perspective is offered that highlights how concerns about victimization and mass shootings within a shared culture of fear can drive cognitive bias and motivated reasoning on both sides of the gun debate. Despite common fears, differences in attitudes and feelings about guns themselves manifest in variable degrees of support for or opposition to gun control legislation that are often exaggerated within caricatured depictions of polarization. A psychological perspective suggests that consensus on gun legislation reform can be achieved through understanding differences and diversity on both sides of the debate, working within a common middle ground, and more research to resolve ambiguities about how best to minimize fear while maximizing personal and public safety.
Simultaneous measurement of the thickness and the lifetime of a foam lamella
Authors: Feucht Dominik C. , Hofmann Matthias J. , Motschmann Hubert
Published: December 2019

Despite the important role of foams in industrial applications, few methods for determining the stability are present. By extending the existing light reflection-based apparatus, additional information about a single foam lamella can be obtained. Evaluation of these data delivers insight into the thinning process of the lamella. The potential of this technique is shown for the analysis of two surfactants with different head group lengths (Lutensol XP 100 and Lutensol XP 140).
Dynamic plasma/metal/dielectric photonic crystals in the mm-wave region: Electromagnetically-active artificial material for wireless communications and sensors
Authors: Sun Peter P. , Zhang Runyu , Chen Wenyuan , Braun Paul V. , Eden J. Gary
Published: December 2019

Inexorable demand for increasing bandwidth is driving future wireless communications systems into the 100 GHz–1 THz region, thereby fueling demand for new sources and modulators but also complementary devices such as resonators, phase shifters, and filters. Few such devices exist at present, and the electromagnetic properties of those available at millimeter-wavelengths are generally fixed and characterized by broad (i.e., low Q) resonances. We introduce a class of 3D plasma/metal/dielectric photonic crystals (PPCs), operating in the 120–170 GHz spectral range, that are dynamic (tunable and reconfigurable at electronic speeds) and possess attenuation and transmission resonances with bandwidths below 50 MHz. Interference between sublattices of the crystal, which controls the resonance line shapes, is manipulated through the crystal structure. Incorporating Bragg arrays of low-temperature plasma microcolumns into a dielectric/metal scaffold that is itself a static crystal forms two interwoven and electromagnetically coupled crystals. Plasma-scaffold lattices produce multiple, narrowband attenuation resonances that shift monotonically to higher frequencies by as much as 1.6 GHz with increasing plasma electron density. Controlling the longitudinal geometry of the PPC through electronic activation of successive Bragg planes of plasma columns reveals an unexpected double-crystal symmetry interaction at 138.4 GHz and resonance Q values above 5100. The introduction of point or line defects into plasma column/polymer/metal crystals increases transparency at resonances of the scaffold (Borrmann effect) and yields Fano line shapes characteristic of coupled resonators. The experimental results suggest the suitability of PPC-based metamaterials for applications including multichannel communications, millimeter-wave spectroscopy, and fundamental studies of multiple, coupled resonators.
Prediction of the impact of support structures on the aerodynamic performance of large wind farms
Authors: Ma Lun , Nishino Takafumi , Antoniadis Antonios F.
Published: December 2019

An extended theoretical model based on a two-scale coupled momentum balance method is proposed to estimate aerodynamic effects of wind turbine towers on the performance of both ideal (infinitely large) and more realistic (large but finite-size) wind farms. A key implication of the extended model is that a normalized support-structure drag, AS/A×CD*, where A and AS are the rotor swept area and support-structure frontal projected area, respectively, and CD* is an effective support-structure drag coefficient, may play an important role in the design of future large wind farms. For the infinitely large case, the theoretical model shows that the optimal turbine spacing should increase with the value of AS/A×CD*, whereas for the large finite case, this also depends on an additional parameter describing the response characteristics of the atmospheric boundary layer to the total farm drag. To validate the theoretical model for the infinitely large case, Wall-Modeled Large-Eddy Simulations of a periodic array of actuator disks with and without support structures are conducted. The results show a reasonably good agreement (within 10% in the prediction of power) with the theoretical model.
Electrically small particles for infrared imaging applications
Authors: AlShareef Mohammed R. , Abdel-Rahman Mohamed Ramy
Published: December 2019

A special arrangement of electrically small particles for infrared imaging application is presented. The proposed configuration is composed of split ring resonators surrounding eight tapered microstrip lines and sits on a dielectric substrate with a backed metallic layer. Simulation and numerical calculations are carried out to investigate and prove the proposed structure's power absorption ability. The structure is designed to absorb incident infrared radiation in the 8–12 μm band. Approximately 52% absorption efficiency is achieved during this study. An absorption efficiency of more than 90% is realized by utilizing an infinite array of the proposed structure.
Pulsed power driven cylindrical wire array explosions in different media
Authors: Yanuka D. , Theocharous S. , Bland S. N.
Published: December 2019

Cylindrical copper wire array explosions were carried out in de-ionized water, sodium polytungstate solution, nitromethane, and polyester in order to obtain high energy density conditions in the vicinity of implosion using the generated converging shock waves. The use of different materials in which the array is immersed can contribute to this goal with higher density resulting in higher shock velocities and possible combustion. The generated shock waves were captured by a framing and a streak camera, and shock velocities were calculated and compared. The pressure behind the shock front was calculated using the known hydrodynamic relations (for water, polytungstate, and polyester) and compared to two-dimensional hydrodynamic simulations coupled with the equations of state (for water and polyester). It was shown that despite lower shock wave velocity in polytungstate solution than in water, the pressures generated are similar in both materials. In polyester, both shock velocities and generated pressures are 2–4 times higher than in water. It was also shown that it is possible to carry out these explosions in a solid which has several advantages compared to liquids, such as not relying on waterproof systems and easier transportation.
Excess thermal energy and latent heat in nanocluster collisional growth
Authors: Yang Huan , Drossinos Yannis , Hogan Christopher J.
Published: December 2019

Nanoclusters can form and grow by nanocluster-monomer collisions (condensation) and nanocluster-nanocluster collisions (coagulation). During growth, product nanoclusters have elevated thermal energies due to potential and thermal energy exchange following a collision. Even though nanocluster collisional heating may be significant and strongly size dependent, no prior theory describes this phenomenon for collisions of finite-size clusters. We derive a model to describe the excess thermal energy of collisional growth, defined as the kinetic energy increase in the product cluster, and latent heat of collisional growth, defined as the heat released to the background upon thermalization of the nonequilibrium cluster. Both quantities are composed of a temperature-independent term related to potential energy minimum differences and a size- and temperature-dependent term, which hinges upon heat capacity and energy partitioning. Example calculations using gold nanoclusters demonstrate that collisional heating can be important and strongly size dependent, particularly for reactive collisions involving nanoclusters composed of 14–20 atoms. Excessive latent heat release may have considerable implications in cluster formation and growth.
On an initial boundary value problem for gas dynamics in thermal nonequilibrium
Authors: Chang Der-Chen , Luo Tao , Zhong Hua
Published: December 2019

For gas dynamics with several thermal nonequilibrium modes, the global existence of smooth solutions to an initial boundary value problem is established. The key difference compared with the initial value problem studied by Zeng [Arch. Ration. Mech. Anal. 150, 225–279 (1999); ibid. 196, 191–225 (2010)] is the boundary effects, e.g., boundary layers. Moreover, the exponential decay of solutions to an initial boundary value problem of the linearized system with a vibrational nonequilibrium mode is proved via the Fourier analysis, which illustrates a key distinction from that for the initial value problem without a boundary for which the decay is only algebraic.
Phonon dispersion in two-dimensional solids from atomic probability distributions
Authors: Ramírez R. , Herrero C. P.
Published: December 2019

We propose a harmonic linear response (HLR) method to calculate the phonon dispersion relations of two-dimensional layers from equilibrium simulations at finite temperatures. This HLR approach is based on the linear response of the system, as derived from the analysis of its centroid density in equilibrium path integral simulations. In the classical limit, this approach is closely related to those methods that study vibrational properties by the diagonalization of the covariance matrix of atomic fluctuations. The validity of the method is tested in the calculation of the phonon dispersion relations of a graphene monolayer, a graphene bilayer, and graphane. Anharmonic effects in the phonon dispersion relations of graphene are demonstrated by the calculation of the temperature dependence of the following observables: the kinetic energy of the carbon atoms, the vibrational frequency of the optical E2g mode, and the elastic moduli of the layer.
Resistance to degradation and effect of the herbicide glyphosate on the bacterioplankton community of a large river system dominated by agricultural activities
Authors: Piccini Claudia , Fazi Stefano , Pérez Germán , Batani Giampiero , Martínez de la Escalera Gabriela , Sotelo-Silveira José Roberto
Published: December 2019

Glyphosate-based herbicides are widely used for several crops, such as transgenic soybean and forestry. The aim of this study was to determine the effect of glyphosate on the community structure of riverine bacterioplankton and to evaluate the potential of bacterioplankton to degrade the herbicide. River water to which 13C-labelled glyphosate (10, 100µgL–1) was added or not (control) was incubated for 6 days at the temperature measured in situ (20°C). Significant differences in bacterioplankton community composition, as assessed by microfluidics-based automated ribosomal intergenic spacer analysis, were found among treatments, with differences in the presence of 100µgL–1 of glyphosate being more pronounced, namely significant decreases in bacterial richness and diversity. The glyphosate degradation product aminomethylphosphonic acid (AMPA) was detected, accounting for 1.2% of glyphosate conversion in water with 100µgL–1 of 13C-labelled glyphosate, together with a significant enrichment of 13C in the bacterial biomass. These findings suggest that glyphosate had a direct detrimental effect on most bacterioplankton taxa, but enriched those that were able to degrade the herbicide. Together, the results indicate that glyphosate degradation in the river assessed would be a slow process (months–years), taking place through the AMPA degradation pathway and meaning glyphosate accumulate in the ecosystem.
Modeling active sensing reveals echo detection even in large groups of bats
Authors: Beleyur Thejasvi , Goerlitz Holger R.
Published: December 2019

Active sensing animals perceive their surroundings by emitting probes of energy and analyzing how the environment modulates these probes. However, the probes of conspecifics can jam active sensing, which should cause problems for groups of active sensing animals. This problem was termed the cocktail party nightmare for echolocating bats: as bats listen for the faint returning echoes of their loud calls, these echoes will be masked by the loud calls of other close-by bats. Despite this problem, many bats echolocate in groups and roost socially. Here, we present a biologically parametrized framework to quantify echo detection in groups. Incorporating properties of echolocation, psychoacoustics, acoustics, and group flight, we quantify how well bats flying in groups can detect each other despite jamming. A focal bat in the center of a group can detect neighbors in group sizes of up to 100 bats. With increasing group size, fewer and only the closest and frontal neighbors are detected. Neighbor detection is improved by longer call intervals, shorter call durations, denser groups, and more variable flight and sonar beam directions. Our results provide a quantification of the sensory input of echolocating bats in collective group flight, such as mating swarms or emergences. Our results further generate predictions on the sensory strategies bats may use to reduce jamming in the cocktail party nightmare. Lastly, we suggest that the spatially limited sensory field of echolocators leads to limited interactions within a group, so that collective behavior is achieved by following only nearest neighbors.
CRISPR/Cas9-based targeted genome editing for correction of recessive dystrophic epidermolysis bullosa using iPS cells
Authors: Jacków Joanna , Guo Zongyou , Hansen Corey , Abaci Hasan E. , Doucet Yanne S. , Shin Jung U , Hayashi Ryota , DeLorenzo Dominick , Kabata Yudai , Shinkuma Satoru , Salas-Alanis Julio C. , Christiano Angela M.
Published: December 2019

Significance

This study demonstrates a therapeutic option using induced pluripotent stem cells (iPSCs), gene editing, and tissue engineering techniques for the development of a long-lasting treatment that will result in the permanent closure of nonhealing wounds in dystrophic epidermolysis bullosa (DEB), especially for recessive DEB (RDEB). Here, we demonstrated that the combination of iPSCs, gene editing, and tissue engineering allows us to perform efficient gene correction by homology-directed repair with the CRISPR-Cas9 gRNA ribonucleoprotein complex system, differentiate the gene-corrected RDEB patient iPSCs into skin cells, and generate human skin equivalents (HSEs) that show skin integrity and type VII collagen restoration after grafting them onto nude mice. The results from this study serve as a foundation to translate this treatment into the clinic.
A population shift between two heritable cell types of the pathogen
Candida albicans
is based both on switching and selective proliferation
Authors: Dalal Chiraj K. , Zuleta Ignacio A. , Lohse Matthew B. , Zordan Rebecca E. , El-Samad Hana , Johnson Alexander D.
Published: December 2019

Significance

The fungal species
Candida albicans
thrives in diverse niches of its mammalian hosts, an ability attributed, in part, to its different morphological forms. We examined one morphological change, known as white–opaque switching, in which cells switch between their typical round-to-oval morphology (white) and an elongated cell type (opaque). Switching is typically rare; however, specific conditions can shift an entire population of opaque cells to white cells. We show that opaque-to-white switching is common in conditions where white cells thrive. We hypothesize that other microbial pathogens may employ similar strategies, matching switching between states to proliferation rates, to thrive in diverse environments.
Cryptochrome 2 competes with COP1 substrates to repress COP1 ubiquitin ligase activity during
Arabidopsis
photomorphogenesis
Authors: Ponnu Jathish , Riedel Tabea , Penner Eva , Schrader Andrea , Hoecker Ute
Published: December 2019

Significance

Plants adapt their growth and development to ambient light conditions by modulating the activity of the COP1/SPA ubiquitin ligase. In
Arabidopsis
, photoactivated cryptochromes interact directly with COP1/SPA to suppress the activity of COP1 in blue light. The molecular mechanisms of CRY-mediated inhibition of COP1 are not fully understood. Here we show that CRY2 inhibits COP1 by displacing degradation substrates from COP1. This mechanism requires a valine-proline (VP) motif present in the C-terminal domain of CRY2. These amino acids are also present in interactors of
Arabidopsis
and human COP1 and have been previously shown to directly bind the WD repeat of
Arabidopsis
and human COP1. Thus, the evolution of the plant-specific, VP-containing C-terminal domain of CRY2 might have allowed for light control of COP1 activity.
A
cis
-element within the
ARF
locus mediates repression of
p16

INK4A

expression via long-range chromatin interactions
Authors: Zhang Yang , Hyle Judith , Wright Shaela , Shao Ying , Zhao Xujie , Zhang Hui , Li Chunliang
Published: December 2019

Loss of function of
CDKN2A
/
B
, also known as
INK4
/
ARF
[encoding p16
INK4A
, p15
INK4B
, and p14
ARF
(mouse p19
Arf
)], confers susceptibility to cancers, whereas its up-regulation during organismal aging provokes cellular senescence and tissue degenerative disorders. To better understand the transcriptional regulation of
p16

INK4A

, a CRISPR screen targeting open, noncoding chromatin regions adjacent to
p16

INK4A

was performed in a human
p16

INK4A-P2A-mCherry

reporter cell line. We identified a repressive element located in the 3′ region adjacent to the
ARF
promoter that controls
p16

INK4A

expression via long-distance chromatin interactions. Coinfection of lentiviral dCas9-KRAB with selected single-guide RNAs against the repressive element abrogated the
ARF
/
p16

INK4A

chromatin contacts, thus reactivating
p16

INK4A

expression. Genetic CRISPR screening identified candidate transcription factors inhibiting
p16

INK4A

regulation, including ZNF217, which was confirmed to bind the
ARF
/
p16

INK4A

interaction loop. In summary, direct physical interactions between
p16

INK4A

and
ARF
genes provide mechanistic insights into their cross-regulation.
Pancreatic cancer organoids recapitulate disease and allow personalized drug screening
Authors: Driehuis Else , van Hoeck Arne , Moore Kat , Kolders Sigrid , Francies Hayley E. , Gulersonmez M. Can , Stigter Edwin C. A. , Burgering Boudewijn , Geurts Veerle , Gracanin Ana , Bounova Gergana , Morsink Folkert H. , Vries Robert , Boj Sylvia , van Es Johan , Offerhaus G. Johan A. , Kranenburg Onno , Garnett Mathew J. , Wessels Lodewyk , Cuppen Edwin , Brosens Lodewijk A. A. , Clevers Hans
Published: December 2019

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target
MTAP
(a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.
The γ-tubulin complex protein GCP6 is crucial for spindle morphogenesis but not essential for microtubule reorganization inArabidopsis
Authors: Miao Huiying , Guo Rongfang , Chen Junlin , Wang Qiaomei , Lee Yuh-Ru Julie , Liu Bo
Published: December 2019

Significance

γ-Tubulin is essential for eukaryotic cells to produce new microtubules that are assembled into arrays like mitotic spindles, and its function depends on proteins that form complexes with it. In centrosome-lacking cells, the generation of new microtubules is dependent on formation of the γ-tubulin ring complex (γTuRC). Our experiments reveal γ-tubulin–dependent but γTuRC-independent phenomena of microtubule generation during mitotic cell division in the plants that lack the centrosome. We conclude that the γTuRC plays a critical role in spindle pole organization, but that plant cells still complete cell division in its absence. Therefore, this work in plant cells advances our knowledge of acentrosomal microtubule organization in general.
Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model
Authors: Yu Kwang-Min , Park Su-Jin , Yu Min-Ah , Kim Young-Il , Choi Younho , Jung Jae U. , Brennan Benjamin , Choi Young Ki
Published: December 2019

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the
Banyangvirus
genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization’s Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP
102
A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP
102
A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV.
Evolutionary transition from degenerate to nonredundant cytokine signaling networks supporting intrathymic T cell development
Authors: Lawir Divine-Fondzenyuy , Hess Isabell , Sikora Katarzyna , Iwanami Norimasa , Siamishi Iliana , Schorpp Michael , Boehm Thomas
Published: December 2019

In mammals, T cell development critically depends on the IL-7 cytokine signaling pathway. Here we describe the identification of the zebrafish ortholog of mammalian IL-7 based on chromosomal localization, deduced protein sequence, and expression patterns. To examine the biological role ofil7in teleosts, we generated anil7allele lacking most of its coding exons using CRISPR/Cas9-based mutagenesis.il7-deficient animals are viable and exhibit no obvious signs of immune disorder. With respect to intrathymic T cell development,il7deficiency is associated with only a mild reduction of thymocyte numbers, contrasting with a more pronounced impairment of T cell development inil7r-deficient fish. Genetic interaction studies betweenil7andil7rmutants, andil7andcrlf2(tslpr) mutants suggest the contribution of additional, as-yet unidentified cytokines to intrathymic T cell development. Such activities were also ascertained for other cytokines, such as il2 and il15, collectively indicating that in contrast to the situation in mammals, T cell development in the thymus of teleosts is driven by a degenerate multicomponent network of γccytokines; this explains why deficiencies of single components have little detrimental effect. In contrast, the dependence on a single cytokine in the mammalian thymus has catastrophic consequences in cases of congenital deficiencies in genes affecting the IL-7 signaling pathway. We speculate that the transition from a degenerate to a nonredundant cytokine network supporting intrathymic T cell development emerged as a consequence of repurposing evolutionarily ancient constitutive cytokine pathways for regulatory functions in the mammalian peripheral immune system.
Extracellular electron transfer powers flavinylated extracellular reductases in Gram-positive bacteria
Authors: Light Samuel H. , Méheust Raphaël , Ferrell Jessica L. , Cho Jooyoung , Deng David , Agostoni Marco , Iavarone Anthony T. , Banfield Jillian F. , D’Orazio Sarah E. F. , Portnoy Daniel A.
Published: December 2019

Significance

Strategies of energy metabolism are variable across the microbial world and fundamentally reflect distinct ecological dynamics. The complex electron transfer mechanisms that support many such processes take place in the cell membrane but can be wired to the exterior of the cell in some circumstances. The results presented here reveal a family of extracellular reductases that possess a post-translationally flavinylated sequence motif. This motif provides a conserved framework that mediates electron transfer from the membrane to different extracellular small molecules. These findings advance our understanding of microbial energy metabolism and identify a generalized and modular electron transfer strategy that could be exploited for applications in metabolic engineering.
Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in
Enterococcus faecalis
Authors: Khan Ayesha , Davlieva Milya , Panesso Diana , Rincon Sandra , Miller William R. , Diaz Lorena , Reyes Jinnethe , Cruz Melissa R. , Pemberton Orville , Nguyen April H. , Siegel Sara D. , Planet Paul J. , Narechania Apurva , Latorre Mauricio , Rios Rafael , Singh Kavindra V. , Ton-That Hung , Garsin Danielle A. , Tran Truc T. , Shamoo Yousif , Arias Cesar A.
Published: December 2019

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant
Enterococcus faecalis,
an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the
Caenorhabditis elegans
model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions.
SUMO1 modification of PKD2 channels regulates arterial contractility
Authors: Hasan Raquibul , Leo M. Dennis , Muralidharan Padmapriya , Mata-Daboin Alejandro , Yin Wen , Bulley Simon , Fernandez-Peña Carlos , MacKay Charles E. , Jaggar Jonathan H.
Published: December 2019

PKD2 (polycystin-2, TRPP1) channels are expressed in a wide variety of cell types and can regulate functions, including cell division and contraction. Whether posttranslational modification of PKD2 modifies channel properties is unclear. Similarly uncertain are signaling mechanisms that regulate PKD2 channels in arterial smooth muscle cells (myocytes). Here, by studying inducible, cell-specific
Pkd2
knockout mice, we discovered that PKD2 channels are modified by SUMO1 (small ubiquitin-like modifier 1) protein in myocytes of resistance-size arteries. At physiological intravascular pressures, PKD2 exists in approximately equal proportions as either nonsumoylated (PKD2) or triple SUMO1-modifed (SUMO-PKD2) proteins. SUMO-PKD2 recycles, whereas unmodified PKD2 is surface-resident. Intravascular pressure activates voltage-dependent Ca
2+
influx that stimulates the return of internalized SUMO-PKD2 channels to the plasma membrane. In contrast, a reduction in intravascular pressure, membrane hyperpolarization, or inhibition of Ca
2+
influx leads to lysosomal degradation of internalized SUMO-PKD2 protein, which reduces surface channel abundance. Through this sumoylation-dependent mechanism, intravascular pressure regulates the surface density of SUMO-PKD2−mediated Na
+
currents (I
Na
) in myocytes to control arterial contractility. We also demonstrate that intravascular pressure activates SUMO-PKD2, not PKD2, channels, as desumoylation leads to loss of I
Na
activation in myocytes and vasodilation. In summary, this study reveals that PKD2 channels undergo posttranslational modification by SUMO1, which enables physiological regulation of their surface abundance and pressure-mediated activation in myocytes and thus control of arterial contractility.
Role of traditional Chinese philosophies and new product development under circular economy in private manufacturing enterprise performance
Authors: Subramanian Nachiappan , Gunasekaran Angappa , Wu Lin , Shen Tinghua
Published: December 2019

The new product development (NPD) process–performance link has been sufficiently studied in academic research. However, recent NPD process is significantly different from the conventional NPD specifically with the inclusion of sustainability considerations under circular economy
(CE) context. In theory, NPD with CE considerations (CE-NPD), compared with the conventional NPD, is associated with higher costs and longer development times. This study empirically examines the effect of the CE-NPD process on both time-to-market (TTM) and profit performance in the context
of Chinese private enterprises. In addition, the role of traditional Chinese philosophies of Confucianism and Taoism in influencing the CE-NPD process–performance link is also investigated. We find that Confucianism positively moderates the relationship between the CE-NPD process and
TTM performance. However, it negatively moderates the CE-NPD-profit link. On the other hand, the moderating effect of Taoism is negative on both the CE-NPD-TTM and CE-NPD-profit links. An interesting finding of this study is that the coexistence of Confucian and Taoist values in NPD workers
has the strongest positive impact on the relationship between the CE-NPD process and performance. Our study provides insights on the way in which companies should plan to apply Chinese philosophies during the CE-NPD process to maximise the benefits.
Out Damn Bot, Out: Recruiting Real People into Substance use Studies on the Internet
Authors: Godinho Alexandra , Schell Christina , Cunningham John A.
Published: December 2019

While the Internet has become a popular and effective strategy for recruiting substance users into research, there is a large risk of recruiting duplicate individuals and Internet bots that pose as humans. Strategies to mitigate these issues are outlined and categorized into two groups: (1) automatic techniques which are often embedded into surveys and (2) ongoing manual techniques implemented during recruitment. Potential limitations of these strategies are discussed, and an example of the prevalence of duplicate data within a substance using sample is provided. Overall, it is recommended that researchers consider the use of routine strategies to mitigate the risks associated with recruiting online samples such as: verifying participant contact information, IP address checks, and ongoing cross-checking of participant information for duplicates, similarities and inconsistencies.