bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional characterization and structural bases of two class I diterpene synthases in pimarane-type diterpene biosynthesis
Authors: Xing Baiying , Yu Jiahui , Chi Changbiao , Ma Xueyang , Xu Qingxia , Li Annan , Ge Yuanjie , Wang Zhengdong , Liu Tan , Jia Hongli , Yin Fuling , Guo Juan , Huang Luqi , Yang Donghui , Ma Ming
Published: September 2021

Pimarane-type diterpenoids are widely distributed in all domains of life, but no structures or catalytic mechanisms of pimarane-type diterpene synthases (DTSs) have been characterized. Here, we report that two class I DTSs, Sat1646 and Stt4548, each accept copalyl diphosphate (CPP) as the substrate to produce isopimara-8,15-diene (1). Sat1646 can also accept syn-CPP and produce syn-isopimaradiene/pimaradiene analogues (2–7), among which 2 possesses a previously unreported "6/6/7" ring skeleton. We solve the crystal structures of Sat1646, Sat1646 complexed with magnesium ions, and Stt4548, thereby revealing the active sites of these pimarane-type DTSs. Substrate modeling and subsequent site-directed mutagenesis experiments demonstrate different structural bases of Sat1646 and Stt4548 for 1 production. Comparisons with previously reported DTSs reveal their distinct carbocation intermediate stabilization mechanisms, which control the conversion of a single substrate CPP into structurally diverse diterpene products. These results illustrate the structural bases for enzymatic catalyses of pimarane-type DTSs, potentially facilitating future DTS engineering and combinatorial biosynthesis.
Pervasive detachment faults within the slow spreading oceanic crust at the poorly coupled Antilles subduction zone
Authors: Marcaillou Boris , Klingelhoefer Frauke , Laurencin Muriel , Lebrun Jean-Frédéric , Laigle Mireille , Lallemand Serge , Schenini Laure , Gay Aurélien , Boucard Milton , Ezenwaka Kingsley , Graindorge David
Published: September 2021

Oceanic crust formed at slow-spreading ridges is currently subducted in only a few places on Earth and the tectonic and seismogenic imprint of the slow-spreading process is poorly understood. Here we present seismic and bathymetric data from the Northeastern Lesser Antilles Subduction Zone where thick sediments enable seismic imaging to greater depths than in the ocean basins. This dataset highlights a pervasive tectonic fabric characterized by closely spaced sequences of convex-up Ridgeward-Dipping Reflectors, which extend down to about 15 km depth with a 15-to-40° angle. We interpret these reflectors as discrete shear planes formed during the early stages of exhumation of magma-poor mantle rocks at an inside corner of a Mid-Atlantic Ridge fracture zone. Closer to the trench, plate bending could have reactivated this tectonic fabric and enabled deep fluid circulation and serpentinization of the basement rocks. This weak serpentinized basement likely explains the very low interplate seismic activity associated with the Barbuda-Anegada margin segment above.
Dye-sensitized solar cells strike back
Authors: Muñoz-García Ana Belén , Benesperi Iacopo , Boschloo Gerrit , Concepcion Javier J. , Delcamp Jared H. , Gibson Elizabeth A. , Meyer Gerald J. , Pavone Michele , Pettersson Henrik , Hagfeldt Anders , Freitag Marina
Published: September 2021

Dye-sensitized solar cells (DSCs) are celebrating their 30thbirthday and they are attracting a wealth of research efforts aimed at unleashing their full potential. Righteous font designed by Astigmatic and licensed under the Open Font License.
Iridium-catalyzed regio- and enantioselective allylic esterification of secondary allylic alcohols with carboxylic acids
Authors: Tang Shengbiao , Zhang Peng , Wang Changkai , Shao Ying , Sun Jiangtao
Published: September 2021

We report herein an iridium-catalyzed asymmetric allylic esterification of racemic secondary allylic alcohols with carboxylic acids under mild conditions with broad functional group tolerance, exhibiting excellent regio- (b/l > 19 : 1) and enantioselectivity (up to >99% ee).
Celebrating the 75th Anniversary of the Korean Chemical Society
Authors: Lim Mi Hee , Jeong Nak Cheon , Ok Kang Min , Jung Ok-Sang
Published: September 2021

The 52nd President of the Korean Chemical Society (2020–2021).
Emerging investigator series: electrochemically-mediated remediation of GenX using redox-copolymers
Authors: Baldaguez Medina Paola , Cotty Stephen , Kim Kwiyong , Elbert Johannes , Su Xiao
Published: September 2021

GenX is a major per- and polyfluoroalkyl substance (PFAS) of environmental concern. Redox-copolymers are explored as selective adsorbents for the electrochemically-mediated separation and remediation of GenX from water.
Fe-MIL-101 modified by isatin-Schiff-base-Co: a heterogeneous catalyst for C–C, C–O, C–N, and C–P cross coupling reactions
Authors: Rouzifar Majid , Sobhani Sara , Farrokhi Alireza , Sansano José Miguel
Published: September 2021

Fe-MIL-101-isatin-Schiff-base-Co was synthesized and applied as a catalyst for Ullmann-type, Buchwald–Hartwig, Hirao, Hiyama and Mizoroki–Heck cross-coupling reactions of aryl halides.
Effect of ethane and ethylene on catalytic non oxidative coupling of methane
Authors: Postma Rolf S. , Lefferts Leon
Published: September 2021

Ethane and ethylene are radical initiators in non-oxidative coupling of methane at high temperature, without adverse effect on product selectivity, when compared to the Fe/SiO2 catalyst.
Multi‐view facial action unit detection via deep feature enhancement
Authors: Tang Chuangao , Lu Cheng , Zheng Wenming , Zong Yuan , Li Sunan
Published: September 2021

Multi‐view facial action unit (AU) analysis has been a challenging research topic due to multiple disturbing variables, including subject identity biases, variational facial action unit intensities, facial occlusions and non‐frontal head‐poses. A deep feature enhancement (DFE) framework is presented to tackle some of these coupled complex disturbing variables for multi‐view facial action unit detection. The authors' DFE framework is a novel end‐to‐end three‐stage feature learning model with taking subject identity biases, dynamic facial changes and head‐pose into consideration. It contains three feature enhancement modules, including coarse‐grained local and holistic spatial feature learning (LHSF), spatio‐temporal feature learning (STF) and head‐pose feature disentanglement (FD). Experimental results show that the proposed method achieved state‐of‐the‐art recognition performance on the FERA2017 dataset. The code is released at http://aip.seu.edu.cn/cgtang/.
Detecting exoplanets with the false inclusion probability
Authors: Hara Nathan C. , Unger Nicolas , Delisle Jean-Baptiste , Díaz Rodrigo F. , Ségransan Damien
Published: September 2021

Context.It is common practice to claim the detection of a signal if, for a certain statistical significance metric, the signal significance exceeds a certain threshold fixed in advance. In the context of exoplanet searches in radial velocity data, the most common statistical significance metrics are the Bayes factor and the false alarm probability (FAP). Both criteria have proved useful, but do not directly address whether an exoplanet detection should be claimed. Furthermore, it is unclear which detection threshold should be taken and how robust the detections are to model misspecification.

Aims.The aim of the present work is to define a detection criterion that conveys as precisely as possible the information needed to claim an exoplanet detection, as well as efficient numerical methods to compute it. We compare this new criterion to existing ones in terms of sensitivity and robustness to a change in the model.

Methods.We define a general detection criterion called the false inclusion probability (FIP). In the context of exoplanet detections it provides the posterior probability of presence of a planet with a period in a certain interval. Posterior distributions are computed with the nested sampling packagePOLYCHORD. We show that for FIP and Bayes factor calculations, defining priors on linear parameters as Gaussian mixture models can significantly speed up computations. The performance of the FAP, Bayes factor, and FIP are studied via simulations and analytical arguments. We compare the methods assuming the model is correct, then evaluate their sensitivity to the prior and likelihood choices.

Results.Among other properties, the FIP offers ways to test the reliability of the significance levels; it is a particularly efficient way to account for aliasing, and it allows the presence of planets to be excluded with a certain confidence. In our simulations, we find that the FIP outperforms existing detection metrics. We show that low amplitude planet detections are sensitive to priors on period and semi-amplitude, which will require further attention for the detection of Earth-like planets. We recommend to let the parameters of the noise model free in the analysis, rather than fixing a noise model based on a fit to ancillary indicators.
Einsatz eines Wendelappens zur Wiederherstellung des Volumens im Achselbereich – ein neuer Behandlungsansatz für die operative Versorgung von sekundären Lymphödemen nach Brustkrebstherapie
Authors: Marx Mario , Geßner Michael , Florek Alexander , Morgenstern Susanne , Passin Stefan , Brucker Sara Y. , Wallwiener Diethelm , Hahn Markus
Published: September 2021

Einleitung Narbige Verengungen und ein Volumendefizit im Bereich der Axilla können zu einem anhaltenden Lymphödem führen und zählen zu den häufigsten Nebenwirkungen nach einer Brustkrebstherapie im Achselbereich. Ziel dieser Arbeit ist die Vorstellung einer Operationstechnik zur Reduzierung von Lymphödemen mithilfe eines Turn-Over Flaps.

Material und Methoden Zwischen Oktober 2016 und Mai 2018 wurden 5 Patientinnen mit einem Lymphödem Grad 2 nach Mammakarzinomtherapie mit dieser neuen Methode behandelt. Dabei erfolgte die vollständige Entfernung der kompromittierenden Narbenstränge der Axilla, gefolgt von einer Reaugmentation der Axilla mittels Turn-Over Flap. Danach wurde bei allen Patientinnen eine Brustrekonstruktion mit einer an die thorakodorsalen Gefäße angeschlossenen Fernlappenplastik durchgeführt. Prä- und postoperativ wurden der Umfang beider Arme, die Lebensqualität und die Schmerzen gemessen.

Ergebnisse Im Durchschnitt sanken die Schmerzen im ipsilateralen Arm von 6 auf 1 auf der numerischen Schmerzskala, und die Lebensqualität verbesserte sich merklich (2,8 vs. 7,0). Es zeigte sich eine deutliche Verringerung des Lymphödems, vor allem im Oberarm. Komplikationen wie sekundäre Blutungen, Infektionen oder Lappenverlust sind nicht aufgetreten.

Schlussfolgerung Eine vollständige Entfernung der nach Brustkrebsbehandlungen entstandenen Vernarbungen im Bereich der Axilla und eine Reaugmentation der Axilla mittels Turn-Over Flap führten zu einer Verringerung des ipsilateralen Lymphödems und zu einer Verbesserung der Schmerzen und der Lebensqualität. Wir deuten dieses Outcome als Ergebnis der physiologischen Ausrichtung der Lymphgefäße und eines lymphknotenhaltigen Transpositionslappens. Die Reaugmentation der Axilla mittels Turn-Over Flap könnte eine wirksame, nicht mikrochirurgische Alternative zur Lymphknotentransplantation darstellen.
Update Mammakarzinom 2020 Teil 5 – Einführung von Substanzen aus der metastasierten Therapiesituation in die frühe Therapiesituation
Authors: Lux Michael P. , Schneeweiss Andreas , Hartkopf Andreas D. , Müller Volkmar , Janni Wolfgang , Belleville Erik , Stickeler Elmar , Thill Marc , Fasching Peter A. , Kolberg Hans Christian , Untch Michael , Harbeck Nadia , Wöckel Achim , Thomssen Christoph , Schulmeyer Carla E. , Welslau Manfred , Overkamp Friedrich , Schütz Florian , Lüftner Diana , Ditsch Nina
Published: September 2021

Bei neuen Therapieansätzen des Mammakarzinoms sind insbesondere bei Patientinnen mit HER2-positivem und HER2-negativem/hormonrezeptorpositivem (HR+) Mammakarzinom in den letzten Jahren deutliche Fortschritte gesehen worden. Bei HER2-positiven Tumoren müssen in dem Zusammenhang Pertuzumab, T‑DM1, Neratinib und bald auch Tucatinib und Trastuzumab-Deruxtecan (beide in Europa noch nicht zugelassen) genannt werden. Bei den Patientinnen mit HER2−/HR+-Mammakarzinom sind insbesondere die CDK4/6-Inhibitoren und der PIK3CA-Inhibitor Alpelisib zu nennen. Weitere, neue Therapien wie Akt-Kinase-Inhibitoren und orale SERDs (selective estrogen receptor down-regulators) werden bereits in laufenden klinischen Studien untersucht. Nicht nur bei den HER2-positiven Tumoren halten die Therapien Einzug in die kurative, (neo-) adjuvante Therapiesituation, sondern es wurde nun eine erste positive Studie mit Abemaciclib in der adjuvanten Situation vorgestellt. Bei Patientinnen mit einem triple-negativen Mammakarzinom ist nach vielen Jahren mit negativen Studienergebnissen mit dem Trop-2-Antikörper-Wirkstoff-Konjugat (antibody drug conjugate, ADC) Sacituzumab-Govitecan eine randomisierte Studie veröffentlicht worden, die einen deutlichen Therapiefortschritt bedeuten kann. Diese Übersichtsarbeit beschreibt die neuesten Entwicklungen beim Mammakarzinom nach dem ESMO-Kongress 2020.
Uretroplastia bulbar con injerto: Una actualización sobre las diferentes técnicas quirúrgicas
Authors: Rodríguez Eduar S. , Serna Laura A. , Agressot Wilmer A.
Published: September 2021

En pacientes con estrechez uretral bulbar de una longitud mayor a 2 cm, que no sean candidatos a otras técnicas, se realiza uretroplastia con injerto. Actualmente se emplean diversas técnicas, cada una con ventajas y desventajas propias.

Describir las ventajas y desventajas de las técnicas quirúrgicas empleadas actualmente en la uretroplastia con injerto, así como sus tasas de éxito.

Se hizo una búsqueda en PubMed, ClinicalKey y en ScienceDirect, utilizando las palabras claves: “urethral stricture,” “urethroplasty,” “oral graft” y “flap.” Se utilizaron los estudios más relevantes, tanto originales como revisiones sistemáticas y meta-análisis, en inglés y en español.

Las diferentes técnicas quirúrgicas ofrecen ventajas y desventajas teóricas frente a las otras, aunque las tasas de éxito en todas es cercana al 90%, sin ser una francamente superior frente a las demás.

La elección de la técnica quirúrgica a realizar depende de las preferencias y experiencia del cirujano, dado que la tasa de éxito para todas las técnicas es similar.
Urological Cancer Treatment by a Multidisciplinary Team throughout the Covid-19 Pandemic: What Have We Learned?
Authors: Chavarriaga Julián , Cataño Juan-Guillermo , Villanueva Juliana , Sáenz Daniel , Suso-Palau Daniel , Rodríguez Santiago , Villaquiran Catalina , Galvis Juan , Pinilla Paola , Morales Angélica , Patiño German
Published: September 2021

Introduction It is known that cancer care is best approached by a multidisciplinary team (MDT). This became specifically true in the Covid-19 pandemic in which choices for urological cancer treatment are influenced by many factors. In some cases, delayed treatment may have consequences regarding the patient's oncological outcomes. The aim of the present article is to report our experience throughout the Covid-19 pandemic treating patients with urological neoplasms at a high-volume center.

Methods We used a convenience sampling method. Cases were evaluated and discussed on an individual basis at the MDT meetings, and, after a consensus regarding delaying or scheduling treatment, patients were scheduled according to the risk of postponing the procedures. The Medically Necessary, Time-Sensitive (MeNTS) scoring system was measured in each patient; all patients answered the Centers for Disease Control and Prevention (CDC) Covid-19 self-screening questionnaire prior to surgery. The Covid-19-free survival rate was estimated.

Results A total of 194 patients were assessed by the multidisciplinary team and finally treated, with median follow-up of 4 (interquartile range [IQR]: 2.75 to 6) months. Only two patients had Covid-19 confirmed by real-time polymerase chain reaction (RT-PCR). In total, 54 patients underwent oncological surgery, 129 were treated with radiotherapy, and 11 were treated with intravenous chemotherapy. The median age was 66 years (IQR: 59 to 94 years), and the median MeNTS score in the surgically-treated cohort was 35 points (IQR: 31 to 47 points).

Conclusions The evaluation and treatment of urological cancer should be conducted by an MDT; this is of utmost importance, especially during the Covid-19 pandemic. The data collected in our institution showed that most patients could be safely treated by taking all necessary precautions and discussing each case individually in the MDT meetings and performing a close follow-up.
Síndrome compartimental bilateral de pierna tras posición de litotomía prolongada. Presentación de un caso clínico
Authors: Díez-Albero Luis , Moril-Peñalver Lorena , Lapeña-Martínez Andrés , López-Prats Fernando
Published: September 2021

Introducción El síndrome compartimental es una complicación infrecuente pero severa que puede aparecer ante una posición de litotomía prolongada y el uso de perneras.

Objetivo Presentar un caso de síndrome compartimental bilateral tras posición de litotomía prolongada asociada con el uso de perneras.

Material y Métodos Paciente varón de 43 años sometido a una cirugía urológica en posición habitual de litotomía durante un periodo de 6 horas. A las 2 horas de finalizar la cirugía, el paciente presentó dolor intenso y endurecimiento de compartimento anterior y lateral de ambas piernas, junto con una elevación de la creatina quinasa sérica (valor incial de 109 U/L que se elevó hasta 7.689 U/L a las 12 horas) y una imposibilidad para la flexión dorsal pasiva de ambos tobillos. El paciente no sentía dolor en el resto de los compartimentos.

Resultados Ante la sospecha de un síndrome compartimental anterolateral, se realizó fasciotomía bilateral urgente, y se observó una disminución de la perfusión muscular y mejoría de la misma tras apertura de la fascia. Se realizaron curas periódicas cada 48 horas, y se observó viabilidad del tejido hasta su cierre definitivo a los 4 días. A las 2 semanas, el paciente presentó fatiga ligera para la deambulación sin ayuda, con tumefacción en el compartimento lateral de ambas piernas. A los 10 meses de evolución, el paciente caminaba sin ayuda y con función muscular completa.

Conclusiones El conocimiento de la asociación del síndrome compartimental y la cirugía laparoscópica prolongada es esencial para un diagnóstico precoz y un tratamiento quirúrgico inmediato, para evitar graves secuelas. Los buenos resultados de nuestro paciente se deben a la rápida actuación, ya que normalmente se suele demorar. Para evitar su aparición o disminuir su incidencia, la posición de litotomía debería limitarse a aquellos momentos de la cirugía en los que sea imprescindible, modificando la posición de las piernas cada dos horas en caso de cirugías prolongadas, para prevenir dicha complicación.
Information Security Awareness and Behaviors of Health Care Professionals at Public Health Care Facilities
Authors: Alhuwail Dari , Al-Jafar Eiman , Abdulsalam Yousef , AlDuaij Shaikha
Published: September 2021

Objectives This study investigated information security behaviors of professionals working in the public health sector to guide policymakers toward focusing their investments in infrastructure and training on the most vulnerable segments. We sought to answer the following questions: (1) Are certain professional demographics more vulnerable to cybersecurity threats? (2) Do professionals in different institution types (i.e., hospitals vs. primary care clinics) exhibit different cybersecurity behaviors? (3) Can Internet usage behaviors by professionals be indicative of their cybersecurity awareness and the risk they introduce?

Methods A cross-sectional, anonymous, paper-based survey was distributed among professionals working in public health care organizations in Kuwait. Data were collected about each professional's role, experience, work environment, cybersecurity practices, and understanding to calculate a cybersecurity score which indicates their level of compliance to good cybersecurity practices. We also asked about respondents' internet usage and used K-means cluster analysis to segment respondents into three groups based on their internet activities at work. Ordinary least squares regression assessed the association between the collected independent variables in question on the overall cybersecurity behavior.

Results A total of 453/700 (64%) were responded to the survey. The results indicated that professionals with more work experience demonstrated higher compliance with good cybersecurity practices. Interestingly, nurses demonstrate higher cybersecurity aptitude relative to physicians. Professionals that were less inclined to use the internet for personal use during their work demonstrated higher cybersecurity aptitude.

Conclusion Our findings provide some guidance regarding how to target health care professional training to mitigate cybersecurity risks. There is a need for ensuring that physicians receive adequate cybersecurity training, despite the opportunity costs and other issues competing for their attention. Additionally, classifying professionals based on their internet browsing patterns may identify individuals vulnerable to cybersecurity incidents better than more discrete indicators such as age or gender.
Protrusio acetabular en artroplastía total de cadera: diez tácticas para un buen resultado quirúrgico
Authors: Bengoa Francisco , López Alberto , Dabed David , Rojas Nicolas , Diaz-Ledezma Claudio
Published: September 2021

Los pacientes candidatos a artroplastía total de cadera con protrusio acetabular asociada generan distintos desafíos en los equipos quirúrgicos. Múltiples estrategias han sido utilizadas a lo largo de los años para optimizar los resultados. Mediante una revisión de la evidencia actualizada disponible, proponemos diez tácticas a realizar en el manejo de estos pacientes que pueden mejorar y hacer predecible el tratamiento de un paciente con protrusio acetabular al que se le realiza una artroplastía total de cadera.

Nivel de Evidencia V.
Reconstrucción del ligamento patelofemoral medial mediante suturas transóseas patelares: estudio transversal de 34 pacientes
Authors: Pakuts Andrés , Martin Luis Fernando , Riquoir Christophe , Schadenberg Alex
Published: September 2021

Introducción La inestabilidad rotuliana recurrente puede conducir a malos resultados funcionales y daño articular progresivo a largo plazo, y con frecuencia se aborda mediante la reconstrucción del ligamento patelofemoral medial (RLPFM), con múltiples técnicas que suelen diferir en el método de fijación de la rótula.

Objetivo Evaluar los resultados de RLPFM utilizando una técnica novedosa de fijación rotuliana mediante suturas transóseas. El objetivo principal es determinar las tasas de reluxación y los resultados funcionales incluyendo retorno deportivo. Los objetivos secundarios incluyen la evaluación de las complicaciones y de otras variables relacionadas, y la comparación entre los resultados de RLPFM aislada y asociada a una osteotomía de la tuberosidad tibial.

Métodos Estudio transversal de 34 pacientes sometidos a RLPFM desde 2013 hasta 2019 con un seguimiento mínimo de 12 meses. La reconstrucción fue realizada por el mismo primer cirujano con autoinjerto de gracilis de doble banda en todos los casos. La fijación del injerto en la cara medial de la rótula se realizó utilizando dos puntos de fijación transóseos independientes con suturas de alta resistencia, y la fijación femoral anatómica, con un tornillo interferencial mediante referencias anatómicas y radiológicas. Hubo 27 pacientes con RLPFM aislada, y 7 con osteotomía de la tuberosidad tibial asociada.

Resultados La edad media fue de 22,8 años (desviación estándar [DE]: 9,1). El 50% eran hombres. El seguimiento desde la cirugía hasta el cuestionario fue de 30,4 meses (rango: 12 a 72 meses). La puntuación media de Kujala en el seguimiento fue de 89,4 (DE: 12,8; mediana: 93,5; rango: 51 a 100). No hubo casos de reluxación. No se identificaron otras complicaciones durante el seguimiento. El 81% de los pacientes regresó a los deportes, y el 47% regresó a su nivel previo de participación. No se encontraron diferencias significativas al comparar RLPFM aislada con grupos de osteotomía asociada.

Conclusión La RLPFM mediante sutura transósea para fijación en la rótula mostró que la estabilidad rotuliana fue restaurada en el corto y mediano plazo. Esta técnica es segura, tiene excelentes resultados funcionales, y evita posibles complicaciones de los túneles rotulianos o morbilidad asociada al uso de implantes.
Transport and mixing by metachronal waves in nonreciprocal soft robotic pneumatic artificial cilia at low Reynolds numbers
Authors: Zhang Rongjing , den Toonder Jaap , Onck Patrick R.
Published: September 2021

Cilia are widely employed by living systems to manipulate fluid flow in various functions, such as feeding, pumping, and locomotion. Mimicking the intricate ciliary asymmetry in combination with collective metachronal beating may find wide application in fluid transport and mixing in microfluidic systems. Here, we numerically analyze the metachronal beating of pneumatic artificial cilia. We specifically address three aspects of ciliary motion: (i) pumping in the backflow region, (ii) mixing in the cilia region, and (iii) the transport—mixing transition region. Our results show that antiplectic metachrony leads to the highest mixing efficiency and transport rate in two distinct regions, i.e., below and above the ciliary surface, respectively. We find that the ciliary motion strongly enhances the diffusivity when advection is dominant at high Péclet numbers, with a factor 3 for symplectic metachrony and a factor 4 for antiplectic metachrony and synchronous beating. In addition, we find an increase with a factor 1.5 for antiplectic metachrony and a decrease with a factor 2.5 for symplectic metachrony compared with synchronous beating for fluid pumping. To investigate the higher transport rate compared to symplectic metachrony, we develop a simple two-cilia model and demonstrate that the shielding of flow between neighboring cilia is the main reason for the higher antiplectic transport rate.
Machine learning dynamic correlation in chemical kinetics
Authors: Kim Changhae Andrew , Ricke Nathan D. , Van Voorhis Troy
Published: September 2021

Lattice models are a useful tool to simulate the kinetics of surface reactions. Since it is expensive to propagate the probabilities of the entire lattice configurations, it is practical to consider the occupation probabilities of a typical site or a cluster of sites instead. This amounts to a moment closure approximation of the chemical master equation. Unfortunately, simple closures, such as the mean-field and the pair approximation (PA), exhibit weaknesses in systems with significant long-range correlation. In this paper, we show that machine learning (ML) can be used to construct accurate moment closures in chemical kinetics using the lattice Lotka–Volterra model as a model system. We trained feedforward neural networks on kinetic Monte Carlo (KMC) results at select values of rate constants and initial conditions. Given the same level of input as PA, the ML moment closure (MLMC) gave accurate predictions of the instantaneous three-site occupation probabilities. Solving the kinetic equations in conjunction with MLMC gave drastic improvements in the simulated dynamics and descriptions of the dynamical regimes throughout the parameter space. In this way, MLMC is a promising tool to interpolate KMC simulations or construct pretrained closures that would enable researchers to extract useful insight at a fraction of the computational cost.
The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity
Authors: Snoznik Carley , Medvedeva Valentina , Mojsilovic-Petrovic Jelena , Rudich Paige , Oosten James , Kalb Robert G. , Lamitina Todd
Published: September 2021

Significance

The G
4
C
2
repeat expansion in the
C9orf72
gene is a major cause of frontotemporal dementia and amyotrophic lateral sclerosis. Unusual translation of the repeat sequence produces two highly toxic dipeptide repeat proteins (DPRs), PR
X
and GR
X
, which accumulate in the brain tissue of individuals with these diseases. Here, we show that PR and GR toxicity in both
Caenorhabditis elegans
and mammalian neurons depends on the E3 ubiquitin ligase adaptor
SPOP
.
SPOP
acts through bromodomain proteins to mediate dipeptide toxicity.
SPOP
inhibitors, which are currently being developed to treat
SPOP
-dependent renal cancer, also protect neurons against DPR toxicity. Our findings identify a highly conserved and “druggable” pathway that may represent a strategy for treating these currently incurable diseases.
The interaction between atomic-scale pores and particles
Authors: Hassani Nasim , Neek-Amal Mehdi
Published: September 2021

Using first-principles calculations for angstrom-sized pores (3–10 Å), we investigate pore-particle interaction. The translocation energy barrier (TEB) plays important role for the angstrom-scale pores created in 2D-materials such as graphene which is calculated for the translocation of rare gases (He, Ne, Ar, Xe), diatomic molecules (H2 and N2), CO2, and CH4. The critical incident angle (the premeance beyond that is zero) was found to be 40°, which is different from classical model’s prediction of 19–37°. The calculated TEB (Δ) and the surface diffusion energy barrier (Δ′) for the particles with small kinetic diameter (He, Ne and H2), show that the direct flow is the dominant permeation mechanism (Δ ≈ 0 and Δ′ > 30 meV). For the other particles with larger kinetic diameters (Ar, Kr, N2, CH4 and CO2), we found that both surface diffusion and direct flow mechanisms are possible, i.e. Δ and Δ′ ≠ 0. This work provides important insights into the gas permeation theory and into the design and development of gas separation and filtration devices.
Conic formulation of fluence map optimization problems
Authors: ten Eikelder S C M , Ajdari A , Bortfeld T , den Hertog D
Published: September 2021

The convexity of objectives and constraints in fluence map optimization (FMO) for radiation therapy has been extensively studied. Next to convexity, there is another important characteristic of optimization functions and problems, which has thus far not been considered in FMO literature: conic representation. Optimization problems that are conically representable using quadratic, exponential and power cones are solvable with advanced primal-dual interior-point algorithms. These algorithms guarantee an optimal solution in polynomial time and have good performance in practice. In this paper, we construct conic representations for most FMO objectives and constraints. This paper is the first that shows that FMO problems containing multiple biological evaluation criteria can be solved in polynomial time. For fractionation-corrected functions for which no exact conic reformulation is found, we provide an accurate approximation that is conically representable. We present numerical results on the TROTS data set, which demonstrate very stable numerical performance for solving FMO problems in conic form. With ongoing research in the optimization community, improvements in speed can be expected, which makes conic optimization a promising alternative for solving FMO problems.
Experimental validation of daily adaptive proton therapy
Authors: Nenoff Lena , Matter Michael , Charmillot Marjolaine , Krier Serge , Uher Klara , Weber Damien Charles , Lomax Antony John , Albertini Francesca
Published: September 2021

Anatomical changes during proton therapy require rapid treatment plan adaption to mitigate the associated dosimetric impact. This in turn requires a highly efficient workflow that minimizes the time between imaging and delivery. At the Paul Scherrer Institute, we have developed an online adaptive workflow, which is specifically designed for treatments in the skull-base/cranium, with the focus set on simplicity and minimizing changes to the conventional workflow. The dosimetric and timing performance of this daily adaptive proton therapy (DAPT) workflow has been experimentally investigated using an in-house developed DAPT software and specifically developed anthropomorphic phantom. After a standard treatment preparation, which includes the generation of a template plan, the treatment can then be adapted each day, based on daily imaging acquired on an in-room CT. The template structures are then rigidly propagated to this CT and the daily plan is fully re-optimized using the same field arrangement, DVH constraints and optimization settings of the template plan. After a dedicated plan QA, the daily plan is delivered. To minimize the time between imaging and delivery, clinically integrated software for efficient execution of all online adaption steps, as well as tools for comprehensive and automated QA checks, have been developed. Film measurements of an end-to-end validation of a multi-fraction DAPT treatment showed high agreement to the calculated doses. Gamma pass rates with a 3%/3 mm criteria were >92% when comparing the measured dose to the template plan. Additionally, a gamma pass rate >99% was found comparing measurements to the Monte Carlo dose of the daily plans reconstructed from the logfile, accumulated over the delivered fractions. With this, we experimentally demonstrate that the described adaptive workflow can be delivered accurately in a timescale similar to a standard delivery.
Morphology of positive ionization waves in atmospheric pressure air: influence of electrode set-up geometry
Authors: Bourdon Anne , Péchereau François , Tholin Fabien , Bonaventura Zdenek
Published: September 2021

A numerical parametric study on positive diffuse discharges in point-to-plane geometry in air at atmospheric pressure is presented. Different discharge characteristics are studied: ignition time, connection time to the grounded cathode plane, shape of the discharge and its maximum radius at the connection time, evolution of the maximum electric field in the discharge front and velocity of the ionization front during its propagation. First, a case at a DC voltage of 50 kV applied on a rod anode ended by a semi-sphere with a radius of 100 μm set at 1.6 cm from a grounded cathode plane is considered. The influence of the rod radius, the position of a disc holder, the shape of the anode electrode and the radial extension of the computational domain are studied. The radius of curvature of the anode tip (varied between 100 and 1000 μm) and the shape of the anode electrode (rod or hyperbola) are shown to have a negligible influence on discharge characteristics. Conversely, the presence of a disc holder or a small radial computational domain lead to a decrease of the maximum discharge radius at the connection time and a change in the discharge shape from a conical to an ellipsoidal shape. These changes on the discharge morphology have only a limited impact on the propagation velocity of the discharge front and maximum electric field on the discharge axis. Then, a point-to-plane geometry with a rod electrode of 50 μm radius, in a 1.6 cm gap, with a 100 kV voltage applied with a rise time of 1 ns is studied. The influence of a disc holder on the discharge characteristics is the same as for lower DC voltages. Finally, the time evolution of the absolute value of the electric field at different test points on the discharge axis is studied. Close to the anode tip, rapidly after the peak of electric field due to the passage of the ionization front, the electric field in the discharge channel is shown to increase to values higher than the breakdown field.
Changes in Brain Dopamine Extracellular Concentration after Ethanol Administration; Rat Microdialysis Studies
Authors: Dahchour Abdelkader , Ward Roberta J
Published: September 2021

Aims

The purpose of this review is to evaluate microdialysis studies where alterations in the dopaminergic system have been evaluated after different intoxication states, in animals showing preference or not for alcohol, as well as during alcohol withdrawal.

Methods

Ethanol administration induces varying alterations in dopamine microdialysate concentrations, thereby modulating the functional output of the dopaminergic system.

Results

Administration of low doses of ethanol, intraperitoneally, intravenously, orally or directly into the nucleus accumbens, NAc, increases mesolimbic dopamine, transmission, as shown by increases in dopamine content. Chronic alcohol administration to rats, which show alcohol-dependent behaviour, induced little change in basal dopamine microdialysis content. In contrast, reduced basal dopamine content occurred after ethanol withdrawal, which might be the stimulus to induce alcohol cravings and consumption. Intermittent alcohol consumption did not identify any consistent changes in dopamine transmission. Animals which have been selectively or genetically bred for alcohol preference did not show consistent changes in basal dopamine content although, exhibited a significant ethanol-evoked dopamine response by comparison to non-preference animals.

Conclusions

Microdialysis has provided valuable information about ethanol-evoked dopamine release in the different animal models of alcohol abuse. Acute ethanol administration increases dopamine transmission in the rat NAc whereas chronic ethanol consumption shows variable results which might reflect whether the rat is prior to or experiencing ethanol withdrawal. Ethanol withdrawal significantly decreases the extracellular dopamine content. Such changes in dopamine surges will contribute to both drug dependence, e.g. susceptibility to drug withdrawal, and addiction, by compromising the ability to react to normal dopamine fluctuations.
‘In defence of the empire’: Mauritius’ government slaves in eighteenth-century Mauritius
Authors: Teelock Vijayalakshmi
Published: September 2021

Mauritius' Government slaves form a unique body of slaves emerging out of its French colonial past. Slaves bought by the colonial administration formed part of the 'public works' department and built the infrastructure of the islans as well as manning forts, manufacturing gunpowder and even being recruited in the French naval squadrons going to fight the British in India.
The fobitools framework: the first steps towards food enrichment analysis
Authors: Castellano-Escuder Pol , Andrés-Lacueva Cristina , Sánchez-Pla Alex
Published: September 2021

Motivation

The FOBI ontology can be of great help in nutrimetabolomic studies due to its wide variety of applications, including the possibility of performing different enrichment analyses. However, the programming skills required to query and explore it may limit its use by the scientific community.

Results

Here, we present the fobitools framework, comprised of an R/Bioconductor package and its complementary web interface. These two tools allow researchers to interact and explore the FOBI ontology in a highly user-friendly way. The fobitools framework is focused on the novel concept of food enrichment analysis in nutrimetabolomic studies. However, other useful features, such as the network interactive visualization of FOBI and the automatic annotation of dietary free-text data are also presented.

Availability and implementation

Both the fobitools R/Bioconductor package and the fobitoolsGUI web-based application, together with their installation instructions and examples, are freely available at https://github.com/nutrimetabolomics/fobitools and https://github.com/nutrimetabolomics/fobitoolsGUI, respectively.

Supplementary information

Supplementary data are available at Bioinformatics online.
Accelerating Big Data Analysis through LASSO-Random Forest Algorithm in QSAR Studies
Authors: Motamedi Fahimeh , Pérez-Sánchez Horacio , Mehridehnavi Alireza , Fassihi Afshin , Ghasemi Fahimeh
Published: September 2021

Motivation

The aim of quantitative structure–activity prediction (QSAR) studies is to identify novel drug-like molecules that can be suggested as lead compounds by means of two approaches, which are discussed in this article. First, to identify appropriate molecular descriptors by focusing on one feature-selection algorithms; and second to predict the biological activities of designed compounds. Recent studies have shown increased interest in the prediction of a huge number of molecules, known as Big Data, using deep learning models. However, despite all these efforts to solve critical challenges in QSAR models, such as over-fitting, massive processing procedures, is major shortcomings of deep learning models. Hence, finding the most effective molecular descriptors in the shortest possible time is an ongoing task. One of the successful methods to speed up the extraction of the best features from big datasets is the use of least absolute shrinkage and selection operator (LASSO). This algorithm is a regression model that selects a subset of molecular descriptors with the aim of enhancing prediction accuracy and interpretability because of removing inappropriate and irrelevant features.

Results

To implement and test our proposed model, a random forest was built to predict the molecular activities of Kaggle competition compounds. Finally, the prediction results and computation time of the suggested model were compared with the other well-known algorithms, i.e. Boruta-random forest, deep random forest and deep belief network model. The results revealed that improving output correlation through LASSO-random forest leads to appreciably reduced implementation time and model complexity, while maintaining accuracy of the predictions.

Supplementary information

Supplementary data are available at Bioinformatics online.
RLM: fast and simplified extraction of read-level methylation metrics from bisulfite sequencing data
Authors: Hetzel Sara , Giesselmann Pay , Reinert Knut , Meissner Alexander , Kretzmer Helene
Published: September 2021

Bisulfite sequencing data provide value beyond the straightforward methylation assessment by analyzing single-read patterns. Over the past years, various metrics have been established to explore this layer of information. However, limited compatibility with alignment tools, reference genomes or the measurements they provide present a bottleneck for most groups to routinely perform read-level analysis. To address this, we developed RLM, a fast and scalable tool for the computation of several frequently used read-level methylation statistics. RLM supports standard alignment tools, works independently of the reference genome and handles most sequencing experiment designs. RLM can process large input files with a billion reads in just a few hours on common workstations.

Availability and implementation

https://github.com/sarahet/RLM.

Supplementary information

Supplementary data are available at Bioinformatics online.
Prediction of antimicrobial resistance based on whole-genome sequencing and machine learning
Authors: Ren Yunxiao , Chakraborty Trinad , Doijad Swapnil , Falgenhauer Linda , Falgenhauer Jane , Goesmann Alexander , Hauschild Anne-Christin , Schwengers Oliver , Heider Dominik
Published: September 2021

Motivation

Antimicrobial resistance (AMR) is one of the biggest global problems threatening human and animal health. Rapid and accurate AMR diagnostic methods are thus very urgently needed. However, traditional antimicrobial susceptibility testing (AST) is time-consuming, low throughput and viable only for cultivable bacteria. Machine learning methods may pave the way for automated AMR prediction based on genomic data of the bacteria. However, comparing different machine learning methods for the prediction of AMR based on different encodings and whole-genome sequencing data without previously known knowledge remains to be done.

Results

In this study, we evaluated logistic regression (LR), support vector machine (SVM), random forest (RF) and convolutional neural network (CNN) for the prediction of AMR for the antibiotics ciprofloxacin, cefotaxime, ceftazidime and gentamicin. We could demonstrate that these models can effectively predict AMR with label encoding, one-hot encoding and frequency matrix chaos game representation (FCGR encoding) on whole-genome sequencing data. We trained these models on a large AMR dataset and evaluated them on an independent public dataset. Generally, RFs and CNNs perform better than LR and SVM with AUCs up to 0.96. Furthermore, we were able to identify mutations that are associated with AMR for each antibiotic.

Availability and implementation

Source code in data preparation and model training are provided at GitHub website (https://github.com/YunxiaoRen/ML-iAMR).

Supplementary information

Supplementary data are available at Bioinformatics online.
Quiet flight, the leading edge comb, and their ecological correlates in owls (Strigiformes)
Authors: Le Piane Krista , Clark Christopher J
Published: September 2021

Owls have evolved sensitive hearing facilitated by a facial disc, and flight that is quieted in part by a leading-edge comb on their wing. This comb is a series of modified barbs, or serrations, which project up from the outermost primary feathers on the leading edge of the wing. Here we explore the evolution of comb and facial disc morphology. We measured leading-edge comb morphology on museum skins of 147 owl species, and facial disc morphology from photos, as well as ecological traits, on 66 species. The first principal component of comb morphology loaded on serration length, which varied between 0 and ~6 mm long in the species we sampled. Comb size (PC1) was correlated with relative facial disc size, suggesting that owls with good hearing also tend to have quiet flight. Two non-exclusive hypotheses for why quiet flight evolved are for stealth, allowing the owl to approach prey undetected; or to reduce self-masking, enabling the owl to hear prey better midflight. We examined whether ecological variables (prey type, active period and habitat) suggest whether stealth or self-masking better explain the evolution of comb size. Phylogenetic analyses suggested support for both the stealth and the self-masking hypotheses for the evolution of quiet flight.
The Mindfulness-Based Social Work and Self-Care Programme: A Mixed Methods Evaluation Study
Authors: Maddock Alan , McCusker Pearse , Blair Carolyn , Roulston Audrey
Published: September 2021

During their social work education, students engage in a number of stressful learning activities, often simultaneously, which can negatively impact their well-being, mental health and social work practice. Mindfulness practices are beginning to be integrated into social work curricula globally to enhance student self-care along with key social work practice skills and values. This mixed methods study examined the effects of a bespoke six-week online mindfulness-based social work and self-care (MBSWSC) programme on the stress, burnout, well-being, anxiety and depression levels of thirty social work students from two universities in the UK. This study also examined the effects of MBSWSC on a number of mindfulness-based mediators of change in these outcomes. Participant perceptions of the benefits of the MBSWSC programme on their well-being and social work practice are further explored via a thematic analysis of an open-ended questionnaire. Statistically significant changes in all variables were found post-programme except for depression and loss of empathy/depersonalisation, a facet of burnout. The qualitative data provided a deeper insight into the potential benefits of the programme for the enhancement of student well-being, mental health and anti-oppressive social work practice (AOP).