bluuebunny/crossref_metadata_2025 huggingface dataset:
DHHC5 facilitates oligodendrocyte development by palmitoylating and activating STAT3
Authors: Ma Yanchen , Liu Huiqing , Ou Zhimin , Qi Chen , Xing Rui , Wang Shiyun , Han Yinuo , Zhao Tong‐Jin , Chen Ying
Published: November 2021

Myelin sheath is an important structure to maintain functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin‐forming proteins to the myelin membrane, however, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp‐His‐His‐Cys (DHHC) motif‐containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by reducing total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation and suppresses STAT3 phosphorylation and activation. As a result, the transcription of the myelin‐related and anti‐apoptosis genes is inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate a key role DHHC5 in controlling myelinogenesis.
Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein of the testis carcinoma and other cancers: Results of a Phase I/II open‐label, dose escalation study
Authors: Cousin Sophie , Blay Jean‐Yves , Garcia Irene Braña , de Bono Johann S. , Le Tourneau Christophe , Moreno Victor , Trigo Jose , Hann Christine L. , Azad Arun A. , Im Seock‐Ah , Cassier Philippe A. , French Christopher A. , Italiano Antoine , Keedy Vicki L. , Plummer Ruth , Sablin Marie‐Paule , Hemming Matthew L. , Ferron‐Brady Geraldine , Wyce Anastasia , Khaled Ahmed , Datta Antara , Foley Shawn W. , McCabe Michael T. , Wu Yuehui , Horner Thierry , Kremer Brandon E. , Dhar Arindam , O'Dwyer Peter J. , Shapiro Geoffrey I. , Piha‐Paul Sarina A.
Published: November 2021

Molibresib is an orally bioavailable, selective, small molecule BET protein inhibitor. Results from a first time in human study in solid tumors resulted in the selection of a 75 mg once daily dose of the besylate formulation of molibresib as the recommended Phase 2 dose (RP2D). Here we present the results of Part 2 of our study, investigating safety, pharmacokinetics, pharmacodynamics and clinical activity of molibresib at the RP2D for nuclear protein in testis carcinoma (NC), small cell lung cancer, castration‐resistant prostate cancer (CRPC), triple‐negative breast cancer, estrogen receptor‐positive breast cancer and gastrointestinal stromal tumor. The primary safety endpoints were incidence of adverse events (AEs) and serious AEs; the primary efficacy endpoint was overall response rate. Secondary endpoints included plasma concentrations and gene set enrichment analysis (GSEA). Molibresib 75 mg once daily demonstrated no unexpected toxicities. The most common treatment‐related AEs (any grade) were thrombocytopenia (64%), nausea (43%) and decreased appetite (37%); 83% of patients required dose interruptions and 29% required dose reductions due to AEs. Antitumor activity was observed in NC and CRPC (one confirmed partial response each, with observed reductions in tumor size), although predefined clinically meaningful response rates were not met for any tumor type. Total active moiety median plasma concentrations after single and repeated administration were similar across tumor cohorts. GSEA revealed that gene expression changes with molibresib varied by patient, response status and tumor type. Investigations into combinatorial approaches that use BET inhibition to eliminate resistance to other targeted therapies are warranted.
Improved Sensitivity of Ultrasound‐Based Subharmonic Aided Pressure Estimation Using Monodisperse Microbubbles
Authors: van Hoeve Wim , de Vargas Serrano Miguel , te Winkel Lisa , Forsberg Flemming , Dave Jaydev K. , Sarkar Kausik , Wessner Corinne E. , Eisenbrey John R.
Published: November 2021

Objectives

Subharmonic aided pressure estimation (SHAPE) has been shown effective for noninvasively measuring hydrostatic fluid pressures in a variety of clinical applications. The objective of this study was to explore potential improvements in SHAPE sensitivity using monodisperse microbubbles.

Methods

Populations of monodisperse microbubbles were created using a commercially available microfluidics device (Solstice Pharmaceuticals). Size distributions were assessed using a Coulter Counter and stability of the distribution following fabrication was evaluated over 24 hours. Attenuation of the microbubble populations from 1 to 10 MHz was then quantified using single element transducers to identify each formulation's resonance frequency. Frequency spectra over increasing driving amplitudes were investigated to determine the nonlinear phases of subharmonic signal generation. SHAPE sensitivity was evaluated in a hydrostatic pressure‐controlled water bath using a Logiq E10 scanner (GE Healthcare).

Results

Monodisperse lipid microbubble suspensions ranging from 2.4 to 5.3 μm in diameter were successfully created and they showed no discernable change in size distribution over 24 hours following activation. Calculated resonance frequencies ranged from 2.1 to 6.3 MHz and showed excellent correlation with microbubble diameter (R2 > 0.99). When investigating microbubble frequency response, subharmonic signal occurrence was shown to begin at 150 kPa peak negative pressure, grow up to 225 kPa, and saturate at approximately 250 kPa. Using the Logiq E10, monodisperse bubbles demonstrated a SHAPE sensitivity of −0.17 dB/mmHg, which was nearly twice the sensitivity of the commercial polydisperse microbubble currently being used in clinical trials.

Conclusions

Monodisperse microbubbles have the potential to greatly improve the sensitivity of SHAPE for the noninvasive measurement of hydrostatic pressures.
The Effect of Povidone‐Iodine Nasal Spray on Nasopharyngeal SARS‐CoV‐2 Viral Load: A Randomized Control Trial
Authors: Zarabanda David , Vukkadala Neelaysh , Phillips Katie M. , Qian Z. Jason , Mfuh Kenji O. , Hatter Matthew J. , Lee Ivan T. , Rao Vidya K. , Hwang Peter H. , Domb George , Patel Zara M. , Pinsky Benjamin A. , Nayak Jayakar V.
Published: November 2021

Objectives/Hypothesis

To determine the effect of povidone‐iodine (PVP‐I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold (Ct) on quantitative polymerase chain reaction (qPCR) of SARS‐CoV‐2 in outpatients.

Study Design

Three arm, triple blinded, randomized, placebo‐controlled clinical trial.

Methods

Participants were randomized within 5 days of testing positive for COVID‐19 to receive nasal sprays containing placebo (0.9% saline), 0.5% PVP‐I, or 2.0% PVP‐I. NP swabs for qPCR analysis were taken at baseline, 1‐hour post‐PVP‐I spray (two sprays/nostril), and 3 days post‐PVP‐I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.

Results

Mean Ct values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP‐I groups. The 2.0% PVP‐I group showed statistically significant improvement in all symptom categories; however, it also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment.

Conclusions

Saline and low concentration PVP‐I nasal sprays are well tolerated. Similar reductions in SARS‐CoV‐2 NP viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP‐I nasal spray are safe for topical use in the nasal cavity, but that PVP‐I does not demonstrate virucidal activity in COVID‐19 positive outpatients.

Level of Evidence

2 Laryngoscope, 132:2089–2095, 2022
Identification of modes of tumor regression in non‐small cell lung cancer patients during radiotherapy
Authors: Amugongo Lameck Mbangula , Green Andrew , Cobben David , van Herk Marcel , McWilliam Alan , Osorio Eliana Vasquez
Published: November 2021

Purpose

Observed gross tumor volume (GTV) shrinkage during radiotherapy (RT) raises the question of whether to adapt treatment to changes observed on the acquired images. In the literature, two modes of tumor regression have been described: elastic and non‐elastic. These modes of tumor regression will affect the safety of treatment adaptation. This study applies a novel approach, using routine cone‐beam computed tomography (CBCT) and deformable image registration to automatically distinguish between elastic and non‐elastic tumor regression.

Methods

In this retrospective study, 150 locally advanced non‐small cell lung cancer patients treated with 55 Gray of radiotherapy were included. First, the two modes of tumor regression were simulated. For each mode of tumor regression, one timepoint was simulated. Based on the results of simulated data, the approach used for analysis in real patients was developed. CBCTs were non‐rigidly registered to the baseline CBCT using a cubic B‐spline algorithm, NiftyReg. Next, the Jacobian determinants were computed from the deformation vector fields. To capture local volume changes, 10 Jacobian values were sampled perpendicular to the surface of the GTV, across the lung‐tumor boundary. From the simulated data, we can distinguish elastic from non‐elastic tumor regression by comparing the Jacobian values samples between 5 and 12.5 mm inside and 5 and 12.5 mm outside the planning GTV. Finally, morphometric results were compared between tumors of different histologies.

Results

Most patients (92.3%) in our cohort showed stable disease in the first week of treatment and non‐elastic shrinkage in the later weeks of treatment. At week 2, 125 patients (88%) showed stable disease, three patients (2.1%) disease progression, and 11 patients (8%) regression. By treatment completion, 91 patients (64%) had stable disease, one patient (0.7%) progression and 46 patients (32%) regression. A slight difference in the mode of tumor change was observed between tumors of different histologies.

Conclusion

Our novel approach shows that it may be possible to automatically quantify and identify global changes in lung cancer patients during RT, using routine CBCT images. Our results show that different regions of the tumor change in different ways. Therefore, careful consideration should be taken when adapting RT.
Cutaneous silent period in ulnar neuropathy at the elbow
Authors: Mondelli Mauro , Aretini Alessandro
Published: November 2021

Introduction/Aims

The cutaneous silent period (CSP) reflects the function of A‐delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small‐diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP.

Methods

We consecutively evaluated UNE patients at one electrodiagnostic laboratory. The CSP was obtained upon stimulating the fifth (D5) and third digits, recording from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles.

Results

We enrolled 37 UNE patients (mean age 55.4 ± 11.2 y) and 30 controls (mean age 51.2 ± 11.1 y). The combinations of the D5‐APB and D5‐FDI mean onset latencies of CSP were significantly more prolonged in patients (83.7 ± 6.8 and 84.5 ± 8 ms, respectively) than in controls (78.2 ± 8.1 and 79.4 ± 7.6 ms, respectively). The D5‐FDI duration of CSP was shorter in patients (52.2 ± 8.3 ms) than in controls (55.8 ± 7 ms). The mean of the onset latencies of D5‐FDI and D5‐APB was related to the clinical severity (P = .013 and .0025, respectively). D5‐APB and D5‐FDI onset latencies were more prolonged and the duration was shorter in the UNE group with absent ulnar sensory nerve action potentials (SNAPs) and axonal motor damage than in patients with preserved SNAPs and with demyelinating damage.

Discussion

CSP was able to demonstrate abnormalities of small‐diameter myelinated sensory fibers. This damage was directly related to UNE severity and to axonal damage of motor fibers. Absence of a sensory large‐diameter fiber response did not exclude preserved residual small fiber conduction.
Gurgeltests an der Universität
Authors: Zbikowski Frauke
Published: November 2021

Konstanzer Wissenschaftler haben ein PCR‐Testverfahren entwickelt, und die Universität hat es zum Wintersemester 2020/2021 eingeführt. Die Hintergründe erläutert Daniel Dietrich vom Fachbereich Biologie.
Material modeling for parametric, anisotropic finite strain hyperelasticity based on machine learning with application in optimization of metamaterials
Authors: Fernández Mauricio , Fritzen Felix , Weeger Oliver
Published: November 2021

Mechanical metamaterials such as open‐ and closed‐cell lattice structures, foams, composites, and so forth can often be parametrized in terms of their microstructural properties, for example, relative densities, aspect ratios, material, shape, or topological parameters. To model the effective constitutive behavior and facilitate efficient multiscale simulation, design, and optimization of such parametric metamaterials in the finite deformation regime, a machine learning‐based constitutive model is presented in this work. The approach is demonstrated in application to elastic beam lattices with cubic anisotropy, which exhibit highly nonlinear effective behaviors due to microstructural instabilities and topology variations. Based on microstructure simulations, the relevant material and topology parameters of selected cubic lattice cells are determined and training data with homogenized stress‐deformation responses is generated for varying parameters. Then, a parametric, hyperelastic, anisotropic constitutive model is formulated as an artificial neural network, extending a recent work of the author extending a recent work of the author, Comput Mech., 2021;67(2):653‐677. The machine learning model is calibrated with the simulation data of the parametric unit cell. The authors offer public access to the simulation data through the GitHub repository
https://github.com/CPShub/sim‐data. For the calibration of the model, a dedicated sample weighting strategy is developed to equally consider compliant and stiff cells and deformation scenarios in the objective function. It is demonstrated that this machine learning model is able to represent and predict the effective constitutive behavior of parametric lattices well across several orders of magnitude. Furthermore, the usability of the approach is showcased by two examples for material and topology optimization of the parametric lattice cell.
Liquid–liquid phase separation in aqueous solutions of poly(ethylene glycol) methacrylate homopolymers
Authors: Constantinou Anna P. , Tall Amy , Li Qian , Georgiou Theoni K.
Published: November 2021

Here, the liquid–liquid phase separation (LLPS) in aqueous solutions containing poly(ethylene glycol) (PEG) methacrylate homopolymers is reported for the first time. In this study, the thermoresponse of concentrated solutions of DEGMA60 (two ethylene glycol, EG, groups) TEGMA71 (three EG groups), OEGMA300x (4.5 in average EG groups) of varying molar masses (MM), and OEGMA50028 (nine in average EG groups) is discussed. Interestingly, the temperature of LLPS (TLLPS) is controlled by the length of the PEG side chain, the MM of the OEGMA300x and the polymer concentration. More specifically, the transition temperature decreases with: (i) Decrease in the length of the PEG side chain, (ii) increase in MM of the OEGMA300x, and increase in concentration. In addition, LLPS is also observed in mixtures of OEGMA300x with Pluronic® F127. In conclusion, these systems present a thermally induced LLPS, with the transition temperature being finely tuned to room temperature when DEGMA is used. These systems find potential use in numerous applications, varying from purification to “water‐in‐water” emulsions.
3D Arrangement of Magnetic Particles in Thin Polymer Films Assisted by Magnetically Patterned Exchange Bias Layer Systems
Authors: Koch Iris , Langner Markus , Holzinger Dennis , Merkel Maximilian , Reginka Meike , Huhnstock Rico , Tomiţa Andreea , Jauregui Caballero Claudia , Greiner Andreas , Ehresmann Arno
Published: November 2021

The possibility to arrange and embed magnetic micro‐ and nanoparticles in thin polymer film systems using flat magnetically patterned substrate templates is investigated. In contrast to self‐organized particle rows forming by applying a homogeneous magnetic field, particles adapt to the magnetic field landscape of the substrate's magnetic pattern prior to polymer crosslinking. Crosslinking then fixes the particle positions in the polymer. The process is tested for composites of hydrophobic polydimethylsiloxane (PDMS) and maghemite nanoparticles as well as for hydrophilic polyvinyl alcohol (PVOH) and hydrophilic functionalized, superparamagnetic core–shell microspheres. The substrate template is an exchange bias layer system magnetically patterned into parallel‐stripe domains with in‐plane magnetizations and head‐to‐head/tail‐to‐tail remanent magnetization orientation in adjacent magnetic domains. A high occupancy percentage of magnetic beads on a domain wall as well as anisotropic actuation of the composite is achieved.
Bortezomib is significantly beneficial for de novo pediatric AML patients with low phosphorylation of the NF‐κB subunit RelA
Authors: van Dijk Anneke D. , Hoff Fieke W. , Qiu Yihua , Gerbing Robert B. , Gamis Alan S. , Aplenc Richard , Kolb E. Anders , Alonzo Todd A. , Meshinchi Soheil , Jenkins Gaye N. , de Bont Eveline S. J. M. , Kornblau Steven M. , Horton Terzah M.
Published: November 2021

Purpose: The addition of the proteasome inhibitor (PI) bortezomib to standard chemotherapy (ADE: cytarabine [Ara‐C], daunorubicin, and etoposide) did not improve overall outcome of pediatric AML patients in the Children's Oncology Group AAML1031 phase 3 randomized clinical trial (AAML1031) . Bortezomib prevents protein degradation, including RelA via the intracellular NF‐kB pathway. In this study, we hypothesized that subgroups of pediatric AML patients benefitting from standard therapy plus bortezomib (ADEB) could be identified based on pre‐treatment RelA expression and phosphorylation status.

Experimental design: RelA‐total and phosphorylation at serine 536 (RelA‐pSer536) were measured in 483 patient samples using reverse phase protein array technology.

Results: In ADEB‐treated patients, low‐RelA‐pSer536 was favorably prognostic when compared to high‐RelA‐pSer536 (3‐yr overall survival (OS): 81% vs. 68%, p = 0.032; relapse risk (RR): 30% vs. 49%, p = 0.004). Among low‐RelA‐pSer536 patients, RR significantly decreased with ADEB compared to ADE (RR: 30% vs. 44%, p = 0.035). Correlation between RelA‐pSer536 and 295 other assayed proteins identified a strong correlation with HSF1‐pSer326, another protein previously identified as modifying ADEB response. The combination of low‐RelA‐pSer536 and low‐HSF1‐pSer326 was a significant predictor of ADEB response (3‐yr OS: 86% vs. 67%, p = 0.013).

Conclusion and clinical relevance: Bortezomib may improve clinical outcome in a subgroup of AML patients identified by low‐RelA‐pSer536 and low‐HSF1‐pSer326.
Electronic and magnetic properties of one‐dimensional sandwich transition metal‐anthracene molecular wires
Authors: Yang Guang , Zhang Huiyang , Yang Yijun , Wang Yudi , Xv Xinzi , Zhao Xinli , Meng Lijuan , Yao Xiaojing , Zhang Xiuyun , Liu Yongjun
Published: November 2021

Organometallic sandwich complexes have been attracting interest for their potential applications in electronics and spintronics. Here, we systematically studied the structures, electronic and magnetic properties of one‐dimensional (1D) transition metal (TM)‐anthracene (Ant) sandwich molecular wires (SMWs), [TM2Ant]∞, and [TM3Ant]∞ (TM = Ti, V, Cr, Mn), based on density functional theory calculations. Our results show that all the 1D SMWs display normal sandwich configurations with their binding energies closely related to the choice of TM atoms. Excepting 1D [Mn2Ant]∞ and [Fe3Ant]∞ favoring antiferromagnetic ordering, most 1D [TM2Ant]∞ and [TM3Ant]∞ SMWs display robust ferromagnetic (FM) features. Particularly, 1D [Cr3Ant]∞ SMW is revealed to be FM half‐metal (HM), and 1D [Cr2Ant]∞, [Fe2Ant]∞ and [Mn3Ant]∞ SMWs are FM quasi HMs. Of which, high magnetic transform temperature up to 310 and 220 K are identified for 1D [V2Ant]∞ and [Fe2Ant]∞, respectively. Further spintransport calculations demonstrated that 1D Cr2‐Ant and Cr3‐Ant molecule lines are good spintransport devices. Our findings shed light on the properties of 1D Ant based SMWs and propose a new way to design potential electronic and spintronic devices.
Oxidative derivatization of V‐type nerve agents as a tool for their structural elucidation by liquid chromatography/tandem mass spectrometry
Authors: Shamai Yamin Tamar , Madmon Moran , Prihed Hagit , Blanca Merav , Weissberg Avi
Published: November 2021

Rationale

The identification of V‐type nerve agents poses an analytical challenge. Their spectra obtained by electron ionization mass spectrometry (EI‐MS) and electrospray ionization tandem mass spectrometry (ESI‐MS/MS) are dominated by ions originating from the N,N‐dialkylaminoethyl moiety, while ions representative of the alkyl phosphonothiolate part are absent from the spectra or present at negligible abundance. Hence, analogs or isomers with the same amine residue exhibit similar mass spectral patterns, leading to unavoidable ambiguity in their identification.

Methods

Chemical derivatization was utilized for the structural elucidation of a series of five V‐type nerve agents, including O‐ethyl S‐(2‐diisopropylamino)ethyl methylalkyl phosphonothiolate (VX), O‐isobutyl S‐(2‐diethylamino)ethyl methylalkyl phosphonothiolate (RVX) and O‐ethyl S‐(2‐diethylamino)ethyl methylalkyl phosphonothiolate (VM). The procedure consisted of “in‐vial” oxidation of the tertiary amine group with 3‐chloroperbenzoic acid (m‐CPBA) at ambient temperature followed by liquid chromatography (LC)/Orbitrap‐ESI‐MS/MS analysis with no other sample preparation.

Results

The generated N‐oxide of the V‐type nerve agents altered the charge distribution occurring during fragmentation and produced informative ESI‐MS/MS spectra characteristic of the alkyl phosphonothiolate structure, enabling a higher degree of certainty in their identification. Moreover, two VX isomers possessing an identical tertiary amine moiety that coeluted at practically the same retention time and displayed high mass spectral similarity were easily differentiated, and their structures elucidated once derivatized.

Conclusions

In contrast to the ESI‐MS/MS spectra of the V‐type nerve agents, which exhibited mostly/only information on the amine‐containing residue, the ESI‐MS/MS spectra of the V‐type nerve agent N‐oxides revealed ions indicative of both the alkyl phosphonothiolate and the amine parts, enabling their reliable structural elucidation.
Lightweight, Thermally Conductive Liquid Metal Elastomer Composite with Independently Controllable Thermal Conductivity and Density
Authors: Krings Ethan J. , Zhang Haipeng , Sarin Suchit , Shield Jeffery E. , Ryu Sangjin , Markvicka Eric J.
Published: November 2021

Lightweight and elastically deformable soft materials that are thermally conductive are critical for emerging applications in wearable computing, soft robotics, and thermoregulatory garments. To overcome the fundamental heat transport limitations in soft materials, room temperature liquid metal (LM) has been dispersed in elastomer that results in soft and deformable materials with unprecedented thermal conductivity. However, the high density of LMs (>6 g cm−3) and the typically high loading (⩾85 wt%) required to achieve the desired properties contribute to the high density of these elastomer composites, which can be problematic for large‐area, weight‐sensitive applications. Here, the relationship between the properties of the LM filler and elastomer composite is systematically studied. Experiments reveal that a multiphase LM inclusion with a low‐density phase can achieve independent control of the density and thermal conductivity of the elastomer composite. Quantitative design maps of composite density and thermal conductivity are constructed to rationally guide the selection of filler properties and material composition. This new multiphase material architecture provides a method to fine‐tune material composition to independently control material and functional properties of soft materials for large‐area and weight‐sensitive applications.
English Medium Instruction, English‐Enhanced Instruction, or English without Instruction: The Affordances and Constraints of Linguistically Responsive Practices in the Higher Education Classroom
Authors: Chang Sin‐Yi
Published: November 2021

The promotion of English medium instruction (EMI) in higher education has been a widely adopted institutional response to the forces of globalization in the 21st century. However, while EMI has received much enthusiasm in policy discourse, little research has been conducted to explore whether it effectively addresses the new demands of an increasingly multilingual student body. To fill this gap, in this study I draw on extensive literature on linguistically responsive instruction (LRI) to examine: 1) the practices that are linguistically responsive in higher education EMI classrooms, and 2) the affordances and constraints of such practices. The data for this study – taken from a larger research project that looked into different instructional outcomes of EMI – show that approaches to LRI were manifested in three main ways: technical, facilitative, and sociocultural. To illustrate what these labels mean, a close‐up look into three classroom profiles and interviews conducted with the lecturers of each of these classes are provided. Importantly, the multiple approaches to LRI pointed toward a common concern that centered on students’ English proficiency. While LRI may have helped resolve immediate comprehension issues and low participation in classroom interactions, the increased attention to language in content courses posed a potential threat to the teaching of the subject discipline. This study, therefore, argues that aside from equipping individual lecturers with the knowledge, skills, and dispositions to be linguistically responsive, introducing wider structural changes is also necessary so that different student needs (e.g., linguistic, cultural, academic) can be more sustainably supported.
Women’s Agency in a World of Flux: On Silesian Energy Transition
Authors: Iwińska Katarzyna , Bukowska Xymena
Published: November 2021

The chapter introduces a gender and energy nexus and presents an Upper Silesia case study of the energy transition as viewed locally. The main aim of this text is to explain some of the historical and industrial contexts of the “black gold” region when seen through a gender and ecofeminist lens. We present the recent processes of deindustrialization and decarbonization in Upper Silesia and show how these changes affect people living in an intensive flux. We emphasize the need to overcome the gender inequality in energy transition and to study the situation of women in the region. This chapter also presents some theoretical inspirations which link subsequent chapters—particularly modernization, feminism, and subjectivity/agency. We illustrate here the mosaic image of how women’s and cultural studies are intertwined with environmental and energy issues within shifting structural and economic contexts.
Mouse models of aneuploidy to understand chromosome disorders
Authors: Tosh Justin , Tybulewicz Victor , Fisher Elizabeth M. C.
Published: November 2021

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.
A pilot randomized controlled trial comparing THUNDERBEAT to the Maryland LigaSure energy device in laparoscopic left colon surgery
Authors: Milsom Jeffrey W. , Trencheva Koianka , Momose Kota , Peev Miroslav P. , Christos Paul , Shukla Parul J. , Garrett Kelly
Published: November 2021

Background

The THUNDERBEAT is a multi-functional energy device which delivers both ultrasonic and bipolar energy, but there are no randomized trials which can provide more rigorous evaluation of the clinical performance of THUNDERBEAT compared to other energy-based devices in colorectal surgery. The aim of this study was to compare the clinical performance of THUNDERBEAT energy device to Maryland LigaSure in patients undergoing left laparoscopic colectomy.

Methods

Prospective randomized trial with two groups: Group 1 THUNDERBEAT and Group 2 LigaSure in a single university hospital. 60 Subjects, male and female, of age 18 years and above undergoing left colectomy for cancer or diverticulitis were included. The primary outcome was dissection time to specimen removal (DTSR) measured in minutes from the start of colon mobilization to specimen removal from the abdominal cavity. Versatility (composite of five variables) was measured by a score system from 1 to 5 (1 being worst and 5 the best), and adjusted/weighted by coefficient of importance with distribution of the importance as follow: hemostasis 0.275, sealing 0.275, cutting 0.2, dissection 0.15, and tissue manipulation 0.1. Other variables were: dryness of surgical field, intraoperative and postoperative complications, and mortality. Follow-up time was 30 days.

Results

60 Patients completed surgery, 31 in Group 1 and 29 in Group 2. There was no difference in the DTSR between the groups, 91 min vs. 77 min (p = 0.214). THUNDERBEAT showed significantly higher score in dissecting and tissue manipulation in segment 3 (omental dissection), and in overall versatility score (p = 0.007) as well as versatility score in Segment 2 (retroperitoneal dissection p = 0.040) and Segment 3 (p = 0.040). No other differences were noted between the groups.

Conclusions

Both energy devices can be employed effectively and safely in dividing soft tissue and sealing mesenteric blood vessels during laparoscopic left colon surgery, with THUNDERBEAT demonstrating some advantages over LigaSure during omental dissection and tissue manipulation.

ClinicalTrial.gov # NCT02628093.
Updated GNSS velocity solution in the Nordic and Baltic countries with a semi-automatic offset detection method
Authors: Lahtinen Sonja , Jivall Lotti , Häkli Pasi , Nordman Maaria
Published: November 2021

In Fennoscandia, the Glacial Isostatic Adjustment (GIA) causes intraplate deformations that affect the national static reference frames. The GNSS-determined velocities are important data for constraining the GIA models, which are necessary for maintaining the national reference frames. The Nordic Geodetic Commission (NKG) has published a dense and consistent GNSS station velocity solution in 2019, and we present now an update of the solution covering additional 3.5 years of data. Undetected positional offsets are the main factor decreasing the accuracy of the velocity estimates. We developed a method for the semi-automatic offset detection to improve the quality of our solution. The results show that we could correctly detect 74% of the manually determined offsets, and the undetected offsets would have caused a median 0.1 mm/y bias in trend. The method pointed out some otherwise unnoticed offsets and will decrease the need for manual analysis in the future. The updated velocity solution especially improves the velocity estimates of the newly established stations and the quality of the velocity estimates in Baltic countries. The formal uncertainties estimated using the power-law plus white noise model were at a median of 0.06 and 0.15 mm/y for horizontal and vertical velocities, respectively. However, we concluded that the systematic velocity uncertainties due to the reference frame alignment were approximately at the same level.
Diversity, dependence and independence
Authors: Galliani Pietro , Väänänen Jouko
Published: November 2021

We propose a very general, unifying framework for the concepts of dependence and independence. For this purpose, we introduce the notion of diversity rank. By means of this diversity rank we identify total determination with the inability to create more diversity, and independence with the presence of maximum diversity. We show that our theory of dependence and independence covers a variety of dependence concepts, for example the seemingly unrelated concepts of linear dependence in algebra and dependence of variables in logic.
Ecological stoichiometry as a foundation for omics-enabled biogeochemical models of soil organic matter decomposition
Authors: Graham Emily B. , Hofmockel Kirsten S.
Published: November 2021

Coupled biogeochemical cycles drive ecosystem ecology by influencing individual-to-community scale behaviors; yet the development of process-based models that accurately capture these dynamics remains elusive. Soil organic matter (SOM) decomposition in particular is influenced by resource stoichiometry that dictates microbial nutrient acquisition (‘ecological stoichiometry’). Despite its basis in biogeochemical modeling, ecological stoichiometry is only implicitly considered in high-resolution microbial investigations and the metabolic models they inform. State-of-science SOM decomposition models in both fields have advanced largely separately, but they agree on a need to move beyond seminal pool-based models. This presents an opportunity and a challenge to maximize the strengths of various models across different scales and environmental contexts. To address this challenge, we contend that ecological stoichiometry provides a framework for merging biogeochemical and microbiological models, as both explicitly consider substrate chemistries that are the basis of ecological stoichiometry as applied to SOM decomposition. We highlight two gaps that limit our understanding of SOM decomposition: (1) understanding how individual microorganisms alter metabolic strategies in response to substrate stoichiometry and (2) translating this knowledge to the scale of biogeochemical models. We suggest iterative information exchange to refine the objectives of high-resolution investigations and to specify limited dynamics for representation in large-scale models, resulting in a new class of omics-enabled biogeochemical models. Assimilating theoretical and modelling frameworks from different scientific domains is the next frontier in SOM decomposition modelling; advancing technologies in the context of stoichiometric theory provides a consistent framework for interpreting molecular data, and further distilling this information into tractable SOM decomposition models.
Bringing physical reasoning into statistical practice in climate-change science
Authors: Shepherd Theodore G.
Published: November 2021

The treatment of uncertainty in climate-change science is dominated by the far-reaching influence of the ‘frequentist’ tradition in statistics, which interprets uncertainty in terms of sampling statistics and emphasizesp-values and statistical significance. This is the normative standard in the journals where most climate-change science is published. Yet a sampling distribution is not always meaningful (there is only one planet Earth). Moreover, scientific statements about climate change are hypotheses, and the frequentist tradition has no way of expressing the uncertainty of a hypothesis. As a result, in climate-change science, there is generally a disconnect between physical reasoning and statistical practice. This paper explores how the frequentist statistical methods used in climate-change science can be embedded within the more general framework of probability theory, which is based on very simple logical principles. In this way, the physical reasoning represented in scientific hypotheses, which underpins climate-change science, can be brought into statistical practice in a transparent and logically rigorous way. The principles are illustrated through three examples of controversial scientific topics: the alleged global warming hiatus, Arctic-midlatitude linkages, and extreme event attribution. These examples show how the principles can be applied, in order to develop better scientific practice.

“La théorie des probabilités n’est que le bon sens reduit au calcul.” (Pierre-Simon Laplace,Essai Philosophiques sur les Probabilités, 1819).

“It is sometimes considered a paradox that the answer depends not only on the observations but on the question; it should be a platitude.” (Harold Jeffreys,Theory of Probability, 1st edition, 1939).
A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer
Authors: Huang Meijuan , Liu Yongmei , Yu Min , Li Yanying , Zhang Yan , Zhu Jiang , Li Li , Lu You
Published: November 2021

Background. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.
Education, taxation and the perceived effects of sin good consumption
Authors: Immordino Giovanni , Menichini Anna Maria C. , Romano Maria Grazia
Published: November 2021

In a setting in which an agent has a behavioral bias that causes an underestimation or an overestimation of the health consequences of sin goods consumption, the paper studies how a social planner can affect the demand of such goods through education and taxation. When only optimistic consumers are present, depending on the elasticity of demand of the sin good with respect to taxation, the two instruments can be substitutes or complements. When consumers are heterogeneous, the correcting effect that taxation has on optimistic consumers has unintended distorting effects on both pessimistic and rational ones. In this framework, educational measures, by aligning biased consumers’ perceptions closer to the true probability of health damages, are more effective than taxation.
Asymptotic Dynamics of Young Differential Equations
Authors: Duc Luu Hoang , Hong Phan Thanh
Published: November 2021

We provide a unified analytic approach to study the asymptotic dynamics of Young differential equations, using the framework of random dynamical systems and random attractors. Our method helps to generalize recent results (Duc et al. in J Differ Equ 264:1119–1145, 2018, SIAM J Control Optim 57(4):3046–3071, 2019; Garrido-Atienza et al. in Int J Bifurc Chaos 20(9):2761–2782, 2010) on the existence of the global pullback attractors for the generated random dynamical systems. We also prove sufficient conditions for the attractor to be a singleton, thus the pathwise convergence is in both pullback and forward senses.
Bias and Modality in Conditionals: Experimental Evidence and Theoretical Implications
Authors: Liu Mingya , Rotter Stephanie , Giannakidou Anastasia
Published: November 2021

The concept of bias is familiar to linguists primarily from the literature on questions. Following the work of Giannakidou and Mari (Truth and Veridicality in Grammar and Thought: Modality, Mood, and Propositional Attitudes, University of Chicago Press, Chicago, 2021), we assume “nonveridical equilibrium” (implying thatpand¬pas equal possibilities) to be the default for epistemic modals, questions and conditionals. The equilibrium of conditionals, as that of questions, can be manipulated to produce bias (i.e., reduced or higherspeaker commitment). In this paper, we focus on three kinds of modal elements in German that create bias in conditionals and questions: the adverbwirklich‘really’, the modal verbsollte‘should’, and conditional connectives such asfalls‘if/in case’. We conducted two experiments collecting participants’ inference about speaker commitment in different manipulations, Experiment 1 onsollte/wirklichinob-questions andwenn-conditionals, and Experiment 2 onsollte/wirklichinwenn/falls/V1-conditionals. Our findings are that bothob-questions andfalls-conditionals express reduced speaker commitment about the modified (antecedent) proposition in comparison towenn-conditionals, which did not differ from V1-conditionals. In addition,sollte/wirklichin the antecedent of conditionals both create negative bias about the antecedent proposition. Our studies are among the first that deal with bias in conditionals (in comparison to questions) and contribute to furthering our understanding of bias.
Educating for Responsible Research Practice in Biomedical Sciences
Authors: Gerrits Elianne M. , Bredenoord Annelien L. , van Mil Marc H. W.
Published: November 2021

New developments in the field of biomedicine can have extensive implications for society. To steer research efforts in a responsible direction, biomedical scientists should contribute to a forward-looking ethical, and societal evaluation of new developments. However, the question remains how to equip students sufficiently with the skills they need to contribute to this evaluation. In this paper, we examine how the four dimensions of Responsible Research and Innovation (anticipation, reflexivity, inclusivity, and responsiveness) inform the identification of learning goals and teaching approaches that contribute to developing these skills in biomedical scientists. We suggest that these educational approaches focus on the skills to anticipate intended and unintended outcomes, reflect on the epistemological and moral aspects of research practice, and be inclusive of the variety of voices in society. We argue that if these dimensions are properly integrated into biomedical curricula, they will help students develop the attitudinal aspects necessary for becoming responsive, and prepare them for implementing the dimensions of responsible research into their daily practice. This paper focuses specifically on skills biomedical scientists need for the responsible conduct of research. Therefore, our analysis results, at least in part, in domain-specific recommendations. We invite educators from other disciplines to do the same exercise, as we believe this could lead to tailored educational approaches by which students from various disciplinary backgrounds learn how they each have a role in contributing to socially robust and morally responsible research practice.
Geographical Differences in the Quality of Life in Poland: Challenges of Regional Policy
Authors: Churski Paweł , Perdał Robert
Published: November 2021

Commonly used in human geography, quality of life (QOL) refers to the way and degree to which objective human needs are met, not only existential ones, but also those regarding the development of the human personality. This article diagnoses QOL understood in this way in Poland and its changes between 2004 and 2018 (i.e. during modernization), which saw the continuation of systemic transformation after joining the EU. To fully identify the regularity of spatial differences in the analysed phenomenon, 380 local units are used as reference points. First, we formulated an operational definition of multifaceted QOL with its separate dimensions, as well as selecting and constructing organized indicators that can be determined at the local level. Then we quantified local differences in the rate of growth and the level of QOL using multivariate analysis. Third, on the basis of the obtained results, we sought to reach the most significant conclusions: (1) the dynamic economic growth, enjoyed in Poland in 2004–2018, did not change significantly the spatial diversity of the quality of life on a local level. (2) To a large extent, the persistent differences in the quality of life in Poland are related to the historical spatial differences in the level of urbanisation and the well-established, traditional economic structure of the specific territorial units. (3) A higher degree of urbanisation coupled with the service- and service and industry-related functional nature of the local units in Poland are conducive to a better quality of life. This confirms the regularities observed in the countries on the verge of a rapid economic development.
Participatory Budgeting as a Method for Improving Public Spaces in Major Polish Cities
Authors: Szczepańska A. , Zagroba M. , Pietrzyk K.
Published: November 2021

One of the forms of public participation in the local governance system is civic budgeting which actively engages residents in developing projects and voting on the submitted proposals. Civic budgeting aims to involve local communities in deciding how a defined portion of public resources should be allocated by means of a democratic debate. Public spaces are the essence of urban life; therefore, the aim of the study was to analyze civic budget records relating to public spaces. The study was conducted in the largest Polish cities. The research involved quantitative and comparative analytical methods. The analysis focused on community involvement and local community needs, represented by a wide array of public space-related project categories. The analyzed cities were ranked according to their civic engagement, and the resulting classification was compared with voter turnout during polls on the proposals adopted as part of the CB process. The results revealed considerable diversity in both civic engagement and local needs, and they could be used to develop guidelines for designing public spaces in the urban planning process. The present findings are also a valuable source of information for local governments in their efforts to improve the functioning, attractiveness and development of user-friendly spaces in citizen-oriented cities.