bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of proteins and amino acids with iso-α-acids during wort preparation in the brewhouse
Authors: Gänz Nele , Becher Tobias , Drusch Stephan , Titze Jean
Published: December 2021

This paper investigates the binding behavior of iso-α-acids from hops on free wort amino acids and proteins concerning the wort production process in breweries. The studies were carried out with different amino acids, bovine serum albumin and wort. To identify the nature of reaction between iso-α-acids and these substances, analyses of free amino nitrogen, HPLC and isothermal titration calorimetry were performed. According to the results, the iso-α-acids do not form covalent bonds with free amino acids of wort. However, iso-α-acids, especially isohumulone and isoadhumulone, form ionic bonds with wort proteins. A distinction must be made between proteins that are present in the hot trub, and those that are still dissolved in the hot wort. Proteins that are already coagulated and precipitated no longer react with iso-α-acids. Future experiments will investigate whether the established ionic bonds between iso-α-acids and proteins from the wort preparation process are maintained during fermentation until the finished beer or beer foam. If this is the case, which is induced by the experiments, there is a measurable loss of iso-α-acids in the hot wort, but at the same time, a gain for the later beer foam retention, as the iso-α-acids will stabilize it.
Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study
Authors: Prudente Cecília N. , Chen Mo , Stipancic Kaila L. , Marks Katherine L. , Samargia-Grivette Sharyl , Goding George S. , Green Jordan R. , Kimberley Teresa J.
Published: December 2021

Purpose

The effects of neuromodulation are virtually unexplored in adductor laryngeal dystonia (AdLD), a disorder characterized by involuntary contraction of intrinsic laryngeal muscles. Recent findings indicated that intracortical inhibition is reduced in people with AdLD. Low-frequency repetitive transcranial magnetic stimulation (rTMS) induces prolonged intracortical inhibition, but the effects in AdLD are unexplored. This pilot and feasibility study aimed to examine the safety, feasibility, and effects of a single session 1 Hz rTMS over the laryngeal motor cortex (LMC) in people with AdLD and healthy individuals.

Methods

The stimulation location was individualized and determined through TMS-evoked responses in the thyroarytenoid muscles using fine-wire electrodes. 1200 pulses of 1 Hz rTMS were delivered to the left LMC in two groups: Control (n = 6) and AdLD (n = 7). Tolerance, adverse effects, intracortical inhibition, and voice recordings were collected immediately before and after rTMS. Voice quality was assessed with acoustic-based and auditory-perceptual measures.

Results

All participants tolerated the procedures, with no unexpected adverse events or worsening of symptoms. No significant effects on intracortical inhibition were observed. In the AdLD group, there was a large-effect size after rTMS in vocal perturbation measures and a small-effect size in decreased phonatory breaks.

Conclusions

One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in AdLD. These preliminary findings support further investigation to assess clinical benefits in a future randomized sham-controlled trial.

ClinicalTrials.gov

NCT02957942, registered on November 8, 2016.
Clostridium perfringens Beta2 toxin forms highly cation-selective channels in lipid bilayers
Authors: Benz Roland , Piselli Claudio , Hoxha Cezarela , Koy Cornelia , Glocker Michael O. , Popoff Michel R.
Published: December 2021

Clostridium perfringens is a potent producer of a variety of toxins. Well studied from these are five toxins (alpha, Beta (CPB), epsilon, iota and CPE) that are produced by seven toxinotype strains (A–G) of C. perfringens. Besides these toxins, C. perfringens produces also another toxin that causes necrotizing enterocolitis in piglets. This toxin termed consensus Beta2 toxin (cCPB2) has a molecular mass of 27,620 Da and shows only little homology to CPB and no one to the other toxins of C. perfringens. Its primary action on cells remained unknown to date. cCPB2 was heterogeneously expressed as fusion protein with GST in Escherichia coli and purified to homogeneity. Although cCPB2 does not exhibit the typical structure of beta-stranded pore-forming proteins and contains no indication for the presence of amphipathic alpha-helices we could demonstrate that cCPB2 is a pore-forming component with an extremely high activity in lipid bilayers. The channels have a single-channel conductance of about 700 pS in 1 M KCl and are highly cation-selective as judged from selectivity measurements in the presence of salt gradients. The high cation selectivity is caused by the presence of net negative charges in or near the channel that allowed an estimate of the channel size being about 1.4 nm wide. Our measurements suggest that the primary effect of cCPB2 is the formation of cation-selective channels followed by necrotic enteritis in humans and animals. We searched in databases for homologs of cCPB2 and constructed a cladogram representing the phylogenetic relationship to the next relatives of cCPB2.
The effectiveness of manual therapy on pain, physical function, and nerve conduction studies in carpal tunnel syndrome patients: a systematic review and meta-analysis
Authors: Jiménez-del-Barrio Sandra , Cadellans-Arróniz Aida , Ceballos-Laita Luis , Estébanez-de-Miguel Elena , López-de-Celis Carles , Bueno-Gracia Elena , Pérez-Bellmunt Albert
Published: December 2021

Aim of the study

Systematic review and meta-analysis to assess the effectiveness of manual therapy in improving carpal tunnel syndrome (CTS) symptoms, physical function, and nerve conduction studies.

Method

MEDLINE, Web of Science, SCOPUS, Cochrane Library, TRIP database, and PEDro databases were searched from the inception to September 2021. PICO search strategy was used to identify randomized controlled trials applying manual therapy on patients with CTS. Eligible studies and data extraction were conducted independently by two reviewers. Methodology quality and risk of bias were assessed by PEDro scale. Outcomes assessed were pain intensity, physical function, and nerve conduction studies.

Results

Eighty-one potential studies were identified and six studies involving 401 patients were finally included. Pain intensity immediately after treatment showed a pooled standard mean difference (SMD) of − 2.13 with 95% confidence interval (CI) (− 2.39, − 1.86). Physical function with Boston Carpal Tunnel Syndrome Questionnaire (BCTS-Q) showed a pooled SMD of − 1.67 with 95% CI (− 1.92, − 1.43) on symptoms severity, and a SMD of − 0.89 with 95% CI (− 1.08, − 0.70) on functional status. Nerve conduction studies showed a SMD of − 0.19 with 95% CI (− 0.40, − 0.02) on motor conduction and a SMD of − 1.15 with 95% CI (− 1.36, − 0.93) on sensory conduction.

Conclusions

This study highlights the effectiveness of manual therapy techniques based on soft tissue and neurodynamic mobilizations, in isolation, on pain, physical function, and nerve conduction studies in patients with CTS.
Inanspruchnahme von Unterstützungsangeboten in Familien mit einem psychisch belasteten Elternteil
Authors: Schunke Annika , Reim Julia , Lux Ulrike , Walper Sabine
Published: December 2021

Hintergrund

Kinder psychisch erkrankter Eltern sind vielfach mit familialen Belastungen konfrontiert und haben ein erhöhtes Risiko, selbst an einer psychischen Störung zu erkranken. Präventionsangebote auf Eltern- und Kindebene haben entsprechend hohe Relevanz. Wenig Beachtung in der Forschung fand bislang die Frage, inwieweit therapeutische und beratende Unterstützungsangebote für psychisch belastete Eltern auch der gesundheitlichen Versorgung ihrer Kinder zugutekommen.

Fragestellung

Die vorliegende Studie untersucht eltern- und kindbezogene Prädiktoren der Inanspruchnahme von therapeutischen und familienbezogenen Unterstützungsangeboten bei Eltern mit selbstberichteter psychischer Belastung. Zusammenhänge zur Inanspruchnahme von Kinder- und Jugendtherapie, auch in Abhängigkeit von der kindlichen psychischen Gesundheit, werden geprüft.

Material und Methode

Ausgehend von 844 Eltern mit 1146 Kindern im Alter von 7 bis 16 Jahren, die in den Wellen 11 und 12 des pairfam-Panels befragt wurden, umfasst die Stichprobe der Hauptanalysen 161 Kinder, deren Elternteil über Depressionssymptome oder eine psychische Erkrankung berichtete. Angaben zur Inanspruchnahme von Therapie und weiteren Angeboten stammen von dem Elternteil, Angaben zur psychischen Gesundheit der Kinder von diesen selbst.

Ergebnisse

Etwa ein Drittel der Eltern mit selbstberichteter psychischer Belastung nimmt eine Therapie in Anspruch. Hierbei werden häufiger auch weitere Angebote für Familien und Kinder genutzt. Selbstberichtete Verhaltensauffälligkeiten der Kinder haben jedoch keinen weiteren Effekt auf ihre Versorgungslage.

Schlussfolgerung

Die Befunde sprechen für eine unzureichende Versorgungslage von auffälligen Kindern psychisch belasteter Eltern, auch dann, wenn die Eltern selbst in Behandlung sind.
Functional results of endoscopic arytenoid abduction lateropexy for bilateral vocal fold palsy
Authors: Rovó László , Matievics Vera , Sztanó Balázs , Szakács László , Pálinkó Dóra , Wootten Christopher T. , Pfiszterer Péter , Tóbiás Zoltán , Bach Ádám
Published: December 2021

Purpose

Endoscopic arytenoid abduction lateropexy (EAAL) is a reliable surgical solution for the minimally invasive treatment of bilateral vocal fold palsy (BVFP), providing a stable airway by the lateralization of the arytenoid cartilages with a simple suture. The nondestructive manner of the intervention theoretically leads to higher regeneration potential, thus better voice quality. The study aimed to investigate the respiratory and phonatory outcomes of this treatment concept.

Methods

61 BVFP patients with significant dyspnea associated with thyroid/parathyroid surgery were treated by unilateral EAAL. Jitter, Shimmer, Harmonics to Noise Ratio, Maximum Phonation Time, Fundamental frequency, Voice Handicap Index, Dysphonia Severity Index, Friedrich’s Dysphonia Index, Global-Roughness-Breathiness scale, Quality of Life, and Peak Inspiratory Flow were evaluated 18 months after EAAL.

Results

All patients had a stable and adequate airway during the follow-up. Ten patients (16.4%) experienced complete bilateral motion recovery with objective acoustic parameters in the physiological ranges. Most functional results of the 13 patients (21.3%) with unilateral recovery also reached the normal values. Fifteen patients (24.6%) had unilateral adduction recovery only, with slightly impaired voice quality. Eleven patients (18.0%) had false vocal fold phonation with socially acceptable voice. In 12 patients (19.7%) no significant motion recovery was detected on the glottic level.

Conclusion

EAAL does not interfere with the potential regeneration process and meets the most important phoniatric requirements while guaranteeing the reversibility of the procedure—therefore serving patients with transient palsy. Further, a socially acceptable voice quality and an adequate airway are ensured even in cases of permanent bilateral vocal fold paralysis.
Integrating trauma, self-disturbances, cognitive biases, and personality into a model for the risk of psychosis: a longitudinal study in a non-clinical sample
Authors: Pionke-Ubych Renata , Frydecka Dorota , Cechnicki Andrzej , Krężołek Martyna , Nelson Barnaby , Gawęda Łukasz
Published: December 2021

The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in non-clinical as well. The aim of this longitudinal study was to investigate self-disturbances (SD), a risk factor that has attracted substantial interest over the last two decades, in combination with trauma, cognitive biases and personality, and to test whether SD are associated with subclinical positive symptoms (PS) over a 12-month follow-up period. Our study was conducted in a non-clinical sample of 139 Polish young adults (81 females, ageM = 25.32, SD = 4.51) who were selected for frequent experience of subclinical PS. Participants completed self-report questionnaires for the evaluation of SD (IPASE), trauma (CECA.Q), cognitive biases (DACOBS) and personality (TCI), and were interviewed for subclinical PS (CAARMS). SD and subclinical PS were re-assessed 12 months after baseline measurement. The hypothesized model for psychosis risk was tested using path analysis. The change in SD and subclinical PS over the 12-month period was investigated with non-parametric equivalent of dependent sample t-tests. The models with self-transcendence (ST) and harm avoidance (HA) as personality variables were found to be well-fitted and explained 34% of the variance in subclinical PS at follow-up. Moreover, we found a significant reduction of SD and subclinical PS after 12 months. Our study suggests that combining trauma, cognitive biases, SD and personality traits such as ST and HA into one model can enhance our understanding of appearance as well as maintenance of subclinical PS.
Targeting abundant survivin expression in liposarcoma: subtype dependent therapy responses to YM155 treatment
Authors: Vay Christian , Schlünder Philipp M. , Dizdar Levent , Esposito Irene , Ghadimi Markus P. H. , Knoefel Wolfram T. , Krieg Andreas
Published: December 2021

Purpose

Liposarcoma (LPS) represent the largest group of malignant soft tissue tumours comprising a heterogeneous group of subtypes in which the degrees of chemoresistance and radiosensitivity strongly vary. Consequently, it is of utmost interest to establish novel therapeutic regimens based on molecular targets.

Methods

Immunohistochemical staining of survivin was performed in tissue microarrays comprising 49 primary LPS specimens. LPS cell lines were treated with survivin antagonist YM155 and doxorubicin or etoposide alone as well as in combination. Changes in cell viability were investigated and the synergistic effect of a combined therapy analysed.

Results

Immunohistochemistry revealed an abundant expression of survivin in LPS that significantly concurred with less-differentiated tumour subtypes and grading. In vitro, we demonstrated the impact of the survivin inhibitor YM155 on dedifferentiated LPS (DDLPS) and, even more imposing, pleomorphic LPS (PLS) tumour cell viability with a strong induction of apoptosis. A combined treatment of doxorubicin or etoposide with YM155 augmented the cytotoxic effects on DDLPS and PLS cells.

Conclusion

These findings support the significant role of survivin in the oncogenesis and progression of LPS subtypes providing a rationale to target survivin in eligible in-vivo models and to pioneer clinical applications of survivin-specific substances unfolding their therapeutic potential in LPS patients prospectively.
Fine structure of mushroom bodies and the brain in Sthenelais boa (Phyllodocida, Annelida)
Authors: Beckers Patrick , Pein Carla , Bartolomaeus Thomas
Published: December 2021

Mushroom bodies are known from annelids and arthropods and were formerly assumed to argue for a close relationship of these two taxa. Since molecular phylogenies univocally show that both taxa belong to two different clades in the bilaterian tree, similarity must either result from convergent evolution or from transformation of an ancestral mushroom body. Any morphological differences in the ultrastructure and composition of mushroom bodies could thus indicate convergent evolution that results from similar functional constraints. We here study the ultrastructure of the mushroom bodies, the glomerular neuropil, glia-cells and the general anatomy of the nervous system in Sthenelais boa. The neuropil of the mushroom bodies is composed of densely packed, small diameter neurites that lack individual or clusterwise glia enwrapping. Neurites of other regions of the brain are much more prominent, are enwrapped by glia-cell processes and thus can be discriminated from the neuropil of the mushroom bodies. The same applies to the respective neuronal somata. The glomerular neuropil of insects and annelids is a region of higher synaptic activity that result in a spheroid appearance of these structures. However, while these structures are sharply delimited from the surrounding neuropil of the brain by glia enwrapping in insects, this is not the case in Sthenelais boa. Although superficially similar, there are anatomical differences in the arrangement of glia-cells in the mushroom bodies and the glomerular neuropil between insects and annelids. Hence, we suppose that the observed differences rather evolved convergently to solve similar functional constrains than by transforming an ancestral mushroom body design.
Basement and cover architecture in the Central Pyrenees constrained by gravity data
Authors: Clariana P. , Soto R. , Ayala C. , Casas-Sainz A. M. , Román-Berdiel T. , Oliva-Urcia B. , Pueyo E. L. , Beamud E. , Rey-Moral C. , Rubio F. , Margalef A. , Schamuells S. , Bach N. , Martí J.
Published: December 2021

A new gravity survey (1164 gravity stations and 180 samples for density analysis) combined with two new geological cross sections has been carried out in a sector of the Central Pyrenees in order to improve the characterization of basement and cover architecture. From North to South, the study area comprises the southern half of the Axial Zone and the northernmost part of the South-Pyrenean Zone. New gravity data were combined with previous existing databases to obtain the Bouguer and residual anomaly maps of the study area. The two cross sections, oriented NNE–SSW, were built from field data and previous surficial and subsurface data and cross the La Maladeta plutonic complex. The residual anomaly map shows values ranging from −18 to 16 mGal and anomalies mainly oriented N120E. The two 2.5D modelled cross sections show similar observed gravity curves coinciding with similar interpreted structural architecture. Data show a gravity high oriented N120E coinciding with the Orri basement thrust sheet and an important gravity depression, with the same orientation, coinciding with the leading edge at depth of the Rialp basement thrust sheet and interpreted as linked to a large subsurface accumulation of Triassic evaporites. The volume at depth of the La Maladeta and Arties granites has been constrained through gravity modelling. This work highlights that the combination of structural geology and gravity modelling can help to determine the structural architecture of an orogen and localize accumulations of evaporites at depth.
On the incorporation of strontium into the crystal structure of bredigite: structural effects and phase transition
Authors: Kahlenberg Volker , Prosser Lukas , Salzmann Michael F. , Hejny Clivia
Published: December 2021

Sr-substitution in the crystal structure of bredigite has been studied in detail. Samples of a hypothetical solid-solution series with nominal composition Ca7-xSrxMg[SiO4]4 (x = 0, 2, …,7) have been prepared from sinter reactions in the temperature range between 1275 and 1325 °C and characterized using powder and single-crystal X-ray diffraction. Synthesis runs between x = 1 and x = 4 resulted in compounds with increasing Sr contents, for which single-crystal diffraction studies revealed the following Sr/(Sr + Ca) atomic ratios: 0.133,0.268, 0.409 and 0.559. They are isostructural to the pure calcium end-member (x = 0) and adopt the orthorhombic space group Pnnm. Evolution of the unit-cell parameters and cell volumes of the solid-solution series are defined by linear or nearly linear trends when plotted against the Sr/(Sr + Ca) atomic ratio. Replacement of calcium with strontium atoms on the different sites shows clear preferences for specific positions. For the experiment with x = 5, formation of bredigite-related single-crystals with Sr/(Sr + Ca) = 0.675 was observed. These samples, however, exhibited a halved c lattice parameter when compared with the corresponding value in the Pnnm structure, pointing to a compositionally induced phase transition somewhere in region between Sr/(Sr + Ca) = 0.559 and 0.675. The crystal structure of this new phase with composition Ca2.32Sr4.82Mg0.86[SiO4]4 was successfully determined in space group Pbam. Basic crystallographic data are as follows: a = 18.869(2) Å, b = 6.9445(8) Å, c = 5.5426(6) Å, V = 726.28(14) Å3, Z = 2. Structure determination was accomplished using charge flipping. Subsequent least-squares refinements resulted in a residual of R(|F|) = 2.70% for 822 independent reflections and 87 parameters. The Pbam- and the Pnnm-structures are in a group-subgroup relationship and topologically related. Both are based on so-called pinwheel-like MSi6O24 clusters consisting of a central magnesium-dominated [MO6]-octahedron as well as six attached [SiO4]-tetrahedra. The clusters are linked into chain-like elements running along [001]. Linkage between the chains is provided by mixed Sr/Ca positions with 6 to 10 oxygen ligands. Differences between the two phases result from changes in Sr-Ca site occupancies in combination with displacements of the atoms and tilts of the tetrahedra. The distortion pattern has been studied using group-theoretical methods including mode analysis. Notably, for the samples with x = 6 and x = 7—the latter corresponding to the hypothetical pure strontium end-member composition—no bredigite-type phases could be identified, indicating that there is an upper limit for the Sr-uptake.
Institutions and institutional changes: aquatic food production in Central Luzon, Philippines
Authors: Manlosa Aisa O. , Hornidge Anna-Katharina , Schlüter Achim
Published: December 2021

Aquaculture is the most rapidly growing food production sector globally. In certain coastal social-ecological systems, this has resulted in significant changes and sustainability challenges. In particular, coastal environments which used to support only capture fisheries are becoming sites for brackish water aquaculture production; this impacts the sustainability of aquatic food production. Sustainability challenges associated with aquaculture expansion and intensification necessitate a contextually rooted understanding of institutions and institutional changes which can be used as an informed basis for leveraging institutions to achieve desirable sustainability outcomes in the aquatic food sector. This research used a qualitative empirical case study involving in-depth interviews, participant observation, and analysis of institutional documents in the region of Central Luzon, Philippines. It applied the inter-institutional systems concept which considers multiple institutions with distinct but linked purposes and functions in the societal spheres of state, market, and civil society. The study found that aquaculture emerged as an important livelihood because of rice farmers’ need to adapt to saltwater intrusion into what were formerly rice farms. It grew into an industry due to developments in the availability and accessibility of inputs such as fingerlings and feeds. This process was also driven by the high demand and high profitability of fish farming at the time. Regulatory institutions have not adequately adapted to protect the environment. Market institutions adapted but the changes mostly benefited consignacions (middlemen) and large-scale players. However, organised groups of collaborating smallholder fishers and fish farmers are helping to address the disadvantages they face.
Sensitivity analysis for unobserved confounding in causal mediation analysis allowing for effect modification, censoring and truncation
Authors: Lindmark Anita
Published: December 2021

Causal mediation analysis is used to decompose the total effect of an exposure on an outcome into an indirect effect, taking the path through an intermediate variable, and a direct effect. To estimate these effects, strong assumptions are made about unconfoundedness of the relationships between the exposure, mediator and outcome. These assumptions are difficult to verify in a given situation and therefore a mediation analysis should be complemented with a sensitivity analysis to assess the possible impact of violations. In this paper we present a method for sensitivity analysis to not only unobserved mediator-outcome confounding, which has largely been the focus of previous literature, but also unobserved confounding involving the exposure. The setting is estimation of natural direct and indirect effects based on parametric regression models. We present results for combinations of binary and continuous mediators and outcomes and extend the sensitivity analysis for mediator-outcome confounding to cases where the continuous outcome variable is censored or truncated. The proposed methods perform well also in the presence of interactions between the exposure, mediator and observed confounders, allowing for modeling flexibility as well as exploration of effect modification. The performance of the method is illustrated through simulations and an empirical example.
Model-driven development of asynchronous message-driven architectures with AsyncAPI
Authors: Gómez Abel , Iglesias-Urkia Markel , Belategi Lorea , Mendialdua Xabier , Cabot Jordi
Published: December 2021

In the Internet-of-Things (IoT) vision, everyday objects evolve into cyber-physical systems. The massive use and deployment of these systems has given place to the Industry 4.0 or Industrial IoT (IIoT). Due to its scalability requirements, IIoT architectures are typically distributed and asynchronous. In this scenario, one of the most widely used paradigms is publish/subscribe, where messages are sent and received based on a set of categories or topics. However, these architectures face interoperability challenges. Consistency in message categories and structure is the key to avoid potential losses of information. Ensuring this consistency requires complex data processing logic both on the publisher and the subscriber sides. In this paper, we present our proposal relying on AsyncAPI to automate the design and implementation of these asynchronous architectures using model-driven techniques for the generation of (part of) message-driven infrastructures. Our proposal offers two different ways of designing the architectures: either graphically, by modeling and annotating the messages that are sent among the different IoT devices, or textually, by implementing an editor compliant with the AsyncAPI specification. We have evaluated our proposal by conducting a set of experiments with 25 subjects with different expertise and background. The experiments show that one-third of the subjects were able to design and implement a working architecture in less than an hour without previous knowledge of our proposal, and an additional one-third estimated that they would only need less than two hours in total.
G protein-coupled receptors that influence lifespan of human and animal models
Authors: Lagunas-Rangel Francisco Alejandro
Published: December 2021

Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.
Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial
Authors: Turner Nicholas , Dent Rebecca A. , O’Shaughnessy Joyce , Kim Sung-Bae , Isakoff Steven J. , Barrios Carlos , Saji Shigehira , Bondarenko Igor , Nowecki Zbigniew , Lian Qinshu , Reilly Sarah-Jayne , Hinton Heather , Wongchenko Matthew J. , Kovic Bruno , Mani Aruna , Oliveira Mafalda
Published: December 2021

Purpose

PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC).

Methods

Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse < 1 year since (neo)adjuvant chemotherapy were ineligible. Patients were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, plus paclitaxel (80 mg/m2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS).

Results

Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%).

Conclusion

Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects.

Trial registration NCT03337724.
Examining the Mental Health Presentations of Treatment-Seeking Transgender and Gender Nonconforming (TGNC) Youth
Authors: Stewart Shannon L. , Van Dyke Jocelyn N. , Poss Jeffrey W.
Published: December 2021

Recent research suggests that transgender and/or gender nonconforming (TGNC) youth present with heightened levels of mental health problems compared to peers. This study seeks to examine the mental health needs of a large sample of treatment-seeking TGNC youth by comparing them to cisgender males and females. Participants were 94,804 children and youth ages 4–18 years (M = 12.1, SD = 3.72) who completed the interRAI Child and Youth Mental Health Instrument (ChYMH) or Screener (ChYMH-S) at participating mental health agencies in the Ontario, Canada. Overall, the mental health presentations of TGNC youth were similar to cisgender females but at higher acuity levels. TGNC youth showed significantly higher levels of anxiety, depression, social disengagement, positive symptoms, risk of suicide/self-harm, and were more likely to report experiencing emotional abuse, past suicide attempts, and a less strong, supportive family relationship than cisgender females and males. Clinical implications of these findings are discussed.
Flow, force, behaviour: assessment of a prototype hydraulic barrier for invasive fish
Authors: Wiegleb Joschka , Hirsch Philipp E. , Seidel Frank , Rauter Georg , Burkhardt-Holm Patricia
Published: December 2021

Migration barriers being selective for invasive species could protect pristine upstream areas. We designed and tested a prototype protective barrier in a vertical slot fish pass. Based on the individuals’ swimming responses to the barrier flow field, we assumed this barrier would block the ascension of the invasive round goby, but allow comparable native species (gudgeon and bullhead) to ascend. The barrier was tested in three steps: flow description, quantification of forces experienced by preserved fish in the flow field, and tracking the swimming trajectories of ca. 43 live fish per trial and species. The flow and the forces were homogenous over the barrier, though gudgeon experienced significantly smaller forces than round goby or bullhead. The swimming trajectories were distinct enough to predict the fish species with a random forest machine learning approach (92.16% accuracy for gudgeon and 85.24% for round goby). The trajectories revealed round goby and gudgeon exhibited increased, but varied, swimming speeds and straighter paths at higher water discharge. These results suggest that passage of round goby was prevented at 130 L/s water discharge, whereas gudgeon and bullhead could pass the barrier. Our findings open a new avenue of research on hydraulic constructions for species conservation.
Breast histopathological image analysis using image processing techniques for diagnostic purposes: A methodological review
Authors: Rashmi R , Prasad Keerthana , Udupa Chethana Babu K
Published: December 2021

Breast cancer in women is the second most common cancer worldwide. Early detection of breast cancer can reduce the risk of human life. Non-invasive techniques such as mammograms and ultrasound imaging are popularly used to detect the tumour. However, histopathological analysis is necessary to determine the malignancy of the tumour as it analyses the image at the cellular level. Manual analysis of these slides is time consuming, tedious, subjective and are susceptible to human errors. Also, at times the interpretation of these images are inconsistent between laboratories. Hence, a Computer-Aided Diagnostic system that can act as a decision support system is need of the hour. Moreover, recent developments in computational power and memory capacity led to the application of computer tools and medical image processing techniques to process and analyze breast cancer histopathological images. This review paper summarizes various traditional and deep learning based methods developed to analyze breast cancer histopathological images. Initially, the characteristics of breast cancer histopathological images are discussed. A detailed discussion on the various potential regions of interest is presented which is crucial for the development of Computer-Aided Diagnostic systems. We summarize the recent trends and choices made during the selection of medical image processing techniques. Finally, a detailed discussion on the various challenges involved in the analysis of BCHI is presented along with the future scope.
Prompt and delayed gamma rays induced by epithermal and fast neutrons with indium
Authors: Mauerhofer Eric , Ilic Zeljko , Stieghorst Christian , Révay Zsolt , Rossbach Matthias , Li Jingjing , Randriamalala Tsitohaina H. , Brückel Thomas
Published: December 2021

The emission of prompt and delayed gamma rays from (n,γ) and (n,n´γ) reactions induced by irradiation of indium with epithermal and fast neutrons was investigated with the instrument FaNGaS operated at Heinz-Maier-Leibnitz Zentrum (MLZ) in Garching. The average neutron energy of the neutron spectrum was 2.30 MeV. The measurement was done at an angle of 90° between neutron beam and detector. A total of 136 prompt gamma lines from which 42 are related to the capture of epithermal and fast neutrons and 94 to the inelastic scattering of fast neutrons were detected together with the delayed gamma lines of the activation products 113mIn, 114m2In, 115mIn, 116m2In and 116mIn. Intensities and neutron spectrum averaged isotopic partial cross section of the gamma lines are presented. Additionally the neutron spectrum averaged cross sections of the reactions, 113In(n,n´)113mIn, 113In(n,γ)114m2In, 115In(n,n´)15mIn, 115In(n, γ)116m2In and 115In(n, γ)116mIn were determined from the corresponding delayed gamma rays of the formed isotopes as 143 ± 22, 288 ± 13 194 ± 18, 201 ± 10 and 508 ± 24 mb respectively. The various results obtained were found consistent with the literature data. However, our measurement indicate the need to reevaluate the cross section of the 115In(n,γ)116m2In reaction for thermal neutrons.
Train here, drive there: ROS based end-to-end autonomous-driving pipeline validation in CARLA simulator using the NHTSA typology
Authors: Gómez-Huélamo Carlos , Del Egido Javier , Bergasa Luis M. , Barea Rafael , López-Guillén Elena , Arango Felipe , Araluce Javier , López Joaquín
Published: December 2021

Urban complex scenarios are the most challenging situations in the field of Autonomous Driving (AD). In that sense, an AD pipeline should be tested in countless environments and scenarios, escalating the cost and development time exponentially with a physical approach. In this paper we present a validation of our fully-autonomous driving architecture using the NHTSA (National Highway Traffic Safety Administration) protocol in the CARLA simulator, focusing on the analysis of our decision-making module, based on Hierarchical Interpreted Binary Petri Nets (HIBPN). First, the paper states the importance of using hyper-realistic simulators, as a preliminary help to real test, as well as an appropriate design of the traffic scenarios as the two current keys to build safe and robust AD technology. Second, our pipeline is introduced, which exploits the concepts of standard communication in robotics using the Robot Operating System (ROS) and the Docker approach to provide the system with isolation, flexibility and portability, describing the main modules and approaches to perform the navigation. Third, the CARLA simulator is described, outlining the steps carried out to merge our architecture with the simulator and the advantages to create ad-hoc driving scenarios for use cases validation instead of just modular evaluation. Finally, the architecture is validated using some challenging driving scenarios such as Pedestrian Crossing, Stop, Adaptive Cruise Control (ACC) and Unexpected Pedestrian. Some qualitative (video files: Simulation Use Cases) and quantitative (linear velocity and trajectory splitted in the corresponding HIBPN states) results are presented for each use case, as well as an analysis of the temporal graphs associated to the Vulnerable Road Users (VRU) cases, validating our architecture in simulation as a preliminary stage before implementing it in our real autonomous electric car.
Benchmarking the Viability of 3D Printed Micromodels for Single Phase Flow Using Particle Image Velocimetry and Direct Numerical Simulations
Authors: Patsoukis Dimou Alexandros , Menke Hannah P. , Maes Julien
Published: December 2021

Holistic understanding of multiphase reactive flow mechanisms such as CO2 dissolution, multiphase displacement, and snap-off events is vital for optimisation of large-scale industrial operations like CO2 sequestration, enhanced oil recovery, and geothermal energy. Recent advances in three-dimensional (3D) printing allow for cheap and fast manufacturing of complex porosity models, which enable investigation of specific flow processes in a repeatable manner as well as sensitivity analysis for small geometry alterations. However, there are concerns regarding dimensional fidelity, shape conformity and surface quality, and therefore, the printing quality and printer limitations must be benchmarked. We present an experimental investigation into the ability of 3D printing to generate custom-designed micromodels accurately and repeatably down to a minimum pore-throat size of 140 μm, which is representative of the average pore-throat size in coarse sandstones. Homogeneous and heterogeneous micromodel geometries are designed, then the 3D printing process is optimised to achieve repeatable experiments with single-phase fluid flow. Finally, Particle Image Velocimetry is used to compare the velocity map obtained from flow experiments in 3D printed micromodels with the map generated with direct numerical simulation (OpenFOAM software) and an accurate match is obtained. This work indicates that 3D printed micromodels can be used to accurately investigate pore-scale processes present in CO2 sequestration, enhanced oil recovery and geothermal energy applications more cheaply than traditional micromodel methods.
Mechanical properties of steel slag replaced mineral aggregate for road base/sub-base application based Vietnam and Japan standard
Authors: Dang Dang Tung , Nguyen Manh Tuan , Nguyen Tan Phong , Isawa Tomoo , Ta Yasutaka , Sato Ryoichi
Published: December 2021

Steelmaking slag is one of the most massive industrial by-products generated during steelmaking processes. This paper presents the current steelmaking slag production status and its potential to use as mineral aggregates in base/sub-base layer of road pavement. The mechanical properties of steelmaking slag were confirmed by the test method specified in Vietnam specification. The volume stability test of the slag was conducted based on JIS A 5015-2018 (Japanese Industrial Standard: Iron and steel slag for road construction). From the results, it was confirmed that steelmaking slag can satisfy all the mechanical requirements specified in Vietnam specification and the requirements regarding stability specified in JIS A 5015-2018. In addition, it was found that the elastic modulus of steelmaking slag applied as a base or sub-base layer in pavement was higher than that of the conventional graded aggregate made from mineral aggregate. Therefore, the thickness of pavement can be reduced by using steelmaking slag, and the construction cost can be lower.
Acute and chronic health risk assessment for inhalation and ingestion exposure in acrylic acid leak accidents
Authors: Lim Hui-Been , Park Si-Hyun , Hong Hyong-Jin , Jeong Ji-Yun , Kim Hee-Seok , Lee Cheol-Min
Published: December 2021

We established a hypothetical acrylic acid leak accident scenario, conducted a health risk assessment of local residents, and compared an actual accident case to the hypothetical scenario. The exposed subjects were divided into four age groups, and a noncarcinogenic health risk assessment was conducted for inhalation and soil ingestion. In the hypothetical scenario, 40 tons of acrylic acid was leaked in Ulsan for 1 h from midnight on January 1, 2017. In the actual accident case, 3 L of acrylic acid was leaked in Hwaseong, Gyeonggi Province, for 1 h from 11:00 am on March 5, 2020. The environmental concentration of acrylic acid was calculated using the dynamic multimedia environmental model. Noncarcinogenic assessment of the hypothetical scenario showed the hazard quotient exceeded 1 across all age groups, suggesting that a health risk is likely to occur due to inhalation exposure to acrylic acid resulting from a chemical accident. In addition, Hazardacute exceeded 1 until 2 h after the accident under the hypothetical scenario, indicating the likelihood of a health risk. Thus, we propose a methodology that can assess changing concentrations in a hazardous chemical leak from a chemical accident based on the time, place, the chemical’s behaviors in different environmental media, and the health risk posed by the exposure of the chemical to local residents in the area affected by the accident.
A workflow to investigate the impacts of weathered multi-walled carbon nanotubes to the mud snail Lymnaea stagnalis
Authors: Weise Katrin , Kurth Thomas , Politowski Irina , Winkelmann Carola , Schäffer Andreas , Kretschmar Susanne , Berendonk Thomas Ulrich , Jungmann Dirk
Published: December 2021

Although the development and application of nanomaterials is a growing industry, little data is available on the ecotoxicological effects on aquatic organisms. Therefore, we set up a workflow to address the potential uptake of weathered multi-walled carbon nanotubes (wMWCNTs) by a model organism, the pulmonary mud snail Lymnaea stagnalis (L. stagnalis), which plays an important role in the food web. It represents a suitable organism for this approach because as a grazer it potentially ingests large amounts of sedimented wMWCNTs. As food source for L. stagnalis, benthic biofilm was investigated by the use of a transmission electron microscope (TEM) and a scanning electron microscope (SEM) after exposure with wMWCNTs. In addition, isotopic labeling was applied with 14C-wMWCNTs (0.1 mg/L) to quantify fate, behavior, and enrichment of 14C-wMWCNTs in benthic biofilm and in L. stagnalis. Enrichment in benthic biofilm amounted to 529.0 µg wMWCNTs/g dry weight and in L. stagnalis to 79.6 µg wMWCNTs/g dry weight. A bioconcentration factor (BCF) for L. stagnalis was calculated (3500 L/kg). We demonstrate the accumulation of wMWCNTs (10 mg/L) in the digestive tract of L. stagnalis in an effect study. Moreover, the physiological markers glycogen and triglycerides as indicators for the physiological state, as well as the RNA/DNA ratio as growth indicator, were examined. No significant differences between exposed and control animals were analyzed for glycogen and triglycerides after 24 days of exposure, but a decreasing trend is recognizable for triglycerides. In contrast, the significant reduction in the RNA/DNA ratio of L. stagnalis indicated an inhibition of growth with a following recovery after depuration. The described workflow enables a comprehensive determination of the fate and the behavior of wMWCNTs specifically and in general all kinds of CNTs in the aquatic environment and therefore contributes to a holistic risk assessment of wMWCNTs.
A DEA MCDM Approach Applied to ESS8 Dataset for Measuring Immigration and Refugees Citizens’ Openness
Authors: Martín Juan Carlos , Indelicato Alessandro
Published: December 2021

The current refugees’ crisis is undermining the main government coalitions of many countries in the European Union (EU), and tolerant attitudes and open admission policies toward immigrants seem to be part of the recent past history. The dilemma is gaining a lot of media attention as the public and political debate on migration is now playing an important role in all the European elections. Thus, the aim of this paper twofold. First, an analytical tool is developed to measure two synthetic indicators: (1) the citizens’ openness towards immigration for 23 countries—18 EU Countries, plus Iceland, Israel, Norway, Switzerland, and Russia—included in the 2016 European Social Survey; and (2) the citizens’ openness towards immigrants and refugees for 22 countries (same set without Hungary). And second, the effects of political orientation of citizens over the last synthetic indicator (immigrants and refugees) are studied. The approach of Data Envelopment Analysis (DEA) will be adopted here, with the purpose of identifying which countries are more, or less, open to the phenomenon of immigration and refugees. The results show that the Nordic countries and leftist are those which show more openness to immigration and refugees.