bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma
Authors: Gong Jun , Thomassian Shant , Kim Sungjin , Gresham Gillian , Moshayedi Natalie , Ye Jason Y. , Yang Julianne C. , Jacobs Jonathan P. , Lo Simon , Nissen Nick , Gaddam Srinivas , Tighiouart Mourad , Osipov Arsen , Hendifar Andrew 
Published: September 2022

AbstractIn this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (−3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (−0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.
Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma
Authors: Cleary James M. , Rouaisnel Betty , Daina Antoine , Raghavan Srivatsan , Roller Lauren A. , Huffman Brandon M. , Singh Harshabad , Wen Patrick Y. , Bardeesy Nabeel , Zoete Vincent , Wolpin Brian M. , Losman Julie-Aurore 
Published: September 2022

AbstractThe mutant IDH1 inhibitor ivosidenib improves outcomes for patients with IDH1-mutated cholangiocarcinoma, but resistance inevitably develops. Mechanisms of resistance and strategies to overcome resistance are poorly understood. Here we describe two patients with IDH1 R132C-mutated metastatic cholangiocarcinoma who developed acquired resistance to ivosidenib. After disease progression, one patient developed an oncogenic IDH2 mutation, and the second patient acquired a secondary IDH1 D279N mutation. To characterize the putative IDH1 resistance mutation, cells expressing the double-mutant were generated. In vitro, IDH1 R132H/D279N produces (R)-2HG less efficiently than IDH1 R132H. However, its binding to ivosidenib is impaired and it retains the ability to produce (R)-2HG and promote cellular transformation in the presence of ivosidenib. The irreversible mutant IDH1 inhibitor LY3410738 binds and blocks (R)-2HG production and cellular transformation by IDH1 R132H/D279N. These resistance mechanisms suggest that IDH1-mutated cholangiocarcinomas remain dependent on (R)-2HG even after prolonged ivosidenib treatment. Sequential mutant IDH inhibitor therapy should be explored as a strategy to overcome acquired resistance to mutant IDH inhibitors.
Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations
Authors: Trombetta Claudia Maria , Piccini Giulia , Pierleoni Giulio , Leonardi Margherita , Dapporto Francesca , Marchi Serena , Andreano Emanuele , Paciello Ida , Benincasa Linda , Lovreglio Piero , Buonvino Nicola , Decaro Nicola , Stufano Angela , Lorusso Eleonora , Bombardieri Emilio , Ruello Antonella , Viviani Simonetta , Rappuoli Rino , Molesti Eleonora , Manenti Alessandro , Montomoli Emanuele 
Published: September 2022

AbstractThe SARS-CoV-2 Omicron variant has rapidly replaced the Delta variant of concern. This new variant harbors worrisome mutations on the spike protein, which are able to escape the immunity elicited by vaccination and/or natural infection. To evaluate the impact and susceptibility of different serum samples to the Omicron variant BA.1, samples from COVID-19 patients and vaccinated individuals were tested for their ability to bind and neutralize the original SARS-CoV-2 virus and the Omicron variant BA.1. COVID-19 patients show the most drastic reduction in Omicron-specific antibody response in comparison with the response to the wild-type virus. Antibodies elicited by a triple homologous/heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1. Overall, these findings confirm that vaccination of COVID-19 survivors and booster dose to vaccinees with mRNA vaccines is the correct strategy to enhance the antibody cross-protection against Omicron variant BA.1.
Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice
Authors: Gu Shanshan , Chen Zhongyan , Meng Xiangfu , Liu Ge , Xu He , Huang Liying , Wu Linwei , Gong Jixing , Chen Ding , Xue Bingqing , Zhu Lihang , Wan Zhongjun , Lin Jianqing , Cai Xiaolong , Zhang Xiaoyan , Wang Jia , Zhang Donghui , Cao Nan 
Published: September 2022

AbstractAn unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.
Ecological effects of stress drive bacterial evolvability under sub-inhibitory antibiotic treatments
Authors: Vasse Marie , Bonhoeffer Sebastian , Frenoy Antoine 
Published: September 2022

Abstract
Stress is thought to increase mutation rate and thus to accelerate evolution. In the context of antibiotic resistance, sub-inhibitory treatments could then lead to enhanced evolvability, thereby fuelling the adaptation of pathogens. Combining wet-lab experiments, stochastic simulations and a meta-analysis of the literature, we found that the increase in mutation rates triggered by antibiotic treatments is often cancelled out by reduced population size, resulting in no overall increase in genetic diversity. A careful analysis of the effect of ecological factors on genetic diversity showed that the potential for regrowth during recovery phase after treatment plays a crucial role in evolvability, being the main factor associated with increased genetic diversity in experimental data.
Validation of Muscle Fiber Architecture of the Human Tongue Revealed by Diffusion Magnetic Resonance Imaging With Histology Verification
Authors: Liang Xiao , Elsaid Nahla M. H. , Jiang Li , Roys Steve , Puche Adam C. , Gullapalli Rao P. , Stone Maureen , Prince Jerry L. , Zhuo Jiachen 
Published: September 2022

Purpose:
The goal of this study is to validate the muscle architecture derived from both ex vivo and in vivo diffusion-weighted magnetic resonance imaging (dMRI) of the human tongue with histology of an ex vivo tongue.

Method:
dMRI was acquired with a 200-direction high angular resolution diffusion imaging (HARDI) diffusion scheme for both a postmortem head (imaged within 48 hr after death) and a healthy volunteer. After MRI, the postmortem head was fixed and the tongue excised for hematoxylin and eosin (H&E) staining and histology imaging. Structure tensor images were generated from the stained images to better demonstrate muscle fiber orientations. The tongue muscle fiber orientations, estimated from dMRI, were visualized using the tractogram, a novel representation of crossing fiber orientations, and compared against the histology images of the ex vivo tongue.

Results:
Muscle fibers identified in the tractograms showed good correspondence with those appearing in the histology images. We further demonstrated tongue muscle architecture in in vivo tractograms for the entire tongue.

Conclusion:
The study demonstrates that dMRI can accurately reveal the complex muscle architecture of the human tongue and may potentially benefit planning and evaluation of oral surgery and research on speech and swallowing.
Speech Perception Variability in Childhood Apraxia of Speech: Implications for Assessment and Intervention
Authors: Spencer Caroline , Davison Kelsey E. , Boucher Alyssa R. , Zuk Jennifer 
Published: September 2022

Purpose:
Beyond hallmark production deficits characterizing childhood apraxia of speech (CAS), largely attributed to disruption(s) in speech motor planning, children with CAS often present with co-occurring speech perception and language difficulties. Thus, careful consideration of the potential for speech perception difficulties to have cascading downstream effects on intervention responsiveness and real-life functioning for some children with CAS is highly important. The purpose of this tutorial was to consider the impact of speech perception abilities in children with CAS, which carries implications for caring for the needs of the whole child.

Method:
This tutorial summarizes the current literature on speech perception and how it relates to speech production, language, and reading abilities for children with CAS. We include case illustrations that are adapted from real clinical scenarios illustrating how speech perception difficulties may impact some children with CAS and provide recommendations for incorporating speech perception into assessment and intervention practices.

Results:
Although speech perception difficulties do not seem to be a core deficit of CAS, they are strongly linked to language difficulties, which are highly prevalent among children with CAS. Speech perception and language difficulties are also associated with reading difficulties and risk for lower academic achievement.

Conclusions:
Children with CAS who have co-occurring language difficulties likely also demonstrate speech perception deficits, which puts them at heightened risk for reading difficulties and struggles with academic achievement. Comprehensive assessment of children with CAS should address speech perception and production, language, and reading abilities, which carries important implications for multifaceted approaches to intervention.
School-Based Speech-Language Pathologists' Attitudes and Knowledge About Trauma-Informed Care
Authors: Roberson Mikayla M. , Lund Emily 
Published: September 2022

Purpose:
The purpose of this study was to evaluate the attitudes and knowledge of school-based speech-language pathologists toward trauma-informed care.

Method:

School-based speech-language pathologists (
N
= 116) completed the Attitudes Related to Trauma-Informed Care Scale Version 45 Education (ARTIC-45) survey via an online survey platform and provided information about their work experience, history with trauma training, and demographic variables.

Results:
Although speech-language pathologists had responses that, on average, aligned with trauma-informed perspectives, those perspectives varied and were not at ceiling. Characteristics such as age, years of experience, and foster care experience did not significantly influence the results, but self-rating of trauma-informed care knowledge did correlate with the ARTIC-45 survey. Participants who had engaged in trauma-informed care trainings had more trauma-informed perspectives and knowledge than participants who had not.

Conclusions:
The results of this study provide preliminary evidence that trauma-informed care trainings may benefit those speech-language pathologists working with children who have experienced trauma. This study also provides preliminary evidence supporting the validity of the ARTIC-45 for use with speech-language pathologists.
An improved Chase–Pyndiah algorithm in the iterative decoding of turbo product codes
Authors: Yang Tao , Xi Zhiyu , Sun Qifu Tyler 
Published: September 2022

AbstractThis paper considers the design of turbo product codes (TPCs) for short and bursty packages, which is suitable for low latency machine‐to‐machine type communication. A new soft syndrome‐based approach is proposed to compute the weighting factors in the iterative Chase–Pyndiah decoding of TPCs. A new soft syndrome estimation method is developed which has a manageable computational complexity. Numerical results show that the bit error rate performance is improved by using this simple approach for short package sizes for TPCs with high coding rates.
Characterization of the MASCOT landing area by Hayabusa2
Authors: Schröder Stefan , Sakatani Naoya , Honda Rie , Tatsumi Eri , Yokota Yasuhiro , Domingue Deborah , Cho Yuichiro , Kameda Shingo , Kitazato Kohei , Kouyama Toru , Matsuoka Moe , Miura Akira , Morota Tomokatsu , Okada Tatsuaki , Sawada Hirotaka , Senshu Hiroki , Shimaki Yuri , Sugita Seiji , Tanaka Satoshi , Yabuta Hikaru , Yamada Manabu , Grott Matthias , Hamm Maximilian , Ho Tra-Mi , Jaumann Ralf , Mottola Stefano , Otto Katharina , Schmitz Nicole , Scholten Frank 
Published: September 2022

Context. After landing on C-type asteroid Ryugu, MASCOT imaged brightly colored, submillimeter-sized inclusions in a small rock. Hayabusa2 successfully returned a sample of small particles from the surface of Ryugu, but none of these appear to harbor such inclusions. The samples are considered representative of Ryugu.
Aims. To understand the apparent discrepancy between MASCOT observations and Ryugu samples, we assess whether the MASCOT landing site, and the rock by implication, is perhaps atypical for Ryugu.
Methods. We analyzed observations of the MASCOT landing area acquired by three instruments on board Hayabusa2: a camera (ONC), a near-infrared spectrometer (NIRS3), and a thermal infrared imager. We compared the landing area properties thus retrieved with those of the average Ryugu surface.
Results. We selected several areas and landforms in the landing area for analysis: a small crater, a collection of smooth rocks, and the landing site itself. The crater is relatively blue and the rocks are relatively red. The spectral and thermophysical properties of the landing site are very close to those of the average Ryugu surface. The spectral properties of the MASCOT rock are probably close to average, but its thermal inertia may be somewhat higher.
Conclusions. The MASCOT rock can also be considered representative of Ryugu. Some of the submillimeter-sized particles in the returned samples stand out because of their atypical spectral properties. Such particles may be present as inclusions in the MASCOT rock.
KMT-2017-BLG-0673Lb and KMT-2019-BLG-0414Lb: Two microlensing planets detected in peripheral fields of KMTNet survey
Authors: Han Cheongho , Lee Chung-Uk , Gould Andrew , Jung Youn Kil , Albrow Michael D. , Chung Sun-Ju , Hwang Kyu-Ha , Kim Doeon , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Yang Hongjing , Yee Jennifer C. , Zang Weicheng , Cha Sang-Mok , Kim Dong-Jin , Kim Seung-Lee , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W. 
Published: September 2022

Aims. We investigate the microlensing data collected during the 2017–2019 seasons in the peripheral Galactic bulge fields with the aim of finding planetary signals in microlensing light curves observed with relatively sparse coverage.
Methods. We first sort out lensing events with weak short-term anomalies in the lensing light curves from the visual inspection of all non-prime-field events, and then test various interpretations of the anomalies. From this procedure, we find two previously unidentified candidate planetary lensing events KMT-2017-BLG-0673 and KMT-2019-BLG-0414. It is found that the planetary signal of KMT-2017-BLG-0673 was produced by the source crossing over a planet-induced caustic, but it was previously missed because of the sparse coverage of the signal. On the other hand, the possibly planetary signal of KMT-2019-BLG-0414 was generated without caustic crossing, and it was previously missed due to the weakness of the signal. We identify a unique planetary solution for KMT-2017-BLG-0673. However, for KMT-2019-BLG-0414, we identify two pairs of planetary solutions, for each of which there are two solutions caused by the close-wide degeneracy, and a slightly less favored binary-source solution, in which a single lens mass gravitationally magnified a rapidly orbiting binary source with a faint companion (xallarap).
Results. From Bayesian analyses, it is estimated that the planet KMT-2017-BLG-0673Lb has a mass of 3.7−2.1+2.2 MJ, and it is orbiting a late K-type host star with a mass of 0.63−0.35+0.37 M⊙. Under the planetary interpretation of KMT-2010-BLG-0414L, a star with a mass of 0.74−0.38+0.43 M⊙ hosts a planet with a mass of ~3.2–3.6 MJ depending on the solution. We discuss the possible resolution of the planet-xallarap degeneracy of KMT-2019-BLG-0414 by future adaptive-optics observations on 30 m class telescopes. The detections of the planets indicate the need for thorough investigations of non-prime-field lensing events for the complete census of microlensing planet samples.
Teilhabebeeinträchtigung und deren Prädiktion bei
Opfern von Gewalttaten im Verfahren nach dem Opferentschädigungsgesetz:
Eine aktenbasierte explorative Kohortenstudie
Authors: Wulfes Nele , Mitschke Astrid-Christine , Wehrmeyer Matthias , von Drehle Christina , Kröger Christoph 
Published: September 2022

ZusammenfassungNach einer Gewalttat entstehen bei Betroffenen nicht nur psychische und
körperliche Schäden, sondern auch eine Beeinträchtigung
in der beruflichen, sozialen und gesellschaftlichen Teilhabe. Bislang fehlen
allerdings Studien zur Ausprägung der Teilhabebeeinträchtigung
und prognostisch relevanter Merkmale. Anhand eines Kategoriensystems wurden aus
Akten soziodemographische Angaben, trauma-, tat- und gesundheitsspezifische
Merkmale erwachsener Opfer von Gewalttaten, deren Anspruch auf Leistungen nach
dem Opferentschädigungsgesetz (OEG) anerkannt waren, erfasst. Basierend
auf psychiatrischen Gutachten zur Schädigungsfolge wurde ferner die
Teilhabebeeinträchtigung orientiert an der International Classification
of Functioning, Disability and Health (ICF) post-hoc beurteilt. Die Daten
beruhen auf 99 Akten; 72 der Betroffenen waren weiblich. Das durchschnittliche
Alter der Opfer bei der Tat betrug 25 Jahre. 53 waren Opfer von Gewalttaten
gegen die sexuelle Selbstbestimmung, 24 Opfer von Formen von
Körperverletzung und 45 Opfer anderer Gewalttaten. 29 wurden Opfer
mehrerer Arten von Gewalttaten. Bei allen Personen lag mindestens eine
psychische Störung mit Krankheitswert vor. Zwischen dem ersten und
zweiten Gutachten vergingen im Durchschnitt vier Jahre. Während 85 der
Betroffenen angegeben hatten, vor der Tat berufstätig gewesen zu sein,
waren dies nach der Tat noch 53. Die ausgeprägteste
Beeinträchtigung der Teilhabefähigkeit zeigte sich in der
beruflichen Teilhabe. Mithilfe einer multiplen Regressionsanalyse wurde
deutlich, dass eine höhere Teilhabebeeinträchtigung mit einer
fehlenden Berufstätigkeit und einem höheren Grad der
Schädigung nach der Tat sowie der persönlichen Bekanntheit des
Opfers mit dem Täter assoziiert war; nicht aber mit dem Vorliegen einer
psychischen Störung oder das Fehlen vertrauensvoller Beziehungen des
Opfers. Zukünftig sollte die Teilhabebeeinträchtigung
regulär während der psychiatrischen Begutachtung ICF-basiert
eingeschätzt werden. Die Ergebnisse sprechen dafür, dass
insbesondere Leistungen zur beruflichen Teilhabe im Rahmen des OEGs zu
gewähren sind.
Homeopathic Products as a Complementary Dietary Additive for Pigs in their Growing and Finishing Phases
Authors: Wendt Geraldyne Nunes , Genova Jansller Luiz , de Azevedo Liliana Bury , Rupolo Paulo Evaristo , Gregory Cristine Regina , Volpato Josiane Aparecida , Carvalho Silvana Teixeira , de Oliveira Carvalho Paulo Levi , Pasquetti Tiago Junior 
Published: September 2022

Abstract
Background Homeopathic products (HP) have been proposed for the prevention of disease and as a complementary dietary additive in pig farming, with resulting improved performance and quality of life of the animals and with benefits for food safety. The aim of this study was to assess the addition of HP to pig feed and its effects on growth performance, dietary protein utilization, nutrient digestibility, meat quality, and economic feasibility.
Methods A total of 80 male pigs, body weight 32.8±2.3kg, were allocated in a randomized design, with two treatments of 10 replications and four animals per experimental unit. Treatments were composed of a control diet (CD) or CD+HP (Finalvitaplus+Figotonus, 1.1kg/ton feed of each product). The outcome measures used were growth performance (body weight gain) and feed efficiency (body weight gain per unit of feed consumed), efficiency of dietary protein utilization (blood urea nitrogen), nutrient digestibility (apparent digestibility coefficient and apparent nutrient digestibility), meat quality (including pH, temperature, color, liquid loss by cooking and thawing, intramuscular fat and meat tenderness), and economic feasibility (cost of the diets).
Results There was no effect (p >0.05) of treatments on growth performance of the pigs, though the group that received HP showed an 8.93% greater feed efficiency than the control group (p=0.077). The animals in the control group had a 14.37% higher blood urea nitrogen concentration in the finishing I phase (70–100kg body weight) compared with those fed HP (p=0.028), indicating lower protein utilization in the controls. There was comparative improvement in digestibility coefficient and in nutrient digestibility in pigs fed HP in the growing–finishing phase (p <0.05). There was no differential effect of treatments on meat quality or economic feasibility (p >0.05).
Conclusion The addition of HP to the diet of growing–finishing pigs produced some improvement in their dietary protein utilization, nutrient digestibility and feed efficiency, though it did not affect their growth performance, meat quality or economic feasibility.