bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted siRNA nanocarrier: a platform technology for cancer treatment
Authors: Bäumer Nicole , Tiemann Jessica , Scheller Annika , Meyer Theresa , Wittmann Lisa , Suburu Matias Ezequiel Gutierrez , Greune Lilo , Peipp Matthias , Kellmann Neele , Gumnior Annika , Brand Caroline , Hartmann Wolfgang , Rossig Claudia , Müller-Tidow Carsten , Neri Dario , Strassert Cristian A. , Rüter Christian , Dersch Petra , Lenz Georg , Koeffler H. Phillip , Berdel Wolfgang E. , Bäumer Sebastian 
Published: February 2022

AbstractThe small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi.
Increased retention of tau PET ligand [18F]-AV1451 in Alzheimer’s Disease Psychosis
Authors: Gomar J. J. , Tan G. , Halpern J. , Gordon M. L. , Greenwald B. , Koppel J. 
Published: February 2022

AbstractPsychosis in Alzheimer’s disease (AD) represents a distinct disease subtype with a more rapid progression of illness evidenced by an increased velocity of cognitive decline and a hastened mortality. Previous biomarker and post-mortem studies have implicated tau neuropathology as a possible mediator of the accelerated decline in AD psychosis. Tau positron emission tomography (PET) neuroimaging provides the opportunity to evaluate tau pathology in-vivo, so that clinical symptomatology can be correlated with disease pathology. [18F]-AV1451 (Flortaucipir) is a PET ligand with high affinity for insoluble paired-helical filaments (PHFs) of hyperphosphorylated tau. In order to determine whether the development of psychosis and worsened prognosis in AD is associated with an increased burden of tau pathology that can be identified with tau imaging, we identified subjects within the Alzheimer’s disease neuroimaging initiative (ADNI) who had [18F]-AV1451 imaging at baseline and became psychotic over the course of the study (N = 17) and matched them 1:3 for gender, age, and education to subjects who had [18F]-AV1451 imaging at baseline and did not become psychotic (N = 50). We compared baseline [18F]-AV1451 retention, in addition to cognitive and functional baseline and longitudinal change, in those who became psychotic over the course of participation in ADNI with those who did not. Results suggest that increases in tau pathology in frontal, medial temporal, and occipital cortices, visualized with [18F]-AV1451 binding, are associated with psychosis and a more rapid cognitive and functional decline.
Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort
Authors: Pierce Meghan E. , Hayes Jasmeet , Huber Bertrand Russell , Jeromin Andreas , Fortier Catherine B. , Fonda Jennifer R. , Lasseter Heather , Chaby Lauren , McGlinchey Regina , Milberg William 
Published: February 2022

AbstractMild traumatic brain injury (mTBI) is among the most common injuries sustained by post-9/11 veterans; however, these injuries often occur within the context of psychological trauma. Blast exposure, even in the absence of a diagnosable TBI, leads to changes in neural connectivity and congitive functioning. Therefore, considering clinical comorbidities and injury characteristics is critical to understanding the long-term effects of mTBI. Research is moving towards identifying diagnostic and prognostic blood-based biomarkers for TBI; however, few studies include other prevalent clinical and medical comorbidities related to deployment. Here, we present the initial cross-sectional relationships between plasma biomarkers, clinical, and medical comorbidities in a well-characterized longitudinal sample of 550 post-9/11 veteran men and women. We examined biomarkers associated with inflammation (interleukin 6 and 10, tumor necrosis factor α, and eotaxin) and neurodegeneration (neurofilament light, glial fibrillary acidic protein (GFAP), tau, brain derived neurotrophic factor, amyloid ß 40 and 42, phosphorylated neurofilament heavy chain, and neuron specific enolase). Univariate analyses of covariance (ANCOVA) were conducted to determine mean level differences between close blast (blasts that occur within 0–10 meters) and mTBI groups. Our primary findings were twofold: (1) Inflammatory markers were consistently higher in participants exposed to close blasts and were strongly related to deployment-related psychopathology. (2) GFAP was consistently lower in participants exposed to blast and mTBI and lower GFAP was associated with more severe psychological symptoms. More research is clearly needed; however, our findings indicate that chronic increased inflammation and decreased GFAP may be related to close blast exposure.
Generation of functional oligopeptides that promote osteogenesis based on unsupervised deep learning of protein IDRs
Authors: Cai Mingxiang , Xiao Baichuan , Jin Fujun , Xu Xiaopeng , Hua Yuwei , Li Junhui , Niu Pingping , Liu Meijing , Wu Jiaqi , Yue Rui , Zhang Yong , Wang Zuolin , Zhang Yongbiao , Wang Xiaogang , Sun Yao 
Published: March 2022

AbstractDeep learning (DL) is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data. However, progress in oligopeptide drug development has been limited, likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models. Here, we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of ~171 known osteogenic proteins. Subsequently, oligopeptides were generated from this semantic pattern based on Monte Carlo simulation, followed by in vivo functional characterization. A five amino acid oligopeptide (AIB5P) had strong bone-formation-promoting effects, as determined in multiple mouse models (e.g., osteoporosis, fracture, and osseointegration of implants). Mechanistically, we showed that AIB5P promotes osteogenesis by binding to the integrin α5 subunit and thereby activating FAK signaling. In summary, we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.
Multiple pollutants in groundwater near an abandoned Chinese fluorine chemical park: concentrations, correlations and health risk assessments
Authors: Tang Jiaxi , Zhu Yongle , Xiang Biao , Li Yu , Tan Ting , Xu Ying , Li Mengxue 
Published: March 2022

AbstractContamination and adverse effects from various pollutants often appear in abandoned industrial regions. Thus, nine groundwater samples were collected from the vicinity of the fluorochemical industry in Fuxin City, Liaoning Province, to determine concentrations of the ten heavy metals arsenic (As), chromium (Cr), cadmium (Cd), lead (Pb), nickel (Ni), copper (Cu), manganese (Mn), zinc (Zn), iron (Fe) and mercury(Hg), as well as those of fluorine (F−) and eighteen poly- and perfluorinated substances (PFASs), analyse correlation relationships, and assess the health risks for different age groups. The results showed that the levels of fluorine (F−) (0.92–4.42 mg·L−1), Mn (0.0005–4.91 mg·L−1) and Fe (1.45–5.61 mg·L−1) exceeded the standard limits for drinking water. Short chain perfluorobutanoic acid (PFBA) (4.14–2501.42 ng·L−1), perfluorobutane sulfonate (PFBS) (17.07–51,818.61 ng·L−1) and perfluorohexanoic acid (PFHxA) (0.47–936.32 ng·L−1) were the predominant substances from the PFASs group. No individual PFASs levels had significant relationships with F− or heavy metal contents. There was a positive relationship between short chain PFASs concentrations and water depth and a negative relationship between long chain PFASs concentration and water depth. The hazard quotient (HQ) decreased in the order F− > heavy metals > PFASs and also decreased for older age groups. In addition, As, Fe, Mn and perfluorooctanoic acid (PFOA) were the main sources of risk from the heavy metal and PFASs groups, respectively.
A deep learning system for prostate cancer diagnosis and grading in whole slide images of core needle biopsies
Authors: Singhal Nitin , Soni Shailesh , Bonthu Saikiran , Chattopadhyay Nilanjan , Samanta Pranab , Joshi Uttara , Jojera Amit , Chharchhodawala Taher , Agarwal Ankur , Desai Mahesh , Ganpule Arvind 
Published: March 2022

AbstractGleason grading, a risk stratification method for prostate cancer, is subjective and dependent on experience and expertise of the reporting pathologist. Deep Learning (DL) systems have shown promise in enhancing the objectivity and efficiency of Gleason grading. However, DL networks exhibit domain shift and reduced performance on Whole Slide Images (WSI) from a source other than training data. We propose a DL approach for segmenting and grading epithelial tissue using a novel training methodology that learns domain agnostic features. In this retrospective study, we analyzed WSI from three cohorts of prostate cancer patients. 3741 core needle biopsies (CNBs) received from two centers were used for training. The κquad (quadratic-weighted kappa) and AUC were measured for grade group comparison and core-level detection accuracy, respectively. Accuracy of 89.4% and κquad of 0.92 on the internal test set of 425 CNB WSI and accuracy of 85.3% and κquad of 0.96 on an external set of 1201 images, was observed. The system showed an accuracy of 83.1% and κquad of 0.93 on 1303 WSI from the third institution (blind evaluation). Our DL system, used as an assistive tool for CNB review, can potentially improve the consistency and accuracy of grading, resulting in better patient outcomes.
Music modulates emotional responses in growing pigs
Authors: Zapata Cardona Juliana , Ceballos Maria Camila , Tarazona Morales Ariel Marcel , David Jaramillo Edimer , Rodríguez Berardo de Jesús 
Published: March 2022

AbstractThere is a lack of clarity on whether pigs can emotionally respond to musical stimulation and whether that response is related to music structure. Qualitative Behavioral Assessment (QBA) was used to evaluate effects of 16 distinct musical pieces (in terms of harmonic structure) on emotional responses in nursery pigs (n = 30) during four periods: “habituation”, “treatments”, “breaks” and “final”. Data were evaluated using Principal component analysis (PCA). Two principal components (PC) were considered in the analysis: PC1, characterized as a positive emotions index, included the emotional responses content, playful, sociable, and happy, whereas PC2, characterized as a negative emotions index, included fearful, inquisitive, and uneasy with positive loadings, and relaxed and calm with negative loadings. Musical stimulation (treatment) increased (P < 0.01) both emotional indices, compared to other periods and this response was influenced by harmonic characteristics of the music. We concluded that pigs have a wide variety of emotional responses, with different affective states related to the music structure used, providing evidence of its potential use as environmental enrichment for this species.
Visualization and quantum control of light-accelerated condensates by terahertz multi-dimensional coherent spectroscopy
Authors: Mootz Martin , Luo Liang , Wang Jigang , Perakis llias E. 
Published: March 2022

AbstractCharacterizing and controlling high-order correlation of quantum systems is key for developing quantum devices and switching technologies. Although conventional static and ultrafast spectroscopy gives access to collective excitations characterizing quantum states, more exotic correlations cannot be easily separated from other contributions. Here we develop density matrix simulations to show that seventh-order-wave-mixing peaks with distinct temperature and field dependences in two-dimensional terahertz nonlinear spectra reveal light-induced correlations in non-equilibrium superconducting states. Above critical terahertz driving, these emerging peaks split from conventional peaks along the second axis introduced by pump-probe relative phase in two-dimensional frequency space. They are photo-generated by correlations between two-photon fluctuations and interacting quasi-particle and quasi-particle/Higgs superconductor excitations. By photo-inducing persistent symmetry breaking via light-wave propagation, we also demonstrate seventh-order-wave-mixing sensing of Higgs collective modes. Our theory suggests to use multi-dimensional spectroscopy for quantum sensing of light-driven superconductivity and paves a path for quantum operations by few-cycle-THz-periodic photocurrent modulation.
t
BuOLi-promoted terminal alkyne functionalizations by aliphatic thiols and alcohols
Authors: Pramanik Milan , Mathuri Ashis , Mal Prasenjit 
Published: March 2022

t
BuOLi (tert-butoxide) in EtOH is a radical initiator for thiols. Selective addition of aliphatic thiols and alcohols to N-phenylpropiolamides (terminal alkynes) using tBuOLi in EtOH led to the thioacetals and acetals, respectively.
Intensive Voice Treatment (Lee Silverman Voice Treatment [LSVT LOUD]) for Children With Down Syndrome: Phase I Outcomes
Authors: Boliek Carol A. , Halpern Angela , Hernandez Keren , Fox Cynthia M. , Ramig Lorraine 
Published: March 2022

Purpose:
This study examined the effects of an intensive voice treatment Lee Silverman Voice Treatment (LSVT LOUD) on children with Down syndrome (DS) and motor speech disorders.

Method:
A Phase I, multiple baseline, single-subject design with replication across nine participants with DS was used. Single-word intelligibility, acoustic measures of vocal functioning, and parent perceptions of pre- and posttreatment communication function were used as treatment outcome measures.

Results:
All participants completed the full dose of LSVT LOUD and showed gains on one or more of the outcome measures. Patterns of posttreatment improvements were not consistent across participants but were more frequently observed on trained maximum performance tasks compared to tasks reflecting generalization of the treatment skillset. Some participants exhibited a stronger response to treatment, whereas others showed a mixed or weaker response. Parents liked the treatment protocol, perceived benefits from intensive intervention, and indicated they would strongly recommend LSVT LOUD to other parents who have children with DS and motor speech disorders.

Conclusions:
These preliminary results show that children with DS tolerated intensive voice treatment without adverse effects and made select meaningful therapeutic gains. The treatment evidence from this study warrants Phase II treatment studies using LSVT LOUD with a larger group of children with DS.
Caregiver Language Input Supports Sentence Diversity in Young Children With Autism Spectrum Disorder
Authors: Clark-Whitney Elysha , Klein Claire Brito , Hadley Pamela A. , Lord Catherine , Kim So Hyun 
Published: March 2022

Purpose:Sentence diversity is a measure of early language development that has yet to be applied to individuals with autism spectrum disorder (ASD). The primary aim of this study was to identify whether children with ASD show change in sentence diversity over 6 months of treatment with Naturalistic Developmental Behavioral Intervention (NDBI). The secondary aim was to examine possible predictors of changes in children's sentence diversity, including caregiver use of NDBI strategies, naturally occurring instances of caregiverToy Talk,and child characteristics.Method:Fifty children with ASD (ages 2–4 years) and their caregivers, who were receiving NDBI, engaged in two 10-min video-recorded play interactions, 6 months apart. Child speech was transcribed and coded for sentence diversity. Caregiver input was transcribed and coded for naturally occurringToy Talk. Zero-inflated negative binomial mixed models were used to explore predictors of change in child sentence diversity.Results:Children's sentence diversity improved over time. Changes in caregiver NDBI strategy use and caregiver baselineToy Talkwere significant predictors of changes in sentence diversity, as were baseline age, nonverbal ratio IQ, and child sex. Additionally, a significant interaction of caregiver baselineToy Talkand change in caregiver NDBI strategies emerged; the effect of caregiver baselineToy Talkon children's sentence diversity change was stronger when NDBI strategy use improved.Conclusions:Sentence diversity is a developmentally sensitive measure of language development in ASD. NDBI strategies that facilitate reciprocal social communication, combined with input composed of declarative sentences with noun or third-person pronoun subjects, may provide optimal support for children's sentence development.
Spectroscopic evolution of very massive stars at Z = 1/2.5 Z⊙
Authors: Martins F. , Palacios A. 
Published: March 2022

Context. Stars with masses in excess of 100 M⊙ are observed in the Local Universe, but they remain rare objects. Because of the shape of the mass function, they are expected to be present only in the most massive and youngest clusters. They may thus be formed in number in highly star-forming galaxies.
Aims. Very massive stars (VMSs) experience strong stellar winds that are stronger than those of their less massive OB-type counterparts. These strong winds therefore need to be taken into account in evolutionary models and synthetic spectra to properly predict the appearance of VMS.
Methods. We present evolutionary models computed with the code STAREVOL. They include a recent mass-loss recipe that is relevant for VMSs. We subsequently calculated atmosphere models and synthetic spectra along the resulting tracks with the code CMFGEN. We studied stars with masses between 150 and 400 M⊙ and focused on a metallicity Z = 1/2.5 Z⊙. We studied the impact of our VMS spectra on the spectral energy distribution of young starbursts.
Results. We show that the optical and UV range is dominated by He II 4686 and He II 1640 emission for almost the entire main-sequence evolution of VMSs, in contrast to less massive stars. In the UV spectral range, carbon, nitrogen, and iron lines shape the spectra of VMSs, which appear for most of their evolution as WNh objects. The morphology of the synthetic spectra is similar to that of VMSs in the Large Magellanic Cloud. We show that stars with masses higher than 100 M⊙ emit nearly as much light as all other stars in young starbursts. The integrated UV spectrum of these starbursts is significantly affected by the presence of VMSs.
Conclusions. We conclude that a consistent treatment of the evolution and the atmospheres of VMSs is mandatory to properly study spatially unresolved regions of intense star formation. We make our synthetic spectra and spectral energy distributions available to the community.
Evaluation of a Zingiber officinale and Bixa orellana
Supplement on the Gut Microbiota of Male Athletes: A Randomized
Placebo-Controlled Trial
Authors: Domínguez-Balmaseda Diego , Bressa Carlo , Fernández-Romero Arantxa , de Lucas Beatriz , Pérez-Ruiz Margarita , San Juan Alejandro F. , Roller Marc , Issaly Nicolas , Larrosa Mar 
Published: March 2022

AbstractThe gut microbiota has emerged as a factor that influences exercise performance
and recovery. The present study aimed to test the effect of a polyherbal
supplement containing ginger and annatto called “ReWin(d)” on the gut microbiota
of recreational athletes in a pilot, randomized, triple-blind,
placebo-controlled trial. Thirty-four participants who practice physical
activity at least three times weekly were randomly allocated to two groups, a
ReWin(d) group or a maltodextrin (placebo) group. We evaluated the gut
microbiota, the production of short-chain fatty acids, and the serum levels of
interleukin-6 and lipopolysaccharide at baseline and after 4 weeks. Results
showed that ReWin(d) supplementation slightly increased gut microbiota
diversity. Pairwise analysis revealed an increase in the relative abundance of
Lachnospira (β-coefficient = 0.013; p = 0.001),
Subdoligranulum (β-coefficient = 0.016; p = 0.016),
Roseburia (β-coefficient = 0.019; p = 0.001), and
Butyricicoccus (β-coefficient = 0.005; p = 0.035) genera in
the ReWin(d) group, and a decrease in Lachnoclostridium
(β-coefficient = − 0.008; p = 0.009) and the Christensenellaceae R7 group
(β-coefficient = − 0.010; p < 0.001). Moreover, the
Christensenellaceae R-7 group correlated positively with serum interleukin-6
(ρ = 0.4122; p = 0.032), whereas the Lachnospira genus correlated
negatively with interleukin-6 (ρ = − 0.399; p = 0.032). ReWin(d) supplementation
had no effect on short-chain fatty acid production or on interleukin-6 or
lipopolysaccharide levels.
Gesundheitsversorgung in Deutschland durch Mitarbeit von Physician
Assistants im ärztlichen Team
Authors: Meyer-Treschan Tanja , Stegemann Ann Kathrin , Sebastian Julia , Hatwich Sara , Beiderlinden Martin , Siepe Ralf B. , Veltjens Barbara , Farhan Nabeel , Siegmüller Julia 
Published: February 2022

Zusammenfassung
Ziel der Studie ÄrztInnen in Deutschland sind überlastet.
Entlastung könnte durch Delegation von ärztlichen Aufgaben an
Physician Assistants (PA) geschaffen werden. Obwohl seit 2012 PA im deutschen
Gesundheitswesen mitarbeiten, gibt es wenig Daten. Wir haben die Vor- und
Nachteile der Delegation aus Sicht von ÄrztInnen, die seit Jahren an PA
delegieren, sowie die Arbeitsbedingungen, die Zufriedenheit und Prozesszeiten
von PA untersucht.
Methodik Semi-quantitative Querschnittserhebung an einer Abschlusskohorte
des Studienganges PA und den an diese seit drei Jahren delegierenden
ÄrztInnen. Retrospektive Analyse von Wartezeiten und Aufenthaltsdauer in
einer interdisziplinären Notaufnahme.
Ergebnisse Die ÄrztInnen waren mit den PA sehr zufrieden und gaben
eine deutliche Entlastung durch diese an. Auch die PA zeigten eine sehr hohe
berufliche Zufriedenheit. Prozesszeiten in der Notaufnahme wurden durch die
Mitarbeit einer PA nicht verlängert.
Schlussfolgerung ÄrztInnen, die seit Jahren an PA delegieren, sind
entlastet und mit den PA zufrieden, gleichermaßen sind PA zufrieden mit
ihrem Beruf.