bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2
Authors: Grisé Kenneth N. , Coles Brenda L. K. , Bautista Nelson X. , van der Kooy Derek 
Published: October 2021

Abstract
Background
The adult mammalian retina does not have the capacity to regenerate cells lost due to damage or disease. Therefore, retinal injuries and blinding diseases result in irreversible vision loss. However, retinal stem cells (RSCs), which participate in retinogenesis during development, persist in a quiescent state in the ciliary epithelium (CE) of the adult mammalian eye. Moreover, RSCs retain the ability to generate all retinal cell types when cultured in vitro, including photoreceptors. Therefore, it may be possible to activate endogenous RSCs to induce retinal neurogenesis in vivo and restore vision in the adult mammalian eye.

Methods
To investigate if endogenous RSCs can be activated, we performed combinatorial intravitreal injections of antagonists to BMP and sFRP2 proteins (two proposed mediators of RSC quiescence in vivo), with or without growth factors FGF and Insulin. We also investigated the effects of chemically-induced N-methyl-N-Nitrosourea (MNU) retinal degeneration on RSC activation, both alone and in combination withthe injected factors. Further, we employed inducible Msx1-CreERT2 genetic lineage labeling of the CE followed by stimulation paradigms to determine if activated endogenous RSCs could migrate into the retina and differentiate into retinal neurons.

Results
We found that in vivo antagonism of BMP and sFRP2 proteins induced CE cells in the RSC niche to proliferate and expanded the RSC population. BMP and sFRP2 antagonism also enhanced CE cell proliferation in response to exogenous growth factor stimulation and MNU-induced retinal degeneration. Furthermore, Msx1-CreERT2 genetic lineage tracing revealed that CE cells migrated into the retina following stimulation and/or injury, where they expressed markers of mature photoreceptors and retinal ganglion cells.

Conclusions
Together, these results indicate that endogenous adult mammalian RSCs may have latent regenerative potential that can be activated by modulating the RSC niche and hold promise as a means for endogenous retinal cell therapy to repair the retina and improve vision.
Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial
Authors: Chen Cheng-Fong , Hu Chih-Chien , Wu Chen-Te , Wu Hung-Ta H. , Chang Chun-Shin , Hung Yi-Pei , Tsai Chia-Chu , Chang Yuhan 
Published: October 2021

Abstract
Objective
To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis.

Methods
This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs).

Results
No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group.

Conclusions
ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group.
Trial registration: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964
[68Ga]Ga-4HMSA a promising new PET tracer for imaging inflammation
Authors: Kahn Ali Shigufa , Ait-Mohand Samia , Dumulon-Perreault Véronique , Guérin Brigitte 
Published: October 2021

AbstractBackgroundImaging diagnosis of inflammation has been challenging for many years. Inflammation imaging agents commonly used in nuclear medicine, such as [67Ga]Ga-citrate and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed some limitations. The identification of a radiotracer with high specificity and low radiation dose is clinically important. With the commercialization of68Ge/68Ga generators and the high68Ga cyclotron production capacity, the study of68Ga-based tracer for inflammation has increased and shown good potential. In the present work, we report the synthesis of 4HMSA, a new acyclic chelator, and its first investigation for68Ga complexation and as a new positron emission tomography (PET) imaging agent of inflammation in comparison to [68Ga]Ga-citrate.ResultsThe present experimental studies have shown that the novel [68Ga]Ga-4HMSA is stable allowing imaging of inflammation in a preclinical model of adjuvant- and pathogen-based inflammation involving intraplantar injection of complete Freund’s adjuvant (CFA). We also found that [68Ga]Ga-4HMSA displayed similar uptakes in the inflamed paw than [68Ga]Ga-citrate, which are superior compared to those of contralateral (non-injected) paws at days 1–3 from PET imaging. [68Ga]Ga-citrate accumulated in the upper body of the animal such as the liver, lungs and the heart, whereas the [68Ga]Ga-4HMSA revealed low uptakes in the majority of the organs and was cleared relatively rapidly from blood circulation through the kidneys and bladder.ConclusionThe results highlight the potential of [68Ga]Ga-4HMSA as an interesting alternative to [68Ga]Ga-citrate for inflammation imaging by PET. The new PET tracer also offers additional advantages than [68Ga]Ga-citrate in term of dosimetry and lower overall background activity.
Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor
Authors: Keerthiga Rajendiran , Pei De-Sheng , Fu Ailing 
Published: October 2021

AbstractIn modern research, mitochondria are considered a more crucial energy plant in cells. Mitochondrial dysfunction, including mitochondrial DNA (mtDNA) mutation and denatured protein accumulation, is a common feature of tumors. The dysfunctional mitochondria reprogram molecular metabolism and allow tumor cells to proliferate in the hostile microenvironment. One of the crucial signaling pathways of the mitochondrial dysfunction activation in the tumor cells is the retrograde signaling of mitochondria-nucleus interaction, mitochondrial unfolded protein response (UPRmt), which is initiated by accumulation of denatured protein and excess ROS production. In the process of UPRmt, various components are activitated to enhance the mitochondria-nucleus retrograde signaling to promote carcinoma progression, including hypoxia-inducible factor (HIF), activating transcription factor ATF-4, ATF-5, CHOP, AKT, AMPK. The retrograde signaling molecules of overexpression ATF-5, SIRT3, CREB, SOD1, SOD2, early growth response protein 1 (EGR1), ATF2, CCAAT/enhancer-binding protein-d, and CHOP also involved in the process. Targeted blockage of the UPRmtpathway could obviously inhibit tumor proliferation and metastasis. This review indicates the UPRmtpathways and its crucial role in targeted therapy of metastasis tumors.
Characteristics of Sepsis-2 septic shock patients failing to satisfy the Sepsis-3 septic shock definition: an analysis of real-time collected data
Authors: Vermassen Joris , Decruyenaere Johan , De Bus Liesbet , Depuydt Pieter , Colpaert Kirsten 
Published: October 2021

Abstract
Background
Baseline characteristics and disease severity of patients with septic shock according to the new Sepsis-3 definition may differ from patients that only comply with the Sepsis-2 definition. We conducted a retrospective cohort study on the ICU of a Belgian tertiary care facility to seek out differences between these two patient groups and to identify variables associated with no longer satisfying the latest definition of septic shock.

Results
Of 1198 patients with septic shock according to the Sepsis-2 consensus definition, 233 (19.4%) did not have septic shock according to the Sepsis-3 shock definition. These patients more often had medical admission reasons and a respiratory infection as cause for the septic shock. They less often had surgery on admission and were less likely to have chronic liver disease (5.6% vs 16.2%, absolute difference 10.6% (95% CI 6.4–14.1%). Patients with septic shock only according to the old definition had significant lower APACHE II and SOFA scores and lower hospital mortality (31.6% vs 55.3%, p < 0.001). In a multivariate analysis, following variables were associated with Sepsis-2 shock patients no longer being defined as such by the Sepsis-3 definition: respiratory infection (OR 1.485 (95% CI 1.56–2.089), p = 0.023), a medical admission reason (OR 1.977 (95% CI 1.396–2.800) and chronic liver disease (OR 0.345 (95% CI 0.181–0.660), p < 0.001).

Conclusions
One in five patients with septic shock according to the Sepsis-2 consensus definition is no longer considered as such when the Sepsis-3 shock criteria are applied. A medical admission reason, a respiratory infection and absence of chronic liver disease are independently associated with no longer being identified as having septic shock by the Sepsis-3 criteria.
Comparative evaluation of interpolation methods for the directivity of musical instruments
Authors: Ackermann David , Brinkmann Fabian , Zotter Franz , Kob Malte , Weinzierl Stefan 
Published: October 2021

AbstractMeasurements of the directivity of acoustic sound sources must be interpolated in almost all cases, either for spatial upsampling to higher resolution representations of the data, for spatial resampling to another sampling grid, or for use in simulations of sound propagation. The performance of different interpolation techniques applied to sparsely sampled directivity measurements depends on the sampling grid used but also on the radiation pattern of the sources themselves. Therefore, we evaluated three established approaches for interpolation from a low-resolution sampling grid using high-resolution measurements of a representative sample of musical instruments as a reference. The smallest global error on average occurs for thin plate pseudo-spline interpolation. For interpolation based on spherical harmonics (SH) decomposition, the SH order and the spatial sampling scheme applied have a strong and difficult to predict influence on the quality of the interpolation. The piece-wise linear, spherical triangular interpolation provides almost as good results as the first-order spline approach, albeit with on average 20 times higher computational effort. Therefore, for spatial interpolation of sparsely sampled directivity measurements of musical instruments, the thin plate pseudo-spline method applied to absolute-valued data is recommended and, if necessary, a subsequent modeling of the phase.
Discrete epidemic models with two time scales
Authors: Bravo de la Parra Rafael , Sanz-Lorenzo Luis 
Published: October 2021

AbstractThe main aim of the work is to present a general class of two time scales discrete-time epidemic models. In the proposed framework the disease dynamics is considered to act on a slower time scale than a second different process that could represent movements between spatial locations, changes of individual activities or behaviors, or others.To include a sufficiently general disease model, we first build up from first principles a discrete-time susceptible–exposed–infectious–recovered–susceptible (SEIRS) model and characterize the eradication or endemicity of the disease with the help of its basic reproduction number $\mathcal{R}_{0}$

R
0

.Then, we propose a general full model that includes sequentially the two processes at different time scales and proceed to its analysis through a reduced model. The basic reproduction number $\overline{\mathcal{R}}_{0}$

R
‾

0

of the reduced system gives a good approximation of $\mathcal{R}_{0}$

R
0

of the full model since it serves at analyzing its asymptotic behavior.As an illustration of the proposed general framework, it is shown that there exist conditions under which a locally endemic disease, considering isolated patches in a metapopulation, can be eradicated globally by establishing the appropriate movements between patches.
Low frequency of community-acquired bacterial co-infection in patients hospitalized for COVID-19 based on clinical, radiological and microbiological criteria: a retrospective cohort study
Authors: Coenen Sophie , de la Court Jara R. , Buis David T. P. , Meijboom Lilian J. , Schade Rogier P. , Visser Caroline E. , van Hest Reinier , Kuijvenhoven Marianne , Prins Jan M. , Nijman Suzan F. M. , Sieswerda Elske , Sigaloff Kim C. E. 
Published: October 2021

Abstract
Background
We defined the frequency of respiratory community-acquired bacterial co-infection in patients with COVID-19, i.e. patients with a positive SARS-CoV-2 PCR or a COVID-19 Reporting and Data System (CO-RADS) score ≥ 4, based on a complete clinical assessment, including prior antibiotic use, clinical characteristics, inflammatory markers, chest computed tomography (CT) results and microbiological test results.

Methods
Our retrospective study was conducted within a cohort of prospectively included patients admitted for COVID-19 in our tertiary medical centres between 1-3-2020 and 1-6-2020. A multidisciplinary study team developed a diagnostic protocol to retrospectively categorize patients as unlikely, possible or probable bacterial co-infection based on clinical, radiological and microbiological parameters in the first 72 h of admission. Within the three categories, we summarized patient characteristics and antibiotic consumption.

Results
Among 281 included COVID-19 patients, bacterial co-infection was classified as unlikely in 233 patients (82.9%), possible in 35 patients (12.4%) and probable in 3 patients (1.1%). Ten patients (3.6%) could not be classified due to inconclusive data. Within 72 h of hospital admission, 81% of the total study population and 78% of patients classified as unlikely bacterial co-infection received antibiotics.

Conclusions
COVID-19 patients are unlikely to have a respiratory community-acquired bacterial co-infection. This study underpins recommendations for restrictive use of antibacterial drugs in patients with COVID-19.
Antimicrobial property of recombinant Lactolisterin BU in vitro and its initial application in pork refrigerated storage
Authors: Dong Bin , Zhou Guowen , Lin Yanjun , Yu Cailing , Wang Jun , Sun Chunlong , Wu Tao 
Published: October 2021

AbstractLactolisterin BU is a novel bacteriocin identified from Lactococcus lactis in 2017. It exhibits antimicrobial activity against food spoilage and foodborne pathogens. In this study, Lactolisterin BU was expressed in Pichia pastoris (P.pastoris) and isolated from the supernatant of yeast culture for the first time. It was found to exhibit a broad antimicrobial spectrum and rapid bactericidal activity against foodborne bacterial pathogens, both gram-positive and gram-negative ones, with minimum inhibition concentrations ranging within 10–60 μg/mL. The recombinant Lactolisterin BU (rLactolisterin BU) also had an antioxidant effect and was resistant to heating, acid–base, and high-dose-saline treatments and barely had any hemolytic activity or cytotoxicity. Moreover, rLactolisterin BU effectively suppressed the growth of bacterial pathogens; suppressed the increases in pH, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS) of pork samples; and maintained a high quality of fresh pork during storage at 4 ℃. Furthermore, rLactolisterin BU effectively inhibited the growth of three kinds of bacteria in a pork-spoilage model. Taken together, rLactolisterin BU could be a promising preservative for food storage.
The effects and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis: a meta-analysis and systematic review
Authors: Zang Chenchen , Zheng Yan , Wang Yanqing , Li Lisha 
Published: October 2021

Abstract
Background
It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF).

Methods
Pubmed et al. databases were searched up to March 15, 2021 for randomized controlled trials (RCT) of pirfenidone in the treatment of IPF. Two authors collected and compared the indicators including progression-free survival (PFS), vital capacity (VC), forced vital capacity (FVC), and adverse reactions. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis.

Results
A total of 8 reports with 9 RCTs involving 1824 IPF patients were included. Meta-analysis results showed that compared with the control group, pirfenidone could prolong the PFS phase of IPF patients (HR = 0.65, 95% CI 0.55 ~ 0.76, P < 0.001), slow down the VC of IPF patients (SMD = 0.43, 95% CI 0.21 ~ 0.66, P < 0.001), and decrease FVC (SMD = 0.31, 95% CI 0.14 ~ 0.48, P < 0.001). The main adverse reactions of pirfenidone were gastrointestinal reactions, photosensitivity and skin rashes.

Conclusion
Pirfenidone is beneficial to prolong the PFS of IPF patients, improve lung function, and it is safe for clinical use. However, more high-quality RCTs are still needed to provide reliable evidence for the treatment of IPF.
Acceptability and face validity of two mental health screening tools for use in the routine surgical setting
Authors: McBride Kate E. , Steffens Daniel , Lambert Tim , Glozier Nick , Roberts Rachael , Solomon Michael J. 
Published: October 2021

Abstract
Background
Preoperative assessment of mental health rarely occurs within routine surgery. Any screening tool selected to form part of this process must be deemed practical, acceptable and valid by clinicians and consumers alike. This study aims to assess the acceptability and face validity of two existing mental health screening tools to select one for further development and use in the routine surgical setting.

Methods
A survey of clinicians and consumers was conducted from October 2020 to March 2021 at a tertiary hospital in Sydney, Australia. Using a Likert scale (1–5, lowest to highest rating), the clinicians evaluated four domains for acceptability and two for validity (six overall) and the consumers four domains for acceptability and one for validity (five overall) on the preoperative use of the amended Kessler Psychological Distress Scale (K10) and the Somatic and Psychological Health Report-12 (SPHERE-12). Consensus was achieved through a rating of 4 or 5 being given by 70% or more of participants with domains able to remain unchanged. Free text responses were analysed into themes.

Results
A total of 73 participants (51 clinicians; 22 consumers) were included. The K10 received consensus scores (≥ 70%) in four out of six domains for clinicians (4/4 acceptability; 0/2 validity), and all five domains for consumers (4/4 acceptability; 1/1 validity). The SPHERE-12 received consensus scores (≥ 70%) in three domains for clinicians (3/4 acceptability; 0/2 validity), and three domains for consumers (3/4 acceptability; 0/1 validity). Six qualitative themes were described including (1) amendments to tool structure and language; (2) scale response options; (3) difficulty with somatic questions; (4) practicality and familiarity with K10; (5) challenges for specific patient cohorts and (6) timing considerations for patients.

Conclusion
Adequate acceptability was established for the K10. However further development is required to strengthen its validity for this specific surgical cohort and purpose. Future research to determine the feasibility and acceptability of implementing and using the K10 in the routine surgical setting is now needed.
Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson’s disease and dementia with Lewy bodies
Authors: Brockmann Kathrin , Quadalti Corinne , Lerche Stefanie , Rossi Marcello , Wurster Isabel , Baiardi Simone , Roeben Benjamin , Mammana Angela , Zimmermann Milan , Hauser Ann-Kathrin , Deuschle Christian , Schulte Claudia , Waniek Katharina , Lachmann Ingolf , Sjödin Simon , Brinkmalm Ann , Blennow Kaj , Zetterberg Henrik , Gasser Thomas , Parchi Piero 
Published: October 2021

AbstractThe clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (α-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded α-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to α-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC α-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive α-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive α-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between α-Syn seeding activity and reduced CSF levels of proteins linked to α-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF.These findings highlight the value of α-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting α-Syn.