bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of regulatory T cells with Lactococcus lactis expressing enterotoxigenic E. coli colonization factor antigen 1 retains salivary flow in a genetic model of Sjögren’s syndrome
Authors: Akgul Ali , Maddaloni Massimo , Jun Sang Mu , Nelson Andrew S. , Odreman Vanessa Aguilera , Hoffman Carol , Bhagyaraj Ella , Voigt Alexandria , Abbott Jeffrey R. , Nguyen Cuong Q. , Pascual David W. 
Published: April 2021

Abstract
Background
Sjögren’s syndrome (SjS), one of the most common autoimmune diseases, impacts millions of people annually. SjS results from autoimmune attack on exocrine (salivary and lacrimal) glands, and women are nine times more likely to be affected than men. To date, no vaccine or therapeutic exists to treat SjS, and patients must rely on lifelong therapies to alleviate symptoms.

Methods
Oral treatment with the adhesin from enterotoxigenic Escherichia coli colonization factor antigen I (CFA/I) fimbriae protects against several autoimmune diseases in an antigen (Ag)-independent manner. Lactococcus lactis, which was recently adapted to express CFA/I fimbriae (LL-CFA/I), effectively suppresses inflammation by the induction of infectious tolerance via Ag-specific regulatory T cells (Tregs), that produce IL-10 and TGF-β. To test the hypothesis that CFA/I fimbriae can offset the development of inflammatory T cells via Treg induction, oral treatments with LL-CFA/I were performed on the spontaneous, genetically defined model for SjS, C57BL/6.NOD-Aec1Aec2 mice to maintain salivary flow.

Results
Six-week (wk)-old C57BL/6.NOD-Aec1Aec2 mice were orally dosed with LL-CFA/I and treated every 3 wks; control groups were given L. lactis vector or PBS. LL-CFA/I-treated mice retained salivary flow up to 28 wks of age and showed significantly reduced incidence of inflammatory infiltration into the submandibular and lacrimal glands relative to PBS-treated mice. A significant increase in Foxp3+ and IL-10- and TGF-β-producing Tregs was observed. Moreover, LL-CFA/I significantly reduced the expression of proinflammatory cytokines, IL-6, IL-17, GM-CSF, and IFN-γ. Adoptive transfer of CD4+ T cells from LL-CFA/I-treated, not LL vector-treated mice, restored salivary flow in diseased SjS mice.

Conclusion
These data demonstrate that oral LL-CFA/I reduce or halts SjS progression, and these studies will provide the basis for future testing in SjS patients.
Biocompatibility and radioprotection by newly characterized melanin pigment and its production from Dietzia schimae NM3 in optimized whey medium by response surface methodology
Authors: Eskandari Sahar , Etemadifar Zahra 
Published: April 2021

Abstract
Purpose
To characterize and optimize the productivity of melanin using an extremotolerant actinobacterium, Dietzia schimae NM3, for the first time.

Methods
An extracellular brown pigment produced by D. schimae NM3 in the nutrient broth and cheese whey medium by adding L-tyrosine. The extracted melanin was analyzed by UV-visible, HPLC, and FTIR assays. The radical scavenging activity (by DPPH) and sun protection factor (SPF) of the extracted melanin were measured. The melanin cytotoxicity was assayed by MTT and chromate biosorption was measured by atomic absorption spectroscopy. Finally, melanin production by D. schimae NM3 was optimized by response surface methodology (RSM) using Box-Behnken design in the whey medium.

Result
The purified melanin showed similar peak to the standard melanin (SIGMA) at 3.5 min in HPLC, and C=O bands, NH2, CH, C-N, and aromatic groups by FTIR. The radical scavenging activity (by DPPH) and SPF of the extracted melanin were obtained 188.9% and 20.22, respectively. Using MTT assay, the melanin revealed non-toxic effect on the normal human fibroblast (HFB) cell culture. The melanin yield 790 mg l−1, and tyrosinase activity 3400 U ml−1 were obtained in the medium contained whey powder [5% (w v−1)], L-tyrosine 2.5 g l−1, CuSO4 0.013 g l−1, and pH 10.5, incubated at 32 °C for 3 days. The ANOVA results indicated significant P-value, model F-value, and probability, with insignificant lack of fit. After optimization with mono-factors, the nutrient broth came up with melanin yield as 1.2 g l−1 and tyrosinase activity as 4040 U ml−1.

Conclusion
This is the first report of melanin production by D. schimae NM3 and this natural melanin showed valuable biological properties such as high antioxidant activity and radioprotection (SPF) and the biocompatibility to human cell line.
Secretomes of human pluripotent stem cell-derived smooth muscle cell progenitors upregulate extracellular matrix metabolism in the lower urinary tract and vagina
Authors: Zhuang Guobing , Wen Yan , Briggs Mason , Shao Qingchun , Tran Darlene , Wang Hongbo , Chen Bertha 
Published: April 2021

Abstract
Background
Adult mesenchymal stem cells (MSCs) have been studied extensively for regenerative medicine; however, they have limited proliferation in vitro, and the long culture time induces cell senescence. MSCs also contribute to tissue repair through their paracrine function. In this study, we sought to examine the paracrine effects of human smooth muscle cell progenitors (pSMC) on the urethra and adjacent vagina of stress urinary incontinence rodents. We use human pluripotent stem cell (PSC) lines to derive pSMCs to overcome the issue of decreased proliferation in tissue culture and to obtain a homogenous cell population.

Method
Three human PSC lines were differentiated into pSMCs. The conditioned medium (CM) from pSMC culture, which contain pSMC secretomes, was harvested. To examine the effect of the CM on the extracellular matrix of the lower urinary tract, human bladder smooth muscle cells (bSMCs) and vaginal fibroblasts were treated with pSMC-CM in vitro. Stress urinary incontinence (SUI) was induced in rats by surgical injury of the urethra and adjacent vagina. SUI rats were treated with pSMC-CM and monitored for 5 weeks. Urethral pressure testing was performed prior to euthanasia, and tissues were harvested for PCR, Western blot, and histological staining. Kruskal-Wallis one-way ANOVA test and Student t test were used for statistical comparisons.

Results
pSMC-CM upregulated MMP-2, TIMP-2, collagen, and elastin gene expression, and MMP-9 activity in the human bladder and vaginal cells consistent with elastin metabolism modulation. pSMC-CM treatment in the SUI rat improved urethral pressure (increase in leak point pressure compared to intact controls, p < 0.05) and increased collagen and elastin expression in the urethra and the adjacent vagina.

Conclusion
Conditioned media from smooth muscle cell progenitors derived from human pluripotent stem cells improved urethral leak point pressure and collagen and elastin content in the SUI rat. These findings suggest a novel therapeutic potential for PSC-based treatments for SUI and pelvic floor disorders where tissues are affected by collagen, elastin, and smooth muscle loss.
Subconjunctival administration of low-dose murine allogeneic mesenchymal stromal cells promotes corneal allograft survival in mice
Authors: Treacy Oliver , Lynch Kevin , Murphy Nick , Chen Xizhe , Donohoe Ellen , Canning Aoife , Lohan Paul , Shaw Georgina , Fahy Gerry , Ryan Aideen E. , Ritter Thomas 
Published: April 2021

Abstract
Background
Systemic administration of mesenchymal stromal cells (MSCs) has been efficacious in many inflammatory disease settings; however, little data are available on the potential immunomodulatory effects following local MSC administration in the context of corneal transplantation. The purpose of this study was to assess the potential of subconjunctival injection of MSCs to promote corneal allograft survival.

Methods
MSCs were isolated from female C57BL/6 (H-2k) or Balb/c (H-2d) mice and extensively characterized. An allogeneic mouse corneal transplant model was used with Balb/c mice as recipients of C57BL/6 grafts. A dose-finding study starting with 5 × 105 MSCs injected subconjunctivally at day − 7 was tested first followed by a more clinically translatable low-dose single or dual injection strategy on day − 1 and day + 1 before/after transplantation. Graft transparency served as the primary indicator of transplant rejection while neovascularization was also recorded. Lymphocytes (from draining lymph nodes) and splenocytes were isolated from treatment groups on day 2 post-transplantation and characterized by flow cytometry and qRT-PCR.

Results
Both high- and low-dose injection of allogeneic MSCs on day − 7 led to 100% graft survival over the observation period. Moreover, low-dose dual subconjunctival injection of 5 × 104 allogeneic MSCs on day − 1 or day + 1 led to 100% allograft survival in transplant recipients (n = 7). We also demonstrate that single administration of allogeneic MSCs on either day − 1 or day + 1 promotes rejection-free graft survival in 100% (n = 8) and 86% (n = 7) of transplanted mice, respectively. Early time point ex vivo analysis suggests modulation of innate immune responses towards anti-inflammatory, pro-repair responses by local MSC administration.

Conclusion
This work demonstrates that low-dose subconjunctival injection of allogeneic MSCs successfully promotes corneal allograft survival and may contribute to refining future MSC immunotherapies for prevention of corneal allograft rejection.
Limits of temperature adaptation and thermopreferendum
Authors: Aslanidi K. B. , Kharakoz D. P. 
Published: April 2021

AbstractBackgroundManaging the limits of temperature adaptation is relevant both in medicine and in biotechnology. There are numerous scattered publications on the identification of the temperature limits of existence for various organisms and using different methods. Dmitry Petrovich Kharakoz gave a general explanation for many of these experimental results. The hypothesis implied that each cycle of synaptic exocytosis includes reversible phase transitions of lipids of the presynaptic membrane due to the entry and subsequent removal of calcium ions from the synaptic terminal. The correspondence of the times of phase transitions has previously been experimentally shown on isolated lipids in vitro. In order to test the hypothesis of D.P. Kharakoz in vivo, we investigated the influence of the temperature of long-term acclimatization on the temperature of heat and cold shock, as well as on the kinetics of temperature adaptation in zebrafish. Testing the hypothesis included a comparison of our experimental results with the results of other authors obtained on various models from invertebrates to humans.ResultsThe viability polygon for Danio rerio was determined by the minimum temperature of cold shock (about 6 °C), maximum temperature of heat shock (about 43 °C), and thermopreferendum temperature (about 27 °C). The ratio of the temperature range of cold shock to the temperature range of heat shock was about 1.3. These parameters obtained forDanio reriodescribe with good accuracy those for the planarianGirardia tigrina, the ground squirrelSermophilus undulatus, and forHomo sapiens.ConclusionsThe experimental values of the temperatures of cold shock and heat shock and the temperature of the thermal preferendum correspond to the temperatures of phase transitions of the lipid-protein composition of the synaptic membrane between the liquid and solid states. The viability range for zebrafish coincides with the temperature range, over which enzymes function effectively and also coincides with the viability polygons for the vast majority of organisms. The boundaries of the viability polygon are characteristic biological constants. The viability polygon of a particular organism is determined not only by the genome, but also by the physicochemical properties of lipids that make up the membrane structures of synaptic endings. The limits of temperature adaptation of any biological species are determined by the temperature range of the functioning of its nervous system.
Treatment outcomes of patients with multidrug and extensively drug-resistant tuberculosis in Zhejiang, China
Authors: Zhang Ming-Wu , Zhou Lin , Zhang Yu , Chen Bin , Peng Ying , Wang Fei , Liu Zheng-Wei , Wang Xiao-Meng , Chen Song-Hua 
Published: April 2021

AbstractBackgroundThe aim of this study was to assess the treatment outcomes of multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) in Zhejiang, China and to evaluate possible risk factors associated with poor outcomes of M/XDR-TB.MethodsTwo-hundred-and-sixty-two patients having M/XDR-TB who received the diagnosis and treatment at nine referral hospitals from 1 January 2016 to 31 December 2016 in Zhejiang, China were included. All patients received second-line regimens recommended by WHO under the DOTS-Plus strategy.ResultsAmong the 262 patients, the treatment success rate was 55.34% (n = 145) with 53.44% (n = 140) cured and 1.91% (n = 5) who completed treatment, 62 (23.66%) failed, 27 (10.31%) died, 16 (6.11%) defaulted and 12 (4.58%) transferred out. Forty (64.52%) of the 62 M/XDR-TB patients who failed treatment were due to adverse effects in the first 10 months of treatment. Eighteen patients (6.37%) had XDR-TB. Treatment failure was significantly higher among patients with XDR-TB at 50% than that among patients with non-XDR-TB at 21.72% (P = 0.006). Failure outcomes were associated with a baseline weight less than 50 kg (OR, 8.668; 95% CI 1.679–44.756;P = 0.010), age older than 60 years (OR, 9.053; 95% CI 1.606–51.027;P = 0.013), hemoptysis (OR, 8.928; 95% CI 1.048–76.923;P = 0.045), presence of cavitary diseases (OR, 10.204; 95% CI 2.032–52.631;P = 0.005), or treatment irregularity (OR, 47.619; 95% CI 5.025–500;P = 0.001).ConclusionTreatment outcomes for M/XDR-TB under the DOTS-Plus strategy in Zhejiang, China were favorable but still not ideal. Low body weight (< 50 kg), old age (> 60 years), severe symptoms of TB including cavitary disease, hemoptysis and irregular treatment were independent prognostic factors for failure outcomes in patients with M/XDR-TB.
Effect of sterilization on 3-point dynamic response to in vitro bending of an Mg implant
Authors: Becerra Luis Humberto Campos , Rodríguez Marco Antonio Loudovic Hernández , Arroyo Raúl Lesso , Solís Hugo Esquivel , Castro Alejandro Torres 
Published: April 2021

Abstract

Background
The aim of the study is to characterize a biomedical magnesium alloy and highlighting the loss of mechanical integrity due to the sterilization method. Ideally, when using these alloys is to delay the onset of degradation so that the implant can support body loads and avoid toxicological effects due to the release of metal ions into the body.

Methods
Standardized procedures according to ASTM F-1264 and ISO-10993-5 were used, respecting detailed methodological controls to ensure accuracy and reproducibility of the results, this testing methodology is carried out in accordance with the monographs of the Pharmacopoeia for the approval of medical devices and obtaining a health registration. An intramedullary implant (IIM) manufactured in magnesium (Mg) WE43 can support loads of the body in the initial period of bone consolidation without compromising the integrity of the fractured area. A system with these characteristics would improve morbidity and health costs by avoiding secondary surgical interventions.

Results
As a property, the fatigue resistance of Mg in aggressive environments such as the body environment undergoes progressive degradation, however, the autoclave sterilization method drastically affects fatigue resistance, as demonstrated in tests carried out under in vitro conditions. Coupled with this phenomenon, the relatively poor biocompatibility of Mg WE43 alloys has limited applications where they can be used due to low acceptance rates from agencies such as the FDA. However, Mg alloy with elements such as yttrium and rare earth elements (REEs) have been shown to delay biodegradation depending on the method of sterilization and the physiological solution used. With different sterilization techniques, it may be possible to keep toxicological effects to a minimum while still ensuring a balance between the integrity of fractured bone and implant degradation time. Therefore, the evaluation of fatigue resistance of WE43 specimens sterilized and tested in immersion conditions (enriched Hank’s solution) and according to ASTM F-1264, along with the morphological, crystallinity, and biocompatibility characterization of the WE43 alloy allows for a comprehensive evaluation of the mechanical and biological properties of WE43.

Conclusions
These results will support decision-making to generate a change in the current perspective of biomaterials utilized in medical devices (MDs), to be considered by manufacturers and health regulatory agencies. An implant manufactured in WE43 alloy can be used as an intramedullary implant, considering keeping elements such as yttrium-REEs below as specified in its designation and with the help of a coating that allows increasing the life of the implant in vivo.
Expert camouflage-breakers can accurately localize search targets
Authors: Branch Fallon , Lewis Allison JoAnna , Santana Isabella Noel , Hegdé Jay 
Published: April 2021

AbstractCamouflage-breaking is a special case of visual search where an object of interest, or target, can be hard to distinguish from the background even when in plain view. We have previously shown that naive, non-professional subjects can be trained using a deep learning paradigm to accurately perform a camouflage-breaking task in which they report whether or not a given camouflage scene contains a target. But it remains unclear whether such expert subjects can actually detect the target in this task, or just vaguely sense that the two classes of images are somehow different, without being able to find the target per se. Here, we show that when subjects break camouflage, they can also localize the camouflaged target accurately, even though they had received no specific training in localizing the target. The localization was significantly accurate when the subjects viewed the scene as briefly as 50 ms, but more so when the subjects were able to freely view the scenes. The accuracy and precision of target localization by expert subjects in the camouflage-breaking task were statistically indistinguishable from the accuracy and precision of target localization by naive subjects during a conventional visual search where the target ‘pops out’, i.e., is readily visible to the untrained eye. Together, these results indicate that when expert camouflage-breakers detect a camouflaged target, they can also localize it accurately.
When and why do people act on flawed science? Effects of anecdotes and prior beliefs on evidence-based decision-making
Authors: Michal Audrey L. , Zhong Yiwen , Shah Priti 
Published: April 2021

AbstractToday’s citizens are expected to use evidence, frequently presented in the media, to inform decisions about health, behavior, and public policy. However, science misinformation is ubiquitous in the media, making it difficult to apply research appropriately. Across two experiments, we addressed how anecdotes and prior beliefs impact readers’ ability to both identify flawed science and make appropriate decisions based on flawed science in media articles. Each article described the results of flawed research on one of four educational interventions to improve learning (Experiment 1 included articles about having a tidy classroom and exercising while learning; Experiment 2 included articles about using virtual/augmented reality and napping at school). Experiment 1 tested the impact of a single anecdote and found no significant effect on either participants’ evidence evaluations or decisions to implement the learning interventions. However, participants were more likely to adopt the more plausible intervention (tidy classroom) despite identifying that it was unsupported by the evidence, suggesting effects of prior beliefs. In Experiment 2, we tested whether this intervention effect was driven by differences in beliefs about intervention plausibility and included two additional interventions (virtual reality = high plausible, napping = low plausible). We again found that participants were more likely to implementhigh plausiblethanlow plausibleinterventions, and that evidence quality was underweighed as a factor in these decisions. Together, these studies suggest that evidence-based decisions are more strongly determined by prior beliefs than beliefs about the quality of evidence itself.
Preliminary numerical study on seismic response of ordinary long-span suspension bridges crossing active faults
Authors: Jia Hongyu , Jia Kang , Sun Caizhi , Li Yanqiang , Zhang Chao , Zheng Shixiong 
Published: April 2021

AbstractThe objective of this paper is to expediently expose the seismic performance pertinent to demand and capacity of general long-span suspension bridges crossing active faults. Firstly three dimensional finite element model of the ordinary long-span suspension bridge is established based on the powerful and attractive finite element software ANSYS. Secondly a series of appropriate fault ground motions with different target final permanent displacements (Tectonic displacements or ground offset) in the direction perpendicular to the fault plane are assumed and applied to the employed long-span suspension bridge. And then the Newmark method is utilized to solve the equation of motion of the long-span suspension bridge structure subjected to fault ground motions in the elastic range. Finally some important conclusions are drawn that the final permanent displacements in the direction perpendicular to the fault plane has significant influence on the seismic responses and demands of general long-span suspension bridges crossing active faults. And the resultant conclusions deliver explicitly and directly specifications and guidelines for seismic design of ordinary long-span suspension bridges across fault-rupture zones.
Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic
Authors: Wadasadawala Tabassum , Kumar Anuj , Laskar Sarbani Ghosh , Gondhowiardjo Soehartati , Mokal Smruti , Goswami Savita , Giselvania Angela , Kapoor Rakesh , Das Abhijit , Pradhan Satyajit , Pujari Lincoln , Acharya Bibek , Chapagain Sandhya , Mahantshetty Umesh , Vadgaonkar Rohit , Hussain Qazi Mushtaq , Akbarov Kamal , Agarwal Jai Prakash 
Published: April 2021

PURPOSE To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) ( P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.