Miracle-dz/UniFAR-FTUs huggingface dataset:
The microtubule regulator ringer functions downstream from the RNA repair/splicing pathway to promote axon regeneration

Promoting axon regeneration in the central and peripheral nervous system is of clinical importance in neural injury and neurodegenerative diseases. Both pro‐ and antiregeneration factors are being identified. We previously reported that the Rtca mediated RNA repair/splicing pathway restricts axon regeneration by inhibiting the nonconventional splicing of Xbp1 mRNA under cellular stress. However, the downstream effectors remain unknown. Here, through transcriptome profiling, we show that the tubulin polymerization‐promoting protein (TPPP) ringmaker/ringer is dramatically increased in Rtca‐deficient Drosophila sensory neurons, which is dependent on Xbp1. Ringer is expressed in sensory neurons before and after injury, and is cell‐autonomously required for axon regeneration. While loss of ringer abolishes the regeneration enhancement in Rtca mutants, its overexpression is sufficient to promote regeneration both in the peripheral and central nervous system. Ringer maintains microtubule stability/dynamics with the microtubule‐associated protein futsch/MAP1B, which is also required for axon regeneration. Furthermore, Ringer lies downstream from and is negatively regulated by the microtubule‐associated deacetylase HDAC6, which functions as a regeneration inhibitor. Taken together, our findings suggest that ringer acts as a hub for microtubule regulators that relays cellular status information, such as cellular stress, to the integrity of microtubules in order to instruct neuroregeneration. Future studies include developing small‐molecule inhibitors for Rtca and further elucidating TPPP’s conserved function in regeneration.
The 24-hour urinary cortisol in post-traumatic stress disorder: A meta-analysis

Objective Previous studies found inconsistent results on the relationship between post-traumatic stress disorder (PTSD) and concentrations of 24-hour (24-h) urinary cortisol. This study performed a systematic review and meta-analysis to summarize previous findings on this relationship. Methods We searched in the databases of Web of Science, PubMed, Embase, and Psyc-ARTICLES for articles published before September 2018. We used the random-effects model with restricted maximum-likelihood estimator to synthesize the effect sizes by calculating the standardized mean difference (SMD) and assessing its significance. Results Six hundred and nineteen articles were identified from the preceding databases and 20 of them were included in the meta-analysis. Lower concentrations of 24-h urinary cortisol were observed in patients with PTSD when compared with the controls (SMD = -0.49, 95%CI [-0.91; -0.07], p = 0.02). Subgroup analysis revealed that the concentrations of 24-h urinary cortisol were lower in PTSD patients than in the controls for studies that included female participants or studies that included participants from the United States of America. Conclusions Overall, decreased levels of 24-h urinary cortisol were linked with the pathophysiology of PTSD. Nonetheless, more studies should be conducted to validate the molecular underpinnings of urine cortisol degeneration in PTSD.
Understanding public-stigma and self-stigma in the context of dementia: A systematic review of the global literature

Stigma negatively impact quality of life of people with dementia and their family members. Yet the literature in stigma and dementia remains scant. This article systematically reviews manifestations of and associated factors with public-stigma and self-stigma in the context of dementia. After searching and screening on the three major databases of PubMed, Embase, and psycINFO, 26 articles, including 17 quantitative papers and nine qualitative papers, were selected for synthesis. Results show consistently limited knowledge, as well as stereotype, prejudice, and discrimination of public toward people with dementia and their family caregivers. Demographic characteristics of general public were found to be associated with the level of their stigma against dementia. People with dementia and their family caregivers also perceived negative stereotype, prejudice, and discrimination from general public and healthcare professionals. They reported negative feelings of themselves and tended to delay help-seeking. Psychological factors rather than sociodemographic factors shaped self-stigma of people with dementia and their families. This systematic review highlights the need of future studies in both public-stigma and self-stigma in dementia research in different contexts and cultures, as well as the development of evidence-based and culturally competent interventions and mass media campaigns to reconstruct public perception of dementia.
Mesenchymal stromal cell based therapies for the treatment of immune disorders: recent milestones and future challenges

ABSTRACT Introduction: Mesenchymal stromal cells (MSCs) present unique immunomodulatory properties that make them promising candidates for the treatment of inflammatory and immune disorders. MSC-mediated immunomodulation is a complex combination of mechanisms, in which the secretome plays a fundamental role. The plethora of bioactive molecules MSCs produce, such as indoleamine 2,3-dioxygenase (IDO) or prostaglandin E2 (PGE2), efficiently regulates innate and adaptive immunity. As a result, MSCs have been extensively employed in preclinical studies, leading to the conduction of multiple clinical trials. Areas covered: This review summarizes the effects of some of the key biomolecules in the MSC secretome and the advances in preclinical studies exploring the treatment of disorders including graft-versus-host disease (GvHD) or inflammatory bowel disease (IBD). Further, late-stage clinical trials and the first MSC-based therapies that recently obtained regulatory approval are discussed. Expert opinion: Extensive research supports the potential of MSC-based immunomodulatory therapies. However, to establish the bases for clinical translation, the future of study lies in the standardization of protocols and in the development of strategies that boost the therapeutic properties of MSCs.
Adaptive landscape flattening allows the design of both enzyme: Substrate binding and catalytic power

Designed enzymes are of fundamental and technological interest. Experimental directed evolution still has significant limitations, and computational approaches are complementary. A designed enzyme should satisfy multiple criteria: stability, substrate binding, transition state binding. Such multi-objective design is computationally challenging. Two recent studies used adaptive importance sampling Monte Carlo to redesign proteins for ligand binding. By first flattening the energy landscape of the apo protein, they obtained positive design for the bound state and negative design for the unbound. We extend the method to the design of an enzyme for specific transition state binding, i.e., for catalytic power. We consider methionyl-tRNA synthetase (MetRS), which attaches methionine (Met) to its cognate tRNA, establishing codon identity. MetRS and other synthetases have been extensively redesigned by experimental directed evolution to accept noncanonical amino acids as substrates, leading to genetic code expansion. We redesigned MetRS computationally to bind several ligands: the Met analog azidonorleucine, methionyl-adenylate (MetAMP), and the activated ligands that form the transition state for MetAMP production. Enzyme mutants known to have azidonorleucine activity were recovered, and mutants predicted to bind MetAMP were characterized experimentally and found to be active. Mutants predicted to have low activation free energies for MetAMP production were found to be active and the predicted reaction rates agreed well with the experimental values. We expect the present method will become the paradigm for computational enzyme design.
Uniting generations: A research protocol examining the impacts of an intergenerational learning program on participants and organisations

Economic, health and social issues associated with the ageing population and the disconnect between the generations call for novel approaches to care services. Intergenerational programs are known to enhance engagement between generations, improve health and well‐being and create a stronger sense of community. While the health and social benefits are well documented, little attention has been given to the operational aspects of intergenerational programs within care facilities. This paper describes the research protocol used to develop, implement and evaluate an intergenerational learning program for preschool‐aged children and older people attending care services. The research focuses on five key areas: (a) impact on older people and children; (b) intergenerational learning; (c) workforce development; (d) socio‐economic implications and costs; and (e) program fidelity and sustainability. Findings from this research are expected to contribute to building age‐friendly communities through the development of practical operational guidelines for intergenerational learning programs to be implemented more broadly across Australia.
Simultaneous Multislice Diffusion-Weighted Imaging of the Kidneys at 3 T.

PURPOSE The aim of this study was to compare respiratory-triggered diffusion-weighted imaging with simultaneous-multislice acceleration (SMS-RT-DWI) to a standard free-breathing echoplanar DWI (s-DWI) for 3 T renal imaging with respect to image quality and artifacts. MATERIALS AND METHODS A total of 40 patients who had undergone renal magnetic resonance imaging were included in this retrospective analysis of a prospectively planned cohort study. All examinations were performed on a 3 T whole-body magnetic resonance system. Both s-DWI and SMS-RT-DWI were obtained and images were independently reviewed by 2 radiologists on a 5-point Likert scale with respect to overall preference and image quality, renal edge and parenchymal sharpness, cortico-medullary differentiation, and sequence-related artifacts. Furthermore, discernibility of renal lesions was assessed. The signal-to-noise ratio (SNR) was measured from SNR maps. The derived mean apparent diffusion coefficients were also compared. Qualitative parameters were assessed with the Wilcoxon rank-sum test, and quantitative parameters, with the Student t test. RESULTS Overall image quality, renal edge, and parenchymal sharpness of SMS-RT-DWI were rated as superior to s-DWI by the readers, with fewer sequence-related artifacts (P < 0.01 for all). Lesion discernibility was significantly improved for SMS-RT-DWI (P < 0.01). Both readers preferred SMS-RT-DWI to s-DWI in all cases (40/40). The acquisition time for SMS-RT-DWI was 30% shorter than for s-DWI. Mean SNR heterogeneity of SMS-RT-DWI at b = 800 s/mm was statistically significantly lower than s-DWI, whereas mean SNR was significantly higher for SMS-RT-DWI. Mean apparent diffusion coefficient values from both sequences were comparably homogeneous throughout the kidneys. CONCLUSION Simultaneous multislice DWI of the kidney at 3 T with respiratory triggering yields substantially improved image quality and lesion discernibility compared with standard single-shot echoplanar DWI with a 30% reduction in scan acquisition time.
Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries

Purpose: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. Methods: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. Results: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. Conclusions: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics. Perioperative antibiotics do not appear to decrease the already low incidence of surgical site infection in patients undergoing orbital surgery.
Exercise-induced vasodilation is not impaired following radial artery catheterization in coronary artery disease patients.

Diagnosis and treatment for coronary artery disease (CAD) often involves angiography and/or percutaneous coronary intervention. However, the radial artery catheterization required during both procedures may result in acute artery dysfunction/damage. Whilst exercise-based rehabilitation is recommended for CAD patients following catheterization, it is not known if there is a period when exercise may be detrimental due to catheter-induced damage. Animal studies have demonstrated exercise-induced paradoxical vasoconstriction post-catheterization. This study aimed to examine arterial responses to acute exercise following catheterization. Thirty-three CAD patients (65.8±7.3yr, 31.5±6.3kg.m-2, 82%♂) undergoing transradial catheterization were assessed pre- and 1 week post-catheterization. Radial artery (RA) diameter and shear rate were assessed during handgrip exercise (HE), in both the catheterized (CATH) and control (CON) arms. Endothelial function was also assessed via simultaneous bilateral radial flow mediated dilation (FMD) at both time-points. We found that the increase in RA diameter and shear stress in response to HE (P<0.0001) was maintained post-catheterization in both the CATH and CON arms, whereas FMD following catheterization was impaired in the CATH [6.5±3.3% to 4.7±3.5% (P=0.005)] but not in the CON [6.2±2.6% to 6.4±3.5% (P=0.797)] limb. Whilst endothelial dysfunction, assessed by FMD, was apparent 1 week post-catheterization, the ability of the RA to dilate in response to exercise was not impaired. The impact of catheterization and consequent endothelial denudation on vascular dys/function in humans may therefore be stimulus specific and a highly level of redundancy appears to exist that preserves exercise-mediated vasodilator responses.
Opportunities to debottleneck the downstream processing of the oncolytic measles virus

Abstract Oncolytic viruses (including measles virus) offer an alternative approach to reduce the high mortality rate of late-stage cancer. Several measles virus strains infect and lyse cancer cells efficiently, but the broad application of this therapeutic concept is hindered by the large number of infectious particles required (108–1012 TCID50 per dose). The manufacturing process must, therefore, achieve high titers of oncolytic measles virus (OMV) during upstream production and ensure that the virus product is not damaged during purification by applying appropriate downstream processing (DSP) unit operations. DSP is currently a production bottleneck because there are no specific platforms for OMV. Infectious OMV must be recovered as intact, enveloped particles, and host cell proteins and DNA must be reduced to acceptable levels to meet regulatory guidelines that were developed for virus-based vaccines and gene therapy vectors. Handling such high viral titers and process volumes is technologically challenging and expensive. This review considers the state of the art in OMV purification and looks at promising DSP technologies. We discuss here the purification of other enveloped viruses where such technologies could also be applied to OMV. The development of DSP technologies tailored for enveloped viruses is necessary to produce sufficient titers for virotherapy, which could offer hope to millions of patients suffering from incurable cancer.
Anterior Cruciate Ligament Reconstruction in High School and College-Aged Athletes: Does Autograft Choice Influence Anterior Cruciate Ligament Revision Rates?

Background: Physicians’ and patients’ decision-making process between bone–patellar tendon–bone (BTB) and hamstring tendon autografts for anterior cruciate ligament (ACL) reconstruction (ACLR) may be influenced by a variety of factors in the young, active athlete. Purpose: To determine the incidence of both ACL graft revisions and contralateral ACL tears resulting in subsequent ACLR in a cohort of high school– and college-aged athletes who initially underwent primary ACLR with either a BTB or a hamstring autograft. Study Design: Cohort study; Level of evidence, 2. Methods: Study inclusion criteria were patients aged 14 to 22 years who were injured in sports, had a contralateral normal knee, and were scheduled to undergo unilateral primary ACLR with either a BTB or a hamstring autograft. All patients were prospectively followed for 6 years to determine whether any subsequent ACLR was performed in either knee after their initial ACLR. Multivariable regression modeling controlled for age, sex, ethnicity/race, body mass index, sport and competition level, baseline activity level, knee laxity, and graft type. The 6-year outcomes were the incidence of subsequent ACLR in either knee. Results: A total of 839 patients were eligible, of which 770 (92%) had 6-year follow-up for the primary outcome measure of the incidence of subsequent ACLR. The median age was 17 years, with 48% female, and the distribution of BTB and hamstring grafts was 492 (64%) and 278 (36%), respectively. The incidence of subsequent ACLR at 6 years was 9.2% in the ipsilateral knee, 11.2% in the contralateral normal knee, and 19.7% for either knee. High-grade preoperative knee laxity (odds ratio [OR], 2.4 [95% confidence interval [CI], 1.4-3.9]; P = .001), autograft type (OR, 2.1 [95% CI, 1.3-3.5]; P = .004), and age (OR, 0.8 [95% CI, 0.7-1.0]; P = .009) were the 3 most influential predictors of ACL graft revision in the ipsilateral knee. The odds of ACL graft revision were 2.1 times higher for patients receiving a hamstring autograft than patients receiving a BTB autograft (95% CI, 1.3-3.5; P = .004). No significant differences were found between autograft choices when looking at the incidence of subsequent ACLR in the contralateral knee. Conclusion: There was a high incidence of both ACL graft revisions and contralateral normal ACL tears resulting in subsequent ACLR in this young athletic cohort. The incidence of ACL graft revision at 6 years after index surgery was 2.1 times higher with a hamstring autograft compared with a BTB autograft.
Design and construction of a Maxwell-type induction coil for magnetic nanoparticle hyperthermia

Abstract Purpose We describe a modified Helmholtz induction coil, or Maxwell coil, that generates alternating magnetic fields (AMF) having field uniformity (≤10%) within a = 3000 cm3 volume of interest for magnetic hyperthermia research. Materials and methods Two-dimensional finite element analysis (2D-FEA) was used for electromagnetic design of the induction coil set and to develop specifications for the required matching network. The matching network and induction coil set were fabricated using best available practices and connected to a 120 kW industrial induction heating power supply. System performance was evaluated by magnetic field mapping with a magnetic field probe, and tests were performed using gel phantoms. Results Tests verified that the system generated a target peak AMF amplitude along the coil axis of ∼35 kA/m (peak) at a frequency of 150 ± 10 kHz while maintaining field uniformity to >90% of peak for a volume of ∼3000 cm3. Conclusions The induction coil apparatus comprising three independent loops, i.e., Maxwell-type improves upon the performance of simple solenoid and Helmholtz coils by providing homogeneous flux density fields within a large volume while minimizing demands on power and stray fields. Experiments with gel phantoms and analytical calculations show that future translational research efforts should be devoted to developing strategies to reduce the impact of nonspecific tissue heating from eddy currents; and, that an inductor producing a homogeneous field has significant clinical potential for deep-tissue magnetic fluid hyperthermia.
Evidence for acupoint catgut embedding treatment and TRPV1 gene deletion increasing weight control in murine model

Obesity is a global health problem affecting the general population. Acupoint catgut embedding (ACE) is an alternative treatment that involves the implantation of absorbable catgut suture at acupoints. The transient receptor vanilloid member 1 (TRPV1) is a calcium ion channel that responds to several chemical ligands and is identified in numerous locations throughout the body. The aim of the present study was to examine the effect of ACE treatment on obesity and its associated complications through various neural mechanisms in a murine model. A C57/BL6 wild type (WT) and TRPV1-/- (KO) mouse model was utilized to exclude any psychological factors associated with obesity. The WT-HFD-ACE and WT-HFD-SHAM groups received weekly ACE or placebo treatments at the bilateral ST36 acupoint. The mice were fed with a normal mice chow diet (ND) or a high-fat food diet (HFD; 45 kcal%), and their body weights were recorded once a week. After 8 weeks, the subjects were sacrificed and changes in the levels of a number of biomarkers were investigated using ELISA, immunoblotting and immunofluorescence. The results indicated a significant decrease in body weight variation for the WT-HFD-ACE group compared with the WT-HFD and WT-HFD-SHAM groups, using the WT-ND group as the body weight baseline. By contrast, KO mice fed with ND or HFD demonstrated notable body weight maintenance throughout the experimental period. Similar patterns were observed in adipose tissue mass, glucose, leptin and insulin plasma levels, and protein molecule density of TRPV1 and its associated molecules in the hypothalamus and nucleus tractus solitarii. In contrast, in the prefrontal cortex, significant decreases in the concentrations of MAPK pathway proteins in the WT-HFD and WT-HFD-SHAM groups were observed. The levels of these proteins were significantly increased in the WT-HFD-ACE and KO-HFD groups. These results suggested that TRPV1 and its associated pathways may be involved in body weight maintenance, and may be controlled through ACE treatment or genetic manipulation.