Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative Physiology/Experimental Medicine Critical Role of Tissue Kallikrein in Vessel Formation and Maturation Implications for Therapeutic Revascularization

Objective—Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function polymorphic variant, rs5515 (R53H), which possesses reduced kinin-forming activity. Methods and Results—Here, we demonstrate that tissue kallikrein knockout mice (KLK1 / ) show impaired muscle neovascularization in response to hindlimb ischemia. Gene-transfer of wild-type Ad.hKLK1 but not Ad.R53H-hKLK1 was able to rescue this defect. Similarly, in the rat mesenteric assay, Ad.hKLK1 induced a mature neovasculature with increased vessel diameter through kinin-B2 receptor-mediated recruitment of pericytes and vascular smooth muscle cells, whereas Ad.R53HhKLK1 was ineffective. Moreover, hKLK1 but not R53H-hKLK1 overexpression in the zebrafish induced endothelial precursor cell migration and vascular remodeling. Furthermore, Ad.hKLK1 activates metalloproteinase (MMP) activity in normoperfused muscle and fails to promote reparative neovascularization in ischemic MMP9 / mice, whereas its proarteriogenic action was preserved in ApoE / mice, an atherosclerotic model of impaired angiogenesis. Conclusions—These results demonstrate the fundamental role of endogenous Tissue Kallikrein in vascular repair and provide novel information on the cellular and molecular mechanisms responsible for the robust arterialization induced by hKLK1 overexpression. (Arterioscler Thromb Vasc Biol. 2009;29:657-664.)
Complete mitochondrial genome of the hybrid of Acipenser schrenckii (♀) × Huso dauricus (♂)

Abstract The complete mitochondrial genome sequence of the hybrid of Acipenser schrenckii (♀) × Huso dauricus (♂) (A × H) was first determined by a PCR-based sequencing method in this study. The mitochondrial was 16 687 bp in length, including 13 protein genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. All genes were encoded on the heavy strain except for ND6 and eight tRNA genes. Base composition of the heavy strain was A (29.80%), T (24.42%), C (28.94%), G (16.82%), and with A + T bias of 54.26%. Compared with the complete mitochondrial genome of the parents, results showed the hybrid sturgeon was consistent with a maternal inheritance; however, we also found ND6 and tRNA-Glu which were species-specific for the male parent H. dauricus. The complete mitochondrial genome sequence of the A × H provided an important data set for further study in mitochondrial inheritance mechanism.
Paraspinal Muscle DTI Metrics Predict Muscle Strength

The paraspinal muscles play an important role in the onset and progression of lower back pain. It would be of clinical interest to identify imaging biomarkers of the paraspinal musculature that are related to muscle function and strength. Diffusion tensor imaging (DTI) enables the microstructural examination of muscle tissue and its pathological changes.
Trastuzumab Induced Chemobrain, Atorvastatin Rescued Chemobrain with Enhanced Anticancer Effect and without Hair Loss-Side Effect

The authors identified that chemo-brain was induced after trastuzumab (TZB) therapy. In addition, atorvastatin (ATV) could rescue chemo-brain during trastuzumab (TZB) therapy. Enhanced therapeutic effect of TZB was confirmed after ATV therapy. We also investigated that there was no hair loss side effect due to ATV therapy. In an animal model, 150 μg TZB and five serial doses of 20 mg/kg ATV were administered. 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data were acquired. Statistical parametric mapping analysis and voxel-based morphometry analysis were performed to identify differences in glucose metabolism and gray matter concentration. The enhanced therapeutic efficacy of TZB after ATV treatment was assessed using a human epidermal growth factor receptor 2-positive gastric cancer model. We found a decrease in cerebral glucose metabolism and gray matter concentration in the frontal lobe following TZB therapy (p < 0.005). After subsequent ATV administration, glucose metabolism and regional gray matter concentration were rescued (p < 0.005). Cognitive impairment due to TZB and the rescue effect of ATV were confirmed using a passive avoidance test and quantitative real-time reverse transcription PCR. Furthermore, the penetration and accumulation of TZB in tumors increased by 100% after ATV co-administration, which resulted in an enhanced anti-cancer effect. Our study collectively demonstrates that ATV co-administration with TZB rescued the TZB-induced chemo-brain and enhances the therapeutic efficacy of TZB in tumors. We also showed that there was no hair loss during ATV therapy.
Use of dipeptidyl peptidase‐4 inhibitors and the risk of arthralgia: Population‐based cohort and nested case–control studies

The objective of this study was to investigate the association between the administration of dipeptidyl peptidase‐4 (DPP‐4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case–control study designs.
A Model of Care for Osteoarthritis of the Hip and Knee: Development of a System-Wide Plan for the Health Sector in Victoria, Australia

Osteoarthritis (OA) imposes a significant burden to the person, the health system and the community. Models of Care (MoCs) drive translation of evidence into policy and practice and provide a platform for health system reform. The Victorian MoC for OA of the hip and knee was developed following a best-practice framework, informed by best-evidence and iterative cross-sector consultation, including direct consumer consultation. Governance and external expert advisory committees consisting of local OA care champions facilitated the development and consultation processes. The MoC outlines key components of care, care that is not recommended, and suggests phased implementation strategies. This paper describes the MoC development process and lessons learned.
6‐Phenylpyrrolocytidine: An Intrinsically Fluorescent, Environmentally Responsive Nucleoside Analogue

The detailed synthetic protocols for the preparation of phosphoramidite reagents compatible with standard, automated oligonucleotide synthesis for the 2′‐deoxy‐ and ribo‐6‐phenylpyrrolocyitidine are reported. Each protocol starts with the parent nucleoside and prepares the 5′‐O‐dimethoxytrityl‐N4‐benzoyl‐5‐iodocytosine derivative for the nucleobase modification chemistry. The key step is the direct formation of 6‐phenylpyrrolocytosine aglycon via a sequential, one‐pot Pd‐catalyzed Sonogashira‐type cross‐ coupling followed by a 5‐endo‐dig cyclization. Subsequent standard transformations provide the deoxy‐ and 2′‐O‐tert‐butyldimethysilyl protected ribo‐ nucleoside phosphoramidite reagents. © 2019 by John Wiley & Sons, Inc.
Characterization of a phospholipid‐regulated β‐galactosidase from Akkermansia muciniphila involved in mucin degradation

The gut microbe Akkermansia muciniphila is important for the human health as the occurrence of the organism is inversely correlated with different metabolic disorders. The metabolism of the organism includes the degradation of intestinal mucins. Thus, the gut health‐promoting properties are not immediately obvious and mechanisms of bacteria‐host interactions are mostly unclear. In this study, we characterized a novel extracellular β‐galactosidase (Amuc_1686) with a preference for linkages from the type Galβ1–3GalNAc. Additionally, Amuc_1686 possesses a discoidin‐like domain, which enables the interaction with anionic phospholipids. We detected a strong inhibition by phosphatidylserine, phosphatidylglycerol, phosphatidic acid, and lysophosphatidic acid while phosphatidylcholine and phosphatidylethanolamine had no influence. Amuc_1686 is the first example of a prokaryotic hydrolase that is strongly inhibited by certain phospholipids. These inhibiting phospholipids have important signal functions in immune response and cell clearance processes. Hence, Amuc_1686 might be regulated based on the health status of the large intestine and could therefore contribute to the mutualistic relationship between the microbe and the host on a molecular level. In this sense, Amuc_1686 could act as an altruistic enzyme that does not attack the mucin layer of apoptotic epithelial cells to ensure tissue regeneration, for example, in areas with inflammatory damages.
Using a smart textile system for classifying occupational manual material handling tasks: evidence from lab-based simulations

Abstract Physical monitoring systems represent potentially powerful assessment devices to detect and describe occupational physical activities. A promising technology for such use is smart textile systems (STSs). Our goal in this exploratory study was to assess the feasibility and accuracy of using two STSs to classify several manual material handling (MMH) tasks. Specifically, commercially-available ‘smart’ socks and a custom ‘smart’ shirt were used individually and in combination. Eleven participants simulated nine separate MMH tasks while wearing the STSs, and task classification accuracy was quantified subsequently using several common models. The shirt and socks, both individually and in combination, could classify the simulated tasks with greater than 97% accuracy. Thus, using STSs appears to have potential utility for discriminating occupational physical tasks in the work environment. Practitioner summary: A smart textile system could classify diverse MMH tasks with high accuracy. This technology may help in developing future ergonomic exposure assessment systems, with the goal of preventing occupational injuries.
Burnout in Home Palliative Care: What Is the Role of Coping Strategies?

Objective: The study examines psychophysical distress of health-care professionals providing home-based palliative care. The aim is to investigate potential correlations between dimensions of burnout and different coping strategies. Methods: The present study is an observational cross-sectional investigation. The study involved all the home palliative care teams of an Italian nonprofit organization. Of a total of 275 practitioners working for the organization, 207 (75%) decided to participate in the study and complete questionnaires. Questionnaires employed were Maslach Burnout Inventory, General Health Questionnaire 12, Psychophysiological Questionnaire of CBA 2.0, and Coping Orientation to Problems Experienced. Professionals were physicians (50%), nurses (36%), and psychologists (14%). There were no exclusion criteria. Data were processed by SPSS 23 and analyses employed were Spearman ρ, Mann-Whitney U test, and 1-way analysis of variance on ranks. Results: Among participants, a low number of professionals were emotionally exhausted (11%) or not fulfilled at work (20%), whereas most of them complained of depersonalization symptoms (67%). Emotional exhaustion and depersonalization were found to be associated with avoidance coping strategies, whereas problem-solving and positive attitude were negatively associated with emotional exhaustion and positively with personal accomplishment. Moreover, using avoidance strategies was related to a worse psychological and physical condition. Conclusions: Findings suggest the need to provide professionals training programs about coping and communication skills tailored to fit the professionals’ needs according to their work experience in palliative care and aimed at improving the approach to patients and relatives.
The C. elegans heterochronic gene lin-28 coordinates the timing of hypodermal and somatic gonadal programs for hermaphrodite reproductive system morphogenesis

ABSTRACT C. elegans heterochronic genes determine the timing of expression of specific cell fates in particular stages of developing larvae. However, their broader roles in coordinating developmental events across diverse tissues have been less well investigated. Here, we show that loss of lin-28, a central heterochronic regulator of hypodermal development, causes reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes that act downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of lin-28 in somatic gonadal morphogenesis and fertility. Importantly, we find that hypodermal expression, but not somatic gonadal expression, of lin-28 is sufficient for restoring normal somatic gonadal morphology in lin-28(lf) mutants. We propose that the abnormal somatic gonadal morphogenesis of lin-28(lf) hermaphrodites results from temporal discoordination between the accelerated hypodermal development and normally timed somatic gonadal development. Thus, our findings exemplify how a cell-intrinsic developmental timing program can also control proper development of other interacting tissues, presumably by cell non-autonomous signal(s). This article has an associated ‘The people behind the papers’ interview. Highlighted Article: By regulating the developmental timing of hypodermal tissues in C. elegans, lin-28 controls signaling between the hypodermis and somatic gonad that is crucial for gonadal morphogenesis.
Loudness Trumps Pitch in Politeness Judgments: Evidence from Korean Deferential Speech

Social meaning is not conveyed through words alone, but also through how words are produced phonetically. This paper investigates the role of loudness and pitch in determining the perception of politeness-related judgments in Korean. It has been proposed that high pitch is universally associated with polite or deferential social meanings. In contrast to this, Experiment 1 examined the perceptual effect of pitch and found no effect. Experiment 2 tested the effect of loudness, and found that listeners associate quieter speech with deference. Finally, Experiment 3 investigated the simultaneous effects of loudness and pitch, and found again that loudness had a consistent effect, whereas pitch only had a weak effect. Analyses of individual differences suggest that in contrast to loudness, which is interpreted uniformly across Korean listeners, pitch has more variegated social meanings: Some listeners associate high pitch with deferential meaning, others associate low pitch with deferential meaning. Thus, we find loudness to be a more unambiguous indicator of deferential speech than pitch. These findings shed light on how different acoustic properties contribute to the indexing of social stances, and they suggest that the role of pitch in conveying politeness may have been overstated in past research.
The Addition of Hip Arthroscopy to Periacetabular Osteotomy Does Not Increase Complication Rates: A Prospective Case Series

Background: Previous studies on periacetabular osteotomy (PAO) reported complication and reoperation rates of 5.9% and 10%, respectively. Hip arthroscopy is increasingly utilized as an adjunct procedure to PAO to precisely treat associated intra-articular pathology. The addition of this procedure has the potential of further increasing complication rates. Purpose: To determine the rates of complication and reoperation of combined hip arthroscopy and PAO for the treatment of acetabular deformities and associated intra-articular lesions. Study Design: Case series; Level of evidence, 4. Methods: Using a prospective database, the authors retrospectively reviewed 248 hips (240 patients) that underwent combined hip arthroscopy and PAO between 2007 and 2016. Data were collected at scheduled follow-up visits at approximately 1 month, 3 to 4 months, and 1 and 2 years after surgery. Mean follow-up from surgery was 3 years (range, 1-8 years). A total of 220 PAOs were done for symptomatic acetabular dysplasia, 18 for symptomatic acetabular retroversion, and 10 for combined acetabular dysplasia and acetabular retroversion. Central compartment arthroscopy was performed for treatment of intra-articular chondrolabral pathology in all cases. Select cases underwent femoral head-neck junction osteochondroplasty either arthroscopically before the PAO or through an open approach after it. Complications were graded according to the modified Dindo-Clavien complication scheme, which was validated for hip preservation procedures. Reoperations (excluding hardware removal) were recorded. Results: Grade III complications occurred among 7 patients (3%) while there were no grade IV complications. Grade III complications included deep infection (n = 3), wound dehiscence (n = 1), hematoma requiring exploration (n = 1), symptomatic heterotopic ossification requiring excision (n = 1), and deep venous thrombosis (n = 1). There were 13 reoperations (5%), and 3 were repeat hip arthroscopy. Univariate Cox hazard models were used to estimate the relative risk factors for complication and reoperation. Increased age (per decade) showed over twice the increased likelihood for complications (hazard ratio, 2.5; 95% CI, 1.67-3.74). Also, preoperative diagnosis of acetabular retroversion, not acetabular dysplasia, showed >3 times the increased risk of reoperation (hazard ratio, 3.05; 95% CI, 1.41-6.61). Conclusion: The rate of complications reported is comparable (3%) with previously published complication rates of PAO without hip arthroscopy. In this cohort, increasing age and diagnosis of acetabular retroversion were associated with higher complication and reoperation rates.
Mannitol for Paraphimosis Reduction

Introduction: Paraphimosis is a urologic emergency. Many treatment options have been devised for managing this entity. The osmotic method is one of them. We used an osmotic diuretic, mannitol, for reducing paraphimosis. Mannitol is commonly used for conditions like head injury to decrease cerebral oedema, partial nephrectomy and hepatorenal syndrome; we attempted using this diuretic for reducing paraphimosis. This is a novel technique and an application of mannitol which has never been reported before. Methods: Starting in February 2011, we used mannitol 20% in patients presenting to urologic emergency with uncomplicated paraphimosis. Mannitol-soaked gauzes were wrapped around the oedematous prepuce, followed by minimal intermittent hand compression and frequent resoaking of the gauze with 20% mannitol. No needle punctures were made. The soaked gauze was removed and the paraphimosis was reduced easily. Results: A complete reduction of paraphimosis occurred after mannitol-soaked gauze had been placed over the oedematous prepuce for about 30–45 min in 6 of our patients. This is a novel agent used for this entity; it reduces paraphimosis in a minimal time with no pain, with the added advantage of the least risk of infection after the procedure as opposed to granulated sugar or 50% dextrose previously used as osmotic agents. Conclusions: Mannitol can be applied in clinical practice for reducing paraphimosis. It requires no anaesthesia and is associated with minimal/no patient discomfort unlike that seen with multiple needle punctures and the various other non-osmotic methods of reducing paraphimosis.
Tumour parcellation and quantification (TuPaQ): a tool for refining biomarker analysis through rapid and automated segmentation of tumour epithelium

Immunohistochemistry (IHC) is an essential component of biomarker research in cancer. Automated biomarker quantification is hampered by the failure of computational algorithms to discriminate ‘negative’ tumour cells from ‘negative’ stromal cells. We sought to develop an algorithm for segmentation of tumour epithelium in colorectal cancer (CRC), irrespective of the biomarker expression in the cells.
NIR Biosensing of Neurotransmitters in Stem Cell‐Derived Neural Interface Using Advanced Core–Shell Upconversion Nanoparticles

Nondestructive neurotransmitter detection and real‐time monitoring of stem cell differentiation are both of great significance in the field of neurodegenerative disease and regenerative medicine. Although luminescent biosensing nanoprobes have been developed to address this need, they have intrinsic limitations such as autofluorescence, scattering, and phototoxicity. Upconversion nanoparticles (UCNPs) have gained increasing attention for various biomedical applications due to their high photostability, low auto‐fluorescent background, and deep tissue penetration; however, UCNPs also suffer from low emission intensities due to undesirable energy migration pathways. To address the aforementioned issue, a single‐crystal core–shell–shell “sandwich” structured UCNP is developed that is designed to minimize deleterious energy back‐transfer to yield bright visible emissions using low power density excitations. These UCNPs show a remarkable enhancement of luminescent output relative to conventional β‐NaYF4:Yb,Er codoped UCNPs and β‐NaYF4:Yb,Er@NaYF4:Yb “active shell” alike. Moreover, this advanced core–shell–shell UCNP is subsequently used to develop a highly sensitive biosensor for the ultrasensitive detection of dopamine released from stem cell‐derived dopaminergic‐neurons. Given the challenges of in situ detection of neurotransmitters, the developed NIR‐based biosensing of neurotransmitters in stem cell‐derived neural interfaces present a unique tool for investigating single‐cell mechanisms associated with dopamine, or other neurotransmitters, and their roles in neurological processes.
Changes in understandings and perceptions of individuals, significant others and community supporters involved in a theatre company for adults with intellectual disabilities

BACKGROUND Theatre companies to show positive capabilities and identities of people with intellectual disabilities have been established. Existing research focuses upon sole theatre performances and rarely includes the impacts on those in the immediate and wider contexts of people with intellectual disabilities. METHODS The impacts of a theatre company on understandings and perceptions of intellectual disabilities from multiple perspectives were explored. Interviews with members with intellectual disabilities (n = 14), and focus groups with significant people in their lives (n = 11) and community supporters (n = 10) were conducted and analysed using thematic analysis. RESULTS Four superordinate and nine subordinate themes were identified. The theatre company increased members' connectivity, allowed them to experience parts of life they are often excluded from, and enabled growth for all participants, leading to a desire to extend the theatre company's ethos elsewhere. CONCLUSIONS The importance of such organisations to improve perceptions of people with intellectual disabilities is emphasized.