Miracle-dz/UniFAR-FTUs huggingface dataset:
Collaboration for children with complex needs: What adolescents, parents, and practitioners tell us

Children with complex needs require coordinated care and collaboration between the different sectors in child mental health care. These needs and service issues are individually defined and therefore challenging for the mental health system to respond effectively. Different barriers at the organizational and policy level to initiate and maintain collaborative relationships are reported. This research explores the reality of working with a protocol for collaboration (Client Network Consultation (CNC)) by questioning the experiences of adolescents, parents, and practitioners. A qualitative design with semistructured individual interviews is used, guided by the questions from the Wraparound Fidelity Index. Useful and practical insights on effective collaboration result from the in-depth analysis of the interviews. A neutral chairperson, the presence of specialist practitioners, visualization, participation of adolescents, and parents are among the effective elements reported. Some challenges remain; the principle of equality, monitoring the action points resulting from the collaboration and effective crisis management seem very difficult to fully achieve in practice. These results present experiences from adolescents, parents, and practitioners to support an effective collaborative process for working together with children and families with complex needs.
Divergence and heterogeneity of neoplastic PD‐L1 expression: Two autopsy case reports of intravascular large B‐cell lymphoma

Intravascular large B‐cell lymphoma (IVLBCL) is a distinct disease, but the neoplastic PD‐L1 expression on tumor cells may vary among cases. We evaluated 10 IVLBCL autopsy cases for neoplastic PD‐L1 expression, and had positive results in two cases. In one case, neoplastic PD‐L1 expression (SP142, 28‐8, and E1J2J clones) was dependent on the organ and anatomical site (capillaries vs. vessels) of the tumor tissue. Neoplastic PD‐L1 expression was found in tumor cells located in capillaries in the central nervous system, pituitary gland, kidneys, lung, and gastrointestinal tract; sinuses/sinusoids of the spleen, liver, bone marrow, and lymph nodes; and an extravascular location. However, this expression was not detected in tumor cells located in the adrenal gland, thyroid gland, pancreas, ovaries, uterus, pleura, and small or larger‐sized vessels of the lung. The other case showed constant neoplastic PD‐L1 expression on the tumor cells, and in addition to the affected organs, capillaries, and vessels with two anti‐PD‐L1 antibodies (28‐8 and E1J2J, but not SP142). The divergence and heterogeneity of neoplastic PD‐L1 expression were clearly demonstrated in our cases. To the best of our knowledge, this is the first description of divergent neoplastic PD‐L1 expression among the affected organs and anatomical sites in IVLBCL.
MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling

MAPK4 is an atypical MAPK. Currently, little is known about its physiological function and involvement in diseases, including cancer. A comprehensive analysis of 8887 gene expression profiles in The Cancer Genome Atlas (TCGA) revealed that MAPK4 overexpression correlates with decreased overall survival, with particularly marked survival effects in patients with lung adenocarcinoma, bladder cancer, low-grade glioma, and thyroid carcinoma. Interestingly, human tumor MAPK4 overexpression also correlated with phosphorylation of AKT, 4E-BP1, and p70S6K, independent of the loss of PTEN or mutation of PIK3CA. This led us to examine whether MAPK4 activates the key metabolic, prosurvival, and proliferative kinase AKT and mTORC1 signaling, independent of the canonical PI3K pathway. We found that MAPK4 activated AKT via a novel, concerted mechanism independent of PI3K. Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308. It also activated mTORC2 to phosphorylate AKT at serine 473 for full activation. MAPK4 overexpression induced oncogenic outcomes, including transforming prostate epithelial cells into anchorage-independent growth, and MAPK4 knockdown inhibited cancer cell proliferation, anchorage-independent growth, and xenograft growth. We concluded that MAPK4 can promote cancer by activating the AKT/mTOR signaling pathway and that targeting MAPK4 may provide a novel therapeutic approach for cancer.
Reversal of Ketosis in Type 1 Diabetes Is Not Adversely Affected by SGLT2 Inhibitor Therapy.

OBJECTIVE We have shown that "euglycemic DKA" in patients with type 1 diabetes receiving a sodium-glucose cotransporter 2-inhibitor (SGLT2i) is due to normal increases in rates of ketogenesis but blunted increases in plasma glucose levels. In this analysis, we assessed whether rescue treatment of early ketoacidosis with insulin is altered by SGLT2i use. RESEARCH DESIGN AND METHODS Participants received 0.2 U/kg of aspart insulin after two 6-h interruptions of basal insulin that increased beta-hydroxybutyrate (BHB) by 1.2 ± 0.7 mmol/L before and by 1.5 ± 0.2 mmol/L during canagliflozin treatment. BHB and free fatty acid (FFA) were monitored every 30 min for 120 min after receiving a 0.2 U/kg subcutaneous injection of aspart insulin. RESULTS Ten adults (23 ± 5 years) were studied. During the 120 min after rescue therapy with insulin, the reductions in BHB and FFA were nearly identical between the pre- and during canagliflozin treatment studies, respectively (-1.27 ± 0.76 and -1.13 ± 0.69, P = 0.671 for BHB and -0.50 ± 0.35 vs. -0.41 ± 0.41, P = 0.603 for FFA). CONCLUSION These data indicate that turning ketogenesis off, as well as on, does not appear to be affected by SGLT2i use.
2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation.

Writing Group Members* Craig T. January, MD, PhD, FACC (Chair), L. Samuel Wann, MD, MACC, FAHA (Vice Chair), Hugh Calkins, MD, FACC, FAHA, FHRS,* Lin Y. Chen, MD, MS, FACC, FAHA, FHRS, Joaquin E. Cigarroa, MD, FACC, Joseph C. Cleveland Jr., MD, FACC,*,x Patrick T. Ellinor, MD, PhD,* Michael D. Ezekowitz, MBChB, DPhil, FACC, FAHA,*,k Michael E. Field, MD, FACC, FAHA, FHRS,k Karen L. Furie, MD, MPH, FAHA,k Paul A. Heidenreich, MD, FACC, FAHA,{ Katherine T. Murray, MD, FACC, FAHA, FHRS,k Julie B. Shea, MS, RNCS, FHRS,*,k Cynthia M. Tracy, MD, FAHA,k Clyde W. Yancy, MD, MACC, FAHAk
A 2 . 08 Å resolution structure of HLB 5 , a novel cellulase from the anaerobic gut bacterium Parabacteroides johnsonii DSM 18315

Cellulases play a significant role in the degradation of complex carbohydrates. In the human gut, anaerobic bacteria are essential to the well-being of the host by producing these essential enzymes that convert plant polymers into simple sugars that can then be further metabolized by the host. Here, we report the 2.08 Å resolution structure of HLB5, a chemically verified cellulase that was identified previously from an anaerobic gut bacterium and that has no structural cellulase homologues in PDB nor possesses any conserved region typical for glycosidases. We anticipate that the information presented here will facilitate the identification of additional cellulases for which no homologues have been identified to date and enhance our understanding how these novel cellulases bind and hydrolyze their substrates.
Synthesis, characterization, antimicrobial and antimetastatic activity of silver nanoparticles synthesized from Ficus ingens leaf

Abstract Cancer incidence is still increasing due to inadequate responsive treatments. Inertness and biocompatibility of nanoparticles synthesized using plant extracts have shown therapeutic applications and make it to be a good anti-cancer candidates. This study is a recent novel spotlight that synthesized silver nanoparticle from Ficus ingens leaf extract (FILE) and studied its anti-metastatic and anti-bacterial activity. The chemical and surface analysis of the synthesized FILE silver nanoparticles (FILE-AgNPs) was studied using UV–visible, Fourier transform infrared (FTIR), X-ray diffraction (XRD), zeta sizer, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Gas chromatography mass spectrometric (GC–MS) and quantitative photochemical analyses were also carried out. The antimicrobial activity of FILE-AgNPs was found to be effective with MIC of 10 µg/mL for E. coli and 20 µg/mL for S. typhi and B. cereus with significance difference. Toxicity, proliferation and anti-metastatic potential of FILE-AgNPs were studied on MDA-MB 231 cell models using tryphan blue, MTT and wound heal assay, respectively. FILE-AgNPs showed the ability to inhibit metastasis of MDA-MB 231 cells in dose-dependent manner in which 10 μg/mL and 5 μg/mL inhibit by 96% and 75%, respectively. The synthesized FILE-AgNPs are remarkable candidates for treatment of cancer cases and other cancer related cases.
Crocin and voluntary exercise promote heart angiogenesis through Akt and ERK1/2 signalling in type 2 diabetic rats.

signalling. METHODS Animals were divided into 4 groups as follows: diabetes (Dia), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p., 35 mg/kg). Animals received crocin orally (50 mg/kg), voluntary exercise was performed alone or together with crocin for 8 weeks. Akt and ERK1/2 levels were measured by ELISA and CD31 was detected by immunohistochemistry. RESULTS Akt and ERK1/2 levels in crocin and exercise groups were significantly higher than in diabetic group. Levels of Akt and ERK1/2 proteins and CD31 immunostaining were also significantly higher in crocin-voluntary exercise group in comparison to the other groups. CONCLUSION Our results revealed that treatments with crocin and voluntary exercise had synergistic effect on angiogenesis. Protective effects of these interventions are probably through the activation of Akt and ERK 1/2 signalling pathways in the heart of diabetic rats (Fig. 3, Ref. 40).
Ecdysone receptor isoforms play distinct roles in larval–pupal–adult transition in Leptinotarsa decemlineata

A heterodimer of two nuclear receptors, ecdysone receptor (EcR) and ultraspiracle, mediates 20‐hydroxyecdysone (20E) signaling to modulate many aspects in insect life, such as molting and metamorphosis, reproduction, diapause and innate immunity. In the present paper, we intended to determine the isoform‐specific roles of EcR during larval–pupal–adult transition in the Colorado potato beetle. Double‐stranded RNAs (dsRNAs) were prepared using the common (dsEcR) or isoform‐specific (dsEcRA, dsEcRB1) regions of EcR as templates. Ingestion of either dsEcR or dsEcRA, rather than dsEcRB1, by the penultimate (3rd) and final (4th) instar larvae caused failure of larval–pupal and pupal–adult ecdysis. The RNA interference (RNAi) larvae remained as prepupae, or became deformed pupae and adults. Determination of messenger RNA (mRNA) levels of EcR isoforms found that LdEcRA regulates the expression of LdEcRB1. Moreover, silencing the two EcR transcripts, LdEcRA or LdEcRB1 reduced the mRNA levels of Ldspo and Ldsad, and lowered 20E titer. In contrast, the expression levels of HR3, HR4, E74 and E75 were significantly decreased in the LdEcR or LdEcRA RNAi larvae, but not in LdEcRB1 depleted specimens. Dietary supplement with 20E did not restore the expression of five 20E signaling genes (USP, HR3, HR4, E74 and E75), and only partially alleviated the pupation defects in dsEcR‐ or dsEcRA‐fed beetles. These data suggest that EcR plays isoform‐specific roles in the regulation of ecdysteroidogenesis and the transduction of 20E signal in L. decemlineata.
Low Concentrations of a Silver-Based Nanocomposite to Manage Bacterial Spot of Tomato in the Greenhouse.

Bacterial spot, caused by four Xanthomonas spp. , is one of the most damaging diseases of tomato worldwide. Due to limited disease management options, growers rely heavily on copper-based bactericides, which are often ineffective due to the presence of copper-resistant Xanthomonas strains. This study was undertaken to characterize the antibacterial activity of a silver-based nanocomposite, Ag-dsDNA-GO, and its potential as an alternative to copper. Ag-dsDNA-GO at rates as low as 10 μg/ml killed all bacterial cells of copper-tolerant and -sensitive Xanthomonas perforans strains in suspensions containing approximately 103 CFU/ml within 15 min of exposure in vitro, whereas equivalent rates of copper (10, 25, and 50 μg/ml) were unable to significantly reduce populations compared with the untreated control after 24 h of exposure (P = 0.05). All copper concentrations killed the copper-sensitive X. perforans strain but required exposure for ≥1 h. Ag-dsDNA-GO also exhibited antibacterial activity against copper-tolerant X. vesicatoria, X. euvesicatoria, and X. gardneri strains. In greenhouse studies, tomato plants treated with Ag-dsDNA-GO at either 75 or 100 μg/ml prior to artificial inoculation significantly reduced disease severity when compared with copper-mancozeb and negative controls (P = 0.05). This study highlights the potential of Ag-dsDNA-GO as an alternative to copper in tomato transplant production.
How brains create the world: The dynamical legacy of Walter J Freeman in olfactory system physiology.

I wandered into Walter Freeman’s office in 1991 as a graduate student and chose to work in his lab for all the wrong reasons. I enjoyed talking to him, and his bookshelves were lined with volumes of philosophy and poetry. I came to his lab with a background in philosophy and mathematics from St. John’s College, several years working for GenBank at Los Alamos National Laboratory, and several more years as a programmer. I was a poet, philosopher and mathematician, and I wanted to do modeling. He chewed on the cigar stump in the corner of his mouth and said, “we’ll see. ” He gave me a data set to analyze and no instruction or guidance on what the neural signals meant. I also enrolled in his graduate seminar in which we attempted to decipher the collection of papers that later became Neurodynamics: An Exploration in Mesoscopic Brain Dynamics [1]. Within a few weeks I was convinced that I was too stupid to be a graduate student, and after a few more weeks I realized that the papers were more difficult than most. Things got easier, but never easy. As I plowed ahead with my plan to study mathematics, I was intrigued by something I saw in the data, but the data I had did not allow me to go further with my question. I did an experiment, then a few more. I have been a physiologist for 25 years now. It took me some time to get to the modeling; the first modeling paper exclusively from my lab was accepted for publication the morning after Walter died [2]. There have been other such full circles. The year I started my position at the University of Chicago, Walter closed his laboratory at UC Berkeley. My students still use some of the instruments he gave me, engraved with WJF, along with other antique pieces of equipment. I have in my possession the apparatus and templates used to make ECoG arrays for his seminal papers on AM patterns in rabbit cortical areas [3], [4], as well as what is likely one of the first motorized electrode drives used for recording neurons in cats, ca. 1960s [5]. When Walter visited the University of Chicago in about 2003, we discovered that the rooming house he lived in as an undergraduate at the University of Chicago, where his landlady warned him against bringing loose women up to his room, is now a 6-flat three doors down from my house.
A positive deviance approach to improve familial authorization for organ donation

The current study evaluates the Positive Deviance Donation Collaborative, a communication training program designed to identify and disseminate behaviors of requesters with above‐average rates of familial authorization to organ donation. The program initiated with a cohort of 99 requesters from 11 OPOs. Requesters’ quarterly authorization rates were monitored for 33 months, and their pre‐/post‐intervention skills in active‐empathic listening and self‐efficacy to request donation were assessed. Overall, requesters’ mean quarterly authorization rate was 53.69% (SD = 4.54). Multilevel models were used to examine change in authorization rates and communication skills, as well as associations between skills and authorization. Low intraclass correlation coefficients for authorization rates established that most variance was due to within‐requester variation, rather than OPOs (ρ = 0.0129) or requesters within OPOs (ρ = 0.0221). Models indicated that authorization rates and communication skills failed to improve following intervention and did not identify an association between post‐intervention communication skills and authorization. Results provide a framework to discuss programmatic challenges including extensive requester turnover (ie, ~60%), management of data collection across multi‐site interventions, and program content.
Bringing Personalized Medicine to a PACT Program: A Quality Improvement Project

INTRODUCTION: Programs for assertive community treatment (PACT) serve persons with severe mental illness who have been unsuccessful with traditional outpatient services. Many PACT clients struggle to obtain symptom relief with medications that often have poor efficacy and undesired side effects, which can result in nonadherence, relapse, and increased health care utilization with associated costs. AIMS: This quality improvement project aimed to improve client and PACT program outcomes by incorporating pharmacogenomic testing into the psychopharmacological decision-making process. METHODS: The project used a pre–posttest design with each client serving as their own control to evaluate changes in clients’ symptoms and program outcomes resulting from pharmacogenomics-guided medication management. RESULTS: Following project implementation, clients’ symptoms were decreased and both engagement in care and stability in the community increased. Psychiatric hospitalizations and associated costs decreased. CONCLUSIONS: This project suggests utility for using pharmacogenomics testing to personalize care for persons with severe mental illness.
Effect of Tuberosity Healing on Clinical Outcomes in Elderly Patients Treated With a Reverse Shoulder Arthroplasty for 3- and 4-Part Proximal Humerus Fractures

Objectives: To evaluate tuberosity union rate and clinical outcome after 3- and 4-part proximal humerus fractures in the elderly. Design: Retrospective, multicenter database cohort study. Setting: Level I and Level II trauma centers. Patients: Fifty-five patients older than 65 years had insertion of reverse shoulder arthroplasty (RTSA) for OTA/AO 11-B and 11-C proximal humerus fractures. Intervention: Treatment with RTSA using a dedicated low profile onlay fracture stem using variable tuberosity fixation. Main Outcome Measures: Constant score, the American Shoulder and Elbow Surgeons score, Shoulder Pain and Disability Index score, University of California at Los Angeles score, Simple Shoulder Test score, visual analog pain score, shoulder function score, active range of motion, external rotation (ER)-specific tasks and position, rate of greater tuberosity healing, effect of tuberosity healing on overall clinical metrics, incidence of humeral lucency, and scapular notching. Results: Eighty-three percent of the greater tuberosities that were repaired united. Greater tuberosity union resulted in greater active ER (P = 0.0415). There was a statistically significant difference in the ability to do ER-type activities between the 2 cohorts reflected in the ability to position one's hand behind their head with the elbow forward (P = 0.002) and comb their hair (P < 0.001). Conclusion: The use of a low profile onlay fracture stem in RTSA for acute 3- and 4-part proximal humerus fractures in the elderly can result in a high tuberosity union rate. Greater tuberosity healing significantly influences ER and ER-type activities that are not apparent by analysis of the overall metrics studied. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients (male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls (male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume (GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital (approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry (ISRCTN18238599).
Braided stents and their impact in intracranial aneurysm treatment for distal locations: from flow diverters to low profile stents

ABSTRACT Introduction: Intracranial aneurysms in distal locations are sometimes difficult to treat due to their branching locations and the presence of blister-like or very wide-necked aneurysms. Braided intracranial stents, including flow diverters (FDs) and low-profile braided intracranial stents (LPBSs) may provide additional advantages, due to their flow-diverting properties. Areas covered: The use of FDs in off-label, distal intracranial locations has been increasing with promising outcomes and has given rise to the LPBS, which has less flow-diverting properties, allowing for easier use in distal branching sites through 0. 017ʹ microcatheters. These devices have shifted the interest from the aneurysm’s sac filling to the regional remodeling through the effect of flow diversion. The purpose of this article is to discuss their functionality, safety, performance, and perspectives through a critical review of important publications of the last 11.5 years (January 2007 to July 2018) on the use of these devices at and beyond the circle of Willis. Expert opinion: FDs modify the regional anatomy thus careful pre-procedural consideration of the regional hemodynamic equilibrium is mandatory, as well as effective antiplatelet regimen. LPBSs provide moderate flow-diversion effect, which may be an advantage, especially for very distal and small aneurysms.