Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycosis fungoides and Sézary syndrome: Australian clinical practice statement

Primary cutaneous lymphomas represent a heterogeneous group of T‐ and B‐cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T‐cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).
Loss of endocytosis-associated RabGEF1 causes aberrant morphogenesis and altered autophagy in photoreceptors leading to retinal degeneration

Rab-GTPases and associated effectors mediate cargo transport through the endomembrane system of eukaryotic cells, regulating key processes such as membrane turnover, signal transduction, protein recycling and degradation. Using developmental transcriptome data, we identified Rabgef1 (encoding the protein RabGEF1 or Rabex-5) as the only gene associated with Rab GTPases that exhibited strong concordance with retinal photoreceptor differentiation. Loss of Rabgef1 in mice (Rabgef1-/-) resulted in defects specifically of photoreceptor morphology and almost complete loss of both rod and cone function as early as eye opening; however, aberrant outer segment formation could only partly account for visual function deficits. RabGEF1 protein in retinal photoreceptors interacts with Rabaptin-5, and RabGEF1 absence leads to reduction of early endosomes consistent with studies in other mammalian cells and tissues. Electron microscopy analyses reveal abnormal accumulation of macromolecular aggregates in autophagosome-like vacuoles and enhanced immunostaining for LC3A/B and p62 in Rabgef1-/- photoreceptors, consistent with compromised autophagy. Transcriptome analysis of the developing Rabgef1-/- retina reveals altered expression of 2469 genes related to multiple pathways including phototransduction, mitochondria, oxidative stress and endocytosis, suggesting an early trajectory of photoreceptor cell death. Our results implicate an essential role of the RabGEF1-modulated endocytic and autophagic pathways in photoreceptor differentiation and homeostasis. We propose that RabGEF1 and associated components are potential candidates for syndromic traits that include a retinopathy phenotype.
Purinergic signaling is enhanced in the absence of UT‐A1 and UT‐A3

ATP is an important paracrine regulator of renal tubular water and urea transport. The activity of P2Y2, the predominant P2Y receptor of the medullary collecting duct, is mediated by ATP, and modulates urinary concentration. To investigate the role of purinergic signaling in the absence of urea transport in the collecting duct, we studied wild‐type (WT) and UT‐A1/A3 null (UT‐A1/A3 KO) mice in metabolic cages to monitor urine output, and collected tissue samples for analysis. We confirmed that UT‐A1/A3 KO mice are polyuric, and concurrently observed lower levels of urinary cAMP as compared to WT, despite elevated serum vasopressin (AVP) levels. Because P2Y2 inhibits AVP‐stimulated transport by dampening cAMP synthesis, we suspected that, similar to other models of AVP‐resistant polyuria, purinergic signaling is increased in UT‐A1/A3 KO mice. In fact, we observed that both urinary ATP and purinergic‐mediated prostanoid (PGE2) levels were elevated. Collectively, our data suggest that the reduction of medullary osmolality due to the lack of UT‐A1 and UT‐A3 induces an AVP‐resistant polyuria that is possibly exacerbated by, or at least correlated with, enhanced purinergic signaling.
Electron band structure of the high pressure cubic phase of AlH3

The electronic band structure of the cubic Pm3n phase of AlH3 stable above 100 GPa is examined with semi-local, Tran-Blaha modified Becke-Johnson local density approximation (TB-mBJLDA), screened hybrid density functionals and GW methods. The shift of the conduction band to higher energy with increasing pressure is predicted by all methods. However, there are significant differences in detail band structure. In the pressure range from 90 to160 GPa, semi-local, hybrid functional and TB-mBJLDA calculations predicted that AlH3 is a poor metal. In comparison, GW calculations show a gap opening at 160 GPa and AlH3 becomes a small gap semi-conductor. From the trends of the calculated band shifts, it can be concluded that the favourable conditions leading to the nesting of Fermi surfaces predicted by semi-local calculation have disappeared if the exchange term is included. The results highlight the importance of the correction to the exchange energy on the band structure of hydrogen dominant dense metal hydrides at high pressure hydrides and may help to rationalize the absence of superconductivity in AlH3 from experimental measurements.
Source Trust and COVID-19 Information Sharing: The Mediating Roles of Emotions and Beliefs About Sharing

Health information sharing has become especially important during the COVID-19 (coronavirus disease 2019) pandemic because people need to learn about the disease and then act accordingly. This study examines the perceived trust of different COVID-19 information sources (health professionals, academic institutions, government agencies, news media, social media, family, and friends) and sharing of COVID-19 information in China. Specifically, it investigates how beliefs about sharing and emotions mediate the effects of perceived source trust on source-specific information sharing intentions. Results suggest that health professionals, academic institutions, and government agencies are trusted sources of information and that people share information from these sources because they think doing so will increase disease awareness and promote disease prevention. People may also choose to share COVID-19 information from news media, social media, and family as they cope with anxiety, anger, and fear. Taken together, a better understanding of the distinct psychological mechanisms underlying health information sharing from different sources can help contribute to more effective sharing of information about COVID-19 prevention and to manage negative emotion contagion during the pandemic.
Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation

Rationale: Prone positioning is an appealing therapeutic strategy for nonintubated hypoxic patients with coronavirus disease (COVID-19), but its effectiveness remains to be established in randomized controlled trials. Objectives: To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for nonintubated hypoxic patients with COVID-19. Methods: We conducted a cluster randomized pilot trial at a quaternary care teaching hospital. Five inpatient medical service teams were randomly allocated to two treatment arms: 1) usual care (UC), consisting of current, standard management of hypoxia and COVID-19; or 2) the Awake Prone Positioning Strategy (APPS) plus UC. Included patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing or suspected COVID-19 pneumonia and oxygen saturation less than 93% or new oxygen requirement of 3 L per minute or greater and no contraindications to prone positioning. Oxygenation measures were collected within 48 hours of eligibility and included nadir oxygen saturation to fraction of inspired oxygen (S/F) ratio and time spent with S/F ratio less than 315. Concurrently, we conducted an embedded implementation evaluation using semistructured interviews with clinician and patient participants to determine contextual factors relevant to the successful conduct of a future clinical trial. The primary outcomes were drawn from an implementation science framework including acceptability, adoption, appropriateness, effectiveness, equity, feasibility, fidelity, and penetration. Results: Forty patients were included in the cluster randomized trial. Patients in the UC group (n = 13) had a median nadir S/F ratio over the 48-hour study period of 216 (95% confidence interval [95% CI], 95–303) versus 253 (95% CI, 197–267) in the APPS group (n = 27). Patients in the UC group spent 42 hours (95% CI, 13–47) of the 48-hour study period with an S/F ratio below 315 versus 20 hours (95% CI, 6–39) for patients in the APPS group. Mixed-methods analyses uncovered several barriers relevant to the conduct of a successful definitive randomized controlled trial, including low adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and diffusion of prone positioning into usual care. Conclusions: A definitive trial evaluating the effect of prone positioning in nonintubated patients with COVID-19 is warranted, but several barriers must be addressed to ensure that the results of such a trial are informative and readily translated into practice.
Extended Use of the Control-IQ Closed-Loop Control System in Children With Type 1 Diabetes

OBJECTIVE To further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes. RESEARCH DESIGN AND METHODS After a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children 6–13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks. RESULTS In the SAP-CLC cohort, mean percentage of time in range 70–180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time <54 mg/dL <1% compared with 14% when using SAP (P = 0.03). Substantial improvement in TIR was seen after the 1st day of CLC. Time <70 mg/dL decreased from 1.80% to 1.34% (P < 0.001). In the CLC-CLC cohort, mean TIR increased from 53 ± 17% prerandomization to 67 ± 10% during the RCT and remained reasonably stable at 66 ± 10% through the 12 weeks post-RCT. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either cohort. CONCLUSIONS This further evaluation of the Control-IQ CLC system supports the findings of the preceding RCT that use of a closed-loop system can safely improve glycemic control in children 6–13 years old with type 1 diabetes from the 1st day of use and demonstrates that these improvements can be sustained through 28 weeks of use.
Critical role of the bending stiffness of the monolayer black phosphorus in its mechanical behaviors: molecular dynamics simulation

Black phosphorus (BP) is a novel two-dimensional nanostructure with wide potential applications in such areas as nanoresonators and nanosensors. In this study, we concentrate on the role of the bending stiffness of the BP monolayer in its mechanical performances, including tension, compression, buckling and bending. Firstly, the stress–strain curve and Young’s modulus of the single layer black phosphorus (SLBP) nanoribbon with different chiral structures are obtained in the tension process via the molecular dynamics (MD) simulation. Next, the loading behavior of the SLBP nanoribbon during compression is simulated via MD. It was found that the bending stiffness of the nanoribbon has an essential effect on its postbuckling behaviors, and an empirical formula is proposed which can accurately depict the postbuckling process. Eventually, the bending properties of chiral SLBP nanoribbons are explored via the MD simulation, and the modified expression of the bending stiffness can better predict its large deflection. These findings are beneficial for us to fully understand mechanical responses of BP, which hold implications in engineering new materials and devices at nanoscale.
Maximum axonal following frequency separates classes of cutaneous unmyelinated nociceptors in the pig

C‐nociceptors are generally assumed to have a low maximum discharge frequency of 10–30 Hz. However, only mechano‐insensitive ‘silent’ C‐nociceptors cannot follow electrical stimulation at 5 Hz (75 pulses) whereas polymodal C‐nociceptors in the pig follow stimulation at up to 100 Hz without conduction failure. Sensitization by nerve growth factor increases the maximum following frequency of ‘silent’ nociceptors in pig skin and might thereby contribute in particular to intense pain sensations in chronic inflammation. A distinct class of C‐nociceptors with mechanical thresholds >150 mN resembles ‘silent’ nociceptors at low stimulation frequencies in pigs and humans, but is capable of 100 Hz discharge and thus is suited to encode painfulness of noxious mechanical stimuli.
ATHEROGENIC INDICES IN THE ASSESSMENT OF CARDIOVASCULAR DISEASE RISK IN CHILDREN WITH OBESITY AND SUBCLINICAL HYPOTHYROIDISM.

Background The frequency of subclinical hypothyroidism (SH) in patients with obesity is increased compared with the normal population. However, data on the risk of cardiovascular disease (CVD) in patients with SH are still scarce. Lipid parameters are strong predictors of early CVD. We aimed to investigate the role of lipid indices in predicting CVD risk compared to conventional lipid components. Methods A total of 220 euthyroid obese children (EU) and 90 obese children with SH were included in the study. All data were collected from hospital files. Lipid indices were evaluated. Atherogenic index of plasma (AIP), cardiac risk ratio (CRR) and atherogenic coefficient (AC) were calculated. AIP>0.24, CRR>5 ve AC>3 were considered as cardiovascular risk criteria. Results The presence of SH increased the risk of higher AIP and the risk of CRR, compared to euthyroid obese children. Conclusion Subclinical hypothyroidism in obese children may cause dislipidemia carrying a high cardiovascular disease risk.
Effects of Discontinuation of Drugs Used for Augmentation Therapy on Treatment Outcomes in Depression: A Systematic Review and Meta-analysis

Abstract Introduction There has been no consensus on whether and how long add-on drugs for augmentation therapy should be continued in the treatment of depression. Methods Double-blind randomized controlled trials that examined the effects of discontinuation of drugs used for augmentation on treatment outcomes in patients with depression were identified. Meta-analyses were performed to compare rates of study withdrawal due to any reason, study-defined relapse, and adverse events between patients who continued augmentation therapy and those who discontinued it. Results Seven studies were included (n=841 for continuing augmentation therapy; n=831 for discontinuing augmentation therapy). The rate of study withdrawal due to any reason was not significantly different between the 2 groups (risk ratio [RR]=0.86, 95% confidence interval [CI]=0.69–1.08, p=0.20). Study withdrawal due to relapse was less frequent in the continuation group than in the discontinuation group (RR=0.61, 95% CI=0.40–0.92, p=0.02); however, this statistical significance disappeared when one study using esketamine as augmentation was excluded. Analysis of the data from 5 studies that included a stabilization period before randomization found less frequent relapse in the continuation group than in the discontinuation group (RR=0.47, 95% CI=0.36–0.60, p<0.01). This finding was repeated when the esketamine study was excluded. Discussion No firm conclusions could be drawn in light of the small number of studies included. Currently available evidence suggests that add-on drugs, other than esketamine, used for augmentation therapy for depression may be discontinued. This may not be the case for patients who are maintained with augmentation therapy after remission.
Microbiota‐gut‐brain axis as a regulator of reward processes

Our gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non‐natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota‐gut‐brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy.
Particles Size and Conductivity Study of P-Type Copper (I) Iodide (CuI) Thin Film for Solid State Dye-Sensitized Solar Cells

Copper Iodide based dye-sensitized solar cells (DSSC) has been reported either deliver small photocurrents or highly unstable. In this research, by added in a small amount of Tetra-methyl-ethylene-diamine (TMED) into CuI sol-gel (CuI in acetonitrile), performance of electrical properties and optical properties of CuI based DSSC have been studied. Particles size and conductivity of CuI solution were measured when addition of TMED to the sol at 0.05M concentrations. Spin-coating technique has been explored to prepare nano-crystalline CuI films at room temperature. The film was examined for their surface morphology, optical and electrical properties by field emission scanning electron microscope (FESEM), ultraviolet visible spectroscopy (UV-Vis), Photoluminescence (PL) and current-voltage (I-V) measurement respectively. The results were then compared with CuI sol-gel which prepared by dissolving CuI powder with acetonitrile only. It showed some improvement to the CuI-based DSSC by incorporation of a small quantity of TMED in the solution of precursor.
Improved Antitumor Activity of the Fluoropyrimidine Polymer CF10 in Preclinical Colorectal Cancer Models through Distinct Mechanistic and Pharmacologic Properties

Chemotherapy regimens that include 5-fluorouracil (5-FU) are central to colorectal cancer treatment; however, risk/benefit concerns limit 5-FU’s use, necessitating development of improved fluoropyrimidine (FP) drugs. In our study, we evaluated a second-generation nanoscale FP polymer, CF10, for improved antitumor activity. CF10 was more potent than the prototype FP polymer F10 and much more potent than 5-FU in multiple colorectal cancer cell lines including HCT-116, LS174T, SW480, and T84D. CF10 displayed improved stability to exonuclease degradation relative to F10 and reduced susceptibility to thymidine antagonism due to extension of the polymer with arabinosyl cytidine. In colorectal cancer cells, CF10 strongly inhibited thymidylate synthase (TS), induced Top1 cleavage complex formation and caused replication stress, while similar concentrations of 5-FU were ineffective. CF10 was well tolerated in vivo and invoked a reduced inflammatory response relative to 5-FU. Blood chemistry parameters in CF10-treated mice were within normal limits. In vivo, CF10 displayed antitumor activity in several colorectal cancer flank tumor models including HCT-116, HT-29, and CT-26. CF10’s antitumor activity was associated with increased plasma levels of FP deoxynucleotide metabolites relative to 5-FU. CF10 significantly reduced tumor growth and improved survival (84.5 days vs. 32 days; P < 0.0001) relative to 5-FU in an orthotopic HCT-116-luc colorectal cancer model that spontaneously metastasized to liver. Improved survival in the orthotopic model correlated with localization of a fluorescent CF10 conjugate to tumor. Together, our preclinical data support an early-phase clinical trial of CF10 for treatment of colorectal cancer.
New developments in corneal endothelial cell replacement

Corneal transplantation is currently the most effective treatment to restore corneal clarity in patients with endothelial disorders. Endothelial transplantation, either by Descemet membrane endothelial keratoplasty (DMEK) or by Descemet stripping (automated) endothelial keratoplasty (DS(A)EK), is a surgical approach that replaces diseased Descemet membrane and endothelium with tissue from a healthy donor eye. Its application, however, is limited by the availability of healthy donor tissue. To increase the pool of endothelial grafts, research has focused on developing new treatment options as alternatives to conventional corneal transplantation. These treatment options can be considered as either ‘surgery‐based’, that is tissue‐efficient modifications of the current techniques (e.g. Descemet stripping only (DSO)/Descemetorhexis without endothelial keratoplasty (DWEK) and Quarter‐DMEK), or ‘cell‐based’ approaches, which rely on in vitro expansion of human corneal endothelial cells (hCEC) (i.e. cultured corneal endothelial cell sheet transplantation and cell injection). In this review, we will focus on the most recent developments in the field of the ‘cell‐based’ approaches. Starting with the description of aspects involved in the isolation of hCEC from donor tissue, we then describe the different natural and bioengineered carriers currently used in endothelial cell sheet transplantation, and finally, we discuss the current ‘state of the art’ in novel therapeutic approaches such as endothelial cell injection.
Microwave ablation determines similar survival outcomes as compared to radiofrequency ablation for the treatment of hepatocellular carcinoma

ABSTRACT Objectives It is still unclear whether microwave ablation (MWA) outperforms radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). Aim of this manuscript is to compare the two treatments through a meta-analysis of randomized-controlled trials (rcts). Methods Computerized bibliographic search was performed on main databases through August 2020. The primary outcome was the complete response rate, with survival rate, disease-free survival rate, and adverse event rate as secondary outcomes. Results were expressed in terms of risk ratio (RR) and 95% confidence interval (CI) Results Seven rcts enrolling 1143 patients were included. Rates of complete response were similar (RR 1.01, 95% CI 0.99–1.02); likewise, survival rates were constantly similar, with rrs ranging from 1.05 (0.96–1.15) at 1-year to 0.91 (0.81–1.03) at 5-year. Disease-free survival at 1-, 2-, and 3-year was similar between the two groups with RR 1.00 (0.96–1.04), 0.94 (0.84–1.06), and 1.06 (0.93–1.21), respectively. On the other hand, RR for disease-free survival at 5-year was significantly in favor of MWA (3.66, 1.32–42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48–2.34), with bleeding and hematoma as most frequent complications. Conclusions MWA seems to determine similar outcomes as compared to RFA.