Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating cytokine profile and modulation of regulatory T cells in chronic hepatitis B patients with type 2 diabetes mellitus

The risk of hepatitis B virus (HBV) infection is higher in patients with diabetes mellitus, and diabetes mellitus is one of the metabolic complications of HBV infection. However, the cytokine profile of chronic hepatitis B (CHB) patients with type 2 diabetes mellitus (T2DM) is not fully understood. The aim of this study was to investigate the cytokine expression profile in CHB patients with T2DM, and to assess the regulatory function of cytokines to regulatory T cells (Tregs). Forty-four T2DM patients, 39 CHB patients, 17 patients with CHB and T2DM, and 21 control subjects were enrolled. Cytokine levels in the plasma were measured by Luminex multiplex assay. CD4+CD25+CD127dim/− Tregs were detected by flow cytometry. Tregs were purified and stimulated with recombinant human interleukin-15 (IL-15). The regulation of IL-15 on Tregs function was investigated by measuring cell number, IL-10/IL-35 secretion, and mRNA expression of immune checkpoint molecules in a Tregs + PBMC co-culture system. We found that levels of IL-1α, IL-6, and IL-33 were upregulated, while interferon-α, IL-2, IL-7, and IL-15 were downregulated in T2DM and CHB patients. CHB patients with T2DM had even lower plasma IL-7 and IL-15 levels. Tregs proportion was elevated in T2DM and CHB patients. CHB patients with T2DM had increased levels of Tregs, which correlated negatively with IL-15. Tregs showed stronger inhibitory activity in CHB patients with T2DM than in controls, T2DM, and CHB patients, which presented as reduction in cellular proliferation and induction of IL-10/IL-35 secretion. IL-15 suppressed Tregs function and inhibited the expression of immune checkpoint molecules in Tregs. The current data suggest that insufficient IL-15 levels and decreased responsiveness of Tregs to IL-15 signaling might contribute to strong immune dysfunction in CHB patients with T2DM.
Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Abstract Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.
Sedation in specialized palliative care: A cross-sectional study

Background Palliative sedation is used to relieve refractory symptoms and is part of clinical practice in Sweden. Yet we do not know how frequently this practice occurs, how decision-making takes place, or even which medications are preferentially used. Objectives To understand the current practice of palliative sedation in Sweden. Methods We conducted a retrospective cross-sectional medical record-based study. For 690 consecutive deceased patients from 11 of 12 specialized palliative care units in the southernmost region of Sweden who underwent palliative sedation during 2016, we collected data on whether the patient died during sedation and, for sedated patients, the decision-making process, medication used, and depth of sedation. Results Eight percent of patients were sedated. Almost all (94%) were given midazolam, sometimes in combination with propofol. The proportions of sedation were similar in the patient groups with and without cancer. The largest proportion of the sedated patients died in inpatient care, but 23% died at home, with specialized palliative home care. Among the patients with a decision to sedate, 42% died deeply unconscious, while for those without such a decision the corresponding figure was 16%. In only one case was there more than one physician involved in the decision to use palliative sedation. Conclusion 8% of patients in specialized palliative care received palliative sedation, which is lower than international measures but much increased compared to an earlier Swedish assessment. The level of consciousness achieved often did not correspond to the planned level; this, together with indications of a scattered decision process, shows a need for clear guidelines.
Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

Protease‐free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir–velpatasvir in participants with HCV and compensated cirrhosis in Japan.
A Potential Role of Cholinergic Dysfunction on Impaired Colon Motility in Experimental Intestinal Chagas Disease

Background/Aims Chagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi-induced progressive colonic structural changes modulate the colonic contractile pattern activity. Methods We developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction. Results In the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters. Conclusions T. cruzi-induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic.
The Effect of K-Carrageenan Addition to the Characteristics of Jicama Starch-Based Edible Coating and Its Potential Application on The Grapevine

Public awareness of food quality is an essential thing during the packaging application. Considering the environment issue, edible coating with starch-based has been applied as packaging with environment-friendly. The high quality of starch is also produced by jicama ( Pachyrhizus erosus ). However, the application of jicama as an edible coating for grapevine ( Vitis vinira L ) remains unknown. Therefore, this research aims to determine the influence of k-carrageenan addition with various concentration to the physical and chemical characteristics of Jicama ( Pachyrhizus erosus ) starch-based edible coating and its potential application on Grapevines ( Vitis vinira L.) . This research was using randomized design with one addition factor (k-carrageenan): A1 =k-carrageenan 0.5% (w/v); A2 =k-carrageenan 1% (w/v); A3 =k-carrageenan 1.5% (w/v); A4 =k-carrageenan 2% (w/v); A5 =k-carrageenan 2% w/v). All measurements are repeated three times. The collected data were analyzed by variance analysis (p 0.05).
Role of Nutrient Drinking Test in Functional Dyspepsia

c 2022 The Korean Society of Neurogastroenterology and Motility J Neurogastroenterol Motil, Vol. 28 No. 3 July, 2022 www.jnmjournal. org Functional dyspepsia (FD) is common prevalent. At least 1 in 10 people suffers from FD. To date, the pathophysiology of FD is not well understood. However, several mechanisms contributing to FD have been suggested. It can be distinguished from environmental, biological, psychologic, and physiological factors. Among these mechanisms, there are physiologic factor such as acid, gastric accommodation (GA), hypersensitivity to gastric distension, and delayed gastric emptying. Considering these aspects, FD is probably a heterogeneous disorders of gastric sensorimotor function. Given the abnormality of the sensorimotor function, it is possible to develop physiologic test in FD, as high-resolution manometry is a golden standard diagnostic test of achalasia. The most common pathophysiological mechanism in FD is impaired GA, which appears in 40% of patients, with hypersensitivities to gastric distention in about one-third of patients and delayed gastric emptying in about 25% of patients. In the case of FD, tests that diagnose or predict to treatment responses are insufficient. Slow nutrient drinking testing (NDT) in FD has been proposed as a potential biomarker for the presence and severity of gastric sensorimotor dysfunction. In particular, NDT is a useful method to check for abnormalities in GA. A slow NDT was the first test to report by Tack et al in the literature, in a 1998 article evaluated the role of impaired GA in FD. After this, many NDT studies show the most consistent distinction between health person and FD patient, relevance with impaired GA and reproducibility. Most of the studies are from Western and Europe, and there are very few studies in Asia. In this issue of Journal of Neurogastroenterology and Motility, Watanabe et al reported efficacy of slow nutrient drinking test among patients with FD in Japan. NDT was applied to total 42 participants (26 healthy controls and 16 FD patients). The primary outcome is the ending time of the NDT, which help to distinguish Japanese patients with FD from healthy controls. The test ending time was significantly shorter in patients with FD than in healthy controls (22.3 ± 10.6 vs 45.0 ± 7.5 minutes, respectively; P < 0.001, Fig. 1A and 1B). The optimal cut-off time differentiated patients with FD from healthy controls was 30 minutes. At the cutoff time, the area under the curve was 0.91 with 87.5% sensitivity and 92.3 specificity (Fig. 2). This result is those that have already been proven in previous studies. Interestingly, in this study, FD patients were classified into epigastric pain syndrome (EPS), postprandial distress syndrome (PDS), and both mixed groups, and each patient group was 3, 6, and 7, respectively. The difference in the severity of meal-related JNM J Neurogastroenterol Motil, Vol. 28 No. 3 July, 2022 pISSN: 2093-0879 eISSN: 2093-0887 https://doi.org/10.5056/jnm22074 Editorial Journal of Neurogastroenterology and Motility
Subcortical and hippocampal brain segmentation in 5‐year‐old children: Validation of FSL‐FIRST and FreeSurfer against manual segmentation

Developing accurate subcortical volumetric quantification tools is crucial for neurodevelopmental studies, as they could reduce the need for challenging and time‐consuming manual segmentation. In this study, the accuracy of two automated segmentation tools, FSL‐FIRST (with three different boundary correction settings) and FreeSurfer, were compared against manual segmentation of the hippocampus and subcortical nuclei, including the amygdala, thalamus, putamen, globus pallidus, caudate and nucleus accumbens, using volumetric and correlation analyses in 80 5‐year‐olds.
Advanced optical fibre communication via nonlinear Fourier transform

Optical fibre communication using the Nonlinear Fourier transform (NFT) is one of the potential solutions to tackle the so-called capacity crunch problem in long-haul optical fibre networks. The NFT transforms the nonlinear propagation of temporal signal, governed by the nonlinear Schrödinger equation (NLSE), into simple linear evolutions of continuous and discrete spectra in the so-called nonlinear spectral domain. These spectra and the corresponding nonlinear spectral domain, defined by the NFT, are the generalized counterparts of the linear spectrum and frequency domain defined by the ordinary Fourier transform. Using the NFT, the optical fibre channel is effectively linearised, and the basic idea is to utilize degrees of freedom in the nonlinear spectral domain for data transmission. However, many aspects of this concept require rigorous investigation due to complexity and infancy of the approach. In this thesis, the aim is to provide a comprehensive investigation of data transmission over mainly the continues spectrum (CS) and partly over of the discrete spectrum (DS) of nonlinear optical fibres. First, an optical fibre communication system is defined, in which solely the CS carries the information. A noise model in the nonlinear spectral domain is derived for such a system by asymptotic analysis as well as extensive simulations for different scenarios of practical interest. It is demonstrated that the noise added to the signal in CS is severely signal-dependent such that the effective signalling space is limited. The variance normalizing transform (VNT) is used to mathematically verify the limits of signalling spaces and also estimate the channel capacity. The numerical results predict a remarkable capacity for signalling only on the CS (e.g., 6 bits/symbol for a 2000-km link), yet it is demonstrated that the capacity saturates at high power. Next, the broadening effect of chromatic dispersion is analysed, and it is confirmed that some system parameters, such as symbol rate in the nonlinear spectral domain, can be optimized so that the required temporal guard interval between the subsequently transmitted data packets is minimized, and thus the effective data rate is significantly enhanced. Furthermore, three modified signalling techniques are proposed and analysed based on the particular statistics of the noise added to the CS. All proposed methods display improved performance in terms of error rate and reach distance. For instance, using one of the proposed techniques and optimized
Anti-oncogenic and pro-myogenic action of the MKK6/p38/AKT axis induced by targeting MEK/ERK in embryonal rhabdomyosarcoma

Insights into the molecular and cellular biology of embryonal rhabdomyosarcoma (ERMS), an aggressive paediatric tumour, are required in order to identify new targets for novel treatments that may benefit patients with this disease. The present study examined the functional effects of MKK3 and MKK6, two upstream kinases of p38, and found that the ectopic expression of MKK6 led to rapid p38 activation and the myogenic differentiation of ERMS cells, whereas MKK3 failed to induce differentiation, while maintaining the proliferation state. Myogenin and myosin heavy chain were induced in MKK6-overexpressing ERMS cells and were inhibited by the p38 inhibitor, SB203580. The expression of Myc and ERK-PO4 increased under the effect of SB203580, whereas it decreased in MKK6-overexpressing cells. AKT activation was part of the myogenic program triggered by MKK6 overexpression alone. To the best of our knowledge, the present study demonstrates, for the first time, that the endogenous MKK6 pathway may be recovered by MEK/ERK inhibition (U0126 and trametinib) and that it concomitantly induces the reversal of the oncogenic pattern and the induction of the myogenic differentiation of ERMS cell lines. The effects of MEK/ERK inhibitors markedly increase the potential clinical applications in ERMS, particularly on account of the MEK inhibitor-induced early MKK6/p38 axis activation and of their anti-oncogenic effects. The findings presented herein lend further support to the antitumour effects of MKK6; MKK6 may thus represent a novel target for advanced personalised treatments against ERMS.
Work stress and motivation in psychologists in the hospital setting: the role of primary cognitive appraisal

ABSTRACT The aim of this study was to explore in a hospital setting the relationships between work motivation and stress among psychologists working in hospitals. The second aim was to identify the respective roles of threat appraisal and challenge appraisal in this population. We expected work stress to have a motivational impact in the workplace, with primary cognitive appraisal (e.g., threat or challenge) playing a crucial role. The study included a large sample of 430 French psychologists recruited in French hospitals with a mean age of 33.68 ± 8.73 years. We assessed perceived work stress, work motivation, and primary cognitive appraisal. Analysis showed two main outcomes. First, perceived stress in the workplace impacts work motivation; specifically, the higher the perceived stress, the less motivation is self-determined. Second, threat cognitive appraisal has a direct and negative motivational impact, but also an indirect impact via perceived stress. However, appraisal of work as a cognitive challenge also directly and positively impacts motivation in the workplace, without indirect effects. Finally, work stress, work motivation and primary cognitive appraisals are significantly related with the workplace. These relationships support complementarity with the Transactional Model of Stress and SDT motivational approach in a theoretical and practical perspective in the workplace.
Differences in body mass index trajectories of adolescent psychiatric inpatients by sex, age, diagnosis and medication: an exploratory longitudinal, mixed effects analysis

Background Adolescents in secure psychiatric care typically report high obesity rates. However, longitudinal research exploring the rate and extent of change is sparse. This study aimed to analyse sex differences in longitudinal body mass index (BMI) change for adolescents receiving treatment in a secure psychiatric hospital. Methods The sample comprised 670 adolescents in secure psychiatric care. BMI trajectories from admission to 50 months of hospitalisation were produced using sex‐stratified multilevel models. Systematic difference in mean BMI trajectories according to age at admission (14, 15, 16, or 17 years), medication (Olanzapine or Sodium Valproate), and primary diagnosis (Psychotic, non‐Psychotic or Functional/behavioural disorders) were investigated. Results Together, males and females experienced a mean BMI increase of 2.22 m/kg2 over the 50‐month period. For females, BMI increased from 25.69 m/kg2 to 30.31 m/kg2, and for males, reduced from 25.01 m/kg2 to 23.95 m/kg2. From 30 to 50 months, a plateau was observed for females and a reduction in BMI observed for males. Psychotic disorders in males (β 3.87; CI 1.1–6.7) were associated with the greatest rate of BMI change. For medication, Olanzapine in females was associated with the greatest rate of change (β1.78; CI −.89–4.47). Conclusions This is the first longitudinal study exploring longitudinal BMI change for adolescent inpatients. Results highlight that individual differences in adolescent inpatients result in differing levels of risk to weight gain in secure care. Specifically, males with psychotic disorders and females taking Olanzapine present the greatest risk of weight gain. This has implications for the prioritisation of interventions for those most at risk of weight gain.
Empirical models of the electron concentration of the ionosphere and their value for radio communications purposes

The availability of representative empirical models of the variation of the electron concentration with height in the ionosphere is one critical element in the development of practical schemes for providing reliable HF radio propagation predictions. The degree to which a specific model succeeds must be judged against three criteria: (1) quality of profile match: the model must reproduce the range of N(h) profiles encountered in practice; this match should be maintained in the first and second derivatives with height; (2) availability and simplicity of the external data required for profile specification: input data which consist of only those parameters routinely scaled from ionograms and available from CCIR predictions best fit this criterion; (3) numerical complexity: preferably the mathematical algorithms describing the model should be as simple as possible. These criteria conflict so that schemes have been developed optimized with respect to one or two of them at the expense of the other(s), the choice being driven by the application. In this paper, four such schemes are reviewed and contrasted in the light of these criteria and usage in practice. It is concluded that the Booker (1977) “skeleton” profile approach is best for simulating a known profile for precision radio wave studies, while the Dudeney (1978) technique provides good overall performance for general purpose communications predictions. The performance of the scheme currently recommended by the CCIR (Bradley and Dudeney, 1973a) cannot match these two, and should be superceded except where the need for mathematical simplicity is of overriding importance. The International Reference Ionosphere profile is found to have significant disadvantages for communications work with respect to all three criteria.
Lupus‐like reaction following imiquimod treatment for actinic keratoses

Dear Editor, A 73-year-old man presented with an asymptomatic, well-demarcated, infiltrated, erythematous plaque on the left cheek (Figure 1A). Five months earlier, he had been treated for actinic keratosis in this location with imiquimod 5% cream three times a week for 4 weeks. The patient had no personal or family history of autoimmune disease. Skin biopsy revealed a dense superficial and deep perivascular and periadnexal lymphoid infiltrate reaching the dermo-hypodermal junction (Figure 1B). There was a well-developed interface lesion with dyskeratotic keratinocytes predominantly affecting the follicular epithelium, and infundibular hyperkeratosis (Figure 1C). Immunohistochemistry showed a clear predominance of T over B cells and similar proportions of CD4 and CD8. No mucin deposits were demonstrated. A complete blood test with immunological profile showed negative antinuclear, anti-double stranded DNA, antiextractable nuclear antigen, and anti-histone antibodies. Based on these findings, a diagnosis of discoid lupus-like reaction to imiquimod was established. The lesion resolved after a 4-week treatment with clobetasol propionate cream. Imiquimod is a topical inmunomodulator with antiviral and antineoplastic properties widely used in dermatology. Beyond the approved indications (treatment of actinic keratosis, superficial