Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase‐2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts

Fedratinib, an oral Janus kinase‐2 (JAK2) inhibitor, is approved for patients with myelofibrosis (MF) and platelet counts ≥50 × 109/l, based on outcomes from the phase 3, placebo‐controlled JAKARTA trial in JAK‐inhibitor‐naïve MF, and the phase 2, single‐arm JAKARTA2 trial in patients previously treated with ruxolitinib. We evaluated the efficacy and safety of fedratinib 400 mg/day in patients with baseline platelet counts 50 to <100 × 109/l (“Low‐Platelets” cohorts), including 14/96 patients (15%) in JAKARTA and 33/97 (34%) in JAKARTA2. At 24 weeks, spleen response rates were not significantly different between the Low‐Platelets cohort and patients with baseline platelet counts ≥100 × 109/l (“High‐Platelets” cohort), in JAKARTA (36% vs. 49%, respectively; p = 0.37) or JAKARTA2 (36% vs. 28%; p = 0.41). Symptom response rates were also not statistically different between the Low‐ and High‐Platelets cohorts. Fedratinib was generally well‐tolerated in both platelet‐count cohorts. New or worsening thrombocytopaenia was more frequent in the Low‐Platelets (44%) versus the High‐Platelets (9%) cohort, but no serious thrombocytopaenia events occurred. Thrombocytopaenia was typically managed with dose modifications; only 3/48 Low‐Platelets patients discontinued fedratinib due to thrombocytopaenia. These data indicate that fedratinib 400 mg/day is safe and effective in patients with MF and low pretreatment platelet counts, and no initial fedratinib dose adjustment is required for these patients.
MIMO antennas with diversity and mutual coupling reduction techniques: a review

Multiple input multiple output (MIMO) antenna is at core of the presently available wireless technologies. The design of MIMO antennas over a limited space requires various approaches of mutual coupling reduction, otherwise gain, efficiency, diversity gain, and radiation patterns will be severely affected. Various techniques have been reported in literature to control this degrading factor and to improve the performance of the MIMO antennas. In this review paper, we have carried out an extensive thorough investigation of diversity and mutual coupling (correlation) reduction techniques in compact MIMO antennas.
Manufacturing clinical‐grade human induced pluripotent stem cell‐derived beta cells for diabetes treatment

The unlimited proliferative capacity of human pluripotent stem cells (hPSCs) fortifies it as one of the most attractive sources for cell therapy application in diabetes. In the past two decades, vast research efforts have been invested in developing strategies to differentiate hPSCs into clinically suitable insulin‐producing endocrine cells or functional beta cells (β cells). With the end goal being clinical translation, it is critical for hPSCs and insulin‐producing β cells to be derived, handled, stored, maintained and expanded with clinical compliance. This review focuses on the key processes and guidelines for clinical translation of human induced pluripotent stem cell (hiPSC)‐derived β cells for diabetes cell therapy. Here, we discuss the (1) key considerations of manufacturing clinical‐grade hiPSCs, (2) scale‐up and differentiation of clinical‐grade hiPSCs into β cells in clinically compliant conditions and (3) mandatory quality control and product release criteria necessitated by various regulatory bodies to approve the use of the cell‐based products.
Child Feeding Practices of Childbearing Mothers and Their Household Food Insecurity in a Coastal Region of Bangladesh

The current condition of ensuring WHO-recommended newborn and young child feeding practice is becoming a challenge in many developing nations, particularly in places where family food security is threatened. Because many households in underdeveloped nations frequently face acute food shortage due to poverty, optimal child nutrition is jeopardized. The purpose of this study was to analyze the child feeding behaviors of mothers with children aged 0-24 months and to investigate their household food insecurity in a coastal region of Bangladesh, Suborno Char (one of Noakhali District’s coastal neighbourhoods) was studied from October 2019 to April 2020. In this study, a cross-sectional survey with multistage sampling technique was employed, and Suborno Char of Noakhlai district was purposely sampled of 400 women and their children aged 0-24 months. Data were obtained using a standard questionnaire and were analyzed using statistical functions in SPSS 20.0. 0. Exclusive breastfeeding 53.5%, timely supplemental feeding 75.5%, and feeding children meals from homemade, canned/formula/fortified, both homemade and canned, milk these 4 food groups were at 22.2%. The moms' education level was strongly associated with their child feeding practices. Mothers from food insecure homes were less likely to exclusively breastfeed than mothers from food secure households after drawing interpretation of univariate & multivariate analysis of variables crude odds ratio (COR) and adjusted odds ratio (AOR) and confidence interval (CI) (COR .233 at 95% CI 0.083, .655 and AOR .478 at 95% CI 0.133, 1.713). Similar outcomes were seen for early complementary feeding and minimal dietary diversification of children. In conclusion, this study discovered a less dietary inclusion trend of child feeding practices among moms (0-24 months childbearing) in Bangladesh’s coastal region.
Can improving quality of sleep reduce the symptoms of cancer‐related fatigue in adults?: A systematic review

Abstract Purpose Cancer‐related fatigue (CRF) results in reduced quality of life for cancer patients. The relationship between tiredness and fatigue has been established in cancer patients and has been shown to be reciprocal, meaning the relationship is somewhat ‘chicken or the egg’ with tiredness influencing fatigue and vice versa. The aim of this study is to determine whether an improvement in sleep quality can ease the symptoms of CRF and whether this can support the theory that CRF symptoms stem from the effect of tiredness. Method Three databases were searched producing 259 papers. The papers were filtered using several inclusion criteria, resulting in a final list of 20 papers for analysis. The remaining papers (20) were critically appraised using the Critical Appraisals Skills Programme (CASP) randomised control trial checklist and assessed for bias using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials. Results Fourteen papers showed an increase in sleep quality that also resulted in an improvement in fatigue symptoms. Cognitive behavioural therapy was shown to be the most effective intervention with a statistically significant decrease in fatigue alongside significant improvement in sleep quality shown in six of the papers (p < 0.05). Sleep education also had a positive impact on both sleep and fatigue scores with three papers showing significant improvements. Three papers focusing on exercise interventions produced a significant improvement in fatigue symptoms and quality of sleep. Conclusion Improving quality of sleep does ease the symptoms of CRF; however, the ‘chicken or the egg’ question regarding CRF and tiredness cannot be answered at this stage.
Lipid liquid-crystalline nanoparticles sustained teicoplanin delivery for treatment of chronic osteomyelitis: in vitro and in vivo studies

Abstract The aim of our work is to formulate teicoplanin-loaded lipid liquid-crystalline (cubosomes) nanoparticles laden gel to sustain the release of teicoplanin for effective treatment of infected bone. Cubosomal gels were prepared by emulsification technique. The batches were characterised for morphology, size, entrapment efficacy, viscosity, in-vitro flux, in-vivo drug release and histopathological studies. Transmission electron microscopy images confirmed the bi-continuous liquid crystalline phase. The size (61–202 nm), viscosity (12 138–13 132 cp), and entrapment efficacy (69.0–81.8% w/w) increase with the level of glycerol monooleate. The in-vitro flux data showed sustain teicoplanin release from the cubosomal gels for 36 days, compared to 48 h from the control gel. The in-vivo teicoplanin release study (osteomyelitis induced by S. aureus) showed low serum drug-concentration from the gel (up to 14 days) compared to high-serum drug-concentration using intravenous injections. In conclusion the study demonstrated the potential of cubosomes for effective delivery of teicoplanin to replace injections.
Cost-effectiveness analysis of sintilimab + chemotherapy versus camrelizumab + chemotherapy for the treatment of first-line locally advanced or metastatic nonsquamous NSCLC in China

Abstract Background and objective Sintilimab is a selective PD-1 inhibitor with efficacy in advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC) patients. This study evaluated the cost-effectiveness of sintilimab + chemotherapy versus camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in Chinese patients. In addition, this study aimed to reveal the impact of the reference treatment choice on the incremental cost-effectiveness ratio (ICER) results. Methods A partitioned survival model (PSM) with three health states was constructed in a 3-week cycle with a lifetime horizon from the Chinese healthcare system perspective. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from Orient-11. Sintilimab + chemotherapy was chosen as the reference treatments in scenarios 1 and 2, while the camrelizumab + chemotherapy was chosen as the reference treatments in scenario 3. The utility values of different health states were derived from the patient-level European Organization for Research and Treatment Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scores by mapping to the EQ-5D-5L, and QALYs were calculated as the health outcomes. One-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were performed to explore model uncertainty. Results Compared to camrelizumab + chemotherapy, sintilimab + chemotherapy was associated with higher effectiveness (incremental QALYs ranged from 0.13–0.62) and lower total costs (incremental costs ranged from $1,099–$5,201), resulting in an ICER ranging from $6,440–$8,454/QALY. Conclusions Sintilimab + chemotherapy is a cost-effective option compared with camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in China.
Chronic Sigma 1 receptor activation alleviates right ventricular dysfunction secondary to pulmonary arterial hypertension

ABSTRACT Sigma 1 receptor (S1R) has shown a preferable protective effect on left ventricular function, but whether it protects right ventricular (RV) function is still elusive.This study aimed to determine the effects of S1R on RV dysfunction secondary to pulmonary arterial hypertension.Sixty wild-type male Sprague–Dawley rats were randomly divided into the control group, the fluvoxamine group, the pulmonary arterial hypertension group and the pulmonary arterial hypertension combined with fluvoxamine group. Monocrotaline (60 mg/kg) was administered to induce pulmonary arterial hypertension, and fluvoxamine was given for 21 consecutive days to activate S1R after one week of monocrotaline administration. Echocardiographic, serologic, and histologic parameters, qRT-PCR, and western blotting were conducted after 4 weeks of monocrotaline administration.The expression of S1R was decreased in the right ventricle in pulmonary arterial hypertension. TAPSE, and the FAC of the right ventricle were significantly decreased, and RV EDP and the plasma concentration of N-terminal pro-B-type natriuretic peptide was increased in the pulmonary arterial hypertension group, but fluvoxamine partly restored those abnormalities (all P < 0.05). Moreover, pulmonary arteriole remodeling, and fibrosis and hypertrophy in the RV were shown in the pulmonary arterial hypertension group; interestingly, fluvoxamine recovered RV structural remodeling (all P < 0.05) but neither alleviated pulmonary arteriole remodeling nor reduced pulmonary artery pressure. Furthermore, S1R activation protects RV function by upgrading the NRF 2/HO 1-mediated antioxidant stress pathway. In conclusion, chronic S1R activation ameliorates structural remodeling and RV dysfunction secondary to pulmonary arterial hypertension without altering pulmonary artery pressure.
Association of No Evidence of Disease Activity With No Long-term Disability Progression in Multiple Sclerosis

Background and Objectives We conducted a systematic review and meta-analysis to evaluate the relationship between no evidence of disease activity (NEDA) and no long-term disability progression on low- and high-efficacy therapy in relapsing-remitting multiple sclerosis (RRMS). Methods MEDLINE, Embase, and the Cochrane Database were searched from January 1, 2006, to January 26, 2021. We selected studies that evaluated NEDA-3 (no relapse, new MRI lesion, or confirmed disability progression) at 1 or 2 years and had a minimum of 4 years of follow-up for determination of disability progression. Data were extracted by 2 independent reviewers and were meta-analyzed with a random-effects model. Primary outcome of no disability progression was defined as no confirmed progression on the Expanded Disability Status Scale during follow-up. We assessed the odds ratio (OR) for no disability progression with NEDA vs evidence of disease activity (EDA). Positive predictive value (PPV) of NEDA for no disability progression was summarized for studies with prevalence of no progression >80% vs ≤80% separately. Results We included 29 studies in our qualitative synthesis, of which 27 (16 low efficacy, 11 high efficacy) were included in the meta-analysis (N = 10,935 participants). Median follow-up was 5.6 years (interquartile range 4.3–8.0 years). The pooled ORs for no progression with NEDA-3 vs EDA were 2.32 (95% CI 1.58–3.42; I2 = 73%) for low-efficacy therapy and 3.19 (95% CI 1.86–5.47; I2 = 86%) for high-efficacy therapy. Among studies with prevalence of no progression at follow-up >80%, the pooled PPV for low efficacy therapy was 91% (95% CI 89%–93%) and for high-efficacy therapy was 92% (95% CI 88%–94%). Among studies with prevalence of no progression ≤80%, the pooled PPV for low-efficacy therapy was 81% (95% CI 75%–86%) and for high-efficacy therapy was 86% (95% CI 80%–90%). Discussion NEDA-3 is associated with no long-term disability progression in RRMS on both low- and high-efficacy therapies. Further studies of early composite outcome measures incorporating easily measurable biomarkers and longer follow-up may help to improve the prognostic value of NEDA-3 in RRMS. Trial Registration Information International Prospective Register of Systematic Reviews Identifier: CRD42020189316.
The biological function of the long non-coding RNA endogenous born avirus-like nucleoprotein in lung adenocarcinoma is mediated through the microRNA-655-3p/B-cell lymphoma-2 axis

ABSTRACT Lung adenocarcinoma (LUAD) is a subtype of lung cancer, and therapy remains a great challenge. A growing body of evidence shows that long-chain non-coding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. This study investigated the roles and mechanisms of action of EBLN3P in LUAD. The bioinformatics software starBase and TargetScan were used to predict the binding sites of the lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) and microRNA (miR)-655-3p in LUAD. The regulatory role of EBLN3P and miR-655-3p in cell proliferation was verified through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay. The binding sites between EBLN3P, miR-655-3p, and B-cell lymphoma-2 (Bcl-2) were assessed using dual-luciferase reporter assay, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Flow cytometry (FCM) was performed to analyze the apoptotic rates of A549 cells after transfection. The results revealed that EBLN3P was upregulated, whereas miR-655-3p was downregulated in LUAD cell lines (A549 and NCI-H23). Bioinformatics analysis and dual-luciferase reporter assays indicated that EBLN3P interacted with miR-655-3p. Knockdown of EBLN3P notably inhibited the bioactivity and induced apoptosis in A549 cells by upregulating miR-655-3p. Mechanistically, miR-655-3p inhibits cell viability and induces apoptosis by inhibiting Bcl-2 expression. The high expression of Bcl-2 reversed the impact of miR-655-3p on the inhibition of cell bioactivity and induction of apoptosis in A549 cells. In conclusion, this study demonstrated that EBLN3P silencing inhibits bioactivity and induces apoptosis via the miR-655-3p/Bcl-2 axis, providing a potential therapeutic target for lung adenocarcinoma. Graphical abstract
Prognostic Value of Pathological Personality Traits for Treatment Outcome in Anxiety and Depressive Disorders

Abstract Previous studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic value of PPT (Dimensional Assessment of Personality Pathology–Short Form) on treatment outcome (Brief Symptom Inventory [BSI-posttreatment]) among patients with depressive and/or anxiety disorders (N = 5689). Baseline symptom level (BSI-pretreatment) was taken into account as a mediator or moderator variable. Results showed significant effects of PPT on outcome, of which Emotional Dysregulation demonstrated the largest association (β = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect (β = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect β = 0.061, p < 0.001) and Inhibition (interaction effect β = 0.062, p < 0.001), but not Compulsivity or Dissocial Behavior, were moderated by the baseline symptom level. PPT predicts higher symptom levels, both before and after treatment, but yields relatively small direct effects on symptom decline when the effect of pretreatment severity is taken into account.
A newly developed droplet digital PCR for Ehrlichia canis detection: comparisons to conventional PCR and blood smear techniques

Canine monocytic ehrlichiosis caused by Ehrlichia canis infection is a life-threatening vector-borne disease in dogs worldwide. Routine blood smear has very low sensitivity and cannot accurately provide a quantitative result. Conventional PCR (cPCR) and real-time PCR (qPCR) are widely used as molecular methods for E. canis detection. qPCR is quantitative but relies on standard curves of known samples. To overcome this difficulty, this study developed a new E. canis quantitative detection method, using droplet digital polymerase chain reaction (ddPCR). ddPCR was evaluated against cPCR and blood smears. PCR amplicons and genomic DNA (gDNA) from 12 microscopic positive samples were used to identify the limits of detection (LODs) in ddPCR and cPCR. Our ddPCR was assessed in 92 field samples, it was compared with cPCR and blood smears. ddPCR showed LOD=1.6 copies/reaction, or 78 times more sensitive than cPCR (LOD=126 copies/reaction), using PCR amplicons as a template, whereas both ddPCR and cPCR had equal LODs at 0.02 ng gDNA/reaction. In addition, ddPCR had 100% sensitivity and 75% specificity for E. canis detection compared to cPCR and no cross-reaction with other blood pathogens was observed. ddPCR identified more positive samples than cPCR and blood smear. ddPCR improved the overall performance of E. canis detection, with a better LOD and comparable sensitivity and specificity to cPCR. The technique might be helpful for diagnosis of E. canis in light infection, evaluating the number of E. canis and follow-up after treatment.
Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1

ABSTRACT Euphorbia factor L3 (EFL3) is extracted from Euphorbia lathyris and is known for its anti-inflammatory properties. This study focused on the potential anti-inflammatory and therapeutic effects of EFL3 on rheumatoid arthritis (RA) using fibroblast-like synoviocytes (FLSs) and arthritis animal models. Functional analysis showed that EFL3 could ameliorate the inflammatory phenotype of FLSs derived from RA patients, as evidenced by the decreases in cell viability, migration, invasion and cytokine production. Luciferase activity, Western blotting and immunofluorescence assays demonstrated that EFL3 inhibited the nuclear translocation of the p65 subunit and the subsequent activation of the nuclear factor kappa-Β (NF-κB) pathway. Furthermore, the therapeutic effects of EFL3 against arthritic progression were evidenced by decreases in joint swelling, arthritis scores, inflammatory factor production, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) and tumor necrosis factor-α (TNF-α) transgenic (TNF-tg) mouse models. Molecular analysis identified Rac family small GTPase 1 (Rac1) as the potential target that was required for EFL3-mediated suppression of the inflammatory RA FLS phenotype. In summary, this study uncovered the therapeutic potential of EFL3 in RA, which suggests its future clinical use. GRAPHICAL ABSTRACT
Trauma-Informed Ethics and Relational Health

team or family, but continues to harm the patient. In this way the cost of addressing stakeholder trauma needs to be balanced against the burdens accruing to the patient. Despite shared interest in creating morally habitable spaces, circumstances that clinical ethicists encounter will force consultants to betray the principle of habitability in order to prioritize superseding values. Because of the nature of ethics dilemmas, there are going to be inhospitable aspects of the spaces ethicists inhabit because of the brutish nature of suffering that occurs in a healthcare setting. We need more training on identifying signs of unresolved traumas, recognizing acute re-traumatization requiring actions of other professionals, and facilitating choices regarding patient care that do not place unreasonable burden on the most vulnerable. FUNDING
Effects of acute caffeine intake on combat sports performance: A systematic review and meta-analysis

Abstract The interest in the benefits of caffeine in combat sports has grown exponentially in the last few years, evidenced by the significant rise of post-competition urine caffeine concentration. We conduct a systematic review and meta-analysis on the effects of caffeine on different performance variables in combat sports athletes. In total, we included 25 studies. All studies included had blinded, and cross-over experimental designs, and we conducted a risk of bias analysis. For nonspecific outcomes, there was an ergogenic effect of caffeine on vertical jump height (SMD: 0.38; 95% CI: 0.04, 0.71) and reaction time (SMD: −0.98, 95% CI: −1.46,−0.50). For outcomes specific to combat sports, there was an increase in the number of throws with caffeine in the Special Judo Fitness Test (SMD: 0.62; 95% CI: 0.14, 1.09). Caffeine ingestion increased the number of offensive actions during combats (SMD: 0.40; 95% CI: 0.06, 0.74). Caffeine ingestion increased the duration of offensive actions during combat (SMD: 0.58; 95% CI: 0.21, 0.96). Finally, caffeine ingestion increased blood lactate concentration after bout 1 (SMD: 1.35) bout 2 (SMD: 1.43) and bout 3 (SMD: 1.98). Overall, athletes competing in combat sports may consider supplementing with caffeine for an acute increase in exercise performance.