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2022 ◽  
Vol 8 ◽  
Author(s):  
Zeyu Zhang ◽  
Zhijie Xu ◽  
Yuanliang Yan

Background: Pyroptosis is a newly recognized form of cell death. Emerging evidence has suggested the crucial role of long non-coding RNAs (lncRNAs) in the tumorigenesis and progression of ovarian cancer (OC). However, there is still poor understanding of pyroptosis-related lncRNAs in OC.Methods: The TCGA database was accessed for gene expression and clinical data of 377 patients with OC. Two cohorts for training and validation were established by random allocation. Correlation analysis and Cox regression analysis were performed to identify pyroptosis-related lncRNAs and construct a risk model.Results: Six pyroptosis-related lncRNAs were included in the final signature with unfavorable survival data. Subsequent ROC curves showed promising predictive value of patient prognosis. Further multivariate regression analyses confirmed the signature as an independent risk factor in the training (HR: 2.242, 95% CI: 1.598–3.145) and validation (HR: 1.884, 95% CI: 1.204–2.95) cohorts. A signature-based nomogram was also established with a C-index of.684 (95% CI: 0.662–0.705). Involvement of the identified signature in multiple immune-related pathways was revealed by functional analysis. Moreover, the signature was also associated with higher expression of three immune checkpoints (PD-1, B7-H3, and VSIR), suggesting the potential of the signature as an indicator for OC immunotherapies.Conclusion: This study suggests that the identified pyroptosis-related lncRNA signature and signature-based nomogram may serve as methods for risk stratification of OC. The signature is also associated with the tumor immune microenvironment, potentially providing an indicator for patient selection of immunotherapy in OC.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261877
Author(s):  
Rachael M. Burke ◽  
Saulos Nyirenda ◽  
Hussein H. Twabi ◽  
Marriott Nliwasa ◽  
Elizabeth Joekes ◽  
...  

Background People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. Design and methods An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. Discussion Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.


2021 ◽  
Vol VI (IV) ◽  
pp. 54-63
Author(s):  
Mahmood Ahmed Dool ◽  
Naeem Akhtar ◽  
Najmunnisa Khan

Inquiry-based learning (IBL) is a student-centered approach of instruction that aims at increasing students' active engagement and their skills of investigation, reflection, and critical thinking within real-world expressions and practices. This literature review includes mostly those research studies in which a quasiexperimental approach was used, followed by a pretest-posttest design with random allocation of research participants. As per the aim of this literature review, those research studies were included where elementary grade students were selected as research participants to investigate the effects of IBL approaches on students' science literacy and skills. One of the engaging lessons from this review shows that IBL approach science skills are described as two sides of the same coin. Additionally, almost all reviewed studies defined IBL as students centered approach. Moreover, the effects of IBL are also discussed in detail


2021 ◽  
pp. 074171362110688
Author(s):  
Stephan L. Thomsen ◽  
Insa Weilage

Language skills are central to refugee integration and the availability of language courses could thus be a limiting factor. We explore how the most important provider of language courses in Germany, adult education centers (VHS), adapted their course supply to the refugee wave of 2015/2016. Our results highlight two channels through which the local environment can affect opportunities for participation in adult learning: First, exploiting the quasi-random allocation of refugees to counties, we causally estimate by how much VHS scaled up their German language course (DAF) supply as a reaction. Moreover, we show that DAF courses were created almost exclusively at the cost of other courses, that is, by crowding out. Second, we uncover heterogeneities in scaling success. VHS with more prior DAF course experience and larger VHS adapted better, which shows the relevance of initial conditions in course offers.


Author(s):  
Jim Rogers

This article assesses the guidelines and protocols that Hahnemann developed for homeopathic pathogenetic trials (HPTs) - often referred to as proving - and reappraise them in the light of more recent knowledge and protocols for clinical trials involving human subjects. Innovative features and methods introduced by Hahnemann and aimed at reducing bias are noted. A number of features which are now known to lead to bias in trials and which may be included in the reporting of symptoms are discussed in relation to HPTs. These features include: absence of control groups, absence of random allocation, absence of blinding, the inclusion of trivial and pre-existing symptoms, the inclusion of well-known acquaintances as trial participants, and the lack of definition of the healthy state. Advice from experts and papers published in recent decades related to the design of HPTs are discussed. The importance of developing methods to screen participants in HPTs for susceptibility to the tested medicine is discussed. The absence of trials meeting high quality standards in their design is highlighted. The article concludes with a plea for researchers to show the same desire for rigour and innovation that Hahnemann did in the development of HPTs, whilst fully recognising the requirements and protocols necessary for any trial of medicines on human beings, so that, as Hahnemann wanted, only reliable symptoms from HPTs will be admitted in the materia medica and clinical practice.


2021 ◽  
Vol 9 (4) ◽  
pp. e001452
Author(s):  
Navindra Persaud ◽  
Kevin E Thorpe ◽  
Michael Bedard ◽  
Stephen W Hwang ◽  
Andrew Pinto ◽  
...  

ObjectiveTo evaluate the effect of a one-time cash transfer of $C1000 in people who are unable to physically distance due to insufficient income.DesignOpen-label, multi-centre, randomised superiority trial.SettingSeven primary care sites in Ontario, Canada; six urban sites associated with St. Michael’s Hospital in Toronto and one in Manitoulin Island.Participants392 individuals who reported trouble affording basic necessities due to disruptions related to COVID-19.InterventionAfter random allocation, participants either received the cash transfer of $C1000 (n=196) or physical distancing guidelines alone (n=196).Main outcome measuresThe primary outcome was the maximum number of symptoms consistent with COVID-19 over 14 days. Secondary outcomes were meeting clinical criteria for COVID-19, SARS-CoV-2 presence, number of close contacts, general health and ability to afford basic necessities.ResultsThe primary outcome of number of symptoms reported by participants did not differ between groups after 2 weeks (cash transfer, mean 1.6 vs 1.9, ratio of means 0.83; 95% CI 0.56 to 1.24). There were no statistically significant effects on secondary outcomes of the meeting COVID-19 clinical criteria (7.9% vs 12.8%; risk difference −0.05; 95% CI −0.11 to 0.01), SARS-CoV-2 presence (0.5% vs 0.6%; risk difference 0.00 95% CI −0.02 to 0.02), mean number of close contacts (3.5 vs 3.7; rate ratio 1.10; 95% CI 0.83 to 1.46), general health very good or excellent (60% vs 63%; risk difference −0.03 95% CI −0.14 to 0.08) and ability to make ends meet (52% vs 51%; risk difference 0.01 95% CI −0.10 to 0.12).ConclusionsA single cash transfer did not reduce the COVID-19 symptoms or improve the ability to afford necessities. Further studies are needed to determine whether some groups may benefit from financial supports and to determine if a higher level of support is beneficial.Trial registration numberNCT04359264.


BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050804
Author(s):  
Yolanda Ramallo-Fariña ◽  
Amado Rivero-Santana ◽  
Lidia García-Pérez ◽  
Miguel Angel García-Bello ◽  
Ana Maria Wägner ◽  
...  

ObjectiveThis study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients’ (T2DM) reported outcomes measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions.ParticipantsA total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres.SettingPrimary Care Centers in Canary Islands (Spain).InterventionThe intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients’ results. A third group received both PTI and PFI (combined intervention, CBI).Outcome measureCognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables.ResultsCompared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group).ConclusionsAssessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits.Trial registration numberClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260007
Author(s):  
Cristian Jianu ◽  
Corina Itu-Mureşan ◽  
Cristina Drugan ◽  
Irina Filipescu ◽  
Adriana Violeta Topan ◽  
...  

In this observational pilot study, we investigated the impact of Dolutegravir, Raltegravir, Elvitegravir (Integrase Strand Transfer Inhibitors, INSTIs), or boosted Darunavir (a Protease Inhibitor, PI) in combination with two nucleoside reverstranscriptase inhibitors (Emtricitabine/Tenofovir disoproxil or Lamivudine/Tenofovir disoproxil, NRTI) on four interleukins (IL-4, IL-10, IL-13, and IL-21) as immune activation markers in naïve HIV(Human Immunodeficiency Virus)-infected patients during the first six months of combined standard-of-care antiretroviral therapy (cART). Newly diagnosed with HIV-infected subjects and without any disease that could affect the immune activation markers were evaluated. The patients’ physicians recommended the cART as standard-of-care and the ILs were measured before cART and six months of cART. The levels of CD4+ T-cells count and CD4+/CD8+ ratio significantly increased at six months (P-value<0.02) regardless of the drugs, INSTIs or PI. However, a CD4+/CD8+ >1 was observed in 25% of patients treated with Raltegravir and half of those treated with Dolutegravir. At six months of cART, viral load was detectable in only 6/31 individuals. IL-21 had an undetectable level in 30/31 patients after six months of cART. Our results suggest the potency in restoring immune markers in HIV-infected patients with all investigated drugs. Dolutegravir showed a tendency to statistically significant changes in IL-4 and IL-10. A clinical trial with random allocation of medication and an extensive follow-up is needed to replicate this research and validate the usefulness of evaluated ILs as markers of cART effectiveness.


2021 ◽  
Author(s):  
Irma Lusiana Tantri ◽  
Pryambodho Pryambodho ◽  
Raden Besthadi Sukmono ◽  
Ponco Birowo

BACKGROUND Erector spinae plane block (ESP) block is a novel interfacial block with a high margin of safety and highly effective for providing postoperative analgesia in Percutaneous Nephrolithotomy (PCNL). Combined with sedation, it may provide adequate surgical anesthesia with various advantages for PCNL procedure. OBJECTIVE The aim is to compare the effectiveness of ESP and subarachnoid block based on its conversion to a general anesthesia, interleukin-6 levels, postoperative pain, and opioid consumption in patients undergoing PCNL surgery. METHODS This is a randomized controlled trial on patients undergoing elective PCNL. All informed consent were obtained prior to the procedure. Patients were categorized into either ESP group or spinal group (1:1 ratio) with minimum sample size of 26 subjects in each arm using random allocation sampling. All patients were sedated using TCI propofol prior to receiving ultrasound-guided ESP block or spinal block. Sedation was maintained throughout the procedure. Sensory loss was evaluated by performing skin clamping at level of the incision before the surgery. RESULTS A total of 19 patients have been included in the study (7 ESP and 12 spinal subjects). A pilot study regarding its feasibility has been going as per February 2021. Primary results based on the pilot study are expected to be available by the early of 2022. CONCLUSIONS The randomized controlled trial is designed to provide high-quality evidence on comparison of effectiveness between erector spinae plane (ESP) block and spinal block as regional anaesthesia for percutaneous nephrolithotomy. CLINICALTRIAL ClinicalTrials.gov ID: NCT04947072


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