Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Two EGFR Mutation Tests on Tumor and Plasma from Patients with Non-Small Cell Lung Cancer

Epidermal growth factor receptor (EGFR) mutation testing is essential for individualized treatment using tyrosine kinase inhibitors. We evaluated two EGFR mutation tests, cobas v2 and PANAMutyper, for detection of EGFR activating mutations Ex19del, L858R, and T790M in tumor tissue and plasma from 244 non-small cell lung cancer (NSCLC) patients. The Kappa coefficient (95% CI) between the tests was 0.82 (0.74–0.92) in tumor samples (suggesting almost perfect agreement) and 0.69 (0.54–0.84) in plasma (suggesting substantial agreement). In plasma samples, both tests showed low to moderate sensitivity depending on disease stage but high diagnostic precision (86%–100%) in all disease stages (sensitivity: percentage of mutations in tumors that are also detected in plasma; precision: percentage of mutations in plasma which are also detected in tumors). Among the 244 patients, those previously diagnosed as T790M carriers who received osimertinib treatment showed dramatically better clinical outcomes than T790M carriers without osimertinib treatment. Taken together, our study supports interchangeable use of cobas v2 and PANAMutyper in tumor and plasma EGFR testing. Both tests have high diagnostic precision in plasma but are particularly valuable in late-stage disease. Our clinical data in T790M carriers strongly support the clinical benefits of osimertinib treatment guided by both EGFR mutation tests.
LABORATORY MEDICINE PRACTICE GUIDELINES — Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease

Monografija pod nazivom “ LABORATORY MEDICINE PRACTICE GUIDELINES — Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease” , objavljena na (http://www.nacb.org/), nastala je kao trud svjetskih organizacija i autoritativnih tijela u istraživanju i objavljivanju standarda za lijecenje bolesti stitnjace u pojedinim regijama svijeta: American Association of Clinical Endocrinologists (AACE), Asia & Oceania Thyroid Association (AOTA), American Thyroid Association (ATA), British Thyroid Association (BTA), European Thyroid Association (ETA) i Latin American Thyroid Society (LATS). Urednici: Laurence M.Demers, Ph.D., F.A.C.B. , Carole A.Spencer Ph.F.A.C.B. Kvalitetne laboratorijske pretrage neophodna su podrska lijecnicima za pravilnu dijagnostiku i ekonomicnu obradu bolesnika s bolestima stitnjace. Laboratorijskim pretragama jednostavno se potvrđuje hipertireoza kod mladih osoba te postojanje naglog bujanja tkiva stitnjace. U tim se primjerima sumnja jednostavno potvrđuje u laboratorijima mjerenjem koncentracije hormona stitnjace. Međutim, u vecini bolesnika simptomi su prikriveni tako da se bolest može otkriti jedino biokemijskim pretragama ili citopatoloskom procjenom. Bez obzira bili problemi jasni ili nejasni, otvorena suradnja između lijecnika i medicinskog biokemicara osnova je za optimalnu, ekonomicnu obradu bolesnika s bolestima stitnjace.
Improved two-stage estimation to adjust for treatment switching in randomised trials: g-estimation to address time-dependent confounding

In oncology trials, control group patients often switch onto the experimental treatment during follow-up, usually after disease progression. In this case, an intention-to-treat analysis will not address the policy question of interest – that of whether the new treatment represents an effective and cost-effective use of health care resources, compared to the standard treatment. Rank preserving structural failure time models (RPSFTM), inverse probability of censoring weights (IPCW) and two-stage estimation (TSE) have often been used to adjust for switching to inform treatment reimbursement policy decisions. TSE has been applied using a simple approach (TSEsimp), assuming no time-dependent confounding between the time of disease progression and the time of switch. This is problematic if there is a delay between progression and switch. In this paper we introduce TSEgest, which uses structural nested models and g-estimation to account for time-dependent confounding, and compare it to TSEsimp, RPSFTM and IPCW. We simulated scenarios where control group patients could switch onto the experimental treatment with and without time-dependent confounding being present. We varied switching proportions, treatment effects and censoring proportions. We assessed adjustment methods according to their estimation of control group restricted mean survival times that would have been observed in the absence of switching. All methods performed well in scenarios with no time-dependent confounding. TSEgest and RPSFTM continued to perform well in scenarios with time-dependent confounding, but TSEsimp resulted in substantial bias. IPCW also performed well in scenarios with time-dependent confounding, except when inverse probability weights were high in relation to the size of the group being subjected to weighting, which occurred when there was a combination of modest sample size and high switching proportions. TSEgest represents a useful addition to the collection of methods that may be used to adjust for treatment switching in trials in order to address policy-relevant questions.
Improved confidence intervals for a difference of two cause‐specific cumulative incidence functions estimated in the presence of competing risks and random censoring

A cause‐specific cumulative incidence function (CIF) is the probability of failure from a specific cause as a function of time. In randomized trials, a difference of cause‐specific CIFs (treatment minus control) represents a treatment effect. Cause‐specific CIF in each intervention arm can be estimated based on the usual non‐parametric Aalen–Johansen estimator which generalizes the Kaplan–Meier estimator of CIF in the presence of competing risks. Under random censoring, asymptotically valid Wald‐type confidence intervals (CIs) for a difference of cause‐specific CIFs at a specific time point can be constructed using one of the published variance estimators. Unfortunately, these intervals can suffer from substantial under‐coverage when the outcome of interest is a rare event, as may be the case for example in the analysis of uncommon adverse events. We propose two new approximate interval estimators for a difference of cause‐specific CIFs estimated in the presence of competing risks and random censoring. Theoretical analysis and simulations indicate that the new interval estimators are superior to the Wald CIs in the sense of avoiding substantial under‐coverage with rare events, while being equivalent to the Wald CIs asymptotically. In the absence of censoring, one of the two proposed interval estimators reduces to the well‐known Agresti–Caffo CI for a difference of two binomial parameters. The new methods can be easily implemented with any software package producing point and variance estimates for the Aalen–Johansen estimator, as illustrated in a real data example.
Achieving Minimal Heat Conductivity by Ballistic Confinement in Phononic Metalattices.

Controlling the thermal conductivity of semiconductors is of interest to the design of thermoelectric and phononic devices. The insertion of inclusions of nanometer size in a semiconductor is an effective means of achieving such control; it has been proposed that the thermal conductivity of silicon could be reduced to 1 W/m/K using this approach and that a minimum in the thermal conductivity would be reached for some optimal size of the inclusions. Yet, the practical verification of this design rule has been limited. In this work, we address this question by studying the thermal properties of silicon metalattices that consist of a periodic distribution of spherical inclusions with radii from 7 to 30 nm, embedded into silicon. Experimental measurements confirm that the thermal conductivity of silicon metalattices is as low as 1 W/m/K for silica inclusions, and that this value can be further reduced to 0.16 W/m/K for silicon metalattices with empty pores. A detailed model of ballistic phonon transport suggests that this thermal conductivity is close to the lowest achievable by tuning the radius and spacing of the periodic inhomogeneities. This study is a significant step in elucidating the scaling laws that dictate ballistic heat transport at the nanoscale in silicon and other semiconductors.
Repeated sprint cycling performance is not enhanced by ischaemic preconditioning or muscle heating strategies

ABSTRACT Introduction: Both ischaemic preconditioning (IPC) and muscle heat maintenance can be effective in enhancing repeated-sprint performance (RSA) when applied individually, acting mechanisms of these interventions, however, likely differ. It is unclear if, when combined, these interventions could further improve RSA. Methods: Eleven trained cyclists undertook experimental test sessions, whereby IPC (4 × 5-min at 220 mmHg) and SHAM (4 × 5-min at 20 mmHg) were each performed on two separate visits, each combined with either passive muscle heating or thermoneutral insulation prior to an “all-out” repeated-sprint task (10 × 6-s sprints with 24-s recovery). Primary outcome measures were peak and average power output (W), whist secondary measures were muscular activation and muscular oxygenation, measured via Electromyography (EMG) and Near-infrared spectroscopy (NIRS), respectively. Results: IPC did not enhance peak [6 (−14–26)W; P = 0.62] or average [12 (−7–31)W; P = 0.28] power output versus SHAM. Additionally, no performance benefits were observed when increasing muscle temperature in combination with IPC [5 (−14–19) watts; P = 0.67], or in isolation to IPC [9 (−9–28)W; P = 0.4] versus SHAM. No changes in EMG or microvascular changes were present (P > 0.05, respectively) between conditions. Conclusion: Overall, neither IPC, muscle heating, or a combination of both enhances RSA cycling performance in trained individuals.
The Effects of Dextrose Prolotherapy in Symptomatic Knee Osteoarthritis: A Randomized Controlled Study.

Objective: To investigate the effects of dextrose prolotherapy in patients with knee osteoarthritis (KOA). Design: A prospective, randomized-controlled interventional trial. Setting: An outpatient pain medicine clinic. Participants: The study included 66 patients aged 40-70 years with chronic knee pain refractory to conservative therapy and diagnosed as Grade II or III KOA according to the Kellgren-Lawrence classification. The patients were assigned to the dextrose prolotherapy group (PG; n = 22), saline group (SG; n = 22), or control group (CG; n = 22). Interventions: The intra- and extra-articular dextrose prolotherapy and saline injections were administered to the PG and SG, respectively, at 0, 3, and 6 weeks. The patients were blinded to their injection group status. A home-based exercise program was prescribed for all patients in three groups. Outcome measures: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, activity pain, stiffness severity measured using a visual analog scale (VAS), and the health-related quality of life (HRQoL) scores measured using the Short Form-36 (SF-36) subscales were recorded at the baseline at the baseline, 6-week, and 18-week follow-ups. Results: The WOMAC-pain and VAS-activity pain scores decreased significantly in the PG compared to the SG (p = 0.002 and p < 0.001, respectively) and CG (p < 0.001 and p < 0.001, respectively) at 18 weeks. The WOMAC-stiffness scores decreased in the PG compared to the CG at 18 weeks (p < 0.001). The WOMAC physical functioning scores were improved in the PG compared to the CG at 18 weeks (p < 0.001). The physical component scores of the HRQoL were significantly improved in the PG compared to the CG at 18 weeks (p = 0.016), but the mental component scores of the HRQoL showed no significant differences. Conclusions: These findings suggest that dextrose prolotherapy is effective at reducing pain and improving the functional status and quality of life of patients with KOA.
The Effect of the Promotion of Vegetables by a Social Influencer on Adolescents’ Subsequent Vegetable Intake: A Pilot Study

Marketers have found new ways of reaching adolescents on social platforms. Previous studies have shown that advertising effectively increases the intake of unhealthy foods while not so much is known about the promotion of healthier foods. Therefore, the main aim of the present experimental pilot study was to examine if promoting red peppers by a popular social influencer on social media (Instagram) increased subsequent actual vegetable intake among adolescents. We used a randomized between-subject design with 132 adolescents (age: 13–16 y). Adolescents were exposed to an Instagram post by a highly popular social influencer with vegetables (n = 44) or energy-dense snacks (n = 44) or were in the control condition (n = 44). The main outcome was vegetable intake. Results showed no effect of the popular social influencer promoting vegetables on the intake of vegetables. No moderation effects were found for parasocial interaction and persuasion knowledge. Bayesian results were consistent with the results and supported evidence against the effect of the experimental condition. Worldwide, youth do not consume the recommended amount of fruit and vegetables, making it important to examine if mere exposure or different forms of food promotion techniques for healthier foods are effective in increasing the intake of these foods.
Innovative practice in the process of patient management in palliative care

This thesis examines the management of multidisciplinary teams in a highly innovative environment through a study of multidisciplinary patient care teams in palliative care. It investigates management that enables spontaneous innovation where necessary, yet maintains discipline and compliance with legislation, regulation and policy. To assist the explanation a model of palliative care multidisciplinary team management and operation is developed, building on work described in the continuous innovation and organisational configuration literatures. This thesis describes innovative practices as focusing on changing the organisation’s social potential, when necessary, in order to match changes in an individual patient’s situation. A definition of innovation suitable to this environment is developed here, adapted from the innovation literature. A definition of social potential suitable to this environment is also developed, based primarily in the literature of the socialisation of organisations. In palliative care organisations, care is delivered to the patient and any group of people supporting the patient during the end of life process. Care provided to these supporters, referred to in this thesis as patient-based carers, can extend beyond the death of the patient. Palliative care is more than symptom management during the dying process and can involve an interaction lasting weeks or months between the organisation and patients and patient-based carers. A patient’s situation is described at many levels and involves a number of aspects of the patient’s condition and life; for example medical, social, psychosocial, spiritual and physical. In palliative care, patients and patient-based carers are the major sources of information about their situation and changes to it. This makes them active participants in the care team, although some patients and patient-based carers choose not to take this role. Every patient and every group of patient-based carers creates individualised situations when progressing through their end of life processes, requiring individualised care from teams that can change the membership mix to suit the situation. Palliative care professionals can be members of multiple individual patient care teams simultaneously and teams can include heads of discipline (managers). Multidisciplinary palliative care teams can be managed from inside or outside the
Screen-Printed Electrodes for the Voltammetric Sensing of Benzotriazoles in Water

Benzotriazoles (BZTs) are high production volume industrial chemicals that are used in various applications such as corrosion inhibitors, antifreeze agents, and UV radiation stabilizers. Given their potential ecotoxicological implications for different ecosystems and in human health, as well as their poor biodegradability, they are of increasing concern. In this study, a new voltammetric method using commercial screen-printed electrodes (SPEs) has been developed for the sensing of BZTs in water samples to help in their environmental monitoring. To this end, different types of SPEs based on carbon nanoallotropes and copper were tested under several experimental conditions to determine the two BZTs most frequently detected in the environment: 1H-benzotriazole (BZT) and 5-methyl-1H-benzotriazole (Me-BZT, tolyltriazole) as model compounds for BZTs. Carbon nanofibers electrodes exhibited the best performance, allowing detection limits as low as 0.4 mg L−1 for both BZTs, with repeatability and reproducibility of ca. 5%. The applicability of the method was tested through the determination of BZT in spiked drinking water samples, suggesting its suitability for the sensing of samples heavily polluted with BZTs.
Preparation of Isotopically Labelled Standards of Creatinine Via H/D Exchange and Their Application in Quantitative Analysis by LC-MS

Kidneys play a crucial role in maintaining metabolic homeostasis in a body. Serum creatinine concentration is a simple test used as an indicator of renal function. One of the known ways of quantifying creatinine concentration is the liquid chromatography-mass spectrometry (LC-MS) method, using an isotopically labeled analog of creatinine as an internal standard. Unfortunately, such isotope-labeled analogs are expensive and their synthesis is complex. Here we demonstrate a facile preparation of deuterated analogues of creatinine, via the H/D exchange of hydrogens located at the α-carbon (α-C) of the N-methylated amino acid part, under basic conditions. The stability of retrieved isotopologues was analyzed under both neutral or acidic conditions, and the results revealed that the introduced deuterons do not undergo back-exchange. In addition, the coelution of deuterated and non-deuterated forms under acidic and neutral conditions was observed. The prepared isotopologues were successfully applied in the quantitative LC-MS analysis of urine samples, and the results demonstrated that the presented strategy is novel and inexpensive, and that the quantification correlates with the commonly used Jaffe test method.
Rivaroxaban plus aspirin for the prevention of ischaemic events in patients with cardiovascular disease: a cost-effectiveness study

Background Dual pathway inhibition with 2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily may be a promising alternative to 100 mg aspirin antiplatelet therapy for the prevention of cardiovascular events in patients with coronary artery disease and/or peripheral arterial disease. However, treatment costs and bleeding risks are higher, and there is another treatment option for peripheral arterial disease, 75 mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed. Methods We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a €50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were €32,109 in coronary artery disease and €26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below €20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above €50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years. Conclusion Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach.
Social media for rapid knowledge dissemination: early experience from the COVID‐19 pandemic

The current COVID-19 pandemic is threatening global health. Rates of infection outside of China are rapidly increasing, with confirmed cases reported in over 160 countries as of 19 March 2020 [1]. During the Severe Acute Respiratory Syndrome (SARS) epidemic, 21% of the global cumulative case total were healthcare workers [2], while a recent study from Wuhan, China reported that 1716 healthcare workers were infected with COVID-19, representing 3.8% of confirmed cases [3]. During the SARS epidemic, it is likely that a lack of awareness and preparedness put healthcare workers at risk [4]. Thus, delivering rapid, reliable information that addresses critical infection control issues is of key importance, and tracheal intubation is known to be associated with a high-risk of transmission of viral infections to healthcare workers [5, 6].
Non-Cerebral Coenurosis in Goats-A Case Study

| A rural goat farm with 93non-descript goats were investigated for the complaint of emaciation, weight loss and fluctuating palpable masses in various parts of the body. Out of 93 goats, 12 were found to have cysts on dorsal lumbar, right flank and prescapular areas and identified as Coenurus gaigeri. All the goats were treated with Fenbendazole 7.5mg/kg orally.
Recent Advances and Future Perspectives of In Vivo Targeted Delivery of Genome-Editing Reagents to Germ cells, Embryos, and Fetuses in Mice

The recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) systems that occur in nature as microbial adaptive immune systems are considered an important tool in assessing the function of genes of interest in various biological systems. Thus, development of efficient and simple methods to produce genome-edited (GE) animals would accelerate research in this field. The CRISPR/Cas9 system was initially employed in early embryos, utilizing classical gene delivery methods such as microinjection or electroporation, which required ex vivo handling of zygotes before transfer to recipients. Recently, novel in vivo methods such as genome editing via oviductal nucleic acid delivery (GONAD), improved GONAD (i-GONAD), or transplacental gene delivery for acquiring genome-edited fetuses (TPGD-GEF), which facilitate easy embryo manipulation, have been established. Studies utilizing these techniques employed pregnant female mice for direct introduction of the genome-editing components into the oviduct or were dependent on delivery via tail-vein injection. In mice, embryogenesis occurs within the oviducts and the uterus, which often hampers the genetic manipulation of embryos, especially those at early postimplantation stages (days 6 to 8), owing to a thick surrounding layer of tissue called decidua. In this review, we have surveyed the recent achievements in the production of GE mice and have outlined the advantages and disadvantages of the process. We have also referred to the past achievements in gene delivery to early postimplantation stage embryos and germ cells such as primordial germ cells and spermatogonial stem cells, which will benefit relevant research.