Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost savings and cost avoidance with the inpatient clinical pharmacist interventions in a tertiary cancer care hospital

Background The economic benefit of the clinical pharmacist's role in ensuring the optimum use of medicines is potentially considerable, particularly when it comes to cancer management. We sought to evaluate the overall economic impact of clinical pharmacist interventions in the main cancer setting in Qatar. Methods The total economic benefit of the clinical pharmacy interventions were analyzed from the public hospital perspective. Patient records in March 2018, July/August 2018, and January 2019 were retrospectively reviewed at the National Center for Cancer Care and Research, Qatar. The total benefit from interventions was the total cost avoidance due to preventable adverse drug events plus any cost savings associated with therapeutic-based resource use. Sensitivity analyses confirmed the results’ robustness and increased generalizability. Results A total of 1352 interventions based on 281 patients were analyzed. The majority of the drug-related problems were related to the appropriateness of therapy, followed by dosing and administration. The total population benefit over the 3-months study period was QAR 4,879,185 (USD 1,336,763), constituting cost avoidance of QAR 4,234,012 (USD 1,160,003) and negative resource-use cost savings of −QAR 645,174 (−USD 176,760). Projected annual overall benefit was QAR 14,355,354 (USD 3,932,974). The increase in resource use with therapies was mostly because of the addition of other medications. Cost avoidance was mostly driven by recommending additional medications and discontinuation of medications. The uncertainty analysis demonstrated the robustness of outcomes. Conclusions The clinical pharmacist intervention increased resource use and its cost. In overall, however, taking avoided cost of adverse drug events in consideration, it is an economically beneficial practice in the National Center for Cancer Care and Research setting, associated with adverse drug events prevention and substantial economic benefits.
Antibacterial activity and physicochemical properties of a sealer containing copaiba oil

Abstract This study aimed to evaluate the antimicrobial activity and physicochemical properties of a novel dual-cure endodontic sealer containing copaiba oil. The copaiba oil was obtained and characterized by gas chromatography (GC), and the minimum inhibitory concentration (MIC) was performed. The experimental sealers were formulated with copaiba oil concentrations of 0, 0.5, 1, and 2%, and the RealSeal™ (Sybron endo, Orange, USA) and AH Plus (Dentsply De Trey Gmbh, Konstanz, Germany) were used as the commercial references. The antimicrobial activity of the sealers was evaluated by the direct contact test for 1h and 24h. To evaluate the physicochemical properties of the sealers, the degree of conversion, setting time, film thickness, dimensional stability, and radiopacity tests were performed. The data were statistically analyzed by one-way ANOVA and Tukey’s test (α = 0.05). Concerning the results, the sealers containing copaiba oil showed antimicrobial activity without harming the physicochemical properties.
The application of pancreatic cancer organoids for novel drug discovery

ABSTRACT Introduction Pancreatic ductal adenocarcinoma presents with a dismal prognosis. Personalized therapy is urgently warranted to overcome the treatment limitations of the ‘one-size-fits-all’ scheme. Organoids have emerged as fundamental novel tools to study tumor biology and heterogeneity, hence overcoming limitations of other model systems by better-reflecting tissue heterogeneity and recapitulating in-vivo processes. Besides their crucial role in basic research, they have evolved as tools for translational drug discovery and patient stratification. Areas covered This review highlights the achievements of an organoid-based drug investigation and discovery. The authors present an overview of studies using organoids for drug testing. Further, they pinpoint studies correlating the in vitro prediction of organoids to the actual patient`s response. Furthermore, the authors describe novel model systems and take a thorough overlook of microfluidic chips, synthetic matrices, multicellular systems, bioprinting, and stem cell-derived pancreatic organoid systems Expert opinion Organoid systems promise great potential for future clinical applications. Indeed, they may be implemented into informed decision-making for guiding therapies. However, validation by randomized trials is mandatory. Additionally, organoids in combination with other cellular compartments may be exploited for drug discovery by studying niche-tumor interaction. Yet, several precautions must be kept in mind, such as standardization and reproducibility.
Longitudinal Association Among Illness Perceptions, Coping, and Quality of Life After Extremity Injury

This longitudinal cohort study examined changes in illness perceptions, coping strategies, and quality of life in hospitalized participants who had sustained extremity injuries, and examined the associations among these changes. A sample of 138 patients with extremity injuries was recruited between August 2019 and April 2020 from the trauma units of two similar referral medical centers, each with a capacity of over 200 beds in Surabaya City, Indonesia. Outcome measures were assessed prior to hospital discharge and 3 months post-discharge, including the Brief Illness Perception Questionnaire, the Brief Coping Orientation to Problems Experienced, and the World Health Organization Quality of Life. Hierarchical multiple regression analyses were conducted. We found that lower scores for illness perceptions (i.e., how a participant appraised and understood their medical condition and its possible consequences) and maladaptive coping strategies were significantly associated with lower quality of life scores. In addition, scores for adaptive coping strategies moderated the association between illness perceptions and quality of life. Our findings suggest that clinicians should endeavor to improve patients' illness perceptions and adaptive coping strategies during the first 3 months post-injury to promote improvement in quality of life following extremity injury.
Obstacles to patient inclusion in CPR/DNAR decisions and challenging conversations: A qualitative study with internal medicine physicians in Southern Switzerland

Despite cardiopulmonary resuscitation (CPR) and do-not-attempt-resuscitation (DNAR) decisions are increasingly considered an essential component of hospital practice and patient inclusion in these conversations an ethical imperative in most cases, there is evidence that such discussions between physicians and patients/surrogate decision-makers (the person or people providing direction in decision making if a person is unable to make decisions about personal health care, e.g., family members or friends) are often inadequate, excessively delayed, or absent. We conducted a study to qualitatively explore physician-reported CPR/DNAR decision-making approaches and CPR/DNAR conversations with patients hospitalized in the internal medicine wards of the four main hospitals in Ticino, Southern Switzerland. We conducted four focus groups with 19 resident and staff physicians employed in the internal medicine unit of the four public hospitals in Ticino. Questions aimed to elicit participants’ specific experiences in deciding on and discussing CPR/DNAR with patients and their families, the stakeholders (ideally) involved in the discussion, and their responsibilities. We found that participants experienced two main tensions. On the one side, CPR/DNAR decisions were dominated by the belief that patient involvement is often pointless, even though participants favored a shared decision-making approach. On the other, despite aiming at a non-manipulative conversation, participants were aware that most CPR/DNAR conversations are characterized by a nudging communicative approach where the physician gently pushes patients towards his/her recommendation. Participants identified structural cause to the previous two tensions that go beyond the patient-physician relationship. CPR/DNAR decisions are examples of best interests assessments at the end of life. Such assessments represent value judgments that cannot be validly ascertained without patient input. CPR/DNAR conversations should be regarded as complex interventions that need to be thoroughly and regularly taught, in a manner similar to technical interventions.
Oscillations and Time Trends in Stratospheric Ozone Levels

A functional data analysis approach is presented to study altitude-dependent patterns of ozone variation in data from a sequence of ozonesonde flights. Ozonesondes are balloon-based instruments that measure ozone as the balloon ascends through the troposphere and lower stratosphere. This article concentrates on variation in the altitude range of 15.5–30.5 km, in January–July in 1967–1998. Ozonesonde flights originating at a mid-latitude site, Hohenpeissenberg in Germany, are studied. Estimates are obtained of altitude-dependent nonlinear time trends in ozone partial pressures, together with ozone variation associated with the quasi-biennial oscillation (QBO), an atmospheric process thought to influence global ozone transport. Both methodological and scientific contributions are made. The data analysis approach combines dimension-reduction basis function approximations with low-dimensional spline-based models on the basis function coefficients. This provides an efficient and flexible approach for studying complex time/altitude variation in the ozone partial pressure profiles, including nonlinear time trends. In contrast, the standard approach uses multiple linear regression models to estimate linear or piecewise-linear ozone time trends separately for each altitude level. Scientific results include identifying clear bimodalities (in altitude) in the estimated QBO components of variation in certain months. These may relate to planetary wave transport of ozone from the tropics to mid-latitudes. Additional empirical evidence of an 11-year cycle in ozone levels also is provided, possibly linked with a solar cycle. However, ozone peaks at Hohenpeissenberg do not always coincide with the timing of the maxima of the 11-year solar cycle. This may indicate a transport-related lag in ozone maxima at some altitudes. The estimated QBO features are robust to the presence or absence of the data quality “correction factors” commonly used in ozonesonde studies. However, the nonlinear time trend components show greater sensitivity to these.
Centering Frontline Health Care Workers in Digital Innovation Design to Inform the Optimization of an App for Improved Male Circumcision Follow-up in South Africa: Qualitative Usability Study

Background Voluntary medical male circumcision (VMMC) is a safe and effective HIV prevention strategy. However, adherence to recommended in-person, postoperative follow-up is inefficient for procedures with few adverse events. Two-way texting (2wT)–based follow-up appears to be a safe and an efficient alternative to scheduled clinic visits for low-risk patients who underwent VMMC. To ensure that 2wT responds to the needs of health care workers (HCWs) and patients, HCWs were closely involved in app design using a human-centered design (HCD) approach. Objective Embedded within an ongoing randomized controlled trial of 2wT in South Africa and complementary HCD processes of 2wT app optimization, this qualitative study aimed to use key informant interviews (KIIs) to explore the thoughts, suggestions, and opinions on and perceptions of 2wT’s usability and acceptability among HCWs involved in 2wT implementation in both urban and rural South Africa. Methods A total of 7 HCWs using 2wT in Gauteng and the North West province participated in KIIs regarding the usability and acceptability of 2wT. HCWs were asked for their opinions on 2wT as a viable, useful, appropriate, and accessible method of postoperative VMMC care. They were also asked about 2wT-related working, exploring areas where 2wT could add to or reduce their daily tasks. The KII data were explored, coded, and analyzed by 3 qualitative researchers using thematic content analysis and the ATLAS.ti (ATLAS.ti Scientific Software Development GmbH) software. Results Most HCWs felt confident, comfortable, satisfied, and well supported using a 2wT-based follow-up as an alternative to in-person clinical reviews. They felt that 2wT was easy to use and required little technical support after initial mentoring on how to use the 2wT system. Few noted safety concerns, as men can receive clinical guidance, reassurance, and referral via 2wT. Although fewer in-person visits reduced the in-person review workload and eased clinical flow, HCWs noted the added burden of having to interact with clients via SMS text messages on evenings or weekends. HCWs reinforced the need for enhanced postoperative counseling to ensure that 2wT patients could recognize and understood how to respond to early signs of complications. HCWs suggested a rotation to spread the evening and weekend workload and ensure swift patient responses. Conclusions In this formative qualitative study focused on HCWs, 2wT was a highly usable alternative to in-person postoperative reviews for patients who underwent VMMC in South Africa. The HCD processes likely improved the usability and acceptability of 2wT for HCWs. HCWs supported the scale-up of 2wT given the distance from the clinic to the men’s homes and the potential for reducing workload. To ensure success, providers urged sensitizing patients to the fact that 2wT augments, but does not replace, the existing after-hours and emergency care services.
Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin

Key Points Question What is the clinical benefit associated with online adaptive radiotherapy (ART) for gynecologic tumors compared with image-guided radiotherapy (IGRT)? Findings This comparative effectiveness study comprising 7 consecutive patients with gynecologic tumors found that ART was associated with improved deviation of the delivered generalized equivalent uniform dose (gEUD) for interfractional clinical target volume values from the original dose distribution on the planning computed tomography scan compared with IGRT, without increasing the gEUD for the bladder and rectum for planning target volume margins less than 5 mm. Meaning This study suggests that the advantage associated with ART depends on the number of applied dose fractions and planning target volume margins.
Consequences of adaptation to larval crowding on sexual and fecundity selection in Drosophila melanogaster

Sexual selection is a major force influencing the evolution of sexually reproducing species. Environmental factors such as larval density can manipulate adult condition and influence the direction and strength of sexual selection. While most studies on the influence of larval crowding on sexual selection are either correlational or single‐generation manipulations, it is unclear how evolution under chronic larval crowding affects sexual selection. To answer this, we measured the strength of sexual selection on male and female Drosophila melanogaster that had evolved under chronic larval crowding for over 250 generations in the laboratory, along with their controls which had never experienced crowding, in a common garden high‐density environment. We measured selection coefficients on male mating success and sex‐specific reproductive success, as separate estimates allowed dissection of sex‐specific effects. We show that experimental evolution under chronic larval crowding decreases the strength of sexual and fecundity selection in males but not in females, relative to populations experiencing crowding for the first time. The effect of larval crowding in reducing reproductive success is almost twice in females than in males. Our study highlights the importance of studying how evolution in a novel, stressful environment can shape adult fitness in organisms.
Predicting reprogramming-related gene expression from cell morphology in human induced pluripotent stem cells

Purification is essential before differentiating human induced pluripotent stem cells (hiPSCs) into cells that fully express particular differentiation marker genes. High-quality iPSC clones are typically purified through gene expression profiling or visual inspection of the cell morphology; however, the relationship between the two methods remains unclear. We investigated the relationship between gene expression levels and morphology by analyzing live-cell, phase-contrast images and mRNA profiles collected during the purification process. We employed these data and an unsupervised image feature extraction method to build a model that predicts gene expression levels from morphology. As a benchmark, it was confirmed that the method can predict the gene expression levels from tissue images for cancer genes, performing as well as state-of-the-art methods. We then applied the method to iPSCs and identified two genes that are well predicted from cell morphology. Although strong batch (or possibly donor) effects resulting from the reprogramming process preclude the ability to use the same model to predict across batches, prediction within a reprogramming batch is sufficiently robust to provide a practical approach for estimating expression levels of a few genes and monitoring the purification process.
Surfaces kählériennes de volume fini et équations de Seiberg-Witten

Soit M = P(e) une surface complexe reglee. Nous introduisons des metriques de volume fini sur M dons les singularites sont parametrisees par une structure parabolique sur le fibre e. Nous generalisons alors un resultat de Burns-de Bartolomeis et Le Brun, en montrant que l'existence de metriques kahleriennes singulieres, de volume fini, a courbure scalaire constante negative ou nulle sur M est equivalente a une condition de polystabilite parabolique sur e; de plus ces metriques proviennent toutes de quotients de volume fini de H 2 x CP 1 . En outre nous produisons une solution des equations de Seiberg-Witten pour une metrique singuliere de volume fini afin de demontrer ce theoreme.
Classification of truck-involved crash severity: Dealing with missing, imbalanced, and high dimensional safety data

While the cost of road traffic fatalities in the U.S. surpasses $240 billion a year, the availability of high-resolution datasets allows meticulous investigation of the contributing factors to crash severity. In this paper, the dataset for Trucks Involved in Fatal Accidents in 2010 (TIFA 2010) is utilized to classify the truck-involved crash severity where there exist different issues including missing values, imbalanced classes, and high dimensionality. First, a decision tree-based algorithm, the Synthetic Minority Oversampling Technique (SMOTE), and the Random Forest (RF) feature importance approach are employed for missing value imputation, minority class oversampling, and dimensionality reduction, respectively. Afterward, a variety of classification algorithms, including RF, K-Nearest Neighbors (KNN), Multi-Layer Perceptron (MLP), Gradient-Boosted Decision Trees (GBDT), and Support Vector Machine (SVM) are developed to reveal the influence of the introduced data preprocessing framework on the output quality of ML classifiers. The results show that the GBDT model outperforms all the other competing algorithms for the non-preprocessed crash data based on the G-mean performance measure, but the RF makes the most accurate prediction for the treated dataset. This finding indicates that after the feature selection is conducted to alleviate the computational cost of the machine learning algorithms, bagging (bootstrap aggregating) of decision trees in RF leads to a better model rather than boosting them via GBDT. Besides, the adopted feature importance approach decreases the overall accuracy by only up to 5% in most of the estimated models. Moreover, the worst class recall value of the RF algorithm without prior oversampling is only 34.4% compared to the corresponding value of 90.3% in the up-sampled model which validates the proposed multi-step preprocessing scheme. This study also identifies the temporal and spatial (roadway) attributes, as well as crash characteristics, and Emergency Medical Service (EMS) as the most critical factors in truck crash severity.
Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis

Abstract Aims To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease. Methods and results A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM. Conclusion The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.