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We report the screening of angiotensin converting enzyme (ACE) inhibitors on an origami microfluidic paper-based analytical device (μPAD) using colorimetric detection. The hydrolysis product reacts with ninhydrin, resulting in a purple color at the detection zones. Images of the μPADs are captured using a common cell phone and analyzed with Photoshop software. This platform allows six independent colorimetric reactions to take place simultaneously, and the IC 50 values can be obtained in a single run within 22 min. The relative standard deviations of inhibition efficiencies are generally lower than 4.0 % (n = 5). The IC 50 values of captopril and five products from natural plants were obtained and corresponded well with UV methods. The relative deviations between the two methods are within the range of -5 % to +5 %. This work is a proof-of-concept successfully demonstrating the use of μPADs technology to screen enzyme inhibitors from natural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Identifying medicinally relevant compounds from natural resources generally involves the tedious work of screening plants for the desired activity before capturing the bioactive molecules from them. In this work, we created a paper-based ligand fishing platform to vastly simplify the discovery process. This paper-based method exploits the enzymatic cascade reaction between α-glucosidase (GAA), glucose oxidase (GOx), and horseradish peroxidase (HRP), to simultaneously screen the plants and capture the GAA inhibitors from them. The designed test strip could capture ligands in tandem with screening the plants, and it features a very simply operation based on direct visual assessment. Multiple acylated flavonol glycosides from the leaves of Quercus variabilis Blume were newly found to possess GAA inhibitory activities, and they may be potential leads for new antidiabetic medications. Our study demonstrates the prospect of the newly discovered GAA ligands as potential bioactive ingredients as well as the utility of the paper-based ligand fishing method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Food analysis plays a critical role in assessing human health risks and monitoring food quality and safety. Currently, there is a pressing need for a reliable, portable, and quick recognition element for point-of-care testing (POCT) to better serve the demands of on-site food analysis. Aptamer-modified paper-based analytical devices (Apt-PADs) have excellent characteristics of high portability, high sensitivity, high specificity, and on-site detection, which have been widely used and concerned in the field of food safety. The article reviews the basic components and working principles of Apt-PADs, and introduces their representative applications detecting food hazards. Finally, the advantages, challenges, and future directions of Apt-PADs-based sensing performance are discussed, to provide new directions and insights for researchers to select appropriate Apt-PADs according to specific applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier Inc.)

Phase II metabolites play an important role in diazepam-related cases. The study aimed to assess the stability of diazepam's phase II metabolites in dried blood spots on filter paper., Methods: A piece of filter paper was spotted with 100 µL of whole blood (added 1% sodium fluoride as needed) obtained from participant who received 5 mg diazepam orally, air dried for 2 h at room temperature, and then stored at different conditions. Whole spots were cut at 0.1 cm from the outer edge of blood spots at post-consumption time-points of prior (zero), 5, 16, 35, 61, 120 days and 1, 1.5 years. Analytes were extracted with methanol/water mixture (8:2, v/v) and determined using HPLC-MS/MS. Decomposition rules were analyzed by a statistical software "SPSS"., Results: Temazepam glucuronide remained stable (0.5-18.6% loss) at 20 ℃ and at 20 ℃ with 1% sodium fluoride for 16 days, while it was unstable after 5 days at 4 ℃ (21.1-26.2% loss) and - 20 ℃ (28.9 - 34.4% loss). After 35 days, temazepam glucuronide concentrations began to fluctuate significantly under all conditions, and an obvious increase (290.4-355.1%) was observed in 1.5 years. Oxazepam glucuronide was always unstable after 5 days, the percentage loss was even 100% when it was stored for 61 days and 1.5 years., Conclusions: Dried blood spots on ordinary filter paper are recommended to be stored at 20 ℃ or 20 ℃ with 1% sodium fluoride within 16 days. Samples should be analyzed immediately or stored in sterile and dry media., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The contamination characteristics, migration patterns and health risks of per- and polyfluoroalkyl substances (PFAS) were investigated in 66 Chinese paper products by using target and non-target screening methods. Among 57 target PFASs, 5 and 6 PFASs were found in the hygiene paper products (n F 2n+1 COOH. Microwave heating can increase the release of PFAS in popcorn bags and convert long-chain PFAS into short-chain ones. The migration experiments indicated that the ethanol in food simulants can increase the migration of PFAS, and short-chain PFAS exhibits a greater migration trend. The estimated daily intake (EDI) values for 6 of 18 paper bowls/plates exceeded the recommendation of 0.63 ng/kg bw/day by the European Food Safety Authority (EFSA), posing a potential threat to human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since the inception of the first electrochemical devices on paper substrates, many different reports of microfluidic paper-based electroanalytical devices (μPEDs), innovative hydrophobic barriers and electrode fabrication processes have allowed the incorporation of diverse materials, resulting in different applications and a boost in performance. These advancements have led to the creation of paper-based devices with comparable performance to many standard conventional devices, with the added benefits of pumpless fluidic transport, component separation and reagent storage that can be exploited to automate and handle sample preprocessing. Herein, we review μPEDs, summarize the characteristics and functionalities of μPEDs, such as separation, fluid flow control and storage, and outline the conventional and emerging fabrication and modification approaches for μPEDs. We also examine the recent application of μPEDs in biomedicine, the environment, and food and water safety, as well as some limitations and challenges that must be addressed., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objective: The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS., Methods: A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology., Key Findings and Limitations: Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered., Conclusions and Clinical Implications: The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts)., Patient Summary: The European Association of Urology guidelines on underactive bladder in non-neurogenic adult men are presented here. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This work focuses on a systematic method to produce Ag, Cu, and Ag/Cu metallic nanoparticles (MNPs) in situ assisted with ultrasound on cellulose paper. By tuning the concentration of AgNO 3 and CuSO 4 salt precursors and ultrasound time, combined with a fixed concentration of ascorbic acid (AA) as a reducing agent, it was possible to control the size, morphology, and polydispersity of the resulting MNPs on cellulose papers. Notably, high yield and low polydispersity of MNPs and bimetallic nanoparticles are achieved by increasing the sonication time on paper samples pre-treated with salt precursors before reduction with AA. Moreover, mechanical analysis on paper samples presenting well-dispersed and distributed MNPs showed slightly decreasing values of Young's modulus compared to neat papers. The strain at break is substantially improved in papers containing solely Ag or Cu MNPs. The latter suggests that the elastic/plastic transition and deformation of papers are tuned by cellulose and MNPs interfacial interaction, as indicated by mechanical analysis. The proposed method provides insights into each factor affecting the sonochemistry in situ synthesis of MNPs on cellulose papers. In addition, it offers a straightforward alternative to scale up the production of MNPs on paper, ensuring an eco-friendly method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Multiplex ion analyzers have been introduced recently for the assay of several inorganic ions, whilst electrochemists have extensively employed screen printed sensors for pharmaceutical analyses. This work aims to develop a USB pluggable sensor with a user-friendly design for multiplex analysis of oppositely charged co-formulated organic ions. The miniaturized screen-printed electrode was developed using silver ink on paper substrate. A compact sensor design was attained by including three electrodes, a single reference electrode along with an indicator electrode for each of the determined ions. Optimized PVC membranes were drop-casted over each of the indicator electrodes for the determination of phenylephrine HCl (PHE) and ibuprofen (IBU). The proposed multiplex potentiometric sensors exhibit Nernstian slopes of 59.2 ± 0.26 and -56.8 ± 0.16 mV/decade for PHE and IBU, respectively, with respective detection limits of 1.6 × 10 -7 and 6.53 × 10 -8 mol L -1 . The fast and stable response of the developed sensor enabled the real-time monitoring of the combined dosage form dissolution. The dissolution profiles obtained by this potentiometric analyzer and an off-line separation technique were compared favourably, albeit our proposed in-line sensor reduced waste and time of analysis. The developed method successfully complies with the most demanding stipulations of green analytical chemistry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: In recent years, interest in universal newborn screening for congenital cytomegalovirus (cCMV) has intensified. consequently, reliable and simple methods of mass screening for cCMV, are essential. Herein, we present a novel approach of using polymerase chain reaction (PCR) in saliva with direct inoculation onto Guthrie paper. Our aim was to determine the diagnostic accuracy of real- time PCR in saliva rolled directly onto Guthrie paper in diagnosing cCMV infection., Objectives: To evaluate the diagnostic accuracy of real-time PCR analysis of dried saliva on Guthrie paper as a future approach for mass screening of newborns in diagnosing cCMV infection., Study Design: This prospective, blinded study was performed in a tertiary cytomegalovirus (CMV) clinic from May 2018 through January 2019. Forty-two cCMV positive newborns and 41 without cCMV, were enrolled and tested for CMV using PCR from their saliva placed onto Guthrie paper and from their saliva using standard methods. Specificity and sensitivity of dried saliva PCR versus gold-standard methods were analyzed., Results: Forty-two out of 42 (100 %) CMV positive infants showed positive PCR in the dried saliva on the Guthrie paper. All (100 %) controls exhibited negative PCR results. Congenital CMV infection was identified with a sensitivity of 100 % (95 % C.I. = 91.4%-100.00%) and specificity of 100 % (95 % C.I. = 91.4%-100.00%)., Discussion: CMV testing with saliva real-time PCR on Guthrie paper displayed a high sensitivity and specificity, rendering it a powerful screening test. The accuracy, simplicity of sampling, storage and transportation and the potential reliance on existing logistic resources, establishes this method as a candidate for cCMV universal screening programs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This position paper opens a discussion forum of this Journal dedicated to a scientific debate on Vitamin E nomenclature. With this article we provide the scientific and medical communities with what we consider relevant information in favor of revising the nomenclature of vitamin E. To our knowledge, only RRR-α-tocopherol has been medically used to protect against a deficiency disease in humans, and therefore, it would be appropriate to restrict the term vitamin to this molecule. The direct demonstration of a vitamin function to other tocochromanols (including other tocopherols, tocotrienols and eventually tocomonoenols), has not yet been scientifically shown. In fact, the medical prescription of a molecule against the deficiency disease only because it has been included in the "Vitamin E family", but not tested as vitamin E, could lead to ineffective therapy and potentially dangerous consequences for patients. The idea of this revision launched during the recent 3rd Satellite Symposium on Vitamin E of the 2022 SFRR-Europe meeting, offers a open platform of discussion for the scientists involved in vitamin E research and scientific societies interested to this subject., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Among the analytical tools, paper-based analytical devices (PADs) have become a leading alternative for point-of care testing (POCT). In this study, PADs were fabricated using an office laser printer. Then, the paper zone was modified with graphene oxide (GO) and pyrene derivatives, which provide a sufficient amount of carboxylic groups for conjugating antibodies. At an optimal pH, antibodies were covalently bound onto carboxylated cellulose surface in an oriented manner through a two-step strategy: electrostatic adsorption was followed by EDC/NHS coupling. α-fetoprotein (AFP) as a detection model, we compared with cellulose powder modified and unmodified paper zone. The results showed the color intensity and color uniformity on GO modified paper was improved. The activity of immobilized antibodies on GO/1-pyrenebutyric acid (GO/PBA) modified was three times higher than that of GO modified and about 1.8-fold higher than that of GO/1-pyrenecarboxylic acid (GO/PCA) modified. The GO/PBA modified paper-based immunoassay has enhanced sensitivity and low detection limit. A linear correlation between color intensity and concentration of AFP in the range of 0.01～16.5 ng mL -1 with a detection limit of 9.0 pg mL -1 were achieved, respectively. The obtained results point towards rapid, sensitive, and specific early diagnosis of liver cancer at the point of care and other low-resource settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Context: Lower urinary tract symptoms (LUTS) are common, often bothersome, and have multifactorial aetiology., Objective: To present a summary of the 2023 version of the European Association of Urology guidelines on the management of male LUTS., Evidence Acquisition: A structured literature search from 1966 to 2021 selected the articles with the highest certainty evidence. The Delphi technique consensus approach was used to develop the recommendations., Evidence Synthesis: The assessment of men with LUTS should be practical. A careful medical history and physical examination are essential. Validated symptom scores, urine test, uroflowmetry, and postvoid urine residual, as well as frequency-volume charts for patients with nocturia or predominately storage symptoms should be used. Prostate-specific antigen should be ordered if a diagnosis of prostate cancer changes the treatment plan. Urodynamics should be performed for selected patients. Men with mild symptoms are candidates for watchful waiting. Behavioural modification should be offered to men with LUTS prior to, or concurrent with, treatment. The choice of medical treatment depends on the assessment findings, predominant type of symptoms, ability of the treatment to change the findings, and the expectations to be met in terms of the speed of onset, efficacy, side effects, and disease progression. Surgery is reserved for men with absolute indications, and for patients who fail or prefer not to receive medical therapy. Surgical management has been divided into five sections: resection, enucleation, vaporisation, and alternative ablative and nonablative techniques. The choice of surgical technique depends on patient's characteristics, expectations, and preferences; surgeon's expertise; and availability of modalities., Conclusions: The guidelines provide an evidence-based approach for the management of male LUTS., Patient Summary: A clinical assessment should identify the cause(s) of symptoms and define the clinical profile and patient's expectations. The treatment should aim to ameliorate symptoms and reduce the risk of complications., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Paper-based sleep diaries play an important role in the diagnosis and treatment of insomnia disorder. Accurate self-report data help to guide therapy and track progress, both in the clinic and during research trials. Previous research with paper diaries suggests that timely adherence with self-report diaries may be an issue, which can result in biased event recall., Patients/methods: University students (N = 31) were asked to track their bedtime and wake time within 30 min of these events on paper-based sleep diaries. Specially designed binders covertly timestamped when participants actually wrote on their sleep diary. We assessed adherence by comparing timestamped diary usage with what participants documented in their sleep diary., Results: Participants self-reported they were adherent with sleep diary instructions 97.9% of the time. However, timestamped data revealed that only 37.1% of diary entries were completed within the instructed timeframe. More than half of participants backfilled diary data, and three participants (9.7%) provided data that completely did not match their actual time of completion., Conclusions: When naïve to the objective tracking of their sleep diary usage, participants greatly over-reported the extent of their adherence. Non-adherence with sleep diary protocols poses a challenge for researchers utilizing this tool as a study outcome in clinical trials and for clinicians attempting to implement behavioral therapies for insomnia., Competing Interests: Declaration of competing interest Eric S. Zhou has received grant support from Jazz Pharmaceuticals and Harmony Biosciences, and consulting fees from Samsung and MindUP for work unrelated to this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Patients with multimorbidity increasingly impact healthcare systems, both in primary care and in hospitals. This is particularly true in Internal Medicine. This population associates with higher mortality rates, polypharmacy, hospital readmissions, post-discharge syndrome, anxiety, depression, accelerated age-related functional decline, and development of geriatric syndromes, amongst others. Internists and Hospitalists, in one of their roles as Generalists, are increasingly asked to attend to these patients, both in their own Departments as well as in surgical areas. The management of polypathology and multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience. In addition, patients' needs, health-care environment, and routines have changed, so emerging and re-emerging specific competences and approaches are required to offer the best coordinated, continuous, and comprehensive integrated care to these populations, to achieve optimal health outcomes and satisfaction of patients, their relatives, and staff. This position paper proposes a set of emerging and re-emerging competences for internal medicine specialists, which are needed to optimally address multimorbidity now and in the future., Competing Interests: Declaration of Competing Interest All authors declare that they have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and they declare no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source. Using this system, a continuous solvent flow works as an elution and spray solvent simultaneously. In this method, analyte is adsorbed on a triangular paper with immobilized aptamer and then it is desorbed and ionized by elution solvent and applied high voltage on paper, respectively. The effects of different experimental parameters such as applied voltage, angle of paper tip, distance between paper tip and counter electrode, elution solvent type, and solvent flow rate were optimized. The proposed method was exhaustively validated in terms of sensitivity and reproducibility by analyzing the standard solutions of codeine and acetamiprid. The analytical results obtained are promising enough to ensure the use of immobilized aptamer paper-spray as both the extraction and ionization techniques in IMS for direct analysis of biomedicine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The traditional analytical methods used for biomedical analysis are expensive and not easy to handle and require sophisticated instruments, thus their application is limited in resource-limited settings. Due to their portability, low cost, and ability to be applied to different analytical techniques, paper-based analytical devices are becoming valuable tools for biomedical analysis. The integration of smartphones into analytical devices has provided the ability to build portable, cost-effective, straightforward analytical devices for biomedical analysis and mobile health. The key aim of this review is to emphasize the recent applications of PADs combined with a smartphone for the optical analysis of biomedical species. We started this review by highlighting the type of papers and their modifications with different materials to prepare the PADs. After that, this review presents various detection methods including colorimetry, fluorescence, and luminescence where the smartphone is used for read-out. In the end, we provided the recent applications of the analysis of different biomedical compounds such as cancer and cardiovascular biomarkers, metal ions, glucose, viruses, etc. We believe that the present review will attract a wide scientific community in the areas of analytical chemistry, sensors, and clinical testing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this communication a prototype of paper-based analytical device designed for simultaneous determination of orthophosphate and calcium ions, which levels are significant for hyperphosphatemia diagnostics, is presented. The laboratory-on-paper structure for two analytes detection was wax-printed on the surface of filter paper. These two-analyte disposable paper strips are combined with two paired LED-based fluorescence detectors and simple voltmeter used as recorder of analytical signal, what makes the developed device miniature, extremely low-cost, portable and user-friendly. Thus the developed device allows usage outside of specialized clinical laboratory. Moreover, each paper strip is disposable and its utilization is easy and fast and, additionally, burnt strip tests ensure waste non-infectious. The presented LED&Paper-based analytical device provides low detection limits: 1.4 μmol L -1 and 7.4 μmol L -1 for orthophosphate and calcium ions, respectively. The practical utility of the developed device for calcemia/phosphatemia diagnostics is demonstrated using control serum standards and real human serum., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Paper-based sensors gained almost explosive attention during the last few years. A large number of systems, often destined to resource limited settings is based on enzymatic reactions. Choice of an adequate immobilization method could significantly prolong the shelf-life of such sensors, especially in applications, where exposure to high temperatures during storage and transport is more than a threat. We are seeking to compare a variety of immobilization methods based on different phenomena (adsorption, entrapment in gel, microencapsulation, covalent linkage), with total of 33 methods tested. Glucose oxidase was used as a model enzyme. Enzymatic activity of immobilized samples was accompanied for a period of 24 weeks considering two sets of samples, one stored in 4 °C and other in ambient temperature., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Several factors have been reported to affect the perception of wetness. In the present study, we aimed to examine how wet perception changes when the factors related to thermal and/or wetness stimuli are modulated. First, the percentage of participants experiencing wet perception among filter papers with different water contents (0.00, 3.75, 7.50, 11.25, 15.00, and 18.75 µg/cm 2 , corresponding to 0.00, 0.18, 0.37, 0.55,0.73 and 0.91 µg/mm 3 ) was evaluated during static touch by the right index finger pad. The stimulus temperature was maintained at 30 °C. Second, the wet perception of paper with a water content of 18.75 µg/cm 2 was evaluated at stimulus temperature of 20 °C, 25 °C, 30 °C, 35 °C, and 40 °C. In the first experiment, the percentage of participants experiencing wet perception elevated with the increasing water content; however, the percentage plateaued at 11.25 µg/cm 2 of water (68.1 ± 25.5%). In the second experiment, when the stimulus temperature was < 30 °C, the wet perception increased as the stimulation temperature decreased. However, the wet perception reached a plateau at a stimulation temperature ≥30 °C. Participants experienced wet perception more consistently as the water content increased when the stimulus temperature was 30 ˚C. The effect of temperature on wet perception was limited to the stimulus temperature of <30 °C at which cold sensation was induced. However, no clear relationship between stimulus temperature and wet perception was observed when the stimulus temperature was ≥30 ˚C at which warm/hot sensation was induced., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Frick (2022) presented a narrative review of some literature and made several critical comments regarding the extension of the full psychopathy construct to research and classification of childhood disruptive behavior disorders (DBDs). His arguments cautioned against the use of the multicomponent concept of psychopathy for specification of DBDs for several reasons including definitional issues, symptom sequencing, specifier versus risk factor considerations, potential overlap with other disorders and criteria (e.g., ADHD), and concerns regarding harm. While I agree with Frick (2022) that we need to be cautious when extending personality constructs to the DBDs, the remaining arguments in his paper fall short of calling for the exclusion of psychopathy components in the examination of DBDs. Rather, the counterpoints in this paper further convince that the multidimensional model of psychopathy, when applied to the DBDs, could better facilitate understanding of the etiology and mechanisms for Conduct Disorder (CD), and, it may help us to predict the prognosis and treatment outcomes of children with various forms of DBDs such as CD and Oppositional Defiant Disorder (ODD). To have the most informative designs, future research should examine the broad construct to glean a better understanding of psychopathy and the DBDs. Further, research should continue to examine sequencing and external correlates at the component level and to test the incremental value of the multicomponent model of psychopathy to help us better comprehend how each component may facilitate our understanding of the types and severity of conduct problems exhibited by youth with DBDs (i.e., CD, ODD)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour., Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

A novel paper-based dot immune-graphene-gold filtration assay (DIGGFA) for the detection of breast cancer cells was developed based on the photo-thermal effect of graphene oxide (GO)-Au nanocomposite. Anti-EpCAM antibody which specific to the MCF-7 cell surface antigen, was immobilized on the nitrocellulose paper. The GO-Au-anti-EpCAM composite would interact with the MCF-7 cells captured on the nitrocellulose paper. After the test zone was irradiated by a laser, GO-Au nanocomposite could generate heat, temperature contrast was recorded and positive correlated with the cell number. Standard curve was prepared according to the temperature contrast and the cell number. Under optimal conditions, this method could detect a minimum of 600 MCF-7 cells with a near infrared laser and an infrared temperature gun within 15 min. This simple and rapid method could be applied to the clinical diagnosis in hospitals., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This work describes a 3D, paper-based assay that can isolate sub-populations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O2). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel. Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates sub-populations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The paper-disc soil method is a soil algal bioassay used to assess soil water transfer in polluted soils. Although this ecotoxicological method was first established in 2016 to assess soil pollution, quantitative toxicity assessments of Cu- or Ni-treated soil and in situ or ex situ soils polluted with other heavy metals (HMs) have not been widely conducted. In this study, the paper-disc soil method was validated under different test conditions. The validated paper-disc soil method was used to quantitatively investigate the toxicity of four HMs (As, Cd, Cr, and Zn). Based on the results, the test species, initial inoculation concentration in the algal-dispersed solution, water content, light intensity, and exposure duration were proposed as Chlorococcum infusionum, 3 × 10 6 cells/mL in Bold's basal medium, 80% water-holding capacity, 4000 ± 500 lx, and 6 days, respectively. The toxicity of HMs was quantified using the validated paper-disc soil method, and the half-maximal effective concentration values for biomass were calculated as 22.49 (21.26-23.78) mg Cr/kg dry weight (dw) soil, 42.72 (38.64-47.24) mg Cd/kg dw soil, 57.79 (55.46-60.21) mg As/kg dw soil, and 183.06 (175.38-191.06) mg Zn/kg dw soil. The paper-disc soil method using the soil alga C. infusionum was validated by quantitatively evaluating the test conditions and toxicity of HMs. Our results provide important quantitative toxicity data for soil algae exposed to HMs and a basis for standardizing the paper-disc soil method using soil algae., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bioactive, functional scaffolds are required to improve the regenerative potential of stem cells for tissue reconstruction and functional recovery of damaged tissues. Here, we report a paper-based bioactive scaffold platform for stem cell culture and transplantation for bone reconstruction. The paper scaffolds are surface-engineered by an initiated chemical vapor deposition process for serial coating of a water-repellent and cell-adhesive polymer film, which ensures the long-term stability in cell culture medium and induces efficient cell attachment. The prepared paper scaffolds are compatible with general stem cell culture and manipulation techniques. An optimal paper type is found to provide structural, physical, and mechanical cues to enhance the osteogenic differentiation of human adipose-derived stem cells (hADSCs). A bioactive paper scaffold significantly enhances in vivo bone regeneration of hADSCs in a critical-sized calvarial bone defect. Stacking the paper scaffolds with osteogenically differentiated hADSCs and human endothelial cells resulted in vascularized bone formation in vivo. Our study suggests that paper possesses great potential as a bioactive, functional, and cost-effective scaffold platform for stem cell-mediated bone tissue engineering. To the best of our knowledge, this is the first study reporting the feasibility of a paper material for stem cell application to repair tissue defects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients' clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community., (Copyright © 2022. Published by Elsevier B.V.)

The purification of a protein inhibiting lipid peroxidation led to the discovery of the selenoperoxidase GPx4 forty years ago. Thus, the evidence of the enzymatic activity was reached after identifying the biological effect and unambiguously defined the relationship between the biological function and the enzymatic activity. In the syllogism where GPx4 inhibits lipid peroxidation and its inhibition is lethal, cell death is operated by lipid peroxidation. Based on this rationale, this form of cell death emerged as regulated iron-enforced oxygen toxicity and was named ferroptosis in 2012. In the last decades, we learned that reduction of lipid hydroperoxides is indispensable and, in cooperation with prooxidant systems, controls the critical steady state of lipid peroxidation. This concept defined the GPx4 reaction as both the target for possible anti-cancer therapy and if insufficient, as cause of degenerative diseases. We know the reaction mechanism, but the details of the interaction at the membrane cytosol interface are still poorly defined. We know the gene structure, but the knowledge about expression control is still limited. The same holds true for post-transcriptional modifications. Reverse genetics indicate that GPx4 has a role in inflammation, immunity, and differentiation, but the observations emerging from these studies need a more specifically addressed biochemical evidence. Finally, the role of GPx4 in spermatogenesis disclosed an area unconnected to lipid peroxidation. In its mitochondrial and nuclear form, the peroxidase catalyzes the oxidation of protein thiols in two specific aspects of sperm maturation: stabilization of the mid-piece and chromatin compaction. Thus, although available evidence converges to the notion that GPx4 activity is vital due to the inhibition of lipid peroxidation, it is reasonable to foresee other unknown aspects of the GPx4 reaction to be disclosed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Management of datasets that include health information and other sensitive personal information of European study participants has to be compliant with the General Data Protection Regulation (GDPR, Regulation (EU) 2016/679). Within scientific research, the widely subscribed'FAIR' data principles should apply, meaning that research data should be findable, accessible, interoperable and re-usable. Balancing the aim of open science driven FAIR data management with GDPR compliant personal data protection safeguards is now a common challenge for many research projects dealing with (sensitive) personal data. In December 2020 a workshop was held with representatives of several large EU research consortia and of the European Commission to reflect on how to apply the FAIR data principles for environment and health research (E&H). Several recent data intensive EU funded E&H research projects face this challenge and work intensively towards developing solutions to access, exchange, store, handle, share, process and use such sensitive personal data, with the aim to support European and transnational collaborations. As a result, several recommendations, opportunities and current limitations were formulated. New technical developments such as federated data management and analysis systems, machine learning together with advanced search software, harmonized ontologies and data quality standards should in principle facilitate the FAIRification of data. To address ethical, legal, political and financial obstacles to the wider re-use of data for research purposes, both specific expertise and underpinning infrastructure are needed. There is a need for the E&H research data to find their place in the European Open Science Cloud. Communities using health and population data, environmental data and other publicly available data have to interconnect and synergize. To maximize the use and re-use of environment and health data, a dedicated supporting European infrastructure effort, such as the EIRENE research infrastructure within the ESFRI roadmap 2021, is needed that would interact with existing infrastructures., (Copyright © 2022. Published by Elsevier Ltd.)

The present work deals with application of hydrodynamic cavitation for intensification of delignification of wheat straw as an essential step in the paper manufacturing process. Wheat straw was first treated with potassium hydroxide (KOH) for 48 h and subsequently alkali treated wheat straw was subjected to hydrodynamic cavitation. Hydrodynamic cavitation reactor used in the work is basically a stator and rotor assembly, where the rotor is provided with indentations and cavitational events are expected to occur on the surface of rotor as well as within the indentations. It has been observed that treatment of alkali treated wheat straw in hydrodynamic cavitation reactor for 10-15 min increases the tensile index of the synthesized paper sheets to about 50-55%, which is sufficient for paper board manufacture. The final mechanical properties of the paper can be effectively managed by controlling the processing parameters as well as the cavitational parameters. It has also been established that hydrodynamic cavitation proves to be an effective method over other standard digestion techniques of delignification in terms of electrical energy requirements as well as the required time for processing. Overall, the work is first of its kind application of hydrodynamic cavitation for enhancing the effectiveness of delignification and presents novel results of significant interest to the paper and pulp industry opening an entirely new area of application of cavitational reactors., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To compare accuracy and speed of keyboard and mouse electronic health record (EHR) documentation strategies with those of a paper documentation strategy., Design: Prospective cohort study., Methods: Three documentation strategies were developed: (1) keyboard EHR, (2) mouse EHR, and (3) paper. Ophthalmology trainees recruited for the study were presented with 5 clinical cases and documented findings using each strategy. For each case-strategy pair, findings and documentation time were recorded. Accuracy of each strategy was calculated based on sensitivity (fraction of findings in actual case that were documented by subject) and positive ratio (fraction of findings identified by subject that were present in the actual case)., Results: Twenty subjects were enrolled. A total of 258 findings were identified in the 5 cases, resulting in 300 case-strategy pairs and 77 400 possible total findings documented. Sensitivity was 89.1% for the keyboard EHR, 87.2% for mouse EHR, and 88.6% for the paper strategy (no statistically significant differences). The positive ratio was 99.4% for the keyboard EHR, 98.9% for mouse EHR, and 99.9% for the paper strategy (P < .001 for mouse EHR vs paper; no significant differences between other pairs). Mean ± standard deviation documentation speed was significantly slower for the keyboard (2.4 ± 1.1 seconds/finding) and mouse (2.2 ± 0.7 seconds/finding) EHR compared with the paper strategy (2.0 ± 0.8 seconds/finding). Documentation speed of the mouse EHR strategy worsened with repetition., Conclusions: No documentation strategy was perfectly accurate in this study. Documentation speed for both EHR strategies was slower than with paper. Further studies involving total physician time requirements for ophthalmic EHRs are required., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In pulp and paper mills, mechanical processes such as screening and washing are commonly used to remove accumulated solid suspensions and concentrate the pulp. For environmental reasons and to optimize paper production, an emerging challenge is to develop alternative methods to concentrate paper pulp between 3 % and 6 % consistency for which the mixed pulp-water flow is complex. Among the proposed solutions in the literature, solutions based on acoustic levitation, also referred as acoustophoresis, of low-consistency pulp have been demonstrated as a potential solution for efficient pulp concentration and water recirculation. However, no sensitivity analysis on the ultrasound and physical parameters was proposed, limiting the extension to a realistic application. Thus, this paper presents a numerical modeling of acoustophoresis for pulp flow concentration in a pipe. For this purpose, the pulp flow is defined as a pseudo-homogenous fluid with a turbulent Low Re k- ∊ formalism, and the pulp particles are considered spherical and deflected by two acoustic forces, namely the acoustic radiation force and the Stokes drag force, both induced by an ultrasound wave generated along the walls of a circular pipe. The combined action of these two forces in the pulp flow enables to concentrate the particles at the center of the pipe. The influences of particle size and mechanical properties, fluid properties and ultrasound parameters are analyzed within a parametric study to optimize the particle deflection and the pulp concentration. The experimental feasibility of the industrial use of acoustophoresis for the concentration of paper pulp is demonstrated with a concentration gain up to 15 %., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: "Biological plausibility" is a concept frequently referred to in environmental and public health when researchers are evaluating how confident they are in the results and inferences of a study or evidence review. Biological plausibility is not, however, a domain of one of the most widely-used approaches for assessing the certainty of evidence (CoE) which underpins the findings of a systematic review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) CoE Framework. Whether the omission of biological plausibility is a potential limitation of the GRADE CoE Framework is a topic that is regularly discussed, especially in the context of environmental health systematic reviews., Objectives: We analyse how the concept of "biological plausibility", as applied in the context of assessing certainty of the evidence that supports the findings of a systematic review, is accommodated under the processes of systematic review and the existing GRADE domains., Results and Discussion: We argue that "biological plausibility" is a concept which primarily comes into play when direct evidence about the effects of an exposure on a population of concern (usually humans) is absent, at high risk of bias, is inconsistent, or limited in other ways. In such circumstances, researchers look toward evidence from other study designs in order to draw conclusions. In this respect, we can consider experimental animal and in vitro evidence as "surrogates" for the target populations, exposures, comparators and outcomes of actual interest. Through discussion of 10 examples of experimental surrogates, we propose that the concept of biological plausibility consists of two principal aspects: a "generalisability aspect" and a "mechanistic aspect". The "generalisability aspect" concerns the validity of inferences from experimental models to human scenarios, and asks the same question as does the assessment of external validity or indirectness in systematic reviews. The "mechanistic aspect" concerns certainty in knowledge of biological mechanisms and would inform judgements of indirectness under GRADE, and thus the overall CoE. While both aspects are accommodated under the indirectness domain of the GRADE CoE Framework, further research is needed to determine how to use knowledge of biological mechanisms in the assessment of indirectness of the evidence in systematic reviews., (Copyright © 2022 Paul Whaley, Thomas Piggott, Rebecca L. Morgan, Sebastian Hoffmann, Katya Tsaioun, Lukas Schwingshackl, Mohammed T. Ansari, Kristina A. Thayer, Holger Schünemann. Published by Elsevier Ltd.. All rights reserved.)

An anti-phenolphthalein monoclonal antibody (mAb) was prepared based on the N,N'-Carbonyldiimidazole (CDI) method through phenolphthalein conjugated with proteins. Indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold-based immunochromatographic assay (ICA) methods were used to determine phenolphthalein in slimming products. A standard curve was established, and the IC 50 and limit of detection of ic-ELISA were 0.95 and 0.10 ng/mL with a linear detection range of 0.27-3.37 ng/mL. The developed ICA was used to detect phenolphthalein in tablets, capsules, and slimming tea samples with visual limit of detection values of 10 μg/kg, and cut-off values of 200 μg/kg. The results indicated that these two methods could be used to quickly detect phenolphthalein in slimming products., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since Nicolle, Manceaux and Splendore first described Toxoplasma gondii as a parasite of rodents and rabbits in the early 20th century, a diverse and vigorous research community has been built around studying this fascinating intracellular parasite. In addition to its importance as a pathogen of humans, livestock and wildlife, modern researchers are attracted to T. gondii as a facile experimental system to study many aspects of evolutionary biology, cellular biology, host-microbe interactions, and host immunity. For new researchers entering the field, the extensive literature describing the biology of the parasite, and the interactions with its host, can be daunting. In this review, we examine four foundational studies that describe various aspects of T. gondii biology, presenting a 'journal club'-style analysis of each. We have chosen a paper that established the beguiling life cycle of the parasite (Hutchison et al., 1971), a paper that described key features of its cellular biology that the parasite shares with related organisms (Gustafson et al., 1954), a paper that characterised the origin of the unique compartment in which the parasite resides within host cells (Jones and Hirsch, 1972), and a paper that established a key mechanism in the host immune response to parasite infection (Pfefferkorn, 1984). These interesting and far-reaching studies set the stage for subsequent research into numerous facets of parasite biology. As well as providing new researchers with an entry point into the literature surrounding the parasite, revisiting these studies can remind us of the roots of our discipline, how far we have come, and the new directions in which we might head., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To analyze the effect of blood collection and storage conditions on activity of α-galactosidase A, arylsulfatase B and α-glucosidase., Design and Methods: Blood was collected in EDTA, heparin, or direct spotting on filter paper and stored at different temperatures (-20, 4, 25 and 37°C) and storage times (3, 10, 17 and 180 days). The influence of filter paper size was also assessed (3.0 and 1.2mm)., Results: No statistically significant difference was observed between the three collection methods. α-Glucosidase A activity significantly decreased after the 10th day, while arylsulfatase B activity only differed significantly after the 180th day, and α-galactosidase A activity remained constant throughout this storage time. Excellent correlation coefficients were observed for the two filter paper sizes used., Conclusions: Both paper sizes may be employed. Filter paper specimens should be transported under refrigeration as soon as possible after blood collection., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Final effluent from a pulp and paper kraft mill was exposed to power ultrasound at 357kHz with the aim of reducing color, turbidity, and chemical oxygen demand (COD). Absorbance measurements showed a bleaching of the effluent at wavelengths above 250nm, indicating loss of aromatic chromophores. Effluent turbidity also decreased. Surprisingly, there was no observable decrease in COD, within experimental error. This is attributed to the presence of bicarbonate and sulfate ions in the final effluent, which react with hydroxyl radicals and effectively block the oxidation of organics in the effluent. This was demonstrated by sonicating solutions of potassium hydrogen phthalate (KHP) containing chloride, bicarbonate, or sulfate ions, which are the major inorganic ions in the final effluent studied. A solution containing only 2.3mM KHP showed a 19% reduction in COD after 6h of sonication. An identical solution with 200ppm chloride also showed a 19% COD reduction. However, solutions with 700ppm sulfate and 400ppm bicarbonate showed COD reductions of 11% and 3%, respectively.

Objective: This study analyzed two methods of measuring the absorbing capacity of paper points (PP), testing the hypothesis that there is a positive correlation between the results from the percentage of increase mass (PIM) and the linear dye penetration (LDP) methods., Methods: The initial dry weight (IDW) of each PP was recorded using a digital balance before 1-mm introduction into one of the dye solutions, 1% methylene blue (MB) or 1% rodamine B (RB), for 10s. The PP's were removed from the solution and weighed (final weight - FW). PIM was calculated from the difference between FW and IDW (n=50). The LDP was measured using a stereomicroscope and a ruler (n=50). Data was statistically analyzed using the Pearson correlation and Student's t tests., Results: Moderate positive correlations between LDP and PIM methods were found using methylene blue (r=0.6356) and rodamine B (r=0.7743), partially confirming the study hypothesis, and suggesting that results from these two methods should be confronted carefully., Significance: The results of this study suggest that the most reliable method of measuring the absorbing capacity of paper points is the PIM and investigators should be aware of differences between the two research protocols when comparing results from these two methods (PIM and LDP).