In this study, the desirable amine solution for the natural gas sweetening process was selected. The four parameters of yield, availability, cost, and operational conditions were selected as criteria of this process. Also, seven alternatives (amine solution) were proposed for ascertaining the best amine solution. The AHP results indicated that the MDEA as an alternative and the cost as criteria have the highest preference with 21% and 53%, respectively, in comparison to other criteria and alternatives. According to the objectives functions (The reduction of acid gas contents and reboiler duty), the simulation results reveal the best of feed gas temperature, and MDEA concentration is 30 ºC and 39 wt.%, respectively. In this condition, the MDEA solution consumption and reboiler duty reduced by 5% and approximately 0.04% as compared to the initial conditions, respectively. The amount of hydrogen sulfide and carbon dioxide achieved 2.4 and 88 ppm in the optimal condition.

The increase in healthy lifestyle has resulted in an increased demand of both the avocado fruit and its oil production. The growth in demand has prompted a need for an industry expansion and an efficient process that produces high quality oil. This study therefore explored solid-liquid oil extraction using hexane at different process parameters to determine the optimum conditions which produce a higher yield of avocado oil. Furthermore, the study analysed oil produced from different parameters and evaluated its stability and fatty acid content. The oil stability was evaluated by analyzing oxidative stability and peroxide value. Observations at higher temperatures showed oil production of high stability containing lower content of trans fats, which are undesired and detrimental for human consumption. The efficient extraction conditions found with the aid of response surface methodology (RSM) optimization were found to be a solvent ratio of 1.53 ml/g at a temperature of 60 ̵̊ C for 128 minutes. The overall aim of the study was to improve the efficiency of the extraction process by increasing the yield of oil without compromising quality. The oil production process was found to be efficient such that the industry can be expanded to have avocado cultivars dedicated to oil production using hexane.

Muitos equipamentos são movidos por motores elétricos que usam correias como sistema de transmissão flexível. Embora as correias apresentem um perfil em V, existem também as correias síncronas, que oferecem maior precisão na rotação. No entanto, há poucas atualizações na literatura acadêmica sobre a seleção de correias, o que pode levar a erros na seleção e cálculo. Para resolver esse problema, este artigo apresenta os cálculos consolidados da literatura, atualizados com gráficos e fatores padronizados pelos principais fabricantes de correias. As normas internacionais usadas para a fabricação de correias e polias também são abordadas. Por fim, um estudo de caso é apresentado para consolidar o procedimento de seleção correta de uma correia de transmissão flexível.

ABSTRACT Employee job reviews contain information on many firm characteristics that are unobservable to the public. Job review sites such as Glassdoor and Indeed are used by job hunters and current employees to inform each other of prevailing workplace culture. I collect over 1.2 million job reviews from Indeed.com, matched to firm level data was procured from Compustat. I use machine learning and natural language processing methods to obtain qualitative data about firms across the dimensions of job satisfaction and management sentiment. In the cross-section, I find that a 1% increase in ratings increases market value by approximately 0.68-0.73%, revenue by 0.62-1.01%. However, increases in management sentiment may have a non-monotonic effect on financial performance. These non-monotonic relationships are also present in first difference results, which show that there may be trade-offs involved in improving financial results and workplace culture.

Ecological research is highlighting different kinds of issues concerning biodiversity conservation policies. Based on a historical study on protected areas, we suggest that these issues are not caused by a lack of knowledge or technical tools but rather by a misuse of ecological knowledge during the implementation of policy instruments. We strongly believe that determining the conditions under which ecological science can enlighten policy decisions is now necessary to address current biodiversity conservation issues. This can only be achieved through the promotion of interdisciplinary research.

Biodiversity losses may impact ecosystem processes via food-webs. We hypothesized that time can modulate feedbacks among plant functional diversity, resource quality, prey and predator populations and litter turnover. Thereto we incubated coarse deadwood of 34 woody species, with and without (wood-feeding) termite access, in Chinese subtropical forests with and without (termite-feeding) pangolins. The results supported our hypothesis: in the first 12 months, termites amplified the positive linear relationship between % wood mass loss and initial wood quality (along a wood economics spectrum, WES). In contrast, between 12 and 18 months, termite-mediated consumption, and associated wood mass loss, showed a humpback relation with the initial WES. This shift in termite preference of deadwood species along the WES indicated complementary food availability to termites through time, thereby promoting both termites and endangered pangolins. Thus, plant functional diversity through time can help to sustain keystone consumers, predators and their effects on carbon turnover.

Biological invasions have long fascinated ecologists as they fundamentally alter ecological communities, often in surprising ways. The demography of interacting native and exotic populations are core drivers of invasions. Demographic models estimate the strength of species interactions but have several shortcomings, including disregarding facilitation and focusing only on competition, disregarding individual-level variance in demographic parameters, and focusing on one exotic species at a time. In this study, we investigate the fitness outcomes of eleven native and exotic species from a diverse annual plant community in Western Australia. We use a Bayesian demographic modelling approach that integrates demographic stochasticity and facilitation. Facilitation mediated by exotic species played an integral role in the invaded community, but demographic stochasticity caused many species interactions to vary from facilitative to competitive, regardless of abiotic conditions. Our approach reveals variation that could be responsible for the diverse and unexpected impacts of exotic species on recipient communities.

Introduction: To evaluate the long-term (5 years) effects of perioperative briefing and debriefing on team climate. We explored the barriers and facilitators of the performance of perioperative briefing and debriefing to explain its effects on team climate and to make recommendations for further improvement of surgical safety tools. Methods: A mixed-method evaluation study was carried out among surgical staff at a tertiary care university hospital with 593-bed capacity in the Netherlands. Thirteen surgical teams were included. Team climate inventory and a standardised evaluation questionnaire were used to measure team climate (primary outcome) and experiences with perioperative briefing and debriefing (secondary outcome), respectively. Thirteen surgical team members participated in a semi-structured interview to explore barriers and facilitators of the performance of perioperative briefing and debriefing. Results: The dimension ‘participative safety’ increased significantly 5 years after the implementation of perioperative briefing and debriefing (p = 0.02 (95% confidence interval 1.18–9.25)). Perioperative briefing and debriefing was considered a useful method for improving and sustaining participative safety and cooperation within surgical teams. The positive aspects of briefing were that shared agreements made at the start of the day and that briefing enabled participants to work as a team. Participants were less satisfied regarding debriefing, mostly due to the lack of a sense of urgency and a lack of a safe culture for feedback. Briefing and debriefing had less influence on efficiency. Conclusions: Although perioperative briefing and debriefing improves participative safety, the intervention will become more effective for maintaining team climate when teams are complete, irrelevant questions are substituted by customised ones and when there is a safer culture for feedback.

Natural hybridization is a common key evolutionary process and a long-standing topic in the plant taxon. Hybrid zones, where two closely related species interact, can provide an avenue to insight the process, illuminating the maintenance of the taxon diversity. Incomplete isolation barriers between Ligularia species generally form hybrid zones. In this study, we used the double digest restriction-site associated DNA sequencing technology (ddRAD-seq) to examine genetic structure and estimate introgression in four newly discovered hybrid zones between L. tongolensis and L. cymbulifera. Our results showed high differentiation between parental species, whereas pairwise FST between parents and their hybrids was low, further corroborating sympatric site form hybrid zones. Moreover, most F1 hybrid individuals were observed within the four hybrid zones implying the presence of substantial barriers to interbreeding. An analysis of genomic clines indicated that a large fraction of loci deviated from a model of neutral introgression in the four hybrid zones, of which most loci exhibited selection favouring L. cymbulifera genotypes. Our analysis demonstrated bidirectional but asymmetric introgression appearing in the four hybrid zones. The different habitats among four hybrid zones may affect isolation barriers between both species. Natural hybridization with post-zygotic isolation barriers may significantly contribute to the diversification of Ligularia in the HMR.

Materials and Methods: In the present study, 36 male BALB/c mice aged 6-8 weeks were randomly divided into four groups: the control group (PBS), the T. spiralis infection group (TS), the C. rodentium-induced colon inflammation model group (CR) and the T. spiralis pre-infected and C. rodentium induced colitis group (TS+CR). The mice were sacrificed 7 and 14 days after the establishment of the model. The changes in various colitis indicators were used to investigate the effect of T. spiralis infection on the C. rodentium-induced mouse CD model. Results: The results showed that the weight, DAI score, and macroscopic and microscopic colon damage in the TS+CR group was significantly decreased compared with that observed in the CR group. Flow cytometry results revealed that T. spiralis infection could reduce the expression of IFN-γ, IL-17 and IL-12 and increase that of IL-4 and IL-10 in colitis mice. Compared with that observed in the control group, the number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleens and mesenteric lymph nodes (MLNs) of mice in the TS group was increased (P<0.01). Compared with that observed in the TS group mice, the expression of CD4+CD25+Foxp3+Tregs in the spleens and MLNs of the TS+CR group mice was decreased (P<0.05). ELISA results revealed that compared with the control group, the TS group produced a strong IgG1 response (P<0.001) and low level of IgG2a response (P>0.05), while increased expression of IgG2a in serum was detected in the CR group mice (P<0.05).

Rabies is a viral zoonotic disease present in two thirds of all countries, and causes the death of one person every 10 minutes (~70,000 deaths/year). The reservoirs of the Rabies Virus (RABV) are bats and canids, and it has also been found in other animals, including Cerdocyon thous (crab-eating fox) and Pseudalopex vetulus (hoary fox). Here we used Next Generation Sequencing (NGS), phylogenetic, and in vitro/in vivo analyses, to characterized the genome of a new subtype of RABV circulating in foxes of the Northeastern region of Brazil. We verified that although these variants were similar to existing strains from wild canids and domestic canines from Brazil, the samples contained escape mutants, suggesting that it was a heterogeneous virus population. In all, we used several molecular techniques to characterize a new RABV strain circulating in wild-foxes in Northeastern Brazil, and verified still manifested its notorious pathogenic characteristics.

Completion extracardiac Fontan is the final stage palliation for functional single ventricle. It has been associated with less incidence of atrial arrhythmias and more laminar flow in the Fontan Pathway. Here, we present our technique of off-pump extracardiac Fontan.

The phenomenon of resistance of Escherichia coli strains in free-living animals has been constantly expanding in recent years. However, the data is still fragmented and, due to the growing threat to public health, there is a constant need to search for and analyse new reservoirs and indicate their role and importance in the circulation of resistance genes. Therefore, the target group in this study were free-living non-predatory animals as reservoirs of drug-resistant and potentially virulent E. coli strains. For isolation, we used a combination of selective media with four antimicrobials. After additional two-stage analysis of strain similarity, we obtained 70 different isolates, including 71.4% of multidrug-resistant strains. In strains isolated from all species of animals, we determined high resistance to ampicillin (95.7%), tetracycline (64.3%), streptomycin (51.4%), and chloramphenicol (38.6%). Every third of the E. coli-positive individual was a carrier of more than one resistant clone. Moreover, four isolates among the resistant strains had the ExPEC pathotype, two had the ETEC pathotype, and another two represented EHEC. Our study confirmed that not only free-living predatory animals are reservoirs of resistance but also many synanthropic species of herbivores and omnivores contribute substantially to the spread of resistant and virulent E. coli strains.

Several studies have been carried out in recent months by the World Scientific Community on the novel coronavirus, responsible for the current COVID-19 pandemic. The most relevant works on the main trends were related to the disease, treatment/prevention, and management of COVID-19. Most of the articles focused on understanding the disease, addressing aspects related to its transmission, viral activity period, symptoms and health complications, risk factors, and estimative of new cases and deaths. The papers also focused on the treatment/prevention and management of COVID-19. Several drugs and alternative treatments have been investigated such as the convalescent plasma transfusion and stem cell transplantation, while an efficient vaccine is developed. Prevention and control measures such as social isolation and immediate case identification were also investigated. Thus, this work contributed to the determination of the development level and the research evolution on COVID-19, summarizing the main trends observed by experts on the subject in the first half of 2020.

The aim of this study was to investigate the fracture and hardening behaviors of TRIP steel at different heat-treatments using the uniaxial tensile test and the necking correction method. The uniaxial tensile tests were performed on samples heat-treated through different procedures and strain rates in the range of 0.005--5 s-1. It was observed that the strain rate slightly affects the formability of TRIP steel in different heat-treatment procedures. The obtained results showed that the H3 sample had the highest strain fracture. The nucleation and growth of voids, as well as the dynamic equilibrium between strain hardening and recovery, were reasons for fracture strain increment from 0.005 to 0.1 s-1. However, fracture strain decreased at the strain rate of 0.1--5 s-1 due to the decrease of ductility. Also, TRIP steel characterizations were used for modeling the displacement and stress of the anti-roll bar by ANSYS parametric language and Solid-Works. The displacement and stress results of TRIP steel were compared to other materials.

Influenza A virus (IAV) outbreaks constitute a constant threat to public health and pose a remarkable impact on socio-economic systems worldwide. Interactions between wild and domestic birds, humans, and swine can lead to spillover events. Backyard livestock systems in proximity to wetlands represent a high-risk area for viral spread. However, some gaps remain in our knowledge of IAV transmission at the wildlife – livestock interface in Mexico. Hence, the study aimed at molecular identification and phylogenetic characterization of IAV in the wild duck – backyard livestock interface at a wetland of Mexico. A total of 875 animals were tested by real-time RT-PCR (qRT-PCR). We detected IAV in 3.68% of the wild ducks sampled during the winter season 2016 – 2017. Nonetheless, the samples obtained from backyard poultry and swine tested negative. The highest IAV frequency (11.10%) was found in the Mexican duck (Anas diazi). Subtypes H1N1, H3N2, and H5N2 were detected. Phylogenetic analysis of influenza viruses isolated from wild ducks of the Lerma marshes revealed that hemagglutinin (HA) gene sequences were related to waterfowl, swine, and poultry IAV strains previously isolated in the United States and Mexico. In conclusion, the co-circulation of three IAV subtypes in wild ducks close to backyard farms in Mexico, as well as, the local identification of HA gene sequences genetically related to Mexican livestock IAV strains and also to North American waterfowl IAV strains, highlight the importance of the Lerma marshes for influenza surveillance given the close interaction among wild birds, poultry, pigs, and humans.

Baricitinib is a promising drug in COVID-19 pneumonia. The aim of this study is to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥ 95% (in room air) and return in normal breathing function were lower in case group than the control group [29.4% (n = 17)/10% (n = 20), P < 0.05; 11.8% (n = 17)/5% (n = 20), P > 0.05), respectively]. The requirement of intensive care unit and mechanical ventilation support were higher in control group than the case group. Thus, an additional loading dose of baricitinib revealed better clinical outcome in COVID-19 pneumonia.

Background: Computed tomography (CT) is a useful tool for the identification of calcified lesions in the aorta. However, no quantitative evaluation has been established to assess the applicability of simple anastomosis preoperatively. We conducted this retrospective study to establish a reference range of the maximal CT value for application of simple anastomosis. Methods: 122 consecutive patients underwent replacement of the thoracic aorta between 2007-2011, excluding those with acute aortic dissection. The patients were divided into two groups: those who could undergo simple anastomosis (Simple group:n=105), and those who required endarterectomy prior to anastomosis (Manipulation group:n=17). The maximal CT value at the anastomosis site was calculated by an imaging software. Results: The mean maximal CT value (Hounsfield unit: HU) was significantly higher in the Manipulation group (638.1 ± 269.5 [166-1304]) than in the Simple group (94.7 ± 171.5 [0-790]) (p<0.0001). The maximal CT value enabled us to predict the simple anastomosis with the area under the receiver operating characteristic curve of 0.96 (p<0.0001). The cut-off value was 325 HU (sensitivity 94.1%, specificity 81.7%). The 10-year survival rate was significant lower in the Manupilation group (11.8%) than in the Simple group (43.2%). In the multivariate analysis, age (Hazard Ratio [HR]:1.073), Hypertension (HR:2.382) and maximal CT value (HR:1.001) were independently associated with long-term mortality. Conclusions: Preoperative evaluation of the maximal CT value is a useful tool in predicting whether simple anastomosis is applicable or not, in the thoracic aortic surgery. Maximal CT value is a risk factor for long-term mortality.

As an important soil carbon pool in Qinghai-Tibet Plateau (QTP), alpine peatland are extremely sensitive to global change. Duration of drainage and water table drawdown accelerate peatland degradation as the soils are no longer protected by anaerobic condition, which may worsen under climate warming. Hence, the purpose of our study was to evaluate the effect of drainage on microbial characteristics, greenhouse gas (GHG) emissions and their influencing factors, and further analyze whether the the variability of GHG emissions increases with warming. The results showed that the influence of water table drawdown on microbial communities were greater than that of duration of drainage. Both the fungal and prokaryotic community compositions varied with water table gradient, and soil microbiota may served as a biomarker to analyze the differences in GHG emissions among three different water table treatments. Intriguingly, the GHG emission decreased with the increase of drainage age, while water table drawdown reduced the CO2 and CH4 emission rates, and increased N2O emission rates. In addition, high temperature increased CO2 by 75% and N2O by 42%, but not significantly decreased the CH4 emission rates. Structural equation modeling showed that microbe was the primary factor affecting GHG emissions from drained peatlands, especially prokaryotes. Overall, our results indicate that water table has a greater impact on GHG emissions than duration of drainage, and the variability of GHG emissions increases with warming.

Background and Purpose: Obesity and Type 2 Diabetes are major causes of morbidity-mortality characterized by mitochondrial dysfunction and oxidative-nitrosative stress. Despite intensive research, the events that cause the onset and progression of these diseases are not completely understood. Herein, we investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. Experimental Approach: Mitochondrial dynamics and biogenesis were evaluated in epididymal white adipose tissue and adipocytes from ob/ob mice, an animal model of obesity and diabetes, pharmacological treatment with mdvi-1, a selective inhibitor of Drp1 and leptin. Key Results: A decrease of Mfn2 and OPA-1 protein expression and an increase in Drp1- protein levels were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals. The content of mitochondrial DNA and mRNA expression of PGC-1α, both parameters of mitochondrial biogenesis, were reduced in ob/ob mice. The treatment with leptin or mdvi-1 (Drp1 inhibitor) significantly increased abnormal biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, and adipogenesis, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdvi-1 increase substrates oxidation while in vivo determination of blood glucose showed decreased blood glucose concentration by 50 % in ob/ob mice, almost to the wt level. Conclusion and Implications: In light of these results, pharmacological targeting of Drp1 may be a potential novel therapeutic tool for obesity and diabetes.

Environmental DNA (eDNA) has increasingly been used in the surveillance of imperiled aquatic species. Despite recent efforts in drawing genetic material from the environment, there are still pitfalls surrounding this field. We created a novel protocol which implements loop-mediated isothermal amplification (LAMP) to detect target DNA. Our methods are applied here in the surveillance of Etheostoma trisella, the Trispot Darter, a freshwater fish that recently received protection under the U.S. Endangered Species Act. Water samples (n = 256) were collected at sites in Alabama and Georgia to determine whether E. trisella still occupies historic sites and whether it inhabits previously unknown areas. We found evidence of E. trisella presence in 69 water samples while 187 were negative. Our LAMP protocol is capable of amplifying low quantities of DNA in the water, and is a robust technique for freshwater species surveillance. Verification of positive results from eDNA experiments is essential to confirm reaction reliability. Application of methods such as ours are necessary for recognizing species under threat that require conservation.

Dear Editor, We really appreciate MN van Ijsselmuiden et al. for their efforts in conducting the first ever multicentre randomized controlled trial to compare laparoscopic sacrohysteropexy (LSH) versus sacrospinous hysteropexy (SSHP) .1 It has raised my queries and questions regarding the methodology and results of this trial. I would like to know the reasons to include the patients with history of previous pelvic floor or prolapse surgery in the exclusion criteria. If those above patients were randomly allocated into two surgical group equally, would it have impacts over the study result or design? Moreover, we are really interested and keen to know how to perform the anterior colporrhaphy and posterior colporrhaphy though laparoscopic method as mentioned in the article.There are more patients presented with anterior vaginal wall prolapse: POP-Q stage- Aa or Ba > 0 (LSH group:81%; SSHP group:72.6%) when compared to apical prolapse (LSH group:46.6%; SSHP:45.6%) in Table 1. It seems that the majority of study population had combined anterior and apical compartment prolapse but not with solely apical prolapse. Furthermore, Table 2 showed that overall anterior compartment failure rates are 50.9% and 56.9% in LSH group and SSHP group respectively in 1-year follow-up interval. The failure rate is extraordinarily high compared with previous study.2 Hysteropexy surgeries are useful to treat patients with sorely apical prolapse but not with patients with combine anterior and apical compartment prolapse with prominent cystocele. In controversy, a large majority were satisfied with the one year surgical results and would recommend the surgery to someone else (LSH: 87.7%; SSHP: 89.7%) even though there was a high recurrence rate of anterior wall prolapse in one year follow-up.In the statistical analysis section, there were significantly more additional anterior vaginal wall repairs in the SSHP group compared to LSH group (SSHP: n = 61, 98.4%; LSH: n = 55, 85.9%, P = 0.010). I would like to know how this small number difference (61-55=6) in these two groups can cause significant difference in P value and how to calculate this P value. This trial assumes a failure rate of 3% based on outcomes of SSHP in a previous prospective study. However, the data population is relatively small while the non-inferiority margin was set at 10%.The primary outcome is defined as a composite outcome of surgical failure of the apical compartment at 12 months’ follow-up, defined as recurrence of uterine prolapse (POP-Q ≥ stage 2). Surgical success was defined as no prolapse beyond the hymen. According to POP-Q stage system, POP-Q stage 2 is defined as most distal prolapse is between 1 cm above and 1 cm beyond hymen.3 The most prominent prolapse which descends beyond hymen would be also considered as stage 2 prolapse. It elicits clinical controversy and conflicts in the definition between surgical failure and success. We hope that this letter will deliver the message that precise preoperative patient selection and study design are crucial as they may have critical impacts over clinical outcomes and treatment success.Min-syuan Huang,2, 3 Zi-Xi Loo,1Kun- Ling Lin,1, 2 Cheng-Yu Long1, 21. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan3. Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan

Dear editor/Sir,We thank Song et al. for their insightful comments (1) on our article (2) and commend them for their study about human papillomavirus (HPV)-genotyping on self-samples and their analysis on different triage strategies for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (3). They report that cytology on physician-sampled material has a sensitivity of 74.8% for detecting CIN2+, while HPV-genotyping for 16/18 has a sensitivity of 52.6% for detecting CIN2+. This means that HPV-genotyping in their hands, is still inferior to cytology testing and cannot fully replace this triage strategy. However, adding HPV-genotyping to cytology testing could increase the sensitivity, as has been described by others as well. While our study shows that reflex cytology on self-samples cannot replace triage with regular cytology for HPV-positive women, because of the low sensitivity of 29.4% for detecting CIN2+, it is valuable as an additional method for triage (2). With a positive predictive value (PPV) of 68.1% for detecting CIN2+ it is effective to refer HPV-positive women with abnormal cytology on self-sampling directly for colposcopic evaluation without the requirement of an extra visit to the general practitioner. A PPV of 21.2% for HPV-genotyping for 16/18 on self-samples for detecting CIN2+ is not enough to refer these women directly for colposcopy. We agree that cost-effectiveness is important. It is not sure if 15% of direct referral will completely cover the costs for 85% of double cytology testing. As the collection in PreservCyt (Cytyc Corporation, Boxborough, MA, USA) has already been performed for HPV-testing on the self-samples, extra costs will include the use of ThinPrep slides (Hologic Inc, Marlborough, MA, USA) and cytotechnicians’ time for analysing the slides. On the other hand, there will be a reduction in costs for consulting the general practitioner and for regular cytology testing, including material costs (Cervex brush (Rovers® Medical Devices B.V., Oss, the Netherlands), PreservCyt jar, ThinPrep slide), transportation costs, and cytotechnicians’ time for analysing the slides. However, besides cost-effectiveness, patient comfort is at least as important, as well as reduction in loss-to-follow-up and diagnostic delay, in which the latter also positively influences the costs. It remains a challenge to find a triage method on HPV-positive self-samples which could fully replace regular cytology. Molecular tests, such as methylation markers and microRNA detection, are promising future triage methods (4, 5). They are more objective than cytology testing and highly reproducible, however not ready yet for full implementation in cervical cancer screening. Further research on self-samples is warranted to find an optimal triage strategy. Until then, reflex cytology on self-samples could be easily implemented in the current screening programme and improve cervical cancer prevention.Diede L Loopik 1; Willem JG Melchers 2; Judith EM Vedder 3; Adriaan JC van den Brule4; Leon FAG Massuger 1; Ruud LM Bekkers5; Albert G Siebers 3,61 Department of Obstetrics and Gynaecology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;2 Department of Medical Microbiology, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;3 Department of Pathology, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;4 Department of Pathology, Lab for Molecular Diagnostics, Pathologie-DNA, Jeroen Bosch Hospital, PO Box 90153, 5200ME,‘s-Hertogenbosch, the Netherlands; 5 Department of Obstetrics and Gynaecology, Catharina Hospital, PO Box 1350, 5602ZA, Eindhoven, the Netherlands; 6 PALGA, the nationwide network and registry of histo- and cytopathology, Randhoeve 225a, 3995 GA, Houten, the NetherlandsPresent address Ruud LM Bekkers: GROW, School for Oncology & Developmental Biology, Maastricht University Medical Centre, PO Box 616, 6200MD, Maastricht, the Netherlands

Prostate cancer (PCa) is the second most common malignancy in men, and androgen deprivation therapy (ADT) is the first-line therapy. However, most cases will eventually develop into castration-resistant prostate cancer (CRPC) after ADT treatment. Enzalutamide (Enz) is a second-generation androgen receptor inhibitor approved by the Food and Drug Administration to treat patients with CRPC. Unfortunately, patients receiving Enz treatment will ultimately develop resistance via various complicated mechanisms. In this review, we introduce the emerging information on resistance mechanisms, including androgen receptor-related signalling pathways, glucocorticoid receptor-related pathways, and metabolic mechanisms. Notably, lineage plasticity and phenotype switching, gene polymorphisms, and the relationship between microRNAs and drug resistance are addressed. Furthermore, potential therapeutic strategies for Enz-resistant CRPC treatment are suggested, which can help in the discovery of more effective and specific regimens to overcome Enz resistance.