Practical approaches for supporting informed consent in neonatal clinical trials.

The survival and health of preterm and critically ill infants have markedly improved over the past 50 years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials. CONCLUSION: The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Fetal lung hypoxia and energetic cell failure in the nitrofen-induced congenital diaphragmatic hernia rat model.

PURPOSE: Congenital diaphragmatic hernia (CDH) pathogenesis is poorly understood. We hypothesize that fetal CDH lungs are chronically hypoxic because of lung hypoplasia and tissue compression, affecting the cell bioenergetics as a possible explanation for abnormal lung development. METHODS: To investigate this theory, we conducted a study using the rat nitrofen model of CDH. We evaluated the bioenergetics status using H1 Nuclear magnetic resonance and studied the expression of enzymes involved in energy production, the hypoxia-inducible factor 1α, and the glucose transporter 1. RESULTS: The nitrofen-exposed lungs have increased levels of hypoxia-inducible factor 1α and the main fetal glucose transporter, more evident in the CDH lungs. We also found imbalanced AMP:ATP and ADP:ATP ratios, and a depleted energy cellular charge. Subsequent transcription levels and protein expression of the enzymes involved in bioenergetics confirm the attempt to prevent the energy collapse with the increase in lactate dehydrogenase C, pyruvate dehydrogenase kinase 1 and 2, adenosine monophosphate deaminase, AMP-activated protein kinase, calcium/calmodulin-dependent protein kinase 2, and liver kinase B1, while decreasing ATP synthase. CONCLUSION: Our study suggests that changes in energy production could play a role in CDH pathogenesis. If confirmed in other animal models and humans, this could lead to the development of novel therapies targeting the mitochondria to improve outcomes.

Resistance to loosening of intentionally shortened screws used to solve the unsuccessful removal of fractured prosthetic screws.

STATEMENT OF PROBLEM: Fractured prosthetic implant screws cannot be removed in all patients, ultimately leading to the removal of the implant. Whether an intentionally shortened prosthetic implant screw (SPIS) can provide adequate retention is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the resistance to loosening of SPISs engaging the remaining coronal internal threads as a possible solution to maintaining both implant and restoration. MATERIAL AND METHODS: Fifty grade V titanium SPISs were used to tighten 50 titanium transepithelial abutments on implants to 30 Ncm. The specimens were distributed into 5 groups (n=10) according to the conditions under which the screws were secured to manufacturer-recommended preload: dry (D), moistened in saliva (AS), moistened in chlorhexidine (CLHX), wrapped in polytetrafluoroethylene tape (PTFE), and resin cemented (RE). All groups were subjected to a cyclic loading test (240 000 cycles). The reverse torque value (RTV) of the SPIS was registered twice: 24 hours after initial tightening (T1); and after retightening and the cyclic loading test (T2). The resultant RTV was compared with the 30-Ncm tightening torque to assess torque loosening. The Kruskal-Wallis and Mann-Whitney tests were used for the comparisons between groups and the Wilcoxon test for the intragroup comparisons (α=.05 with Bonferroni correction). RESULTS: At T1, all groups found lower mean±standard deviation RTVs than the reference tightening torque (30 Ncm) (D 24.82±2.34 Ncm, AS 25.56±2.89 Ncm, PTFE 26.02±2.26 Ncm, CLHX 26.26±1.82 Ncm), except the resin-cemented group, which increased its RTV (RE 44.01±19.94 Ncm). At T2, all the groups found lower RTVs than the reference tightening torque, and the torque values at T1 (D 19.81±6.59 Ncm, CLHX 18.98±6.36 Ncm, AS 21.28±7.32 Ncm), with the exception of PTFE (24.07±3.41 Ncm) and RE (41.47±21.68 Ncm), where RTV was similar to that recorded at T1. At T1, significant differences were found among the groups (P=.024). At T2, after cyclic loading, the RE group found the highest RTV, reporting significant differences with the D and CHLX groups (P<.05) and statistically similar to the AS group (P=.068). CONCLUSIONS: PTFE-wrapped screws found similar RTVs after the fatigue test than dry, moistened with saliva, and moistened with chlorhexidine screws. Resin-cemented shortened prosthetic implant screws were found to be the most resistant to loosening after cyclic loading.

Novel DNA-based in situ hybridization method to detect Desmozoon lepeophtherii in Atlantic salmon tissues.

The microsporidian Desmozoon lepeophtherii Freeman and Sommerville, 2009 is considered significant in the pathogenesis of gill disease in Atlantic salmon (Salmo salar Linnaeus, 1758). Due to the difficulty in detecting D. lepeophtherii in tissue sections, infections are normally diagnosed by molecular methods, routine haematoxylin and eosin (H&E) stained gill tissue sections and the use of other histochemical stains and labels to confirm the presence of spores. An in situ hybridization (ISH) protocol specific for D. lepeophtherii was developed using DIG-labelled oligonucleotide probes. Diseased Atlantic salmon gills were analysed by ISH, calcofluor white (CW) and H&E. All methods showed high levels of specificity (100%) in their ability to detect D. lepeophtherii, but the sensitivity was higher with ISH (92%), compared with CW (64%) and the presence of microvesicles on H&E stained sections (52%). High levels of D. lepeophtherii spores were significantly associated (p < .05) with the development of D. lepeophtherii-associated pathology in the gills, with Ct values below 19 and over 100 microsporidia/10 mm2 of gill tissue (from the ISH counts) seemingly necessary for the development of microvesicles. The ISH method has the advantage over other histological techniques in that it allows all life stages of the microsporidian to be detected in infected salmon gill tissue sections.

Evaluation of Acidic Ionic Liquids as Catalysts for Furfural Production from Eucalyptus nitens Wood.

Eucalyptus nitens wood samples were subjected to hydrothermal processing to obtain soluble saccharides from the hemicellulosic fraction. The hemicellulose-derived saccharides were employed as substrates for furfural production in biphasic media made up of water, methyl isobutyl ketone, and one acidic ionic liquid (1-butyl-3-methylimidazolium hydrogen sulfate or 1-(3-sulfopropyl)-3-methylimidazolium hydrogen sulfate). The reactions were carried out in a microwave-heated reactor to assess the effects of the most influential variables. Under selected operational conditions, the molar conversions of the precursors into furfural were within the range of 77-86%. The catalysts conserved their activity after reutilization in five consecutive reaction cycles.

Amoebic gill disease and host response in Atlantic salmon (Salmo salar L.): A review.

Gill health is one of the main health challenges for Atlantic salmon (Salmo salar L.) mariculture worldwide, and amoebic gill disease (AGD), caused by the marine ectoprotozoan Neoparamoeba perurans, is currently one of the most significant diseases in terms of prevalence and economic impact. This review describes the host response of Atlantic salmon to the disease, focusing on the pathological changes, immune response and mechanisms underlying the prominent epithelial proliferation and mucus hypersecretion occurring in affected fish. Health management strategies and risk factors are also discussed.

In vitro comparison of the efficacy of two fractured implant-prosthesis screw extraction methods: Conventional versus mechanical.

STATEMENT OF PROBLEM: Implant-supported prostheses may be subject to esthetic, biological, or mechanical complications. Protocols for dealing with these mechanical problems are sparse. PURPOSE: The purpose of this in vitro study was to compare the efficacy of a mechanical system for extracting fractured implant-prosthesis screws with the conventional method. MATERIAL AND METHODS: A total of 60 screws were divided into 2 groups according to their morphology (flat screws with a smooth shaft and threaded apical area and screws with a completely threaded body) and subjected to fatiguing and static load testing until fracture. The specimens were assigned to 3 operators with varying levels of clinical experience (high, medium, low) in extracting fractured screws by using the conventional method (explorer and ultrasound device) and a mechanical method (extractor kit). The extraction event (whether the screw fragment was extracted or not within 10 minutes) was recorded, and the time taken to perform the extraction was measured for each method in relation to screw type, operator experience, and damage to the threads. The influence of screw morphology, extraction method, operator experience, and fracture type on the time needed to extract a screw fragment was assessed with the Mann-Whitney and Kruskal-Wallis tests. Thread damage was compared by using the Fisher's exact test and the Kruskal-Wallis test (α=.05). RESULTS: The mechanical method was more effective for screw extraction than the conventional method (P=.032). Screw morphology also had a significant influence on extraction, whereby the screw design with apical thread took less time to extract (P=.022). Coronal fractures had a higher probability of extraction than apical fractures (P=.05). CONCLUSIONS: Mechanical extraction is more effective for extracting fractured implant-prosthetic screws, showing a higher probability of extraction than the conventional method. Prosthetic fixing screws with a smooth shaft and threaded apical area are the easiest to extract.

Detection and characterisation of haplosporidian parasites of the blue mussel Mytilus edulis, including description of the novel parasite Minchinia mytili n. sp.

The edible mussel Mytilus edulis is a major aquaculture commodity in Europe, with 168000 t produced in 2015. A number of abundant, well characterised parasites of the species are known, though none are considered to cause significant mortality. Haplosporida (Rhizaria, Endomyxa) is an order of protistan parasites of aquatic invertebrates, the best studied of which are the oyster pathogens Haplosporidium nelsoni and Bonamia ostreae. While these species are well characterised within their hosts, the diversity, life-cycle and modes of transmission of haplosporidians are very poorly understood. Haplosporidian parasites have previously been reported from Mytilus spp., however the majority of these remain uncharacterised, and no molecular data exist for any species. In this study, we identified 2 novel haplosporidian parasites of M. edulis present in the UK. The first of these, observed by light microscopy and in situ hybridisation infecting the gills, mantle, gonadal tubules and digestive connective tissues of mussels in the Tamar estuary, England, we describe as Minchinia mytili on the basis of 18S sequence data. The second, observed infecting a single archive specimen collected in Loch Spelve, Mull, Scotland, infects the foot muscle, gills and connective tissue of the digestive gland. Sequence data places this parasite in an uncharacterised clade of sequences amplified from tropical bivalve guts and water samples, sister to H. nelsoni. Screening of water and sediment samples collected at the sample site in the Tamar estuary revealed the presence of both sequence types in the water column, suggesting host-free or planktonic life stages.

Local and systemic humoral immune response in farmed Atlantic salmon (Salmo salar L.) under a natural amoebic gill disease outbreak.

Amoebic gill disease (AGD), caused by the protozoan parasite Neoparamoeba perurans, is one of the most significant infectious diseases for Atlantic salmon (Salmo salar L.) mariculture. The present study investigated the humoral immune response (both local in gill mucus and systemic in serum) of farmed Atlantic salmon naturally infected with N. perurans in commercial sea pens, at two different stages of the disease and after freshwater treatment. Parameters analysed included activity of immune related enzymes (i.e. lysozyme, peroxidase, protease, anti-protease, esterase, alkaline phosphatase), IgM levels, and the terminal carbohydrate profile in the gill mucus. Overall, greater variations between groups were noted in the immune parameters determined in gill mucus than the equivalent in the serum. In gill mucus, IgM levels and peroxidase, lysozyme, esterase and protease activities were decreased in fish showing longer exposure time to the infection and higher disease severity, then showed a sequential increase after treatment. Results obtained highlight the capacity of gills to elicit a local response to the infection, indicate an impaired immune response at the later stages of the disease, and show partial reestablishment of the host immune status after freshwater treatment. In addition to providing data on the humoral response to AGD, this study increases knowledge on gill mucosal humoral immunity, since some of the parameters were analysed for the first time in gill mucus.

Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. DISCUSSION: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

JAK/STAT blockade reverses the malignant phenotype of Hodgkin and Reed-Sternberg cells.

Constitutive activation of the JAK/STAT pathway is a common phenomenon in classic Hodgkin lymphoma (cHL). The clinical potential of anti-JAK/STAT therapy is being explored in early-stage clinical trials. Notwithstanding, very little information is available about the complex biological consequences of this blockade. Here, we investigated the effects of JAK/STAT pharmacological inhibition on cHL cell models using ruxolitinib, a JAK 1/2 inhibitor that induces apoptosis by concentration- and time-dependent mechanisms. An unbiased whole-transcriptome approach identified expression of the anti-GCSF receptor (CSF3R) as a potential surrogate biomarker of JAK/STAT overactivation. In addition, longitudinal gene expression analyses provided further mechanistic information about pertinent biological pathways involved, including 37 gene pathways distributed in 3 main clusters: cluster 1 was characterized by upregulation of the G2/M checkpoint and major histocompatibility complex-related clusters; 2 additional clusters (2 and 3) showed a progressive downregulation of the tumor-promoting inflammation signatures: JAK/STAT and interleukin 1 (IL-1)/IL-4/IL-13/IL-17. Together, our results confirm the therapeutic potential of JAK/STAT inhibitors in cHL, identify CSF3R as a new biomarker, and provide supporting genetic data and mechanistic understanding.

Uterine sarcomas: clinical practice guidelines for diagnosis, treatment, and follow-up, by Spanish group for research on sarcomas (GEIS).

Uterine sarcomas are very infrequent and heterogeneous entities. Due to its rarity, pathological diagnosis, surgical management, and systemic treatment are challenging. Treatment decision process in these tumors should be taken in a multidisciplinary tumor board. Available evidence is low and, in many cases, based on case series or clinical trials in which these tumors have been included with other soft tissue sarcoma. In these guidelines, we have tried to summarize the most relevant evidence in the diagnosis, staging, pathological disparities, surgical management, systemic treatment, and follow-up of uterine sarcomas.

In Vitro Analysis of the Removability of Fractured Prosthetic Screws within Endosseous Implants Using Conventional and Mechanical Techniques.

STATEMENT OF PROBLEM: The extraction of fractured abutment screws can be a difficult challenge to overcome. PURPOSE: To compare the removal capacity, dental implant connection damage, and time required to remove the fractured abutment screws between three drilling techniques and a conventional method. MATERIALS AND METHODS: A total of 180 prefabricated screw-retained abutments were intentionally fractured in internal connection dental implants after being subjected to a cyclic load and a static compression load. Afterwards, three operators randomly removed the fractured abutment screws with the following drilling techniques and a conventional method: A: a conventional technique using an exploration probe and ultrasonic appliance (n = 45), Rhein83® (n = 45); B: Sanhigia® (n = 45); C: Phibo® (n = 45). Two-way ANOVA models were estimated to evaluate the mean time according to the method and operator used. RESULTS: The probability of removal of the screws with mobility was twelve times higher than that of the screws without mobility (OR = 12.4; p < 0.001). The success rate according to the operators did not show statistically significant differences (p = 0.371). The location of the fractured screw did not affect removal success (p = 0.530). The internal thread of the implant was affected after the removal process in 9.8% of the cases. The mean extraction time was 3.17 ± 2.52 min. The Rhein83® method showed a success rate of 84.4%, followed by the Phibo® and conventional methods (71.1%) and the Sanhigia® method (46.7%). CONCLUSIONS: The Rhein83® drilling technique increases the removal probability of fractured abutment screws. The initial mobility of the fragment is also a significant factor in the removal success.

EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation.

Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (χ(2) <0.001). Most cases showed an activated phenotype (95% non-germinal center (Hans algorithm); 78% activated B cell (Choi algorithm)). Clonality testing demonstrated IgH and/or K/Kde/L monoclonal rearrangements in 64% of cases and clonal T-cell populations in 24% of cases. C-MYC (1 case), BCL6 (2 cases) or IgH (3 cases) translocations were detected by FISH in 18% cases. These tumors had a poor overall survival and progression-free survival (the estimated 2-year overall survival was 40 ± 10% and the estimated 2-year progression-free survival was 36 ± 9%). Thus, alternative therapies, based on the tumor biology, need to be tested in patients with EBV-positive diffuse large B-cell lymphoma of the elderly.

In vitro assessment of the chemotherapeutic action of a specific hydrogen peroxide, peracetic, acetic, and peroctanoic acid-based formulation against the free-living stages of Ichthyophthirius multifiliis (Ciliophora).

Traditionally, malachite green administrated as in-bath treatment was the most effective and common strategy used in freshwater aquaculture systems to control infections of the ciliate protozoan parasite Ichthyophthirius multifiliis Fouquet, 1876. After the ban of malachite green in the USA and Europe to be used in fish for human consumption, there has been extensive research destined to find efficacious replacements. Recently, peracetic acid-based compounds have demonstrated a strong cytotoxic effect in vitro and in vivo against I. multifiliis. In the present study, we tested the efficacy of a hydrogen peroxide, peracetic, acetic and peroctanoic acid-based formulation (HPPAPA) to eliminate the free-living stages of I. multifiliis (tomonts, cysts and theronts). The results obtained showed that the administration of low doses (8, 12 or 15 mg/l) of a specific HPPAPA-based product during a short window of exposure (60 min) kills nearly all free-living stages of I. multifiliis (theronts, tomonts and cysts) within the window of treatment (∼100% mortality for all the stages; one-way ANOVA, P ≤ 0.001). Of note, even the lowest concentration of HPPAPA tested (8 mg/l) was able to disrupt normal cyst development and therefore theront release. The demonstrated in vitro efficacy of the peracetic acid-based product tested on the present study suggests its great potential to control I. multifiliis infections in commercial aquacultural systems.

Persistently positive PCR SARS-CoV-2 at low cycle threshold in an immunosuppressed patient.

We describe the very prolonged course of the disease in an immunosuppressed patient with persistently positive PCR against SARS-CoV-2 with low cycle threshold for at least 114 days.

Cognitive Dysfunction in Multiple Sclerosis: Educational Level as a Protective Factor.

Most people with MS experience cognitive deficits especially in attention, memory, information processing, and executive functions, negatively impacting on their quality of life. Cognitive variables of short-term memory, logical memory, and verbal fluency in 65 patients with multiple sclerosis (MS) were analysed in conjunction with sociodemographic variables such as sex, age, and educational level that might influence disease progression. We found that psychoeducational variables exerted a significant effect on the cognitive status of patients with MS. Thus, when considering sex, age, educational level, and type of MS (SPMS or RRMS), tests for between-subject effects revealed statistically significant differences in all three cognitive variables. In addition, we found that the type of MS and time since onset also generated significant cognitive differences. Our study shows that educational achievement or level is a protective factor against the disease, acting as a source of intellectual enrichment that promotes cognitive reserve in patients with MS. Further longitudinal studies assessing disease progression and prognosis in patients with MS would be useful in order to determine the specific importance of these variables in such patients and in strategies that could enhance their performance in neuropsychological assessment tasks.

Prospective study of monolithic zirconia crowns: clinical behavior and survival rate at a 5-year follow-up.

Purpose To evaluate the clinical behavior and survival of full coverage monolithic zirconia crowns on posterior teeth over a 5-year follow-up.Methods Fifty patients were recruited and underwent restoration with a Lava Plus monolithic zirconia crown (Lava™ Frame Zirconia, 3M Espe, Germany) on premolars or molars. Patients were monitored over a 5-year follow-up (2014-19), recording any biological and/or mechanical complications; these data were used to estimate the crowns' success rate. Periodontal clinical parameters were recorded (pocket probing depth (PPD), plaque index (PLI), bleeding on probing (BOP), and gingival recession (GR)). Wear to the zirconia crowns and antagonist teeth were also evaluated with Geomagic software (3D Systems, U.S.A.). Patients' satisfaction with treatment was evaluated in a questionnaire.Results For the 50 monolithic zirconia crowns analyzed, the survival rate was 98% after 5 years. Only 6% of the crowns presented some type of complication (two debonding and one root fracture). No fracture or fissures were detected. GR and BOP were the only clinical parameters found to be significantly greater around teeth restored with crowns. The monolithic zirconia crowns suffered less wear than the enamel of antagonist teeth. Patient's general satisfaction with treatment was high.Conclusions Monolithic zirconia crowns on posterior teeth are a highly predictable treatment option, with a high survival rate. The single treatment failure was due to a biological complication arising from root fracture. This treatment may be recommended as a treatment that conserves dental structure, and requires minimal dental preparation.

Manufacture of Platform Chemicals from Pine Wood Polysaccharides in Media Containing Acidic Ionic Liquids.

Pinus pinaster wood samples were subjected to chemical processing for manufacturing furans and organic acids from the polysaccharide fractions (cellulose and hemicellulose). The operation was performed in a single reaction stage at 180 or 190 °C, using a microwave reactor. The reaction media contained wood, water, methyl isobutyl ketone, and an acidic ionic liquid, which acted as a catalyst. In media catalyzed with 1-butyl-3-methylimidazolium hydrogen sulfate, up to 60.5% pentosan conversion into furfural was achieved, but the conversions of cellulose and (galacto) glucomannan in levulinic acid were low. Improved results were achieved when AILs bearing a sulfonated alkyl chain were employed as catalysts. In media containing 1-(3-sulfopropyl)-3-methylimidazolium hydrogen sulfate as a catalyst, near quantitative conversion of pentosans into furfural was achieved at a short reaction time (7.5 min), together with 32.8% conversion of hexosans into levulinic acid. Longer reaction times improved the production of organic acids, but resulted in some furfural consumption. A similar reaction pattern was observed in experiments using 1-(3-sulfobutyl)-3-methylimidazolium hydrogen sulfate as a catalyst.

Technologies for Eucalyptus wood processing in the scope of biorefineries: A comprehensive review.

Eucalyptus is the most widely planted type of hardwoods, and represents an important biomass source for the production of fuels, chemicals, and materials. Its industrial benefit can be achieved by processes following the biorefinery concept, which is based on the selective separation ("fractionation") of the major components (hemicelluloses, cellulose and lignin), and on the generation of added-value from the resulting fractions. This article provides a in-depth assessment on the composition of Eucalyptus wood and a critical evaluation of selected technologies allowing its overall exploitation. These latter include treatments with organosolvents and with emerging fractionation agents (ionic liquids and deep eutectic solvents). The comparative evaluation of the diverse processing technologies is carried out in terms of degree of fractionation, yields and selectivities. The weak and strong points, challenges, and opportunities of the diverse fractionation methods are identified, focusing on the integral utilization of the feedstocks.