Consistent changes in muscle phenotype and mitochondrial abundance underlie dive performance across multiple lineages of diving ducks.

Diving animals must sustain high muscle activity with finite oxygen (O2) to forage underwater. Studies have shown that some diving mammals exhibit changes in the metabolic phenotype of locomotory muscles compared to non-divers, but the pervasiveness of such changes across diving animals is unclear, particularly among diving birds. Here, we examine whether changes in muscle phenotype and mitochondrial abundance are associated with dive capacity across 17 species of ducks from three distinct evolutionary clades (tribes) in the subfamily Anatinae - the longest diving sea ducks, the mid-tier diving pochards, and the non-diving dabblers. In the gastrocnemius (the primary swimming and diving muscle), mitochondrial volume density in both oxidative and glycolytic fiber types were 70% and 30% higher in sea ducks compared to dabblers, respectively. These differences were associated with preferential proliferation of the subsarcolemmal subfraction, the mitochondria adjacent to the cell membrane and nearest to capillaries, relative to the intermyofibrillar subfraction. Capillary density and capillary-to-fiber ratio were positively correlated with mitochondrial volume density, with no variation in the density of oxidative fiber types across tribes. In the pectoralis, sea ducks had greater abundance of oxidative fiber types than dabblers, whereas pochards were intermediate between the two. These data suggest that skeletal muscles of sea ducks have a heightened capacity for aerobic metabolism and an enhanced ability to utilize O2 stores in the blood and muscle while diving.

The role of the heart in the evolution of aerobic performance.

Aerobic metabolism underlies vital traits such as locomotion and thermogenesis, and aerobic capacity influences fitness in many animals. The heart is a key determinant of aerobic capacity, but the relative influence of cardiac output versus other steps in the O2 transport pathway remains contentious. In this Commentary, we consider this issue by examining the mechanistic basis for adaptive increases in aerobic capacity (thermogenic V̇O2,max; also called summit metabolism) in deer mice (Peromyscus maniculatus) native to high altitude. Thermogenic V̇O2,max is increased by acclimation to cold hypoxia (simulating high-altitude conditions), and high-altitude populations generally have greater V̇O2,max than their low-altitude counterparts. This plastic and evolved variation in V̇O2,max is associated with corresponding variation in maximal cardiac output, along with variation in other traits across the O2 pathway (e.g. arterial O2 saturation, blood haemoglobin content and O2 affinity, tissue O2 extraction, tissue oxidative capacity). By applying fundamental principles of gas exchange, we show that the relative influence of cardiac output on V̇O2,max depends on the O2 diffusing capacity of thermogenic tissues (skeletal muscles and brown adipose tissues). Functional interactions between cardiac output and blood haemoglobin content determine circulatory O2 delivery and thus affect V̇O2,max, particularly in high-altitude environments where erythropoiesis can increase haematocrit and blood viscosity. There may also be functional linkages between cardiac output and tissue O2 diffusion due to the role of blood flow in determining capillary haematocrit and red blood cell flux. Therefore, the functional interactions between cardiac output and other traits in the O2 pathway underlie the adaptive evolution of aerobic capacities.

Translated and culturally adapted internet-delivered cognitive therapy for social anxiety disorder in Japanese clinical settings: study protocol for a randomised controlled trial.

BACKGROUND: Cognitive therapy for social anxiety disorder (CT-SAD) has extensive empirical support and is recommended in several national guidelines. However, ensuring access to evidence-based psychological therapies such as CT-SAD remains a global challenge. An internet-delivered version of this treatment protocol (iCT-SAD) has recently been developed in the UK as a way to overcome this challenge, demonstrating comparable outcomes to face-to-face CT-SAD whilst requiring less therapist time per client. Initial findings also suggest its cross-cultural transferability, but the previous studies in other cultural settings used the English language programme and only included English-fluent participants as a second language. It is not yet known what outcomes can be achieved once the programme has been translated and adapted for a different cultural context. Therefore, this trial aims to evaluate the clinical efficacy of Japanese iCT-SAD when combined with treatment as usual (TAU) in clients with SAD. METHODS: This two-arm, parallel-group, superiority randomised controlled trial will recruit 60 Japanese participants with SAD, randomly assigning them to either Japanese iCT-SAD + TAU or TAU alone at a ratio of 1:1. The primary outcome measure is the self-report Liebowitz Social Anxiety Scale, and secondary.outcomes include other measures of social anxiety symptoms and processes, general mood and functioning, and response to treatment. We will also assess treatment acceptability and gather participant feedback. Assessments will take place at baseline (week 0), mid-treatment (week 8), and post-treatment (week 15), with a further 3-month follow-up (week 27) for the iCT-SAD + TAU arm. The primary analyses will be conducted on an intent-to-treat basis, comparing the primary and secondary outcome measures between groups using linear mixed-effect models, along with additional mediation analysis. DISCUSSION: Investigating the efficacy of translated and culturally adapted iCT-SAD in different cultural contexts is an important step in evaluating the global reach of internet interventions. This trial will provide valuable insights into the effects of iCT-SAD combined with usual care, and how this treatment could be delivered in routine clinical settings in Japan. TRIAL REGISTRATION: International Standard Randomized Controlled Trials (ISRCTN), ISRCTN82859645, registered on January 19, 2024. UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052702, registered on November 6, 2023.

Local adaptation, plasticity, and evolved resistance to hypoxic cold stress in high-altitude deer mice.

A fundamental question in evolutionary biology concerns the relative contributions of phenotypic plasticity vs. local adaptation (genotypic specialization) in enabling wide-ranging species to inhabit diverse environmental conditions. Here we conduct a long-term hypoxia acclimation experiment to assess the relative roles of local adaptation and plasticity in enabling highland and lowland deer mice (Peromyscus maniculatus) to sustain aerobic thermogenesis at progressively increasing elevations. We assessed the relative physiological performance capacities of highland and lowland natives as they were exposed to progressive, stepwise increases in hypoxia, simulating the gradual ascent from sea level to an elevation of 6000 m. The final elevation of 6000 m far exceeds the highest attainable elevations within the species' range, and therefore tests the animals' ability to tolerate levels of hypoxia that surpass the prevailing conditions within their current distributional limits. Our results demonstrate that highland natives exhibit superior thermogenic capacities at the most severe levels of hypoxia, suggesting that the species' broad fundamental niche and its ability to inhabit such a broad range of elevational zones is attributable to a combination of genetically based local adaptation and plasticity. Transcriptomic and physiological measurements identify evolved changes in the acclimation response to hypoxia that contribute to the enhanced thermogenic capacity of highland natives.

Changes in the prevalence of hepatitis B and C viral infections in Sindh province, Pakistan: Findings from two sero-surveys in 2007 and 2019.

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero-surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)-positive) prevalence and HCV exposure (HCV antibody (HCV-Ab)-positive) prevalence between two sero-surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population-attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2-2.9) in 2007 to 1.1% (95% CI: 0.8-1.3) in 2019, while HCV-Ab prevalence increased from 5.1% (95% CI: 4.6%-5.5%) to 6.2% (95% CI: 5.6%-6.8%). The age and gender-adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1-0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3-0.6) among adults over 2007-2019, while HCV-Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2-0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2-1.7) in adults. HCV-Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5-0.8) and higher (aOR = 0.5, 95%CI:0.3-0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2-2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9-3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6-2.7), being tattooed (aOR = 1.4, 95% CI: 1.0-1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0-1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7-48.4%). Overall HCV has increased over 2007-2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities.

A seabird's eye view: visual fields of some seabirds (Laridae and Procellariidae) from tropical latitudes.

The visual field of a bird defines the amount of information that can be extracted from the environment around it, using the eyes. Previous visual field research has left large phylogenetic gaps, where tropical bird species have been comparatively understudied. Using the ophthalmoscopic technique, we measured the visual fields of seven tropical seabird species, to understand what are the primary determinants of their visual fields. The visual field topographies of the seven seabird species were relatively similar, despite the two groups of Terns (Laridae) and Shearwaters (Procellariidae) being phylogenetically distant. We propose this similarity is due to their largely similar foraging ecology. These findings support previous research that foraging ecology rather than relatedness is the key determining factor behind a bird's visual field topography. Some bird species were identified to have more limited binocular fields, such as Brown Noddies (Anous stolidus) where binocularity onsets lower down within the visual field, resulting in a larger blind area about the head.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context.

BACKGROUND: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. AIMS: The aim of this study was to generate an experts' consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. METHOD: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. RESULTS: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. CONCLUSION: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

Outcome-based analytical performance specifications: current status and future challenges.

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing.

Exercise in a natural environment increases program compliance in people with chronic migraine: A pilot cross-over randomized trial.

Adverse side effects from pharmacological treatments cause people with migraine to delay or avoid taking medication. Exercise is effective, but the effect of environment is unknown. The purpose was to determine if a natural environment affects monthly migraine load. Sedentary individuals (8 female, 1 non-binary) who experienced migraines participated. Participants completed one month of exercise (3 x week, 30-min, 60-70% estimated HRmax) indoors as well as in a natural outdoor environment in a randomized counterbalanced order. Migraine load was determined using the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) at the beginning and end of each month. Data were analyzed using repeated measures ANOVA. No interactions were evident for HIT-6 (p = 0.80), MIDAS (p = 0.72), migraine days (p = 0.508), or pain intensity (p = 0.66). No main effects were noted. Compliance was greater in the outdoor environment, with more exercise sessions completed in nature (Indoor = 72%, Outdoor = 90%, p < 0.001). Exercise environment did not impact MIDAS or HIT-6 questionnaire results, number of migraine days, or pain intensity. While there was no reduction in migraine load, it is possible that other health benefits were experienced due to greater compliance in a natural environment.

Successful remote treatment of a client with Hikikomori using internet-delivered cognitive therapy for social anxiety disorder: a case report.

Hikikomori (prolonged social withdrawal) has been discussed as a hidden worldwide epidemic and a significant social and healthcare issue. Social anxiety disorder is the most common psychiatric disorder preceding the onset of Hikikomori. Although studies exist suggesting the effectiveness of family-support interventions, little is known about psychotherapeutic approaches for Hikikomori individuals. Here, we present a case of Hikikomori wherein an internet-delivered cognitive therapy for social anxiety disorder (iCT-SAD) worked effectively in improving the client's social anxiety symptoms and social interaction behaviors. This case study demonstrates the principle that evidence-based psychological interventions focusing on social anxiety can be effective for clients with Hikikomori. Furthermore, the online mode of treatment delivery, along with a variety of relevant modules, may facilitate clients' engagement with treatment at home. The findings suggest that iCT-SAD might be a promising option for Hikikomori clients who have social anxiety problems, within the recommended stepped-intervention approach.

Applying the Milan models to setting analytical performance specifications - considering all the information.

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting.

Elucidation of the Catalytic Sequence of Dihydroorotate Dehydrogenase B from Lactoccocus lactis: Evidence for Accumulation of a Flavin Bisemiquinone State in Catalysis.

The physiological role of dihydroorotate dehydrogenase (DHOD) enzymes is to catalyze the oxidation of dihydroorotate to orotate in pyrimidine biosynthesis. DHOD enzymes are structurally diverse existing as both soluble and membrane-associated forms. The Family 1 enzymes are soluble and act either as conventional single subunit flavin-dependent dehydrogenases known as Class 1A (DHODA) or as unusual heterodimeric enzymes known as Class 1B (DHODB). DHODBs possess two active sites separated by ∼20 Å, each with a noncovalently bound flavin cofactor. NAD is thought to interact at the FAD containing site, and the pyrimidine substrate is known to bind at the FMN containing site. At the approximate center of the protein is a single Fe2S2 center that is assumed to act as a conduit, facilitating one-electron transfers between the flavins. We present anaerobic transient state analysis of a DHODB enzyme from Lactoccocus lactis. The data presented primarily report the exothermic reaction that reduces orotate to dihydroorotate. The reductive half reaction reveals rapid two-electron reduction that is followed by the accumulation of a four-electron reduced state when NADH is added in excess, suggesting that the initial two electrons acquired reside on the FMN cofactor. Concomitant with the first reduction is the accumulation of a long-wavelength absorption feature consistent with the blue form of a flavin semiquinone. Spectral deconvolution and fitting to a model that includes reversibility for the second electron transfer reveals equilibrium accumulation of a flavin bisemiquinone state that has features of both red and blue semiquinones. Single turnover reactions with limiting NADH and excess orotate reveal that the flavin bisemiquinone accumulates with reduction of the enzyme by NADH and decays with reduction of the pyrimidine substrate, establishing the bisemiquinone as a fractional state of the two-electron reduced intermediate observed.

A New Concept for Reference Change Values-Regression to the Population Mean.

BACKGROUND: Reference change values (RCV) are used to indicate a change in analyte concentration that is unlikely to be due to random variation in the patient or the measurement. Current theory describes RCV relative to a first measurement result (X1). We investigate an alternative view predicting the starting point for RCV calculations from X1 and its location in the reference interval. METHODS: Data for serum sodium, calcium, and total protein from the European Biological Variation study and from routine clinical collections were analyzed for the effect of the position of X1 within the reference interval on the following result from the same patient. A model to describe the effect was determined, and an equation to predict the RCV for a sample in a population was developed. RESULTS: For all data sets, the midpoints of the RCVs were dependent on the position of X1 in the population. Values for X1 below the population mean were more likely to be followed by a higher result, and X1 results above the mean were more likely to be followed by lower results. A model using population mean, reference interval dispersion, and result diagnostic variation provided a good fit with the data sets, and the derived equation predicted the changes seen. CONCLUSIONS: We have demonstrated that the position of X1 within the reference interval creates an asymmetrical RCV. This can be described as a regression to the population mean. Adding this concept to the theory of RCVs will be an important consideration in many cases.

A common tumour in a rare location: a single centre case series of cerebellar glioblastoma.

Although glioblastoma is the commonest primary brain tumour in adults, its location in the cerebellum is extremely rare. We present thirteen cases (3 female, 10 male; median age at presentation 56 [age range 21-77]) of surgically managed, histologically confirmed, primary cerebellar glioblastoma (cGB) over a 17 year period (2005-2022). Pre-operative radiological diagnosis was challenging given cGB rarity, although MRI demonstrated ring enhancement in all cases. Surgical management included posterior fossa craniectomy and debulking in 11 cases and burr hole biopsy in two. CSF diversion was necessary in four cases. No evidence of IDH or ATRX gene mutations was found when tested. Survival ranged from 1 to 22 months after diagnosis (mean 10.9 months). We also seek to understand why glioblastoma is rare in this location and discuss potential reasons for this. We hypothesise that increasing anatomical distance from germinal regions and decreased local endogenous neural stem cell activity (which has been associated with glioblastoma) may explain why glioblastoma is rare in the cerebellum. We hereby seek to add to the limited literature on cGB as this is the largest UK cGB series to date.

Design, Synthesis, and Mechanistic Studies of (R)-3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase.

Human ornithine aminotransferase (hOAT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, has been shown to play an essential role in the metabolic reprogramming and progression of hepatocellular carcinoma (HCC). HCC accounts for approximately 75% of primary liver cancers and is within the top three causes of cancer death worldwide. As a result of treatment limitations, the overall 5-year survival rate for all patients with HCC is under 20%. The prevalence of HCC necessitates continued development of novel and effective treatment methods. In recent years, the therapeutic potential of selective inactivation of hOAT has been demonstrated for the treatment of HCC. Inspired by previous increased selectivity for hOAT by the expansion of the cyclopentene ring scaffold to a cyclohexene, we designed, synthesized, and evaluated a series of novel fluorinated cyclohexene analogues and identified (R)-3-amino-5,5-difluorocyclohex-1-ene-1-carboxylic acid as a time-dependent inhibitor of hOAT. Structural and mechanistic studies have elucidated the mechanism of inactivation of hOAT by 5, resulting in a PLP-inactivator adduct tightly bound to the active site of the enzyme. Intact protein mass spectrometry, 19F NMR spectroscopy, transient state kinetic studies, and X-ray crystallography were used to determine the structure of the final adduct and elucidate the mechanisms of inactivation. Interestingly, despite the highly electrophilic intermediate species conferred by fluorine and structural evidence of solvent accessibility in the hOAT active site, Lys292 and water did not participate in nucleophilic addition during the inactivation mechanism of hOAT by 5. Instead, rapid aromatization to yield the final adduct was favored.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review.

BACKGROUND: Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM: To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS: This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS: Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION: Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Catalytic 2-Ethylhexanoic Acid Promotes Mild Miyaura Borylations.

The Miyaura borylation of aryl and heteroaryl chlorides and bromides using a combination of potassium carbonate and 5 mol % 2-ethylhexanoic acid at 25 °C is reported. The in situ generation of a catalytic amount of potassium 2-ethylhexanoate under these conditions avoids the need for special handling of stoichiometric quantities of hygroscopic potassium 2-ethylhexanoate during the reaction setup as well as difficulties in removing the resulting carboxylic acid during product isolation.