Automated Absolute Binding Free Energy Calculation Workflow for Drug Discovery.

Absolute binding free energies play a crucial role in drug development, particularly as part of the lead discovery process. In recent work, we showed how in silico predictions directly could support drug development by ranking and recommending favorable ideas over unfavorable ones. Here, we demonstrate a Python workflow that enables the calculation of ABFEs with minimal manual input effort, such as the receptor PDB and ligand SDF files, and outputs a .tsv file containing the ranked ligands and their corresponding binding free energies. The implementation uses Snakemake to structure and control the execution of tasks, allowing for dynamic control of parameters and execution patterns. We provide an example of a benchmark system that demonstrates the effectiveness of the automated workflow.

Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Molecular dating of the teleost whole genome duplication (3R) is compatible with the expectations of delayed rediploidization.

Vertebrate evolution has been punctuated by three whole genome duplication (WGD) events that have been implicated causally in phenotypic evolution, from the origin of phenotypic novelties to explosive diversification. Arguably the most dramatic of these is the 3R WGD event associated with the origin of teleost fishes which comprise more than half of all living vertebrate species. However, tests of a causal relationship between WGD and teleost diversification have proven difficult due to the challenge of establishing the timing of these phenomena. Here we show, based on molecular clock dating of concatenated gene alignments, that the 3R WGD event occurred in the early-middle Permian (286.18-267.20 Million years ago; Ma), 52.02-12.84 million years (Myr) before the divergence of crown-teleosts in the latest-Permian-earliest Late Triassic (254.36-234.16 Ma) and long before the major pulses of teleost diversification in Ostariophysi and Percomorpha (56.37-100.17 Myr and at least 139.24-183.29 Myr later, respectively). The extent of this temporal gap between putative cause and effect precludes 3R as a deterministic driver of teleost diversification. However, these age constraints remain compatible with the expectations of a prolonged rediploidization process following WGD which, through the effects of chromosome rearrangement and gene loss, remains a viable mechanism to explain the evolution of teleost novelties and diversification.

Towards a Standardization of Learning Curve Assessment in Minimally Invasive Liver Surgery.

OBJECTIVE: The aim was to analyze the learning curves of minimal invasive liver surgery(MILS) and propose a standardized reporting. SUMMARY BACKGROUND DATA: MILS offers benefits compared to open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization. METHODS: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves, and characterization of different learning phases(competency, proficiency and mastery). RESULTS: 60 articles with 12'241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42) and postoperative complications (n=38). Overall competency, proficiency and mastery were reached after 34 (IQR 19-56), 50 (IQR 24-74), 58 (IQR 24-100) procedures respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: -13%, 2%; blood loss: competency to proficiency to mastery: -33%, 0%; conversion rate (competency to proficiency to mastery; -21%, -29%), whereas postoperative complications improved later (competency to proficiency to mastery: -25%, -41%). CONCLUSIONS: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized three-phase reporting of learning phases (competency, proficiency, mastery) is proposed and should be followed.

Structural polymorphism and diversity of human segmental duplications.

Segmental duplications (SDs) contribute significantly to human disease, evolution, and diversity yet have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies where the majority of SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms, we identify 173.2 Mbp of duplicated sequence (47.4 Mbp not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable with rare events mapping near their progenitor sequences. African genomes harbor significantly more intrachromosomal SDs and are more likely to have recently duplicated gene families with higher copy number when compared to non-African samples. A comparison to a resource of 563 million full-length Iso-Seq reads identifies 201 novel, potentially protein-coding genes corresponding to these copy number polymorphic SDs.

Cognitive Functioning in Youth with Anxiety Disorders: A Systematic Review.

Anxiety disorders are disorders involving cognition. Research on cognition in youth with anxiety can focus on cognitive content (e.g., self-talk) as well cognitive functioning. The present review examines domains of cognitive functioning (i.e., episodic memory, language, attention, executive functioning, motor skills, and visual functioning) in youth diagnosed with an anxiety disorder. A database search of Embase, PsycINFO, and PubMed yielded 28 studies that met inclusion criteria of youth aged 17 years or younger, a sample diagnosed with a principal anxiety disorder and a comparison sample of controls, a comparison between those samples, and use of a behavioral measure of neuropsychological performance. Findings did not identify any cognitive functioning strengths for anxious youth. Deficits were found in two domains (i.e., receptive language and motor skills) whereas no deficits were found in attention, visuospatial skills and one domain of executive functioning (i.e., inhibition). Most domains had mixed findings. Additional analysis indicated that anxiety disorders in youth are not associated with diminished IQ. Directions for future research are identified including (a) the prioritization of studies with larger, representative samples (b) the role of cognitive functioning as a predictor of anxiety treatment outcome (c) the examination of the effect of treatment on cognitive performance, and (d) the course of anxiety and potential impairment in cognitive functioning.

Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites.

Knowledge of Cambrian animal anatomy is limited by preservational processes that result in compaction, size bias, and incompleteness. We documented pristine three-dimensional (3D) anatomy of trilobites fossilized through rapid ash burial from a pyroclastic flow entering a shallow marine environment. Cambrian ellipsocephaloid trilobites from Morocco are articulated and undistorted, revealing exquisite details of the appendages and digestive system. Previously unknown anatomy includes a soft-tissue labrum attached to the hypostome, a slit-like mouth, and distinctive cephalic feeding appendages. Our findings resolve controversy over whether the trilobite hypostome is the labrum or incorporates it and establish crown-group euarthropod homologies in trilobites. This occurrence of moldic fossils with 3D soft parts highlights volcanic ash deposits in marine settings as an underexplored source for exceptionally preserved organisms.

Floral scent changes in response to pollen removal are rare in buzz-pollinated Solanum.

MAIN CONCLUSION: One of seven Solanum taxa studied displayed associations between pollen presence and floral scent composition and volume, suggesting buzz-pollinated plants rarely use scent as an honest cue for foraging pollinators. Floral scent influences the recruitment, learning, and behaviour of floral visitors. Variation in floral scent can provide information on the amount of reward available or whether a flower has been visited recently and may be particularly important in species with visually concealed rewards. In many buzz-pollinated flowers, tubular anthers opening via small apical pores (poricidal anthers) visually conceal pollen and appear similar regardless of pollen quantity within the anther. We investigated whether pollen removal changes floral scent composition and emission rate in seven taxa of buzz-pollinated Solanum (Solanaceae). We found that pollen removal reduced both the overall emission of floral scent and the emission of specific compounds (linalool and farnesol) in S. lumholtzianum. Our findings suggest that in six out of seven buzz-pollinated taxa studied here, floral scent could not be used as a signal by visitors as it does not contain information on pollen availability.

Tuberculosis care provided by private practitioners in an urban setting in Indonesia: Findings from a standardized patient study.

In Indonesia, government-owned Community Health Centers (CHCs) spearhead tuberculosis (TB) care at the primary level, but a substantial proportion of individuals with pulmonary TB also seek care from Private Practitioners (PPs). However, little is known about PPs' practice in managing patients with TB-associated symptoms. To avoid bias associated with self-administered surveys, we used standardized patients (SPs) to evaluate PPs' adherence to the national TB guidelines. Four clinical scenarios of individuals presenting complaints suggestive of TB, accompanied by different sputum smear results or TB treatment histories were developed. We assigned 12 trained SPs to PPs practicing in 30 CHC catchment areas in Bandung city, Indonesia. For comparison, two scenarios were also presented to the CHCs. A total of 341 successful SP visits were made to 225 private general practitioners (GPs), 29 private specialists, and 30 CHCs. When laboratory results were not available, adherence to the recommended course of action, i.e., sputum examination, was low among private GPs (31%) and private specialists (20%), while it was requested in 87% of visits to the CHCs. PPs preferred chest X-ray (CXR) in all scenarios, with requests made in 66% of visits to private GPs and 84% of visits to private specialists (vs. 8% CHCs). Prescriptions of incorrect TB drug regimens were reported from 7% and 13% of visits to private GPs and specialists, respectively, versus none of the CHCs. Indonesian PPs have a clear preference for CXR over microbiological testing for triaging presumptive TB patients, and inappropriate prescription of TB drugs is not uncommon. These findings warrant actions to increase awareness among PPs about the importance of microbiological testing and of administering appropriate TB drug regimens. SP studies can be used to assess the impact of these interventions on providers' adherence to guidelines.

Elevated nuclear TDP-43 induces constitutive exon skipping.

BACKGROUND: Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate in vitro and in vivo model systems. METHODS: We analyzed RNA-seq datasets from mouse and human neurons overexpressing TDP-43 to explore species specific splicing patterns. We explored the dynamics between TDP-43 levels and exon repression in vitro. Furthermore we analyzed human brain samples and publicly available RNA datasets to explore the relationship between exon repression and disease. RESULTS: Our study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific. Furthermore, while aberrant exon skipping is detected in some human brains, it is not correlated with disease, unlike the incorporation of cryptic exons that occurs after loss of TDP-43. CONCLUSIONS: Our findings emphasize the need for caution in interpreting TDP-43 overexpression data and stress the importance of controlling for exon skipping when generating models of TDP-43 proteinopathy.

A tuberculosis elimination-focused geospatial approach to optimising access to diagnostic GeneXpert machines in Fiji.

OBJECTIVES: Fiji could be the first country to eliminate tuberculosis. To inform this strategy, we aimed to identify how many GeneXpert® machines are required to enable over 90% of Fijians to be within one-hour easy access. METHODS: We used Geographic Information System (Quantum GIS; QGIS), OpenStreetMap and population data (Kontur) to map possible facilities in relation to QGIS generated 60-min drive-time isochrones, with correction for missing road data. For outer islands, we calculated a distance to nearest hub operation. RESULTS: The solution comprised 24 GeneXpert® machines, allocating 7 GeneXpert® to Viti Levu, 6 GeneXpert® to Vanua Levu and 11 to other islands. This resulted in 827,810 people, 93.6% of Fiji's population, being within 1 h of a machine. Twenty-one thousand four hundred seventy-nine people on outer islands were an average of 43 km by water from the nearest facility. CONCLUSIONS: We conclude that over 90% of Fijians could be within an hour of a GeneXpert® machine with placement of 24 machines.

Metagenome-assembled genome of the glacier alga Ancylonema yields insights into the evolution of streptophyte life on ice and land.

Contemporary glaciers are inhabited by streptophyte algae that balance photosynthesis and growth with tolerance of low temperature, desiccation and UV radiation. These same environmental challenges have been hypothesised as the driving force behind the evolution of land plants from streptophyte algal ancestors in the Cryogenian (720-635 million years ago). We sequenced, assembled and analysed the metagenome-assembled genome of the glacier alga Ancylonema nordenskiöldii to investigate its adaptations to life in ice, and whether this represents a vestige of Cryogenian exaptations. Phylogenetic analysis confirms the placement of glacier algae within the sister lineage to land plants, Zygnematophyceae. The metagenome-assembled genome is characterised by an expansion of genes involved in tolerance of high irradiance and UV light, while lineage-specific diversification is linked to the novel screening pigmentation of glacier algae. We found no support for the hypothesis of a common genomic basis for adaptations to ice and to land in streptophytes. Comparative genomics revealed that the reductive morphological evolution in the ancestor of Zygnematophyceae was accompanied by reductive genome evolution. This first genome-scale data for glacier algae suggests an Ancylonema-specific adaptation to the cryosphere, and sheds light on the genome evolution of land plants and Zygnematophyceae.

Full robotic versus open ALPPS: a bi-institutional comparison of perioperative outcomes.

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.

The effect of oral probiotics on response to vaccination in older adults: a systematic review of randomised controlled trials.

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this.

Habitat use of Amazonian birds varies by age and foraging guild along a disturbance gradient.

Patterns of habitat use directly influence a species' fitness, yet for many species an individual's age can influence patterns of habitat use. However, in tropical rainforests, which host the greatest terrestrial species diversity, little is known about how age classes of different species use different adjacent habitats of varying quality. We use long-term mist net data from the Amazon rainforest to assess patterns of habitat use among adult, adolescent (teenage) and young understory birds in forest fragments, primary and secondary forest at the Biological Dynamics of Forest Fragments Project in Brazil. Insectivore adults were most common in primary forest, adolescents were equally likely in primary and secondary forest, and all ages were the least common in forest fragments. In contrast to insectivores, frugivores and omnivores showed no differences among all three habitat types. Our results illustrate potential ideal despotic distributions among breeding populations of some guilds of understory birds where adult insectivores may competitively exclude adolescent individuals from primary forest. Secondary forest recovery appears to hold promise as a breeding habitat for frugivore and omnivore species but only as a pre-breeding habitat for insectivores, but as the forest ages, the demographic structure of bird populations should match that of primary forest.

Clinical management and outcome of head and neck paragangliomas (HNPGLs): A single centre retrospective study.

CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.

Population pharmacokinetic modelling and simulation of tranexamic acid in adult trauma patients.

AIMS: The aim of this study is to describe the disposition of tranexamic acid (TXA) in adult trauma patients and derive a dosing regimen that optimizes exposure based on a predefined exposure target. METHODS: We performed a population pharmacokinetic (popPK) analysis of participants enrolled in the Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial (≥18 years with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room) who were randomized to a single dose of either 2 or 4 g of TXA ≤2 h from time of injury. PopPK analysis was conducted using nonlinear mixed-effects modelling (NONMEM). Simulations were then performed using the final model to generate estimated plasma TXA concentrations in 1000 simulated participants. Dosing schemes were evaluated to determine maintenance of TXA plasma concentrations >10 mg/L for ≥8 h after administration of the initial dose. RESULTS: TXA PK was best described by a two-compartment model with proportional residual error and allometric scaling on all parameters. Platelet count, skeletal muscle oxygen saturation measured by near-infrared spectroscopy and interleukin-8 concentration were significant covariates on TXA clearance. Based on simulations, a 2 g IV bolus dose, repeated 3 h later, best achieved the target exposure. CONCLUSIONS: According to simulations from a popPK model of TXA, a 2 g IV bolus with a repeated dose 3 h later would be most likely to maintain concentrations >10 mg/L for 8 h in >95% of adult trauma patients and should be considered for patients with ongoing haemorrhage.

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Temporal and Spectral Models as Correlates to Auditory-Perceptual Judgments of Overall Severity and Listener Comfort in Tracheoesophageal Voice.

INTRODUCTION: This study pursued two objectives: (1) to determine the potential association between listener (n = 51) judgments of 20 male tracheoesophageal speaker samples for two auditory-perceptual dimensions of voice, overall severity (OS) and listener comfort (LC); and (2) to assess the temporal and spectral acoustic correlates for these auditory-perceptual dimensions. METHODOLOGY: Three separate correlation analyses were performed to evaluate the association between OS and LC. First, scores of OS and LC from all listeners were pooled together, and then the correlation between OS and LC was computed. Second, scores of OS and LC were averaged over all listeners to derive a single estimate of OS and LC for each TE speaker sample; the correlation between the average OS and LC was then computed. Third, listener-to-listener variability in the association between OS and LC was evaluated by computing the correlation between OS and LC scores from each listener across all TE samples. Finally, two stepwise multiple regression models were created to relate the average LC score to spectral and temporal variation in the acoustic signal. RESULTS: While the pooled OS and LC scores had a moderate positive correlation (r = 0.66, p < 0.00001), the averaged OS and LC exhibited a near perfect positive correlation (r = 0.99, p < 0.00001). The significant differences between the pooled and averaged scores were explained by significant listener-to-listener variability in the association between OS and LC. OS and LC scores from 5 listeners had non-significant correlations, 10 had moderate correlations (r < 0.7), 35 listeners had high correlations (0.7 < r < 0.9), and 1 listener had a very high correlation (r < 0.9 < 1). Finally, the acoustic models created based on the spectral and temporal variations in the signal were able to account for 87.7% and 61.8% of variation in the average LC score. CONCLUSIONS: The strong correlations between OS and LC suggest that LC may, in fact, provide a more comprehensive auditory-perceptual surrogate for the voice quality of TE speakers. Although OS and LC are distinct conceptual dimensions, LC appears to have the advantage of assessing the social impact and potential communication disability that may exist in interactions between TE speakers and listeners.

Expert consensus report on lipid mediators: Role in resolution of inflammation and muscle preservation.

This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations.