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1.
J Chem Phys ; 161(1)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38953441

ABSTRACT

Our recently published [Weike et al., J. Chem. Phys. 159, 244119 (2023)] spin-orbit coupled diabatic potential energy model for HI is used in a thorough analysis of bound and quasi-bound states as well as elastic and inelastic processes in H + I collisions. The potential energy model, designed explicitly for studying scattering, accurately describes the various couplings in the system, which lead to complex dynamics. Ro-vibronic bound and quasi-bound states related to the adiabatic electronic ground state and an excited electronic state are analyzed. Calculations using the full 104 × 104 diabatic matrix model or a single adiabatic state are compared in order to investigate approximations in the latter. Elastic and inelastic scattering cross sections as well as thermal rates between the ground and first excited fine structure levels of iodine are computed for collision energies up to 12 500 cm-1. Resonances related to the quasi-bound states are analyzed in terms of their energy, width, lifetime, and decay probabilities. The effect of different resonances on the thermal rates is discussed. Resonances between 30 000 and 40 000 cm-1 are also studied for selected values of the total angular momentum, in particular their decay probabilities into different final states of iodine and hence their potential effect on branching ratios in photodissociation of HI.

2.
bioRxiv ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38948790

ABSTRACT

Background: The first year of life is a period of rapid immune development that can impact health trajectories and the risk of developing respiratory-related diseases, such as asthma, recurrent infections, and eczema. However, the biology underlying subsequent disease development remains unknown. Methods: Using weighted gene correlation network analysis (WGCNA), we derived modules of highly correlated immune-related proteins in plasma samples from children at age 1 year (N=294) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). We applied regression analyses to assess relationships between protein modules and development of childhood respiratory diseases up to age 6 years. We then characterized genomic, environmental, and metabolomic factors associated with modules. Results: WGCNA identified four protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (Padj range: 0.02-0.03), respiratory infections (Padj range: 6.3×10-9-2.9×10-6), and eczema (Padj=0.01) by age 6 years; three modules were associated with at least one environmental exposure (Padj range: 2.8×10-10-0.03) and disrupted metabolomic pathway(s) (Padj range: 2.8×10-6-0.04). No genome-wide SNPs were identified as significant genetic risk factors for any protein module. Relationships between protein modules with clinical, environmental, and 'omic factors were temporally sensitive and could not be recapitulated in protein profiles at age 6 years. Conclusion: These findings suggested protein profiles as early as age 1 year predicted development of respiratory-related diseases through age 6 and were associated with changes in pathways related to amino acid and energy metabolism. These may inform new strategies to identify vulnerable individuals based on immune protein profiling.

3.
Sci Rep ; 14(1): 15559, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38969675

ABSTRACT

Subsurface barriers have been proposed to protect coastal aquifers from sea-level rise induced seawater intrusion, but the potential for groundwater emergence near subsurface barriers remains unknown. Here, we investigated how emergence changes groundwater flow conditions and influences the protective performance of subsurface barriers with sea-level rise. We tested the subterranean consequences of sea-level rise for cutoff walls and subsurface dams with cross-shore groundwater flow and salt transport models, investigating how barrier design, aquifer properties, and hydrological conditions control the potential for emergence, groundwater partitioning at the barrier, and seawater intrusion with sea-level rise. We find that most subsurface infrastructure cannot prevent seawater intrusion and emergence simultaneously. Subsurface dams spanning more than half of the aquifer thickness created emergence hazards and subsequent groundwater partitioning for all scenarios tested. Cutoff walls were less effective at reducing seawater intrusion for all opening sizes but could reduce the emergence potential compared to similarly sized subsurface dams. Our results demonstrate the challenging trade-offs in mitigating the coastal groundwater hazards of seawater intrusion and emergence with sea-level rise, where groundwater flooding inland of protective infrastructure would require combinations of subsurface impoundments and other mitigation techniques, such as pumping or drains.

5.
Bioresour Technol ; 406: 131065, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969241

ABSTRACT

Lithium-sulfur batteries are a promising alternative to lithium-ion batteries as they can potentially offer significantly increased capacities and energy densities. The ever-increasing global battery market demonstrates that there will be an ongoing demand for cost effective battery electrode materials. Materials derived from waste products can simultaneously address two of the greatest challenges of today, i.e., waste management and the requirement to develop sustainable materials. In this study, we detail the carbonisation of gelatin from blue shark and chitin from prawns, both of which are currently considered as waste biproducts of the seafood industry. The chemical and physical properties of the resulting carbons are compared through a correlation of results from structural characterisation techniques, including electron imaging, X-ray diffraction, Raman spectroscopy and nitrogen gas adsorption. We investigated the application of the resulting carbons as sulfur-hosting electrode materials for use in lithium-sulfur batteries. Through comprehensive electrochemical characterisation, we demonstrate that value added porous carbons, derived from marine waste are promising electrode materials for lithium-sulfur batteries. Both samples demonstrated impressive capacity retention when galvanostatically cycled at a rate of C/5 for 500 cycles. This study highlights the importance of looking towards waste products as sustainable feeds for battery material production.

6.
J Gastric Cancer ; 24(3): 267-279, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38960886

ABSTRACT

PURPOSE: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. MATERIALS AND METHODS: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. RESULTS: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. CONCLUSIONS: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Esophagogastric Junction , Stomach Neoplasms , Humans , Male , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/classification , Female , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/classification , Stomach Neoplasms/surgery , Middle Aged , Esophagogastric Junction/pathology , Esophagogastric Junction/surgery , Retrospective Studies , Aged , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Esophageal Neoplasms/surgery , Prognosis , Gastrectomy , Adult , Survival Rate , Esophagectomy , Aged, 80 and over
7.
Magn Reson Med ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38946234

ABSTRACT

PURPOSE: Serine is a major source of one-carbon units needed for the synthesis of nucleotides and the production of intramitochondrial nicotinamide adenine dinucleotide phosphate (NADPH), and it plays an important role in cancer cell proliferation. The aim of this study was to develop a deuterium (2H) MRS imaging method for imaging tumor serine metabolism. METHODS: Sequential (2H) spectra and spectroscopic images were used to monitor the metabolism of [2,3,3-2H3]serine in patient-derived glioblastoma cells in vitro and in tumors obtained by their orthotopic implantation in mouse brain. RESULTS: [14,14-2H2] 5,10-methylene-tetrahydrofolate, [2H]glycine, [2H]formate, and labeled water were detected in cell suspensions and water labeling in spectroscopic images of tumors. Studies in cells and tumors with variable mitochondrial content and inhibitor studies in cells demonstrated that most of the labeled serine was metabolized in the mitochondria. Water labeling in the cell suspensions was correlated with formate labeling; therefore, water labeling observed in tumors could be used to provide a surrogate measure of flux in the pathway of one-carbon metabolism in vivo. CONCLUSION: The method has the potential to be used clinically to select patients for treatment with inhibitors of one-carbon metabolism and subsequently to detect their early responses to such treatment.

8.
Dis Colon Rectum ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959470

ABSTRACT

BACKGROUND: Checkpoint kinase 2 is a tumor suppressor gene in the deoxyribonucleic acid damage checkpoint system that may be mutated in several cancers. Patients with germline checkpoint kinase 2 mutations and multiple colon polyps were noted during routine care, and genetic testing is recommended for patients with as few as 10 lifetime polyps. OBJECTIVE: This study assessed whether checkpoint kinase 2 is associated with attenuated or oligopolyposis and characterized the gastrointestinal clinicopathologic profile. DESIGN: Retrospective observational study. SETTINGS: Records from patients harboring germline checkpoint kinase 2 mutations from 1999-2020 were reviewed. PATIENTS: A total of 45 patients with germline checkpoint kinase 2 mutations with endoscopic examinations. MAIN OUTCOME MEASURES: Description of clinicopathologic variables. RESULTS: Twenty-five of 45 patients had polyps: 3 with only upper gastrointestinal polyps, 17 with only lower gastrointestinal polyps and 5 with both upper and lower gastrointestinal polyps. The most common germline checkpoint kinase 2 mutations in patients with polyps were p.S428F (n = 10), p.I157T (n = 4) and p.T476M (n = 2), with other mutations present in 1 patient each. Among patients with lower gastrointestinal polyps, 9 had adenomas, 6 had serrated polyps, 1 had an inflammatory polyp and 6 had both adenomatous and serrated polyps. Three patients (p.I157T, n = 2; p.R117G, n = 1) had >10 adenomas, and 1 (p.G259fs) had 18 serrated polyps. Five patients (11.1%) developed colorectal adenocarcinoma, including 2 with >10 adenomas. Five patients with p.S428F (50%) exclusively had right- sided adenomas. LIMITATIONS: Single-center descriptive study. CONCLUSIONS: Germline checkpoint kinase 2 mutations should be considered in patients with polyposis. The preponderance of right- sided adenomas in patients with p.S428F mutations suggests the importance of right-sided colonoscopy in these patients. See Video Abstract.

9.
PLoS One ; 19(7): e0305899, 2024.
Article in English | MEDLINE | ID: mdl-38954676

ABSTRACT

In the southeastern United States, wood ducks (Aix sponsa) have historically experienced interspecific brood parasitism (IBP) primarily from hooded mergansers (Lophodytes cucullatus), but the recent northward expansion of black-bellied whistling-ducks (Dendrocygna autumnalis) has added a new complexity to these interactions. We monitored nest boxes in Louisiana to evaluate the influence IBP had on wood duck daily nest survival rate (after, DSR) and duckling recruitment. We monitored 1,295 wood duck nests from 2020-2023 and found 112 (8.7%) were parasitized by hooded mergansers and 148 (11.5%) by whistling-ducks. Parasitic egg-laying by hooded mergansers lowered wood duck DSR, while DSR for nests parasitized by whistling-ducks was comparable to clutches containing only wood duck eggs. We considered the wood duck capture histories of 2,465 marked female ducklings and 540 banded adult females to estimate a duckling recruitment probability for the entire study period. We recaptured 50 ducklings as adults; 6 (12.0%) hatched from clutches parasitized by hooded mergansers, 1 (2.0%) from a clutch parasitized by a whistling-duck, and 43 (86.0%) from clutches containing only wood duck eggs. The duckling recruitment probability was 0.039 (95% credible interval = 0.028, 0.051). Nest initiation date had a negative effect on recruitment, wherein most recruits hatched from nests initiated earlier in the season. Given only ~9% of wood duck nests contained hooded merganser eggs, we conclude IBP writ large had no detrimental effect on DSR at a population level. The lower DSR of clutches parasitized by hooded mergansers is potentially linked to a high abundance of early-season parasites that produce "dump nests" and these clutches are often abandoned without being incubated. Despite ongoing parasitism by hooded mergansers and the range expansion of whistling-ducks, wood duck productivity in Louisiana appears to be minimally affected by interspecific brood parasitism.


Subject(s)
Ducks , Nesting Behavior , Animals , Ducks/parasitology , Nesting Behavior/physiology , Female , Louisiana
10.
Drug Metab Rev ; : 1-33, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989688

ABSTRACT

This annual review marks the eighth in the series starting with Baillie et al. (2016) Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation. Its format is to highlight important aspects captured in synopsis followed by a commentary with relevant figure and references.

11.
Ecol Evol ; 14(7): e11721, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38994215

ABSTRACT

Conspecific and interspecific brood parasitism are alternate reproductive strategies more pervasive in waterfowl than in any other group of birds. While previous research has measured costs incurred by nest hosts incubating parasitized clutches, few studies have focused on the relative success of parasites. Here, we evaluated the success of wood duck (Aix sponsa) and hooded merganser (Lophodytes cucullatus) eggs laid parasitically in Louisiana and Mississippi. We monitored nest boxes, assigned eggs in each nest as host or parasitic, and determined the number of eggs that hatched and failed. Across all study areas (1994-1999 and 2020-2023), we monitored 1750 wood duck and 377 hooded merganser nests; ~13% of wood duck and ~24% of hooded merganser nests were interspecifically parasitized. We modeled egg survival of 2925 host and 691 parasitic eggs from 197 successful nests (≥1 hatched egg, regardless of species). Wood duck eggs laid in hooded merganser nests had lower survival [0.293, CI = 95% credible intervals (after, CI) = 0.176, 0.439] than hooded merganser eggs (0.762, CI = 0.704, 0.810) laid in wood duck nests. Clutch size negatively influenced parasitic wood duck egg survival (ß = -.24, CI = -0.39, -0.10) but had a slight positive influence on parasitic hooded merganser eggs (ß = .08, CI = 0.04, 0.12). Our results revealed that hooded merganser eggs experience higher success when laid parasitically in wood duck nests, whereas wood duck eggs experience lower success when laid parasitically in hooded merganser nests. Our results reveal new complexity in waterfowl interspecific brood parasitism, where the success of parasitic eggs is species-, host-, and context-specific.

12.
Sci Immunol ; 9(97): eadn0178, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996010

ABSTRACT

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell death induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well studied in myeloid cells but less in its primary host cell type, angiotensin-converting enzyme 2 (ACE2)-expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis in HAE organotypic cultures. Single-cell and limiting-dilution analysis revealed that necroptosis is the primary cell death event in infected cells, whereas uninfected bystanders undergo apoptosis, and pyroptosis occurs later during infection. Mechanistically, necroptosis is induced by viral Z-RNA binding to Z-DNA-binding protein 1 (ZBP1) in HAE and lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more severe disease than Omicron (B1.1.529) in humans, is associated with orders of magnitude-greater Z-RNA/ZBP1 interactions, necroptosis, and disease severity in animal models. Thus, Delta induces robust ZBP1-mediated necroptosis and more disease severity.


Subject(s)
COVID-19 , Necroptosis , Pyroptosis , RNA-Binding Proteins , Respiratory Mucosa , SARS-CoV-2 , Humans , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/pathology , Necroptosis/immunology , Animals , Respiratory Mucosa/virology , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Mice , Cell Death/immunology , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Apoptosis/immunology
14.
Phys Chem Chem Phys ; 26(27): 19021-19034, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38953877

ABSTRACT

First-principles based kinetic modeling is essential to gain insight into the governing chemistry of nitrogen-containing compounds over a wide range of technologically important processes, e.g. pyrolysis, oxidation and combustion. It also enables the development of predictive, fundamental models key to improving understanding of the influence of nitrogen-containing compounds present as impurities or process additives, considering safety, operability and quality of the product streams. A prerequisite for the generation of detailed fundamental kinetic models is the availability of accurate thermodynamic properties. To address the scarcity of thermodynamic properties for nitrogen-containing compounds, a consistent set of 91 group additive values and three non-nearest-neighbor interactions has been determined from a dataset of CBS-QB3 calculations for 300 species, including 104 radicals. This dataset contains a wide range of nitrogen-containing functionalities, i.e. imine, nitrile, nitro, nitroso, nitrite, nitrate and azo functional groups. The group additivity model enables the approximation of the standard enthalpy of formation and standard entropy at 298 K as well as the standard heat capacities over a large temperature range, i.e. 300-1500 K. For a test set of 27 nitrogen-containing compounds, the group additivity model succeeds in approximating the ab initio calculated values for the standard enthalpy of formation with a MAD of 2.3 kJ mol-1. The MAD for the standard entropy and heat capacity is lower than 4 and 2 J mol-1 K-1, respectively. For a test set of 11 nitrogen-containing compounds, the MAD between experimental and group additivity approximated values for the standard enthalpy of formation amounts to 2.8 kJ mol-1.

15.
Quant Imaging Med Surg ; 14(7): 4362-4375, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39022288

ABSTRACT

Background: Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imaging (MRI) could provide a biomarker to predict growth rate facilitating better-informed disease management and better clinical outcomes. We assessed the ability of putative quantitative and qualitative MRI predictive factors to predict UF growth rate. Methods: Twenty women with UFs were recruited and completed baseline and follow-up MRI exams, 1-2.5 years apart. The subjects filled out symptom severity and health-related quality of life questionnaires at each visit. A standard clinical pelvic MRI non-contrast exam was performed at each visit, followed by a contrast-enhanced multi-parametric quantitative MRI (mp-qMRI) exam with T2, T2*, and apparent diffusion coefficient (ADC) mapping and dynamic contrast-enhanced MRI. Up to 3 largest fibroids were identified and outlined on the T2-weighted sequence. Fibroid morphology and enhancement patterns were qualitatively assessed on dynamic contrast-enhanced MRI. The UFs' volumes and average T2, T2*, and ADC values were calculated. Pearson correlation coefficients were calculated between UF growth rate and T2, T2*, ADC, and baseline volume. Multiple logistic regression and receiver operating characteristic (ROC) analysis were performed to predict fast-growing UFs using combinations of up to 2 significant predictors. A significance level of alpha =0.05 was used. Results: Forty-four fibroids in 20 women had growth rate measurement available, and 36 fibroids in 16 women had follow-up quantitative MRI available. The distribution of fibroid growth rate was skewed, with approximately 20% of the fibroids exhibiting fast growth (>10 cc/year). However, there were no significant changes in median baseline and follow-up values of symptom severity and health-related quality of life scores. There was no change in average T2, T2*, and ADC at follow-up exams and there was a moderate to strong correlation to the fibroid growth rate in baseline volume and average T2 and ADC in slow-growing fibroids (<10 cc/year). A multiple logistic regression to identify fast growing UFs (>10 cc/year) achieved an area under the curve (AUC) of 0.80 with specificity of 69% at 100% sensitivity. Conclusions: The mp-qMRI parameters T2, ADC, and UF volume obtained at the time of initial fibroid diagnosis may be able to predict UF growth rate. Mp-qMRI could be integrated into the management of UFs, for individualized care and improved clinical outcomes.

16.
Adv Sci (Weinh) ; : e2308176, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39024521

ABSTRACT

Microbial carbon (C) use efficiency (CUE) delineates the proportion of organic C used by microorganisms for anabolism and ultimately influences the amount of C sequestered in soils. However, the key factors controlling CUE remain enigmatic, leading to considerable uncertainty in understanding soil C retention and predicting its responses to global change factors. Here, we investigate the global patterns of CUE estimate by stoichiometric modeling in surface soils of natural ecosystems, and examine its associations with temperature, precipitation, plant-derived C and soil nutrient availability. We found that CUE is determined by the most limiting resource among these four basic environmental resources within specific climate zones (i.e., tropical, temperate, arid, and cold zones). Higher CUE is common in arid and cold zones and corresponds to limitations in temperature, water, and plant-derived C input, while lower CUE is observed in tropical and temperate zones with widespread limitation of nutrients (e.g., nitrogen or phosphorus) in soil. The contrasting resource limitations among climate zones led to an apparent increase in CUE with increasing latitude. The resource-specific dependence of CUE implies that soils in high latitudes with arid and cold environments may retain less organic C in the future, as warming and increased precipitation can reduce CUE. In contrast, oligotrophic soils in low latitudes may increase organic C retention, as CUE could be increased with concurrent anthropogenic nutrient inputs. The findings underscore the importance of resource limitations for CUE and suggest asymmetric responses of organic C retention in soils across latitudes to global change factors.

17.
Curr Opin Struct Biol ; 88: 102877, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39024941

ABSTRACT

RNA molecules fold to form complex internal structures. Many of these RNA structures populate ensembles with rheostat-like properties, with each state having a distinct function. Until recently, analysis of RNA structures, especially within cells, was limited to modeling either a single averaged structure or computationally-modeled ensembles. These approaches obscure the intrinsic heterogeneity of many structured RNAs. Single-molecule correlated chemical probing (smCCP) strategies are now making it possible to measure and deconvolute RNA structure ensembles based on efficiently executed chemical probing experiments. Here, we provide an overview of fundamental single-molecule probing principles, review current ensemble deconvolution strategies, and discuss recent applications to diverse biological systems. smCCP is enabling a revolution in understanding how the plasticity of RNA structure is exploited in biological systems to respond to stimuli and alter gene function. The energetics of RNA ensembles are often subtle and a subset can likely be targeted to modulate disease-associated biological processes.

18.
Mod Pathol ; : 100567, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025407

ABSTRACT

Several professional society guidelines suggest germline genetic testing for colorectal polyposis syndromes in patients with ≥10 lifetime adenomatous polyps. This study evaluated factors associated with genetic testing decisions and outcomes when germline testing was recommended per guidelines. Surgical archives revealed 145 patients with a recommendation for germline genetic polyposis testing based on guidelines. Demographic data and medical history were collected to examine for association with testing decisions and results. Germline genetic testing was ordered in 90/145 patients and was ordered in younger patients with more lifetime adenomas. Pathogenic alterations were detected in 12/53 patients who completed testing. Younger age and higher numbers of lifetime adenomas were not associated with the detection of germline genetic alterations. In fact, patients with a pathogenic germline alteration had higher median ages and fewer lifetime adenomas than those without an alteration. Half of the twelve patients with a pathogenic germline mutation were not White non-Hispanic, though White non-Hispanic patients comprised 75.5% of those tested. This study supports the 10 adenomatous polyp threshold for recommending germline genetic polyposis testing, as an alteration was detected in a sizable proportion (>20%) of patients tested. Though younger age and a higher number of lifetime adenomas were associated with an increased likelihood of ordered tests, no evidence was found to support these additional factors in testing decisions.

19.
PLoS Pathog ; 20(7): e1012338, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008527

ABSTRACT

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.

20.
Int J Speech Lang Pathol ; : 1-9, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028220

ABSTRACT

PURPOSE: To enable the codesign of a training framework for brain-computer interfaces for augmentative and alternative communications access (BCI-AAC), the aim of this study is to evaluate the initial BCI-AAC training needs and preferred learning strategies of speech-language pathologists (SLPs) with AAC experience. METHOD: Eleven SLPs employed across a broad range of settings completed a semi-structured interview. A grounded theory approach alongside peer debriefing and review, member checking, and triangulation procedures were utilised for thematic analysis to help ensure data reliability and credibility. RESULT: Regarding critical training needs, SLPs identified the subthemes of (a) personalisation of intervention, (b) technical aspects, (c) BCI-AAC system types and access, and (d) how to support stakeholders in BCI-AAC implementation. Regarding learning strategy preferences, participants discussed (a) expert guidance and demonstrations, (b) hands-on experience, alongside (c) media and presentations. CONCLUSION: Findings present a continuum of critical training needs ranging from more foundational information to more personalised assessment and intervention consideration. These thematic results present a first step in developing a basic framework for SLP training in BCI-AAC to utilise and build from as technology development continues, and provides an important initial starting point for the codesign of clinically focused BCI-AAC trainings.

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