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1.
Res Sq ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38746293

RESUMO

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.

2.
Bioinformatics ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796681

RESUMO

MOTIVATION: Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinations of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs on the same protein molecule, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even PTMs at distant sites to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein. RESULTS: We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I2MS) data. I2MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. The algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I2MS data and experimental I2MS data for the tumor suppressor protein p53. We show that MSModDetector is a useful tool for comparing a protein's PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes. AVAILABILITY: The source code is available at https://github.com/marjanfaizi/MSModDetector. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

3.
Nat Chem Biol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773328

RESUMO

A timely inflammatory response is crucial for early viral defense, but uncontrolled inflammation harms the host. Retinoic acid-inducible gene I (RIG-I) has a pivotal role in detecting RNA viruses, yet the regulatory mechanisms governing its sensitivity remain elusive. Here we identify PTENα, an N-terminally extended form of PTEN, as an RNA-binding protein with a preference for the CAUC(G/U)UCAU motif. Using both in vivo and in vitro viral infection assays, we demonstrated that PTENα restricted the host innate immune response, relying on its RNA-binding capacity and phosphatase activity. Mechanistically, PTENα directly bound to viral RNA and enzymatically converted its 5'-triphosphate to 5'-monophosphate, thereby reducing RIG-I sensitivity. Physiologically, brain-intrinsic PTENα exerted protective effects against viral inflammation, while peripheral PTENα restricted host antiviral immunity and, to some extent, promoted viral replication. Collectively, our findings underscore the significance of PTENα in modulating viral RNA- and RIG-I-mediated immune recognition, offering potential therapeutic implications for infectious diseases.

4.
Cell Div ; 19(1): 18, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734666

RESUMO

BACKGROUND: The precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE. METHODS: Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay. RESULTS: PPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment. CONCLUSION: PPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.

6.
Insights Imaging ; 15(1): 119, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755299

RESUMO

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

7.
Langmuir ; 40(17): 9120-9133, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38629900

RESUMO

Nanostructured activated carbon (AC) adsorbents derived from woody biomass have garnered attention for their potential usage to remove toxic substances from the environment due to their high specific surface area, superior micro/mesoporosity, and tunable surface chemistry profile. However, chemical dopants widely used to enhance the chemical reactivity with heavy metals would pollute the environment and conflict with the vision of a cleaner and sustainable environment. Herein, we report a facile, green, and sustainable approach using fungi modification combined with alkali activation to produce AC for heavy metal removal. The decayed wood-derived AC (DAC) exhibited a high specific surface area of 2098 m2/g, and the content of O and N functional groups was 18 and 2.24%, respectively. It showed remarkable adsorption capacity toward Cd2+ of 148.7 mg/g, which was much higher than most reported Cd2+ adsorbents. Such excellent adsorption capacity was primarily based on enhanced physical adsorption (pore filling, π-π) and chemical adsorption (functional group complexation, ion exchange, and precipitation). Additionally, the DAC showed rapid kinetics and remarkable applicability in both dynamic environments and actual water samples. These results suggest that decayed wood has excellent potential for efficient use in the removal of Cd2+ from wastewater. Furthermore, these results indicate that decayed wood can be cleanly produced into high efficiency heavy metal adsorbents to realize value-added utilization of decayed wood.

8.
bioRxiv ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38645206

RESUMO

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.

9.
Dalton Trans ; 53(18): 7965-7970, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38647331

RESUMO

Organic crystal materials with metal-free feature and intrinsically low molecular mass are highly desirable for applications in flexible smart devices. Here, we reported a plastic crystal, tris(hydroxymethyl)aminomethane perchlorate (Tris-HClO4), which crystallizes in the R3̄ space group at room temperature and undergoes plastic phase transition at 369 K, showing a large entropy gain of 70.5 J mol-1 K-1, much higher than its fusion entropy gain (12.9 J mol-1 K-1). PXRD measurement indicates that it has cubic lattice symmetry in the high-temperature phase. Moreover, it exhibits excellent dielectric permittivity switching properties and robust cyclic stability. This work could be the pathway for chemical designing multifunctional switchable materials with the motive of combining the idea of symmetry breaking and plastic phase transition.

10.
Prev Med ; 183: 107955, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641082

RESUMO

BACKGROUND: The impact of various exercise modalities on the improvement of sleep quality in adults remains controversial. OBJECTIVE: This study aimed to perform a network meta-analysis to analyze the effects of different exercise interventions on sleep quality in adults. METHODS: The PubMed, Cochrane, Embase, Web of Science, and EBSCO databases were searched for studies published from March 18, 1993, to March 18, 2023. The Cochrane risk of bias tool was used to assess the quality of the included studies. Then, a random-effects network meta-analysis was conducted within a frequentist framework. RESULTS: A total of 2142 participants from 27 randomized controlled trials were included in the analysis. Exercise modalities such as Pilates, yoga, and traditional Chinese exercises were found to significantly improve sleep quality when compared to a no-exercise control group, with Pilates exhibiting the most potent effect at a 95.3% improvement level. CONCLUSION: This study demonstrates that exercise interventions are effective in enhancing sleep quality in adults. Adapting exercise to individual preferences and needs may maximize the sleep-related benefits of the activity. REGISTRATION: The review was registered with PROSPERO, registration number CRD42023434565.


Assuntos
Exercício Físico , Metanálise em Rede , Qualidade do Sono , Humanos , Exercício Físico/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Terapia por Exercício/métodos , Yoga
11.
Microbes Infect ; : 105344, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670218

RESUMO

To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.

13.
Anal Chem ; 96(15): 5824-5831, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38573047

RESUMO

Infectious diseases pose a significant threat to global health, yet traditional microbiological identification methods suffer from drawbacks, such as high costs and long processing times. Raman spectroscopy, a label-free and noninvasive technique, provides rich chemical information and has tremendous potential in fast microbial diagnoses. Here, we propose a novel Combined Mutual Learning Net that precisely identifies microbial subspecies. It demonstrated an average identification accuracy of 87.96% in an open-access data set with thirty microbial strains, representing a 5.76% improvement. 50% of the microbial subspecies accuracies were elevated by 1% to 46%, especially for E. coli 2 improved from 31% to 77%. Furthermore, it achieved a remarkable subspecies accuracy of 92.4% in the custom-built fiber-optical tweezers Raman spectroscopy system, which collects Raman spectra at a single-cell level. This advancement demonstrates the effectiveness of this method in microbial subspecies identification, offering a promising solution for microbiology diagnosis.


Assuntos
Escherichia coli , Pinças Ópticas , Análise Espectral Raman/métodos
14.
J Health Popul Nutr ; 43(1): 55, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654371

RESUMO

PURPOSE: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. METHODS: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. RESULTS: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. CONCLUSION: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.


Assuntos
Glicemia , COVID-19 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Humanos , COVID-19/complicações , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glicemia/análise , Idoso , Diabetes Mellitus/sangue , SARS-CoV-2 , Adulto
15.
BMC Pregnancy Childbirth ; 24(1): 175, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448875

RESUMO

OBJECTIVE: To investigate the regulatory role of miR-223-3p in the inflammatory response of PE placenta. METHODS: PE and normal placental tissues were collected to measure the expression of NLRP3 and miR-223-3p. The targeting relationship between NLRP3 and miR-223-3P was verified by bioinformatics analysis and classical double-luciferase reporter gene assay. Lipopolysaccharide (LPS) was used to induce HTR8/SVneo cells as PE placental cell inflammation model. Then we transfected miR-223-3p overexpression/miR-223-3p negative control plasmid into the LPS-induced HTR8/SVneo cells. Next, the expressions of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 were evaluated to elucidate the regulatory effect of miR-223-3p on the inflammatory response mediated by NLRP3 in PE placenta. RESULTS: Compared with normal controls, NLRP3 was significantly up-regulated in PE placenta, while miR-223-3p was down-regulated. In addition, NLRP3 was a direct target of miR-223-3p. Further research revealed that the expression of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 could be obviously promoted in HTR8/SVneo cells treated with LPS (500 ng/ml) for 24 h, nevertheless it could be significantly suppressesed under the overexpression of miR-223-3p. CONCLUSION: MiR-223-3p suppressed NLRP3 inflamariomes activation, downstream inflammatory factors secretion and pyroptosis in LPS-induced HTR8/SVneo cells indicating that miR-223-3p could serve as an anti-inflammatory factor in preeclampsia.


Assuntos
MicroRNAs , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Caspases , Interleucina-18 , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Placenta , Pré-Eclâmpsia/genética
16.
Front Biosci (Landmark Ed) ; 29(3): 120, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38538251

RESUMO

BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.


Assuntos
Adenina , Neoplasias Ósseas , Metaloproteinase 2 da Matriz , Osteossarcoma , Humanos , Adenina/análogos & derivados , Epigênese Genética , Ligases/genética , Metaloproteinase 2 da Matriz/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Osteossarcoma/genética , Osteossarcoma/secundário , Proteínas do Grupo Polycomb/genética , RNA Mensageiro/genética , RNA Interferente Pequeno , Neoplasias Ósseas/patologia
17.
Water Res ; 255: 121488, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38513371

RESUMO

Waste activated sludge (WAS) is a significant phosphorus (P) repository, and there is a growing interest in P recovery from WAS. Typically, the commercial technology for treating WAS involves thermal hydrolysis pretreatment (THP) coupled with anaerobic digestion (AD). However, there is ongoing debate regarding the transformation and distribution of P throughout this process. To address this, a long-term THP-AD process was operated in this study to comprehensively investigate P transformation and distribution. The results revealed that a substantial biodegradation of dissolved organic nitrogen (DON) raised the pH of the digestate to 8.3 during the AD process. This increased pH facilitated the dissolution of Al, leading to a reduction of 6.92 mg/L of NaOH-P. Simultaneously, sulfate reduction contributed to a decrease of 11.04 mg/L of Bipy-P in the solid. However, the reduction of Bipy-P and NaOH-P in the solid did not result in an improved P release to the supernatant. Conversely, a decrease of 23.60 mg/L P in the aqueous phase was observed after anaerobic digestion. The disappeared P was primarily precipitated with Mg and Ca, driven by the increased pH, and it contributed to the increase of HCl-P in the solid from 107.80 to 144.52 mg/L. These findings were further confirmed by results obtained from scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and solid-state 31P nuclear magnetic resonance (NMR) spectroscopy. This study provides valuable insights into the mechanisms of P transformation during THP-AD process that is nearly opposite from conventional AD system.

18.
CPT Pharmacometrics Syst Pharmacol ; 13(5): 870-879, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38465417

RESUMO

Noncompartmental analysis (NCA) is a model-independent approach for assessing pharmacokinetics (PKs). Although the existing NCA algorithms are very well-established and widely utilized, they suffer from low accuracies in the setting of sparse PK samples. In response, we developed Deep-NCA, a deep learning (DL) model to improve the prediction of key noncompartmental PK parameters. Our methodology utilizes synthetic PK data for model training and uses an innovative patient-specific normalization method for data preprocessing. Deep-NCA demonstrated adequate performance across six previously unseen simulated drugs under multiple dosing, showcasing effective generalization. Compared to traditional NCA, Deep-NCA exhibited superior performance for sparse PK data. This study advances the application of DL to PK studies and introduces an effective method for handling sparse PK data. With further validation and refinement, Deep-NCA could significantly enhance the efficiency of drug development by providing more accurate NCA estimates while requiring fewer PK samples.


Assuntos
Aprendizado Profundo , Farmacocinética , Humanos , Algoritmos , Simulação por Computador , Modelos Biológicos , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/administração & dosagem , Desenvolvimento de Medicamentos/métodos
19.
Innovation (Camb) ; 5(2): 100580, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38476202

RESUMO

Various lines of evidence have been used to infer the origin of human bipedalism, but the paucity of hominoid postcranial fossils and the diversity of inferred locomotor modes have tended to confound the reconstruction of ancestral morphotypes. Examination of the bony labyrinth morphology of the inner ear of extinct and living hominoids provides independent evidence for inferring the evolution of hominoid locomotor patterns. New computed tomography data and morphometric analyses of the Late Miocene ape Lufengpithecus indicate that it and other stem great apes possess labyrinths similar to one another and show that hominoids initially evolved from a positional repertoire that included orthogrady, below-branch forelimb suspension and progression, above-branch bipedalism, climbing, clambering, and leaping (hylobatid-like) to one that comprised above-branch quadrupedalism, below-branch forelimb suspension, vertical climbing, limited leaping, terrestrial quadrupedal running and walking, possibly with knuckle walking, and short bouts of bipedalism (chimpanzee-like). The bony labyrinth morphology of Lufengpithecus indicates that it probably conforms more closely to the last common ancestors of crown hominoids and hominids in its locomotor behavior than do other Miocene hominoids. Human bipedalism evolved from this common archetypal Lufengpithecus-like locomotor repertoire. The low evolutionary rate of semicircular canal morphology suggests that Lufengpithecus experienced a relative stasis in locomotor behavior, probably due to the uplift of the Tibetan Plateau, which created a stable environment in the Miocene of southwestern China.

20.
Ear Nose Throat J ; : 1455613241231120, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426441

RESUMO

Poor blood glucose control is a common predisposing factor for parotid abscesses; however, extensive skin necrosis secondary to parotid abscesses has rarely been reported. In this article, we present the case of a 70-year-old man with poor glycemic control admitted to our hospital with swelling, congestion, and pain in the right parotid region that had gradually increased over 15 days prior to presentation. Based on the clinical, imaging, and laboratory findings, the patient was diagnosed with a giant parotid abscess with extensive skin necrosis caused by Klebsiella pneumoniae. The abscess responded poorly to long-term treatment with intravenous broad-spectrum antibiotics, and the patient underwent daily Bacillus exchange with blood glucose level management and electrolyte monitoring via routine blood tests. At the 3 month follow-up, complete resolution of the right parotid gland abscess and skin rupture was observed.

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