-
Bioinformatics (Oxford, England) Jun 2024High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to...
MOTIVATION
High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. Simultaneously, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops and other stochastic contacts.
RESULTS
We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17% in mean squared error and 26% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 14% relative to existing methods. We further show that our multiview idea can also be used to improve several existing methods, HiCARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix.
AVAILABILITY AND IMPLEMENTATION
Implementation of Capricorn and source code for reproducing all figures in this paper are available at https://github.com/CHNFTQ/Capricorn.
Topics: Chromatin; Machine Learning; Humans; Computational Biology; Algorithms; Software
PubMed: 38940142
DOI: 10.1093/bioinformatics/btae211 -
Journal of Integrative Neuroscience Jun 2024To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in...
PURPOSE
To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 ().
METHODS
This cross-sectional study included 36 individuals without SCD without (healthy control, HC group), 21 individuals with SCD with (APOEε4+ group), and 33 individuals with SCD without (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups.
RESULTS
Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group ( < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group.
CONCLUSIONS
Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.
Topics: Humans; Apolipoprotein E4; White Matter; Male; Female; Cognitive Dysfunction; Cross-Sectional Studies; Aged; Middle Aged; Nerve Net; Diffusion Tensor Imaging; Diagnostic Self Evaluation
PubMed: 38940088
DOI: 10.31083/j.jin2306117 -
Veterinary Radiology & Ultrasound : the... Jun 2024A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary...
A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary differential diagnosis was a portosystemic shunt (PSS). Three-phase computed tomographic angiography findings were consistent with a transhepatic portosystemic shunt. Percutaneous liver biopsy confirmed severe diffuse hepatic changes, most likely due to chronic pyrrolizidine alkaloid toxicosis, and medical management was elected. Based on an extensive literature review, this is the first report of a transhepatic portosystemic collateral vessel in a horse. Computed tomographic angiography is feasible and useful for the diagnosis of PSS in miniature horses.
PubMed: 38940068
DOI: 10.1111/vru.13401 -
Annals of Ibadan Postgraduate Medicine Apr 2024The white cerebellum sign (WCS) is a classical but rare radiological finding usually associated with irreversible diffuse hypoxic-ischemic cerebral injury. Very few...
INTRODUCTION
The white cerebellum sign (WCS) is a classical but rare radiological finding usually associated with irreversible diffuse hypoxic-ischemic cerebral injury. Very few cases exist in the literature globally, especially from the West African region, as a potential hallmark of poor prognostic outcome. We describe the white cerebellum sign in a Nigerian pediatric patient, managed for severe head injury.
CASE PRESENTATION
A fourteen-year old boy presented to our emergency department with loss of consciousness following a pedestrian road traffic accident. Physical examination revealed a critically ill boy with fever, hypotension, tachycardia, gasping respiration, GCS 3, bilateral dilated unreactive pupils, absent corneal, gag and oculocephalic reflexes. He was thus diagnosed of severe traumatic brain injury and brainstem dysfunction. He had endotracheal intubation, ventilatory and inotropic support. Cranial computerized tomography scan of the patient showed radiological features in keeping with the WCS. His clinical status remained poor until he suffered a cardiac arrest about twelve hours after admission.
CONCLUSION
WCS has been reported in relation to child abuse, anoxic-ischemic brain injury, inflammatory and metabolic brain disorders and trauma. It is a classical radiological description of diffuse cerebral edema alongside relatively normal cerebellar hemispheres and brainstem. Management of this pathology is symptomatic, and aims to ameliorate the associated raised intracranial pressure, control seizures and prevent cerebral infarction. The index patient, who presented 24 hours after severe head injury with associated early post-traumatic seizures, respiratory failure and brainstem dysfunction, had an unfavourable outcome consistent with previous reports of WCS. We have reported the rare but classical white cerebellum sign. It remains a grave prognosticator of cerebral injury and should be sought for in the neuroimaging of patients with acute brain insults.
PubMed: 38939880
DOI: No ID Found -
Leukemia Research Reports 2024Preventing central nervous system (CNS) relapse is a major challenge in the treatment of diffuse large B-cell lymphoma (DLBCL). However, no previous studies have...
Preventing central nervous system (CNS) relapse is a major challenge in the treatment of diffuse large B-cell lymphoma (DLBCL). However, no previous studies have examined the efficacy of polatuzumab vedotin (PV)-containing regimens in preventing CNS relapse in patients with DLBCL. Here, we report two cases of CNS relapse after PV-containing chemotherapy for DLBCL. CNS relapse developed during combination therapy with PV, bendamustine, and rituximab (PV-BR) in one patient and six months after PV-BR in the other patient. PV-containing chemotherapy may be ineffective as a prophylaxis against CNS relapse; therefore, additional strategies for preventing CNS relapse in DLBCL patients are required.
PubMed: 38939513
DOI: 10.1016/j.lrr.2024.100467 -
Frontiers in Oncology 2024Based on comparison of different machine learning (ML) models, we developed the model that integrates traditional hand-crafted (HC) features and ResNet50 network-based...
PURPOSE
Based on comparison of different machine learning (ML) models, we developed the model that integrates traditional hand-crafted (HC) features and ResNet50 network-based deep transfer learning (DTL) features from multiparametric MRI to predict Ki-67 status in sinonasal squamous cell carcinoma (SNSCC).
METHODS
Two hundred thirty-one SNSCC patients were retrospectively reviewed [training cohort (n = 185), test cohort (n = 46)]. Pathological grade, clinical, and MRI characteristics were analyzed to choose the independent predictor. HC and DTL radiomics features were extracted from fat-saturated T2-weighted imaging, contrast-enhanced T1-weighted imaging, and apparent diffusion coefficient map. Then, HC and DTL features were fused to formulate the deep learning-based radiomics (DLR) features. After feature selection and radiomics signature (RS) building, we compared the predictive ability of RS-HC, RS-DTL, and RS-DLR.
RESULTS
No independent predictors were found based on pathological, clinical, and MRI characteristics. After feature selection, 42 HC and 10 DTL radiomics features were retained. The support vector machine (SVM), LightGBM, and ExtraTrees (ET) were the best classifier for RS-HC, RS-DTL, and RS-DLR. In the training cohort, the predictive ability of RS-DLR was significantly better than those of RS-DTL and RS-HC (p< 0.050); in the test set, the area under curve (AUC) of RS-DLR (AUC = 0.817) was also the highest, but there was no significant difference of the performance between DLR-RS and HC-RS.
CONCLUSIONS
Both the HC and DLR model showed favorable predictive efficacy for Ki-67 expression in patients with SNSCC. Especially, the RS-DLR model represented an opportunity to advance the prediction ability.
PubMed: 38939344
DOI: 10.3389/fonc.2024.1305836 -
Frontiers in Microbiology 2024This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics...
This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect and . The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). in 79.2% and in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.
PubMed: 38939191
DOI: 10.3389/fmicb.2024.1366719 -
Chemical Science Jun 2024Metathesis reactions are widely used in synthetic chemistry. While state-of-the-art organic metathesis involves highly controlled processes where specific bonds are...
Metathesis reactions are widely used in synthetic chemistry. While state-of-the-art organic metathesis involves highly controlled processes where specific bonds are broken and formed, inorganic metathesis reactions are often extremely exothermic and, consequently, poorly controlled. Ternary nitrides offer a technologically relevant platform for expanding synthetic control of inorganic metathesis reactions. Here, we show that energy-controlled metathesis reactions involving a heterovalent exchange are possible in inorganic nitrides. We synthesized ZnWN by swapping Zn and Li between LiWN and ZnX (X = Br, Cl, F) precursors. The synchrotron powder X-ray diffraction and differential scanning calorimetry show that the reaction onset is correlated with the ZnX melting point and that product purity is inversely correlated with the reaction's exothermicity. Therefore, careful choice of the halide counterion (, ZnBr) allows the synthesis to proceed in a swift but controlled manner at a surprisingly low temperature for an inorganic nitride (300 °C). High resolution synchrotron powder X-ray diffraction and diffuse reflectance spectroscopy confirm the synthesis of a cation-ordered ZnWN semiconducting material. We hypothesize that this synthesis strategy is generalizable because many Li-M-N phases are known (where M is a metal) and could therefore serve as precursors for metathesis reactions targeting new ternary nitrides. This work expands the synthetic control of inorganic metathesis reactions in a way that will accelerate the discovery of novel functional ternary nitrides and other currently inaccessible materials.
PubMed: 38939135
DOI: 10.1039/d4sc00322e -
Chemical Science Jun 2024Lanthanide(iii) (Ln) complexes have desirable photophysical properties for optical bioimaging. However, despite their advantages over organic dyes, their use for...
Lanthanide(iii) (Ln) complexes have desirable photophysical properties for optical bioimaging. However, despite their advantages over organic dyes, their use for microscopy imaging is limited by the high-energy UV excitation they require and their poor ability to cross the cell membrane and reach the cytosol. Here we describe a novel family of lanthanide-based luminescent probes, termed dTAT[Ln·L], based on (i) a DOTA-like chelator with a picolinate moiety, (ii) a two-photon absorbing antenna to shift the excitation to the near infrared and (ii) a dimeric TAT cell-penetrating peptide for cytosolic delivery. Several Tb and Eu probes were prepared and characterized. Two-photon microscopy of live cells was attempted using a commercial microscope with the three probes showing the highest quantum yields (>0.15). A diffuse Ln emission was detected in most cells, which is characteristic of cytosolic delivery of the Ln complex. The cytotoxicity of these three probes was evaluated and the IC ranged from 7 μM to >50 μM. The addition of a single positive or negative charge to the antenna of the most cytotoxic compound was sufficient to lower significantly or suppress its toxicity under the conditions used for two-photon microscopy. Therefore, the design reported here provides excellent lanthanide-based probes for two-photon microscopy of living cells.
PubMed: 38939128
DOI: 10.1039/d4sc00896k -
Frontiers in Bioengineering and... 2024Combination therapy with oral administration of several active ingredients is a popular clinical treatment for cancer. However, the traditional method has poor...
Combination therapy with oral administration of several active ingredients is a popular clinical treatment for cancer. However, the traditional method has poor convenience, less safety, and low efficiency for patients. The combination of traditional pharmaceutical techniques and advanced material conversion methods can provide new solutions to this issue. In this research, a new kind of hybrid film was created via coaxial electrospraying, followed by a casting process. The films were composed of Reglan and 5-fluorouracil (5-FU)-loaded cellulose acetate (CA) core-shell particles in a polyvinylpyrrolidone (PVP) film matrix. Microscopic observations of these films demonstrated a solid cross section loaded with core-shell particles. X-ray diffraction and Fourier-transform infrared tests verified that the Reglan and 5-FU loaded in the films showed amorphous states and fine compatibilities with the polymeric matrices, i.e., PVP and CA, respectively. dissolution tests indicated that the films were able to provide the desired asynchronous dual-drug delivery, fast release of Reglan, and sustained release of 5-FU. The controlled release mechanisms were shown to be an erosion mechanism for Reglan and a typical Fickian diffusion mechanism for 5-FU. The protocols reported herein pioneer a new approach for fabricating biomaterials loaded with multiple drugs, each with its own controlled release behavior, for synergistic cancer treatment.
PubMed: 38938981
DOI: 10.3389/fbioe.2024.1398730