"Very early" intrahepatic cholangiocarcinoma (≤ 2.0 cm): MRI manifestation and prognostic potential.

AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.

Cryo-storage of porcine hides at the industrial scale for tissue engineering and regenerative medicine application.

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

Viscoelastic properties of decellularized and freeze-dried human dermis between i909c and 40cC.

BACKGROUND: Human donor skin is processed to make the acellular dermis matrix (ADM) for tissue repair and regeneration. There is no data on the viscoelastic properties of ADM at room and subzero temperatures. OBJECTIVE: The work evaluated the temperature dependence of viscoelastic properties of freeze-dried ADM. MATERIALS AND METHODS: Donor skin was de-epidermized, de-cellularized and freeze-dried with trehalose as the lyo-protectant. Glass transition of freeze-dried ADM was measured by differential scanning calorimeter (DSC), and viscoelastic properties were examined by dynamic mechanical analyzer (DMA). RESULTS: At the low moisture range (1.4 +/- 0.5%), the glass transition temperature (Tg) of freeze-dried ADM was 90 degree C to 100 degree C. As the moisture content increased, the Tg decreased steadily. At the high moisture range (10.8 +/- 2.9%), the Tg was 40 degree C to 60 degree C. There were large donor-to-donor variations in viscoelastic properties of freeze-dried ADM as demonstrated by the changes in storage modulus (G'), loss modulus (G") and damping factor tan delta (G"/G'). However, the trends of the temperature dependence for G', G" and tan delta were similar among all 8 donors. For each donor, changes in G' and G" were relatively small between -90 degree C and 40 degree C, and G' was at least one order of magnitude greater than G". Two viscoelastic relaxations were observed in freeze-dried ADM, one at -20 degree C and the other at -60 degree C respectively. CONCLUSION: Freeze-dried ADM was protected in the glassy carbohydrate matrix. DMA observed two viscoelastic relaxations (i.e., alpha process at -20 degree C and beta process at -60 degree C). Overall changes in G' and G'' of freeze-dried ADM were relatively small within one order of magnitude between -90 degree C and 40 degree C. https://doi.org/10.54680/fr24110110612.

Influence of intracranial hemorrhage on clinical outcome in acute vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND AND PURPOSE: The effect of intracranial hemorrhage (ICH) on the outcome of patients with large-vessel occlusion undergoing endovascular treatment (EVT) has mainly focused on the anterior circulation. Knowledge of the relationship between ICH and outcomes in patients with acute vertebrobasilar artery occlusion (VBAO) receiving EVT is limited. We aimed to assess whether ICH is a prognostic marker for acute VBAO following EVT. METHODS: Patients who underwent EVT for acute VBAO in the acute posterior circulation ischemic stroke (PERSIST) registry were included. All patients were classified as having no or any-ICH. Any-ICH was subdivided into asymptomatic and symptomatic ICH. A multivariate regression analysis was performed to evaluate the association between ICH and functional outcomes in patients with acute VBAO after receiving EVT. RESULTS: Five hundred and forty-seven patients, including 107 patients with ICH (19.6%): 38 (7.0%) and 69 (12.6%) with symptomatic and asymptomatic ICH, respectively. After adjustment for potential confounders, any-ICH was independently associated with reduced chance of favorable outcome (OR 0.39, 95% CI 0.21-0.72, P=0.003), functional independence (OR 0.24, 95% CI 0.16-0.52, P<0.001), and excellent outcome (OR 0.34, 95% CI 0.15-0.75, P=0.008), and increased mortality risk (OR 2.14, 95% CI 1.30-3.51, P=0.003). Symptomatic ICH had a similar association. Moreover, asymptomatic ICH was a negative predictor of functional independence (OR 0.39, 95% CI 0.17-0.88, P=0.024). CONCLUSION: Any- and symptomatic ICH were strongly associated with worse clinical outcomes and increased mortality in patients with acute VBAO who underwent EVT. Asymptomatic ICH was an inverse predictor of functional independence.

[The clinical value of heat shock protein 90α in predicting the prognosis of interventional therapy for hepatocellular carcinoma].

Objective: To evaluate the relationship between plasma heat shock protein 90α (HSP90α) levels and treatment response after four weeks and long-term prognosis after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Methods: The clinical data of HCC patients who underwent TACE in the Department of Interventional Radiology, Cancer Hospital of Chinese Academy of Medical Sciences from August 2017 to December 2018 were retrospectively collected. Chi-square tests were used to analyze the relationship between plasma HSP90α level and clinicopathological features before TACE treatment. Univariate and multivariate logistic regression analysis was used to analyze the influencing factors of TACE treatment response. Univariate and multivariate Cox regression analysis was used to analyze the influencing factors of progression-free survival (PFS) after TACE treatment. Results: The expression level of plasma HSP90α in 96 patients before TACE treatment was (99.70 ± 66.61) ng/ml. Compared with the low HSP90α group (n=66), the high HSP90α group (n=30) had larger tumors, higher alpha-fetoprotein enrichment, more positive vascular invasions, and more advanced Barcelona Clinic Liver Cancer (BCLC) stages (all P<0.05). After four weeks of TACE treatment, 41 patients in the response group and 55 patients in the non-response group were evaluated. The difference of HSP90α expression levels between the response group and the non-response group before and after TACE treatment was (-32.20±22.79) ng/ml and (7.20±51.94) ng/ml, respectively, and the difference was statistically significant (P<0.001). Multivariate logistic regression analysis showed that Child-Pugh classification (OR=0.186, P=0.046), vascular invasion (OR=0.132, P=0.025), and the percentage reduction of plasma HSP90α after TACE treatment (percentage reduction 25%-50%: OR=5.061, P=0.013; percentage reduction >50%: OR= 86.831, P<0.001) were independent influencing factors for the response to TACE treatment in HCC. The median PFS of the 96 patients was 8.7 months. Multivariate Cox regression analysis showed that BCLC stage (stage B: HR=2.804, P=0.008; stage C: HR=4.628, P<0.001) and the percentage reduction of plasma HSP90α after TACE treatment (percentage reduction 25%-50%: HR=0.569, P=0.051; percentage reduction >50%: HR=0.198, P<0.001) were independent influence factors for the PFS in these HCC patients after TACE treatment. Conclusion: Plasma HSP90α may represent a novel biomarker for predicting efficacy of TACE and PFS of patients with HCC.

[Treatment strategy for low-risk papillary thyroid carcinoma with diameter smaller than 1 cm: immediate surgery vs active surveillance].

The incidence of differentiated thyroid cancer is increasing rapidly worldwide, with subcentimeter papillary thyroid carcinoma (SPTC) with a diameter of less than 1 cm accounting for more than 50%. Active surveillance (AS) as an alternative to immediate surgery for low-risk SPTC was launched in Japan in the 1990s and has been implemented in several countries, including Japan and the United States. However, the indications and safety of performing AS for low-risk SPTC remain controversial. In this article, the author summarizes the existing literature and explores its limitations of AS implementation, the effectiveness of surgical treatment, and the different attitudes of countries on AS, aiming to provide some references for the treatment options of low-risk SPTC.

Two-Stage Treatment Protocol of Fungal Periprosthetic Hip and Knee Joint Infections: the Clinical Experience from a Single Center Experience.

PURPOSE OF THE STUDY: To evaluate the clinical results and safety of fungal periprosthetic joint Infections (fPJIs) using two-stage treatment protocol. MATERIAL AND METHODS: 8 patients with fPJIs (3 hips and 5 knees) using two-stage revision were reviewed retrospectively and followed up at least 2 years. The preoperative demographic data, two-stage treatment protocol, results of microbiology and histologic workup and postoperative follow-up results (reimplantation success rate and infection free time) were recorded. RESULTS: 7 patients got successful reimplantation, with a 75% reimplantation success rate. Two patients got knee arthrodesis eventually. All patients were infection free with a median follow-up of 4.0 ± 2.0 years (range, 2-7 years). Of them, Candida species were found in 7 patients, while non-Candida specimen was only isolated in 1 patient with Aspergillus. Only 2 patients had coexisting bacterial infection (Methicillin-resistant coagulase-negative Staphylococci and Proteus mirabilis respectively). The average interval between the initial surgery and diagnosis of fPJIs was 21.50±34.79 months (range, 4-104 months). The mean time of spacer implantation was 7.75±2.77 months (range, 6-14 months). None serious complication or above knee amputation was found. DISCUSSION: fPJIs are very rare and considerable challenge after total hip or knee arthroplasty. The goal of therapy is to eradicate local infection and maintain function. Candida species were the most common pathogen. The duration between spacer placement and staged reimplantation was highly variable, and generally dependent upon the results of joint aspirates and infl ammatory markers. The current study shows that the two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. CONCLUSIONS: The two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. The safety and effi cacy of biantibiotical impregnated (antifungal + antibiotics) cement spacer is confi rmed. Further evidence-based work is needed to determine the optimal drug dose and reimplantation time. KEY WORDS: two-stage treatment protocol, fungal periprosthetic infections, hip spacer, knee spacer.

[Hymenolepis diminuta infection in an adult's lung: a case report].

Hymenolepis diminuta is a common parasite of rats and mice, but is very rare in humans with cases reported from various parts of the world. Here, we reported a case of Hymenolepis diminuta infection involving both the respiratory and digestive tracts in a 49-year-old male patient whose initial imaging and symptoms were strikingly similar to pneumonia. Since no disease-causing pathogens were found during routine examinations, we considered respiratory infection by specific pathogens before metagenomic next-generation sequencing of broncho-alveolar lavage fluid confirmed the diagnosis of Hymenolepis diminuta. After confirming the diagnosis, we retested the patient's stool repeatedly and found Hymenolepis diminuta eggs finally. To help doctors better understand this condition and avoid misdiagnosis, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for infection by Hymenolepis diminuta.

Galectin-8 involves in arthritic condylar bone loss via podoplanin/AKT/ERK axis-mediated inflammatory lymphangiogenesis.

OBJECTIVE: The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. Galectin-8 (Gal-8) regulates pathological lymphangiogenesis but the effects of which on inflammation-related condylar bone loss in temporomandibular joint (TMJ) have not been well studied. DESIGN: We used TNFα-transgenic (TNFTG) mice and their wildtype (WT) littermates to compare their inflammatory phenotype in TMJs. Next, lymphatic endothelial cells (LECs) were used to examine the effects of which on osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis with or without thiodigalactoside (TDG, a Gal-8 inhibitor) treatment. At last, two murine models (TNFTG arthritic model and forced mouth opening model) were used to explore TDG as a potential drug for the treatment of inflammation-related condylar bone loss. RESULTS: In comparison to WT mice, lymphatic areas of lymphatic vessel endothelial receptor 1 (LYVE1)+/podoplanin (PDPN)+ and Gal-8+/PDPN+, TRAP-positive osteoclast number, and condylar bone loss are increased in TNFTG mice. Inhibition of Gal-8 in LECs by TDG, reduces TNFα-induced osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis. In addition, Gal-8 promotes TNFα-activated AKT/ERK/NF-κB pathways by binding to PDPN. Finally, the administration of TDG attenuates inflammatory lymphangiogenesis, inhibits osteoclast activity, and reduces condylar bone loss in TNFTG arthritic mice and forced mouth opening mice. CONCLUSIONS: Our findings reveal the important role of Gal-8-promoted pathological lymphangiogenesis in inflammation-related condylar bone loss.

Regional and global climate risks for reef corals: Incorporating species-specific vulnerability and exposure to climate hazards.

Climate change is driving rapid and widespread erosion of the environmental conditions that formerly supported species persistence. Existing projections of climate change typically focus on forecasts of acute environmental anomalies and global extinction risks. The current projections also frequently consider all species within a broad taxonomic group together without differentiating species-specific patterns. Consequently, we still know little about the explicit dimensions of climate risk (i.e., species-specific vulnerability, exposure and hazard) that are vital for predicting future biodiversity responses (e.g., adaptation, migration) and developing management and conservation strategies. Here, we use reef corals as model organisms (n = 741 species) to project the extent of regional and global climate risks of marine organisms into the future. We characterise species-specific vulnerability based on the global geographic range and historical environmental conditions (1900-1994) of each coral species within their ranges, and quantify the projected exposure to climate hazard beyond the historical conditions as climate risk. We show that many coral species will experience a complete loss of pre-modern climate analogs at the regional scale and across their entire distributional ranges, and such exposure to hazardous conditions are predicted to pose substantial regional and global climate risks to reef corals. Although high-latitude regions may provide climate refugia for some tropical corals until the mid-21st century, they will not become a universal haven for all corals. Notably, high-latitude specialists and species with small geographic ranges remain particularly vulnerable as they tend to possess limited capacities to avoid climate risks (e.g., via adaptive and migratory responses). Predicted climate risks are amplified substantially under the SSP5-8.5 compared with the SSP1-2.6 scenario, highlighting the need for stringent emission controls. Our projections of both regional and global climate risks offer unique opportunities to facilitate climate action at spatial scales relevant to conservation and management.

Enhancement of blue and ultraviolet components in PCF-based supercontinuum generation through inter-modal dispersive-wave radiation.

Broadband supercontinuum (SC) light sources generated through nonlinear effects in solid-core photonic crystal fibers (PCFs) have been widely used in spectroscopy, metrology, and microscopy, leading to great application successes. The short-wavelength extension of such SC sources, a longstanding challenge, has been the subject of intensive study over the past two decades. However, the exact mechanism of blue and ultraviolet light generation, especially for some resonance spectral peaks in the short-wavelength regime, is not yet fully understood. Here, we demonstrate that the effect of inter-modal dispersive-wave radiation, which results from phase matching between pump pulses at the fundamental optical mode and packets of linear waves at some higher-order modes (HOMs) propagating in the PCF core, might be one of the critical mechanisms that can result in some resonance spectral components with wavelengths much shorter than that of the pump light. We observed in an experiment that several spectral peaks resided in the blue and ultraviolet regimes of the SC spectrum, whose central wavelengths can be tuned by varying the PCF-core diameter. These experimental results can be interpreted well using the inter-modal phase-matching theory, providing some useful insights into the SC generation process.

Exploring the risks and benefits of flexibility in biodiversity offset location in a case study of migratory shorebirds.

Biodiversity offsets aim to counterbalance the residual impacts of development on species and ecosystems. Guidance documents explicitly recommend that biodiversity offset actions be located close to the location of impact because of higher potential for similar ecological conditions, but allowing greater spatial flexibility has been proposed. We examined the circumstances under which offsets distant from the impact location could be more likely to achieve no net loss or provide better ecological outcomes than offsets close to the impact area. We applied a graphical model for migratory shorebirds in the East Asian-Australasian Flyway as a case study to explore the problems that arise when incorporating spatial flexibility into offset planning. Spatially flexible offsets may alleviate impacts more effectively than local offsets; however, the risks involved can be substantial. For our case study, there were inadequate data to make robust conclusions about the effectiveness and equivalence of distant habitat-based offsets for migratory shorebirds. Decisions around offset placement should be driven by the potential to achieve equivalent ecological outcomes; however, when considering more distant offsets, there is a need to evaluate the likely increased risks alongside the potential benefits. Although spatially flexible offsets have the potential to provide more cost-effective biodiversity outcomes and more cobenefits, our case study showed the difficulty of demonstrating these benefits in practice and the potential risks that need to be considered to ensure effective offset placement.

Estudio de los riesgos y beneficios de la flexibilidad en la ubicación de compensación de la biodiversidad en el estudio de caso de aves costeras migratorias Resumen Las compensaciones de la biodiversidad buscan contrabalancear el impacto residual que tiene el desarrollo sobre las especies y los ecosistemas. Los documentos guía recomiendan explícitamente que las acciones de estas compensaciones estén ubicadas cerca del lugar del impacto debido al potencial elevado de que haya condiciones ecológicas similares, aunque ya hay propuestas de una mayor flexibilidad espacial. Analizamos las circunstancias bajo las cuales las compensaciones alejadas del lugar de impacto tendrían mayor probabilidad de lograr pérdidas netas nulas o de proporcionar mejores resultados ecológicos que las compensaciones cercanas al área de impacto. Aplicamos un modelo gráfico para las aves costeras migratorias en el corredor aéreo asiático-australasiático del este como estudio de caso para estudiar los problemas que surgen cuando se incorpora la flexibilidad espacial a la planeación de las compensaciones. Las compensaciones espacialmente flexibles pueden mitigar los impactos más efectivamente que las compensaciones locales; sin embargo, los riesgos que esto involucra pueden ser considerables. En nuestro estudio de caso hubo datos insuficientes para concluir contundentemente sobre la efectividad y equivalencia de las compensaciones basadas en los hábitats distantes para las aves costeras migratorias. Las decisiones en torno a la ubicación de las compensaciones deberían estar impulsadas por el potencial para obtener resultados ecológicos equivalentes; sin embargo, al considerar compensaciones más alejadas, existe la necesidad de evaluar el incremento probable de riesgos junto a los beneficios potenciales. Aunque las compensaciones espacialmente flexibles tienen el potencial para proporcionar resultados más rentables y más beneficios colaterales, nuestro estudio de caso mostró la dificultad para demostrar estos beneficios en la práctica y los riesgos potenciales que necesitan considerarse para asegurar una ubicación efectiva de las compensaciones.

Whole-genome sequencing analysis in fetal structural anomalies: novel phenotype-genotype discoveries.

OBJECTIVES: The identification of structural variants and single-nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole-genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. METHODS: We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ-T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). RESULTS: Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon-level copy-number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. CONCLUSIONS: Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, where routine genetic tests have failed to diagnose. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

Quantitative image features of gadoxetic acid-enhanced MRI for predicting glypican-3 expression of small hepatocellular carcinoma ≤3 cm.

AIM: To explore the value of quantitative image features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting Gglypican-3 (GPC3) expression of single hepatocellular carcinoma (HCC) ≤3 cm. MATERIALS AND METHODS: One hundred and forty-nine patients with histopathologically confirmed HCC were included retrospectively. Quantitative image features and clinicopathological parameters were analysed. The significant predictors for GPC3 expression were identified using multivariate logistic regression analyses. Nomograms were constructed from the prediction model and the progression-free survival (PFS) rate was evaluated by the Kaplan-Meier method. RESULTS: The tumour-to-liver signal intensity (SI) ratio on the hepatobiliary phase (HBP; odds ratio [OR] = 0.004; p=0.001), serum alpha-fetoprotein (AFP) > 20 ng/ml (OR=6.175; p<0.001), and non-smooth tumour margin (OR=4.866; p=0.002) were independent significant factors for GPC3 expression. When the three factors were combined, the diagnostic specificity was 97.7% (42/43). The nomogram based on the predictive model performed satisfactorily (C-index: 0.852). Kaplan-Meier curves showed that patients with GPC3-positive HCCs have lower PFS rates than patients with GPC3-negative HCCs (Log-rank test, p=0.006). CONCLUSION: The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.

TBMaLT, a flexible toolkit for combining tight-binding and machine learning.

Tight-binding approaches, especially the Density Functional Tight-Binding (DFTB) and the extended tight-binding schemes, allow for efficient quantum mechanical simulations of large systems and long-time scales. They are derived from ab initio density functional theory using pragmatic approximations and some empirical terms, ensuring a fine balance between speed and accuracy. Their accuracy can be improved by tuning the empirical parameters using machine learning techniques, especially when information about the local environment of the atoms is incorporated. As the significant quantum mechanical contributions are still provided by the tight-binding models, and only short-ranged corrections are fitted, the learning procedure is typically shorter and more transferable as it were with predicting the quantum mechanical properties directly with machine learning without an underlying physically motivated model. As a further advantage, derived quantum mechanical quantities can be calculated based on the tight-binding model without the need for additional learning. We have developed the open-source framework-Tight-Binding Machine Learning Toolkit-which allows the easy implementation of such combined approaches. The toolkit currently contains layers for the DFTB method and an interface to the GFN1-xTB Hamiltonian, but due to its modular structure and its well-defined interfaces, additional atom-based schemes can be implemented easily. We are discussing the general structure of the framework, some essential implementation details, and several proof-of-concept applications demonstrating the perspectives of the combined methods and the functionality of the toolkit.

Newly proposed survival staging system for poorly differentiated thyroid cancer: a SEER-based study.

OBJECTIVE: Despite the recent release of the 8th edition TNM staging system, the risk stratification for poorly differentiated thyroid cancer (PDTC) remains controversial. STUDY DESIGN: Retrospective study. SETTING: SEER database and the First Hospital of China Medical University (FHCMU) database. METHODS: Between 2004 and 2015, 1201 PDTC patients from the SEER database were enrolled to propose a new staging system. 38 PDTC patients were included from the FHCMU. RESULTS: A retrospective analysis of 1201 PDTC cases was performed, and a new staging classification was developed as follows: stage I: age < 55 and T1/any N/M0 (n = 127, 10.57%); stage II: age < 55 and T2-4/any N/M0 or age ≥ 55 and T1-2/any N/M0 (n = 523, 43.55%); stage III: age < 55 and any T/N0/M1 or age ≥ 55 and any T3/any N/M0 (n = 239, 19.90%); stage IV: age < 55 and any T/N1/M1 or age ≥ 55 and T4/any N/M0, and T/any N/M1 (n = 312, 25.98%). The 10-year disease-specific survival rates of patients in the new stages I, II, III, and IV were 97.9%, 77.9%, 35.3%, and 12.1%, respectively. The proportion of variation explained (PVE) for disease-specific survival of the proposed system was higher than that of the 8th AJCC TNM staging (30.61% vs. 27.15%). The accuracy of the staging system was verified in 38 PDTC patients from the FHCMU. CONCLUSION: The proposed staging system provided a more accurate risk stratification for PDTC patients. The new staging model may facilitate the design of personalized treatment strategies for PDTC patients.

Effect of antioxidant procyanidin b2 (pcb2) on ovine oocyte developmental potential in response to in vitro maturation (ivm) and vitrification stress.

BACKGROUND: It was demonstrated that external stress, such as in vitro maturation (IVM) and vitrification process can induce significantly reduced development capacity in oocytes. Previous studies indicated that antioxidants play a pivotal part in the acquisition of adaptation in changed conditions. At present, the role of the natural potent antioxidant PCB2 in response to IVM and vitrification during ovine oocyte manipulation has not been explored. OBJECTIVE: To investigate whether PCB2 treatment could improve the developmental potential of ovine oocytes under IVM and vitrification stimuli. MATERIALS AND METHODS: The experiment was divided into two parts. Firstly, the effect of PCB2 on the development of oocytes during IVM was evaluated. Un-supplemented and 5 ug per mL PCB2-supplemented in the IVM solution were considered as control and experimental groups (C + 5 ug per mL PCB2). The polar body extrusion (PBE) rate, mitochondrial membrane potential (MMP), ATP, reactive oxygen species (ROS) levels and early apoptosis of oocytes were measured after IVM. Secondly, we further determine whether PCB2 could improve oocyte quality under vitrification stress. The survival rate, PBE rate and early apoptosis of oocytes were compared between fresh group, vitrified group and 5 ug per mL PCB2-supplemented in the IVM solution after vitrification (V + 5 ug per mL PCB2). RESULTS: Compared to the control group, adding PCB2 significantly increased PBE rate (79.4% vs. 62.8%, P < 0.01) and MMP level (1.9 +/- 0.08 vs. 1.3 +/- 0.04, P < 0.01), and decreased ROS level (47.1 +/- 6.3 vs. 145.3 +/- 8.9, P < 0.01). However, there was no significant difference in ATP content and early apoptosis. Compared to the fresh group, vitrification significantly reduced oocytes viability (43.0% vs. 90.8%, P < 0.01) as well as PBE rate (24.2% vs. 60.6%, P < 0.05). However, 5 ug per mL PCB2-supplemention during maturation had no effect on survival, PBE or early apoptosis in vitrified oocytes. CONCLUSION: PCB2 could effectively antagonise the oxidative stress during IVM and promote oocyte development. DOI: 10.54680/fr23210110412.

[Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma].

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

[Association between lesion location and depressive symptoms in acute ischemic stroke patients using voxel-based lesion-symptom mapping].

Objective: The study aimed to investigate the association between lesion location and post-stroke depression (PSD) in acute ischemic stroke patients. Methods: In this case-control study, acute ischemic stroke patients were recruited from the Department of Neurology, First Affiliated Hospital of the University of Science and Technology of China (USTC), between September 2020 and June 2021. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, the patients were divided into the PSD and non-PSD groups. The 24-item Hamilton Rating Scale (HAMD) was used to evaluate the severity of depression. The Student's t-test, Mann-Whitney test, and Chi-square test were used to compare the clinical baseline characteristics of PSD and non-PSD groups. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and depression occurrence and severity. Results: A total of 70 and 173 patients were admitted to the PSD and non-PSD groups, respectively. The mean age of patients was 59 years (23-86). There were 153 males and 90 females. Univariate analysis showed a significant difference only in Hamilton Anxiety (P=0.025) and Depression (P<0.001) scores between the PSD and non-PSD groups. VLSM analysis identified clusters within the anterior cingulate gyrus (Z=-3.05, P<0.001), left hippocampus (Z=-3.15, P<0.001), and left lingual lobe (Z=-3.08, P<0.001) where lesions were significantly associated with PSD. Additionally, the severity of PSD was associated with damage in the anterior cingulate gyrus (Z=-3.64, P<0.001), left hippocampus (Z=-3.51, P<0.001), left lingual lobe (Z=-4.18, P<0.001), and pericalcarine cortex (Z=-3.65, P<0.001). Conclusion: VLSM demonstrated that lesion location could be used to predict the occurrence of PSD in patients with acute ischemic stroke.