Selecting serum-free hepatocyte cryopreservation stage and storage temperature for the application of an "off-the-shelf" bioartificial liver system.

The bioartificial liver (BAL) system can potentially rescue acute liver failure (ALF) patients by providing partial liver function until a suitable donor liver can be found or the native liver has self-regenerated. In this study, we established a suitable cryopreservation process for the development of an off-the-shelf BAL system. The viability of hepatocyte spheroids cryopreserved in liquid nitrogen was comparable to that of fresh primary hepatocyte spheroids. When hepatocyte spheroids were subjected to cryopreservation in a deep freezer, no statistically significant differences were observed in ammonia removal rate or urea secretion rate based on the cryopreservation period. However, the functional activity of the liver post-cryopreservation in a deep freezer was significantly lower than that observed following liquid nitrogen cryopreservation. Moreover, cryopreserving spheroid hydrogel beads in a deep freezer resulted in a significant decrease (approximately 30%) in both ammonia removal and urea secretion rates compared to the group cryopreserved in liquid nitrogen. The viabilities of spheroid hydrogel beads filled into the bioreactor of a BAL system were similar across all four groups. However, upon operating the BAL system for 24 h, the liver function activity was significantly higher in the group comprising hydrogel beads generated after thawing hepatocyte spheroids cryopreserved in liquid nitrogen. Consequently, the manufacturing of beads after the cryopreservation of hepatocyte spheroids is deemed the most suitable method, considering efficiency, economic feasibility, and liver function activity, for producing a BAL system.

[18F]FDG PET/CT is useful in discriminating invasive adenocarcinomas among pure ground-glass nodules: comparison with CT findings-a bicenter retrospective study.

PURPOSE: Predicting the malignancy of pure ground-glass nodules (GGNs) using CT is challenging. The optimal role of [18F]FDG PET/CT in this context has not been clarified. We compared the performance of [18F]FDG PET/CT in evaluating GGNs for predicting invasive adenocarcinomas (IACs) with CT. METHODS: From June 2012 to December 2020, we retrospectively enrolled patients with pure GGNs on CT who underwent [18F]FDG PET/CT within 90 days. Overall, 38 patients with 40 ≥ 1-cm GGNs were pathologically confirmed. CT images were analyzed for size, attenuation, uniformity, shape, margin, tumor-lung interface, and internal/surrounding characteristics. Visual [18F]FDG positivity, maximum standardized uptake value (SUVmax), and tissue fraction-corrected SUVmax (SUVmaxTF) were evaluated on PET/CT. RESULTS: The histopathology of the 40 GGNs were: 25 IACs (62.5%), 9 minimally invasive adenocarcinomas (MIA, 22.5%), and 6 adenocarcinomas in situ (AIS, 15.0%). No significant differences were found in CT findings according to histopathology, whereas visual [18F]FDG positivity, SUVmax, and SUVmaxTF were significantly different (P=0.001, 0.033, and 0.018, respectively). The size, visual [18F]FDG positivity, SUVmax, and SUVmaxTF showed significant diagnostic performance to predict IACs (area under the curve=0.693, 0.773, 0.717, and 0.723, respectively; P=0.029, 0.001, 0.018, and 0.013, respectively). In the multivariate logistic regression analysis, visual [18F]FDG positivity discriminated IACs among GGNs among various CT and PET findings (P=0.008). CONCLUSIONS: [18F]FDG PET/CT demonstrated superior diagnostic performance compared to CT in differentiating IAC from AIS/MIA among pure GGNs, thus it has the potential to guide the proper management of patients with pure GGNs.

The downregulation of Kv1 channels in Lgi1-/-mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels.

In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with a marked increase in bursting patterns. Finally, mass spectrometry uncovered key modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.

Optimized combination of Cervus nippon (Sika deer), Angelica (Dangui), and Rehmannia (Suk-jihwang) mitigates LPS-induced inflammation: exploring signaling pathways through plasma metabolomics.

This study aimed to determine the optimal combination of three anti-inflammatory materials [i.e., Cervus nippon Temminck (CT), Angelica gigas Nakai (AN), and Rehmannia glutinosa (RG)] for the strongest anti-inflammatory potential. Eighteen combinations of the three materials were tested in LPS-stimulated RAW264.7 cells via assessing nitric oxide (NO). The best combination from in vitro studies was administered to LPS-treated C57BL/6J mice for five days. Subsequently, plasma metabolites were profiled by bioinformatics analyses and validations. As results, 2, 20, and 50 µg/mL of CT, AN, and RG (TM) were the most effective combination suppressing inflammation. In mice, TM mitigated hepatic inflammatory markers. Similarly, the metabolomics indicated that TM may suppress NF-κB signaling pathway, thereby alleviating hepatic inflammation. TM also decreased systemic and hepatic pro-inflammatory cytokines. Collectively, we found the optimal combination of TM for mitigating inflammation; thus further studies on safety, mechanisms, and clinical models are warranted for human applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01476-x.

A novel method of evaluating the non-invasive tear film break-up time and progression of corneal opacification in dogs using imaging video.

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (≥ 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (≥ 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 (n = 28), 0.10 ± 0.32 (n = 10), 0.19 ± 0.40 (n = 16). The NIBUT groups were significantly correlated with COS (p-value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 (p-value = 0.041) and between Groups 1 and 3 (p-value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS.

Improvement of Transfusion Practice in Cardiothoracic Surgery Through Implementing a Patient Blood Management Program.

Background: In this study, we examined the impact of a patient blood management (PBM) program on red blood cell (RBC) transfusion practices in cardiothoracic surgery. Methods: The PBM program had 3 components: monitoring transfusions through an order communication system checklist, educating the medical team about PBM, and providing feedback to ordering physicians on the appropriateness of transfusion. The retrospective analysis examined changes in the hemoglobin levels triggering transfusion and the proportions of appropriate RBC transfusions before, during, and after PBM implementation. Further analysis was focused on patients undergoing cardiac surgery, with outcomes including 30-day mortality, durations of intensive care unit and hospital stays, and rates of pneumonia, sepsis, and wound complications. Results: The study included 2,802 patients admitted for cardiothoracic surgery. After the implementation of PBM, a significant decrease was observed in the hemoglobin threshold for RBC transfusion. This threshold dropped from 8.7 g/dL before PBM to 8.3 g/dL during the PBM education phase and 8.0 g/dL during the PBM feedback period. Additionally, the proportion of appropriate RBC transfusions increased markedly, from 23.9% before PBM to 34.9% and 58.2% during the education and feedback phases, respectively. Among the 381 patients who underwent cardiac surgery, a significant reduction was noted in the length of hospitalization over time (p<0.001). However, other clinical outcomes displayed no significant differences. Conclusion: PBM implementation effectively reduced the hemoglobin threshold for RBC transfusion and increased the rate of appropriate transfusion in cardiothoracic surgery. Although transfusion practices improved, clinical outcomes were comparable to those observed before PBM implementation.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Unveiling synergistic QTLs associated with slow wilting in soybean (Glycine max [L.] Merr.).

KEY MESSAGE: A stable QTL qSW_Gm10 works with a novel locus, qSW_Gm01, in a synergistic manner for controlling slow-wilting traits at the early vegetative stage under drought stress in soybean. Drought is one of the major environmental factors which limits soybean yield. Slow wilting is a promising trait that can enhance drought resilience in soybean without additional production costs. Recently, a Korean soybean cultivar SS2-2 was reported to exhibit slow wilting at the early vegetative stages. To find genetic loci responsible for slow wilting, in this study, quantitative trait loci (QTL) analysis was conducted using a recombinant inbred line (RIL) population derived from crossing between Taekwangkong (fast-wilting) and SS2-2 (slow-wilting). Wilting score and leaf moisture content were evaluated at the early vegetative stages for three years. Using the ICIM-MET module, a novel QTL on Chr01, qSW_Gm01 was identified, together with a previously known QTL, qSW_Gm10. These two QTLs were found to work synergistically for slow wilting of the RILs under the water-restricted condition. Furthermore, the SNP markers from the SoySNP50K dataset, located within these QTLs, were associated with the wilting phenotype in 30 diverse soybean accessions. Two genes encoding protein kinase 1b and multidrug resistance-associated protein 4 were proposed as candidate genes for qSW_Gm01 and qSW_Gm10, respectively, based on a comprehensive examination of sequence variation and gene expression differences in the parental lines under drought conditions. These genes may play a role in slow wilting by optimally regulating stomatal aperture. Our findings provide promising genetic resources for improving drought resilience in soybean and give valuable insights into the genetic mechanisms governing slow wilting.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

CREB5 promotes the proliferation and self-renewal ability of glioma stem cells.

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Does Sacral Slanting Affect Postoperative Shoulder Balance in Patients With Lenke Type 2A Adolescent Idiopathic Scoliosis?

OBJECTIVE: Even minor sacral slanting can influence T1 tilt and shoulder balance. Yet, the relationship between sacral slanting and postoperative shoulder imbalance (PSI) has not been previously explored. To determine risk factors for PSI in Lenke 2A adolescent idiopathic scoliosis (AIS) patients, with an emphasis on sacral slanting. METHODS: The study encompassed 96 consecutive patients who had undergone posterior correction and fusion surgery for Lenke type 2A AIS. Patients were grouped into PSI(+) and PSI(-) based on postoperative outcomes. Additionally, they were classified into left-sided slanting, no slanting, and right-sided slanting groups according to the degree of sacral slanting. Various radiological measures were compared. RESULTS: Patients in the PSI(+) group exhibited a smaller preoperative proximal thoracic curve and a higher main thoracic curve correction rate than those in the PSI(-) group. The presence or absence of sacral slanting did not exhibit a significant variation in PSI occurrence. However, the right-sided sacral slanting group showed a larger delta radiologic shoulder height compared to the other 2 groups (7.1 mm vs. 1.5 & 3.3 mm). CONCLUSION: Sacral slanting was not directly linked to the development of PSI. Despite the common postoperative elevation of the left shoulder, the shoulder height differences decreased over the follow-up period. Especially in cases with a right-sided tilted sacrum, the PSI demonstrated progressive improvement, with an associated increase in the rightward distal wedging angle, leading to distal adding-on.

Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation.

The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, ß-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.

Lower-Body Fractures and the Risk of Dementia: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: The association between physical activity and dementia has been shown in various observational studies. We aimed to determine the risk of dementia in the elderly with lower-body fractures. METHODS: We reconstructed a population-based matched cohort from the National Health Insurance Service-Senior Cohort data set that covers 511,953 recipients of medical insurance in South Korea. RESULTS: Overall 53,776 subjects with lower-body fractures were identified during 2006-2012, and triplicate control groups were matched randomly by sex, age, and years from the index date for each subject with a fracture. There were 3,573 subjects (6.6%) with and 7,987 subjects (4.9%) without lower-body fractures who developed dementia from 2008 up to 2015. Lower-body fractures were independently associated with a subsequent dementia diagnosis with a higher adjusted hazard ratio (aHR) (1.55, 95% confidence interval [CI]=1.49-1.62) compared with upper-body fractures (aHR=1.19, 95% CI=1.14-1.23). CONCLUSIONS: These results support the protective role of physical activity against dementia and highlight the importance of promoting fracture prevention in the elderly.

Ceramide promotes lytic reactivation of Epstein-Barr virus in gastric carcinoma.

Epstein-Barr virus (EBV) has a lifelong latency period after initial infection. Rarely, however, when the EBV immediate early gene BZLF1 is expressed by a specific stimulus, the virus switches to the lytic cycle to produce progeny viruses. We found that EBV infection reduced levels of various ceramide species in gastric cancer cells. As ceramide is a bioactive lipid implicated in the infection of various viruses, we assessed the effect of ceramide on the EBV lytic cycle. Treatment with C6-ceramide (C6-Cer) induced an increase in the endogenous ceramide pool and increased production of the viral product as well as BZLF1 expression. Treatment with the ceramidase inhibitor ceranib-2 induced EBV lytic replication with an increase in the endogenous ceramide pool. The glucosylceramide synthase inhibitor Genz-123346 inhibited C6-Cer-induced lytic replication. C6-Cer induced extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB phosphorylation, c-JUN expression, and accumulation of the autophagosome marker LC3B. Treatment with MEK1/2 inhibitor U0126, siERK1&2, or siCREB suppressed C6-Cer-induced EBV lytic replication and autophagy initiation. In contrast, siJUN transfection had no impact on BZLF1 expression. The use of 3-methyladenine (3-MA), an inhibitor targeting class III phosphoinositide 3-kinases (PI3Ks) to inhibit autophagy initiation, resulted in reduced beclin-1 expression, along with suppressed C6-Cer-induced BZLF1 expression and LC3B accumulation. Chloroquine, an inhibitor of autophagosome-lysosome fusion, increased BZLF1 protein intensity and LC3B accumulation. However, siLC3B transfection had minimal effect on BZLF1 expression. The results suggest the significance of ceramide-related sphingolipid metabolism in controlling EBV latency, highlighting the potential use of drugs targeting sphingolipid metabolism for treating EBV-positive gastric cancer.IMPORTANCEEpstein-Barr virus remains dormant in the host cell but occasionally switches to the lytic cycle when stimulated. However, the exact molecular mechanism of this lytic induction is not well understood. In this study, we demonstrate that Epstein-Barr virus infection leads to a reduction in ceramide levels. Additionally, the restoration of ceramide levels triggers lytic replication of Epstein-Barr virus with increase in phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB. Our study suggests that the Epstein-Barr virus can inhibit lytic replication and remain latent through reduction of host cell ceramide levels. This study reports the regulation of lytic replication by ceramide in Epstein-Barr virus-positive gastric cancer.

Paravertebral Nerve Block for Procedural Pain in Percutaneous Vertebroplasty.

OBJECTIVES: This study aimed to unidimensionally measure procedural pain at each percutaneous vertebroplasty (PVP) stage and evaluate the effectiveness of paravertebral nerve block (PVNB) in reducing procedural pain. METHODS: A retrospective study of prospectively collected data was conducted on 66 patients who underwent PVP for osteoporotic vertebral compression fractures. The patients were divided into 2 groups: group A (fluoroscopic-guided PVNB; 5 cm 3 of 0.75% ropivacaine on each side) and group B (local anesthesia). To investigate procedural pain associated with PVP, the visual analog scale score was assessed at each surgical stage: before the incision (stage 1), transpedicular approach (stage 2), and polymethylmethacrylate cement injection (stage 3). After the procedure, patients were asked about their surgical experience and satisfaction using the Iowa Satisfaction with Anesthesia Scale. Periprocedural complications were also recorded. RESULTS: A total of 63 patients (78.65 y of age) were finally enrolled: 30 from group A and 33 from group B. In both groups, a significant ≥2-point increase in procedural pain was observed during PVP compared with that during stage 1 ( P < 0.001). In stages 2 and 3, the pain intensity was significantly lower in group A ( P < 0.001). Upon discharge, the visual analog scale score improved in all groups; however, the Iowa Satisfaction with Anesthesia Scale score was significantly higher in group A ( P < 0.001). There was no difference in periprocedural complications between the two groups ( P = 0.743). CONCLUSION: PVP causes significant procedural pain, and PVNB is a potentially effective modality for enhancing patient satisfaction and reducing procedural pain.

Differential involvement of mitochondria in post-tetanic potentiation at intracortical excitatory synapses of the medial prefrontal cortex.

Post-tetanic Ca2+ release from mitochondria produces presynaptic residual calcium, which contributes to post-tetanic potentiation. The loss of mitochondria-dependent post-tetanic potentiation is one of the earliest signs of Alzheimer's model mice. Post-tetanic potentiation at intracortical synapses of medial prefrontal cortex has been implicated in working memory. Although mitochondrial contribution to post-tetanic potentiation differs depending on synapse types, it is unknown which synapse types express mitochondria-dependent post-tetanic potentiation in the medial prefrontal cortex. We studied expression of mitochondria-dependent post-tetanic potentiation at different intracortical synapses of the rat medial prefrontal cortex. Post-tetanic potentiation occurred only at intracortical synapses onto layer 5 corticopontine cells from commissural cells and L2/3 pyramidal neurons. Among post-tetanic potentiation-expressing synapses, L2/3-corticopontine synapses in the prelimbic cortex were unique in that post-tetanic potentiation depends on mitochondria because post-tetanic potentiation at corresponding synapse types in other cortical areas was independent of mitochondria. Supporting mitochondria-dependent post-tetanic potentiation at L2/3-to-corticopontine synapses, mitochondria-dependent residual calcium at the axon terminals of L2/3 pyramidal neurons was significantly larger than that at commissural and corticopontine cells. Moreover, post-tetanic potentiation at L2/3-corticopontine synapses, but not at commissural-corticopontine synapses, was impaired in the young adult Alzheimer's model mice. These results would provide a knowledge base for comprehending synaptic mechanisms that underlies the initial clinical signs of neurodegenerative disorders.

ChatGPT-assisted deep learning for diagnosing bone metastasis in bone scans: Bridging the AI Gap for Clinicians.

Background: Bone scans are often used to identify bone metastases, but their low specificity may necessitate further studies. Deep learning models may improve diagnostic accuracy but require both medical and programming expertise. Therefore, we investigated the feasibility of constructing a deep learning model employing ChatGPT for the diagnosis of bone metastasis in bone scans and to evaluate its diagnostic performance. Method: We examined 4626 consecutive cancer patients (age, 65.1 ± 11.3 years; 2334 female) who had bone scans for metastasis assessment. A nuclear medicine physician developed a deep learning model using ChatGPT 3.5 (OpenAI). We employed ResNet50 as the backbone network and compared the diagnostic performance of four strategies (original training set, original training set with 1:10 class weight, 10-fold data augmentation for positive images only, and 10-fold data augmentation for all images) to address the class imbalance. We used a class activation map algorithm for visualization. Results: Among the four strategies, the deep learning model with 10-fold data augmentation for positive cases only, using a batch size of 16 and an epoch size of 150, achieved the area under curve of 0.8156, the sensitivity of 56.0 %, and specificity of 88.7 %. The class activation map indicated that the model focused on disseminated bone metastases within the spine but might confuse them with benign spinal lesions or intense urinary activity. Conclusions: Our study illustrates that a clinical physician with rudimentary programming skills can develop a deep learning model for medical image analysis, such as diagnosing bone metastasis in bone scans using ChatGPT. Model visualization may offer guidance in enhancing deep learning model development, including preprocessing, and potentially support clinical decision-making processes.

A simplified risk scoring system for predicting high-risk groups in gene expression tests for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-positive breast cancer.

Purpose: The gene expression test (GET) was used to predict the response to chemotherapy and the recurrence risk. Several randomized clinical trials have demonstrated that some patients with node-positive disease can achieve favorable survival outcomes even without adjuvant chemotherapy. This study aimed to predict the results of Oncotype DX (Genomic Health) and MammaPrint (Agendia) using traditional clinicopathological factors. Methods: We reviewed the records of 311 patients who underwent GET for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative primary invasive breast cancer with node-positive disease between 2015 and 2022 at Severance Hospital and Gangneung Asan Medical Center. Univariate and multivariate logistic regression analyses assessed the relationships between clinicopathological variables and risk stratification using the GET results. Results: A simple scoring system was created by assigning integer values to each variable. A score of 3 was assigned for histological grade 3, a score of 2 for pathologic T2 or above, and a score of 1 for a lower progesterone receptor (1-20 or Alled score 3-6), HER2 2-positive, and high Ki-67 (>20). In the validation cohort, overall accuracy was 0.798 (95% confidence interval, 0.744-0.844). Conclusion: The high GET risk results can be predicted using traditional clinicopathological factors: tumor size, progesterone receptor, histological grade, HER2, and Ki-67. These results will be useful for treatment decision-making among clinically high-risk patients with HR-positive/HER2-negative and node-positive disease, helping to identify patients to whom the GET assay may not apply.