Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model.

Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer's disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics.

Influence of Oxygen Vacancies Introduced via Acceptor (Gadolinium) Doping to the Pseudocapacitive Properties of Nano-Sized Cerium Oxide.

The voluntary introduction of defects can be considered an effective strategy for enhancing the electrochemical properties of metal oxide electrodes. In this study, the enhanced pseudocapacitive properties of an acceptor (Gd) doped cerium oxide nanoparticle-a sustainable metal oxide with low environmental and human toxicity-are investigated in depth using ex situ X-ray photoemission spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Interestingly, with 15 at% Gd doping (15GDC), the specific capacitance of the nanoparticles measured at 1 A g-1 enhanced to 547.8 F g-1, which is fivefold higher than undoped CeO2 (98.7 F g-1 at 1 A g-1). The rate-dependent capacitance is also improved for 15GDC, which showed a 31.0% decrease in the specific capacitance upon a tenfold increase in the current density, while CeO2 showed a 49.9% decrease. The enhanced electrochemical properties are studied in depth via ex situ XPS and EIS analysis, which revealed that the oxygen vacancies at the surface of the nanoparticles played important roles in enhancing both the specific capacitance and the high-rate performance of 15GDC by acting as the active site for pseudocapacitive redox reaction and allowing fast diffusion of oxygen ions at the surface of 15GDC nanoparticles.

GV1001 modulates neuroinflammation and improves memory and behavior through the activation of gonadotropin-releasing hormone receptors in a triple transgenic Alzheimer's disease mouse model.

GV1001 protects neural cells from amyloid-ß (Aß) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Aß oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro, GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Aß oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways.

Current updates relating to treatment for interstitial cystitis/bladder pain syndrome: systematic review and network meta-analysis.

BACKGROUND: Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). METHODS: We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges' g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. RESULTS: A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. CONCLUSION: This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. TRIAL REGISTRATION: PROSPERO CRD42022384024.

Comparison of the diagnostic performance of the Swischuk line method and the anterior atlantodental interval method in atlantodental subluxation.

BACKGROUND: Atlantodental subluxation (ADS) is a serious condition that can result in sudden death. Measuring the anterior atlantodental interval (AADI method) is the gold standard for diagnosis but the complex anatomy of this region can make diagnosis difficult, especially for beginners. Therefore, we would like to use a simpler method, the Swischuk line method, to diagnose ADS. The purpose of our study was to evaluate the diagnostic performance of the Swischuk line method for ADS on lateral cervical spine radiographs compared to the AADI method. METHODS: A retrospective study was conducted with patients who presented with ADS (ADS group, n = 32, mean age 57.78 years, age range 34-82 years, 10 men, 21 women) and an age- and sex-matched control group (n = 32). The diagnostic performance of the AADI method and the Swischuk line method for ADS was assessed using lateral cervical radiographs in both flexion and neutral postures by an experienced musculoskeletal radiologist (reader 1), a senior resident (reader 2), and a junior resident (reader 3) in the radiologic department. RESULTS: In the flexion posture, the AADI method and the Swischuk line method showed excellent diagnostic performance with AUCs > 0.9 for readers 1 2 and reader 3. In a neutral posture, the diagnostic performance of the AADI and Swischuk line methods was decreased. With a 1 mm cut-off value using the Swischuk line method in flexion posture, the sensitivity was 75% or more, the specificity was 100%, and the accuracy was 87.50% or more 90.63% for all readers. With a 2 mm cut-off value, the sensitivity was low (37.50-46.88%) but the specificity was 100% for all three readers. In a neutral posture, the sensitivity for both methods decreased, though specificity remained high (> 80%). CONCLUSIONS: The Swischuk line method was found to be reliable and showed high sensitivity and specificity with a cut-off value of 1 mm for the diagnosis of ADS in cervical lateral radiographs in flexion posture. It can be used as a complement to the AADI method.

Clinical Characteristics and Relevance of Dizziness in Patients with de novo Parkinson's Disease.

BACKGROUND: The purpose of this study was to determine the detailed characteristics of dizziness in patients with de novo Parkinson's disease (PD) and the clinical implications of dizziness. METHODS: Ninety-three people with de novo PD were enrolled between July 2017 and August 2022 for this retrospective study. Using each representative scale, various motor and non-motor symptoms were assessed. In addition, clinical manifestations of dizziness in those patients, including its presence, type, frequency, and duration of occurrence, were investigated. RESULTS: Thirty-nine patients with de novo PD reported dizziness, with presyncope being the most common (38%). The most common frequency was several times a week (51%). The most common duration was a few seconds (67%). Multivariable logistic regression analysis showed that dizziness was more common in women than in men {odds ratio (OR): 3.3601, 95% confidence interval (CI): 1.0820-10.4351, p = 0.0361}. Dizziness was significantly related to non-motor symptoms of low global cognition (OR: 0.8372, 95% CI: 0.7285-0.9622, p = 0.0123) and severe autonomic dysfunction (OR: 1.1112, 95% CI: 1.0297-1.1991, p = 0.0067). A post-hoc analysis revealed that dizziness was only associated with cardiovascular dysautonomia (adjusted OR: 10.2377, 95% CI: 3.3053-31.7098, p < 0.0001) among several domains of dysautonomia. CONCLUSIONS: About 42% of patients with de novo PD complained of dizziness. The occurrence of dizziness in those people was highly associated with female gender women, cognitive impairment, and cardiovascular dysautonomia. These results suggest that clinicians should pay close attention when patients with PD complain of dizziness.

Development of a Normal Porcine Cell Line Growing in a Heme-Supplemented, Serum-Free Condition for Cultured Meat.

A key element for the cost-effective development of cultured meat is a cell line culturable in serum-free conditions to reduce production costs. Heme supplementation in cultured meat mimics the original meat flavor and color. This study introduced a bacterial extract generated from Corynebacterium that was selected for high-heme expression by directed evolution. A normal porcine cell line, PK15, was used to apply the bacterial heme extract as a supplement. Consistent with prior research, we observed the cytotoxicity of PK15 to the heme extract at 10 mM or higher. However, after long-term exposure, PK15 adapted to tolerate up to 40 mM of heme. An RNA-seq analysis of these heme-adapted PK15 cells (PK15H) revealed a set of altered genes, mainly involved in cell proliferation, metabolism, and inflammation. We found that cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), lactoperoxidase (LPO), and glutathione peroxidase 5 (GPX5) were upregulated in the PK15H heme dose dependently. When we reduced serum serially from 2% to serum free, we derived the PK15H subpopulation that was transiently maintained with 5-10 mM heme extract. Altogether, our study reports a porcine cell culturable in high-heme media that can be maintained in serum-free conditions and proposes a marker gene that plays a critical role in this adaptation process.

Prediction of complete response after neoadjuvant chemotherapy for invasive breast cancers: The utility of shear wave elastography and superb microvascular imaging in pretreatment breast ultrasound.

PURPOSE: To investigate whether multiparametric parameters of pretreatment breast ultrasound (US) and clinicopathologic factors are associated with pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer. METHODS: Between November 2018 and September 2022, 88 patients who underwent NAC and subsequent surgery were included in this study (median age, 55 years; interquartile range [IQR], 45, 59.3). Multiparametric breast US including grayscale, shear wave elastography (SWE) and superb microvascular imaging (SMI) of pathologically proven invasive breast cancers were retrospectively reviewed. Clinicopathological and multiparametric parameters of breast US, including size, SWEmax, SWEratio and vascular index on SMI (SMIVI) were compared between the groups. Univariate and multivariate logistic regression analyses were performed to determine factors predicting pCR after NAC. AUROC curve analysis was performed to determine the predictors' optimal cut-off values and diagnostic performance. RESULTS: The pCR group (n = 24) showed a significantly smaller tumor size, lower SWEmax, higher Ki-67 index, higher hormone receptor negativity and negative axillary lymph node metastasis compared to the non-pCR group (n = 64). Multivariate regression analysis showed that SWEmax (adjusted odds ratio[aOR] = 0.956, 95 % confidence interval [CI] = 0.919-0.994, P = 0.025) and Ki-67 index (aOR = 1.083, 95 % CI = 1.012-1.159, P = 0.021) were independently associated with pathologically complete response. The optimal cut-off values for predicting pCR were 27.5 % for Ki-67 with an AUC of 0.743 and 134.8 kPa for SWEmax with an AUC of 0.779. A combination model including clinical factors and SWEmax showed the best diagnostic performance with an AUC of 0.876. CONCLUSION: A higher Ki-67 index and lower SWEmax measured on pretreatment breast US were independently associated with pCR in invasive breast cancer after NAC.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study.

PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls. METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007). CONCLUSIONS: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of Extracellular Calcium Concentration on Hepatic Ischemia-Reperfusion Injury in a Rat Model.

OBJECTIVES: Hypocalcemia is frequently identified during liver transplant. However, supplementation of extracellular calcium could induce increased intracellular calcium concentration, as a potential factor for injury to the liver graft. We evaluated the effects of regulating extracellular calcium concentrations on hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 24 Sprague-Dawley rats into 3 groups: group C received normal saline (n = 8), group L received citrate to induce hypocalcemia (n = 8), and group L-Co received citrate followed by calcium gluconate to ameliorate hypocalcemia (n = 8). Liver enzyme levels and extracellular calcium were measured before surgery, 1 hour after ischemia, and 2 hours after reperfusion. The primary outcome was liver enzyme levels measured 2 hours after reperfusion. In addition, we evaluated intracellular calcium levels, lactate dehydrogenase activity, and histopathological results in liver tissue. RESULTS: Three groups demonstrated significant differences in extracellular calcium concentrations, but intracellular calcium concentrations in liver tissue were not significantly different. Group L showed significantly lower mean arterial pressure than other groups at 1 hour after ischemia (93.6 ± 20.8 vs 69.4 ± 14.2 vs 86.6 ± 10.4 mmHg; P = .02, for group C vs L vs L-Co, respectively). At 2 hours after reperfusion, group L showed significantly higher liver enzymes than other groups (aspartate aminotransferase 443.0 ± 353.2 vs 952.3 ± 94.8 vs 502.4 ± 327.3 U/L, P = .01; and alanine aminotransferase 407.9 ± 406.5 vs 860.6 ± 210.9 vs 333.9 ± 304.2 U/L, P = .02; for group C vs L vs L-Co, respectively). However, no significant difference was shown in lactate dehydrogenase and histological liver injury grade. CONCLUSIONS: Administering calcium to rats with hypocalcemia did not increase intracellular calcium accumulation but instead resulted in less hepatic injury compared with rats with low extracellular calcium concentrations in this rat model study.

Transperineal versus transrectal prostate fiducial insertion in radiation treatment of prostate cancer: a systematic review and meta-analysis.

PURPOSE: To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR. METHODS: A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates. RESULTS: The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach. CONCLUSION: The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

Underlying Microstructure of the Lamina Cribrosa at the Site of Microvasculature Dropout.

Purpose: To determine the microstructure of the lamina cribrosa (LC) associated with microvasculature dropout (MvD) of the deep optic nerve head (ONH) in primary open-angle glaucoma (POAG) and to identify factors related to the presence of MvD. Methods: POAG eyes that exhibited MvD in the LC (MvD-LC) or MvD in the peripapillary choroid (MvD-PC) underwent optical coherence tomography and optical coherence tomography angiography (OCTA) to evaluate the structure and microvasculature of the deep ONH, respectively. The presence of MvD-LC or MvD-PC was determined using en face OCTA images of the deep ONH. The sectoral LC thickness (LCT) and LC curvature index (LCCI) (at MvD-LC site, when applicable), the mean LCT and LCCI of the global ONH, and other clinical characteristics were measured and compared between eyes with and without MvD-LC. Results: The study included 93 eyes with and 51 without MvD-LC. The presence of MvD-LC was associated with lower sectoral LCT (odds ratio [OR] = 0.96, P < 0.001) and mean LCT (OR = 0.97, P = 0.032), larger visual field pattern standard deviation (PSD; OR = 1.20, P = 0.038), and higher pretreatment intraocular pressure (IOP; OR = 1.22, P = 0.012). Fifteen percent of the eyes with MvD-LC (14/93) did not present MvD-PC. Those eyes had younger age (P = 0.043), thicker juxtapapillary choroid (P = 0.018), larger sectoral LCCI (P = 0.040), thicker retinal nerve fiber layer (P = 0.024), smaller PSD (P = 0.008), and higher pretreatment IOP (P = 0.006) than those with both MvD-LC and MvD-PC. Conclusions: MvD-LC was associated with a localized morphologic alteration of the LC, and eyes with MvD-LC tended to have a higher pretreatment IOP. The clinical implications of MvD-LC should differ from those of MvD-PC in eyes with POAG.

Evaluation of stability and safety of equine mesenchymal stem cells derived from amniotic fluid for clinical application.

Amniotic fluid mesenchymal stem cells (AF-MSCs), which can be obtained from fetal tissue, reportedly have self-renewal capacity and multi-lineage differentiation potential. The aim of this study was to identify the biological characteristics of AF-MSCs and evaluate their stability and safety in long-term culture. To confirm the biological characteristics of AF-MSCs, morphology, proliferation capacity, karyotype, differentiation capacity, gene expression level, and immunophenotype were analyzed after isolating AF-MSCs from equine amniotic fluid. AF-MSCs were differentiated into adipocytes, chondrocytes, and osteocytes. Immunophenotype analyses revealed expression levels of ≥95% and ≤ 2% of cells for a positive and negative marker, respectively. Analysis of the MSCs relative gene expression levels of AF-MSCs was approximately at least twice that of the control. The endotoxin level was measured to verify the safety of AF-MSCs and was found to be less than the standard value of 0.5 EU/ml. AF-MSCs were cultured for a long time without any evidence of abnormalities in morphology, proliferation ability, and karyotype. These results suggest that amniotic fluid is a competent source for acquiring equine MSCs and that it is valuable as a cell therapy due to its high stability.

Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin.

OBJECTIVE: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION: During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

Association Between Baseline Gait Parameters and Future Fall Risk in Patients With De Novo Parkinson's Disease: Forward Versus Backward Gait.

BACKGROUND AND PURPOSE: Falls are not uncommon even in patients with early stages of Parkinson's disease (PD). The aims of this study were to determine the relationships between gait parameters and falls and identify crucial gait parameters for predicting future falls in patients with de novo PD. METHODS: We prospectively recruited patients with de novo PD, and evaluated their baseline demographics, global cognitive function on the Montreal Cognitive Assessment test, and parkinsonian motor symptoms including their subtypes. Both forward gait (FG) and backward gait (BG) were measured using the GAITRite system. The history of falls in consecutive patients with de novo PD was examined along with 1 year of follow-up data. RESULTS: Among the 76 patients with de novo PD finally included in the study, 16 (21.1%) were classified as fallers. Fallers had slower gait and shorter stride for FG and BG parameters than did non-fallers, while stride-time variability was greater in fallers but only for BG. Multivariable logistic regression analysis revealed that slow gait was an independent risk factor in BG. CONCLUSIONS: Among the patients with de novo PD, gait speed and stride length were more impaired for both FG and BG in fallers than in non-fallers. It was particularly notable that slow BG was significantly associated with future fall risk, indicating that BG speed is a potential biomarker for predicting future falls in patients with early-stage PD.

Systemic immune-inflammation index as a predictor of early stroke progression/recurrence in acute atherosclerotic ischemic stroke.

OBJECTIVES: Although the systemic immune-inflammatory index (SII) has recently been correlated with stroke severity and functional outcome, the underlying pathogenesis remains largely unknown. The objective of this study was to explore whether SII could predict early neurologic deterioration (END) in different etiologies of acute ischemic stroke. MATERIALS AND METHODS: From January 2019 to December 2021, a total of 697 consecutive patients with acute ischemic stroke, admitted within 72 hours from stroke onset, were prospectively enrolled. The patients were categorized into 4 groups based on quartiles of SII, calculated as platelets multiplied by neutrophils divided by lymphocytes. END and stroke progression/recurrence were assessed during the first 7 days after stroke onset using predetermined definitions. Logistic regression analysis was conducted to evaluate the association between SII and END, while considering the variation in association across stroke etiologies. RESULTS: END occurred in 135 patients: 24 (3.4%) for Group I, 25 (3.6%) for Group II, 33 (4.7%) for Group III, and 53 (7.6%) for Group IV. Among the END subtypes, stroke progression/recurrence stroke was the most prevalent. In the logistic regression model, the adjusted odds ratios (ORs) of END and stroke progression/recurrence for group IV were 2.51 (95% CI, 1.27-4.95) and 1.98 (95% CI, 1.03-3.89), respectively. Among the stroke etiologies, group IV showed a significant increase in END (OR 4.24; 95% CI, 1.42-12.64) and stroke progression/recurrence (OR 4.13; 95% CI, 1.39-12.27) specifically in case of large artery atherosclerosis. CONCLUSIONS: SII independently predicts early stroke progression/recurrence in patients with acute atherosclerotic ischemic stroke.

Imaging and Clinical Findings of Primary Malignant Fibrous Histiocytoma of the Urinary Bladder: A Case Report.

Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder. Unlike urothelial carcinoma, which accounts for most bladder cancers, it occurs in the submucosal portion of the bladder wall and consists of the lamina propria, muscularis propria, and adventitia. It is presumed to originate from poorly differentiated pluripotent mesenchymal cells in which fibroblasts and histiocytes are partially differentiated. Radiologically, it is known as the "non-papillary tumor" and is commonly diagnosed as a large mass without necrosis, which shows invasion beyond the muscularis propia. Although the prognosis of this rare malignancy depends on pathological parameters, it generally has a poor prognosis with high local tumor recurrence. Here, we present a case of primary MFH in the urinary bladder with clinical symptoms of lower abdominal pain without gross hematuria that recurred rapidly and showed an aggressive disease course.

Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial).

BACKGROUND/AIM: Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. PATIENTS AND METHODS: We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. RESULTS: There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. CONCLUSION: Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).

SiMPl-GS: Advancing Cell Line Development via Synthetic Selection Marker for Next-Generation Biopharmaceutical Production.

Rapid and efficient cell line development (CLD) process is essential to expedite therapeutic protein development. However, the performance of widely used glutamine-based selection systems is limited by low selection efficiency, stringency, and the inability to select multiple genes. Therefore, an AND-gate synthetic selection system is rationally designed using split intein-mediated protein ligation of glutamine synthetase (GS) (SiMPl-GS). Split sites of the GS are selected using a computational approach and validated with GS-knockout Chinese hamster ovary cells for their potential to enable cell survival in a glutamine-free medium. In CLD, SiMPl-GS outperforms the wild-type GS by selectively enriching high producers. Unlike wild-type GS, SiMPl-GS results in cell pools in which most cells produce high levels of therapeutic proteins. Harnessing orthogonal split intein pairs further enables the selection of four plasmids with a single selection, streamlining multispecific antibody-producing CLD. Taken together, SiMPl-GS is a simple yet effective means to expedite CLD for therapeutic protein production.

Development of advanced cardiac progenitor cell culture system through fibronectin and vitronectin derived peptide coated plate.

Cardiovascular disease remains a global health concern. Stem cell therapy utilizing human cardiac progenitor cells (hCPCs) shows promise in treating cardiac vascular disease. However, limited availability and senescence of hCPCs hinder their widespread use. To address these challenges, researchers are exploring innovative approaches. In this study, a bioengineered cell culture plate was developed to mimic the natural cardiac tissue microenvironment. It was coated with a combination of extracellular matrix (ECM) peptide motifs and mussel adhesive protein (MAP). The selected ECM peptide motifs, derived from fibronectin and vitronectin, play crucial roles in hCPCs. Results revealed that the Fibro-P and Vitro-P coated plates significantly improved hCPC adhesion, proliferation, migration, and differentiation compared to uncoated plates. Additionally, long-term culture on the coated plates delayed cellular senescence and maintained hCPC stemness. These enhancements were attributed to the activation of integrin downstream signaling pathways. The findings suggest that the engineered ECM peptide motif-MAP-coated plates hold potential for enhancing the therapeutic efficacy of stem cell-based therapies in cardiac tissue engineering and regenerative medicine.