Long-Duration Neoadjuvant Therapy with FOLFIRINOX Yields Favorable Outcomes for Patients Who Undergo Surgery for Pancreatic Cancer.

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

Development and validation of a self-management self-efficacy scale for premature birth prevention (SMSE-PBP) for women of childbearing age.

BACKGROUND: This study aimed to develop and evaluate the validity and reliability of a self-management self-efficacy for premature birth prevention (SMSE-PBP) in women of childbearing age (WCA). METHODS: Instrument development and validation were undertaken in three phases: conceptualization, item generation and evaluation of content validity, and evaluation of construct and concurrent validity and reliability. Data were analyzed using exploratory and second-order confirmatory factor analyses, and concurrent validity was examined using Pearson's correlation coefficients. The reliability was analyzed using omega hierarchical and Cronbach's ⍺. RESULTS: Content validity was assessed by experts and cognitive interviews of WCA. The SMSE-PBP consists of a second-order 3-dimension and 10-factor scale with 60 items; therefore, the construct and concurrent validity of the SMSE-PBP were supported. The omega values were 0.93 for pre-pregnancy SMSE-PBP, 0.92 for pregnancy SMSE-PBP, and 0.94 for hospital SMSE-PBP. Cronbach's ⍺ was 0.88 for pre-pregnancy SMSE-PBP, 0.96 for pregnancy SMSE-PBP, and 0.96 for hospital SMSE-PBP. CONCLUSIONS: The SMSE-PBP scale is valid and reliable for WCA; it is helpful for WCA and health professionals to assess women's SMSE-PBP and pre-pregnancy, pregnancy, or hospital SMSE-PBP. The next steps should include assessing the relationship with pregnancy health behaviors.

Assessment of Genetic Stability in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Using Droplet Digital PCR.

Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. Moreover, conventional genetic stability testing methods are limited by low sensitivity, which is an issue that remains unsolved. In this study, we assessed the genetic stability of hiPSCs and hiPSC-derived cardiomyocytes using various testing methods, including karyotyping, CytoScanHD chip analysis, whole-exome sequencing, and targeted sequencing. Two specific genetic mutations in KMT2C and BCOR were selected from the 17 gene variants identified by whole-exome and targeted sequencing methods, which were validated using droplet digital PCR. The applicability of this approach to stem cell-based therapeutic products was further demonstrated with associated validation according to the International Council for Harmonisation (ICH) guidelines, including specificity, precision, robustness, and limit of detection. Our droplet digital PCR results showed high sensitivity and accuracy for quantitatively detecting gene mutations, whereas conventional qPCR could not avoid false positives. In conclusion, droplet digital PCR is a highly sensitive and precise method for assessing the expression of mutations with tumorigenic potential for the development of stem cell-based therapeutics.

Viral detection from negative mumps cases with respiratory symptoms in Gwangju, South Korea in 2021.

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were codetected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.

Soluble Expression of a Neo2/15-Conjugated Single Chain Fv against PD-L1 in Escherichia coli.

Immunocytokines, antibody-cytokine fusion proteins, have the potential to improve the therapeutic index of cytokines by delivering the cytokine to the site of localized tumor cells using antibodies. In this study, we produced a recombinant anti-programmed death-ligand 1 (PD-L1) scFv, an antibody fragment against PD-L1 combined with a Neo2/15, which is an engineered interleukin with superior function using an E. coli expression system. We expressed the fusion protein in a soluble form and purified it, resulting in high yield and purity. The high PD-L1-binding efficiency of the fusion protein was confirmed via enzyme-linked immunosorbent assay, suggesting the application of this immunocytokine as a cancer-related therapeutic agent.

DFT-Net: Deep Feature Transformation Based Network for Object Categorization and Part Segmentation in 3-Dimensional Point Clouds.

Unlike 2-dimensional (2D) images, direct 3-dimensional (3D) point cloud processing using deep neural network architectures is challenging, mainly due to the lack of explicit neighbor relationships. Many researchers attempt to remedy this by performing an additional voxelization preprocessing step. However, this adds additional computational overhead and introduces quantization error issues, limiting an accurate estimate of the underlying structure of objects that appear in the scene. To this end, in this article, we propose a deep network that can directly consume raw unstructured point clouds to perform object classification and part segmentation. In particular, a Deep Feature Transformation Network (DFT-Net) has been proposed, consisting of a cascading combination of edge convolutions and a feature transformation layer that captures the local geometric features by preserving neighborhood relationships among the points. The proposed network builds a graph in which the edges are dynamically and independently calculated on each layer. To achieve object classification and part segmentation, we ensure point order invariance while conducting network training simultaneously-the evaluation of the proposed network has been carried out on two standard benchmark datasets for object classification and part segmentation. The results were comparable to or better than existing state-of-the-art methodologies. The overall score obtained using the proposed DFT-Net is significantly improved compared to the state-of-the-art methods with the ModelNet40 dataset for object categorization.

Job change among early career nurses and related factors: A postgraduation 4-year follow-up study.

AIMS: This study aimed to identify the job change status and related factors among nurses during the first 4 years of their professional life. BACKGROUND: The early turnover and job change of nurses results in negative patient and nurse outcomes and financial losses. METHODS: A prospective longitudinal observational design and convenience sampling were used. From five nursing schools in South Korea, 526 individuals participated in the first survey conducted before graduation; 317 and 338 individuals participated in the second and third surveys, respectively (4 months after employment, and 4 years after graduation). RESULTS: In total, 42.0% of the participants remained at the hospital of their first job, 26.6% switched hospitals, and 12.1% moved to a nonhospital job. Multinomial logistic regression analyses showed that switching hospitals was associated with nurses' grade point average, type of hospital, first job satisfaction, and current pay. Moving to a nonhospital job was related to gender, type of hospital, current pay, and work-life balance. CONCLUSION: To reduce the early turnover and job change, hospitals should provide educational programmes for nurses, support male nurses, and increase job satisfaction and work-life balance. IMPLICATIONS FOR NURSING MANAGEMENT: Since this study addresses the working conditions and satisfaction of individuals who were re-employed after experiencing job turnover, it clarifies how nurse managers may reduce turnover. Namely, nurse managers should establish a work environment promoting good work-life balance.

The dNTPase activity of SAMHD1 is important for its suppression of innate immune responses in differentiated monocytic cells.

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase (dNTPase) with a nuclear localization signal (NLS). SAMHD1 suppresses innate immune responses to viral infection and inflammatory stimuli by inhibiting the NF-κB and type I interferon (IFN-I) pathways. However, whether the dNTPase activity and nuclear localization of SAMHD1 are required for its suppression of innate immunity remains unknown. Here, we report that the dNTPase activity, but not nuclear localization of SAMHD1, is important for its suppression of innate immune responses in differentiated monocytic cells. We generated monocytic U937 cell lines stably expressing WT SAMHD1 or mutated variants defective in dNTPase activity (HD/RN) or nuclear localization (mNLS). WT SAMHD1 in differentiated U937 cells significantly inhibited lipopolysaccharide-induced expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) mRNAs, as well as IFN-α, IFN-ß, and TNF-α mRNA levels induced by Sendai virus infection. In contrast, the HD/RN mutant did not exhibit this inhibition in either U937 or THP-1 cells, indicating that the dNTPase activity of SAMHD1 is important for suppressing NF-κB activation. Of note, in lipopolysaccharide-treated or Sendai virus-infected U937 or THP-1 cells, the mNLS variant reduced TNF-α or IFN-ß mRNA expression to a similar extent as did WT SAMHD1, suggesting that SAMHD1-mediated inhibition of innate immune responses is independent of SAMHD1's nuclear localization. Moreover, WT and mutant SAMHD1 similarly interacted with key proteins in NF-κB and IFN-I pathways in cells. This study further defines the role and mechanisms of SAMHD1 in suppressing innate immunity.

Parp3 promotes long-range end joining in murine cells.

Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. We show here that in contrast to classic (c-NHEJ) factors, Parp3 also promotes rearrangements in murine cells, including translocations in murine embryonic stem cells (mESCs), class-switch recombination in primary B cells, and inversions in tail fibroblasts that generate Eml4-Alk fusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at translocation junctions. This was corroborated using next-generation sequencing of Eml4-Alk junctions in tail fibroblasts and is consistent with a role for Parp3 in promoting the processing of DNA double-strand breaks. We confirmed a previous report that Parp1 also promotes rearrangement formation. In contrast with Parp3, rearrangement junctions in the absence of Parp1 had longer deletion lengths, suggesting that Parp1 may suppress double-strand break processing. Together, these data indicate that Parp3 and Parp1 promote rearrangements with distinct phenotypes.

15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury.

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.

Molecular characteristics of terminal deoxynucleotidyl transferase negative precursor B-cell phenotype Burkitt leukemia with IGH-MYC rearrangement.

Precursor B cell phenotype Burkitt lymphoma/leukemia with IGH-MYC is a rare subtype of Burkitt lymphoma (BL). BL and B lymphoblastic leukemia/lymphoma (B-ALL/LBL) differ as regards treatment and the distinction between these two entities is crucial. Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)-positive precursor B cell phenotype with IGH-MYC rearrangement have been reported to be molecularly distinct from BL and closer to B-ALL/LBL. We investigated the molecular characteristics of two cases of a rare but distinct TdT-negative precursor B cell phenotype BL. Both patients showed FAB L3 morphology with IGH-MYC translocation, but had precursor B cell immunophenotypes including dim to moderate expression of CD45 and absence of BCL6, CD20, monoclonal kappa, and lambda light chain expression. To characterize the molecular features, we performed exome sequencing and analyzed the breakpoint junction of the IGH-MYC rearrangement. We detected KMT2D mutations in both cases, a rarely acquired chromatin modifying gene mutation in BL. The breakpoint analysis revealed that the IGH-MYC rearrangement occurred due to an aberrant VDJ recombination in one case. The treatment protocols differed, including high-grade lymphoma treatment and standard B-ALL treatment. Complete remission was achieved in the patient who received B-ALL treatment. The degree of resemblance of BL and B-ALL differed between two cases, but the molecular pathogenesis and manifesting features of both TdT-negative precursor B cell phenotype BL case were distinct from classic BL, which indicates the need for a better understanding of this uncommon entity that does not fit in current diagnostic and classification categories.

Laparoscopic pancreatectomy for cancer in high volume centers is associated with an increased use and fewer delays of adjuvant chemotherapy.

BACKGROUND: This study aimed to investigate the relationship between hospital case volume, surgical approach and AC-use in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients were divided into quartiles by institutional pancreatectomy case volume, resection type (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or total pancreatectomy [TP]) and surgical approach (laparoscopic vs. open). The rates and contributing factors of AC administration and delay >90 days were compared among volume quartiles and surgical approaches. RESULTS: This study identified 23,494 patients who had undergone pancreatectomy for PDAC between 2010 and 2016 and met inclusion criteria. After correcting for confounders, compared to low volume hospitals patients at high-case-volume hospitals had the highest rates of AC administration after PD and DP. Moreover, compared to open surgery for all resection types, laparoscopic surgery was associated with a higher rate of AC use at high and highest-case-volume hospitals and less delay to chemotherapy at high-volume hospitals. For DP, laparoscopic approach had a positive impact on AC delay >90-day at the highest volume institutions only. CONCLUSIONS: Laparoscopic surgery for pancreatic cancer leads to higher utilization and lower probability of delay of AC in high and highest volume hospitals.

Inhibition of 15-PGDH prevents ischemic renal injury by the PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A receptors.

In the present study, we demonstrated the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia-reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. PGE2 is vasodilatory in the kidney, but it is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury scores and tubular apoptosis and markedly reduced biomarkers of renal injury that included blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high-mobility group box 1, and malondialdehyde. Protective effects of SW033291 were mediated by PGE2 signaling, as they could be blocked by pharmacological inhibition of PGE2 synthesis. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 receptors and cAMP, along with other vasodilatory effectors, including AMP, adenosine, and the adenosine A2A receptor. The protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Inhibition of 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.

Cyclic Neutropenia From a Novel Mutation Ala57Asp of ELANE: Phenotypic Variability in Neutropenia From Mutated Ala57 Residue.

ELANE-related neutropenia includes severe congenital neutropenia and cyclic neutropenia. Both are clinically characterized by recurrent fever, skin and oropharyngeal inflammation. We report a novel mutation in ELANE in a 20-year-old man with a history of self-limiting febrile episodes and neutropenia with a cyclic pattern since 7 years of age. Direct sequencing analysis of ELANE revealed he was heterozygous for a novel missense mutation (p.Ala57Asp). The Ala57 residue is a mutation hotspot, and all previously reported missense mutations (Ala57Ser/Thr/Val) were observed in severe congenital neutropenia cases. Thus, the present case demonstrates a phenotypic variability in ELANE-related neutropenia from mutated Ala57.

Next-generation sequencing reveals unique combination of mutations in cis of CSF3R in atypical chronic myeloid leukemia.

BACKGROUND: Atypical chronic myeloid leukemia (aCML) is a hematologic disorder characterized by leukocytosis with increased dysplastic neutrophils and their precursors. In CSF3R gene, the activation mutation including T618I is frequently reported in aCML but is rarely accompanied by truncation mutations. Herein, we report a unique aCML patient with two CSF3R mutations (T618I and Y779*) in the same DNA strand. METHODS: High-coverage next-generation sequencing for 40 genes related with myeloid leukemia was performed. Sanger sequencing was performed to confirm CSF3R mutations. To confirm whether two CSF3R mutations are in cis or not, TA cloning was used. Clinical information and bone marrow pathology were reviewed by two hematopathologists. RESULTS: In the patient diagnosed with aCML in bone marrow study, two CSF3R mutations, (T618I and Y779*) a SETBP1 mutation (G870S) and an U2AF1 mutation (Q157P), were identified by high-coverage next-generation sequencing. The two CSF3R mutations were confirmed to be located in the same DNA strand by TA cloning, indicating that the two mutations are harbored in one malignant clone. The SETBP1 mutation is known to be related with poor prognosis in aCML. Likewise, the patient was refractory to hydroxyurea and showed disease progression. Additionally, we discussed the potential therapeutic targets by reviewing the molecular profile of the patient. CONCLUSION: We believe that the accurate diagnosis and maximum therapeutic chance could be achieved by profiling the mutations and their characteristics.

An Innovative Multi-Model Neural Network Approach for Feature Selection in Emotion Recognition Using Deep Feature Clustering.

Emotional awareness perception is a largely growing field that allows for more natural interactions between people and machines. Electroencephalography (EEG) has emerged as a convenient way to measure and track a user's emotional state. The non-linear characteristic of the EEG signal produces a high-dimensional feature vector resulting in high computational cost. In this paper, characteristics of multiple neural networks are combined using Deep Feature Clustering (DFC) to select high-quality attributes as opposed to traditional feature selection methods. The DFC method shortens the training time on the network by omitting unusable attributes. First, Empirical Mode Decomposition (EMD) is applied as a series of frequencies to decompose the raw EEG signal. The spatiotemporal component of the decomposed EEG signal is expressed as a two-dimensional spectrogram before the feature extraction process using Analytic Wavelet Transform (AWT). Four pre-trained Deep Neural Networks (DNN) are used to extract deep features. Dimensional reduction and feature selection are achieved utilising the differential entropy-based EEG channel selection and the DFC technique, which calculates a range of vocabularies using k-means clustering. The histogram characteristic is then determined from a series of visual vocabulary items. The classification performance of the SEED, DEAP and MAHNOB datasets combined with the capabilities of DFC show that the proposed method improves the performance of emotion recognition in short processing time and is more competitive than the latest emotion recognition methods.

Mitochondrial dynamic alterations regulate melanoma cell progression.

Research on mitochondrial fusion and fission (mitochondrial dynamics) has gained much attention in recent years, as it is important for understanding many biological processes, including the maintenance of mitochondrial functions, apoptosis, and cancer. The rate of mitochondrial biosynthesis and degradation can affect various aspects of tumor progression. However, the role of mitochondrial dynamics in melanoma progression remains controversial and requires a mechanistic understanding to target the altered metabolism of cancer cells. Therefore, in our study, we disrupted mitochondrial fission with mdivi-1, the reported inhibitor of dynamin related protein 1 (Drp1), and knocked down Drp1 and Mfn2 to evaluate the effects of mitochondrial dynamic alterations on melanoma cell progression. Our confocal study results showed that mitochondrial fission was inhibited both in mdivi-1 and in Drp1 knockdown cells and, in parallel, mitochondrial fusion was induced. We also found that mitochondrial fission inhibition by mdivi-1 induced cell death in melanoma cells. However, silencing Drp1 and Mfn2 did not affect cell viability, but enhanced melanoma cell migration. We further show that dysregulated mitochondrial fusion by Mfn2 knockdowns suppressed the oxygen consumption rate of melanoma cells. Together, our findings suggest that mitochondrial dynamic alterations regulate melanoma cell migration and progression.

Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.

Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated SOCE and on intracellular Ca2+ oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and Orai1-SOCE signaling pathway in cancer cells.-Choi, S., Cui, C., Luo, Y., Kim, S.-H., Ko, J.-K., Huo, X., Ma, J., Fu, L.-W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.

Clonal dominance of a donor-derived del(20q) clone after allogeneic hematopoietic stem cell transplantation in an acute myeloid leukemia patient with del(20q).

Del(20q) is the most frequently detected large structural genetic mosaicism alteration in the healthy aging population, occurring in approximately 0.1% of older persons. Age-related clonal hematopoiesis of copy number variations (CNVs) is linked to an increased risk of hematologic malignancies, but the clinical impact of hematopoietic stem cells (HSCs) harboring such CNVs, such as del(20q), is not clearly understood. Here, we report an acute myeloid leukemia (AML) patient with known del(20q) who acquired donor-derived del(20q) after allogeneic hematopoietic stem cell transplantation (HSCT). The HSCs with del(20q) engrafted and expanded over time, but the patient did not clinically progress to myeloid neoplasm. Although donor-derived del(20q) from a healthy donor has been reported previously, our case is the first to review the clonal dynamics of a del(20q) clone and its post-transplantation impact. Since recurrent hematology neoplasm-associated CNVs, including del(20q), may not be rare among aged HSCT donors, identifying the origin of such a CNV is necessary for clinical decisions when clonal abnormality appears after HSCT, even in recipients who previously had the same abnormality.

Evaluation of Propofol in Comparison with Other General Anesthetics for Surgery in Children Younger than 3 Years: a Systematic Review and Meta-Analysis.

BACKGROUND: Despite well-known advantages, propofol remains off-label in many countries for general anesthesia in children under 3 years of age due to insufficient evidence regarding its use in this population. This study aimed to evaluate the efficacy and safety of propofol compared with other general anesthetics in children under 3 years of age undergoing surgery through a systematic review and meta-analysis of existing randomized clinical trials. METHODS: A comprehensive literature search was conducted of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to find all randomized clinical trials comparing propofol with another general anesthetic that included children under 3 years of age. The relative risk or arcsine-transformed risk difference for dichotomous outcomes and the weighted or standardized mean difference for continuous outcomes were estimated using a random-effects model. RESULTS: A total of 249 young children from 6 publications were included. The children who received propofol had statistically significantly lower systolic and diastolic blood pressures, but hypotension was not observed in the propofol groups. The heart rate, stroke volume index, and cardiac index were not significantly different between the propofol and control groups. The propofol groups showed slightly shorter recovery times and a lower incidence of emergence agitation than the control groups, while no difference was observed for the incidence of hypotension, desaturation, and apnea. CONCLUSION: This systematic review and meta-analysis indicates that propofol use for general anesthesia in young healthy children undergoing surgery does not increase complications and that propofol could be at least comparable to other anesthetic agents.