Successful pregnancy outcome via in-vitro fertilization and laparoscopic resection of non-communicating rudimentary horn pregnancy containing early pregnancy: a case report.

BACKGROUND: Non-communicating rudimentary horn pregnancy (NCRHP) lead to life-threatening condition for both mother and fetus. Early diagnosis of NCRHP and laparoscopic resection is important to prevent catastrophic conditions. However, delayed diagnosis until the second or third trimester makes it difficult to accurately diagnose between NCRHP and bicornuate uterine pregnancy, as both conditions present uterine rupture and massive hemoperitoneum. Furthermore, these rare cases are challenging in pregnancy trials and associated with adverse outcomes in subsequent pregnancies. CASE PRESENTATION: A 31-year-old gravida 1 para 0 Korean woman visited our infertility center with a confirmed positive urine pregnancy test after timed intercourse. Before she was scheduled to have timed intercourse, a unicornuate uterus with a non-communicating right uterine horn was suspected based on an ultrasound scan and hysterosalpingography during the initial infertility workup. A gestational sac was observed in the right non-communicating rudimentary horn at 5 weeks of gestation. Serum beta-human chorionic gonadotropin (b-hCG) level was 2052.0mIU/mL. An elective laparoscopic resection of the right rudimentary horn containing a gestational sac, along with ipsilateral salpingectomy, was performed with no adverse event. After 3-month of recovery period and three cycles of conceptional trials involving timed intercourse and intrauterine insemination, in-vitro fertilization (IVF) was performed using the antagonist protocol, and successful pregnancy was confirmed. The patient had been hospitalized from 21 + 6 weeks to 35 + 6 weeks of gestation, underwent cerclage placement and tocolytics with corticosteroid treatment. She delivered an early-term male baby by cesarean section. CONCLUSION: In this rare case, the successful pregnancy achieved through IVF following the appropriate management of NCRHP under laparoscopy underscores the critical importance of early diagnosis and intervention in cases of NCRHP. Timely identification and management of NCRHP are vital to prevent the occurrence of catastrophic conditions and to enhance the prognosis of a successful pregnancy through assisted reproductive technology (ART). Therefore, a high index of suspicion for NCRHP is important and employs a range of diagnostic modalities.

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination.

BACKGROUND: Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. METHODS: We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. RESULTS: We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell-matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. CONCLUSION: We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.

Survey-Based Analysis of the Clinical Treatment Status of Irritable Bowel Syndrome in Korea.

BACKGROUND: The quality-of-life of patients with irritable bowel syndrome is low; incorrect diagnosis/treatment causes economic burden and inappropriate consumption of medical resources. This survey-based study aimed to analyze the current status of irritable bowel syndrome treatment to examine differences in doctors' perceptions of the disease, and treatment patterns. METHODS: From October 2019 to February 2020, the irritable bowel syndrome and Intestinal Function Research Study Group of the Korean Society of Neurogastroenterology and Motility conducted a survey on doctors working in primary, secondary, and tertiary healthcare institutions. The questionnaire included 37 items and was completed anonymously using the NAVER platform (a web-based platform), e-mails, and written forms. RESULTS: A total of 272 doctors responded; respondents reported using the Rome IV diagnostic criteria (amended in 2016) for diagnosing and treating irritable bowel syndrome. Several differences were noted between the primary, secondary, and tertiary physicians' groups. The rate of colonoscopy was high in tertiary healthcare institutions. During a colonoscopy, the necessity of random biopsy was higher among physicians who worked at tertiary institutions. 'The patient did not adhere to the diet' as a reason for ineffectiveness using low-fermentable oligo-, di-, and mono-saccharides, and polyols diet treatment was higher among physicians in primary/secondary institutions, and 'There are individual differences in terms of effectiveness' was higher among physicians in tertiary institutions. In irritable bowel syndrome constipation predominant subtype, the use of serotonin type 3 receptor antagonist (ramosetron) and probiotics was higher in primary/secondary institutions, while serotonin type 4 receptor agonist was used more in tertiary institutions. In irritable bowel syndrome diarrhea predominant subtype, the use of antispasmodics was higher in primary/secondary institutions, while the use of serotonin type 3 receptor antagonist (ramosetron) was higher in tertiary institutions. CONCLUSION: Notable differences were observed between physicians in primary/secondary and tertiary institiutions regarding the rate of colonoscopy, necessity of random biopsy, the reason for the ineffectiveness of low-fermentable oligo-, di-, and mono-saccharides, and polyols diet, and use of drug therapy in irritable bowel syndrome. In South Korea, irritable bowel syndrome is diagnosed and treated according to the Rome IV diagnostic criteria, revised in 2016.

Obstetrical outcomes of embryo reduction and fetal reduction compared to non-reduced twin pregnancies.

PURPOSE: To prevent perinatal morbidity and mortality of high-order multiple pregnancy (HOMP), multifetal pregnancy reduction (MPR) is offered to some patients. In this study, we investigated whether twin pregnancies derived from MPRs carry a higher adverse obstetrical outcome compared to non-reduced control group of twins. METHODS: We retrospectively analyzed the data from HOMPs on which transvaginal ER (n = 153) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 59) at a mean gestational age of 12.4 weeks was performed between December 2006 and January 2018. The risk of each procedure was evaluated by comparing obstetrical outcome with that of a control population of 157 non-reduced twins conceived by infertility treatment. RESULTS: The mean gestational ages at delivery were 35.2 weeks in the ER group, 35.7 weeks in the FR group, and 34.1 weeks in the control group (P = NS). Compared with those in the control group, the ER group had higher miscarriage (1.3% vs. 6.5%; P = 0.047; OR 0.21; 95% CI 0.45-0.898) and higher overall fetal loss (3.8% vs. 14.4%; P = 0.003; OR 0.24; 95% CI 0.09-0.60) rates. Differently compared with those in the control group, the FR group had no statistical difference in miscarriage (2.5% vs. 1.7%; P=NS) and overall fetal loss (3.8% vs. 6.8%; P=NS) rates. CONCLUSIONS: Compared with the control group, ER in twins had a higher miscarriage and fetal loss rate, whereas FR in twins was similar to the control group. So, the FR procedure is overall a better and safer approach of MPR in reducing morbidity and mortality in HOMPs.

You are my happiness: Socially enriched happiness belief predicts life satisfaction, especially among the poor.

What three words come to your mind in response to "happiness"? Using a free-association task [cf. Nelson, D. L., McEvoy, C. L., & Dennis, S. (2000). What is free association and what does it measure? Memory and Cognition, 28, 887-899], this research finds that the number of social words (e.g. family, love) provided in link to happiness predicts people's actual life satisfaction level. However, this association was significantly moderated by the person's self-perceived financial state. The contingency between holding a socially-oriented belief about happiness and experienced life satisfaction was significant among members of low socioeconomic status (SES), but not among the high SES group. This pattern was replicated across two divergent samples (Asian college students, Study 1; American adults, Study 2), regardless of one's extraversion level (Studies 1, 2) and availability of social support (number of friends, Study 2). Given the overlapping function of money and social relationships (instrumental in promoting survival), believing in the social nature of happiness seems to be more central in the life satisfaction of those with less financial resource.

Geographic distribution and molecular analysis of porcine reproductive and respiratory syndrome viruses circulating in swine farms in the Republic of Korea between 2013 and 2016.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes devastating disease characterized by reproductive failure and respiratory problems in the swine industry. To understand the recent prevalence and genetic diversity of field PRRSVs in the Republic of Korea, open reading frames (ORFs) 5 and 7 of PRRSV field isolates from 631 PRRS-affected swine farms nationwide in 2013-2016 were analyzed along with 200 Korean field viruses isolated in 2003-2010, and 113 foreign field and vaccine strains. RESULTS: Korean swine farms were widely infected with PRRSVs of a single type (38.4 and 37.4% for Type 1 and Type 2 PRRSV, respectively) or both types (24.2%) with up to approximately 83% nucleotide sequence similarity to prototype PRRSVs (Lelystad or VR2332). Phylogenetic analysis based on the ORF5 nucleotide sequence revealed that Korean Type 1 field isolates were classified as subgroups A, B, and C under subtype 1, while Korean Type 2 field isolates were classified as lineages 1 and 5 as well as three Korean lineages (kor A, B, and C) with the highest infection prevalence in subgroup A (50.5%) and lineage 5 (15.3%) for Type 1 and Type 2 PRRSV, respectively, among ORF5-positive farms. In particular, the lineages kor B and C were identified as novel lineages in this study, and lineage kor B comprised only the field viruses isolated from Gyeongnam Province in 2014-2015, establishing regionally unique genetic characteristics. It has also recently been confirmed that commercialized vaccine-like viruses (subgroup C) of Type 1 PRRSV and NADC30-like viruses of Type 2 PRRSV (lineage 1) are spreading rapidly in Korean swine farms. The Korean field viruses were also expected to be antigenically variable as shown in the high diversity of neutralizing epitopes and N-glycosylation sites. CONCLUSIONS: This up-to-date information regarding recent field PRRSVs should be taken into consideration when creating strategies for the application of PRRS control measures, including vaccination in the field.

Mechanisms of IL-8 suppression by Treponema denticola in gingival epithelial cells.

The purpose of this study was to investigate the mechanism(s) of interleukin (IL)-8 suppression by Treponema denticola, one of the major periodontal pathogens, in gingival epithelial cells. Immortalized human gingival epithelial HOK-16B cells were infected with wild-type (WT), dentilisin-deficient (K1) or flagellin-deficient (flgE) T. denticola in the presence or absence of 2% human serum for 24 h. The levels of IL-8 expression were measured with real-time reverse transcription PCR and ELISA. In the absence of human serum, the WT and flgE, but not K1, substantially reduced not only the levels of IL-8 protein but also of IL-8 mRNA. Such downregulation of IL-8 mRNA was independent of bacterial invasion. Degradation of cytokine mixture by the WT, K1 and flgE revealed dentilisin-dependent preferential degradation of tumor necrosis factor (TNF)-α, an IL-8-inducing cytokine. WT and flgE significantly decreased the levels of TNFα secreted by HOK-16B cells, suggesting modulation of IL-8 through dentilisin-mediated degradation of TNFα. The addition of human serum to the culture potentiated the suppressive effect of T. denticola, resulting in substantial reductions of IL-8 and TNFα levels, even by K1. The serum-dependent effects of T. denticola were attributed to its ability to suppress the accumulation of intracellular reactive-oxygen species (ROS), a group of ubiquitous signaling molecules. Pretreatment with an antioxidant suppressed TNFα-induced IL-8 expression, confirming the role of ROS in TNFα signaling. Collectively, T. denticola targeted a key inflammatory cytokine and its signaling molecule to modulate the host innate immune response, which provides a new insight into modulation of host immunity by a periodontal pathogen.

Predictive factors for early clinical improvement after intra-arterial thrombolytic therapy in acute ischemic stroke.

BACKGROUND: In acute ischemic stroke, the speed of improvement after intra-arterial thrombolytic therapy (IAT)-mediated recanalization varies. This study aimed to identify clinical and radiological variables that are predictive of early improvement (EI) after IAT in acute ischemic stroke. METHODS: This single-center retrospective cohort study included 141 consecutive patients who underwent IAT for terminal internal carotid and/or middle cerebral artery (MCA) occlusions. EI was defined as a National Institutes of Health Stroke Scale (NIHSS) score less than 3 or NIHSS score improvement of 8 points or more within 72 hours of IAT. The EI and non-EI groups were compared in terms of clinical and radiological findings before and after IAT. RESULTS: Forty-nine patients showed EI (34.8%). Multivariate analysis revealed that atrial fibrillation (odds ratio [OR] .35, 95% confidence interval [CI] .14-.89, P = .028) and hyperdense MCA sign (OR .39, CI .15-.97, P = .042) were related with lack of EI. The independent EI predictors were less extensive parenchymal lesion on baseline computed tomography (OR 4.92, CI 1.74-13.9, P = .003), intermediate to good collaterals (OR 3.28, CI 1.16-9.31, P = .026), and recanalization within 6 hours of symptom onset (OR 5.2, CI 1.81-14.94, P = .002). EI associated with favorable outcomes (modified Rankin scale score 0-2) at discharge (88% versus 7%; P < .001) and 3 months after discharge (92% versus 18%; P < .001). CONCLUSIONS: The clinical and radiological variables maybe useful for predicting EI and favorable long-term outcomes after IAT.

DNA Checkpoint Gene Mutation as a Biomarker for Immune Checkpoint Inhibitor Therapy in Advanced Biliary Tract Cancer.

BACKGROUND/AIM: The DNA checkpoint (DNACHK) pathway is engaged in signaling the need for cell cycle arrest. This pathway is being actively researched to assess its role in cancer immunotherapy. PATIENTS AND METHODS: A total of 62 patients participated in this study. These patients were treated with immune checkpoint inhibitors (ICIs) for advanced biliary tract cancers (BTCs) from March 2020 to August 2022 at Samsung Medical Center. DNACHK mutated were defined as genomic alterations, such as single nucleotide variants, multi-nucleotide variants, and short insertion and deletions in seven genes; checkpoint kinase 1 (CHEK1), checkpoint kinase 2 (CHEK2), BRCA1, DNA repair-associated (BRCA1), the serine/threonine kinase ATM, the serine/threonine kinase ATR, mediator of DNA damage checkpoint 1 (MDC1) and tumor protein p53 binding protein 1 (TP53BP1). We analyzed the effect of DNACHK mutations on the efficacy of ICIs in advanced BTCs. RESULTS: Patient median age at diagnosis was 68.0 years. 10 patients (16.1%) had GB cancer; the remaining patients (n=52, 83.9%) were diagnosed with cholangiocarcinoma. Thirty-seven (59.7%) patients were categorized into the DNACHK wild-type (WT) group and 25 (40.3%) into the DNACHK mutated (MT) group. The most observed DNA checkpoint mutations were ATM mutations (n=14). Patients in the DNACHK MT group had better disease control rate (DCR) than patients in the DNACHK WT (60.0% vs. 48.6%, p=0.53). Median overall survival (OS) was 8.1 months (95% CI 5.1-22.8) in the MT group and 5.6 months (95%CI 3.1-11.0) in the WT group (p=0.33). CONCLUSION: The DNACHK pathway is expected to serve as a potential biomarker for ICI treatment.

Gene-gene interaction analysis for age at onset of bipolar disorder in a Korean population.

BACKGROUND: Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. METHODS: The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. RESULTS: The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3, KIAA1217, OPCML, CAMSAP2, and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E-07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E-6). The SNPs showing significant interactions were located in the KIAA1217, RBFOX3, SDK2, CYP19A1, NTM, SMYD3, and RBFOX1 genes. CONCLUSIONS: Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary.

Initial and 5-day positivity rate of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) in exposed inpatients within shared rooms during the omicron-variant dominant period.

In this observational study conducted in 2022, 12.3% of patients who shared a room with a patient positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) also had a positive polymerase chain reaction (PCR) test, either at initial screening or during a 5-day quarantine. Therefore, screening and quarantine are still necessary within hospitals for close-contact inpatients during the SARS-CoV-2 omicron-variant dominant period.

Effect of COVID-19 infection and vaccination on SARS-CoV-2 antibody titer change following ovarian stimulation: Prospective analysis of IVF outcomes.

The coronavirus disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has affected various medical fields worldwide. However, relatively few studies have examined the impact of COVID-19 infection and vaccination on in vitro fertilization (IVF) outcomes and changes in SARS-CoV-2 antibody concentration in follicular fluid (FF). A total of 45 women were prospectively recruited and assigned to 3 groups: uninfected and non-vaccinated control group (Control group), infected group (COVID + group), and vaccinated group (Vaccination group). Serum and follicular fluid (FF) estradiol, progesterone, and SARS-CoV-2 antibody concentrations were measured. There were no statistical differences in the total number of retrieved oocytes (P = .291), mature oocytes (P = .416), and good-quality embryos (P = .694) among the 3 groups. In the vaccination group, BNT162b2 exhibited a significantly lower trigger-day serum estradiol/MII oocyte level (110.6 pg/mL) than other vaccines (289.5 pg/mL) (P = .006). No statistical differences in serum (P = .687) and FF (P = .108) SARS-CoV-2 antibody changes were noted among the 3 groups. Only FF antibody changes exhibited statistically significant differences between the BNT162b2 and other vaccine subgroups (P = .047). COVID-19 infection and vaccination do not affect IVF outcomes. However, the effect of BNT162b2 on steroidogenesis of the mature oocyte and FF SARS-CoV2 antibody titer should be further investigated.

The Efficacy and Safety of GF101 and Its Antioxidant Effect on In Vitro Fertilization Outcomes: A Double-Blind, Non-Inferiority, Randomized, Controlled Trial with Coenzyme Q10.

(1) Background: Oxidative stress adversely affects fertility by impairing oocyte fertilization potential, primarily due to meiotic segregation errors and cohesion loss. Superoxide dismutase (SOD) and Coenzyme Q10 (CoQ10) are prominent antioxidants known to mitigate oxidative damage. (2) Methods: This study recruited 86 patients undergoing in vitro fertilization (IVF) at a single center for a 12-week, randomized, double-blind, active-comparator-controlled trial. Participants were allocated into two groups: one receiving CoQ10 as an antioxidant (the CoQ10 group) and the other receiving GF Bacillus antioxidative enzyme SOD (the GF101 group). The primary endpoints were changes in serum oxidative markers (SOD and catalase) and IVF outcomes, including clinical pregnancy, miscarriage, and live birth rates. Follicular fluid (FF) SOD and catalase concentrations on the day of retrieval, the metaphase II (MII) oocyte rate, the fertilization rate, and lipid profiles were measured. (3) Results: Initially, 86 patients were enrolled, with 65 completing the protocol (30 in the GF101 group and 34 in the CoQ10 group). There were no significant differences between the GF101 and CoQ10 groups in serum SOD (p = 0.626) and catalase levels (p = 0.061) over 12 weeks. However, within the GF101 group, a significant increase in serum catalase from baseline to 12 weeks was observed (p = 0.004). The non-inferiority analysis for IVF outcomes indicated risk differences in the clinical pregnancy rate, live birth rate, and miscarriage rate of -6.27% (95% CI: -30.77% to 18.22%), -1.18% (95% CI: -25.28% to 22.93%), and -13.49% (95% CI: -41.14% to 14.15%), respectively, demonstrating non-inferiority for the GF101 group. Furthermore, the GF101 group experienced significant reductions in total cholesterol (p = 0.006) and low-density lipoprotein (LDL) levels (p = 0.009) in intra-group comparisons, with both groups exhibiting comparable safe profiles. (4) Conclusions: GF101 may be non-inferior to CoQ10 in treating infertility in women and potentially offers additional benefits for women with dyslipidemia.

Reprogramming anchorage dependency to develop cell lines for recombinant protein expression.

As the biopharmaceutical industry continues to mature in its cost-effectiveness and productivity, many companies have begun employing larger-scale biomanufacturing and bioprocessing protocols. While many of these protocols require cells with anchorage-independent growth, it remains challenging to induce the necessary suspension adaptations in many different cell types. In addition, although transfection efficiency is an important consideration for all cells, especially for therapeutic protein production, cells in suspension are generally more difficult to transfect than adherent cells. Thus, much of the biomanufacturing industry is focused on the development of new human cell lines with properties that can support more efficient biopharmaceutical production. With this in mind, we identified a set of "Adherent-to-Suspension Transition" (AST) factors, IKZF1, BTG2 and KLF1, the expression of which induces adherent cells to acquire anchorage-independent growth. Working from the HEK293A cell line, we established 293-AST cells and 293-AST-TetR cells for inducible and reversible reprogramming of anchorage dependency. Surprisingly, we found that the AST-TetR system induces the necessary suspension adaptations with an accompanying increase in transfection efficiency and protein expression rate. Our AST-TetR system therefore represents a novel technological platform for the development of cell lines used for generating therapeutic proteins.

A periodontal pathogen Treponema denticola hijacks the Fusobacterium nucleatum-driven host response.

Periodontitis is a polymicrobial disease that arises from the dysbiosis of the plaque biofilm. To study polymicrobial interactions with gingival epithelial cells, the oral commensal Fusobacterium nucleatum and the periodontal pathogen Treponema denticola were chosen due to their opposing effects on the expression of human beta-defensins (HBDs) and interleukin (IL)-8 in gingival epithelial cells. Immortalized gingival epithelial HOK-16B cells were infected with either F. nucleatum or T. denticola alone or together, and the expression of HBDs and IL-8 was investigated. Coinfection with F. nucleatum and T. denticola neutralized the stimulatory and suppressive effects on the expression of HBD-2 and -3, but the suppressive effect of T. denticola on IL-8 expression remained. In CHO/CD14/TLR2 reporter cells, T. denticola attenuated F. nucleatum-induced activation of TLR2, a receptor that mediates HBD induction. Although F. nucleatum facilitated the invasion of T. denticola into host cells, T. denticola interfered with the fusion of internalized F. nucleatum with lysosomes, which may avert TLR9-dependent IL-8 induction. Furthermore, T. denticola suppressed the F. nucleatum-stimulated accumulation of intracellular reactive oxygen species (ROS), a group of essential signaling molecules for the TLR2 and TLR9 pathways. The elimination of ROS using N-acetyl cysteine completely blocked the inductions of HBD-3 and IL-8 and significantly reduced HBD-2 induction by F. nucleatum, confirming the importance of ROS in the host response. In sum, T. denticola incapacitates the F. nucleatum-induced expression of HBDs and IL-8 in gingival epithelial cells by interrupting endo-lysosomal maturation and ROS-dependent TLR activation. These results may provide new insights into polymicrobial interactions in the gingival sulcus.

Radiofrequency and ethanol ablation for the treatment of recurrent thyroid cancers: current status and challenges.

PURPOSE OF REVIEW: To review the role and safety of radiofrequency ablation (RFA) and ethanol ablation for the treatment of recurrent thyroid cancers in patients at high risk of surgery. RECENT FINDINGS: RFA and ethanol ablation are currently used as local tumor control methods for the treatment of recurrent thyroid cancers. The therapeutic success rates of RFA and ethanol ablation have been reported to be 75-91.6 and 70.8-98%, respectively. Local tumor recurrence has been reported to be 0-25% following RFA and 3.2-33% following ethanol ablation. Various complications have also been reported, such as discomfort, pain, skin burning, and changes in voice, but not life-threatening complications. All patients with changes in their voice received treatment to the central neck area, and permanent injury has been reported in patients who received RFA. SUMMARY: RFA and ethanol ablation could be considered as nonsurgical treatment options for recurrent thyroid cancers in patients at high risk of surgery. Efficacy seems to be higher for RFA, but complications seem to be lower for ethanol ablation.

Orientation of the ultrasound probe to identify the taller-than-wide sign of thyroid malignancy: a registry-based study with the Thyroid Imaging Network of Korea.

PURPOSE: Although the taller-than-wide (TTW) sign has been regarded as one of the most specific ultrasound (US) features of thyroid malignancy, uncertainty still exists regarding the US probe's orientation when evaluating it. This study investigated which US plane would be optimal to identify the TTW sign based on malignancy risk stratification using a registry-based imaging dataset. METHODS: A previous study by 17 academic radiologists retrospectively analyzed the US images of 5,601 thyroid nodules (≥1 cm, 1,089 malignant and 4,512 benign) collected in the webbased registry of Thyroid Imaging Network of Korea through the collaboration of 26 centers. The present study assessed the diagnostic performance of the TTW sign itself and fine needle aspiration (FNA) indications via a comparison of four international guidelines, depending on the orientation of the US probe (criterion 1, transverse plane; criterion 2, either transverse or longitudinal plane). RESULTS: Overall, the TTW sign was more frequent in malignant than in benign thyroid nodules (25.3% vs. 4.6%). However, the statistical differences between criteria 1 and 2 were negligible for sensitivity, specificity, and area under the curve (AUC) based on the size effect (all P<0.05, Cohen's d=0.19, 0.10, and 0.07, respectively). Moreover, the sensitivity, specificity, and AUC of the four FNA guidelines were similar between criteria 1 and 2 (all P>0.05, respectively). CONCLUSION: A longitudinal US probe orientation provided little additional diagnostic value over the transverse orientation in detecting the TTW sign of thyroid nodules.