Jekyll and Hyde: Activating the Hypoxic Translational Machinery.

Global translational remodeling has emerged as a principal mechanism of biological adaptation. Oxygen deficiency (hypoxia) disables the basal protein synthesis machinery ('Jekyll') and activates a hypoxic translational architecture ('Hyde') to drive translatome remodeling. Independent from mRNA-level fluctuations, this newer paradigm modernizes a field traditionally dominated by the hypoxia-inducible factor (HIF) transcriptional program.

Dyad and group-based interventions in physical activity, diet, and weight loss: a systematic review of the evidence.

Studies show that interpersonal relations impact behavior change. Yet, a comprehensive review of their efficacy remains unclear. This systematic review examines the efficacy of dyadic and group-based studies that intervened on primary endpoints: diet, PA, and weight loss in adults and their networks. We searched five databases for eligible articles published from 1980 to present. Final inclusion and risk of bias were independently determined and agreed upon by two of the paper's co-authors. Nine dyads and twelve group-based studies were eligible. Of the studies, 36% (4/11) of PA studies, 60% (3/5) of diet studies and 57% (8/14) of studies with weight loss as primary outcomes, reported significant findings. Compared to dyadic interventions, a greater proportion of group-based interventions demonstrated efficacy in PA gain and weight loss as outcomes. Approximately 43% of studies demonstrated low to moderate methodological quality. This systematic review synthesized the evidence of dyadic and group studies that intervened on PA, diet, and weight in adults from the same network. Moderately-high risk of bias and lack of diverse representation restricts inferences around efficacy. High-quality rigorous research is needed to understand the efficacy of dyadic and group-based interventions in addressing these co-occurring endpoints of interest.

Genome-wide gene expression responses to experimental manipulation of Saccharomyces cerevisiae repressor activator protein 1 (Rap1) expression level.

Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.

A multi-centre retrospective study of Nocardia speciation and antimicrobial susceptibility in Queensland, Australia.

The study aims to characterise the species identification and antimicrobial susceptibility testing (AST) results of Nocardial isolates from adult patients across major public hospitals in Queensland, Australia, over a 15-year period. A multi-centre retrospective observational study of Nocardia sp. isolates was conducted from 7 major public hospitals in Queensland, Australia, over a 15-year period. Clinical samples from patients aged ≥ 18 years that isolated Nocardia sp. were included. Demographic and clinical data were collected, along with species identification and AST results. Overall, 484 Nocardia sp. were isolated. Most patients were male (297, 61%) with a mean (IQR) age of 60 (51-75) and a median (IQR) Charlson Comorbidity Index of 4 (2-6). Of these, 239 (49%) patients were immunosuppressed. Organisms were most frequently isolated from sputum (174, 36%), and superficial swabs (102, 21%). Patients presented with pulmonary infections (165, 35%) and superficial skin and soft tissue infections (87, 18%) most commonly. One hundred (21%) isolates were deemed pulmonary colonisation and were not treated. Of the speciated organisms, N. nova complex was the most common (93, 19%), followed by N. farcinica complex (79, 16%). Organisms were reliably susceptible to linezolid (240/245, 98%), amikacin (455/470, 97%), and trimethoprim/sulfamethoxazole (459/476, 96%), but less so to imipenem (243/472, 51%) and ceftriaxone (261/448, 58%). This is the largest Australian description of Nocardia sp. to date. Given antimicrobials are often commenced prior to AST results and sometimes even speciation, characterisation of local species and antibiogram data is important to guide empiric choices and local guidelines.

[A neonate with a swelling in the floor of the mouth]. / Een pasgeborene met een zwelling in de mondbodem.

A significant swelling was seen in the floor of the mouth of a newborn girl. The girl could only drink with difficulty. On examination, a soft-elastic swelling was seen beneath the tongue. Ultrasonography and MRI showed a mass located above the hyoid bone. Upon the initial differential diagnosis of a dermoid cyst, an enucleation of the lesion was performed. Histopathological examination suggested a branchiogenic cyst or a digestive duplication cyst. Given the inconclusiveness of additional diagnostic examination, the lesion was diagnosed as a developmental cyst. Six months after enucleation, the infant girl's tongue motility was not restricted and there were no indications of a recurrence. This rare case illustrates the variety in differential diagnosis and the limitations of additional diagnostic examination.

Epigenetic Heterogeneity and Mitotic Heritability Prime Endothelial Cell Gene Induction.

Homogeneous populations of mature differentiated primary cell types can display variable responsiveness to extracellular stimuli, although little is known about the underlying mechanisms that govern such heterogeneity at the level of gene expression. In this article, we show that morphologically homogenous human endothelial cells exhibit heterogeneous expression of VCAM1 after TNF-α stimulation. Variability in VCAM1 expression was not due to stochasticity of intracellular signal transduction but rather to preexisting established heterogeneous states of promoter DNA methylation that were generationally conserved through mitosis. Variability in DNA methylation of the VCAM1 promoter resulted in graded RelA/p65 and RNA polymerase II binding that gave rise to a distribution of VCAM1 transcription in the population after TNF-α stimulation. Microarray analysis and single-cell RNA sequencing revealed that a number of cytokine-inducible genes shared this heterogeneous response pattern. These results show that heritable epigenetic heterogeneity is fundamental in inflammatory signaling and highlight VCAM1 as a metastable epiallele.

Prenatal exposure to nickel and atopic dermatitis at age 3 years: a birth cohort study with cytokine profiles.

BACKGROUND: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. OBJECTIVES: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. METHODS: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. RESULTS: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 µg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1ß, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. CONCLUSIONS: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.

[Patient-specific joint prothesis for ankylotic temporomandibular joints]. / Individueel vervaardigde prothesen voor ankylotische kaakgewrichten.

A 49-year-old woman who suffered from severe obstructive sleep apnea (OSA) was referred to the department of Oral-, Maxillofacial Surgery department due to progressive limitation of the mouth opening and chronic pain in both temporomandibular joints. Based on clinical and radiological examinations, the patient was diagnosed with recurrent ankylosis of the temporomandibular joints. The patient was treated with 2 patient-specific implants of the temporomandibular joint combined with a Le Fort I osteotomy, and a genioplasty including a genioglossus advancement. This treatment may have advantages for the patient such as a lower recurrence rate of ankylosis, improved maximal mouth opening, pain reduction and improved aesthetic results.

Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA.

Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell type-specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for spliced-transcript endothelial-enriched lncRNA (STEEL) in angiogenic potential, macrovascular/microvascular identity, and shear stress responsiveness. STEEL is expressed from the terminus of the HOXD locus and is transcribed antisense to HOXD transcription factors. STEEL RNA increases the number and integrity of de novo perfused microvessels in an in vivo model and augments angiogenesis in vitro. The STEEL RNA is polyadenylated, nuclear enriched, and has microvascular predominance. Functionally, STEEL regulates a number of genes in diverse ECs. Of interest, STEEL up-regulates both eNOS and the transcription factor Kruppel-like factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear-augmented KLF2. Mechanistically, STEEL up-regulation of eNOS and KLF2 is transcriptionally mediated, in part, via interaction of chromatin-associated STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the phenotypic adaptation of ECs to both body position and hemodynamic forces and establishes a newer role for lncRNAs in the transcriptional regulation of EC identity.

Systemic medication requirement in post-surgical patients with eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS. METHODS: Consecutive adult patients (>18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control. RESULTS: 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count >0.455 x109/L was 9.27 times more likely to require for systemic medication. CONCLUSION: Pre-operative blood eosinophil count >0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.

Paediatric glaucoma in Hong Kong: a multicentre retrospective analysis of epidemiology, presentation, clinical interventions, and outcomes.

PURPOSE: To document the epidemiology, presentation, clinical interventions, and outcomes of paediatric glaucoma in Hong Kong. METHODS: This multicentre territory-wide retrospective study was performed by reviewing charts of patients with paediatric glaucoma in six clusters of the Hong Kong Hospital Authority and The Chinese University of Hong Kong from 2006 to 2015. RESULTS: This study included 150 eyes of 98 patients with paediatric glaucoma (presenting age: 5.2±5.7 years). Of them, 35 eyes (23.3%) had primary congenital glaucoma, 22 eyes (14.7%) had juvenile open-angle glaucoma, and 93 eyes (62.0%) had secondary glaucoma. The most prevalent types of secondary glaucoma were lens-related after cataract extraction (18.0%), Axenfeld-Rieger anomaly (5.3%), uveitis (5.3%), Sturge-Weber syndrome (4.7%), and traumatic (3.3%). The most common clinical presentations were parental concerns (20.7%) including cloudy cornea (12.7%) and tearing/photophobia (8.0%), followed by poor visual acuity (18.0%), high intraocular pressure (13.3%), and strabismus (6.0%). The follow-up duration was 8.46±6.51 years. Furthermore, 63.2% of eyes with primary glaucoma and 45.2% of eyes with secondary glaucoma were treated surgically. The final visual acuity was 0.90±0.98 LogMAR; intraocular pressure was 18.4±6.6 mm Hg; and number of glaucoma medications was 2.22±1.61. CONCLUSION: Primary congenital glaucoma was most prevalent, followed by juvenile open-angle glaucoma and aphakic glaucoma. Most eyes with primary glaucoma required surgical treatment. Parental concerns were important clinical presentations. Basic assessments by healthcare providers to identify glaucoma signs (eg, poor visual acuity, high intraocular pressure, and strabismus) warranted prompt referral to an ophthalmologist.

Oral Health-related quality of life after coronectomy for impacted mandibular third molar in the first postoperative week.

BACKGROUND: Coronectomy of a mandibular impacted third molar is a surgical treatment to minimize the risk for inferior alveolar nerve damage. We aimed to determine whether this procedure affected the oral health-related quality of life (OHRQoL) within the first postoperative week. MATERIAL AND METHODS: This prospective study included 50 patients that underwent a coronectomy for an impacted mandibular third molar. The patients completed the Oral Health Impact Profile-14 (OHIP-14) questionnaire and questions about pain and analgesic intake on every day during the first postoperative week. RESULTS: Mean OHIP-14 scores were highest during the first three postoperative days; the highest mean score (26.40, SD: 8.67) was observed on the first postoperative day. Mean OHIP scores gradually declined during the first postoperative week, and the mean OHIP-14 score was 9.82 (SD: 9.15) on the seventh day. Physical pain was the highest contributor to the overall OHIP-14 score. Pain gradually declined with time; the lowest mean pain score (3.38, SD: 2.2) was observed on the seventh day. OHIP-14 and pain scores were not significantly different between sexes or between different grades of impaction. OHIP-14 scores were positively correlated with pain scores. CONCLUSIONS: A mandibular third molar coronectomy had a strong effect on patient OHRQoL, particularly during the first three postoperative days.

[Solitary angiokeratoma of the tongue]. / Solitair angiokeratoom van de tong.

A 41-year-old woman, who was referred with a reddish purple like lesion on the left side of the tongue, appeared to have an angiokeratoma after histopathological examination. Because of the benign character of this lesion and the absence of any complaints, no adjuvant treatment after excisional biopsy was indicated. Angiokeratomas rarely appear as solitary oral lesions. More often they are seen as part of an underlying systemic disease, mostly Fabry disease. Due to widespread skin involvement of angiokeratomas with Fabry disease, referral to a dermatologist is indicated when oral lesions are encountered. Esthetically unpleasing or painful angiokeratomas can be locally excised or treated by laser- or cryotherapy.

A Cap for Every Occasion: Alternative eIF4F Complexes.

The eukaryotic translation initiation factor 4F (eIF4F) has become essentially synonymous with 5' cap-dependent mRNA translation. Recent studies demonstrate that cells assemble variants of eIF4F to produce adaptive, cap-dependent translatomes during physiological conditions that inhibit eIF4F. These findings challenge us to reassess classical perceptions of cellular translational pathways.

Picosecond-Domain Fractional Laser Treatment Over Hyaluronic Acid Fillers: In Vivo and Clinical Studies.

BACKGROUND AND OBJECTIVES: Combined sequential treatments with multiple modalities such as lasers and soft-tissue fillers are commonly required for the treatment of atrophic acne scars. Recently, fractional treatment with picosecond-domain lasers has proven to be effective for skin rejuvenation and scar treatment. However, little is known about the effects of picosecond-domain fractional laser treatment over hyaluronic acid fillers (HAFs). We aimed to evaluate the in vivo tissue responses to 1064 nm picosecond-domain fractional neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatments using microlens array (MLA) applied over pre-injected HAF in rats. In addition, we evaluated the efficacy and safety of this combined same-day treatment for atrophic acne scars in patients. STUDY DESIGN/MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 1064 nm picosecond-domain fractional Nd:YAG laser treatment immediately after HAF dermal injection. Skin specimens were histologically evaluated on days 0, 7, and 21. In a clinical study, 36 patients with acne scars were treated concurrently with 1064 nm MLA-type picosecond lasers and HAFs. The patients were scheduled to receive two consecutive treatments at 4-week intervals, with a follow-up visit at 12 weeks after the final treatment. Acne scar photographs were graded using the Goodman and Baron's qualitative and quantitative scales at baseline and 12 weeks post-procedure. RESULTS: Picosecond-domain fractional laser treatment immediately after the dermal injection of HAF into rats did not cause any histological changes in the filler or surrounding skin. In a clinical study, treated subjects (n = 36) achieved significant improvement in acne scars and patient satisfaction. No serious adverse events were observed. CONCLUSIONS: Combined picosecond laser and HAF treatment were proven to be safe and effective based on in vivo and clinical study results. Facial rejuvenation and scar treatment using a picosecond-domain fractional laser may be performed immediately after HAF injection. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Dermanyssus gallinae and chicken egg production: impact, management, and a predicted compatibility matrix for integrated approaches.

The poultry red mite, Dermanyssus gallinae, is a worldwide threat to egg production and animal and human welfare. This mite is also a potential vector for several significant diseases. EU regulation that forbids the use of conventional cages for egg-laying hens may favour the growth of D. gallinae, a species known to thrive in more complex housing systems. Current control measures emphasize the use of chemical acaricides, which may have limited efficacy on D. gallinae considering its temporary blood-feeding behaviour. In integrated pest management (IPM), two or more compatible measures targeting physical, environmental, and/or biological aspects could be judiciously combined to enhance the effectiveness against D. gallinae infestation. To inform current and future IPM for D. gallinae, a compatibility matrix is proposed to guide the selection of control measures for field application.

Histone acetyltransferase 7 (KAT7)-dependent intragenic histone acetylation regulates endothelial cell gene regulation.

Although the functional role of chromatin marks at promoters in mediating cell-restricted gene expression has been well characterized, the role of intragenic chromatin marks is not well understood, especially in endothelial cell (EC) gene expression. Here, we characterized the histone H3 and H4 acetylation profiles of 19 genes with EC-enriched expression via locus-wide chromatin immunoprecipitation followed by ultra-high-resolution (5 bp) tiling array analysis in ECs versus non-ECs throughout their genomic loci. Importantly, these genes exhibit differential EC enrichment of H3 and H4 acetylation in their promoter in ECs versus non-ECs. Interestingly, VEGFR-2 and VEGFR-1 show EC-enriched acetylation across broad intragenic regions and are up-regulated in non-ECs by histone deacetylase inhibition. It is unclear which histone acetyltransferases (KATs) are key to EC physiology. Depletion of KAT7 reduced VEGFR-2 expression and disrupted angiogenic potential. Microarray analysis of KAT7-depleted ECs identified 263 differentially regulated genes, many of which are key for growth and angiogenic potential. KAT7 inhibition in zebrafish embryos disrupted vessel formation and caused loss of circulatory integrity, especially hemorrhage, all of which were rescued with human KAT7. Notably, perturbed EC-enriched gene expression, especially the VEGFR-2 homologs, contributed to these vascular defects. Mechanistically, KAT7 participates in VEGFR-2 transcription by mediating RNA polymerase II binding, H3 lysine 14, and H4 acetylation in its intragenic region. Collectively, our findings support the importance of differential histone acetylation at both promoter and intragenic regions of EC genes and reveal a previously underappreciated role of KAT7 and intragenic histone acetylation in regulating VEGFR-2 and endothelial function.

Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort Study of 10 964 Patients in Vietnam.

BACKGROUND: Tuberculosis is the leading infectious cause of death. Steep reductions in tuberculosis-related mortality are required to realize the World Health Organization's "End Tuberculosis Strategy." However, accurate mortality estimates are lacking in many countries, particularly following discharge from care. This study aimed to establish the mortality rate among patients with pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this population. METHODS: We conducted a prospective cohort study among adult patients treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam. People living in the same households were recruited as controls. Participants were re-interviewed and their survival was established at least 2 years after their treatment with an 8-month standardized regimen. The presence of relapse was established by linking identifying data on patients and controls to clinic registries. Verbal autopsies were performed. The cumulative mortality among patients was compared to that among a control population, adjusting for age and gender. RESULTS: We enrolled 10964 patients and 25707 household controls. Among enrolled tuberculosis patients, 9% of patients died within a median follow-up period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge. The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among patients with tuberculosis, compared to the control population. Tuberculosis was the likely cause of death for 44.7% of these deceased patients. CONCLUSIONS: Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.

Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders.

Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3'UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease.

Pathologic complete response to chemoembolization improves survival outcomes after curative surgery for hepatocellular carcinoma: predictive factors of response.

BACKGROUND: We identified the predictive factors and prognostic significance of transarterial chemoembolization (TACE) for achieving pathologic complete response (pCR) before curative surgery for hepatocellular carcinoma (HCC) in hepatitis B-endemic areas. METHODS: Among 753 HCC patients treated with surgery, 124 patients underwent preoperative TACE before liver resection (LR), and 166 before liver transplantation (LT) between 2005 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Pathologic response (PR) was defined as the mean percentage of necrotic area, and pCR was defined as the absence of viable tumor. RESULTS: A total of 34 (27%) and 38 (23%) patients had pCR before LR and LT, respectively. Alpha-fetoprotein (AFP) < 100 ng/mL and single tumor were significant preoperative predictors of pCR. OS and RFS were significantly improved in patients with pCR or a PR ≥ 90%, but not in patients with PR ≥ 50% after LR and LT. On multivariate analyses, PR ≥ 90% remained an independent predictor of better OS and RFS in LR and LT groups. CONCLUSION: Overall, our data clearly demonstrate that pCR predicts favorable prognosis after curative surgery for HCC, and predictors of pCR are AFP <100 ng/mL and single tumor.