Enhancing deep learning classification performance of tongue lesions in imbalanced data: mosaic-based soft labeling with curriculum learning.

BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.

In Vivo Serotonin 5-HT2A Receptor Availability and Its Relationship with Aggression Traits in Healthy Individuals: A Positron Emission Tomography Study with C-11 MDL100907.

Serotonergic neurotransmission has been associated with aggression in several psychiatric disorders. Human aggression is a continuum of traits, ranging from normal to pathological phenomena. However, the individual differences in serotonergic neurotransmission and their relationships with aggression traits in healthy individuals remain unclear. In this study, we explored the relationship between 5-HT2A receptor availability in vivo and aggression traits in healthy participants. Thirty-three healthy participants underwent 3-Tesla magnetic resonance imaging and positron emission tomography (PET) with [11C]MDL100907, a selective radioligand for 5-HT2A receptors. To quantify 5-HT2A receptor availability, the binding potential (BPND) was derived using the basis function implementation of the simplified reference tissue model, with the cerebellum as the reference region. The participants' aggression levels were assessed using the Buss-Perry Aggression Questionnaire. The voxel-based correlation analysis with age and sex as covariates revealed that the total aggression score was significantly positively correlated with [11C]MDL100907 BPND in the right middle temporal gyrus (MTG) pole, left fusiform gyrus (FUSI), right parahippocampal gyrus, and right hippocampus. The physical aggression subscale score had significant positive correlations with [11C]MDL100907 BPND in the left olfactory cortex, left orbital superior frontal gyrus (SFG), right anterior cingulate and paracingulate gyri, left orbitomedial SFG, left gyrus rectus, left MTG, left inferior temporal gyrus, and left angular gyrus. The verbal aggression subscale score showed significant positive correlations with [11C]MDL100907 BPND in the bilateral SFG, right medial SFG, left FUSI, and right MTG pole. Overall, our findings suggest the possibility of positive correlations between aggression traits and in vivo 5-HT2A receptor availability in healthy individuals. Future research should incorporate multimodal neuroimaging to investigate the downstream effects of 5-HT2A receptor-mediated signaling and integrate molecular and systems-level information in relation to aggression traits.

Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.

Selected nasogastric lavage in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Risk stratification before endoscopy is crucial for proper management of patients suspected as having upper gastrointestinal bleeding (UGIB). There is no consensus regarding the role of nasogastric lavage for risk stratification. In this study, we investigated the usefulness of nasogastric lavage to identify patients with UGIB requiring endoscopic examination. METHODS: From January 2017 to December 2018, patients who visited the emergency department with a clinical suspicion of UGIB and who underwent nasogastric lavage before endoscopy were eligible. Patients with esophagogastric variceal bleeding were excluded. The added predictive ability of nasogastric lavage to the Glasgow-Blatchford score (GBS) was estimated using category-free net reclassification improvement and integrated discrimination improvement. RESULTS: Data for 487 patients with nonvariceal UGIB were analyzed. The nasogastric aspirate was bloody in 67 patients (13.8 %), coffee-ground in 227 patients (46.6 %), and clear in 193 patients (39.6 %). The gross appearance of the nasogastric aspirate was associated with the presence of UGIB. Model comparisons showed that addition of nasogastric lavage findings to the GBS improved the performance of the model to predict the presence of UGIB. Subgroup analysis showed that nasogastric lavage improved the performance of the prediction model in patients with the GBS ≤ 11, whereas no additive value was found when the GBS was greater than 11. CONCLUSIONS: Nasogastric lavage is useful for predicting the presence of UGIB in a subgroup of patients, while its clinical utility is limited in high-risk patients with a GBS of 12 or more.

Clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal tract.

BACKGROUND: Ingested foreign objects frequently require emergency removal. This study aimed to investigate the clinical outcomes of endoscopic removal of foreign bodies from the upper gastrointestinal tract and the risk factors for adverse events. METHODS: Adults (> 18 years) who underwent endoscopic management of ingested foreign bodies at two centers, one inland and one on the coast, between January 2008 and December 2017 were eligible. Clinical characteristics and procedure-related outcomes were retrospectively reviewed. Patients were divided into two groups, based on whether the foreign bodies were sharp or blunt in shape. RESULTS: A total of 853 patients aged 19-96 years were analyzed. Ingestion of fish bones was more common in the coastal area, whereas ingestion of food boluses was more common in the inland area. The duration of impaction ranged from 1 h to over 1 month and was significantly longer in patients who ingested blunt than sharp foreign bodies (15 vs. 5 h, p < 0.001). Most (98.9%) foreign bodies were successfully removed. Adverse events occurred in 31.2 % of patients, including ulcers (4.0%) and perforations (3.3 %). Multivariate analysis showed that age (odds ratio [OR] 1.015, p = 0.012), sharp foreign bodies (OR 5.133, p < 0.001), location in the esophagus (OR 2.723, p = 0.018), and duration of impaction (OR 1.431, p < 0.001) were factors associated with adverse events. CONCLUSIONS: Early recognition and timely endoscopic removal of ingested foreign bodies, particularly in elderly patients and those with sharp foreign bodies, may improve clinical outcomes.

Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors.

Frequent oxidative modification of the neural genome is a by-product of the high oxygen consumption of the nervous system. Rapid correction of oxidative DNA lesions is essential, as genome stability is a paramount determinant of neural homeostasis. Apurinic/apyrimidinic endonuclease 1 (APE1; also known as "APEX1" or "REF1") is a key enzyme for the repair of oxidative DNA damage, although the specific role(s) for this enzyme in the development and maintenance of the nervous system is largely unknown. Here, using conditional inactivation of murine Ape1, we identify critical roles for this protein in the brain selectively after birth, coinciding with tissue oxygenation shifting from a placental supply to respiration. While mice lacking APE1 throughout neurogenesis were viable with little discernible phenotype at birth, rapid and pronounced brain-wide degenerative changes associated with DNA damage were observed immediately after birth leading to early death. Unexpectedly, Ape1Nes-cre mice appeared hypothermic with persistent shivering associated with the loss of thermoregulatory serotonergic neurons. We found that APE1 is critical for the selective regulation of Fos1-induced hippocampal immediate early gene expression. Finally, loss of APE1 in combination with p53 inactivation resulted in a profound susceptibility to brain tumors, including medulloblastoma and glioblastoma, implicating oxidative DNA lesions as an etiologic agent in these diseases. Our study reveals APE1 as a major suppressor of deleterious oxidative DNA damage and uncovers specific and broad pathogenic consequences of respiratory oxygenation in the postnatal nervous system.

Optimal Timing of Feeding After Endoscopic Hemostasis in Patients With Peptic Ulcer Bleeding: A Randomized, Noninferiority Trial (CRIS KCT0001019).

OBJECTIVES: The optimal duration of fasting after endoscopic hemostasis in patients with peptic ulcer bleeding has not yet been determined. We investigated the appropriate timing of feeding after endoscopic hemostasis in patients with high-risk peptic ulcer bleeding. METHODS: This study was a randomized, single center, noninferiority trial. Between February 2014 and March 2019, consecutive patients with peptic ulcer bleeding were randomized to resume feeding either 24 or 48 hours after successful endoscopic hemostasis. A total of 209 eligible patients were included in the intention-to-treat analysis and 200 in the per-protocol (PP) analysis. The primary outcome measure was recurrent bleeding within 7 days of hemostasis. Noninferiority testing was performed in the PP population, and the noninferiority margin was set at 10%. Secondary outcomes included 30-day rebleeding and mortality, transfusion requirements, and length of hospital stay. RESULTS: Recurrent bleeding rates at 7 days were 7.9% in the 24-hour group and 4.0% in the 48-hour group in the PP analysis; tests for noninferiority did not reach statistical significance (difference: 3.9%, 95% confidence interval [CI]: -2.7 to 10.5, P value for noninferiority = 0.034). The recurrent bleeding rates within 30 days were 10.9% and 4.0% in the 24- and 48-hour groups (difference: 6.9%, 95% CI: -0.5 to 14.2), and the 30-day mortality rates were 5.9% and 14.1%, respectively (difference: -8.2%, 95% CI: -16.5 to 0.1) in the PP analysis. The transfusion requirement and the length of hospital stay were similar between the 2 groups. DISCUSSION: Early refeeding at 24 hours after endoscopic hemostasis is not noninferior to later refeeding at 48 hours for rebleeding in patients with high-risk peptic ulcer bleeding. Our results do not allow a recommendation of refeeding at 24 hours, rather than later refeeding in this population.

Prevalence, incidence and risk factors of tamoxifen-related non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Tamoxifen is associated with an increased risk of developing fatty liver. The aim of this systematic review and meta-analysis was to evaluate the prevalence and incidence of fatty liver developed after tamoxifen treatment in breast cancer patients. METHODS: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library and other databases was performed for this review. The abstracts obtained from the search were reviewed by two investigators who chose manuscripts for full-text review. The event rates were calculated with a random-effects model and quality-effects model. RESULTS: The search yielded 165 references. Of these, 24 were included in the quantitative summary. We analysed the data of a total of 6,962 patients treated with tamoxifen and 975 patients not treated with tamoxifen. The prevalence of fatty liver among patients with breast cancer taking tamoxifen was 40.25 per 100 patients and the incidence rate was 12.37 per 100 person-years. The incidence of fatty liver was much higher in the tamoxifen group than in the control group [incidence rate ratio: 3.12, 95% CI (confidence interval): 2.05-4.75, I2  = 61%], regardless of region. The main risk factors were body mass index (BMI) [hazard ratio (HR): 1.15, 95% CI: 1.09-1.22] and hypercholesterolaemia (HR: 1.01, 95% CI: 1.00-1.02). CONCLUSION: The use of tamoxifen was associated with increased risks in the incidence and prevalence of fatty liver, especially in patients with high BMI and hypercholesterolaemia.

Improved detection of hepatocellular carcinoma by dynamic computed tomography in cirrhotic patients with chronic hepatitis B: A multicenter study.

BACKGROUND AND AIMS: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasonography (US). However, sensitivities of US to detect early-stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very-early-stage HCC in two groups: group A, undergoing 6-monthly US versus group B, undergoing 6-monthly US alternating with dynamic computed tomography (CT). METHODS: This retrospective multicenter study assessed 1235 cirrhotic patients with CHB under entecavir/tenofovir therapy from 2007 to 2016. The primary endpoint was overall survival rates between the two groups. The Cox proportional hazards model and propensity score matching analyses were used to assess the effect of surveillance modalities on overall survival and detection of Barcelona Clinic Liver Cancer stage 0 HCC after balancing. RESULTS: During a median follow-up of 4.5 years, 10-year cumulative HCC incidence rates of 16.3% were significantly higher in group B (n = 576) than 13.7% in group A (n = 659; P < 0.001). However, in patients with HCC, 10-year overall survival rates of 85.1% were significantly higher in group B than 65.6% in group A (P = 0.001 by log-rank test). CT exam alternating with US was independently associated with reduced overall mortality (hazard ratio 0.47, P = 0.02). Cumulative incidence of Barcelona Clinic Liver Cancer stage 0 HCC was significantly higher in group B than in group A (hazard ratio 2.82, P < 0.001). CONCLUSION: In cirrhotic patients with CHB, dynamic CT exam alternating with US led to higher detection rates of very-early-stage HCC and benefit of overall survival than did US exams.

Highly Hydrophilic Polyurethane Foam Dressing Versus Early Hydrophilic Polyurethane Foam Dressing on Skin Graft Donor Site Healing in Patients with Diabetes: An Exploratory Clinical Trial.

OBJECTIVE: To compare the effects of early hydrophilic polyurethane (EHP) foam dressing and highly hydrophilic polyurethane (HHP) foam dressing on wound healing in patients with diabetes. METHODS: Twenty patients with diabetes with skin graft donor sites on the lateral thigh were enrolled in this study. Each donor site was divided into two equal-sized areas for the application of HHP or EHP foam dressing. The study endpoint was the time required for healing, defined as complete epithelialization of the donor site without discharge. All possible adverse events were also documented. MAIN RESULTS: Donor site healing was faster in 15 patients on the HHP half and 1 patient on the EHP half. In four patients, healing rates were the same between the HHP and EHP areas. Donor sites treated with HHP and EHP foam dressings healed in 17.2 ± 4.4 and 19.6 ± 3.7 days (P = .007), respectively. During the study period, no adverse event associated with the dressings occurred in either group. CONCLUSIONS: The HHP foam dressing might provide faster healing than EHP foam dressing for skin graft donor sites in patients with diabetes.

Annual patterns of ocular melatonin level in the female grass puffer, Takifugu alboplumbeus: possible involvement in seasonal reproductive response.

The aim of this study was to investigate the expression patterns of ocular melatonin in the annual reproductive cycle of the female grass puffer. Spawning season of the female grass puffer is from June to July in Jeju, South Korea. Time-resolved fluoroimmunoassay revealed that levels of ocular melatonin, which show an annual change, peaked in May (spawning season). Additionally, expression of reproductive-related genes also showed annual patterns: GnRH1 peaked in August, GnRH2 peaked in February, GnRH3, Kiss2, and LPXRFa peaked in November. These results suggest that ocular melatonin may be related to the annual reproductive cycle in the grass puffer. To better understand the photic regulation of AANAT1a mRNA in the retina, we observed the nocturnal pattern of ocular melatonin levels daily, which shows a nocturnal pattern in both short photoperiod (SD) and long photoperiod (LD) conditions. In the brain, AANAT2 mRNA also shows a nocturnal pattern in both SD and LD; however, the time of peak expression of AANAT2 mRNA was unchanged in both conditions. Following intraperitoneal injection of melatonin for 2 weeks, expression of GnRH2 and LPXRFa mRNA in the brain significantly increased, while that of Kiss2 mRNA was decreased, suggesting that melatonin has a reproduction-related effect. Furthermore, under SD and LD conditions for 14 weeks, the gonadosomatic index more increased and the maturity of the ovary progressed under LD compared with those under SD, suggesting that the SD photoperiodic signal inactivated ovarian development. These results indicate that the ocular melatonin may have a possible role in the reproductive endocrinology of the grass puffer.

Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex.

BACKGROUND & AIMS: Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis. METHODS: This study included 779 consecutive cirrhotic patients who underwent 51Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT. RESULTS: Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR. CONCLUSIONS: The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance. LAY SUMMARY: Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine.

Relationship of self-transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [18 F]fallypride PET and fMRI study.

Genetic research has implicated dopamine neurotransmission in the expression of the self-transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self-transcendence trait and in vivo dopamine D2/3 receptor availability using [18 F]fallypride positron emission tomography (PET). We next conducted seed-based functional connectivity analyses using resting-state functional magnetic resonance imaging (rs-fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D2/3 receptor availability foci associated with the self-transcendence trait. Twenty-one healthy subjects underwent high-resolution PET with [18 F]fallypride and a subset of 18 subjects also completed 3-Tesla rs-fMRI. The Temperament and Character Inventory was used to measure the self-transcendence trait. A voxel-based whole brain analysis revealed that the [18 F]fallypride binding potential (BPND ) within the cluster of the left insula was significantly positively correlated with self-transcendence trait scores. A region-of-interest analysis also showed a significant positive correlation between self-transcendence and [18 F]fallypride BPND in the left insula. The exploratory [18 F]fallypride BPND seed-based rs-fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self-transcendence trait scores. The results of the present study suggest that D2/3 receptor-mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self-transcendence trait. The negative associations between BPND seed-based functional connectivity and self-transcendence trait scores may suggest reduced prefrontal control in this personality trait.

Dynamics of alveolar bone healing after the removal of orthodontic temporary anchorage devices.

OBJECTIVE: The aim of this study was to investigate the dynamics of alveolar bone formation and healing pattern after the removal of orthodontic temporary anchorage devices (TADs). METHODS: Miniscrews (N = 32) were inserted into the buccal inter-radicular alveolar bone in beagle dogs. Afterward, miniscrews were removed at different time points during a 13-week period and six different in vivo fluorescent markers were injected at 1, 2, 6, 8, 10, and 12 weeks. Serial changes in bone apposition at the removal and intact control sites were evaluated using µCT, histology, and bone histomorphometry. RESULTS: Gradual bone apposition at the TAD removal site was noted with bone volume/tissue volume (BV/TV) reaching the level of the control alveolar bone by 7 weeks. Histologically, newly formed woven bone was detected within the removal site which was distinct from the surrounding pre-existing alveolar bone at 13 weeks. Accelerated mineral apposition rate (MAR) and bone formation rate (BFR) were noted between 2 and 6 weeks in the removal site (P < 0.05). Although MAR and BFR gradually decreased after its peak at 2-4 weeks, BFR in the removal site was still higher than the control site at 10-12 weeks (P < 0.05). CONCLUSIONS: Spontaneous bone healing was noted after TAD removal with regional acceleration of MAR and BFR within 2-6 weeks. However, the removal site was mainly filled with woven bone even after 13 weeks, suggesting a longer healing period is required for the quality of the alveolar bone to reach levels comparable to the surrounding alveolar bone.

Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in Go-deficient mice.

In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.

Association between delayed recall and T2* relaxation time of the subiculum in adolescents: Implications for ultra-high-field magnetic resonance imaging.

AIM: The aim of this study was to assess neuropsychological correlations with the T2* relaxation time (T2*-RT) of hippocampal subregions in adolescents using ultra-high-field (UHF) 7.0-T magnetic resonance imaging (MRI). METHODS: We assessed the T2*-RT of hippocampal subregions in 31 healthy 11th- or 12th-grade high school students using an UHF 7.0-T MRI system. T2*-RT of the cornu ammonis (CA) 1, CA2, CA3, and CA4 subregions and the subiculum were calculated for both the left and right hippocampus. Seven subtests of the Cambridge Neuropsychological Test Automated Battery were administered to the subjects to assess visuospatial memory. RESULTS: Poor performances in delayed recall in the pattern-recognition test were significantly correlated with longer T2*-RT in the bilateral subiculum (right, r = -0.480, P = 0.006; left, r = -0.648, P < 0.001) and the left CA2 (r = -0.480, P = 0.006). CONCLUSION: This study showed that longer T2*-RT in the subiculum were associated with poorer performances in delayed recall in the visual memory tasks. This finding suggests that the subiculum might play a predominant role in delayed recall in adolescents.

Phase 2 Study of an Intravenous Busulfan and Melphalan Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (KMM150).

This prospective study evaluated the efficacy and toxicity of intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99 patients with MM, enrolled between January 2013 and March 2016, received intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) before ASCT. The median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT within 12 months of the diagnosis. The overall response rate after ASCT was 94.0%, including 43.5% with a stringent complete response/complete response, 27.3% with very good partial response, and 23.2% with partial response. The most common severe nonhematologic toxicity (grade 3 to 4) was infection (26.3%) and stomatitis (15.2%). Three (3.2%) patients developed veno-occlusive disease. No treatment-related mortality was observed. After a median follow-up of 26.1 months, the median progression-free survival was 27.2 months (range, 13.0 to 41.4 months) and median overall survival was not reached. In conclusion, a conditioning regimen of intravenous busulfan and melphalan was effective and tolerable. ClinicalTrials.gov. number: NCT01923935.

Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy.

BACKGROUND & AIMS: Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to improve the predictive performance. METHODS: From 2007 to 2017, we examined 3,001 Asian patients with CHB receiving entecavir/tenofovir therapy. We assessed the performances of PAGE-B, THRI, CU-HCC, GAG-HCC, and REACH-B for HCC development. A modified PAGE-B score (mPAGE-B) was developed (derivation set, n = 2,001) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation set, n = 1,000) were performed. RESULTS: The five-year cumulative HCC incidence rates were 6.6% and 7.2% in the derivation and validation datasets after entecavir/tenofovir onset. In the derivation dataset, age, gender, serum albumin levels, and platelet counts were independently associated with HCC. The mPAGE-B score was developed based on age, gender, platelet counts, and serum albumin levels (time-dependent area under receiver operating characteristic curves [AUROC] = 0.82). In the validation set, the PAGE-B and THRI showed similar AUROCs to CU-HCC, GAG-HCC, and REACH-B at five years (0.72 and 0.73 vs. 0.70, 0.71, and 0.61 respectively; all p >0.05 except REACH-B), whereas the AUROC of mPAGE-B at five years was 0.82, significantly higher than the five other models (all p <0.01). HCC incidence rates after initiation of entecavir/tenofovir therapy in patients with CHB were significantly decreased in all risk groups in long-term follow-up periods. CONCLUSION: Although PAGE-B and THRI are applicable in Asian patients with CHB receiving entecavir/tenofovir therapy, mPAGE-B scores including additional serum albumin levels showed better predictive performance than the PAGE-B score. LAY SUMMARY: PAGE-B scores and Toronto HCC risk index were developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with CHB under potent antiviral therapy. This study validated these two scores in Asian patients with CHB and suggested that modified PAGE-B scores could improve the predictive performance. A modified PAGE-B score, which is based only on a patient's age, gender, baseline platelet counts, and serum albumin levels at treatment initiation, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in Asian patients with CHB. With a scoring range from 0 to 21 points, a modified PAGE-B score differentiates the HCC risk. A modified PAGE-B score significantly differentiates the five-year HCC risk: low ≤8 points and high ≥13 points.

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18 F]fallypride PET and functional MRI study.

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlations of dopamine D2/3 receptor availability between striatal and extrastriatal regions using [18 F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [18 F]fallypride binding potential (BPND ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BPND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naïve patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.

Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder

Background: Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus­pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods: In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results: The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus­pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations: Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion: The insomnia group showed decreased integrity in the left thalamus­pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.