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Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes and identified 14 loci with genome-wide significance (p

Abstract Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Abstract Orthodontic treatment with premolar extractions is typically used to relieve dental crowding and retract anterior teeth for lip profile improvement. The aim of the study is to compare the changes in regional pharyngeal airway space (PAS) after orthodontic treatment with Class II malocclusion and to identify the correlations between questionnaire results and PAS dimensions after orthodontic treatment. In this retrospective cohort study, 79 consecutive patients were divided into normodivergent nonextraction, normodivergent extraction, and hyperdivergent extraction groups. Serial lateral cephalograms were used to evaluate the patients’ PASs and hyoid bone positions. The Pittsburgh Sleep Quality Index and STOP-Bang questionnaire were used for sleep quality evaluation and obstructive sleep apnea (OSA) risk assessment, respectively, after treatment. The greatest airway reduction was observed in hyperdivergent extraction group. However, the changes in PAS and hyoid positions did not differ significantly among three groups. According to questionnaire results, all three groups had high sleep quality and low risk of OSA, with no significant intergroup differences. Moreover, pretreatment-to-posttreatment changes in PAS were not correlated with sleep quality or risk of OSA. Orthodontic retraction with premolar extractions nither exhibit significant reduction in airway dimensions nor increase their risk of OSA.

Summary: Neural progenitor cells lengthen their cell cycle to prime themselves for differentiation as development proceeds. It is currently not clear how they counter this lengthening and avoid being halted in the cell cycle. We show that N6-methyladenosine (m6A) methylation of cell-cycle-related mRNAs ensures the proper cell-cycle progression of late-born retinal progenitor cells (RPCs), which are born toward the end of retinogenesis and have long cell-cycle length. Conditional deletion of Mettl14, which is required for depositing m6A, led to delayed cell-cycle exit of late-born RPCs but has no effect on retinal development prior to birth. m6A sequencing and single-cell transcriptomics revealed that mRNAs involved in elongating the cell cycle were highly enriched for m6A, which could target them for degradation and guarantee proper cell-cycle progression. In addition, we identified Zfp292 as a target of m6A and potent inhibitor of RPC cell-cycle progression.

Background: Orthognathic Surgery (OGS) is a surgery for patients with dento-facial deformity but not all patients are satisfied with its outcome. The purpose of this study is to find out the short-term and long-term psychological impact and quality-of-life of OGS. Methods: 77 participants receiving OGS and 32 age and gender-matched controls were enrolled. The data of questionnaires were collected before OGS, one month and 9 months after OGS, including short form of the Derriford-Appearance-Scale (DAS-24), Big-Five-Inventory (BFI), Hospital-Anxiety-and-Depression-Scale (HADS), Pittsburgh-sleep-quality-index (PSQI), and 36-Item Short-Form-Health-Survey (SF-36). Variables were presented as mean ± standard deviation or frequency. Paired t-test, ANOVA and MANOVA were used to evaluate the pre-and post-surgery data. Results: Short-term and long-term satisfaction of OGS was high. Before OGS, BFI showed the extraversion had significant difference between the male and female OGS subgroups. Several domains of DAS-24 were significantly different between the OGS and the control groups. Both groups had no significant difference in PSQI, HADS and SF-36, except sleep-efficiency. After OGS, many domains of DAS-24 were significantly improved and the improvement persisted to 9 months later. Sleep-latency, physical-function, role-limitations-due-to-physical-health and social-functioning exacerbated after OGS. Sleep-latency, physical-function, and social-functioning were improved 9 months after OGS, but sleep-efficiency and role-limitations-due-to-physical-health were still significantly worse than controls. Conclusion: People received OGS for unfavorable appearance and the surgery could decrease their distress of appearance and impact to their daily living. Through long-term assessment, we should pay attention to sleep problems and role-limitations-due-to-physical-health after OGS.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon entity characterized by papillary growth within the bile duct lumen. IPNB is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas, which sometimes complicates with fistula formation to adjacent organs, mainly due to high-pressure related erosion from mucin-filled ducts. However, fistula formation from IPNB is quite rare. Here we report a case of IPNB complicated with hepatogastric fistula. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed disproportional dilatation of left intrahepatic duct with intraluminal soft tissue nodules and fistulous connections to gastric high body. Endoscopy revealed ulcers with two fistulous orifices at upper gastric body. The patient underwent left hepatectomy with gastric wedge resection. Histopathology examination revealed IPNB with invasive cholangiocarcinoma, directly invading to gastric wall leading to hepatogastric fistula. In summary, we have presented the clinical, imaging and pathological findings, along with a comprehensive review of relevant literature, in order to enhance the understanding of this rare condition.

Abstract Predictors of needle-knife pre-cut papillotomy (NKP) failure for patients with difficult biliary cannulation has not been reported. Between 2004 and 2016, 390 patients with difficult biliary cannulation undergoing NKP were included in this single-center study. Following NKP, deep biliary cannulation failed in 95 patients (24.4%, NKP-failure group) and succeeded in 295 patients (75.6%, NKP-success group). Patient and technique factors were used to identify the predictors of initial NKP failure. Compared with the NKP-success group, periampullary diverticulum (28.4% vs. 18%, p = 0.028), surgically altered anatomy (13.7% vs. 7.1%, p = 0.049), number of cases performed by less experienced endoscopists, and bleeding during NKP (38.9% vs. 3.4%, p

Duodenal obstruction is often accompanied with unresectable malignant distal biliary obstruction in patients who have undergone biliary self-expandable metal stent (SEMS) placement. Duodenobiliary reflux (DBR) is a major cause of recurrent biliary obstruction (RBO) after covered biliary SEMS placement. We analyzed the risk factors for DBR-related SEMS dysfunction following treatment for malignant duodenal obstruction. Sixty-one patients with covered SEMS who underwent treatment for duodenal obstruction were included. We excluded patients with tumor-related stent dysfunction (n = 6) or metal stent migration (n = 1). Fifty-four patients who underwent covered biliary SEMS placement followed by duodenal metal stenting or surgical gastrojejunostomy were included. Eleven patients had DBR-related biliary SEMS dysfunction after treatment of duodenal obstruction. There was no difference between the duodenal metal stenting group and the surgical gastrojejunostomy group. Duodenal obstruction below the papilla of Vater and a score of ≤2 on the Gastric Outlet Obstruction Scoring System after treatment for duodenal obstruction were associated with DBR-related covered biliary SEMS dysfunction. Thus, creating a reliable route for ensuring good oral intake and avoiding DBR in patients with duodenal obstruction below the papilla of Vater are both important factors in preventing DBR-related covered biliary SEMS dysfunction.

Abstract Endoscopic retrograde cholangiopancreatography is not always successful even with needle knife precut sphincterotomy (NKPS). How to manage these patients with initial NKPS failure has not been well studied. We report the outcomes of patients who received endoscopic and non-endoscopic rescue treatment after the initial NKPS failure. During the 15 years from 2004 to 2018, 87 patients with initial NKPS failure received interval endoscopic treatment (IET group, n = 43), percutaneous transhepatic biliary drainage (PTBD group, n = 25), or bile duct surgery (BDS group, n = 19) were retrospectively studied. Compared with the PTBD group, the prevalence of choledocholithiasis was higher (69.8% vs. 16.0%, p

Objective: The study investigated the preoperative anatomical variables that affect the outcome of surgical correction in patients with Class III facial asymmetry. Methods: The study recruited 37 consecutive patients with facial asymmetry who had 2-jaw orthognathic surgery. They were divided into two groups based on the surgical outcome: symmetrical (S group) or asymmetrical (A group), according to the asymmetry index. The CBCT images were obtained before surgery (T0) and after debond (T1). The 3D dentofacial measurements were compared between groups S and A by the Mann–Whitney test. Spearman correlation analysis was performed to examine the relationship of all dentoskeletal variables in T0 with the facial symmetry outcome. Results: Significant between-group differences were observed in preoperative time, including maxillary anterior occlusal canting, maxillary posterior occlusal canting, the gonion–Frankfort horizontal plane (FHP) distance, the mandibular ramus axis–FHP distances, and sagittal and transverse of condyle position. Conclusions: For patients with severe skeletal Class III asymmetry, preoperative anatomical variables, particularly preoperative “roll” and “yaw” discrepancies and anatomical limitations of the mandible, should be considered for favorable asymmetry correction. Based on the anatomic variables that affect the outcomes of facial asymmetry correction, prognosis and treatment limitation could be predicted before treatment.

Summary: Ocular drug implants (ODIs) are beneficial for treating ocular diseases. However, the lack of a robust injection approach for small-eyed model organisms has been a major technical limitation in developing ODIs. Here, we present a cost-effective, minimally invasive protocol to deliver ODIs into the mouse vitreous called Mouse Implant Intravitreal Injection (MI3). MI3 provides two alternative surgical approaches (air-pressure or plunger) to deliver micro-scaled ODIs into milli-scaled eyes, and expands the preclinical platforms to determine ODIs’ efficacy, toxicity, and pharmacokinetics.For complete details on the use and execution of this protocol, please refer to Sun et al. (2021).

Facial symmetry affects the perception of facial beauty. Overall, facial harmony with an appropriate facial proportion and satisfactory midline facial symmetry are crucial factors for facial attractiveness. The role of orthodontists in correcting facial asymmetry begins with providing suitable diagnosis of the condition and identifying patients’ expectations. Through a thorough, subjective clinical evaluation of dentofacial asymmetry, the procedures for the surgical orthodontic management of facial asymmetry are discussed. The aim of this clinical review is to provide information on surgical indications for facial asymmetry, optimal treatment goals, presurgical orthodontic preparation, the surgery-first approach, three-dimensional (3D) surgical simulation, postsurgical orthodontic finishing, and treatment outcome evaluation. A comprehensive 3D diagnosis with appropriate planning, accurate transference of surgical simulation to real surgery, slight overcorrection, periodic assessment of treatment outcomes, and awareness of treatment limitations are essential to improve treatment outcomes of facial asymmetry.

We conducted this retrospective study to identify potential clinical, polysomnographic, and cephalometric predictors for the treatment outcomes of a tongue-beaded oral appliance (OA) in children with obstructive sleep apnea syndrome (OSAS). In total, 63 patients—50 boys and 13 girls ranging in age from 4 to 16 years—underwent OA treatment nightly for at least 6 months. A baseline digital lateral cephalometric radiograph was obtained for each patient. Multivariate logistic regression analysis was performed to examine predictors for the treatment outcome based on the clinical and cephalometric measurements. Overall, 28 patients responded to the treatment (post-treatment improvement > 50% or apnea–hypopnea index (AHI) < 1/h), and 35 did not (post-treatment improvement < 50% and AHI ≥ 1/h). Significantly larger cranial base angle (SNBa), smaller lower gonial angle (LGo Angle), and shorter length of anterior cranial base (SN) were found in responders. Smaller lower gonial angle (LGo Angle) and smaller anterior cranial base (SN) predict a favorable outcome for pediatric OSAS using a tongue-beaded OA. This finding will equip practitioners with additional insights when selecting suitable candidates for OA therapy in pediatric patients.

Introduction: Glioblastoma multiforme (GBM) is the most aggressive glioma, and its diffuse nature makes resection of it difficult. Moreover, even with the administration of postoperative radiotherapy and chemotherapy, prolonged remission is often not achieved. Hence, innovative or alternative treatments for GBM are urgently required. Traditional Chinese herbs and their functional components have long been used in the treatment of various cancers, including GBM. The current study investigated the antitumor activity of Wedelia chinensis and its major functional components, luteolin and apigenin, on GBM. Materials and Methods: MTT assay, Transwell migration assay, and flow cytometry analysis were adopted to assess the cell viability, invasive capability, and cell cycle. Immunofluorescence staining and Western blotting were used to detect the expressions of apoptotic and autophagy-related signaling molecules. Results: The W. chinensis extract (WCE) significantly inhibited the proliferation and invasive ability of both GBM8401 and U-87MG cells in a dose-dependent manner. Moreover, differential effects of WCE on GBM8401 and U-87MG cells were observed: WCE induced apoptosis in GBM8401 cells and autophagy in U-87MG cells. Notably, WCE had significant effects in reducing the cell survival and invasive capability of both GBM8401 and U-87MG cells than the combination of luteolin and apigenin. Conclusions: Taken together, these findings indicate the potential of using WCE and the combination of luteolin and apigenin for GBM treatment. However, further investigations are warranted before considering recommending the clinical use of WCE or the combination of luteolin and apigenin as the standard for GBM treatment.

Stock enhancement is considered to be a valuable approach for restoring fishery resources. Because no specific official institution in Taiwan is responsible for the production of fry, the released fry are purchased directly from the private sector. However, fishermen from the private industry have not established a genetic background, so the genetic composition for each batch of released fry is unclear. Mangrove red snapper (Lutjanus argentimaculatus), a prominent species released in Taiwan, was collected after its official release. One hundred and two field samples were compared with four batches of hatchery fry (n = 685) by using a microsatellite-based multiplex PCR assay. Four of the field samples (3.9%; 4/102) were revealed to be from a fish farm and most likely from a single batch. This study revealed that wild mangrove red snappers are genetically different from those originating from farms, and their origins can be traced through molecular markers, even without information on breeding stocks.

Background/Aims: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. Methods: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. Results: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. Conclusion: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Background: Non-absorbable materials (nylon) are always used in cinch sutures to maintain nasal width and to improve harmonious facial symmetry in orthognathic surgery. However, a few drawbacks of nylon materials have been clinically reported following orthognathic surgery, such as nasal irritation and exposure of the sutures. An absorbable material (PDS) has been proposed in cinch sutures, not only to avoid the complications of nylon but also to stabilize the nasal width for a long-term follow-up. Methods: Fifty-seven patients with Angle’s malocclusion classification III receiving orthognathic surgery were enrolled in this study. A non-absorbable material (nylon) and an absorbable material (PDS) were utilized for the cinch sutures. Pre-operative (T1) and post-operative six-month (T2) craniofacial 3D images were collected for all patients to measure the alar curvature (Ac) width and the alar base (Al) width. A significance level of p < 0.05 was applied in the statistical analysis. Results: With the approval of IRB, cinch suturing was performed with nylon in 29 patients and with PDS in 28 patients. Pre-operative Ac and Al distances showed no significant difference between these two groups. There were also no significant differences between the suture materials in the peri-operative change in nasal width, including Ac (nylon: 1.999 ± 1.40; PDS: 1.484 ± 0.97; p = 0.112) and Al (nylon: 1.861 ± 1.66; PDS: 1.115 ± 0.92; p = 0.056). Conclusions: For cinch sutures in orthognathic surgery, PDS can maintain the peri-operative nasal width similarly to nylon; additionally, it can be absorbed in a timely manner without the drawbacks of non-absorbable materials.

Stock enhancement is a method for replenishing depleted wild finfish populations by supplementing them with hatchery-raised fish. In Taiwan, silver sea bream (Rhabdosargus sarba) is a predominant commercial species involved in stock enhancement projects. Although management agencies conduct stock enhancement projects, there are a lot of private releases without records. Stock enhancement is performed by the private aquaculture sector without accurate genetic records, potentially leading to unintended consequences for wild populations. We analyzed the genetics of 459 wild and 701 hatchery-reared specimens from nine batches produced by various hatcheries. Wild and hatchery-reared samples could be considered two separate clades by using a set of stable and informative microsatellite markers including type I (from gene introns and 3′UTR) and type II markers (randomly picked up from genome). Type I microsatellite markers could more sensitively reflect the loss of genetic diversity more than type II markers in the domestication process. All specimens were considered native by using mtDNA COI and microsatellites. The genetic composition of the wild population is relatively simple, and the estimated low contribution rate of the hatchery stock (1.3–10.9%; 6–50/459) indicated a weak but significant genetic effect of stock enhancement. Therefore, establishing standards for the stock enhancement of silver sea bream for more effective supplementation of wild populations is imperative.

N-retinylidene-N-retinylethanolamine (A2E) and other bisretinoids are components of lipofuscin and accumulate in retinal pigment epithelial (RPE) cells—these adducts are recognized in the pathogenesis of retinal degeneration. Further, blue light-emitting diode (LED) light (BLL)-induced retinal toxicity plays an important role in retinal degeneration. Here, we demonstrate that low-luminance BLL enhances phototoxicity in A2E-laden RPE cells and rats. RPE cells were subjected to synthetic A2E, and the effects of BLL on activation of apoptotic biomarkers were examined by measuring the levels of cleaved caspase-3. BLL modulates the protein expression of zonula-occludens 1 (ZO-1) and paracellular permeability in A2E-laden RPE cells. Early inflammatory and angiogenic genes were also screened after short-term BLL exposure. In this study, we developed a rat model for A2E treatment with or without BLL exposure for 21 days. BLL exposure caused fundus damage, decreased total retinal thickness, and caused neuron transduction injury in the retina, which were consistent with the in vitro data. We suggest that the synergistic effects of BLL and A2E accumulation in the retina increase the risk of retinal degeneration. These outcomes help elucidate the associations between BLL/A2E and angiogenic/apoptotic mechanisms, as well as furthering therapeutic strategies.

PT-peptide is derived from the anti-lipopolysaccharide factor of the swimming crab Portunus trituberculatus. The peptide, consisting of 34 amino acids, contains a lipopolysaccharide binding domain. In this study, we investigated the effect of PT-peptide encapsulated in raw milk-derived extracellular vesicles (EVs), designated as EVs-PT peptide, on immune regulation. The results showed that raw milk-derived EVs efficaciously delivered the PT-peptide into monocytes and elevated immune activity, including reactive oxygen species level, superoxide anion production, and phagocytosis. PT-peptide and EVs-PT peptide also elevated the secretion of cytokines, such as interferon-γ, interleukin-6, and tumor necrosis factor-α in human monocytic THP-1 cells. These results suggest that the PT-peptide could be developed as an immune stimulator.

Community-acquired pneumonia (CAP) remains a significant cause of childhood morbidity worldwide. We analyzed the etiologies and the clinical characteristics of children who died from CAP. This study aimed at early identification of the poor prognostic factors in order to improve the efficiency of pneumonia management and prevent deaths. Methods: A retrospective chart review was performed for children younger than 18 years admitted to Shin Kong Wu Ho-Su Memorial Hospital between September 1992 and August 2010 with a diagnosis of pneumonia on admission. Twenty-one patients who died with the diagnosis of pneumonia and its complications were included in the study, along with 63 age- and year-matched survival controls. Results: Twelve patients (57.1%) were younger than 2 years. Gram-negative bacteria (7 patients) were the most frequently identified pathogen, followed by Mycoplasma pneumoniae (6 patients). Four of these six M. pneumoniae infected patients were co-infected with other pathogens. Among the clinical characteristics, fatal CAP was associated mainly with initial presentations of anemia, lymphopenia, thrombocytopenia, bandemia, hyponatremia, sepsis, meningitis, metabolic acidosis, disseminated intravenous coagulopathy, and underlying congenital diseases. In multivariate logistic regression analysis, metabolic acidosis (odds ratio = 8.50; 95% confidence interval = 2.82–25.60; p

Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality.

The antitumor activity of pardaxin, a fish antimicrobial peptide, has not been previously examined in in vitro and in vivo systems for treating murine fibrosarcoma. In this study, the antitumor activity of synthetic pardaxin was tested using murine MN-11 tumor cells as the study model. We show that pardaxin inhibits the proliferation of MN-11 cells and reduces colony formation in a soft agar assay. Transmission electron microscopy (TEM) showed that pardaxin altered the membrane structure similar to what a lytic peptide does, and also produced apoptotic features, such as hollow mitochondria, nuclear condensation, and disrupted cell membranes. A qRT-PCR and ELISA showed that pardaxin induced apoptosis, activated caspase-7 and interleukin (IL)-7r, and downregulated caspase-9, ATF 3, SOCS3, STAT3, cathelicidin, p65, and interferon (IFN)-γ suggesting that pardaxin induces apoptosis through the death receptor/nuclear factor (NF)-κB signaling pathway after 14 days of treatment in tumor-bearing mice. An antitumor effect was observed when pardaxin (25 mg/kg; 0.5 mg/day) was used to treat mice for 14 days, which caused significant inhibition of MN-11 cell growth in mice. Overall, these results indicate that pardaxin has the potential to be a novel therapeutic agent to treat fibrosarcomas.

Neonates with a single umbilical artery (SUA) are considered at increased risk for chromosomal and structural abnormalities, and an increased adverse perinatal outcome. Objective: The specific aims of our study were to evaluate (1) the association of asymptomatic infants with isolated SUA and perinatal outcomes and (2) whether asymptomatic neonates with isolated SUA at birth need full investigation. Methods: The inclusion criteria for the study were full-term neonates with isolated SUA delivered from January 1996 to December 2006. For a control group, we used the next consecutive two newborns delivered after the SUA case in the same maternity ward with matched gestational age and without phenotypic features suspicious for aneuploidy delivered after each SUA group subject. All prenatal, peripartum and delivery records were reviewed for maternal demographics, associated anomalies, karyotypic analysis, pregnancy complications and perinatal outcomes. All SUA cases had undergone sonogram for renal anomalies. Results: We enrolled 14 and 28 cases into the SUA and control groups respectively. There was all normal karyotyping for the 14 cases. The placental weight in SUA was significantly lighter compared to that in the control group (597.1 ± 175.4 vs. 709.3 ± 95.2 g, p = 0.010). All renal sonographic screens and karyotyping in the SUA group were normal. The incidence of small for gestational age (SGA) in SUA group was higher compared to control group (SGA, 5/14, 35.7% vs. 1/28, 3.6%, p= 0.011) and less body length (48.7 ± 5.0 vs. 50.8 ± 1.8 cm, p = 0.028). Conclusion: SUA is a relatively rare finding. When a SUA is identified, the routine check of karyotyping and kidney sonography for possible chromosome and associated renal anomalies may be unnecessary. According to lighter placental weight probably causing the higher incidence of small for gestational age (SGA), pregnancies with isolated SUA should be carefully monitored for evidence of fetal growth restriction.

The majority of children born with very low birth weight (VLBW; < 1500 g) enter mainstream schools. They experience significant neurodevelopmental disabilities during childhood. The specific aims of our study were to evaluate the neonatal outcomes of VLBW infants and whether they would influence intelligence quotient (IQ), cognitive function and learning disabilities at the age of 6 or 8 years. Methods: We enrolled VLBW neonates who weighed less than 1500 g and who were delivered at Shin-Kong Wu Ho-Su Memorial Hospital in 1996 and 1999. The psychological assessments were applied with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) for age 6 and Wechsler Intelligence Scale for Children-Third Edition (WISC-III) for age 8. We recorded their demographic data, ventilation duration by days, length of stay, use of surfactant, respiratory distress syndrome (RDS), and other complications. Results: According to whether the full scale intelligence quotient (FSIQ) was above or below the average score (FSIQ = 90), we divided VLBW children into two groups (< 90, n = 17; ≥ 90, n = 21). The children with lower gestational age had lower FSIQ (p = 0.013). The higher FSIQ group (≥ 90) showed more prenatal steroid use (5/17, 29.4% vs. 14/21, 66.7%; p = 0.049). There were more boys in the lower FSIQ group (< 90, 13/17, 76.5% vs. ≥90, 7/21, 33.3%; p = 0.011). The average IQ scores were 78.11 ± 9.05 and 102.57 ± 8.89 in the FSIQ < 90 and FSIQ < 90 groups, respectively. The groups were similar in ventilation duration by days, use of surfactant, frequency of sepsis, RDS, bronchopulmonary dysplasia, patent ductus arteriosus, intraventricular hemorrhage and retinopathy of prematurity. Conclusion: Conclusion: In our study, the children with lower gestational age had lower FSIQ. There was no significant association between small for gestational age and IQ performance. The neonatal outcomes of VLBW infants did have less impact on IQ performance later in life.

Chorioamnionitis (CAM) is one of the main causes of preterm labor. The specific aim of our study was to evaluate neonatal outcome and anthropometric growth at the corrected age of 2 years after exposure to an adverse intrauterine event of CAM in very low birth weight (VLBW, < 1500 g) infants. Methods: One hundred and nineteen VLBW infants had adequate placental histological data available for the study. Maternal and perinatal characteristics and neonatal morbidity were determined. The infants were followed up prospectively and their anthropometric growth was recorded in the neonatal follow-up clinic for 2 years. Results: Histological CAM was evident in 64 cases (53.8%, CAM group). Patients with histological CAM delivered earlier (27.8 ± 2.9 vs. 29.6 ± 3.6 weeks, p = 0.003), and they had higher incidence of preterm premature rupture of membranes (PPROM, p < 0.001) and longer ventilation days (p = 0.001). After adjusting for gestational age, sepsis (aOR, 3.355), bronchopulmonary dysplasia (aOR, 3.018) and mechanical ventilation (aOR, 4.094) had a higher incidence in the CAM group. At the corrected ages of 6, 12, 18 and 24 months, anthropometric measurements, including body weight, body height and head circumference, were similar for the study and control infants. Conclusion: Histological CAM was associated with a higher incidence of PPROM, sepsis, bronchopulmonary dysplasia, more mechanical ventilation and longer ventilation days. However, at the age of 2 years, CAM had no impact on anthropometric growth.

Background and study aims: Data on double-balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatogrphy (ERCP) in patients with Billroth II gastrectomy and the use of endoscopic papillary large-balloon dilation (EPLBD) for the removal of common bile duct stones in Billroth II anatomy are limited. The aims of the study were to evaluate the success of DBE-assisted ERCP in patients with Billroth II gastrectomy and examine the efficacy of EPLBD ( ≥ 10 mm) for the removal of common bile duct stones. Patients and methods: A total of 77 patients with Billroth II gastrectomy in whom standard ERCP had failed underwent DBE-assisted ERCP. DBE success was defined as visualizing the papilla and ERCP success as completing the intended intervention. The clinical results of EPLBD for the removal of common bile duct stones were analyzed. Results: DBE was successful in 73 of 77 patients (95 %), and ERCP success was achieved in 67 of these 73 (92 %). Therefore, the rate of successful DBE-assisted ERCP was 87 % (67 of a total of 77 patients). The reasons for ERCP failure (n = 10) included tumor obstruction (n = 2), adhesion obstruction (n = 2), failed cannulation (n = 3), failed stone removal (n = 2), and bowel perforation (n = 1). Overall DBE-assisted ERCP complications occurred in 5 of 77 patients (6.5 %). A total of 48 patients (34 male, mean age 75.5 years) with common bile duct stones underwent EPLBD. Complete stone removal in the first session was accomplished in 36 patients (75 %); mechanical lithotripsy was required in 1 patient. EPLBD-related mild perforation occurred in 2 patients (4 %). No acute pancreatitis occurred. Conclusions: DBE permits therapeutic ERCP in patients who have a difficult Billroth II gastrectomy with a high success rate and acceptable complication rates. EPLBD is effective and safe for the removal of common bile duct stones in patients with Billroth II anatomy.

We present a full-term female infant with a difficult delivery course complicated with Escherichia coli sepsis and bilateral adrenal abscesses. She developed renal failure and received peritoneal dialysis. Peritonitis of Candida parapsilosis developed later. The infant was successfully treated with hemofiltration and a combination of antifungal agents.

The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive.A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) ≥ 2.5). Paired t-tests were used to compare the pre- and post-treatment variables.Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p

This research proposes a two-stage user-based collaborative filtering process using an artificial immune system for the prediction of student grades, along with a filter for professor ratings in the course recommendation for college students. We test for cosine similarity and Karl Pearson (KP) correlation in affinity calculations for clustering and prediction. This research uses student information and professor information datasets of Yuan Ze University from the years 2005–2009 for the purpose of testing and training. The mean average error and confusion matrix analysis form the testing parameters. A minimum professor rating was tested to check the results, and observed that the recommendation systems herein provide highly accurate results for students with higher mean grades.

BackgroundThe aim of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.MethodsPatients were assessed with the FACT/GOG-Ntx subscale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Scale 20 (EORTC QLQ-CIPN20), National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE), and light touch test using 10 g monofilament for up to ten assessment points from baseline (prior to initiation of first chemotherapy), after the end of each cycle (up to 6 cycles, 3 weeks per cycle), and at 6, 9, and 12 months after starting chemotherapy. Psychometric analyses included internal consistency reliability, convergent validity, factorial validity, sensitivity to change and responsiveness (minimal clinically important difference, MCID).ResultsCronbach's alpha coefficients of the FACT/GOG-Ntx subscale were 0.82-0.89 across assessment points. The subscale strongly correlated with the EORTC QLQ-CIPN20 (r = 0.79-0.93) but low-to-moderately correlated with the NCI-CTCAE sensory (rs = 0.23-0.45) and motor items (rs = 0.15-0.50) as well as the monofilament test (rs = 0.23-0.47). The hypothesized 4-factor structure of the FACT/GOG-Ntx subscale was not confirmed at assessment points (χ2/df = 2.26-8.50; all P

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p

BackgroundThere are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy.Patients and methodsMulti-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.ResultsIn total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2-53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (rs = 0.15,p

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a significant and difficult to manage side effect of neurotoxic chemotherapies. Several risk factors for CIPN have been identified to date, but inconsistencies and methodological limitations exist in past research. Also, a limited number of potential risk factors has been investigated in the past.AimThe objective of this study was to assess the relative contribution of a wider range of risk factors in the development of CIPN.MethodsThis analysis used the 6-month data after starting chemotherapy from a larger prospective observational study on CIPN risk, prevalence, and quality of life. Patients were assessed at recruitment for possible CIPN risk factors, including prior history of neuropathies, current/past infectious diseases; neurotoxic medication history; personal and treatment characteristics; smoking history, alcohol use, and vegetable/fruit intake. Neuropathy was assessed at 6-months after starting chemotherapy with the neuropathy (motor/sensory) items of the NCI-CTCAE scale and the WHO criterion for neuropathy. Data on symptom burden were also collected.ResultsData were available from 255 patients from three cancer centers in Hong Kong, Singapore, and UK. The use of different scales did not always identify the same predictor variables. Key risk factors in multivariate regression models included older age (highest OR = 1.08, p