Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation.

The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

Rationale and Trial Protocol for a Double-Blinded Randomized Controlled Trial to assess the Impact of a Concomitant Crural Repair during Laparoscopic Sleeve Gastrectomy in Patients with a Lax Gastroesophageal Junction without Frank Hiatal Hernia (REPAIR trial protocol).

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative gastroesophageal reflux disease (GERD) and erosive esophagitis (EE). The role of crural repair during LSG is still controversial. The preoperative laxity of the gastroesophageal junction (GEJ), graded by the Hill's classification, is more predictive for postoperative GERD and EE after LSG than the presence of a hiatal hernia seen on endoscopy. Thus, the authors hypothesize that a concomitant crural repair in a specific subgroup of patients with a lax GEJ (Hill's III) may reduce the incidence of postoperative GERD and EE. METHODS: A double-blinded, randomized controlled trial of patients with Hill's III GEJ undergoing LSG will be randomized to a concomitant crural repair (experimental) versus LSG alone (control). Primary outcome measures will be presence of EE at 1-year. Secondary outcome measures will include proton pump inhibitor use, postoperative complications, operative time, blood loss, quality of life, GERD and gastrointestinal symptoms. CONCLUSION: Conflicting crural repair results may be explained by differences in preoperative GEJ laxity. Patients with a frank hiatal hernia and patulous GEJ (Hill's IV) have a very high, while patients with an apposed GEJ (Hill's I, Hill's II) have a low incidence of postoperative GERD and EE respectively. Thus, the authors hypothesize that patients with a lax GEJ without frank hiatal hernia (Hill's III), might benefit from a crural repair. This study results can potentially highlight the clinical importance of preoperative endoscopic evaluation of the GEJ in all patients planned for LSG, to determine which subgroup patients may benefit from a crural repair. (Clinicaltrials.gov: NCT05330910, Registered 15-April-2022).

First Report of bacterial wilt disease of banana caused by Klebsiella variicola in Malaysia.

In Malaysia, bananas (Musa spp.) are the second most cultivated fruit and the fourth most cultivated fruit in terms of export revenue. In October 2018, about 5.0 out of 6.6 hectares of a banana plantation located in Teluk Intan, Malaysia, was impacted by an outbreak of banana disease. The onset of bacterial wilt symptoms is characterized by initial leaf wilting, followed by the subsequent withering of the entire plant during later stages, fruit stalk and fruit pulp discoloration, fruit rotting, and pseudostem necrosis. The diseased banana's symptomatic pseudostems and fruit pulps were surface-sterilised in 70% ethanol for 30 s, followed by 2% NaClO for 3 min, rinsed three times in sterilised water, and cut into small pieces approximately 5 mm2 in size. The tissues were macerated in a sterilised 0.85% NaCl solution for 5 min, and the resulting suspension was streaked onto nutrient agar, followed by incubation at 28°C for 2 days. After incubation, bacterial colonies with five unique morphological characteristics were observed. Two colonies of each unique morphological type were randomly chosen and subjected to preliminary bacterial identification by 16S rRNA gene sequencing. Based on BLASTn analysis, the five unique morphological types of bacteria were preliminarily identified as Enterobacter cloacae, Citrobacter farmeri, Klebsiella variicola, Kosakonia radicincitans, and Phytobacter ursingii. Previous reports identified K. variicola and K. radicincitans as banana pathogens, but Malaysia has yet to report the former. The amplified partial 16S rDNA sequences of both K. variicola isolates (designated as UTAR-BC1 and UTAR-BC2; GenBank accession numbers: PP531448 and PP531460, respectively), which were chosen to be the focus of this study, exhibited complete similarity to each other and were 100% identical (1426/1426 identity and 1420/1420 identity, respectively) to K. variicola (CP026013.1). To verify the identity of the bacterial isolate, three housekeeping genes, namely, infB(PP538994), rpoB (PP538995), and gyrB (PP538996) of UTAR-BC1, were amplified, sequenced, and subjected to multilocus phylogenetic analysis via the neighbour-joining method (1,000 bootstrap values). Phylogenetic analysis revealed that UTAR-BC1 belongs to the K. variicola clade. A pathogenicity assay of UTAR-BC1 was conducted on 4-month-old healthy banana plantlets (cv. Nangka) using the pseudostem injection method (Tripathi et al., 2008). First, UTAR-BC1 was grown overnight in nutrient broth and then adjusted to 108 CFU/ml in a sterile 10 mM MgCl2 solution. A total volume of 100 µL of the bacterial suspension was injected into the pseudostem of five healthy banana plantlets via a syringe with a needle. Control plants were mock-inoculated with a sterile 10 mM MgCl2 solution. The experiments were replicated thrice and inoculated plants were maintained at room temperature with natural sunlight and humidity, which resembled the field conditions. Two months after inoculation, all of the UTAR-BC1 inoculated spots of banana plantlets showed severe necrosis, while the banana leaves showed symptoms of wilted appearance, whereas the control plants remained symptomless. The reisolated pathogen from 90% of the symptomatic pseudostems and leaf blades shares the same morphological and molecular features as UTAR-BC1, thus fulfilling Koch's postulates. Previously, K. variicola has been reported to be a banana pathogen causing rhizome rot in India (Loganathan et al., 2021), plantain soft rot in Haiti (Fulton et al. 2020), and sheath rot and bulb rot in China (Sun et al., 2023; Jiang et al., 2024). To the best of our knowledge, this is the first report of bacterial wilt disease in bananas attributed to K. variicola in Malaysia. This finding will facilitate the surveillance of K. variicola as an emerging pathogen in banana plants in this region, thereby safeguarding the country's food security and promoting socio-economic growth.

Skeletal expansion via craniofacial distraction osteogenesis technique in syndromic craniosynostosis: impact on ophthalmic parameters.

BACKGROUND: This study aims to compare the changes in ophthalmic parameters among syndromic craniosynostosis patients who underwent craniofacial skeletal expansion procedures via distraction osteogenesis (DO). METHOD: A retrospective study was conducted involving syndromic craniosynostosis patients who underwent surgical expansion via the DO technique from the year 2012 to March 2022. Changes in six parameters which consist of visual acuity, refractive error, optic disc health, intraocular pressure, degree of proptosis and orbital volume were measured objectively pre and post-surgery. For categorical parameters, the Chi-square cross-tab test was done. Paired sample T-test was used for normally distributed variables. Wilcoxon signed-rank test was used for non-normally distributed data. RESULTS: Visual impairment was present in 21.4% of eyes before surgery and increased to 28.5% post-surgery. Three patients had changes of refractive error post-surgery with one developed hypermetropia, another developed anisometropia and the last had improvement to no refractive error. Two patients had optic disc swelling which was resolved post-surgery. Intraocular pressure changes were inconsistent post-surgery. All patients achieved a significant reduction in the degree of proptosis post-surgery. Orbital volume calculation using computed tomography (CT) scans shows a significant increase in volume post-surgery for all patients. CONCLUSION: Our study shows a significant increase in orbital volume post-surgery with a reduction in the degree of proptosis. Optic disc and nerve health improved after the surgery. Changes in terms of visual acuity, refractive error and IOP were inconsistent after the surgical intervention.

Study on weight loss outcomes after bariatric surgery to determine a metric least influenced by preoperative BMI.

BACKGROUND: Percentage excess weight loss (%EWL) and percentage total weight loss (%TWL) are used for reporting outcomes after bariatric surgery. However, they are not ideal for comparing outcomes on populations of varied initial body mass index (BMI). This study aimed to validate a recently introduced metric - percentage alterable weight loss (%AWL), after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB). METHODS: Analysis of weight data of all patients who had undergone LSG and LRYGB until the end of the year 2021. Outcomes for both procedures were analyzed separately. The patients were divided into quartile subgroups Q1 (lowest BMI) to Q4 (highest BMI) and weight loss up to 5 years postoperatively was compared using %EWL, %TWL and %AWL metrics. An intermediary metric was also tested for its effect on the weight loss patterns for both procedures. RESULTS: The cohort included 1020 LSG and 322 LRYGB patients, with initial mean BMI of 43.5 ± 7.5 and 41.9 ± 8.3 kg/m2, respectively. %EWL significantly favors lower BMI subgroups for both procedures. %TWL is ideal for comparing weight loss during the first 6 months but it then favors higher BMI subgroups beyond 6 months. %AWL with reference BMI of 13 kg/m2 seems the best metric for medium-term comparison of weight loss for LRYGB and an intermediary metric based on BMI 8 kg/m2 provides the best fit for medium-term comparison for LSG. CONCLUSIONS: %TWL is least influenced by initial BMI during short-term follow-up after LSG and LRYGB. For medium-term comparison, %AWL is best suited for LRYGB while an intermediary metric is found to provide the best fit for LSG.

Pepsin in saliva for the diagnosis of erosive esophagitis post-sleeve gastrectomy: a prospective observational study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, new onset erosive esophagitis (EE) is a major shortcoming. Current recommendation is esophago-gastro-duodenoscopy (EGD) should be performed routinely at 1 year and subsequently every 2-3 years to enable the early detection of Barrett's or esophageal adenocarcinoma. This would put significant strains on resources and costs of bariatric program. Our study assesses the association between and diagnostic value of salivary pepsin concentration and endoscopically proven EE in post-LSG patients as a surrogate for EGD. METHODS: Twenty patients on routine post-LSG endoscopy between June and September 2022 were recruited for this correlational pilot study. Under supervision, fasting and post-prandial saliva sample was collected and analyzed by Peptest lateral flow device. EGD examinations were performed, and patients completed a validated 25-item QoLRAD questionnaire. RESULTS: We found a significant correlation between positive endoscopy findings of EE and salivary pepsin concentrations. The normal group had a lower mean fasting pepsin level (13.13 ng/mL ± 18.97) versus the EE-group (90.55 ng/mL ± 81.28, p = 0.009) and lower mean post-prandial pepsin level (30.50 ng/mL ± 57.72) versus the EE-group (135.09 ng/mL ± 130.17, p = 0.02). The predictive probabilities from the binary regression of fasting and post-prandial pepsin concentrations yield AUC of 0.955 ± 0.044 (95% CI 0.868 to 1.000, p < 0.001). CONCLUSION: Our study distinctively identified salivary pepsin to have excellent sensitivity and negative predictive value in EE, potentially useful to preclude the need for post-LSG EGD in asymptomatic patients with low salivary pepsin.

Cost-savings of short stay sleeve gastrectomy and walk-in hydration clinic versus conventional inpatient care.

OBJECTIVE: We aim to evaluate the cost-saving of the short stay ward (SSW) versus conventional inpatient care following sleeve gastrectomy (LSG). We also compared the readmission rates pre- and post-inception of the intravenous hydration clinic and analyzed the cost-savings. METHODS: Patients who underwent LSG between December 2021 to March 2022 with SSW care were compared with standard inpatient care. Total costs were analyzed using univariate analysis. With a separate cohort of patients, 30-day readmission rates in the 12-months preceding and following implementation of the IV hydration clinic and associated cost-savings were evaluated. RESULTS: After matching on the propensity score to within ± 0.1, 20-subjects pairs were retained. The total cost per SSW-subject was significantly lower at $13,647.81 compared to $15,565.27 for conventional inpatient care (p = 0.0302). Lower average ward charges ($667.76 vs $1371.34, p < 0.0001), lower average daily treatment fee per case ($235.68 vs $836.54, p < 0.0001), and lower average laboratory investigation fee ($612.31 vs $797.21, p < 0.0001) accounted for the difference in costs between the groups. Thirty-day readmission rate reduced from 8.9 to 1.8% after implementation of the hydration clinic (p < 0.01) with decreased 30-day readmission cost (S$96,955.57 vs. S$5910.27, p < 0.01). CONCLUSION: SSW for LSG is cost-effective and should be preferred to inpatient management. Walk-in hydration clinics significantly reduced readmission rates and result in tremendous cost-savings.

Effect of mindfulness intervention on anxiety, distress, and depression for chronic diseases: a scoping review.

This scoping review describes the research-based mindfulness intervention on anxiety, distress, and depression. The search strategy retrieved articles published in English from 2014 to 2019 and were retrieved across Scopus, Web of Science, Science Direct, CINAHL, and Google Scholar. The PRISMA-Scr checklist is a tool to evaluate the quality of the articles. The selection criteria initially included all original articles in English, with 1,527 that were related to mindfulness intervention for anxiety, distress, and depression. A total of 490 full texts were retrieved, and after the abstracts were reviewed, 124 full-text articles were included for eligibility, and the final eight studies were determined. The articles were reviewed and screened for relevance to mindfulness intervention in reducing anxiety, distress, and depression among those with chronic diseases. The results have shown that mindfulness intervention reduces anxiety, distress, and depression among patients with chronic diseases. The review contributes further insight into the fact that mindfulness intervention is also appropriate for other conditions to facilitate reducing psychological symptoms.

Ictal Electroencephalogram Visual Pattern Recognition of Seizure Adequacy During Electroconvulsive Therapy Treatment: A Step-by-Step Approach.

Background: The NEURON (Neuropsychiatry and Neuromodulation Unit) electroconvulsive therapy electroencephalogram (ECT-EEG) Algorithmic Rating Scale (NEARS) is a step-by-step approach to ictal electroencephalogram visual pattern recognition of seizure adequacy based on recruitment, amplitude, symmetry, duration and degree of post-ictal suppression. The objectives of this clinical audit were to determine the degree of agreement on the NEARS operational criteria between two neuropsychiatrists, the reliability of electroconvulsive therapy practitioners' administration of NEARS during ECT procedures and the correlation of NEARS scores with Clinical Global Impression scale scores after each ECT treatment session. Methods: Systematic random sampling was conducted. Even numbers of ictal tracings were selected for analysis from the total samples collected over 8 consecutive days of ECT overseen by a total of eight different ECT practitioners. Cohen's kappa coefficient was used to measure the inter-rater reliability of the two neuropsychiatrists and determine the level of agreement between NEARS scores and those of the ECT practitioners. The correlation using NEARS scores and post-ECT Clinical Global Impression scores was measured with Spearman's test. The significance level was set at P < 0.05. Results: Cohen's kappa showed perfect agreement between the two neuropsychiatrists, at κ = 1.00 (SE = 0.001; P < 0.001), and strong agreement between NEARS scores of overall seizure adequacy and the scores interpreted by the ECT practitioners, at κ = 0.83 (95% CI: 0.66, 0.99; P < 0.001). Spearman's test showed a weak negative association between NEARS scores and post-ECT Clinical Global Impression scores (r = -0.018; P = 0.900). Conclusion: NEARS may facilitate a brief, objectively reliable and practical assessment of ictal electroencephalogram quality. The scale is readily applicable by any trained ECT practitioner during an ongoing ECT procedure, especially when a prompt treatment decision is required.

In Situ Synthesis and Microfabrication of High Entropy Alloy and Oxide Compounds by Femtosecond Laser Direct Writing under Ambient Conditions.

Synthesis and coating of multi-metal oxides (MMOs) and alloys on conductive substrates are indispensable to electrochemical applications, yet demand multiple, resource-intensive, and time-consuming processes. Herein, an alternative approach to the synthesis and coating of alloys and MMOs by femtosecond laser direct writing (FsLDW) is reported. A solution-based precursor ink is deposited and dried on the substrate and illuminated by a femtosecond laser. During the illumination, dried precursor ink is transformed to MMO/alloys and is simultaneously bonded to the substrate. The formulation of the alloy and MMO precursor ink for laser processing is universally applicable to a large family of oxides and alloys. The process is conducted at room temperature and in an open atmosphere. To demonstrate, a large family of 57 MMOs and alloys are synthesized from a group of 13 elements. As a proof of concept, Ni0.24 Co0.23 Cu0.24 Fe0.15 Cr0.14 high entropy alloy synthesized on stainless-steel foil by FsLDW is used for the oxygen evolution reaction, which achieves a current density of 10 mA cm-2 at a significantly low overpotential of 213 mV. Further, FsLDW can also achieve microfabrication of alloys/MMO with feature sizes down to 20 µm.

Introduction of IgM testing for the diagnosis of acute Lyme borreliosis: a study of the benefits, limitations and costs.

Testing for IgM antibodies to Borrelia burgdorferi in Scottish patients with suspected Lyme borreliosis was introduced in 2018 to supplement the IgG testing already in situ. Results from 2018 to 2020 were assessed alongside available clinical data to evaluate the utility of IgM testing in serum. An estimated false positive rate of 25.5% was observed with IgM immunoblot vs 80.1% for IgM chemiluminescent immunoassay (CLIA). IgM testing can aid earlier diagnoses if used within a selective two-tier testing protocol: only patients with acute onset of symptoms should be tested for IgM CLIA but confirmation by immunoblot and consideration of clinical picture is necessary.

Perception and reaction of Nanyang Technological University (NTU) researchers to different forms of research integrity education modality.

BACKGROUND: Research and academic institutions use various delivery channels to deliver Research Integrity (RI) education in their communities. Yet there is no consensus on the best delivery method and the effectiveness of these channels in inculcating a positive RI culture varies across institutions. Hence, this study aimed to understand the preferences of the research community in Nanyang Technological University (NTU), Singapore. METHODS: An online survey was conducted on NTU research community to understand their experience with, and preference for each RI education mode offered in NTU. The RI education modes surveyed in the general ranking question are Data Management Plan (DMP) workshops, Epigeum e-Learning, Compass e-newsletter (email), and NTU policy on Research Integrity and Responsible Conduct of Research. There were 242 responses, comprising 50% research students, 32.2% research staff and 17.8% faculty members. Non-parametric statistical techniques were used to analyse preferences across different RI education modes and within sub-groups (i.e., fields, age, native language, roles in research community). RESULTS: More than 92% of respondents subscribed to the importance of RI education, but with different preferences for education modes. With respect to RI education in NTU, Compass e-newsletters were ranked the lowest (p < 0.05). Most felt that they were too wordy and unengaging, making it difficult to absorb information. Similarly, Epigeum e-Learning (p < 0.05) and 'policy' (p < 0.05) were found to be too lengthy in presentation. The compulsory NTU RI education modes (Epigeum e-learning and 'policy') enjoyed higher participation rates of 70-80% compared with 32-37% for the self-regulated modes (DMP workshop and e-newsletter). This suggests that regulatory mechanisms are still necessary to promote participation in RI education, and thus, core RI education content should be made compulsory in research/academic institutions. Although Epigeum is a compulsory course, some may not have participated in the programme due to technical issues or they might have forgotten to participate in the programme within the permissible timeframe. For all four RI education modes in NTU, the lack of awareness was among the top cited reasons for not participating. CONCLUSIONS: Most NTU researchers perceived RI education positively although they may have reservations for some approaches. Conversely, e-Learning is favored over all the other modes except for the mode of Policy. Findings from this study are useful for improving the design of RI education strategies to be more appealing to the research community by enhancing user experience in terms of user-friendliness, relevance to specialisation, providing concise information and better presentation of materials For institutions with similar modes of RI education as NTU, these results may be relevant in improving participation rates and presentation of RI education modes, such as the use of infographics and more concise information.

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15-0.85; P = .02; I2 = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10-0.83; P = .02; I2 = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43-1.08; P = .10; I2 = 0%) and length of hospitalization (mean difference, -0.32; 95% CI, -1.88 to 1.24; P = .69; I2 = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09-97.98; I2 = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00-1.28; I2 = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.

Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm.

Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.

Natural orifice transluminal endoscopic one-anastomosis gastric bypass: a feasibility study using porcine model.

INTRODUCTION: Endoscopic bariatric therapies (EBT) are emerging as effective therapies in the management of overweight patient with or without metabolic syndrome. Unfortunately most procedures only restrict the gastric volume without altering the underlying metabolism which is seen in surgical patients. The aim of this study was to investigate the feasibility and limitations of a natural orifice trans-luminal endoscopic surgery (NOTES) one anastomosis gastric bypass (OAGB). METHODS: NOTES OAGB was performed in three porcine models. The steps of the procedure can be divide as follows: (1) Endoscopic sleeve gastroplasty. (2) Trans-gastric access to peritoneal cavity. (3) Identification of a loop of jejunum. (4) Introduction of the jejunal loop into the stomach. (5) Creation of the gastro-jejunostomy with lumen-apposing metal stent (LAMS). (6) Closure of gastric pylorus with overstitch system. RESULTS: All the animals underwent successful NOTES of OAGB. The mean weight for the animals was 34.3 kg (32-37 kg). The mean procedure time was 250 min (300 min for first animal and 180 min for third animal). The average bypassed bilio-pancreatic limb was 98 cm (range 65-130 cm). CONCLUSIONS: This study has provided proof-of-principle in a preclinical model that a NOTES approach can be used to perform OAGB and, therefore, merits additional evaluation and consideration.

Leaf transcriptomic signatures for somatic embryogenesis potential of Elaeis guineensis.

KEY MESSAGE: Potentially embryogenic oil palms can be identified through leaf transcriptomic signatures. Differential expression of genes involved in flowering time, and stress and light responses may associate with somatic embryogenesis potential. Clonal propagation is an attractive approach for the mass propagation of high yielding oil palms. A major issue hampering the effectiveness of oil palm tissue culture is the low somatic embryogenesis rate. Previous studies have identified numerous genes involved in oil palm somatic embryogenesis, but their association with embryogenic potential has not been determined. In this study, differential expression analysis of leaf transcriptomes from embryogenic and non-embryogenic mother palms revealed that transcriptome profiles from non- and poor embryogenic mother palms were more similar than highly embryogenic palms. A total of 171 genes exhibiting differential expression in non- and low embryogenesis groups could also discriminate high from poor embryogenesis groups of another tissue culture agency. Genes related to flowering time or transition such as FTIP, FRIGIDA-LIKE, and NF-YA were up-regulated in embryogenic ortets, suggesting that reproduction timing of the plant may associate with somatic embryogenesis potential. Several light response or photosynthesis-related genes were down-regulated in embryogenic ortets, suggesting a link between photosynthesis activity and embryogenic potential. As expression profiles of the differentially expressed genes are very similar between non- and low embryogenic groups, machine learning approaches with several candidate genes may generate a more sensitive model to better discriminate non-embryogenic from embryogenic ortets.

Deep Temporal Convolution Network for Time Series Classification.

A neural network that matches with a complex data function is likely to boost the classification performance as it is able to learn the useful aspect of the highly varying data. In this work, the temporal context of the time series data is chosen as the useful aspect of the data that is passed through the network for learning. By exploiting the compositional locality of the time series data at each level of the network, shift-invariant features can be extracted layer by layer at different time scales. The temporal context is made available to the deeper layers of the network by a set of data processing operations based on the concatenation operation. A matching learning algorithm for the revised network is described in this paper. It uses gradient routing in the backpropagation path. The framework as proposed in this work attains better generalization without overfitting the network to the data, as the weights can be pretrained appropriately. It can be used end-to-end with multivariate time series data in their raw form, without the need for manual feature crafting or data transformation. Data experiments with electroencephalogram signals and human activity signals show that with the right amount of concatenation in the deeper layers of the proposed network, it can improve the performance in signal classification.

Age-related bone loss is associated with FGF21 but not IGFBP1 in healthy adults.

What is the central question of this study? Fibroblast growth factor 21 (FGF21) plays important therapeutic roles in metabolic diseases but is associated with bone loss, through insulin-like growth factor binding protein 1 (IGFBP1), in animals. However, the effect of the FGF21-IGFBP1 axis on age-related bone loss has not been explored in humans. What is the main finding and its importance? Using 'genetically linked' parent and child family pairs, we show that the FGF21 concentration, but not the IGFBP1 concentration, is higher in older than in younger adults. Our results suggest that age-associated decline in bone mineral density is associated with FGF21 and increased bone turnover but not likely to involve IGFBP1 in healthy humans. ABSTRACT: Bone fragility increases with age. The fibroblast growth factor 21 (FGF21)-insulin-like growth factor binding protein 1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age-associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21-regulatory axis in bone turnover and the age-related decline in bone mineral density (BMD). Twenty 'genetically linked' family (parent and child) pairs were recruited. Younger adults were 22-39 years old and older adults 60-71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor-κB ligand (RANKL), tartrate-resistant acid phosphatase 5b (TRAP5b) and bone-specific alkaline phosphatase (BAP) were measured. Older adults had 10-18% lower BMD at the hip and spine (P < 0.008) and a twofold higher FGF21 concentration (P < 0.001). The IGFBP1 concentration was similar in younger and older adults (P = 0.961). The RANKL concentration was 44% lower (P = 0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P = 0.01 and P = 0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r = -0.460, P = 0.003), but not with the IGFBP1 concentration (r = -0.144, P = 0.374). The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P > 0.05). In humans, FGF21 might be involved in the age-associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age-associated decline in BMD and in RANKL-associated osteoclast differentiation.

Fate of the Retained Acetabular Component During Revision Total Hip Arthroplasty: A Meta-Analysis and Systematic Review.

BACKGROUND: The aim of this meta-analysis and systematic review is to estimate re-revision rates due to aseptic loosening of retained acetabular components after revision total hip arthroplasty. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched until June 11, 2018. Data were extracted by 2 independent investigators and consensus was reached with the involvement of a third investigator. Rates of re-revision due to aseptic loosening from 6 studies were aggregated using random effects model after a logit transformation and were grouped by study and population level characteristics. RESULTS: An assessment of the re-revision rates of retained acetabular components due to aseptic loosening in revision total hip arthroplasty was reported in 6 studies involving 669 cases. The pooled re-revision rate was 12.6% (95% confidence interval 8.4-18.4) with a mean study follow-up of 8.6 years. The rate of re-revision due to aseptic loosening of retained acetabular components was 6.8% (95% confidence interval 3.4-13.3). In the univariate meta-regression analysis, mean age at index revision surgery was significantly associated with the rate of re-revision due to aseptic loosening (R2 = 99.98%, P < .0001). CONCLUSION: Based on this exploratory analysis, revision hip procedures with retentions of well-fixed acetabular components generally have a low risk of failure during mid-term to long-term follow-ups.

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal.

Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self-renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self-renewal and that they function, in part, through promotion of high MINDY1 levels. Stem Cells 2018;36:1170-1178.