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We consider the problem of accurately identifying cell boundaries and labeling individual cells in confocal microscopy images, specifically, 3D image stacks of cells with tagged cell membranes. Precise identification of cell boundaries, their shapes, and quantifying inter-cellular space leads to a better understanding of cell morphogenesis. Towards this, we outline a cell segmentation method that uses a deep neural network architecture to extract a confidence map of cell boundaries, followed by a 3D watershed algorithm and a final refinement using a conditional random field. In addition to improving the accuracy of segmentation compared to other state-of-the-art methods, the proposed approach also generalizes well to different datasets without the need to retrain the network for each dataset. Detailed experimental results are provided, and the source code is available on GitHub 1.

This paper introduces a novel methodology to integrate human brain connectomics and parcellation for brain tumor segmentation and survival prediction. For segmentation, we utilize an existing brain parcellation atlas in the MNI152 1 mm space and map this parcellation to each individual subject data. We use deep neural network architectures together with hard negative mining to achieve the final voxel level classification. For survival prediction, we present a new method for combining features from connectomics data, brain parcellation information, and the brain tumor mask. We leverage the average connectome information from the Human Connectome Project and map each subject brain volume onto this common connectome space. From this, we compute tractographic features that describe potential neural disruptions due to the brain tumor. These features are then used to predict the overall survival of the subjects. The main novelty in the proposed methods is the use of normalized brain parcellation data and tractography data from the human connectome project for analyzing MR images for segmentation and survival prediction. Experimental results are reported on the BraTS2018 dataset.

We present an unsupervised three-dimensional feature clustering algorithm to gather the mTOP2016 challenge data into 3 groups. We use the brain MR-T1, diffusion tensor fractional anisotropy, and diffusion tensor mean diffusivity images provided by the mTOP2016 competition. A distance-based size constraint method for data clustering is used. The proposed approach achieves 0.267 adjusted rand index and 0.3556 homogeneity score within the 15 labeled subjects, corresponding to 10 correctly classified data items. Based on visual exploration of the data, we believe that a localized analysis of the lesion regions, using the computed tractography data, is a promising direction to pursue.

Dual-ion batteries (DIBs) are garnering immense attention for their capability to operate without the expensive elements required by lithium-ion batteries. Phenylenediamine serves as a versatile and sustainable resource, enabling the efficient preparation of both cathode and anode materials through precise molecular control and straightforward synthesis. The innovative asymmetrical DIBs based on amine-rich poly(phenylenediamine) cathodes and imine-rich poly(phenylenediamine) anodes enable oxidative and reductive states, providing a transition metal-free rechargeable battery. The polarity difference between amine and imine redox groups in the polymeric structure resulted in a high cell voltage of 2.2 V and a specific capacity of 100 mAh g -1 , yielding an energy density of 220 Wh kg -1 . The radical cation generated at the cathode found stability through aromatic resonance, while the radical anion formed at the anode is supported by the quinoid structure. The exciting insights in energy storage promise a revolution with rechargeable batteries using abundant elements, offering sustainable energy solutions., (© 2024 Wiley‐VCH GmbH.)

Lynch syndrome (LS) is an autosomal dominant disorder characterized by increased risks of colorectal and endometrial cancers. LS is defined by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, and MSH6. Data on the prevalence and associated cancer risks of LS in the Han Chinese population remain limited. In this study, using a broad biobank approach through the Taiwan Precision Medicine Initiative (TPMI), we identified LS-associated MMR gene variants within a cohort of 42,828 participants from a Taiwanese medical center. A total of 89 individuals were found to carry pathogenic MMR variants: MLH1 (n = 22, 25%), MSH2 (n = 47, 53%), and MSH6 (n = 20, 22%). The overall prevalence of MMR variants was calculated, and cancer incidence rates among carriers were determined. The prevalence of MMR variants in the study population was 1 in 481. The distribution of MLH1, MSH2, and MSH6 variants were 24.7%, 52.8%, and 22.5%, respectively. Cumulative cancer incidence rates of carriers were 40.9% for MLH1 carriers, 29.8% for MSH2, and 40% for MSH6. Among the 19 individuals who underwent colonoscopy screening, the prevalence of polyps was similar to that of the control group (adenoma detection rate: 32% vs 26%, p = 0.585). A meticulous analysis of the detected polyps in seven participants, considering factors such as location, size, morphology, and pathological features, showed no significant differences from controls. A significant cancer risk is associated with LS-related MMR variants in the Taiwanese population. The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.

Background: Mechanical Ventilation (MV) is an essential life support machine, frequently utilized in an Intensive Care Unit (ICU). Recently, a growing number of clinical trials have investigated the effect of acupuncture treatment on MV outcomes., Objectives: This study investigated the safety and efficacy of acupuncture treatment for critically ill patients under MV., Methods: In this systematic review and meta-analysis of randomized controlled trials, the efficacy of acupuncture related interventions was compared to routine ICU treatments, and sham/control acupuncture as control interventions applied to ICU patients undergoing MV. The databases of PubMed, Cochrane Library, and Web of Science were extensively searched in the month of April 2022. The primary outcome measurements were defined as total MV time, ICU length of stay, and mortality. The Cochrane Collaboration risk of bias tool was employed to analyze the severity of bias. The meta-analysis was conducted using Review Manager 5.3 software. The quality of evidence was evaluated according to the GRADE approach., Results: A total of 10 clinical trials were included in this investigation. When comparing the performance of acupuncture-related interventions to that of the reported control interventions, the results of the meta-analysis revealed a significant reduction in the total number of MV days as well as the duration of ICU length of stay following acupuncture treatment (MD -2.06 [-3.33, -0.79] P = 0.001, I 2  = 55 %, MD-1.26 [-2.00, -0.53] P = 0.0008, I 2  = 77 %, respectively). A reduction in the total mortality was similarly observed (RR = 0.67 [0.47, 0.94] P = 0.02, I 2  = 0 %)., Conclusion: This systematic review and meta-analysis identified a noteworthy reduction in the total MV days, time spent in the ICU, as well as the total mortality following acupuncture related interventions. However, the small sample size, risk of bias and existing heterogeneity should be taken into consideration. The results of this study are promising and further investigations in this field are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured., Methods: In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality., Results: A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I 2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I 2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference -1.45 [-11.94, -10.97], P = 0.00001, I 2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I 2 = 0%)., Conclusion: There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142131, identifier: CRD42020142131., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ben-Arie, Lottering, Chen, Ho, Lee, Inprasit and Kao.)

De novo drug design with desired biological activities is crucial for developing novel therapeutics for patients. The drug development process is time- and resource-consuming, and it has a low probability of success. Recent advances in machine learning and deep learning technology have reduced the time and cost of the discovery process and therefore, improved pharmaceutical research and development. In this paper, we explore the combination of two rapidly developing fields with lead candidate discovery in the drug development process. First, artificial intelligence has already been demonstrated to successfully accelerate conventional drug design approaches. Second, quantum computing has demonstrated promising potential in different applications, such as quantum chemistry, combinatorial optimizations, and machine learning. This article explores hybrid quantum-classical generative adversarial networks (GAN) for small molecule discovery. We substituted each element of GAN with a variational quantum circuit (VQC) and demonstrated the quantum advantages in the small drug discovery. Utilizing a VQC in the noise generator of a GAN to generate small molecules achieves better physicochemical properties and performance in the goal-directed benchmark than the classical counterpart. Moreover, we demonstrate the potential of a VQC with only tens of learnable parameters in the generator of GAN to generate small molecules. We also demonstrate the quantum advantage of a VQC in the discriminator of GAN. In this hybrid model, the number of learnable parameters is significantly less than the classical ones, and it can still generate valid molecules. The hybrid model with only tens of training parameters in the quantum discriminator outperforms the MLP-based one in terms of both generated molecule properties and the achieved KL divergence. However, the hybrid quantum-classical GANs still face challenges in generating unique and valid molecules compared to their classical counterparts.

Introduction: Esophagus cancer patients are at risk for malnourishment. Feeding jejunostomy is used in advanced esophagus cancer patients in order to support and supplement the patients' nutrition needs. In dumping syndrome, the food is rapidly introduced into the intestine at a rate that is faster than normal, it is associated with both digestive system and vasoactive symptoms. Dumping syndrome has an association with both esophagus cancer patients and feeding jejunostomy. In the mid and long term, dumping syndrome is an important issue that contributes to the risk of malnourishment in advanced esophagus cancer patients. In recent studies, acupuncture was effective in regulating digestive symptoms. Acupuncture is considered to be a safe intervention, that was previously shown to be effective in treating digestive-related symptoms., Methods: Sixty advanced esophageal cancer patients post-feeding jejunostomy will be divided into 2 equal groups, an intervention group (n = 30) and a control group (n = 30). Patients in the intervention group will receive acupuncture using the following acupoints: ST36 (Zusanli), ST37 (Shangjuxu), ST39 (Xiajuxu), PC6 (Neiguan), LI4 (Hegu), and Liv 3 (Taichung). Patients in the control group will receive shallow acupuncture on 12 non-acupoints (sham points), 1 cm from the above mention points. Patients and assessors will be blind to trial allocation. Both groups will receive acupuncture twice a week for 6 weeks. The main outcome measurements are: body weight, BMI, Sigstad's score, and the Arts' dumping questionnaire., Discussion: There are no previous studies that have examined the use of acupuncture on patients with dumping syndrome. This single-blind randomized control trial will investigate the effect of acupuncture on dumping syndrome in advanced esophagus cancer patients with feeding jejunostomy. The results will determine if verum acupuncture can affect dumping syndrome and prevent weight loss., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Here in this study we adopted genome-wide association studies (GWAS) to investigate the genetic components of the personality constructs in the Chinese Personality Assessment Inventory 2 (CPAI-2) in Taiwanese Hakka populations, who are likely the descendants of a recent admixture between a group of Chinese immigrants with high emigration intention and a group of the Taiwanese aboriginal population generally without it. A total of 279 qualified participants were examined and genotyped by an Illumina array with 547,644 SNPs to perform the GWAS. Although our sample size is small and that unavoidably limits our statistical power (Type 2 error but not Type 1 error), we still found three genomic regions showing strong association with Enterprise, Diversity, and Logical vs. Affective Orientation, respectively. Multiple genes around the identified regions were reported to be nervous system related, which suggests that genetic variants underlying the certain personalities should indeed exist in the nearby areas. It is likely that the recent immigration and admixture history of the Taiwanese Hakka people created strong linkage disequilibrium between the emigration intention-related genetic variants and their neighboring genetic markers, so that we could identify them despite with only limited statistical power., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous studies and meta-analyses have explored the relationship among testosterone, muscle strength, and physical function, to the best of our knowledge, no meta-analysis has investigated the effects of testosterone replacement therapy (TRT) on subgroup of relatively hypogonadal older men., Objective: The aim of this study was to evaluate the effect of TRT in older men with low testosterone levels., Methods: PubMed, Embase, and Web of Science were systematically searched for articles published between January 1990 and April 2020. We included randomized controlled studies that investigated the effect of TRT and included older men (age >60 years) with relatively low testosterone levels. Studies were extracted following the PRISMA flowchart, and the included randomized controlled trials were evaluated using RoB 2.0. Our main outcome was muscle strength changes after TRT evaluated using a metaregression of confounding factors. Secondary outcomes included changes in physical performance and the risk ratio of adverse events. Random-effects meta-analyses of TRT on muscle strength and physical function were performed., Results: Thirteen studies with 2,043 patients were included. The mean age of subjects in various studies ranged from 65.9 years to 76 years. Transdermal testosterone dosages ranged from 5 to 10 g/day, while intramuscular options were 125 mg/week or 200 mg every 2 weeks. Oral testosterone supplementation was given at 160 mg/day in one study. Pooled meta-analyses revealed greater muscle strength improvement after TRT compared with placebo (Hedges' g = 0.21; 95% CI: = 0.15-0.28). Intramuscular administration of TRT had greater efficacy (Hedges' g = 0.74; 95% CI: = 0.34-1.14) than transdermal and oral TRT (p < 0.001). A metaregression revealed that baseline serum total testosterone was associated with muscle strength improvement (β = -0.004, p = 0.002). The risk ratios of adverse events, including elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer, were not significantly different., Conclusion: TRT improved muscle strength in older, relatively hypogonadal men. The effect was more pronounced in populations with lower baseline testosterone levels., (© 2023 S. Karger AG, Basel.)

Oral cancer is frequently associated with smoking, alcohol consumption, and betel quid chewing, which are common harmful behaviors observed in certain cohorts of the Taiwanese population. Some reports have explored the potential therapeutic effect of certain herbal remedies on cancer treatments and the outcomes thereof. However, supportive evidence regarding the specific use of traditional Chinese medicine (TCM) in oral cancer treatment is lacking and deserves further investigation. This study measured the use of TCM therapies for oral cancer in a Taiwanese population-based retrospective longitudinal cohort study. The Taiwan National Health Insurance Research Database was utilized to conduct this study. The study population was limited to oral cancer patients diagnosed between 2000 and 2009, which were followed up for at least 5 years. Therapeutic strategies investigated included acupuncture and the Chinese herbs and formula used. Additionally, the frequency of TCM treatment visits, total medical costs, and all-cause mortality were also analyzed. Between 2000 and 2009, a total of 951 patients were diagnosed with various oral cancers. 13.7% of the diagnosed patients utilized TCM treatment measures. The majority of the patients were males. The top 3 common single herbs used were Xuán shēn (Radix Scrophulariae), Shí hú (Herba Dendrobii), and Mài mén dōng (Ophiopogon Japonicus). Then, Gān lù yǐn, Zhī bǎi dì huáng wán, and Sàn zhǒng kuì jiān tāng were the most frequently used herbal formulas. The survival probability was higher in TCM users when compared to non-TCM users in 5- and 12-year all-cause mortality (P < .05). This study explored the use of TCM therapies in oral cancer patients and identified essential information regarding the specifics of conventional herbal medicine used, affiliated medical costs, survival probability, and common symptoms observed in Taiwanese oral cancer patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Absolute pose regression (APR) for camera localization is a single-shot approach that encodes the information of a 3D scene in an end-to-end neural network. The camera pose result of APR methods can be observed as the linear combination of the base poses. Previous APR methods' base poses are learned from training data. However, the training data can limit the performance of the methods, which cannot be generalized to cover the entire scene. To solve this issue, we use handcrafted base poses instead of learning-based base poses, which prevents overfitting the camera poses of the training data. Moreover, we use a dual-stream network architecture to process color and depth images separately to get more accurate localization. On the 7 Scenes dataset, the proposed method is among the best in median rotation error, and in median translation error, it outperforms previous APR methods. On a more difficult dataset- Oxford RobotCar dataset, the proposed method achieves notable improvements in median translation and rotation errors compared to the state-of-the-art APR methods.

Designing a low-cost, highly efficient, and stable electrocatalyst that can synergistically speed up the reduction of polysulfide electrolytes while operative for long periods in the open air is critical for the practical application of quantum dot-sensitized solar cells (QDSSCs), but it remains a challenging task. Herein, a simple, straightforward, and two-step nanocomposite engineering approach that simultaneously combines metallic copper chalcogenides (MC) either Cu 2- x S or Cu 2- x Se with S, N dual-doped carbon (SNC) sources for devising high-quality counter electrode (CE) film are reported. First, the hierarchically assembled MC nanostructures are obtained using microwave-assisted synthesis. Second, these MCs are embedded within an ordered macro-meso-microporous carbon matrix to obtain Cu 2- x S@C or Cu 2- x SeS@C CE. These CEs are demonstrated to have composition dependents crystal structure, surface morphologies, photovoltaic performance, and electrochemical properties. In terms of power conversion efficiency (PCE), the Cu 2- x SeS@C (9.89%) and Cu 2- x S@C-CE (8.96%) constructed QDSSCs outperform both Cu 2- x Se (8.96%) and Cu 2- x S-constructed (7.79%) QDSSCs, respectively. The enhanced PCE could be attributed to the synergistic interaction of S and N dopants with MC interfaces that can not only enrich electric conductivity, and a higher surface-to-volume ratio but also offers a 3D network for superior charge transport at the interface., (© 2022 Wiley-VCH GmbH.)

Objectives: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design., Methods: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups., Results: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05)., Conclusions: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed., Clinical Trial Registration: clinicaltirl.gov: NCT04318496., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient., Methods: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER). From 2003 to 2018, we identified 4986 patients whose data constituted the first 24-h CrCl measurement data in the Clinical Research Data Repository of China Medical University Hospital and were followed up for at least 5 years after careful exclusion. Three GFR estimation equations [the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Taiwanese MDRD], 24-h CrCl, and 24-h U-CER-adjusted eGFR were used., Results: A high correlation was observed among the eGFR levels derived from the equation methods (0.995-1.000); however, the correlation decreased to 0.895-0.914 when equation methods were compared with the 24-h CrCl or 24-h U-CER-adjusted equation-based eGFR. In the Bland-Altman plots, the average discrepancy between the equation methods and the 24-h CrCl method was close to zero (maximal bias range: 5.12 for the Taiwanese MDRD equation vs. 24-h CrCl), but the range in limit of agreement was wide, from ±43.7 mL/min/1.73 m 2 for the CKD-EPI equation to ±54.3 mL/min/1.73 m 2 for the Taiwanese MDRD equation. A J-shaped dose-response relationship was observed between all equation-based eGFRs and all-cause mortality. Only 24-h CrCl exhibited a non-linear negative dose-response relationship with all-cause mortality. After adjustment for 24-h U-CER in the statistical model, the paradoxical increase in mortality risk for an eGFR of >90 mL/min/1.73 m 2 returned to null. When 24-h U-CER was used directly to correct eGFR, the monotonic non-linear negative relationship with all-cause mortality was almost identical to that of 24-h CrCl., Conclusions: The 24-h U-CER-adjusted eGFR and 24-h CrCl are viable options for informing mortality risk. The 24-h U-CER adjustment method can be practically implemented to eGFR-based care and effectively mitigate the inherent confounding biases from individual's muscle mass amount due to both sex and racial differences., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Given the prevalent use of tobacco and betel nut in the Taiwanese community, an increase risk of oral, oropharynx, and hypopharynx cancers (head and neck cancers) is apparent. The use of Traditional Chinese Medicine (TCM) and acupuncture is both common and conveniently accessible in Taiwan, with treatments being financially supported by the National Health Insurance (NHI). This study aims to investigate the use of TCM in head and neck cancers in Taiwan through a longitudinal cohort study., Methods: The Taiwan National Health Insurance Research Database (NHIRD) was utilized in order to conduct this study. The study populations consisted of oral, oropharynx, nasopharynx, and hypopharynx cancers (head and neck cancer) patients in 2002, which were then followed up until 2007 in regards to TCM use, until 2013 in regards to acupuncture use and until 2014 for all-cause mortality. Patients were divided into 4 groups. Common symptoms, Chinese herbs and formula used, TCM visits and 5 and 12 years all-cause mortality were analyzed., Results: The use of TCM was increased in the second to fourth-year post-diagnosis. TCM use in nasopharynx cancer patients was higher compared to other cancers. The number of TCM visits per patient was increased post-diagnosis. The findings suggest a non-significant reduction in 5 and 12 years all-cause mortality between TCM II and CON II groups., Conclusion: The use of TCM in new patients suffering from head and neck cancers was increased in close proximity to the cancer diagnosis. The relation between TCM use and mortality of head and neck cancer should be investigated through larger scale studies.

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

Malnourishment is prevalent in patients suffering from head and neck cancer. The postoperative period is crucial in terms of nutritional support, especially after composite resection and reconstruction surgery. These patients present with a number of risk factors that aggravate feeding intolerance, including postoperative status, prolonged immobility, decreased head elevation, mechanical ventilation, and applied sedative agents. Routine management protocols for feeding intolerance include prokinetic drug use and post-pyloric tube insertion, which could be both limited and accompanied by detrimental adverse events. This single-blind clinical trial aimed to investigate the effects of acupuncture in postoperative feeding intolerance in critically ill oral and hypopharyngeal cancer patients. Twenty-eight patients were randomized into two groups: Intervention group and Control group. Interventions were administered daily over three consecutive postoperative days. The primary outcome revealed that the intervention group reached 70% and 80% of target energy expenditure (EE) significantly earlier than the control group (4.00 ± 1.22 versus 6.69 ± 3.50 days, p = 0.012), accompanied by higher total calorie intake within the first postoperative week (10263.62 ± 1086.11 kcals versus 8384.69 ± 2120.05 kcals, p = 0.004). Furthermore, the intervention group also needed less of the prokinetic drug (Metoclopramide, 20.77 ± 48.73 mg versus 68.46 ± 66.56 mg, p = 0.010). In conclusion, digestion-specific acupuncture facilitated reduced postoperative feeding intolerance in oral and hypopharyngeal cancer patients.

Introduction: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients., Methods: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months., Expected Outcome: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture., Other Information: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022., Protocol Registration: (CMUH109-REC1-002), (NCT04318496)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Frozen shoulder (FS) is associated with pain, reduced range of motion (ROM), and shoulder function. The condition occurs in 2-5% of the population, and it is especially common around the age of 50 years. FS symptoms will recover after 1-4 years. Many patients turn to acupuncture in order to alleviate the FS symptoms., Objective: In this review, we will investigate the efficiency of acupuncture as a FS treatment., Methods: A literature search of acupuncture and FS-related keywords was performed in the following databases: PubMed, Cochrane Library, Embase, and Web of Science. Thirteen publications were included for a systematic review, and a meta-analysis was done using the following measurements: visual analogue scale (VAS) for pain, Constant-Murley Shoulder Outcome Score (CMS) for shoulder function, and active shoulder ROM including flexion, abduction, and external rotation. The Cochrane Collaboration's risk of bias tool and quality of evidence GRADE recommendations and STRICTA 2010 were used to grade the included publications., Results: A meta-analysis on VAS pain score showed significant pain reduction, restoring CMS shoulder function, and flexion ROM in favor of acupuncture versus the control. In external rotation and abduction ROM, a meta-analysis was not significant. The most used acupoints are Jian Yu (LI15) and Jian Liao (TB14)., Conclusions: The results indicate that acupuncture could be safe and effective for pain reduction, restoring shoulder function, and restoring flexion ROM for FS patients in the short term and midterm. However, the level of evidence was very low. More high-quality and longer studies are needed in order to robust the evidence., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Eyal Ben-Arie et al.)

The manual brain tumor annotation process is time consuming and resource consuming, therefore, an automated and accurate brain tumor segmentation tool is greatly in demand. In this paper, we introduce a novel method to integrate location information with the state-of-the-art patch-based neural networks for brain tumor segmentation. This is motivated by the observation that lesions are not uniformly distributed across different brain parcellation regions and that a locality-sensitive segmentation is likely to obtain better segmentation accuracy. Toward this, we use an existing brain parcellation atlas in the Montreal Neurological Institute (MNI) space and map this atlas to the individual subject data. This mapped atlas in the subject data space is integrated with structural Magnetic Resonance (MR) imaging data, and patch-based neural networks, including 3D U-Net and DeepMedic, are trained to classify the different brain lesions. Multiple state-of-the-art neural networks are trained and integrated with XGBoost fusion in the proposed two-level ensemble method. The first level reduces the uncertainty of the same type of models with different seed initializations, and the second level leverages the advantages of different types of neural network models. The proposed location information fusion method improves the segmentation performance of state-of-the-art networks including 3D U-Net and DeepMedic. Our proposed ensemble also achieves better segmentation performance compared to the state-of-the-art networks in BraTS 2017 and rivals state-of-the-art networks in BraTS 2018. Detailed results are provided on the public multimodal brain tumor segmentation (BraTS) benchmarks., (Copyright © 2020 Kao, Shailja, Jiang, Zhang, Khan, Chen and Manjunath.)

The volume of stroke lesion is the gold standard for predicting the clinical outcome of stroke patients. However, the presence of stroke lesion may cause neural disruptions to other brain regions, and these potentially damaged regions may affect the clinical outcome of stroke patients. In this paper, we introduce the tractographic feature to capture these potentially damaged regions and predict the modified Rankin Scale (mRS), which is a widely used outcome measure in stroke clinical trials. The tractographic feature is built from the stroke lesion and average connectome information from a group of normal subjects. The tractographic feature takes into account different functional regions that may be affected by the stroke, thus complementing the commonly used stroke volume features. The proposed tractographic feature is tested on a public stroke benchmark Ischemic Stroke Lesion Segmentation 2017 and achieves higher accuracy than the stroke volume and the state-of-the-art feature on predicting the mRS grades of stroke patients. Also, the tractographic feature yields a lower average absolute error than the commonly used stroke volume feature.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The G AL4 T echnique for R eal-time a nd C lonal E xpression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide., (Copyright © 2019 Olson et al.)

Introduction: Head and neck cancer patients are at a high risk to suffer from malnourishment, a risk that increases in postoperative condition and with the use of enteral nutrition (EN). Until now patients who are suffering from indigestion in the intensive care unit (ICU) received treatment in the form of prokinetic drugs, drugs that can lead to serious side effects and only can partially improve digestion functions. Acupuncture was used successfully in several clinical trials to improve postoperative indigestion in cancer patients without any reported adverse events. The study aims are to investigate acupuncture effect in combination with prokinetic drugs in the treatment of indigestion in postoperative oral and hypopharyngeal cancer patients in the ICU., Methods: Single-center, double-blind randomized control trial will compare between 2 equal groups. A total of 28 patients that will meet the inclusion criteria: age 30 to 80, postplastic surgery for oral cancer or hypopharyngeal cancer, developed feeding intolerance 2 times in the first postoperative day, Apache score <20, and needed EN. Patients will be randomly divided (1:1) into treatment group or control group for 3 treatments in 3 days along with routine ICU treatment. The main outcome measurement will be the number of days a patient needs to reach his total energy expenditure., Expected Outcome: The results will shed light on the effectiveness and safety of acupuncture in a double-blind design treating postoperative ICU cancer patients. In addition, the study presents a revolutionary double-blind design that if, will prove as successful might influence the way double-blind acupuncture studies are performed today., Other Information: The study will be conducted in the surgical ICU department, of China medical university hospital, Taichung 404, Taiwan. The study is conducted on stable ICU patients and is anticipated to have minimum risk for adverse events. Patients enrollment and data collection will start from May 15, 2019. The study expected completion time: June 2021.

Purpose: To evaluate the outcomes of patients who underwent thoracoscopic wedge resection without chest drain placement., Methods: The subjects of this retrospective study were 89 patients, who underwent thoracoscopic wedge resection at our hospital between January, 2013 and July, 2015. A total of 45 patients whose underlying condition did not meet the following criteria were assigned to the "chest drain placement group" (group A): peripheral lesions, healthy lung parenchyma, no intraoperative air leaks, hemorrhage or effusion accumulation, and no pleural adhesion. The other 44 patients whose underlying condition met the criteria were assigned to the "no chest drain placement group" (group B). Patient characteristics, specimen data, and postoperative conditions were analyzed and compared between the groups., Results: Group A patients had poorer forced expiratory volume in one second (FEV1) values, less normal spirometric results, significantly higher resected lung volume, a greater maximum tumor-pleura distance, and a larger maximum tumor size. They also had a longer postoperative hospital stay. There was no difference between the two groups in postoperative complications., Conclusions: Avoiding chest drain placement after a thoracoscopic wedge resection appears to be safe and beneficial for patients who have small peripheral lesions and healthy lung parenchyma.

The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons.

Objectives: To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD)., Design: Cross-sectional study., Setting: Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong., Participants: Chinese individuals with (n = 426) and without (n = 350) AD., Measurements: All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1))., Results: Apart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε4 status, their genetic effects continued to be significant in the APOE ε4-negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene-level analysis confirmed the above association between ESR2 and CYP11A1, and pathway-level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway-level P = .03)., Conclusion: Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Background: Genome-wide association studies (GWAS) is a major method for studying the genetics of complex diseases. Finding all sequence variants to explain fully the aetiology of a disease is difficult because of their small effect sizes. To better explain disease mechanisms, pathway analysis is used to consolidate the effects of multiple variants, and hence increase the power of the study. While pathway analysis has previously been performed within GWAS only, it can now be extended to examining rare variants, other "-omics" and interaction data., Scope of Review: 1. Factors to consider in the choice of software for GWAS pathway analysis. 2. Examples of how pathway analysis is used to analyse rare variants, other "-omics" and interaction data., Major Conclusions: To choose appropriate software tools, factors for consideration include covariate compatibility, null hypothesis, one- or two-step analysis required, curation method of gene sets, size of pathways, and size of flanking regions to define gene boundaries. For rare variants, analysis performance depends on consistency between assumed and actual effect distribution of variants. Integration of other "-omics" data and interaction can better explain gene functions., General Significance: Pathway analysis methods will be more readily used for integration of multiple sources of data, and enable more accurate prediction of phenotypes., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Liver transplant is now considered to be a successful treatment modality for early hepatocellular carcinoma. In addition, advances in immunosuppressive therapy have greatly prolonged posttransplant survival of patients with hepatocellular carcinoma. However, both the posttransplant physiologic condition and immunosuppressive therapy affect the patient's natural immunity, resulting in accumulating and more problematic complications. Three years after a male patient with hepatocellular carcinoma underwent living-donor liver transplant, he presented with esophageal metastasis from recurrence of hepatocellular carcinoma. This is an extremely rare complication, perhaps with an ominous prognosis, and, to the best of our knowledge, the first such case to be published in the English literature.

Purpose: Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DDD., Methods: Patients (<40 years) with lumbar disc degeneration were evaluated with MRI imaging (1.5 Tesla) and genetic association analysis for 58 single nucleotide polymorphism (SNP) of 35 candidate genes was performed. Disc degeneration of individual discs of lumbar spine from L1 to S1 was graded by Pfirrmann's grading. The subjects were stratified into two groups based on Total Disc Degenerative Score (TDDS). Based on TDDS, the severity of DDD was classified as mild (Group A: TDDS <10) and severe (Group B: TDDS >10)., Results: 695 Indian subjects including 308 with mild TDDS and 387 with severe TDDS were studied. The mean age of the patients was 29.6 ± 6.9 years in group A and 31.7 ± 6.1 in group B (p < 0.05). Five of the 35 candidate genes viz., rs1337185 of COL11A (p = 0.02), rs5275 (p = 0.03) and rs5277 (p = 0.05) of COX2, rs7575934 of IL1F5 (p = 0.04), rs3213718 of CALM1 (p = 0.04) and rs162509 of ADAMTS5 (p = 0.04) were found to be significantly associated with severe TDDS., Conclusion: The study identifies specific SNP associations of five genes in young adults with severe lumbar disc degeneration. These five genes (COL11A1, ADAMTS5, CALM1, IL1F5 and COX2) have different functions in the matrix metabolism, intracellular signalling and inflammatory cascade. This shows that disc degeneration is a complex disease with an intricate interplay of multiple genetic polymorphisms.

Aim: Reliable biomarkers are in urgent need for diagnosis, outcome prediction and treatment-effect monitoring for upper tract urothelial carcinomas (UTUC). Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor cells in more than half of the patients with UTUC investigated, the genomic contribution of COX2 to UTUC has not been studied. The study aimed to evaluate the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese population., Materials and Methods: A total of 218 patients with UTUC and 580 healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G-765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their association with UTUC risk., Results: The distribution of genotypes of COX2 G-765C and intron 5 were significantly different between patient and control groups (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The haplotype analysis showed that compared to the GG/TT haplotype of COX2 G-765C/intron 5, those carrying GG/AT variants have a significantly increased risk of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence interval=0.14-0.49)., Conclusion: Our results suggest that individual and combined COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and UTUC development., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The aggregation of the 37-amino acid polypeptide islet amyloid polypeptide (IAPP, amylin), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic β-islet cells in type 2 diabetes. It is believed that inhibiting the aggregation of IAPP may slow down, if not prevent entirely, the progression of this disease. Extracts of thirteen different common fruits were analyzed for their ability to prevent the aggregation of amyloidogenic IAPP. Thioflavin T binding, immuno-detection and circular dichroism assays were performed to test the in vitro inhibitory potential of each extract. Atomic force microscopy was used to visualize the formation of amyloid fibrils with and without each fruit extract. Finally, extracts were tested for their ability to protect living mammalian cells from the toxic effects of amyloid IAPP. Several fruits showed substantial ability to inhibit IAPP aggregation and protect living cells from toxic IAPP amyloid.

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family–based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.

The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.

In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different between LOAD patients and nondemented controls. For PICALM, LOAD association was found only in the APOE ε4 (-) subgroup (rs3851179 adjusted allelic p = 0.028; adjusted genotypic p = 0.013). Our findings showed evidence of CR1, CLU, and PICALM and LOAD susceptibility in an independent southern Chinese population, which provides additional evidence for LOAD association apart from prior genome-wide association studies in Caucasian populations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD., Methods: We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging., Results: Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96) and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89)., Conclusion: Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.

Lumbar disk degeneration (LDD) is a common musculoskeletal condition. Genetic risk factors have been suggested to play a major role in its cause. This article reviews the main research strategies that have been used to study the genetics of LDD, and the genes that thus far have been identified to influence susceptibility to LDD. With the rapid progress in genomic technologies, further advances in the genetics of LDD are expected in the next few years., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Summary: There is an urgent and increasing demand for integrating large genotype datasets across genome-wide association studies and HapMap project for whole-genome imputation and individual-level meta-analysis. A new algorithm was developed to efficiently merge raw genotypes across large datasets and implemented in the latest version of IGG, IGG3. In addition, IGG3 can integrate the latest phased and unphased HapMap genotypes and can flexibly generate complete sets of input files for six popular genotype imputation tools. We demonstrated the efficiency of IGG3 by simulation tests, which could rapidly merge genotypes in tens of thousands of large genotype chips (e.g. Affymetrix Genome-Wide Human SNP Array 6.0 and Illumina Human1m-duo) and in HapMap III project on an ordinary desktop computer., Availability: (http://bioinfo.hku.hk/iggweb) (version 3.0).

Background: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D), the -1607 promoter polymorphism, of the MMP1 gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD., Methods: Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test., Results: Our results showed substantial evidence of association between -1607 promoter polymorphism of MMP1 and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04-1.90) while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01-2.24). Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033-2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029-2.029). Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele., Conclusion: We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of MMP1 are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.