Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Effect of digital inclusive finance on environmental efficiency of Chinese industry.

China's industrial economic model of high emissions and low efficiency has caused a series of environmental problems. Improving energy efficiency is an inevitable choice to solve the dual dilemma of pollution and energy shortage and to achieve carbon peak and neutrality. It is difficult to achieve green development solely through traditional governance; therefore, digital inclusive finance (DIF) is considered a new measure to help the green transformation of China's industry. Based on the assessment of industrial environmental efficiency (IEE) of 30 provinces from 2011 to 2021 by combining the super-efficiency EBM model and the group frontier technology considering provincial heterogeneity, the paper investigates the impact of DIF on the environmental efficiency of Chinese industry and its internal mechanism. The results show that DIF has a driving effect on industrial green transformation, especially the deep development of DIF, which can play a positive role in environmental efficiency for a long time and can give full play to the targeting feature of big data, focusing on regions with serious pollution, financing difficulties, high natural resource, and poor financial endowment. DIF can reduce enterprise financing costs and drive industrial innovation; however, the path of promoting industrial green transformation through regional servitization needs to be improved. In addition, under appropriate regulatory constraints, DIF has a more positive driving effect on the environmental efficiency of the Chinese industry. This article is useful to address the issue of industrial green transformation by interdisciplinary research.

Engineering low-salt growth Halomonas Bluephagenesis for cost-effective bioproduction combined with adaptive evolution.

Halophilic Halomonas bluephagenesis has been engineered to produce various added-value bio-compounds with reduced costs. However, the salt-stress regulatory mechanism remained unclear. H. bluephagenesis was randomly mutated to obtain low-salt growing mutants via atmospheric and room temperature plasma (ARTP). The resulted H. bluephagenesis TDH4A1B5 was constructed with the chromosomal integration of polyhydroxyalkanoates (PHA) synthesis operon phaCAB and deletion of phaP1 gene encoding PHA synthesis associated protein phasin, forming H. bluephagenesis TDH4A1B5P, which led to increased production of poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-4-hydrobutyrate) (P34HB) by over 1.4-fold. H. bluephagenesis TDH4A1B5P also enhanced production of ectoine and threonine by 50% and 77%, respectively. A total 101 genes related to salinity tolerance was identified and verified via comparative genomic analysis among four ARTP mutated H. bluephagenesis strains. Recombinant H. bluephagenesis TDH4A1B5P was further engineered for PHA production utilizing sodium acetate or gluconate as sole carbon source. Over 33% cost reduction of PHA production could be achieved using recombinant H. bluephagenesis TDH4A1B5P. This study successfully developed a low-salt tolerant chassis H. bluephagenesis TDH4A1B5P and revealed salt-stress related genes of halophilic host strains.

Comparison of exergy and exergy economic evaluation of different geothermal cogeneration systems for optimal waste energy recovery.

Since energy sources are limited, any activity aimed at recycling energy waste or facilitating energy conversion systems is invaluable. Against this background, most scientists focus on the integration of energy systems and the coupling of different technologies. In this study, a variety of power systems are investigated for optimal power conversion configurations of geothermal sources. Three configurations, Organic Rankine Cycle Geothermal Cooling (GPR/ORC), Kalina Cycle Geothermal Cooling (GPR/Kalina), and Rankine Cycle and Feed water Heater (GPR/FWH) Geothermal Cooling, are classified according to exergy and Study energy economic analysis. Calculations show that the GPR/FWH system has the highest net output power of 2963 kW. In addition, the GPR/Kalina system has the lowest output power and lowest energy efficiency among the systems launched. Across the three proposed systems, the fuel cell generates 1254 kW of electricity, while the Kalina cycle in the GPR/Kalina system generates 487 kW. Exergy studies show that the GPR/Kalina and GPR/FWH systems have the lowest and highest irreversibility (3795.4 kW and 4365.56 kW, respectively). Furthermore, the fuel cell was found to have the greatest exergy destruction rate among the three configurations. The results of the economic analysis show that the fuel cell has the highest cost ratio among all designs. In addition, the values of the dissipation factor show that the absorption chiller has the highest dissipation factor value among the three configurations. Furthermore, the comparative parametric analysis provides new aspects to introduce into the system.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

Halomonas spp., as chassis for low-cost production of chemicals.

Halomonas spp. are the well-studied platform organisms or chassis for next-generation industrial biotechnology (NGIB) due to their contamination-resistant nature combined with their fast growth property. Several Halomonas spp. have been studied regarding their genomic information and molecular engineering approaches. Halomonas spp., especially Halomonas bluephagenesis, have been engineered to produce various biopolyesters such as polyhydroxyalkanoates (PHA), proteins including surfactants and enzymes, small molecular compounds including amino acids and derivates, as well as organic acids. This paper reviews all the progress reported in the last 10 years regarding this robust microbial cell factory. KEY POINTS: • Halomonas spp. are robust chassis for low-cost production of chemicals • Genomic information of some Halomonas spp. has been revealed • Molecular tools and approaches for Halomonas spp. have been developed • Halomonas spp. are becoming more and more important for biotechnology.

A multimodal clinical data resource for personalized risk assessment of sudden unexpected death in epilepsy.

Epilepsy affects ~2-3 million individuals in the United States, a third of whom have uncontrolled seizures. Sudden unexpected death in epilepsy (SUDEP) is a catastrophic and fatal complication of poorly controlled epilepsy and is the primary cause of mortality in such patients. Despite its huge public health impact, with a ~1/1,000 incidence rate in persons with epilepsy, it is an uncommon enough phenomenon to require multi-center efforts for well-powered studies. We developed the Multimodal SUDEP Data Resource (MSDR), a comprehensive system for sharing multimodal epilepsy data in the NIH funded Center for SUDEP Research. The MSDR aims at accelerating research to address critical questions about personalized risk assessment of SUDEP. We used a metadata-guided approach, with a set of common epilepsy-specific terms enforcing uniform semantic interpretation of data elements across three main components: (1) multi-site annotated datasets; (2) user interfaces for capturing, managing, and accessing data; and (3) computational approaches for the analysis of multimodal clinical data. We incorporated the process for managing dataset-specific data use agreements, evidence of Institutional Review Board review, and the corresponding access control in the MSDR web portal. The metadata-guided approach facilitates structural and semantic interoperability, ultimately leading to enhanced data reusability and scientific rigor. MSDR prospectively integrated and curated epilepsy patient data from seven institutions, and it currently contains data on 2,739 subjects and 10,685 multimodal clinical data files with different data formats. In total, 55 users registered in the current MSDR data repository, and 6 projects have been funded to apply MSDR in epilepsy research, including three R01 projects and three R21 projects.

Characterizing cancer and COVID-19 outcomes using electronic health records.

PURPOSE: Patients with cancer often have compromised immune system which can lead to worse COVID-19 outcomes. The purpose of this study is to assess the association between COVID-19 outcomes and existing cancer-specific characteristics. PATIENTS AND METHODS: Patients aged 18 or older with laboratory-confirmed COVID-19 between June 1, 2020, and December 31, 2020, were identified (n = 314 004) from the Optum® de-identified COVID-19 Electronic Health Record (EHR) derived from more than 700 hospitals and 7000 clinics in the United States. To allow sufficient observational time, patients with less than one year of medical history in the EHR dataset before their COVID-19 tests were excluded (n = 42 365). Assessed COVID-19 outcomes including all-cause 30-day mortality, hospitalization, ICU admission, and ventilator use, which were compared using relative risks (RRs) according to cancer status and treatments. RESULTS: Among 271 639 patients with COVID-19, 18 460 had at least one cancer diagnosis: 8034 with a history of cancer and 10 426 with newly diagnosed cancer within one year of COVID-19 infection. Patients with a cancer diagnosis were older and more likely to be male, white, Medicare beneficiaries, and have higher prevalences of chronic conditions. Cancer patients had higher risks for 30-day mortality (RR 1.07, 95% CI 1.01-1.14, P = 0.028) and hospitalization (RR 1.04, 95% CI 1.01-1.07, P = 0.006) but without significant differences in ICU admission and ventilator use compared to non-cancer patients. Recent cancer diagnoses were associated with higher risks for worse COVID-19 outcomes (RR for mortality 1.17, 95% CI 1.08-1.25, P<0.001 and RR for hospitalization 1.10, 95% CI 1.06-1.14, P<0.001), particularly among recent metastatic (stage IV), hematological, liver and lung cancers compared with the non-cancer group. Among COVID-19 patients with recent cancer diagnosis, mortality was associated with chemotherapy or radiation treatments within 3 months before COVID-19. Age, black patients, Medicare recipients, South geographic region, cardiovascular, diabetes, liver, and renal diseases were also associated with increased mortality. CONCLUSIONS AND RELEVANCE: Individuals with cancer had higher risks for 30-day mortality and hospitalization after SARS-CoV-2 infection compared to patients without cancer. More specifically, patients with a cancer diagnosis within 1 year and those receiving active treatment were more vulnerable to worse COVID-19 outcomes.

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies.

A gender-related disparity exists in asthma morbidity and mortality, which shifts at around puberty from a male predominance to a female predominance. This is clinically reflected in the fact that asthma that occurs in childhood (childhood-onset asthma) mainly affects boys, and that asthma that occurs in adulthood (adult-onset asthma) mainly affects women. Adult-onset asthma is often non-atopic, more severe, and associated with a poorer prognosis, thus posing a marked burden to women's health and healthcare system. Many factors have been indicated to explain this gender-related disparity, including sociocultural and environmental factors as well as biological sex differences (genetic, pulmonary and immunological factors). It has long been suggested that sex hormones may be implicated in at least these biological sex differences. Overall, the evidence remains equivocal for the role of most sex hormones in asthma pathogenesis and clinical outcomes. Well-designed randomized clinical trials are required assessing the potential preventive or therapeutic effects of hormonal contraceptives on asthma in women, thereby helping to advance the evidence to inform future practice guidelines. The mechanisms underlying the role of sex hormones in asthma are complex, and our understanding is not yet complete. Additional mechanistic studies elucidating sex hormone signaling pathways and their interactions involved in the pathogenesis and clinical manifestations of asthma will help to identify potential sex hormone-driven asthma endotypes and novel therapeutic targets, providing the basis for a more personalized asthma management strategy.

An assessment of morphological and pathological changes in paravertebral muscle degeneration using imaging and histological analysis: a cross-sectional study.

BACKGROUND: The high signal of paravertebral muscle (PVM) on T2-weighted image (T2WI) is usually considered to be fatty degeneration. However, it is difficult to distinguish inflammatory edema from fatty degeneration on T2WI. The purpose of this study was to identify different types of PVM high signal in patients with low back pain (LBP) through magnetic resonance imaging (MRI) and histology. METHODS: Seventy patients with LBP underwent MRI. The signal change of multifidus both on T2WI and fat suppression image (FSI) was quantified by Image J. Furthermore, 25 of the 70 patients underwent surgery for degenerative lumbar disease and their multifidus were obtained during the operation. Histological analysis of the samples was performed by HE staining. RESULT: Three types of PVM signal changes were identified from the MRI. Type 1 (n = 36) indicated fatty degeneration characterized by a high signal on T2WI and low signal on FSI. High signal on both T2WI and FSI, signifying type 2 meant inflammatory edema (n = 9). Type 3 (n = 25) showed high signal on T2WI and partial signal suppression on FSI, which meant a combination of fatty degeneration and inflammatory edema. Histological results were consistent with MRI. Among the 25 patients who underwent surgery, type 1 (n = 14) showed adipocytes infiltration, type 2 (n = 3) showed inflammatory cells infiltration and type 3 (n = 8) showed adipocytes and inflammatory cells infiltration. CONCLUSION: From our results, there are three types of pathological changes in patients with PVM degeneration, which may help to decide on targeted treatments for LBP.

Risk assessment of paternal depression in relation to partner delivery during COVID-19 pandemic in Wuhan, China.

BACKGROUND: The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk. METHODS: A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis. RESULTS: Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks. CONCLUSIONS: A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.

Polyhydroxyalkanoates and biochar from green macroalgal Ulva sp. biomass subcritical hydrolysates: Process optimization and a priori economic and greenhouse emissions break-even analysis.

Although macroalgae biomass is an emerging sustainable feedstock for biorefineries, the optimum process parameters for their hydrolysis and fermentation are still not known. In the present study, the simultaneous production of polyhydroxyalkanoates (PHA) and biochar from green macroalgae Ulva sp. is examined, applying subcritical water hydrolysis and Haloferax mediterranei fermentation. First, the effects of temperature, treatment time, salinity, and solid load on the biomass and PHA productivity were optimized following the Taguchi method. Hydrolysis at 170 °C, 20 min residence time, 38 g L-1 salinity with a seaweed solid load of 5% led to the maximum PHA yield of 0.104 g g-1Ulva and a biochar yield of 0.194 ± 1.23 g g-1Ulva. Second, the effect of different initial culture densities on the biomass and PHA productivity was studied. An initial culture density of 50 g L-1 led to the maximum volumetric PHA productivity of 0.024 ± 0.002 g L-1 h-1 with a maximum PHA content of 49.38 ± 0.3% w/w Sensitivity analysis shows that within 90% confidence, the annual PHA production from Ulva sp. is 148.14 g PHA m-2 year-1 with an annual biochar production of 42.6 g m-2 year-1. Priori economic and greenhouse gas break-even analyses of the process were done to estimate annual revenues and allowable greenhouse gas emissions. The study illustrates that PHA production from seaweed hydrolysate using extreme halophiles coupled to biochar production could become a benign and promising step in a marine biorefinery.

Concentration, spatial distribution, and health risk assessment of PFASs in serum of teenagers, tap water and soil near a Chinese fluorochemical industrial plant.

Discharges released from fluorochemical industrial plants lead to severe contamination of the environment with per- and polyfluoroalkyl substances (PFASs), which may pose risks to human health. In this study, 187 serum samples from teenagers (age = 14 years), 22 tap water samples and 40 soil samples were collected in areas within 0-11 km of a fluorochemical industrial plant in Huantai County, Shandong Province, and concentrations of 18 PFASs were quantified by UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was found to be predominant, concentrations of which ranged from 40.4 to 845 ng/mL in serum, from 2.88 to 19.3 ng/L in tap water, from 4.40 to 189 ng/g in soil, and accounting for 84.1-98.6%, 15.9-79.8%, and 73.8-96.7% of the total PFASs, respectively. Statistical analysis demonstrated that concentrations of perfluorinated carboxylic acids (PFCAs) in soil (C5-C9) and serum (C8-C10) were associated with the industrial plant. And PFOA concentrations in tap water were not relevant to the industrial plant, which were comparable with the non-contaminated area and lower than the threshold value recommended by U.S. EPA (70 ng/mL), indicating that the contribution to the high concentration of serum PFOA of local teenagers by drinking water was limited. Moreover, PFCAs in soil only made a limited contribution to the serum PFCAs of local residents by direct inhalation and dermal exposure, but the potential health risk by the soil via food chain should be paid attention to. Furthermore, health risk assessment demonstrated that high concentrations of PFOA in serum could pose potential health risk to local teenagers. Therefore, effective measures should be taken to attenuate the health risks caused by the industrial plant to local residents, and further epidemiological studies should be carried out in the future.

Categorisation of EEG suppression using enhanced feature extraction for SUDEP risk assessment.

BACKGROUND: Sudden Unexpected Death in Epilepsy (SUDEP) has increased in awareness considerably over the last two decades and is acknowledged as a serious problem in epilepsy. However, the scientific community remains unclear on the reason or possible bio markers that can discern potentially fatal seizures from other non-fatal seizures. The duration of postictal generalized EEG suppression (PGES) is a promising candidate to aid in identifying SUDEP risk. The length of time a patient experiences PGES after a seizure may be used to infer the risk a patient may have of SUDEP later in life. However, the problem becomes identifying the duration, or marking the end, of PGES (Tomson et al. in Lancet Neurol 7(11):1021-1031, 2008; Nashef in Epilepsia 38:6-8, 1997). METHODS: This work addresses the problem of marking the end to PGES in EEG data, extracted from patients during a clinically supervised seizure. This work proposes a sensitivity analysis on EEG window size/delay, feature extraction and classifiers along with associated hyperparameters. The resulting sensitivity analysis includes the Gradient Boosted Decision Trees and Random Forest classifiers trained on 10 extracted features rooted in fundamental EEG behavior using an EEG specific feature extraction process (pyEEG) and 5 different window sizes or delays (Bao et al. in Comput Intell Neurosci 2011:1687-5265, 2011). RESULTS: The machine learning architecture described above scored a maximum AUC score of 76.02% with the Random Forest classifier trained on all extracted features. The highest performing features included SVD Entropy, Petrosan Fractal Dimension and Power Spectral Intensity. CONCLUSION: The methods described are effective in automatically marking the end to PGES. Future work should include integration of these methods into the clinical setting and using the results to be able to predict a patient's SUDEP risk.

Impact of household quarantine on SARS-Cov-2 infection in mainland China: A mean-field modelling approach.

The novel coronavirus, named SARS-Cov-2, has raged in mainland China for more than three months, and it causes a huge threat to people's health and economic development. In order to curb the SARS-Cov-2 prevalence, the Chinese government enacted a series of containment strategies including household quarantine, traffic restriction, city lockdowns etc. Indeed, the pandemic has been effectively mitigated, but the global transmission is not still optimistic. Evaluating such control measures in detail plays an important role in limiting SARS-Cov-2 spread for public health decision and policymakers. In this paper, based on the cumulative numbers of confirmed cases and deaths of SARS-Cov-2 infection, from January 31st to March 31st, announced by the National Health Commission of the People's Republic of China, we established a mean-field model, considering the substantial contact change under some restrictive measures, to study the dynamics of SARS-Cov-2 infection in mainland China. By the Metropolis-Hastings (M-H) algorithm of Markov Chain Monte Carlo numerical method, our model provided a good fitting to the overall trends of SARS-Cov-2 infections and discovers the transmission heterogeneities by some extreme containment strategies to some extent. The basic reproduction number was approximated to be 2.05 (95% CI [1.35,2.87]); the hospitalized cases arrived at the peak of 29766 (95% CI [29743,29868]) on February 7th (95% CI [Feb.6th, Feb.8th]). Importantly, we identified that the highest risk group of SARS-Cov-2 was the family of four, which has the biggest probability of degree distributions at such node, suggesting that contact patterns play an important role in curtailing the disease spread.

Cost-Effectiveness of Tofacitinib for Patients with Moderate-to-Severe Rheumatoid Arthritis in China.

BACKGROUND: Patients with moderate-to-severe rheumatoid arthritis have a heavy financial burden. The cost-effectiveness of introducing tofacitinib to the current treatment sequence for patients with moderate-to-severe rheumatoid arthritis who have inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs-IR) in China remains unknown. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of introducing tofacitinib into the current treatment sequence in China for patients with moderate-to-severe rheumatoid arthritis who have csDMARDs-IR. METHODS: A Markov model was constructed from the perspective of the Chinese healthcare system to compare treatment sequences with and without first-line tofacitinib for patients with rheumatoid arthritis with csDMARDs-IR. The treatment sequence without tofacitinib included adalimumab, etanercept, recombinant human tumor necrosis factor receptor-Fc fusion protein, infliximab, and tocilizumab. Costs were derived from publicly available sources. Clinical trials, network meta-analysis, and real-world data were used to generate quality-adjusted life-years (QALYs), transition probabilities, and the incidence of adverse events. Mortality probabilities were estimated from rheumatoid arthritis-based, Chinese all-cause mortality data. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. In addition, the cost-effectiveness of adding tofacitinib as second- and third-line treatment options was evaluated in our analyses. Costs and effects were discounted at 5% per anum. RESULTS: Compared to the current treatment sequence, adding tofacitinib as first-line treatment led to a cost-saving of $US880.11 (2018 values) and incremental QALYs of 1.34. Sensitivity analyses showed the results to be robust. Adding tofacitinib at second-line therapy was also a cost-saving option with a cost saving of $US653.65 and incremental QALYs of 1.34, while the incremental cost-effectiveness ratio of adding tofacitinib at third-line therapy was $US5588.14 per QALY gained. CONCLUSIONS: Using the WHO-recommended ICER acceptability threshold of ≤ 1-time per capita Gross Domestic Product (GDP), our analysis suggests that the introduction of tofacitinib into the current treatment sequence for moderate-to-severe RA patients with csDMARDs-IR in China was a cost saving option as first- and second-line treatment, and cost-effective as a third-line treatment option. Of note, use of tofacitinib as first- and second-line treatment post-csDMARDs-IR appeared to be cost saving.

Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy.

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.

Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma.

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.

Engineering biosynthesis of polyhydroxyalkanoates (PHA) for diversity and cost reduction.

PHA, a family of natural biopolymers aiming to replace non-degradable plastics for short-term usages, has been developed to include various structures such as short-chain-length (scl) and medium-chain-length (mcl) monomers as well as their copolymers. However, PHA market has been grown slowly since 1980s due to limited variety with good mechanical properties and the high production cost. Here, we review most updated strategies or approaches including metabolic engineering, synthetic biology and morphology engineering on expanding PHA diversity, reducing production cost and enhancing PHA production. The extremophilic Halomonas spp. are taken as examples to show the feasibility and challenges to develop next generation industrial biotechnology (NGIB) for producing PHA more competitively.

Assessment of the oral health behavior, knowledge and status among dental and medical undergraduate students: a cross-sectional study.

BACKGROUND: It is widely accepted that oral health plays an important role in overall health. Both dental and medical students are expected to possess good oral health awareness and work together for public oral health promotion especially in developing countries like China. The aim of this study was to assess the oral health knowledge, behavior and status of dental and medical undergraduate students in the first (fresh) and third year (before specialized courses) study. METHODS: A self-administered structured questionnaire with 13 questions was designed based on oral health knowledge, behavior and status and a cross-sectional study was conducted among the 1st, 3rd year dental students (1DS, 3DS) and medical students (1MS, 3MS) of Sichuan University in Chengdu, China, in the period of September-December 2017. The data was analyzed by chi-square test using IBM SPSS Statistics v. 21.0. RESULTS: The oral health behavior, consciousness and status of the 1st, 3rd year medical and dental students were not optimistic. Dental freshmen were slightly superior to the medical ones in terms of the brushing methods and the awareness of oral disease-systemic disease relationship. The junior dental students showed highly significant improvement than their counterparts, mainly in the items about frequency of brushing teeth, brushing methods of vertical scrub or Bass technique (66.3%), usage of floss or mouth wash (49.7%), causes of caries, periodontal diseases and system diseases (56.9-83.4%). The rates mentioned above were 36.1, 15.8%, 26.7-43.6% among 3MS, respectively. In terms of oral health status, significant differences were only observed in junior students. The prevalence rates of bad breath, gum bleeding, and tooth discoloration among 3DS were obviously lower than those of 3MS. However, only a total of 17.2% junior students had a good oral health, including 23.8% dental students and 11.4% medical students. CONCLUSIONS: Our study provided a new understanding of oral health knowledge, behavior and status among dental and medical students, which may help to promote the reform of oral health education and establish a model for clinicians and dentists to work together for improving oral health.