State-of-the-Art Evidence Retriever for Precision Medicine: Algorithm Development and Validation.

BACKGROUND: Under the paradigm of precision medicine (PM), patients with the same disease can receive different personalized therapies according to their clinical and genetic features. These therapies are determined by the totality of all available clinical evidence, including results from case reports, clinical trials, and systematic reviews. However, it is increasingly difficult for physicians to find such evidence from scientific publications, whose size is growing at an unprecedented pace. OBJECTIVE: In this work, we propose the PM-Search system to facilitate the retrieval of clinical literature that contains critical evidence for or against giving specific therapies to certain cancer patients. METHODS: The PM-Search system combines a baseline retriever that selects document candidates at a large scale and an evidence reranker that finely reorders the candidates based on their evidence quality. The baseline retriever uses query expansion and keyword matching with the ElasticSearch retrieval engine, and the evidence reranker fits pretrained language models to expert annotations that are derived from an active learning strategy. RESULTS: The PM-Search system achieved the best performance in the retrieval of high-quality clinical evidence at the Text Retrieval Conference PM Track 2020, outperforming the second-ranking systems by large margins (0.4780 vs 0.4238 for standard normalized discounted cumulative gain at rank 30 and 0.4519 vs 0.4193 for exponential normalized discounted cumulative gain at rank 30). CONCLUSIONS: We present PM-Search, a state-of-the-art search engine to assist the practicing of evidence-based PM. PM-Search uses a novel Bidirectional Encoder Representations from Transformers for Biomedical Text Mining-based active learning strategy that models evidence quality and improves the model performance. Our analyses show that evidence quality is a distinct aspect from general relevance, and specific modeling of evidence quality beyond general relevance is required for a PM search engine.

Leveraging online shopping behaviors as a proxy for personal lifestyle choices: New insights into chronic disease prevention literacy.

Objective: Ubiquitous internet access is reshaping the way we live, but it is accompanied by unprecedented challenges in preventing chronic diseases that are usually planted by long exposure to unhealthy lifestyles. This paper proposes leveraging online shopping behaviors as a proxy for personal lifestyle choices to improve chronic disease prevention literacy, targeted for times when e-commerce user experience has been assimilated into most people's everyday lives. Methods: Longitudinal query logs and purchase records from 15 million online shoppers were accessed, constructing a broad spectrum of lifestyle features covering various product categories and buyer personas. Using the lifestyle-related information preceding online shoppers' first purchases of specific prescription drugs, we could determine associations between their past lifestyle choices and whether they suffered from a particular chronic disease. Results: Novel lifestyle risk factors were discovered in two exemplars-depression and type 2 diabetes, most of which showed reasonable consistency with existing healthcare knowledge. Further, such empirical findings could be adopted to locate online shoppers at higher risk of these chronic diseases with decent accuracy [i.e. (area under the receiver operating characteristic curve) AUC=0.68 for depression and AUC=0.70 for type 2 diabetes], closely matching the performance of screening surveys benchmarked against medical diagnosis. Conclusions: Mining online shopping behaviors can point medical experts to a series of lifestyle issues associated with chronic diseases that are less explored to date. Hopefully, unobtrusive chronic disease surveillance via e-commerce sites can grant consenting individuals a privilege to be connected more readily with the medical profession and sophistication.

Varicella incidence and vaccination of children in kindergarten and primary school of Longhua District in Shenzhen / 中国学校卫生

Objective@#To understand the situation of varicella prevalence and vaccination of susceptible population in Longhua District，and to provide reference for the varicella immunization program.@*Methods@#A total of 23 706 children from 30 childcare facilities and primary schools in 6 streets were randomly selected throughout the Longhua District. Date on age, grade, recent year and dosage of vaccination, varicella incidence, the overview of vaccination were collected and analyzed.@*Results@#The rate of vaccination in childcare facilities and primary schools was 86.01%, including 55.61% of 1 dose and 30.41% of 2 doses of vaccine. The differences of rate vaccination rate between the childcare facilities and primary schools had statistical significance(χ2=154.95, P<0.05).Rate of no-vaccination,1 dose vaccination and 2 doses vaccination across 6 streets differed significantly(χ2=146.09, 103.93, 127.31, 146.09, P<0.05). There was an increasing positive association between grades and attack rate(χ2=8.65，P<0.05). The differences of attack rate between the childcare facilities and primary schools was of statistical significance(χ2=478.69, P<0.05). The differences of attack rate in street of no vaccination,1 dose vaccination and total attack rate showed statistical significance(χ2=54.49, 74.59, 151.49，P<0.05). There was an increasing linear trend of attack rate of primary school childrenby each year(χ2=24.28，P<0.05). The attack rate increased with time after 1 dose vaccination, immune protection was obtuined for a longer period time after additional doses of vaccine.Negative association was found between grades and protective efficacy rate of varicella. The protective rate and efficacy index of different doses of vaccine in different grades were correlated(r=0.80，0.63，P<0.05). It was most effective after 1 dose vaccination among children in junior grade in kindergarten and 2 dose vaccination in senior grade.@*Conclusion@#After the implementation of vaccination program in Longhua District, the vaccination rate of 2 doses significantly increased, but not for a long time. Varicella vaccine should be included in immunization programme to protect vulnerable populations.

[Umbilical therapy combined with moxibustion for autumn diarrhea in children].

OBJECTIVE: To observe the efficacy differences between moxibustion combined with umbilical therapy and oral administration of montmorillonite powder (smecta) on diarrhea symptoms in children of different ages. METHODS: A total of 120 children were randomly divided into an observation group and a control group, 60 cases in each group. In the observation group, the children aged under 3 years old were treated with moxibustion at Shenque (CV 8), Zhongwan (CV 12) and Tianshu (ST 25), and each acupoint was treated for less than 3 min, and the total treatment duration was no more than 10 min; the children aged between 3 to 7 years old were treated with moxibustion at Shenque (CV 8), Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Zusanli (ST 36), Pishu (BL 20), Shenshu (BL 23) and Dachangshu (BL 25), each acupoint was treated for less than 3 min, and the total treatment duration was no more than 20 min. After moxibustion, traditional Chinese medicine patch (clove, cinnamon, rhizoma zingiberis, fructus evodiae, hawthorn, rhizoma atractylodis) was applied at Shenque (CV 8). For the children under 1 year old, the medical bag with 30 g powder was heated to 50 ℃ and used for about 30 min; for children over 1 year old, 2-5 g powder was mixed with vinegar and used for 4-8 h each time. The treatment was given once a day, three times as a course of treatment, and a total of one course of treatment was given. The children in the control group were treated with oral administration of montmorillonite powder, 3 g per day for children under 1 year old, 3-6 g per day for children aged 1-2 years old and 6-9 g per day for children over 2 years old. The montmorillonite powder was taken three times a day for 3 days. The diarrhea symptom scores before and after treatment were observed and the clinical efficacy was evaluated. From the first treatment, the recovery cases and recovery time in the two groups were recorded, the recovery cases and recovery time in acute and chronic stages were compared between different age groups. The recurrence was observed 3 months after treatment. RESULTS: Compared before treatment, the diarrhea symptom score after treatment was decreased in the observation group (P<0.05), while there was no significant difference before and after treatment in the control group (P>0.05). After treatment, the score of diarrhea symptoms in the observation group was lower than that in the control group (P<0.05). The total effective rate was 95.0% (57/60) in the observation group, which was superior to 76.7% (46/60) in the control group (P<0.05). The recovery cases of acute stage aged ≤ 1 year old and 5-7 years old, and chronic stage of different age stages in the observation group was insignificantly higher than that in the control group (P>0.05). The recovery time of different age stages and average recovery time in the observation group were shorter than those in the control group (P<0.05). The recovery time of children in acute stage>1 year old and ≤5 years old and average recovery time in the observation group were shorter than those in the control group (P<0.05), while the average recovery time of children in chronic stage in the observation group was shorter than that in the control group (P<0.05). Three months after treatment, the recurrence rate was 0% (0/36) in acute phase and 4.8% (1/21) in chronic phase in the observation group, which were superior to 9.7% (3/31) in acute phase and 46.7% (7/15) in chronic phase in the control group (P<0.05). CONCLUSION: The umbilical therapy combined with moxibustion could improve the symptoms of diarrhea and shorten the recovery time in children of different ages with autumn diarrhea, which have better efficacy than montmorillonite powder.

edge2vec: Representation learning using edge semantics for biomedical knowledge discovery.

BACKGROUND: Representation learning provides new and powerful graph analytical approaches and tools for the highly valued data science challenge of mining knowledge graphs. Since previous graph analytical methods have mostly focused on homogeneous graphs, an important current challenge is extending this methodology for richly heterogeneous graphs and knowledge domains. The biomedical sciences are such a domain, reflecting the complexity of biology, with entities such as genes, proteins, drugs, diseases, and phenotypes, and relationships such as gene co-expression, biochemical regulation, and biomolecular inhibition or activation. Therefore, the semantics of edges and nodes are critical for representation learning and knowledge discovery in real world biomedical problems. RESULTS: In this paper, we propose the edge2vec model, which represents graphs considering edge semantics. An edge-type transition matrix is trained by an Expectation-Maximization approach, and a stochastic gradient descent model is employed to learn node embedding on a heterogeneous graph via the trained transition matrix. edge2vec is validated on three biomedical domain tasks: biomedical entity classification, compound-gene bioactivity prediction, and biomedical information retrieval. Results show that by considering edge-types into node embedding learning in heterogeneous graphs, edge2vec significantly outperforms state-of-the-art models on all three tasks. CONCLUSIONS: We propose this method for its added value relative to existing graph analytical methodology, and in the real world context of biomedical knowledge discovery applicability.

A new method for calculating the desired laminoplasty opening size based on the target sagittal canal diameter before single-door cervical laminoplasty.

PURPOSE: To build a mathematical model which could calculate the desired laminoplasty opening size (LOS) based on the target sagittal canal diameter (SCD) before single-door cervical laminoplasty (SDCL) when taking the effects of surgery drill into consideration. METHODS: The model was based on geometric analysis on deformation of spinal canal; the formula was derived and characterized as: y (mm) = 2 [Formula: see text] × sin(ß/2) = c - d (y is the size of LOS, [Formula: see text] the size of transverse canal diameter, ß the size of laminoplasty opening size, c the size of mini-plate and d the diameter of the drill bit used during the surgery operation). The parameters of pre- and postoperative computed tomography scans of 20 patients who had undergone SDCL were measured by the picture archiving and communication system (PACS) software and a new instrument named as Lei's ruler, respectively. RESULTS: The effects of surgery SDCL were very significant; for each patient, the SCD was enlarged dramatically after the surgery (P < 0.01). The differences between the data obtained by PACS and Lei's ruler were no statistically significant (P > 0.05). According to the derived formula, the 95% confidence intervals of SCD after the surgery were within the range of 14 mm and 14.5 mm. CONCLUSION: Applying the mathematical model and derived formula, the desired LOS could be calculated according to the target SCD which could help the surgeon select an optimum mini-plate before SDCL. At the same time, a new measuring device named Lei's ruler is designed for the convenience of the derived formula. These slides can be retrieved under Electronic Supplementary Material.

Skill discrepancies between research, education, and jobs reveal the critical need to supply soft skills for the data economy.

Rapid research progress in science and technology (S&T) and continuously shifting workforce needs exert pressure on each other and on the educational and training systems that link them. Higher education institutions aim to equip new generations of students with skills and expertise relevant to workforce participation for decades to come, but their offerings sometimes misalign with commercial needs and new techniques forged at the frontiers of research. Here, we analyze and visualize the dynamic skill (mis-)alignment between academic push, industry pull, and educational offerings, paying special attention to the rapidly emerging areas of data science and data engineering (DS/DE). The visualizations and computational models presented here can help key decision makers understand the evolving structure of skills so that they can craft educational programs that serve workforce needs. Our study uses millions of publications, course syllabi, and job advertisements published between 2010 and 2016. We show how courses mediate between research and jobs. We also discover responsiveness in the academic, educational, and industrial system in how skill demands from industry are as likely to drive skill attention in research as the converse. Finally, we reveal the increasing importance of uniquely human skills, such as communication, negotiation, and persuasion. These skills are currently underexamined in research and undersupplied through education for the labor market. In an increasingly data-driven economy, the demand for "soft" social skills, like teamwork and communication, increase with greater demand for "hard" technical skills and tools.

Analyzing cross-college course enrollments via contextual graph mining.

The ability to predict what courses a student may enroll in the coming semester plays a pivotal role in the allocation of learning resources, which is a hot topic in the domain of educational data mining. In this study, we propose an innovative approach to characterize students' cross-college course enrollments by leveraging a novel contextual graph. Specifically, different kinds of variables, such as students, courses, colleges and diplomas, as well as various types of variable relations, are utilized to depict the context of each variable, and then a representation learning algorithm node2vec is applied to extracting sophisticated graph-based features for the enrollment analysis. In this manner, the relations between any pair of variables can be measured quantitatively, which enables the variable type to transform from nominal to ratio. These graph-based features are examined by the random forest algorithm, and experiments on 24,663 students, 1,674 courses and 417,590 enrollment records demonstrate that the contextual graph can successfully improve analyzing the cross-college course enrollments, where three of the graph-based features have significantly stronger impacts on prediction accuracy than the others. Besides, the empirical results also indicate that the student's course preference is the most important factor in predicting future course enrollments, which is consistent to the previous studies that acknowledge the course interest is a key point for course recommendations.

Copper-catalyzed synthesis of 2,4-disubstituted allenoates from α-diazoesters.

A Cu-catalyzed method for coupling α-substituted-α-diazoesters with terminal alkynes to give substituted allenoates is described. Key to the development of a selective method was the recognition that an adventitous base catalyzes the isomerization to form the allenoate product. A plausible mechanism is proposed, based in part on evidence against a mechanism that involves a Cu(I)-acetylide as a low-valent intermediate.

Directed carbozincation reactions of cyclopropene derivatives.

A diastereoselective procedure has been developed for the Cu-catalyzed addition of diorganozinc reagents to cyclopropene derivatives. Ester and oxazolidinone functions direct the addition of a variety of organozinc reagents with excellent facial selectivity. The resulting cyclopropylzinc reagents can be captured via stereospecific reactions with electrophiles. Cycloprop-2-ene carboxylic esters, which are directly available from the transition-metal-catalyzed reactions of alkynes with alpha-diazo esters, can be utilized directly in carbozincation protocols. Both diastereoselectivity and regioselectivity are high for the carbozincation reactions of 2-alkylcycloprop-2-ene carboxylate esters. The scope of the method is broadened by the ability to utilize organozinc reagents that have been generated in situ from Grignard reagents. Chiral oxazolidinone auxilaries are effective in controlling the diastereoselectivity of the carbometalation reactions.

Photosynthetic acclimation to high temperatures associated with heat tolerance in creeping bentgrass.

Photosynthetic responses to increasing temperatures play important roles in regulating heat tolerance. The objectives of this study were to determine photosynthetic acclimation to increasing temperatures for creeping bentgrass (Agrostis stolonifera L.) and to examine changes in major photosynthetic components (photosynthetic pigments, photochemical efficiency, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) activity, and activation state of rubisco) involved in heat responses of photosynthesis. 'Penncross' was exposed to 20, 25, 30, and 35 degrees C for 7d at each temperature (acclimated) before being exposed to 40 degrees C for 28d or directly exposed to 40 degrees C for 28d from 20 degrees C (non-acclimated) in growth chambers. Leaf net photosynthetic rate (Pn), photochemical efficiency, rubisco activity, rubisco activation state, chlorophyll content, and carotenoid content decreased when grasses were subjected to severe heat stress at 40 degrees C for 28d. The declines in rubisco activity and activation state were most dramatic among different photosynthetic components examined in this study. Heat-acclimated plants were able to maintain significantly higher Pn, the content of chlorophyll and carotenoid, and the level of rubisco activity and activation state during subsequent exposure to severe heat stress, compared to non-acclimated plants. These results suggested that photosynthetic acclimation to increasing temperatures contributed to creeping bentgrass tolerance to severe heat stress, which was associated with the maintenance of both higher light-harvesting capacity and carbon fixation activity during heat stress.

Synthesis of stable derivatives of cycloprop-2-ene carboxylic acid.

Large-scale syntheses of 3-(cycloprop-2-en-1-oyl)oxazolidinones from acetylene and ethyl diazoacetate are described. Unlike other cyclopropenes that bear a single substitutent at C-3, these compounds are stable to long-term storage. Although the cyclopropene derivatives are unusually stable, they are reactive toward cyclic and acyclic dienes in stereoselective Diels-Alder reactions.

Facially selective and regioselective carbometalation of cyclopropenes by aryl Grignard reagents.

Described is a Cu-catalyzed methodology for adding aryl Grignard reagents to 3-hydroxymethylcyclopropene derivatives with high regio- and diastereoselectivity. The cyclopropylmetals can be trapped with a variety of electrophiles to generate highly substituted cyclopropanes.

Two-dimensional scaffolds for the parallel alignment of rod-shaped conjugated molecules.

Described is a method for creating two-dimensional, ordered arrays of linear, conjugated organic molecules on polyimide scaffolds. Key to the design was the enforcement of consecutive 90 degrees twist angles along the polyimide backbone. Rod molecules that are templated by such scaffolds are held parallel and in the same plane and have optical properties that are similar to those of monomeric analogues. As supporting evidence for the structures of the polymers, a series of model compounds were synthesized and characterized by X-ray crystallography. The polymeric materials are soluble and have been characterized by 1H NMR, 13C NMR, MALDI-TOF, and UV-vis spectroscopy.

Preparation of partially substituted 1-halo- and 1,4-dihalo-1,3-dienes via reagent-controlled desilylation of halogenated 1,3-dienes.

Depending on the desilylation reagents used, 1-halo-1,4-bis(trimethylsilyl)-1,3-butadienes afforded either 1-halo-1-trimethylsilyl-1,3-butadienes or 1-halo-4-trimethylsilyl-1,3-butadienes in excellent yields with excellent selectivity, respectively, when treated with CF3COOH or with NaOMe. These monosilylated 1,3-butadiene products could be further desilylated to generate their corresponding halobutadienes via the above reagent-controlled desilylation reaction. When 1,4-dihalo-1,4-bis(trimethylsilyl)-1,3-dienes were treated with MeONa/MeOH at room temperature, desilylation of both of the two trimethylsilyl groups took place to afford their corresponding 1,4-dihalo-1,3-dienes in excellent yields. The commonly used desilylation reagent CF3COOH did not work for these dihalobutadienes.

Enantioselective, facially selective carbomagnesation of cyclopropenes.

Described is the facially selective and enantioselective addition of carbon nucleophiles to prochiral 3-hydroxymethylcyclopropenes. The process creates up to four stereocenters in a tandem addition/capture sequence that combines three simple materials to give complex and diverse products. The asymmetry is induced by the inexpensive and recoverable ligand (S)-N-methylprolinol. The enantioselectivity (90-98% ee with MeMgCl) is high for a range of cyclopropenes and electrophiles. Importantly, the diastereoselectivity is complementary to that obtained by enantioselective cyclopropanation with aryldiazoacetates. High enantioselectivities are obtained only when methoxide is included in the reaction. Evidence is provided that at least two chiral ligands are involved in the enantioselectivity-determining step.

Synthesis of 1,1,4,4-tetrabromo-2-butenes and related compounds via desilylation-bromination of silylated 1,3-butadiene derivatives.

The combination of zirconocene-mediated coupling of silylated alkynes with a protonation-desilylation or bromination-desilylation process afforded otherwise unavailable butadiene derivatives. When (E,E)-2,3-dialkyl-1,4-bis(trimethylsilyl)-1,3-butadienes were treated with 3 equiv of Br(2) in CH(2)Cl(2), (E)-2,3-dialkyl-1,1,4,4-tetrabromo-2-butenes were obtained in excellent yields with perfect stereoselectivity.