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1.
Res Sq ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39011112

ABSTRACT

Critical evaluation of computational tools for predicting variant effects is important considering their increased use in disease diagnosis and driving molecular discoveries. In the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, a dataset of 28 STK11 rare variants (27 missense, 1 single amino acid deletion), identified in primary non-small cell lung cancer biopsies, was experimentally assayed to characterize computational methods from four participating teams and five publicly available tools. Predictors demonstrated a high level of performance on key evaluation metrics, measuring correlation with the assay outputs and separating loss-of-function (LoF) variants from wildtype-like (WT-like) variants. The best participant model, 3Cnet, performed competitively with well-known tools. Unique to this challenge was that the functional data was generated with both biological and technical replicates, thus allowing the assessors to realistically establish maximum predictive performance based on experimental variability. Three out of the five publicly available tools and 3Cnet approached the performance of the assay replicates in separating LoF variants from WT-like variants. Surprisingly, REVEL, an often-used model, achieved a comparable correlation with the real-valued assay output as that seen for the experimental replicates. Performing variant interpretation by combining the new functional evidence with computational and population data evidence led to 16 new variants receiving a clinically actionable classification of likely pathogenic (LP) or likely benign (LB). Overall, the STK11 challenge highlights the utility of variant effect predictors in biomedical sciences and provides encouraging results for driving research in the field of computational genome interpretation.

2.
Chem Sci ; 15(25): 9557-9565, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38939138

ABSTRACT

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

3.
Food Chem ; 446: 138900, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38428074

ABSTRACT

The fat in coconut milk contributes to unique flavour, while increasing fat content affects stability of the coconut milk. In this study, coconut water and fat were separated, recombined, and homogenized to obtain coconut milk with different fat contents (0-20 %). Emulsifying properties, stability, and digestibility of coconut milk with different fat contents were comprehensively evaluated. The results showed that as the fat content increased from 0 to 20 %, the droplet size increased from 2.18 to 4.70 µm and the viscosity showed an increasing trend. During storage and freeze-thaw, coconut milk with 5 % and 10 % fat content showed excellent stability. In addition, coconut milk with 10 % fat content had superior fat digestibility, which was related to high affinity of pancrelipase. In short, this study revealed that fat content below 10 % can withstand environmental factors such as storage, lipid oxidation, and freeze-thaw, which can be accurately developed as coconut milk products.


Subject(s)
Cocos , Milk , Animals , Viscosity
4.
J Colloid Interface Sci ; 665: 693-701, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38552584

ABSTRACT

Metal-Organic Framework (MOF) membranes act as selective layers have offered unprecedented opportunities for energy-efficient and cost-effective gas separation. Searching for the green and sustainable synthesis method of dense MOF membrane has received huge attention in both academia and industry. In this work, we demonstrate an in situ electrochemical potential-induced synthesis strategy to aqueously fabricate Metal Azolate Framework-4 (MAF-4) membranes on polypropylene (PP) support. The constant potential can induce the heterogeneous nucleation and growth of MAF-4, resulting an ultrathin membrane with the thickness of only 390 nm. This high-quality membrane exhibits a high H2/CO2 separation performance with the H2 permeance as high as 1565.75 GPU and selectivity of 11.6. The deployment of this environment friendly one-step fabrication method under mild reaction conditions, such as low-cost polymer substrate, water instead of organic solvent, room temperature and ambient pressure shows great promise for the scale-up of MOF membranes.

5.
Food Chem X ; 20: 100954, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38144812

ABSTRACT

Coconut milk is an unstable emulsion system, mainly stabilized by proteins, which limits the development of the food industry. The aim of this study was to investigate mechanisms for increasing emulsion stability through the interaction between coffee polyphenols (CPs) and coconut globulin (CG), the main protein in coconut milk. Caffeic acid (CA), chlorogenic acid (CHA), and ferulic acid (FA) were selected as CP models. The results showed that hydrogen bond interactions mainly occurred between CG and CPs (CG-FA < CG-CA < CG-CHA). CHA containing quinic acid preferentially formed a strong interaction with CG. The interaction changed the lipophilicity of CG and facilitated the formation of a dense and thick interfacial film at the oil-water interface. Furthermore, the emulsion stabilized by CG-CPs showed excellent stability after storage, centrifugation, pH, and salt treatment, especially CG-CHA. This study could provide a theoretical basis for improving the stability of coconut milk products.

6.
Int Ophthalmol ; 43(12): 4443-4450, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37875682

ABSTRACT

PURPOSE: To determine the accuracy of manual compass measurement and trigonometric determination of proptosis (MCMATDP). METHODS: This agreement study included 120 eyes without eye diseases or injury of 60 patients who visited the ophthalmic clinic of Peking University Shenzhen Hospital from February 2020 to June 2020. The absolute values of proptosis were measured by MCMATDP and computed tomography (CT). The differences between the two methods were shown by Bland-Altman plot. RESULTS: The cohort comprised 25 males and 35 females (average age 38.3 years). The absolute value of proptosis measured by CT was correlated with the MCMATDP. Further analysis showed that a 95% limit of agreement (LoA) was - 0.53 to 0.60 mm in the right eye and - 0.46 to 0.55 mm in the left eye between CT and MCMATDP. In addition, the 95% LoA was - 0.49 to 0.60 mm in both eyes between the two methods. All points were < 5% in Bland-Altman plots. CONCLUSIONS: Compared to CT, MCMATDP is rather consistent in proptosis measurement. The new method is feasible in clinical practice when measuring proptosis. With the development of non-contact intelligent measurement software and the continuous improvement in measurement accuracy, a non-invasive, simple, and inexpensive measurement mode is true based on the theory of MCMATDP.


Subject(s)
Exophthalmos , Male , Female , Humans , Adult , Exophthalmos/diagnosis , Eye , Tomography, X-Ray Computed/methods , Software
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(1): 15-23, 2023 Jan 28.
Article in English, Chinese | MEDLINE | ID: mdl-36935173

ABSTRACT

OBJECTIVES: Cervical squamous cell carcinoma is the most common cancer in female reproductive system. This study aims to explore the effect of microRNA-9-5p (miR-9-5p) on the migration, invasion, and epithelial-mesenchymal transition (EMT) process of cervical squamous cells. METHODS: Bioinformatics were used to predict the miRNAs that could bind to E-cadherin (E-cad). The Cancer Genome Atlas (TCGA) database was used to analyze and extract significantly differentially expressed miRNAs from part of cervical squamous cell carcinoma tissues and normal cervical tissues, and miR-9-5p was selected as the main research target. The translated regions (UTR) of wild-type E-cad (E-cad-WT 3'-UTR) or the 3'-UTR of mutant E-cad (E-Cad-MUT 3'-UTR) was transfected with miR-9-5p mimic normal control (NC), and miR-9-5p mimic was co-transfected human embryonic kidney cells (293T). The relationship between miR-9-5p and E-cad was detected by double luciferase assay. The expression of miR-9-5p in normal cervical epithelial cell lines (H8) and cervical squamous cell lines (C33A, siha, caski and Me180) were detected by quantitative real-time PCR. Then, the experiments were divided into groups as follows: a block control group, an overexpression control group (mimic-NC group), a miR-95p overexpression group (mimic group), an inhibitory expression control group (inhibitor-NC group), and a miR-9-5p inhibitory expression group (inhibitor group). The changes of migration ability were detected by scratch assay. Transwell invasion assay was used to analyze the changes of invasion ability, and the mRNA and protein changes of E-cad and vimentin were detected by quantitative real-time PCR and Western blotting. RESULTS: MiR-9-5p had a targeting binding relationship with E-cad. Compared with the normal cervical tissue H8 cell line, the miR-9-5p was highly expressed in cervical cancer cell lines (C33A, siha, caski and Me180) (all P<0.05). The luciferase activity of E-cad-MUT was increased compared with that of E-cad-WT in miR-9-5p mimic cells (P<0.05). Compared with the blank control group, the protein and mRNA expressions of E-cad were decreased in the miR-9-5p mimic group (both P<0.05), which were increased in the miR-9-5p inhibitor group (both P<0.05). Compared with H8 cell line, the miR-9-5p was highly expressed in the cervical squamous cell lines (all P<0.05). Compared with the mimic-NC group, the distance of wound healing, the number of caski and Me180 cells invaded below the membrane, and the mRNA and protein expressions of vimentin were all increased in the miR-9-5p mimic group (all P<0.05), while the mRNA and protein of E-cad were decreased (both P<0.05). Compared with the inhibitor-NC group, the distance of wound healing, the number of caski and Me180 cells invading the membrane, and the mRNA and protein expressions of vimentin were decreased in the miR-9-5p inhibitor group (all P<0.05), but the mRNA and protein expressions of E-cad were increased (both P<0.05). CONCLUSIONS: The miR-9-5p is highly expressed in cervical squamous cell carcinoma, which can increase the migration and invasion ability, and promote the EMT process of cancer cells.


Subject(s)
Carcinoma, Squamous Cell , MicroRNAs , Uterine Cervical Neoplasms , Humans , Female , Cell Line, Tumor , Vimentin/genetics , Vimentin/metabolism , Uterine Cervical Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Carcinoma, Squamous Cell/genetics , Cell Movement/genetics , RNA, Messenger , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic
8.
Article in English | MEDLINE | ID: mdl-36901150

ABSTRACT

The Macau peninsula is close to the tropical ocean, with a high population density and a large number of high-rise buildings, which require a windy environment with good ventilation and heat dissipation. Based on residential samples and the degree of agglomeration, the high-rise residential area in Areia Preta was selected as the focus of this study. Meanwhile, summer typhoons pose serious safety risks to high-rise buildings. Therefore, it is necessary to study the connection between spatial form and the wind environment. First of all, this research is based on relevant concepts and the wind environment evaluation system of high-rise buildings and conducts research on high-rise residential areas in Areia Preta. PHOENICS software is used to simulate the prevailing monsoon in winter and summer, as well as a typhoon in an extreme wind environment, and summarize the wind environment's characteristics. Secondly, by comparing the parameter calculation and simulation results, the possible relationship between the causes of each wind field is studied. Finally, conclusions are drawn about the urban form and wind environment of the site, and corresponding control strategies are proposed to reduce the shielding effect between buildings and typhoon damage. It can be used as a theoretical basis and reference point for urban construction and high-rise building planning and layout.


Subject(s)
Software , Wind , Macau , Computer Simulation , Seasons
9.
Front Big Data ; 6: 1008292, 2023.
Article in English | MEDLINE | ID: mdl-36760879

ABSTRACT

Machine learning (ML) is an innovative method that is widely used in data prediction. Predicting the COVID-19 distribution using ML is essential for urban security risk assessment and governance. This study uses conditional generative adversarial network (CGAN) to construct a method to predict the COVID-19 hotspot distribution through urban texture and business formats and establishes a relationship between urban elements and COVID-19 so that machines can automatically predict the epidemic hotspots in cities. Taking Macau as an example, this method is used to determine the correlation between the urban texture and business hotspots of Macau and the new epidemic hotspot clusters. Different types of samples afforded different epidemic prediction accuracies. The results show the following: (1) CGAN can accurately predict the distribution area of COVID-19, and the accuracy can exceed 70%. (2) The results of predicting the COVID-19 distribution through urban texture and POI data of hospitals and stations are the best, with an accuracy of more than 60% in experiments in different regions of Macau. (3) The proposed method can also predict other areas in the city that may be at risk of COVID-19 and help urban epidemic prevention and control.

10.
Article in English | MEDLINE | ID: mdl-36833855

ABSTRACT

This paper takes the garden road system as the research object and proposes a method of generating paths for classical gardens based on parametric design. Firstly, by studying the distribution characteristics of roads, the data on the curvature, angle, and view area of roads were collected. Secondly, the obtained data were transferred to the parameterized platform, and a method of intelligent generation was used for calculation. Finally, the road system was optimized by the genetic algorithm for better application in modern landscape design. According to the current situation, the road system plan generated by the algorithm inherits the characteristics of classical garden roads. This method can be applied to the courtyard, the community park, the urban park, and other objects. This research not only identifies the characteristics of landscape cultural heritage, but also produces an innovative, intelligent design tool. It provides new methods for the parameterized inheritance and application of traditional landscape heritage.


Subject(s)
Gardens , Parks, Recreational , Gardening , Algorithms
11.
Pac Symp Biocomput ; 28: 323-334, 2023.
Article in English | MEDLINE | ID: mdl-36540988

ABSTRACT

The accurate interpretation of genetic variants is essential for clinical actionability. However, a majority of variants remain of uncertain significance. Multiplexed assays of variant effects (MAVEs), can help provide functional evidence for variants of uncertain significance (VUS) at the scale of entire genes. Although the systematic prioritization of genes for such assays has been of great interest from the clinical perspective, existing strategies have rarely emphasized this motivation. Here, we propose three objectives for quantifying the importance of genes each satisfying a specific clinical goal: (1) Movability scores to prioritize genes with the most VUS moving to non-VUS categories, (2) Correction scores to prioritize genes with the most pathogenic and/or benign variants that could be reclassified, and (3) Uncertainty scores to prioritize genes with VUS for which variant pathogenicity predictors used in clinical classification exhibit the greatest uncertainty. We demonstrate that existing approaches are sub-optimal when considering these explicit clinical objectives. We also propose a combined weighted score that optimizes the three objectives simultaneously and finds optimal weights to improve over existing approaches. Our strategy generally results in better performance than existing knowledge-driven and data-driven strategies and yields gene sets that are clinically relevant. Our work has implications for systematic efforts that aim to iterate between predictor development, experimentation and translation to the clinic.


Subject(s)
Genetic Predisposition to Disease , Genetic Testing , Humans , Genetic Testing/methods , Genetic Variation , Computational Biology/methods
12.
Front Med ; 17(1): 93-104, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36422763

ABSTRACT

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/drug therapy , Prospective Studies , Quality of Life , Neoplasm Staging , Chemoradiotherapy , Chemotherapy, Adjuvant/adverse effects , Adjuvants, Immunologic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies
13.
BMC Cancer ; 22(1): 1270, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36471257

ABSTRACT

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.


Subject(s)
Neoadjuvant Therapy , Uterine Cervical Neoplasms , Female , Humans , Neoadjuvant Therapy/methods , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Prospective Studies , Neoplasm Staging , Retrospective Studies , Treatment Outcome , Chemotherapy, Adjuvant/methods , Hysterectomy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
14.
Nat Commun ; 13(1): 5968, 2022 10 10.
Article in English | MEDLINE | ID: mdl-36216793

ABSTRACT

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3-TACC3 and ANKRD12-NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.


Subject(s)
Alphapapillomavirus , Carcinoma, Small Cell , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Microtubule-Associated Proteins/genetics , N-Myc Proto-Oncogene Protein/genetics , Nuclear Proteins/genetics , Papillomaviridae/genetics , Uterine Cervical Neoplasms/pathology , Virus Integration/genetics
15.
Front Surg ; 9: 974341, 2022.
Article in English | MEDLINE | ID: mdl-36034382

ABSTRACT

Purpose: The biomechanical characteristics of the trauma size and postoperative drainage of different incisions for high complex anal fistula surgery were compared by numerical simulation analysis to provide a theoretical basis for the clinical selection of minimally invasive incisions for surgery. Methods: Using FLUENT finite element software, a typical incision finite element model was established to obtain incision areas, and the total mass outlet flow within 200 s was calculated to evaluate the drainage effect of each incision. Results: The incisions with the largest to smallest areas were the curved, spindle, and curved plus extended groove incision, indicating that the curved plus extended groove incision caused the least damage to the perianal skin muscles. Conversely, the incisions with the largest to smallest total outlet flow were as follows: curved plus extended groove, spindle, curved, and straight incision, suggesting that the curved plus extended groove model had the best diversion effect, and the curved incision had better diversion effect than that of the straight incision. Conclusion: The curved plus extended groove surgical incision had the smallest incision area, minimized damage to the perianal skin and muscle tissue, conformed to the concept of minimally invasive surgery, ensured adequate drainage of exudate, maintained the normal growth of granulation tissue on the wound surface, preserved the original form of the anus, and thus better protected the function of the anus. This improved the quality of life of patients requiring high complex anal fistulas.

16.
Int Ophthalmol ; 42(9): 2645-2649, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35947252

ABSTRACT

PURPOSE: To compare the pupil size of the original mydriasis and repeat mydriasis at the pupil shrinkage stage. METHODS: Randomized prospective study. In total, 60 eyes of 30 patients aged 50-70 with age-related cataracts were included. Pupil sizes were measured by the Sirius system before mydriasis, after the first batch of mydriasis, and after the second batch of mydriasis which was 5 h later. Statistical analysis was performed using MedCalc statistical software version 20.0.3 RESULTS: The pupil size of the second batch of mydriasis 5 h later was smaller than the first batch of mydriasis (3.94 ± 0.88 mm vs 5.12 ± 0.96 mm, P < 0.0001). CONCLUSIONS: Less efficiency repeat mydriasis several hours later compared with original mydriasis in our study suggests that preparation of mydriasis at an appropriate time is necessary for ophthalmological operations. The effect of repeat mydriasis again by tropicamide at the shrinkage stage still needs to be explored.


Subject(s)
Mydriasis , Mydriatics , Pupil , Dilatation , Humans , Phenylephrine , Prospective Studies , Pupil/physiology , Tropicamide
17.
Gigascience ; 112022 02 15.
Article in English | MEDLINE | ID: mdl-35166340

ABSTRACT

BACKGROUND: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns' health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24-28 gestational weeks. RESULTS: A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e-04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth. CONCLUSIONS: Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.


Subject(s)
Premature Birth , Case-Control Studies , Female , Gestational Age , Humans , Infant , Infant, Newborn , Lipids , Pregnancy , Premature Birth/metabolism , Prospective Studies
18.
JAMA Oncol ; 7(3): 361-369, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33443541

ABSTRACT

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.


Subject(s)
Uterine Cervical Neoplasms , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Cisplatin/therapeutic use , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Treatment Outcome , Uterine Cervical Neoplasms/pathology
19.
PLoS One ; 15(6): e0234016, 2020.
Article in English | MEDLINE | ID: mdl-32480401

ABSTRACT

PURPOSE: We propose a new method to calculate proptosis by using the simple Heron's formula and analyze its feasibility. METHOD: It was a none-inferiority trial. The registration number was ChiCTR1900026490. The absolute value of proptosis in 120 eyes, 60 patients without eye injury or diseases, was measured by computed tomography (CT) and simple Heron's formula. We did regression analysis and analyzed the differences between the two methods with Medcalc software version 19.0.4. The result was showed by Passing-Bablok regression analysis diagram and Bland and Altman plot. RESULTS: The Passing-Bablok showed that the result of proptosis measured by CT and simple Heron's formula showed good positive correlation. A 95% limit of agreement in proptosis between CT and Heron's formula method was -0.46 to 0.54 mm in right eye and -0.45 to 0.46 mm in left eye. 1.66% (1/60) point was outside 95% LoA in both eyes. Moreover, a 95% limit of agreement between CT and Heron's formula method was -0.42 to 0.56 mm in difference of both eyes. 3.33% (2/60) points were outside 95% LoA. The points in all Bland and Altman plots were lower than 5%. It means that the results of comparison between the two methods had a good consistency in the measurement of proptosis. CONCLUSIONS: Heron's formula could be applied to calculate proptosis and has a good consistency compared with computed tomography (CT). This method is practical in proptosis assessment because of its accuracy, reliability and simplicity.


Subject(s)
Anthropometry/methods , Exophthalmos/diagnosis , Adult , Anthropometry/instrumentation , Eye/diagnostic imaging , Feasibility Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Tomography, X-Ray Computed , Young Adult
20.
J Cataract Refract Surg ; 46(3): 465-473, 2020 03.
Article in English | MEDLINE | ID: mdl-32142042

ABSTRACT

To analyze the visual acuity and complications between primary intraocular lens (IOL) implantation and contact lens wearing, this literature search was performed with data on patients with congenital cataract younger than 2 years published in March 2019. Seven identified studies enrolling 675 eyes were selected for analysis. Patients with primary IOL implantation owned better visual acuity than those with aphakia who wore the contact lens (weighted mean difference = 0.161; 95% CI, 0.108-0.214). For visual axis opacification (VAO), primary IOL implantation increases the incidence of VAO compared with contact lens wearing (relative risk = 0.23; 95% CI, 0.13-0.42). No statistically significant difference was found between the 2 groups about the prevalence of glaucoma and strabismus. Primary IOL implantation achieved better visual outcomes after cataract extraction in patients younger than 2 years. In addition, no higher risk for complications among primary IOL implantation compared with contact lens wearing was noted. Therefore, implanting a primary IOL during congenital cataract surgery is a better therapy for children younger than 2 years than wearing a contact lens.


Subject(s)
Aphakia, Postcataract/physiopathology , Cataract/congenital , Lens Implantation, Intraocular , Phacoemulsification , Postoperative Complications , Pseudophakia/physiopathology , Visual Acuity/physiology , Contact Lenses/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Male
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