Nevin Manimala

Protein Sci. 2022 Dec 23:e4555. doi: 10.1002/pro.4555. Online ahead of print.

ABSTRACT

The development of efficient computational methods for drug target protein identification can compensate for the high cost of experiments and is therefore of great significance for drug development. However, existing structure-based drug target protein-identification algorithms are limited by the insufficient number of proteins with experimentally resolved structures. Moreover, sequence-based algorithms cannot effectively extract information from protein sequences and thus display insufficient accuracy. Here, we combined the sequence-based self-supervised pre-training protein language model ESM1b with a graph convolutional neural network (GCN) classifier to develop an improved, sequence-based drug target protein identification method. This complete model, named QuoteTarget, efficiently encodes proteins based on sequence information alone and achieves an accuracy of 95% with the non-redundant drug target and non-drug target datasets constructed for this study. When applied to all proteins from Homo sapiens, QuoteTarget identified 1,213 potential undeveloped drug target proteins. We further inferred residue-binding weights from the well-trained network using the gradient-weighted class activation mapping (Grad-Cam) algorithm. Notably, we found that without any binding site information input, significant residues inferred by the model closely match the experimentally confirmed drug molecule-binding sites. Thus, our work provides a highly effective sequence-based identifier for drug target proteins, as well to yield new insights into recognizing drug molecule-binding sites. The entire model is available at https://github.com/Chenjxjx/drug-target-prediction. This article is protected by copyright. All rights reserved.

PMID:36564866 | DOI:10.1002/pro.4555

Personal Ment Health. 2022 Dec 23. doi: 10.1002/pmh.1575. Online ahead of print.

ABSTRACT

Obesity is a chronic disorder associated with high mortality rates and high morbidity. The risk of obesity is associated with certain personality traits (PTs). Some studies have found correlations among some PTs and gender. Additionally, obesity implies higher costs in daily living. The aim of this paper is to overcome this problem in the literature and estimate the association between PTs and obesity by taking into account the economic situation of the individual. This study employs data from the English Longitudinal Study of Ageing (ELSA). We focus on waves 5 and 6 of the ELSA with a sample of 6562 individuals. The results suggests that the traits of agreeableness ( ) and openness ( ) are positively and significantly associated with obesity. On the other hand, consciousness has a negative and statistically significant effect on obesity . Results are robust to the inclusion/exclusion of different regressors.

PMID:36564862 | DOI:10.1002/pmh.1575

Protein Sci. 2022 Dec 23:e4554. doi: 10.1002/pro.4554. Online ahead of print.

ABSTRACT

Designing novel proteins to perform desired functions, such as binding or catalysis, is a major goal in synthetic biology. A variety of computational approaches can aid in this task. An energy-based framework rooted in the sequence-structure statistics of tertiary motifs (TERMs) can be used for sequence design on pre-defined backbones. Neural network models that use backbone coordinate-derived features provide another way to design new proteins. In this work, we combine the two methods to make neural structure-based models more suitable for protein design. Specifically, we supplement backbone-coordinate features with TERM-derived data, as inputs, and we generate energy functions as outputs. We present two architectures that generate Potts models over the sequence space: TERMinator, which uses both TERM-based and coordinate-based information, and COORDinator, which uses only coordinate-based information. Using these two models, we demonstrate that TERMs can be utilized to improve native sequence recovery performance of neural models. Furthermore, we demonstrate that sequences designed by TERMinator are predicted to fold to their target structures by AlphaFold. Finally, we show that both TERMinator and COORDinator learn notions of energetics, and these methods can be fine-tuned on experimental data to improve predictions. Our results suggest that using TERM-based and coordinate-based features together may be beneficial for protein design and that structure-based neural models that produce Potts energy tables have utility for flexible applications in protein science. This article is protected by copyright. All rights reserved.

PMID:36564857 | DOI:10.1002/pro.4554

Pilot Feasibility Stud. 2022 Dec 23;8(1):263. doi: 10.1186/s40814-022-01220-y.

ABSTRACT

BACKGROUND: Children with congenital heart disease (CHD) undergoing open-heart surgery are at risk for developmental impairments with motor delay manifesting first and contributing to parental concerns. Only a few interventional studies aim to improve neuromotor development in infants with CHD with inconclusive results. We thus developed a family-tailored early motor intervention (EMI-Heart), which aims to promote motor development and family well-being in the first year of life after open-heart surgery. The primary aim described in this protocol is to evaluate feasibility of EMI-Heart. The secondary aim is to describe the difference between the intervention and control group in motor outcomes and family well-being at baseline, post-treatment, and follow-up.

METHODS: This prospective, parallel single-center feasibility randomized controlled trial (RCT) will compare EMI-Heart with standard of care in infants with complex CHD. Sixteen infants and their families, randomly allocated to EMI-Heart or the control group, will participate within the first 5 months of life. Infants assigned to EMI-Heart will receive early motor intervention for 3 months. The intervention’s key is to promote infants’ postural control to enhance motor development and partnering with parents to encourage family well-being. Feasibility outcomes will be (a) clinical recruitment rate and percentage of families completing EMI-Heart, (b) average duration and number of sessions, and (c) acceptability of EMI-Heart using a parental questionnaire post-treatment, and descriptive acceptability of EMI-Heart to the pediatric physiotherapist. Secondary outcomes of the intervention and control group will be infants’ motor outcomes and questionnaires assessing family well-being at 3-5 months (baseline), at 6-8 months (post-treatment), and at 12 months of age (follow-up). We will evaluate feasibility using descriptive statistics. Non-parametric statistical analysis of secondary outcomes will assess differences between the groups at baseline, post-treatment, and follow-up.

DISCUSSION: This feasibility RCT will provide information about a newly developed family-tailored early motor intervention in infants with complex CHD. The RCT design will provide a foundation for a future large-scale interventional trial for infants with CHD after open-heart surgery.

TRIAL REGISTRATION: This study protocol (version 1.3, 01.02.2022) was approved by the Cantonal Ethics Commission Zurich (BASEC-Nr. 2019-01,787) and is registered by Clinicaltrials.gov (NCTT04666857).

PMID:36564855 | DOI:10.1186/s40814-022-01220-y

Radiat Oncol. 2022 Dec 23;17(1):211. doi: 10.1186/s13014-022-02183-3.

ABSTRACT

OBJECTIVE: To establish the dose effect relationship between the dose parameters of stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) and the local tumor control rate.

MATERIALS AND METHODS: A comprehensive literature search was conducted using PubMed, the Web of Science and the Cochrane databases to determine the articles treated with SBRT in early-stage NSCLC. Original studies with complete prescription dose information, tumor local control rate and other important parameters were screened and reported. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as a statistically significant level.

RESULTS: After literature screening, 22 eligible studies were included in probit model regression analysis, involving 1861 patients. There is no significant dose effect relationship between nominal BED₁₀ and peripheral BED₁₀ versus 3 years local control probability. There were significant dose effect relationships between the center BED₁₀ and the average BED₁₀ versus the 3 years local control probability, with P values are 0.001 and < 0.0001, respectively. According to the results of this model, the 3 years local control rate of 90.5% (87.5-92.1%) and 89.5% (86.7-91.0%) can be expected at the center BED₁₀ of 180 Gy or the average BED₁₀ of 140 Gy, prospectively.

CONCLUSIONS: For NSCLC treated with SBRT, more attention should be paid to the central dose and average dose of PTV. A set of clear definition in the dose prescription should be established to ensure the effectiveness and comparability of treatment.

PMID:36564845 | DOI:10.1186/s13014-022-02183-3

BMC Health Serv Res. 2022 Dec 23;22(1):1576. doi: 10.1186/s12913-022-08853-y.

ABSTRACT

BACKGROUND: The indiscriminate use of antimicrobials is considered a major contributing factor to the increase in antimicrobial resistance. Community pharmacies are the main source of access to antimicrobials, and pharmacists are in a strategic position to promote rational use of these medicines. Therefore, it is important to know dispensing service quality.

OBJECTIVE: To evaluate the behavior of pharmacists in dispensing antimicrobials in community pharmacies in northeast Brazil.

METHODS: This cross-sectional pilot study was conducted from August to October 2021 in a private community pharmacy chain in Sergipe. Dispensing was evaluated using the simulated patient (SP) technique. Two SP asked the pharmacists for the antimicrobials (case clinic 1: upper respiratory infection; case clinic 2: urinary tract infection) and recorded the service through audio. Dispensing practices were independently analyzed by two researchers based on the tools available in the literature. Data were presented using descriptive statistics.

RESULTS: A total of 54 simulated patient visits were conducted. Based on the 12 steps recommended by the research team for good dispensing, pharmacists asked an average of 1 (±1.17) question for upper respiratory infections and 0.3 (±0.54) for urinary tract infections, as well as provided counseling (mean number of recommendations, 2.6 (±1.44) and 4.5 (±2.35), respectively). As for communication skills, pharmacists had a regular score (3.07 ± 0.34). Furthermore, there was no significant difference in the number of steps and counseling recommendations by pharmacists in dispensing clinical cases 1 and 2 (p = 0.0674).

CONCLUSION: The quality of antimicrobial dispensing was evaluated as suboptimal, requiring improvements in practice and multifaceted strategies to promote continuing education of these professionals. In addition, awareness actions for the population must be implemented to promote the rational use of antimicrobials and reduce microbial resistance.

PMID:36564839 | DOI:10.1186/s12913-022-08853-y

Cost Eff Resour Alloc. 2022 Dec 23;20(1):72. doi: 10.1186/s12962-022-00398-5.

ABSTRACT

OBJECTIVES: Surgical lung resection involves a critical task of stapled ligation and transection of major vascular structures and tissue, which may lead to bleeding and complications. A newer powered stapling system with Gripping Surface Technology (GST) was introduced to account for tissue movements. This study aimed to examine the real-world effectiveness of GST system on intraoperative and postoperative outcomes of pulmonary resection.

METHODS: A retrospective analysis was conducted using the electronic medical records of Sichuan Provincial People’s Hospital between July 2020 and March 2021 in China. Patients who underwent their first procedures of single-port lobectomy or multi-port segmentectomy by video-assisted thoracoscopic surgery were identified and grouped as GST group or manual stapler group (manual group) by the stapler types. The intraoperative outcomes such as bleeding rate, blood loss volume, and intervention rate at the staple line (including intraoperative pressure, suture, and electrocoagulation) were documented by trained nurses during the surgery. Propensity score matching was performed between the two groups, controlling forage, BMI, smoking history, history of surgery, complications, and level of complexity of pneumonectomy.

RESULTS: A total of 108 matched patients were included in the analysis (54 in the GST group and 54 in the manual group). GST group had lower risks for intraoperative bleeding (22.8% vs 51.9%; p = 0.003) and intraoperative interventions (31.5% vs 55.6%; p = 0.02), compared to the manual group. A decrease in the intraoperative blood loss was observed in the GST group, but not statistically significant (134.39 ± 52.82 ml vs 158.11 ± 73.14 ml, p = 0.102). The use of NEOVEIL (reinforcement material to prevent air leakage from the staple line) intraoperatively during surgery was significantly lower in the GST group (24.1%) than in the manual group (50%, p = 0.01).

CONCLUSION: The GST system was associated with better intraoperative outcomes in clinical practice in China.

PMID:36564821 | DOI:10.1186/s12962-022-00398-5

Gut Pathog. 2022 Dec 23;14(1):49. doi: 10.1186/s13099-022-00525-w.

ABSTRACT

BACKGROUND: Microbial dysbiosis has been closely linked with colorectal cancer development. However, data is limited regarding the relationship of the mucosal microbiome, adenomatous polyps and dietary habits. Understanding these associations may elucidate pathways for risk stratification according to diet.

RESULTS: Patients undergoing screening colonoscopy were included in our prospective, single center study and divided into adenoma or no adenoma cohorts. Oral, fecal, and mucosal samples were obtained. Microbial DNA was extracted, and amplicon libraries generated using primers for the 16S rRNA gene V4 region. Patient and dietary information was collected. Of 104 participants, 44% presented with polyps, which were predominantly tubular adenomas (87%). Adenoma formation and multiple patient dietary and lifestyle characteristics were associated with mucosal microbiome diversity. Lifestyle factors included age, body mass index, adenoma number, and dietary consumption of red meats, processed meats, vegetables, fruit, grain, fermented foods and alcohol.

CONCLUSION: In this study we showed associations between dietary habits, adenoma formation and the mucosal microbiome. These early findings suggest that ongoing research into diet modification may help reduce adenoma formation and subsequently the development of CRC.

PMID:36564812 | DOI:10.1186/s13099-022-00525-w

J Ovarian Res. 2022 Dec 23;15(1):135. doi: 10.1186/s13048-022-01082-1.

ABSTRACT

OBJECTIVE: The aim of the present study is to evaluate the long-term outcomes in patients with early stage ovarian cancer undergoing fertility-sparing surgery.

METHODS: The present study performed a retrospective analysis of recurrence, pregnancy and survival of a total of 66 patients who were diagnosed with early stage ovarian cancer (stage I) in XXX Faculty of Medicine Hospital between 2004 and 2019. Of these patients, 16 had undergone fertility-sparing surgery, and the remaining 50 patients had undergone radical surgery.

RESULTS: Of 66 eligible patients, 16 had undergone fertility-sparing surgery, and the remaining 50 patients had undergone radical complete surgery. When demographic and descriptive data are taken into consideration, the mean age was 32.6 ± 6.76 years in patients undergoing fertility-sparing surgery and 54.05 ± 10.8 years in patients undergoing complete surgery, and the difference between the groups was statistically significant (p = 0.001). Of patients undergoing fertility-sparing surgery, 11 (16.7%) had stage Ia disease (most common), 5 (7.5%) had stage Ic disease, whereas no patient with stage Ib disease was detected. Of patients undergoing complete radical surgery, 32 (48.5%) had stage Ia disease (most common), 1 (1.5%) had stage Ib disease with bilateral ovarian involvement, and stage Ic was the second most common disease stage. Also, stage Ic3 was the most common disease stage (8 patients, 12.1%) among those with stage Ic disease. The rate of recurrence was 4.5% (3 patients) in patients undergoing fertility-sparing surgery, and recurrences occurred at 37 months, 69 months, and 76 months, respectively. A patient with stage Ic3 disease and endometrioid type tumor who developed recurrence at 37 months died at 130 months. Of patients undergoing complete surgery, ten patients (15.2%) developed recurrence, and there was no significant difference between the two groups in terms of recurrence (p = 1.00). At the end of 15-year follow-up period, there was no significant difference between patients undergoing fertility-preserving surgery and those undergoing complete surgery in terms of mortality (p = 0.668).

CONCLUSION: The observation of significant findings in terms of the rate of recurrence and disease-free survival following fertility-sparing surgery in patients with low-risk early stage ovarian cancer suggests that survival is positively affected in early stage ovarian cancer.

PMID:36564811 | DOI:10.1186/s13048-022-01082-1

J Orthop Surg Res. 2022 Dec 23;17(1):563. doi: 10.1186/s13018-022-03462-1.

ABSTRACT

BACKGROUND: The shortening length of the lower extremity after the proximal femoral osteotomy is an important issue to be considered in preoperative planning of developmental dysplasia of the hip (DDH) in children. There is still a lack of research on shortening the length of the lower extremities in different proximal femoral osteotomy varus styles. We aimed to verify the relationship between the shortening length after “point-to-face” and “face-to-face” varus osteotomy and proposed a formula for calculating the difference in shortening length and verified its feasibility.

METHODS: Fifty-five children with unilateral DDH were enrolled. The preoperative hip CT data were imported into mimics 21, 3-Matic 10 (Materialise, Leuven, Belgium) for femoral reconstruction and simulated osteotomy, and the difference (t) was calculated by directly measuring the length of the proximal femur after osteotomy. d* sinθ was measured in a three-dimensional environment to calculate the difference in femoral shortening length between the two osteotomy methods (t’).

RESULTS: The results of the direct measurement method and the formula measurement method are shown in the table; the differences in the results of the femoral shortening length difference were not statistically significant (P > 0.05). The limits of agreement (95%) of the difference values using Bland-Altman analysis were between – 0.50 and 0.46 mm, with a mean of – 0.02 mm, indicating a high agreement between the two methods. r = 0.99 (P < 0.05) for the Pearson correlation analysis between the direct measurement method and the calculated method showed that the two methods were significantly correlated.

CONCLUSIONS: The derived formula can accurately calculate the difference in the shortening length of the proximal femur after “point-to-face” and “face-to-face” varus osteotomy in children with DDH, which is suitable for clinical application.

PMID:36564807 | DOI:10.1186/s13018-022-03462-1