bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMbed: transmembrane proteins predicted through language model embeddings
Authors: Bernhofer Michael , Rost Burkhard 
Published: August 2022

Abstract
Background
Despite the immense importance of transmembrane proteins (TMP) for molecular biology and medicine, experimental 3D structures for TMPs remain about 4–5 times underrepresented compared to non-TMPs. Today’s top methods such as AlphaFold2 accurately predict 3D structures for many TMPs, but annotating transmembrane regions remains a limiting step for proteome-wide predictions.

Results
Here, we present TMbed, a novel method inputting embeddings from protein Language Models (pLMs, here ProtT5), to predict for each residue one of four classes: transmembrane helix (TMH), transmembrane strand (TMB), signal peptide, or other. TMbed completes predictions for entire proteomes within hours on a single consumer-grade desktop machine at performance levels similar or better than methods, which are using evolutionary information from multiple sequence alignments (MSAs) of protein families. On the per-protein level, TMbed correctly identified 94 ± 8% of the beta barrel TMPs (53 of 57) and 98 ± 1% of the alpha helical TMPs (557 of 571) in a non-redundant data set, at false positive rates well below 1% (erred on 30 of 5654 non-membrane proteins). On the per-segment level, TMbed correctly placed, on average, 9 of 10 transmembrane segments within five residues of the experimental observation. Our method can handle sequences of up to 4200 residues on standard graphics cards used in desktop PCs (e.g., NVIDIA GeForce RTX 3060).

Conclusions
Based on embeddings from pLMs and two novel filters (Gaussian and Viterbi), TMbed predicts alpha helical and beta barrel TMPs at least as accurately as any other method but at lower false positive rates. Given the few false positives and its outstanding speed, TMbed might be ideal to sieve through millions of 3D structures soon to be predicted, e.g., by AlphaFold2.
Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer
Authors: Peng Yilin , Zhao Min , Hu Yinying , Guo Hongyan , Zhang Yanyan , Huang Yanqin , Zhao Lin , Chai Yong , Wang Zhigang 
Published: August 2022

Abstract
Background
Tumor-associated macrophages are considered to be a major contributor affecting the development of tumors. Recently, numerous studies have shown that tumor cells were able to educate their microenvironment by delivering a significant amount of exosomes, however, the mechanism that exosomes from PCa cells work in macrophage polarization remains obscure. Therefore, we sought to determine whether blockade of exosome generation by GW4869, an inhibitor of exosome biogenesis, would impede macrophages from differentiating into M2 cells.

Results
In this study, we first obtained exosomes from the supernatant media of PCa cells cultured with exosome-free serum using the Magcapture™ Exosome Isolation Kit PS, and then investigated their effects on macrophages. Our data confirmed that exosomes released by prostate cancer cells can induce macrophages to differentiate into M2 cells. Mechanistically speaking, exosomes exert their effects on macrophages through activating the AKT and STAT3 signaling pathways. Importantly, treatment with GW4869 significantly inhibited the release of exosomes from PCa cells, and further impaired M2 differentiation of macrophages and their pro-tumor activity. We also demonstrated that GW4869 was able to inhibit the education of M2 macrophages, and then inhibit the progression of prostate cancer in vivo.

Conclusions
In brief, our findings indicated that GW4869 impeded the PCa exosome-induced M2 differentiation of macrophages and the progression of prostate cancer, suggesting that GW4869 could play an important role in the treatment of prostate cancer metastasis as an inhibitor of tumor exosome secretion.
Integrated metabolomic and transcriptomic analyses of the parasitic plant Cuscuta japonica Choisy on host and non-host plants
Authors: Guo Chenglin , Qin Liuyan , Ma Yongling , Qin Jianlin 
Published: August 2022

Abstract
Background
Cuscuta japonica Choisy (Japanese dodder) is a parasitic weed that damages many plants and affects agricultural production. The haustorium of C. japonica plays a key role during parasitism in host plants; in contrast, some non-host plants effectively inhibit its formation. However, the metabolic differences between normal dodder in host plants and dodder inhibition in non-host plants are largely unknown. Here, we utilized an integrative analysis of transcriptomes and metabolomes to compare the differential regulatory mechanisms between C. japonica interacting with the host plant Ficus microcarpa and the non-host plant Mangifera indica.

Results
After parasitization for 24 h and 72 h, the differentially abundant metabolites between these two treatments were enriched in pathways associated with α-linolenic acid metabolism, linoleic acid metabolism, phenylpropanoid biosynthesis, and pyrimidine metabolism. At the transcriptome level, the flavor biosynthesis pathway was significantly enriched at 24 h, whereas the plant–pathogen interaction, arginine and proline metabolism, and MARK signaling-plant pathways were significantly enriched at 72 h, based on the differentially expressed genes between these two treatments. Subsequent temporal analyses identified multiple genes and metabolites that showed different trends in dodder interactions between the host and non-host plants. In particular, the phenylpropanoid biosynthesis pathway showed significant differential regulation between C. japonica in host and non-host plants.

Conclusions
These results provide insights into the metabolic mechanisms of dodder–host interactions, which will facilitate future plant protection from C. japonica parasitism.
Nutrition mediates the relationship between number of teeth and sarcopenia: a pathway analysis
Authors: Xia Xin , Xu Zhigang , Hu Fengjuan , Hou Lisha , Zhang Gongchang , Liu Xiaolei 
Published: August 2022

Abstract
Objectives
The relationship between the number of teeth and sarcopenia remains poorly investigated. Although nutrition plays an important role in maintaining bone and muscle health, the complex relationship between number of teeth and nutrition in the pathogenesis of sarcopenia remains to be elucidated.

Methods
A large multi-ethnic sample of 4149 participants aged over 50 years old from West China Health and Aging Trend (WCHAT) study was analyzed. We examined the associations between number of teeth with nutritional status and sarcopenia, and the mediating role of nutrition in the association between number of teeth and sarcopenia. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. We assessed nutrition using Mini Nutrition Assessment-Short Form (MNA-SF) scale. Direct relationships between number of teeth, nutrition and sarcopenia were assessed using multiple linear regression. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition in the relationship between number of teeth and sarcopenia.

Results
Of 4149 participants aged 50 years old or older, the prevalence of sarcopenia was 22.5, 9.0% for moderate sarcopenia, and 13.5% for severe sarcopenia, respectively. Regression analysis indicated a total association between number of teeth (β = − 0.327, 95% CI − 0.471 to − 0.237, p < 0.001) and sarcopenia. After adjusted MNA-SF scores, the association between number of teeth and sarcopenia was still significant (β = − 0.269, 95% CI − 0.364 to − 0.175, p < 0.001), indicating a partial mediation effect of nutrition. Mediation analysis verified nutrition partially mediate the associations between number of teeth and sarcopenia (indirect effect estimate = − 0.0272, bootstrap 95% CI − 0.0324 to − 0.0222; direct effect estimate = − 0.0899, bootstrap 95% CI − 0.1049 to − 0.0738). And this mediation effect was through impacting SMI (indirect effect estimate = − 0.0283, bootstrap 95% CI − 0.0336 to − 0.0232) and grip strength (indirect effect estimate = − 0.0067, bootstrap 95% CI − 0.0094 to − 0.0043). Structural equation model (SEM) framework pathway analysis confirmed the association between number of teeth, nutrition, and sarcopenia.

Conclusions
Our findings indicated that sarcopenia was associated with number of teeth and poorer nutritional status, with nutrition partially mediating the association between number of teeth and sarcopenia. Our findings supported early nutritional assessment and intervention in oral health to mitigate the risk of sarcopenia.
LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells
Authors: Li Li , Li Fengyang , Hu Xiuhong , Wu Zengshuai , Ren Wenbo , Wang Tingting , Ji Zhengchao , Li Na , Gu Jingmin , Sun Changjiang , Feng Xin , Han Wenyu , Huang Jing , Lei Liancheng 
Published: August 2022

Abstract
Background
IFN-γ has been traditionally recognized as an inflammatory cytokine that involves in inflammation and autoimmune diseases. Previously we have shown that sustained IFN-γ induced malignant transformation of bovine mammary epithelial cells (BMECs) via arginine depletion. However, the molecular mechanism underlying this is still unknown.

Methods
In this study, the amino acids contents in BMECs were quantified by a targeted metabolomics method. The acquisition of differentially expressed genes was mined from RNA-seq dataset and analyzed bioinformatically. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) assay were performed to detect gene mRNA and protein expression levels. CCK-8 and would healing assays were used to detect cell proliferation and migration abilities, respectively. Cell cycle phase alternations were analyzed by flow cytometry.

Results
The targeted metabolomics analysis specifically discovered IFN-γ induced arginine depletion through accelerating arginine catabolism and inhibiting arginine anabolism in BMECs. Transcriptome analysis identified leucine aminopeptidase 3 (LAP3), which was regulated by p38 and ERK MAPKs, to downregulate arginine level through interfering with argininosuccinate synthetase (ASS1) as IFN-γ stimulated. Moreover, LAP3 also contributed to IFN-γ-induced malignant transformation of BMECs by upregulation of HDAC2 (histone deacetylase 2) expression and promotion of cell cycle proteins cyclin A1 and D1 expressions. Arginine supplementation did not affect LAP3 and HDAC2 expressions, but slowed down cell cycle process of malignant BMECs. In clinical samples of patients with breast cancer, LAP3 was confirmed to be upregulated, while ASS1 was downregulated compared with healthy control.

Conclusions
These results demonstrated that LAP3 mediated IFN-γ-induced arginine depletion to malignant transformation of BMECs. Our findings provide a potential therapeutic target for breast cancer both in humans and dairy cows.
Do hospital workers experience a higher risk of respiratory symptoms and loss of lung function?
Authors: Heibati Behzad , Jaakkola Maritta S. , Lajunen Taina K. , Ducatman Alan , Veysi Rahmat , Karimi Ali , Jaakkola Jouni J. K. 
Published: August 2022

Abstract
Background
Hospital work environment contains various biological and chemical exposures that can affect indoor air quality and have impact on respiratory health of the staff. The objective of this study was to investigate potential effects of occupational exposures on the risk of respiratory symptoms and lung function in hospital work, and to evaluate potential interaction between smoking and occupational exposures.

Methods
We conducted a cross-sectional study of 228 staff members in a hospital and 228 employees of an office building as the reference group in Shiraz, Iran. All subjects completed a standardized ATS respiratory questionnaire and performed a spirometry test.

Results
In Poisson regression, the adjusted prevalence ratios (aPR) among the hospital staff were elevated for cough (aPR 1.90, 95% CI 1.15, 3.16), phlegm production (aPR 3.21, 95% CI 1.63, 6.32), productive cough (aPR 2.83, 95% CI 1.48, 5.43), wheezing (aPR 3.18, 95% CI 1.04, 9.66), shortness of breath (aPR 1.40, 95% CI 0.93, 2.12), and chest tightness (aPR 1.73, 95% CI 0.73, 4.12). Particularly laboratory personnel experienced increased risks of most symptoms. In linear regression adjusting for confounding, there were no significant differences in lung function between the hospital and office workers. There was an indication of synergism between hospital exposures and current smoking on FEV1/FVC% (interaction term β = − 5.37, 95% CI − 10.27, − 0.47).

Conclusions
We present significant relations between hospital work, especially in laboratories, and increased risks of respiratory symptoms. Smoking appears to enhance these effects considerably. Our findings suggest that policymakers should implement evidence-based measures to prevent these occupational exposures.
Oncologic and functional outcomes of different reconstruction modalities after resection of chondrosarcoma of the scapula: a medium- to long-term follow-up study
Authors: Yu Xiao-Jun , Liu Qi-Kun , Wang Ying-Guang , Wang Shan-Xi , Lu Rui , Xu Hao-Ran , Wan Jun-Lai , Kang Hao 
Published: August 2022

Abstract
Objectives
To evaluate the oncologic and functional results of scapular reconstruction after partial or total scapulectomy for chondrosarcoma.

Materials and methods
Twenty-one patients with chondrosarcoma who underwent partial or total scapulectomy between January 2005 and July 2019 were reviewed retrospectively.

Results
At a mean follow-up of 62.6 months (range, 13–123 months), four patients developed local recurrence, and three developed distant metastases, one of which developed both recurrence and metastasis. The overall survival rate of patients at 5 years was 84.6%, the disease-free survival rate was 69.3%, and the complication rate was 19% (4/21). The 1993 American Musculoskeletal Tumor Society (MSTS93) scores of patients in the partial scapulectomy group, total scapulectomy + humeral suspension group and prosthetic reconstruction group were 26.50 ± 1.38, 19.00 ± 2.58, and 21.38 ± 2.62, respectively. There was a statistically significant difference between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group ( P = 0.006 and 0.0336, respectively). The range of motion of the shoulder joint for forward flexion was 80.83° ± 11.14°, 51.25° ± 21.36°, and 52.50° ± 11.02°, respectively. The p-values for the comparison between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group were 0.0493 and 0.0174, respectively. And the range of motion of abduction was 75.00° ± 10.49°, 32.50° ± 11.90°, 41.88° ± 11.63°, respectively. Patients in the partial scapulectomy group had significantly better postoperative shoulder abduction function than the total scapulectomy + humeral suspension or prosthetic reconstruction group (P = 0.0035 and 0.0304, respectively). There was no significant difference in MSTS93 scores and flexion and abduction function of the shoulder joint in the upper extremity after total scapulectomy with humeral suspension or prosthetic reconstruction (P > 0.05).

Conclusions
Surgical treatment of chondrosarcoma of the scapula can achieve a satisfactory prognosis and shoulder function. Total scapulectomy followed by prosthetic reconstruction or humeral suspension are both feasible treatments.
Quality assessment and relevant clinical impact of randomized controlled trials on chronic prostatitis/chronic pelvic pain syndrome
Authors: Zhao Ming , Gao Qing-He , Liu Sheng-Jing , Deng Ying-Jun , Wang Hao , Yu Wen-Xiao , Guo Jun 
Published: August 2022

Abstract
Objective
This study evaluated the quality of randomized controlled trials (RCTs) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods
We searched PubMed, Web of Science, and Embase for RCTs (original articles) on CP/CPPS published from database establishment to 2021. The RCT quality assessment was performed using the Consolidated Standards of Reporting of Trials (CONSORT) statement and the improved Jadad scale.

Results
In total, 77 RCTs were included. According to the evaluation, 26 (33.77%) papers presented the description of the specific random methods, only 6 (7.79%) papers described the allocation concealment methods, and 26 (33.77%) articles referred to the “blind method”. Of the RCTs, 34 (44.16%) papers recorded the number of patients who withdrew from the study, and 67 (87.01%) papers reported adverse reactions. However, few reports mentioned the sample size calculation, clinical trial registration, or information about the relevant research programs and funding. In addition, 19 (24.68%) reports had Jadad scale scores of ≥ 4 points, and 58 (75.32%) reports had Jadad scale scores of ≤ 3 points.

Conclusion
To date, the quality of RCT reports on CP/CPPS needs to be further improved, and the results of the RCTs should be accepted and utilized cautiously. It is suggested that researchers should follow the CONSORT statement and the improved Jadad scale to standardize the design and implementation of RCTs to improve the quality of RCTs and provide reliable evidence for the treatment of CP/CPPS.
3D printed scaffold for repairing bone defects in apical periodontitis
Authors: Li Cong , Xu Xiaoyin , Gao Jing , Zhang Xiaoyan , Chen Yao , Li Ruixin , Shen Jing 
Published: August 2022

Abstract
Objectives
To investigate the feasibility of the 3D printed scaffold for periapical bone defects.

Methods
In this study, antimicrobial peptide KSL-W-loaded PLGA sustainable-release microspheres (KSL-W@PLGA) were firstly prepared followed by assessing the drug release behavior and bacteriostatic ability against Enterococcus faecalis and Porphyromonas gingivalis. After that, we demonstrated that KSL-W@PLGA/collagen (COL)/silk fibroin (SF)/nano-hydroxyapatite (nHA) (COL/SF/nHA) scaffold via 3D-printing technique exhibited significantly good biocompatibility and osteoconductive property. The scaffold was characterized as to pore size, porosity, water absorption expansion rate and mechanical properties. Moreover, MC3T3-E1 cells were seeded into sterile scaffold materials and investigated by CCK-8, SEM and HE staining. In the animal experiment section, we constructed bone defect models of the mandible and evaluated its effect on bone formation. The Japanese white rabbits were killed at 1 and 2 months after surgery, the cone beam computerized tomography (CBCT) and micro-CT scanning, as well as HE and Masson staining analysis were performed on the samples of the operation area, respectively. Data analysis was done using ANOVA and LSD tests. (α = 0.05).

Results
We observed that the KSL-W@PLGA sustainable-release microspheres prepared in the experiment were uniform in morphology and could gradually release the antimicrobial peptide (KSL-W), which had a long-term antibacterial effect for at least up to 10 days. HE staining and SEM showed that the scaffold had good biocompatibility, which was conducive to the adhesion and proliferation of MC3T3-E1 cells. The porosity and water absorption of the scaffold were (81.96 ± 1.83)% and (458.29 ± 29.79)%, respectively. Histological and radiographic studies showed that the bone healing efficacy of the scaffold was satisfactory.

Conclusions
The KSL-W@PLGA/COL/SF/nHA scaffold possessed good biocompatibility and bone repairing ability, and had potential applications in repairing infected bone defects.
Clinical significance The 3D printed scaffold not only has an antibacterial effect, but can also promote bone tissue formation, which provides an alternative therapy option in apical periodontitis.
Examining the adoption and implementation of behavioral electronic health records by healthcare professionals based on the clinical adoption framework
Authors: Yoo Sooyoung , Lim Kahyun , Jung Se Young , Lee Keehyuck , Lee Donghyun , Kim Seok , Lee Ho-Young , Hwang Hee 
Published: August 2022

Abstract
Background
While various quantitative studies based on the Unified Theory of Acceptance and Use of Technology (UTAUT) and Technology Acceptance Models (TAM) exist in the general medical sectors, just a few have been conducted in the behavioral sector; they have all been qualitative interview-based studies.

Objective
The purpose of this study is to assess the adoption dimensions of a behavioral electronic health record (EHR) system for behavioral clinical professionals using a modified clinical adoption (CA) research model that incorporates a variety of micro, meso, and macro level factors.

Methods
A questionnaire survey with quantitative analysis approach was used via purposive sampling method. We modified the existing CA framework to be suitable for evaluating the adoption of an EHR system by behavioral clinical professionals. We designed and verified questionnaires that fit into the dimensions of the CA framework. The survey was performed in five US behavioral hospitals, and the adoption factors were analyzed using a structural equation analysis.

Results
We derived a total of seven dimensions, omitting those determined to be unsuitable for behavioral clinical specialists to respond to. We polled 409 behavioral clinical experts from five hospitals. As a result, the ease of use and organizational support had a substantial impact on the use of the behavioral EHR system. Although the findings were not statistically significant, information and service quality did appear to have an effect on the system's ease of use. The primary reported benefit of behavioral EHR system adoption was the capacity to swiftly locate information, work efficiently, and access patient information via a mobile app, which resulted in more time for better care. The primary downside, on the other hand, was an unhealthy reliance on the EHR system.

Conclusions
We demonstrated in this study that the CA framework can be a useful tool for evaluating organizational and social elements in addition to the EHR system's system features. Not only the EHR system's simplicity of use, but also organizational support, should be considered for the effective implementation of the behavioral EHR system.
Trial Registration: The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No.: B-1904-534-301).