bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychotropic medication use in people living with severe and persistent mental illness in the Australian community: a cross-sectional study
Authors: Hu Jie , McMillan Sara S , Theodoros Theo , Collins Jack C , El-Den Sarira , O’Reilly Claire L , Wheeler Amanda J 
Published: November 2022

Abstract
Background
Psychotropic polypharmacy and high-dose prescribing may play a role in therapy, however, with associated risks. The aim of this study was to describe current prescribing practices and use of four psychotropic medication groups (antipsychotics, antidepressants, mood stabilisers and benzodiazepines), focusing on polypharmacy (across and within groups) and high-dose prescribing in adults experiencing severe and persistent mental illness (SPMI) in the Australian community.

Methods
318 people taking psychotropic medication for SPMI had a medication review undertaken by a community pharmacist. Participants were recruited as part of an RCT from three Australian states/territories between September 2020-July 2021. All psychotropic medication and daily doses were recorded and reviewed for alignment with current clinical guidelines. Univariate and multiple logistic regression models investigated factors associated with antipsychotic, antidepressant, and mood stabiliser polypharmacy, and antipsychotic and antidepressant high-dose therapy. Variables included age, gender, geographic location, self- reported mental illness(es), hospital admission(s) in previous 6-months and prescriber type.

Results
806 psychotropic medications were prescribed for the 318 participants. Mood stabiliser polypharmacy was recorded in 19.0% of participants prescribed mood stabilisers; antipsychotic polypharmacy in 18.4% of participants prescribed antipsychotics; antidepressant polypharmacy in 11.3% of those prescribed antidepressants; and three participants (5.1%) were prescribed two benzodiazepines concurrently. Almost 18.6% of the cohort was receiving high-dose treatment; 18 participants were prescribed high-dose antipsychotics and 39 high-dose antidepressants, with two participants prescribed both. Adjusted logistic regression for polypharmacy found male gender, psychiatrist as sole prescriber, or multiple prescribers, were associated with antipsychotic polypharmacy. The adjusted model for high-dose therapy found psychiatrist as sole prescriber was significantly associated with antipsychotic and antidepressant high-dose prescribing.

Conclusion
Psychotropic polypharmacy was common in this community cohort experiencing SPMI. Whilst polypharmacy is not always inappropriate, it is a complex construct with potential benefits alongside potential risks. Benefits and harms need to be balanced however this practice is not supported by clear guidance to assist health practitioners. This study highlights the important need for regular medication reviews and strengthened communication between consumers and all healthcare professionals involved in community mental health care, to support safe and effective use of psychotropic medications.
The predictive role of coping styles and sense of coherence in the post-traumatic growth of mothers with disabled children: a cross-sectional study
Authors: Farhadi Akram , Bahreini Masoud , Moradi Ainaz , Mirzaei Kamran , Nemati Reza 
Published: November 2022

Abstract
Background
Coping and accepting stressful events can lead to positive psychological changes, growth, and excellence. In this regard, the present study was conducted to determine the relationship between coping styles and sense of coherence with post-traumatic growth in mothers with disabled children in Bushehr (a southern city in Iran).

Methods
The present cross-sectional study was performed on 260 mothers with children with disabilities who were filed in the rehabilitation centers covered by the Welfare Department of Bushehr in 2018. Demographic information form, Tedeschi and Calhoun post-traumatic growth questionnaire, Antonovsky sense of coherence, and Billings and Moos coping styles were employed to collect data. Data were analyzed by SPSS software using Pearson correlation coefficient and linear regression analysis at a significance level of less than 0.05.

Results
The mean age and standard deviation were 35.83 ± 7.41 for the mothers, and 7.20 ± 4.05 for the children. The mean and standard deviation of post-traumatic growth was 64.88 ± 14.90, sense of coherence was 116.36 ± 22.65 and coping styles was 30.59 ± 6.39. The results of linear regression show that only the two dimensions of meaningfulness (p = 0.013 and β = 0.170) and manageability from the sense of coherence (p = 0.001 and β = 0.432) can predict post-traumatic growth in mothers with disabled children in Bushehr. Also, from the coping style dimensions, only the emotion-focused variable (p = 0.001 and β = 0.353) is a predictor of post-traumatic growth.

Conclusion
Considering the role of sense of coherence and coping style in predicting post-traumatic growth, to implement rehabilitation programs and support the families of these children, it is essential to plan for the development of social and psychological support for mothers with disabled children.
A simple method for restoring the femoral head center in hip arthroplasty: a 3-dimensional analysis in the Chinese population
Authors: Tian Zui , Mao Xingjia , Gao Zhenzhong , Chen Bohong , Wang Zehua , Yin Zhiwen , Guo Zijian , Gao Ze , Xiang Chuan 
Published: November 2022

AbstractBackgroundVarious authors have successfully demonstrated that the distance from the greater trochanter to the femoral head center (GTFHC) and the distance from the lesser trochanter to the femoral head center (LTFHC) can be used as parameters to determine the recovery of the femoral head center (FHC) during hip arthroplasty. It is necessary to undertake an anatomical study concerning the correlations between the greater trochanter (GT), the lesser trochanter (LT), and the FHC using data obtained from the 3D-CT reconstruction method.MethodsThe study comprised 293 patients (151 males and 142 females), with an average age of 65.06 years. The femoral head diameter(FHD), the linear distance from FHC to GT (GTFHC), and the linear distance from FHC to LT(LTFHC) were all measured and recorded data. The correlation between FHD with LTFHC and GTFHC was assessed using Pearson correlation coefficients, and the ratio of LTFHC and GTFHC to FHD was calculated from this ratio. All measured parameters were compared between the left and right sides and the sexes of the participants.ResultsThe average ratios of GTFHC/FHD and LTFHC/FHD were 0.99 and 0.95, respectively .96% of the LTFHC had absolute lateral differences of < 4 mm . 92% of the GTFHC had absolute lateral differences of < 4 mm.ConclusionLTFHC and GTFHC are reliable reference parameters for preoperative planning and reconstruction of FHC of hip arthroplasty. The ratio displayed in this research may yield insight into a practical and straightforward method for orthopedic surgeons to perform hip arthroplasty in patients with femoral neck fractures. Ratios from studies based on the same race may be desirable for future work.
Identifying the key genes regulating mesenchymal stem cells chondrogenic differentiation: an in vitro study
Authors: Liang Tongzhou , Li Pengfei , Liang Anjing , Zhu Yuanxin , Qiu Xianjian , Qiu Jincheng , Peng Yan , Huang Dongsheng , Gao Wenjie , Gao Bo 
Published: November 2022

Abstract
Background
Mesenchymal stem cells (MSCs) possess the potential to differentiate into chondrocytes, which makes them an ideal source for healing cartilage defects. Here, we seek to identify the essential genes participating in MSCs chondrogenesis.

Methods
Human MSCs were induced for chondrogenesis for 7, 14, and 21 days using a high-density micromass culture system, and RNA was extracted for RNA-seq.

Results
A total of 6247 differentially expressed genes (DEGs) were identified on day 7, and 85 DEGs were identified on day 14. However, no significant DEGs was identified on day 21. The top 30 DEGs at day 7, including COL9A3, COL10A1, and CILP2, are closely related to extracellular matrix organization. While the top 30 DEGs at day 14 revealed that inflammation-related genes were enriched, including CXCL8, TLR2, and CCL20. We also conducted protein–protein interaction (PPI) networks analysis using the search tool for the retrieval of interacting genes (STRING) database and identified key hub genes, including CXCL8, TLR2, CCL20, and MMP3. The transcriptional factors were also analyzed, identifying the top 5 TFs: LEF1, FOXO1, RORA, BHLHE41, and SOX5. We demonstrated one particular TF, RORA, in promoting early MSCs chondrogenesis.

Conclusions
Taken together, our results suggested that these DEGs may have a complex effect on MSCs chondrogenesis both synergistically and solitarily.
The original and two new derivative versions of the COMPERA 2.0 risk assessment model: useful tools for guiding balloon pulmonary angioplasty
Authors: Zhang Yi , Li Xin , Jin Qi , Luo Qin , Zhao Qing , Yang Tao , Zeng Qixian , Yan Lu , Duan Anqi , Huang Zhihua , Hu Meixi , Xiong Changming , Zhao Zhihui , Liu Zhihong 
Published: November 2022

Abstract
Background
The COMPERA 2.0 4-stratum (4-S) risk score has been demonstrated superior over the 3-stratum (3-S) one in patients with pulmonary arterial hypertension and medically managed patients with chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to determine the prognostic value of the original 4-S and 3-S COMPERA 2.0 risk score and two new derivative versions in CTEPH patients who underwent balloon pulmonary angioplasty (BPA).

Methods
We retrospectively enrolled 175 BPA-treated patients with CTEPH. We assessed the risk stratification before and after each BPA session of CTEPH patients by the original 4-S and 3-S COMPERA 2.0 risk score (by rounding decimal to the nearest integer) and two new proposed derivative versions: the modified version (by rounding decimal to the next integer) and a hybrid version that fuses the original and modified versions. The primary endpoint was clinical worsening events. The secondary outcomes were achieving low-risk profile and mean pulmonary arterial pressure (mPAP) < 30 mmHg at follow-up. We used the Kaplan–Meier curve analysis to assess the survival differences between stratified patients. The comparative model’s performance was evaluated in terms of discrimination by Harrell’s C-index.

Results
All versions of COMPERA 2.0 4-S model outperformed the 3-S one in discriminating the differences in echocardiographic and hemodynamic parameters and clinical worsening-free survival rates. The original and hybrid 4-S model could independently predict the primary and secondary endpoints, and the hybrid version seemed to perform better. The first BPA session could significantly improve risk profiles, and these changes were associated with the likelihood of experiencing clinical worsening events, achieving a low-risk profile and mPAP < 30 mmHg at follow-up. The number of BPA sessions required to achieve low risk/mPAP < 30 mmHg increased as the baseline risk score escalated.

Conclusions
The COMPERA 2.0 4-S model outperformed the 3-S one in BPA-treated patients with CTEPH. The 4-S model, especially its hybrid version, could be used to predict clinical outcome before the initiation of BPA and monitor treatment response.
Prediction and prognosis of adverse maternal and foetal/neonatal outcomes in pulmonary hypertension: an observational study and nomogram construction
Authors: Chen Yuqin , Zhou Dansha , Xiong Mingmei , Xi Xin , Zhang Wenni , Zhang Ruifeng , Chen Lishi , Jiang Qian , Lai Ning , Li Xiang , Luo Jieer , Li Xuanyi , Feng Weici , Gao Chuhui , Chen Jiyuan , Fu Xin , Hong Wei , Jiang Mei , Yang Kai , Lu Wenju , Luo Yiping , Zhang Jun , Cheng Zhe , Liu Chunli , Wang Jian 
Published: November 2022

Abstract
Background
Pregnant women with pulmonary hypertension (PH) have higher mortality rates and poor foetal/neonatal outcomes. Tools to assess these risk factors are not well established.

Methods
Predictive and prognostic nomograms were constructed using data from a “Development” cohort of 420 pregnant patients with PH, recorded between January 2009 and December 2018. Logistic regression analysis established models to predict the probability of adverse maternal and foetal/neonatal events and overall survival by Cox analysis. An independent “Validation” cohort comprised data of 273 consecutive patients assessed from January 2019 until May 2022. Nomogram performance was evaluated internally and implemented with online software to increase the ease of use.

Results
Type I respiratory failure, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide $$\ge$$
≥
1400 ng/L, arrhythmia, and eclampsia with pre-existing hypertension were independent risk factors for maternal mortality or heart failure. Type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, New York Heart Association functional class, and N-terminal pro-brain natriuretic peptide $$\ge$$
≥
1400 ng/L were independent predictors of pulmonary hypertension survival during pregnancy. For foetal/neonatal adverse clinical events, type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, parity, platelet count, fibrinogen, and left ventricular systolic diameter were important predictors. Nomogram application for the Development and Validation cohorts showed good discrimination and calibration; decision curve analysis demonstrated their clinical utility.

Conclusions
The nomogram and its online software can be used to analyse individual mortality, heart failure risk, overall survival prediction, and adverse foetal/neonatal clinical events, which may be useful to facilitate early intervention and better survival rates.
Enhancement of fatty acid degradation pathway promoted glucoamylase synthesis in Aspergillus niger
Authors: Qi Jie , Xiao Xianzun , Ouyang Liming , Yang Chenghan , Zhuang Yingping , Zhang Lixin 
Published: November 2022

AbstractBackgroundOur recent multi-omics analyses of glucoamylase biosynthesis inAspergillus niger(A. niger) suggested that lipid catabolism was significantly up-regulated during high-yield period under oxygen limitation. Since the catabolism of fatty acids can provide energy compounds such as ATP and important precursors such as acetyl-CoA, we speculated that enhancement of this pathway might be beneficial to glucoamylase overproduction.ResultsBased on previous transcriptome data, we selected and individually overexpressed five candidate genes involved in fatty acid degradation under the control of the Tet-on gene switch inA. niger. Overexpression of thefadE,fadAandcypgenes increased the final specific enzyme activity and total secreted protein on shake flask by 21.3 ~ 31.3% and 16.0 ~ 24.2%, respectively. And a better inducible effect by doxycycline was obtained from early logarithmic growth phase (18 h) than stationary phase (42 h). Similar with flask-level results, the glucoamylase content and total extracellular protein in engineered strains OE-fadE(overexpressingfadE) and OE-fadA(overexpressingfadA) on maltose-limited chemostat cultivation were improved by 31.2 ~ 34.1% and 35.1 ~ 38.8% compared to parental strain B36. Meanwhile, intracellular free fatty acids were correspondingly decreased by 41.6 ~ 44.6%. The metabolomic analysis demonstrated intracellular amino acids pools increased 24.86% and 18.49% in two engineered strains OE-fadEand OE-fadAcompared to B36. Flux simulationrevealed that increased ATP, acetyl-CoA and NADH was supplied into TCA cycle to improve amino acids synthesis for glucoamylase overproduction.ConclusionThis study suggested for the first time that glucoamylase production was significantly improved inA. nigerby overexpression of genesfadEandfadAinvolved in fatty acids degradation pathway. Harnessing the intracellular fatty acids could be a strategy to improve enzyme production inAspergillus nigercell factory.
New strategy for antimetastatic treatment of lung cancer: a hypothesis based on circulating tumour cells
Authors: Que Zujun , Tian Jianhui 
Published: November 2022

AbstractMetastasis is the primary cause of death in lung cancer patients. However, until now, effective drugs and intervention strategies for treating lung cancer metastasis have been lacking. This hypothesis focuses on circulating tumour cells (CTCs) to develop a new antimetastatic therapeutic strategy for lung cancer. Here, we outline the role of CTCs in tumour metastasis and their functional effects during the treatment of lung cancer patients. Additionally, we hypothesized the possibility of CTCs as a novel biomarker and therapeutic target in preventing and treating metastasis in patients with early-stage lung cancer. We hope that the realization of this hypothesis will improve the overall survival of lung cancer.
Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC)
Authors: Katase Naoki , Nishimatsu Shin-ichiro , Yamauchi Akira , Okano Shinji , Fujita Shuichi 
Published: November 2022

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck. We identified cancer-specific genes in HNSCC and focused on DKK3 expression. DKK3 gene codes two isoforms of proteins (secreted and non-secreted) with two distinct cysteine rich domains (CRDs). It is reported that DKK3 functions as a negative regulator of oncogenic Wnt signaling and, is therefore, considered to be a tumor suppressor gene. However, our series of studies have demonstrated that DKK3 expression is specifically high in HNSCC tissues and cells, and that DKK3 might determine the malignant potentials of HNSCC cells via the activation of Akt. Further analyses strongly suggested that both secreted DKK3 and non-secreted DKK3 could activate Akt signaling in discrete ways, and consequently exert tumor promoting effects. We hypothesized that DKK3 might be a specific druggable target, and it is necessary to establish a DKK3 inhibitor that can inhibit both secreted and non-secreted isoforms of DKK3.

Methods
Using inverse polymerase chain reaction, we generated mutant expression plasmids that express DKK3 without CRD1, CRD2, or both CRD1 and CRD2 (DKK3ΔC1, DKK3ΔC2, and DKK3ΔC1ΔC2, respectively). These plasmids were then transfected into HNSCC-derived cells to determine the domain responsible for DKK3-mediated Akt activation. We designed antisense peptides using the MIMETEC program, targeting DKK3-specific amino acid sequences within CRD1 and CRD2. The structural models for peptides and DKK3 were generated using Raptor X, and then a docking simulation was performed using CluPro2. Afterward, the best set of the peptides was applied into HNSCC-derived cells, and the effects on Akt phosphorylation, cellular proliferation, invasion, and migration were assessed. We also investigated the therapeutic effects of the peptides in the xenograft models.

Results
Transfection of mutant expression plasmids and subsequent functional analyses revealed that it is necessary to delete both CRD1 and CRD2 to inhibit Akt activation and inhibition of proliferation, migration, and invasion. The inhibitory peptides for CRD1 and CRD2 of DKK3 significantly reduced the phosphorylation of Akt, and consequently suppressed cellular proliferation, migration, invasion and in vivo tumor growth at very low doses.

Conclusions
This inhibitory peptide represents a promising new therapeutic strategy for HNSCC treatment.
Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial
Authors: Simpson Rupert F. G. , Dankiewicz Josef , Karamasis Grigoris V. , Pelosi Paolo , Haenggi Matthias , Young Paul J. , Jakobsen Janus Christian , Bannard-Smith Jonathan , Wendel-Garcia Pedro D. , Taccone Fabio Silvio , Nordberg Per , Wise Matt P. , Grejs Anders M. , Lilja Gisela , Olsen Roy Bjørkholt , Cariou Alain , Lascarrou Jean Baptiste , Saxena Manoj , Hovdenes Jan , Thomas Matthew , Friberg Hans , Davies John R. , Nielsen Niklas , Keeble Thomas R. 
Published: November 2022

Abstract
Background
Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes.

Methods
In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4–6 on modified Rankin scale).

Results
A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84–1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80–1.26).

Conclusions
Using a hospital’s average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.
Functional analysis of the dehydratase domains of the PUFA synthase from Emiliania huxleyi in Escherichia coli and Arabidopsis thaliana
Authors: Chen Bihan , Wang Feng , Xie Xi , Liu Huifan , Liu Dongjie , Ma Lukai , Xiao Gengsheng , Wang Qin 
Published: November 2022

Abstract
Background
Polyunsaturated fatty acid (PUFA) synthase is a multi-domain mega-enzyme that effectively synthesizes a series of PUFAs in marine microorganisms. The dehydratase (DH) domain of a PUFA synthase plays a crucial role in double bond positioning in fatty acids. Sequencing results of the coccolithophore Emiliania huxleyi (E. huxleyi, Eh) indicated that this species contains a PUFA synthase with multiple DH domains. Therefore, the current study, sought to define the functions of these DH domains (EhDHs), by cloning and overexpressing the genes encoding FabA-like EhDHs in Escherichia coli (E. coli) and Arabidopsis thaliana (A. thaliana).

Results
A complementation test showed that the two FabA-like DH domains could restore DH function in a temperature-sensitive (Ts) mutant. Meanwhile, overexpression of FabA-like EhDH1 and EhDH2 domains increased the production of unsaturated fatty acids (UFAs) in recombinant E. coli by 43.5–32.9%, respectively. Site-directed mutagenesis analysis confirmed the authenticity of active-site residues in these domains. Moreover, the expression of tandem EhDH1-DH2 in A. thaliana altered the fatty acids content, seed weight, and germination rate.

Conclusions
The two FabA-like DH domains in the E. huxleyi PUFA synthase function as 3-hydroxyacyl-acyl carrier protein dehydratase in E. coli. The expression of these domains in E. coli and A. thaliana can alter the fatty acid profile in E. coli and increase the seed lipid content and germination rate in A. thaliana. Hence, introduction of DH domains controlling the dehydration process of fatty acid biosynthesis in plants might offer a new strategy to increase oil production in oilseed plants.