bluuebunny/crossref_metadata_2025 huggingface dataset:
Ceramide kinase mediates intrinsic resistance and inferior response to chemotherapy in triple‐negative breast cancer by upregulating Ras/ERK and PI3K/Akt pathways
Authors: Zhu Shan , Xu Yulin , Wang Lijun , Liao Shichong , Wang Yuan , Shi Manman , Tu Yi , Zhou Yurong , Wei Wen
Published: January 2021

Background

Clinical management of triple-negative breast cancer (TNBC) patients remain challenging because of the development of chemo-resistance. Identification of biomarkers for risk stratification of chemo-resistance and therapeutic decision-making to overcome such resistance is thus necessary.

Methods

Retrospective analysis was performed to identify potential stratification biomarkers. The levels of ceramide kinase (CERK) was determined in breast cancer patients. The roles of CERK and its downstream signaling pathways were analysed using cellular and biochemical assays.

Results

CERK upregulation was identified as a biomarker for chemotherapeutic response in TNBC. A > 2-fold change in CERK (from tumor)/CERK (from normal counterpart) was significantly associated with chemo-resistance (OR = 2.66, 95% CI 1.18–7.34), P = 0.04. CERK overexpression was sufficient to promote TNBC growth and migration, and confer chemo-resistance in TNBC cell lines, although this resistance could be overcome via CERK inhibition. Mechanistic studies suggest that CERK mediates intrinsic resistance and inferior response to chemotherapy in TNBC by regulating multiple oncogenic pathways such as Ras/ERK, PI3K/Akt/mTOR, and RhoA.

Conclusions

Our work provides an explanation for the heterogeneity of chemo-response across TNBC patients and demonstrates that CERK inhibition offers a therapeutic strategy to overcome treatment resistance.
RETRACTED ARTICLE: Transcription elongation factor A-like 7, regulated by miR-758-3p inhibits the progression of melanoma through decreasing the expression levels of c-Myc and AKT1
Authors: Liu Xilin , Song Xianji , Li Hong
Published: January 2021

Background

Ectopic expression of transcription elongation factor A (SII)-like 7 (TCEAL7) has been observed in several kinds of cancers, but its role in melanoma is still unclear. This study was carried out to investigate TCEAL7 role in melanoma progression, and uncover the underlying mechanisms.

Methods

TCEAL7 expression levels in melanoma tissues and cells were determined by using real-time quantitative PCR (RT-PCR) and western blotting. CCK-8, transwell chambers, flow cytometry, starch assay and tumorigenesis assay were applied to detect cell growth, invasion, apoptosis, migration and tumorigenesis, respectively.

Results

A low expression level of TCEAL7 was observed in melanoma tissues and cells, which was associated with malignant clinical process and poor prognosis. TCEAL7 negatively modulated AKT1, AKT2, c-Myc, N-cadherin and PCNA expression and inhibited cancer progression via decreasing AKT1 and c-Myc levels. In addition, TCEAL7 was negatively modulated by miR-758-3p which promoted melanoma progression. Moreover, overexpression of TCEAL7 abolished miR-758-3p role in promoting melanoma progression.

Conclusion

This study demonstrated that TCEAL7, regulated by miR-758-3p inhibited melanoma progression through decreasing the expression levels of c-Myc and AKT1.
Decreased expression of METTL14 predicts poor prognosis and construction of a prognostic signature for clear cell renal cell carcinoma
Authors: Wang Yi , Cong Rong , Liu Shouyong , Zhu Bingye , Wang Xing , Xing Qianwei
Published: January 2021

Background

METTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC).

Methods

We collected ccRCC patients’ clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens.

Results

Differently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e−05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-β pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e−16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided.

Conclusions

Our results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.
Retraction Note to: Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation
Authors: Gao Jin , Yuan Yuan , Zhang Lili , Yu Shaorong , Lu Jianwei , Feng Jifeng , Hu Sainan
Published: January 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12935-021-01759-5.
Evaluation of cardiovascular risk factors in patients with familial hypercholesterolemia from the North-Eastern area of Romania
Authors: Vlad Cristiana-Elena , Foia Liliana , Florea Laura , Costache Irina-Iuliana , Covic Andreea , Popescu Roxana , Reurean-Pintilei Delia , Covic Adrian
Published: January 2021

Background

Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents.

Methods

This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included.

Results

Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them.

Conclusions

In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.
The impact of family planning on maternal mortality in Indonesia: what future contribution can be expected?
Authors: Utomo Budi , Sucahya Purwa Kurnia , Romadlona Nohan Arum , Robertson Annette Sachs , Aryanty Riznawaty Imma , Magnani Robert Joseph
Published: January 2021

Background

Although efforts to reduce high maternal mortality in countries such as Indonesia tend to focus on addressing health risks among pregnant women, family planning has been shown globally to reduce maternal mortality by reducing both total and higher-risk pregnancies. This article assesses past contributions of family planning to the reduction of maternal mortality in Indonesia and the potential future contribution toward achieving the 2030 SDG maternal mortality goal.

Methods

The study takes advantage of data from long series of population censuses and large-scale surveys that are available in few other low- and middle-income countries. We use the decomposition method suggested by (Matern Child Health J, 16:456–463, 2012) and regression-based policy simulations to estimate the number of maternal deaths averted during 1970–2017 due to contraceptive use and project potential future contributions to the year 2030.

Results

It is estimated that between 523,885 and 663,146 maternal deaths were averted from 1970 to 2017 due to contraceptive use, a 37.5–43.1% reduction. If the contraceptive prevalence rate (CPR) were to rise from 63% in 2017 to 70% in 2030 and unmet need for family planning were to fall to from 10 to 7%, an additional 34,621–37,186 maternal deaths would be averted, an 18.9–20.0% reduction. A 2030 CPR of 75% and unmet need for family planning of 5% would result in 51,971–54,536 maternal deaths being averted, a 28.4–29.4% reduction. However, the CPR growth rate would have to nearly double the 2000–2017 rate to reach 70% CPR by 2030 and more than triple to reach 75%. Achieving the most ambitious target would still leave the maternal mortality ratio at 125 in 2030 without corresponding improvements in maternal health services.

Conclusions

Although substantial reductions in maternal mortality between 1970 and 2017 can be attributed to contraceptive use and further contributions to the year 2030 are probable, smaller contributions are likely due to the already relatively high CPR and the challenges that must be overcome to move the CPR significantly higher. The ability of Indonesia to reach the 2030 SDG maternal mortality target of 70 maternal deaths per 100,000 live births will depend primarily upon health system effectiveness in addressing health risks to women once they are pregnant.
PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors
Authors: Videira Alexandre , Beckedorff Felipe C. , daSilva Lucas F. , Verjovski-Almeida Sergio
Published: January 2021

Background

Androgen receptor (AR) and polycomb repressive complex 2 (PRC2) are known to co-occupy the loci of genes that are downregulated by androgen-stimulus. Long intergenic non-coding RNA (lincRNA)PVT1is an overexpressed oncogene that is associated with AR in LNCaP prostate cancer cells, and with PRC2 in HeLa and many other types of cancer cells. The possible involvement ofPVT1in mediating androgen-induced gene expression downregulation in prostate cancer has not been explored.

Methods

LNCaP cell line was used. Native RNA-binding-protein immunoprecipitation with anti-AR or anti-EZH2 was followed by RT-qPCR with primers forPVT1. Knockdown ofPVT1with specific GapmeRs (or a control with scrambled GapmeR) was followed by differentially expressed genes (DEGs) determination with Agilent microarrays and with Significance Analysis of Microarrays statistical test. DEGs were tested as a tumor risk classifier with a machine learning Random Forest algorithm run with gene expression data from all TCGA-PRAD (prostate adenocarcinoma) tumors as input. ChIP-qPCR was performed for histone marks at the promoter of one DEG.

Results

We show thatPVT1knockdown in androgen-stimulated LNCaP cells caused statistically significant expression upregulation/downregulation of hundreds of genes. Interestingly,PVT1knockdown caused upregulation of 160 genes that were repressed by androgen, including a significantly enriched set of tumor suppressor genes, and among themFAS,NOV/CCN3, BMF,HRK, IFIT2, AJUBA, DRAICandTNFRSF21. A 121-gene-set (out of the 160) was able to correctly predict the classification of all 293 intermediate- and high-risk TCGA-PRAD tumors, with a mean ROC area under the curve AUC = 0.89 ± 0.04, pointing to the relevance of these genes in cancer aggressiveness. Native RIP-qPCR in LNCaP showed thatPVT1was associated with EZH2, a component of PRC2.PVT1knockdown followed by ChIP-qPCR showed significant epigenetic remodeling at the enhancer and promoter regions of tumor suppressor geneNOV, one of the androgen-repressed genes that were upregulated uponPVT1silencing.

Conclusions

Overall, we provide first evidence thatPVT1was involved in signaling a genome-wide androgen-dependent transcriptional repressive program of tumor suppressor protein-coding genes in prostate cancer cells. Identification of transcriptional inhibition of tumor suppressor genes byPVT1highlights the pathway to the investigation of mechanisms that lie behind the oncogenic role ofPVT1in cancer.
A meta-analysis of the reproducibility of food frequency questionnaires in nutritional epidemiological studies
Authors: Cui Qi , Xia Yang , Wu Qijun , Chang Qing , Niu Kaijun , Zhao Yuhong
Published: January 2021

Background

Reproducibility of FFQs measures the consistency of the same subject at different time points. We performed a meta-analysis to explore the reproducibility of FFQs and factors related to reproducibility of FFQs.

Methods and findings

A systematic literature review was performed before July 2020 using PubMed and Web of Science databases. Pooled intraclass and Spearman correlation coefficients (95% confidence interval) were calculated to assess the reproducibility of FFQs. Subgroup analyses based on characteristics of study populations, FFQs, or study design were performed to investigate factors related to the reproducibility of FFQs. A total of 123 studies comprising 20,542 participants were eligible for the meta-analysis. The pooled crude intraclass correlation coefficients ranged from 0.499 to 0.803 and 0.499 to 0.723 for macronutrients and micronutrients, respectively. Energy-adjusted intraclass correlation coefficients ranged from 0.420 to 0.803 and 0.507 to 0.712 for macronutrients and micronutrients, respectively. The pooled crude and energy-adjusted Spearman correlation coefficients ranged from 0.548 to 0.851 and 0.441 to 0.793, respectively, for macronutrients; and from 0.573 to 0.828 and 0.510 to 0.744, respectively, for micronutrients. FFQs with more food items, 12 months as dietary recall interval (compared to less than 12 months), and a shorter time period between repeated FFQs resulted in superior FFQ reproducibility.

Conclusions

In conclusion, FFQs with correlation coefficients greater than 0.5 for most nutrients may be considered a reliable tool to measure dietary intake. To develop FFQs with higher reproducibility, the number of food items and dietary recall interval should be taken into consideration.
Towards TB elimination: how are macro-level factors perceived and addressed in policy initiatives in a high burden country?
Authors: Adu Prince A. , Spiegel Jerry M. , Yassi Annalee
Published: January 2021

Background

Notwithstanding extensive general discussion of the effects of upstream forces on health, there has been limited empirical examination, let alone systematic evidence documenting policy responses to such pathways in the area of tuberculosis (TB) management and control. Our study aimed to gain insight into how macro level drivers of TB are perceived by key stakeholders involved in TB management and control in a high-endemic country, and to assess how such concerns are being addressed in policy initiatives in this setting. South Africa was chosen for this case study due to our team’s long-standing collaborations there, its very high burden of TB, and its introduction of a strategic plan to combat this disease.

Method

Semi-structured interviews were conducted with 20 key informants who were purposively selected for their knowledge and expertise of TB in South Africa. South Africa’s National Strategic Plan for HIV, TB and STIs 2017–2022 was then reviewed to examine how identified themes from the interviews were reflected in this policy document.

Results

A history of colonization, the migrant labour system, economic inequality, poor shelter, health system challenges including TB governance, the HIV epidemic, and pertinent socio-cultural factors were all perceived to be major drivers of the epidemic. Although South Africa’s current National Strategic Plan makes a firm discursive commitment to addressing the structural or macro-level drivers of TB, our analysis revealed that this commitment was not clearly reflected in projected budgetary allocations.

Conclusion

As in many other high burden settings, macro-level drivers of TB are widely recognized. Nonetheless, while micro-level (biomedical and clinical) measures, such as improving diagnostic procedures and investment in more efficacious drugs, are being (and well should be) implemented, our findings showed that macro-level drivers of TB are underrepresented in budgeting allocations for initiatives to combat this disease. Although it could be argued that structural drivers that undermine health-promoting actions are beyond the purview of the health sector itself, we argue that strategic plans to combat TB in high burden settings need more attention to directly considering such drivers to prompt the necessary changes and reduce the burden of this and other such diseases.
The impact of sharing physical activity experience on social network sites on residents’ social connectedness:a cross-sectional survey during COVID-19 social quarantine
Authors: Zuo Yifan , Ma Yudan , Zhang Mu , Wu Xiaoyuan , Ren Zhanbing
Published: January 2021

Background

During isolation, sharing physical activity experiences on social network sites (SNS) can enhance individual social connectedness. The objective of the present study was to examine the associations between sharing physical activity experiences on SNS, positive self-presentation, positive feedback, and social connectedness during isolation.

Methods

Based on the Physical Activity Experience Sharing Scale, Social Connectedness Scale, Positive Self-Presentation Scale, and Online Positive Feedback Scale, we collected 460 questionnaires online from across 31 provinces, municipalities and autonomous regions in China. We used multiple linear regression models to investigate the relationship between variables, and used bootstrapping to test for mediation..

Results

During isolation, sharing physical activity experiences was positively associated with social connectedness (b = 0.308, p < 0.001), as well as with positive self-presentation(b = 0.956, p < 0.001)and positive feedback(b = 0.421, p < 0.001). In addition,we found that positive self-presentation showed a significant positive impact on positive feedback (b = 0.563, p < 0.001), and that positive self-presentation(b = 0.331, p < 0.001) and positive feedback(b = 0.311, p < 0.001) were positively associated with social connectedness. Finally, we found an effect on sharing physical activity experiences indirectly through positive self-presentation (b = 0.316, 95% CI: [0.180, 0.463]),and positive feedback (b = 0.131, 95% CI: [0.063, 0.207]) and that the mediation chain between the two also had a significant impact on social connectedness (b = 0.167, 95% CI: [0.088, 0.251]).

Conclusions

During the COVID-19 pandemic, sharing physical activity experiences on SNS can create a positive, healthy, and energetic personal image, gain recognition from others, and establish new interpersonal relationships.
Skills, attitudes and uptake of evidence-based practice: a cross-sectional study of chiropractors in the Swedish Chiropractic Association
Authors: Leach Matthew J. , Palmgren Per J. , Thomson Oliver P. , Fryer Gary , Eklund Andreas , Lilje Stina , Adams Jon , Skillgate Eva , Sundberg Tobias
Published: January 2021

Background

Evidence-based practice (EBP) is integral to the delivery of high-quality health care. Chiropractic has been a licensed health profession in Sweden since 1989, but little is known of the uptake of EBP in this professional group. This study explored the self-reported skills, attitudes and uptake of EBP, and the enablers and barriers of EBP uptake, among licensed chiropractors in Sweden.

Methods

Licensed chiropractors (n = 172) of the Swedish Chiropractic Association (Legitimerade Kiropraktorers Riksorganisation) were invited to participate in an anonymous online questionnaire, using the Evidence-Based Practice Attitude and Utilisation Survey (EBASE) in February 2019.

Results

Fifty-six (33%) chiropractors completed the survey. Participants were predominantly male, aged 30–49 years, held a Master’s degree, and had received their highest qualification and practiced chiropractic for over a decade. Chiropractors rated their EBP skill-level mostly in the moderate to moderate-high range. The majority of chiropractors reported positive attitudes towards EBP, with most agreeing or strongly agreeing that EBP is necessary in the practice of chiropractic, and that EBP assists in making decisions about patient care. Chiropractors reported an average level of engagement in EBP activities. All participants indicated professional literature and research findings were useful in their day-to-day chiropractic practice. The main perceived enabler of EBP uptake was internet access in the workplace, whereas the main barrier to EBP uptake was lack of clinical evidence in chiropractic.

Conclusions

Participating chiropractors of the Swedish Chiropractic Association were generally favourable of EBP, though only reported modest levels of EBP-related skills and engagement in EBP activities. Our findings suggest future studies investigating interventions focussed on improving chiropractors’ skills and uptake of EBP are warranted.
What is the impact of infrapopliteal endovascular intervention on free flap survival in diabetic foot reconstruction?
Authors: Thai Duy Quang , Lee Dong Hwan , Lee Woo Beom , Hahn Hyung Min , Lee Il Jae
Published: January 2021

Background

The combination of endovascular intervention and microvascular free flap transfer has been effectively used for chronic ischemic wounds of lower limb. The aim of this study was to determine the influence of angioplasty on free flap survival in diabetic foot ulcer reconstruction.

Methods

A retrospective research was conducted for 46 diabetic patients with chronic ulcer of the foot. All patients underwent free flap reconstruction because of their non-healing wound with tendon or bone exposure. Patient’s demography, clinical data related to vascular status, vascular intervention, and free flap transfer procedure were collected. Flap survival rate was compared between the group with severe arterial stenosis group and non-severe stenosis group. It was also compared among groups with different revascularization results.

Results

The average age of patients was 56.2 ± 10.8 years. There were 14 (30.4%) men and 32 (69.6%) women. Of 46 patients, 23 (50%) had severe infrapopliteal arterial stenosis. All 23 patients underwent endovascular intervention. Their final results of the pedal arch were type 1 in 13 patients, type 2A in 7 patients, type 2B in 2 patients, and type 3 in 1 patient. Total flap necrosis was found in 5 (10.9%) cases, marginal necrosis in 4 (8.7%) cases, and wound dehiscence in 4 (8.7%) cases. There was no significant difference in flap loss between severe arterial stenosis patients and non-severe arterial stenosis patients. In the severe arterial stenosis group, after endovascular intervention, patients with type 1 of pedal arch had a significantly lower rate of total flap necrosis than others. There was no association between the use of revascularized recipient artery and flap survival.

Conclusions

Our study revealed that the quality of pedal arch was crucial for free flap survival. Thus, PTA should aim to re-establish a complete pedal arch to increase wound healing rate and flap success.
Comparison of postoperative effectiveness of less invasive short external rotator sparing approach versus standard posterior approach for total hip arthroplasty
Authors: Wang Tianbao , Zhou Yongwei , Li Xiaofei , Gao Siqi , Yang Qining
Published: January 2021

Background

Most of the studies assessing the corrective posterior total hip arthroplasty (THA) mainly focused on the mini-incision approach. Studies exploring the short external rotator sparing approach are rare. Therefore, this study aimed to compare the effectiveness of standard posterior approach and short external rotator sparing approach.

Methods

This prospective observational study included 126 patients who underwent THA in June 2017–June 2018. Patients were assigned to standard (standard posterior approach) and corrective (short external rotator sparing approach) groups based on the surgical method. Surgical data were recorded postoperatively. Postoperative hip joint recovery was assessed using the times to ambulation and independent stair use, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Harris score, and Oxford hip score (OHS) at 2 and 8 postoperative weeks. The visual analog scale (VAS) was used for postoperative pain assessment.

Results

Postoperative changes of creatine kinase (CK), myoglobin, CRP, and prosthesis position were similar in both groups (P > 0.05). However, intraoperative blood loss (P < 0.001) and postoperative 6-h drainage volume (P = 0.03), hospital stay, blood transfusion rate, and times to ambulation and independent stair use were significantly reduced in the corrective group. Postoperatively, Oxford, and WOMAC scores significantly decreased in both groups. After surgery, the VAS score was more overtly decreased in the corrective group compared with the standard group.

Conclusions

This study concluded that the less invasive short external rotator sparing approach for THA caused less damage, reducing perioperative blood loss, shortening functional recovery time, maintaining prosthesis stability, and improving postoperative pain.
Cephalo-medullary nailing versus dynamic hip screw with trochanteric stabilisation plate for the treatment of unstable per-trochanteric hip fractures: a meta-analysis
Authors: Selim Amr , Ponugoti Nikhil , Naqvi Ali Zain , Magill Henry
Published: January 2021

Background

The use of cephalo-medullary nails (CMN) is a widely accepted management option for the treatment of unstable per-trochanteric hip fractures. A growing body of literature has reported good functional and radiological outcomes in patients managed with a dynamic hip screw supplemented with a trochanteric stabilisation plate (DHS w/ TSP). However, a robust meta-analysis does not exist in the current literature comparing the two fixation methods.

Purposes

Management of these kinds of injuries is very challenging in orthopaedic practice, yet no strong evidence is in place to delineate which implant gives the best results. This meta-analysis is the first to determine the efficacy of CMN versus DHS w/ TSP.

Methods

An up-to-date literature search was performed using a predetermined search strategy and eligibility criteria. All suitable literature was appraised for methodological quality using the Cochrane’s collaboration tool. Hospital stay, operative time, intra-operative complication rate, mechanical failure rate, infection rates, revision rates and functional outcomes were all considered.

Results

A total of five studies were included in the meta-analysis. The results of this analysis suggest that CMN is only associated with lower revision rates when compared to DHS w/ TSP; however, no significant difference was found in terms of hospital stay, operative time, blood transfusion, complications rate and functional outcome.

Conclusion

Both CMN and DHS w/TSP proved to be reliable in the management of unstable per-trochanteric fractures; however, more extensive datasets are required to draw robust conclusions.
Fingerprint analysis of phenolic acid extract of Salvia miltiorrhiza by digital reference standard analyzer with one or two reference standards
Authors: Wang Qingjun , Yu Xinlan , Sun Lei , Tian Runtao , He Huaizhen , Wang Sicen , Ma Shuangcheng
Published: January 2021

Background

Fingerprint analysis and simultaneous multi-components determination are crucial for the holistic quality control of traditional Chinese medicines (TCMs). Yet, reference standards (RS) are often commercially unavailable and with other shortages, which severely impede the application of these technologies.

Methods

A digital reference standard (DRS) strategy and the corresponding software called DRS analyzer, which supports chromatographic algorithms, spectrum algorithms, and the combination of these algorithms, was developed. The extensive function also enabled the DRS analyzer to recommend the chromatographic column based on big data.

Results

Various quality control methods of fingerprints of 11 compounds in polyphenolic acid extract of Salvia miltiorrhiza (S. miltiorrhiza) were developed based on DRS analyzer, involving relative retention time (RRT) method, linear calibration using two reference substances (LCTRS) technique, RRT combined with Photon Diode Array (PDA) method, LCTRS combined with PDA method. Additionally, the column database of samples was established. Finally, our data demonstrated that the DRS analyzer could accurately identify 11 compounds of the samples, using only one or two physical RSs.

Conclusions

The DRS strategy is an automated, intelligent, objective, accurate, eco-friendly, universal, sharing, and promising method for overall quality control of TCMs that requires the usage of fewer RSs.
Efficacy and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: a systematic literature review of randomized controlled trials
Authors: Liang Zuanji , Chen Xianwen , Shi Junnan , Hu Hao , Xue Yan , Ung Carolina Oi Lam
Published: January 2021

Background

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that may progress into, in the absence of proper treatment, severe liver damage. While the optimal pharmacotherapy for NAFLD remains uncertain and the adherence to lifestyle interventions is challenging, the use of herbal medicines such as traditional Chinese medicines (TCMs) to manage the condition is common. The evidence about TCMs in the management of NAFLD is continuously developing through randomized controlled trials (RCTs). This study aims to identify and evaluate the emerging evidence about the efficacy and safety of TCMs for NAFLD.

Methods

A systematic literature search was conducted to identify RCTs which investigated TCMs in the management of NAFLD published in 6 electronic databases including PubMed, the Cochrane Library, EMBASE, Web of Science, Scopus and China National Knowledge Infrastructure since inception to September 2020. RCTs comparing TCMs with no treatment, placebo, non-pharmacological and/or pharmacological interventions were included irrespective of language or blinding. The quality of reporting was evaluated using the Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM). Risk-of-bias for each study was assessed using the Cochrane risk of bias tool.

Results

A total of 53 RCTs involving 5997 participants with NAFLD were included in this review. Each included RCT tested a different TCMs giving a total of 53 TCMs identified in this study. Based on the evaluation of the RCT results, TCMs might have various beneficial effects such as improving TCM syndrome score, liver function, and body lipid profile. A range of non-serious, reversible adverse effects associated with the use of TCMs were also reported. However, no conclusion about the efficacy and safety of TCMs in NAFLD can be made. The quality of reporting was generally poor and the risks of bias was mostly uncertain in all trials.

Conclusions

There is some evidence from RCTs that supported the effectiveness and safety of TCMs for NAFLD. However, no conclusive recommendations can be made due to the questionable quality of the RCTs. Improvement in the RCT protocol, the use of a larger sample size, a setting of multicenter, and a more focused approach in selecting TCMs are recommended for developing high quality evidence about the use of TCMs in managing NAFLD.
Community mental health care in Mexico: a regional perspective from a mid-income country
Authors: Carmona-Huerta Jaime , Durand-Arias Sol , Rodriguez Allen , Guarner-Catalá Carmen , Cardona-Muller David , Madrigal-de-León Eduardo , Alvarado Rubén
Published: January 2021

Background

Access to mental health care is a worldwide public health challenge. In Mexico, an unacceptably high percentage of the population with mental disorders does not receive the necessary treatment, which is mainly due to the lack of access to mental health care. The community mental health care model was created and has been implemented to improve this situation. In order to properly plan and implement this model a precise situational diagnosis of the mental health care network is required, thus this is a first approach to evaluate the community mental health networks in the state of Jalisco.

Methods

Two components from the EvaRedCom–TMS instrument were used including a general description and accessibility of the community mental health care network. A geographic and economic accessibility evaluation was carried out for the different regions of the state ranging from scattered rural to urban communities using information gathered from health institutions, telephone interviews and computer applications.

Results

Jalisco’s community mental health network includes a total of 31 centers and 0.64 mental health workers for every 10,000 inhabitants > 15 years of age. The mean transportation cost required to access mental health care was 16.25 USD per visit. The time needed to reach the closest mental health center in 7 of the 13 analyzed regions was more than 30 min and the mean time required to reach a prolonged stay center was 172.7 min with transportation cost (taxi, private and public transport) of 22.3 USD. Some marginalized regions in the state have a mean 114 min required to reach the closest mental health care center and 386 min to reach a prolonged stay center.

Conclusions

This first approach to evaluate the mental health networks in Mexico showed that there are multiple barriers to access its care including an unfavorable number of human resources, long distances, and high costs. The identification of Jalisco’s mental health network deficiencies is the first step towards establishing a properly planned community mental health care model within the country.
Roles of palmitoylation in structural long-term synaptic plasticity
Authors: Ji Benjun , Skup Małgorzata
Published: January 2021

Long-term potentiation (LTP) and long-term depression (LTD) are important cellular mechanisms underlying learning and memory processes. N-Methyl-d-aspartate receptor (NMDAR)-dependent LTP and LTD play especially crucial roles in these functions, and their expression depends on changes in the number and single channel conductance of the major ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) located on the postsynaptic membrane. Structural changes in dendritic spines comprise the morphological platform and support for molecular changes in the execution of synaptic plasticity and memory storage. At the molecular level, spine morphology is directly determined by actin cytoskeleton organization within the spine and indirectly stabilized and consolidated by scaffold proteins at the spine head. Palmitoylation, as a uniquely reversible lipid modification with the ability to regulate protein membrane localization and trafficking, plays significant roles in the structural and functional regulation of LTP and LTD. Altered structural plasticity of dendritic spines is also considered a hallmark of neurodevelopmental disorders, while genetic evidence strongly links abnormal brain function to impaired palmitoylation. Numerous studies have indicated that palmitoylation contributes to morphological spine modifications. In this review, we have gathered data showing that the regulatory proteins that modulate the actin network and scaffold proteins related to AMPAR-mediated neurotransmission also undergo palmitoylation and play roles in modifying spine architecture during structural plasticity.
Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons
Authors: Akman Muhlis , Belisario Dimas Carolina , Salaroglio Iris Chiara , Kopecka Joanna , Donadelli Massimo , De Smaele Enrico , Riganti Chiara
Published: January 2021

Solid tumors often grow in a micro-environment characterized by < 2% O2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases the amount and activity of the hypoxia-inducible factor-1α (HIF-1α), a transcription factor that controls up to 200 genes involved in neoangiogenesis, metabolic rewiring, invasion and drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, a condition that triggers cell death, if cells are irreversibly damaged, or cell survival, if the stress is mild.

Hypoxia and chronic ER stress both induce chemoresistance. In this review we discuss the multiple and interconnected circuitries that link hypoxic environment, chronic ER stress and chemoresistance. We suggest that hypoxia and ER stress train and select the cells more adapted to survive in unfavorable conditions, by activating pleiotropic mechanisms including apoptosis inhibition, metabolic rewiring, anti-oxidant defences, drugs efflux. This adaptative process unequivocally expands clones that acquire resistance to chemotherapy.

We believe that pharmacological inhibitors of HIF-1α and modulators of ER stress, although characterized by low specificty and anti-cancer efficacy when used as single agents, may be repurposed as chemosensitizers against hypoxic and chemorefractory tumors in the next future.
Ventilator-associated pneumonia in critically ill patients with COVID-19
Authors: Maes Mailis , Higginson Ellen , Pereira-Dias Joana , Curran Martin D. , Parmar Surendra , Khokhar Fahad , Cuchet-Lourenço Delphine , Lux Janine , Sharma-Hajela Sapna , Ravenhill Benjamin , Hamed Islam , Heales Laura , Mahroof Razeen , Soderholm Amelia , Forrest Sally , Sridhar Sushmita , Brown Nicholas M. , Baker Stephen , Navapurkar Vilas , Dougan Gordon , Bartholdson Scott Josefin , Conway Morris Andrew
Published: January 2021

Background

Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).

Objectives

To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.

Methods

In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020.

Results

COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19.

Conclusion

COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.
BlastFrost: fast querying of 100,000s of bacterial genomes in Bifrost graphs
Authors: Luhmann Nina , Holley Guillaume , Achtman Mark
Published: January 2021

BlastFrost is a highly efficient method for querying 100,000s of genome assemblies, building on Bifrost, a dynamic data structure for compacted and colored de Bruijn graphs. BlastFrost queries a Bifrost data structure for sequences of interest and extracts local subgraphs, enabling the identification of the presence or absence of individual genes or single nucleotide sequence variants. We show two examples using Salmonella genomes: finding within minutes the presence of genes in the SPI-2 pathogenicity island in a collection of 926 genomes and identifying single nucleotide polymorphisms associated with fluoroquinolone resistance in three genes among 190,209 genomes. BlastFrost is available at https://github.com/nluhmann/BlastFrost/tree/master/data.
The impact of computer-based cognitive training intervention on the quality of life among elderly people: a randomized clinical trial
Authors: kazazi Leila , Shati Mohsen , Mortazavi Seyede Salehe , Nejati Vahid , Foroughan Mahshid
Published: January 2021

Background

Through the process of normal aging, cognitive decline would cause a lower level of functioning in real life. This flow might interfere with health-related quality of life (QoL). The purpose of this study is to investigate the effect of computer-based cognitive intervention on increasing QoL of elderly people.

Methods

A total number of 52 community-dwelling older adults participated in this study. This community scored ≥ 21 in the Mini-Mental State Examination (MMSE) and a clock drawing test score ≥ 4 from health centers in Tehran, Iran. This study is a parallel group stratified randomized clinical trial. The intervention group received a 45-min cognitive training session twice a week for 10 sessions, using Attentive Rehabilitation of Attention and Memory (ARAM) software focusing on selective attention and working memory. QoL was evaluated as a primary outcome. The control group participated in educational workshops.

Results

From fifty-two persons, only one participant was excluded from the study in the intervention group during follow-up. Results revealed by increasing cognitive function, improvement occurred in QoL (F = 13.417, p value < 0.001, partial eta-squared = 0.324) as a primary outcome in the intervention group. Among eight domains of QoL, there was significant increasing in domain of role limitations due to emotional problems (F = 4.007, p value = 0.021, partial eta-squared = 0.059), social functioning (F = 2.423, p value = 0.044, partial eta-squared = 0.004), and role limitations due to physical health (F = 10.749, p value < 0.001, partial eta-squared = 0.026).

Conclusions

Based on the results, ARAM showed transition and long-term effects on QoL in elderly people by improving cognitive functions such as selective attention and working memory.

Trial registration

Iranian Registry of Clinical Trials IRCT2016122731602N1. Registered on June 21, 2017
Characterization of polysaccharides from different species of brown seaweed using saccharide mapping and chromatographic analysis
Authors: Chen Shengqin , Sathuvan Malairaj , Zhang Xiao , Zhang Wancong , Tang Shijie , Liu Yang , Cheong Kit-Leong
Published: January 2021

Brown seaweed polysaccharides (BSPs) are one of the primary active components from brown seaweed that has a range of pharmaceutical and biomedical applications. However, the quality control of BSPs is a challenge due to their complicated structure and macromolecule. In this study, saccharide mapping based on high-performance liquid chromatography (HPLC), multi-angle laser light scattering, viscometer, and refractive index detector (HPSEC-MALLS-Vis-RID), and Fourier transform infrared (FT-IR) were used to discriminate the polysaccharides from nine different species of brown algae (BA1-9). The results showed that BSPs were composed of β-D-glucans and β-1,3−1,4-glucan linkages. The molecular weight, radius of gyration, and intrinsic viscosity of BSPs were ranging from 1.718 × 105 Da to 6.630 × 105 Da, 30.2 nm to 51.5 nm, and 360.99 mL/g to 865.52 mL/g, respectively. Moreover, α values of BSPs were in the range of 0.635 to 0.971, which indicated a rigid rod chain conformation. The antioxidant activities of BSPs exhibited substantial radical scavenging activities against DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2, 2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) radicals, which indicated that the use of BSPs might be a potential approach for antioxidant supplements. Thus, this study gives insights about the structure-function relationship of BSPs, which will be beneficial to improve the quality of polysaccharides derived from marine algae.
Spatio-temporal analysis of the main dengue vector populations in Singapore
Authors: Sun Haoyang , Dickens Borame L , Richards Daniel , Ong Janet , Rajarethinam Jayanthi , Hassim Muhammad E. E. , Lim Jue Tao , Carrasco L. Roman , Aik Joel , Yap Grace , Cook Alex R. , Ng Lee Ching
Published: January 2021

Background

Despite the licensure of the world’s first dengue vaccine and the current development of additional vaccine candidates, successful Aedes control remains critical to the reduction of dengue virus transmission. To date, there is still limited literature that attempts to explain the spatio-temporal population dynamics of Aedes mosquitoes within a single city, which hinders the development of more effective citywide vector control strategies. Narrowing this knowledge gap requires consistent and longitudinal measurement of Aedes abundance across the city as well as examination of relationships between variables on a much finer scale.

Methods

We utilized a high-resolution longitudinal dataset generated from Singapore’s islandwide Gravitrap surveillance system over a 2-year period and built a Bayesian hierarchical model to explain the spatio-temporal dynamics of Aedes aegypti and Aedes albopictus in relation to a wide range of environmental and anthropogenic variables. We also created a baseline during our model assessment to serve as a benchmark to be compared with the model’s out-of-sample prediction/forecast accuracy as measured by the mean absolute error.

Results

For both Aedes species, building age and nearby managed vegetation cover were found to have a significant positive association with the mean mosquito abundance, with the former being the strongest predictor. We also observed substantial evidence of a nonlinear effect of weekly maximum temperature on the Aedes abundance. Our models generally yielded modest but statistically significant reductions in the out-of-sample prediction/forecast error relative to the baseline.

Conclusions

Our findings suggest that public residential estates with older buildings and more nearby managed vegetation should be prioritized for vector control inspections and community advocacy to reduce the abundance of Aedes mosquitoes and the risk of dengue transmission.

Graphical Abstract