bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of C-reactive protein to albumin ratio for mortality in acute kidney injury
Authors: Liu Baohua , Lv Dezhao
Published: February 2023

Background

Inflammation plays an important role in the development of acute kidney injury (AKI). However, there are few studies exploring the prognostic influence of C-reactive protein to albumin ratio (CAR) among AKI patients. In this study, we investigated whether CAR could be a useful marker to predict the mortality of AKI.

Methods

A total of 358 AKI patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. C-reactive protein (CRP) and albumin were measured at ICU admission. The clinical outcome was 365-day mortality. Cox proportional hazards model and Kaplan-Meier survival analysis were conducted to evaluate the association between CAR and outcome.

Results

Compared with patients in the survival group, nonsurvivors had higher CAR levels. The area under the receiver operating characteristic (ROC) curve of CAR was higher than that of CRP and albumin for mortality (0.64 vs. 0.63, 0.59, respectively). The cut-off point of CAR for mortality was 7.23. In Cox proportional-hazard regression analysis, CAR (hazards ratio (HR) =2.04, 95% confidence interval (CI) =1.47-2.85, p < 0.001 for higher CAR) and Simplified Acute Physiology Score II (HR = 1.02, 95%CI = 1.00-1.03, p = 0.004) were independent predictors of 365-day mortality.

Conclusions

Our study demonstrated that a higher level of CAR was associated with 365-day mortality in AKI patients.
Climate change and health risks in Mukuru informal settlement in Nairobi, Kenya – knowledge, attitudes and practices among residents
Authors: Greibe Andersen Johanne , Kallestrup Per , Karekezi Catherine , Yonga Gerald , Kraef Christian
Published: February 2023

Background

Residents of informal settlements in Sub-Sahara Africa (SSA) are vulnerable to the health impacts of climate change. Little is known about the knowledge, attitudes and practices (KAP) of inhabitants of informal settlements in SSA regarding climate change and its health impacts. The aim of this study was to investigate how inhabitants of an informal settlement in SSA experience climate change and its health impacts and assess related knowledge, attitudes and practices. The study was conducted in Mukuru informal settlement in Nairobi City County, Kenya.

Methods

A cross-sectional study was conducted in September 2021 using a structured, semi-closed KAP questionnaire. Inclusion criteria were ≥ 18 years of age and living in one of the three main sections in Mukuru: Kwa Njenga, Kwa Reuben or Viwandani. By spinning a pen at the geographic centre of each section, a random direction was selected. Then, in every second household one individual was interviewed, creating a representative mix of ages and genders of the local community. To assess participant characteristics associated with climate change knowledge multivariable logistic regression was used. Thematic content analysis was performed for qualitative responses.

Results

Out of 402 study participants, 76.4% (n = 307) had heard of climate change before the interview, 90.8% (n = 365) reported that climate change was affecting their community, and 92.6% (n = 372) were concerned with the health-related impact of climate change. Having lived in Mukuru for more than 10 years and living in a dwelling close to the riverside were factors significantly associated with having heard of climate change before (aOR 3.1, 95%CI 1.7 – 5.8 and aOR 2.6, 95%CI 1.1 – 6.1, respectively) and experiencing a climate change related impact on the community (aOR 10.7, 95%CI 4.0 – 28.4 and aOR 7.7; 95%CI 1.7 – 34.0, respectively). Chronic respiratory conditions, vector-borne diseases, including infectious diarrhoea, malnutrition and cardiovascular diseases were identified by respondents as climate related health risks.

Conclusions

Most respondents were knowledgeable about climate change and were experiencing its (health-related) impact on their community. This study provides insights which may prove useful for policy makers, intervention planners and researchers to work on locally adapted mitigation and adaption strategies.
High reproducibility of a novel supported anterior drawer test for diagnosing ankle instability
Authors: Murahashi Yasutaka , Teramoto Atsushi , Takahashi Katsunori , Okada Yohei , Okimura Shinichiro , Imamura Rui , Kawai Makoto , Watanabe Kota , Yamashita Toshihiko
Published: February 2023

Background

The manual traditional anterior drawer test (ADT) is essential for deciding the treatment for chronic ankle instability, but it has been shown to have a comparatively low reproducibility and accuracy, especially in less experienced hands. To clarify the inter-examiner reproducibility, we compared the actual distance of anterior translation between junior and senior examiners in ADT. We also evaluated the diagnostic abilities of traditional ADT, and a novel modified ADT (supported ADT).

Methods

Thirty ankles were included in this study, and ankle instability was defined using stress radiography. All subjects underwent two methods of manual ADT by junior and senior examiners, and ankle instability was judged in a blinded fashion. The anterior drawer distance was calculated from the lengthening measured using a capacitance-type sensor device.

Results

The degree of anterior translation determined by the junior examiner was significantly lower than that determined by the senior examiner when traditional ADT was performed (3.3 vs. 4.5 mm, P = 0.016), but there was no significant difference in anterior translation between the two examiners when supported ADT was performed (4.6 vs. 4.1 mm, P = 0.168). The inter-examiner reliability of supported ADT was higher than that of traditional ADT. For the junior examiner, the diagnostic accuracy of supported ADT was higher than that of traditional ADT (sensitivity, 0.40 vs. 0.80; specificity, 0.75 vs. 0.80).

Conclusion

Supported ADT may have the advantage of being a simple manual test of ankle instability with less error between examiners.
The psycho-social impact of obstetric fistula and available support for women residing in Nigeria: a systematic review
Authors: Nduka Ifunanya Roseline , Ali Nasreen , Kabasinguzi Isabella , Abdy David
Published: February 2023

Background

Obstetric fistula continues to affect the social and mental wellbeing of women living in Nigeria giving rise to poor maternal health outcome. While the World Health Organisation (WHO) has recommended the introduction of psycho-social interventions in the management of obstetric fistula women, psycho-social support for women living with obstetric fistula in Nigeria, are limited. This systematic review aimed to synthesise the psycho-social impact of obstetric fistula on women living in Nigeria as well as the available psycho-social support for these affected women.

Methods

Following a keyword strategy, Medline, CINAHL, Google scholar, ScienceDirect, Cochrane library, PsychINFO, AMED, British Nursing database, Pubmed central, TRIP database, UK Pubmed central, socINDEX, Annual reviews, ISI Web of Science, Academic search complete, Credo reference, Sage premier and Scopus databases were searched alongside hand searching of articles. The inclusion criteria were set as articles published between 2000 and 2020, on the psychosocial consequences of obstetric fistula in Nigeria. The Critical Appraisal Skills Program (CASP) tool was used to appraise the quality of the included studies. The data was extracted and then analysed using narrative synthesis.

Results

620 relevant citations were identified, and 8 studies were included. Women with obstetric fistula, living in Nigeria were found to be ostracised, abandoned by families and friends, stigmatised and discriminated against, which led to depression, loneliness, loss of self-esteem, self-worth and identity. Psycho-social interventions for women who experienced obstetric fistula are not widely available.

Conclusion

There is a need for the introduction of more rehabilitation and reintegration programs across the country. The psychosocial effect of obstetric fistula is significant and should be considered when developing interventions. Further, more research is needed to evaluate the sustainability of psychosocial interventions in Nigeria.
Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial
Authors: Sandsdal Rasmus M. , Juhl Christian R. , Jensen Simon B. K. , Lundgren Julie R. , Janus Charlotte , Blond Martin B. , Rosenkilde Mads , Bogh Adrian F. , Gliemann Lasse , Jensen Jens-Erik B. , Antoniades Charalambos , Stallknecht Bente M. , Holst Jens J. , Madsbad Sten , Torekov Signe S.
Published: February 2023

Background

Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss.

Methods

This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model.

Results

The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (− 0.37, 95% CI − 0.58 to − 0.16, P < 0.001) and the combination treatment (− 0.48, 95% CI − 0.70 to − 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03).

Conclusion

The combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments.

Trial registration EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716
Chimeric Hepatitis B core virus-like particles harboring SARS-CoV2 epitope elicit a humoral immune response in mice
Authors: Sazegari Sima , Akbarzadeh Niaki Malihe , Afsharifar Alireza , Niazi Ali , Derakhshandeh Abdollah , Moradi Vahdat Maryam , Hemmati Farshad , Eskandari Mohammad Hadi
Published: February 2023

Background

Virus-like particles are an interesting vector platform for vaccine development. Particularly, Hepatitis B virus core antigen has been used as a promising VLP platform. It is highly expressed in different recombinant expression systems, such as E. coli, and self-assembled in vitro. It effectively improves the immunogenicity of foreign antigenic epitopes on its surface. Various foreign antigens from bacteria, viruses, and protozoa can be genetically inserted into such nanoparticles. The effective immunogenicity due to VLP vaccines has been reported. However, no research has been performed on the SARS-CoV2 vaccine within this unique platform through genetic engineering. Considering the high yield of target proteins, low cost of production, and feasibility of scaling up, E. coli is an outstanding expression platform to develop such vaccines. Therefore, in this investigation, we planned to study and develop a unique HBc VLP-based vaccine against SARS-Cov2 utilizing the E. coli expression system due to its importance.

Results

Insertion of the selected epitope was done into the major immunodominant region (MIR) of truncated (149 residues) hepatitis B core capsid protein. The chimeric protein was constructed in PET28a+ and expressed through the bacterial E. coli BL21 expression system. However, the protein was expressed in inclusion body forms and extracted following urea denaturation from the insoluble phase. Following the extraction, the vaccine protein was purified using Ni2 + iminodiacetic acid (IDA) affinity chromatography. SDS-PAGE and western blotting were used to confirm the protein expression. Regarding the denaturation step, the unavoidable refolding process was carried out, so that the chimeric VLP reassembled in native conformation. Based on the transmission electron microscopy (TEM) analysis, the HBC VLP was successfully assembled. Confirming the assembled chimeric VLP, we explored the immunogenic effectivity of the vaccine through mice immunization with two-dose vaccination with and without adjuvant. The utilization of adjuvant was suggested to assess the effect of adjuvant on improving the immune elicitation of chimeric VLP-based vaccine. Immunization analysis based on anti-spike specific IgG antibody showed a significant increase in antibody production in harvested serum from immunized mice with HBc-VLP harboring antigenic epitope compared to HBc-VLP- and PBS-injected mice.

Conclusions

The results approved the successful production and the effectiveness of the vaccine in terms of humoral IgG antibody production. Therefore, this platform can be considered a promising strategy for developing safe and reasonable vaccines; however, more complementary immunological evaluations are needed.
A novel circRNA, hsa_circ_0069382, regulates gastric cancer progression
Authors: Wang Haoying , Yuan Hao , Guo Qinghong , Zeng Xi , Liu Mengxiao , Ji Rui , Chen Zhaofeng , Guan Quanlin , Zheng Ya , Wang Yuping , Zhou Yongning
Published: February 2023

Aberrant expression of circRNAs is closely associated with the progression of gastric cancer; however, the specific mechanisms involved remain unclear. Our aim was to identify new gastric cancer biomarkers and explore the molecular mechanisms of gastric cancer progression. Therefore, we analyzed miRNA and circRNA microarrays of paired early-stage gastric cancer samples. Our study identified a new circRNA called hsa_circ_0069382, that had not been reported before and was expressed at low levels in gastric cancer tissues. Our study also included bioinformatics analyses which determined that the high expression of hsa_circ_0069382 regulated the BTG anti-proliferation factor 2 (BTG2)/ focal adhesion kinase (FAK) axis in gastric cancer lines by sponging for miR-15a-5p. Therefore, proliferation, invasion, and migration of gastric cancer is impacted. miR-15a-5p overexpression partially restored the effects of hsa_circ_0069382. This study provides potential new therapeutic options and a future direction to explore for gastric cancer treatment, and biomarkers.

Graphical Abstract
A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1
Authors: Numata Masashi , Haginoya Noriyasu , Shiroishi Machiko , Hirata Tsuyoshi , Sato-Otsubo Aiko , Yoshikawa Kenji , Takata Yoshimi , Nagase Reina , Kashimoto Yoshinori , Suzuki Makoto , Schulte Nina , Polier Gernot , Kurimoto Akiko , Tomoe Yumiko , Toyota Akiko , Yoneyama Tomoko , Imai Emi , Watanabe Kenji , Hamada Tomoaki , Kanada Ryutaro , Watanabe Jun , Kagoshima Yoshiko , Tokumaru Eri , Murata Kenji , Baba Takayuki , Shinozaki Taeko , Ohtsuka Masami , Goto Koichi , Karibe Tsuyoshi , Deguchi Takao , Gocho Yoshihiro , Yoshida Masanori , Tomizawa Daisuke , Kato Motohiro , Tsutsumi Shinji , Kitagawa Mayumi , Abe Yuki
Published: February 2023

Background

Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule–mediated inhibition of the protein‒protein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts.

Methods

We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models.

Results

Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values < 30 nM. Compared with cytrabine, the standard chemotherapy drug as AML therapy, both DS-1594a·HCl and DS-1594a·succinate mediated the eradication of potential leukemia-initiating cells by enhancing differentiation and reducing serial colony-forming potential in MLL1-r AML cells in vitro. The results were confirmed by flow cytometry, RNA sequencing, RT‒qPCR and chromatin immunoprecipitation sequencing analyses. DS-1594a·HCl and DS-1594a·succinate exhibited significant antitumor efficacy and survival benefit in MOLM-13 cell and patient-derived xenograft models of MLL1-r or NPM1c acute leukemia in vivo.

Conclusion

We have generated a novel, potent, orally available small-molecule inhibitor of the Menin-MLL1 interaction, DS-1594a. Our results suggest that DS-1594a has medicinal properties distinct from those of cytarabine and that DS-1594a has the potential to be a new anticancer therapy and support oral dosing regimen for clinical studies (NCT04752163).
Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
Authors: Zhou Zekun , Tang Jianfei , Lu Yixuan , Jia Jia , Luo Tiao , Su Kaixin , Dai Xiaohan , Zhang Haixia , Liu Ousheng
Published: February 2023

Background

Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC.

Methods

We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed.

Results

Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype.

Conclusion

The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.
Puff, Puff, Don’t Pass: harm reduction for cannabis use during a viral respiratory pandemic
Authors: Assaf Ryan D. , Javanbakht Marjan , Gorbach Pamina M. , Arah Onyebuchi A. , Shoptaw Steven J. , Cooper Ziva D.
Published: February 2023

Background

Prior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns.

Methods

This cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis.

Results

Overall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p < 0.01); less respondents shared most of the time (19.5% before; 11.2% during; p < 0.01) and always during the pandemic (5.2% before; 3.1% during; p < 0.01). After adjusting for covariates, the odds of any sharing during the pandemic for those who reported ≥ weekly cannabis use was 0.53 (95% CI 0.38, 0.75) compared to those who reported ≤ monthly.

Conclusions

Sharing of prepared cannabis and cannabis-related paraphernalia decreased during the COVID-19 pandemic compared to before the pandemic. This finding suggests potential risk mitigation strategies taken by participants for COVID-19 prevention either directly through behavior change or indirectly through adherence to COVID-19 prevention recommendations. Harm reduction messaging around sharing of cannabis during surges of COVID-19 or other respiratory infections may provide benefit in reducing infection among those who use cannabis, especially as cannabis use in the USA continues to increase.
Modeling the enigma of complex disease etiology
Authors: Schriml Lynn M. , Lichenstein Richard , Bisordi Katharine , Bearer Cynthia , Baron J. Allen , Greene Carol
Published: February 2023

Background

Complex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors.

Methods

Here we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model.

Results

We provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. The model is robust and flexible to capture new information as the understanding of complex disease improves.

Conclusions

The Human Disease Ontology’s Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The new model facilitates the comparison of etiological factors between complex, common and rare diseases and is available at the Human Disease Ontology website.
The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration
Authors: Ren Jianhan , Fok Melissa Rachel , Zhang Yunfan , Han Bing , Lin Yifan
Published: February 2023

Periodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the “gold standard” treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk–benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.
Muscle distribution in relation to all-cause and cause-specific mortality in young and middle-aged adults
Authors: Liu Chen-An , Liu Tong , Ge Yi-Zhong , Song Meng-Meng , Ruan Guo-Tian , Lin Shi-Qi , Xie Hai-Lun , Shi Jin-Yu , Zheng Xin , Chen Yue , Shen Liuyi , Deng Li , Shi Han-Ping
Published: February 2023

Background

The relationship between muscle and prognosis, especially that between muscle distribution across different body parts, and the related prognosis is not well established.

Objective

To investigate the relationship between muscle distribution and all-cause and cause-specific mortality and their potential modifiers.

Design

Longitudinal cohort study. C-index, IDI, and NRI were used to determine the best indicator of prognosis. COX regression analysis was performed to explore the relationship between variables and outcomes. Interaction and subgroup analyses were applied to identify the potential modifiers.

Participants

A total of 5052 participants (weighted: 124,841,420) extracted from the NHANES 2003–2006 of median age 45 years and constituting 50.3% men were assessed. For validation, we included 3040 patients from the INSCOC cohort in China.

Main measures

Muscle mass and distribution.

Key Results

COX regression analysis revealed that upper limbs (HR = 0.41, 95% CI 0.33–0.51), lower limbs (HR = 0.54, 95% CI 0.47–0.64), trunk (HR = 0.71, 95% CI, 0.59–0.85), gynoid (HR = 0.47, 95% CI 0.38–0.58), and total lean mass (HR = 0.55, 95% CI 0.45–0.66) were all associated with the better survival of participants (P trend < 0.001). The changes in the lean mass ratio of the upper and lower limbs and the lean mass ratio of the android and gynoid attenuated the protective effect of lean mass. Age and sex acted as potential modifiers, and the relationship between lean mass and the prognosis was more significant in men and middle-aged participants when compared to that in other age groups. Sensitive analyses depicted that despite lean mass having a long-term impact on prognosis (15 years), it has a more substantial effect on near-term survival (5 years).

Conclusion

Muscle mass and its distribution affect the prognosis with a more significant impact on the near-term than that on the long-term prognosis. Age and sex acted as vital modifiers.
LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages
Authors: Zheng Jinsen , Dou Rongzhang , Zhang Xinyao , Zhong Bo , Fang Chenggang , Xu Qian , Di Ziyang , Huang Sihao , Lin Zaihuan , Song Jialin , Wang Shuyi , Xiong Bin
Published: February 2023

Background

The interaction between the tumor-microenvironment (TME) and the cancer cells has emerged as a key player in colorectal cancer (CRC) metastasis. A small proportion of CRC cells which undergo epithelial-mesenchymal transition (EMT) facilitate the reshaping of the TME by regulating various cellular ingredients.

Methods

Immunohistochemical analysis, RNA immunoprecipitation (RIP), RNA Antisense Purification (RAP), dual luciferase assays were conducted to investigate the biological function and regulation of LINC00543 in CRC. A series in vitro and in vivo experiments were used to clarify the role of LINC00543 in CRC metastasis.

Results

Here we found that the long non-coding RNA LINC00543, was overexpressed in colorectal cancer tissues, which correlated with advanced TNM stage and poorer prognosis of CRC patients. The overexpression of LINC00543 promoted tumorigenesis and metastasis of CRC cells by enhancing EMT and remodeling the TME. Mechanistically, LINC00543 blocked the transport of pre-miR-506-3p across the nuclear-cytoplasmic transporter XPO5, thereby reducing the production of mature miR-506-3p, resulting in the increase in the expression of FOXQ1 and induction of EMT. In addition, upregulation of FOXQ1 induced the expression of CCL2 that accelerated the recruitment of macrophages and their M2 polarization.

Conclusions

Our study showed that LINC00543 enhanced EMT of CRC cells through the pre-miR-506-3p/FOXQ1 axis. This resulted in the upregulation of CCL2, leading to macrophages recruitment and M2 polarization, and ultimately stimulating the progression of CRC.
TREM2 mediates physical exercise-promoted neural functional recovery in rats with ischemic stroke via microglia-promoted white matter repair
Authors: Xu Jinghui , Zhang Liying , Li Mingyue , He Xiaofei , Luo Jing , Wu Rui , Hong Zhongqiu , Zheng Haiqing , Hu Xiquan
Published: February 2023

Background

The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebral artery occlusion (tMCAO).

Methods

Male Sprague–Dawley rats (weighing 250–280 g) were subjected to tMCAO. AAV-shRNA was injected into the lateral ventricle to silence the Trem2 gene before the operation. The rats in the physical exercise group started electric running cage training at 48 h after the operation. The Morris water maze and novel object recognition test were used to evaluate cognitive function. Luxol fast blue staining, diffusion tensor imaging, and electron microscopy were used to observe myelin injury and repair. Immunofluorescence staining was applied to observe the proliferation and differentiation of oligodendrocyte precursor cells (OPCs). Expression of key molecules were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and Enzyme-linked immunosorbent assay, respectively.

Results

PE exerted neuroprotective efects by modulating microglial state, promoting remyelination and recovery of neurological function of rats over 35 d after stroke, while silencing Trem2 expression in rats suppressed the aforementioned effects promoted by PE. In addition, by leveraging the activin-A neutralizing antibody, we found a direct beneficial effect of PE on microglia-derived activin-A and its subsequent role on oligodendrocyte differentiation and remyelination mediated by the activin-A/Acvr axis.

Conclusions

The present study reveals a novel regenerative role of PE in white matter injury after stroke, which is mediated by upregulation of TREM2 and microglia-derived factor for oligodendrocytes regeneration. PE is an effective therapeutic approach for improving white matter integrity and alleviating neurological function deficits after ischemic stroke.
Identification of novel miRNAs potentially involved in the pathogenesis of adult T-cell leukemia/lymphoma using WGCNA followed by RT-qPCR test of hub genes
Authors: Shayeghpour Ali , Forghani-Ramandi Mohammad-Moien , Solouki Setayesh , Hosseini Amin , Hosseini Parastoo , Khodayar Sara , Hasani Mahsa , Aghajanian Sepehr , Siami Zeinab , Zarei Ghobadi Mohadeseh , Mozhgani Sayed-Hamidreza
Published: February 2023

Background

Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers.

Methods

Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein–protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network.

Results

After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein–protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients.

Conclusion

The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.
Development of outcomes for evaluating emergency care triage: a Delphi approach
Authors: Johansson André , Ekwall Anna , Forberg Jakob Lundager , Ekelund Ulf
Published: February 2023

Background

Triage is used as standard of care for prioritization and identification of time-critical patients in the emergency department (ED) globally, but it is unclear what outcomes should be used to evaluate triage. Currently used outcomes do not include important time-critical diagnoses and conditions.

Method

We used 18 Swedish triage experts to collect and assess outcomes for the evaluation of 5-level triage systems. The experts suggested 68 outcomes which were then tested through a modified Delphi approach in three rounds. The outcomes aimed to identify correctly prioritized red patients (in need of a resuscitation team), and orange patients (other time critical conditions). Consensus was pre-defined as 70% dichotomized (positive/negative) concordance.

Results

Diagnoses, interventions, mortality, level of care and lab results were included in the outcomes. Positive consensus was reached for 49 outcomes and negative consensus for 7 outcomes, with an 83% response rate. The five most approved outcomes were the interventions Percutaneous coronary intervention, Surgical airway and Massive transfusion together with the diagnoses Tension pneumothorax and Intracerebral hemorrhage that received specific interventions. The outcomes with the clearest disapproval included Admittance to a ward, Treatment with antihistamines and The ordering of a head computed tomography scan. The outcomes were considered valid only if occurring in or from the ED.

Conclusion

This study proposes a standard of 49 outcomes divided into two sets tied to red and orange priority respectively, to be used when evaluating 5-level priority triage systems; Lund Outcome Set for Evaluation of Triage (LOSET). The proposed outcomes include diagnoses, interventions and laboratory results. Before widespread implementation of LOSET, prospective testing is needed, preferably at multiple sites.
Population structure in diverse pepper (Capsicum spp.) accessions
Authors: McCoy Jack , Martínez-Ainsworth Natalia , Bernau Vivian , Scheppler Hannah , Hedblom Grant , Adhikari Achuyt , McCormick Anna , Kantar Michael , McHale Leah , Jardón-Barbolla Lev , Mercer Kristin L. , Baumler David
Published: February 2023

Background

Peppers, bell and chile, are a culturally and economically important worldwide. Domesticated Capsicum spp. are distributed globally and represent a complex of valuable genetic resources.

Objectives

Explore population structure and diversity in a collection of 467 peppers representing eight species, spanning the spectrum from highly domesticated to wild using 22,916 SNP markers distributed across the twelve chromosomes of pepper.

Results

These species contained varied levels of genetic diversity, which also varied across chromosomes; the species also differ in the size of genetic bottlenecks they have experienced. We found that levels of diversity negatively correlate to levels of domestication, with the more diverse being the least domesticated.
Unilateral transverse testicular ectopia with recurrence of inguinal hernia: a case report
Authors: Gholizadeh Mahsa , Fakhre yasseri Ali Mohammad
Published: February 2023

Background

Crossed testicular ectopia or transverse testicular ectopia is an extremely rare urogenital anomaly. In this condition, on average at 4 years of age the testes migrate through the inguinal canal and one or both testes may turn up in the abdomen, inguinal region, or in the hemiscrotum, with an empty contralateral hemiscrotum. Our case report documents transverse testicular ectopia in a 5-year-old boy who presented with right inguinal hernia and nonpalpable left testis. He underwent previous right herniorrhaphy at the age of 1 year.

Case presentation

A 5-year-old Iranian boy was diagnosed with a right inguinal hernia. He underwent right inguinal herniorrhaphy at the age of 1 year. For this case report, the hernia symptoms had returned. Both testicles were palpated in the right scrotum, an ultrasound examination also revealed both testicles to be present in the right scrotum, and a hernia sac located in the right inguinal region with an internal ring. The patient was recommended to undergo a surgical reconstruction. Surgical reconstruction was performed by crossing the left testis in the transseptal orchiopexy technique.

Conclusion

In patients with cryptorchidism on one side and an inguinal hernia on the other side, the surgeon must consider a rare condition known as transverse testicular ectopia. Sonography can be helpful for diagnosing cases where transverse testicular ectopia is suspected, evaluating other anomalies, and selecting the most appropriate treatment.
Tracheoarterial fistula in a patient with amyotrophic lateral sclerosis successfully managed by overinflation of the tracheostomy tube cuff alone: a case report
Authors: Hosaka Takashi , Furuno Shintaro , Terada Makoto , Hamano Yumiko , Komatsu Kenichi , Okubo Katsuichiro , Koyama Yasuaki , Suzuki Tetsu , Tsuji Hiroshi , Tamaoka Akira , Mizutani Taro
Published: February 2023

Background

Tracheoarterial fistula is the most devastating complication after tracheostomy, and its mortality, without definitive treatment, approaches 100%. In general, the combination of bedside emergency management, that is, overinflation of the tracheostomy tube cuff, and definitive treatment such as surgical or endovascular intervention is necessary to prevent the poor outcome. Patients with neuromuscular diseases such as amyotrophic lateral sclerosis are susceptible to tracheoarterial fistula because of long-term mechanical ventilation and muscle weakness.

Case presentation

We describe a case of tracheoarterial fistula in a Japanese 39-year-old patient with amyotrophic lateral sclerosis with long-term ventilator management. The patient was clinically diagnosed with a tracheoarterial fistula because of massive bleeding following sentinel hemorrhage. The massive hemorrhage was controlled by overinflation of the tracheostomy tube cuff alone, without definitive treatment.

Conclusions

This case suggests overinflation of the tracheostomy tube cuff alone plays an important role, semi-permanently, in the management of tracheoarterial fistula, especially in cases where surgical or endovascular intervention is not indicated. Clinicians taking care of patients with tracheostomy undergoing long-term mechanical ventilation should be aware that tracheoarterial fistula might occur following tracheostomy.
Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study—an ancillary study of a randomized controlled trial
Authors: Roux Damien , Benichou Nicolas , Hajage David , Martin-Lefèvre Laurent , de Prost Nicolas , Lerolle Nicolas , Titeca-Beauport Dimitri , Boulet Eric , Mayaux Julien , Mégarbane Bruno , Mahjoub Khaoula , Carpentier Dorothée , Nseir Saad , Tubach Florence , Ricard Jean-Damien , Dreyfuss Didier , Gaudry Stéphane ,   for the AKIKI Study group
Published: February 2023

Background

Sepsis prognosis correlates with antibiotic adequacy at the early phase. This adequacy is dependent on antibacterial spectrum, bacterial resistance profile and antibiotic dosage. Optimal efficacy of beta-lactams mandates concentrations above the minimal inhibitory concentration (MIC) of the targeted bacteria for the longest time possible over the day. Septic acute kidney injury (AKI) is the most common AKI syndrome in ICU and often mandates renal replacement therapy (RRT) initiation. Both severe AKI and RRT may increase outside target antibiotic concentrations and ultimately alter patient’s prognosis.

Patients and methods

This is a secondary analysis of a randomized controlled trial that compared an early RRT initiation strategy with a delayed one in 620 critically ill patients undergoing severe AKI (defined by KDIGO 3). We compared beta-lactam trough concentrations between the two RRT initiation strategies. The primary outcome was the proportion of patients with sufficient trough plasma concentration of beta-lactams defined by trough concentration above 4 times the MIC. We hypothesized that early initiation of RRT could be associated with an insufficient antibiotic plasma trough concentration compared to patients allocated to the delayed strategy.

Results

One hundred and twelve patients were included: 53 in the early group and 59 in the delayed group. Eighty-three patients (74%) had septic shock on inclusion. Trough beta-lactam plasma concentration was above 4 times the MIC breakpoint in 80.4% (n = 90) of patients of the whole population, without differences between the early and the delayed groups (79.2% vs. 81.4%, respectively, p = 0.78). On multivariate analysis, the presence of septic shock and a higher mean arterial pressure were significantly associated with a greater probability of adequate antibiotic trough concentration [OR 3.95 (1.14;13.64), p = 0.029 and OR 1.05 (1.01;1.10), p = 0.013, respectively). Evolution of procalcitonin level and catecholamine-free days as well as mortality did not differ whether beta-lactam trough concentration was above 4 times the MIC or not.

Conclusions

In this secondary analysis of a randomized controlled trial, renal replacement therapy initiation strategy did not significantly influence plasma trough concentrations of beta-lactams in ICU patients with severe AKI. Presence of septic shock on inclusion was the main variable associated with a sufficient beta-lactam concentration.

Trial registration: The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.
Characterization of macrophage activation after treatment with polysaccharides from ginseng according to heat processing
Authors: Kim Sung Jin , Baek Seung-Hoon , Kang Ki Sung , Shin Myoung-Sook
Published: February 2023

The worldwide persistence of infectious diseases is a significant public health issue. Consequently, studying immunomodulatory ingredients present in natural products, such as ginseng, is important for developing new treatment options. Here, we extracted three different types of polysaccharides from white (P-WG), red (P-RG), and heat-processed (P-HPG) ginseng and analyzed their chemical properties and immunostimulatory activity against RAW 264.7 murine macrophages. Carbohydrates were the main components of all three polysaccharide types, while uronic acid and protein levels were relatively low. Chemical analysis indicated that the content of carbohydrates (total sugar) increased with processing temperature, while that of uronic acid decreased. Treatment with P-WG, P-RG or P-HPG stimulated nitric oxide (NO) production and increased tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 levels in RAW 264.7 macrophages, with P-WG showing the highest activity among the three polysaccharides. The expression of inducible NO synthase, which affects NO secretion, was highest in the macrophages treated with P-WG. Analysis of intracellular signaling pathways showed that mitogen-activated protein kinases (ERK, JNK, and p38) and NF-kB p65 were strongly phosphorylated by P-WG in macrophages but were only moderately phosphorylated by P-RG and P-HPG. Collectively, these results suggest that the polysaccharides isolated from ginseng undergo different changes in response to heat processing and display different chemical compositions and immune-enhancing activities.