bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic regulation and functions of mRNA m6A modification
Authors: Wang Shanshan , Lv Wei , Li Tao , Zhang Shubing , Wang Huihui , Li Xuemei , Wang Lianzi , Ma Dongyue , Zang Yan , Shen Jilong , Xu Yuanhong , Wei Wei
Published: January 2022

N6-Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.
Iodine nutrition status and thyroid autoimmunity during pregnancy: a cross-sectional study of 4635 pregnant women
Authors: Chen Xiao , Wu Chunfeng , Wang Zhengyuan , Wu Chunxiang , Guo Yan , Zhu Xiaoxia , Hu Yan Ping , Shi Zehuan , Song Qi , Cui Xueying , Su Jin , Zang Jiajie
Published: January 2022

Background

Pregnant women in Shanghai have long been at risk for mild iodine deficiency. Because thyroid autoimmunity in pregnant women can lead to premature birth and miscarriage as well as neurodevelopmental deficits in the fetus, the aim of this study was to explore the association of iodine nutrition status with thyroid antibodies during pregnancy.

Methods

A pregnancy-birth cohort was conducted including 4635 pregnant women in Shanghai, China. The eligible participants underwent a face-to-face interview and completed questionnaire surveys to collect baseline information and diet intake. Spot urine samples were collected to test urine iodine. Thyroid antibodies including thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyrotrophic antibodies (TRAb) were tested. Single-factor analysis and logistic regression were used to evaluate the association between iodine status and thyroid autoimmunity during pregnancy.

Results

The median urinary iodine excretion level in the sample was 138.14 μg/L (interquartile range [IQR] 80.90–219.00 μg/L). Among all the subjects, 25.9% consumed non-iodized salt, 54.5% had iodine deficiency, and 31.0% had thyroid autoimmunity. The proportion of patients with iodine deficiency was significantly higher among those who consumed non-iodized salt (36.9% vs. 33.1%; p = 0.04). After adjusting for age, educational status, former smoker status, former drinker status, first pregnancy, and previous thyroid disease, non-iodized salt (odds ratio [OR] = 1.394 [confidence interval, CI, 1.165–1.562]; p = 0.003), iodine-rich food (OR = 0.681 [CI 0.585–0.793]; p = 0.003), iodized nutritional supplements (OR = 0.427 [CI 0.347–0.526]; p = 0.003), were found to be individually associated with thyroid autoimmunity in all participants. The results of the multivariable restricted cubic spline regression analysis showed a non-linear relationship between the continuous change in iodine intake and thyroid autoimmunity (p = 0.019). Participants with iodine deficiency (urinary iodine concentration, UIC,< 100 μg/L) had an increased risk of testing positive for thyroid antibodies (TPOAb/TgAb/TRAb[+]; OR = 1.324 [CI 1.125–1.559]; p < 0.001). Moreover, this associated existed even after removing participants with previous thyroid disease.

Conclusion

Inadequate iodine nutrition in pregnant women is an independent risk factor for thyroid autoimmunity in Shanghai. It’s important to maintain the adequate iodine status in pregnant women.
A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model
Authors: Liu Xiang-Yu , Zhu Mao-Hua , Wang Xiao-Yu , Dong Xiao , Liu Hai-Jun , Li Rui-Yang , Jia Shi-Chong , Lu Qin , Zhao Mei , Sun Peng , Chen Hong-Zhuan , Fang Chao
Published: January 2022

Background

Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy.

Methods

NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated.

Results

Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice.

Conclusions

The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.

Graphical Abstract
How has the COVID-19 epidemic affected the risk behaviors of people who inject drugs in a city with high harm reduction service coverage in Vietnam? A qualitative investigation
Authors: Nguyen Trang Thu , Hoang Giang Thi , Nguyen Duc Quang , Nguyen Anh Huu , Luong Ngoc Anh , Laureillard Didier , Nagot Nicolas , Des Jarlais Don , Duong Huong Thi , Nham Thanh Thi Tuyet , Khuat Oanh Thi Hai , Pham Khue Minh , Le Mai Sao , Michel Laurent , Rapoud Delphine , Le Giang Minh
Published: January 2022

Introduction

The COVID-19 outbreak disproportionally affects vulnerable populations including people who inject drugs (PWID). Social distancing and stay-at-home orders might result in a lack of access to medical and social services, poorer mental health, and financial precariousness, and thus, increases in HIV and HCV risk behaviors. This article explores how the HIV/HCV risk behaviors of PWID in Haiphong, a city with high harm reduction service coverage in Vietnam, changed during the early phase of the COVID-19 pandemic, and what shaped such changes, using the risk environment framework.

Method

We conducted three focus group discussions with peer outreach workers in May 2020 at the very end of the first lockdown, and 30 in-depth interviews with PWID between September and October 2020, after the second wave of infection in Vietnam. Discussions and interviews centered on the impact of the COVID-19 pandemic on their lives, and how their drug use and sexual behaviors changed as a result of the pandemic.

Results

The national shutdown of nonessential businesses due to the COVID-19 epidemic caused substantial economic challenges to participants, who mostly were in a precarious financial situation before the start of the epidemic. Unsafe injection is no longer an issue among our sample of PWID in Haiphong thanks to a combination of different factors, including high awareness of injection-related HIV/HCV risk and the availability of methadone treatment. However, group methamphetamine use as a means to cope with the boredom and stress related to COVID-19 was common during the lockdown. Sharing of smoking equipment was a standard practice. Female sex workers, especially those who were active heroin users, suffered most from COVID-related financial pressure and may have engaged in unsafe sex.

Conclusion

While unsafe drug injection might no longer be an issue, group methamphetamine use and unsafe sex were the two most worrisome HIV/HCV risk behaviors of PWID in Haiphong during the social distancing and lockdown periods. These elevated risks could continue beyond the enforced lockdown periods, given PWID in general, and PWID who are also sex workers in particular, have been disproportionately affected during the global crisis.
Rural population’s preferences matter: a value set for the EQ-5D-3L health states for China’s rural population
Authors: Liu Gordon G. , Guan Haijing , Jin Xuejing , Zhang Han , Vortherms Samantha A. , Wu Hongyan
Published: January 2022

Purpose

To develop an EQ-5D-3L social value set based on Chinese rural population’s preferences using the time trade-off (TTO) method, and to compare the differences in preferences on health states between China urban and rural population.

Methods

Between Sep 2013 and Nov 2013, a total of 1201 participants were recruited from rural areas of five Chinese cities (Beijing, Chengdu, Guiyang, Nanjing, and Shenyang) using a quota sampling method. Each respondent valued 13 health states using the TTO, and a total of 97 EQ-5D-3L health states were directly valued for estimating the value set. Various models with different specifications were explored at both aggregate and individual levels. The final model was determined by a set of predefined selection criteria.

Findings

An ordinary least square model at the aggregate level included 10 dummy variables for specifying the level 2 and 3 for each dimension and an N3 term presenting any dimension on level 3 was selected as the final model. The final model provides a value set ranges from − 0.218 to 0.859. The predicted utility values were highly correlated with but consistently lower than that of the published Chinese EQ-5D-3L value set (for urban population).

Conclusion

The availability of the China rural value set provides a set of social preferences weights for researchers and policy decision-makers for use in China rural area.
Quality of life of women with breast cancer in a tertiary referral university hospital
Authors: Yusoff Jamilah , Ismail Aniza , Abd Manaf Mohd Rizal , Ismail Fuad , Abdullah Norlia , Muhammad Rohaizak , Abdullah Suhaimi Shahrun Niza , Mat Zin Reena Rahayu
Published: January 2022

Background

Quality of life (QoL) is one of the treatment outcome measures in patients with breast cancer. In this study, we measured the QoL of women with breast cancer at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and identified the associated factors.

Methodology

This cross-sectional study was conducted from October 2017 to December 2017 and involved female patients with breast cancer. The QoL scores and domains were determined using the EuroQol EQ-5D-5L, and were presented as the utility value and visual analog scores, respectively.

Results

We recruited a total of 173 women, aged 33–87 years. The median VA score was 80.00 (interquartile range [IQR] 70.00–90.00); the median utility value was 0.78 (interquartile range [IQR] 0.65–1.00. Women who did not take traditional medicine had a higher utility index score of 0.092 (95% CI 0.014–0.171), and women with household income of RM3000–5000 had a higher utility index score of 0.096 (95% CI 0.011–0.180).

Conclusion

Traditional medicine consumption and household income were significantly associated with lower QoL. The pain/discomfort domain was the worst affected QoL domain and was related to traditional medicine use and household income. Addressing pain management in patients with breast cancer and the other factors contributing to lower QoL may improve the QoL of breast cancer survivors in the future.
Online faculty development in low- and middle-income countries for health professions educators: a rapid realist review
Authors: Keiller Lianne , Nyoni Champion , van Wyk Chantel
Published: January 2022

Background

Health professions educators require support to develop teaching and learning, research, educational leadership, and administrative skills to strengthen their higher education role through faculty development initiatives. Where administration has pursued face-to-face and online faculty development initiatives, results have positively influenced health professions educators. There is limited evidence demonstrating how online faculty development works for health professions educators in low- and middle-income countries who engage in online health professions education (HPE) faculty development.

Methods

A Conjecture Map for online HPE faculty development courses identified candidate theories for a rapid realist review. The Conjecture Map and candidate theories, Community of Inquiry and the Conversational Framework guided the development of search terms and analysis for this review. Three searches using EbscoHost databases yielded 1030 abstracts. A primary and secondary research team participated in a multi-reviewer blinded process in assessing abstracts, selecting full-text articles, and data extraction. The primary research team analysed eight articles for this rapid realist review to answer the research question: How do online HPE faculty development courses work, or not work, in low- and middle-income countries? Data were analysed and mapped to the initial Conjecture Map and the research question.

Results

The research references US-based organisations forming partnerships with low- and middle-income countries, and who provide funding for online HPE faculty development initiatives. These initiatives design courses that facilitate learning through engagement from which participants report beneficial outcomes of professional and career development. The review does not clarify if the reported outcomes are generalisable for facilitators from low-and middle-income countries. The findings of this review demonstrate the role of a community of practice as the dominant mechanism through which the outcomes are achieved, based on a design that incorporates six triggering events. The design aligns the triggering events with the three categories of the Community of Inquiry—a theory for designing online learning environments.

Conclusion

Health professions educators in low- and middle-income countries can develop professional and interpersonal skills through a well-designed, specifically constructed online community that prioritises active discussion.
Subtyping of sarcomas based on pathway enrichment scores in bulk and single cell transcriptomes
Authors: Li Shengwei , Liu Qian , Zhou Haiying , Lu Hui , Wang Xiaosheng
Published: January 2022

Background

Sarcomas are highly heterogeneous in molecular, pathologic, and clinical features. However, a classification of sarcomas by integrating different types of pathways remains mostly unexplored.

Methods

We performed hierarchical clustering analysis of sarcomas based on the enrichment scores of 14 pathways involved in immune, stromal, DNA damage repair (DDR), and oncogenic signatures in three bulk tumor transcriptome datasets.

Results

Consistently in the three datasets, sarcomas were classified into three subtypes: Immune Class (Imm-C), Stromal Class (Str-C), and DDR Class (DDR-C). Imm-C had the strongest anti-tumor immune signatures and the lowest intratumor heterogeneity (ITH); Str-C showed the strongest stromal signatures, the highest genomic stability and global methylation levels, and the lowest proliferation potential; DDR-C had the highest DDR activity, expression of the cell cycle pathway, tumor purity, stemness scores, proliferation potential, and ITH, the most frequentTP53mutations, and the worst survival. We further validated the stability and reliability of our classification method by analyzing a single cell RNA-Seq (scRNA-seq) dataset. Based on the expression levels of five genes in the pathways of T cell receptor signaling, cell cycle, mismatch repair, focal adhesion, and calcium signaling, we built a linear risk scoring model (ICMScore) for sarcomas. We demonstrated that ICMScore was an adverse prognostic factor for sarcomas and many other cancers.

Conclusions

Our classification method provides novel insights into tumor biology and clinical implications for sarcomas.
The ILEI/LIFR complex induces EMT via the Akt and ERK pathways in renal interstitial fibrosis
Authors: Zhou Jieqing , Jiang Hong , Jiang Hongkun , Fan Yan , Zhang Jing , Ma Xiaoxue , Yang Xuewei , Sun Yu , Zhao Xing
Published: January 2022

Background

Chronic kidney disease (CKD) is characterized by high morbidity and mortality and is difficult to cure. Renal interstitial fibrosis (RIF) is a major determinant of, and commonly occurs within, CKD progression. Epithelial mesenchymal transition (EMT) has been identified as a crucial process in triggering renal interstitial fibrosis (RIF). Interleukin‐like EMT inducer (ILEI) is an important promotor of EMT; this study aims to elucidate the mechanisms involved.

Methods

Male C57BL6/J mouse were randomly divided into 6 groups: sham (n = 10), sham with negative control (NC) shRNA (sham + NC, n = 10), sham with ILEI shRNA (sham + shILEI, n = 10), unilateral ureteral obstruction (UUO, n = 10), UUO with NC (UUO + NC, n = 10) and UUO with ILEI shRNA (UUO + shILEI, n = 10). Hematoxylin and eosin (H&E), Masson, and immunohistochemical (IHC) staining and western blotting (WB) were performed on murine kidney tissue to identify the function and mechanism of ILEI in RIF. In vitro, ILEI was overexpressed to induce EMT in HK2 cells and analyzed via transwell, WB, real-time PCR, and co-immunoprecipitation. Finally, tissue from 12 pediatric CKD patients (seven with RIF and five without RIF) were studied with H&E, Masson, and IHC staining.

Results

Our in vitro model revealed that ILEI facilitates RIF in the UUO model via the Akt and ERK pathways. Further experiments in vivo and in vitro revealed that ILEI promotes renal tubular EMT by binding and activating leukemia inhibitory factor receptor (LIFR), in which phosphorylation of Akt and ERK is involved. We further find markedly increased expression levels of ILEI and LIFR in kidneys from pediatric CKD patients with RIF.

Conclusion

Our results indicate that ILEI may be a useful biomarker for renal fibrosis and a potential therapeutic target for modulating RIF.
Information-seeking behavior on sexually transmitted infections and its associated factors among university students in Ethiopia: a cross-sectional study
Authors: Shimie Aynadis Worku , Gashu Kassahun Dessie , Shiferaw Atsede Mazengia , Mengiste Shegaw Anagaw
Published: January 2022

Background

Sexually Transmitted Infections (STIs) are infections commonly spread through sexual contact and transmitted by bacteria, viruses, or parasites. In today’s world, STI-related information-seeking behavior is often vital for the advancement of knowledge, behavioral changes, health decisions, and the sharing of sexual health information among youths. However, paucity of evidence on information-seeking behavior among students in higher education institutions. This study aimed to assess STI-related information-seeking behavior and its associated factors among students at the University of Gondar.

Methods

An institution-based cross-sectional quantitative study was conducted among students at the University of Gondar from January 15 to February 15, 2021. A total of 832 participants were selected using a stratified two-stage sampling method. A structured self-administered questionnaire was used to collect the required data. STI information-seeking behavior questionnaire was adapted from health information national survey tool (HINTS). Descriptive statistics, bi-variable, and multivariable logistic regression analyses were applied using SPSS version 26.

Result

The proportion of STI related information-seeking among university students was 462 (55.5%) with 95% CI (52.3, 58.9). About 263 (56.9%) of students preferred internet as a primary source for STI related information. Year of study being 4th (AOR = 4.77, 95% CI = 2.75, 8.29) and 5th year (AOR = 5.45, 95% CI = 2.48, 12.01), field of study being health (AOR = 2.19, 95% CI = 1.16, 4.11), sexual experiences (AOR = 2.33, 95% CI = 1.56, 3.48), ever had STI symptoms (AOR = 4.19, 95% CI = 2.14, 8.18), perceived susceptibility (AOR = 5.05, 95% CI = 3.29, 7.75), and perceived severity (AOR = 2.16,95% CI = 1.45, 3.22) were significant factors for good STI information-seeking.

Conclusion

the proportion of STI information-seeking among university students was low. Students' STI information-seeking behavior could be improved by increasing digital literacy and enhancing computer and internet access across the campus.
Factors affecting optimal adherence to antiretroviral therapy and viral suppression amongst HIV-infected prisoners in South Ethiopia: a comparative cross-sectional study
Authors: Fuge Terefe Gone , Tsourtos George , Miller Emma R.
Published: January 2022

Background

Maintaining optimal adherence and viral suppression in people living with HIV (PLWH) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of treatment adherence and viral suppression in incarcerated populations in low-income countries is unknown. This study aimed to determine factors affecting optimal adherence to antiretroviral therapy and viral suppression amongst HIV-infected prisoners in South Ethiopia.

Methods

A comparative cross-sectional study was conducted between June 1, 2019 and May 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWH. Patient information including demographic, socio-economic, behavioral, and incarceration-related characteristics were collected using a structured questionnaire. Medication adherence was assessed according to self-report and pharmacy refill. Plasma viral load measurements undertaken within the study period were prospectively extracted to determine viral suppression. Univariate and multivariate logistic and fractional regression models were used to analyse data.

Results

Seventy-four inmates living with HIV (ILWH) and 296 non-incarcerated PLWH participated in the study. While ILWH had a significantly higher pharmacy refill adherence compared to non-incarcerated PLWH (89 vs 75%), they had a slightly lower dose adherence (81% vs 83%). The prevalence of viral non-suppression was also slightly higher in ILWH (6.0%; 95% confidence interval (CI): 1.7–14.6%) compared to non-incarcerated PLWH (4.5%; 95%CI: 2.4–7.5%). Overall, missing ART appointments, dissatisfaction with ART services, inability to comply with a specified medication schedule, and types of methods used to monitor the schedule (e.g., news time on radio/TV or other social cues) were significantly associated with non-adherence according to self-report. In ILWH specifically, accessing ART services from a hospital, inability to properly attend clinic appointments, depressive symptoms, and lack of social support predicted NA. Viral non-suppression was significantly higher in males, people of age 31to 35 years and in those who experienced social stigma, regardless of their incarceration status.

Conclusions

Sub-optimal dose adherence and viral suppression are generally higher in HIV-infected prisoners in South Ethiopia compared to their non-incarcerated counterparts. A multitude of factors were found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.
Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B
Authors: Laras Andreas , Papatheodoridi Margarita , Panopoulou Eleni , Papatheodoridis George V. , Hadziyannis Stephanos J. , Hadziyannis Emilia
Published: January 2022

Background

Serum hepatitis B virus (HBV) RNA is a surrogate biomarker for intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity and persistence. In this retrospective study, we investigated its presence, levels and composition in ab initio Hepatitis B e antigen (HBeAg) negative chronically infected patients and examined possible associations with disease activity and the outcome of nucleos(t)ide analogue (NA) discontinuation.

Methods

We developed a sensitive real time polymerase chain reaction (RT-PCR) for the specific detection of HBV pregenomic RNA (pgRNA) and precore (preC) mRNA and analyzed 220 serum specimens, 160 under NA treatment, from 116 Greek patients initially negative for HBeAg.

Results

HBV pgRNA was detected in 31% and preC mRNA in 15% of samples, at lower levels representing a small fraction (3.4%) of total core promoter produced transcripts. In the absence of NAs, pgRNA was detected in 57% of samples with median value of 5.19 (2.61–8.35) log10 cp/mL, at lower levels than HBV DNA and correlated significantly with ALT (r = 0.764) and serum HBV DNA (r = 0.906). A wide range of HBV DNA/pgRNA ratio was observed with significant inter- and intra-patient variation. During NA treatment, pgRNA displayed low detectability (22%) and variable levels, median 3.97 (2.30– 8.13) log10 cp/mL, as well as, a significant inverse correlation with the duration of treatment (r = − 0.346, p < 0.01). In 74 events of NA discontinuation, end-of-treatment pgRNA-positive compared to pgRNA-negative cases, experienced more frequently virological (p = 0.016) and clinical (p = 0.011) relapse.

Conclusions

In genotype D ab initio HBeAg negative patients, serum HBV RNA is primarily composed of pgRNA plus a minor fraction of preC mRNA transcripts. Serum pgRNA is associated with disease activity, suggesting lysis of infected hepatocytes as a possible source of serum HBV RNA in untreated patients and in the early phase of NA treatment. During long term NA treatment, detectable serum pgRNA predicts viral rebound and clinical relapse following treatment discontinuation and may thus serve as a marker for the decision of cessation of therapy.
Dosimetric evaluation of photons versus protons in postmastectomy planning for ultrahypofractionated breast radiotherapy
Authors: Oonsiri Puntiwa , Nantavithya Chonnipa , Lertbutsayanukul Chawalit , Sarsitthithum Thanaporn , Vimolnoch Mananchaya , Tawonwong Tanawat , Saksornchai Kitwadee
Published: January 2022

Background

Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning.

Materials and methods

Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were four scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy(RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses.

Results

The PTV-D95 was kept above 24.7 Gy(RBE) in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy(RBE) for IMPT, while the VMAT delivered approximately 3 Gy(RBE). The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose.

Conclusion

Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan.
Application of computerized virtual preoperative planning procedures in comminuted posterior wall acetabular fractures surgery
Authors: Zheng Yifan , Chen Jianan , Yang Siyu , Ke Xi , Xu Dan , Wang Guodong , Cai Xianhua , Liu Ximing
Published: January 2022

Background

The treatment of comminuted posterior wall acetabular fractures remains challenging due to the difficulty in understanding of fracture patterns and lack of appropriate preoperative planning process. Virtual preoperative planning procedures are now being commonly used in orthopedic surgery to aid in management of such complex problems. Our aim was to evaluate the feasibility and clinical value of a new method by applying computerized virtual preoperative planning procedures in the treatment of comminuted posterior wall acetabular fractures.

Methods

A total of 45 patients with comminuted posterior wall acetabular fractures from June 2014 to December 2018 were retrospectively analyzed. Based on the usage of computerized virtual preoperative planning procedures, they were assigned to group A and group B. In group A (24 patients), the new method was applied before surgery. In group B (21 patients), the conventional surgery was performed without assistance of computerized virtual preoperative planning procedures. The two groups were assessed in terms of blood loss, surgical time, reduction quality, fracture healing time, postoperative complications, and hip function.

Results

There were no significant differences in demographic data between the two groups. Patients in group A had significantly less intraoperative blood loss (429.58 vs 570.24 ml, P < 0.001) and shorter operation time (154.79 vs 181.90 min, P < 0.01) compared to group B. Using the Matta scoring system, the reduction was graded as anatomic in 20 cases, imperfect in three cases and poor in one case in group A, versus 16 cases was graded as anatomic, three as imperfect and two as poor for group B. According to the modified Merle d’Aubigné score, hip function was graded as excellent in 15 cases, good in seven cases, fair in one and poor in one for group A in comparison to 11 cases, seven cases, two cases, and one case for group B, respectively. The reduction quality and hip function did not differ within the two groups (P > 0.05). The general postoperative complication rate in group A and group B was 12.5% and 28.6%, respectively, but the difference between the two groups was not statistically significant.

Conclusion

The application of computerized virtual preoperative planning procedures is feasible in comminuted posterior wall acetabular fractures. It helps orthopedic surgeons better understand the fracture characteristics, enables simulation of the reduction process and preoperative planning of internal fixation methods. This new preoperative planning method using a 3D virtual model is a more effective method than conventional method in surgical treatment of comminuted posterior wall acetabular fractures.

Trial registration retrospectively registered.
Circ_0001947 promotes cell proliferation, invasion, migration and inflammation and inhibits apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes through miR-671-5p/STAT3 axis
Authors: Yang Yang , Lin Shudian , Yang Zhou , Huang Yanyan , Zhan Feng
Published: January 2022

Background

Circular RNAs (circRNAs) have emerged as vital regulators in the development of rheumatoid arthritis (RA). In this study, we aimed to explore the functions and mechanisms of circ_0001947 in RA.

Methods

The expression of circ_0001947, microRNA-671-5p (miR-671-5p) and signal transducer and activator of transcription 3 (STAT3) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell Counting Kit-8 (CCK-8) assay, 5′-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry analysis, transwell assay and wound-healing assay were performed to assess cell proliferation, apoptosis, invasion and migration. The concentrations of inflammatory factors were examined with enzyme-linked immunosorbent assay (ELISA) kits. Dual-luciferase reporter assay was used to analyze the relationships of circ_0001947, miR-671-5p and STAT3.

Results

Circ_0001947 was upregulated in RA patients and RA-FLSs. Knockdown of circ_0001947 repressed cell proliferation, invasion, migration and inflammatory response and facilitated apoptosis in RA-FLSs. Circ_0001947 served as the sponge for miR-671-5p and the inhibitory effect of circ_0001947 in RA-FLS progression was reversed by miR-671-5p inhibition. STAT3 was the target gene of miR-671-5p. MiR-671-5p overexpression restrained RA-FLS growth, invasion, migration and inflammation and promoted apoptosis, but STAT3 upregulation reversed the impacts.

Conclusion

Circ_0001947 contributed to the progression of RA-FLSs by elevating STAT3 through adsorbing miR-671-5p.
Fractures of the distal femur in elderly patients: retrospective analysis of a case series treated with single or double plate
Authors: Nam Dae Jin , Kim Min Seok , Kim Tae Ho , Kim Min Woo , Kweon Suc Hyun
Published: January 2022

Introduction

We evaluated the radiologic and clinical outcomes of a lateral incision single plate with and a single-incision double plating in elderly patients with osteoporotic distal femoral fractures.

Materials and methods

We performed a retrospective study of 82 cases of distal femoral fractures from May 2004 to June 2018. Group A consisted of 42 patients who underwent single-plate fixation. Group B consisted of 40 patients who underwent double-plate fixation. The mean patient age was 77 years (67–87 years) and 76 years (64–86 years) in groups A and B, respectively. All patients were evaluated for procedure duration, time to union, range of knee motion, Lysholm knee score, and presence of complications.

Results

The average procedure time was 81 min (66–92 min) and 110 min (95–120 min) in groups A and B, respectively (p = 0.33). One case in group B required bone grafting after 5 months. The average time to union was 14 weeks (9–19 weeks) and 12.2 weeks (8–19 weeks) (p = 0.63), and the mean range of knee motion was 105° (90–125°) and 110.7° (90°–130°) (p = 0.37) in groups A and B, respectively. There was no significant statistical difference between the two groups in the Lysholm knee score (p = 0.44) and knee society score (p = 0.53).

Conclusion

The clinical and radiological outcomes were similar in the 2 groups. In elderly patients, double plate fixation for distal femoral fractures is an useful method for several advantages such as adequate exposure, easy manipulation, anatomical reduction and stable fixation.
Posterior minimally invasive scoliosis surgery versus the standard posterior approach for the management of adolescent idiopathic scoliosis: an updated meta-analysis
Authors: Yang Honghao , Jia Xiangyuan , Hai Yong
Published: January 2022

Background

Surgical management of adolescent idiopathic scoliosis (AIS) can be performed using standard posterior spinal fusion (PSF) or with a posterior minimally invasive approach. Minimally invasive scoliosis surgery (MISS) has several theoretical advantages, such as less tissue dissection, less blood loss, and earlier recovery. However, the difference in safety and effectiveness between MISS and PSF still needs to be clarified. This updated meta-analysis aimed to compare the outcomes of MISS and standard PSF for the management of AIS.

Methods

A comprehensive literature search of PubMed, EMBASE, MEDLINE, and Cochrane Library without time restriction was performed to identify relevant studies. MISS and PSF were compared in terms of radiographic parameters, estimated blood loss (EBL), blood transfusion rate, operative time (ORT), length of hospital stay (LOS), overall Scoliosis Research Society-22 (SRS-22) score, postoperative pain, and complication rate.

Results

A total of seven studies comprising 767 patients (329 MISS and 438 PSF) with AIS were included. MISS and PSF yielded comparable deformity correction at the last follow-up. There were no significant differences in the overall SRS-22 scores or complication rates between the groups. Nevertheless, greater restoration of thoracic kyphosis (WMD, 2.98; 95% CI 0.58 to 5.37, P = 0.015), less EBL (WMD, −218.76; 95% CI −256.41 to −181.11, P < 0.001), a lower blood transfusion rate (RR, 0.31; 95% CI 0.20 to 0.48, P < 0.001), a shorter LOS (WMD, −1.48; 95% CI −2.48 to −0.48, P = 0.004), less postoperative pain (WMD, 0.57; 95% CI 0.16 to 0.98, P = 0.006), and a longer ORT (WMD, 84.85; 95% CI 33.30 to 136.40, P = 0.001) were observed in the MISS group.

Conclusion

Despite its inherent technical challenges, MISS is a feasible and effective alternative to standard PSF for AIS patients with moderate and flexible curves. MISS was associated with adequate deformity correction, better restoration of sagittal alignment, less EBL, fewer transfusions, shorter LOS, and better pain management compared to PSF. Further research is required to determine the detailed indications for the MISS procedure.
Accuracies of bone resection, implant position, and limb alignment in robotic-arm-assisted total knee arthroplasty: a prospective single-centre study
Authors: Li Chenkai , Zhang Zian , Wang Guanrong , Rong Chun , Zhu Wanping , Lu Xinzhe , Liu Yikai , Zhang Haining
Published: January 2022

Objective

This study assessed the accuracy of robotic-arm-assisted total knee arthroplasty (RATKA) for bone resection, component size prediction, implant placement, and limb alignment.

Methods

This prospective cohort study included 36 patients. All procedures were performed by a single experienced surgeon, using an identical approach and implant designs. The MAKO RIO Robotic Interactive Orthopaedic Arm (Stryker, Mahwah, NJ, USA) system was used. The actual bone resection, implant placement, component size, and postoperative mechanical alignment were recorded, then compared with the preoperative plan.

Results

The mean absolute differences from the plan for the distal (medial and lateral) and posterior (medial and lateral) femoral cuts were 0.39 mm (0.62), 0.49 mm (0.70), 0.62 mm (0.79), and 0.65 mm (0.81), respectively, with 0.57° (0.65) varus. The mean absolute differences in the medial and lateral tibial cuts were 0.56 mm (0.75) and 0.58 mm (0.76), with 0.48° (0.16) varus and 0.54° (0.25) anterior/posterior slope. Of 192 bone resections, 176 (91.7%) were within ≤ 1 mm of the preoperative plan. The accuracies of femoral and tibial component size prediction were 100% and 97.22%, respectively. The mean absolute difference in final limb coronal alignment was 0.92° (0.65). Of the alignments, 18 (75.0%) were within ≤ 1.00° of the plan, and 100% were within ≤ 3.00° of the plan.

Conclusion

RATKA could accurately predict the component size and execute a preoperative plan to achieve precise bone resection, and implant placement, thereby reducing alignment outliers.
Not all patients benefit from the postoperative antifibrinolytic treatment: clinical evidence against the universal use of tranexamic acid following total knee arthroplasty
Authors: Liu Jiacheng , Wang Han , Wu Xiangdong , Lei Yiting , Huang Wei
Published: January 2022

Background

The empirical use of tranexamic acid (TXA) for bleeding remains controversial because of the distinct fibrinolytic phenotypes observed after injury. This study sought to assess the efficacy of postoperative TXA in patients presenting with different fibrinolytic phenotypes after total knee arthroplasty (TKA).

Methods

This retrospective study included 270 patients who underwent primary TKA. The patients were divided into two groups: Group A, received no postoperative TXA, and Group B, received postoperative TXA; they were further categorized into four subgroups based on postoperative fibrinolytic phenotypes (non-fibrinolytic shutdown [NFSD] and fibrinolytic shutdown [FSD]). Fibrinolytic phenotypes were determined using percentage of clot lysis 30 min after maximum strength (LY30) level measured on postoperative day 1 (POD1). Data on perioperative hidden blood loss (HBL), decrease in the hemoglobin level (ΔHb), allogeneic blood transfusion (ABT) rate, fibrin degradation product (FDP) level, D-dimer (D-D) level, prothrombin time (PT), and activated partial thromboplastin time (APTT) as well as clinical baseline data were collected and compared.

Results

No differences in baseline clinical data were noted. Among patients presenting with NFSD, those in Group B had significantly lower HBL and ΔHb on POD1 and POD3 than those in Group A. Among patients presenting with FSD, perioperative HBL and ΔHb were similar between the two groups. No differences were observed in perioperative ABT rate, FDP level, D-D level, PT, and APTT.

Conclusions

Patients exhibit various fibrinolytic phenotypes after TKA. Postoperative antifibrinolytic strategies may be beneficial for patients presenting with NFSD, but not for those presenting with FSD. The LY30 level may guide targeted TXA administration after TKA. However, well-designed prospective randomized controlled trials are needed to obtain more robust data.
Accuracy and reliability of tridimensional electromagnetic sensor system for elbow ROM measurement
Authors: Yamaura Kohei , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Kataoka Takeshi , Kurosawa Takashi , Mukohara Shintaro , Hoshino Yuichi , Niikura Takahiro , Nagamune Kouki , Kuroda Ryosuke
Published: January 2022

Background

While the precise measurement of the range of motion (ROM) of the elbow joint is important for clinical assessment and rehabilitation, problems include low accuracy and reproducibility in goniometer measurements due to the influence of soft tissue. The purpose of this study was to validate elbow joint motion analysis using a three-dimensional electromagnetic sensor system (EMS).

Methods

The accuracy and reproducibility of the EMS system were evaluated at four angles (0°, 45°, 90°, and 135°) using a model bone of the humerus and forearm. In addition, the maximum extension and maximum flexion of six elbows of six healthy volunteers were assessed by radiographic and EMS measurements. Accuracy was assessed by calculating the mean value of the measurement angle, standard deviation, Pearson’s correlation coefficient, and the Bland–Altman method. Reproducibility was assessed by calculating the intra-rater and inter-rater reliabilities using intraclass correlation coefficients.

Results

In the model bone evaluation, the mean angles of the EMS measurement were 1.2° ± 2.0°, 45.4° ± 2.1°, 91.7° ± 2.4°, and 134.6° ± 2.7° at 0°, 45°, 90°, and 135°, respectively. In the in vivo evaluation, the elbow angles at the maximum extension with the EMS and radiographic angles were 4.7° ± 3.0° and 2.7° ± 2.0°, respectively, and the angles at maximum flexion were 131.8° ± 13.0° and 130.8° ± 4.5°, respectively. There were statistically significant correlations between the EMS and radiographic measurements; the Bland–Altman plots indicated that the two methods were almost in agreement for both extension and flexion.

Conclusions

This method of measuring ROM of the elbow joint using EMS showed high accuracy, reliability, and reproducibility. The current results demonstrated the possibility of using the electromagnetic system to provide an accurate evaluation of the elbow joint in clinical settings.
Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy
Authors: Korb Manisha , Peck Allison , Alfano Lindsay N. , Berger Kenneth I. , James Meredith K. , Ghoshal Nupur , Healzer Elise , Henchcliffe Claire , Khan Shaida , Mammen Pradeep P. A. , Patel Sujata , Pfeffer Gerald , Ralston Stuart H. , Roy Bhaskar , Seeley William W. , Swenson Andrea , Mozaffar Tahseen , Weihl Conrad , Kimonis Virginia ,   the VCP Standards of Care Working Group, Fanganiello Roberto , Lee Grace , Mahoney Ryan Patrick , Diaz-Manera Jordi , Evangelista Teresinha , Freimer Miriam , Lloyd Thomas E. , Keung Benison , Kushlaf Hani , Milone Margherita , Needham Merrilee , Palmio Johanna , Stojkovic Tanya , Villar-Quiles Rocío-Nur , Wang Leo H. , Wicklund Matthew P. , Singer Frederick R. , Jones Mallory , Miller Bruce L. , Ahmad Sajjadi S. , Obenaus Andre , Geschwind Michael D. , Al-Chalabi Ammar , Wymer James , Chen Nita , Kompoliti Katie , Wang Stephani C. , Boissoneault Catherine A. , Cruz-Coble Betsaida , Garand Kendrea L. , Rinholen Anna J. , Tabor-Gray Lauren , Rosenfeld Jeffrey , Guo Ming , Peck Nathan
Published: January 2022

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget’s disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group’s conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally.