bluuebunny/crossref_metadata_2025 huggingface dataset:
Associating Social Determinants of Health With PROMIS CAT Scores and Health Care Utilization After ACL Reconstruction
Authors: Ziedas Alexander , Castle Joshua P. , Abed Varag , Swantek Alexander , Chaides Sarah , Elhage Kareem , Fife Johnathan , Moutzouros Vasilios , Makhni Eric C.
Published: January 2023

Background:

The term “social determinants of health” (SDOH) refers to social and economic factors that influence a patient’s health status. The effect of SDOH on the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive test (CAT) scores and postoperative resource utilization in patients with anterior cruciate ligament reconstruction (ACLR) have yet to be thoroughly studied.

Purpose:

To investigate the impact SDOH have on PROMIS CAT outcomes and postoperative resource utilization in patients with ACLR.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

The electronic medical record was used to identify the SDOH for patients who underwent ACLR by 1 of 3 sports medicine fellowship–trained orthopaedic surgeons between July 2017 and April 2020. PROMIS CAT measures of Physical Function (PROMIS-PF), Pain Interference (PROMIS-PI), and Depression (PROMIS-D) were completed at the preoperative, 6-month postoperative, and 12-month postoperative time points. Postoperative health care utilization was recorded as well. Independent 2-group t tests and Wilcoxon rank-sum tests were used to analyze mean differences between patient groups based on SDOH.

Results:

Two-hundred and thirty patients who underwent ACLR were included (mean age, 27 years; 59% male). Compared with White patients, Black patients were represented more frequently in the lowest median household income (MHI) quartile (63% vs 23%, respectively; P < .001). White patients were represented more frequently in the highest area deprivation index (ADI) quartile when compared with Black patients (67% vs 12%, respectively; P = .006). Significantly worse PROMIS-PF, PROMIS-PI, and PROMIS-D scores at all 3 time points were found among patients who were Black, female, smokers, and in the lower MHI quartiles, with higher ADI and public health care coverage. In terms of resource utilization, Black patients attended significantly fewer postoperative physical therapy visits when compared with their respective counterparts. Those in the lower MHI quartiles attended significantly fewer postoperative imaging encounters, and female patients attended significantly more postoperative virtual encounters than male patients.

Conclusion:

Specific SDOH variables, particularly those that reflect racial and socioeconomic disparities, were associated with differences in postoperative health care utilization and ACLR outcomes as measured by PROMIS CAT domains.
Strategic incapacitation, scaled up: National security influence on protest policing for the 2018 Quebec G7 summit
Authors: Crosby Andrew , Walby Kevin
Published: January 2023

In June 2018, the 44th Group of Seven (G7) Summit was held in La Malbaie in the Province of Quebec, Canada. Drawing from geographic and sociological literature on protest and social movement policing and applying the concept of scale, we examine techniques of summit security deployed for the event. Analysing the results of access to information requests, we investigate pre-summit planning as well as the surveillance operations undertaken by military and national security agencies in conjunction with corporate players. We demonstrate how pre-summit training, threat assessments, surveillance, and securitisation practices at the summit framed protests and social movements as the predominant threat to security. Drawing from critical geographies of security, we argue that G7 Summit planning and the security operations that followed are an example of strategic incapacitation, scaled up.
Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge
Authors: Hadžisejdić Ita , Klarica Lucia , Babarović Emina , Marijić Blažen , Valković Toni , Jonjić Nives
Published: January 2023

Non-Hodgkin lymphomas are most frequently classified based on the lineage marker expression. However, lymphomas with aberrant marker expression as well as monoclonal IgH/IgΚ and TCR gene rearrangements may co-exist which can be misleading and confusing. Primary CD20 negative diffuse large B-cell lymphomas (DLBCL) represent a rare entity, and they account for 1% to 3% of cases. However, some CD20 negative DLBCLs could not be classified into known variants, creating both diagnostic and therapeutic dilemma’s. Primary CD20 negative DLBCL are more likely to have a non-germinal centre subtype, a higher proliferation index, more frequent extra-nodal involvement, a poorer response, and poorer prognosis to conventional treatment compared to CD20 positive DLBCL. A 66- year-old postmenopausal lady, presented with palpable, bilateral neck lymphadenopathy and difficulty swallowing. She also had left leg lymphoedema, poor appetited, fatigue and weight loss. Her symptoms lasted approximately 1 month. After histological, immunohistochemical and clonality analysis of the lymph node the patient was diagnosed with primary nodal CD20 and PAX-5 negative DLBCL with dual immunoglobulin light-chain kappa ( IgK) and T-cell receptor ( TCR) gene rearrangement. This unusual and unique case presented a diagnostic challenge because it was CD20 and PAX-5 negative, had dual IgK and TCR gene rearrangement and, it could not be classified within the known and well established CD20 negative DLBCL variants. Describing such cases emphasises the fact that lymphomas unclassifiable within known variants of CD20 negative DLBCL do exist and that range and heterogeneity of CD20 negative DLBCL continues to evolve, and pathologist should be aware of these uncommon, atypical mature B-cell neoplasms.
Understanding ecosystem services in a metacoupled world
Authors: Sun Jing
Published: January 2023

Driven by intensive globalization and technological development, shifting from place-based research on ecosystem services to an understanding of multiple human and natural interactions within the focal system, as well as between adjacent and distant systems, is becoming an urgent necessity. An integrated framework of metacoupling (socio-economic-environmental interactions within and across borders) is proposed to address this shift. Here, I have demonstrated the utility of the metacoupling framework, which includes intracoupling, pericoupling, and telecoupling, in the assessment of ecosystem services. I have referred to three examples from China (water supply, soybean production and trade, banana planation and displacement). I have also provided regulations and cautions in the application of the metacoupling framework. Strengthening the assessment of ecosystem services with the metacoupling framework can yield important insights toward sustaining ecosystem service provisions, balancing trade, offs, promoting regional and global cooperation, and achieving the United Nation’s Sustainable Development Goals.
Placental DNA methylation profile as predicting marker for autism spectrum disorder (ASD)
Authors: Ravaei Amin , Emanuele Marco , Nazzaro Giovanni , Fadiga Luciano , Rubini Michele
Published: January 2023

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impairs normal brain development and socio-cognitive abilities. The pathogenesis of this condition points out the involvement of genetic and environmental factors during in-utero life. Placenta, as an interface tissue between mother and fetus, provides developing fetus requirements and exposes it to maternal environment as well. Therefore, the alteration of DNA methylation as epigenetic consequence of gene-environmental interaction in the placenta could shed light on ASD pathogenesis. In this study, we reviewed the current findings on placental methylation status and its association with ASD. Differentially methylated regions (DMRs) in ASD-developing placenta were found to be mainly enriched in ASD gene loci affecting synaptogenesis, microtubule dynamics, neurogenesis and neuritogenesis. In addition, non-genic DMRs in ASD-placenta proposes an alternative contributing mechanism for ASD development. Our study highlights the importance of placental DNA methylation signature as a biomarker for ASD prediction.
Medium-term real-world data for erenumab in 177 treatment resistant or difficult to treat chronic migraine patients: persistence and patient reported outcome measures after 17–30 months
Authors: Troy Emma , Shrukalla Arif A. , Buture Alina , Conaty Katie , Macken Esther , Lonergan Roisin , Melling Jane , Long Niamh , Shaikh Eamonn , Birrane Kieran , Tomkins Esther M. , Goadsby Peter J. , Ruttledge Martin H.
Published: January 2023

Background

Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide monoclonal antibodies are a relatively novel molecular treatment for episodic and chronic migraine that have been shown to be effective in short duration clinical trials in approximately 40–50% of all chronic migraine patients. Patient Related Outcome Measures (PROM) or Quality of Life (QoL) questionnaires are used to help measure response to treatment in migraine. Although some open label extension studies have become available for erenumab, there is a lack of real-world data pertaining to quality of life in the medium to long-term for chronic and treatment resistant migraine patients.

Methods

A total of 177 treatment resistant CM patients were started on erenumab (70 mg or 140 mg subcutaneous injection every 4 weeks) in our three specialist Headache Clinics. Of these, 174 had their first injection between December 2018 and October 2019. All patients were evaluated with the following PROM: the Headache Impact Test− 6, Migraine Associated Disability Assessment test and Migraine-Specific QoL Questionnaire, before starting treatment with erenumab and at intervals of 3–12 months after starting treatment. The decision to continue treatment was based on subjective clinical improvement of at least 30% (as reported by the patient), supported with diaries and QoL questionnaires. We present here the QoL measurements for this group of 177 patients. Prior preventive migraine treatments included conventional oral prophylactic medications (such as topiramate, candesartan, propranolol, or amitriptyline), at least two cycles of PREEMPT protocol onabotulinumtoxin A or (in a small number of cases) neuromodulation with single pulse Transcranial Magnetic Stimulation.

Results

Of the 177 patients who started treatment with erenumab, 68/177 (38.4%) stopped during the first year, either due to lack of efficacy (no significant benefit or only minimal improvement) and/or possible side effects. 109/177 (61.6%) patients reported clinically significant improvement after 6–12 months and wished to stay on treatment. Twelve of these 109 patients subsequently stopped treatment in the period between 1 year and up to June 2021 (mainly due to a worsening of their migraine). Therefore, a total of 97/177 patients (54.8%) remained on treatment as of June 2021 (duration of treatment 17–30 months, median of 25 months).

Conclusion

Approximately 55% of treatment resistant or difficult to treat CM patients who trialled erenumab in our clinics reported a subjective benefit and were still on treatment after 17–30 months.
Integrated transcriptome and proteome revealed that the declined expression of cell cycle-related genes associated with follicular atresia in geese
Authors: Yang Wanli , Chen Xingyong , Liu Zhengquan , Zhao Yutong , Chen Yufei , Geng Zhaoyu
Published: January 2023

Background

Geese exhibit relatively low reproductive performance, and follicular atresia is an important factor that restricts the egg production of geese. Systematic analysis of the regulation of follicle atresia in geese through transcriptome and proteome levels could provide meaningful information on clarifying the mechanism of follicle atresia in poultry.

Result

The granulosa cell layer was loose, disintegrated and showed apoptosis in atretic follicles and remained intact in normal follicles. The hormone levels of FSH and LH were significantly decreased in the atresia follicles compared to the normal follicles (P < 0.05). A total of 954 differentially expressed genes (DEGs, 315 increased and 639 decreased) and 161 differentially expressed proteins (DEPs, 61 increased and 100 decreased) were obtained in atresia follicles compared to normal follicles, of which, 15 genes were differentially expressed in both transcriptome and proteome. The DEGs were mainly enriched in sodium transmembrane transport, plasma membrane, and transmembrane transporter activity based on the GO enrichment analysis and in the cell cycle pathway based on the KEGG enrichment analysis. The DEPs were mainly enriched in localization, lysosome, and phospholipid-binding based on the GO enrichment analysis. Candidate genes Smad2/3, Smad4, Annexin A1 (ANXA1), Stromelysin-1 (MMP3), Serine/threonine-protein kinase (CHK1), DNA replication licensing factor (MCM3), Cyclin-A2 (CCNA2), mitotic spindle assembly checkpoint protein (MAD2), Cyclin-dependent kinase 1 (CDK1), fibroblast growth factor 12 (FGF12), and G1/S-specific cyclin-D1 (CCND1) were possibly responsible for the regulation of atresia.

Conclusion

The cell cycle is an important pathway for the regulation of follicular atresia. Sodium outflow and high expression of MMP3 and MMP9 could be responsible for structural destruction and apoptosis of follicular cells.
Transcriptome analysis reveals the effect of grafting on gossypol biosynthesis and gland formation in cotton
Authors: Ye Kun , Teng Teng , Yang Teng , Zhao Degang , Zhao Yichen
Published: January 2023

Background

Gossypol is a unique secondary metabolite and sesquiterpene in cotton, which is mainly synthesized in the root system of cotton and exhibits many biological activities. Previous research found that grafting affected the density of pigment glands and the gossypol content in cotton.

Results

This study performed a transcriptome analysis on cotton rootstocks and scions of four grafting methods. The gene expression of mutual grafting and self-grafting was compared to explore the potential genes involved in gossypol biosynthesis. A total of six differentially expressed enzymes were found in the main pathway of gossypol synthesis-sesquiterpene and triterpene biosynthesis (map00909): lupeol synthase (LUP1, EC:5.4.99.41), beta-amyrin synthase (LUP2, EC:5.4.99.39), squalene monooxygenase (SQLE, EC:1.14.14.17), squalene synthase (FDFT1, EC:2.5.1.21), (-)-germacrene D synthase (GERD, EC:4.2.3.75), ( +)-delta-cadinene synthase (CADS, EC:4.2.3.13). By comparing the results of the gossypol content and the density of the pigment gland, we speculated that these six enzymes might affect the biosynthesis of gossypol. It was verified by qRT-PCR analysis that grafting could influence gene expression of scion and stock. After suppressing the expression of the LUP1, FDFT1, and CAD genes by VIGS technology, the gossypol content in plants was significantly down-regulated.

Conclusions

These results indicate the potential molecular mechanism of gossypol synthesis during the grafting process and provide a theoretical foundation for further research on gossypol biosynthesis.
Responses of roots and rhizosphere of female papaya to the exogenous application of GA3
Authors: Zhou Yongmei , Pang Ziqin , Jia Haifeng , Yuan Zhaonian , Ming Ray
Published: January 2023

Exogenous GAs have an indeterminate effect on root development. Our current study used female papaya to reveal how the roots and rhizosphere respond to the exogenous application of GA3 by investigating the transcriptome profile in roots, metabolic profile and microbial community in both roots and rhizosphere of GA3-treated and control female papaya. The results demonstrated that exogenous GA3 treatment enhanced female papaya lateral root development, which gave plants physical advantages of water and nutrient uptake. In addition, it was likely that GA3 spraying in papaya shoot apices increased the level of auxin, which was transported to roots by CpPIN1, where auxin upregulated CpLBD16 and repressed CpBP to promote the lateral root initiation and development. In papaya roots, corresponding transporters (CpTMT3, CpNRT1:2, CpPHT1;4, CpINT2, CpCOPT2, CpABCB11, CpNIP4;1) were upregulated and excretion transporters were downregulated such as CpNAXT1 for water and nutrients uptake with exogenous GA3 application. Moreover, in GA3-treated papaya roots, CpALS3 and CpMYB62 were downregulated, indicating a stronger abiotic resistance to aluminum toxic and phosphate starvation. On the other hand, BRs and JAs, which involve in defense responses, were enriched in the roots and rhizosphere of GA3-treated papayas. The upregulation of the two hormones might result in the reduction of pathogens in roots and rhizosphere such as Colletotrichum and Verticillium. GA3-treated female papaya increased the abundance of beneficial bacteria species including Mycobacterium, Mitsuaria, and Actinophytocola, but decreased that of the genera Candidatus and Bryobacter for that it required less nitrate. Overall, the roots and rhizosphere of female papaya positively respond to exogenous application of GA3 to promote development and stress tolerance. Treatment of female papaya with GA3 might result in the promotion of lateral root formation and development by upregulating CpLBD16 and downregulating CpBP. GA3-treated papaya roots exhibited feedback control of brassinolide and jasmonate signaling in root development and defense. These findings revealed complex response to a growth hormone treatment in papaya roots and rhizosphere and will lead to investigations on the impact of other plant hormones on belowground development in papaya.
Implication of changes in xanthine oxidase activity following hemodialysis
Authors: Fujioka Hayato , Koike Tsutomu , Imamura Teruhiko , Kakeshita Kota , Yamazaki Hidenori , Kinugawa Koichiro
Published: January 2023

Background

Xanthine oxidase activity has a key role in the development of oxidative stress and progression of cardiovascular diseases. However, the change of xanthine oxidase activity following hemodialysis and its prognostic impact remain uncertain.

Methods

We prospectively included hemodialysis patients who did not take any anti-hyperuricemic agents and measured their xanthine oxidase activity before and after the index hemodialysis. The impact of change in xanthine oxidase activity during hemodialysis on cardiovascular death were investigated.

Results

A total of 46 patients (median 72 years old, 29 men) were included. During hemodialysis, a common logarithm of xanthine oxidase activity decreased significantly from 1.16 (0.94, 1.27) to 1.03 (0.80, 1.20) (p < 0.01). Of them, xanthine oxidase activity remained unchanged or increased in 16 patients, who had a greater decrease in blood pressure and more hemoconcentration compared with others. Two–year survival from cardiovascular death was not significantly stratified by the changes in xanthine oxidase activity (p = 0.43).

Conclusions

During hemodialysis, xanthine oxidase activity decreased among the overall cohort, whereas some patients experienced its increases, which might be associated with hypotension and hemoconcentration during hemodialysis. Further larger-scale studies are required to validate our findings and find clinical implication of change in xanthine oxidase activity during hemodialysis.
Predictors of do-not-attempt-resuscitation decisions in patients with infratentorial or large supratentorial intracerebral hemorrhages and consequences thereafter: a register-based, longitudinal study in Sweden
Authors: Soomägi Amanda , Viktorisson Adam , Sunnerhagen Katharina S.
Published: January 2023

Objectives

Do-not-attempt-resuscitation (DNAR) decisions for patients with infratentorial or large supratentorial intracerebral hemorrhages (ICHs) pose clinical and ethical challenges. We aimed to investigate factors associated with DNAR decisions in patients with infratentorial or large (≥30 mL) supratentorial ICH, and differences in complications, treatment, and mortality.

Materials & methods

This longitudinal, observational study comprised all patients treated for ICH at three stroke units in Gothenburg, Sweden, between November 2014 and June 2019. Patients were identified in the local stroke register, and additional data were collected from medical records and national registries. Mortality rates were followed 1 year after incident ICHs. Factors associated with DNAR decisions, and one-year mortality were explored.

Results

Of 307 included patients, 164 received a DNAR decision. Most (75%) decisions were made within 24 h. DNAR decisions were associated with higher age, pre-stroke dependency, stroke severity, and intraventricular hemorrhage. Patients without DNAR decisions received thrombosis prophylaxis, oral antibiotics, and rehabilitative evaluations more frequently. The one-year survival probability was 0.16 (95% confidence interval [CI] 0.11–0.23) in patients with DNAR decisions, and 0.87 (95% CI 0.81–0.92) in patients without DNAR decision. DNAR decisions, higher age, stroke severity, hematoma volume, and comorbidities were associated with increased one-year mortality. Thrombosis prophylaxis and living alone were associated with a lower hazard.

Conclusion

The majority of DNAR decisions for patients with infratentorial or large supratentorial ICH were made within 48 h. Higher age, pre-stroke dependency, high stroke severity, and intraventricular hemorrhage predicted receiving a DNAR decision. DNAR decisions were strongly associated with increased short- and long-term mortality.
Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging
Authors: Wang Changyuan , Wang Yang , Xiao Wangchuan , Chen Xiaohua , Li Renfu , Shen Zhiyong , Lu Fengchun
Published: January 2023

Background

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents.

Methods

Superparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed.

Results

The synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn’t change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging.

Conclusion

These data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.
Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment
Authors: Huang Kai , Luo Wenwu , Fang Jinmei , Yu Changjun , Liu Guangjie , Yuan Xiaodong , Liu Yun , Wu Wenyong
Published: January 2023

Background

Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear.

Methods

The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo.

Results

Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment.

Conclusion

Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.
Phosphorylation of TGIF2 represents a therapeutic target that drives EMT and metastasis of lung adenocarcinoma
Authors: Du Renle , Wang Chen , Liu Jingjing , Wang Keyan , Dai Liping , Shen Wenzhi
Published: January 2023

Background

TGF-β-induced factor homeobox 2 (TGIF2) is a transcription regulator that is phosphorylated by EGFR/ERK signaling. However, the functions of phosphorylated (p)-TGIF2 in cancer are largely unknown. Here, we investigated the roles of p-TGIF2 in promoting epithelial–mesenchymal transition (EMT) and metastasis in lung adenocarcinoma (LUAD).

Methods

In vitro and in vivo experiments were conducted to investigate the role of TGIF2 in LUAD EMT and metastasis. Dual-luciferase reporter and ChIP assays were employed to observe the direct transcriptional regulation of E-cadherin by TGIF2 and HDAC1. Co-immunoprecipitation was performed to identify the interaction between TGIF2 and HDAC1.

Results

Downregulating the expression of TGIF2 inhibited LUAD cell migration, EMT and metastasis in vitro and in vivo. Phosphorylation of TGIF2 by EGFR/ERK signaling was required for TGIF2-promoted LUAD EMT and metastasis since phosphorylation-deficient TGIF2 mutant lost these functions. Phosphorylation of TGIF2 was necessary to recruit HDAC1 to the E-cadherin promoter sequence and subsequently suppress E-cadherin transcription. Meanwhile, inhibition of HDAC1 repressed the TGIF2 phosphorylation-induced migration and EMT of LUAD cells. In xenograft mouse models, both inhibition of ERK and HDAC1 could significantly inhibited TGIF2-enhanced metastasis. Furthermore, TGIF2-positive staining was significantly correlated with E-cadherin-negative staining in human lung cancer specimens.

Conclusions

Our study reveals the novel function of p-TGIF2 in promoting EMT and metastasis in LUAD; p-TGIF2 could be a potential therapeutic target to inhibit LUAD metastasis.
The burden of Parkinson’s disease in the Middle East and North Africa region, 1990–2019: results from the global burden of disease study 2019
Authors: Safiri Saeid , Noori Maryam , Nejadghaderi Seyed Aria , Mousavi Seyed Ehsan , Sullman Mark J. M. , Araj-Khodaei Mostafa , Singh Kuljit , Kolahi Ali-Asghar , Gharagozli Kurosh
Published: January 2023

Background

Parkinson’s disease (PD) remains a common disabling progressive neurodegenerative disorder. We aimed to report the prevalence, death and disability-adjusted life-years (DALYs) attributable to PD in the Middle East and North Africa (MENA) region and its 21 countries by age, sex and socio-demographic index (SDI), between 1990 and 2019.

Methods

Publicly available data on the burden of PD in the MENA countries were retrieved from the Global Burden of Disease (GBD) 2019 project. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs).

Results

In 2019, PD had an age-standardised point prevalence of 82.6 per 100,000 population in MENA and an age-standardised death rate of 5.3, which have increased from 1990 to 2019 by 15.4% and 2.3%, respectively. In 2019, the age-standardised DALY rate of PD was 84.4, which was 0.9% higher than in 1990. The highest and lowest age-standardised DALY rates of PD in 2019 were found in Qatar and Kuwait, respectively. Also in 2019, the highest number of prevalent cases and number of DALYs were found in the 75–79 age group for both sexes. In 2019, females in MENA had an overall higher DALY rate. Furthermore, from 1990 to 2019 the burden of PD generally decreased with increasing socio-economic development, up to an SDI of around 0.4, and then increased with higher levels of SDI.

Conclusion

An upward trend was observed in the point prevalence of PD over the last three decades. This highlights the need to allocate more resources for research. Furthermore, properly equipped healthcare services are needed for the increasing number of patients with PD.
Diffuse pigmented villonodular synovitis treated with arthroscopic total synovial peel
Authors: Song Hao-Qiang , Wu Guo-Feng , Qi Wei-Zhong , Lin Li-Jun
Published: January 2023

Background

Diffuse pigmented villonodular synovitis (PVNS) is prone to recurrence after surgery, and it is difficult to achieve a long-term complete cure.

Objective

To reduce the recurrence rate of PVNS, the author pioneered the arthroscopic total synovial peel (ATSP).

Methods

From March 2014 to July 2020, a total of 19 patients (6 males and 13 females) with diffuse PVNS of the knee were treated in our department and underwent ATSP. It’s ‘peel’ rather than simple excision. This method is similar to peeling bark. Relapse rates and functional scores were determined, with follow-ups ranging from 12 to 72 months, on average 36 months.

Results

Treatment efficacy was assessed by imaging and functional scores. Imaging results indicated a recurrence rate of 10.5%. In patients without recurrence, the visual analog score (VAS) decreased from 4.76 ± 2.02 preoperatively to 1.56 ± 1.15 postoperatively. The Tegner-Lysholm knee function score (TLS) score increased from 67.76 ± 15.64 preoperatively to 90.32 ± 8.32 postoperatively. Compared with the literature, ATSP significantly reduces the postoperative recurrence rate of diffuse PVNS. The preliminarily findings suggest that this approach could greatly reduce the recurrence rate of postoperative PVNS in follow-up studies.

Conclusion

This approach may be a viable option for treating diffuse PVNS via arthroscopy and is worthy of clinical consideration.
Exploring the mechanism of the Fructus Mume and Rhizoma Coptidis herb pair intervention in Ulcerative Colitis from the perspective of inflammation and immunity based on systemic pharmacology
Authors: Yang Yatian , Qian Chengcheng , Wu Rui , Wang Rui , Ou Jinmei , Liu Shoujin
Published: January 2023

Purpose

Ulcerative Colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Fructus Mume (FM) and Rhizoma Coptidis (RC) exert effects on inflammatory and immune diseases. We evaluated the hypothesis of the FM and RC (FM-RC) herb pair remedy in alleviating dextran sulfate sodium (DSS)-induced colitis, through network pharmacology-based analyses, molecular docking, and experimental validation.

Methods

The Traditional Chinese medicine systematic pharmacology analysis platform(TCMSP) and Swiss database were used to predict potential targets of FM-RC and the GeneCards database was utilized to collect UC genes. Cytoscape software was used to construct and analyze the networks, and DAVID was utilized to perform enrichment analysis. AutoDock software was used to dock the core chemical components of the FM-RC herb pair with key UC targets. Animal experiments were performed to validate the prediction results and general conditions and body weight were observed. Pathological changes in colon tissue were observed by staining with hematoxylin and eosin. The levels of TNF-α, IL-8, IL-17, and IL-4 in serum and colon tissue were detected by ELISA.

Results

Eighteen effective components of the herb couple were screened, and their potential therapeutic targets in the treatment of UC were acquired from 110 overlapped targets. GO and KEGG analyses revealed that these targets were highly correlated with protein autophosphorylation, plasma membrane, ATP binding, cancer pathways, the PI3K-AKt signaling pathway, and the Rap1 signaling pathway. Molecular docking established the core protein interactions with compounds having a docking energy < 0 kJ·mol−1, indicating the core active components had strong binding activities with the core targets. FM-RC herb pair relieved pathological indicators and reduced the concentration of TNF-α, IL-8, and IL-17 and increased IL-4 levels in the serum and colon tissues of UC rats.

Conclusion

Collectively, FM-RC herb pair administration alleviated UC. These beneficial effects targeted MAPK1 signaling related to inflammation and immunity, which provided a basis for a better understanding of FM-RC in the treatment of UC.
Fragmented understanding: exploring the practice and meaning of informed consent in clinical trials in Ho Chi Minh City, Vietnam
Authors: Nguyen Yen Hong Thi , Dang Thuan Trong , Lam Ngoc Bao Hong , Le Phuong Thanh , Nguyen Phu Hoan , Bull Susan , Kestelyn Evelyne , Van Nuil Jennifer Ilo
Published: January 2023

Background

The informed consent process in clinical trials has been extensively studied to inform the development processes which protect research participants and encourage their autonomy. However, ensuring a meaningful informed consent process is still of great concern in many research settings due to its complexity in practice and interwined socio-cultural factors.

Objectives

This study explored the practices and meaning of the informed consent process in two clinial trials conducted by Oxford University Clinical Research Unit in collaboration with the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

Methods

We used multiple data collection methods including direct observervations, in-depth interviews with study physicians and trial participants, review of informed consent documents from 2009 to 2018, and participant observation with patients’ family members. We recruited seven physicians and twenty-five trial participants into the study, of whom five physicians and thirteen trial participants completed in-depth interviews, and we held twenty-two direct observation sessions.

Results

We use the concept “fragmented understanding” to describe the nuances of understanding about the consent process and unpack underlying reasons for differing understandings.

Conclusions

Our findings show how practices of informed consent and different understanding of the trial information are shaped by trial participants’ characteristics and the socio-cultural context in which the trials take place.
Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration
Authors: Abbasizanjani Hoda , Torabi Fatemeh , Bedston Stuart , Bolton Thomas , Davies Gareth , Denaxas Spiros , Griffiths Rowena , Herbert Laura , Hollings Sam , Keene Spencer , Khunti Kamlesh , Lowthian Emily , Lyons Jane , Mizani Mehrdad A. , Nolan John , Sudlow Cathie , Walker Venexia , Whiteley William , Wood Angela , Akbari Ashley ,   CVD-COVID-UK/COVID-IMPACT Consortium
Published: January 2023

Background

The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.

Methods

Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.

Results

Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.

Conclusions

We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.
Approaches to clinical guideline development in healthcare: a scoping review and document analysis
Authors: De Leo Annemarie , Bloxsome Dianne , Bayes Sara
Published: January 2023

Background

Over the past decade, an industry has emerged around Clinical Practice Guideline (CPG) development in healthcare, which has increased pressure on guideline-producing organisations to develop CPGs at an accelerated rate. These are intended to improve the quality of care provided to patients while containing healthcare costs and reducing variability in clinical practice. However, this has inadvertently led to discrepancies in CPG recommendations between health organisations, also challenging healthcare providers who rely on these for decision-making and to inform clinical care. From a global perspective, although some countries have initiated national protocols regarding developing, appraising and implementing high-quality CPGs, there remains no standardised approach to any aspect of CPG production.

Methods

A scoping review of the literature and document analysis were conducted according to Joanna Brigg’s Institute methodology for scoping reviews. This comprised two qualitative methods: a comprehensive review of the literature (using CINAHL, Scopus and PubMeD) and a document analysis of all national and international guideline development processes (manual search of health-related websites, national/international organisational health policies and documents).

Results

A set of clear principles and processes were identified as crucial to CPG development, informing the planning, implementation and dissemination of recommendations. Fundamentally, two common goals were reported: to improve the quality and consistency of clinical practice (patient care) and to reduce the duplication or ratification of low-grade CPGs.

Conclusions

Consultation and communication between CPG working parties, including a wide range of representatives (including professional organisations, regional and local offices, and relevant national bodies) is essential. Further research is required to establish the feasibility of standardising the approach and disseminating the recommendations.
Thyroid dysfunction in Chinese nasopharyngeal carcinoma after anti-PD-1 therapy and its association with treatment response
Authors: Chen Zi-Hang , Zheng Wei-Hong , Wu Chen-Fei , Kou Jia , Yang Xing-Li , Lin Li , Lv Jia-Wei , Sun Ying , Zhou Guan-Qun
Published: January 2023

Background

Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated efficacy in nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse events. This study aimed to explore the clinical pattern of thyroid dysfunction and its relationship with survival marker in nonmetastatic NPC after immunotherapy.

Methods

From January 1, 2019, to December 31, 2021, 165 pairs of nonmetastatic NPC patients (165 with and 165 without anti-PD-1 immunotherapy) matched by the propensity score matching method were included in this study. Thyroid function was assessed retrospectively before the first treatment and during each immunotherapy cycle.

Results

The spectrum of thyroid dysfunction was different between the immunotherapy and control groups (P < 0.001). Compared with the control group, patients in the immunotherapy group developed more hypothyroidism (14.545% vs. 7.273%), less hyperthyroidism (10.909% vs. 23.636%), and a distinct pattern, biphasic thyroid dysfunction (3.030% vs. 0%). Immunotherapy also accelerates the onset of hypothyroidism, which was earlier with a median onset time difference of 32 days (P < 0.001). Patients who acquired thyroid dysfunction during immunotherapy had better complete biological response to treatment (OR, 10.980; P = 0.042).

Conclusions

For nonmetastatic NPC, thyroid dysfunction was associated with better response to treatment in immunotherapy but not in routine treatment. Thyroid function could be used as a predictor for survival and should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy for nonmetastatic NPC.
The impact of alcohol taxation increase on all-cause mortality inequalities in Lithuania: an interrupted time series analysis
Authors: Manthey Jakob , Jasilionis Domantas , Jiang Huan , Meščeriakova Olga , Petkevičienė Janina , Radišauskas Ričardas , Štelemėkas Mindaugas , Rehm Jürgen
Published: January 2023

Background

Taxation increases which reduce the affordability of alcohol are expected to reduce mortality inequalities. A recent taxation increase in Lithuania offers the unique possibility to test this hypothesis.

Methods

Census-linked mortality data between 2011 and 2019 were used to calculate monthly sex- and education-stratified age-standardized mortality rates for the population aged 40 to 70 years. As primary outcome, we analysed the difference in age-standardized all-cause mortality rates between the population of lowest versus highest educational achievement. The impact of the 2017 taxation increase was evaluated using interrupted time series analyses. To identify whether changes in alcohol use can explain the observed effects on all-cause mortality, the education-based mortality differences were then decomposed inton = 16 cause-of-death groupings.

Results

Between 2012 and 2019, education-based all-cause mortality inequalities in Lithuania declined by 18% among men and by 14% among women. Following the alcohol taxation increase, we found a pronounced yet temporary reduction of mortality inequalities among Lithuanian men (− 13%). Subsequent decomposition analyses suggest that the reduction in mortality inequalities between lower and higher educated men was mainly driven by narrowing mortality differences in injuries and infectious diseases.

Conclusions

A marked increase in alcohol excise taxation was associated with a decrease in mortality inequalities among Lithuanian men. More pronounced reductions in deaths from injuries and infectious diseases among lower as compared to higher educated groups could be the result of differential changes in alcohol use in these populations.
Simultaneous detection and identification of Peste des petits ruminants Virus Lineages II and IV by MCA-Based real-time quantitative RT-PCR assay within single reaction
Authors: Tang Jingyu , Du Hanyu , Tang Aoxing , Jia Nannan , Zhu Jie , Li Chuanfeng , Meng Chunchun , Liu Guangqing
Published: January 2023

Background

Peste des petits ruminants (PPR) disease is a cross-species infectious disease that severely affects small ruminants and causes great losses to livestock industries in various countries. Distinguishing vaccine-immunized animals from naturally infected animals is an important prerequisite for the eradication of PPR. At present PPRV are classified into lineages I through IV, and only one vaccination strain, Nigeria/75/1, belongs to lineage II, but all of the epidemic strains in China at present are from lineage IV.

Results

To achieve this goal, we developed an SYBR Green I real-time qRT-PCR method for rapid detection and identification of PPRV lineages II and IV by analyzing different melting curve analyses. The negative amplification of other commonly circulating viruses such as orf virus, goat poxvirus, and foot-and-mouth disease virus demonstrated that primers targeting the L gene of PPRV were extremely specific. The sensitivity of the assay was assessed based on plasmid DNA and the detection limit achieved was 100 copies of PPRV lineages II and IV.

Conclusion

Since the method has high sensitivity, specificity, and reproducibility, it will be effectively differentiated PPRV lineages II from PPRV lineages IV in PPRV infected animals.
Increasing the production of the bioactive compounds in medicinal mushrooms: an omics perspective
Authors: Arshadi Nooshin , Nouri Hoda , Moghimi Hamid
Published: January 2023

Macroscopic fungi, mainly higher basidiomycetes and some ascomycetes, are considered medicinal mushrooms and have long been used in different areas due to their pharmaceutically/nutritionally valuable bioactive compounds. However, the low production of these bioactive metabolites considerably limits the utilization of medicinal mushrooms both in commerce and clinical trials. As a result, many attempts, ranging from conventional methods to novel approaches, have been made to improve their production. The novel strategies include conducting omics investigations, constructing genome-scale metabolic models, and metabolic engineering. So far, genomics and the combined use of different omics studies are the most utilized omics analyses in medicinal mushroom research (both with 31% contribution), while metabolomics (with 4% contribution) is the least. This article is the first attempt for reviewing omics investigations in medicinal mushrooms with the ultimate aim of bioactive compound overproduction. In this regard, the role of these studies and systems biology in elucidating biosynthetic pathways of bioactive compounds and their contribution to metabolic engineering will be highlighted. Also, limitations of omics investigations and strategies for overcoming them will be provided in order to facilitate the overproduction of valuable bioactive metabolites in these valuable organisms.