bluuebunny/crossref_metadata_2025 huggingface dataset:
Propofol Disrupts Clear Cell Renal Cell Carcinoma Tumorigenesis by Regulating circFBXW7/miR-942 Axis
Authors: Huang Yunfeng , Wu Yuanbo , Lu Shengqiang
Published: March 2022

Background: Propofol is a commonly used intravenous anesthetic and has been found to perform anticancer effects in many cancers. However, the effects and mechanisms of propofol in clear cell renal cell carcinoma (ccRCC) remain largely undefined. Methods: The expression of circular RNA FBXW7 (circFBXW7) and miR-942 was detected by qRT-PCR. Cell proliferation, apoptosis, migration, and invasion capacities were analyzed using cell counting kit-8, colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the expression levels of PCNA, Cleaved-caspase 3 and MMP protein. The bindings between miR-942 and circFBXW7 were verified using RNA pull-down, dual-luciferase reporter, and RIP assays. Xenograft tumor analysis was employed to detect tumorigenesis in vivo. Results: Propofol alleviated cell proliferation, migration, invasion, and induced apoptosis in vitro and impeded tumor growth in vivo in ccRCC. Propofol elevated the level of circFBXW7, which knockdown reversed the anticancer effects of propofol on ccRCC cell tumorigenesis. CircFBXW7 directly bound to miR-942, and suppressed ccRCC cell malignant biological behaviors via targeting miR-942. Besides that, propofol decreased miR-942 expression, and miR-942 overexpression attenuated the effects of propofol on ccRCC cells. Moreover, propofol could regulate miR-942 expression through circFBXW7. Conclusion: Propofol suppressed the growth, migration, and invasion of ccRCC cells by regulating circFBXW7/miR-942 axis, suggesting a potential therapeutic strategy for the intervention of human ccRCC development.
Management for Ureterovaginal Fistula: A Retrospective Study Comparing Early and Delayed Ureteral Reimplantation
Authors: Long Gongwei , Ouyang Wei , Huang Dajun , Hu Zhiquan , Wang Shaogang , Liu Zheng , Li Heng
Published: March 2022

Introduction: The timing of surgical repair for ureterovaginal fistula (UVF) is under debate, here we introduce our experience to compare the safety and efficacy between early and delayed ureteral reimplantation for UVF. Methods: Between January 2012 and January 2020, 22 patients who were diagnosed with UVF had received ureteral reimplantation. Baseline characteristics, history of previous abdominal surgery, operative profile, and follow-up data were collected and analyzed. Results: Among 22 patients diagnosed with UVF, 12 patients received early ureteral reimplantation and others received delayed ureteral reimplantation. Both groups were comparable in baseline characteristics and detailed history of previous operations. The mean operative time of the early surgery group was 140.83 ± 35.28 min, while that of the delayed surgery group was 181.00 ± 43.83 min (p = 0.027). Patients of the early surgery group (183.33 ± 107.31 mL) had less blood loss compared with that of the delayed surgery group (285.00 ± 94.43 mL) (p = 0.030). After an overall mean follow-up of 34.55 months, the ureteral stricture rate of two groups was not statistically significantly different (16.67% in early repair vs. 40.00% in delayed repair, p = 0.348). Conclusion: With similar long-term outcomes, the early ureteral reimplantation had a shorter operative time and less blood loss. Moreover, the stress during the waiting period could be minimized. High-quality clinical studies with larger sample size are needed to confirm the superior nature of early surgery.
O projeto dos planos de saúde acessíveis: prejuízo para beneficiários e para o sistema público
Authors: Romão Ana Luisa Pereira Agudo , Bucci Maria Paula Dallari , Haddad Frederico
Published: March 2022

O presente trabalho analisou, sob a perspectiva econômica da concretização do direito à saúde, o Projeto de Lei dos Planos de Saúde Acessíveis (PL n. 7.419/2006), apensado ao projeto geral de reforma da Lei n. 9.656/1998, desenvolvido pelo Ministério da Saúde em 2016 e atualmente em tramitação na Câmara dos Deputados. Para isso, os documentos oficiais da proposta foram analisados à luz de suas justificativas econômicas e da amplitude do acesso a serviços. As principais diretrizes do projeto, destacando-se os novos modelos de planos, evidenciam a criação de entraves burocráticos à realização de procedimentos, além da flexibilização do rol de cobertura dos planos de acordo com a infraestrutura local, em desacordo com a cobertura mínima prevista na regulação atual. A proposta favorece economicamente as operadoras de planos de saúde ao estabelecer a coparticipação de 50% e o reajuste conforme tabela de custos. Além disso, na prática, o projeto apresenta um duplo prejuízo: ao beneficiário, que arca com os custos do plano e, no momento de maior necessidade, de procedimentos de urgência ou de maior complexidade por não estar amparado pela cobertura; e ao sistema público, que deve suprir as deficiências da cobertura privada, o que, em um momento de maior demanda e recursos limitados, pode levá-lo à sobrecarga.
Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis
Authors: Stein Elliot J. , Fearon William F. , Elmariah Sammy , Kim Juyong B. , Kapadia Samir , Kumbhani Dharam J. , Gillam Linda , Whisenant Brian , Quader Nishath , Zajarias Alan , Welt Frederick G. , Bavry Anthony A. , Coylewright Megan , Piana Robert N. , Mallugari Ravinder R. , Clark Daniel E. , Patel Jay N. , Gonzales Holly , Gupta Deepak K. , Vatterott Anna , Jackson Natalie , Huang Shi , Lindman Brian R.
Published: March 2022

Background

Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown.

Methods and Results

In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (
P
<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01–1.77,
P
=0.043). cTnT and NT‐proBNP each risk stratified patients with moderate/severe LVH (
P
<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45–3.00,
P
<0.001) and elevated NT‐proBNP (aHR, 1.46; 95% CI 1.00–2.11,
P
=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (
P
=0.15).

Conclusions

Elevations in circulating cTnT and NT‐proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT‐proBNP predict post‐transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.
Persistent Markers of Kidney Injury in Children Who Developed Acute Kidney Injury After Pediatric Cardiac Surgery: A Prospective Cohort Study
Authors: Van den Eynde Jef , Salaets Thomas , Louw Jacoba J. , Herman Jean , Breysem Luc , Vlasselaers Dirk , Desmet Lars , Meyns Bart , Budts Werner , Gewillig Marc , Mekahli Djalila
Published: March 2022

Background

Acute kidney injury (AKI) after pediatric cardiac surgery is common. Longer‐term outcomes and the incidence of chronic kidney disease after AKI are not well‐known.

Methods and Results

All eligible children (aged <16 years) who had developed AKI following cardiac surgery at our tertiary referral hospital were prospectively invited for a formal kidney assessment ≈5 years after AKI, including measurements of estimated glomerular filtration rate, proteinuria, α
1
‐microglobulin, blood pressure, and kidney ultrasound. Longer‐term follow‐up data on kidney function were collected at the latest available visit. Among 571 patients who underwent surgery, AKI occurred in 113 (19.7%) over a 4‐year period. Fifteen of these (13.3%) died at a median of 31 days (interquartile range [IQR], 9–57) after surgery. A total of 66 patients participated in the kidney assessment at a median of 4.8 years (IQR, 3.9–5.7) after the index AKI episode. Thirty‐nine patients (59.1%) had at least 1 marker of kidney injury, including estimated glomerular filtration rate <90 mL/min per 1.73 m
2
in 9 (13.6%), proteinuria in 27 (40.9%), α
1
‐microglobinuria in 5 (7.6%), hypertension in 13 (19.7%), and abnormalities on kidney ultrasound in 9 (13.6%). Stages 1 to 5 chronic kidney disease were present in 18 (27.3%) patients. Patients with CKD were more likely to have an associated syndrome (55.6% versus 20.8%,
P
=0.015). At 13.1 years (IQR, 11.2–14.0) follow‐up, estimated glomerular filtration rate <90 mL/min per 1.73 m² was present in 18 of 49 patients (36.7%), suggesting an average estimated glomerular filtration rate decline rate of −1.81 mL/min per 1.73 m² per year.

Conclusions

Children who developed AKI after pediatric cardiac surgery showed persistent markers of kidney injury. As chronic kidney disease is a risk factor for cardiovascular comorbidity, long‐term kidney follow‐up in this population is warranted.
DIŞ BORÇ İSTİHDAMI ARTIRIR MI? TÜRKİYE’DEN AMPİRİK BİR KANIT
Authors: YILDIZ Furkan
Published: March 2022

Bu çalışmanın temel amacı Türkiye’nin dış borçlanma politikasının istihdamı artırıp artırmadığını tespit etmektir. Bu amaca uygun olarak Türkiye’nin 1960-2019 yıllık verileri kullanılarak VAR eş bütünleşme ve nedensellik analizleri uygulanmıştır. Çalışmanın ampirik bulguları Türkiye’de işsizlik oranı ve dış borç stoku arasında çift yönlü bir nedensellik ilişkisinin olduğunu göstermektedir. Türkiye’de kısa dönemde dış borç stokundaki artış işsizlik oranını azaltmaktayken, uzun dönemde ise işsizlik oranını artırmaktadır. Bu sonuçlar Türkiye’nin kullandığı dış borcu uzun dönemde yüksek katma değer yaratacak biçimde kullanamadığını göstermektedir. Bu nedenle alınan dış borç yüksek artı değer yaratacak karlı yatırımlarda kullanılmalıdır.
Jordan
Authors: Alawamleh Kamal Jamal
Published: March 2022

This survey seeks to illustrate the most important legal developments the Hashemite Kingdom of Jordan has witnessed during the year 2021. As the main and first source of law in Jordan is legislation, this survey will mainly focus on the different pieces of legislation that have been passed or amended during this period.
A New Game Changer in BOT Contracts in Egypt – The Dipco Case
Authors: El Sawah Sally
Published: March 2022

Construction contracts in Egypt are governed by a myriad of rules. BOT and other similar contracts are of a mixed nature, which entails the application of both public and private law rules. Therefore, the solution to issues like Variation of Works or Termination will depend on whether or not the contract is characterized as an administrative contract. Adding another layer of complication, the Dipco judgment has reopened the debate about arbitrating BOT and other contracts of similar nature, a subject supposedly closed since 1997 by Article 1(2) of the Arbitration Law.
New polymer nano-biomaterials in rehabilitation nursing of orthopedic surgery injuries
Authors: Hou Ji-Dan , Zhang Yun-Ping , Tang Chun-Ju
Published: March 2022

Changes in nano-bio materials’ surface electronic structure and crystal structure produce small-size effects that macroscopic objects do not have. This makes it have a series of excellent macroscopic properties such as force, magnetism, electricity, optics, chemistry, and biology
that traditional materials do not have. This article studies the application of new polymer nano-bio materials in orthopedic trauma. We study the effect of nanolevel hydroxyapatite gradient coating on the expression of osteoblast phenotypic factors. The shear strength of the implant-bone interface
is better than the titanium alloy group and the titanium alloy group. So we can conclude that the nano-grade hydroxyapatite gradient coating material has good biological characteristics. It can promote the early healing of the bone trauma interface. This material is worthy of clinical application.
Telework potential in the Philippines
Authors: Gaduena Ammielou , Caboverde Christopher Ed , Flaminiano John Paul
Published: March 2022

Using work from home (WFH) scores obtained by matching Philippine occupations with U.S. O*NET occupations, this paper estimates that only 12.38% of all workers can WFH and 25.7% of Philippine occupations are teleworkable––mostly from the following occupational groups: professionals, clerical support workers, and technicians and associate professionals. The education, real estate and, professional, scientific and technical sectors account for the largest share of teleworkable jobs. Those workers belonging to lower per capita income deciles, who are male, who have lower levels of education, who are self-employed, aged 55 and older, and who are working in sectors such as agriculture and retail, are also less likely to be in teleworkable occupations.
Slave “Corrections” in Luanda, Angola from 1836 to 1869
Authors: Lopes Tracy
Published: March 2022

This paper uses thousands of cases of imprisonment published under the police section of a weekly gazette entitled Boletim Oficial do Governo da Província de Angola to explore the connections between slavery and the “birth of the prison” in Luanda, the capital of the Portuguese colony of Angola between 1836 and 1869. It demonstrates that as the colonial administration gradually abolished the institution of slavery in the mid-nineteenth century, masters and mistresses sent thousands of captives to jail for “correction,” which could include imprisonment, beatings, and forced labour. By focusing on “correction” cases, this paper problematizes the dichotomy between pre-modern and modern types of punishment and demonstrates that the prison in Luanda reinforced the violence of the slaveholding class.
Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study
Authors: Senker Wolfgang , Aspalter Stefan , Radl Christian , Pichler Josef , Doppler Stefan , Weis Serge , Webersinke Christine , Wagner Helga , Hermann Philipp , Aichholzer Martin , Aufschnaiter-Hießböck Kathrin , Thomae Wolfgang , Stroh Nico , Hauser Thomas , Gruber Andreas
Published: March 2022

Study design

Monocentric, prospective, observational study.

Objective

The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs.

Methods

We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months.

Results

Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred.

Conclusions

With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations.

Level of Evidence

III.

Trial registration: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www.clinicaltrials.gov/ct2/show/study/NCT04712487).
Changing tracks: identifying and tackling bottlenecks in European rail passenger transport
Authors: Witlox Frank , Zwanikken Tim , Jehee Linde , Donners Barth , Veeneman Wijnand
Published: March 2022

For Europe's urban agglomerations to be economically competitive, it is vital that international destinations be easily accessible. Although much has been invested in the construction of European rail infrastructure over the past century, passenger transport by rail has not grown as fast as transport by road and air. So why do people not use international trains more, even though they have an extensive international rail network at their disposal? Based on a series of in-depth interviews with relevant public and private stakeholders and two expert meetings, we identify the main bottlenecks and constraints. In order to understand the complexity of international rail transport, we have divided the existing bottlenecks into four groups corresponding to four layers of the rail transport system: mobility services, transport services, traffic services, and the physical and digital infrastructure. We formulate concrete policy recommendations for improvements to be made in the various components of the rail transport system.
Bioinformatical analysis of the key differentially expressed genes and associations with immune cell infiltration in development of endometriosis
Authors: Chen Shengnan , Chai Xiaoshan , Wu Xianqing
Published: March 2022

Background

This study explored the key genes related to immune cell infiltration in endometriosis.

Results

The Gene Expression Omnibus (GEO) datasets (GSE7305, GSE7307, and GSE11691), containing a total of 37 endometriosis and 42 normal tissues, were retrieved and analyzed to determine the differentially expressed genes (DEGs). Gene ontology (GO) annotations and Kyoto Encyclopedia of Genes (KEGG) analysis were performed to identify the pathways that were significantly enriched. The xCell software was used to analyze immune cell infiltration and correlation analyses were performed to uncover the relationship between key genes and immune cells. The analysis identified 1031 DEGs (581 upregulated and 450 downregulated DEGs), while GO analysis revealed altered extracellular matrix organization, collagen-containing extracellular matrix, and glycosaminoglycan binding and KEGG enrichment showed genes related to metabolic pathways, pathways in cancer, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling, proteoglycans in cancer, and the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, the protein–protein interaction network revealed 10 hub genes, i.e.,IL6,FN1,CDH1,CXCL8,IGF1,CDK1,PTPRC,CCNB1,MKI67, andESR1. The xCell analysis identified immune cells with significant changes in all three datasets, including CD4+and CD8+T cells, CD8+Tem, eosinophils, monocytes, Th1 cells, memory B-cells, activated dendritic cells (aDCs), and plasmacytoid dendritic cells (pDCs). These 10 hub genes were significantly associated with at least three types of immune cells.

Conclusions

Aberrant gene expression was related to abnormal infiltration of different immune cells in endometriosis and was associated with endometriosis development by affecting the tissue microenvironment and growth of ectopic endometrial cells.
Identifying genes with conserved splicing structure and orthologous isoforms in human, mouse and dog
Authors: Guillaudeux Nicolas , Belleannée Catherine , Blanquart Samuel
Published: March 2022

Background

In eukaryote transcriptomes, a significant amount of transcript diversity comes from genes’ capacity to generate different transcripts through alternative splicing. Identifying orthologous alternative transcripts across multiple species is of particular interest for genome annotators. However, there is no formal definition of transcript orthology based on the splicing structure conservation. Likewise there is no public dataset benchmark providing groups of orthologous transcripts sharing a conserved splicing structure.

Results

We introduced a formal definition of splicing structure orthology and we predicted transcript orthologs in human, mouse and dog. Applying a selective strategy, we analyzed 2,167 genes and their 18,109 known transcripts and identified a set of 253 gene orthologs that shared a conserved splicing structure in all three species. We predicted 6,861 transcript CDSs (coding sequence), mainly for dog, an emergent model species. Each predicted transcript was an ortholog of a known transcript: both share the same CDS splicing structure. Evidence for the existence of the predicted CDSs was found in external data.

Conclusions

We generated a dataset of 253 gene triplets, structurally conserved and sharing all their CDSs in human, mouse and dog, which correspond to 879 triplets of spliced CDS orthologs. We have released the dataset both as an SQL database and as tabulated files. The data consists of the 879 CDS orthology groups with their detailed splicing structures, and the predicted CDSs, associated with their experimental evidence. The 6,861 predicted CDSs are provided in GTF files. Our data may contribute to compare highly conserved genes across three species, for comparative transcriptomics at the isoform level, or for benchmarking splice aligners and methods focusing on the identification of splicing orthologs. The data is available at https://data-access.cesgo.org/index.php/s/V97GXxOS66NqTkZ.
GIF1 controls ear inflorescence architecture and floral development by regulating key genes in hormone biosynthesis and meristem determinacy in maize
Authors: Li Manfei , Zheng Yuanyuan , Cui Di , Du Yanfang , Zhang Dan , Sun Wei , Du Hewei , Zhang Zuxin
Published: March 2022

Background

Inflorescence architecture and floral development in flowering plants are determined by genetic control of meristem identity, determinacy, and maintenance. The ear inflorescence meristem in maize (Zea mays) initiates short branch meristems called spikelet pair meristems, thus unlike the tassel inflorescence, the ears lack long branches. Maize growth-regulating factor (GRF)-interacting factor1 (GIF1) regulates branching and size of meristems in the tassel inflorescence by binding to Unbranched3. However, the regulatory pathway of gif1 in ear meristems is relatively unknown.

Result

In this study, we found that loss-of-function gif1 mutants had highly branched ears, and these extra branches repeatedly produce more branches and florets with unfused carpels and an indeterminate floral apex. In addition, GIF1 interacted in vivo with nine GRFs, subunits of the SWI/SNF chromatin-remodeling complex, and hormone biosynthesis-related proteins. Furthermore, key meristem-determinacy gene RAMOSA2 (RA2) and CLAVATA signaling-related gene CLV3/ENDOSPERM SURROUNDING REGION (ESR) 4a (CLE4a) were directly bound and regulated by GIF1 in the ear inflorescence.

Conclusions

Our findings suggest that GIF1 working together with GRFs recruits SWI/SNF chromatin-remodeling ATPases to influence DNA accessibility in the regions that contain genes involved in hormone biosynthesis, meristem identity and determinacy, thus driving the fate of axillary meristems and floral organ primordia in the ear-inflorescence of maize.
All-cause mortality and cardiovascular events in a Spanish nonagenarian cohort according to type 2 diabetes mellitus status and established cardiovascular disease
Authors: Salinero-Fort MA , Mostaza J. , Lahoz C. , Cárdenas-Valladolid J. , Vicente-Díez J. I. , Gómez-Campelo P. , de Miguel-Yanes J. M.
Published: March 2022

Background

Despite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population.

Methods

We analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression).

Results

Mean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01).

Conclusions

In Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.
Periconceptional folic acid supplementation is a risk factor for childhood asthma: a case-control study
Authors: Chu Shuyuan , Zhang Jun
Published: March 2022

Background

Several studies found an association between periconceptional folic acid supplementation and the risk of childhood asthma. But the epidemiologic evidence is still inconsistent and the underlying biological mechanisms remain unclear.

Methods

We conducted a hospital-based case-control study on childhood asthma with 548 cases and 816 normal controls in Shanghai, China. Mothers of the asthma children were asked about folic acid supplementation before and during pregnancy. Unconditional logistic regression models were employed to control for potential confounders.

Results

Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma after adjusting for potential confounders (adjusted OR = 1.28 [95% CI 1.14–1.43]). Moreover, the adjusted OR varied by the timing of starting folic acid supplementation: before gestation: 1.31 [95% CI 1.01–1.70]; in the 1st month of gestation: 1.09 [95% CI 0.96–1.23]; and after the 1st month of gestation: 1.90 [95% CI 1.56–2.30]. We further found that the adjusted OR was the highest when periconceptional folic acid supplementation lasted more than 6 months (< 4 months: 1.21 [95% CI 1.07–1.37]; 4–6 months: 1.06 [95% CI 0.88–1.27]; > 6 months: 1.75 [95% CI 1.35–2.27]).

Conclusions

Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma in offspring. Further research on this issue is warranted.
Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation
Authors: Kamai Takao , Murakami Satoshi , Arai Kyoko , Nishihara Daisaku , Uematsu Toshitaka , Ishida Kazuyuki , Kijima Toshiki
Published: March 2022

Background

Pheochromocytomas (PCC) and paragangliomas (PGL) are catecholamine-producing neuroendocrine tumors. According to the World Health Organization Classification 2017, all PCC/PGL are considered to have malignant potential. There is growing evidence that PCC/PGL represent a metabolic disease that leads to aerobic glycolysis. Cellular energy metabolism involves both transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and succinate dehydrogenase (SDH) subtypes, but the association of these substances with PCC/PGL is largely unknown.

Methods

We investigated SDHB gene mutation and protein expressions for SDHB and Nrf2 in surgical specimens from 29 PCC/PGL. We also assessed preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography and mRNA levels for Nrf2.

Results

Among 5 PCC/PGL with a PASS Score ≥ 4 or with a moderately to poorly differentiated type in the GAPP Score, 4 were metastatic and found to be SDHB mutants with homogeneous deletion of SDHB protein. SDHB mutants showed a higher expression of Nrf2 protein and a higher preoperative SUVmax than non-SDHB mutants with a PASS < 4 or a well-differentiated GAPP type. Furthermore, protein expression of Nrf2 was positively associated with preoperative SUVmax. The Nrf2 mRNA level positively correlated with malignant phenotype, higher expression for Nrf2 protein and SDHB gene mutant, but negatively correlated with expression for SDHB protein. There was also a positive correlation between Nrf2 mRNA level and SUVmax.

Conclusion

These results suggest that activation of Nrf2 and elevated metabolism play roles in PCC/PGL with malignant potential that have SDHB gene mutation and SDHB deficiency.
Current situation of pediatric clinical trials in China: focus on trials for drug marketing application and administrative approval
Authors: Song Lin , Jia Yuntao , Ran Sujuan , Li Bin , Xu Jin , Huo Bennian , Yin Nange , Ai Maolin , Liu Yao
Published: March 2022

Background

Research and development of pediatric drug faces many difficulties and pediatric clinical trials remain a challenge. Since 2011, a series of measures have been taken to encourage research, development of drugs for pediatric patients in China. In this study, we analyzed pediatric clinical trials conducted in China to provide reference for research and development of pediatric drugs and formulation of relevant policies.

Methods

We conducted a cross-sectional observational study of pediatric trials registered in the Drug Trial Registration and Information Publication Platform before Oct. 31, 2021. All trials that recruited children (under 18 years old as defined in China) were retrieved and general characteristics of the trials and the research drugs were extracted and analyzed. The data were extracted and statistically analyzed by excel 2010 and SPSS 22.0, respectively.

Results

There were 588 registered pediatric clinical trials, which accounted for 3.94% of the total registered trials. The overall average annual growth rate of the number of trials from 2013 to 2020 was 14.47% (P < 0.01). Of the 588 trials included, there were 312 trials (53.06%) with only children as subjects, 127 trials (21.60%) with research drugs only for children use, and the median of target subject number was 320 with the range of 8 to 600,000. The sponsors and the principal investigators were mainly located in the eastern and northern China. 325 trials were vaccine trials, and the dosage form was mainly injection. There were 98 non-vaccine biological product trials (mainly injections), 135 chemical compound drug trials (mainly tablets), 30 traditional Chinese medicine/natural drugs (mainly granules). Indications of the non-vaccine drugs were mainly diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism.

Conclusion

The number of pediatric clinical trials in China has increased these years. To further promote pediatric clinical trials and motivate pediatric appropriate drug marketing application and administrative approval, conducting large pediatric clinical trials, further development of dosage forms suitable for children with special attention to neonates and prematurity, and improving uneven geographical distribution of sponsors and researchers are the current challenges.
Experiences of new diagnoses among HIV-positive persons: implications for public health
Authors: Owusu Adobea Yaa
Published: March 2022

Background

Ready acceptance of experiences of new diagnoses among HIV-positive persons is a known personal and public health safety-net. Its beneficial effects include prompt commencement and sustenance of HIV-positive treatment and care, better management of transmission risk, and disclosure of the HIV-positive status to significant others. Yet, no known study has explored this topic in Ghana; despite Ghana’s generalised HIV/AIDS infection rate. Existing studies have illuminated the effects of such reactions on affected significant others; not the infected.

Methods

This paper studied qualitatively the experiences of new diagnoses among 26 persons living with HIV/AIDS. Sample selection was random, from two hospitals in a district in Ghana heavily affected by HIV/AIDS. The paper applied the Hopelessness Theory of Depression.

Results

As expected, the vast majority of respondents experienced the new diagnoses of their HIV-positive infection with a myriad of negative psychosocial reactions, including thoughts of committing suicide. Yet, few of them received the news with resignation. For the vast majority of respondents, having comorbidities from AIDS prior to the diagnosis primarily shaped their initial reactions to their diagnosis. The respondents’ transitioning to self-acceptance of their HIV-positive status was mostly facilitated by receiving counselling from healthcare workers.

Conclusions

Although the new HIV-positive diagnosis was immobilising to most respondents, the trauma faded, paving the way for beneficial public health actions. The results imply the critical need for continuous education on HIV/AIDS by public health advocates, using mass media, particularly, TV. Healthcare workers in VCTs should empathise with persons who experience new diagnoses of their HIV-positive status.
Research on exercise fatigue estimation method of Pilates rehabilitation based on ECG and sEMG feature fusion
Authors: Li Dujuan , Chen Caixia
Published: March 2022

Purpose

Surface electromyography (sEMG) is vulnerable to environmental interference, low recognition rate and poor stability. Electrocardiogram (ECG) signals with rich information were introduced into sEMG to improve the recognition rate of fatigue assessment in the process of rehabilitation.

Methods

Twenty subjects performed 150 min of Pilates rehabilitation exercise. Twenty subjects performed 150 min of Pilates rehabilitation exercise. ECG and sEMG signals were collected at the same time. Aftering necessary preprocessing, the classification model of improved particle swarm optimization support vector machine base on sEMG and ECG data fusion was established to identify three different fatigue states (Relaxed, Transition, Tired). The model effects of different classification algorithms (BPNN, KNN, LDA) and different fused data types were compared.

Results

IPSO-SVM had obvious advantages in the classification effect of sEMG and ECG signals, the average recognition rate was 87.83%. The recognition rates of sEMG and ECG fusion feature classification models were 94.25%, 92.25%, 94.25%. The recognition accuracy and model performance was significantly improved.

Conclusion

The sEMG and ECG signal after feature fusion form a complementary mechanism. At the same time, IPOS-SVM can accurately detect the fatigue state in the process of Pilates rehabilitation. On the same model, the recognition effect of fusion of sEMG and ECG(Relaxed: 98.75%, Transition:92.25%, Tired:94.25%) is better than that of only using sEMG signal or ECGsignal. This study establishes technical support for establishing relevant man–machine devices and improving the safety of Pilates rehabilitation.
Global burden and inequality of iron deficiency: findings from the Global Burden of Disease datasets 1990–2017
Authors: Wang Mengying , Gao He , Wang Jianing , Cao Chenliang , Ying Xiaoling , Wei Yingming , Yu Zhiying , Shao Jie , Dong Hengjin , Yang Min
Published: March 2022

Background

Iron deficiency (ID) impairs patient physical activity, recognition and life quality, which is difficult to perceive but should not be underestimated. Worldwide efforts have been made to lower ID burden, however, whether it decreased equally in different regions and sexes is unclear. This study is to examine regional and sex inequalities in global ID from 1990 to 2017.

Methods

We conducted a longitudinal, comparative burden-of-disease study. Disability-adjusted life-years (DALYs) of ID were obtained from Global Burden of Disease Report 2017. Human Development Index (HDI) data were obtained from Human Development Report 2017. Gini coefficient and the concentration index were calculated to assess the equities in global burden of ID.

Results

A downward trend of global ID burden (from 569.3 (95% Uncertainty Interval [UI]: 387.8–815.6) to 403.0 (95% UI: 272.4–586.6), p < 0.001), age-adjusted DALYs per 100,000 population) but an uptrend of its inequalities (from 0.366 to 0.431, p < 0.001, Gini coefficients) was observed between 1990 and 2017. ID burden was heavier in women than that in men ([age-adjusted DALYs per 100,000 population from 742.2 to 514.3] vs [from 398.5 to 291.9]), but its inequalities were higher in men since 1990. The between-sex gap of ID burden was narrowed with higher HDI (β =  − 364.11, p < 0.001). East Asia & Pacific and South Asia regions made a big stride for ID control in both sexes over decades [age-adjusted DALYs per 100,000 population from 378.7 (95% UI: 255.8–551.7) in 1990 to 138.9 (95%UI: 91.8–206.5) in 2017], while a heavy burden among Sub-Saharan African men was persistent[age-adjusted DALYs per 100,000 population, 572.5 (95% UI: 385.3–815) in 1990 and 562.6 (95% UI: 367.9–833.3) in 2017].

Conclusions

Redistributing attention and resources to help countries with low HDI, especially take care of women with low socioeconomic status (SES) and men under high ID burden may help hold back the expanding ID inequality.
Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer
Authors: Zhai Bing-Tao , Tian Huan , Sun Jing , Zou Jun-Bo , Zhang Xiao-Fei , Cheng Jiang-Xue , Shi Ya-Jun , Fan Yu , Guo Dong-Yan
Published: March 2022

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.
Obesity prevention practices in early care and education settings: an adaptive implementation trial
Authors: Swindle Taren , Rutledge Julie M. , Selig James P. , Painter Jacob , Zhang Dong , Martin Janna , Johnson Susan L. , Whiteside-Mansell Leanne , Almirall Daniel , Barnett-McElwee Tracey , Curran Geoff M.
Published: March 2022

Background

Despite the potential for Early Care and Education (ECE) settings to promote healthy habits, a gap exists between current practices and evidence-based practices (EBPs) for obesity prevention in childhood.

Methods

We will use an enhanced non-responder trial design to determine the effectiveness and incremental cost-effectiveness of an adaptive implementation strategy for Together, We Inspire Smart Eating (WISE), while examining moderators and mediators of the strategy effect. WISE is a curriculum that aims to increase children’s intake of carotenoid-rich fruits and vegetables through four evidence-based practices in the early care and education setting. In this trial, we will randomize sites that do not respond to low-intensity strategies to either (a) continue receiving low-intensity strategies or (b) receive high-intensity strategies. This design will determine the effect of an adaptive implementation strategy that adds high-intensity versus one that continues with low-intensity among non-responder sites. We will also apply explanatory, sequential mixed methods to provide a nuanced understanding of implementation mechanisms, contextual factors, and characteristics of sites that respond to differing intensities of implementation strategies. Finally, we will conduct a cost effectiveness analysis to estimate the incremental effect of augmenting implementation with high-intensity strategies compared to continuing low-intensity strategies on costs, fidelity, and child health outcomes.

Discussion

We expect our study to contribute to an evidence base for structuring implementation support in real-world ECE contexts, ultimately providing a guide for applying the adaptive implementation strategy in ECE for WISE scale-up. Our work will also provide data to guide implementation decisions of other interventions in ECE. Finally, we will provide the first estimate of relative value for different implementation strategies in this setting.

Trial registration

NCT05050539; 9/20/21.
Transtibial versus independent femoral tunnel drilling techniques for anterior cruciate ligament reconstruction: evaluation of femoral aperture positioning
Authors: Haroun Haitham K. , Abouelsoud Maged M. , Allam Mohamed R. , Abdelwahab Mahmoud M.
Published: March 2022

Background

Femoral tunnel can be drilled through tibial tunnel (TT), or independent of it (TI) by out-in (OI) technique or by anteromedial (AM) technique. No consensus has been reached on which technique achieves more proper femoral aperture position because there have been evolving concepts in the ideal place for femoral aperture placement. This meta-analysis was performed to analyze the current literature comparing femoral aperture placement by TI versus TT techniques in ACL reconstruction.

Methods

We performed a comprehensive systematic review and meta-analysis of English-language literature in PubMed, Cochrane, and Web of Science databases for articles comparing femoral aperture placement by TI versus TT techniques with aperture position assessed by direct measurement or by postoperative imaging, PXR and/or CT and/or MRI.

Results

We included 55 articles with study population of 2401 knees of whom 1252 underwent TI and 1149 underwent TT techniques. The relevant baseline characteristics, whenever compared, were comparable between both groups. There was nonsignificant difference between TI and TT techniques in the distance from aperture center to footprint center and both techniques were unable to accurately recreate the anatomic footprint position. TI technique significantly placed aperture at more posterior position than TT technique. TI technique significantly lowered position of placed aperture perpendicular to Blumensaat’s line (BL) than TT technique, and modifications to TT technique had significant effect on this intervention effect. Regarding sagittal plane aperture placement along both AP anatomical axis and BL, there was nonsignificant difference between both techniques.

Conclusion

Modifications to TT technique could overcome limitations in aperture placement perpendicular to BL. The more anterior placement of femoral aperture by TT technique might be considered, to some extent, a proper position according to recent concept of functional anatomical ACL reconstruction.
Immature instars of three species of Rhodnius Stål, 1859 (Hemiptera, Reduviidae, Triatominae): morphology, morphometry, and taxonomic implications
Authors: Lázari Cacini Gustavo , de Oliveira Jader , Belintani Tiago , dos Santos Souza Éder , Olaia Nicoly , Pinto Mara Cristina , da Rosa João Aristeu
Published: March 2022

Background

Among the 18 genera of the Triatominae subfamily, three stand out for their diversity and epidemiological importance:Triatoma,Panstrongylus, andRhodnius.Rhodniusincludes 21 species that can transmitTrypanosoma cruzi(the etiological agent of Chagas disease, also known as American trypanosomiasis) andTrypanosoma rangeli. TheRhodnius prolixuscomplex comprises seven species, includingRhodnius marabaensis,Rhodnius prolixus, andRhodnius robustus, which occur in the northern region of Brazil. Since both adults and immatures can carryT. cruzi, in this study the five nymphal instars of the three species mentioned were dorsally characterized.

Methods

Using microscopy, morphometrics, and geometric morphometrics, the present work measures and describes the morphological characters of the five nymphal instars ofR. marabaensis,R. prolixus, andR. robustus.

Results

The study enabled the characterization of all five nymphal instars, as well as the distinction between the three species in each of their instars.

Conclusions

The morphological, morphometrics of the head, thorax, and abdomen and geometric morphometrics studies of the head enabled the specific distinction of these three species in all five instars.

Graphical Abstract