bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Clinical Outcomes of the Active Seal Technology of the AFX Endovascular Aortic Aneurysm System With the VELA Cuff for Patients With a Conical Proximal Neck
Authors: Fujimura Naoki , Obara Hideaki , Nagano Takaaki , Ogawa Yukihisa , Kobayashi Taira , Ohmine Takahiro , Ozeki Yasuhiro , Sakaguchi Shoji , Yamaoka Terutoshi , Ueda Hideki , Sumi Makoto , Taniguchi Satoshi , Ichihashi Shigeo
Published: January 2022

Purpose:

To evaluate the efficacy of the Active Seal technology employed in the AFX endovascular aortic aneurysm system (AFX), during endovascular aneurysm repair (EVAR) in patients with abdominal aortic aneurysms (AAAs) having a conical proximal neck.

Materials and Methods:

A retrospective analysis of the EVAR for AAA with a conical proximal neck using the AFX was performed at 17 Japanese hospitals between January 2016 and August 2020. The conical proximal neck was defined as a cone-shaped proximal neck, with more than 10% diameter increase within a 15 mm length at the proximal landing zone. All anatomical analyses were performed in the core laboratory, and cases with parallel walls within the proximal neck adequate for the landing zone were excluded from the study.

Results:

This study included 53 patients, but only 39 patients (mean age, 76.6 ± 6.7 years; 87.0% males; mean aneurysm diameter, 52.0 ± 8.0 mm) were analyzed after being characterized as having a pure conical neck by the core laboratory. The mean proximal neck diameters at the lower renal artery and proximal edge of the aneurysm were 20.0 ± 2.9 mm and 27.5 ± 4.9 mm, respectively. The mean proximal neck length was 21.5 ± 6.0 mm. Instructions for use violations other than the conical neck were observed in 15 patients (38.5%). The VELA cuff was used in all cases; however, additional proximal cuff was required in 9 more cases (23.1%). The Active Seal technology was able to significantly extend the proximal sealing zone from 21.5 ± 6.0 to 26.0 ± 12.2 mm ( p = .047). Thirty-six patients completed the 12-month follow-up (one patient was lost to follow-up, and 2 patients died from causes unrelated to the aneurysm), and there were no type-1a and 3 endoleaks with only one reintervention (2.6%) related to type 1b endoleak in the 12-month period. Furthermore, there was no significant enlargement of the proximal neck diameter at 12 months (at 1 month: 20.6 ± 3.4 mm and at 12 months: 21.3 ± 3.8 mm; p = .420).

Conclusion:

The Active Seal technology of the AFX significantly extended the proximal seal zone and no type-1a endoleak and proximal neck dilation was observed in patients with conical proximal neck at 12 months.
Diagnostic value of combined prealbumin-to-fibrinogen and albumin-to-fibrinogen ratios in Hp-negative gastric cancer
Authors: Zhang Linyan , Qin Simeng , Lu Liuyi , Huang Li , Li Shan
Published: January 2022

Background

This study aimed to investigate the diagnostic value of prealbumin-to-fibrinogen ratio (PFR) and albumin-to-fibrinogen ratio (AFR) alone or in combination in Helicobacter pylori-negative gastric cancer (Hp-NGC) patients.

Methods

This study included 171 healthy controls, 180 Hp-NGC patients, and 215 Helicobacter pylori-negative chronic gastritis (HpN) patients. We compared the differences of various indicators and pathological characteristics between groups with Mann–Whitney U test and Chi-square test. The diagnostic value of PFR and AFR alone or in combination for Hp-NGC patients was assessed by the receiver operating characteristic (ROC) curve.

Results

PFR and AFR were related to the progression and clinicopathological characteristics of Hp-NGC. As the disease progressed, PFR and AFR values gradually decreased and were negatively related to the tumor size and depth of invasion. In addition, the area under the curves (AUCs) that resulted from combining PFR and AFR to distinguish Hp-NGC patients from healthy controls and HpN patients were 0.908 and 0.654, respectively. When combined with PFR and AFR in the differential diagnosis of tumors with a maximum diameter ≥ 5 cm and the T3 + T4 stage, the AUCs were 0.949 and 0.922; the sensitivity was 86.32% and 80.74%; and the specificity was 94.74% and 92.98%, respectively.

Conclusions

PFR and AFR may be used as diagnostic biomarkers for Hp-NGC. The combination of PFR and AFR was more valuable than each indicator alone in the diagnosis of Hp-NGC.
Radial spoiled gradient T1 weighted imaging of the internal auditory canal: Is Scarpa’s ganglion now an expected finding and source of fundal enhancement?
Authors: Munawar Kamran , Raz Eytan , Dehkharghani Seena , Fatterpekar Girish M , Block Tobias K , Lui Yvonne W
Published: January 2022

StarVIBE is a 3D gradient-echo sequence with a radial, stack-of-stars acquisition having spatial resolution and tissue contrast. With newer sequences, it is important to be familiar with sequence tissue contrasts and appearance of anatomical variants. We evaluated 450 patients utilizing this sequence; 35 patients demonstrated fluffy “cotton wool” enhancement at the internal auditory canal fundus without clear pathology. We favor this represents anatomic neurovascular enhancement that StarVIBE is sensitive to and is a touch-me-not finding.
A Cross-Sectional Study of Undergraduate Teaching of Trauma and Orthopaedics in the UK and the Relationship Between Medical Schools and Interest in Trauma and Orthopaedics as a Career
Authors: Choi Sarah , Ooi Setthasorn , Carpenter Eleanor
Published: January 2022

INTRODUCTION

Adequate exposure and teaching of Trauma and Orthopaedics (T&O) to medical students is fundamental in order to obtain sufficient knowledge and sustain their interest in T&O as a career. The primary aim is to assess the exposure and delivery of T&O at all medical schools in the UK. The secondary aim is to determine whether there are any associations between attending a particular medical school and having a strong interest in pursuing a career in T&O.

METHODS

To explore the primary aim, all 33 UK medical schools were investigated in the study, by means of a questionnaire distributed to medical students. This did not include ‘new’ medical schools, defined as those established from 2014 onwards. To investigate the secondary aim of exploring associations between students’ and alumni's medical schools and their interest in T&O as a career, British Orthopaedic Training Association (BOTA) members were reviewed, using the General Medical Council register to identify the universities from which members had graduated. The authors have made the assumption that membership of BOTA signified an interest in T&O as a career.

RESULTS

Results were obtained for all 33 medical schools. The mean total teaching time specifically for T&O throughout medical school was 18 days, ranging from 3 to 60 days in total. 118 BOTA members were reviewed. No member of BOTA in the study had attended medical school in Keele, Liverpool, Plymouth or Lancashire. These universities taught below the national average number of days in T&O.

DISUCSSION

There is a large national variance in the number of compulsory teaching days provided for T&O. The authors advocate medical schools to aim for at least the national average in duration of T&O of 18 days.
Genomic landscape of TCRαβ and TCRγδ T-large granular lymphocyte leukemia
Authors: Cheon HeeJin , Xing Jeffrey C. , Moosic Katharine B. , Ung Johnson , Chan Vivian W. , Chung David S. , Toro Mariella F. , Elghawy Omar , Wang John S. , Hamele Cait E. , Hardison Ross C. , Olson Thomas L. , Tan Su-Fern , Feith David J. , Ratan Aakrosh , Loughran Thomas P.
Published: January 2022

Large granular lymphocyte (LGL) leukemia comprises a group of rare lymphoproliferative disorders whose molecular landscape is incompletely defined. We leveraged paired whole-exome and transcriptome sequencing in the largest LGL leukemia cohort to date, which included 105 patients (93 T-cell receptor αβ [TCRαβ] T-LGL and 12 TCRγδ T-LGL). Seventy-six mutations were observed in 3 or more patients in the cohort, and out of those, STAT3, KMT2D, PIK3R1, TTN, EYS, and SULF1 mutations were shared between both subtypes. We identified ARHGAP25, ABCC9, PCDHA11, SULF1, SLC6A15, DDX59, DNMT3A, FAS, KDM6A, KMT2D, PIK3R1, STAT3, STAT5B, TET2, and TNFAIP3 as recurrently mutated putative drivers using an unbiased driver analysis approach leveraging our whole-exome cohort. Hotspot mutations in STAT3, PIK3R1, and FAS were detected, whereas truncating mutations in epigenetic modifying enzymes such as KMT2D and TET2 were observed. Moreover, STAT3 mutations co-occurred with mutations in chromatin and epigenetic modifying genes, especially KMT2D and SETD1B (P < .01 and P < .05, respectively). STAT3 was mutated in 50.5% of the patients. Most common Y640F STAT3 mutation was associated with lower absolute neutrophil count values, and N647I mutation was associated with lower hemoglobin values. Somatic activating mutations (Q160P, D170Y, L287F) in the STAT3 coiled-coil domain were characterized. STAT3-mutant patients exhibited increased mutational burden and enrichment of a mutational signature associated with increased spontaneous deamination of 5-methylcytosine. Finally, gene expression analysis revealed enrichment of interferon-γ signaling and decreased phosphatidylinositol 3-kinase–Akt signaling for STAT3-mutant patients. These findings highlight the clinical and molecular heterogeneity of this rare disorder.
Clonotype pattern in T-cell lymphomas map the cell of origin to immature lymphoid precursors
Authors: Iyer Aishwarya , Hennessey Dylan , Gniadecki Robert
Published: January 2022

Mature T-cell lymphomas (TCLs) are rare, clinically heterogeneous hematologic cancers with high medical need. TCLs have an inferior prognosis which is attributed to poor understanding of their pathogenesis. On the basis of phenotypic similarities between normal and neoplastic lymphocytes, it has been assumed that TCLs develop in the periphery, directly from various subtypes of normal T cells. To address the debated question of the cell of origin in TCLs, we attempted to identify the highly variable complementarity-determining regions (CDRs) of T-cell receptors (TCRs) to trace the clonal history of the T cells. We have collected previously published whole-genome, whole-exome, and whole-transcriptome sequencing data from 574 patients with TCL. TCR clonotypes were identified by de novo assembly of CDR3 regions of TCRα, TCRβ, and TCRγ. We have found that the vast majority of TCLs are clonotypically oligoclonal, although the pattern of oligoclonality varied. Anaplastic large-cell lymphoma was the most diverse comprising multiple clonotypes of TCRα, TCRβ, and TCRγ, whereas adult TCL or leukemia and peripheral TCLs often showed monoclonality for TCRβ and TCRγ but had diverse TCRα clonotypes. These patterns of rearrangements indicated that TCLs are initiated at the level of the lymphoid precursor. In keeping with this hypothesis, TCR rearrangements in TCLs resembled the pattern seen in the human thymus, which showed biased usage of V (variable) and J (joining) segments of high combinatorial probability resulting in recurrent public CDR3 sequences shared across unrelated patients and different clinical TCL entities. Clonotypically diverse initiating cells may seed target tissues that are then responsible for disease relapses after therapy.
Stating the obvious: intravenous magnesium sulphate should be the first parenteral bronchodilator in paediatric asthma exacerbations unresponsive to first-line therapy
Authors: Erumbala Gokul , Anzar Sabu , Tonbari Amjad , Salem Ramadan , Powell Colin
Published: January 2022

What is the most appropriate second-line intravenous bronchodilator treatment when a child with a severe asthma attack is not responsive to initial inhaled therapy? The second-line treatment options for acute asthma include parenteral β2-agonists, methylxanthine and magnesium sulphate (MgSO4). There is a poor evidence-base to inform this decision. This review argues that intravenous MgSO4is the obvious treatment of choice for this situation as the initial treatment based on current knowledge.  We describe the mode of action, scope and limitations of MgSO4, safety profile, economic impact, comparisons of the alternatives, and finally, what the guidelines say.  This review explores the suitability of intravenous MgSO4 as a pragmatic and safe initial second-line therapy for children unresponsive to initial asthma management.
New insights into the role of cyanide in the promotion of seed germination in tomato
Authors: Yu Lu-Lu , Liu Cui-Jiao , Peng Ye , He Zheng-Quan , Xu Fei
Published: January 2022

Background

Cyanide is a natural metabolite that exists widely in plants, and it is speculated to be involved in the regulation of various growth and development processes of plants in addition to being regarded as toxic waste. Previous studies have shown that exogenous cyanide treatment helps to improve seed germination, but the mechanism is still unclear. In this study, tomato (Solanum lycopersicum cv. Alisa Craig) was used as the material, and the effects of cyanide pretreatment at different concentrations on tomato seed germination were investigated.

Results

The results showed that exogenous application of a lower concentration of cyanide (10 μmol/L KCN) for 12 h strongly increased the tomato seed germination rate. RNA-Seq showed that compared with the control, a total of 15,418 differentially expressed genes (P<0.05) were obtained after pretreatment with KCN for 12 h, and in the next 12 h, a total of 13,425 differentially expressed genes (P<0.05) were regulated. GO and KEGG analyses demonstrated that exogenous KCN pretreatment was involved in regulating the expression (mainly downregulation) of seed storage proteins, thereby accelerating the degradation of stored proteins for seed germination. In addition, KCN pretreatment was also involved in stimulating glycolysis, the TCA cycle and oxidative phosphorylation. Notably, it is shown that KCN acted on the regulation of plant hormone biosynthesis and perception, i.e., down-regulated the gene expression of ABA biosynthesis and signal transduction, but up-regulated the expression of genes related to GA biosynthesis and response. Consistent with this, plant hormone measurements confirmed that the levels of ABA were reduced, but GA levels were induced after pretreatment with KCN.

Conclusion

These findings provide new insights into the regulation of seed germination by cyanide, that is cyanide-mediated seed germination occurs in a time- and dose-dependent manner, and is related to the mobilization of energy metabolism and the regulation of some plant hormone signals.
The shift from old age to very old age: an analysis of the perception of aging among older people
Authors: Escourrou Emile , Laurent Sarah , Leroux Jacques , Oustric Stéphane , Gardette Virginie
Published: January 2022

Background

The oldest-old (individuals over 90 years) are a fast-growing population. Understanding the perceptions of older people about very old age is the first step towards developing optimal geriatric care for an aging population. This study aimed to explore the potential shift from old age to very old age through the exploration of older people’s perception of aging.

Methods

Qualitative study conducted through individual interviews in the homes of older people. We voluntarily chose to include persons a decade under and above 90 years old to explore other factors than age that could participate in the shift from old age to very old age. The sampling was theoretical. We carried out the analyses using an inductive approach based on the phases of grounded theory. The researchers used triangulation. Collection was concluded when theoretical saturation was reached.

Results

Fourteen participants were interviewed. The shift from old age to very old age was not based on age but occurred when participants became conscious of the irreversibility of aging and its effects, and when they started living day-by-day, renouncing to any plan in a near future. The transition to very old age seemed to be preceded by a progressive disengagement from non-essentials activities. Participants reported a sensation of progressive social exclusion due to the loss of contemporaries or spouse, the difficulty to connect with younger generations or the absence of relationships in their neighborhood. The last step of life was feared, not because of the idea of death itself but because of the associated suffering and loss of autonomy.

Conclusion

Precipitating and slowing factors of the shift to very old age were identified to help general practitioners support older patients throughout their life trajectories.
Relationship between childhood sexual abuse and attitudes toward premarital sexual permissiveness among middle school students in Luzhou, China
Authors: Rong Zhang , Wen Zhang , Maoxu Liao , Ya Liu , Song Fan , Hui Wei , Xiaozhen Tan , Yunli Ye
Published: January 2022

Background

In recent years, the number of adolescents engaging in premarital sex has increased, and an increasing number of childhood sexual abuse (CSA) cases have been reported in China. Many studies have indicated that CSA has a well-established association with risky sexual activities. However, only a limited number of studies have explored possible reasons for this association among middle school students, a population that may engage in premarital sex, which is critical for the development of interventions to prevent risky sexual behavior. Based on random samples of middle school students from a Chinese city, this article investigated the relationship between CSA and students’ premarital sexual permissiveness (PSP).

Methods

In a cross-sectional study conducted between 2016 and 2017 in Luzhou, China, 2292 middle school and high school students aged 12–18 years were recruited by multistage random sampling. All students were administered anonymous questionnaires. Multiple linear regression and binary logistic regression analyses were conducted to analyze the relationship between CSA and PSP.

Results

The prevalence of CSA was 15.4% (354/2292; 95% CI: 14–16.9%). A higher percentage of male respondents (18.2%) than female respondents (12.9%) had experienced CSA. A positive association between CSA and PSP was found among students. Respondents who had suffered CSA exhibited greater PSP, and this relationship was observed in the male sample, female sample and the total student sample in Luzhou (β = − 3.76, P < 0.05; β = − 2.79, P < 0.05; and β = − 2.84, P < 0.05, respectively). Respondents who had suffered CSA were also more likely to express a double standard about premarital sex (odds ratio [OR] =1.41, P < 0.05), especially among male students (odds ratio [OR] =1.63, P < 0.05).

Conclusions

Sex differences in CSA and the relationship between CSA and PSP were significant among this large sample of middle school students in Luzhou (China). The findings suggest that experiencing CSA may be closely related to youth attitudes toward premarital sex, especially among males. Therefore, it is important to emphasize the prevention of CSA and provide adolescent reproductive health programs to reduce the impact of CSA on sexual cognition and attitude, prevent premarital sex and promote positive attitudes toward sexual equality for middle school students.
Discussing patient preferences for levels of life-sustaining treatment: development and pilot testing of a Danish POLST form
Authors: Tuesen Lone Doris , Bülow Hans-Henrik , Ågård Anne Sophie , Strøm Sverre Mainz , Fromme Erik , Jensen Hanne Irene
Published: January 2022

Background

Medically frail and/or chronically ill patients are often admitted to Danish hospitals without documentation of patient preferences. This may lead to inappropriate care. Modelled on the American Physician Orders for Life-Sustaining Treatment (POLST) form, the purpose of the study was to develop and pilot test a Danish POLST form to ensure that patients’ preferences for levels of life-sustaining treatment are known and documented.

Methods

The study was a mixed methods study. In the initial phase, a Danish POLST form was developed on the basis of literature and recommendations from the National POLST organisation in the US. A pilot test of the Danish POLST form was conducted in hospital wards, general practitioners’ clinics, and nursing homes. Patients were eligible for inclusion if death was assessed as likely within 12 months. The patient and his/her physician engaged in a conversation where patient values, beliefs, goals for care, diagnosis, prognosis, and treatment alternatives were discussed. The POLST form was completed based on the patient’s values and preferences. Family members and/or nursing staff could participate. Participants’ assessments of the POLST form were evaluated using questionnaires, and in-depth interviews were conducted to explore experiences with the POLST form and the conversation.

Results

In total, 25 patients participated, 45 questionnaires were completed and 14 interviews were conducted. Most participants found the POLST form readable and understandable, and 93% found the POLST form usable to a high or very high degree for discussing preferences regarding life-sustaining treatment. Three themes emerged from the interviews: (a) an understandable document is essential for the conversation, (b) handling and discussing wishes, and (c) significance for the future.

Conclusion

The Danish version of the POLST form is assessed by patients, families, physicians, and nurses as a useful model for obtaining and documenting Danish patients’ preferences for life-sustaining treatment. However, this needs to be confirmed in a larger-scale study.
Magnitude of infertility and associated factors among women attending selected public hospitals in Addis Ababa, Ethiopia: a cross-sectional study
Authors: Akalewold Mekdes , Yohannes Getachew W. , Abdo Ziyad Ahmed , Hailu Yonas , Negesse Aynye
Published: January 2022

Introduction

The World Health Organization estimated that approximately 48 million couples and 186 million people are infertile worldwide. Although the problem of infertility is increasing worldwide, as well as in Ethiopia, there are limited studies done. Therefore, this study aims to determine the magnitude of infertility and the major risk factors in three governmental hospitals in Addis Ababa, Ethiopia.

Method

An institutional-based cross-sectional study design was used to conduct the study. The participants were selected by using a systematic random sampling technique. Data were collected through an interview using a structured questionnaire. The data were entered into Epi Data version 3.1 and exported to SPSS version 25 for analysis. Logistic regression was used to identify the predictor variables. Statistical significance was considered at a P < 0.05 with an adjusted odds ratio calculated at 95% CI.

Result

The overall prevalence of infertility was 27.6% (95%CI = 23.2, 32.0). Of these, 14.4% had primary infertility, and 13.2% had secondary infertility. Those whose duration of marriage was less than 60 months [AOR = 3.85; 95%CI 1.39, 10.64], had a history of fallopian tube obstructions [AOR = 8.27; 95%CI 2.36, 28.91], had irregular frequency of coitus [AOR = 37.4; 95%CI 11.29, 124.114], had more than one sex partner [AOR = 3.51; 95%CI 1.64, 7.54], had an abortion greater than 3 times [AOR = 6.89; 95%CI 1.28, 37.09], and had partners who currently consumed alcohol [AOR = 1.31; 95%CI 1.11, 1.86] were more likely to be infertile than their counterparts.

Conclusion

According to the results of this study, the prevalence of infertility was high compared to the global estimate of the World Health Organization. The government, health care providers, and researchers should emphasize developing appropriate strategies, research, education, and awareness creation of infertility and its potential causes.
Research, development, and evaluation of the practical effect of a storage inflow and outflow management system for consumables in the endocrinology department of a hospital
Authors: Luo Jiang , Wang Yan , Zhang Yongze , Yan Xiaofang , Huang Xiaoting , Zhao Fengying
Published: January 2022

Background

This study was designed for the research and development (R&D) and application of a storage inflow and outflow management system enabling departments to perform efficient, scientific, and information-based consumable management.

Methods

In the endocrinology department of a hospital, expert and R&D teams in consumable management were set up, and an information-based storage inflow and outflow management system for consumables was designed and developed. The system was operated on a personal computer and was divided into three modules: public consumables, bed consumables, and quality control management. The functions of the system included storage inflow and outflow, early warnings, response to user queries, and statistics on consumables. Data were derived from the hospital information system (HIS,ZHIY SOFTWARE HIS VERSION4.0) and a questionnaire survey. Economic indicators, work efficiency of consumable management, nurse burnout, consumable stockroom management, and staff satisfaction were compared under manual management, Excel-based management, and the consumable storage inflow and outflow management system. The results of the questionnaire were analysed using the R software, version 4.1.0.

Results

Dates were obtained from manual management, Excel-based management and the consumable storage inflow and outflow management system. Under these three methods, the daily prices of department consumables per bed were 53.43 ± 10.27 yuan, 38.65 ± 8.56 yuan, and 31.98 ± 7.36 yuan, respectively, indicating that the new management system reduced costs for the department. The time spent daily on consumable management was shortened from 119.5 (106.75, 123.5) min to 56.5 (48.5, 60.75) to 20 (17.25, 24.25) min. Nurses’ emotional fatigue and job indifference scores, respectively, decreased from 22.90 ± 1.65 and 8.75 ± 1.25 under manual management to 19.70 ± 1.72 and 6.90 ± 1.37 under Excel-based management and to 17.20 ± 2.04 and 6.00 ± 1.30 under the novel system; the satisfaction of the warehouse keeper and collection staff, respectively, increased from 76.62% and 80.78% to 91.6% and 90.5% to 98.8% and 98.5% under the three successive systems.

Conclusions

The storage inflow and outflow management system achieved produced good results in the storage and classification of consumables.
Notch4 mediates vascular remodeling via ERK/JNK/P38 MAPK signaling pathways in hypoxic pulmonary hypertension
Authors: Guo Mingzhou , Zhang Mengzhe , Cao Xiaopei , Fang Xiaoyu , Li Ke , Qin Lu , He Yuanzhou , Zhao Jianping , Xu Yongjian , Liu Xiansheng , Li Xiaochen
Published: January 2022

Background

Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling.

Methods

Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated.

Results

In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats.

Conclusions

These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.
Short-term starvation synergistically enhances cytotoxicity of Niraparib via Akt/mTOR signaling pathway in ovarian cancer therapy
Authors: Zhi Wang , Li Suting , Wan Yuting , Wu Fuwen , Hong Li
Published: January 2022

Background

Short-term starvation (STS) has gradually been confirmed as a treatment method that synergistically enhances the effect of chemotherapy on malignant tumours. In clinical applications, there are still some limitations of poly (ADP-ribose) polymerase inhibitors (PARPi), including understanding their effectiveness and side effects. Here, we sought to investigate the effect and mechanism of the combined use of STS and niraparib in the treatment of ovarian cancer.

Methods

In in vitro experiments, SKOV3 and A2780 ovarian cancer cells were treated with STS and niraparib alone or in combination. Cell viability was assessed with CCK-8, and cell cycle, apoptosis, DNA damage repair and autophagy were examined to explore the molecular mechanisms. Akt and mTOR inhibitors were used to examine any changes in DNA damage repair levels. Xenograft animal models were treated with STS and niraparib, and HE staining and immunohistochemistry were performed to examine the effects.

Results

The combined use of STS and niraparib inhibited cell proliferation and increased apoptosis more than niraparib application alone. In addition, compared with the niraparib group, the STS + niraparib group had increased G2/M arrest, DNA damage and autophagy, which indicated that STS pretreatment enhanced the cytotoxicity of niraparib. In animal experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib. In in vivo experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib and reduced the small intestinal side effects caused by niraparib chemotherapy.

Conclusion

STS pretreatment can synergistically enhance the cytotoxicity of niraparib. STS + niraparib is a potentially effective strategy in the maintenance therapy of ovarian cancer.
PTBP3 regulates proliferation of lung squamous cell carcinoma cells via CDC25A‐mediated cell cycle progression
Authors: Chen Yingji , Ji Ying , Liu Suo , Liu Yicai , Feng Wei , Jin Longyu
Published: January 2022

Background

The roles of Polypyrimidine tract-binding protein 3 (PTBP3) in regulating lung squamous cell carcinoma (LUSC) cells progression is unclear. The aim of this study was to investigate the role of PTBP3 in LUSC.

Methods

Expression and survival analysis of PTBP3 was firstly investigated using TCGA datasets. Quantitative reverse transcription PCR and Western blot were performed to detect PTBP3 expression in clinical samples. Moreover, cell counting kit 8 (CCK-8) assays, colony formation assays and in vivo tumor formation assays were used to examine the effects of PTBP3 on LUSC cell proliferation. RNA-sequence and analysis explores pathways regulated by PTBP3.Flow cytology was used analyzed cell cycle. Cell cycle-related markers were analyzed by Western blot.

Results

PTBP3 was found to be overexpressed in LUSC tissues compared with normal tissues. High PTBP3 expression was significantly correlated with poor prognosis. In vitro and vivo experiments demonstrated that PTBP3 knockdown caused a significant decrease in the proliferation rate of cells. Bioinformatics analysis showed that PTBP3 involved in cell cycle pathway regulation in LUSC. Furthermore, PTBP3 knockdown arrested cell cycle progression at S phase via decreasing CDK2/Cyclin A2 complex. In addition, downregulation of PTBP3 significantly decreased the expression of CDC25A.

Conclusions

Our results suggest that PTBP3 regulated LUSC cell proliferation via cell cycle and might be a potential target for molecular therapy of LUSC.
Comparative efficacy of two pyrethroid-piperonyl butoxide nets (Olyset Plus and PermaNet 3.0) against pyrethroid resistant malaria vectors: a non-inferiority assessment
Authors: Ngufor Corine , Fagbohoun Josias , Agbevo Abel , Ismail Hanafy , Challenger Joseph D. , Churcher Thomas S. , Rowland Mark
Published: January 2022

Background

Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus.

Methods

An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts.

Results

With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net.

Conclusion

Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa.
The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019
Authors: Yao Yiyi , Lin Xiangjie , Li Fenglin , Jin Jie , Wang Huafeng
Published: January 2022

Background

Chronic lymphocytic leukemia (CLL) is the most prevalent subtype of leukemia in Western countries, causing a substantial health burden on patients and society. Comprehensive evaluation of the epidemiological characteristics of CLL is warranted, especially in the current context of global population aging. The main objective of this study is evaluating the disease burden of CLL at global, regional, and national levels from 1990 to 2019. As secondary objectives, we studied the influence of demographic factors and performed risk factor analysis. We hope this study could provide evidence for the evaluation of the effectiveness of previous prevention strategies and the formulation of future global health policies.

Results

Based on data of CLL between 1990 to 2019 from the Global Burden of Disease (GBD) study 2019, we depicted the age, gender, and regional structure of the CLL burden population and described the impact of social development on the disease burden of CLL. The distribution and changing trends of attributable risk factors were also investigated. The global burden of CLL has increased dramatically. A high incidence has been achieved in males and elder people. Countries and territories with high social-demographic index (SDI) tended to have higher global burden than low-SDI region. Of risk factors, high body mass index and smoking were the major contributors for CLL-related mortality and disability adjusted life-years (DALYs).

Conclusion

In summary, the global CLL burden continues to rise over the past 30 years. The relocation of medical resource should be considered on a global scale.

Graphical Abstract
Functionalization of screw implants with superelastic structured Nitinol anchoring elements
Authors: Hamann Isabell , Schleifenbaum Stefan , Rotsch Christian , Drossel Welf-Guntram , Heyde Christoph-Eckhard , Leimert Mario
Published: January 2022

Background

Demographic change is leading to an increase in the number of osteoporotic patients, so a rethink is required in implantology in order to be able to guarantee adequate anchoring stability in the bone. The functional modification of conventional standard screw implants using superelastic, structured Ti6Al4V anchoring elements promises great potential for increasing anchoring stability.

Methods

For this purpose, conventional screw implants were mechanically machined and extended so that structured-superelastic-positionable-Ti6Al4V anchoring elements could be used. The novel implants were investigated with three tests. The setup of the anchoring elements was investigated in CT studies in an artificial bone. In a subsequent simplified handling test, the handling of the functional samples was evaluated under surgical conditions. The anchorage stability compared to standard screw implants was investigated in a final pullout test according to ASTM F543—the international for the standard specification and test methods for metallic medical bone screws.

Results

The functionalization of conventional screw implants with structured superelastic Ti6Al4V anchoring elements is technically realizable. It was demonstrated that the anchoring elements can be set up in the artificial bone without any problems. The anchorage mechanism is easy to handle under operating conditions. The first simplified handling test showed that at the current point of the investigations, the anchoring elements have no negative influence on the surgical procedure (especially under the focus of screw implantation). Compared to conventional standard screws, more mechanical work is required to remove the functional patterns completely from the bone.

Conclusion

In summary, it was shown that conventional standard screw implants can be functionalized with Ti6Al4V-structured NiTi anchoring elements and the new type of screws are suitable for orthopedic and neurosurgical use. A first biomechanical test showed that the anchoring stability could be increased by the anchoring elements.
Detection and analysis of long noncoding RNA expression profiles related to epithelial–mesenchymal transition in keloids
Authors: Chen Zhixiong , Chu Xi , Xu Jinghong
Published: January 2022

Background

The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of keloids is currently raising increasing attention. Long noncoding RNAs (lncRNAs) govern a variety of biological processes, such as EMT, and their dysregulation is involved in many diseases including keloid disease. The aim of this study was to identify differentially expressed EMT-related lncRNAs in keloid tissues versus normal tissues and to interpret their functions.

Results

Eleven lncRNAs and 16 mRNAs associated with EMT were identified to have differential expression between keloid and normal skin tissues (fold change > 1.5, P < 0.05). Gene Ontology (GO) analysis showed that these differentially expressed mRNAs functioned in the extracellular matrix, protein binding, the positive regulation of cellular processes, the Set1C/COMPASS complex and histone acetyltransferase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these mRNAs are involved in pathways in cancer. The lncRNA, XLOC_000587 may promote cell proliferation and migration by enhancing the expression of ENAH, while AF268386 may facilitate the invasive growth of keloids by upregulating DDR2.

Conclusions

We characterized the differential expression profiles of EMT-related lncRNAs and mRNAs in keloids, which may contribute to preventing the occurrence and development of keloids by targeting the corresponding signaling pathways. These lncRNAs and mRNAs may provide biomarkers for keloid diagnosis and serve as potential targets for the treatment of this disease.
Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer
Authors: Kalantari Elham , Taheri Tahereh , Fata Saba , Abolhasani Maryam , Mehrazma Mitra , Madjd Zahra , Asgari Mojgan
Published: January 2022

Background

The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients.

Methods

This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides.

Results

Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P= 0.02), tumor stage (P= 0.007), tumor differentiate (P= 0.005), vascular (P= 0.01), neural (P= 0.01), and lymph node (P= 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P= 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P= 0.03), tumor differentiation (P= 0.05), neural, and lymph node invasion (P=0.01).

Conclusions

The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.
Application of X-ray computed tomography to analyze the structure of sorghum grain
Authors: Crozier Daniel , Riera-Lizarazu Oscar , Rooney William L.
Published: January 2022

Background

The structural characteristics of whole sorghum kernels are known to affect end-use quality, but traditional evaluation of this structure is two-dimensional (i.e., cross section of a kernel). Current technology offers the potential to consider three-dimensional structural characteristics of grain. X-ray computed tomography (CT) presents one such opportunity to nondestructively extract quantitative data from grain caryopses which can then be related to end-use quality.

Results

Phenotypic measurements were extracted from CT scans of grain sorghum caryopses. Extensive phenotypic variation was found for embryo volume, endosperm hardness, endosperm texture, endosperm volume, pericarp volume, and kernel volume. CT derived estimates were strongly correlated with ground truth measurements enabling the identification of genotypes with superior structural characteristics.

Conclusions

Presented herein is a phenotyping pipeline developed to quantify three-dimensional structural characteristics from grain sorghum caryopses which increases the throughput efficiency of previously difficult to measure traits. Adaptation of this workflow to other small-seeded crops is possible providing new and unique opportunities for scientists to study grain in a nondestructive manner which will ultimately lead to improvements end-use quality.
Comparison between external locking plate fixation and conventional external fixation for extraarticular proximal tibial fractures: a finite element analysis
Authors: Blažević Dejan , Kodvanj Janoš , Adamović Petra , Vidović Dinko , Trobonjača Zlatko , Sabalić Srećko
Published: January 2022

Background

Good clinical outcomes for locking plates as an external fixator to treat tibial fractures have been reported. However, external locking plate fixation is still generally rarely performed. This study aimed to compare the stability of an external locking plate fixator with that of a conventional external fixator for extraarticular proximal tibial fractures using finite element analysis.

Methods

Three models were constructed: (1) external locking plate fixation of proximal tibial fracture with lateral proximal tibial locking plate and 5-mm screws (ELP), (2) conventional external fixation of proximal tibial fracture with an 11-mm rod and 5-mm Schanz screws (EF-11), and (3) conventional external fixation of a proximal tibial fracture with a 7-mm rod and 5-mm Schanz screws (EF-7). The stress distribution, displacement at the fracture gap, and stiffness of the three finite element models at 30-, 40-, 50-, and 60-mm plate–rod offsets from the lateral surface of the lateral condyle of the tibia were determined.

Results

The conventional external fixator showed higher stiffness than the external locking plate fixator. In all models, the stiffness decreased as the distance of the plate–rod from the bone surface increased. The maximum stiffness was 121.06 N/mm in the EF-11 model with 30-mm tibia–rod offset. In the EF-7 model group, the maximum stiffness was 40.00 N/mm in the model with 30-mm tibia–rod offset. In the ELP model group, the maximum stiffness was 35.79 N/mm in the model with 30-mm tibia–plate offset.

Conclusions

Finite element analysis indicated that external locking plate fixation is more flexible than conventional external fixation and can influence secondary bone healing. External locking plate fixation requires the placement of the plate as close as possible to the skin, which allows for a low-profile design because the increased distance from the plate to the bone can be too flexible for bone healing. Further experimental mechanical model tests are necessary to validate these finite element models, and further biological analysis is necessary to evaluate the effect of external locking plate fixation on fracture healing.