bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic ultrasound-guided superselective portal vein injection combined with real-time indocyanine green fluorescence imaging and navigation for accurate resection of localized intrahepatic bile duct dilatation: a case report
Authors: Lai Ming-chun , Geng Lei , Zheng Shu-sen , Deng Jun-fang
Published: August 2021

Background

Primary intrahepatic bile duct dilatation can be very harmful to patients although it belongs to benign biliary disease. It can occur in any part of the liver, intraoperative laparoscopic ultrasound (LUS) guidance combine with real-time indocyanine green (ICG) fluorescence navigation are the means of choice for accurate surgical resection.

Case presentation

Herein we reported a 43-year-old female patient presented with repeated right upper abdominal pain and distension for 3 years and aggravated for half a year, without fever and jaundice. A diagnosis of localized bile duct dilatation with lithiasis in segment 4 (S4) was made on the basis of preoperative imaging. Correspondingly, we selected to perform a laparoscopic surgery with LUS guided real time ICG fluorescence imaging (ICG-FI) and navigation to make the operation more simply and accurately, as well as to retain normal tissues in a certain extent. Laparoscopic resection of S4b and partial S4a was successfully performed, without any complications.

Conclusion

Laparoscopic anatomical surgery for intrahepatic bile duct dilatation is a technically challenging operation. The combined use of preoperative three-dimensional computerized tomography (CT) planning, intraoperative LUS guided super-selection, ICG hepatic segment staining and real-time fluorescence navigation could help surgeons accurately complete the segmentectomy or subsegmentectomy with minimized trauma and maximized liver tissue preservation.
Combination of pioglitazone and clomiphene citrate versus clomiphene citrate alone for infertile women with the polycystic ovarian syndrome
Authors: Amirian Maliheh , Shariat Moghani Sedigheh , Jafarian Faezeh , Mirteimouri Masoumeh , Nikdoust Shima , Niroumand Shabnam , Salehi Maryam , Payrovnaziri Aryan
Published: August 2021

Background

Anovulation is one of the common causes of infertility. Polycystic ovary syndrome (PCOS) is the most common disorder with chronic Anovulation. To the best of our knowledge, insulin resistance relates significantly to PCOS. Therefore administration of insulin-sensitizing drugs such as pioglitazone can be used for ovulation stimulation in PCO patients.

Methods

After obtaining approval from the Ethics Committee of Mashhad University of Medical Sciences, 61 patients with PCOS were enrolled in the study based on inclusion/ exclusion criteria. Patients were divided into two groups. The first group received 30 mg (mg) of pioglitazone daily from the second day of the menstrual period. The second one received a placebo. 150 mg clomiphene citrate was administered from the third to the seventh day of the menstrual cycle. Vaginal sonography was performed in all women, and in cases with the mature follicle, intrauterine insemination was conducted after human chorionic gonadotropin injection. Ovary stimulation and pregnancy rate were compared between groups.

Results

There were no differences between groups regard to demographic characteristics and infertility type. Body mass index was higher in the pioglitazone group (28.3 ± 3.8 versus 26.2 ± 3.5, P value = 0.047). The size of the follicle was not significantly different between groups (2.2 ± 1.4 versus 1.3 ± 1.1, P value = 0.742). pregnancy rate [4 (12.9%) versus 4 (13.3%), P value = 1] had no differences between groups.

Conclusion

Although the number of follicles was higher in the pioglitazone group, our study showed no differences in ovary stimulation and pregnancy rate.
Transfer of communication teaching skills from university to the clinical workplace – does it happen? A mixed methods study
Authors: Møller Jane Ege , Kjaer Louise Binow , Helledie Emma , Nielsen Lone Folmer , Malling Bente Vigh
Published: August 2021

Background

Communication skills learned in the classroom do not transfer easily into clinical practice because they are not reinforced by teachers in the workplace setting and because lack of faculty training restricts the transfer of communication skills in real patient encounters. Trained university-based communication skills teachers often work simultaneously as doctors in clinics. This study explored if and how the skills of these teachers play a role in communication skills training in the clinical workplace.

Methods

We used an exploratory sequential design: a mixed method approach that combined a survey with communication skills teachers, and qualitative individual interviews with these teachers and their educational leaders in clinical departments. The questionnaire was analysed using descriptive statistics. The interviews were analysed using content analysis.

Results

The response rate was 34 %. A majority (93 %) used their communication skills when communicating with patients and relatives. Less than half taught communication in clinical departments. Approximately half of the respondents stated that encouragement from their leaders or colleagues would inspire them to use their teaching skills in the workplace. However, only 20 % had told their leaders about their competencies in teaching communication. One third thought that they needed further teacher training to teach in the clinical workplace.

Qualitative analysis showed that teaching opportunities existed but mainly consisted of random, one-off sessions that came about through the initiative of the communication skills teachers themselves. The teachers described several barriers, such as the challenge of teaching colleagues, as communication relates to identity and hierarchical structures, as well as a lack of requests from colleagues or management, and department culture prioritizing topics relating to medical expertise. None of the educational leaders made use of the teachers’ specific communication skills in a structured way: some saw it as unimportant, while others saw it as a potential resource.

Conclusion

Transfer of the teaching skills of communication skills teachers trained for university-based clinical communication training happened, but to a limited degree. Although both opportunities and barriers for transferring communication skills existed, barriers seemed to dominate, and opportunities for communication skills training in the workplace setting were not used to their full potential.
Evaluation frameworks for digital nursing technologies: analysis, assessment, and guidance. An overview of the literature
Authors: Krick Tobias
Published: August 2021

Background

The evaluation of digital nursing technologies (DNT) plays a major role in gaining knowledge about certain aspects of a technology such as acceptance, effectiveness, or efficiency. Evaluation frameworks can help to classify the success or failure of a DNT or to further develop the technology. In general, there are many different evaluation frameworks in the literature that provide overviews of a wide variety of aspects, which makes this a highly diverse field and raises the question how to select a suitable framework. The aim of this article is to provide orientation in the field of comprehensive evaluation frameworks that can be applied to the field of DNT and to conduct a detailed analysis and assessment of these frameworks to guide field researchers.

Methods

This overview was conducted using a three-component search process to identify relevant frameworks. These components were (1) a systematized literature search in PubMed; (2) a narrative review and (3) expert consultations. Data relating to the frameworks’ evaluation areas, purpose, perspectives, and success definitions were extracted. Quality criteria were developed in an expert workshop and a strength and weakness assessment was carried out.

Results

Eighteen relevant comprehensive evaluation frameworks for DNT were identified. Nine overarching evaluation areas, seven categories of purposes, five evaluation perspectives and three categories of success definitions could be identified. Eleven quality criteria for the strengths and weaknesses of DNT-related evaluation frameworks were developed and the included frameworks were assessed against them.

Conclusion

Evaluators can use the concise information and quality criteria of this article as a starting point to select and apply appropriate DNT evaluation frameworks for their research projects or to assess the quality of an evaluation framework for DNT, as well as a basis for exploring the questions raised in this article. Future research could address gaps and weaknesses in existing evaluation frameworks, which could improve the quality of future DNT evaluations.
A conceptual model of nurses’ workplace social capital: a theory synthesis
Authors: Xu Jiamin , Stark Azadeh T.
Published: August 2021

Background

Research has confirmed the importance of workplace social capital in the nursing workforce. Integration of the empirical evidence about nurses’ workplace social capital into a scientific collection can provide a comprehensive presentation of this concept. This scientific collection can be a conduit for further research and advancement of nursing management and leadership. The purpose of this paper, therefore, is to discuss the process of developing a conceptual model of nurses’ workplace social capital, an effective and concise approach to illustrate a scientific phenomenon.

Methods

The model of nurses’ workplace social capital was developed following Walker and Avant’s strategy of theory synthesis. Empirical evidence relevant to nurses’ workplace social capital was synthesized by systematically examining the existing literature. PubMed, CINAHL, Web of Science and Google Scholar were searched periodically from October 2017 to July 2020.

Results

Our proposed conceptual model lays out the determinants and outcomes of nurses’ workplace social capital and specifies the relational statements among these concepts. Nurses’ workplace social capital is influenced by the organizational and individual determinants shaped by multiple layers of sub-concepts. The development and implementation of nurses’ workplace social capital has three themes of consequences: 1) nurses’ outcomes; 2) patients’ outcomes; and 3) organizational outcomes. All the concepts and statements have been organized and aligned with the principles of “inventory of determinants or results” and “theoretical blocks”.

Conclusion

Our theoretical synthesis offers a comprehensive picture of the current knowledge of nurses’ workplace social capital. Efforts should be dedicated to evaluating, revising, and revamping this newly developed model based on future empirical evidence. Our synthesized conceptual model is the segue to more comprehensive studies about nurses’ workplace social capital. Interventional programs for the development of social capital can be structured based on the identified determinants.
‘Professional-supportive’ versus ‘economic-operational’ management: the relationship between leadership style and hospital physicians’ organisational climate
Authors: Martinussen Pål E. , Davidsen Tonje
Published: August 2021

Background

Health systems across the world have implemented reforms that call for a reconsideration of the role of management in hospitals, which is increasingly seen as important for performance. These reorganisation efforts of the hospitals have challenged and supplemented traditional profession-based management with more complex systems of management inspired by the business sector. Whereas there is emerging evidence on how medical professionals in their role as leaders and managers adapt to the new institutional logics of the health care sector with increasing demands for efficiency and budgetary discipline, no previous studies have investigated whether leaders’ emphasis on clinical or financial priorities is related to how hospital physicians’ view their working situation. The purpose of this study was therefore to examine the relationship between leadership style and hospital physicians’ organisational climate.

Methods

We utilised data from a survey among 3000 Norwegian hospital physicians from 2016. The analysis used three additive indexes as dependent variables to reflect various aspects of the organisational climate: social climate, innovation climate and engagement at the workplace. The variables reflecting leadership style were based on an item in the survey asking the respondents to rate the leadership qualities of their proximate leaders (department chair) on 11 specific dimensions. We used factor analysis to identify two types of leadership styles: a traditional profession-based leadership style that emphasises the promotion of professional standards and quality in patient treatment, and a leadership style that reflects the emerging management philosophy with focus on economic administration and budgetary control. Controlling for demographic background, leader role, foreign medical exam and specialty, the empirical model was estimated via multivariate regression.

Results

The results documented a clear relationship between leadership style and organisational climate: a ‘professional-supportive’ leadership style is associated with better social climate, innovation climate and engagement at the workplace, while an ‘economic-operational’ leadership style is associated with a poorer social climate.

Conclusions

The cross-sectional study design makes it impossible to draw inferences about direction of causality and causal pathways. However, the positive relationship between professional-supportive leadership and organisational climate is a matter, which should be seriously considered regardless of direction of causality.
Community health workers: challenges and vulnerabilities of Accredited Social Health Activists working in conflict-affected settings in the state of Assam, India
Authors: Rajbangshi Preety R , Nambiar Devaki , Srivastava Aradhana
Published: August 2021

Introduction

It is well acknowledged that India’s community health workers known as Accredited Social Health Activists (ASHA) are the bedrock of its health system. Many ASHAs are currently working in fragile and conflict-affected settings. No efforts have yet been made to understand the challenges and vulnerabilities of these female workers. This paper seeks to address this gap by bringing attention to the situation of ASHAs working in the fragile and conflict settings and how conflict impacts them and their work.

Methods

Qualitative fieldwork was undertaken in four conflict-affected villages in two conflict-affected districts -Kokrajhar and Karbi Anglong of Assam state situated in the North-East region of India. Detailed account of four ASHAs serving roughly 4000 people is presented. Data transliterated into English were analysed by authors by developing a codebook using grounded theory and thematic organisation of codes.

Results

ASHAs reported facing challenges in ensuring access to health services during and immediately after outbreaks of conflict. They experienced difficulty in arranging transport and breakdown of services at remote health facilities. Their physical safety and security were at risk during episodes of conflict. ASHAs reported hostile attitudes of the communities they served due to the breakdown of social relations, trauma due to displacement, and loss of family members, particularly their husbands.

Conclusions

Conflict must be recognised as an important context within which community health workers operate, with greater policy focus and research devoted to understanding and addressing the barriers they face as workers and as persons affected by conflict.
Compound heterozygous variants including a novel copy number variation in a child with atypical ataxia-telangiectasia: a case report
Authors: Lee Hoo Young , Jang Dae-Hyun , Kim Jae-Won , Lee Dong-Woo , Jang Ja-Hyun , Joo Joungsu
Published: August 2021

Background

Ataxia-telangiectasia is a rare autosomal recessive, neurodegenerative disorder caused by alterations in theATMgene. The majority ofATMpathogenic variants are frameshift or nonsense variants which are predicted to truncate the whole ATM protein. Herein, we report on an ataxia telangiectasia child with atypical phenotype who was identified as compound heterozygous for twoATMvariants involving a previously described pathogenic single nucleotide variation (SNV) and a novel copy number variation (CNV).

Case presentation

A 6-year-old boy presented with delayed development and oculomotor apraxia. Brain magnetic resonance imaging showed interval development of mild atrophy in the cerebellum. Serum alpha fetoprotein level was in normal range. Next-generation sequencing and single-nucleotide polymorphism array tests were performed. Next-generation sequencing revealed a heterozygous nonsense pathogenic variant inATM, c.742C > T (p.Arg248Ter) inherited from the father. Single-nucleotide polymorphism array revealed a compound heterozygous CNV, arr[GRCh37] 11q22.3(10851766–108183226) × 1, 31460 bp (exons 24–40 deletion ofATM) inherited from the mother, which was validated by reverse transcription-polymerase chain reaction analysis (RT-PCR). We demonstrated that this variant (NM_000051.4:c.3403_6006del) generated a product of in-frame deletion of exon 24–40 ofATM(p.Ser1135_Gln2002del).

Conclusions

The compound heterozygosity forATMvariants involving a previously described pathogenic SNV and a novel CNV may be associated with the atypical clinical manifestations. This clinical report extends the genetic and phenotypic spectrum ofATMpathogenic variants in atypical ataxia-telangiectasia, thus making implementation of advanced analysis beyond the routine next-generation sequencing an important consideration in diagnosis and rehabilitation services for children with ataxia-telangiectasia.
Metformin exerts anti-AR-negative prostate cancer activity via AMPK/autophagy signaling pathway
Authors: Chen Chunyang , Wang He , Geng Xinyu , Zhang Dongze , Zhu Zhengyu , Zhang Guangbo , Hou Jianquan
Published: August 2021

Background

Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer.

Methods

Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo.

Results

The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators.

Conclusion

This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.
An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration
Authors: Ding Tian , Kang Wenyan , Li Jianhua , Yu Lu , Ge Shaohua
Published: August 2021

Background

The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes.

Results

Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration.

Conclusions

Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials.

Graphic Abstract
Identification of a novel circ_0018289/miR-183-5p/TMED5 regulatory network in cervical cancer development
Authors: Zou Heng , Chen Huijia , Liu Shuaibin , Gan Xiaoling
Published: August 2021

Background

Circular RNAs (circRNAs) are increasingly implicated in regulating human carcinogenesis. Previous work showed the oncogenic activity of circ_0018289 in cervical cancer. However, the molecular basis underlying the modulation of circ_0018289 in cervical carcinogenesis is still not fully understood.

Methods

The levels of circ_0018289, microRNA (miR)-183-5p, and transmembrane p24 trafficking protein 5 (TMED5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Ribonuclease (RNase) R and subcellular localization assays were used to characterize circ_0018289. Cell proliferation was detected by the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis and tube formation were assessed by flow cytometry and tube formation assays, respectively. A dual-luciferase reporter assay was performed to confirm the direct relationship between miR-183-5p and circ_0018289 or TMED5. The role of circ_0018289 in tumor growth was gauged by mouse xenograft experiments.

Results

Circ_0018289 was overexpressed in cervical cancer tissues and cells. Circ_0018289 silencing impeded cell proliferation, enhanced cell apoptosis, and suppressed angiogenesis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0018289 targeted and regulated miR-183-5p by binding to miR-183-5p, and circ_0018289 regulated cervical cancer development and angiogenesis partially through miR-183-5p. Moreover, TMED5 was directly targeted and inhibited by miR-183-5p through the perfect complementary sites in TMED5 3′UTR, and TMED5 knockdown phenocopied miR-183-5p overexpression in suppressing cervical cancer development and angiogenesis. Furthermore, circ_0018289 induced TMED5 expression by competitively binding to shared miR-183-5p.

Conclusion

Our observations identified the circ_0018289/miR-183-5p/TMED5 regulatory network as a novel molecular basis underlying the modulation of cervical carcinogenesis.
Gastric cancer with positive peritoneal cytology: survival benefit after induction chemotherapy and conversion to negative peritoneal cytology
Authors: Valletti Massimiliano , Eshmuminov Dilmurodjon , Gnecco Nicola , Gutschow Christian Alexander , Schneider Paul Magnus , Lehmann Kuno
Published: August 2021

Background

The optimal treatment in patients with gastric cancer and peritoneal disease remains controversial. Some guidelines indicate palliative treatment only, while others consider surgical treatment in case of positive lavage cytology (CY+) or limited peritoneal disease. Here, we analyzed the role of peritoneal disease in patients with gastric cancer, and the prognostic relevance of response to neoadjuvant therapy.

Methods

In this retrospective cohort analysis, we analyzed patients with adenocarcinoma of the stomach or esophago-gastric junction from a single center operated between 2011 and 2019. According to histology and lavage cytology, patients were classified into four risk groups: (A) no peritoneal disease, (B) CY+ who converted to negative lavage cytology (CY−) after neoadjuvant chemotherapy, (C) CY+ without conversion after chemotherapy, and (D) patients with visible peritoneal metastasis.

Results

Overall, n = 172 patients were included. At initial presentation, n = 125 (73%) had no peritoneal disease, and about a third of patients (n = 47, 27%) had microscopic or macroscopic peritoneal disease. Among them, n = 14 (8%) were CY+ without visible peritoneal metastasis, n = 9 converted to CY− after chemotherapy, and in n = 5 no conversion was observed. Median overall survival was not reached in patients who had initially no peritoneal disease and in patients who converted after chemotherapy, resulting in 3-year survival rates of 65% and 53%. In contrast, median overall survival was reduced to 13 months (95% CI 8.7–16.7) in patients without conversion and was 16 months (95% CI 12–20.5) in patients with peritoneal metastasis without difference between the two groups (p = .364). The conversion rate from CY+ to CY− was significantly higher after neoadjuvant treatment with FLOT (5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel) compared to ECF (epirubicin, cisplatin, and 5-fluorouracil) (p = 0.027).

Conclusion

Conversion of CY+ to CY− after neoadjuvant chemotherapy with FLOT is a significant prognostic factor for a better overall survival. Surgical treatment in well-selected patients should therefore be considered. However, peritoneal recurrence remains frequent despite conversion, urging for a better local control.
Maternal and infant outcomes during the COVID-19 pandemic: a retrospective study in Guangzhou, China
Authors: Wang Jingyun , Wang Yun , He Mei-yao , Li Yi-xiao , Cheng Xin , Yang Xuesong , Li Rui-man , Wang Guang
Published: August 2021

In late December 2019, the COVID-19 pandemic caused a great threat to people’s lives worldwide. As a special category of the population, pregnant women are vulnerable during emergencies. This study was designed to explore whether or not the COVID-19 pandemic has influenced maternal and infant outcomes. We collected maternal characteristics, laboratory results, condition in the third trimester, maternal outcome, fetal or neonatal outcomes, and characteristics of amniotic fluid, umbilical cord and placenta from pregnant women and fetals or newborns in the first affiliated hospital of Jinan university from 24 January to 31 March 2020 (peak period), chose the same types of data at the hospital during the same period in 2019 and 1 January—23 January 2020 (prior to the outbreak of COVID-19 in 2020) as a control. Our study focused on uncomplicated singleton pregnancies among women not infected by COVID-19. The results demonstrated that there was not an increase in adverse outcomes of pregnant women and newborns during the COVID-19 pandemic; This might be associated with the updated design of major epidemic prevention and control systems in Guangzhou, and the extension of pregnant women’s rest time during the third trimester of pregnancy. Nevertheless, the survey showed an increased incidence rate of 25-hydroxyvitamin D and zinc deficiency in newborns during the epidemic, implying that pregnant women should participate in appropriate physical exercise, increase their exposure to outdoor sunlight and improve nutrition intake to ensure healthy newborns during the quarantine period. Our study has provided some guidance for maternal management during the COVID-19 pandemic.
Retention of visa-trainee post-graduate residents in Canada: a retrospective cohort study
Authors: Mathews Maria , Koudieh Dania , Yi Yanqing , Hedden Lindsay , Marshall Emily Gard , Samarasena Asoka , Barnum Geoff , Bourgeault Ivy
Published: August 2021

Background

Visa trainees (international medical graduates [IMG] who train in Canada under a student or employment visa) are expected to return home after completing their training. We examine the retention patterns of visa trainee residents funded by Canadian (regular ministry and other), foreign, or mixed sources.

Methods

We linked data from the Canadian Post-MD Medical Education Registry with Scott’s Medical Database for a retrospective cohort study. Eligible trainees were IMG visa trainees as of their first year of training, started their residency program no earlier than 2000, and exited training between 2006 and 2016. We used Cox regression to compare the retention of visa trainees by funding source.

Results

Of 1,913 visa trainees, 431(22.5%), 1353 (70.7%) and 129 (6.8%) had Canadian, foreign, or mixed funding, respectively. The proportion of trainees remaining in Canada decreased over time, with 35.5% (679/1913); 17.7% (186/1052); 10.8% (11/102) in Canada one, five, and ten years, respectively after their exit from PGME training. Trainees who remained on visas (HR: 1.91; [95% CI 1.59, 2.30]), were funded exclusively by foreign sources (HR: 1.46; [95% CI 1.25, 1.69]), and who had graduated from ‘Western’ countries (HR: 1.39; [95% CI 1.06, 1.84]) were more likely to leave Canada compared to trainees who became citizens/permanent residents, were funded by Canadian sources, or were visa graduates of Canadian medical schools, respectively.

Conclusions

Most visa trainees leave Canada following their training. Trainees with Canadian connections (funding and/or change in legal status) were more likely to remain in Canada.
Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine
Authors: Cao Jin , Zhang Yue , Li Hui , Yan Zhaoxian , Liu Xian , Hou Xiaoyan , Chen Weicui , Hodges Sierra , Kong Jian , Liu Bo
Published: August 2021

Background

A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine.

Methods

Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest.

Results

Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS.

Conclusions

Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.
Urinary small extracellular vesicles derived CCL21 mRNA as biomarker linked with pathogenesis for diabetic nephropathy
Authors: Feng Ye , Zhong Xin , Ni Hai-Feng , Wang Cui , Tang Tao-Tao , Wang Li-Ting , Song Kai-Yun , Tang Ri-Ning , Liu Hong , Liu Bi-Cheng , Lv Lin-Li
Published: August 2021

Background

Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking.

Methods

Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ.

Results

The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model.

Conclusions

Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.
Comparison of minimally invasive percutaneous fixation and open reduction internal fixation for patella fractures: a meta-analysis
Authors: Lo Chun-Hong , Chen Chih-Hwa
Published: August 2021

Background

Open reduction internal fixation (ORIF) has long been the conventional procedure for managing displaced patella fracture. This surgical approach has certain drawbacks, which might affect clinical outcomes and patient prognosis. Minimally invasive percutaneous fixation (MIPF) was proposed to overcome these disadvantages. Few in-depth investigations have been performed to determine the superiority of MIPF over ORIF. The aim of this study was to compare the efficacies of MIPF and ORIF for patella fractures.

Methods

The PubMed, Cochrane Library, Embase, and Scopus databases were searched for relevant studies from November 26 to December 17, 2020. Non-English publications and pediatric orthopedic articles were excluded. Statistical analysis was performed using Review Manager, version 5.4, with mean differences (MDs), standardized mean differences (SMDs), odds ratios (ORs), and respective 95% confidence intervals (CIs) calculated using a random effects model. The primary outcomes were the pain score, knee range of motion, and joint functionality. The secondary outcomes were the surgical time, complications, and implant removal rate.

Results

Six articles with a total of 304 patients were included in the meta-analysis. Pooled analysis revealed that patients with MIPF had a significantly reduced pain score (MD = − 1.30, 95% CI = − 1.77 to −0.82; p < 0.00001) and increased knee extension angles (MD = 0.72, 95% CI = 0.18 to 1.25; p = 0.009) at 3-month follow-up. Furthermore, knee flexion angles (MD = 8.96, 95% CI = 5.81 to 12.1; p < 0.00001) and joint functionality (SMD = 0.54, 95% CI = 0.21 to 0.86; p = 0.001) had statistically improved at 2 years. However, no difference was observed between MIPF and ORIF with regard to the surgical time. The risk of complications (OR = 0.10, 95% CI = 0.05 to 0.18; p < 0.00001) and implant removal rate (OR = 0.20, 95% CI = 0.07 to 0.57; p = 0.003) were significantly lower with MIPF than with ORIF.

Conclusions

MIPF is more favorable than ORIF in terms of the pain score, knee range of motion, joint functionality, complications, and implant removal rate. Thus, it can be adopted as an alternative to ORIF.
Clinicopathological and prognostic features of hepatitis B virus-associated diffuse large B-cell lymphoma: a single-center retrospective study in China
Authors: Chen Dao-guang , Chen Gang , Wang Chang , Ke Long-feng , Wu Hui , He Hong-ming , Yang Yu , Chen Yan-ping
Published: August 2021

Background

While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known about the pathological characteristics and outcome of DLBCL arising in patients with HBV infection.

Methods

We retrospectively studied a cohort of 420 patients with DLBCL for the incidence of HBV infection, and the clinicopathologic features and prognostic factors in HBsAg-positive DLBCL patients in China, a hepatitis B endemic area.

Results

In our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P = 0.002), more frequent involvement of the spleen (19.7% vs. 6.1%, P < 0.001), less frequent involvement of the small and large intestine (2.3% vs. 11.2%, P = 0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P = 0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P = 0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P = 0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients.

Conclusions

Our study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients, and the use of rituximab significantly improved OS in HBsAg-positive DLBCL patients.
Complement inhibitor CSMD1 modulates epidermal growth factor receptor oncogenic signaling and sensitizes breast cancer cells to chemotherapy
Authors: Gialeli Chrysostomi , Tuysuz Emre Can , Staaf Johan , Guleed Safia , Paciorek Veronika , Mörgelin Matthias , Papadakos Konstantinos S. , Blom Anna M.
Published: August 2021

Background

Human CUB and Sushi multiple domains 1 (CSMD1) is a large membrane-bound tumor suppressor in breast cancer. The current study aimed to elucidate the molecular mechanism underlying the effect of CSMD1 in highly invasive triple negative breast cancer (TNBC).

Methods

We examined the antitumor action of CSMD1 in three TNBC cell lines overexpressing CSMD1, MDA-MB-231, BT-20 and MDA-MB-486, in vitro using scanning electron microscopy, proteome array, qRT-PCR, immunoblotting, proximity ligation assay, ELISA, co-immunoprecipitation, immunofluorescence, tumorsphere formation assays and flow cytometric analysis. The mRNA expression pattern and clinical relevance of CSMD1 were evaluated in 3520 breast cancers from a modern population-based cohort.

Results

CSMD1-expressing cells had distinct morphology, with reduced deposition of extracellular matrix components. We found altered expression of several cancer-related molecules, as well as diminished expression of signaling receptors including Epidermal Growth Factor Receptor (EGFR), in CSMD1-expressing cells compared to control cells. A direct interaction of CSMD1 and EGFR was identified, with the EGF-EGFR induced signaling cascade impeded in the presence of CSMD1. Accordingly, we detected increased  ubiquitination levels of EGFR upon activation in CSMD1-expressing cells, as well as increased degradation kinetics and chemosensitivity. Accordingly, CSMD1 expression rendered tumorspheres pretreated with gefitinib more sensitive to chemotherapy. In addition, higher mRNA levels of CSMD1 tend to be associated with better outcome of triple negative breast cancer patients treated with chemotherapy.

Conclusions

Our results indicate that CSMD1 cross-talks with the EGFR endosomal trafficking cascade in a way that renders highly invasive breast cancer cells sensitive to chemotherapy. Our study unravels one possible underlying molecular mechanism of CSMD1 tumor suppressor function and may provide novel avenues for design of better treatment.
Clinical significance for combined coagulation indexes in epithelial ovarian cancer prognosis
Authors: Yang Jiani , Jin Yue , Cheng Shanshan , Wang Chao , Zhang Nan , Huang Shan , Zhao Yaqian , Wang Yu
Published: August 2021

Background

Increasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC).

Methods

A retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis.

Results

We involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047;p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491;p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768;p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894;p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241;p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS andp = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS andp = 0.0180 for OS).

Conclusion

Our findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.
Chlorhexidine–alcohol versus povidone–iodine as preoperative skin antisepsis for prevention of surgical site infection in cesarean delivery—a pilot randomized control trial
Authors: Luwang Athokpam Lenin , Saha Pradip Kumar , Rohilla Minakshi , Sikka Pooja , Saha Lekha , Gautam Vikas
Published: August 2021

Objectives

To compare the efficacy of chlorhexidine–alcohol and povidone–iodine as preoperative antiseptic skin preparation for prevention of surgical site infection (SSI) after cesarean delivery (CD).

Materials and methods

A total of 311 eligible women who underwent CS were recruited in the study after fulfilling all the eligibility and exclusion criteria. Patients were randomized into two groups (153 in chlorhexidine–alcohol group and 158 in povidone–iodine group) by a computer-generated randomization table. Patients were followed for a period of 30 days in postoperative period to monitor for SSI.

Results

The rate of SSI in the chlorhexidine–alcohol group is 5.4% and that of the povidone–iodine group is 8.6%. E. coli, K. pneumoniae, and Acinetobacter baumannii were the most common organisms isolated. E. coli was found in 9.5% of the total SSI cases.

Conclusions

The study found that the patients who received chlorhexidine–alcohol as skin antiseptic had less chance of developing SSI than those who received povidone–iodine; however, it did not reach a statistical significance.

Trial registration

Clinical Trials Registry of India CTRI/2018/05/014294. Registered on May 31, 2018
Evaluating implementation of LEAPS, a youth-led early childhood care and education intervention in rural Pakistan: protocol for a stepped wedge cluster-randomized trial
Authors: Yousafzai Aisha K. , Sudfeld Christopher R. , Franchett Emily E. , Siyal Saima , Rehmani Karima , Bhamani Shelina , Dai Quanyi , Reyes Chin R. , Fink Günther , Ponguta Liliana A.
Published: August 2021

Background

The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan’s large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18–24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5–5.5 years, in rural Sindh, Pakistan.

Methods

We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children’s school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children’s IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5–5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3.

Discussion

Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets.

Trial registration

ClinicalTrials.govNCT03764436. Registered on December 5, 2018.