bluuebunny/crossref_metadata_2025 huggingface dataset:
What Helps, What Hinders? Undergraduate Nursing Students’ Perceptions of Clinical Placements Based on a Thematic Synthesis of Literature
Authors: Cant Robyn , Ryan Colleen , Hughes Lynda , Luders Elise , Cooper Simon
Published: September 2021

Introduction

Clinical placements are a mandatory component of nursing students’ education internationally. Despite clinical education being a key to nursing students’ achievement of nursing competencies, few studies have reviewed students’ narratives to describe their experiences of learning during clinical placement. Such studies may be important in offering a deeper insight into clinical learning experiences than quantitative surveys.

Methods

A systematic thematic synthesis of qualitative studies between 2010 and June 2020 was conducted. English language studies that offered a thematic analysis of undergraduate nursing students’ experiences of learning during placement were sought. A search was made of five databases PubMed, Ovid Medline, CinahlPlus, SCOPUS, and Google Scholar. The study was guided by the ENTREQ statement for enhancing transparency in reporting the synthesis of qualitative research.

Results

Twenty-seven qualitative studies were included in the review. A thematic synthesis showed over 100 themes and subthemes across the studies. A cluster analysis revealed positive elements and others that were seen in the studies as a barrier (hindrance) to clinical learning. Positive elements included supportive instructors, close supervision, and belonging (in the team). Unsupportive instructors, a lack of supervision and not being included were seen as a hindrance. Three key overarching themes that could describe a successful placement were revealed as “Preparation,” “Welcomed and wanted” and “Supervision experiences”. A conceptual model of clinical placement elements conducive to nursing students’ learning was developed to enhance understanding of the complexities associated with supervision. The findings and model are presented and discussed.

Conclusion

The conceptual model presents positive elements that influence students’ clinical placement experiences of learning. This model may provide a framework to guide professional development programs and strategies to support students and supervisors alike, an important step forward in moving beyond the current clinical placement rhetoric.
Politics of Inclusion: Review Essay
Authors: Husain Zeeshan , Gochhayat Rajanikanta
Published: September 2021

Politics of Inclusion (2009) is an unusual book as its major arguments are not merely valid but are increasingly relevant. Published over a decade ago, it remains a must read for policymakers, political scientists and developmental experts. This review essay has tried to lay down eight key arguments that the book made. These are expanding the ambit of the definition of discrimination from only historical to both past and present forms; accepting that Muslims are not only a poor community but also suffer a peculiar form of discrimination which is increasing; discrimination and backwardness both criterion must be fulfilled for any kind of affirmative action to be institutionalized; state should be welfare in nature and protect all vulnerable social groups; acknowledging that Hindutva is not only against religious minorities but also against women; political representation must be on the four axes of caste, ethnicity, religion and gender; for proper representation of Dalits, tribes, Muslims and women we need electoral reforms and lastly, Scheduled Caste (SC) status must be conferred to Dalit Muslims and Dalit Christians. Rather than simply summing up the book, this review essay uses arguments from various contemporary political theorists and social scientists.
A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma
Authors: Qazilbash Muzaffar H. , Saini Neeraj Y. , Cha Soung-chul , Wang Zhe , Stadtmauer Edward A. , Baladandayuthapani Veerabhadran , Lin Heather , Tross Beryl , Honhar Medhavi , Rao Sheetal S. , Kim Kunhwa , Popescu Michael , Szymura Szymon , Zhang Tiantian , Anderson Aaron , Bashir Qaiser , Shpall Elizabeth J. , Orlowski Robert Z. , Levine Bruce L. , Kerr Naseem , Garfall Alfred , Cohen Adam , Vogl Dan T. , Dengel Karen , June Carl H. , Champlin Richard , Kwak Larry W.
Published: September 2021

We hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)–keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.
Biological and socioeconomic factors as moderator in relationship between leisure-time physical activity and cardiometabolic risk in adolescents from southern Brazil
Authors: Sehn Ana Paula , Tornquist Debora , Tornquist Luciana , Brazo-Sayavera Javier , Reuter Cézane Priscila
Published: September 2021

Background

Given the important repercussions that sociodemographic factors can have on physical activity, especially in the field of leisure, and cardiometabolic risk, it seems relevant to analyze the implications of these variables on the relationship between physical activity in leisure time (LTPA) and cardiometabolic risk. In this sense, the present study aims to verify the moderating role of biologic and socioeconomic factors in the relationship between LTPA and cardiometabolic risk in adolescents in southern Brazil.

Methods

Cross-sectional study that included 1596 adolescents selected at random (58.2% girls), aged between 10 and 17 years. LTPA, biological and socioeconomic factors were assessed using a self-reported questionnaire and the cardiometabolic risk score (total cholesterol/HDL-c ratio, triglycerides, fasting glucose, systolic blood pressure, and waist circumference, considering the participant’s age and sex) was included as an outcome. Associations and moderations were tested by multiple linear regression models.

Results

It was observed a positive interaction of LTPA and sex (p = 0.048) and LTPA and school system (p = 0.037), and negative interaction of LTPA and skin color (p = 0.040), indicating that these factors were moderators in the relationship between LTPA and clustered cardiometabolic risk score (cMetS) in adolescents. A reduction in cardiometabolic risk was observed according to the increase in weekly minutes of LTPA among boys, non-white adolescents, and students from municipal schools.

Conclusions

The association between LTPA and cardiometabolic risk was moderated by sex, skin color, and school system in adolescents from southern Brazil.
The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
Authors: Mompart Florence , Kamgoué Alain , Lahbib-Mansais Yvette , Robelin David , Bonnet Agnès , Rogel-Gaillard Claire , Kocanova Silvia , Yerle-Bouissou Martine
Published: September 2021

Background

The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essential role on genome function regulation. We analyzed the spatial arrangement of the three MHC regions (class I, III and II) in macrophages using 3D-FISH. Since this complex presents major differences in humans and pigs with, notably, the presence of the centromere between class III and class II regions in pigs, the analysis was implemented in both species to determine the impact of this organization on the 3D conformation of the MHC. The expression level of the three genes selected to represent each MHC region was assessed by quantitative real-time PCR. Resting and lipopolysaccharide (LPS)-activated states were investigated to ascertain whether a response to a pathogen modifies their expression level and their 3D organization.

Results

While the three MHC regions occupy an intermediate radial position in porcine macrophages, the class I region was clearly more peripheral in humans. The BAC center-to-center distances allowed us to propose a 3D nuclear organization of the MHC in each species. LPS/IFNγ activation induces a significant decompaction of the chromatin between class I and class III regions in pigs and between class I and class II regions in humans. We detected a strong overexpression of TNFα (class III region) in both species. Moreover, a single nucleus analysis revealed that the two alleles can have either the same or a different compaction pattern. In addition, macrophage activation leads to an increase in alleles that present a decompacted pattern in humans and pigs.

Conclusions

The data presented demonstrate that: (i) the MHC harbors a different 3D organization in humans and pigs; (ii) LPS/IFNγ activation induces chromatin decompaction, but it is not the same area affected in the two species. These findings were supported by the application of an original computation method based on the geometrical distribution of the three target genes. Finally, the position of the centromere inside the swine MHC could influence chromatin reorganization during the activation process.
The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background
Authors: Ducoli Luca , Agrawal Saumya , Hon Chung-Chau , Ramilowski Jordan A. , Sibler Eliane , Tagami Michihira , Itoh Masayoshi , Kondo Naoto , Abugessaisa Imad , Hasegawa Akira , Kasukawa Takeya , Suzuki Harukazu , Carninci Piero , Shin Jay W. , de Hoon Michiel J. L. , Detmar Michael
Published: September 2021

Background

The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism’s physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner.

Results

To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background.

Conclusion

In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.
Choice of pre-processing pipeline influences clustering quality of scRNA-seq datasets
Authors: Shainer Inbal , Stemmer Manuel
Published: September 2021

Background

Single-cell RNA sequencing (scRNA-seq) has quickly become one of the most dominant techniques in modern transcriptome assessment. In particular, 10X Genomics’ Chromium system, with its high throughput approach, turn key and thorough user guide made this cutting-edge technique accessible to many laboratories using diverse animal models. However, standard pre-processing, including the alignment and cell filtering pipelines might not be ideal for every organism or tissue. Here we applied an alternative strategy, based on the pseudoaligner kallisto, on twenty-two publicly available single cell sequencing datasets from a wide range of tissues of eight organisms and compared the results with the standard 10X Genomics’ Cell Ranger pipeline.

Results

In most of the tested samples, kallisto produced higher sequencing read alignment rates and total gene detection rates in comparison to Cell Ranger. Although datasets processed with Cell Ranger had higher cell counts, outside of human and mouse datasets, these additional cells were routinely of low quality, containing low gene detection rates. Thorough downstream analysis of one kallisto processed dataset, obtained from the zebrafish pineal gland, revealed clearer clustering, allowing the identification of an additional photoreceptor cell type that previously went undetected. The finding of the new cluster suggests that the photoreceptive pineal gland is essentially a bi-chromatic tissue containing both green and red cone-like photoreceptors and implies that the alignment and pre-processing pipeline can affect the discovery of biologically-relevant cell types.

Conclusion

While Cell Ranger favors higher cell numbers, using kallisto results in datasets with higher median gene detection per cell. We could demonstrate that cell type identification was not hampered by the lower cell count, but in fact improved as a result of the high gene detection rate and the more stringent filtering. Depending on the acquired dataset, it can be beneficial to favor high quality cells and accept a lower cell count, leading to an improved classification of cell types.
Genomic variation in captive deer mouse (Peromyscus maniculatus) populations
Authors: Lucius Matthew D. , Ji Hao , Altomare Diego , Doran Robert , Torkian Ben , Havighorst Amanda , Kaza Vimala , Zhang Youwen , Gasparian Alexander V. , Magagnoli Joseph , Shankar Vijay , Shtutman Michael , Kiaris Hippokratis
Published: September 2021

Background

Deer mice (genus Peromyscus) are the most common rodents in North America. Despite the availability of reference genomes for some species, a comprehensive database of polymorphisms, especially in those maintained as living stocks and distributed to academic investigators, is missing. In the present study we surveyed two populations of P. maniculatus that are maintained at the Peromyscus Genetic Stock Center (PGSC) for polymorphisms across their 2.5 × 109 bp genome.

Results

High density of variation was identified, corresponding to one SNP every 55 bp for the high altitude stock (SM2) or 207 bp for the low altitude stock (BW) using snpEff (v4.3). Indels were detected every 1157 bp for BW or 311 bp for SM2. The average Watterson estimator for the BW and SM2 populations is 248813.70388 and 869071.7671 respectively. Some differences in the distribution of missense, nonsense and silent mutations were identified between the stocks, as well as polymorphisms in genes associated with inflammation (NFATC2), hypoxia (HIF1a) and cholesterol metabolism (INSIG1) and may possess value in modeling pathology.

Conclusions

This genomic resource, in combination with the availability of P. maniculatus from the PGSC, is expected to promote genetic and genomic studies with this animal model.
Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease
Authors: Wen Jinhua , Zhao Menghua , Sun Wenxiong , Cheng Xiaohua , Yu Luyi , Cao Duanwen , Li Pu
Published: September 2021

Background

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD.

Results

In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain.

Conclusions

This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.
Extensive genomic rearrangements mediated by repetitive sequences in plastomes of Medicago and its relatives
Authors: Wu Shuang , Chen Jinyuan , Li Ying , Liu Ai , Li Ao , Yin Mou , Shrestha Nawal , Liu Jianquan , Ren Guangpeng
Published: September 2021

Background

Although plastomes are highly conserved with respect to gene content and order in most photosynthetic angiosperms, extensive genomic rearrangements have been reported in Fabaceae, particularly within the inverted repeat lacking clade (IRLC) of Papilionoideae. Two hypotheses, i.e., the absence of the IR and the increased repeat content, have been proposed to affect the stability of plastomes. However, this is still unclear for the IRLC species. Here, we aimed to investigate the relationships between repeat content and the degree of genomic rearrangements in plastomes of Medicago and its relatives Trigonella and Melilotus, which are nested firmly within the IRLC.

Results

We detected abundant repetitive elements and extensive genomic rearrangements in the 75 newly assembled plastomes of 20 species, including gene loss, intron loss and gain, pseudogenization, tRNA duplication, inversion, and a second independent IR gain (IR ~ 15 kb in Melilotus dentata) in addition to the previous first reported cases in Medicago minima. We also conducted comparative genomic analysis to evaluate plastome evolution. Our results indicated that the overall repeat content is positively correlated with the degree of genomic rearrangements. Some of the genomic rearrangements were found to be directly linked with repetitive sequences. Tandem repeated sequences have been detected in the three genes with accelerated substitution rates (i.e., accD, clpP, and ycf1) and their length variation could be explained by the insertions of tandem repeats. The repeat contents of the three localized hypermutation regions around these three genes with accelerated substitution rates are also significantly higher than that of the remaining plastome sequences.

Conclusions

Our results suggest that IR reemergence in the IRLC species does not ensure their plastome stability. Instead, repeat-mediated illegitimate recombination is the major mechanism leading to genome instability, a pattern in agreement with recent findings in other angiosperm lineages. The plastome data generated herein provide valuable genomic resources for further investigating the plastome evolution in legumes.
Efficiency of complete omentectomy in patients with resectable gastric cancer: a meta‑analysis and systematic review
Authors: Zhu Akao , Yin Guang , Liu Xinchun , Kong Wencheng , Zhang Yu , Shan Yuqiang , Ying Rongchao , Zhang Jian , Zhou Chunhua
Published: September 2021

Background

We performed a meta-analysis to investigate the efficacy of complete omentectomy (CO) in patients undergoing radical gastrectomy for gastric cancer.

Methods

We conducted a literature search in PubMed, Web of Science, and the Cochrane Library databases for clinical research that compared CO with non-complete omentectomy (NCO). These articles were published prior to April 2021. Overall survival (OS) rates, relapse-free survival (RFS) rates, recurrence rates, operation times, estimates of blood loss, numbers of harvested lymph nodes, complications, and lengths of hospital stays were compared using relative risks (RRs) and weighted mean differences (WMDs). RevMan 5.3 software was used for statistical analysis.

Results

Nine studies that included 3329 patients (1960 in the CO group) and 1369 in the NCO group comprised the analysis. The meta-analysis showed that CO was associated with a decreased 3-year OS rate (RR = 0.94, 95% CI 0.90–0.98, P = 0.005) and 5-year OS rate (RR = 0.93, 95% CI 0.88–0.98, P = 0.007). However, it was not associated with the 3-year RFS rate (RR = 0.97, 95% CI 0.90–1.04, P = 0.44), 5-year RFS (RR = 0.98, 95% CI 0.90–1.06, P = 0.60), or recurrence rate (RR = 1.17, 95% CI 0.95–1.45, P = 0.15) compared to the NCO group. For surgical-related outcomes, significant heterogeneity existed between the studies. Compared to the NCO group, CO was found to be associated with significantly more estimated blood loss (WMD = 250.90, 95% CI 105.90–396.28, P = 0.0007) and less harvested lymph nodes (WMD = − 3.59, 95% CI − 6.88, − 0.29, P = 0.03). Although, there was no significant difference in the surgical time (WMD = 15.93, 95% CI − 0.21, 32.07, P = 0.05). No statistically significant differences were observed in the rates of overall (P = 0.79) and major complications (P = 0.90), or the lengths of hospital stays (P = 0.11) between the two groups.

Conclusions

Based on the available evidence, CO is not superior to NCO in terms of survival. CO is not recommended as a routine surgery for gastric cancer. Future well-designed high-quality RCTs are warranted.
Prevalence estimates of genital Chlamydia trachomatis infection in Belgium: results from two cross-sectional studies
Authors: Fischer Natalie , Peeters Ilse , Klamer Sofieke , Montourcy Marion , Cuylaerts Vicky , Van Beckhoven Dominique , De Baetselier Irith , Van der Heyden Johan , Vanden Berghe Wim
Published: September 2021

Background

Chlamydia trachomatis (chlamydia) is the most diagnosed sexually transmitted infection in Belgium. Screening programs focus on young women, due to the implications of chronic asymptomatic infections for reproductive health. Thereby, the frequency of infections in men and older adults is underestimated. This study aimed to estimate the point-prevalence of chlamydia in the broader Belgian population, to inform evidence-based prevention and control strategies.

Methods

We conducted two cross-sectional prevalence studies of chlamydia infection in the population of Belgium aged 16–59 years, 2018–2020. In the CT1 study 12,000 representative individuals were randomly selected from the national register and invited by letter to collect a urine sample at home. The CT2 study used urine samples collected through the Belgian Health Examination Survey. Molecular detection of chlamydia DNA was performed using Xpert® or Abbott Real-Time CT/NG assays. Weighted estimated prevalence and 95% confidence interval (CI) was calculated per gender and age groups of 16/18–29, 30–44 and 45–59 years, relative to the general Belgian population. Data collected on sociodemographic variables and sexual behavior were used to identify potential risk factors for chlamydia infection through calculation of the odds ratio (OR).

Results

The population-wide weighted estimated prevalence was 1.54% (95% CI 0.78–3) in CT1 and 1.76% (95% CI 0.63–4) in CT2. We observed no statistically significant difference between men and women or age groups. Civil relationship status (OR = 14.1 (95% CI 1.78–112), p < 0.01), sexual intercourse with a casual partner (OR = 6.31 (95% CI 1.66–24.1), p < 0.01) and > 3 sexual partners in the last 12 months (OR = 4.53 (95% CI 1.10–18.6), p = 0.02) were associated with higher relative risk for chlamydia infection.

Conclusion

Nationwide prevalence studies are relevant to assess the distribution of chlamydia and inform public health actions. The overall low prevalence and heterogeneous distribution of chlamydia in the general Belgian population needs to be considered for future strategies and potential harm of testing and treating asymptomatic individuals need to be taken into account. Effective case management should include appropriate treatment of symptomatic patients and partner notification, and prevention strategies should encourage behaviors such as condom use.
The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study
Authors: Simbwa Brenda Nakafeero , Katamba Achilles , Katana Elizabeth B. , Laker Eva A. O. , Nabatanzi Sandra , Sendaula Emmanuel , Opio Denis , Ictho Jerry , Lochoro Peter , Karamagi Charles A. , Kalyango Joan N. , Worodria William
Published: September 2021

Background

Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB.

Methods

We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews.

Results

The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552–110.135) and drug stock-outs aOR 0.027 (95%CI 0.002–0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB.

Conclusion

Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.
Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma
Authors: Hong Duo , Zhou Yi , Wan Xiaoting , Su Hongying , Shao Haibo
Published: September 2021

Background

There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT).

Methods

Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival.

Results

No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’s ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3.

Conclusions

The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.
Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study
Authors: Erman Mustafa , Biswas Bivas , Danchaivijitr Pongwut , Chen Lingwu , Wong Yoke Fui , Hashem Tarek , Lim Chun Sen , Karabulut Bulent , Chung Hsiao-Jen , Chikatapu Chandrasekhar , Ingles Sara , Slimane Khemaies , Kanesvaran Ravindran
Published: September 2021

Background

Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

Methods

PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

Results

Overall, 190 patients with a median age of 61 years (range: 22.0–96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48–11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).

Conclusions

Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
Prevalence and associations of axillary web syndrome in Asian women after breast cancer surgery undergoing a community-based cancer rehabilitation program
Authors: Tay Matthew Rong Jie , Wong Chin Jung , Aw Hui Zhen
Published: September 2021

Background

Patients who have breast cancer surgery are at risk of axillary web syndrome (AWS), an under-recognized postsurgical complication which can result in shoulder morbidity and functional impairment. Emerging studies have indicated that AWS may persist beyond the first few months after surgery, although few studies have assessed the prevalence and association of AWS beyond a year after diagnosis. Therefore, the aim of this study was to investigate the prevalence and associations for AWS in post-operative breast cancer patients up to 3 years after surgery.

Methods

This cross sectional observational study was conducted at a community-based cancer rehabilitation center. Patients were evaluated for the presence of AWS via physical examination. Disease-related data was obtained from clinical review and medical records. Descriptive statistics were utilized to illustrate patient demographics and clinical characteristics. Logistic regression analyses were used to determine associations of AWS.

Results

There were 111 Asian women who were recruited, who had undergone breast surgery and were referred to a national outpatient rehabilitation center. The prevalence of AWS in this population was 28.9%. In the multivariate regression model, significant factors were age < 50 years (OR = 3.51; 95% CI = 1.12–11.0; p = 0.031) and ALND (OR = 6.54; 95% CI = 1.36–31.3; p = 0.019). There was reduced shoulder flexion ROM (p < 0.001) in patients with AWS compared to patients without AWS.

Conclusions

A high prevalence of AWS was reported in breast cancer survivors even at 3 years after breast surgery. Our findings highlight the need to identify breast cancer survivors with AWS even in the survivorship phase, and develop strategies to raise awareness and minimize functional impairment in these patients.
Transition to retirement impact on health and lifestyle habits: analysis from a nationwide Italian cohort
Authors: Vigezzi Giacomo Pietro , Gaetti Giovanni , Gianfredi Vincenza , Frascella Beatrice , Gentile Leandro , d’Errico Angelo , Stuckler David , Ricceri Fulvio , Costa Giuseppe , Odone Anna ,   on behalf of the Italian Working Group on Retirement and Health, Amerio Andrea , Ardito Chiara , Carioli Greta , Costa Giuseppe , d’Errico Angelo , Fontana Dario , Frascella Beatrice , Gaetti Giovanni , Gentile Leandro , Gianfredi Vincenza , Leombruni Roberto , Odone Anna , Ricceri Fulvio , Sacerdote Carlotta , Stuckler David , Vigezzi Giacomo Pietro , Zengarini Nicolas
Published: September 2021

Background

Retirement is a life-course transition likely to affect, through different mechanisms, behavioural risk factors’ patterns and, ultimately, health outcomes. We assessed the impact of transitioning to retirement on lifestyle habits and perceived health status in a nationwide cohort of Italian adults.

Methods

We analysed data from a large cohort of Italian adults aged 55–70, derived from linking six waves of the Participation, Labour, Unemployment Survey (PLUS), a national survey representative of the Italian workforce population, conducted between 2010 and 2018. We estimated relative-risk ratios (RRR) of transition to retirement and their corresponding 95% confidence intervals (CIs) for selected behavioural risk factors and health outcomes using multivariable logistic regression models. We used propensity score matching (PSM) to account for potential confounders.

Results

We included 5169 subjects in the study population, of which 1653 retired between 2010 and 2018 (exposed, 32%). Transition to retirement was associated with a 36% increased probability of practising sports (RRR 1.36, 95% CI 1.12–1.64). No statistically significant changes were reported for smoking habit (current smoker RRR: 1.18, 95% CI 0.94–1.46) and BMI (overweight/obese RRR: 0.96, 95% CI 0.81–1.15). Overall, retiring was associated with improved self-rated health status (RRR 1.26, 95% CI 1.02–1.58).

Conclusion

Individual data-linkage of multiple waves of the PLUS can offer great insight to inform healthy ageing policies in Italy and Europe. Transition to retirement has an independent effect on perceived health status, physical activity and selected behavioural risk factors. It should be identified as a target moment for preventive interventions, with particular reference to primary prevention so as to promote health and wellbeing in older ages.
A potential mechanism of the onset of immune-related pneumonitis triggered by anti-PD-1 treatment in a patient with advanced adenocarcinoma lung cancer: case report
Authors: Feng Yu , Chen Cuncun , Zhao Liming , Zhu Xuyou , Zhu Xiaoping , Li Qiang
Published: September 2021

Background

In recent years, the application of immunotherapy combined with chemotherapy in the first-line lung cancer has showed significant benefit in improving long-term survival. Immunotherapy also has risks of immune-related pneumonitis (IRP) after long-term treatment. Despite the treatment strategy of the IRP has been very clear. However, the mechanism is unclear.

Case presentation

A 73-year-old male patient was diagnosed with left lung adenocarcinoma IVa, EGFR, ALK, ROS1 negative. The patient received anti-PD1 antibody combined with pemetrexed and cisplatin. After 5 cycles of treatment, partial response was obtained. Subsequently, the patient continued the treatment of anti-PD1 antibody combined with pemetrexed. Before the 7th cycle, the CT found a new lesion in the basal segment of the right lower lobe. It was diagnosed with IRP and pneumocystis jirovecii. The patient did not give trimethoprim–sulphamethoxazole (TMP–SMX) and corticosteroids, symptoms and radiological lesions had improved. We describe the report of immune-related pneumonitis trigged by anti PD-1 and monitored the dynamic changes of CD4+, CD8+ T lymphocytes, MDSC and Treg cells in the bilateral bronchoalveolar alveolar lavage fluid. From the point of view of immune cells, the mechanism of immune reconstitution inflammatory syndrome is confirmed. Based on the current case report and literature, this study proposes a potential mechanism of the onset.

Conclusion

Immune reconstitution inflammatory syndrome may be potential mechanism of IRP. This study may improve our understanding of the pathogenesis underlying IRP. We believe the detection and dynamic monitoring CD4+, CD8+ T lymphocytes, MDSC and Treg cells can provide more accurate procedures.
Influence of sagittal root positions on the stress distribution around custom-made root-analogue implants: a three-dimensional finite element analysis
Authors: Lin Chunping , Hu Hongcheng , Zhu Junxin , Wu Yuwei , Rong Qiguo , Tang Zhihui
Published: September 2021

Background

Stress concentration may cause bone resorption even lead to the failure of implantation. This study was designed to investigate whether a certain sagittal root position could cause stress concentration around maxillary anterior custom-made root-analogue implants via three-dimensional finite element analysis.

Methods

The von Mises stresses in the bone around implants in different groups were compared by finite element analysis. Six models were constructed and divided into two groups through Geomagic Studio 2012 software. The smooth group included models of unthreaded custom-made implants in Class I, II or III sagittal root positions. The threaded group included models of reverse buttress-threaded implants in the three positions. The von Mises stress distributions and the range of the stresses under vertical and oblique loads of 100 N were analyzed through ANSYS 16.0 software.

Results

Stress concentrations around the labial lamella area were more prominent in the Class I position than in the Class II and Class III positions under oblique loading. Under vertical loading, the most obvious stress concentration areas were the labial lamella and palatal apical areas in the Class I and Class III positions, respectively. Stress was relatively distributed in the labial and palatal lamellae in the Class II position. The maximum von Mises stresses in the bone around the custom-made root-analogue implants in this study were lower than around traditional implants reported in the literature. The maximum von Mises stresses in this study were all less than 25 MPa in cortical bone and less than 6 MPa in cancellous bone. Additionally, compared to the smooth group, the threaded group showed lower von Mises stress concentration in the bone around the implants.

Conclusions

The sagittal root position affected the von Mises stress distribution around custom-made root-analogue implants. There was no certain sagittal root position that could cause excessive stress concentration around the custom-made root-analogue implants. Among the three sagittal root positions, the Class II position would be the most appropriate site for custom-made root-analogue implants.
Factors of decisive importance for being in work or not during two years after breast cancer surgery: content analysis of 462 women’s open answers
Authors: Wennman-Larsen Agneta , Svärd Veronica , Alexanderson Kristina , Friberg Emilie
Published: September 2021

Background

Paid work is one of the most important aspects in life among working-aged women diagnosed with breast cancer. Despite several attempts, no previous study provides a comprehensive overview from the women’s perspective about factors of importance for being able to work or not. Therefore, the aim of this study was to gain knowledge about factors that women themselves state are of decisive importance for being able to work or not during the first two years after breast cancer surgery.

Methods

Data was collected in a two-year follow-up questionnaire within the frame of a prospective cohort study of working-aged women who had undergone breast cancer surgery. 749 were included in the questionnaire study and of the 616 (82%) responding women, 462 (75%) wrote statements on an open-ended question about factors of decisive importance for being able to work or not work during the past two years. The statements were analyzed with content analysis.

Results

Five categories of factors of importance for being able to  work or not were identified, each covering several sub-categories: Health and wellbeing, Contacts and encounters, Flexibility and adjustment possibilities, Socioeconomic consequences from working/not working, and Own motivation and characteristics. A wide variety of factors were mentioned by the women and the findings give a multifaceted picture of many single but interrelated factors of decisive importance for being able to work/not work. The importance of flexibility in the return-to-work process was stressed, as well as the importance of supportive encounters from, e.g., colleagues, managers, as well as relatives.

Conclusions

The results give a comprehensive overview over a variety of different types of factors for being able to return to/remain in work or to not work after breast cancer surgery, adding new knowledge about e.g. the importance of colleagues, and the women’s own preferences or characteristics. These are factors that different stakeholders, both from healthcare but also from the work place and the insurance office, need to be aware of and collaborate around to support women with breast cancer during the period of treatment, rehabilitation and return to work.
Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial
Authors: Kusunose Kenya , Imai Takumi , Tanaka Atsushi , Dohi Kaoru , Shiina Kazuki , Yamada Takahisa , Kida Keisuke , Eguchi Kazuo , Teragawa Hiroki , Takeishi Yasuchika , Ohte Nobuyuki , Yamada Hirotsugu , Sata Masataka , Node Koichi ,   CANDLE Trial Investigators
Published: September 2021

Background

Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline.

Methods

Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function.

Results

The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89–1.08) in the canagliflozin group and 1.07 (95% CI 0.97–1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82–1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e′) showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e′ < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66–1.04).

Conclusions

In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.