bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Swedish physicians’ attitudes towards physician-assisted suicide: a cross-sectional study
Authors: Lynøe Niels , Lindblad Anna , Engström Ingemar , Sandlund Mikael , Juth Niklas
Published: July 2021

Aims

To examine attitudes towards physician-assisted suicide (PAS) among physicians in Sweden and compare these with the results from a similar cross-sectional study performed in 2007.

Participants

A random selection of 250 physicians from each of six specialties (general practice, geriatrics, internal medicine, oncology, surgery and psychiatry) and all 127 palliative care physicians in Sweden were invited to participate in this study.

Setting

A postal questionnaire commissioned by the Swedish Medical Society in collaboration with Karolinska Institute in Stockholm.

Results

The total response rate was 59.2%. Slightly fewer than half [47.1% (95% CI 43.7–50.5)] of the respondents from the six specialties accepted PAS, which is significantly more than accepted PAS in the 2007 study [34.9% (95% CI 31.5–38.3)]. Thirty-three percent of respondents were prepared to prescribe the needed drugs. When asked what would happen to the respondent’s own trust in healthcare, a majority [67.1% (95% CI 63.9–70.3)] stated that legalizing PAS would either not influence their own trust in healthcare, or that their trust would increase. This number is an increase compared to the 2007 survey, when just over half [51.9% (95% CI 48.0–55.2)] indicated that their own trust would either not be influenced, or would increase.

Conclusions

The study reveals a shift towards a more accepting attitude concerning PAS among physicians in Sweden. Only a minority of the respondents stated that they were against PAS, and a considerable proportion reported being prepared to prescribe the needed drugs for patient self-administration if PAS were legalized.
Perspective of potential patients on the hospital volume-outcome relationship and the minimum volume threshold for total knee arthroplasty: a qualitative focus group and interview study
Authors: Kugler Charlotte M. , De Santis Karina K. , Rombey Tanja , Goossen Kaethe , Breuing Jessica , Könsgen Nadja , Mathes Tim , Hess Simone , Burchard René , Pieper Dawid
Published: July 2021

Background

Total knee arthroplasty (TKA) is performed to treat end-stage knee osteoarthritis. In Germany, a minimum volume threshold of 50 TKAs/hospital/year was implemented to ensure outcome quality. This study, embedded within a systematic review, aimed to investigate the perspectives of potential TKA patients on the hospital volume-outcome relationship for TKA (higher volumes associated with better outcomes).

Methods

A convenience sample of adults with knee problems and heterogeneous demographic characteristics participated in the study. Qualitative data were collected during a focus group prior to the systematic review (n = 5) and during telephone interviews, in which preliminary results of the systematic review were discussed (n = 16). The data were synthesised using content analysis.

Results

All participants (n = 21) believed that a hospital volume-outcome relationship exists for TKA while recognising that patient behaviour or the surgeon could also influence outcomes. All participants would be willing to travel longer for better outcomes. Most interviewees would choose a hospital for TKA depending on reputation, recommendations, and service quality. However, some would also choose a hospital based on the results of the systematic review that showed slightly lower mortality/revision rates at higher-volume hospitals. Half of the interviewees supported raising the minimum volume threshold even if this were to increase travel time to receive TKA.

Conclusions

Potential patients believe that a hospital volume-outcome relationship exists for TKA. Hospital preference is based mainly on subjective factors, although some potential patients would consider scientific evidence when making their choice. Policy makers and physicians should consider the patient perspectives when deciding on minimum volume thresholds or recommending hospitals for TKA, respectively.
Who are the beneficiaries and what are the reasons for non-utilization of care respite and support services? A cross-sectional study on family caregivers
Authors: Huang Jianan , Münzel Nadja , Scheel-Sailer Anke , Gemperli Armin
Published: July 2021

Background

Family caregivers assume substantial caregiving responsibilities for persons with chronic conditions, such as individuals with spinal cord injury, which leads to negative impacts on their lives. Respite care and other services are provided as a temporary relief and support for them. Design of appropriate respite care programs depends on identification of beneficiary subgroups for the different types of service. This study aimed to quantify the uptake of different respite and support services for family caregivers, the reasons for non-use, and to explore the respective predictors.

Methods

A cross-sectional survey of family caregivers of persons with spinal cord injury was conducted nationwide in Switzerland. The use of 11 different respite and support services during the previous 12 months was investigated, along with caregivers’ reasons for not using any respite. Classification trees were used to characterize the beneficiaries and reasons for not using respite.

Results

About a third of family caregivers used at least one type of respite or support service during the previous 12 months. Utilization of respite care was greater among those who employed professional home care (57% vs 24% of those without professional home care). Marked cantonal differences were also observed in utilization of respite care. The primary reason for not using respite services was “no demand” (80% of non-users of respite services), mainly among caregivers who were less emotionally affected by their caregiving tasks.

Conclusions

Utilization of respite and support services depends more on place of residence and use of home care services than on functional status of the care recipient. Accordingly, programs should be tailored to the cultural context of their potential users. This is best achieved through coordination with local health care professionals who can identify needs, provide information, initiate referrals, and integrate the care into a larger support plan.
A qualitative study on professionals’ attitudes and views towards the introduction of patient reported measures into public maternity care pathway
Authors: Chen An , Väyrynen Kirsi , Leskelä Riikka-Leena , Heinonen Seppo , Lillrank Paul , Tekay Aydin , Torkki Paulus
Published: July 2021

Background

The importance and potential benefits of introducing patient reported measures (PRMs) into health care service have been widely acknowledged, yet the experience regarding their implementation into practice is limited. There is a considerable paucity of research in adopting PRMs in maternity care routine. This study, which utilizes the PRMs included in Pregnancy and Childbirth (PCB) outcome set developed by International Consortium for Health Outcomes Measurement (ICHOM) as sample measures, aims to elicit Finnish professionals’ views on PRMs and to explore the applicability of PRMs in Finnish public maternity care.

Methods

This qualitative study, applying semi-structured interviews, described the local professionals’ views towards the application of PRMs in Finnish public maternity care. Professionals were asked to assess the PRMs defined in ICHOM PCB set and provide their expectations and concerns on the implementation of PRMs in Finnish public maternity service.

Results

Twenty professionals participated in the interviews. Participants agreed on the importance and relevance of the PRMs questions included in ICHOM PCB set for delivering and developing maternity care in Finland. However, they criticized the number and length of questions as well as the recommended time points of data collection. In addition, for a successful implementation, various steps like developing suitable questions, redesigning service pathway and protocols, and motivating women to respond to PRMs questions were considered to be important. Also, some potential obstacles, difficulties and risks associated with the implementation were underlined.

Conclusion

This study indicates that the implementation of PRMs into Finnish public maternity service is possible, highly relevant and important. However, the adoption of PRMs into routine practice may be challenging and will require a series of efforts. This study shows viewpoints from Finnish professionals who have not participated in developing the ICHOM PCB standard set and provides important insights on the development and implementation of PRMs.
Early response of methanogenic archaea to H2 as evaluated by metagenomics and metatranscriptomics
Authors: Kakuk Balázs , Wirth Roland , Maróti Gergely , Szuhaj Márk , Rakhely Gábor , Laczi Krisztián , Kovács Kornél L. , Bagi Zoltán
Published: July 2021

Background

The molecular machinery of the complex microbiological cell factory of biomethane production is not fully understood. One of the process control elements is the regulatory role of hydrogen (H2). Reduction of carbon dioxide (CO2) by H2 is rate limiting factor in methanogenesis, but the community intends to keep H2 concentration low in order to maintain the redox balance of the overall system. H2 metabolism in methanogens becomes increasingly important in the Power-to-Gas renewable energy conversion and storage technologies.

Results

The early response of the mixed mesophilic microbial community to H2 gas injection was investigated with the goal of uncovering the first responses of the microbial community in the CH4 formation and CO2 mitigation Power-to-Gas process. The overall microbial composition changes, following a 10 min excessive bubbling of H2 through the reactor, was investigated via metagenome and metatranscriptome sequencing. The overall composition and taxonomic abundance of the biogas producing anaerobic community did not change appreciably 2 hours after the H2 treatment, indicating that this time period was too short to display differences in the proliferation of the members of the microbial community. There was, however, a substantial increase in the expression of genes related to hydrogenotrophic methanogenesis of certain groups of Archaea. As an early response to H2 exposure the activity of the hydrogenotrophic methanogenesis in the genus Methanoculleus was upregulated but the hydrogenotrophic pathway in genus Methanosarcina was downregulated. The RT-qPCR data corroborated the metatranscriptomic

Results

H2 injection also altered the metabolism of a number of microbes belonging in the kingdom Bacteria. Many Bacteria possess the enzyme sets for the Wood-Ljungdahl pathway. These and the homoacetogens are partners for syntrophic community interactions between the distinct kingdoms of Archaea and Bacteria.

Conclusions

External H2 regulates the functional activity of certain Bacteria and Archaea. The syntrophic cross-kingdom interactions in H2 metabolism are important for the efficient operation of the Power-to-Gas process. Therefore, mixed communities are recommended for the large scale Power-to-Gas process rather than single hydrogenotrophic methanogen strains. Fast and reproducible response from the microbial community can be exploited in turn-off and turn-on of the Power-to-Gas microbial cell factories.
A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer
Authors: Liu Lei , Pang Honglin , He Qiao , Pan Biran , Sun Xiaobin , Shan Jing , Wu Liping , Wu Kaiwen , Yao Xue , Guo Yuanbiao
Published: July 2021

Background

Gastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. The aim of the present study was to screen candidate biomarkers associated with the pathogenesis and prognosis of GC by a novel strategy.

Methods

The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as “positive”, and the top 5% genes with “positive rate” were filtered out as candidate diagnostic biomarkers in three Gene Expression Omnibus (GEO) datasets. Further, a prognostic risk model was constructed by multivariate Cox regression analysis in GEO dataset and validated in The Cancer Genome Atlas (TCGA). The expression level of candidate biomarkers was determined in serum and serum-derived exosomes of GC patients. Moreover, the effect of biomarkers in exosomes on migration of GC cells was analyzed by transwell assay.

Results

Ten candidate biomarkers (AGT, SERPINH1, WNT2, LIPG, PLAU, COL1A1, MMP7, MXRA5, CXCL1 and COL11A1) were identified with efficient diagnostic value in GC. A prognostic gene signature consisted of AGT, SERPINH1 and MMP7 was constructed and showed a good performance in predicting overall survivals in TCGA. Consistently, serum levels of the three biomarkers also showed high sensitivity and specificity in distinguishing GC patients from controls. In addition, the expression level of the three biomarkers were associated with malignant degree and decreased after surgery in GC patients. Moreover, the expression level of AGT and MMP7 in exosomes correlated positively with serum level. The exosomes derived from serum of GC patients can promote migration of SGC‐7901 cells. After neutralized the expression level of three proteins in exosomes with antibodies, the migration of GC cells was obviously suppressed.

Conclusions

Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that the three-gene signature was a candidate diagnostic and prognostic biomarker for patients with GC.
Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis
Authors: Guan Huapeng , Xu Hao , Chen Jinshui , Wu Weishan , Chen Dongfeng , Chen Yungang , Sun Jianzhong
Published: July 2021

Background

Osteosarcoma (OS) is a common type of bone malignancy that often occurs in children and adolescents. Chemoresistance is a huge barrier to cancer therapy. This study aimed to investigate the role and potential mechanism of circ_0001721 in doxorubicin (DXR) resistance and OS development.

Methods

The levels of circ_0001721, miR-758 and transcription factor 4 (TCF4) were detected by quantitative real-time polymerase chain reaction or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to calculate the half inhibition concentration (IC50) of DXR and assess cell viability. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was monitored by flow cytometry. The levels of multidrug resistance-related and Wnt/β-catenin pathway-related proteins were measured by western blot assay. The interaction among circ_0001721, miR-758 and TCF4 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. The xenograft model was established to analyze tumor growth in vivo.

Results

Circ_0001721 and TCF4 were upregulated, whereas miR-758 was down-regulated in DXR-resistant OS tissues and cells. Circ_0001721 silence reduced DXR resistance of KHOS/DXR and MG63/DXR cells. Circ_0001721 regulated DXR resistance via sponging miR-758. Moreover, miR-758 modulated DXR resistance by targeting TCF4. Besides, circ_0001721 knockdown inhibited tumor growth in vivo.

Conclusion

Circ_0001721 potentiated DXR resistance and facilitated the progression of OS by regulating miR-758/TCF4 axis, which provides promising therapeutic targets for OS treatment.
DNA double-strand break repair gene mutation and the risk of papillary thyroid microcarcinoma: a case–control study
Authors: Qin Jiali , Fan Jie , Li Gang , Liu Shanting , Liu Zhensheng , Wu Yao
Published: July 2021

Objective

To study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC).

Methods

One hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student’s t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC.

Results

The DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P < 0.05). Multivariate logistic regression analysis of age, sex, obesity status, radiation and other factors showed that radiation exposure was positively correlated with reduced DSB repair capacity(OR = 3.642; 95% CI 1.484–8.935, P = 0.020). Moreover, univariate analysis showed that a reduction in DSB repair capacity was a risk factor for PTMC(OR = 2.333; 95% CI 1.027–5.300, P = 0.043).Targeted next-generation DNA sequencing was performed on the DSB repair genes discovered, and those that were mutated in association with PTMC were Rad50 and FANCA; Rad51 mutations were related to BTN.

Conclusion

Radiation exposure is positively associated with induced DSB repair gene mutations, which may cause a reduced capacity for DSB repair and eventually lead to PTMC.
Fatty acid oxidation: driver of lymph node metastasis
Authors: Li Mao , Xian Hong-chun , Tang Ya-Jie , Liang Xin-hua , Tang Ya-ling
Published: July 2021

Fatty acid oxidation (FAO) is the emerging hallmark of cancer metabolism because certain tumor cells preferentially utilize fatty acids for energy. Lymph node metastasis, the most common way of tumor metastasis, is much indispensable for grasping tumor progression, formulating therapy measure and evaluating tumor prognosis. There is a plethora of studies showing different ways how tumor cells metastasize to the lymph nodes, but the role of FAO in lymph node metastasis remains largely unknown. Here, we summarize recent findings and update the current understanding that FAO may enable lymph node metastasis formation. Afterward, it will open innovative possibilities to present a distinct therapy of targeting FAO, the metabolic rewiring of cancer to terminal cancer patients.
Health and socio-demographic implications of the Covid-19 second pandemic wave in Israel, compared with the first wave
Authors: Birenbaum-Carmeli Daphna , Chassida Judith
Published: July 2021

Background

Israel’s containment of the first wave of Covid-19 was relatively successful. Soon afterwards, however, in the summer months, a harsher pandemic wave developed, resulting in many more seriously ill and dead Israelis. Israel was the world’s first country to impose a second general lockdown. The present study outlines the early months of Israel’s second pandemic wave, until the imposition of the second general lockdown, and their impact on various communities. The investigation is conducted in conjunction with five sociodemographic variables: population density, socioeconomic status, rate of elderly population, minority status (Jewish / Arab identity) and religiosity (Ultra-Orthodox vs. other Jewish communities).

Methods

The analysis is based on a cross sectional study of morbidity rates, investigated on a residential community basis. Following the descriptive statistics, we move on to present a multivariate analysis to explore associations between the five aforementioned sociodemographic variables and Covid-19 morbidity in Israel in the early second pandemic wave vs. the first Covid-19 outbreak.

Results

Both the descriptive statistics and regressions show morbidity rates to be significantly and positively associated with communities’ population density and significantly and negatively associated with socioeconomic status (SES) and the size of elderly population. These results differ from Wave I morbidity, which was not significantly associated with SES. Another difference vis-a-vis Wave I is the rise of morbidity in Arab communities that led to the disappearance of the previously observed significant negative association of morbidity with minority (Arab) status. Exceptional morbidity was found in Ultra-Orthodox Jewish communities.

Conclusion

The second wave of Covid-19 in Israel has profoundly affected marginalized communities characterized by high residential density, low SES and minority status. Other marginalized and disempowered communities have also been badly hit. While acknowledging the potential contribution of various possible causes, we highlight the policy response of Israel’s government during the early weeks of the second Covid-19 outbreak, suggesting that the severe second wave might possibly be associated with belated, undecided government response during this period.
RGD-modified multifunctional nanoparticles encapsulating salvianolic acid A for targeted treatment of choroidal neovascularization
Authors: Zhang Junxiu , Zhu Jingyi , Zhao Lingzhou , Mao Ke , Gu Qing , Li Dongli , Zhao Jinhua , Wu Xingwei
Published: July 2021

Background

The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4′-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA.

Results

We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by retinal pigment epithelium (RPE) cells which highly expressed ɑvβ5 integrin receptors in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confirmed the biocompatibility of RGD-PEI/SAA.

Conclusions

The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

Graphic abstract
Validation and reliability testing of the Breast-Q latissimus dorsi questionnaire: cross-cultural adaptation and psychometric properties in a Swedish population
Authors: Kamya Lynne , Hansson Emma , Weick Linn , Hansson Emma
Published: July 2021

Background

The main aim of post-mastectomy breast reconstruction is to improve the patient’s quality of life, which makes high-quality and validated patient-reported outcome measurements essential. None of the established instruments include evaluation of donor-site morbidity, such as impact on upper extremity and back function, when a latissimus dorsi (LD) muscle is used; and BREAST-Q LD questionnaire was therefore recently developed for this purpose. The aim of this study was to translate into Swedish and culturally adapt the BREAST-Q LD questionnaire’s two subscales, appearance and function, and perform a psychometric evaluation of the subscales in a Swedish population of patients.

Methods

This was a cross-sectional study. The questionnaire was translated according to established guidelines. The questionnaires were sent to all patients operated using an LD flap between 2007 and 2017. Internal consistency was assessed using Cronbach’s α. Inter-item correlations and corrected item-total correlations were calculated using the Pearson’s correlation coefficient. Convergent validity was evaluated by comparing the BREAST-Q LD questionnaire to the Western Ontario Osteoarthritis of the Shoulder Index, using the Spearman correlation coefficient. Test–retest reliability was tested with intraclass correlation coefficients (ICCs), and the coefficient of variation and Bland–Altman plots were drawn. Floor and ceiling effects were calculated. Known-group validation was tested by comparing scores from the patients and from normal controls using the Mann–Whitney U-test and by calculating eta squared effect size.

Results

The questionnaires were sent to 176 eligible patients and 125 responded (71%). The patients had been operated a mean of 6.6 years ago, and most (92%) had previous radiation. Internal consistency was satisfactory for both subscales. The correlation coefficients between questions were r > 0.30 for all items of both scales. The corrected item-total correlation coefficient ranged from 0.62 to 0.90. As hypothesised, the function scale was correlated with the WOOS “Physical symptoms” subscale. Reliability was adequate according to the ICCs. The ceiling effect threshold for the appearance scale was reached and that for the back scale was almost reached. There were significant differences between patients and controls, in the hypothesised direction.

Conclusions

The results of this study support a good internal consistency, convergent validity, test–retest reliability and known-group validation for the Swedish BREAST-Q LD questionnaire. However, it may be difficult to discriminate between patients with very mild and those with no symptoms using the appearance scale.

Trial registration: ClinicalTrials.Gov identifier NCT04526561.
Down-regulation of S100P induces apoptosis in endometrial epithelial cell during GnRH antagonist protocol
Authors: Zhang Dan , Han Mi , Zhou Mingjuan , Liu Mengyu , Li Yan , Xu Bufang , Zhang Aijun
Published: July 2021

Background

The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear.

Methods

Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis.

Results

Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishikawa cells induced apoptosis, decreased expression of Bcl-2, while overexpression of S100P caused the opposite effects and decreased expression of Bax. Furthermore, endometrial epithelial cells exposed to GnRH antagonist expressed lower levels of S100P and Bcl-2, increased expression of Bax, and had higher rates of apoptosis. The increased apoptosis induced by GnRH antagonist treatment could be rescued by overexpression of S100P.

Conclusions

We found that GnRH antagonist treatment induced endometrial epithelial cell apoptosis by down-regulating S100P, which was detrimental to endometrial receptivity. These results further define a mechanistic role for S100P in contributing to endometrial apoptosis during GnRH antagonist treatment, and suggest that S100P is a potential clinical target to improve the success of IVF using the GnRH antagonist protocol.
Effect of HSP90AB1 and CC domain interaction on Bcr-Abl protein cytoplasm localization and function in chronic myeloid leukemia cells
Authors: Peng Yuhang , Huang Zhenglan , Zhou Fangzhu , Wang Teng , Mou Ke , Feng Wenli
Published: July 2021

Background

The fusion oncoprotein Bcr-Abl is mostly located in the cytoplasm, which causes chronic myeloid leukemia (CML). After moving into the nucleus, the fusion protein can induce apoptosis of CML cells. The coiled-coil domain (CC domain) of Bcr-Abl protein plays a central role in the subcellular localization. However, how CC domain affects subcellular localization of Bcr-Abl remains unclear.

Methods

Herein, the key proteins interacting with the Bcr-Abl CC domain were screened by immunoprecipitation binding mass spectrometry. The specific site of Bcr-Abl CC domain binding to target protein was predicted by Deep Viewer. Immunoprecipitation assay was used to confirmed the specific sites of protein binding. IF and western blot were used to observe the subcellular localization of target protein. Western blot was used to examine the protein changes. CCK-8, clonal formation test and FCM cycle detection were used to observe the effect of inhibitor on the proliferation ability of CML cells. FCM apoptosis detection was used to observe the level of cells apoptosis.

Results

HSP90AB1 interacts with Bcr-Abl CC domain via N-terminal domain (NTD), preventing the transport of Bcr-Abl protein to the nucleus and maintaining the activation of Bcr-Abl tyrosine kinase. The nucleus-entrapped Bcr-Abl markedly inhibits the proliferation and induces apoptosis of CML cells by activating p73 and repressing the expression of cytoplasmic oncogenic signaling pathways mediated by Bcr-Abl. Moreover, the combination of 17AAG (Tanespimycin) with Leptomycin B (LMB) considerably decreased the proliferation of CML cells.

Conclusion

Our study provides evidence that it is feasible to transport Bcr-Abl into the nucleus as an alternative strategy for the treatment of CML, and targeting the NTD of HSP90AB1 to inhibit the interaction with Bcr-Abl is more accurate for the development and application of HSP90 inhibitor in the treatment of CML and other Bcr-Abl-addicted malignancies.
Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial
Authors: Fukui Saori , Seki Mitsuru , Minami Takaomi , Kotani Kazuhiko , Oka Kensuke , Yokomizo Akiko , Matsubara Daisuke , Sato Tomoyuki , Nozaki Yasuyuki , Saito Mari , Kikuchi Yutaka , Miyamoto Kenji , Monden Yukifumi , Yamagata Takanori
Published: July 2021

Background

High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds.

Methods

This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration.

Results

A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01).

Conclusion

The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed).

Trial registration

University Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058
Return to pregnancy after contraceptive discontinuation to become pregnant: a pooled analysis of West and East African populations
Authors: Barden-O’Fallon Janine , Speizer Ilene S. , Calhoun Lisa M. , Moumouni Nouhou Abdoul
Published: July 2021

Background

The fear of infertility or delayed return to fertility is a common barrier to contraceptive use in sub-Saharan Africa, particularly among young or nulliparous women. Global evidence on return to pregnancy after method discontinuation suggests these fears may be misplaced; yet the topic has not been widely studied in sub-Saharan Africa nor by age and parity group.

Methods

Reproductive calendar data from recent Demographic and Health Surveys of 15 sub-Saharan African countries were used to analyze time-to-pregnancy following discontinuation of a contraceptive method with the reason to become pregnant. The probability of pregnancy at 12 months was estimated using single-decrement life tables run by type of method discontinued, age and parity. Results are presented by region: francophone West Africa, anglophone West Africa and East Africa.

Results

The 12-month probability of pregnancy after discontinuation of contraception to become pregnant was 73.0% in francophone West Africa, 78.8% in anglophone West Africa, and 82.0% in East Africa. Our results showed significant regional differences in return to pregnancy by 12 months, with probabilities in francophone West Africa being significantly lower than in anglophone West Africa or East Africa. A lower return to pregnancy by 12 months was seen among women ages 35–49 years and was lowest after discontinuation of a hormonal method for all age groups. Differences by parity group were only evident after discontinuation of hormonal methods in francophone West Africa.

Conclusions

Sustainable gains in increasing contraceptive uptake, especially among youth, may be difficult to achieve without information and counseling that address concerns about infertility and potential delays in return to pregnancy following use of hormonal methods.
Effect on breastfeeding practices of providing in-home lactation support to vulnerable women through the Canada Prenatal Nutrition Program: protocol for a pre/post intervention study
Authors: Mildon Alison , Francis Jane , Stewart Stacia , Underhill Bronwyn , Ng Yi Man , Richards Elle , Rousseau Christina , Di Ruggiero Erica , Dennis Cindy-Lee , O’Connor Deborah L. , Sellen Daniel W.
Published: July 2021

Background

Only one-third of Canadian infants are exclusively breastfed for the first 6 months of life as recommended. Skilled lactation support in the early postpartum period is one strategy for improving breastfeeding outcomes by building breastfeeding self-efficacy and resolving difficulties. Access to such support is limited among vulnerable women, including those who are new immigrants, low income, under-educated, young or single. The Canada Prenatal Nutrition Program (CPNP) aims to improve birth and breastfeeding outcomes among vulnerable women, but currently lacks a formal framework for providing postpartum lactation support.

Methods

This pre/post intervention study will examine the effect on breastfeeding outcomes of an evidence-based in-home lactation support intervention provided through the CPNP. We will enrol 210 pregnant women who intend to breastfeed and are registered CPNP clients at two sites in Toronto, Canada. During the intervention phase, postpartum home visits by International Board Certified Lactation Consultants (IBCLCs) will be pro-actively offered to registered clients of the two sites. Double-electric breast pumps will also be provided to those who meet specific criteria. Infant feeding data will be collected prospectively at seven time points from 2 weeks to 6 months postpartum. Descriptive and regression analyses will be conducted to measure intervention effects. The primary outcome is exclusive breastfeeding at 4 months postpartum. Secondary outcomes include the duration of any and exclusive breastfeeding, timing of introduction of breastmilk substitutes and timing of introduction of solid foods. Breastfeeding self-efficacy will be assessed prenatally and at 2 weeks and 2 months postpartum. Other measures include maternal socio-demographics, infant feeding intentions, maternal depression and anxiety, and household food insecurity. Monitoring data will be used to assess the reach, uptake and fidelity of intervention delivery.

Discussion

Increasing access to skilled lactation support through the CPNP may be an effective means of improving breastfeeding practices among vulnerable women and thereby enhancing health and development outcomes for their infants. This pre/post intervention study will contribute evidence on both the effectiveness and feasibility of this approach, in order to guide the development and further testing of appropriate models of integrating lactation support into the CPNP.

Trial registration

ClinicalTrials.gov(NCT03589963) registered July 18, 2018.
Trends in breastfeeding practices and mothers’ experience in the French NutriNet-Santé cohort
Authors: Courtois Frédéric , Péneau Sandrine , Salanave Benoît , Andreeva Valentina A. , Roland-Cachera Marie Françoise , Touvier Mathilde , Galan Pilar , Hercberg Serge , Fezeu Léopold K.
Published: July 2021

Background

France has one of the lowest rates in the world regarding breastfeeding initiation and duration. Few studies have explored breastfeeding practices in France since the middle of the twentieth century, or following from initiation to cessation. The purpose of our study was to determine trends in breastfeeding over the past decades regarding public health recommendations, and to examine mothers’ perceptions about factors known to have an impact on breastfeeding support and cessation.

Methods

From the NutriNet-Santé cohort, 29,953 parous women (launched in 2009 to study relation between nutrition and health), were included in the present study. Using web-questionnaires, they were asked retrospectively if they had breastfed their youngest child or not, and if so, the duration of exclusive and total breastfeeding. For those who had breastfed, we investigated their perceptions about support at initiation and during the entire breastfeeding period and reasons for breastfeeding cessation. We also asked those who did not breastfeed about their perceptions and reasons for infant formula feeding their youngest child. Analyses were weighted according to the French census data.

Results

In the NutriNet-Santé cohort, 67.3% of mothers breastfed their youngest child. The proportion of breastfed children increased over the past few decades, from 55.0% (95% CI 54.3, 55.6) in the 1970s to 82.9% (82.4, 83.4) in the 2010s. Total and exclusive breastfeeding duration went from 3.3 months and 2.4 months respectively in the 1970s to 5.9 months and 3.2 months respectively in the 2010s. Most mothers felt supported at initiation and during the breastfeeding period. A reported desire to have breastfed longer than two months was 59.5%. Mothers who did not breastfeed did it by choice (64.3%). They did not feel guilty (78.2%) and did not perceive a problem not to breastfeed (58.8%), but almost half of them would have liked to have breastfed (45.9%).

Conclusion

Breastfeeding duration has increased in the past decades but did not reach the public health recommendations threshold. Targets other than mothers have to be considered for breastfeeding education, like the partner and her environment, to increase breastfeeding practices.

Trial registration

The study was registered at ClinicalTrials.gov (NCT03335644).
Identification and validation of key long non-coding RNAs in resveratrol protect against IL-1β-treated chondrocytes via integrated bioinformatic analysis
Authors: Yi Hong , Zhang Wei , Cui Sheng-Yu , Fan Jian-Bo , Zhu Xin-Hui , Liu Wei
Published: July 2021

Background

Long non-coding RNAs (lncRNAs) participate in regulation of gene transcription, but little is known about the correlation among resveratrol and lncRNAs. This study aimed to identify and validate the key lncRNAs in resveratrol protect against IL-1β-treated chondrocytes.

Methods

In this experiment, high-throughput sequencing technique was performed to identify the differentially expressed lncRNAs, miRNAs, and mRNAs between IL-1β-treated chondrocytes with or not resveratrol. Moreover, gene ontology and KEGG pathway of the differentially expressed genes were carried out by R software. Then, lncRNA-miRNA-mRNA network was constructed by Cytoscape software. Venn diagram was performed to identify the potentially target miRNAs of LINC00654. Then, real-time polymerase chain reaction (RT-PCR) was performed to validate the most significantly differentially expressed lncRNAs.

Results

Totally, 1016 differentially expressed lncRNAs were identified (493 downregulated) between control and resveratrol-treated chondrocytes. Totally, 75 differentially expressed miRNAs were identified (downregulated = 54, upregulated = 21). Totally, 3308 differentially expressed miRNAs were identified (downregulated = 1715, upregulated = 1593). GO (up) were as follows: skin development, response to organophosphorus. GO (down) mainly included visual perception, single fertilization, and sensory perception of smell. KEGG (up) were as follows: TNF signaling pathway and TGF-beta signaling pathway. KEGG (down) were as follows: viral protein interaction with cytokine and cytokine receptor. We identified that LINC00654 and OGFRL1 were upregulated in resveratrol-treated chondrocytes. However, miR-210-5p was downregulated in resveratrol-treated chondrocytes.

Conclusion

In sum, the present study for the first time detected the differential expressed lncRNAs involved in resveratrol-treated chondrocytes via employing bioinformatic methods.
Biomechanical study of transsacral-transiliac screw fixation versus lumbopelvic fixation and bilateral triangular fixation for “H”- and “U”-type sacrum fractures with traumatic spondylopelvic dissociation: a finite element analysis study
Authors: Peng Ye , Zhang Gongzi , Zhang Shuwei , Ji Xinran , Li Junwei , Du Chengfei , Zhao Wen , Zhang Lihai
Published: July 2021

Objective

To compare the biomechanical stability of transsacral-transiliac screw fixation and lumbopelvic fixation for “H”- and “U”-type sacrum fractures with traumatic spondylopelvic dissociation.

Methods

Finite element models of “H”- and “U”-type sacrum fractures with traumatic spondylopelvic dissociation were created in this study. The models mimicked the standing position of a human. Fixation with transsacral-transiliac screw fixation, lumbopelvic fixation, and bilateral triangular fixation were simulated. Biomechanical tests of instability were performed, and the fracture gap displacement, anteflexion, rotation, and stress distribution after fixation were assessed.

Results

For H-type fractures, the three kinds of fixation ranked by stability were bilateral triangular fixation > lumbopelvic fixation > transsacral-transiliac screw fixation in the vertical and anteflexion directions, bilateral triangular fixation > transsacral-transiliac S1 and S2 screw fixation > lumbopelvic fixation in rotation. The largest displacements in the vertical, anteflexion, and rotational directions were 0.57234 mm, 0.37923 mm, and 0.13076 mm, respectively. For U-type fractures, these kinds of fixation ranked by stability were bilateral triangular fixation > lumbopelvic fixation > transsacral-transiliac S1 and S2 screw fixation > transsacral-transiliac S1 screw fixation in the vertical, anteflexion, and rotational directions. The largest displacements in the vertical, anteflexion, and rotational directions were 0.38296 mm, 0.33976 mm, and 0.05064 mm, respectively.

Conclusion

All these kinds of fixation met the mechanical criteria for clinical applications. The biomechanical analysis showed better bilateral balance with transsacral-transiliac screw fixation. The maximal displacement for these types of fixation was less than 1 mm. Percutaneous transsacral-transiliac screw fixation can be considered the best option among these kinds of fracture fixation.
Economic burden and health-related quality of life in tenosynovial giant-cell tumour patients in Europe: an observational disease registry
Authors: Lopez-Bastida J. , Aranda-Reneo I. , Rodríguez-Sánchez B. , Peña-Longobardo L. M. , Ye X. , Laeis P. , Fronk E. M. , Palmerini E. , Leithner A. , Van de Sande M. A. J.
Published: July 2021

Background

Tenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden—from a societal perspective—associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries.

Methods

This article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients’ health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up.

Results

146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up.

Conclusion

The results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required—in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.