bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the impact of SARS-CoV infection on the immunologic status and lung function after 15 years
Authors: Li Jia , Zheng Yali , Zhao Lili , Yue Zhihong , Pan Feng , Chen Yuehong , Yu Bing , Chen Yanwen , Zhao Guangyu , Zhou Yusen , Gao Zhancheng
Published: November 2021

Background

We investigate the long-term effects of SARS-CoV on patients’ lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003–2004.

Methods

We enrolled 58 healthcare workers from Peking University People’s Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera.

Results

After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25–75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05).

Conclusions

SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit.

Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018
The CKD bowel health study: understanding the bowel health and gastrointestinal symptom management in patients with chronic kidney disease: a mixed-methods observational longitudinal study (protocol)
Authors: Cooper Tess E. , Dalton Amy , Kieu Anh , Howell Martin , Jayanti Sumedh , Khalid Rabia , Lim Wai H. , Scholes-Robertson Nicole , Craig Jonathan C. , Teixeira-Pinto Armando , Bourke Michael J. , Tong Allison , Wong Germaine
Published: November 2021

Background

Gastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney transplants. Symptoms of GI intolerance (diarrhoea, constipation, bloating, abdominal pain, heart burn, and reflux) are associated with significant reduction in quality of life, morbidity, and increased used of healthcare resources. Having chronic kidney disease (CKD), together with related changes in diet and medication, may alter the gut microbiota and the microbial-derived uraemic metabolites that accumulate in kidney failure, and contribute to various complications including chronic diarrhoea, opportunistic infections, and drug-related colitis. Despite the high disease burden among patients with kidney replacement therapies, GI symptoms are often under-recognised and, consequently limited resources and strategies are devoted to the management of gastrointestinal complications in patients with CKD.

Methods

The CKD Bowel Health Study is a multi-centre mixed-methods observational longitudinal study to better understand the bowel health and GI symptom management in patients with CKD. The program comprises of a longitudinal study that will assess the burden and risk factors of GI intolerance in patients treated with maintenance dialysis; a semi-structured interview study that will describe experiences of GI intolerance (including symptoms, treatment, self-management) in transplant candidates and recipients; and a discrete choice experience to elicit patient preferences regarding their experiences and perspectives of various intervention strategies for the management of GI symptoms after kidney transplantation.

Discussion

This proposed program of work aims to define the burden the GI intolerance in patients with kidney failure and generate evidence on the patients’ experiences of GI intolerance and their perspectives on their clinical and own management strategies of these symptoms, ensuring a patient-centred approach to guide clinical decision making and to inform the best study design for intervention trials.

Trial registration

This study is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000548831. This study has been approved by the Western Sydney Local Health District Human Research Ethics Committee of New South Wales Health (HREC ETH03007). This study is supported by a National Health and Medical Research Council (NHMRC) Australia Investigator Grant (APP1195414), and an NHMRC Australia Postgraduate Scholarship (APP2005244).
Phase 1 trial of entinostat as monotherapy and combined with exemestane in Japanese patients with hormone receptor-positive advanced breast cancer
Authors: Masuda Norikazu , Tamura Kenji , Yasojima Hiroyuki , Shimomura Akihiko , Sawaki Masataka , Lee Min-Jung , Yuno Akira , Trepel Jane , Kimura Ryoko , Nishimura Yozo , Saji Shigehira , Iwata Hiroji
Published: November 2021

Background

Entinostat is an oral inhibitor of class I histone deacetylases intended for endocrine therapy-resistant patients with hormone receptor-positive (HR+) advanced or metastatic breast cancer (BC). We examined the safety, efficacy, and pharmacokinetics of entinostat monotherapy and combined entinostat/exemestane in Japanese patients.

Methods

This phase 1 study (3 + 3 dose-escalation design) enrolled postmenopausal women with advanced/metastatic HR+ BC previously treated with nonsteroidal aromatase inhibitors. Dose-limiting toxicities (DLTs) of entinostat monotherapy (3 mg/qw, 5 mg/qw, or 10 mg/q2w) and entinostat+exemestane (5 mg/qw + 25 mg/qd) were assessed. Pharmacokinetics, lysine acetylation (Ac-K), and T-cell activation markers were measured at multiple time points.

Results

Twelve patients were enrolled. No DLTs or grade 3–5 adverse events (AEs) occurred. Drug-related AEs (≥ 2 patients) during DLT observation were hypophosphatemia, nausea, and platelet count decreased. Six patients (50%) achieved stable disease (SD) for ≥ 6 months, including one treated for > 19 months. Median progression-free survival was 13.9 months (95% CI 1.9–not calculable); median overall survival was not reached. Area under the plasma concentration-time curve and Ac-K in peripheral blood CD19+ B cells increased dose-proportionally. The changing patterns of entinostat concentrations and Ac-K levels were well correlated. T-cell activation markers increased over time; CD69 increased more in patients with SD ≥ 6 months vs. SD < 6 months.

Conclusions

Entinostat monotherapy and combined entinostat/exemestane were well tolerated in Japanese patients, with no additional safety concerns compared with previous reports. The correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, and also T-cell activation markers, merits further investigation.

Trial registration

JAPIC Clinical Trial Information, JapicCTI-153066. Registered 12 November 2015. ClinicalTrials.gov, NCT02623751. Registered 8 December 2015.
Spatial determinants of excess all-cause mortality during the first wave of the COVID-19 epidemic in France
Authors: Pilkington Hugo , Feuillet Thierry , Rican Stéphane , Goupil de Bouillé Jeanne , Bouchaud Olivier , Cailhol Johann , Bihan Hélène , Lombrail Pierre , Julia Chantal
Published: November 2021

Background

The first wave of the COVID-19 pandemic in France was associated with high excess mortality, and anecdotal evidence pointed to differing excess mortality patterns depending on social and environmental determinants. In this study we aimed to investigate the spatial distribution of excess mortality during the first wave of the COVID-19 pandemic in France and relate it at the subnational level to contextual determinants from various dimensions (socioeconomic, population density, overall health status, healthcare access etc.). We also explored whether the determinants identified at the national level varied depending on geographical location.

Methods

We used available national data on deaths in France to calculate excess mortality by department for three age groups: 0–49, 50–74 and > 74 yrs. between March 1st and April 27th, 2020. We selected 15 variables at the department level that represent four dimensions that may be related to overall mortality at the ecological level, two representing population-level vulnerabilities (morbidity, social deprivation) and two representing environmental-level vulnerabilities (primary healthcare supply, urbanization). We modelled excess mortality by age group for our contextual variables at the department level. We conducted both a global (i.e., country-wide) analysis and a multiscale geographically weighted regression (MGWR) model to account for the spatial variations in excess mortality.

Results

In both age groups, excess all-cause mortality was significantly higher in departments where urbanization was higher (50–74 yrs.: β = 15.33,p < 0.001; > 74 yrs.: β = 18.24,p < 0.001) and the supply of primary healthcare providers lower (50–74 yrs.: β = − 8.10,p < 0.001; > 74 yrs.: β = − 8.27,p < 0.001). In the 50–74 yrs. age group, excess mortality was negatively associated with the supply of pharmacists (β = − 3.70,p < 0.02) and positively associated with work-related mobility (β = 4.62,p < 0.003); in the > 74 yrs. age group our measures of deprivation (β = 15.46,p < 0.05) and morbidity (β = 0.79,p < 0.008) were associated with excess mortality. Associations between excess mortality and contextual variables varied significantly across departments for both age groups.

Conclusions

Public health strategies aiming at mitigating the effects of future epidemics should consider all dimensions involved to develop efficient and locally tailored policies within the context of an evolving, socially and spatially complex situation.
Inferior vena cava interruption in renal cell carcinoma with tumor thrombus: surgical strategy and perioperative results
Authors: Liu Zhuo , Zhang Qiming , Zhao Xun , Zhu Guodong , Tang Shiying , Hong Peng , Ge Liyuan , Zhang Shudong , Wang Guoliang , Tian Xiaojun , Zhang Hongxian , Liu Cheng , Ma Lulin
Published: November 2021

Background

To analyze the influence of inferior vena cava (IVC) interruption for perioperative and oncological results in patients with renal cell carcinoma and tumor thrombus and summarize the surgical strategies of IVC interruption for different situations.

Methods

We retrospectively analyzed the clinical and pathological data of 103 patients in our center. Patients were divided into two groups with 32 cases (31.1%) underwent IVC interruption (Group 1) while 71 cases (68.9%) did not. For comparison of continuous variables, the Mann–Whitney U test was used. For comparison of categorical variables, Chi-square tests were used. A propensity score based matching method was used to eliminate possible bias. Kaplan–Meier plots were performed to evaluate the influence of IVC interruption on overall survival and cancer specific survival. All the statistical analyses were performed using SPSS 24. A P value < 0.05 was considered statistically significant.

Results

Among the 32 patients who underwent IVC interruption, the median age was 61 years and the median tumor size was 7.7 cm. There were 28 males and 23 tumors were on the right side. We successfully matched 29 patients who underwent IVC interruption to 29 patients without this procedure in 1:1 ratio. No significant differences existed in baseline characteristics between the groups. The comparison of perioperative data showed that patients who underwent IVC interruption had significantly longer median postoperative hospital stays (13 vs 9 days, P = 0.022) and a higher overall postoperative complication rate (79.3 vs 51.7%, P = 0.027). According to the side and shape of tumor thrombus, it could be divided into four categories. There were 15 cases (46.9%) with right filled-type tumor thrombus (RFTT), 8 cases (25.0%) with right non-filled-type tumor thrombus (RNFTT), 1 case (3.1%) with left filled-type tumor thrombus (LFTT) and 8 cases (25.0%) with left non-filled-type tumor thrombus (LNFTT). According to different categories, different surgical procedures were adopted.

Conclusions

IVC interruption will increase the incidence of overall postoperative complications, but not the risk of major postoperative complications. Tumor thrombus should be divided into four categories, and different sides and shapes of renal tumor thrombus need different operative procedure of IVC interruption.
Cultures that collide: an ethnographic study of the introduction of a palliative care consultation team on acute wards
Authors: Friedrichsen Maria , Hajradinovic Yvonne , Jakobsson Maria , Brachfeld Kerstin , Milberg Anna
Published: November 2021

Background

Acute care and palliative care (PC) are described as different incompatible organisational care cultures. Few studies have observed the actual meeting between these two cultures. In this paper we report part of ethnographic results from an intervention study where a palliative care consultation team (PCCT) used an integrative bedside education approach, trying to embed PC principles and interventions into daily practice in acute wards.

Purpose

To study the meeting and interaction of two different care cultures, palliative care and curative acute wards, when a PCCT introduces consulting services to acute wards regarding end-of-life palliative care, focusing on the differences between the cultures.

Methods

An ethnographic study design was used, including observations, interviews and diary entries. A PCCT visited acute care wards during 1 year. The analysis was inspired by Spradleys ethnography.

Results

Three themes were found: 1) Anticipations meets reality; 2) Valuation of time and prioritising; and 3) The content and creation of palliative care.

Conclusion

There are many differences in values, and the way PC are provided in the acute care wards compared to what a PCCT expects. The didactic challenges are many and the PC require effort.
Exploring socioeconomic inequities in access to palliative and end-of-life care in the UK: a narrative synthesis
Authors: French Maddy , Keegan Thomas , Anestis Eleftherios , Preston Nancy
Published: November 2021

Background

Efforts to tackle socioeconomic inequities in access to palliative and end-of-life care require comprehensive understanding about the extent of and reasons for inequities. Most research on this topic examines differences in receipt of care. There is a need, particularly in the UK, for theoretically driven research that considers both receipt of care and the wider factors influencing the relationship between socioeconomic position and access to palliative and end-of-life care.

Methods

This is a mixed studies narrative synthesis on socioeconomic position and access to palliative and end-of-life care in the UK. Study searches were conducted in databases AMED, Medline, Embase, CINAHL, SocIndex, and Academic Literature Search, as well as grey literature sources, in July 2020. The candidacy model of access, which describes access as a seven-stage negotiation between patients and providers, guided study searches and provided a theoretical lens through which data were synthesised.

Results

Searches retrieved 5303 studies (after de-duplication), 29 of which were included. The synthesis generated four overarching themes, within which concepts of candidacy were evident: identifying needs; taking action; local conditions; and receiving care.

Conclusion

There is not a consistent or clear narrative regarding the relationship between socioeconomic position and receipt of palliative and end-of-life care in the UK. Attempts to address any inequities in access will require knowledge and action across many different areas. Key evidence gaps in the UK literature concern the relationship between socioeconomic position, organisational context, and assessing need for care.
Factors associated with health-related quality of life in women using path analyses: mediation effect of the adiposity traits
Authors: Khodarahmi Mahdieh , Farhangi Mahdieh Abbasalizad , Khoshro Sahar , Dehghan Parvin
Published: November 2021

Background

The current work aimed to investigate the mediating role of adiposity traits in the relationship between eating behaviors, sleep quality, socio-demographic factors, and the health-related quality of life in women of reproductive age in northwest of Iran.

Methods

In the current cross-sectional study, a total of 278 overweight and obese women of reproductive age (20–49 y) were enrolled. Anthropometric assessments were performed. Pittsburgh sleep quality index (PSQI) was used for assessment of sleep quality while Short Form 36 (SF-36) questionnaire was used to measure health-related quality of life (HRQoL). Three-Factor Eating Questionnaire-R18 (TFEQ-R18) was used to measure eating behaviors. Path analysis was used to test the relationships between parameters.

Results

Age was found to be indirectly and negatively associated with mental component score (MCS) (B = − 0.040; P = 0.049) and physical component score (PCS) (B = − 0.065; P = 0.036) through mediatory effects of obesity. Additionally, education was seen to be indirectly and positively related to MCS (B = 0.529; P = 0.045) and PCS (B = 0.870; P = 0.019), respectively. On the other hand, obesity (B = 0.608; P = 0.018) and PSQI score (B = − 0.240; P = 0.034) had direct associations with MCS. Age (B = − 0.065; P = 0.036) and education (B = 0.870; P = 0.019) were also directly associated with obesity.

Conclusions

Obesity seemed to mediate the effects of socio-demographic parameters on HRQoL. Poor sleep quality was also related to impairment of HRQoL. Further studies are needed to confirm these results.
Influence of new coronavirus pandemic on behavior and awareness of young nurses and nursing students in Japan
Authors: Hasuike Mitsuto , Hara Yoshiaki , Mori Hiroko-Miyuki , Ideguchi Norio , Shirai Fumie , Yoshimura Yasuko , Murakami Ikumi , Kawahata Hirohisa , Aoki Motokuni , Ogihara Toshio
Published: November 2021

Background

Although mental health disorders of health care workers in the coronavirus disease 2019 (COVID-19) pandemic have been focused, little is known about the psychological impact on nurses and the influence on their behavior and awareness, such as professionalism and views on life and death, in Japan where there are fewer cases of infection and deaths than in other countries. Moreover, the influence of the pandemic on nursing students is still unclear.

Methods

An online questionnaire survey was conducted among nurses and nursing students. Feelings during the state of emergency (at the peak of the pandemic) in Japan, changes in behavior and awareness after the rise of COVID-19, and the associated factors influencing these changes were analyzed, comparing nurses with nursing students.

Results

Significantly increased scores of anxiety/fear (p < .005) and voluntary restraint (p < .005) and significantly decreased score of motivation (p < .005) were observed during the state of emergency in both nurses and students. Scores of experience of discrimination (p < .005) and consideration of premature retirement (p < .01) were significantly increased in nurses. Moreover, preventive behavior (p < .005), lifestyle (p < .005), anxiety about nursing (p < .005) and views on life and death (p < .005) significantly changed after the rise of COVID-19 in both nurses and students. Only nurses reported significant damage to their professionalism (p < .01). Anxiety/fear and/or voluntary restraint and/or decreased motivation during the state of emergency were major factors associated with these changes. Also, the type of hospital, experience of care of infected patients and sex affected some of the changes. Voluntary restraint (p = .008), increased preventive behavior (p = .021) and decreased motivation (p = .005) were more marked in nurses than in students, while change in views on life and death was greater in students than in nurses (p = .002).

Conclusion

The COVID-19 pandemic has had a psychological impact on nurses and nursing students, associated with changes in behavior and awareness even in Japan. Of note, the COVID-19 pandemic has affected nurses’ professionalism and views on life and death. This study demonstrates the importance of having a coping strategy for anxiety and damaged professionalism in nurses, and education on life and death in nursing students.
Factors associated with using the internet for medical information based on the doctor-patient trust model: a cross-sectional study
Authors: Fu Yang , Tang Tianwei , Long Junhao , Lin Bohuai , Li Jiayue , Quan Guohong , Yang Hanwen , Zhao Chongbang , Yin Mei , Shi Lei
Published: November 2021

Background

Internet medical care has been advancing steadily, especially during the coronavirus disease 2019 pandemic, the development momentum of Internet medical care in China is more vigorous. This study aimed to explore the factors associated with using the Internet for medical information, to examine the popularisation and implementation of Internet medical treatment and feasible strategies, and promote the further development of Internet medical treatment.

Methods

A cross-sectional study was conducted on 408 medical patients who had used online medical services. The one-way analysis of variance or independent samples t-test was used to compare the differences in the influence of demographic characteristics on behavioural intentions of different people seeking medical care. Pearson’s correlation was used to evaluate the correlation between different measurement variables. A mediation regression analysis was used to explore the mediating role of trust in Internet medical care.

Results

The difference in the influence of Internet medical use frequency on the behavioural intention of different participants was statistically significant (F = 3.311, P = 0.038). Among the influencing factors, personal trust propensity (r = 0.387, P < 0.01), website credibility (r = 0.662, P < 0.01), hospital credibility (r = 0.629, P < 0.01), doctor’s credibility (r = 0.746, P < 0.01), and online patient trust (r = 0.874, P < 0.01) were positively correlated with patients’ behavioural intentions. In the analysis of intermediary factors, the total effect of the credibility of the diagnosis and treatment website on the behavioural intention of patients was 0.344. The total effect of the credibility of the diagnosis and treatment hospital on the behavioural intention of patients was 0.312; the total effect of the service doctor’s credibility on the patient’s behavioural intention was 0.385; the total effect of the personal trust tendency on the patient’s behavioural intention was 0.296.

Conclusions

This study found defects in various factors that produce distrust in Internet medical treatment. It also reveals the positive effect of trust factors on the development and implementation of Internet medical treatment and provides some ideas for improving the use of Internet medical treatment by the masses.
Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis
Authors: Li Yumiao , Yu Xiaoxue , Zhang Yuhao , Wang Xiaofang , Zhao Linshan , Liu Dan , Zhao Guofa , Gao Xiangpeng , Fu Jiejun , Zang Aimin , Jia Youchao
Published: November 2021

Background

Lung adenocarcinoma (LUAD) is the most common subtype of nonsmall-cell lung cancer (NSCLC) and has a high incidence rate and mortality. The survival of LUAD patients has increased with the development of targeted therapeutics, but the prognosis of these patients is still poor. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. The purpose of this study was to identify novel abnormally regulated lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks that may suggest new therapeutic targets for LUAD or relate to LUAD prognosis.

Methods

We used the SBC human ceRNA array V1.0 to screen for differentially expressed (DE) lncRNAs and mRNAs in four paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database, and Kaplan–Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA–miRNA–mRNA ceRNA regulatory network. Then, quantitative real-time PCR (qRT-PCR) was used to validate the DE lncRNAs in 7 LUAD cell lines.

Results

A total of 2819 DE lncRNAs and 2396 DE mRNAs (P < 0.05 and fold change ≥ 2 or ≤ 0.5) were identified in four paired LUAD tissue samples. In total, 255 of the DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation, and were closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by qRT-PCR validation in 7 LUAD cell lines; however, only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P = 0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD.

Conclusion

ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 was associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results suggest new potential prognostic and therapeutic biomarkers for LUAD.
A systematic review of racial/ethnic and socioeconomic disparities in COVID-19
Authors: Khanijahani Ahmad , Iezadi Shabnam , Gholipour Kamal , Azami-Aghdash Saber , Naghibi Deniz
Published: November 2021

Background

Preliminary evidence from the COVID-19 pandemic shows the presence of health disparities, especially in terms of morbidity and mortality. This study aimed to systematically review the evidence on the association of racial/ethnic and socioeconomic status (SES) with health outcomes and access to healthcare services during the COVID-19 pandemic.

Methods

We retrieved published evidence from late December 2019 through March 1, 2021. The target population was the population of the countries during the COVID-19 pandemic. The exposures were defined as belonging to racial/ethnic minority groups and/or low SES. The primary outcomes of interest include (1) death from COVID-19, (2) COVID-19 incidence/infection, (3) COVID-19 hospitalization, (4) ICU admission, (5) need for mechanical ventilation, (6) confirmed diagnosis, and (7) access to testing. We systematically synthesized the findings from different studies and provided a narrative explanation of the results.

Results

After removing the duplicate results and screening for relevant titles and abstracts, 77 studies were selected for full-text review. Finally, 52 studies were included in the review. The majority of the studies were from the United States (37 studies). Despite the significant incongruity among the studies, most of them showed that racial/ethnic minority groups had higher risks of COVID-19 infection and hospitalization, confirmed diagnosis, and death. Additionally, most of the studies cited factors such as low level of education, poverty, poor housing conditions, low household income, speaking in a language other than the national language in a country, and living in overcrowded households as risk factors of COVID-19 incidence/infection, death, and confirmed diagnosis. However, findings in terms of the association of lack of health insurance coverage and unemployment with the outcome measures as well as the association of requiring mechanical ventilation, ICU admission, and access to testing for COVID-19 with race/ethnicity were limited and inconsistent.

Conclusion

It is evident that racial/ethnic minority groups and those from low SES are more vulnerable to COVID-19; therefore, public health policymakers, practitioners, and clinicians should be aware of these inequalities and strive to narrow the gap by focusing on vulnerable populations. This systematic review also revealed a major incongruity in the definition of the racial/ethnic minority groups and SES among the studies.

Systematic review registration

PROSPERO CRD42020190105.
Predictors of worsening TR severity after right ventricular lead placement: any added value by post-procedural fluoroscopy versus three –dimensional echocardiography?
Authors: Poorzand Hoorak , Tayyebi Mohammad , Hosseini Sara , Bakavoli Alireza Heidari , Keihanian Faeze , Jarahi Lida , Hamadanchi Ali
Published: November 2021

Background

The effect of right ventricular (RV) leads on tricuspid valve has been already raised concerns, especially in terms of prognostic implication. For such assessment, three-dimensional transthoracic echocardiography (3D-TTE) has been used previously but there was no data on the use of post-procedural fluoroscopy in the literature.

Methods

We prospectively enrolled 59 patients who underwent clinically indicated placement of pacemaker or implantable cardioverter defibrillator (ICD). Vena contracta (VC) and tricuspid regurgitation (TR) severity were measured using two-dimensional transthoracic echocardiography (2D-TTE) at baseline. Follow up 3D-TTE was performed 6 months after device implantation to assess TR severity and RV lead location.

Results

Lead placement position in TV was defined in 51 cases.TR VC was increased after the lead placement, compared to the baseline study (VC: 3.86 ± 2.32 vs 3.18 ± 2.39; p = 0.005), with one grade worsening in TR in 25.4% of cases. The mean changes in VC levels were 1.14 ± 0.67 mm. Among all investigated parameters, VC changes were predicted based on lead placement position only in 3D-TTE (p < 0.001) while the other variables including fluoroscopy parameters were not informative.

Conclusion

The RV Lead location examined by 3D-TTE seems to be a valuable parameter to predict the changes in the severity of the tricuspid regurgitation. Fluoroscopy findings did not improve the predictive performance, at least in short term follow up.
Gelatinase-sensitive nanoparticles loaded with photosensitizer and STAT3 inhibitor for cancer photothermal therapy and immunotherapy
Authors: Bu Lin-Lin , Wang Han-Qi , Pan Yuanwei , Chen Lei , Wu Hao , Wu Xianjia , Zhao Chenchen , Rao Lang , Liu Bing , Sun Zhi-Jun
Published: November 2021

Matrix metalloproteinase (MMP) 2 and 9 are the family members of proteases normally up-regulated in tumor to enhance the invasion and metastatic of tumor cells, and are associated with poor outcome of head and neck squamous cell carcinomas (HNSCCs). In the present work, MMPs-degradable gelatin nanoparticles (GNPs) are simultaneously loaded with photosensitizer indocyanine green (ICG) along with signal transducer activator of transcription 3 (STAT3) inhibitor NSC74859 (NSC, N) for efficient photothermal therapy (PTT) and immunotherapy of HNSCCs. In the tumor tissue, Gel-N-ICG nanoparticle was degraded and encapsulated ICG and NSC were effectively released. Under near-infrared (NIR) irradiation, the released ICG nanoparticles enabled effective photothermal destruction of tumors, and the STAT3 inhibitor NSC elicited potent antitumor immunity for enhanced cancer therapy. Based on two HNSCC mouse models, we demonstrated that Gel-N-ICG significantly delayed tumor growth without any appreciable body weight loss. Taken together, the strategy reported here may contribute that the stimuli-responsive proteases triggered nanoplatform could reduce tumor size more effectively in complex tumor microenvironment (TME) through combination of PTT and immunotherapy.

Graphical Abstract
Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612
Authors: Ge Lite , Xun Chengfeng , Li Wenshui , Jin Shengyu , Liu Zuo , Zhuo Yi , Duan Da , Hu Zhiping , Chen Ping , Lu Ming
Published: November 2021

Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, the molecular mechanisms underlying hypoxic MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators of cell-to-cell communication and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of EVs from human hypoxic olfactory mucosa MSCs (OM-MSCs) on angiogenesis and its underlying mechanism. EVs were isolated from normoxic (N) OM-MSCs (N-EVs) and hypoxic (H) OM-MSCs (H-EVs) using differential centrifugation and identified by transmission electron microscopy and flow cytometry. In vitro and in vivo, both types of OM-MSC-EVs promoted the proliferation, migration, and angiogenic activities of human brain microvascular endothelial cells (HBMECs). In addition, angiogenesis-stimulatory activity in the H-EV group was significantly enhanced compared to the N-EV group. MicroRNA profiling revealed a higher abundance of miR-612 in H-EVs than in N-EVs, while miR-612 inactivation abolished the N-EV treatment benefit. To explore the roles of miR-612, overexpression and knock-down experiments were performed using a mimic and inhibitor or agomir and antagomir of miR-612. The miR-612 target genes were confirmed using the luciferase reporter assay. Gain- and loss-of-function studies allowed the validation of miR-612 (enriched in hypoxic OM-MSC-EVs) as a functional messenger that stimulates angiogenesis and represses the expression of TP53 by targeting its 3′-untranslated region. Further functional assays showed that hypoxic OM-MSC-EVs promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular endothelial growth factor (VEGF) signaling in HBMECs via the exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest that hypoxic OM-MSC-EVs may represent a promising strategy for ischemic disease by promoting angiogenesis via miR-612 transfer.

Graphical Abstract
Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics
Authors: Zhu Menglu , Shi Yi , Shan Yifan , Guo Junyan , Song Xuelong , Wu Yuhua , Wu Miaolian , Lu Yan , Chen Wei , Xu Xiaoling , Tang Longguang
Published: November 2021

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.

Graphical Abstract
Quality of life in patients with stable coronary artery disease submitted to percutaneous, surgical, and medical therapies: a cohort study
Authors: da Silveira Lucas Molinari Veloso , Almeida Adriana Silveira , Fuchs Felipe C. , Silva Aline Gonçalves , Lucca Marcelo Balbinot , Scopel Samuel , Fuchs Sandra C. , Fuchs Flávio D.
Published: November 2021

Background

Clinical, surgical, and percutaneous strategies similarly prevent major cardiovascular events in patients with stable coronary artery disease (CAD). The possibility that these strategies have differential effects on health-related quality of life (HRQoL) has been debated, particularly in patients treated outside clinical trials.

Methods

We assigned 454 patients diagnosed with CAD during an elective diagnostic coronary angiography to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical treatment (OMT), and followed them for an average of 5.2 ± 1.5 years. HRQoL was assessed using a validated Brazilian version of the 12-Item Short-Form Health Survey questionnaire. The association between therapeutic strategies and quality of life scores was tested using variance analysis and adjusted for confounders in a general linear model.

Results

There were no differences in the mental component summary scores in the follow-up evaluation by therapeutic strategies: 51.4, 53.7, and 52.3 for OMT, PCI, and CABG, respectively. Physical component summary scores were higher in the PCI group than the CABG and OMT groups (46.4 vs. 42.9 and 43.8, respectively); however, these differences were no longer different after adjustment for confounding variables.

Conclusion

In a long-term follow-up of patients with stable CAD, HRQoL did not differ in patients treated by medical, percutaneous, or surgical treatments.
Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group’s analysis
Authors: Graziosi Luigina , Marino Elisabetta , Bencivenga Maria , D’Ignazio Alessia , Solaini Leonardo , Ministrini Silvia , Caprioli Michela , Sacco Michele , Marrelli Daniele , Mura Gianni , Degiuli Maurizio , Morgagni Paolo , Tiberio Guido Alberto Massimo , De Manzoni Giovanni , Roviello Franco , Donini Annibale
Published: November 2021

Background

The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.

Methods

It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.

Results

Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.

Conclusion

The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review
Authors: Li Hong-Bo , Yang Zi-Han , Guo Qing-Qu
Published: November 2021

Pancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting.
High efficiency closed-system gene transfer using automated spinoculation
Authors: Remley Victoria Ann , Jin Jianjian , Sarkar Sarmila , Moses Larry , Prochazkova Michaela , Cai Yihua , Shao Lipei , Liu Hui , Fuksenko Tatyana , Jin Ping , Stroncek David F. , Highfill Steven L.
Published: November 2021

Background

Gene transfer is an important tool for cellular therapies. Lentiviral vectors are most effectively transferred into lymphocytes or hematopoietic progenitor cells using spinoculation. To enable cGMP (current Good Manufacturing Practice)-compliant cell therapy production, we developed and compared a closed-system spinoculation method that uses cell culture bags, and an automated closed system spinoculation method to decrease technician hands on time and reduce the likelihood for microbial contamination.

Methods

Sepax spinoculation, bag spinoculation, and static bag transduction without spinoculation were compared for lentiviral gene transfer in lymphocytes collected by apheresis. The lymphocytes were transduced once and cultured for 9 days. The lentiviral vectors tested encoded a CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR), a FGFR4-CAR, or a CD22-CAR. Sepax spinoculation times were evaluated by testing against bag spinoculation and static transduction to optimize the Sepax spin time. The Sepax spinoculation was then used to test the transduction of different CAR vectors. The performance of the process using healthy donor and a patient sample was evaluated. Functional assessment was performed of the CD19/22 and CD22 CAR T-cells using killing assays against the NALM6 tumor cell line and cytokine secretion analysis. Finally, gene expression of the transduced T-cells was examined to determine if there were any major changes that may have occurred as a result of the spinoculation process.

Results

The process of spinoculation lead to significant enhancement in gene transfer. Sepax spinoculation using a 1-h spin time showed comparable transduction efficiency to the bag spinoculation, and much greater than the static bag transduction method (83.4%, 72.8%, 35.7% n = 3). The performance of three different methods were consistent for all lentiviral vectors tested and no significant difference was observed when using starting cells from healthy donor versus a patient sample. Sepax spinoculation does not affect the function of the CAR T-cells against tumor cells, as these cells appeared to kill target cells equally well. Spinoculation also does not appear to affect gene expression patterns that are necessary for imparting function on the cell.

Conclusions

Closed system-bag spinoculation resulted in more efficient lymphocyte gene transfer than standard bag transductions without spinoculation. This method is effective for both retroviral and lentiviral vector gene transfer in lymphocytes and may be a feasible approach for gene transfer into other cell types including hematopoietic and myeloid progenitors. Sepax spinoculation further improved upon the process by offering an automated, closed system approach that significantly decreased hands-on time while also decreasing the risk of culture bag tears and microbial contamination.
Going digital: added value of electronic data collection in 2018 Afghanistan Health Survey
Authors: Mergenthaler Christina , Yadav Rajpal Singh , Safi Sohrab , Rood Ente , Alba Sandra
Published: November 2021

Background

Through a nationally representative household survey in Afghanistan, we conducted an operational study in two relatively secure provinces comparing effectiveness of computer-aided personal interviewing (CAPI) with paper-and-pencil interviewing (PAPI).

Methods

In Panjshir and Parwan provinces, household survey data were collected using paper questionnaires in 15 clusters, and OpenDataKit (ODK) software on electronic tablets in 15 other clusters. Added value was evaluated from three perspectives: efficient implementation, data quality, and acceptability. Efficiency was measured through financial expenditures and time stamped data. Data quality was measured by examining completeness. Acceptability was studied through focus group discussions with survey staff.

Results

Survey costs were 68% more expensive in CAPI clusters compared to PAPI clusters, due primarily to the upfront one-time investment for survey programming. Enumerators spent significantly less time administering surveys in CAPI cluster households (248 min survey time) compared to PAPI (289 min), for an average savings of 41 min per household (95% CI 25–55). CAPI offered a savings of 87 days for data management over PAPI.

Among 49 tracer variables (meaning responses were required from all respondents), small differences were observed between PAPI and CAPI. 2.2% of the cleaned dataset’s tracer data points were missing in CAPI surveys (1216/ 56,073 data points), compared to 3.2% in PAPI surveys (1953/ 60,675 data points). In pre-cleaned datasets, 3.9% of tracer data points were missing in CAPI surveys (2151/ 55,092 data points) compared to 3.2% in PAPI surveys (1924/ 60,113 data points).

Enumerators from Panjsher and Parwan preferred CAPI over PAPI due to time savings, user-friendliness, improved data security, and less conspicuity when traveling; however approximately half of enumerators trained from all 34 provinces reported feeling unsafe due to Taliban presence. Community and household respondent skepticism could be resolved by enumerator reassurance. Enumerators shared that in the future, they prefer collecting data using CAPI when possible.

Conclusions

CAPI offers clear gains in efficiency over PAPI for data collection and management time, although costs are relatively comparable even without the programming investment. However, serious field staff concerns around Taliban threats and general insecurity mean that CAPI should only be conducted in relatively secure areas.