bluuebunny/crossref_metadata_2025 huggingface dataset:
Burdens on caregivers of patients with stroke during a pandemic: relationships with support satisfaction, psychological distress, and fear of COVID-19
Authors: Liu Chieh-hsiu , Chen Yi-Jung , Chen Jung-Sheng , Fan Chia-Wei , Hsieh Meng-Tsang , Lin Chung-Ying , Pakpour Amir H.
Published: December 2022

Background

Caregivers have faced unprecedented circumstances throughout the COVID-19 pandemic, but previous research only minimally addresses the caregivers' burden. Therefore, this study aimed to investigate the relationship between caregiver burden, psychological stress, satisfaction with support, and fear of COVID-19 in caregivers of patients with stroke during the pandemic.

Methods

A cross-sectional survey study with total of 171 caregivers of patients with stroke in a community hospital in Taiwan. All participants completed the Zarit Burden Interview, Depression, Anxiety, Stress Scale (DASS-21), satisfaction of support survey, and Fear of COVID-19 Scale. Pearson correlations were used to examine the bivariate correlations between study variables. Then, with the control of demographic confounders, a multiple linear regression model was applied with significant variables to construct and explain caregiver burden.

Results

The proposed model significantly explained the caregiver burden of caregivers of patients with stroke. Specifically, the caregiver burden was negatively correlated with satisfaction with family support, but positively with psychological distress and the fear of COVID-19.

Conclusions

Caregivers of patients with stroke will suffer a greater burden if they have lower satisfaction with family support, experienced higher psychological distress, and perceived more fear of the COVID-19 pandemic. Health professionals must address these concerns, support caregivers, and enhance available resources.
Classifying caesarean section to understand rising rates among Palestinian refugees: results from 290,047 electronic medical records across five settings
Authors: Jamaluddine Zeina , Paolucci Gloria , Ballout Ghada , Al-Fudoli Hussam , Day Louise T. , Seita Akihiro , Campbell Oona M. R.
Published: December 2022

Background

Rising caesarean-section rates worldwide are driven by non-medically indicated caesarean-sections. A systematic review concluded that the ten-group classification system (Robson) is the most appropriate for assessing drivers of caesarean deliveries. Evidence on the drivers of caesarean-section rates from conflict-affected settings is scarce. This study examines caesareans-section rates among Palestinian refugees by seven-group classification, compares to WHO guidelines, and to rates in the host settings, and estimates the costs of high rates.

Methods

Electronic medical records of 290,047 Palestinian refugee women using UNRWA’s (United Nations Relief and Works Agency for Palestine Refugees in the Near East) antenatal service from 2017–2020 in five settings (Jordan, Lebanon, Syria, West Bank, Gaza) were used. We modified Robson criteria to compare rates within each group with WHO guidelines. The host setting data were extracted from publicly available reports. Data on costs came from UNRWA’s accounts.

Findings

Palestinian refugees in Gaza had the lowest caesarean-section rates (22%), followed by those residing in Jordan (28%), West Bank (30%), Lebanon (50%) and Syria (64%). The seven groups caesarean section classification showed women with previous caesarean-sections contributed the most to overall rates. Caesarean-section rates were substantially higher than the WHO guidelines, and excess caesarean-sections (2017–2020) were modelled to cost up to 6.8 million USD. We documented a steady increase in caesarean-section rates in all five settings for refugee and host communities; refugee rates paralleled or were below those in their host country.

Interpretation

Caesarean-section rates exceed recommended guidance within most groups. The high rates in the nulliparous groups will drive future increases as they become multiparous women with a previous caesarean-section and in turn, face high caesarean rates. Our analysis helps suggest targeted and tailored strategies to reduce caesarean-section rates in priority groups (among low-risk women) organized by those aimed at national governments, and UNRWA, and those aimed at health-care providers.
Performance of Sonoelastography for predicting malignancy in soft tissue
Authors: Bodard Sylvain , Lassalle Louis , Larousserie Frédérique , Guinebert Sylvain , Hacquart Thomas , Campagna Raphael , Biau David , Regnard Noreddine , Feydy Antoine
Published: December 2022

Background

Separating benign from malignant soft-tissue masses often requires a biopsy. The objective of this study was to assess whether shear-wave elastography (SWE) helped to separate benign from malignant soft-tissue masses.

Methods

In 2015–2016, we prospectively included patients with soft-tissue masses deemed by our multidisciplinary sarcoma board to require a diagnostic biopsy. All patients underwent ultrasonography (US) followed by SWE to measure elasticity. We compared benign and malignant tumors, overall and after separating tumors with vs. without a fatty component. The biopsy findings, and surgical-specimen histology when available, served as the reference standard.

Results

We included 136 patients, 99 with non-fatty and 37 with fatty soft-tissue masses. Mean elasticity and tumor-to-fat elasticity ratio (T/F) values were significantly lower for the benign than the malignant soft-tissue masses in the overall cohort (30.9 vs. 50.0 kilopascals (kPa), P = 0.03; and 2.55 vs. 4.30, P = 0.046) and in the non-fatty subgroup (37.8 ± 31.9 vs. 58.9 ± 39.1 kPa, P = 0.049 and 2.89 ± 5.25 vs. 5.07 ± 5.41, P = 0.046). Data for fatty tumors were non relevant due to lack of conclusive results. By receiver operating characteristics curve analysis, a T/F cutoff of 3.5 had 46% sensitivity and 84% specificity for separating benign and malignant soft-tissue masses.

Conclusions

SWE had good specificity and poor sensitivity for separating benign from malignant soft-tissue masses.
Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases
Authors: Fidelman Nicholas , Atreya Chloe E. , Griffith Madeline , Milloy M. Alexandra , Carnevale Julia , Cinar Pelin , Venook Alan P. , Van Loon Katherine
Published: December 2022

Background

Extrahepatic disease progression limits clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer.

Methods

Sequential lobar TARE using 90Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE.

Results

A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%).

Conclusions

The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieves disease control within the liver.

Trial registration

ClinicalTrials.gov identifier NCT02602327 (first posted 11/11/2015).
Learning burnout and its association with perceived stress, social support, and the Big Five personality traits in Chinese medical students during the COVID-19 pandemic: a cross-sectional study
Authors: Wang Simeng , Li Honghe , Chen Xin , Yan Nan , Wen Deliang
Published: December 2022

Background

Owing to the coronavirus disease 2019, medical learning burnout has attracted increasing attention in educational research. It has a serious negative impact on medical students and their service quality. This could impair the professional development of medical students; weaken their personal and professional quality; and lead to problems such as increased medical errors and reduced patient care quality and satisfaction. This study aimed to examine the effects of perceived stress, social support, and the Big Five personality traits on learning burnout among medical students.

Methods

In November 2021, a cross-sectional survey was conducted at three medical universities in China. A self-administered questionnaire was distributed to 616 third- year students. Learning burnout, perceived stress, social support, and the Big Five personality traits (neuroticism, extroversion, openness, agreeableness, and conscientiousness) were anonymously measured. A total of 583 students were included in the final sample. Hierarchical linear regression was performed to explore the effects of perceived stress, social support, and Big Five personality traits on medical students’ learning burnout.

Results

Perceived stress was positively associated with learning burnout (emotional exhaustion: ß = 0.577, p < 0.001; cynicism: ß = 0.543, p < 0.001; low professional efficacy: ß = 0.455, p < 0.001) whereas social support was negatively related with it (low professional efficacy: ß = -0.319, p < 0.001). Neuroticism had a positive effect on emotional burnout (ß = 0.152, p = 0.009). Extraversion (ß = -0.116, p = 0.006) and conscientiousness (ß = -0.363, p < 0.001) had a negative effect on low professional efficacy. Agreeableness negatively affected emotional exhaustion (ß = -0.181, p < 0.001) and cynicism (ß = -0.245, p < 0.001) and positively affected low professional efficacy (ß = 0.098, p = 0.008). The associated factors together accounted for an additional variance of learning burnout (emotional exhaustion: 39.0%; cynicism: 36.8%; low professional efficacy: 48.7%).

Conclusions

Social support is a positive resource for fighting medical students’ burnout. Perceived stress was the strongest indicator of learning burnout. In addition to reducing perceived stress, developing extraversion, agreeableness, and conscientiousness should be included in burnout prevention and treatment strategies, particularly for medical students.
Major complications and mortality after ventral hernia repair: an eleven-year Swedish nationwide cohort study
Authors: Lindmark Mikael , Löwenmark Thyra , Strigård Karin , Gunnarsson Ulf
Published: December 2022

Background and aims

Ventral hernia repair is one of the most common surgical procedures performed worldwide. Despite the large volume, consensus is lacking regarding indications for repair or choice of surgical method used for reconstruction. The aim of this study was to explore the risk for major complications and mortality in ventral hernia repair using data from a nationwide patient register.

Method

Patient data of individuals over 18 years of age who had a ventral hernia procedure between 2004 and 2014 were retrieved from the Patient Register kept by the Swedish National Board of Health and Welfare. After exclusion of patients with concomitant bowel surgery, 45 676 primary surgical admissions were included. Procedures were dichotomised into laparoscopic and open surgery, and stratified for primary and incisional hernias.

Results

A total of 45 676 admissions were analysed. The material comprised 36% (16 670) incisional hernias and 64% (29 006) primary hernias. Women had a higher risk for reoperation during index admission after primary hernia repair (OR 1.84 (1.29–2.62)). Forty-three patients died of complications within 30 days of index surgery. Patients aged 80 years and older had a 2.5 times higher risk for a complication leading to reoperation, and a 12-fold higher mortality risk than patients aged 70–79 years.

Conclusion

Age is the dominant mortality risk factor in ventral hernia repair. Laparoscopic surgery was associated with a lower risk for reoperation during index admission. Reoperation seems to be a valid outcome variable, while registration of complications is generally poor in this type of cohort.
Predictors of modern contraceptive use among reproductive age women in high fertility countries in sub-Saharan Africa: evidence from demographic and health surveys
Authors: Negash Wubshet Debebe , Eshetu Habitu Birhan , Asmamaw Desale Bihonegn
Published: December 2022

Background

The world’s population has increased faster than expected due to high fertility rates, with sub-Saharan Africa accounting for most of the increase. Modern contraceptive use is the best option to reduce the high fertility rate. There is limited information on the prevalence of modern contraception and its predictors in sub-Saharan Africa’s high-fertility countries. Therefore, this study aimed to assess the prevalence and predictors of modern contraception among reproductive-age women in high fertility countries in sub-Saharan Africa.

Methods

We used Demographic and Health Survey data sets from the top 10 high fertility countries in sub-Saharan Africa. Stata version 16.0 software was used to analyze the data, and all statistical analyses were completed after the data had been weighted. Multilevel binary logistic regression was performed to identify factors associated with modern contraceptive use. Adjusted odds ratio with a 95% confidence interval, and a p value < 0.05 was used to declare statistical significance.

Results

The prevalence of modern contraceptive use in all the countries considered in this study was 10.72% (95% CI 10.57, 10.87). In terms of the predictor variables, young aged women, those who had attended a primary or secondary level of formal education, women who received antenatal care follow up, women who reported distance to the health facility as not a big problem, and women from rich families were more likely to use modern contraceptives.

Conclusion

Only one in 10 women of reproductive age used modern contraceptive methods in high fertility countries in sub-Saharan Africa. To improve the use of modern contraceptives, governments and non-governmental organizations studied in the countries should intensify programs that focus on those women who are economically poor, those with no formal education, no media exposure, and those with no antenatal care follow up.
eOSCE stations live versus remote evaluation and scores variability
Authors: Bouzid Donia , Mullaert Jimmy , Ghazali Aiham , Ferré Valentine Marie , Mentré France , Lemogne Cédric , Ruszniewski Philippe , Faye Albert , Dinh Alexy Tran , Mirault Tristan ,   on behalf of Université Paris Cité Osce study group, Smadja Nathan Peiffer , Muller Léonore , Pierrotin Laure Falque , Thy Michael , Assadi Maksud , Yung Sonia , de Tymowski Christian , le Hingrat Quentin , Eyer Xavier , Wicky Paul Henri , Oualha Mehdi , Houdouin Véronique , Jabre Patricia , Vodovar Dominique , Dioguardi Burgio Marco , Zucman Noémie , Tsopra Rosy , Tazi Asmaa , Ressaire Quentin , Nguyen Yann , Girard Muriel , Frachon Adèle , Depret François , Pellat Anna , de Masson Adèle , Azais Henri , de Castro Nathalie , Jeantrelle Caroline , Javaud Nicolas , Malmartel Alexandre , de Margerie Constance Jacquin , Chousterman Benjamin , Fournel Ludovic , Holleville Mathilde , Blanche Stéphane
Published: December 2022

Background

Objective structured clinical examinations (OSCEs) are known to be a fair evaluation method. These recent years, the use of online OSCEs (eOSCEs) has spread. This study aimed to compare remote versus live evaluation and assess the factors associated with score variability during eOSCEs.

Methods

We conducted large-scale eOSCEs at the medical school of the Université de Paris Cité in June 2021 and recorded all the students’ performances, allowing a second evaluation. To assess the agreement in our context of multiple raters and students, we fitted a linear mixed model with student and rater as random effects and the score as an explained variable.

Results

One hundred seventy observations were analyzed for the first station after quality control. We retained 192 and 110 observations for the statistical analysis of the two other stations. The median score and interquartile range were 60 out of 100 (IQR 50–70), 60 out of 100 (IQR 54–70), and 53 out of 100 (IQR 45–62) for the three stations. The score variance proportions explained by the rater (ICC rater) were 23.0, 16.8, and 32.8%, respectively. Of the 31 raters, 18 (58%) were male. Scores did not differ significantly according to the gender of the rater (p = 0.96, 0.10, and 0.26, respectively). The two evaluations showed no systematic difference in scores (p = 0.92, 0.053, and 0.38, respectively).

Conclusion

Our study suggests that remote evaluation is as reliable as live evaluation for eOSCEs.
Digital technologies in routine palliative care delivery: an exploratory qualitative study with health care professionals in Germany
Authors: May Susann , Bruch Dunja , Gehlhaar Anne , Linderkamp Felizitas , Stahlhut Kerstin , Heinze Martin , Allsop Matthew , Muehlensiepen Felix
Published: December 2022

Objective

To explore health care professionals’ (HCPs) perspectives, experiences and preferences towards digital technology use in routine palliative care delivery.

Methods

HCPs (n = 19) purposively selected from a sample of settings that reflect routine palliative care delivery (i.e. specialized outpatient palliative care, inpatient palliative care, inpatient hospice care in both rural and urban areas of the German states of Brandenburg and Berlin) participated in an explorative, qualitative study using semi-structured interviews. Interview data were analyzed using structured qualitative content analysis.

Results

Digital technologies are widely used in routine palliative care and are well accepted by HCPs. Central functions of digital technologies as experienced in palliative care are coordination of work processes, patient-centered care, and communication. Especially in outpatient care, they facilitate overcoming spatial and temporal distances. HCPs attribute various benefits to digital technologies that contribute to better coordinated, faster, more responsive, and overall more effective palliative care. Simultaneously, participants preferred technology as an enhancement not replacement of care delivery. HCPs fear that digital technologies, if overused, will contribute to dehumanization and thus significantly reduce the quality of palliative care.

Conclusion

Digital technology is already an essential part of routine palliative care delivery. While generally perceived as useful by HCPs, digital technologies are considered as having limitations and carrying risks. Hence, their use and consequences must be carefully considered, as they should discreetly complement but not replace human interaction in palliative care delivery.
Using patient flow analysis with real-time patient tracking to optimize radiation oncology consultation visits
Authors: Mesko Shane , Weng Julius , Das Prajnan , Koong Albert C. , Herman Joseph M. , Elrod-Joplin Dorothy , Kerr Ashley , Aloia Thomas , Frenzel John , French Katy E. , Martinez Wendi , Recinos Iris , Alshaikh Abdulaziz , Daftary Utpala , Moreno Amy C. , Nguyen Quynh-Nhu
Published: December 2022

Purpose

Clinical efficiency is a key component of the value-based care model and a driver of patient satisfaction. The purpose of this study was to identify and address inefficiencies at a high-volume radiation oncology clinic.

Methods and materials

Patient flow analysis (PFA) was used to create process maps and optimize the workflow of consultation visits in a gastrointestinal radiation oncology clinic at a large academic cancer center. Metrics such as cycle times, waiting times, and rooming times were assessed by using a real-time patient status function in the electronic medical record for 556 consults and compared between before vs after implementation of the PFA recommendations.

Results

The initial PFA revealed four inefficiencies: (1) protracted rooming time, (2) inefficient communications, (3) duplicated tasks, and (4) ambiguous clinical roles. We analyzed 485 consult-visits before the PFA and 71 after the PFA. The PFA recommendations led to reductions in overall median cycle time by 21% (91 min vs 72 min, p < 0.001), in cumulative waiting times by 64% (45 min vs 16 min; p < 0.001), which included waiting room time (14 min vs 5 min; p < 0.001) and wait for physician (20 min vs. 6 min; p < 0.001). Slightly less than one-quarter (22%) of consult visits before the PFA lasted > 2 h vs. 0% after implementation of the recommendations (p < 0.001). Similarly, the proportion of visits requiring < 1 h was 16% before PFA vs 34% afterward (p < 0.001).

Conclusions

PFA can be used to identify clinical inefficiencies and optimize workflows in radiation oncology consultation clinics, and implementing their findings can significantly improve cycle times and waiting times. Potential downstream effects of these interventions include improved patient experience, decreased staff burnout, financial savings, and opportunities for expanding clinical capacity.
Egfr signaling promotes juvenile hormone biosynthesis in the German cockroach
Authors: Li Zhaoxin , Zhou Caisheng , Chen Yumei , Ma Wentao , Cheng Yunlong , Chen Jinxin , Bai Yu , Luo Wei , Li Na , Du Erxia , Li Sheng
Published: December 2022

Background

In insects, an interplay between the activities of distinct hormones, such as juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulates the progression through numerous life history hallmarks. As a crucial endocrine factor, JH is mainly synthesized in the corpora allata (CA) to regulate multiple physiological and developmental processes, including molting, metamorphosis, and reproduction. During the last century, significant progress has been achieved in elucidating the JH signal transduction pathway, while less progress has been made in dissecting the regulatory mechanism of JH biosynthesis. Previous work has shown that receptor tyrosine kinase (RTK) signaling regulates hormone biosynthesis in both insects and mammals. Here, we performed a systematic RNA interference (RNAi) screening to identify RTKs involved in regulating JH biosynthesis in the CA of adult Blattella germanica females.

Results

We found that the epidermal growth factor receptor (Egfr) is required for promoting JH biosynthesis in the CA of adult females. The Egf ligands Vein and Spitz activate Egfr, followed by Ras/Raf/ERK signaling, and finally activation of the downstream transcription factor Pointed (Pnt). Importantly, Pnt induces the transcriptional expression of two key enzyme-encoding genes in the JH biosynthesis pathway: juvenile hormone acid methyltransferase (JHAMT) and methyl farnesoate epoxidase (CYP15A1). Dual-luciferase reporter assay shows that Pnt is able to activate a promoter region of Jhamt. In addition, electrophoretic mobility shift assay confirms that Pnt directly binds to the − 941~ − 886 nt region of the Jhamt promoter.

Conclusions

This study reveals the detailed molecular mechanism of Egfr signaling in promoting JH biosynthesis in the German cockroach, shedding light on the intricate regulation of JH biosynthesis during insect development.
Outcomes and risk factors with COVID-19 or influenza in hospitalized asthma patients
Authors: Dupont Axelle , Couffignal Camille , Arias Camila , Salah Kankoe , Phillips-Houlbraq Mathilde , Le Brun Mathilde , Taillé Camille
Published: December 2022

Background

At the time of the SARS-CoV-2 emergence, asthma patients were initially considered vulnerable because respiratory viruses, especially influenza, are associated with asthma exacerbations, increased risk of hospitalization and more severe disease course. We aimed to compare the asthma prevalence in patients hospitalized for COVID-19 or influenza and risk factors associated with poor prognosis with the diseases.

Methods

This retrospective cohort study used the Paris university hospitals clinical data warehouse to identify adults hospitalized for COVID-19 (January to June 2020) or influenza (November 2017 to March 2018 for the 2017–2018 influenza period and November 2018 to March 2019 for the 2018–2019 period). Asthma patients were identified with J45 and J46 ICD-10 codes. Poor outcomes were defined as admission in intensive care or death.

Results

Asthma prevalence was significantly higher among influenza than COVID-19 patients (n = 283/3 119, 9.1%, 95% CI [8.1–10.1] in 2017–2018 and n = 309/3 266, 9.5%, 95% CI [8.5–10.5] in 2018–2019 versus n = 402/9 009, 4.5%, 95% CI [4.0–4.9]). For asthma patients, 31% with COVID-19 were admitted to an intensive care unit versus 23% and 21% with influenza. Obesity was a risk factor for the 2017–2018 influenza period, smoking and heart failure for the 2018–2019 period. Among COVID-19 patients with asthma, smoking and obesity were risk factors for the severe form.

Conclusions

In this study, patients with an asthma ICD-10 code were less represented among COVID-19 patients than among influenza-infected ones. However, outcomes were poorer for COVID-19 than influenza patients, both with asthma. These data highlight the importance of protective shields and vaccination against influenza and COVID-19 in this population.
Gaseous nitric oxide tumor ablation induces an anti-tumor abscopal effect
Authors: Confino Hila , Dirbas Frederick M. , Goldshtein Matan , Yarkoni Shay , Kalaora Rinat , Hatan Meital , Puyesky Shani , Levi Yakir , Malka Lidor , Johnson Matt , Chaisson Selena , Monson Jedidiah M. , Avniel Amir , Lisi Steve , Greenberg David , Wolf Ido
Published: December 2022

Background

In-situ tumor ablation provides the immune system with the appropriate antigens to induce anti-tumor immunity. Here, we present an innovative technique for generating anti-tumor immunity by delivering exogenous ultra-high concentration (> 10,000 ppm) gaseous nitric oxide (UHCgNO) intratumorally.

Methods

The capability of UHCgNO to induce apoptosis was tested in vitro in mouse colon (CT26), breast (4T1) and Lewis lung carcinoma (LLC-1) cancer cell lines. In vivo, UHCgNO was studied by treating CT26 tumor-bearing mice in-situ and assessing the immune response using a Challenge assay.

Results

Exposing CT26, 4T1 and LLC-1 cell lines to UHCgNO for 10 s–2.5 min induced cellular apoptosis 24 h after exposure. Treating CT26 tumors in-situ with UHCgNO followed by surgical resection 14 days later resulted in a significant secondary anti-tumor effect in vivo. 100% of tumor-bearing mice treated with 50,000 ppm UHCgNO and 64% of mice treated with 20,000 ppm UHCgNO rejected a second tumor inoculation, compared to 0% in the naive control for 70 days. Additionally, more dendrocytes infiltrated the tumor 14 days post UHCgNO treatment versus the nitrogen control. Moreover, T-cell penetration into the primary tumor was observed in a dose-dependent manner. Systemic increases in T- and B-cells were seen in UHCgNO-treated mice compared to nitrogen control. Furthermore, polymorphonuclear-myeloid-derived suppressor cells were downregulated in the spleen in the UHCgNO-treated groups.

Conclusions

Taken together, our data demonstrate that UHCgNO followed by the surgical removal of the primary tumor 14 days later induces a strong and potent anti-tumor response.
circCYP24A1 facilitates esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB-induced CCL5 secretion
Authors: Gu Lina , Sang Yang , Nan Xixi , Zheng Yang , Liu Fei , Meng Lingjiao , Sang Meixiang , Shan Baoen
Published: December 2022

Background

Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor, while the molecular mechanisms have not been fully elucidated. Multiple circular RNAs have been reported to involve in the onset and progression of malignant tumors through various molecular mechanisms. However, the clinical significance and functional mechanism of most circRNAs involved in the progression of ESCC remains obscure.

Methods

RNA-Seq was used to explore potential circRNAs in participated in 5 pairs of ESCC and their corresponding normal esophageal tissues. The up-regulated circCYP24A1 was selected. Fluorescence in situ hybridization was cunducted to verificated the expression and intracellular localization of circCYP24A1 by using the tissue microarray. The Kaplan–Meier method and Cox proportional hazards model was used to examine the potential prognostic value of circCYP24A1 on overall survival of ESCC patients. The biological function were confirmed by gain- and loss-of-function approaches in vivo. mRNA expression profile microarray was proformed to investigate the downstream signaling pathways involved in circCYP24A1. RNA pull-down assay and mass spectrometry were performed to identify the proteins associated with circCYP24A1. Rescue experiments were carried out to identified hypothetical regulatory role of circCYP24A1 on ESCC progression in vivo and in virto.

Results

In this study, we identified circCYP24A1 in ESCC tissues by RNA sequencing, which is up-regulated in 114 cases of ESCC tissues and acts as a novel prognosis-related factor. Moreover, circCYP24A1 promoted the ability of proliferation, migration, invasion and clone formation in vitro, as well as tumor growth in vivo. Mechanistically, chemokine (C-Cmotif) ligand 5 (CCL5) is functional downstream mediator for circCYP24A1, which is screened by mRNA microarray. Moreover, circCYP24A1 physically interacts with M2 isoform of pyruvate kinase (PKM2). Rescue experiments showed that PKM2 knockdown partly reverses the promotional effects of circCYP24A1. It was revealed that circCYP24A1 increases secretion of CCL5 through the mechanism mainly by interacting with PKM2, an activator of NF-κB pathway, and thereby accelerate malignant progression of ESCC.

Conclusions

Up-regulated circCYP24A1 could activate NF-κB pathway by binding PKM2, which promotes the secretion of CCL5 and accelerate malignant progression of ESCC. Our fndings recommended a novel function for circCYP24A1 as a potential effective biomarker for judging prognosis and a therapeutic target in ESCC.
Assessment of the relationship between subclinical hypothyroidism and blood lipid profile: reliable or not?
Authors: Luo Yi , Wu Fei , Huang Zhen , Gong Yan , Zheng Yansong
Published: December 2022

Background

The relationship between subclinical hypothyroidism (SCH) and blood lipid metabolism is controversial. This study is intended to evaluate the relationship between SCH and blood lipid profiles using well defined diagnostic criteria.

Methods

Data from 11,512 physical examinees in our hospital who had finished two tests with an interval of at least 3 months were analyzed, including 685 cases of SCH as stipulated in this study. In addition to common physical examination indicators, other parameters such as thyroid function indices and blood lipids were measured twice with an interval of at least 3 months. Subjects were diagnosed with SCH only when their levels of TT3, TT4, FT3 and FT4 were normal and TSH levels were increased on both tests, which meant these subjects were in a state of SCH for at least 3 months. The results of blood lipids for the second time were analyzed.

Results

Statistically significant differences were found in age, sex, BMI, hemoglobin, total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), and BFP between the SCH and control groups (P < 0.001). However, there were no statistically significant differences in age, sex, blood pressure, blood lipids, blood glucose or BMI between patients with mild SCH and those with severe SCH (P > 0.05). After balancing the age and sex ratio, no factors were confirmed to be statistically significant independent factors of SCH. None of the parameters showed statistically significant differences between patients with mild SCH and those with severe SCH (P > 0.05).

Conclusion

After defining rigorous criteria for the diagnosis of SCH, no definite association between SCH and TC, LDL-C or HDL-C was confirmed in this study. SCH may have no relationship to the most concerning blood lipid profile.
Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury
Authors: Guo Xiaoyu , Hong Ting , Zang Jie , Shao Rongjiao , Hou Xumin , Wang Kai , Liu Weizhuo , Su Fan , He Bin
Published: December 2022

Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects.
Indocyanine green fluorescence imaging during laparoscopic rectal cancer surgery could reduce the incidence of anastomotic leakage: a single institutional retrospective cohort study
Authors: Kondo Akihiro , Kumamoto Kensuke , Asano Eisuke , Feng Dongping , Kobara Hideki , Okano Keiichi
Published: December 2022

Background

There is insufficient evidence on whether indocyanine green (ICG) fluorescence angiography can reduce the incidence of anastomotic leakage (AL). This retrospective cohort study aimed to evaluate the effect of ICG fluorescence angiography on AL rates in laparoscopic rectal cancer surgery at a single institution.

Methods

Patients who underwent laparoscopic low anterior resection or intersphincteric resection with ICG fluorescence angiography (ICG group; n = 73) and patients who underwent a similar surgical procedure for rectal cancer without ICG fluorescence (non-ICG group; n = 114) were enrolled consecutively in this study. ICG fluorescence angiography was performed prior to transection of the proximal colon, and anastomosis was performed with sufficient perfusion using ICG fluorescence imaging. AL incidence was compared between both groups, and the risk factors for AL were analyzed.

Results

AL occurred in 3 (4.1%) and 14 (12.3%) patients in the ICG and non-ICG groups, respectively. In the ICG group, the median perfusion time from ICG injection was 34 s, and 5 patients (6.8%) required revision of the proximal transection line. None of the patients requiring revision of the proximal transection line developed AL. In univariate analysis, longer operating time (odds ratio: 2.758; 95% confidence interval: 1.023–7.624) and no implementation of ICG fluorescence angiography (odds ratio: 3.266; 95% confidence interval: 1.038–11.793) were significant factors associated with AL incidence, although the creation of a diverting stoma or insertion of a transanal tube was insignificant.

Conclusion

ICG fluorescence angiography was associated with a significant reduction in AL during laparoscopic rectal cancer surgery. Changes in the surgical plan due to ICG fluorescence visibility may help improve the short-term outcomes of patients with rectal cancer.
Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma in patients aged 60 and older: a retrospective cohort study
Authors: Wang Jianlei , Wang Wei , Chen Xiaolei , Ma Delin , Du Gang , Xia Tong , Jiang Zhaochen , Jin Bin
Published: December 2022

Objective laparoscopic surgical excision is the recommended treatment for liver cancers, yet its benefits in patients aged 60 and older remain poorly understood. Thus, this study evaluated the feasibility, safety, and clinical outcomes of laparoscopic hepatectomy for patients aged 60 and older with intrahepatic cholangiocarcinoma (ICC).

Methods

After screening, 107 patients who underwent hepatectomy for ICC were enrolled and grouped into either laparoscopic (LH) or open hepatectomy (OH) groups. Baseline characteristics, pathological findings, and long-term outcomes were compared between the two groups. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using univariate and multivariate analyses.

Results

Among baseline characteristics and pathological findings, only pre-operative albumin was higher in the LH group. The LH group had more favorable short-term outcomes such as incision length, level of postoperative total bilirubin, and length of postoperative stays than the OH group. The postoperative complication, lymph node dissection and R0 resection rate, and long-term outcomes including OS and DFS were not significantly different between the two groups. Cancer Antigen-19-9(CA-19-9) and pathological differentiation were independent prognostic factors for OS, whereas CA-19-9 and neutrophil count were independent prognostic factors for DFS.

Conclusion

LH is safe, reliable, and feasible for treatment of ICC patients aged 60 and older as it had better short-term clinical outcomes than OH and achieved long-term prognoses that were comparable to those of OH.
Associations of physical activity intensity with incident cardiovascular diseases and mortality among 366,566 UK adults
Authors: Mu Xuanwen , Liu Shuangyan , Fu Mingjian , Luo Mengyun , Ding Ding , Chen Liangkai , Yu Kuai
Published: December 2022

Background

The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear.

Methods

The present study included 366,566 participants (aged 40–69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes.

Results

During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86–0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78–0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0–150 min/week; VPA, 0–75 min/week), those performing 150–300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79–0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63–0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA.

Conclusions

Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.
Analysis of new treatments proposed for malignant pleural mesothelioma raises concerns about the conduction of clinical trials in oncology
Authors: Meirson Tomer , Nardone Valerio , Pentimalli Francesca , Markel Gal , Bomze David , D’Apolito Maria , Correale Pierpaolo , Giordano Antonio , Pirtoli Luigi , Porta Camillo , Gray Steven G , Mutti Luciano
Published: December 2022

In this commentary, using existing clinical trial data and FDA approvals we propose that there is currently a critical need for an appropriate balancing between the financial impact of new cancer drugs and their actual benefit for patients. By adopting “pleural mesothelioma” as our clinical model we summarize the most relevant pertinent and available literature on this topic, and use an analysis of the reliability of the trials submitted for registration and/or recently published as a case in point to raise concerns with respect to appropriate trial design, biomarker based stratification and to highlight the ongoing need for balancing the benefit/cost ratio for both patients and healthcare providers.
Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR
Authors: Tan Lei , She Han , Zheng Jie , Peng Xiaoyong , Guo Ningke , Zhang Bindan , Sun Yue , Ma Chunhua , Xu Shenglian , Bao Daiqin , Zhou Yuanqun , Li Qinghui , Mao Qingxiang , Liu Liangming , Hu Yi , Li Tao
Published: December 2022

Background

Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied.

Methods

The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed.

Results

Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrappingl-malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing thel-malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury.

Conclusion

MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR.
Association between iron metabolism and non-alcoholic fatty liver disease: results from the National Health and Nutrition Examination Survey (NHANES 2017–2018) and a controlled animal study
Authors: Zhang Xinxin , Zuo Ronghua , Xiao Shengjue , Wang Lirui
Published: December 2022

Background

Iron metabolism may be involved in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). The relationship between iron metabolism and NAFLD has not been clearly established. This study aimed to clarify the relationship between biomarkers of iron metabolism and NAFLD.

Methods

Based on the National Health and Nutrition Examination Survey (NHANES), restricted cubic spline models and multivariable logistic regression were used to examine the association between iron metabolism [serum iron (SI), serum ferritin (SF), transferrin saturation (TSAT), and soluble transferrin receptor (sTfR)] and the risk for NAFLD. In addition, stratified subgroup analysis was performed for the association between TSAT and NAFLD. Moreover, serum TSAT levels were determined in male mice with NAFLD. The expression of hepcidin and ferroportin, vital regulators of iron metabolism, were analyzed in the livers of mice by quantitative real-time PCR (qRT-PCR) and patients with NAFLD by microarray collected from the GEO data repository.

Results

Patients with NAFLD showed decreased SI, SF, and TSAT levels and increased STfR levels based on the NHANES. After adjusting for confounding factors, TSAT was significantly negatively correlated with NAFLD. Of note, the relationship between TSAT and NAFLD differed in the four subgroups of age, sex, race, and BMI (P for interaction < 0.05). Consistently, mice with NAFLD exhibited decreased serum TSAT levels. Decreased hepcidin and increased ferroportin gene expression were observed in the livers of patients and mice with NAFLD.

Conclusion

Serum TSAT levels and hepatic hepcidin expression were decreased in both patients and mice with NAFLD. Among multiple biomarkers of iron metabolism, lower TSAT levels were significantly associated with a higher risk of NAFLD in the U.S. general population. These findings might provide new ideas for the prediction, diagnosis, and mechanistic exploration of NAFLD.
Radiobiological and dosimetric comparison of 60Co versus 192Ir high-dose-rate intracavitary-interstitial brachytherapy for cervical cancer
Authors: Wen Aiping , Wang Xianliang , Wang Bingjie , Yan Chuanjun , Luo Jingyue , Wang Pei , Li Jie
Published: December 2022

Background

High-dose-rate (HDR) intracavitary-interstitial brachytherapy (IC-ISBT) is an effective treatment for bulky, middle, and advanced cervical cancer. In this study, we compared the differences between 60Co and 192Ir HDR IC-ISBT plans in terms of radiobiological and dosimetric parameters, providing a reference for clinical workers in brachytherapy.

Methods

A total of 30 patients with cervical cancer receiving HDR IC-ISBT were included in this study, and IC-ISBT plans for each individual were designed with both 60Co and 192Ir at a prescribed dose of CTV D90 = 6 Gy while keeping the dose to OARs as low as possible. Physical dose and dose–volume parameters of CTV and OARs were extracted from TPS. The EQD2, EUBED, EUD, TCP, and NTCP were calculated using corresponding formulas. The differences between the 60Co and 192Ir IC-ISBT plans were compared using the paired t-test.

Results

In each patient's 60Co and 192Ir IC-ISBT plan, the average physical dose and EQD2 of 60Co were lower than those of 192Ir, and there were statistically significant differences in D2cc and D1cc for the OARs (p < 0.05); there were statistically significant differences in D0.1 cc for the bladder (p < 0.05) and no significant differences in D0.1 cc for the rectum or intestines (p > 0.05). The EUBED ratio (60Co/192Ir) at the CTV was mostly close to 1 when neither 60Co or 192Ir passed their half-lives or when both passed two half-lives, and the difference between them was not significant; at the OARs, the mean value of 60Co was lower than that of 192Ir. There was no statistical difference between 60Co and 192Ir in the EUD (93.93 versus 93.92 Gy, p > 0.05) and TCP (97.07% versus 97.08%, p > 0.05) of the tumors. The mean NTCP value of 60Co was lower than that of 192Ir.

Conclusions

Considering the CTV and OARs, the dosimetric parameters of 60Co and 192Ir are comparable. Compared with 192Ir, the use of 60Co for HDR IC-ISBT can ensure a similar tumor control probability while providing better protection to the OARs. In addition, 60Co has obvious economic advantages and can be promoted as a good alternative to 192Ir.