bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma
Authors: Li Zhiqiang , Gao Hongqiang , Zhang Xiang , Liu Qiyu , Chen Gang
Published: September 2022

Background

The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels.

Methods

Here we first characterized the influencing factors of prognosis of stage I HCC patients by downloading and analyzing the whole-exome somatic mutation data, messenger ribonucleic acid (mRNA) transcription data, along with demographic and clinical information of 163 stage I HCC patients from the TCGA database. The relationship between the influencing factors and HCC prognosis was studied in detail, and a prediction Nomogram model was established. Figures and tables were plotted using the R software.

Results

TP53, CTNNB1, TTN, MUC16 and ALB were the top mutated genes in stage I HCC. A series of co-mutations and mutually exclusive mutations were identified. Twenty-nine genes with significant stratification on prognosis were identified, including highly mutated LRP1B, ARID1A and PTPRQ. Patients with wild type (WT) genes unanimously exhibited significantly better overall survival rate than those with mutants. Patients with the top 10% tumor mutational burden (TMB) exhibited significantly worse prognosis than the rest 90%. Further characterization of transcriptional profile revealed that membrane functions, cell skeleton proteins, ion channels, receptor function and cell cycle were comprehensively altered in stage I HCC. Univariate and multivariate analyses were performed at clinicopathological, mutational and transcriptional levels. The combined analysis revealed sex, race, TMB, neoplasm histologic grade, Child–Pugh grade, MMRN1, OXT and COX6A2 transcription as independent risk factors. These factors were used to establish a Nomogram model to predict the prognosis of individual HCC patients.

Conclusions

The influencing factors of prognosis of stage I HCC have been characterized for the first time at clinicopathological, mutational and transcriptional levels. A Nomogram model has been established to predict the prognosis. Further validation is needed to confirm the effectiveness and reliability of the model.
Use of handgrip strength measurement as an alternative for assessing chewing function in people with dementia
Authors: Jockusch Julia , Hahnel Sebastian , Nitschke Ina
Published: September 2022

Background

Chewing ability and handgrip strength can be independent explanatory factors of physical fitness. The usability of measurement procedures for assessing chewing function in people with dementia seems to be limited. This study aimed to show an association between handgrip strength and chewing function to enable the use of handgrip strength measurement as an alternative for determining chewing parameters in people with dementia. 

Methods

The data analysed here are part of the OrBiD (Oral Health, Bite Force and Dementia) pilot study. A total of 120 participants were assigned to five evaluation groups based on their cognitive abilities using the Mini-Mental State Examination (MMSE). The MMSE groups in this data analysis were “no dementia” (noDem, MMSE 28–30), “mild cognitive impairment” (mCI, MMSE 25–27), and “mild dementia” (mDem, MMSE 18–24). Handgrip strength, maximum occlusal force, and chewing efficiency were measured. 

Results

The Mini-Mental State Examination scores among all participants (n = 71) resulted in a median of 27 and a range of 18–30. An association between maximum handgrip strength and the cognitive impairment of the participants was shown. Nevertheless, the use of handgrip strength measurement as an alternative for determining chewing function was not verified in this study.

Conclusions

The feasibility and reliability of chewing function measurements in people with dementia should be investigated. Existing measurement procedures may need to be adapted or new assessments may need to be developed to be usable in people with dementia.

Trial registration

ClinicalTrials.gov NCT03775772.
Trophoblast cell-surface antigen 2 (TROP2) expression in triple-negative breast cancer
Authors: Jeon Yeonjin , Jo Uiree , Hong Jongmoo , Gong Gyungyub , Lee Hee Jin
Published: September 2022

Background

Trophoblast cell-surface antigen 2 (TROP2) is related to tumor proliferation enhancement and poor prognosis. An antibody targeting TROP2 was developed to treat metastatic triple-negative breast cancer (TNBC) which has a limited treatment modality. To characterize the TROP2 expressing tumors in TNBC, we analyzed TROP2 expression in three cohorts; (1) primary tumor without neoadjuvant chemotherapy, (2) primary tumor with neoadjuvant chemotherapy, and (3) metastatic tumor.

Methods

A total of 807 TNBC cases were evaluated for TROP2 immunohistochemical expression. We evaluated the TROP2 H-score distribution in the three cohorts. Tumors were divided into two groups based on TROP2 expression (high vs. low). We analyzed the relationship between clinicopathologic features and markers, including epidermal growth factor receptor, cytokeratin 5/6, p53, and Ki-67, and prognostic significance at high vs. low TROP2 expression.

Results

There was no difference in TROP2 H-score distribution between the three cohorts. Moderate-to-strong membranous expression of TROP2 in at least 10% of tumor cells was present in 662 cases (82.0%) in Cohort 1, 59 cases (89.4%) in Cohort 2, and 23 cases (88.5%) in Cohort 3. There was no significant difference in clinicopathologic features between high vs. low TROP2 in all cohorts. TROP2 H-score was an independent poor prognostic factor for overall survival in Cohort 3.

Conclusions

TNBC showed similar TROP2 expression regardless of neoadjuvant treatment or primary tumor/metastasis. Although the prognostic significance of TROP2 expression in metastatic TNBC has been revealed, further evaluation of the predictive value of TROP2 expression for targeted therapy is needed.
Patterns of multimorbidity in association with falls among the middle-aged and older adults: results from the China Health and Retirement Longitudinal Study
Authors: Yan Jingzheng , Wang Meijuan , Cao Yingjuan
Published: September 2022

Background

Chronic diseases are important risk factors of falls. However, most studies explored the effect of a single chronic disease on falls and few studies explored the combined effect of multiple chronic diseases on falls. In this study, we examined the associations between falls and multimorbidity and multimorbidity patterns.

Methods

Data collected between 2011 and 2018 were obtained from the China Health and Retirement Longitudinal Study (CHARLS). Multimorbidity was defined as the coexistence of ≥ 2 chronic diseases in the same person. The multimorbidity patterns were identified with exploratory factor analysis (EFA). The longitudinal associations of multimorbidity and multimorbidity patterns with falls were examined with generalized estimating equations methodology.

Results

Compared with patients without chronic conditions, patients with one, two, and ≥ 3 chronic diseases had 37%, 85%, and 175% increased risk of falls, respectively. The EFA identified four multimorbidity patterns and the factor scores in the cardiac-metabolic pattern [adjusted odds ratio (aOR): 1.16, 95% confidence interval (95% CI): 1.12–1.20)], visceral-arthritic pattern (aOR: 1.31, 95% CI: 1.28–1.35), respiratory pattern (aOR: 1.12, 95% CI: 1.10–1.16), and mental-sensory pattern (aOR: 1.31, 95% CI: 1.28–1.35) were all associated with a higher risk of falls.

Conclusion

Multimorbidity and multimorbidity patterns are related to falls. Older adults with multiple chronic diseases require early interventions to prevent falls.
Seasonal influenza vaccine uptake among healthcare workers in tertiary care hospitals, Bangladesh: Study protocol for influenza vaccine supply and awareness intervention
Authors: Hassan Md Zakiul , Shirin Tahmina , Rahman Mahbubur , Alamgir A. S. M. , Jahan Nusrat , Al Jubayer Biswas Md Abdullah , Khan Sazzad Hossain , Basher Md Ahmed Khairul , Islam Md Ariful , Hussain Kamal , Islam Md Nazrul , Rabbany Md Arif , Haque Md Azizul , Chakraborty Shishir Ranjan , Parvin Syeda Rukhshana , Rahman Mahmudur , Chowdhury Fahmida
Published: September 2022

Background

Healthcare workers (HCWs), such as doctors, nurses, and support staffs involved in direct or indirect patient care, are at increased risk of influenza virus infections due to occupational exposures. Vaccination is the most effective way to prevent influenza. Despite the World Health Organization (WHO) recommendations, Bangladesh lacks a seasonal influenza vaccination policy for HCWs, and thus vaccination rates remain low. The current project aims to investigate the effect of interventions on influenza vaccine awareness and availability of vaccine supply, explore HCWs’ knowledge and perceptions about influenza vaccination, understand the barriers and motivators for influenza vaccine uptake, and understand policymakers' views on the practicality of influenza vaccination among HCWs.

Method

We will conduct the study at four tertiary care teaching hospitals in Bangladesh, using a cluster randomized controlled trial approach, with the hospital as the unit of randomization and intervention. The study population will include all types of HCWs.The four different types of intervention will be randomly allocated and implemented in four study hospitals separately. The four interventions will be: i) ensuring the availability of influenza vaccine supply; ii) developing influenza vaccine awareness; iii) both ensuring influenza vaccine supply and developing influenza vaccine awareness and iv) control arm with no intervention. Both quantitative and qualitative approaches will be applied to assess the intervention effect. We will estimate the Difference in Differences (DID) with 95% CI of the proportion of vaccine uptake between each intervention and control (non-intervention) arm, adjusting for the clustering effect. The qualitative data will be summarised using a framework matrix method.

Discussion

The results of this study will inform the development and implementation of a context-specific strategy to enhance influenza vaccination rates among Bangladeshi HCWs.

Trial registration

Clinicaltrials.gov NCT05521763. Version 2.0 was registered in September 2022, and the first participant enrolled in March 2022. Retrospectively registered.
Impacts of life-events on sitting, TV viewing and computer use among women from disadvantaged neighbourhoods
Authors: Nayak Minakshi , Wills Karen , Teychenne Megan , Cleland Verity
Published: September 2022

Background

Little is known about how life events such as changes in parental or employment status influence sedentary behaviour (SB). Women from disadvantaged neighbourhoods are at particular risk of poor health, therefore, in this population group this study aimed to determine between changes in parental and employment status with sitting, television viewing (TV), and computer time.

Methods

Women (18–45 years) from socioeconomically disadvantaged neighbourhoods self-reported their employment status, number of children, sitting, TV, and computer time [(baseline (n = 4349), three (n = 1912) and 5 years (n = 1560)]. Linear (sitting) and negative binomial (TV and computer time) multilevel models adjusted for confounders were used to estimate the SB association with changes in life events.

Results

Compared to women who never had children during the study period, less sitting and computer time was observed for women when number of children remained unchanged, had their first child or additional child, and fewer children (< 18 years). Less TV was observed for women when number of children remained unchanged.

Compared to women who remained employed full-time during the study period, sitting and computer time decreased among women when they decreased or increased their working hours or when remained employed part-time/not working. TV time increased among women when they decreased their working hours.

Conclusion

Among women, declines in SB were observed amongst those experiencing life events. Interventions to decrease SB may consider targeting women with no children, and future research should further explore how changes in employment type (e.g., non-manual to manual jobs) impact SB.
Public health genomics capacity assessment: readiness for large-scale pathogen genomic surveillance in Canada’s public health laboratories
Authors: Nadon C. , Croxen M. , Knox N. , Tanner J. , Zetner A. , Yoshida C. , Van Domselaar G.
Published: September 2022

Background

Along with rapid diagnostic testing, contact tracing, and public health measures, an effective pandemic response incorporates genomics-based surveillance. Large-scale SARS-CoV-2 genome sequencing is a crucial component of the global response to COVID-19. Characterizing the state of genomics readiness among Canada’s public health laboratories was necessary to inform strategic planning and deployment of capacity-building resources in the early stages of the pandemic.

Methods

We used a qualitative study design and focus group discussions, encompassing both technical and leadership perspectives, to perform an in-depth evaluation of the state of pathogen genomics readiness in Canada.

Results

We found substantial diversity in the state of readiness for SARS-CoV-2 genomic surveillance across Canada. Despite this variability, we identified common barriers and needs in the areas of specimen access, data flow and sharing, computing infrastructure, and access to highly qualified bioinformatics personnel.

Conclusions

These findings enable the strategic prioritization and deployment of resources to increase Canada’s ability to perform effective public health genomic surveillance for COVID-19 and prepare for future emerging infectious diseases. They also provide a unique qualitative research model for use in capacity building.
Computer grading of lung disease severity in patients with lymphangioleiomyomatosis referred for transplantation
Authors: Taveira-DaSilva Angelo M. , Gopalakrishnan Vissaagan , Yao Jianhua , Chen Marcus Y. , Julien-Williams Patricia , Jones Amanda M. , Pacheco-Rodriguez Gustavo , Moss Joel
Published: September 2022

Objectives

Lymphangioleiomyomatosis (LAM) patients with severe lung disease may be considered for lung transplantation. Clinical, physiologic, and quality of life data are usually employed for referral. The aim of this study was to determine whether computed tomographic measurement of lung volume occupied by cysts (cyst score) complemented clinical and physiologic data in supporting referral for transplantation.

Methods

Forty-one patients were studied. Pre-referral clinical data, pulmonary function tests, exercise testing, and high-resolution computed tomography (HRCT) scans were obtained. From HRCT, a computer-aided diagnostic program was employed to calculate cyst scores. These data were compared to those of 41 age-matched LAM patients not referred for lung transplantation.

Results

Cyst score, and % predicted FEV1 and DLCO were respectively, 48.1 ± 9.4%, 36.5 ± 9.1%, and 35.0 ± 10.7%. For the control group, cyst score, FEV1, and DLCO were respectively, 14.8 ± 8.3%, 77.2 ± 20.3%, and 66.7 ± 19.3%. Cyst score values showed a normal distribution. However, the frequency distribution of FEV1 was skewed to the right while the distribution of DLCO was bimodal. Correlations between cyst score and FEV1 and DLCO for the study group were respectively, r = − 0.319 and r = − 0.421.

Conclusions

LAM patients referred for lung transplantation had nearly 50% of lungs occupied by cysts. Correlations between cyst score and FEV1 or DLCO were weak; as shown previously, DLCO was better related to cyst number while FEV1 had a better association with cyst size. Given its normal distribution, cyst score measurements may assist in evaluation of pre-transplant severity of lung disease before referral for transplantation.
Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review
Authors: Lin Si-Hong , Zhang Ao , Li Lu-Zhen , Zhao Liang-Chen , Wu Le-Xia , Fang Can-Tu
Published: September 2022

Background

Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy.

Case presentation

A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level.

Conclusions

Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.
Qualitative evaluation of postdoctoral trainee and faculty advisor experiences within a research-intensive school of pharmacy
Authors: McLaughlin JE , Morbitzer KA , Hahn F , Minshew L , Brouwer KLR
Published: September 2022

Background

Postdoctoral trainees play a vital role in securing grant funding, building alliances, and mentoring graduate students under the guidance of a mentor who can help develop their intellectual independence. However, the experiences of postdoctoral trainees, particularly within health professions schools, is largely unexplored. The purpose of this study was to investigate the experiences of postdoctoral trainees and faculty advisors at a public four-year school of pharmacy and identify areas of opportunity to improve postdoctoral training.

Methods

Focus groups and interviews were conducted to elicit participants’ experiences, perceptions, and suggestions for improvement. Stakeholder groups included postdoctoral trainees and faculty who serve as postdoctoral advisors. Thematic coding was used to identify semantic themes, and summaries of participant perceptions were generated. Results were mapped to the identity-trajectory framework.

Results

Participants described various experiences related to intellectual growth, networking opportunities, and institutional support. In addition, participant agency was critical for developing career goals and navigating transitions. COVID-19 introduced unique challenges associated with transitioning to remote work and managing goals/motivation. Areas of opportunity were identified, such as improving infrastructure, enhancing mentoring, and enhancing communication.

Conclusion

Postdoctoral trainees play a critical role in the success of academic institutions. Scholarly endeavors that explore postdoctoral experiences, specifically those utilizing qualitative methods, can help pharmacy education better understand and meet the needs of postdoctoral trainees and faculty advisors. This study provides insight into the experiences of postdoctoral scholars and provides evidence for improving these training programs in schools of pharmacy.
Potential of selected plant extracts to control severe subacute ruminal acidosis in vitro as compared with monensin
Authors: Ahmed Mariam G. , Al-Sagheer Adham A. , El-Zarkouny Samir Z. , Elwakeel Eman A.
Published: September 2022

Background

In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 μg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined.

Results

In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times.

Conclusions

It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.
Factors influencing health workers’ compliance with the WHO intermittent preventive treatment for malaria in pregnancy recommendations in the Northern Region, Ghana
Authors: Mohammed Abdul Gafaru , Duah Dwomoh , Kenu Ernest , Nonvignon Justice , Manu Alex , Bonful Harriet Affran
Published: September 2022

Background

Although IPTp-SP is a lifesaving World Health Organization (WHO) recommended preventive intervention for pregnant women in malaria-endemic regions, IPTp-SP uptake in the Northern region of Ghana is much lower than the sub-optimal national coverage level. Assessing the extent of health workers’ compliance and its associated factors will generate valuable pointers to be targeted at the program level. The study examined the factors influencing health workers’ compliance with the WHO recommended guidelines for IPTp-SP in the Northern Region.

Methods

A cross-sectional study among 315 health workers in the Northern region was conducted. Semi-structured questionnaires were used to collect data on health workers’ sociodemographic characteristics, facility-based factors and knowledge level. Data were collected on health workers’ compliance with the recommended practices through covert observations using a checklist. Facility observations were carried out using a checklist. Crude and adjusted logistic regression were used to determine predictors of health workers’ compliance, at a 5% significance level adjusting for clustering.

Results

Of the 315 health workers studied, the median age was 29 years (26–34 years). Females constituted (80.5%; 252) of the 313 workers. The majority (47.4%;148) of the 312 health workers were midwives. Overall, 56.2% (CI 51.0 – 62.0) were adequately complying with the recommended guidelines. Lower levels of compliance were recorded in health centres 15.6% (5.0 – 33.0) and CHPS compounds 21.2% (11.0 – 35.0). The factors associated with compliance included health workers’ knowledge (aOR = 7.64, 95% CI 4.21 – 13.87, p < 0.001), job satisfaction (aOR 10.87, 95% CI 7.04 – 16.79, p < 0.001), in-service training (aOR 10.11, 95% CI 4.53 – 22.56, p < 0.001), supervision (aOR 4.01, 95% CI 2.09 – 7.68, p < 0.001), availability of job aids (aOR 3.61, 95% CI 2.44 – 5.35, p < 0.001), health workers experience (aOR = 10.64, 95% CI 5.99 – 18.91, p < 0.001) and facility type (aOR 0.03, 95% CI 0.01–0.07, p < 0.001).

Conclusion

Compliance with the recommended IPTp-SP guidelines is suboptimal in the region, with lower-level health facilities recording the least compliance levels. Health centres and CHPS facilities should be prioritized in distributing limited resources to improve health worker quality of care for antenatal care clients.
Application of MOF-based nanotherapeutics in light-mediated cancer diagnosis and therapy
Authors: Zhao Dan , Zhang Wang , Yu Shuang , Xia Si-Lei , Liu Ya-Nan , Yang Guan-Jun
Published: September 2022

Light-mediated nanotherapeutics have recently emerged as promising strategies to precisely control the activation of therapeutic reagents and imaging probe both in vitro and in vivo, largely ascribed to their unique properties, including minimally invasive capabilities and high spatiotemporal resolution. Nanoscale metal–organic frameworks (NMOFs), a new family of hybrid materials consisting of metal attachment sites and bridging ligands, have been explored as a new platform for enhanced cancer diagnosis and therapy due to their tunable size, modifiable surface, good biocompatibility, high agent loading and, most significantly, their ability to be preferentially deposited in tumors through enhanced permeability and retention (EPR). Especially the light-driven NMOF-based therapeutic platform, which not only allow for increased laser penetration depth and enhanced targeting, but also enable imaging-guided or combined treatments. This review provides up-to-date developments of NMOF-based therapeutic platforms for cancer treatment with emphasis on light-triggered therapeutic strategies and introduces their advances in cancer diagnosis and therapy in recent years.

Graphic Abstract
Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure
Authors: Xu Jin , Chen Wen-jie , Wang Zhan , Xin Ming-yuan , Gao Shen-han , Liu Wen-jing , Wang Kai-kun , Ma Jing-wei , Yan Xin-zong , Ren Yan-ming
Published: September 2022

Background

Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive.

Methods

In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia.

Results

The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist.

Conclusions

Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.
Surgical staging of apparent early-stage ovarian mucinous carcinoma
Authors: Yuan Zhen , Zhang Ying , Cao Dongyan , Shen Keng
Published: September 2022

Objectives

The aim of the study was to explore the rate of upstaging after complete surgical staging among patients with apparent FIGO stage I ovarian mucinous carcinoma.

Methods

Ovarian mucinous carcinoma patients with surgical treatment at the Peking Union Medical College Hospital between October 2020 and January 1994 were retrospectively reviewed.

Results

In total, 163 patients were included in this study. Surgical restaging was performed in 89 patients after initial incomplete surgical staging, and one-step complete surgical staging was performed in 74 patients. Among these initially incompletely staged patients, residual tumors were found in 16 patients (16/89, 17.9%). Among the 19 patients with apparent FIGO stage IA, no patient was found to have residual tumors after incomplete staging surgery, according to the final pathology result of restaging surgery. Ovarian cystectomy (OR=4.932, 95% CI= 1.347–18.058, P=0.016) was an independent risk factor for residual tumors after incomplete staging surgery. Among all 163 patients, upstaging occurred in 15 patients (15/163, 9.2%). Among 44 apparent FIGO stage IA patients, no patient was upstaged to FIGO II–IVB. Moreover, both a history of ovarian mucinous tumor (OR=4.745, 95% CI= 1.132–19.886, P=0.033) and bilateral ovary involvement (OR=9.739, 95% CI= 2.016–47.056, P=0.005) were independent risk factors for upstaging to FIGO stage II–IVB.

Conclusions

For patients with apparent FIGO stage IA disease, the possibility of residual tumors and upstaging is relatively low. For patients with cystectomy, bilateral mucinous carcinomas, or a history of ovarian mucinous tumors, complete staging surgery maintains greater significance.
Overexpression of PBK/TOPK relates to poor prognosis of patients with breast cancer: a retrospective analysis
Authors: Qiao Liang , Ba Jinling , Xie Jiping , Zhu Ruiping , Wan Yi , Zhang Min , Jin Zeyu , Guo Zicheng , Yu Jiaxuan , Chen Sijing , Yao Yongqiang
Published: September 2022

Background

PDZ-binding kinase/T-lymphokine-activated killer cell-derived protein kinase (PBK/TOPK) is a potential prognostic indicator for patients with breast cancer. The objective of the present study was to explore the relationship between PBK/TOPK expression and clinicopathological indicators as well as the survival of patients with breast cancer.

Methods

Immunohistochemical staining was used to detect the expression of PBK/TOPK in 202 cases of breast cancer tissues. The relationship between PBK/TOPK and clinicopathological parameters was evaluated using Spearman’s rank-order correlation. The difference in PBK/TOPK expression among different molecular types was analyzed with the chi-square test. Kaplan-Meier analysis was used to create a survival curve and the log rank test was used to analyze the overall survival (OS) and disease-free survival (DFS). Prognostic correlation was assessed using univariate and multivariate Cox regression analyses.

Results

Among 202 breast cancer samples, PBK/TOPK was expressed (“+” and “++”) in 182 samples (90.1%). In addition, the histological grade, TNM stages, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 were positively associated with PBK/TOPK expression. With regard to the molecular type, the expression of PBK/TOPK is different. The expression level of PBK/TOPK was negatively correlated with both the OS and DFS of breast cancer patients. The difference in the above results is meaningful (P < 0.05).

Conclusions

PBK/TOPK is overexpressed in breast cancer, and the expression is closely related to the clinicopathological characteristics of the disease. Breast cancer patients with high expression of PBK/TOPK have a poor prognosis. Therefore, healthcare providers can optimize breast cancer management using this indicator.
Response to comment on “Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma”
Authors: Xie Yu-Fei , Liu Ye-Ling , Guo Xu-Guang
Published: September 2022

This article is a response to “comment on ‘Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma’” by Gopal Sharma. With this comment, author highlighted the strengths and limitations of the study. With this response, we respond to this and make a comparison of the results and conclusions.
Development and validation of a pre- and intra-operative scoring system that distinguishes between non-advanced and advanced axillary lymph node metastasis in breast cancer with positive sentinel lymph nodes: a retrospective study
Authors: Murata Takeshi , Watase Chikashi , Shiino Sho , Kurita Arisa , Ogawa Ayumi , Jimbo Kenjiro , Iwamoto Eriko , Yoshida Masayuki , Takayama Shin , Suto Akihiko
Published: September 2022

Background

There are currently no scoring-type predictive models using only easily available pre- and intraoperative data developed for assessment of the risk of advanced axillary lymph node metastasis (ALNM) in patients with breast cancer with metastatic sentinel lymph nodes (SLNs). We aimed to develop and validate a scoring system using only pre- and intraoperative data to distinguish between non-advanced (≤ 3 lymph nodes) and advanced (> 3 lymph nodes) ALNM in patients with breast cancer with metastatic SLNs.

Methods

We retrospectively identified 804 patients with breast cancer (cT1-3cN0) who had metastatic SLNs and had undergone axillary lymph node dissection (ALND). We evaluated the risk factors for advanced ALNM using logistic regression analysis and developed and validated a scoring system for the prediction of ALNM using training (n = 501) and validation (n = 303) cohorts, respectively. The predictive performance was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration plots.

Results

Ultrasound findings of multiple suspicious lymph nodes, SLN macrometastasis, the ratio of metastatic SLNs to the total number of SLNs removed, and the number of metastatic SLNs were significant risk factors for advanced ALNM. Clinical tumor size and invasive lobular carcinoma were of borderline significance. The scoring system based on these six variables yielded high AUCs (0.90 [training] and 0.89 [validation]). The calibration plots of frequency compared to the predicted probability showed slopes of 1.00 (training) and 0.85 (validation), with goodness-of-fit for the model. When the cutoff score was set at 4, the negative predictive values (NPVs) of excluding patients with advanced ALNM were 96.8% (training) and 96.9% (validation). The AUC for predicting advanced ALNM using our scoring system was significantly higher than that predicted by a single independent predictor, such as the number of positive SLNs or the proportion of positive SLNs. Similarly, our scoring system also showed good discrimination and calibration ability when the analysis was restricted to patients with one or two SLN metastases.

Conclusion

Our easy-to-use scoring system can exclude advanced ALNM with high NPVs. It may contribute to reducing the risk of undertreatment with adjuvant therapies in patients with metastatic SLNs, even if ALND is omitted.
The in-vitro effect of gonadotropins’ type and combination on Granulosa cells gene expressions
Authors: Yung Yuval , Aizer Adva , Tieb Sarah , Maydan Sharon Avhar , Maman Ettie , Haham Lilach Marom , Haas Jigal , Orvieto Raoul
Published: September 2022

Objective

Nowadays, different modes and timing of GnRH-agonist combined with hCG trigger, for final follicular maturation, have been described. While LH + FSH are the naturally occurring final follicular maturation trigger, hCG is commonly use during stimulated cycle, and recently the introduction of the Dual/Double trigger combines LH + FSH + hCG. In the present study we aim to investigate the messenger RNA (mRNA) expression of reproduction-related genes in human granulosa cells (GCs) exposed to the aforementioned different types and combinations of gonadotropins.

Material and methods

Mural GCs were obtained from follicular fluid aspirated during IVF protocol. GCs were seeded in culture for 4 days with daily medium exchange followed by administration of either hCG (1 U/ml); FSH (1 U/ml) and LH (8 U/ml); or hCG (1 U/ml) and FSH (1 U/ml) and LH (8 U/ml) for 16 h. mRNA was purified from harvested GCs and gene expression was quantitative by qPCR.

Main outcome measures

The expression of genes related to steroidogenesis (StAR/ CYP19) and oocyte maturation (COX2/Amphiregulin) in cultured GCs.

Results

The Dual/Double trigger (LH + FSH + hCG) showed higher activation of steroidogenesis (StAR/CYP19) and maturation (COX2/Amphiregulin) as compared to the naturally occurring trigger (LH + FSH) and the hCG triggers. Moreover, while the naturally occurring trigger (LH + FSH) activated maturation significantly and more intensely than the hCG trigger, no in between group differences were observed with regards to steroidogenic related genes.

Conclusions

Our findings are in agreement with clinical experience, demonstrating the superiority of the double/dual (LH + FSH + hCG) trigger over the naturally occurring and the hCG triggers.
A global overview of healthcare workers’ turnover intention amid COVID-19 pandemic: a systematic review with future directions
Authors: Poon Yuan-Sheng Ryan , Lin Yongxing Patrick , Griffiths Peter , Yong Keng Kwang , Seah Betsy , Liaw Sok Ying
Published: September 2022

Background

Globally, the health workforce has long suffered from labour shortages. This has been exacerbated by the workload increase caused by the COVID-19 pandemic. Major collapses in healthcare systems across the world during the peak of the pandemic led to calls for strategies to alleviate the increasing job attrition problem within the healthcare sector. This turnover may worsen given the overwhelming pressures experienced by the health workforce during the pandemic, and proactive measures should be taken to retain healthcare workers. This review aims to examine the factors affecting turnover intention among healthcare workers during the COVID-19 pandemic.

Methods

A mixed studies systematic review was conducted. The PubMed, Embase, Scopus, CINAHL, Web of Science and PsycINFO databases were searched from January 2020 to March 2022. The Joanna Briggs Institute’s Critical Appraisal Tools and the Mixed Methods Appraisal Tool version 2018 were applied by two independent researchers to critically appraise the methodological quality. Findings were synthesised using a convergent integrated approach and categorised thematically.

Results

Forty-three studies, including 39 quantitative, two qualitative and two mixed methods studies were included in this review. Eighteen were conducted in the Middle East, ten in the Americas, nine in the Asia–Pacific region and six in Europe. Nurses (n = 35) were included in the majority of the studies, while physicians (n = 13), allied health workers (n = 11) and healthcare administrative or management staff (n = 7) were included in a smaller proportion. Five themes emerged from the data synthesis: (1) fear of COVID-19 exposure, (2) psychological responses to stress, (3) socio-demographic characteristics, (4) adverse working conditions, and (5) organisational support.

Conclusions

A wide range of factors influence healthcare workers’ turnover intention in times of pandemic. Future research should be more focused on specific factors, such as working conditions or burnout, and specific vulnerable groups, including migrant healthcare workers and healthcare profession minorities, to aid policymakers in adopting strategies to support and incentivise them to retain them in their healthcare jobs.
Which patients bring the most costs for hospital? A study on the cost determinants among COVID-19 patients in Iran
Authors: Ramezani-Doroh Vajihe , Tapak Leili , Hamidi Yadollah , Bashirian Saeid , Soltanian Ali Reza , Motaghed Mahyar , Ghelichkhani Ebrahim , Talebi-Ghane Elaheh
Published: September 2022

Background

Accurate information on the cost determinants in the COVID-19 patients could provide policymakers a valuable planning tool for dealing with the future COVID-19 crises especially in the health systems with limited resources.

Objectives

This study aimed to determine the factors affecting direct medical cost of COVID-19 patients in Hamadan, the west of Iran.

Methods

This study considered 909 confirmed COVID-19 patients with positive real-time reverse-transcriptase polymerase-chain-reaction test which were hospitalized from 1 March to 31 January 2021 in Farshchian (Sina) hospital in Hamadan, Iran. A checklist was utilized to assess the relationship of demographic characteristics, clinical presentation, medical laboratory findings and the length of hospitalization to the direct hospitalization costs in two groups of patients (patients with hospitalization ≤ 9 days and > 9 days). Statistical analysis was performed using chi-square, median test and multivariable quantile regression model at 0.05 significance levels with Stata 14 software program.

Results

The median cost of hospitalization in patients was totally 134.48 dollars (Range: 19.19–2397.54) and respectively 95.87 (Range: 19.19–856.63) and 507.30 dollars (Range: 68.94–2397.54) in patients with hospitalization ≤ 9 days and > 9 days. The adjusted estimates presented that in patients with 9 or less hospitalization days history of cardiovascular disease, wheezing pulmonary lung, SPO2 lower than 90%, positive CRP, LDH higher than 942 U/L, NA lower than 136 mEq/L, lymphosite lower than 20% and patients with ICU experience had significantly positive relationship to the median of cost. Moreover, in patients with more than 9 hospitalization days, history of cardiovascular disease and ICU experience was statistically positive association and age older than 60 years and WBC lower than 4.5 mg/dL had statistically negative relationship to the median of hospitalization cost.

Conclusion

As the length of hospital stay, which can be associated with the severity of the disease, increases, health systems become more vulnerable in terms of resource utilization, which in turn can challenge their responsiveness and readiness to meet the specialized treatment needs of individuals.
Features of effective staff training programmes within school-based interventions targeting student activity behaviour: a systematic review and meta-analysis
Authors: Ryan Mairead , Alliott Olivia , Ikeda Erika , Luan Jian’an , Hofmann Riikka , van Sluijs Esther
Published: September 2022

Background

Evaluations of school-based activity behaviour interventions suggest limited effectiveness on students’ device-measured outcomes. Teacher-led implementation is common but the training provided is poorly understood and may affect implementation and student outcomes. We systematically reviewed staff training delivered within interventions and explored if specific features are associated with intervention fidelity and student activity behaviour outcomes.

Methods

We searched seven databases (January 2015–May 2020) for randomised controlled trials of teacher-led school-based activity behaviour interventions reporting on teacher fidelity and/or students’ device-measured activity behaviour. Pilot, feasibility and small-scale trials were excluded. Study authors were contacted if staff training was not described using all items from the Template for Intervention Description and Replication reporting guideline. Training programmes were coded using the Behaviour Change Technique (BCT) Taxonomy v1. The Effective Public Health Practice Project tool was used for quality assessment. Promise ratios were used to explore associations between BCTs and fidelity outcomes (e.g. % of intended sessions delivered). Differences between fidelity outcomes and other training features were explored using chi-square and Wilcoxon rank-sum tests. Random-effects meta-regressions were performed to explore associations between training features and changes in students’ activity behaviour.

Results

We identified 68 articles reporting on 53 eligible training programmes and found evidence that 37 unique teacher-targeted BCTs have been used (mean per programme = 5.1 BCTs; standard deviation = 3.2). The only frequently identified BCTs were ‘Instruction on how to perform the behaviour’ (identified in 98.1% of programmes) and ‘Social support (unspecified)’ (50.9%). We found moderate/high fidelity studies were significantly more likely to include shorter (≤6 months) and theory-informed programmes than low fidelity studies, and 19 BCTs were independently associated with moderate/high fidelity outcomes. Programmes that used more BCTs (estimated increase per additional BCT, d: 0.18; 95% CI: 0.05, 0.31) and BCTs ‘Action planning’ (1.40; 0.70, 2.10) and ‘Feedback on the behaviour’ (1.19; 0.36, 2.02) were independently associated with positive physical activity outcomes (N = 15). No training features associated with sedentary behaviour were identified (N = 11).

Conclusions

Few evidence-based BCTs have been used to promote sustained behaviour change amongst teachers in school-based activity behaviour interventions. Our findings provide insights into why interventions may be failing to effect student outcomes.

Trial registration

PROSPERO registration number: CRD42020180624
The potential impact of a probiotic: Akkermansia muciniphila in the regulation of blood pressure—the current facts and evidence
Authors: Lakshmanan Arun Prasath , Murugesan Selvasankar , Al Khodor Souhaila , Terranegra Annalisa
Published: September 2022

Akkermansia muciniphila (A. muciniphila) is present in the human gut microbiota from infancy and gradually increases in adulthood. The potential impact of the abundance of A. muciniphila has been studied in major cardiovascular diseases including elevated blood pressure or hypertension (HTN). HTN is a major factor in premature death worldwide, and approximately 1.28 billion adults aged 30–79 years have hypertension. A. muciniphila is being considered a next-generation probiotic and though numerous studies had highlighted the positive role of A. muciniphila in lowering/controlling the HTN, however, few studies had highlighted the negative impact of increased abundance of A. muciniphila in the management of HTN. Thus, in the review, we aimed to discuss the current facts, evidence, and controversy about the role of A. muciniphila in the pathophysiology of HTN and its potential effect on HTN management/regulation, which could be beneficial in identifying the drug target for the management of HTN.