bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modified Iterative Learning Control Approach for the Active Suppression of Rotor Vibration Induced by Coupled Unbalance and Misalignment
Authors: Bao Yifan , Yao Jianfei , Scarpa Fabrizio , Li Yan
Published: February 2024

This paper proposes a modified iterative learning control (MILC) periodical feedback-feedforward algorithm to reduce the vibration of a rotor caused by coupled unbalance and parallel misalignment. The control of the vibration of the rotor is provided by an active magnetic actuator (AMA). The iterative gain of the MILC algorithm here presented has a self-adjustment based on the magnitude of the vibration. Notch filters are adopted to extract the synchronous (1 × Ω) and twice rotational frequency (2 × Ω) components of the rotor vibration. Both the notch frequency of the filter and the size of feedforward storage used during the experiment have a real-time adaptation to the rotational speed. The method proposed in this work can provide effective suppression of the vibration of the rotor in case of sudden changes or fluctuations of the rotor speed. Simulations and experiments using the MILC algorithm proposed here are carried out and give evidence to the feasibility and robustness of the technique proposed.
N6-methyladenosine-modified circ_104797 sustains cisplatin resistance in bladder cancer through acting as RNA sponges
Authors: Xu Congjie , Zhou Jiaquan , Zhang Xiaoting , Kang Xinli , Liu Shuan , Song Mi , Chang Cheng , Lin Youtu , Wang Yang
Published: February 2024

Background

Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments.

Methods

Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies.

Results

Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance.

Conclusions

Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management.
An immunogenic cell death-related gene expression signature in predicting prognosis of pancreatic ductal adenocarcinoma
Authors: Wang Xiaobo , Ren Tianxiang , Liao Chuting , Xie Yong , Cao Jing
Published: February 2024

Background

Immunogenic cell death (ICD) has been identified as regulated cell death, which is sufficient to activate the adaptive immune response. This study aimed to research ICD-related genes and create a gene model to predict pancreatic ductal adenocarcinoma (PAAD) patients’ prognosis.

Methods

The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. The PAAD samples were classified into two subtypes based on the expression levels of ICD-related genes using consensus clustering. Based on the differentially expressed genes (DEGs), a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the prognosis of PAAD patients. Moreover, colony formation assay was performed to confirm the prognostic value of those genes.

Results

We identified two ICD cluster by consensus clustering, and found that the the ICD-high group was closely associated with immune-hot phenotype, favorable clinical outcomes. We established an ICD-related prognostic model which can predict the prognosis of pancreatic ductal adenocarcinoma. Moreover, depletion of NT5E, ATG5, FOXP3, and IFNG inhibited the colony formation ability of pancreatic cancer cell.

Conclusion

We identified a novel classification for PAAD based on the expression of ICD-related genes, which may provide a potential strategy for therapeutics against PAAD.
Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study
Authors: Musafiri Tumusime , Kamali Innocent , Kayihura Casmille , de la Paix Gakuru Jean , Nyirahabihirwe Francoise , Nizeyimana Esdras , Kandamage Pilar , Habinshuti Placide , Sekagarura Raymond , Makuza Jean Damascene , Karema Nadine , Serumondo Janvier , Ntakirutimana Theoneste , Ndahimana Jean d’Amour , Barnhart Dale A.
Published: February 2024

Introduction

Rwanda’s Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative “micro-elimination” strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care.

Methods

This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients’ clinical programs and hepatitis B and C, and reported cascade of care for the two diseases.

Results

Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients < 40 years (2.4%). Increased age was significantly associated with anti-HCV (12.0% among patients ≥ 70 years). Of the 148 individuals who screened positive for HbsAg, 123 had viral load results returned, 101 had detectable viral loads (median viral load: 451 UI/mL), and 12 were linked to care. Of the 507 individuals who screened positive for anti-HCV, 468 had their viral load results returned (median viral load: 1,130,000 UI/mL), 304 had detectable viral loads, and 230 were linked to care.

Conclusion

Anti-HCV prevalence among Rwandan patients with NCD was high, likely due to their older age. NCD-HCV co-infected patients had high HCV viral loads and may be at risk of poor outcomes from hepatitis C. Hepatitis C micro-elimination campaigns among NCD patients are a feasible and acceptable strategy to enhance case detection in this high-prevalence population with elevated viral loads and may support linkage to care for hepatitis C among elderly populations.
Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia
Authors: Li Zong-Ze , Yan Xia-Lin , Zhang Zhao , Chen Jiong-Lai , Li Jiang-Yuan , Bao Jing-Xia , Ru Jia-Tong , Wang Jia-Xin , Chen Xiao-Lei , Shen Xian , Huang Dong-Dong
Published: February 2024

Background

Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia.

Methods

From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery.

Results

A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151–3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421–3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186–2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival.

Conclusion

GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.
A nomogram based on peripheral lymphocyte for predicting 8-year survival in patients with prostate cancer: a single-center study using LASSO-cox regression
Authors: Chen Jiayi , Yu Feng , He Ganyuan , Hao Wenke , Hu Wenxue
Published: February 2024

Purpose

The purpose of this study was to develop a functional clinical nomogram for predicting 8-year overall survival (OS) of patients with prostate cancer (PCa) primary based on peripheral lymphocyte.

Patients and methods

Using data from a single-institutional registry of 94 patients with PCa in China, this study identified and integrated significant prognostic factors for survival to build a nomogram. The discriminative ability was measured by concordance index (C-index) and ROC curves (Receiver Operating Characteristic Curves). And the predictive accuracy was measured by the calibration curves. Decision curve analyses (DCA) was used to measure the clinical usefulness.

Results

A total of 94 patients were included for analysis. Five independent prognostic factors were identified by LASSO-Cox regression and incorporated into the nomogram: age, the T stage, the absolute counts of peripheral CD3(+)CD4(+) T lymphocytes, CD3(-)CD16(+)CD56(+) NK cells and CD4(+)/CD8(+) ratio. The area under the curve (AUC) values of the predictive model for 5-, 8-, and 10-year overall survival were 0.81, 0.76, and 0.73, respectively. The calibration curves for probability of 5-,8- and 10-year OS showed optimal agreement between nomogram prediction and actual observation. The stratification into different risk groups allowed significant distinction. DCA indicated the good clinical application value of the model.

Conclusion

We developed a novel nomogram that enables personalized prediction of OS for patients diagnosed with PCa. This finding revealed a relative in age and survival rate in PCa, and a more favorable prognosis in patients exhibiting higher levels of CD4 + T, CD4+/CD8 + ratio and CD3(-)CD16(+)CD56(+) NK cells specifically. This clinically applicable prognostic model exhibits promising predictive capabilities, offering valuable support to clinicians in informed decision-making process.
Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)
Authors: Lim Sung Hee , Lee Keun-Wook , Kim Jae-Joon , Im Hyeon-Su , Kim In-Ho , Han Hye Sook , Koo Dong-Hoe , Cho Jang Ho , Maeng Chi Hoon , Lee Min-Young , Lee Hyo Jin , Kim Jwa Hoon , Park Sang Gon , Jung Joo Young , Shin Seong-Hoon , Kim Ki Hyang , Kim Hyeyeong , Oh So Yeon , Kang Minsu , Jung Minkyu , Rha Sun Young
Published: February 2024

Background

Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC.

Methods

We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan).

Results

A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy.

Conclusions

No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.

Trial registration

This study was registered in the Clinical Trial Registry of Korea (https://cris.nih.go.kr: KCT 0007732).
Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy
Authors: Chen Yonghe , Chen Xiaojiang , Lin Yi , Zhang Shenyan , Zhou Zhiwei , Peng Junsheng
Published: February 2024

Purpose

This study assesses the metastasis rate of the key distal lymph nodes (KDLN) that are not routinely dissected in proximal gastrectomy, aiming to explore the oncological safety of proximal gastrectomy for upper gastric cancer who underwent neoadjuvant chemotherapy.

Methods

We analyzed a cohort of 150 patients with proximal locally advanced gastric cancer (cT3/4 before chemotherapy) from two high-volume cancer centers in China who received preoperative neoadjuvant chemotherapy (NAC) and total gastrectomy with lymph node dissection. Metastasis rate of the KDLN (No.5/6/12a) and the risk factors were analyzed.

Results

Key distal lymph node metastasis was detected in 10% (15/150) of patients, with a metastasis rate of 6% (9/150) in No. 5 lymph nodes, 6.7% (10/150) in No. 6 lymph nodes, and 2.7% (2/75) in No. 12a lymph nodes. The therapeutic value index of KDLN as one entity is 5.8. Tumor length showed no correlation with KDLN metastasis, while tumor regression grade (TRG) emerged as an independent risk factor (OR: 1.47; p-value: 0.04). Of those with TRG3 (no response to NAC), 80% (12/15) was found with KDLN metastasis.

Conclusion

For cT3/4 proximal locally advanced gastric cancer patients, the risk of KDLN metastasis remains notably high even after NAC. Therefore, proximal gastrectomy is not recommended; instead, total gastrectomy with thorough distal lymphadenectomy is the preferred surgical approach.
Risk factors and scores for prediction of coronary artery aneurysms in Kawasaki disease: a European monocentric study
Authors: La Vecchia Adriano , Stracquadaino Rita , Mauri Lucia , Baselli Lucia Augusta , Abdallah Rozan , Cucchetti Martina , Colli Anna Maria , Agostoni Carlo , Dellepiane Rosa Maria
Published: February 2024

Background

Japanese Kawasaki disease (KD) risk scores cannot be adopted in non-Japanese patients. In North American populations a baseline coronary artery Z-score > 2 and the Son score are associated with coronary artery aneurysms (CAAs) at 4 and 8 weeks from disease onset. In European populations, the Kawanet and Kawanet-echo scores are associated with intravenous immunoglobulin resistance. This study aims to evaluate the association between KD risk scores and baseline coronary artery Z-scores with CAAs at one, two, and six months in a European population.

Methods

Historical cohort study of all the children diagnosed with KD in a tertiary care hospital in Milan, Italy, between 1st January 2015 and 31st May 2021. Univariate and multivariate (adjusting for age and corticosteroid therapy) logistic regression analyses were used to study the association between the risk scores, a baseline Z-score ≥ 2 and ≥ 2.5 with CAAs.

Results

Eighty-nine patients were diagnosed with KD at our Centre, and 12 were excluded based on the exclusion criteria. We included 77 patients, 51 (66%) males, and 26 (34%) females, with a median age at presentation of 27 months (IQR 13–46). A baseline Z-score ≥ 2 was correlated with CAAs at one and two-month follow-ups (odds ratio (OR) 10, 95% confidence interval (CI) 2–72, and OR 18, CI 3-357) but not at six-month follow-up. The Son score showed an association with one and two-month follow-up CAAs (OR 3, CI 1.3-7, and OR 3, CI 1.3-8) but not with a six-month follow-up.

Conclusions

Patients with a baseline Z-score ≥ 2 are at higher risk for CAAs in the long term. The Son score should be tested in larger European samples. Further studies should keep the observational periods longer than 8 weeks from KD onset.
Subjective memory complaints and medication adherence among hypertensive Korean older adults with multimorbidity: mediating effect of depression and social support
Authors: Kim Jeong Sun , Kim Eunji
Published: February 2024

Background & Aim(s)

Medication adherence (MA) is a key factor in maintaining adequate blood pressure and preventing complications. However, some older adults experience difficulties in taking medicine properly due to declines in cognitive function. Although subjective memory complaints (SMC) are recognized as early markers of cognitive impairment, previous studies concerning the relationship between MA and cognitive function have focused only on objective cognitive function. Furthermore, while depression has a high correlation with SMC, low MA, and social support, there is limited evidence on their relationship. This study aims to understand the effect of SMC on MA and the mediating effect of depression and social support.

Method(s)

This study is a descriptive cross-sectional investigation. A sample of 195 community-dwelling hypertensive older adults with multimorbidity from 3 community senior centers in Gwangju, South Korea were recruited through convenience sampling. Data was collected through face-to-face survey from January to March 2018. The PROCESS macro v4.2 program [Model 6] was used to analyze the mediating effect of depression and social support in the relationship between SMC and MA. Data analysis was performed using SPSS/WIN 26.0 and STATA MP 17.0.

Results

The average MA was 6.74. There were significant differences in MA according to awareness of prescribed drugs, awareness of side effects, insomnia, and healthcare accessibility. SMC was positively correlated with depression, while social support and MA were negatively correlated. While depression was a significant mediator of the effect of SMC on MA, the mediating effect of social support was not significant. The multiple mediation effect of depression and social support was not significant.

Conclusion

The results suggest that medication management of older adults in community settings should be accompanied by a comprehensive health assessment of associated factors. Health professionals should explore strategies to improve memory as well as prevent and alleviate depression to increase MA among hypertensive older adults with multimorbidity.
Evaluation of a school-based health education program on hepatitis B virus infection prevention practice in rural South-Western, Nigeria
Authors: Olaoye Titilayo , Osie-Efietie Blessing , Ogunsanmi Ololade O. , Mustapha Adebayo M. , Asekun-Olarinmoye Ifeoluwapo , Atulomah Nnodimele Onuigbo
Published: February 2024

Background

Hepatitis B virus (HBV) infection prevention is most effective early in childhood with vaccination programme. However, where this is missed, primary prevention modes of intervention become an alternative recommendation to be considered before the occurrence of risk exposure to the virus. This study sought to evaluate outcomes of a theory-based HBV infection prevention educational intervention among students from four selected secondary schools in Ogun state, Nigeria.

Methodology

A quasi-experimental design enrolling 256 consenting secondary school students from four schools in Ogun state randomized into three intervention schools consisting teacher-instructed (E1), peer-directed (E2) and combination of the two (E3) respectively with a control group ( C) was implemented. The theory-based educational intervention was for six weeks with follow-up period of 8 weeks. A 66-item validated instrument was used to collect data at three reference points and response items for variables in the study were transformed into weighted-aggregate scores of mean and standard deviation of HBV infection prevention practice of participants. Statistical analysis of ANOVA, paired-sample t-test and Cohen’s D Effect Size (ES) was used to quantify the changes produced by the intervention on the outcome variable at 5% level of significance.

Results

At baseline, there was no significant difference (p > 0.05) in the mean HBV infection prevention practice scores between the four groups E1 (17.21 ± 3.03), E2 (15.57 ± 1.90), E3 (17.90 ± 3.10), and C (15.20 ± 2.44). However, at 14th week follow up, there was observed significant differences in mean scores of HBV infection prevention practices between all four groups E1 (23.09 ± 2.4), E2 (22.6 ± 3.6), E3 (23.82 ± 2.3), and C (15.25 ± 2.4). Paired-sample t-test conducted demonstrated significant differences between baseline and 14th week follow up for E1 (17.21 ± 3.07 and 23.18 ± 2.9; p = 0.001), E2(15.57 ± 1.90 and 23.53 ± 3.12; p = 0.001), E3(17.90 ± 3.10 and 25.1 ± 2.6; p < 0.001), but not for C (15.20 ± 2.44 and 15.25 ± 2.4; p = 0.92), with most significant impact (ES(95%CI) on HBV infection prevention practices observed for E2(3.106 95%CI: [2.66 to 3.55; p = 0.001]). Importantly, the participants in E2 showed more improvement in prevention practices than their counterparts from E1, E3, and control. Therefore, the intervention demonstrated proof-of-concept in facilitating behavior modification expected. Peer education can be utilized as a strategy to promote Hepatitis B infection prevention practices among adolescents.
Comparison of actigraphy with a sleep protocol maintained by professional caregivers and questionnaire-based parental judgment in children and adolescents with life-limiting conditions
Authors: Kubek Larissa Alice , Claus Benedikt , Zernikow Boris , Wager Julia
Published: February 2024

Background

Actigraphy offers a promising way to objectively assess pediatric sleep. Aim of the study was investigating the extent to which actigraphy used in children and adolescents with life-limiting conditions is consistent with two other measures of sleep diagnostics.

Methods

In this monocentric prospective study N = 26 children and adolescents with life-limiting conditions treated on a pediatric palliative care unit were assessed. For three consecutive nights they wore an actigraph; the 24-hours sleep protocol documented by nurses and the Sleep Screening for Children and Adolescents with Complex Chronic Conditions (SCAC) answered by parents were analyzed. Patient characteristics and the parameters sleep onset, sleep offset, wake after sleep onset (WASO), number of wake phases, total sleep time (TST) and sleep efficiency (SE) were descriptively examined. Percentage bend correlations evaluated the three measures’ concordance.

Results

Descriptively, and except for the number of waking episodes, the different measures’ estimations were comparable. Significant correlations existed between actigraphy and the sleep protocol for sleep onset (r = 0.83, p = < 0.001) and sleep offset (r = 0.89, p = < 0.001), between actigraphy and SCAC for SE (r = 0.59, p = 0.02).

Conclusion

Agreement of actigraphy with the focused sleep measures seems to be basically given but to varying degrees depending on the considered parameters.
Improving undergraduate education of occupational health and occupational medicine appling massive open online courses & problem-based learning
Authors: Ding Rui , Cheng Han
Published: February 2024

Background

The learning of Occupational Health and Occupational Medicine in undergraduate college students in China has been hindered by various factors. This study aimed to explore the effects of the application of Massive Open Online Courses (MOOC) & Problem-based learning (PBL) in the learning of Occupational Health and Occupational Medicine in undergraduate college students in China.

Methods

Students enrolled in 2017 and 2018 were categorized in the control group and study group, and received PBL learning and MOOC + PBL learning, respectively. The effects of learning were assessed by scores of final exam, satisfaction degree of students, and feedbacks.

Results

The mean score of the final exam was not significantly different between the two groups. However, the further comparison by levels of scores showed that the percentages of good and excellent were both significantly higher in the study group than control group. The overall satisfaction degree was significantly higher in the study group than control group. In addition, the scores of the 3 dimensions of satisfaction degree, i.e. learning preparation, learning process, and learning effect, were all significantly higher in the study group than control group. The feedbacks of the students showed that they thought MOOC + PBL learning could better improve the learning efficacy, despite a substantial proportion of students reported that MOOC + PBL learning more time-consuming.

Conclusions

The findings showed that the combination of MOOC and PBL in the learning of Occupational Health and Occupational Medicine is an effective method capable of improving the learning efficacy in college students of Prophylactic Medicine. Further efforts are needed to optimize the MOOC platform to provide a friendlier interface.
Factors predictive of hospital admission for children via emergency departments in Australia and Sweden: an observational cross-sectional study
Authors: Crilly Julia , Sweeny Amy , Muntlin Åsa , Green David , Malyon Lorelle , Christofis Luke , Higgins Malcolm , Källberg Ann-Sofie , Dellner Sara , Myrelid Åsa , Djärv Therese , Göransson Katarina E.
Published: February 2024

Background

Identifying factors predictive of hospital admission can be useful to prospectively inform bed management and patient flow strategies and decrease emergency department (ED) crowding. It is largely unknown if admission rate or factors predictive of admission vary based on the population to which the ED served (i.e., children only, or both adults and children). This study aimed to describe the profile and identify factors predictive of hospital admission for children who presented to four EDs in Australia and one ED in Sweden.

Methods

A multi-site observational cross-sectional study using routinely collected data pertaining to ED presentations made by children < 18 years of age between July 1, 2011 and October 31, 2012. Univariate and multivariate analysis were undertaken to determine factors predictive of hospital admission.

Results

Of the 151,647 ED presentations made during the study period, 22% resulted in hospital admission. Admission rate varied by site; the children’s EDs in Australia had higher admission rates (South Australia: 26%, Queensland: 23%) than the mixed (adult and children’s) EDs (South Australia: 13%, Queensland: 17%, Sweden: 18%). Factors most predictive of hospital admission for children, after controlling for triage category, included hospital type (children’s only) adjusted odds ratio (aOR):2.3 (95%CI: 2.2–2.4), arrival by ambulance aOR:2.8 (95%CI: 2.7–2.9), referral from primary health aOR:1.5 (95%CI: 1.4–1.6) and presentation with a respiratory or gastrointestinal condition (aOR:2.6, 95%CI: 2.5–2.8 and aOR:1.5, 95%CI: 1.4–1.6, respectively). Predictors were similar when each site was considered separately.

Conclusions

Although the characteristics of children varied by site, factors predictive of hospital admission were mostly similar. The awareness of these factors predicting the need for hospital admission can support the development of clinical pathways.
Simulating the healthcare workforce impact and capacity for pancreatic cancer care in Victoria: a model-based analysis
Authors: Gao Lan , Ugalde Anna , Livingston Patricia M , White Victoria , Watts Jennifer J , Jongebloed Hannah , McCaffrey Nikki , Menzies David , Robinson Suzanne
Published: February 2024

Background

The incidence of pancreatic cancer is rising. With improvements in knowledge for screening and early detection, earlier detection of pancreatic cancer will continue to be more common. To support workforce planning, our aim is to perform a model-based analysis that simulates the potential impact on the healthcare workforce, assuming an earlier diagnosis of pancreatic cancer.

Methods

We developed a simulation model to estimate the demand (i.e. new cases of pancreatic cancer) and supply (i.e. the healthcare workforce including general surgeons, medical oncologists, radiation oncologists, pain medicine physicians, and palliative care physicians) between 2023 and 2027 in Victoria, Australia. The model compares the current scenario to one in which pancreatic cancer is diagnosed at an earlier stage. The incidence of pancreatic cancer in Victoria, five-year survival rates, and Victoria’s population size were obtained from Victorian Cancer Registry, Cancer Council NSW, and Australian Bureau of Statistics respectively. The healthcare workforce data were sourced from the Australian Government Department of Health and Aged Care’s Health Workforce Data. The model was constructed at the remoteness level. We analysed the new cases and the number of healthcare workforce by profession together to assess the impact on the healthcare workforce.

Results

In the status quo, over the next five years, there will be 198 to 220 stages I-II, 297 to 330 stage III, and 495 to 550 stage IV pancreatic cancer cases diagnosed annually, respectively. Assuming 20–70% of the shift towards pancreatic cancer’s earlier diagnosis (shifting from stage IV to stages I-II pancreatic cancer within one year), the stages I-II cases could increase to 351 to 390 or 598 to 665 per year. The shift to early diagnosis led to substantial survival gains, translating into an additional 284 or 795 out of 5246 patients with pancreatic cancer remaining alive up to year 5 post-diagnosis. Workforce supply decreases significantly by the remoteness levels, and remote areas face a shortage of key medical professionals registered in delivering pancreatic cancer care, suggesting travel necessities by patients or clinicians.

Conclusion

Improving the early detection and diagnosis of pancreatic cancer is expected to bring significant survival benefits, although there are workforce distribution imbalances in Victoria that may affect the ability to achieve the anticipated survival gain.
An unexpected case of a dog from Poland co-infected with Dirofilaria repens and Dirofilaria Immitis
Authors: Pękacz Mateusz , Basałaj Katarzyna , Miterpáková Martina , Rusiecki Zbigniew , Stopka Diana , Graczyk Dominika , Zawistowska-Deniziak Anna
Published: February 2024

Background

Dirofilariasis is a vector-borne disease caused by parasitic nematodes of the genus Dirofilaria spp., considered an emerging concern in both veterinary and human medicine. Climate changes and human activities, such as pet travel, contribute to the spread of diseases to new non-endemic regions. Poland is dominated by subcutaneous dirofilariasis caused by D. repens infections. Cardiopulmonary dirofilariasis, also known as a heartworm disease is much more rare with only single autochthonous cases reported so far. Also, imported infections are observed sporadically in dogs traveling to endemic countries. In this study, we report the first case of a dog in Poland, never having traveled abroad, co-infected with Dirofilaria repens and Dirofilaria immitis.

Case presentation

A 14-year-old mixed breed, an intact male dog with fever, lightly pale mucosal membranes, moderate abdominal pain, and a mild cough was presented in a veterinary clinic in Warsaw, Poland. The examination of the blood sample collected for complete morphology and biochemistry revealed the presence of live microfilariae. Presence of the DNA of both microfilariae species was detected using Real-Time PCR with species-specific primers.

Conclusions

Since the remaining diagnostic methods like Knott’s test, antigen test or echocardiography did not reveal the presence of D. immitis, we discussed the impact of microfilariae periodicity and low worm burden infections on the limited efficiency of these techniques. We strongly recommend using a mixed diagnostic approach for the most sensitive and specific diagnosis since the ideal diagnostic method does not exist, and several factors may contribute to misdiagnosis. Furthermore, we considered factors that contribute to the uncontrolled spread of dirofilariasis such as climate changes, introduction of new species of mosquitoes competent for the transmission of the disease, and wildlife animals as an important reservoir of this parasitosis. Given that Poland shares borders with countries classified as endemic and pre-endemic for D. immitis, such as Slovakia and Ukraine, it is reasonable to anticipate a rise in autochthonous heartworm infections and shifts in the epidemiological pattern of dirofilariasis in the coming years.
Bayesian spatio-temporal analysis of malaria prevalence in children between 2 and 10 years of age in Gabon
Authors: Mougeni Fabrice , Lell Bertrand , Kandala Ngianga-Bakwin , Chirwa Tobias
Published: February 2024

Background

Gabon still bears significant malaria burden despite numerous efforts. To reduce this burden, policy-makers need strategies to design effective interventions. Besides, malaria distribution is well known to be related to the meteorological conditions. In Gabon, there is limited knowledge of the spatio-temporal effect or the environmental factors on this distribution. This study aimed to investigate on the spatio-temporal effects and environmental factors on the distribution of malaria prevalence among children 2–10 years of age in Gabon.

Methods

The study used cross-sectional data from the Demographic Health Survey (DHS) carried out in 2000, 2005, 2010, and 2015. The malaria prevalence was obtained by considering the weighting scheme and using the space–time smoothing model. Spatial autocorrelation was inferred using the Moran’s I index, and hotspots were identified with the local statistic Getis-Ord General Gi. For the effect of covariates on the prevalence, several spatial methods implemented in the Integrated Nested Laplace Approximation (INLA) approach using Stochastic Partial Differential Equations (SPDE) were compared.

Results

The study considered 336 clusters, with 153 (46%) in rural and 183 (54%) in urban areas. The prevalence was highest in the Estuaire province in 2000, reaching 46%. It decreased until 2010, exhibiting strong spatial correlation (P < 0.001), decreasing slowly with distance. Hotspots were identified in north-western and western Gabon. Using the Spatial Durbin Error Model (SDEM), the relationship between the prevalence and insecticide-treated bed nets (ITNs) coverage was decreasing after 20% of coverage. The prevalence in a cluster decreased significantly with the increase per percentage of ITNs coverage in the nearby clusters, and per degree Celsius of day land surface temperature in the same cluster. It slightly increased with the number of wet days and mean temperature per month in neighbouring clusters.

Conclusions

In summary, this study showed evidence of strong spatial effect influencing malaria prevalence in household clusters. Increasing ITN coverage by 20% and prioritizing hotspots are essential policy recommendations. The effects of environmental factors should be considered, and collaboration with the national meteorological department (DGM) for early warning systems is needed.
Mapping socio-geographical disparities in the occurrence of teenage maternity in Colombia using multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)
Authors: Mattsson Hedda , Gustafsson Johanna , Prada Sergio , Jaramillo-Otoya Laura , Leckie George , Merlo Juan , Rodriguez-Lopez Merida
Published: February 2024

Background

The prevalence of teenage pregnancy in Colombia is higher than the worldwide average. The identification of socio-geographical disparities might help to prioritize public health interventions.

Aim

To describe variation in the probability of teenage maternity across geopolitical departments and socio-geographical intersectional strata in Colombia.

Methods

A cross-sectional study based on live birth certificates in Colombia. Teenage maternity was defined as a woman giving birth aged 19 or younger. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied using multilevel Poisson and logistic regression. Two different approaches were used: (1) intersectional: using strata defined by the combination of health insurance, region, area of residency, and ethnicity as the second level (2) geographical: using geopolitical departments as the second level. Null, partial, and full models were obtained. General contextual effect (GCE) based on the variance partition coefficient (VPC) was considered as the measure of disparity. Proportional change in variance (PCV) was used to identify the contribution of each variable to the between-strata variation and to identify whether this variation, if any, was due to additive or interaction effects. Residuals were used to identify strata with potential higher-order interactions.

Results

The prevalence of teenage mothers in Colombia was 18.30% (95% CI 18.20–18.40). The highest prevalence was observed in Vichada, 25.65% (95% CI: 23.71–27.78), and in the stratum containing mothers with Subsidized/Unaffiliated healthcare insurance, Mestizo, Rural area in the Caribbean region, 29.08% (95% CI 28.55–29.61). The VPC from the null model was 1.70% and 9.16% using the geographical and socio-geographical intersectional approaches, respectively. The higher PCV for the intersectional model was attributed to health insurance. Positive and negative interactions of effects were observed.

Conclusion

Disparities were observed between intersectional socio-geographical strata but not between geo-political departments. Our results indicate that if resources for prevention are limited, using an intersectional socio-geographical approach would be more effective than focusing on geopolitical departments especially when focusing resources on those groups which show the highest prevalence. MAIHDA could potentially be applied to many other health outcomes where resource decisions must be made.
Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD
Authors: Mao Zun , Gao Zhi-xiang , Ji Tong , Huan Sheng , Yin Guo-ping , Chen Long
Published: February 2024

Background

Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis.

Methods

Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy.

Results

Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes.

Conclusion

This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.
ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis
Authors: Dong Jian , Li Muzi , Peng Runsheng , Zhang Yuchuan , Qiao Zilin , Sun Na
Published: February 2024

Background

Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose global prevalence is rapidly increasing. Acetyl CoA carboxylases 1 (ACACA) is the key enzyme that controls the rate of fatty acid synthesis. Hence, it is crucial to investigate the function of ACACA in regulating lipid metabolism during the progress of NAFLD.

Methods

Firstly, a fatty liver mouse model was established by high-fat diet at 2nd, 12th, and 20th week, respectively. Then, transcriptome analysis was performed on liver samples to investigate the underlying mechanisms and identify the target gene of the occurrence and development of NAFLD. Afterwards, lipid accumulation cell model was induced by palmitic acid and oleic acid (PA ∶ OA molar ratio = 1∶2). Next, we silenced the target gene ACACA using small interfering RNAs (siRNAs) or the CMS-121 inhibitor. Subsequently, experiments were performed comprehensively the effects of inhibiting ACACA on mitochondrial function and lipid metabolism, as well as on AMPK- PPARα- CPT1A pathway.

Results

This data indicated that the pathways significantly affected by high-fat diet include lipid metabolism and mitochondrial function. Then, we focus on the target gene ACACA. In addition, the in vitro results suggested that inhibiting of ACACA in vitro reduces intracellular lipid accumulation, specifically the content of TG and TC. Furthermore, ACACA ameliorated mitochondrial dysfunction and alleviate oxidative stress, including MMP complete, ATP and ROS production, as well as the expression of mitochondria respiratory chain complex (MRC) and AMPK proteins. Meanwhile, ACACA inhibition enhances lipid metabolism through activation of PPARα/CPT1A, leading to a decrease in intracellular lipid accumulation.

Conclusion

Targeting ACACA can reduce lipid accumulation by mediating the AMPK- PPARα- CPT1A pathway, which regulates lipid metabolism and alleviates mitochondrial dysfunction.
Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model
Authors: Xu Xi , Ma Mengjie , Ye Kunlin , Zhang Dong , Chen Xinhui , Wu Jiayang , Mo Xukai , Xiao Zeyu , Shi Changzheng , Luo Liangping
Published: February 2024

Background

Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model.

Methods

The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points.

Results

The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = − 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001).

Conclusions

The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.