bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the natural products in the treatment of atherosclerosis by increasing HDL-C level based on bioinformatics analysis, molecular docking, and in vitro experiment
Authors: Chen Yilin , Zhang Fengwei , Sun Jijia , Zhang Lei
Published: December 2023

Background

Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the efficacy and safety of natural products in treating atherosclerosis (AS). However, the study of raising HDL-C levels through natural products to treat AS still needs to be explored.

Methods

The gene sets associated with AS were collected and identified by differential gene analysis and database query. By constructing a protein–protein interaction (PPI) network, the core submodules in the network are screened out. At the same time, by calculating node importance (Nim) in the PPI network of AS disease and combining it with Kyoto Encyclopedia of genes and genomes (KEGG) pathways enrichment analysis, the key target proteins of AS were obtained. Molecular docking is used to screen out small natural drug molecules with potential therapeutic effects. By constructing an in vitro foam cell model, the effects of small molecules on lipid metabolism and key target expression of foam cells were investigated.

Results

By differential gene analysis, 451 differential genes were obtained, and a total of 313 disease genes were obtained from 6 kind of databases, then 758 AS-related genes were obtained. The enrichment analysis of the KEGG pathway showed that the enhancement of HDL-C level against AS was related to Lipid and atherosclerosis, Cholesterol metabolism, Fluid shear stress and atherosclerosis, PPAR signaling pathway, and other pathways. Then we intersected 31 genes in the core module of the PPI network, the top 30 genes in Nims, and 32 genes in the cholesterol metabolism pathway, and finally found 3 genes. After the above analysis and literature collection, we focused on the following three related gene targets: APOA1, LIPC, and CETP. Molecular docking showed that Genistein has a good binding affinity for APOA1, CETP, and LIPC. In vitro, experiments showed that Genistein can up-regulated APOA1, LIPC, and CETP levels.

Conclusions

Based on our research, Genistein may have the effects of regulating HDL-C and anti-atherosclerosis. Its mechanism of action may be related to the regulation of LIPC, CETP, and APOA1 to improve lipid metabolism.
Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation
Authors: Zhu Hong , Xiao Feng , Xiao Yao , Guo Yun , Shan Xuesong , Zhang Zhe , Zhang Lieliang , Guo Hua
Published: December 2023

Background

Inflammasomes in astrocytes have been shown to play a crucial role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Cannabinoid Receptor 2(CB2R), a G protein-coupled receptor (GPCR), is considered a promising therapeutic target in inflammation-related disorders. This study aims to explore the role of CB2R in regulating NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated neuroinflammation in astrocytes.

Methods

In an in vivo animal model, specific targeting of astrocytic CB2R was achieved by injecting CB2R-specific adenovirus (or fork head box g1(foxg1) adenovirus) to knock down CB2R or administering CB2R agonists, inhibitors, etc., in the substantia nigra pars compacta (SNc) of mice. A PD mouse model was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induction. Animal behavioral tests, western blot, immunofluorescence, and other experiments were performed to assess the loss of midbrain tyrosine hydroxylase (TH) neurons, activation of astrocytes, and activation of the NLRP3 pathway. Primary astrocytes were cultured in vitro, and NLRP3 inflammasomes were activated using 1-methyl-4-phenylpyridinium (MPP+) or lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Western blot and ELISA experiments were conducted to assess the release of inflammatory factors. Transcriptomic sequencing and CUT&RUN techniques were employed to study the CB2R regulation of the foxg1 binding site on the autophagy molecule microtubule-associated protein 1 light chain 3 beta (MAP1LC3B).

Results

Astrocytic CB2R knockdown impaired the motor abilities of MPTP-induced mice, exacerbated the loss of TH neurons, and induced activation of the NLRP3/Caspase-1/interleukin 1 (IL-1β) pathway. Activation of CB2R significantly alleviated motor impairments in mice while reducing NLRP3 deposition on astrocytes. In vitro cell experiments showed that CB2R activation attenuated the activation of the NLRP3/Caspase-1/IL-1β pathway induced by LPS + ATP or MPP+. Additionally, it inhibited the binding of foxg1 to MAP1LC3B, increased astrocytic autophagy levels, and facilitated NLRP3 degradation through the autophagy–lysosome pathway.

Conclusion

Activation of CB2R on astrocytes effectively mitigates NLRP3-mediated neuroinflammation and ameliorates the disease characteristics of PD in mice. CB2R represents a potential therapeutic target for treating PD.
Adolescent’s and youth’s adherence to antiretroviral therapy for better treatment outcome and its determinants: multi-center study in public health facilities
Authors: Zurbachew Yihenew , Hiko Desta , Bacha Girma , Merga Hailu
Published: December 2023

Background

Low-adherence to Anti-retroviral therapy (ART) negatively affects the clinical, immunological, and virologic outcomes of patients. Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression which ultimately reduces morbidity and mortality. Thus, this study aimed to identify factors affecting adherence to antiretroviral therapy among adolescents and youth living with HIV.

Methods

Facility-based cross-sectional study was conducted from March 21 to April 30, 2020 among 316 respondents in selected five high-loaded hospitals with adolescent and youth clients using systematic random sampling technique. Patients’ adherence was assessed when they had reportedly taken 95% or higher of their prescribed antiretroviral drugs in the five days before the interview. Data were collected, entered into EPI Data and exported to SPSS for analysis. Binary logistic regression was used to see the association between dependent and independent variables.

Results

In this study, 316 respondents participated in the study, with a 99.7% response rate. The mean age of respondents were 17.94 years and majority of them (58.5%) were females. The overall ART adherence among adolescents and youths was found to be 70.6%. Being female (AOR = 0.323, 95% CI, 0.164–0.637), presence of opportunistic infection (AOR = 0.483, 95% CI, 0.249–0.936), taking additional medication beside ART (AOR = 0.436, 95% CI, 0.206–0.922) and availability of youth friendly services within the facility (AOR = 2.206, 95% CI, 1.031–4.721) were found to be predictors.

Conclusion

The adherence rate in this study was low which is below the recommended adherence level. Being female, taking additional medication beside ART and presence of opportunistic infection were determinants of adherence. As a result, significant work must be done on opportunistic infection prevention through health education and promotion for screening and risk reduction. Similarly, adolescents and youths service integration with the ART Clinic is strongly advised.
Gray mold and anthracnose disease detection on strawberry leaves using hyperspectral imaging
Authors: Zhang Baohua , Ou Yunmeng , Yu Shuwan , Liu Yuchen , Liu Ying , Qiu Wei
Published: December 2023

Background

Gray mold and anthracnose are the main factors affecting strawberry quality and yield. Accurate and rapid early disease identification is of great significance to achieve precise targeted spraying to avoid large-scale spread of diseases and improve strawberry yield and quality. However, the characteristics between early disease infected and healthy leaves are very similar, making the early identification of strawberry gray mold and anthracnose still a challenge.

Results

Based on hyperspectral imaging technology, this study explored the potential of combining spectral fingerprint features and vegetation indices (VIs) for early detection (24-h infected) of strawberry leaves diseases. The competitive adaptive reweighted sampling (CARS) algorithm and ReliefF algorithm were used for the extraction of spectral fingerprint features and VIs, respectively. Three machine learning models, Backpropagation Neural Network (BPNN), Support Vector Machine (SVM) and Random Forest (RF), were developed for the early identification of strawberry gray mold and anthracnose, using spectral fingerprint, VIs and their combined features as inputs respectively. The results showed that the combination of spectral fingerprint features and VIs had better recognition accuracy compared with individual features as inputs, and the accuracies of the three classifiers (BPNN, SVM and RF) were 97.78%, 94.44%, and 93.33%, respectively, which indicate that the fusion features approach proposed in this study can effectively improve the early detection performance of strawberry leaves diseases.

Conclusions

This study provided an accurate, rapid, and nondestructive recognition of strawberry gray mold and anthracnose disease in early stage.
Stereotactic radiosurgery of brain metastases: a retrospective study
Authors: Gruber Isabella , Weidner Karin , Treutwein Marius , Koelbl Oliver
Published: December 2023

Background

Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS.

Methods

Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6–22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis.

Results

Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17–0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4–64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40–63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4–26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699).

Conclusions

Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases.

Trial registration

This study is retrospectively registered (ethics approval number 23-3451-104).
Microbiological profile of patients treated for postoperative peritonitis: temporal trends 1999–2019
Authors: Montravers Philippe , Grall Nathalie , Kantor Elie , Augustin Pascal , Boussion Kevin , Zappella Nathalie
Published: December 2023

Background

Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT).

Methods

This retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO.

Results

A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time.

Conclusions

We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO.

Graphical Abstract
Protective factors for resilience in adolescence: analysis of a longitudinal dataset using the residuals approach
Authors: Marquez Jose , Francis-Hew Louis , Humphrey Neil
Published: December 2023

Introduction

The residuals approach, in which residual scores from regression models are used as a proxy for resilient functioning, offers great potential to increase understanding of resilience processes. However, its application in child and adolescent wellbeing research is limited to date. We use this approach to examine how adversity exposure impacts later wellbeing (life satisfaction, and internalising mental health difficulties) in the early-to-middle adolescence transition; whether gender and ethnic differences in resilience exist; which internal and external factors confer protective effects for resilience; and, whether the protective effect of these factors differs by gender and level of adversity exposure.

Method

Secondary analysis of the #BeeWell longitudinal data set (N = 12,130 adolescents, aged 12/13 at T1 and 13/14 at T2, representative of Greater Manchester, England) was undertaken, using a series of linear regressions to establish adversity indices for later wellbeing, before assessing the protective effects of internal and external factors on resilience.

Results

Multiple adversity factors (e.g., home material deprivation, sexuality discrimination, bullying) were found to impact later wellbeing. Girls and white adolescents presented lower levels of resilience than their peers. Internal psychological factors (self-esteem, emotional regulation, optimism) consistently conferred the strongest protective effects, but behavioural/activity factors (physical activity, sleep) also contributed to resilience. Among external factors, friendships and peer support were the most salient. Physical activity yielded stronger protective effects among boys (compared to girls). Effects of protective factors were stronger among those at lower (compared to higher) levels of adversity exposure.

Conclusion

The residuals approach can make a considerable contribution to our understanding of the interplay between adversity exposure and access to protective factors in determining adolescent wellbeing outcomes. Moreover, its application provides clear implications for policy and practice in terms of prevention (of adversity exposure) and intervention (to facilitate resilience).
Activation of PI3K/AKT/mTOR signaling axis by UBE2S inhibits autophagy leading to cisplatin resistance in ovarian cancer
Authors: Zhang Mengjun , Wang Jialin , Guo Yan , Yue Haodi , Zhang Lindong
Published: December 2023

Background

Epithelial ovarian cancer (OC) is the fourth leading cause of cancer-related deaths in women, with a 5-year survival rate of 30%-50%. Platinum resistance is the chief culprit for the high recurrence and mortality rates. Several studies confirm that the metabolic regulation of ubiquitinating enzymes plays a vital role in platinum resistance in OC.

Methods

In this study, we selected ubiquitin-conjugating enzyme E2S (UBE2S) as the candidate gene for validation. The levels of UBE2S expression were investigated using TCGA, GTEx, UALCAN, and HPA databases. In addition, the correlation between UBE2S and platinum resistance in OC was analyzed using data from TCGA. Cisplatin-resistant OC cell lines were generated and UBE2S was knocked down; the transfection efficiency was verified. Subsequently, the effects of knockdown of UBE2S on the proliferation and migration of cisplatin-resistant OC cells were examined through the CCK8, Ki-67 immunofluorescence, clone formation, wound healing, and transwell assays. In addition, the UBE2S gene was also validated in vivo by xenograft models in nude mice. Finally, the relationship between the UBE2S gene and autophagy and the possible underlying regulatory mechanism was preliminarily investigated through MDC and GFP-LC3-B autophagy detection and western blotting experiments. Most importantly, experimental validation of mTOR agonist reversion (the rescuse experiments) was also performed.

Results

UBE2S was highly expressed in OC at both nucleic acid and protein levels. The results of immunohistochemistry showed that the level of UBE2S expression in platinum-resistant samples was significantly higher relative to the platinum-sensitive samples. By cell transfection experiments, knocking down of the UBE2S gene was found to inhibit the proliferation and migration of cisplatin-resistant OC cells. Moreover, the UBE2S gene could inhibit autophagy by activating the PI3K/AKT/mTOR signaling pathway to induce cisplatin resistance in OC in vivo and in vitro.

Conclusion

In conclusion, we discovered a novel oncogene, UBE2S, which was associated with platinum response in OC, and examined its key role through bioinformatics and preliminary experiments. The findings may open up a new avenue for the evaluation and treatment of OC patients at high risk of cisplatin resistance.
Pre-treatment of canine plasma with heat, rather than acid, efficiently enhances Dirofilaria immitis antigen detection
Authors: Murillo Daniel Felipe Barrantes , Wang Chengming
Published: December 2023

Background

The dissociation of antigen-antibody complexes has been utilized to enhance the accuracy of serological tests for infectious diseases, including Dirofilaria immitis. Currently, the antigen detected by available tests is primarily a glycoprotein found in the reproductive tract of female worms. However, this antigen can become inaccessible when bound to excessive circulating antibodies, leading to reduced test sensitivity and false-negative results. Acid and heat treatments of the sera or plasma have been established as reliable methods for inducing immune complex dissociation (ICD). Previous antigen testing for heartworm infection in dogs and cats has demonstrated that these treatments improve the diagnostic sensitivity without compromising specificity. This study aims to evaluate the performance of four distinct ICD methods in the detection of D. immitis antigen.

Methods

We utilized twofold serial dilutions of a well-characterized plasma (ranging from 1:2 to 1:4096) obtained from a D. immitis-infected dog to simulate the diverse antigen levels encountered in real-life infected dogs. The presence of antigen in the diluted samples, both without treatment and treated with four ICD protocols, was assessed in triplicate visually using DiroCHEK® by observing color changes. OD values were also obtained using the microplate reader SpectraMax® i Series-Spectramax Id3. A Factorial ANOVA test was conducted to compare the OD values between samples with and without treatments.

Results

The highest dilution at which color changes were observed was 1:128 for untreated samples and for samples subjected to acid treatments in ICD-3 and the hybrid ICD-4 protocol. In contrast, both heat treatment protocols (ICD-1 and ICD-2) exhibited color changes at a 512-fold dilution. The OD values in samples subjected to heat treatment were significantly higher than those in untreated samples, up to dilutions of 512-fold. Although OD values tended to be higher in samples subjected to acid treatment and the hybrid protocol compared to untreated samples up to a 128-fold dilution, this difference was not significant as the samples underwent further dilution.

Conclusions

Our findings affirm that heat treatments, rather than acid treatment, efficiently enhance the detection of D. immitis antigen by liberating the sequestered antigen from the immune complexes.
Feasibility of preoperative and postoperative physical rehabilitation for cardiac surgery patients – a longitudinal cohort study
Authors: Dijkstra Sandra , Hartog Johanneke , Fleer Joke , van der Harst Pim , van der Woude Lucas H.V. , Mariani Massimo A.
Published: December 2023

Background

This study aimed to determine the feasibility of a preoperative and postoperative (in- and outpatient) physical rehabilitation program, the Heart-ROCQ-pilot program.

Methods

This cohort study included patients undergoing cardiac surgery (including coronary artery bypass graft surgery, valve surgery, aortic surgery, or combinations of these surgeries) and participated in the Heart-ROCQ-pilot program. Feasibility involved compliance and characteristics of bicycle and strength training sessions in the three rehabilitation phases.

Results

Of the eligible patients, 56% (n = 74) participated in the program (41% of exclusions were due to various health reasons). On average across the rehabilitation phases, the compliance rates of bicycle and strength training were 88% and 83%, respectively. Workload to heart rate (W/HR) ratio and total absolute volume load for bicycle and strength training, respectively, improved in each rehabilitation phase (P < 0.05). The W/HR-ratio was higher during the last postoperative session compared to the first preoperative session (0.48 to 0.63 W/beat, P < 0.001) and similar to the last preoperative session (0.65 to 0.64 W/beat, P < 0.497). During less than 1% of the bicycle sessions, patients reported discomfort scores of 5 to 6 (scale 0–10, with higher scores indicating a higher level).

Conclusions

The Heart-ROCQ-pilot program was feasible for patients awaiting cardiac surgery. Patients were very compliant and were able to safely increase the training load before surgery and regained this improvement within eight weeks after surgery.
Global google trends for construction demonstrate low search volume index for stress, mental and suicide
Authors: McLachlan Craig Steven , Truong Hang
Published: December 2023

The comparison of Google internet searches for English words in construction for “construction stress”, “construction mental” and “construction suicide” with reference to “construction worker” has not previously been undertaken. It is important to understand internet interest across these 3 terms as all are relevant to mental health and stress in construction. Suicide risk is significantly complex and multifactorial. Our aim is to investigate internet search interest across construction with a focus on mental, stress and suicide, and determine whether there is consistent interest across these search terms. Methods: Using Google Trends, data on global search queries we compared “construction mental” or “construction stress” and “construction suicide”. Two time periods were compared, the last 5 years and the last 24 months, both till December 8th, 2022. The relationship between web search interest, reflected by search volume index (SVI) for society and community versus the business and industrial category and health category were evaluated. Results: Open category searches on Google trends for the key words “construction mental” or “construction stress” demonstrated moderate SVI peaks over a 5-year period. Sub-group analyses for the industrial and business category demonstrated consistent low interest in suicide compared to search terms related to stress or mental health. Conclusion: There is limited online interest in construction mental and stress and even less interest in suicide.
Endocarditis caused by Aspergillus fumigatus in a patient 9 months after COVID-19 infection recovery: a case report and review of the literature
Authors: Yassin Zeynab , Hajsadeghi Shokoufeh , Shavazi Mohsen Taghavi , Fattahi Mahsa , Ahmadzadeh Koohyar , Farid Armita , Karimi Yeganeh , Seirafianpour Farnoosh , Babaheidarian Pegah , Goodarzi Azadeh
Published: December 2023

Background

Aspergillus spp. are among the fungal pathogens that can cause life-threatening infections in patients with a history of COVID-19.

Case presentation

We present the case of a 58-year-old Iranian woman with post-COVID-19 Aspergillus fumigatus endocarditis complicated by numerous thromboembolisms. She underwent mitral valve replacement surgery and multiple lower extremity embolectomies and was treated with voriconazole, which led to her final recovery.

Conclusions

Aspergillus endocarditis should be considered in any patient with suspected endocarditis who has a history of COVID-19 infection and does not respond to routine antibiotic and antifungal therapy, as COVID-19 interferes with proper immune function, and lack of underlying cardiac conditions and immunodeficiencies does not preclude the diagnosis. Culture and histopathological evaluation of vegetations and emboli, as well as PCR, can confirm the diagnosis. Early initiation of antifungal therapy and surgical removal of infected valves and emboli can improve prognosis in patients with Aspergillus endocarditis.
Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis
Authors: Li Xiao-hui , Zhou En-liang , Dong Xiao-yuan , Zhao Chong-yu , Han Yuan-xia , Cui Bo-kang , Lin Xiao-jun
Published: December 2023

Objective

In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages.

Materials and methods

Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis.

Results

168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively).

Conclusions

The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.
A combined analysis of multi-omics data reveals the prognostic values and immunotherapy response of LAG3 in human cancers
Authors: Peng Jinwu , Du Zhihao , Sun Yuwei , Zhou Zhiyang
Published: December 2023

Lymphocyte-activation gene 3 (LAG3) is a highly anticipated immune checkpoint in the context of cancer, exerting regulatory control over immune cell proliferation and function to reinforce the advancement of cancers. However, the comprehensive functional analysis of LAG3 across various cancer types remains undisclosed; thus, this study aims to investigate the pan-cancer expression profile of LAG3. We have investigated the expression profile, prognostic significance, and genetic alterations of LAG3 in various cancers while elucidating its characteristic in immune response regulation. Our findings demonstrated that elevated LAG3 expression is significantly associated with favorable prognosis in patients with cutaneous melanoma (SKCM), and it may be a potential biomarker for SKCM. Furthermore, multiple immune algorithms have highlighted the important regulatory role of LAG3 for the tumor-infiltrating immune cells including CD8 + T cells, B cells, dendritic cells (DCs), macrophages, and natural killer (NK) cells. We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.
Quality of life among family caregivers of cancer patients: an investigation of SF-36 domains
Authors: Rostami Mina , Abbasi Mahsa , Soleimani Morteza , Moghaddam Zhaleh Karimi , Zeraatchi Alireza
Published: December 2023

Background

With improving survival rates, cancer has become more of a chronic disease with long-term palliative care requirements. Thus, it is even more than ever necessary to pay careful attention to the well-being of family caregivers of cancer patients, as cancer trajectory is a challenging path for both patients and their caregivers. This study focusses on ascertaining the level of quality of life (QoL) domains and their attributable significant factors among a population of cancer family caregivers.

Methods

This was a cross-sectional study. The study population consist of caregivers of adult cancer patients in Zanjan, Iran between 2019 and 2020. Medical Outcomes General Health Survey Short Form 36 (SF-36) was the instrument to measure outcome variables. Clinical and basic characteristics of the caregivers and their patients were also collected using a questionnaire designed for this purpose. Data were analyzed using Independent samples t-test, Analysis of Variance, and stepwise linear regression in SPSS v.26.

Results

Of the caregivers 167 were male and 133 were female. The mean age of the participants was 40.77 ± 12.56, most of whom were offspring of the patients (148, 49.3%), married (239, 79.7%), and self-employed (81, 27.0%). both domains of bodily pain (76.50 ± 16.67) and physical functioning (74.88 ± 20.27) showed the highest scores among caregivers. Age and gender of caregivers, duration of caregiving, Eastern Cooperative Oncology Group (ECOG) performance status scale as well as type and stage of cancer, and type of treatment were among the significant predictors of QoL domains (All, p < 0.001).

Conclusion

Findings of the present study substantiated various significant predictors for QoL along with low levels of QoL domains among the caregivers of cancer patients. Securing such findings proves the magnitude of probable unmet needs and psychological challenges in this population and provides the health policy makers with some valuable clues to draw effective strategies to address such issues.
On conservation of world heritage Beijing-Hangzhou grand canal for enhancing cultural ecosystem services
Authors: Zhang Yixin , Jing Zehui , Huang Qiuyue , Wang Xinyue , Sun Wenxin , Zhang Chenyue , Wang Jieqing , Zhong Yujia , Wang Jiesi , Tan Li , Zheng Li , Wang Bo , Wang Lifen , Sun Xiangli , Zhai Jun , Wang Weizhu , Wu Yongfa , Candeias António
Published: December 2023

The Beijing-Hangzhou Grand Canal carries unique social and cultural significance as a world cultural heritage, but with the acceleration of global urbanization, it has potentially severe environmental risks under continuous anthropogenic disturbances. Therefore, to protect the ecological and cultural values of the Grand Canal, it is necessary to assess the corresponding relationship of water quality to land use and the perception of ecosystem services that focus on cultural ecosystem services (CES). This study aims to analyze the water quality response to land use in the Beijing-Hangzhou Grand Canal, describe the land use types closely related to water quality, and propose corresponding management strategies for enhancing CES. This study investigated the impacts of land use structure and landscape pattern on water quality by calculating the correlation between land use structure and landscape pattern indices and water quality in buffer zones of different distances on both sides of the canal. The results show that green land dominates the land use structure and can effectively reduce water pollution in the canal. On the other hand, urban impervious surfaces showed a significant positive correlation with pollution contributing to low water quality. We accessed the impact of water quality on the perception of CES in the Beijing-Hangzhou Grand Canal and proposed optimization strategies for promoting CES. Both content analysis and thematic analysis were applied to analyze the impact of the water environment quality of the Beijing-Hangzhou Grand Canal on the perception of CES. We found that the perceptions of CES along the Beijing-Hangzhou Grand Canal are associated with the public’s opinions on its cultural heritage services and artistic inspiration services. The perceptions of CES are closely related to the quality of the water environment and riparian greenness, which affect the values of cultural heritage and conservation of the Beijing-Hangzhou Grand Canal.
Mechanical circulatory support in cardiogenic shock
Authors: Nakata Jun , Yamamoto Takeshi , Saku Keita , Ikeda Yuki , Unoki Takashi , Asai Kuniya
Published: December 2023

Cardiogenic shock is a complex and diverse pathological condition characterized by reduced myocardial contractility. The goal of treatment of cardiogenic shock is to improve abnormal hemodynamics and maintain adequate tissue perfusion in organs. If hypotension and insufficient tissue perfusion persist despite initial therapy, temporary mechanical circulatory support (t-MCS) should be initiated. This decade sees the beginning of a new era of cardiogenic shock management using t-MCS through the accumulated experience with use of intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO), as well as new revolutionary devices or systems such as transvalvular axial flow pump (Impella) and a combination of VA-ECMO and Impella (ECPELLA) based on the knowledge of circulatory physiology. In this transitional period, we outline the approach to the management of cardiogenic shock by t-MCS. The management strategy involves carefully selecting one or a combination of the t-MCS devices, taking into account the characteristics of each device and the specific pathological condition. This selection is guided by monitoring of hemodynamics, classification of shock stage, risk stratification, and coordinated management by the multidisciplinary shock team.
Efficacy of the bleeding risk scoring system for optimal prophylactic anticoagulation therapy of venous thromboembolism in trauma patients: a single-center, retrospective, observational cohort study
Authors: Tomizawa Atsushi , Maruhashi Takaaki , Shibuya Akito , Akamine Akihiko , Kuroiwa Masayuki , Kataoka Yuichi , Asari Yasushi , Atsuda Koichiro , Otori Katsuya
Published: December 2023

Background

We developed a bleeding risk scoring system (BRSS) using prophylactic anticoagulation therapy to comprehensively assess the risk of venous thromboembolism (VTE) in trauma patients. This study evaluated the usefulness of this system in trauma patients, with a focus on minimizing the rate of bleeding events associated with prophylactic anticoagulation therapy.

Methods

We retrospectively evaluated the efficacy of BRSS in trauma patients who received prophylactic anticoagulation therapy for VTE at the Kitasato University Hospital Emergency and Critical Care Center between April 1, 2015, and August 31, 2020. To compare the incidence of bleeding events, patients were divided into two groups: one group using the BRSS (BRSS group) and another group not using the BRSS (non-BRSS group).

Results

A total of 94 patients were enrolled in this study, with 70 and 24 patients assigned to the non-BRSS and BRSS groups, respectively. The major bleeding event rates were not significantly different between the two groups (BRSS group, 4.2%; non-BRSS group, 5.7%; p = 1.000). However, minor bleeding events were significantly reduced in the BRSS group (4.2% vs.27.1%; p = 0.020). Multivariate logistic regression analysis showed that BRSS was not an independent influencing factor of major bleeding events (odds ratio, 0.660; 95% confidence interval: 0.067-6.47; p = 0.721). Multivariate logistic regression analysis showed that BRSS was an independent influencing factor of minor bleeding events (odds ratio, 0.119; 95% confidence interval: 0.015-0.97; p = 0.047). The incidence of VTE did not differ significantly between groups (BRSS group, 4.2%; non-BRSS group, 8.6%; p = 0.674).

Conclusions

BRSS may be a useful tool for reducing the incidence of minor bleeding events during the initial prophylactic anticoagulation therapy in trauma patients. There are several limitations of this study that need to be addressed in future research.
Integrating chatbots in education: insights from the Chatbot-Human Interaction Satisfaction Model (CHISM)
Authors: Belda-Medina Jose , Kokošková Vendula
Published: December 2023

Recent advances in Artificial Intelligence (AI) have paved the way for the integration of text-based and voice-enabled chatbots as adaptive virtual tutors in education. Despite the increasing use of AI-powered chatbots in language learning, there is a lack of studies exploring the attitudes and perceptions of teachers and students towards these intelligent tutors. This study aims to compare several linguistic and technological aspects of four App-Integrated Chatbots (AICs) and to examine the perceptions among English as a Foreign Language (EFL) teacher candidates. In this mixed-methods research based on convenience sampling, 237 college students from Spain (n = 155) and the Czech Republic (n = 82) interacted with four AICs over a month, and evaluated them following a rubric based on the Chatbot-Human Interaction Satisfaction Model. This scale was specifically designed to assess different linguistic and technological features of AICs such as response interval, semantic coherence, sentence length, and user interface. Quantitative and qualitative data were gathered through a pre-post-survey, based on the CHISM model and student assessment reports. Quantitative data were analyzed using SPSS statistics software, while qualitative data were examined using QDA Miner software, focusing on identifying recurring themes through frequency analysis. The findings indicated a moderate level of satisfaction with AICs, suggesting that enhancements in areas such as better adapting to learner needs, integrating interactive multimedia, and improving speech technologies are necessary for a more human-like user interaction.
Fabrication and evaluation of smart pH/thermo dual-responsive injectable intratumoral in situ depot hydrogels for controlled 5-FU delivery
Authors: Khan Samiullah , Khan Bangul , Li Huan
Published: December 2023

Background

5-FU has multiple applications in various cancers but has limitations owing to its shorter half-life and rapid metabolism. In this study, injectable intratumoral gels were developed to enhance 5-FU concentrations in tumor vicinity. Sterile tunable poly (N-isopropylacrylamide)-based pH/thermo dual-sensitive self-assembled and in situ crosslinkable injectable depot gels with low viscous grade of chitosan (LVCS) were developed via cold and free radical polymerization method for localized and sustained delivery.

Results

Rheological analysis confirmed the gelation temperature, sol–gel transitions and viscoelastic behavior of in situ gels. Swelling–deswelling–reswelling cycles established the effect of temperature on structural changes. Swelling tests and in vitro drug release conducted in various dissolution media at variable temperatures confirmed pH/thermal dual response of formulations. Methyl thiazolyl tetrazolium assay confirmed that the hydrogels have good cytocompatibility with above 85% cells viability in Vero cells. In vitro cytotoxicity assay against MCF-7 cells displayed that 5-fluorouracil has good anticancer activity in loaded gel form as compared to free 5-FU. The cytotoxic studies showed that IPLVCS-2 and IPLVCS-6 have the highest inhibition (IC50 = 47 ± 1 µg/ml, 34 ± 17 µg/ml) as compared to free 5-FU (IC50 = 52 ± 3 µg/ml).

Conclusion

Current findings conclude that taking the advantage of physiologic environment acidic pH and high temperature of cancer cells, poly(NIPAAm)-g-LVCS formulations can effectively be used as intratumoral controlled depot of 5-FU.

Graphical Abstract
The long-term effects of consecutive COVID-19 waves on mental health
Authors: Novotný Jan Sebastian , Gonzalez-Rivas Juan Pablo , Kunzová Šárka , Skladaná Mária , Pospíšilová Anna , Polcrová Anna , Vassilaki Maria , Medina-Inojosa Jose Ramon , Lopez-Jimenez Francisco , Geda Yonas Endale , Stokin Gorazd Bernard
Published: December 2023

Background

Although several studies have documented the impact of the COVID-19 pandemic on mental health, the long-term effects remain unclear.

Aims

To examine longitudinal changes in mental health before and during the consecutive COVID-19 waves in a well-established probability sample.

Method

An online survey was completed by the participants of the COVID-19 add-on study at four time points: pre-COVID-19 period (2014–2015,n= 1823), first COVID-19 wave (April to May 2020,n= 788), second COVID-19 wave (August to October 2020,n= 532) and third COVID-19 wave (March to April 2021,n= 383). Data were collected via a set of validated instruments, and analysed with latent growth models.

Results

During the pandemic, we observed a significant increase in stress levels (standardisedβ= 0.473,P< 0.001) and depressive symptoms (standardisedβ= 1.284,P< 0.001). The rate of increase in depressive symptoms (std. covariance = 0.784,P= 0.014), but not in stress levels (std. covariance = 0.057,P= 0.743), was associated with the pre-pandemic mental health status of the participants. Further analysis showed that secondary stressors played a predominant role in the increase in mental health difficulties. The main secondary stressors were loneliness, negative emotionality associated with the perception of COVID-19 disease, lack of resilience, female gender and younger age.

Conclusions

The surge in stress levels and depressive symptoms persisted across all three consecutive COVID-19 waves. This persistence is attributable to the effects of secondary stressors, and particularly to the status of mental health before the COVID-19 pandemic. Our findings reveal mechanisms underlying the surge in mental health difficulties during the COVID-19 waves, with direct implications for strategies promoting mental health during pandemics.
DeepPhe-CR: Natural Language Processing Software Services for Cancer Registrar Case Abstraction
Authors: Hochheiser Harry , Finan Sean , Yuan Zhou , Durbin Eric B. , Jeong Jong Cheol , Hands Isaac , Rust David , Kavuluru Ramakanth , Wu Xiao-Cheng , Warner Jeremy L. , Savova Guergana
Published: December 2023

PURPOSE

Manual extraction of case details from patient records for cancer surveillance is a resource-intensive task. Natural Language Processing (NLP) techniques have been proposed for automating the identification of key details in clinical notes. Our goal was to develop NLP application programming interfaces (APIs) for integration into cancer registry data abstraction tools in a computer-assisted abstraction setting.

METHODS

We used cancer registry manual abstraction processes to guide the design of DeepPhe-CR, a web-based NLP service API. The coding of key variables was performed through NLP methods validated using established workflows. A container-based implementation of the NLP methods and the supporting infrastructure was developed. Existing registry data abstraction software was modified to include results from DeepPhe-CR. An initial usability study with data registrars provided early validation of the feasibility of the DeepPhe-CR tools.

RESULTS

API calls support submission of single documents and summarization of cases across one or more documents. The container-based implementation uses a REST router to handle requests and support a graph database for storing results. NLP modules extract topography, histology, behavior, laterality, and grade at 0.79-1.00 F1 across multiple cancer types (breast, prostate, lung, colorectal, ovary, and pediatric brain) from data of two population-based cancer registries. Usability study participants were able to use the tool effectively and expressed interest in the tool.

CONCLUSION

The DeepPhe-CR system provides an architecture for building cancer-specific NLP tools directly into registrar workflows in a computer-assisted abstraction setting. Improved user interactions in client tools may be needed to realize the potential of these approaches.