bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing and evaluating an e-learning and e-assessment tool for organic chemistry in higher education
Authors: Schuessler Katrin , Striewe Michael , Pueschner Daniel , Luetzen Arne , Goedicke Michael , Giese Michael , Walpuski Maik
Published: October 2024

A convincing e-learning system for higher education should offer adequate usability and not add unnecessary (extraneous) cognitive load. It should allow teachers to switch easily from traditional teaching to flipped classrooms to provide students with more opportunities to learn and receive immediate feedback. However, an efficient e-learning and technology-enhanced assessment tool that allows generating digital organic chemistry tasks is yet to be created. The Universities of Bonn and Duisburg-Essen are currently developing and evaluating an e-learning and technology-enhanced assessment tool for organic chemistry. This study compares the effectiveness of traditional paper-pencil-based and digital molecule-drawing tasks in terms of student performance, cognitive load, and usability—factors that all contribute to learning outcomes. Rasch analysis, t-tests, and correlation analyses were used for evaluation, revealing that the developed system can generate digital organic chemistry tasks. Students performed equally well on simple digital and paper-pencil molecule-drawing tasks when they received an appropriate introduction to the digital tool. However, using the digital tool in two of three studies imposes a higher extraneous cognitive load than using paper and pencil. Nevertheless, the students rated the tool as sufficiently usable. A significant negative correlation between extraneous load and tool usability was found, suggesting room for improvement. We are currently concentrating on augmenting the functionality of the new e-learning tool to increase its potential for automatic feedback, even for complex tasks such as reaction mechanisms.
Multiple relocation cases in disaster-related deaths after the Fukushima nuclear accident
Authors: Ito Naomi , Sawano Toyoaki , Uchi Yuna , Kawashima Moe , Kitazawa Kemmei , Moriyama Nobuaki , Amir Isamu , Yoshimura Hiroki , Nonaka Saori , Saito Hiroaki , Ozaki Akihiko , Yamamoto Chika , Abe Toshiki , Murakami Michio , Sato Mika , Matsumoto Chihiro , Yamamura Momoka , Zhao Tianchen , Sakakibara Mamoru , Yagiuchi Kazuko , Otsuki Mako , Oikawa Tomoyoshi , Niwa Shinichi , Tsubokura Masaharu
Published: October 2024

Introduction

Relocation after a disaster often has negative health effects on vulnerable people, particularly older adults. However, little is known about the number of repeated evacuations and relocations after disasters among those experienced disaster-related deaths. This case series aimed to summarize the secondary problems and mortality risks in patients involved in relocation after disasters.

Methods

We analyzed and summarized the data on 520 disaster-related deaths in Minamisoma City, a municipality near the Fukushima Daiichi Nuclear Power Plant, focusing on the number of relocations. Herein, we describe the cases of three individuals over 80 years old, who died after eight or more relocations, which were certified as disaster-related deaths.

Results

We discuss following three cases, which are (1) a female patient in her 90s who had a stroke and was completely disabled, (2) a female patient in her 80s whose cancer was detected later due to her failing to see her family doctor, and (3) a male patient in his 80s whose regular postoperative treatment was disrupted following cancer recurrence.

Discussion

Our findings indicate that evacuation led to the worsening of chronic diseases and eventually to post-disaster death. Prolonged wide-area evacuation and repeated relocation likely interrupted the continuum of care and led to the failure of adequate care provision. To reduce the loss of human life, it is necessary to review the number of wide-area evacuations and relocations over the medium to long term after large-scale disasters, including nuclear disasters, which may occur in the future. Simultaneously, it is important to establish a medical system at the evacuation site so that disaster victims can continue to receive medical care even after evacuation or relocation.
Evidence of apoptosis as an early event leading to cyclophosphamide-induced primordial follicle depletion in a prepubertal mouse model
Authors: Hao Xia , Reyes Palomares Arturo , Anastácio Amandine , Liu Kui , Rodriguez-Wallberg Kenny A.
Published: October 2024

Introduction

The mechanisms leading to ovarian primordial follicle depletion following gonadotoxic chemotherapy with cyclophosphamide and other cytotoxic drugs are currently understood through two main explanatory theories: apoptosis and over-activation. Discrepancies between the findings of different studies investigating these mechanisms do not allow to reach a firm conclusion. The heterogeneity of cell types in ovaries and their different degrees of sensitivity to damage, cell-cell interactions, periodical follicle profile differences, model age-dependent differences, and differences of exposure durations of tested drugs may partially explain the discrepancies among studies.

Methods

This study used intact prepubertal mice ovaries in culture as study model, in which most follicles are primordial follicles. Histological and transcriptional analyses of ovaries exposed to the active metabolite of cyclophosphamide 4-hydroperoxycyclophosphamide (4-HC) were carried out via a time-course experiment at 8, 24, 48, and 72 h.

Results

4-HC treated ovaries showed a significant decrease in primordial follicle density at 24 h, along with active DNA damage (TUNEL) and overexpressed apoptosis signals (cleaved-poly ADP ribose polymerase in immunohistochemistry and western blotting). Meanwhile 4-HC treatment significantly up-regulated H2ax, Casp 6, Casp 8, Noxa, and Bax in ovaries, and up-regulated Puma in primordial follicles (FISH).

Discussion

Our results indicated that cyclophosphamide-induced acute ovarian primordial follicle depletion was mainly related to apoptotic pathways. No evidence of follicle activation was found, neither through changes in the expression of related genes to follicle activation nor in the density of growing follicles. Further validation at protein level in 4-HC-treated prepubertal mice ovaries at 24 h confirmed these observations.
Diagnostic accuracy of a non-invasive spot-check hemoglobin meter, Masimo Rad-67® pulse CO-Oximeter®, in detection of anemia in antenatal care settings in Kenya
Authors: Koech Angela , Mwaniki Isaac , Mutunga Joseph , Mukhanya Moses , Mwadime Emily , Ochieng Marvine , Mwashigadi Grace , Mistry Hiten D. , Craik Rachel , von Dadelszen Peter , Temmerman Marleen , Luchters Stanley , Omuse Geoffrey ,   The PRECISE Network
Published: October 2024

Background

Point of care hemoglobin meters play key roles in increasing access to anemia screening in antenatal care especially in settings with limited access to laboratories. We aimed to determine the diagnostic accuracy of a non-invasive spot-check hemoglobin (SpHb) meter, Masimo Rad-67® Pulse CO-Oximeter®, in the diagnosis of anemia in pregnant women attending antenatal care clinics in Kilifi, Kenya.

Methods

This was a diagnostic accuracy study that retrospectively evaluated SpHb against a validated reference standard of laboratory assessed hemoglobin (Lab Hb) by a SYSMEX XN-330 automated hematology analyzer. The study was nested within a prospective pregnancy cohort study that recruited unselected pregnant women from antenatal care clinics in two public hospitals in Kilifi County, coastal Kenya. Records with both SpHb and Lab Hb were selected from pregnancy visits between May 2021 and December 2022. Linear regression and Bland-Altman analysis were performed to compare the two tests and diagnostic accuracy parameters obtained for the diagnosis of anemia.

Results

A total of 2,975 records (from 2,203 unique participants), with paired SpHb and Lab Hb were analyzed. Linear regression showed a significant but weak positive correlation, a proportional bias of 0.44 (95% CI 0.41–0.47) and a constant of 7.59 (95% CI 7.30–7.87, p < 0.001). The median bias was 1.70 g/dl, with limits of agreement of −0.80 to 4.20. SpHb tended to be higher than Lab Hb on the low hemoglobin range but lower than Lab Hb on the high hemoglobin range. The sensitivity of SpHb in detecting anemia was 18.66%. Prevalence, specificity, positive predictive value, and negative predictive values were 46.37%, 96.77%, 83.33%, and 57.92% respectively.

Conclusion

Overall, SpHb by Masimo Rad-67® Pulse CO-Oximeter® did not accurately identify pregnant women with anemia and many cases would be missed. We would not recommend its use in antenatal care settings.
Surviving septic patients endotyped with a functional assay demonstrate active immune responses
Authors: Price Adam D. , Becker Ellen R. , Barrios Evan L. , Mazer Monty B. , McGonagill Patrick W. , Bergmann Christian B. , Goodman Michael D. , Gould Robert W. , Rao Mahil , Polcz Valerie E. , Kucaba Tamara A. , Walton Andrew H. , Miles Sydney , Xu Julie , Liang Muxuan , Loftus Tyler J. , Efron Philip A. , Remy Kenneth E. , Brakenridge Scott C. , Badovinac Vladimir P. , Griffith Thomas S. , Moldawer Lyle L. , Hotchkiss Richard S. , Caldwell Charles C.
Published: October 2024

Introduction

Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.

Methods

This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an ‘immunocompetent’, ‘immunosuppressed endotype’, and two ‘mixed’ endotypes.

Results

Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. ‘Immunocompetent’ endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the ‘immunosuppressed’ endotype. Similarly, ‘immunocompetent’ endotype patients on day 4 had a higher in-hospital survival compared to the ‘immunosuppressed’ endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality.

Conclusions

Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early ‘immunocompetent’ endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.
Ischemia-induced endogenous Nrf2/HO-1 axis activation modulates microglial polarization and restrains ischemic brain injury
Authors: Kuo Ping-Chang , Weng Wen-Tsan , Scofield Barbara A. , Paraiso Hallel C. , Yu I-Chen Ivorine , Yen Jui-Hung Jimmy
Published: October 2024

Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in the ischemic brain induce oxidative stress and inflammatory responses. Nrf2 is a transcription factor responsible for regulating cellular redox balance through the induction of protective antioxidant and phase II detoxification responses. Although the induction of endogenous Nrf2/HO-1 axis activation has been observed in the ischemic brain, whether ischemia-induced endogenous Nrf2/HO-1 axis activation plays a role in modulating microglia (MG) phenotypes and restraining ischemic brain injury is not characterized and requires further exploration. To investigate that, we generated mice with Nrf2 knockdown specifically in MG to rigorously assess the role of endogenous Nrf2 activation in ischemic brain injury after stroke. Our results showed that MG-specific Nrf2 knockdown exacerbated ischemic brain injury after stroke. We found that Nrf2 knockdown altered MG phenotypes after stroke, in which increased frequency of inflammatory MG and decreased frequency of anti-inflammatory MG were detected in the ischemic brain. Moreover, we identified attenuated Nrf2/HO-1 axis activation led to increased CD68/IL-1β and suppressed CD206 expression in MG, resulting in aggravated inflammatory MG in MG-specific Nrf2 knockdown mice after stroke. Intriguingly, using type II diabetic preclinical models, we revealed that diabetic mice exhibited attenuated Nrf2/HO-1 axis activation in MG and exacerbated ischemic brain injury after stroke that phenocopy mice with MG-specific Nrf2 knockdown. Finally, the induction of exogenous Nrf2/HO-1 axis activation in MG through pharmacological approaches ameliorated ischemic brain injury in diabetic mice. In conclusion, our findings provide cellular and molecular insights demonstrating ischemia-induced endogenous Nrf2/HO-1 axis activation modulates MG phenotypes and restrains ischemic brain injury. These results further strengthen the therapeutic potential of targeting Nrf2/HO-1 axis in MG for the treatment of ischemic stroke and diabetic stroke.
Metapragmatic reflections of adolescents on gender in ironic interactions
Authors: Hess Zimmermann Karina , Avecilla-Ramírez Gloria Nélida , Castillo Romo Abryl Angélica
Published: October 2024

Introduction

While verbal irony is a pragmatic skill that plays a very important role in social interactions, its development has not been sufficiently studied, especially in the context of the Spanish language. This research aims to generate a deeper understanding of the development of irony, specifically among Mexican adolescents. One of the pragmatic aspects identified as an important factor to consider in the comprehension and production of verbal irony is the gender of the participants involved in the communicative interaction. Prior research with adults indicates that ironic statements produced by men are generally associated with positive discursive functions, whereas those made by women are often perceived negatively. This study aims to analyze the metapragmatic reflections of 37 Mexican adolescents aged 12 and 15 years old (20 and 17 participants, respectively, half women) on how the gender of the interlocutors influences the use of irony in various communicative situations.

Methods

Participants were presented with eight written scenarios that concluded with a written ironic statement (in order to minimize the effects of prosody). The scenarios were counterbalanced to account for the type of ironic remark (critical or praise irony), the gender of the ironist, and the gender of the audience. Through a semi- structured oral interview, the adolescents' reflections and the rationale behind their responses were examined.

Results

The results revealed significant differences in the interpretation of irony based on age, type of statement (criticism or praise), and the gender of the interlocutors, though not with respect to the gender of the audience. Additionally, a discrepancy was observed between the metapragmatic reflections expressed by adolescents regarding ironic statements and their actual interpretation of irony.

Discussion

These findings suggest that during adolescence, individuals develop an increasing capacity to consider factors related to gender roles that influence the pragmatic interpretation of ironic statements.
Methylene blue therapy in addition to standard treatment for acute-phase septic shock: a pilot randomized controlled trial
Authors: Luis-Silva Fabio , Menegueti Mayra Gonçalves , Peres Leandro Moreira , Sepeda Corina dos Reis , Jordani Maria Cecília , Mestriner Fabiola , Petroski-Moraes Bruno Cesar , Brito-de-Sousa Joaquim Pedro , Costa-Rocha Ismael Artur , Cruz Bruna Lemos , Donadel Mariana Dermínio , de Souza Felipe Barizza , Reis Gustavo Henrique Martins , Bellissimo-Rodrigues Fernando , Basile-Filho Anibal , Becari Christiane , Evora Paulo Roberto Barbosa , Martins-Filho Olindo Assis , Auxiliadora-Martins Maria
Published: October 2024

Purpose

Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase.

Objective

To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group.

Methods

This was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6).

Results

MB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group.

Conclusion

Early administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock.

Clinical trial registration

https://clinicaltrials.gov/, identifier RBR-96584w4.
Emergence of lineage ST150 and linezolid resistance in Enterococcus faecalis: a molecular epidemiology study of UTIs in Tehran, Iran
Authors: Seyedolmohadesin Maryam , Kouhzad Mobina , Götz Friedrich , Ashkani Maedeh , Aminzadeh Soheila , Bostanghadiri Narjess
Published: October 2024

Background

Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections, with Enterococcus species now recognized as the second leading cause of these infections. This study focused on symptomatic UTI cases to investigate the risk factors associated with Enterococcus faecalis clinical isolates in patients from Tehran, Iran.

Methods

Urine samples were collected from patients presenting with symptomatic UTIs. The identification of E. faecalis isolates was performed using standard microbiological techniques, with confirmation via polymerase chain reaction (PCR). Antibiotic susceptibility testing was conducted using the Kirby–Bauer disc diffusion method. The presence of virulence genes was determined through PCR, and biofilm formation was assessed using the microtiter plate method. Additionally, multi-locus sequence typing (MLST) was utilized to genotype linezolid-resistant isolates.

Results

Out of 300 UTI cases, E. faecalis was identified as the causative agent in 160 instances. Notably, a high proportion of these isolates exhibited resistance to tetracycline (83.8%) and minocycline (82.5%). Linezolid resistance was observed in 1.3% (n = 2) of the isolates. Conversely, the highest susceptibility rates were observed for vancomycin, penicillin G, ampicillin, and nitrofurantoin, each demonstrating a 98.8% susceptibility rate. Biofilm formation was detected in 25% of the E. faecalis isolates. A significant majority (93.8%) of the isolates harbored the efbA and ace genes, with varying frequencies of esp (72.5%), asa1 (61.2%), cylA (52.5%), and gelE (88.8%) genes. MLST analysis demonstrated that both linezolid-resistant isolates, characterized by strong biofilm formation and the presence of virulence genes, were assigned to the ST150 lineage, which has not been previously documented in clinical settings.

Conclusion

The emergence of the ST150 clonal lineage, underscores its clinical significance, particularly in relation to linezolid resistance in E. faecalis. This study adds to the growing body of evidence linking specific clonal lineages with antibiotic resistance, highlighting the critical need for ongoing surveillance and molecular characterization of resistant pathogens.
3'UTR of tobacco vein mottling virus regulates downstream GFP expression and changes in host gene expression
Authors: Sun Zhenqi , Liu Dongyang , Li Bin , Yan Fangfang , Wang Yuhu , Yang Tianqi , Wang Haijuan , Xu Jiaxin , Zhou Hongyou , Zhao Mingmin
Published: October 2024

Introduction

Tobacco vein mottling virus (TVMV) is a member of the family Potyviridae. The 3’ untranslated region (3’UTR) of viral genomic RNA has been reported to significantly impact viral infection. Nevertheless, the role of the TVMV 3’UTR during viral infection remains unknown.

Methods

Here, a 3’UTR-GFP expression vector was transiently expressed in Nicotiana benthamiana, in which the 3’UTR of TVMV was introduced upstream of the green fluorescent protein (GFP) gene. Transcriptome sequencing was performed to analyze the genes associated with plant resistance. The effect of the TVMV 3’UTR on GFP expression was studied using an Agrobacterium-mediated transient expression assay, revealing that the TVMV 3’UTR significantly inhibited GFP expression. Transcriptome analysis of differentially expressed genes in 3’UTR-GFP in N. benthamiana was performed to elucidate the why the TVMV 3’UTR inhibited GFP expression.

Results

Eighty genes related to plant disease resistance were differentially expressed, including 29 upregulated and 51 downregulated genes. Significantly upregulated genes included those encoding the calcium-binding protein CML24, leucine-rich repeat receptor-like tyrosine-protein kinase, and respiratory burst oxidase homolog protein E. The significantly downregulated genes included calcium-binding protein 7, ethylene-responsive transcription factor 10, endoglucanase 5, and receptor-like protein kinase.

Discussion

These findings indicate that the 3’UTR of TVMV may inhibit the expression of GFP gene by inducing the expression of plant resistance genes. This study provides a theoretical basis for further research on the function and mechanism of the TVMV 3’UTR.
Genomic insights and functional evaluation of Lacticaseibacillus paracasei EG005: a promising probiotic with enhanced antioxidant activity
Authors: Kim Jisu , Jo Jinchul , Cho Seoae , Kim Heebal
Published: October 2024

Introduction

Probiotics, such as Lacticaseibacillus paracasei EG005, are gaining attention for their health benefits, particularly in reducing oxidative stress. The goal of this study was to reinforce the antioxidant capacity of EG005, along with comprehensive genomic analysis, with a focus on assessing superoxide dismutase (SOD) activity, acid resistance and bile tolerance, and safety.

Methods

EG005 was screened for SOD activity and change of SOD activity was tested under various pH conditions. Its survival rates were assessed in acidic (pH 2.5) and bile salt (0.3%) conditions and the antibiotic MIC test and hemolysis test were performed to evaluate safety. Genetic analyses including functional identification and phylogenetic tree construction were performed. The SOD overexpression system was constructed using Ptuf, Pldh1, Plhd2, and Pldh3 strong promoters.

Results

EG005 demonstrated higher SOD activity compared to Lacticaseibacillus rhamnosus GG, with optimal activity at pH 7.0. It showed significant acid and bile tolerance, with survival rates recovering to 100% after 3 h in acidic conditions. Phylogenetic analysis confirmed that EG005 is closely related to other L. paracasei strains with ANI values above 98%. Overexpression of SOD using the Ptuf promoter resulted in a two-fold increase in activity compared to the controls. Additionally, EG005 exhibited no hemolytic activity and showed antibiotic susceptibility within safe limits.

Discussion

Our findings highlight EG005’s potential as a probiotic with robust antioxidant activity and high tolerance to gastrointestinal conditions. Its unique genetic profile and enhanced SOD activity through strong promoter support its application in probiotic therapies and functional foods. Further research should be investigated to find the in vivo effects of EG005 on gut health and oxidative stress reduction. In addition, attB and attP-based recombination, combined with CRISPR-Cas9 technologies, could offer a more stable alternative for long-term sodA gene expression in commercial and medical applications.
Breast cancer and neoplasms of the thyroid gland: a bidirectional two-sample Mendelian randomization study
Authors: Sun Yiqi , Wan Bohan , Liu Xin , Dong Jianguo , Yin Shengjie , Wu Yiqi
Published: October 2024

Background

With the rising incidence of breast cancer (BC) and neoplasms of the thyroid gland, a potential link between the two has drawn increasing attention. However, the causal relationship remains unclear due to various confounding factors. This study aims to investigate the causality between BC and thyroid tumors using Mendelian Randomization (MR) analysis.

Methods

We conducted a bidirectional two-sample MR analysis, utilizing breast cancer-associated single nucleotide polymorphisms (SNPs) from the Breast Cancer Association Consortium (BCAC) and thyroid tumor-related SNPs from the FinnGen (https://www.finngen.fi/) database. First, we performed univariable MR (UVMR) to assess the causal relationship between BC and both malignant and benign thyroid tumors, followed by reverse causality analysis. To account for potential confounders, we applied multivariable MR (MVMR). The inverse-variance weighted (IVW) method was primarily used, with secondary analyses performed using the weighted median and MR-Egger regression approaches.

Results

UVMR analysis revealed a significant positive causal relationship between BC and malignant thyroid tumors (odds ratio [OR] and 95% confidence interval [CI]: 1.291, 1.143–1.458, P = 3.90×10-5). No causal relationship was found between BC and benign thyroid tumors. The MVMR analysis, adjusting for confounding factors such as smoking, drinking, and body mass index (BMI), confirmed the robustness of the results.

Conclusion

This study provides genetic evidence supporting a causal relationship between BC and malignant thyroid tumors. These findings highlight the importance of thyroid cancer screening in BC patients. However, further MR studies or randomized controlled trials (RCTs) are necessary to assess small effects accurately.
Antagonistic roles of cGAS/STING signaling in colorectal cancer chemotherapy
Authors: Liang Beiyuan , Xing Xuanxuan , Storts Hayden , Ye Zhen , Claybon Hazel , Austin Ryan , Ding Rachel , Liu Bei , Wen Haitao , Miles Wayne O. , Fishel Richard , Wang Jing J.
Published: October 2024

FOLFOX, composed of 5-FU, oxaliplatin and leucovorin, is a first line chemotherapy regimen for colorectal cancer (CRC) treatment. In this study, we show that 5-FU and oxaliplatin induce DNA damage and activate cGAS/STING signaling leading to enhanced expression of interferon (IFN) β, IFN-stimulated genes and inflammatory cytokines in mouse and human colon cancer cells as well as increased intratumoral CD8+ T cells in mice. Crucially, 5-FU and oxaliplatin increase PD-L1 expression at the mRNA and protein levels, which has been shown to inhibit CD8+ T cell function. Depletion of cGAS, STING, IRF3, or IFNα/β receptor 1 (IFNAR1) abolishes this increase, indicating that 5-FU/oxaliplatin mediated upregulation of PD-L1 expression is dependent on tumor cell intrinsic cGAS/STING signaling. These results imply opposing roles for FOLFOX during cancer treatment. On one hand, 5-FU and oxaliplatin activate the innate immune response to facilitate anti-tumor immunity, and conversely upregulate PD-L1 expression to evade immune surveillance. Analysis of TCGA colon cancer dataset shows a positive correlation between expression of PD-L1 and components of the cGAS/STING pathway, supporting a role for cGAS/STING signaling in upregulating PD-L1 expression in colon cancer patients. Tumor studies in syngeneic immune competent mice demonstrate that the combination of 5-FU/oxaliplatin and anti-PD-1 significantly reduced tumor growth of colon cancer cells compared to 5-FU/oxaliplatin treatment alone. Taken together, our studies have identified a unique pathway leading to chemoresistance and provide a rationale to combine FOLFOX with anti-PD-1/PD-L1 as an effective CRC treatment.
The role of nutrition and gut microbiome in the progression of multiple myeloma and its precursor disease
Authors: Kanellos Panagiotis T. , Baxevanis Georgios K. , Tentolouris Anastasios , Gavriatopoulou Maria , Ntanasis-Stathopoulos Ioannis
Published: October 2024

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by unregulated monoclonal proliferation in the bone marrow. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant conditions that can progress to MM. Identifying etiological risk factors for MM and its precursor diseases is crucial for prevention. Obesity, diet, vitamin D levels, and gut microbiota alterations have been identified as lifestyle factors affecting MM and MGUS risk. Upon disease onset, treatment strategies aim to reduce disease burden, enhance prognosis, and optimize patients’ quality of life. Nutrition and body weight have been shown to affect disease progression and treatment outcomes. MM patients often present with vitamin D, vitamin B12, and folate deficiencies, which worsen disease prognosis. High body mass index is linked to increased death rates among MM patients and an increased risk of MGUS transformation to MM. Gut microbiota has also been associated with disease progression and response to treatment. This literature review aims to summarize the available evidence regarding the impact of nutrition and nutritional status on MM patients beyond prevention, highlighting the significance of gut microbiome and dysbiosis in MM progression.
Multiple mechanisms enable broad-spectrum activity of the Pelargonium sidoides root extract EPs 7630 against acute respiratory tract infections
Authors: Cinatl Jindrich , Wass Mark N. , Michaelis Martin
Published: October 2024

There is clinical evidence showing that the Pelargonium sidoides root extract EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses. Moreover, EPs 7630 has been shown to reduce the use of antibiotics, which is important in the context of rising antibiotic resistance levels. A wide range of mechanisms appears to contribute to the beneficial effects of EPs 7630, e.g. antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities seems to enable the clinical activity of EPs 7630 against multiple respiratory infections. In particular, the combination of antiviral and immunomodulatory effects may enable EPs 7630 to tackle acute viral respiratory infections both in early stages of the disease process, which are driven by virus replication, as well as in later stages, which are caused by an overshooting immune response. Hence, EPs 7630 is a prime example of a plant extract with evidence-based clinical efficacy, including a solid understanding of the underlying mechanisms of action. The example of EPs 7630 demonstrates that plant extracts have a potential role as evidence-based clinical treatments and that they deserve pre-clinical and clinical testing and investigation in the same way as any other drug class.
Remote physiological signal recovery with efficient spatio-temporal modeling
Authors: Zou Bochao , Zhao Yu , Hu Xiaocheng , He Changyu , Yang Tianwa
Published: October 2024

Contactless physiological signal measurement has great applications in various fields, such as affective computing and health monitoring. Physiological measurements based on remote photoplethysmography (rPPG) are realized by capturing the weak periodic color changes. The changes are caused by the variation in the light absorption of skin surface during systole and diastole stages of a functioning heart. This measurement mode has advantages of contactless measurement, simple operation, low cost, etc. In recent years, several deep learning-based rPPG measurement methods have been proposed. However, the features learned by deep learning models are vulnerable to motion and illumination artefacts, and are unable to fully exploit the intrinsic temporal characteristics of the rPPG. This paper presents an efficient spatiotemporal modeling-based rPPG recovery method for physiological signal measurements. First, two modules are utilized in the rPPG task: 1) 3D central difference convolution for temporal context modeling with enhanced representation and generalization capacity, and 2) Huber loss for robust intensity-level rPPG recovery. Second, a dual branch structure for both motion and appearance modeling and a soft attention mask are adapted to take full advantage of the central difference convolution. Third, a multi-task setting for joint cardiac and respiratory signals measurements is introduced to benefit from the internal relevance between two physiological signals. Last, extensive experiments performed on three public databases show that the proposed method outperforms prior state-of-the-art methods with the Pearson’s correlation coefficient higher than 0.96 on all three datasets. The generalization ability of the proposed method is also evaluated by cross-database and video compression experiments. The effectiveness and necessity of each module are confirmed by ablation studies.
Unveiling the proteome of the fasting heart: Insights into HIF-1 pathway regulation
Authors: Benak Daniel , Holzerova Kristyna , Kolar Frantisek , Chalupova Miloslava , Hlavackova Marketa
Published: October 2024

Fasting is a common dietary intervention known for its protective effects against metabolic and cardiovascular diseases. While its effects are mostly systemic, understanding tissue-specific changes in the heart is crucial for the identification of the mechanisms underlying fasting-induced cardioprotection. In this study, we performed a proteomic analysis of the fasting heart and attempted to clarify the molecular basis of fasting-induced cardioprotection. Our investigation identified a total of 4,652 proteins, with 127 exhibiting downregulation and 118 showing upregulation after fasting. Annotation analysis highlighted significant changes in processes such as lipid metabolism, the peroxisome pathway, and reactive oxygen species metabolism. Notably, the HIF-1 signaling pathway emerged as one of the focal points, with various HIF-1 targets exhibiting differential responses to fasting. Further experiments demonstrated downregulation of HIF-1α at both transcript and protein levels. Intriguingly, while gene expression of Egln3 decreased, its protein product PHD3 remained unaffected by fasting. The unchanged levels of pro-inflammatory cytokines indicated that the observed reduction in Hif1a expression did not stem from a decrease in basal inflammation. These findings underscore the complex regulation of the well-established cardioprotective HIF-1 signaling within the heart during 3-day fasting.
Self-regulation and performance among elite youth soccer players: the role of approach-avoidance motivation
Authors: Hamoud Mounir , Sæther Stig Arve , Bjørnebekk Gunnar
Published: October 2024

Introduction and methods

This study aimed to investigate the motivational processes behind self-regulated learning and performance among 192 soccer players (82 girls) for three age groups (14–16 years old) eligible for the Norwegian national football team. A conditional process model was proposed and tested with achievement goals as mediators between achievement motives on the one hand and coach-reported performance and self-regulated learning on the other hand. The probability of success was examined as a potential moderator in the motivational process.

Results

As predicted, motives to achieve success directly influenced planning and reflection/evaluation, whereas the influence of the success motive on regulation of effort was explained partly by task- and self-based approach goals. The motive to achieve success was, however, particularly crucial for maintaining these beneficial regulatory processes when the probability of success was found to be from moderate to low. Concerning the avoidance paths, the data supported only some of our original hypotheses. The motive to avoid failure predicted all three types of avoidance-based (task, self, and other) and other-based approach goals but did not contribute to explaining planning, reflection/evaluation, regulation of effort, or performance. There were no significant correlations between motivation variables and coach-reported performance. Moreover, girls were more motivated to avoid failure than boys, while both sexes achieved similar scores for football-specific self-regulated learning, probability of success, achievement goals, and motive to achieve success.

Discussion

The results are discussed considering a hierarchical motivation model.
“I feel so small and big at the same time”—exploring body experience and binge eating disorder following inpatient treatment: a qualitative study
Authors: Olsen Helene T. , Vangen Sunniva B. , Stänicke Line Indrevoll , Vrabel KariAnne
Published: October 2024

Background

Limited research into binge eating disorder (BED), a low treatment rate, and a lack of treatment rights, reflects a marginalized disorder in society and a treatment context.

Aim

The aim of this study was to gain a deeper understanding of the psychopathology of BED, by exploring the patients’ meanings related to the disorder and the role of the body in the treatment of BED.

Method

Qualitative methodology using a reflexive thematic analysis. The data material is based on semi-structured in-depth interviews with six cis-gendered women who had previously completed an inpatient treatment program for BED at a department for EDs and met the criteria for 307.51 Binge Eating Disorder in DSM-5.

Results

The qualitative analysis rendered two meta-themes comprising six themes and 12 subthemes. The initial meta-theme was “Relational challenges and feelings could not be talked about at home.” The secondary meta-theme was “Body contempt disturbs the experience of self and others” and the third was “Their body has not been a theme in previous treatment.” This categorization depicts a narrative of the disorder in terms of development, current condition, and experiences with prior treatment.

Discussion

The findings indicate that shame and disgust are central to playing pivotal roles in the embodiment of BED, highlighting the significance of addressing one’s relationship with their body for achieving recovery and preventing an experienced repetition of the perceived rejection as a child.
Weathering words: a virtual reality study of environmental influence on reading dynamics
Authors: Rocabado Francisco , Muntini Laís , González Alonso Jorge , Duñabeitia Jon Andoni
Published: October 2024

Introduction

Reading is a fundamental cognitive activity that is influenced by both textual and external environmental factors, although the latter has been less thoroughly explored. This study aims to examine the impact of environmental visual conditions on reading performance using Virtual Reality (VR) technology.

Methods

We conducted two experiments to assess the effects of visual contrast and simulated weather conditions on reading dynamics. In Experiment 1, we measured single-word recognition speed using a lexical decision task under different visual contrasts and weather conditions. In Experiment 2, we assessed reading dynamics during a sentence reading task, analyzing how visual contrast and simulated sunny versus rainy weather conditions affected reading behavior, particularly focusing on reading speed and eye fixations.

Results

In Experiment 1, high visual contrast, particularly under sunny conditions, significantly enhanced single-word recognition speed, indicating a notable influence of environmental visual conditions. In Experiment 2, visual contrast had minimal effect on sentence reading; however, sunny weather facilitated faster reading times, while rainy scenarios increased the number of eye fixations.

Discussion

These findings suggest that environmental factors, such as weather conditions, can significantly affect reading behavior. The study contributes to the understanding of key environmental influences on reading in everyday life contexts and has implications for the ergonomic design of reading materials, especially for outdoor settings and VR environments. Additionally, the integration of controlled stimuli within VR increases the ecological validity of reading research, underscoring the potential of VR as a powerful tool for cognitive research.
Improving mental health among intensive care unit staff with communication skills training
Authors: Holmberg Johan , Rosendahl Ingvar , Andersson Rebecca , Kemani Mike K. , Holmström Linda , Öst Lars-Göran , Wicksell Rikard K.
Published: October 2024

Purpose

Intensive Care Unit (ICU) staff report that a large part of the work-related distress they experience is related to communication situations with colleagues, patients, and relatives. Based on these findings, the aim of the present study was to preliminary evaluate the effects of a novel Communication Skills Training (CST) program on mental health among ICU staff.

Methods

The CST program was delivered to the entire work force of an ICU at a Swedish hospital and was evaluated as an uncontrolled clinical trial with three repeated measures. 100 participants were eligible and included in the analyses. The theoretical framework for the program was learning theory and cognitive behavioral therapy. The program was delivered by two psychologists and included one full-day lecture and three subsequent two-hour supervision sessions. Changes in mental health was evaluated with self-report questionnaires measuring perceived stress, general mental health, work engagement, and psychological flexibility.

Results

Analyses of three repeated measures showed significant improvements with 1.3 points lower perceived stress and 2.0 points lower general mental health after the intervention. No differences were seen in measures of work engagement or psychological flexibility.

Conclusion

Findings of the study supports the utility of the CST program as an intervention to target perceived stress and general mental health within intensive care. These findings should be further validated in trials with improved design.
Institutional investment in addictive industries: an important commercial determinant of health
Authors: Berret Sébastien , Marionneau Virve , Sievänen Riikka , Nikkinen Janne
Published: October 2024

Background

The production of addictive commodities is subject to a range of commercial determinants. There has nevertheless been a gap in understanding how investments into addictive commodities may function as commercial determinants. Institutional investors can yield important financial power with their investment decisions. Many investors apply responsible investment (RI) policies to address environmental, social, and governance concerns. Negative screening is used to exclude certain sectors or companies from investment portfolios, mainly for ethical concerns. Negative screening also affects investment into tobacco and other addictive industries. This article investigates RI policies toward addictive industries among institutional investors that are signatories of the Tobacco-Free Finance Pledge (TFFP; N = 161). The TFFP is an initiative created in 2021 to de-normalize tobacco-related investments.

Methods

The mixed-method study uses descriptive statistics to quantify the extent and scope of exclusion policies as well as institutional and geographical profiles of investors, and a qualitative analysis of the justifications for these exclusion policies.

Results

Some TFFP signatories apply negative screening to other addictive industries (gambling: 35%; alcohol: 24%; cannabis 12% of signatories). There are important differences in the applied exclusion thresholds, with only 47% of TFFP signatories applying a zero-tolerance policy to tobacco. Thresholds are higher for other addictive industries. Signatories also differ in terms of their geographical and investor profiles. Justifications pertaining to compliance with international standards and reputational risks were the most common.

Conclusion

Addictive industries, such as tobacco, alcohol, gambling, and recreational cannabis, are increasingly excluded by investors. However, different understandings of RI influence how sector exclusions are implemented. Divesting from tobacco and other addictive industries is a crucial step toward a public health approach that prioritizes population health over financial profits. Prominent institutional investors are influential opinion leaders who can change the behavior of other investors and de-normalize controversial industries and reduce or prevent harm.