bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of breast and lung cancers
Authors: Najjary Shiva , de Koning Willem , Kros Johan M. , Mustafa Dana A. M.
Published: December 2023

Introduction

The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis.

Methods

To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors.

Results

Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings.

Conclusion

In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.
Optimization design of optical windows for deep-sea pressure-resistant structures based on transition materials
Authors: Wei Yucong , Ma Guoliang , Zhang Hailong , Zhang Xiaowei , Quan Xiangqian
Published: December 2023

Introduction

The design of high-pressure optical windows is one of the key tasks in deep-sea exploration, as it directly determines the reliability and maximum operating depth of underwater optical equipment.

Method

In this paper, mechanical modeling and finite element analysis methods are employed to study optical windows.

Results and discussion

Results show that changes in boundary conditions during loading significantly affect the stress distribution of the window. Based on this conclusion, an optimization design method is proposed, which involves the use of transition materials to reduce the impact of base deformation on the window. The study further analyzes the effects of the transition material’s Young’s modulus, Poisson’s ratio, thickness, and friction coefficient on the stress of the optical window. A calculation method for material selection criteria is proposed to select appropriate transition materials, and actual materials are used for verification. Finally, the reliability of the optimization design scheme based on transition materials is confirmed through high-pressure experiments.
Genetics and Glaucoma: the state of the art
Authors: Tirendi Sara , Domenicotti Cinzia , Bassi Anna Maria , Vernazza Stefania
Published: December 2023

Glaucoma is the second leading cause of irreversible blindness worldwide. Although genetic background contributes differently to rare early-onset glaucoma (before age 40) or common adult-onset glaucoma, it is now considered an important factor in all major forms of the disease. Genetic and genomic studies, including GWAS, are contributing to identifying novel loci associated with glaucoma or to endophenotypes across ancestries to enrich the knowledge about glaucoma genetic susceptibility. Moreover, new high-throughput functional genomics contributes to defining the relevance of genetic results in the biological pathways and processes involved in glaucoma pathogenesis. Such studies are expected to advance significantly our understanding of glaucoma’s genetic basis and provide new druggable targets to treat glaucoma. This review gives an overview of the role of genetics in the pathogenesis or risk of glaucoma.
Giant cell arteritis: incidence and phenotypic distribution in Western Norway 2013–2020
Authors: Skaug H. K. , Fevang B. T. , Assmus J. , Diamantopoulos A. P. , Myklebust G. , Brekke L. K.
Published: December 2023

Objectives

There is an increasing awareness of the spectrum of phenotypes in giant cell arteritis (GCA). However, there is sparse evidence concerning the phenotypic distribution which may be influenced by both genetic background and the environment. We established a cohort of all GCA-patients in the Bergen Health Area (Western Norway), to describe the phenotypic distribution and whether phenotypes differ with regards to incidence and clinical features.

Methods

This is a retrospective cohort study including all GCA-patients in the Bergen Health Area from 2013–2020. Data were collected by reviewing patient records, and patients considered clinically likely GCA were included if they fulfilled at least one set of classification criteria. Temporal artery biopsy (TAB) and imaging results were used to classify the patients according to phenotype. The phenotype “cranial GCA” was used for patients with a positive TAB or halo sign on temporal artery ultrasound. “Non-cranial GCA” was used for patients with positive findings on FDG-PET/CT, MRI-, or CT angiography, or wall thickening indicative of vasculitis on ultrasound of axillary arteries. Patients with features of both these phenotypes were labeled “mixed.” Patients that could not be classified due to negative or absent examination results were labeled “unclassifiable”.

Results

257 patients were included. The overall incidence of GCA was 20.7 per 100,000 persons aged 50 years or older. Overall, the cranial phenotype was dominant, although more than half of the patients under 60 years of age had the non-cranial phenotype. The diagnostic delay was twice as long for patients of non-cranial and mixed phenotype compared to those of cranial phenotype. Headache was the most common clinical feature (78% of patients). Characteristic clinic features occurred less frequently in patients of non-cranial phenotype compared to cranial phenotype.

Conclusion

The overall incidence for GCA was comparable to earlier reports from this region. The cranial phenotype dominated although the non-cranial phenotype was more common in patients under 60 years of age. The diagnostic delay was longer in patients with the non-cranial versus cranial phenotype, indicating a need for examination of non-cranial arteries when suspecting GCA.
Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver disease: a two-sample Mendelian randomization analysis
Authors: Dai Wanhui , Cai Dandong , Zhou Shuai , Li Ang , Xie Jinsong , Zhang Jie
Published: December 2023

Background

Previous observational studies have indicated that an imbalance in gut microbiota may contribute to non-alcoholic fatty liver disease (NAFLD). However, given the inevitable bias and unmeasured confounders in observational studies, the causal relationship between gut microbiota and NAFLD cannot be deduced. Therefore, we employed a two-sample Mendelian randomization (TSMR) study to assess the causality between gut microbiota and NAFLD.

Methods

The gut microbiota-related genome-wide association study (GWAS) data of 18,340 individuals were collected from the International MiBioGen consortium. The GWAS summary data for NAFLD from the Anstee cohort (1,483 cases and 17,781 controls) and the FinnGen consortium (894 cases and 217,898 controls) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was used as the principal method in our Mendelian randomization (MR) study, with sensitivity analyses using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Moreover, a fixed-effect meta-analysis was conducted to verify the robustness of the results.

Results

The gene prediction results showed that at the genus level, four gut microbiota were causally associated with NAFLD in the GWAS conducted by Anstee et al. The relative abundance of Intestinimonas (OR: 0.694, 95%CI: 0.533–0.903, p = 0.006, IVW), Lachnoclostridium (OR: 0.420, 95%CI: 0.245–0.719, p = 0.002, IVW), and Senegalimassilia (OR: 0.596, 95%CI: 0.363–0.978, p = 0.041, IVW) was negatively associated with NAFLD. The relative abundance of Ruminococcus1 (OR: 1.852, 95%CI: 1.179–2.908, p = 0.007, IVW) was positively correlated with NAFLD. Among them, the Lachnoclostridium genus was validated in FinnGen GWAS (OR: 0.53, 95%CI: 0.304–0.928, p = 0.026, IVW). The Lachnoclostridium genus was also significantly associated with NAFLD risk in the meta-analyses (OR: 0.470, 95%CI: 0.319–0.692, p = 0.0001, IVW). No heterogeneity or pleiotropy was observed.

Conclusion

This study provided new evidence of the relationship between the Lachnoclostridium genus and NAFLD, suggesting that augmentation of the relative abundance of the Lachnoclostridium genus through the oral administration of probiotics or fecal microbiota transplantation could be an effective way to reduce the risk of NAFLD.
The undiscovered biosynthetic potential of the Greenland Ice Sheet microbiome
Authors: Jaarsma Ate H. , Zervas Athanasios , Sipes Katie , Campuzano Jiménez Francisco , Smith Andrea Claire , Svendsen Liessel Victoria , Thøgersen Mariane S. , Stougaard Peter , Benning Liane G. , Tranter Martyn , Anesio Alexandre M.
Published: December 2023

The Greenland Ice Sheet is a biome which is mainly microbially driven. Several different niches can be found within the glacial biome for those microbes able to withstand the harsh conditions, e.g., low temperatures, low nutrient conditions, high UV radiation in summer, and contrasting long and dark winters. Eukaryotic algae can form blooms during the summer on the ice surface, interacting with communities of bacteria, fungi, and viruses. Cryoconite holes and snow are also habitats with their own microbial community. Nevertheless, the microbiome of supraglacial habitats remains poorly studied, leading to a lack of representative genomes from these environments. Under-investigated extremophiles, like those living on the Greenland Ice Sheet, may provide an untapped reservoir of chemical diversity that is yet to be discovered. In this study, an inventory of the biosynthetic potential of these organisms is made, through cataloging the presence of biosynthetic gene clusters in their genomes. There were 133 high-quality metagenome-assembled genomes (MAGs) and 28 whole genomes of bacteria obtained from samples of the ice sheet surface, cryoconite, biofilm, and snow using culturing-dependent and -independent approaches. AntiSMASH and BiG-SCAPE were used to mine these genomes and subsequently analyze the resulting predicted gene clusters. Extensive sets of predicted Biosynthetic Gene Clusters (BGCs) were collected from the genome collection, with limited overlap between isolates and MAGs. Additionally, little overlap was found in the biosynthetic potential among different environments, suggesting specialization of organisms in specific habitats. The median number of BGCs per genome was significantly higher for the isolates compared to the MAGs. The most talented producers were found among Proteobacteria. We found evidence for the capacity of these microbes to produce antimicrobials, carotenoid pigments, siderophores, and osmoprotectants, indicating potential survival mechanisms to cope with extreme conditions. The majority of identified BGCs, including those in the most prevalent gene cluster families, have unknown functions, presenting a substantial potential for bioprospecting. This study underscores the diverse biosynthetic potential in Greenland Ice Sheet genomes, revealing insights into survival strategies and highlighting the need for further exploration and characterization of these untapped resources.
Bacteriophage endolysin Ply113 as a potent antibacterial agent against polymicrobial biofilms formed by enterococci and Staphylococcus aureus
Authors: Wang Jing , Liang Siyu , Lu Xiaofeng , Xu Qiu , Zhu Yao , Yu Shenye , Zhang Wanjiang , Liu Siguo , Xie Fang
Published: December 2023

Antibiotic resistance in Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus remains a major public health concern worldwide. Furthermore, these microbes frequently co-exist in biofilm-associated infections, largely nullifying antibiotic-based therapy. Therefore, it is imperative to develop an efficient therapeutic strategy for combating infections caused by polymicrobial biofilms. In this study, we investigated the antibacterial and antibiofilm activity of the bacteriophage endolysin Ply113 in vitro. Ply113 exhibited high and rapid lytic activity against E. faecium, E. faecalis, and S. aureus, including vancomycin-resistant Enterococcus and methicillin-resistant S. aureus isolates. Transmission electron microscopy revealed that Ply113 treatment led to the detachment of bacterial cell walls and considerable cell lysis. Ply113 maintained stable lytic activity over a temperature range of 4–45°C, over a pH range of 5.0–8.0, and in the presence of 0–400 mM NaCl. Ply113 treatment effectively eliminated the mono-species biofilms formed by E. faecium, E. faecalis, and S. aureus in a dose-dependent manner. Ply113 was also able to eliminate the dual-species biofilms of E. faecium–S. aureus and E. faecalis–S. aureus. Additionally, Ply113 exerted potent antibacterial efficacy in vivo, distinctly decreasing the bacterial loads in a murine peritoneal septicemia model. Our findings suggest that the bacteriophage endolysin Ply113 is a promising antimicrobial agent for the treatment of polymicrobial infections.
Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis
Authors: Zheng Qingcong , Wang Du , Lin Rongjie , Chen Yuchao , Huang Haoen , Xu Zixing , Zheng Chunfu , Xu Weihong
Published: December 2023

Background

The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.

Methods

The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran’s Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.

Results

In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685–1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739–1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826–1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849–1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879–1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680–1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486–1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693–1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis.

Conclusion

According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.
Short-term outcomes of enhanced recovery after surgery protocol in robotic-assisted McKeown esophagectomy for esophageal cancer: a single-center retrospective cohort study
Authors: Xu Xia , Xiong Jiajun , Xu Zhijie , Hu Zhi , Alai Guha , Yu Lulu , Xia Shaofeng , Lin Yidan
Published: December 2023

Background

This study aimed to evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in perioperative robotic-assisted McKeown esophagectomy (RAME) among esophageal cancer patients.

Methods

For this retrospective study, all patients who had undergone RAME with esophageal cancer using ERAS protocol and conventional management strategy at the surgery center of our hospital from February 2019 to March 2022 were performed for analysis.

Results

A total of 211 patients were included. Compared to the conventional group, the ERAS group has shorter median operative time [207 (147.5-267.5) vs. 244 (183-305), P<0.001], time to first flatus (P<0.001), time to out-of-bed activity (P=0.045), and time to liquid diet (P<0.001). In addition, the ERAS group has lower postoperative pain scores (3.62 ± 0.87 vs. 4.54 ± 0.91), shorter duration of analgesia pump [2 (1-3) vs. 3 (2.5-5.5)], shorter postoperative hospital stay [(9 (6-47) vs. 11 (6-79)], shorter postoperative hospital stay within neoadjuvant treated patients [8 (7-43) vs. 13 (8-67], shorter postoperative ICU stay [1 (0-7) vs. 2 (0-15)], and less reoperation rate (7.6% vs. 16.8%). Furthermore, the overall complication rate was significantly lower in the ERAS group (26.1%) than in the conventional group (50.4%). Notably, the ERAS group had lower thoracic fluid drainage volume than the conventional group on postoperative 2-7 days (P<0.05).

Conclusions

The application of ERAS protocol in esophageal cancer patients treated with RAME showed advantages of quick postoperative recovery in contrast to the conventional management strategy.
Case Report: Angiomatoid fibrous histiocytoma in the hand: a rare clinical presentation and diagnostic challenge
Authors: Ichikawa Jiro , Kawasaki Tomonori , Imada Hiroki , Wako Masanori , Fujimaki Taro , Tatsuno Rikito , Jubashi Takahiro , Haro Hirotaka
Published: December 2023

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of mesenchymal origin occurring in young adults. Based on its clinical course, it is said to have an intermediate potential. We present a case of a 59-year-old woman with AFH in the hand that was difficult to diagnose. A benign soft tissue tumor was suspected on magnetic resonance imaging, and its size and open biopsy suggested nodular fasciitis or inflammatory myofibroblastic tumor. A diagnosis of AFH was eventually made based on the analysis of the resected specimens. The characteristic findings of histopathology and immunohistochemistry in this case were relatively poor, so fluorescence in situ hybridization contributed to making the correct diagnosis. Considering its prognosis, careful follow-up was decided upon without additional surgery. Our case is a challenging one because of its atypical presentation and inconclusive imaging and histopathological findings.
Ossifying renal tumor of infancy: a case report
Authors: Qu Yu , Du Guoqiang , Guo Feng , Wu Rongde , Liu Wei
Published: December 2023

Ossifying renal tumor of infancy (ORTI) is an extremely rare benign renal solid tumor with typical clinical and pathological features. Most cases are diagnosed in infants that are less than 12 months of age and is more common in males. The first symptom in most patients is painless gross hematuria. Microscopically, the tumor has three main components: an osteoid core, osteoblast-like cells, and spindle cells. We reported a case of a 21-day-old patient diagnosed with ORTI who underwent partial nephrectomy and had good follow-up. The unique features of this case are the strong expression of Wilms Tumor-1 (WT-1) and a high Ki-67 index in the hot spot area. ORTI is considered to have a favorable prognosis. Due to the rarity of WT-1 positivity and high Ki-67 index, we should be highly aware that this patient needs to be followed closely. In addition, we reviewed the available literature on ORTI, with the aim of summarizing the diagnostic and therapeutic experience. The diagnosis needs to be given cautiously on the basis of clinical symptoms, imaging, and pathologic examination. Depending on the location and extent of the tumor, surgery can be performed by partial nephrectomy or nephrectomy to avoid overtreatment.
Emerging therapies in the medical management of thyroid eye disease
Authors: Kamboj Alisha , Harrison Andrew R. , Mokhtarzadeh Ali
Published: December 2023

Introduction

Thyroid eye disease (TED) is an immune-mediated disorder associated with a heterogenous array of manifestations that may unfavorably impact vision and quality of life. As understanding of this entity’s complex pathogenesis has evolved, so have therapies with novel molecular targets offering promise for improved patient outcomes.

Results

Emerging immunologic therapies for the management of thyroid eye disease have diverse mechanisms of actions and routes of administration. Different conventional and biological immunosuppressive agents have been studied as mediators of the autoimmune and autoinflammatory pathways in thyroid eye disease. Teprotumumab – an anti-IGF-1R monoclonal antibody that has recently emerged as a first-line therapy for active, moderate-to-severe TED – has demonstrated statistically significant improvements in proptosis, diplopia, clinical activity score, and quality of life compared to placebo. Currently under investigation are several other agents, with varying administration modalities, that aim to inhibit IGF-1R: VRDN-001 (intravenous), VRDN-002 or VRDN-003 (subcutaneous), lonigutamab (subcutaneous), and linsitinib (oral). Tocilizumab, a monoclonal antibody of interleukin 6, has played a role in the management of multiple autoimmune and inflammatory conditions and may offer promise in TED. Another incipient biologic target for TED management is the neonatal Fc receptor, inhibition of which has potential to decrease recycling of immunoglobulin and antibody levels; agents addressing this target including monoclonal antibodies as well as antibody fragments. Finally, hypolipidemic agents may play a role as mediators of TED-associated inflammation.

Conclusion

Among the agents under investigation that aim to decrease ocular morbidity associated with TED are agents that IGF-1R, interleukin 6, and the neonatal Fc receptor. The management of TED continues to expand with novel immunologic approaches for disease therapy.
In silico design of novel bioactive molecules to treat breast cancer with chlorogenic acid derivatives: a computational and SAR approach
Authors: Sehrawat Renu , Rathee Priyanka , Rathee Pooja , Khatkar Sarita , Akkol Esra Küpeli , Khatkar Anurag , Sobarzo-Sánchez Eduardo
Published: December 2023

Introduction: Cancer is a vast group of diseases comprising abnormal cells that multiply and grow uncontrollably, and it is one of the top causes of death globally. Several types of cancers are diagnosed, but the incidence of breast cancer, especially in postmenopausal women, is increasing daily. Chemotherapeutic agents used to treat cancer are generally associated with severe side effects on host cells, which has led to a search for safe and potential alternatives. Therefore, the present research has been conducted to find novel bioactive molecules to treat breast cancer with chlorogenic acid and its derivatives. Chlorogenic acid was selected because of its known activity in the field.

Methods: Several chlorogenic acid derivatives were subjected to computational studies such as molecular docking, determination of absorption, distribution, metabolism, and excretion (ADME), druglikeness, toxicity, and prediction of activity spectra for substances (PASS) to develop a potential inhibitor of breast cancer. The Protein Data Bank (PDB) IDs used for docking purposes were 7KCD, 3ERT, 6CHZ, 3HB5, and 1U72.

Result: Exhaustive analysis of results has been conducted by considering various parameters, like docking score, binding energy, types of interaction with important amino acid residues in the binding pocket, ADME, and toxicity data of compounds. Among all the selected derivatives, CgE18, CgE11, CgAm13, CgE16, and CgE9 have astonishing interactions, excellent binding energy, and better stability in the active site of targeted proteins. The docking scores of compound CgE18 were −11.63 kcal/mol, −14.15 kcal/mol, and −12.90 kcal/mol against breast cancer PDB IDs 7KCD, 3HB5, and 1U72, respectively. The docking scores of compound CgE11 were −10.77 kcal/mol and −9.11 kcal/mol against breast cancer PDB IDs 3ERT and 6CHZ, respectively, whereas the docking scores of epirubicin hydrochloride were −3.85 kcal/mol, −6.4 kcal/mol, −8.76 kcal/mol, and −10.5 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5. The docking scores of 5-fluorouracil were found to be −5.25 kcal/mol, −3.43 kcal/mol, −3.73 kcal/mol, and −5.29 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5, which indicates the designed compounds have a better docking score than some standard drugs.

Conclusion: Taking into account the results of molecular docking, drug likeness analysis, absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation, and PASS, it can be concluded that chlorogenic acid derivatives hold promise as potent inhibitors for the treatment of breast cancer.
Interleukin-4 during post-exercise recovery negatively correlates with the production of phagocyte-generated oxidants
Authors: Chmielecki Adam , Bortnik Krzysztof , Galczynski Szymon , Kopacz Karolina , Padula Gianluca , Jerczynska Hanna , Stawski Robert , Nowak Dariusz
Published: December 2023

Exhaustive run induced a biphasic oxidative response of circulating phagocytes in 16 amateur sportsmen. The first phase involved an increment just after exercise of enhanced whole blood chemiluminescence normalized per phagocyte count, whereas in the second phase a decrement from 1 h post-exercise and ongoing till 24 h. We tested whether plasma Interleukin IL-4, IL-8, IL-10 and Tumor Necrosis Factor α concentrations change in response to exhaustive run and whether there are associations between their levels and delta resting. Moreover, IL-8 and IL-10 significantly increased immediately post-exercise and after 1 h, but later normalized. Tumor necrosis factor α rose by 1.1-times only just after exercise. However, none of these cytokines showed any correlation with the investigated chemiluminescence. Exercise did not alter plasma concentrations of IL-4. However, pre-exercise IL-4 negatively correlated with measured luminescence just after exercise (ρ = −0.54, p < 0.05), and also tended to be negatively associated with decrements of the second phase at 1 h post-exercise ρ = −0.45, p = 0.08. It is suggested that plasma IL-4, by a negative association with blood phagocytes oxidants production, could be involved in the maintenance of proper balance between oxidants and anti-oxidants during strenuous exercise and post-exercise recovery.
Injection of IK1 through dynamic clamp can make all the difference in patch-clamp studies on hiPSC-derived cardiomyocytes
Authors: Verkerk Arie O. , Wilders Ronald
Published: December 2023

Human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool for studying development, pharmacology, and (inherited) arrhythmias. Unfortunately, hiPSC-CMs are depolarized and spontaneously active, even the working cardiomyocyte subtypes such as atrial- and ventricular-like hiPSC-CMs, in contrast to the situation in the atria and ventricles of adult human hearts. Great efforts have been made, using many different strategies, to generate more mature, quiescent hiPSC-CMs with more close-to-physiological resting membrane potentials, but despite promising results, it is still difficult to obtain hiPSC-CMs with such properties. The dynamic clamp technique allows to inject a current with characteristics of the inward rectifier potassium current (IK1), computed in real time according to the actual membrane potential, into patch-clamped hiPSC-CMs during action potential measurements. This results in quiescent hiPSC-CMs with a close-to-physiological resting membrane potential. As a result, action potential measurements can be performed with normal ion channel availability, which is particularly important for the physiological functioning of the cardiac SCN5A-encoded fast sodium current (INa). We performed in vitro and in silico experiments to assess the beneficial effects of the dynamic clamp technique in dissecting the functional consequences of the SCN5A-1795insD+/− mutation. In two separate sets of patch-clamp experiments on control hiPSC-CMs and on hiPSC-CMs with mutations in ACADVL and GNB5, we assessed the value of dynamic clamp in detecting delayed afterdepolarizations and in investigating factors that modulate the resting membrane potential. We conclude that the dynamic clamp technique has highly beneficial effects in all of the aforementioned settings and should be widely used in patch-clamp studies on hiPSC-CMs while waiting for the ultimate fully mature hiPSC-CMs.
Response of grassland ecosystem function to plant functional traits under different vegetation restoration models in areas of karst desertification
Authors: Song Shuzhen , Xiong Kangning , Chi Yongkuan
Published: December 2023

Plant functional traits serve as a bridge between plants, the environment, and ecosystem function, playing an important role in predicting the changes in ecosystem function that occur during ecological restoration. However, the response of grassland ecosystem function to plant functional traits in the context of ecological restoration in areas of karst desertification remains unclear. Therefore, in this study, we selected five plant functional traits [namely, plant height (H), specific leaf area (SLA), leaf dry matter content (LDMC), root length (RL), and root dry matter content (RDMC)], measured these along with community-weighted mean (CWM) and functional trait diversity, and combined these measures with 10 indexes related to ecosystem function in order to investigate the differences in plant functional traits and ecosystem function, as well as the relationship between plant functional traits and ecosystem functions, under four ecological restoration models [Dactylis glomerata (DG), Lolium perenne (LP), Lolium perenne + Trifolium repens (LT), and natural grassland (NG)]. We found that: 1) the Margalef index and Shannon–Wiener index were significantly lower for plant species in DG and LP than for those in NG (P<0.05), while the Simpson index was significantly higher in the former than in NG (P<0.05); 2) CWMH, CWMLDMC, and CWMRDMC were significantly higher in DG, LP, and LT than in NG, while CWMSLA was significantly lower in the former than in NG (P<0.05). The functional richness index (FRic) was significantly higher in DG and LP than in NG and LT, but the functional dispersion index (FDis) and Rao’s quadratic entropy index (RaoQ) were significantly lower in DG and LP than in NG and LT (P<0.05), and there was no significant difference between DG and LP, or between NG and LT (P>0.05); 3) ecosystem function, including ecosystem productivity, carbon storage, water conservation and soil conservation, was highest in LT and lowest in NG; and 4) CWMLDMC (F=56.7, P=0.024), CWMRL (F=28.7, P=0.024), and CWMH (F=4.5, P=0.048) were the main factors affecting ecosystem function. The results showed that the mixed pasture of perennial ryegrass and white clover was most conductive to restoration of ecosystem function. This discovery has important implications for the establishment of vegetation, optimal utilization of resources, and the sustainable development of degraded karst ecosystems.
“I could do almost nothing without digital technology”: a qualitative exploration of adolescents’ perception of the risks and challenges of digital technology
Authors: Bitto Urbanova Laura , Madarasova Geckova Andrea , Dankulincova Veselska Zuzana , Capikova Silvia , Holubcikova Jana , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: December 2023

Background

The fast development of digital technology and of its use at even younger ages is significantly shaping the current generation of adolescents. This is leading to an almost unlimited accessibility that provides a large number of opportunities, but also to many challenges that adolescents have to face. The aim of our study was to explore the perceptions adolescents have of the risks of digital technology.

Methods

We conducted online semi-structured interviews as a part of the international Health Behaviour in School-aged Children study. The sample consisted of 15 Slovak adolescents (mean age: 15.33; 20% boys). To analyse our data, we used consensual qualitative research and thematic analysis.

Findings

Our findings confirmed that adolescents are aware of the risks associated with the use of digital technology. Regarding their specific types of the perceived risks, we identified four main themes: 1. dependence on the functionality of technology; 2. problematic control; 3. vulnerability in the virtual environment; 4. health risks. Adolescents thus want technology that is functional, safe and does not endanger their health.

Conclusion

Despite the fact that adolescents know of the risks they may experience due the digital technology, they still use it. Preventive strategies should focus on functionality, safety and healthiness; furthermore, they should support the constant development of adolescents’ digital awareness and raising their awareness about effective and non-threating use of technology.
Guilt, shame, and embarrassment: similar or different emotions? A comparison between Italians and Americans
Authors: Giorgetta Cinzia , Strappini Francesca , Capuozzo Alessandra , Evangelista Elisa , Magno Antonella , Castelfranchi Cristiano , Mancini Francesco
Published: December 2023

Introduction

Guilt, shame, and embarrassment represent affective experiences with social implications and diverse self-relevant negative affect. While the distinction between these emotion terms has been extensively investigated, little is known about how they diverge and are related to each other and their crosscultural differences.

Methods

Here, we used a community sample (N = 163) comprised of Americans and Italians and a scenario-based measure in which we asked participants to report the intensity of emotions that the story’s main character would feel. The elements used to build the scenarios were based on a recent theoretical approach that proposes distinguishing cognitive, somatic, interoceptive, and behavioral ingredients to differentiate between these emotions. We hypothesized that these ingredients might effectively elicit the target emotions and that the main differences across these cultures would be associated with the emotion terms of shame/vergogna.

Results

Our findings suggest that these defining elements are effective in evoking experiences of guilt, shame, and embarrassment. Moreover, we found that shame was equally elicited by the Shame and Guilt Scenarios only in the American sample, thus suggesting a proximity between shame and guilt in the American sample compared to the Italian’s terms of vergogna and colpa.

Discussion

These results suggest important implications for the psychology of moral emotions and highlight the importance of taking into account some cognitive factors, such as the quality of self-evaluation, the discrepancy between the actual self and the ideal self vs. the sense of perceived responsibility, and the different domains related to self-esteem.
Identifying complementary and alternative medicine recommendations for anxiety treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines
Authors: Zhao Fei-Yi , Kennedy Gerard A. , Xu Peijie , Conduit Russell , Wang Yan-Mei , Zhang Wen-Jing , Wang Hui-Ru , Yue Li-Ping , Huang Yu-Ling , Wang Yin , Xu Yan , Fu Qiang-Qiang , Zheng Zhen
Published: December 2023

Background

Clinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs.

Methods

Seven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively.

Results

Ten CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind–body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John’s wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as “unclear, unambiguous, or uncertain”. No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism.

Conclusion

Available guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.
The pattern of emergency department length of stay in Saudi Arabia: an epidemiological Nationwide analyses of secondary surveillance data
Authors: Alharbi Abdullah A. , Muhayya Mona , Alkhudairy Reem , Alhussain Ahmed A. , Muaddi Mohammed A. , Alqassim Ahmad Y. , AlOmar Reem S. , Alabdulaali Mohammed K.
Published: December 2023

Background

Emergency department length of stay is a vital performance indicator for quality and efficiency in healthcare. This research aimed to evaluate the length of stay patterns in emergency departments across Saudi Arabia and to identify predictors for extended stays. The study used secondary data from the Ministry of Health’s Ada’a program.

Methods

Using a retrospective approach, the study examined data from the Ada’a program on emergency department length of stay from September 2019 to December 2021. These data covered 1,572,296 emergency department visits from all regions of Saudi Arabia. Variables analyzed included quality indicators, year of visit, shift time, hospital type, and data entry method. The analysis was conducted using multiple linear regression.

Results

The study found that the median length of stay was 61 min, with significant differences among related predictors. All associations were significant with a value of p of less than 0.001. Compared to 2019, the length of stay was notably shorter by 28.5% in 2020 and by 44.2% in 2021. Evening and night shifts had a shorter length of stay by 5.9 and 7.8%, respectively, compared to the morning shift. Length of stay was lower in winter, summer, and fall compared to spring. Patients in levels I and II of the Canadian Triage and Acuity Scales had longer stays than those in level III, with those in level I reaching an increase of 20.5% in length of stay. Clustered hospitals had a longer length of stay compared to the non-clustered ones. Pediatric hospitals had a 15.3% shorter stay compared to general hospitals. Hospitals with data entered automatically had a 14.0% longer length of stay than those entered manually. Patients admitted to the hospital had a considerably longer length of stay, which was 54.7% longer compared to non-admitted patients. Deceased patients had a 20.5% longer length of stay than patients discharged alive.

Conclusion

Data at the national level identified several predictors of prolonged emergency department length of stay in Saudi Arabia, including shift time, season, severity level, and hospital type. These results underline the necessity of continuous monitoring and improvement efforts in emergency departments, in line with policy initiatives aiming to enhance patient outcomes in Saudi Arabia.
How does social integration work when older migrants obtain health services from community? Evidence from national database in China
Authors: Liu Shenshen , Qin Bo , Wang Dongyang
Published: December 2023

Background

The roles of community are often overlooked when studying the older migrants' health issues, and more importantly, the mediating effect of social integration on the health of older migrants were rarely investigated empirically.

Methods

This study developed comprehensive index to explore this relationship. With data from the 2017 China Migrants Dynamic Survey, the study first examined the potential linkage between community-based health services and the health of older migrants. Ordered logit regressions was carried to investigate whether the self-rated health of older migrants is related to health education and health records provided by community, then the Causal Stepwise Regression and bootstrap method was used to looked into the potential mediation effect.

Results

The findings showed that older migrants with more community-based health education had higher self-rated health (β = 0.038, SE = 0.009, p < 0.001). However, the community-based health records were not associated with older migrants' health. Moreover, higher levels of social integration were associated with community health education (β = 0.142, SE = 0.014, p < 0.001), and social integration was positively associated with older migrants' health (β = 0.039, SE = 0.002, p = 0.024), indicating the mediation role of social integration.

Conclusion

The vital role of community-based health education in improving the health of older migrants was found, and social integration plays a mediating role.
Advanced workstations and collaborative robots: exploiting eye-tracking and cardiac activity indices to unveil senior workers’ mental workload in assembly tasks
Authors: Pluchino Patrik , Pernice Gabriella F. A. , Nenna Federica , Mingardi Michele , Bettelli Alice , Bacchin Davide , Spagnolli Anna , Jacucci Giulio , Ragazzon Andrea , Miglioranzi Leonardo , Pettenon Carlo , Gamberini Luciano
Published: December 2023

Introduction: As a result of Industry 5.0’s technological advancements, collaborative robots (cobots) have emerged as pivotal enablers for refining manufacturing processes while re-focusing on humans. However, the successful integration of these cutting-edge tools hinges on a better understanding of human factors when interacting with such new technologies, eventually fostering workers’ trust and acceptance and promoting low-fatigue work. This study thus delves into the intricate dynamics of human-cobot interactions by adopting a human-centric view.

Methods: With this intent, we targeted senior workers, who often contend with diminishing work capabilities, and we explored the nexus between various human factors and task outcomes during a joint assembly operation with a cobot on an ergonomic workstation. Exploiting a dual-task manipulation to increase the task demand, we measured performance, subjective perceptions, eye-tracking indices and cardiac activity during the task. Firstly, we provided an overview of the senior workers’ perceptions regarding their shared work with the cobot, by measuring technology acceptance, perceived wellbeing, work experience, and the estimated social impact of this technology in the industrial sector. Secondly, we asked whether the considered human factors varied significantly under dual-tasking, thus responding to a higher mental load while working alongside the cobot. Finally, we explored the predictive power of the collected measurements over the number of errors committed at the work task and the participants’ perceived workload.

Results: The present findings demonstrated how senior workers exhibited strong acceptance and positive experiences with our advanced workstation and the cobot, even under higher mental strain. Besides, their task performance suffered increased errors and duration during dual-tasking, while the eye behavior partially reflected the increased mental demand. Some interesting outcomes were also gained about the predictive power of some of the collected indices over the number of errors committed at the assembly task, even though the same did not apply to predicting perceived workload levels.

Discussion: Overall, the paper discusses possible applications of these results in the 5.0 manufacturing sector, emphasizing the importance of adopting a holistic human-centered approach to understand the human-cobot complex better.
Radiation Epidemiology: Keeping Space Travelers Safe
Authors: Butler Jennifer , Miller Kathleen B. , Dauer Lawrence T.
Published: December 2023

Did you know that millions of people are exposed to radiation on Earth as part of their jobs or during helpful medical procedures? The branch of medicine that studies the health effects of radiation exposure on large groups of people is called radiation epidemiology. Radiation also exists in space! But how do we study the ways that radiation impacts the body in space when there are so few space travelers? In this article, we will define radiation epidemiology, give some examples of studies that evaluate how radiation on Earth effects people’s health, and explain how we use the information from studies on Earth to better understand the health effects of radiation in space.
Effects of Different Photoperiods on the Growth and Nutritional Characteristics of Two Celery Cultivars in Plant Factory
Authors: Chu Qianwen , Qin Yanmei , Li Chunyan , Cheng Shaobo , Su Lihong , He Zhongqun , Zhou Xiaoting , Shao Dalong , Guo Xin
Published: December 2023

Three different photoperiod treatments (8 h/16 h, 12 h/12 h, and 16 h/8 h of light/dark) were implemented to investigate the impact of growth, biomass, and phytochemical accumulation in two celery cultivars, namely ‘Zhangqiubaoqin’ (BQ) and ‘Hongchenghongqin’ (HQ), within a plant factory setting. The findings demonstrated that the 12 h/12 h photoperiod stimulated the growth of both celery varieties, while the 16 h/8 h photoperiod hindered their growth. Notably, the root length, shoot fresh and dry weight, plant height, chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid content of both celery cultivars exhibited the highest values under the 12 h/12 h light and dark photoperiod. Furthermore, the effective quantum yields of the electron transfer ratio (ETR) and the photochemical quenching coefficient (qP) displayed superior value under the 12 h/12 h light and dark photoperiod. With the exception of cellulose, the levels of soluble sugar, soluble protein, total phenol, and vitamin C were also highest under the 12 h/12 h photoperiod for both cultivars. BQ demonstrated the highest total apigenin content under the 12 h/12 h (light and dark) photoperiod, whereas HQ exhibited the highest content under the 16 h/8 h (light and dark) photoperiod. In summary, celery plants exhibited optimal performance and biomass production when subjected to the 12 h/12 h (light and dark) photoperiod treatment.