bluuebunny/crossref_metadata_2025 huggingface dataset:
Felty’s syndrome
Authors: Wegscheider Christoph , Ferincz Vera , Schöls Karin , Maieron Andreas
Published: October 2023

Felty’s syndrome was first described in 1924 by the US-American physician Augustus Roi Felty as a triad of rheumatoid arthritis, splenomegaly and leucopenia. Even nearly 100 years later, this rare syndrome is still paralleled by diagnostic and therapeutic challenges and its pathogenesis is incompletely understood. Neutropenia with potentially life-threatening infections is the main problem and several pathomechanisms like Fas-mediated apoptosis, anti-neutrophil antibodies, anti-G-CSF antibodies, neutrophil consumption in the context of NETosis and suppression of granulopoiesis by T-LGLs have been suggested. Felty’s syndrome has various differential diagnoses as splenomegaly and cytopenia are common features of different infectious diseases, malignancies and autoimmune disorders. Additionally, benign clonal T-/NK-LGL lymphocytosis is increasingly noticed in Felty’s syndrome, which further complicates diagnosis. Today’s treatment options are still sparse and are largely based on case reports and small case series. Methotrexate is the mainstay of therapy, followed by rituximab, but there is less evidence for alternatives in the case of adverse reactions or failure of these drugs. This article gives an updated review about Felty’s syndrome including its pathogenesis and treatment options.
Landing wise program: feasibility study protocol for Parkinson’s disease
Authors: Fernandes Júlio Belo , Domingos Josefa , Família Carlos , Santos Cátia , Santana Diana , Gregório Francisco , Costa Inês , Afonso Joana , Matos Lúcia , Marques Solange , Santos Tânia , Fernandes Sónia , Santos Isabel , Sousa Natacha , Ramos Catarina , Godinho Catarina
Published: October 2023

Regardless of the benefits of fall prevention programs, people with Parkinson’s disease (PD) will still fall. Therefore, it is crucial to explore novel therapeutic approaches that are well-accepted and effective for addressing fall risk and the fear of falls among this population. The present study aims to assess the feasibility of the Landing Wise program as a therapeutic intervention for reducing the fear of falling in people with PD. A mixed-methods study will be conducted using convenience sampling to recruit 20 people with PD with a moderate concern of falling from a Parkinson’s Patients Association. In addition to usual care, participants will attend 2 days per week, 90 min group sessions for 8 weeks. The intervention combines group cognitive behavioral intervention with the training of safe landing strategies. Feasibility will be assessed by six key domains (recruitment strategy and rates, enrollment, retention, acceptability, reasons for decline/withdrawal, and adverse events). Quantitative data will be analyzed using descriptive statistics to characterize the sample, followed by inferential statistics to evaluate differences in the Short Falls Efficacy Scale-International Scale, Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Timed Up Go, 6-Minutes Walking Distance, and fall frequency and severity scores between baseline and final assessment. Qualitative data will be analyzed using an inductive thematic analysis process. There is a growing interest in developing new effective therapeutic approaches for people with PD. If proven program feasibility, this study precedes a randomized controlled trial to establish the effectiveness of the Landing Wise program.
Assessing residential activity in a home plumbing system simulator: monitoring the occurrence and relationship of major opportunistic pathogens and phagocytic amoebas
Authors: Gomez-Alvarez Vicente , Ryu Hodon , Tang Min , McNeely Morgan , Muhlen Christy , Urbanic Megan , Williams Daniel , Lytle Darren , Boczek Laura
Published: October 2023

Opportunistic premise plumbing pathogens (OPPPs) have been detected in buildings’ plumbing systems causing waterborne disease outbreaks in the United States. In this study, we monitored the occurrence of OPPPs along with free-living amoeba (FLA) and investigated the effects of residential activities in a simulated home plumbing system (HPS). Water samples were collected from various locations in the HPS and analyzed for three major OPPPs: Legionella pneumophila, nontuberculous mycobacterial species (e.g., Mycobacterium avium, M. intracellulare, and M. abscessus), and Pseudomonas aeruginosa along with two groups of amoebas (Acanthamoeba and Vermamoeba vermiformis). A metagenomic approach was also used to further characterize the microbial communities. Results show that the microbial community is highly diverse with evidence of spatial and temporal structuring influenced by environmental conditions. L. pneumophila was the most prevalent pathogen (86% of samples), followed by M. intracellulare (66%) and P. aeruginosa (21%). Interestingly, M. avium and M. abscessus were not detected in any samples. The data revealed a relatively low prevalence of Acanthamoeba spp. (4%), while V. vermiformis was widely detected (81%) across all the sampling locations within the HPS. Locations with a high concentration of L. pneumophila and M. intracellulare coincided with the highest detection of V. vermiformis, suggesting the potential growth of both populations within FLA and additional protection in drinking water. After a period of stagnation lasting at least 2-weeks, the concentrations of OPPPs and amoeba immediately increased and then decreased gradually back to the baseline. Furthermore, monitoring the microbial population after drainage of the hot water tank and partial drainage of the entire HPS demonstrated no significant mitigation of the selected OPPPs. This study demonstrates that these organisms can adjust to their environment during such events and may survive in biofilms and/or grow within FLA, protecting them from stressors in the supplied water.
Midgut microbiota affects the intestinal barrier by producing short-chain fatty acids in Apostichopus japonicus
Authors: Song Mingshan , Zhang Zhen , Li Yanan , Xiang Yangxi , Li Chenghua
Published: October 2023

Introduction

The intestinal microbiota participates in host physiology and pathology through metabolites, in which short-chain fatty acids (SCFAs) are considered principal products and have extensive influence on intestine homeostasis. It has been reported that skin ulceration syndrome (SUS), the disease of Apostichopus japonicus caused by Vibrio splendidus, is associated with the alteration of the intestinal microbiota composition.

Method

To investigate whether the intestinal microbiota affects A. japonicus health via SCFAs, in this study, we focus on the SCFA profiling and intestinal barrier function in A. japonicus treated with V. splendidus.

Results and discussion

We found that V. splendidus could destroy the mid-intestine integrity and downregulate the expression of tight junction proteins ZO-1 and occludin in A. japonicus, which further dramatically decreased microorganism abundance and altered SCFAs contents. Specifically, acetic acid is associated with the largest number of microorganisms and has a significant correlation with occludin and ZO-1 among the seven SCFAs. Furthermore, our findings showed that acetic acid could maintain the intestinal barrier function by increasing the expression of tight junction proteins and rearranging the tight junction structure by regulating F-actin in mid-intestine epithelial cells. Thus, our results provide insights into the effects of the gut microbiome and SCFAs on intestine barrier homeostasis and provide essential knowledge for intervening in SUS by targeting metabolites or the gut microbiota.
10-hydroxy-2-decenoic acid alleviates lipopolysaccharide-induced intestinal mucosal injury through anti-inflammatory, antioxidant, and gut microbiota modulation activities in chickens
Authors: Han Lianquan , Zhang Maolu , Li Fuwei , Su Jing , Wang Ruiming , Li Guiming , Yang Xiaohui
Published: October 2023

Introduction

This study aimed to investigated the effects of 10-hydroxy-2-decenoic acid (10-HDA) on the growth performance, intestinal barrier, inflammatory response, oxidative stress, and gut microbiota of chickens challenged with lipopolysaccharide (LPS).

Methods

A total of 240 one-day-old chickens were randomly assigned to five treatment groups: (1) control group (basal diet + saline); (2) LPS group (basal diet + LPS); (3) Chlortetracycline (CTC) group (basal diet containing 75 mg/kg CTC + LPS); (4) 0.1% 10-HDA group (basal diet containing 1 g/kg 10-HDA + LPS); and (5) 0.5% 10-HDA group (basal diet containing 5 g/kg 10-HDA + LPS). All chickens were injected intraperitoneally with 0.5 mg/kg body weight of either LPS or saline at 17, 19, and 21 days of age.

Results

The results showed that dietary 10-HDA supplementation attenuated the loss in growth performance caused by the LPS challenge (p < 0.05). 10-HDA effectively alleviated LPS-induced intestinal mucosal injury, as evidenced by reduced bleeding, decreased serum diamine oxidase levels (p < 0.05), and increased villus/crypt ratios of the jejunum and ileum (p < 0.05). Dietary treatment with 0.1% 10-HDA reduced the concentrations of inflammatory cytokines (TNF-α, IL-1β, IL-6; p < 0.05), and increased immunoglobulin (IgA, IgG) and antioxidant enzyme levels (CAT, GSH-px, T-SOD) in the serum of LPS-challenged chickens (p < 0.05). These effects were similar to those observed in the CTC group. Moreover, 0.1% 10-HDA treatment reversed the LPS-induced variations in the mRNA expression of genes related to inflammation, antioxidant capacity, and intestinal tight junctions (p < 0.05). 16S rRNA analysis revealed that 10-HDA supplementation increased the relative abundance of Faecalibacterium and Clostridia_UCG-014 (p < 0.05). Additionally, it decreased the abundance of Clostridia_vadinBB60_group, Eubacterium_nodatum_group, and UC5-1-2E3 (p < 0.05). These changes were correlated with reduced inflammation and improved antioxidant capacity in the LPS-challenged chickens.

Conclusion

Collectively, dietary 10-HDA supplementation alleviated LPS-induced intestinal mucosal injury and the loss of growth performance through anti-inflammatory, antioxidant, and gut microbiota modulation activities in chickens. Moreover, 0.1% 10-HDA supplementation had comparable or even better protection for LPS-challenged chickens than supplementation with antibiotics or 0.5% 10-HDA. 10-HDA has the potential to be used as an alternative to antibiotics in protecting the intestinal health and improving the performance of poultry.
Gut microbiome predicts selenium supplementation efficiency across different Chinese adult cohorts using hybrid modeling and feature refining
Authors: Jiang Sikai , Zhang Bailu , Fan Xiaoqian , Chen Yuzhu , Wang Jian , Wu Shunyao , Wang Lijuan , Su Xiaoquan
Published: October 2023

Selenium (Se) is an essential trace element that plays a vital role in various physiological functions of the human body, despite its small proportion. Due to the inability of the human body to synthesize selenium, there has been increasing concern regarding its nutritional value and adequate intake as a micronutrient. The efficiency of selenium absorption varies depending on individual biochemical characteristics and living environments, underscoring the importance of accurately estimating absorption efficiency to prevent excessive or inadequate intake. As a crucial digestive organ in the human body, gut harbors a complex and diverse microbiome, which has been found to have a significant correlation with the host’s overall health status. To investigate the relationship between the gut microbiome and selenium absorption, a two-month intervention experiment was conducted among Chinese adult cohorts. Results indicated that selenium supplementation had minimal impact on the overall diversity of the gut microbiome but was associated with specific subsets of microorganisms. More importantly, these dynamics exhibited variations across regions and sequencing batches, which complicated the interpretation and utilization of gut microbiome data. To address these challenges, we proposed a hybrid predictive modeling method, utilizing refined gut microbiome features and host variable encoding. This approach accurately predicts individual selenium absorption efficiency by revealing hidden microbial patterns while minimizing differences in sequencing data across batches and regions. These efforts provide new insights into the interaction between micronutrients and the gut microbiome, as well as a promising direction for precise nutrition in the future.
Functional and molecular characterization of the Atlantic salmon gill epithelium cell line ASG-10; a tool for in vitro gill research
Authors: Slattery Orla , Dahle Maria K. , Sundaram Arvind Y. M. , Nowak Barbara F. , Gjessing Mona C. , Solhaug Anita
Published: October 2023

Fish gills are not only the respiratory organ, but also essential for ion-regulation, acid-base control, detoxification, waste excretion and host defense. Multifactorial gill diseases are common in farmed Atlantic salmon, and still poorly understood. Understanding gill pathophysiology is of paramount importance, but the sacrifice of large numbers of experimental animals for this purpose should be avoided. Therefore, in vitro models, such as cell lines, are urgently required to replace fish trials. An Atlantic salmon gill epithelial cell line, ASG-10, was established at the Norwegian Veterinary institute in 2018. This cell line forms a monolayer expressing cytokeratin, e-cadherin and desmosomes, hallmarks of a functional epithelial barrier. To determine the value of ASG-10 for comparative studies of gill functions, the characterization of ASG-10 was taken one step further by performing functional assays and comparing the cell proteome and transcriptome with those of gills from juvenile freshwater Atlantic salmon. The ASG-10 cell line appear to be a homogenous cell line consisting of epithelial cells, which express tight junction proteins. We demonstrated that ASG-10 forms a barrier, both alone and in co-culture with the Atlantic salmon gill fibroblast cell line ASG-13. ASG-10 cells can phagocytose and express several ATP-binding cassette transport proteins. Additionally, ASG-10 expresses genes involved in biotransformation of xenobiotics and immune responses. Taken together, this study provides an overview of functions that can be studied using ASG-10, which will be an important contribution to in vitro gill epithelial research of Atlantic salmon.
Comorbidity and outcomes among hospitalized patients with stroke: a nationwide inpatient analysis
Authors: Chen Wei , Li Dong
Published: October 2023

Objective

We aimed to characterize healthcare utilization and comorbidity outcomes among hospitalized elderly stroke patients using a nationally representative dataset in the United States.

Methods

Using the 2019 National Inpatient Sample, patients aged 65 years or older with and without comorbidities who were hospitalized for acute stroke were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Patient comorbidities were identified with the use of the Elixhauser Comorbidity Index. The prevalence of comorbidities, in-hospital mortality, length of stay, and total hospital costs were analyzed for these patients.

Results

Within 451,945 patients (mean age 78 years, 54.1% women, 73.7% white), we observed that more than 90% of patients had a minimum of two comorbidities. The median number of comorbidities was 4.0 (IQR 3.0–6.0). There was significant variation in the prevalence rate of comorbidities. The five most common comorbidities were uncomplicated hypertension (55.4%), paralysis (40.1%), congestive heart failure (39.8%), various neurological illnesses (38.3%), and complex hypertension (32.5%). After adjusting for patient- and hospital-level characteristics, a statistically significant association was observed between comorbidities and various adverse outcomes. Specifically, comorbidities were found to be significantly associated with an increased risk of inpatient mortality (odds ratio: 1.09; 95% CI: 1.08–1.11; P < 0.001), a longer duration of hospitalization (0.68 days; 95% CI: 0.66–0.71; P < 0.001), and higher total cost ($1,874.9; 95% CI: 1,774.6–1,975.2; P < 0.001).

Conclusion

This national data suggests that comorbidity is common among hospitalized older stroke patients and substantially increases the healthcare burden and inpatient mortality in the United States. These findings underscore the integration of comorbidity management into the care of older stroke patients.
Alcoholic drink produced by pea is a risk factor for incident knee surgery in patients with knee osteoarthritis
Authors: Huang Xiaopeng , Zhang Jinshan , Zheng Yongqiang , Liu Xiaofeng , Xu Yongquan , Fang Yangzhen , Lin Zhenyu , Lin Liang , Zhang Hongpeng , Wang Zefeng
Published: October 2023

Objective

The objective of this study is to investigate whether alcohol exposure and specific alcoholic drinks are independent risk factors for incident knee surgery in knee osteoarthritis (KOA) patients.

Methods

We identified all patients who were clinically diagnosed as KOA between January 2010 and January 2018 in our outpatient department. Demographic, clinical, and radiographic data were collected from the database of our hospital. Next, we analyzed the association between alcohol consumption and incident knee surgery.

Results

A total of 4,341 KOA patients completed the current study and were included in the final analysis. Incident knee surgery for the purpose of treating osteoarthritis was observed in 242 patients. Incident knee surgery was significantly associated with age (OR [95%CI], 1.023 [1.009–1.039], P = 0.002), BMI (OR [95%CI], 1.086 [1.049–1.123], P < 0.001), baseline K-L grade 3 (OR [95%CI], 1.960 [1.331–2.886], P = 0.001), baseline K-L grade 4 (OR [95%CI], 1.966 [1.230–3.143], P = 0.005), 7.1–14 drinks per week (OR [95%CI], 2.013 [1.282–3.159], P = 0.002), >14 standard drinks per week (OR [95%CI], 2.556 [1.504–4.344], P = 0.001), and the most common alcoholic drink produced by pea (OR [95%CI], 3.133 [1.715–5.723], P < 0.001).

Conclusion

KOA patients who consumed more than seven standard drinks per week were at substantial risk of incident knee surgery. In addition, alcoholic drink produced by pea is also an independent risk factor.
Application of endoport-assisted neuroendoscopic techniques in lateral ventricular tumor surgery
Authors: Yan Chaolong , Mao Jiannan , Yao Chenbei , Liu Yang , Jin Wei , Yan Huiying
Published: October 2023

Objective

The objective of this study was to investigate the clinical experience and therapeutic efficiency of Endoport-assisted neuroendoscopic surgery for resection of lateral ventricular tumors. The key points and application value of this surgical technique were additionally discussed.

Methods

A retrospective analysis was conducted on the clinical and follow-up data of 16 patients who underwent endoport-assisted neuroendoscopic surgery for lateral ventricular tumors at the Department of Neurosurgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, between January 2018 and September 2020. The surgical procedures, complications and outcomes were analyzed.

Results

The study included a total of 16 patients (5 males and 11 females) with lateral ventricular tumors, with a mean age of 43.2 years (18-70 years old). The tumors were distributed as follows: 5 cases involved the body of the lateral ventricle, 3 involved the frontal horn and body, 3 involved the occipital horn, 2 involved the trigone, 2 involved the frontal horn, and 1 case involved the occipital horn and body. Perioperative complications were analyzed, revealing 1 case of intraoperative acute epidural hematoma intraoperative and 2 cases of postoperative obstructive hydrocephalus. All complications were promptly managed. Postoperative MRI revealed that 14 cases (88%) achieved total resection, while 2 cases (12%) achieved subtotal resection. During the follow-up of 6-38 months, no recurrence was observed. The patient diagnosed with glioblastoma died 16 months after surgery (GOS=1), while the remaining patients have successfully resumed to normal daily life with a GOS score of 5.

Conclusion

In conclusion, endoport-assisted neuroendoscopic surgery proved to be a minimally invasive and effective technique for resecting lateral ventricular tumors, with acceptable complications. It effectively utilizes the benefits of close observation, comprehensive exposure, and reduced tissue damage. Therefore, endoport-assisted neuroendoscopic surgery is suitable for the resection of lateral ventricular tumors.
Transcriptional signature of early cisplatin drug-tolerant persister cells in lung adenocarcinoma
Authors: Chavez-Dominguez Rodolfo , Aguilar-Cazares Dolores , Perez-Medina Mario , Avila-Rios Santiago , Soto-Nava Maribel , Mendez-Tenorio Alfonso , Islas-Vazquez Lorenzo , Benito-Lopez Jesus J. , Galicia-Velasco Miriam , Lopez-Gonzalez Jose S.
Published: October 2023

Resistance to cisplatin is the main cause of treatment failure in lung adenocarcinoma. Drug-tolerant-persister (DTP) cells are responsible for intrinsic resistance, since they survive the initial cycles of treatment, representing a reservoir for the emergence of clones that display acquired resistance. Although the molecular mechanisms of DTP cells have been described, few studies have investigated the earliest molecular alterations of DTP cells in intrinsic resistance to cisplatin. In this work, we report a gene expression signature associated with the emergence of cisplatin-DTP cells in lung adenocarcinoma cell lines. After a single exposure to cisplatin, we sequenced the transcriptome of cisplatin-DTPs to identify differentially expressed genes. Bioinformatic analysis revealed that early cisplatin-DTP cells deregulate metabolic and proliferative pathways to survive the drug insult. Interaction network analysis identified three highly connected submodules in which SOCS1 had a significant participation in controlling the proliferation of cisplatin-DTP cells. Expression of the candidate genes and their corresponding protein was validated in lung adenocarcinoma cell lines. Importantly, the expression level of SOCS1 was different between CDDP-susceptible and CDDP-resistant lung adenocarcinoma cell lines. Moreover, knockdown of SOCS1 in the CDDP-resistant cell line partially promoted its susceptibility to CDDP. Finally, the clinical relevance of the candidate genes was analyzed in silico, according to the overall survival of cisplatin-treated patients from The Cancer Genome Atlas. Survival analysis showed that downregulation or upregulation of the selected genes was associated with overall survival. The results obtained indicate that these genes could be employed as predictive biomarkers or potential targets to improve the effectiveness of CDDP treatment in lung cancer patients.
Radiotherapy for Non-Hodgkin’s lymphoma with cardiac infiltration: A case report
Authors: Wang Weifeng , Zhang Zhuo , Deng Xiaocong , Gu Anqi , Chen Xianzhao , Cai Yizheng , Zhao Yuting
Published: October 2023

Background

Non-Hodgkin’s lymphoma (NHL) with cardiac infiltration has a poor prognosis. The median OS of patients failing to respond to chemotherapy has been reported to be 1 month vs. 18 months in patients responding to chemotherapy.

Case presentation

Herein, we reported a case of a 57-year-old male confirmed with diffuse large B-cell lymphoma who received radiation therapy of 150-cGy daily, administered in 30 fractions to the volume of cardiac infiltration, resulting in complete relief. Chemotherapy had no curative effect. The patient was subsequently enrolled in a clinical trial and received oral administration of zanubrutinib 80mg twice daily, after which he achieved complete remission. The progression-free survival was from diagnosis (January 7, 2020) to the follow-up (September 20, 2022), amounting to 32 months.

Conclusion

Proper irradiation dose and timing of treatment can relieve NHL symptoms.
Efficacy and safety of transarterial chemoembolization combined with lenvatinib and camrelizumab in patients with BCLC-defined stage C hepatocellular carcinoma
Authors: Wu Juan , Zeng Jia , Wang Huiwen , Huo Zhuoni , Hou Xunbo , He Dongfeng
Published: October 2023

Objective

To investigate the effectiveness and safety of combining transarterial chemoembolization (TACE) with lenvatinib and camrelizumab in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).

Methods

We retrospectively analyzed 141 patients with BCLC stage C HCC: 57 were treated with TACE combined with lenvatinib plus camrelizumab (T + L + C), 41 were treated with TACE combined with camrelizumab (T + C), and 43 were treated with TACE (TACE). The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were the objective response rate (ORR) and adverse events (AEs). Factors that affected survival were identified via Cox regression analysis.

Results

Comparison of the three groups revealed a significant difference in the median overall survival (mOS), 19.8 months (95% CI 15.7–23.9) in the T + L + C combined group vs 15.7 (95% CI 13.1–18.3) months in the T + C combined group vs 9.4 (95% CI 6.2–12.5) months in the TACE group (P < 0.001). The median progression-free survival (mPFS) was significantly better in the T + L + C combination group than in the T + C combination group and the TACE group [11.4 (95% CI 7.6–15.3) months vs 8.4 (95% CI 6.2–10.5) months vs 4.8 (95% CI 3.2–6.3) months, respectively, P < 0.001)]. The objective response rate (ORR) (57.9%) and the disease control rate (DCR) (75.4%) patients in the combined T + L + C group were higher than those in the other two groups. More patients in the combined T + L + C group experienced AEs, with 16 (28.1%) patients experiencing AEs of grade 3 or higher.

Conclusions

In patients with BCLC stage C HCC, those receiving the T + L + C combination demonstrated a superior survival benefit and acceptable safety profile compared patients receiving either TACE or the T + C combination.
Overcoming the challenges of drug development in platinum-resistant ovarian cancer
Authors: Eskander Ramez N. , Moore Kathleen N. , Monk Bradley J. , Herzog Thomas J. , Annunziata Christina M. , O’Malley David M. , Coleman Robert L.
Published: October 2023

The definition of “platinum-resistant ovarian cancer” has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations—which advocate against relying solely upon the platinum-free interval—will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.
5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines
Authors: Usman Muhammad , Malik Hurmat , Tokhi Ahmed , Arif Mehreen , Huma Zilli , Rauf Khalid , Sewell Robert D. E.
Published: October 2023

Vincristine is the drug of choice for Hodgkin’s lymphoma, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Despite its significant anticancer effects, it causes dose-dependent neuropathy, leading to compulsive dose reduction. The available drugs used for vincristine-induced neuropathic pain (VINP) have a range of safety, efficacy, and tolerability issues prompting a search for new therapies. 5,7-Dimethoxycoumarin (5,7-DMC) also known as citropten, is a natural coumarin found in the essential oils of citrus plants such as lime, lemons, and bergamots, and it possesses both antidepressant and anti-inflammatory effects. This study was designed to investigate the possible analgesic and antiallodynic effects of 5,7-DMC in a murine model of VINP. Vincristine was administered to groups of BALB/c male mice (0.1 mg/kg intraperitoneally) once daily for 14 days to induce VINP. Thermal hyperalgesia and mechanical allodynia were quantified using the tail immersion test and von Frey filament application method. The levels of monoamine neurotransmitters and vitamin C in frontal cortical, striatal and hippocampal tissues, as well as the TNF-α level in plasma, were quantified using high performance liquid chromatography and ELISA respectively. On day 15 of the protocol, acute treatment with 5,7-DMC clearly reversed VINP thermal hyperalgesia, mechanical static allodynia, mechanical dynamic allodynia, and cold allodynia. The activity of 5,7-DMC against hyperalgesia and allodynia was inhibited by pretreatment with ondansetron but not naloxone, implicating a 5-HT3 receptor involvement. VINP vitamin C levels were restored by 5,7-DMC in the frontal cortex, and changes in serotonin, dopamine, adenosine, inosine and hypoxanthine levels caused by vincristine were reversed either fully or partially. Additionally, the vincristine-induced rise in hippocampal serotonin, dopamine, inosine and striatal serotonin was appreciably reversed by 5,7-DMC. 5,7-DMC also reversed the vincristine-induced increase in the plasma level of TNF-α. In negating the changes in the levels of some neurotransmitters in the brain caused by vincristine, 5,7-DMC showed stronger effects than gabapentin. It was concluded that, there is a potential role of 5-HT3 receptors and monoamines in the amelioration of VINP induced by 5,7-DMC, and the use of this compound warrants further investigation.
Fabrication and optimization of phospholipids-based phase separation in-situ gel loaded with BMP-2 nanosized emulsion for bone defect
Authors: Alissa Mohammed , Hjazi Ahmed , Abusalim Ghadah S. , Aloraini Ghfren S. , Alghamdi Suad A. , Rizg Waleed Y. , Hosny Khaled M. , Bukhary Deena M. , Alkharobi Hanaa
Published: October 2023

Introduction: The health, development, and/or survival of a newborn can be impacted by congenital abnormalities such as cleft lip (CLP) and palate, one of alveolar bone defects that emerge thru pregnancy. Therefore, the primary purpose of this study is to use phospholipids-based phase separation in-situ gel (PPSG) in combination with bone morphogenetic protein-2 nanoemulsion (BMP-2-NE) to aid repairing alveolar bone defects.

Methods: To investigate how formulation parameters, such as the concentrations of BMP-2 aqueous solution, LauroglycolTM FCC, and Labrafac PG oil, affect NE qualities including droplet size and stability index, an l-optimal co-ordinate exchange statistical design was opted. Injectable PPSG with the best NE formulation was tested for viscosity characteristics, gel strength, water absorption, and in-vitro BMP-2 release. In rabbits, the percentage of BMP-2 that was still in the maxilla after 14 days was assessed.

Results: Collected results revealed that the droplet size and stability index of optimal NE were discovered to be 68 2.0 nm and 96 1.3%, respectively. When mixed with water, optimal BMP-2 NE loaded PPSG became viscous and reached a gel strength of 41 s, which is adequate for injectable in-situ gels. In comparison to BMP-2 solution loaded in-situ gel, the in-vivo studies indicated that the newly created BMP-2 NE loaded PPSG produced a sustained and controlled release of BMP-2 that continued for 336 h (14 days). Further, 8% of the BMP-2 was still entrapped and not completely dissolved after 14 days, thus, created formulation allowed a higher percentage of BMP-2 to remain in rabbits’ maxilla for longer time.

Conclusion: PPSG that has been loaded with BMP-2 NE may therefore be a promising, fruitful, and less painful paradigm for the noninvasive therapy of CLP with significant effect and extended release.
A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis
Authors: Wang Huan , Ji Qing , Liao Chao , Tian Li
Published: October 2023

Background: Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine combined with montelukast in the treatment of AR. This study aimed to evaluate the efficacy and safety of the loratadine-montelukast combination on AR.

Methods: In this meta-analysis, searches were conducted on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure (CNKI). The search terms included loratadine, montelukast, allergic rhinitis, and clinical trials. Meta-analyses were conducted using Rev Man 5.3 and Stata 15 statistical software.

Results: A total of 23 studies with 4,902 participants were enrolled. For the primary outcome, pooled results showed that loratadine-montelukast can significantly reduce total nasal symptom scores (TNSS), when compared with loratadine (SMD, −1.00; 95% CI, −1.35 to −0.65, p < 0.00001), montelukast (SMD, −0.46; 95% CI, −0.68 to −0.25, p < 0.0001), or placebo (SMD, −0.93; 95% CI, −1.37 to −0.49, p < 0.00001). For secondary outcomes, pooled results showed that compared with loratadine, loratadine-montelukast can significantly improve nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaires (RQLQ). Compared with montelukast, loratadine-montelukast can significantly improve nasal itching, and nasal sneezing. Compared with placebo, loratadine-montelukast can significantly improve nasal congestion, and RQLQ.

Conclusion: Loratadine-montelukast combination is superior to loratadine monotherapy, montelukast monotherapy, or placebo in improving AR symptoms. Therefore, loratadine-montelukast combination can be an option for patients with moderate-severe AR or poorly response to monotherapy.

Systematic review registration number: clinicaltrials.gov, identifier CRD42023397519.
Energy calibration through X-ray absorption of the DECAL sensor, a monolithic active pixel sensor prototype for digital electromagnetic calorimetry and tracking
Authors: Fasselt Lucian , Allport Philip Patrick , Benhammadi Seddik , Bosley Robert Ross , Dopke Jens , Flynn Samuel , Gonella Laura , Guerrini Nicola , Issever Cigdem , Nikolopoulos Kostas , Kopsalis Ioannis , Philips Peter , Price Tony , Sedgwick Iain , Villani Giulio , Warren Matt , Watson Nigel , Weber Hannsjörg , Winter Alasdair , Wilson Fergus , Worm Steven , Zhang Zhige
Published: October 2023

In calorimetry, the predominant detection principle is to measure the energy deposited by particles within a shower initiated by an incident particle. An alternative concept is a sampling calorimeter where the highly granular active layers rather measure the number of secondary particles in the shower by detecting hits through binary readout similar to sensors for tracking applications. In this context, the DECAL sensor is a fully-depleted monolithic active pixel sensor prototype with reconfigurable readout for digital electromagnetic calorimetry and tracking. Its 64 × 64 pixels with a pitch of 55 µm are fabricated in a modified TowerJazz 180 nm CMOS imaging process using a 25 µm epitaxial silicon layer. The readout at 40 MHz is configurable in counting hits in the sensor grouped as either 64 strips or 4 pads. In this article, we present the energy calibration of this sensor using a gamma source of americium-241 as well as X-ray fluorescence at various wavelengths. The uniformity of the pixel responses is shown, allowing the summation of counts across all pixels. By that, two standalone energy calibration methods are developed that describe the X-ray absorption in the energy range of 4–60 keV and agree with each other. The signal pulse height is related to the absorbed photon energy with a 5.54 ± 0.37 mV/keV scale which corresponds to a conversion gain of cg = 19.95 ± 1.32 μV/e−. The relative energy resolution for photon absorption is found to be σE/E = 11.8 ± 3.0%. The absolute counts observed with the DECAL sensor agree with expectations and substantiate the assumption of a fully depleted epitaxial layer. The understanding of the photon absorption is an important input for further development of the sensor towards a multi-layer calorimeter.
Assessing the adaptive role of cannabidiol (CBD) in Cannabis sativa defense against cannabis aphids
Authors: MacWilliams Jacob , Peirce Erika , Pitt William Jacob , Schreiner Melissa , Matthews Tierra , Yao Linxing , Broeckling Corey , Nachappa Punya
Published: October 2023

Cannabis sativa is known for having unique specialized or secondary metabolites, cannabinoids that are derived from an extension of the terpene pathway in the Cannabis lineage and includes more than 100 other similar metabolites. Despite the assumption that cannabinoids evolved as novel herbivory defense adaptations, there is limited research addressing the role of cannabinoids in C. sativa responses to insect herbivores. Here we investigated the role of cannabidiol (CBD), the predominant cannabinoid in hemp, in plant defense against cannabis aphid (Phorodon cannabis), one of the most damaging pests of hemp. We hypothesize that insect feeding may induce changes in cannabinoids as an adaptive strategy for defense. We found that mean fecundity, net reproductive rate (R0) and adult longevity of cannabis aphids was reduced on the high cannabinoid cultivar compared to the low- cannabinoid cultivar in whole plant assays. In contrast, supplementation of CBD in artificial feeding assays increased aphid fecundity from day 1 to day 3. Additionally, aphid feeding did not impact cannabinoid levels in leaf tissues with the exception of Δ9-tetrahydrocannabinol (THC). This suggests that other cannabinoids and/or metabolites such as terpenes are causing the observed decrease in aphid performance in the whole plant assays. In addition to cannabinoids, C. sativa also possesses a range of defense mechanisms via phytohormone signaling pathways that are well described in other plant species. Indeed, cannabis aphid feeding significantly increased levels of the major phytohormones, salicylic acid, jasmonic acid, and abscisic acid, which are known to be involved in plant defense responses against aphid species. These results highlight the interplay between cannabinoid synthesis and phytohormone pathways and necessitate further investigation into this complex interaction.
Distinct clusters of movement entropy in children’s exploration of a virtual reality balance beam
Authors: Lorås Håvard , Sandseter Ellen Beate Hansen , Sando Ole Johan , Storli Lise
Published: October 2023

Although assessing motor competence is vital to advancing current understandings of motor development and its significance in various fields, no consensus exists on how the construct should be operationalised and measured. Existing approaches to assessing motor competence in children typically involve applying qualitative and/or quantitative scoring procedures in which children’s performance is evaluated according to certain levels of assessment-specific task performance dependent upon predefined sets of instructions and procedures. Building upon ecological dynamics as a framework, different levels of motor competence can be identified in children’s attempts to coordinate their degrees of freedom while trying to complete the interactive task and environmental constraints. Given the dynamic, nonlinear features of that coordinating process, assessments need to consider the inherit structure of inter- and intra-individual variability in patterns of movement. Against that background, we investigated 7–10-year-old children’s (n = 58) whole-body joint kinematics as they freely explored a balance beam in a virtual reality playground. Specifically, we used exploratory cluster analysis to examine the discriminatory capability of utilising joint-specific sample entropy as a window into individual differences in movement coordination that emerged from children’s exploration of the constraints embedded in the virtual task. Among the results, three clusters of children with distinct profiles of movement variability emerged, all of which showed heterogeneous levels of repeatability in joint movements in combination with the level of spatiotemporal exploration on the balance beam that could not be explained by between-cluster differences in age and gender distributions. Those findings suggest that entropy from whole-body movements can be used to cluster children into distinct groups with different profiles regarding the structure of movement variability, which can inform new understandings and the development of gross motor competence assessments for children.
A new perspective of Aristotle’s theory of vision: analysis of the “psycho-physical” intertwined mechanism of vision
Authors: Zhao Qi
Published: October 2023

Aristotle’s visual theory plays a pivotal role in De Anima, he specifically analyzes three fundamental elements required for visual activities, namely, color, transparent substance, and light. Color moves and limits transparent substance, thereby transforming transparent substance from potentiality to actuality through light. However, there is a debate between Physicalism and Spiritualism as to the specific implementation of the visual activity. Through the intertwined mechanism, Aristotle’s theory of vision can be clarified. The visual activity is neither purely psychological nor purely physical, it is the “psycho-physical” intertwined mechanism. This is why Aristotle’s visual theory is closely related to contemporary visual psychology.
What does it mean to be an agent?
Authors: Naidoo Meshandren
Published: October 2023

Artificial intelligence (AI) has posed numerous legal–ethical challenges. These challenges are particularly acute when dealing with AI demonstrating substantial computational prowess, which is then correlated with agency or autonomy. A common response to considering this issue is to inquire whether an AI system is “conscious” or not. If it is, then it could constitute an agent, actor, or person. This framing is, however, unhelpful since there are many unresolved questions about consciousness. Instead, a practical approach is proposed, which could be used to better regulate new AI technologies. The value of the practical approach in this study is that it (1) provides an empirically observable, testable framework that contains predictive value; (2) is derived from a data-science framework that uses semantic information as a marker; (3) relies on a self-referential logic which is fundamental to agency; (4) enables the “grading” or “ranking” of AI systems, which provides an alternative method (as opposed to current risk-tiering approaches) and measure to determine the suitability of an AI system within a specific domain (e.g., such as social domains or emotional domains); (5) presents consistent, coherent, and higher informational content as opposed to other approaches; (6) fits within the conception of what informational content “laws” are to contain and maintain; and (7) presents a viable methodology to obtain “agency”, “agent”, and “personhood”, which is robust to current and future developments in AI technologies and society.
Effect of the hybridization of social and personal responsibility model and sport education model on physical fitness status and physical activity practice
Authors: Quiñonero-Martínez Antonio Luis , Cifo-Izquierdo María Isabel , Sánchez-Alcaraz Martínez Bernardino Javier , Gómez-Mármol Alberto
Published: October 2023

Physical activity patterns, sedentary habits and obesity levels among children and teenagers are indicators of a worrying reality which has been aggravated by the COVID-19 pandemic. In this context, this study has analysed the impact that new methodologies in Physical Education have on physical health aspects. Two teaching methods, namely, Teaching Personal and Social Responsibility and Sport Education Model, were hybridized, in a Secondary School in Murcia (Spain). Controlled quasi-experimental research was completed with a sample of 76 Secondary Education students aged 12–14 (male: 32; female: 44), developing a hybridization of both models in the experimental group. ThePhysician-based Assessment and Counselling for Exercise(PACE) questionnaire and Eurofit and Alpha Fitness motor tests were run to collect the results. Those showed significant improvement in standing long jump and speed-agility results in the control group. In the experimental group, on the contrary, no significant improvement was registered for either test, but out-of-school physical activity rates were higher. Following this research, it is concluded that both models have positive influence on physical activity habits, but the teaching time devoted to the subject of Physical Education is not enough to improve them.
Barriers and facilitators influencing hearing help-seeking behaviors for adults in a peri-urban community in South Africa: a preventive audiology study
Authors: Mtimkulu Thobekile Kutloano , Khoza-Shangase Katijah , Petrocchi-Bartal Luisa
Published: October 2023

Objective

This study aims to examine the barriers and facilitators to accessing ear and hearing care experienced by adults with hearing impairment in a developing South African context.

Methods

A total of 23 participants were recruited through purposive sampling from an audiology department of a public hospital in peri-urban South Africa. Individual semi-structured interviews were conducted to capture a broad range of perspectives. Data were analyzed through thematic analysis.

Results

Socio-economic factors acted as the primary barrier while structural and health system factors were the main facilitator in influencing participants' journeys toward hearing help-seeking.

Conclusion

Help-seeking decisions made by adults with hearing impairment are impacted by numerous factors. Individual, providers, and environmental factors combine to play a significant role in resolving ear and hearing complaints. Socio-economic and healthcare level gaps reveal the inequalities that affect help-seekers, which, therefore, need to be addressed. The provision of equitable audiology services within hearing health policy is critical for the prevention of severe consequences of hearing impairment. Plans to implement universal healthcare through the National Health Insurance (NHI) by the South African government must include the universal access to preventive audiology services.