bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota
Authors: Benameur Tarek , Porro Chiara , Twfieg Mohammed-Elfatih , Benameur Nassima , Panaro Maria Antonietta , Filannino Francesca Martina , Hasan Abeir
Published: August 2023

The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin synthesis, xenobiotic and drug metabolism, maintenance of structural and functional integrity of the gut mucosal barrier, and protection against various pathogens. Inflammation is the innate immune response of living tissues to injury and damage caused by infections, physical and chemical trauma, immunological factors, and genetic derangements. Most diseases are associated with an underlying inflammatory process, with inflammation mediated through the contribution of active immune cells. Current strategies to control inflammatory pathways include pharmaceutical drugs, lifestyle, and dietary changes. However, this remains insufficient. Bioactive compounds (BCs) are nutritional constituents found in small quantities in food and plant extracts that provide numerous health benefits beyond their nutritional value. BCs are known for their antioxidant, antimicrobial, anticarcinogenic, anti-metabolic syndrome, and anti-inflammatory properties. Bioactive compounds have been shown to reduce the destructive effect of inflammation on tissues by inhibiting or modulating the effects of inflammatory mediators, offering hope for patients suffering from chronic inflammatory disorders like atherosclerosis, arthritis, inflammatory bowel diseases, and neurodegenerative diseases. The aim of the present review is to summarise the role of natural bioactive compounds in modulating inflammation and protecting human health, for their safety to preserve gut microbiota and improve their physiology and behaviour.
The Pathogenesis of Disinhibition in Patients with Traumatic Brain Injury: A Two Patient Case Report
Authors: Hiraoka Takashi , Yagi Masami
Published: August 2023

Higher brain dysfunction commonly occurs following traumatic brain injury (TBI), and may manifest in a social behavioral impairment which can significantly impede active social participation. We report two cases, one of voyeurism and the second of alcohol abuse, which might have been caused by TBI resulting in disinhibition, a type of social behavioral impairment. We discuss the underlying pathophysiological mechanisms to raise awareness of such cases and aid the development of effective interventions. Patient 1 suffered a TBI at 18 years of age, 2 years after which he presented repeated episodes of sexually deviant behavior (voyeurism). At 28, he committed suicide, since he was unable to control his aberrant behavior. Patient 2 suffered a TBI at the age of 13. He first displayed problematic behavior 7 years later, which included drinking excessive amounts of alcohol and stealing while inebriated. Despite both patients having sound moral judgment, they had irrational and uncontrollable impulses of desire. Imaging findings could explain the possible causes of impulse control impairments. Damage to the basal ganglia and limbic system, which are involved in social behavior, presumably led to desire-dominated behavior, leading to the patients conducting unlawful acts despite intact moral judgment. It is crucial to educate society about the prevalence of these disorders, explain how these disinhibitions start, and develop effective interventions.
The Effect of Appearance Anxiety on Social Anxiety among College Students: Sequential Mediating Effects of Self-Efficacy and Self-Esteem
Authors: Liao Jieying , Xia Tiansheng , Xu Xuan , Pan Li
Published: August 2023

Social anxiety is a serious psychological problem prevalent among Chinese college students, and appearance anxiety plays an important role in its development. Although some studies have explored the relationship between the two, the mediating mechanism is unclear. This study constructed a sequential mediation model based on the cognitive–behavioral theory of body image disorder and social phobia to explore the mediating role of self-efficacy and self-esteem. A total of 234 college students were recruited using the convenience sampling method, including 68 males (29.10%) and 166 females (70.90%), with an average age of 21.25 years (SD = 1.75). Data were collected using the Social Appearance Anxiety Scale, the General Self-Efficacy Scale, the Self-Esteem Scale, and the Interaction Anxiety Scale. The study’s results demonstrated a significant and positive predictive relationship between appearance anxiety and social anxiety (effect = 0.21, SE = 0.04, 95% CI = [0.13, 0.29], p < 0.001). Appearance anxiety not only directly affects social anxiety but also has three indirect paths affecting social anxiety: the independent mediating effect of self-efficacy (effect = 0.03, SE = 0.01, 95% CI = [0.00, 0.06], p < 0.001), the independent mediating effect of self-esteem (effect = 0.03, SE = 0.02, 95% CI = [0.01, 0.07], p < 0.001), and the serial mediation effect of self-efficacy and self-esteem (effect = 0.01, SE = 0.01, 95% CI = [0.00, 0.03], p < 0.001). Direct and indirect effects accounted for 73.81% and 26.19% of the total effect, respectively. These findings provide new perspectives on the intervention with and treatment of social anxiety in college students.
Experimental Investigation of Shear Behavior in High-Strength Concrete Beams Reinforced with Hooked-End Steel Fibers and High-Strength Steel Rebars
Authors: Alizadeh Amirhassan , Moradi Shaghaghi Taleb , Pourbaba Masoud , Mirrezaei Seyed Saeed , Zandi Yousef
Published: August 2023

Shear failure is an unfavorable phenomenon as it is a brittle type of failure; however, adding rebars and fibers to a concrete beam can minimize its detrimental effects. The objective of this study was to experimentally investigate the shear behavior of high-strength concrete (HC) beams reinforced with hooked-end (H) steel fibers and high-strength steel (HS) rebars under three-point bending tests. For this purpose, nine HC beams (300 × 250 × 1150 mm in dimension) were cast with 0%, 1%, and 2% H fibers by volume in three longitudinal rebar ratios (i.e., 1.5%, 2.0%, and 3.1%) and compared with beams without fibers. Furthermore, numerical analyses were performed to validate the experimental results and compare them with design codes. The results showed that, irrespective of the fiber content or longitudinal rebar ratio, the beams failed in shear. Increasing the rebar ratio and fiber content increased the shear capacity to as high as 100% (for the specimen with 3% rebar and 2% fiber compared to its counterpart with 1% rebar and 2% fiber). In addition, the research-based equations proposed in the literature either overestimated or underestimated the shear capacity of fibrous HC beams significantly. The level of overestimation or underestimation was closely related to the sensitivity of the proposed model to the shear span ratio and the fiber content. Rebars proved to be more beneficial in contributing to the shear capacity, but the rate of this positive contribution decreased as the fiber ratio increased. Finally, the inverse analysis approach adopted herein proved to be an efficient tool in estimating the shear response of fiber-reinforced beams failing in shear (margin of error: less than 10%).
Mechanical Characterization of Geopolymer Paste and Mortar Fabricated from Alum Sludge and Fly Ash
Authors: Odimegwu Temple Chimuanya , Kaish A. B. M. A. , Jamil Maslina , Zain M. F. M. , Turlanbekov Asset , Al Zand Ahmed W.
Published: August 2023

This study evaluated the effect of alum sludge as an alternative to fly ash in fabricating geopolymer paste and mortar. The blending of this industrial waste (alum sludge and fly ash) is not only for the benefit of sustainable construction and disposal of industrial waste but also for the reduction of CO2 emissions due to the increasing production of Portland cement from the cement production industry. A laboratory investigation was carried out on the workability and mechanical properties of geopolymer paste and mortar produced with alum sludge replacement in different proportions (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100). A combination of an alkaline solution of sodium silicate and sodium hydroxide of 14 molarity was employed as an activator for the manufacturing of both paste and mortar geopolymer specimens. It was observed from the findings that geopolymer paste and mortar was flowable and workable when alum sludge is replaced for fly ash at higher replacement content. The addition of alum sludge to the mix improved some properties such as density, strength, water absorption, and the elevated temperature behavior. It was observed that the addition of alum sludge was optimum at the 50% replacement level. The addition of alum sludge up to 50% significantly increased the compressive strength of mortar (up to 80% increase in 28 days strength). The compressive strength of the paste and mortar increased with an increase in curing age. Thus, alum sludge and fly ash can be employed together in the production of eco-friendly cementing material for environmental sustainability.
Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma
Authors: Jain Anish J. , Maxwell Jessica E. , Katz Matthew H. G. , Snyder Rebecca A.
Published: August 2023

Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.
Oncolytic Viruses and Immune Checkpoint Inhibitors: The “Hot” New Power Couple
Authors: Lovatt Charlotte , Parker Alan L.
Published: August 2023

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells, resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity, and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data have demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.
The Role of GAB1 in Cancer
Authors: Pérez-Baena Manuel Jesús , Cordero-Pérez Francisco Josué , Pérez-Losada Jesús , Holgado-Madruga Marina
Published: August 2023

GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 domain-containing proteins like SHP2, PI3K’s p85 subunit, CRK, and others, thereby activating distinct signaling pathways, including MAPK, PI3K/AKT, and JNK. GAB1-deficient embryos succumb in utero, presenting with developmental abnormalities in the heart, placenta, liver, skin, limb, and diaphragm myocytes. Oncogenic mutations have been identified in the context of cancer. GAB1 expression levels are disrupted in various tumors, and elevated levels in patients often portend a worse prognosis in multiple cancer types. This review focuses on GAB1’s influence on cellular transformation particularly in proliferation, evasion of apoptosis, metastasis, and angiogenesis—each of these processes being a cancer hallmark. GAB1 also modulates the resistance/sensitivity to antitumor therapies, making it a promising target for future anticancer strategies.
Easily Applicable Predictive Score for Differential Diagnosis of Prefibrotic Primary Myelofibrosis from Essential Thrombocythemia
Authors: Lekovic Danijela , Bogdanovic Andrija , Sobas Marta , Arsenovic Isidora , Smiljanic Mihailo , Ivanovic Jelena , Bodrozic Jelena , Cokic Vladan , Milic Natasa
Published: August 2023

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments.
Exploiting Long Non-Coding RNAs and Circular RNAs as Pharmacological Targets in Triple-Negative Breast Cancer Treatment
Authors: Palcau Alina Catalina , Brandi Renata , Mehterov Nikolay Hristov , Botti Claudio , Blandino Giovanni , Pulito Claudio
Published: August 2023

Breast cancer is one of the most frequent causes of cancer death among women worldwide. In particular, triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype because it is characterized by the absence of molecular targets, thus making it an orphan type of malignancy. The discovery of new molecular druggable targets is mandatory to improve treatment success. In that context, non-coding RNAs represent an opportunity for modulation of cancer. They are RNA molecules with apparently no protein coding potential, which have been already demonstrated to play pivotal roles within cells, being involved in different processes, such as proliferation, cell cycle regulation, apoptosis, migration, and diseases, including cancer. Accordingly, they could be used as targets for future TNBC personalized therapy. Moreover, the peculiar characteristics of non-coding RNAs make them reliable biomarkers to monitor cancer treatment, thus, to monitor recurrence or chemoresistance, which are the most challenging aspects in TNBC. In the present review, we focused on the oncogenic or oncosuppressor role of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) mostly involved in TNBC, highlighting their mode of action and depicting their potential role as a biomarker and/or as targets of new non-coding RNA-based therapeutics.
Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer
Authors: Lim Stephanie H. , Chua Wei , Ng Weng , Ip Emilia , Marques Tania M. , Tran Nham T. , Gama-Carvalho Margarida , Asghari Ray , Henderson Christopher , Ma Yafeng , de Souza Paul , Spring Kevin J.
Published: August 2023

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.
Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia
Authors: Álvarez-Zúñiga Claudia Daniela , Garza-Veloz Idalia , Martínez-Rendón Jacqueline , Ureño-Segura Misael , Delgado-Enciso Iván , Martinez-Fierro Margarita L.
Published: August 2023

Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL.
Clinical Significance of Non-Coding RNA Regulation of Programmed Cell Death in Hepatocellular Carcinoma
Authors: Chen Wuyu , Ruan Minghao , Zou Minghao , Liu Fuchen , Liu Hui
Published: August 2023

Hepatocellular carcinoma (HCC) is a widely prevalent and malignantly progressive tumor. Most patients are typically diagnosed with HCC at an advanced stage, posing significant challenges in the execution of curative surgical interventions. Non-coding RNAs (ncRNAs) represent a distinct category of RNA molecules not directly involved in protein synthesis. However, they possess the remarkable ability to regulate gene expression, thereby exerting significant regulatory control over cellular processes. Notably, ncRNAs have been implicated in the modulation of programmed cell death (PCD), a crucial mechanism that various therapeutic agents target in the fight against HCC. This review summarizes the clinical significance of ncRNA regulation of PCD in HCC, including patient diagnosis, prognosis, drug resistance, and side effects. The aim of this study is to provide new insights and directions for the diagnosis and drug treatment strategies of HCC.
Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral Neuropathy
Authors: Staff Nathan P. , Hrstka Sybil C. , Dasari Surendra , Capobianco Enrico , Rieger Sandra
Published: August 2023

The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN.
Peripheral T-Cell Lymphoma: From Biological Research to New Therapies
Authors: Nakahata Shingo , Morishita Kazuhiro
Published: August 2023

This series of six articles (four reviews and two original articles) is presented by international leaders on peripheral T-cell lymphomas (PTCL) [...]
A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss of Ppp2r5d
Authors: Domènech Omella Judit , Cortesi Emanuela E. , Verbinnen Iris , Remmerie Michiel , Wu Hanghang , Cubero Francisco J. , Roskams Tania , Janssens Veerle
Published: August 2023

Primary liver cancer (PLC) can be classified in hepatocellular (HCC), cholangiocarcinoma (CCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). The molecular mechanisms involved in PLC development and phenotype decision are still not well understood. Complete deletion of Ppp2r5d, encoding the B56δ subunit of Protein Phosphatase 2A (PP2A), results in spontaneous HCC development in mice via a c-MYC-dependent mechanism. In the present study, we aimed to examine the role of Ppp2r5d in an independent mouse model of diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Ppp2r5d deletion (heterozygous and homozygous) accelerated HCC development, corroborating its tumor-suppressive function in liver and suggesting Ppp2r5d may be haploinsufficient. Ppp2r5d-deficient HCCs stained positively for c-MYC, consistent with increased AKT activation in pre-malignant and tumor tissues of Ppp2r5d-deficient mice. We also found increased YAP activation in Ppp2r5d-deficient tumors. Remarkably, in older mice, Ppp2r5d deletion resulted in cHCC-CCA development in this model, with the CCA component showing increased expression of progenitor markers (SOX9 and EpCAM). Finally, we observed an upregulation of Ppp2r5d in tumors from wildtype and heterozygous mice, revealing a tumor-specific control mechanism of Ppp2r5d expression, and suggestive of the involvement of Ppp2r5d in a negative feedback regulation restricting tumor growth. Our study highlights the tumor-suppressive role of mouse PP2A-B56δ in both HCC and cHCC-CCA, which may have important implications for human PLC development and targeted treatment.
Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy
Authors: Sarfraz Muhammad , Khan Abida , Batiha Gaber El-Saber , Akhtar Muhammad Furqan , Saleem Ammara , Ajiboye Basiru Olaitan , Kamal Mehnaz , Ali Abuzer , Alotaibi Nawaf M. , Aaghaz Shams , Siddique Muhammad Irfan , Imran Mohd
Published: August 2023

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.
Rational Design of the Catalysts for the Direct Conversion of Methane to Methanol Based on a Descriptor Approach
Authors: Li Zhi , Chen Yanjun , Xie Zean , Song Weiyu , Liu Baijun , Zhao Zhen
Published: August 2023

The direct oxidation of methane to methanol as a liquid fuel and chemical feedstock is arguably the most desirable methane conversion pathway. Currently, constructing and understanding linear scaling relationships between the fundamental physical or chemical properties of catalysts and their catalytic performance to explore suitable descriptors is crucial for theoretical research on the direct conversion of methane to methanol. In this review, we summarize the energy, electronic, and structural descriptors used to predict catalytic activity. Fundamentally, these descriptors describe the redox properties of active sites from different dimensions. We further explain the moderate principle of descriptors in methane-to-methanol catalyst design and provide related application work. Simultaneously, the underlying activity limitation of methane activation and active species generation is revealed. Based on the selectivity descriptor, the inverse scaling relationship limitation between methane conversion and methanol selectivity is quantitatively understood. Finally, multiscale strategies are proposed to break the limitation and achieve the simultaneous enhancement of activity and selectivity. This descriptor-based review provides theoretical insights and guidance to accelerate the understanding, optimization, and design of efficient catalysts for direct methane-to-methanol conversion.
Catch of the Day: New Serum Amyloid A (SAA) Antibody Is a Valuable Tool to Study Fish Health in Salmonids
Authors: Buks Ralfs , Alnabulsi Abdo , Zindrili Rodanthi , Alnabulsi Ayham , Wang Alex , Wang Tiehui , Martin Samuel A. M.
Published: August 2023

Serum amyloid A (SAA) proteins belong to a family of acute-phase reactants, playing an integral role in defending the organism from pathological damage. Despite a wealth of data on the regulation of SAA transcripts in teleosts, there is only limited information on these proteins’ abundance in fish. The aim of this study is to characterise SAA protein levels in salmonids using a newly developed antibody specific to salmonid SAA. The salmonid SAA antibody detected SAA and accurately discriminated between stimulated and control specimens from rainbow trout macrophage cell line (RTS-11) in vitro, as well as rainbow trout challenged with Aeromonas salmonicida- or flagellin-stimulated Atlantic salmon in vivo. The presence of SAA protein was analysed in RTS-11 cell line supernatants, liver, and spleen samples using ELISA, immunoblotting, and immunohistochemistry. This study is the first to characterise SAA protein levels in salmonids in vivo and in vitro. The newly developed salmonid SAA antibody was able to discriminate between stimulated and unstimulated specimens, showing that it can be used to study the acute-phase response in salmonids with the potential to be further developed into assays to monitor and evaluate health in wild and farmed fish.
Effect of Expansion Media on Functional Characteristics of Bone Marrow-Derived Mesenchymal Stromal Cells
Authors: Jakl Viktoria , Popp Tanja , Haupt Julian , Port Matthias , Roesler Reinhild , Wiese Sebastian , Friemert Benedikt , Rojewski Markus T. , Schrezenmeier Hubert
Published: August 2023

The therapeutic efficacy of mesenchymal stromal cells (MSCs) has been shown to rely on their immunomodulatory and regenerative properties. In order to obtain sufficient numbers of cells for clinical applications, MSCs have to be expanded ex vivo. Expansion media with xenogeneic-free (XF) growth-promoting supplements like human platelet lysate (PL) or serum- and xenogeneic-free (SF/XF) formulations have been established as safe and efficient, and both groups provide different beneficial qualities. In this study, MSCs were expanded in XF or SF/XF media as well as in mixtures thereof. MSCs cultured in these media were analyzed for phenotypic and functional properties. MSC expansion was optimal with SF/XF conditions when PL was present. Metabolic patterns, consumption of growth factors, and secretome of MSCs differed depending on the type and concentration of supplement. The lactate per glucose yield increased along with a higher proportion of PL. Many factors in the supernatant of cultured MSCs showed distinct patterns depending on the supplement (e.g., FGF-2, TGFβ, and insulin only in PL-expanded MSC, and leptin, sCD40L PDGF-AA only in SF/XF-expanded MSC). This also resulted in changes in cell characteristics like migratory potential. These findings support current approaches where growth media may be utilized for priming MSCs for specific therapeutic applications.
Using Virtual Reality to Reduce Anxiety and Improve Hospital Experience in Paediatric Orthopaedic Patients and Their Parents
Authors: Oh Natasha , Parrish Nina , Lee In Woo , Temple Sasha , Perkins Oliver , Kokkinakis Michail
Published: August 2023

The hospital environment can be a stressful environment for paediatric patients and their parents, which is often characterised by heightened levels of pain and anxiety. To address these challenges, many innovative intervention methods has been explored. For example, immersive virtual reality (VR) headsets as a distraction method has become an increasingly popular intervention in recent years. This study aimed to evaluate the effectiveness of VR using ‘Rescape DR.VR Junior’ in reducing pain, anxiety, and enhancing the overall hospital experience for paediatric orthopaedic patients and their parents. A total of 64 patients aged 4–18 years were included in this study, which utilised a control group (interacting with a play specialist) and a VR intervention group (including pre-operative patients and fracture clinic patients). Anxiety and pain levels were measured using a 10-point Likert scale before and after the intervention, and validated questionnaires were used to assess parental anxiety and overall hospital experience. The results indicated that VR intervention significantly reduced patient and parental anxiety both before surgery and in the fracture clinic setting (p < 0.5). However, no significant reduction in pain scores was observed in either environments. Comparatively, VR intervention was found to be comparable to traditional play methods in terms of reducing anxiety in the pre-operative environment. All patients and parents agreed that the use of VR distraction methods significantly improved their hospital experience. In conclusion, VR is an effective method for reducing child and parental anxiety and enhancing the hospital experience and can be used alone or in conjunction with a play specialist.
Caring for Children with Dravet Syndrome: Exploring the Daily Challenges of Family Caregivers
Authors: Domaradzki Jan , Walkowiak Dariusz
Published: August 2023

While Polish studies focus on the symptoms, causes and treatment of people suffering from Dravet syndrome (DS), much less is known about the situation of the family caregivers of DS children. This study was designed to explore the experiences, daily challenges and needs related to caring for DS children. An anonymous self-administered online questionnaire was developed. The survey was completed by 75 family caregivers affiliated with the Association for People with Severe Refractory Epilepsy DRAVET.PL on Facebook. Most caregivers felt burdened by their children’s reduced mobility (57.3%), mood swings (57.3%), lack of access to rehabilitation and medicine (56%) and healthcare expenses (50.7%). Caregivers also complained of a lack of time to themselves (76%) and work restrictions resulting from caregiving (72%). They consequently reported experiencing fatigue (84%), a deterioration of mental health (60%) and intimacy problems with their spouse/partner (53.4%). An important source of strain was a prolonged diagnostic odyssey and the constant struggle over the healthcare services for DS children. Since DS caregivers’ problems and needs are often overlooked, they may be described as the forgotten people in DS. Healthcare professionals should be educated about the challenges related to caring for DS child, psycho-social status and coping resources of DS caregivers, and should focus on identification, monitoring and supporting caregivers’ physical and mental well-being and needs.
Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland
Authors: Thwaites Philip , Hagmann Cornelia , Schneider Juliane , Schulzke Sven M. , Grunt Sebastian , Nguyen Thi Dao , Bassler Dirk , Natalucci Giancarlo
Published: August 2023

Background: Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. Aim: To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). Methods: In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24–29 weeks gestational age (GA) in Switzerland in 2002–2014, with G3-IVH and/or PVHI. Results: Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002–2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. Conclusion: In 2002–2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results.
Autism and Religion
Authors: Kéri Szabolcs
Published: August 2023

The disease burden of autism spectrum disorder (ASD) is a definitive public health challenge. The quality of life of children with ASD depends on how the cultural environment fits their special needs, including religious and spiritual factors. Does ASD predict low religiosity, and if not, what is the significance for clinical care? To answer this question, we reviewed the literature on the cognitive models of ASD and religious beliefs. We found that the cognitive models of ASD and religious beliefs substantially overlap, which is particularly important from a developmental psychological perspective. These models include Theory of Mind and intentionality, the “broken mirror” hypothesis, central coherence, and the intense world theory. We dispute the assumption that individuals with ASD are inherently less religious and spiritual than the neurotypical population. Religiosity is possibly expressed differently in ASD with unique spiritual experiences and beliefs (“gifted, visionary, and truth-seeker”). In some circumstances, a religious background can be helpful for both children with ASD and their caregivers. These circumstances should not be neglected, and clinicians are encouraged to consider patients’ religious context, resources, and needs.
Exclusive Breastfeeding in Health Personnel: Incidence and Barriers
Authors: Nanthakomon Tongta , Nukaw Sonthaya , Kositamongkol Sudatip
Published: August 2023

Exclusive breastfeeding for 6 months (EBF) in healthcare personnel is challenging due to work schedules, high workloads, or separation issues. This study aimed to evaluate the incidence and factors related to EBF in our hospital personnel. Material and Methods: This was a cross-sectional study. Female employees who took maternity leave within 2 years were approached. A questionnaire regarding factors associated with EBF was sent to participants. Factors associated with EBF were analyzed using logistic regression analysis. Results: There were 110 mothers enrolled. The mean maternal age was 32.5 ± 4.21 years, 66.36% came from the nursing department, the infant’s age was 6–24 months, and 46.4% of mothers had previous breastfeeding experience. Our EBF for 6 months rate was 63.6%. Breastfeeding attitude (OR = 1.12, 95%CI 1.08–1.38), perception of breastfeeding obstacle (OR = 1.45, 95%CI 1.26–1.66), breastfeeding behavior (OR = 1.17, 95%CI 1.08–1.26), and support from health system (OR = 1.09, 95%CI 1.01–1.19) were significantly associated with EBF. From multiple logistic regression models, perception of breastfeeding obstacles (aOR 1.55, 95%CI 1.27–1.90), breastfeeding behavior (aOR 1.12, 95%CI 1.01–1.24), and support from health care system (aOR 0.84, 95%CI 0.72–0.97) remain the significant factors associated with successful EBF. Conclusion: Successful EBF was prevalent in mothers who had good attitudes to breastfeeding, perceived low levels of obstacles, and had support from the health care system.
The Constrained-Disorder Principle Assists in Overcoming Significant Challenges in Digital Health: Moving from “Nice to Have” to Mandatory Systems
Authors: Hurvitz Noa , Ilan Yaron
Published: August 2023

The success of artificial intelligence depends on whether it can penetrate the boundaries of evidence-based medicine, the lack of policies, and the resistance of medical professionals to its use. The failure of digital health to meet expectations requires rethinking some of the challenges faced. We discuss some of the most significant challenges faced by patients, physicians, payers, pharmaceutical companies, and health systems in the digital world. The goal of healthcare systems is to improve outcomes. Assisting in diagnosing, collecting data, and simplifying processes is a “nice to have” tool, but it is not essential. Many of these systems have yet to be shown to improve outcomes. Current outcome-based expectations and economic constraints make “nice to have,” “assists,” and “ease processes” insufficient. Complex biological systems are defined by their inherent disorder, bounded by dynamic boundaries, as described by the constrained disorder principle (CDP). It provides a platform for correcting systems’ malfunctions by regulating their degree of variability. A CDP-based second-generation artificial intelligence system provides solutions to some challenges digital health faces. Therapeutic interventions are held to improve outcomes with these systems. In addition to improving clinically meaningful endpoints, CDP-based second-generation algorithms ensure patient and physician engagement and reduce the health system’s costs.
Breaking through the Thermodynamics “Wilds” of Metal–Organic Chemical Vapor Deposition Precursors: Metal tris-Acetylacetonates
Authors: Makarenko Alexander , Trubin Sergey , Zherikova Kseniya
Published: August 2023

Metal acetylacetonates belong to the β-diketonate family and are considered as classics among precursors for metal–organic chemical vapor deposition (MOCVD). The success of film preparation is crucially dependent on the volatilization thermodynamics of the precursors used. Data on the volatilization thermodynamics of metal acetylacetonates are in huge disarray. We amassed and analyzed experimental data on the vapor pressures and on the enthalpies and entropies of fusion, vaporization, and sublimation of acetylacetonate tris-complexes of metals(III) (Al, Sc, Cr, Mn, Fe, Co, Ru, Rh, In, and Ir) available in the literary sources. In addition, saturated vapor pressures over crystalline Al(III), Cr(III), and In(III) acetylacetonates and corresponding thermodynamic sublimation properties were determined. New findings enabled us to arbitrate the conflict among literature data. The enthalpies and entropies of sublimation, vaporization, and fusion were adjusted to the reference temperature for a correct comparison using the empirically estimated differences in heat capacities. The heat capacity of the crystalline phase was shown to depend weakly on the metal atom. As a result, a reliable set of enthalpies and entropies of the mentioned processes of fundamental importance was derived for ten metal complexes. Relationships between volatility and structure were established depending on the central metal. The suggested algorithm can be fairly easily transferred to the acetylacetonate or other β-diketonate isoligand complexes with metals of different valence.
Effect of Post-Fabrication Heat Treatments on the Microstructure of WC-12Co Direct Energy Depositions
Authors: Morales Cindy , Fortini Annalisa , Soffritti Chiara , Merlin Mattia
Published: August 2023

Laser-Directed Energy Deposition (L-DED) is an additive manufacturing technique that has lately been employed to deposit coatings of cemented carbides, such as WC-Co. During deposition, complex microstructural phenomena usually occur, strongly affecting the microstructural and mechanical behavior of the coatings. Post-fabrication heat treatments (PFHTs) may be applied to homogenize and strengthen the microstructure; nevertheless, to the best of the authors’ knowledge, just a few papers deepened the effect of these treatments on cemented carbides fabricated by additive manufacturing. This work evaluates the influence of four PFHTs on the microstructural evolution and hardness of L-DED WC-12Co. For each treatment, different combinations of solubilization time and temperature (between 30 and 180 min and from 400 °C to 700 °C, respectively) were adopted. The microstructure was investigated by optical and scanning electron microscopy equipped with energy-dispersive spectroscopy, whereas the mechanical properties were determined by Vickers hardness measurements. Based on the results, high microstructural heterogeneity in terms of WC particles, η-phase structures, and Co distribution was observed in the sample in the as-built condition. Some cracking defects were also observed in the samples, irrespective of the heat treatment conditions. Finally, a finer microstructure and a lower amount of brittle ternary η-phase, together with an increase in hardness (1030 ± 95 HV10), were found for the highest dwelling times (180 min) and for solubilization temperatures in the range of 500–600 °C.
A Cost-Effective, Nanoporous, High-Entropy Oxide Electrode for Electrocatalytic Water Splitting
Authors: Liu Bu-Jine , Yin Tai-Hsin , Lin Yu-Wei , Chang Chun-Wei , Yu Hsin-Chieh , Lim Yongtaek , Lee Hyesung , Choi Changsik , Tsai Ming-Kang , Choi YongMan
Published: August 2023

High-entropy materials have attracted extensive attention as emerging electrode materials in various energy applications due to their flexible tunability, unusual outstanding activities, and cost-effectiveness using multiple earth-abundant elements. We introduce a novel high-entropy composite oxide with the five elements of Cu, Ni, Co, Fe, and Cr (HEO-3CNF) for use in the oxygen evolution reaction (OER) in electrocatalytic water splitting. HEO-3CNF is composed of two phases with a non-equimolar, deficient high-entropy spinel oxide of (Cu0.2−xNi0.2Co0.2Fe0.2Cr0.2)3O4 and monoclinic copper oxide (CuO). Electrochemical impedance spectroscopy (EIS) with distribution of relaxation times (DRT) analysis validates that the HEO-3CNF-based electrode exhibits faster charge transfer than benchmark CuO. It results in improved OER performance with a lower overpotential at 10 mA/cm2 and a Tafel slope than CuO (518.1 mV and 119.7 mV/dec versus 615.9 mV and 131.7 mV/dec, respectively) in alkaline conditions. This work may provide a general strategy for preparing novel, cost-effective, high-entropy electrodes for water splitting.