bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Investigations of InAs/InP Quantum-Dash Semiconductor Optical Amplifiers with Different Numbers of Dash Layers
Authors: Mao Youxin , Xie Xiaoran , Song Chunying , Lu Zhenguo , Poole Philip J. , Liu Jiaren , Toreja Mia , Qi Yang , Liu Guocheng , Barrios Pedro , Poitras Daniel , Weber John , Zhao Ping , Vachon Martin , Rahim Mohamed , Ma Penghui , Chen Silas , Atieh Ahmad
Published: December 2023

We present here a performance comparison of quantum-dash (Qdash) semiconductor amplifiers (SOAs) with three, five, eight, and twelve InAs dash layers grown on InP substrates. Other than the number of Qdash layers, the structures were identical. The eight-layer Qdash SOA gave the highest amplified spontaneous emission power (4.3 dBm) and chip gain (26.4 dB) at 1550 nm, with a 300 mA CW bias current and at 25 °C temperature, while SOAs with fewer Qdash layers (for example, three-layer Qdash SOA), had a wider ASE bandwidth (90 nm) and larger 3 dB gain saturated output power (18.2 dBm) in a shorter wavelength range. The noise figure (NF) of the SOAs increased nearly linearly with the number of Qdash layers. The longest gain peak wavelength of 1570 nm was observed for the 12-layer Qdash SOA. The most balanced performance was obtained with a five-layer Qdash SOA, with a 25.4 dB small-signal chip gain, 15.2 dBm 3 dB output saturated power, and 5.7 dB NF at 1532 nm, 300 mA and 25 °C. These results are better than those of quantum well SOAs reported in a recent review paper. The high performance of InAs/InP Qdash SOAs with different Qdash layers shown in this paper could be important for many applications with distinct requirements under uncooled scenarios.
An Investigation in Sub-Millimeter Channel Fabrication by the Non-Aqueous Electrolyte Jet Machining of Zr-Based Bulk Metallic Glasses
Authors: Guo Cheng , Zhou Aixing , He Jingwen , Xiao Huapan , Li Duo
Published: December 2023

Zr-based bulk metallic glasses (BMGs) have many unique properties. Due to their excellent performance and manufacturing process, they have become a research focus in the material science community. Electrolyte Jet Machining (EJM) is a non-contact electrochemical processing method with high surface integrity and high material removal rate (MRR). In this research, the sub-millimeter channels fabricated by EJM on Zr-based BMGs have been studied to explore the dissolution mechanisms and surface integrity under different scanning rates and voltages. The results show that, with other machining parameters holding constant, an increase in voltage leads to a substantial enhancement in both the depth and width of the channels machined on Zr-based BMGs. Notably, the influence of voltage on the depth of the channels is particularly pronounced. Additionally, an escalation in scanning rate correlates with a decrease in channel depth, with minimal variation in channel width. This study indicates that alcohol-based EJM is an effective method to fabricate sub-millimeter channels and modulate structures on Zr-based BMGs.
Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus—A Case Report and Literature Review
Authors: Santini Marija , Ljubić Jelena , Šoštar Nikola , Vilibić-Čavlek Tatjana , Bogdanić Maja , Zakotnik Samo , Avšič-Županc Tatjana , Korva Miša , Kurolt Ivan Christian , Radmanić Leona , Šimičić Petra , Krznarić Juraj , Gjurašin Branimir , Kutleša Marko , Višković Klaudija , Balent Nataša Cetinić , Žunec Renata , Margeta Marić Ivana , Ribarović Ana , Židovec-Lepej Snjezana
Published: December 2023

In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24–73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection.
Diatom–Bacteria Interactions in the Marine Environment: Complexity, Heterogeneity, and Potential for Biotechnological Applications
Authors: Di Costanzo Federica , Di Dato Valeria , Romano Giovanna
Published: December 2023

Diatom–bacteria interactions evolved during more than 200 million years of coexistence in the same environment. In this time frame, they established complex and heterogeneous cohorts and consortia, creating networks of multiple cell-to-cell mutualistic or antagonistic interactions for nutrient exchanges, communication, and defence. The most diffused type of interaction between diatoms and bacteria is based on a win-win relationship in which bacteria benefit from the organic matter and nutrients released by diatoms, while these last rely on bacteria for the supply of nutrients they are not able to produce, such as vitamins and nitrogen. Despite the importance of diatom–bacteria interactions in the evolutionary history of diatoms, especially in structuring the marine food web and controlling algal blooms, the molecular mechanisms underlying them remain poorly studied. This review aims to present a comprehensive report on diatom–bacteria interactions, illustrating the different interplays described until now and the chemical cues involved in the communication and exchange between the two groups of organisms. We also discuss the potential biotechnological applications of molecules and processes involved in those fascinating marine microbial networks and provide information on novel approaches to unveiling the molecular mechanisms underlying diatom–bacteria interactions.
Structure–Activity Studies on Bis-Sulfonamide SHIP1 Activators
Authors: Meyer Shea T. , Fernandes Sandra , Anderson Robert E. , Pacherille Angela , Toms Bonnie , Kerr William G. , Chisholm John D.
Published: December 2023

The SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) enzyme opposes the activity of PI3K and therefore is of interest in the treatment of inflammatory disorders. Recent results also indicate that SHIP1 promotes phagolysosomal degradation of lipids by microglia, suggesting that the enzyme may be a target for the treatment of Alzheimer’s disease. Therefore, small molecules that increase SHIP1 activity may have benefits in these areas. Recently we discovered a bis-sulfonamide that increases the enzymatic activity of SHIP1. A series of similar SHIP1 activators have been synthesized and evaluated to determine structure–activity relationships and improve in vivo stability. Some new analogs have now been found with improved potency. In addition, both the thiophene and the thiomorpholine in the parent structure can be replaced by groups without a low valent sulfur atom, which provides a way to access activators that are less prone to oxidative degradation.
Structural Analysis and Activity Correlation of Amphiphilic Cyclic Antimicrobial Peptides Derived from the [W4R4] Scaffold
Authors: El-Mowafi Shaima A. , Konshina Anastasia G. , Mohammed Eman H. M. , Krylov Nikolay A. , Efremov Roman G. , Parang Keykavous
Published: December 2023

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W4R4], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W4R4] scaffold, including the first synthesis and evaluation of [W4R4(DKP)]. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results revealed distinct SARs linking antimicrobial activity to parameters such as conformational plasticity, immersion depth in the bilayer, and population of the membrane binding mode. Notably, [W4R5] exhibited an optimal “activity/binding to the bacterial membrane” pattern. This multidisciplinary approach efficiently decoded finely regulated SAR profiles, laying a foundation for the rational design of novel antimicrobial peptides.
Understanding the Mechanism of the Structure-Dependent Mechanical Performance of Carbon-Nanotube-Based Hierarchical Networks from a Deformation Mode Perspective
Authors: Shi Xian , He Xiaoqiao , Liu Xuefeng
Published: December 2023

Carbon nanotube (CNT)-based networks have wide applications, in which structural design and control are important to achieve the desired performance. This paper focuses on the mechanism behind the structure-dependent mechanical performance of a CNT-based hierarchical network, named a super carbon nanotube (SCNT), which can provide valuable guidance for the structural design of CNT-based networks. Through molecular dynamic (MD) simulations, the mechanical properties of the SCNTs were found to be affected by the arrangement, length and chirality of the CNTs. Different CNT arrangements cause variations of up to 15% in the ultimate tensile strains of the SCNTs. The CNT length determines the tangent elastic modulus of the SCNTs at the early stage. Changing the CNT chirality could transform the fracture modes of the SCNT from brittle to ductile. The underlying mechanisms were found to be associated with the deformation mode of the SCNTs. All the SCNTs undergo a top-down hierarchical deformation process from the network-level angle variations to the CNT-level elongations, but some vital details vary, such as the geometrical parameters. The CNT arrangement induces different deformation contributors of the SCNTs. The CNT length affects the beginning point of the CNT elongation deformation. The CNT chirality plays a crucial role in the stability of the junction’s atomic topology, where the crack propagation commences.
Novel Effective Photocatalytic Self-Cleaning Coatings: TiO2-Polyfluoroalkoxy Coatings Prepared by Suspension Plasma Spraying
Authors: He Chunyan , He Jialin , Cui Sainan , Fan Xiujuan , Li Shuanjian , Yang Yaqi , Tan Xi , Zhang Xiaofeng , Mao Jie , Zhang Liuyan , Deng Changguang
Published: December 2023

Photocatalytic coatings can degrade volatile organic compounds into non-toxic products, which has drawn the attention of scholars around the world. However, the pollution of dust on the coating adversely affects the photocatalytic efficiency and service life of the coating. Here, a series of TiO2-polyfluoroalkoxy (PFA) coatings with different contents of PFA were fabricated by suspension plasma spraying technology. The results demonstrate that the hybrid coatings contain a large number of circular and ellipsoidal nanoparticles and a porous micron-nano structure due to the inclusion of PFA. According to the optimized thermal spraying process parameters, TiO2 nanoparticles were partially melted to retain most of the anatase phases, whereas PFA did not undergo significant carbonization. As compared to the TiO2 coating, the static contact angle of the composite coating doped with 25 wt.% PFA increased from 28.2° to 134.1°. In addition, PFA strongly adsorbs methylene blue, resulting in a greater involvement of methylene blue molecules in the catalyst, where the catalytic rate of hybrid coatings is up to 95%. The presented nanocomposite coatings possess excellent photocatalytic and self-cleaning properties and are expected to find wider practical applications in the field of photocatalysis.
Multifunctional Core/Shell Diamond Nanoparticles Combining Unique Thermal and Light Properties for Future Biological Applications
Authors: Grudinkin Sergey A. , Bogdanov Kirill V. , Tolmachev Vladimir A. , Baranov Mikhail A. , Kaliya Ilya E. , Golubev Valery G. , Baranov Alexander V.
Published: December 2023

We report the development of multifunctional core/shell chemical vapor deposition diamond nanoparticles for the local photoinduced hyperthermia, thermometry, and fluorescent imaging. The diamond core heavily doped with boron is heated due to absorbed laser radiation and in turn heats the shell of a thin transparent diamond layer with embedded negatively charged SiV color centers emitting intense and narrowband zero-phonon lines with a temperature-dependent wavelength near 738 nm. The heating of the core/shell diamond nanoparticle is indicated by the temperature-induced spectral shift in the intensive zero-phonon line of the SiV color centers embedded in the diamond shell. The temperature of the core/shell diamond particles can be precisely manipulated by the power of the incident light. At laser power safe for biological systems, the photoinduced temperature of the core/shell diamond nanoparticles is high enough to be used for hyperthermia therapy and local nanothermometry, while the high zero-phonon line intensity of the SiV color centers allows for the fluorescent imaging of treated areas.
Correlation between Blood Monocytes and CSF Tau in Alzheimer’s Disease: The Effect of Gender and Cognitive Decline
Authors: Cimiotti Carlotta Ginevra Valentina , Paganetti Paolo , Rossi Stefania , Soldini Emiliano , Sacco Leonardo
Published: December 2023

Neuroinflammation is one of the main mechanisms contributing to the pathogenesis of Alzheimer’s disease (AD), although its key role and the immune cells involved have not yet been identified. Blood monocytes appear to play a role in the clearance of AD-related amyloid-β (Aβ) and tau protein. This retrospective study evaluated a possible correlation between blood monocytes; the concentrations of Aβ, total tau (t-Tau), and phosphorylated tau (p-Tau) in the cerebrospinal fluid (CSF); and cognitive decline assessed according to the Montreal Cognitive Assessment (MoCA). We collected data from 33 patients with AD or mild cognitive impairment (MCI) due to AD (15 men and 18 women) and found, along with a significant reduction in the concentration of blood monocytes in women (p-value = 0.083),significant correlations between the number of blood monocytes and the concentration of t-Tau in CSF (p-value = 0.045) and between blood monocytes and MoCA score (p-value = 0.037). These results confirm the role of blood monocytes in the pathogenesis of AD, provide further evidence of a gender difference in the neuroinflammatory process underlying AD, and show that blood monocyte count may reflect the cognitive impairment of AD patients.
Barriers to and Facilitators of the Implementation of a Micronutrient Powder Program for Children: A Systematic Review Based on the Consolidated Framework for Implementation Research
Authors: Sun Yinuo , Ma Jiyan , Wei Xiaolin , Dong Jingya , Wu Shishi , Huang Yangmu
Published: December 2023

Background: As one of the most cost-effective investments for improving child nutrition, micronutrient powder (MNP) has been widely used in many countries to underpin the Sustainable Development Goals, yet challenges remain regarding its implementation on a large scale. However, few studies have explored the factors that facilitate or impede the implementation process using implementation science theories and frameworks. To address this gap, we adopted the Consolidated Framework of Implementation Research (CFIR) and conducted a systematic review of studies on the implementation barriers to and facilitators of MNP interventions. Method: Five publication databases, including EMBASE, Medline, PubMed, Web of Science, and Scopus, were searched for studies on the influencing factors of MNP interventions. Based on the CFIR framework, the facilitators and barriers for the MNP program implementation reported in the included studies were extracted and synthesized by five domains: intervention characteristics, outer setting, inner setting, individual characteristics, and process. Results: A total of 50 articles were eligible for synthesis. The majority of the studies were conducted in lower-middle-income countries (52%) through the free delivery model (78%). The inner setting construct was the most prominently reported factor influencing implementation, specifically including available resources (e.g., irregular or insufficient MNP supply), structural characteristics (e.g., public-driven community-based approach), and access to information and knowledge (e.g., lack of training for primary-level workers). The facilitators of the engagement of private sectors, external guidelines, and regular program monitoring were also highlighted. On the contrary, monotonous tastes and occasional side effects impede intervention implementation. Additionally, we found that the inner setting had an interrelation with other contributing factors in the MNP program implementation. Conclusion: Our results suggest that MNP program implementation was prominently influenced by the available resources, organizational structure, and knowledge of both providers and users. Mobilizing local MNP suppliers, engaging public-driven free models in conjunction with market-based channels, and strengthening the training for primary-level health workers could facilitate MNP interventions.
Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study
Authors: Sánchez María Carmen , Herráiz Ana , Tigre Sindy , Llama-Palacios Arancha , Hernández Marta , Ciudad María José , Collado Luis
Published: December 2023

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.
Adherence to Mediterranean Diet and Food Neophobia Occurrence in Children: A Study Carried out in Italy
Authors: Di Nucci Annalisa , Pilloni Simone , Scognamiglio Umberto , Rossi Laura
Published: December 2023

Food Neophobia (FN), defined as the reluctance to eat new or unfamiliar foods, mainly concerns fruit, vegetables, and legumes, typical of the Mediterranean Diet (MD). Considering these premises, this study aimed to clarify the relationship between FN and AMD in a sample of Italian children and their association with some socio-demographic factors and children’s nutritional status. A sample of 288 children aged 3–11 years participated in an assessment carried out with a questionnaire evaluating FN and AMD, respectively, with the Child Food Neophobia Scale (CFNS) and the KIDMED test. Most of the sample showed an intermediate (67.3%) or high level of FN (18.1%), with high rates among 6–11-year-old children (63.9%) and especially in those who were the only child (50%). The AMD was mostly low (29.5%) or medium (54.8%) and reached lower levels among higher neophobic children (51.9%; p value < 0.05). The present results confirm the study hypothesis that FN is a driver of MD abandonment and shows the positive effects on children’s eating habits and siblings. Finally, this study proves the relevance of adopting effective feeding strategies against FN to avoid its maintenance in adulthood and the detrimental effects on future overall health and well-being.
Nutritional Modulation of Hepcidin in the Treatment of Various Anemic States
Authors: D’Andrea Patrizia , Giampieri Francesca , Battino Maurizio
Published: December 2023

Twenty years after its discovery, hepcidin is still considered the main regulator of iron homeostasis in humans. The increase in hepcidin expression drastically blocks the flow of iron, which can come from one’s diet, from iron stores, and from erythrophagocytosis. Many anemic conditions are caused by non-physiologic increases in hepcidin. The sequestration of iron in the intestine and in other tissues poses worrying premises in view of discoveries about the mechanisms of ferroptosis. The nutritional treatment of these anemic states cannot ignore the nutritional modulation of hepcidin, in addition to the bioavailability of iron. This work aims to describe and summarize the few findings about the role of hepcidin in anemic diseases and ferroptosis, as well as the modulation of hepcidin levels by diet and nutrients.
Vascular and Platelet Effects of Tomato Soffritto Intake in Overweight and Obese Subjects
Authors: López-Yerena Anallely , Padro Teresa , de Santisteban Villaplana Victoria , Muñoz-García Natàlia , Pérez Antonio , Vilahur Gemma , Badimon Lina
Published: December 2023

Tomatoes are known for their numerous health benefits, including antioxidants, anti-cancer, antimicrobial, anti-inflammatory, anti-neurodegenerative, antiplatelet, and cardio-protective properties. However, their potential health benefits in the Mediterranean diet’s popular soffritto remain largely unexplored in scientific research. The objective was to evaluate the effects of soffritto intake on platelet activity, vascular endothelial function, weight, lipid profile, and blood parameters. In a prospective, controlled, randomized two-arm longitudinal cross-over trial, 40 overweight and obese individuals received 100 g/day of soffritto, or a control, for 42 days. The primary outcome was the effect on vascular endothelial function and platelet activity. As exploratory secondary outcomes, anthropometric measures, serum lipid profile, and hemogram profile were measured before and after a 6-week intervention with or without soffritto supplementation. Compared with the control group, soffritto supplementation for six weeks improved collagen-induced (−5.10 ± 3.06%) platelet aggregation (p < 0.05). In addition, after six weeks, a reduction in ADP-induced aggregation (−3.67 ± 1.68%) was also only observed in the soffritto group (p < 0.05). No significant effects of the soffritto intake were observed on vascular endothelial function, anthropometric measures, serum lipid profile, or blood parameters (p > 0.05). In conclusion, as a basic culinary technique, soffritto may have a role in the primary prevention of cardiovascular disease by reducing platelet activation, which could contribute to a reduction in thrombotic events.
A Correlation Study of Plasma and Breast Milk Retinol Concentrations in Breastfeeding Women in China
Authors: Qin Jing , Zhou Yubo , Li Hongtian , Meng Ying , Tanumihardjo Sherry A. , Liu Jianmeng
Published: December 2023

Retinol in breast milk is related to plasma concentration among breastfeeding women, but the linear or curvilinear relationships between the two remains unclear. We conducted a cross-sectional study in 403 Chinese breastfeeding women at 42 ± 7 days postpartum. Plasma and breast milk samples were assayed using high performance liquid chromatography to determine the concentration of retinol. Partial Spearman correlation and multivariable fractional polynomial regression were used to examine the relationships between the two retinol concentrations and between plasma retinol concentration and milk-to-plasma (M/P) retinol. The median (interquartile range, IQR) of the retinol concentration in the plasma was 1.39 (1.21, 1.63) μmol/L and 1.15 (0.83, 1.49) μmol/L in the breast milk, respectively. The partial correlation coefficient between them was 0.17 (p < 0.01). A linear relationship was observed with an adjusted regression coefficient of 0.34 (95% CI: 0.19, 0.49). The relationship between the plasma retinol and M/P ratio was nonlinear and segmented at 1.00 μmol/L of plasma retinol. The regression coefficients, below and above the segmented point, were −1.69 (95% CI: −2.75, −0.62) and −0.29 (95% CI: −0.42, −0.16), respectively. Plasma and breast milk retinol were positively correlated, whereas women with a low concentration of plasma retinol showed a stronger capacity of transferring retinol to breast milk.
Relative Energy Deficiency in Sport (REDs) Indicators in Male Adolescent Endurance Athletes: A 3-Year Longitudinal Study
Authors: Stenqvist Thomas Birkedal , Melin Anna Katarina , Torstveit Monica Klungland
Published: December 2023

Longitudinal measurements of Relative Energy Deficiency in Sport (REDs) among adolescent male elite athletes are lacking. We aimed to monitor REDs indicators and their possible impact on performance in elite high-school cross-country skiing and biathlon athletes (n = 13) (16.3 ± 0.4 years, 179.4 ± 7.6 cm, 63.6 ± 8.2 kg body mass (BM), and peak oxygen uptake (VO2peak): 61.5 ± 5.3 mL/kg BM/min) every 6 months for 3 years. Protocols included assessments of energy availability (EA), body composition and bone mineral density (BMD), resting metabolic rate (RMR), disordered eating behavior, exercise addiction, VO2peak, and muscle strength. Data were analyzed using a linear mixed model. At baseline, 38% had low lumbar BMD (Z-score ≤ −1), and overall, bone health increased only slightly. VO2peak and muscle strength improved (p < 0.001), RMR decreased (p = 0.016), and no change was observed in EA or physiological or psychological REDs indicators. Conclusively, many of these young male athletes had poor bone health at baseline, and most either lost or did not achieve the expected pubertal bone mineral accrual, although no other indication of REDs was observed, while performance improved during the study period. Our findings highlight the importance of elite sports high schools focusing on screening for early detection of impaired bone health in male athletes.
Learning Lessons for Future Preparedness: Exploring Work Well-Being-Related Leadership Challenges among Paramedics during the Early Stage of the COVID-19 Pandemic—A Qualitative Study
Authors: Pelli Jukka , Nordquist Hilla
Published: December 2023

The beginning of the COVID-19 pandemic majorly impacted the population and public services. In Finland, a state of emergency was declared to ensure the security of healthcare resources, and prehospital emergency medical service (EMS) organizations faced emergency conditions for the first time. This study explores the leadership challenges related to well-being experienced during the early phase of the pandemic. This qualitative study utilized reflective essay material written between August and November 2020 by experienced advanced-level paramedics (n = 30) who participated actively in EMS fieldwork at the beginning of the pandemic. The material (32,621 words) was analyzed with inductive content analysis. The work well-being-related leadership challenges experienced by paramedics during the early phase of the pandemic were divided into four upper categories: inadequate guidance, workplace reorganization, atmosphere mismanagement, and insufficient resources to cope. These upper categories were comprised of 17 subcategories. Several actions can be taken to enhance personnel well-being and prepare for similar challenges. Guidance and support should be clear and timely. Visible leadership should be emphasized and enhanced with modern communication. Efforts should be made to strengthen the work atmosphere to support those on the front lines of healthcare. This study was not registered on a publicly accessible registry.
The Effects of Geranylgeraniol on Blood Safety and Sex Hormone Profiles in Healthy Adults: A Dose-Escalation, Randomized, Placebo-Controlled Trial
Authors: Gheith Raad , Sharp Matthew , Stefan Matthew , Ottinger Charlie , Lowery Ryan , Wilson Jacob
Published: December 2023

Geranylgeraniol (GG), an ingredient extracted from the South American annatto plant, has been shown to benefit bone and muscle health, is crucial in the biosynthesis of menaquinone-4 and coenzyme Q10, and has pain and inflammation reduction activities. However, no known studies to date have demonstrated the safety and impact of GG supplementation in humans. This 8-week, randomized, placebo-controlled, dose-escalated trial was conducted to determine the effect of GG on blood safety and hormone markers in healthy adults. Sixty-six males and females between 30 and 49 years of age were supplemented with either GG or a placebo (PLA) for 8 weeks, with dose escalation from 150 mg to 300 mg occurring after 4 weeks in the treatment group. Changes in complete blood count and comprehensive metabolic panels were analyzed for whole study groups (males and females) while changes in sex hormone panels were analyzed for males and females independently. There were no significant changes in complete blood count, comprehensive metabolic panel, progesterone, estradiol, sex–hormone binding globulin, or dihydrotestosterone (p > 0.05). An exploratory analysis of testosterone levels in a subgroup of males with baseline (Pre) total testosterone < 700 ng/dL (GG = 15; PLA = 13) demonstrated a significant increase (p < 0.05) from Pre to Week 8 in total-, free-, and bioavailable testosterone (+7.5%, +15.0%, and +14.8%, respectively). This study demonstrates that GG does not significantly change the composition of blood chemistry, hematology, or sex hormone profiles in adult males or females. Given the effects observed in the exploratory analysis in a subgroup of males, GG supplementation may be beneficial for testosterone enhancement in male populations subject to low testosterone (i.e., aging males and those with late-onset hypogonadism), but further research is needed.
Preliminary Studies on Site Fidelity, Residence Index, and Population Size of Irrawaddy Dolphins in West Penang, Malaysia
Authors: Ali Nurul Filzati , Rajamani Leela
Published: December 2023

The Irrawaddy dolphin is found in the coastal and estuarine areas of West Penang, Malaysia. Studies were conducted to estimate the site fidelity, residence index, and population size of Irrawaddy dolphins in West Penang. Photo-identification studies were conducted using boat surveys from 2019 to 2021. Thirty-nine marked Irrawaddy dolphins were identified, with thirty-six newly identified individuals and three individuals observed in 2013. Resightings of four individuals indicated that they were found north of Sungai Burung and Sungai Pinang in West Penang. The majority of individuals had low sighting rates, ranging from 2.6 to 7.7%, with three individuals having medium sighting rates, the highest being 15.4%. The residence index was 0.01 for all 36 individuals, and the highest value of 0.36 was recorded for one individual. Using open population models and closed models, the population size was determined to be 64 or and 52, respectively. The results suggest that although there is a population present, it is probably open, as the residence index is low. The population size appeared to be stable from 2013 to 2021. This information will inform conservation managers of the best way forward for the conservation of Irrawaddy dolphins in Penang.
Optimal Agents for Visualizing Collagen Tissue Microarchitecture Using Contrast-Enhanced MicroCT
Authors: Glancy Spencer B. , Morris Herman Douglas , Ho Vincent B. , Klarmann George J.
Published: December 2023

Micro-computed tomography (microCT) is a common tool for the visualization of the internal composition of organic tissues. Collagen comprises approximately 25–35% of the whole-body protein content in mammals, and the structure and arrangement of collagen fibers contribute significantly to the integrity of tissues. Collagen type I is also frequently used as a key structural component in tissue-engineered and bioprinted tissues. However, the imaging of collagenous tissues is limited by their inherently low X-ray attenuation, which makes them indistinguishable from most other soft tissues. An imaging contrast agent that selectively alters X-ray attenuation is thus essential to properly visualize collagenous tissue using a standard X-ray tube microCT scanner. This review compares various contrast-enhanced techniques reported in the literature for MicroCT visualization of collagen-based tissues. An ideal microCT contrast agent would meet the following criteria: (1) it diffuses through the tissue quickly; (2) it does not deform or impair the object being imaged; and (3) it provides sufficient image contrast for reliable visualization of the orientation of individual fibers within the collagen network. The relative benefits and disadvantages of each method are discussed. Lugol’s solution (I3K), phosphotungstic acid (H3PW12O40), mercury(II) chloride (HgCl2), and Wells–Dawson polyoxometalates came closest to fitting the criteria. While none of the contrast agents discussed in the literature met all criteria, each one has advantages to consider in the context of specific lab capabilities and imaging priorities.
Combining Cisplatin with Different Radiation Qualities—Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis
Authors: Runge Roswitha , Reissig Falco , Herzog Nora , Oehme Liane , Brogsitter Claudia , Kotzerke Joerg
Published: December 2023

Background: The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin. Methods: FaDu cells were treated with cisplatin (concentration ≈ 2 µM) and additionally irradiated after two hours with the alpha-emitter 223Ra, the beta-emitter 188Re as well as external X-rays using dose ranges of 2–6 Gy. Cell survival was followed by colony formation assays and plotted against cisplatin concentration and radiation dose. The results were interpreted by isobolograms. Results: Isobolographic analyses revealed a supra-additive cytotoxic effect for the combination of cisplatin and 223Ra. A sub-additive effect was observed for the combination of cisplatin and 188Re, whereas a protective effect was found for the combination with X-rays. Conclusions: The combination of cisplatin and 223Ra may have the potential to create a successfully working therapy scheme for various therapy approaches, whereas the combination with 188Re as well as single-dose X-ray treatment did not lead to a detectable radiosensitizing effect. Thus, the combination with alpha-emitters might be advantageous and, therefore, should be followed in future studies when combined with cytostatic drugs.
The Impact of Sex on the Response to Proton Pump Inhibitor Treatment
Authors: Helgadottir Holmfridur , Björnsson Einar S.
Published: December 2023

Proton pump inhibitor (PPI) treatment is responsible for substantial gastrin elevation secondary to reduced intragastric acidity. Due to the increasing global prevalence of PPI users, concerns have been raised about the clinical significance of continuous gastrin elevation and its potential long-term side effects. Hypergastrinemia secondary to PPIs has trophic effects on gastric mucosa, leading to enterochromaffin-like cell hyperplasia and gastric (fundic) polyp formation, and it is believed to provoke acid rebound following PPI withdrawal that induces PPI overutilization. Previous studies have found higher gastrin release following PPI therapy in females compared with males, and sex differences have also been demonstrated in pharmacokinetic parameters and dose requirements for acid reflux. It is conceivable that females might be at increased risk of PPI overuse, because they often receive higher milligram-per-kilogram doses. The prevalence of PPI use is more common among females, and the female sex is a risk factor for adverse drug reactions. This non-systematic review outlines the current knowledge of the impact of biological sex on the response to PPIs. The aim is to highlight the female sex as a potential risk factor that could be a step toward precision medicine and should be considered in future research on the response to PPI treatment.
Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice
Authors: Khan Mohammad Suhail , Jakob Virginie , Singh Randhir , Rajmani Raju S. , Kumar Sahil , Lemoine Céline , Kleanthous Harry , Ringe Rajesh P. , Dubois Patrice M. , Varadarajan Raghavan
Published: December 2023

Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward.
Effect of Electrical Stimulation on PC12 Cells Cultured in Different Hydrogels: Basis for the Development of Biomaterials in Peripheral Nerve Tissue Engineering
Authors: Olguín Yusser , Selva Mónica , Benavente Diego , Orellana Nicole , Montenegro Ivan , Madrid Alejandro , Jaramillo-Pinto Diego , Otero María Carolina , Corrales Tomas P. , Acevedo Cristian A.
Published: December 2023

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. This research evaluates the neural differentiation of PC12 cells, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different cultivation conditions. Electrical stimuli significantly increase neural differentiation for specific experimental conditions dependent on electrical frequency, not voltage. These backgrounds allow new material treatment schemes to be formulated through electrical stimulation in peripheral nerve tissue engineering.
DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair
Authors: Khazaei Monfared Yousef , Heidari Pedram , Klempner Samuel J. , Mahmood Umar , Parikh Aparna R. , Hong Theodore S. , Strickland Matthew R. , Esfahani Shadi A.
Published: December 2023

DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated. This results in increased mutagenesis and genomic instability within the cancer cells, a known driver of cancer progression and therapeutic resistance. On the other hand, the inherent instability of the genome in rapidly dividing cancer cells can be exploited as a tool to kill by imposing DNA damage with radiopharmaceuticals. As the field of targeted radiopharmaceutical therapy (RPT) is rapidly growing in oncology, it is crucial to have a deep understanding of the impact of systemic radiation delivery by radiopharmaceuticals on the DNA of tumors and healthy tissues. The distribution and activation of DNA damage and repair pathways caused by RPT can be different based on the characteristics of the radioisotope and molecular target. Here we provide a comprehensive discussion of the biological effects of RPTs, with the main focus on the role of varying radioisotopes in inducing direct and indirect DNA damage and activating DNA repair pathways.
Advances in Transdermal Drug Delivery Systems: A Bibliometric and Patent Analysis
Authors: Cammarano Aniello , Dello Iacono Stefania , Meglio Caterina , Nicolais Luigi
Published: December 2023

Transdermal drug delivery systems have become an intriguing research topic in healthcare technology and one of the most frequently developed pharmaceutical products in the global market. In recent years, researchers and pharmaceutical companies have made significant progress in developing new solutions in the field. This study sheds light on current trends, collaboration patterns, research hotspots, and emerging frontiers of transdermal drug delivery. Herein, a bibliometric and patent analysis of data recovered from Scopus and The Lens databases, respectively, is reported over the last 20 years. From 2000 to 2022, the annual global publications increased from 131 in 2000 to 659 in 2022. Researchers in the United States, China, and India produced the highest number of publications. Likewise, most patent applications have been filed in the USA, China, and Europe. The recovered patents are 7275, grouped into 2997 patent families, of which 314 were granted. This study could support the work of decision-makers, scientific managers, or scientists to create new business opportunities or save money, time, and intellectual capital, thereby defining when a research or technology project should be a priority or not.
Colorectal Cancer Stem Cells and Targeted Agents
Authors: Zhao Haobin , Han Ruining , Wang Zhankun , Xian Junfang , Bai Xiaosu
Published: December 2023

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.
Targeted Therapy of Acute Liver Injury via Cryptotanshinone-Loaded Biomimetic Nanoparticles Derived from Mesenchymal Stromal Cells Driven by Homing
Authors: Zhang Xin , Yi Yao , Jiang Yuanyuan , Liao Jinqiu , Yang Ruiwu , Deng Xuexue , Zhang Li
Published: December 2023

Acute liver injury (ALI) has the potential to compromise hepatic function rapidly, with severe cases posing a considerable threat to human health and wellbeing. Conventional treatments, such as the oral administration of antioxidants, can inadvertently lead to liver toxicity and other unwanted side effects. Mesenchymal stromal cells (MSCs) can target therapeutic agents directly to inflammatory sites owing to their homing effect, and they offer a promising avenue for the treatment of ALI. However, the efficacy and feasibility of these live cell products are hampered by challenges associated with delivery pathways and safety concerns. Therefore, in this work, MSC membranes were ingeniously harnessed as protective shells to encapsulate synthesized PLGA nanoparticle cores (PLGA/MSCs). This strategic approach enabled nanoparticles to simulate endogenous substances and yielded a core–shell nano-biomimetic structure. The biomimetic nanocarrier remarkably maintained the homing ability of MSCs to inflammatory sites. In this study, cryptotanshinone (CPT)-loaded PLGA/MSCs (CPT@PLGA/MSC) were prepared. These nanoparticles can be effectively internalized by LO2 cells. They reduced cellular oxidative stress and elevated inflammatory levels. In vivo results suggested that, after intravenous administration, CPT@PLGA/MSCs significantly reduced uptake by the reticuloendothelial system and immune recognition compared to PLGA nanoparticles without MSC membrane coatings, subsequently resulting in their targeted and enhanced accumulation in the liver. The effectiveness of CPT@PLGA/MSCs in alleviating carbon tetrachloride-induced oxidative stress and inflammation in a mouse model was unequivocally demonstrated through comprehensive histological examination and liver function tests. This study introduces a pioneering strategy with substantial potential for ALI treatment.