bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between plasma PSGL‐1 and FIGO stage, tumor metastasis, and survival in epithelial ovarian cancer
Authors: Li WenHui , Fang Cheng , Gao Ya , Gao Yan , Yan FengShang , Chen BiLiang , Xu MingJuan
Published: March 2024

Plasma circulating P‐selectin glycoprotein ligand‐1 (PSGL‐1) levels and its clinical correlation in patients with epithelial ovarian cancer (EOC) are unknown. The study determined plasma PSGL‐1 levels in EOC patients and investigated its relationship with clinicopathological factors and prognosis. Plasma PSGL‐1 levels were measured using ELISA in 69 patients with EOC, 34 patients with benign ovarian cystadenoma, and 36 healthy controls. Subsequently, the relationship between PSGL‐1 levels and clinicopathological characteristics of patients, as well as the prognosis of EOC patients, was examined. Additionally, the specificity and sensitivity of plasma PSGL‐1 were assessed through ROC curve analysis. Plasma PSGL‐1 was upregulated in EOC patients compared with healthy subjects and/or patients with benign ovarian cystadenoma (p < 0.01). Elevated levels of PSGL‐1 in the plasma were positively associated with advanced FIGO stage (p < 0.001), tumor size (p = 0.001), tumor metastasis (p = 0.036), and tumor recurrence (p = 0.013), while was negatively correlated with residual tumor size (p < 0.001). Kaplan–Meier survival analysis showed that high plasma PSGL‐1 levels were associated with progression‐free survival (p = 0.0345). In univariate and multivariate Cox regression analyses, PSGL‐1 (HR = 1.456, p = 0.009) was an independent prognostic marker. Plasma PSGL‐1 levels distinguished EOC patients and healthy individuals (AUC = 0.905), patients at late and early FIGO stages (AUC = 0.886), and metastatic and non‐metastatic EOC (AUC = 0.722). The expression of plasma PSGL‐1 is significantly increased in patients with EOC, serving as a reliable biomarker to differentiate between healthy individuals and those with EOC. Furthermore, PSGL‐1 in patients is correlated with prognostic indicators, such as advanced FIGO stage, tumor lymph node metastasis, and progression‐free survival.
Residence time distribution in continuous virus filtration
Authors: Chen Yu‐Cheng , Recanati Gabriele , De Mathia Fernando , Lin Dong‐Qiang , Jungbauer Alois
Published: March 2024

Regulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing in respect to fluid dynamics and scale‐up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( 0.90). The model enabled the prediction of RTD with variations—for example, in injection volumes, flow rates, tracer concentrations, and filter surface areas—and was validated using stepwise experiments and combined stepwise and pulse injection experiments. All validation experiments achieved  0.97. Notably, if the process includes a porous material—such as a porous chromatography material, ultrafilter, or virus filter—it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end‐to‐end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.
Development of a high‐throughput scale‐down model in Ambr® 250 HT for plasmid DNA fermentation processes
Authors: Fang Shu , Sinanan Dillon J. , Perez Marc H. , Cruz‐Quintero Raúl G. , Jadhav Sachin R.
Published: March 2024

Recent advances in messenger ribonucleic acid (mRNA) vaccines and gene therapy vectors have increased the need for rapid plasmid DNA (pDNA) screening and production within the biopharmaceutical industry. High‐throughput (HT) fermentor systems, such as the Ambr® 250 HT, can significantly accelerate process development timelines of pDNA upstream processes compared to traditional bench‐scale glass fermentors or small‐scale steam‐in‐place (SIP) fermentors. However, such scale‐down models must be qualified to ensure that they are representative of the larger scale process similar to traditional small‐scale models. In the current study, we developed a representative scale‐down model of a Biostat® D‐DCU 30 L pDNA fermentation process in Ambr® 250 HT fermentors using three cell lines producing three different constructs. The Ambr scale‐down model provided comparable process performance and pDNA quality as the 30 L SIP fermentation process. In addition, we demonstrated the predictive value of the Ambr model by two‐way qualification, first by accurately reproducing the prior trends observed in a 30 L process, followed by predicting new process trends that were then successfully reproduced in the 30 L process. The representative and predictive scale‐down Ambr model developed in this study would enable a faster and more efficient approach to strain/clone/host‐cell screening, pDNA process development and characterization studies, process scale‐up studies, and manufacturing support.
Potential Anti‐Gouty Arthritis of Citronella Essential Oil and Nutmeg Essential Oil through Reducing Oxidative Stress and Inhibiting PI3K/Akt/mTOR Activation‐Induced NLRP3 Activity
Authors: Yang Jin Jin , Yu Hongpeng , Wu Kegang , He Dong , Zhang Huadan , Cui Zheng Xiang , Chai Xianghua , Duan Xuejuan
Published: March 2024

Citronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)‐induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU‐induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti‐gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.
Rice dreg protein as a high‐quality plant‐based protein resource: Characterization of structural, functional, and in vitro digestive properties
Authors: Long Yinghui , Gao Zhi , Qiu Chunhong , Chen Jingfeng , Li Mingyang , Dai Shijun , Sun Weizheng , Zhao Mouming , Su Guowan
Published: March 2024

Background and Objectives

Rice dregs, a by‐product of the process of making sugar from broken rice, have a protein content of up to 70%. However, rice dreg protein (RDP) has not yet been fully utilized due to its high‐temperature liquefaction denaturation during sugar production. In this study, the structural, functional, and in vitro digestive properties of rice protein (RP) extracted from broken rice and RDP derived from rice dregs were compared, with a view to providing a basis for further utilization of RDP.

Findings

Although RDP was a heat‐denatured protein, it was found to have relatively better functional properties and a well‐balanced amino acid composition. Structural analysis results revealed that RDP showed a looser and disordered structure. However, SDS‐PAGE results showed that the subunit composition of the two proteins was similar. The in vitro simulated digestion results showed that the digests of RDP had higher antioxidant and ACE inhibitory activity, but RDP showed significantly lower digestibility than RP.

Conclusions

Through relevant modifications of RDP, RDP has the potential to be a good source of high‐quality protein in the human diet as the demand for plant‐based protein increases.

Significance and Novelty

This study can provide a basic theoretical basis for further development and utilization of RDP, which is also of great practical significance for seeking new plant protein resources and increasing the added value of broken rice.
The neurology of creativity: 2023 Hower lecture
Authors: Pearl Phillip L.
Published: March 2024

The neurology of creativity implies network activity; no singular cerebral area is invoked. A clinician‐scientist can develop a creative research project from a single patient, combined with critical scientific alliances, careful observations, and correlations. The developing nervous system poses additional complexity, as changes are expected over time in physiologic circumstances, to which must be added compensatory responses to underlying pathology. The arts represent an especially productive area to study the neurology of creativity, especially with functional imaging, tractography, and intracranial electrophysiology. Music activates widespread bilateral areas, including temporal, orbitofrontal, insular, fusiform, and cerebellar cortex. There are different neuronal clusters for different levels of sound volume, duration, timbre, and pitch. Heschl's gyrus and the arcuate fasciculus correlate with pitch. The orbitofrontal cortex is involved in expectancy generation and appears to be active with no music and then deactivates with music, as if the cortex has an editing function. This appears to correlate with the default mode network being key during improvisation, whereas the central executive network is invoked in effortful, repetitive playing. Furthermore, plasticity is associated with music, from the pathologic development of musicogenic seizures, to protection from musician's dystonia in pianists who begin lessons before age 9 years, to benefits of increased temporal cortex in older adults taking piano lessons after six months. Creativity, reducing negativity bias, and juggling life s priorities are key to countering burnout and building resilience.
Structural Decoration of Porphyrin/Phthalocyanine Photovoltaic Materials
Authors: Mai Sibei , Zhang Weilun , Mu Xijiao , Cao Jing
Published: March 2024

Porphyrin/phthalocyanine compounds with fascinating molecular structures have attracted widespread attention in the field of solar cells in recent years. In this review, we focus on the pivotal role of porphyrin and phthalocyanine compounds in enhancing the efficiency of solar cells. The review seamlessly integrates the intricate molecular structures of porphyrins and phthalocyanines with their proficiency in absorbing visible light and facilitating electron transfer, key processes in converting sunlight into electricity. By delving into the nuances of intramolecular regulation, aggregated states, and surface/interface structure manipulation, it elucidates how various levels of molecular modifications enhance solar cell efficiency through improved charge transfer, stability, and overall performance. This comprehensive exploration provides a detailed understanding of the complex relationship between molecular design and solar cell performance, discussing current advancements and potential future applications of these molecules in solar energy technology.
An isolated sacral promyelocytic sarcoma in a child: A rare case report with emphasis on cytomorphology
Authors: Do Jeongeun , Arshad Talal , Ferreira Juanita Emily , Yenwongfai Leonard Nsoyori , Nebbache Hafsa , Allison Derek Blake , Piecoro Dava West , Kesler Melissa Vandyke
Published: March 2024

Myeloid sarcoma (MS) is an uncommon localized extramedullary tumor composed of immature myeloid precursor cells that can affect any organ. Promyelocytic sarcoma (PS), an extremely rare subtype of MS, is characterized by immature myeloid cells with features of acute promyelocytic leukemia (APL). We describe a case of pediatric PS that presented as a solitary sacral mass without any evidence of systemic or bone marrow involvement. The cytopathologic evaluation using touch imprint demonstrated numerous blasts with bilobed nuclei, cytoplasmic hyper‐granularity, and aggregates of Auer rods, which are typical cytomorphologic features of APL. Herein, we report an extremely rare case of isolated PS in a child, emphasizing the importance of cytomorphologic evaluation, which is complemented by the findings from a comprehensive work‐up.
Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl‐xL, caspase‐3/9, and oxidative stress modulators in HepG2 cell line
Authors: Üremiş Muhammed Mehdi , Türköz Yusuf , Üremiş Nuray
Published: March 2024

Cucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti‐inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl‐2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl‐xL, caspase‐3, and caspase‐9. We evaluated the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose‐dependent manner. The cucurbitacins induced apoptosis by increasing caspase‐3, caspase‐9, and Bax activity, inhibiting Bcl‐xL activation, causing loss of ΔΨm, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl‐xL, caspase‐3/9 signaling, and causing intracellular ROS increase in HepG2 cells.
The origins and drivers of sexual size dimorphism in sharks
Authors: Gayford Joel H. , Sternes Phillip C.
Published: March 2024

While sexual size dimorphism (SSD) is abundant in nature, there is huge variation in both the intensity and direction of SSD. SSD results from a combination of sexual selection for large male size, fecundity selection for large female size and ecological selection for either. In most vertebrates, it is variation in the intensity of male–male competition that primarily underlies variation in SSD. In this study, we test four hypotheses regarding the adaptive value of SSD in sharks—considering the potential for each of fecundity, sexual, ecological selection and reproductive mode as the primary driver of variation in SSD between species. We also estimate past macroevolutionary shifts in SSD direction/intensity through shark phylogeny. We were unable to find evidence of significant SSD in early sharks and hypothesise that SSD is a derived state in this clade, that has evolved independently of SSD observed in other vertebrates. Moreover, there is no significant relationship between SSD and fecundity, testes mass or oceanic depth in sharks. However, there is evidence to support previous speculation that reproductive mode is an important determinant of interspecific variation in SSD in sharks. This is significant as in most vertebrates sexual selection is thought to be the primary driver of SSD trends, with evidence for the role of fecundity selection in other clades being inconsistent at best. While the phylogenetic distribution of SSD among sharks is superficially similar to that observed in other vertebrate clades, the relative importance of selective pressures underlying its evolution appears to differ.
Placebo effects on kayak sprint performance in child athletes
Authors: Szabo Attila
Published: March 2024

Empirical research with adults reveals that performance‐enhancing placebo effects emerge in sports and exercise. However, there is no research on children. Coaches' messages to them could have positive, performance‐improving (placebo) or negative, performance‐impairing (nocebo) effects. This experiment examined the former by ascribing fictive performance‐enhancing properties to an ingredient of the Tic Tac mint to 12 children (aged 12.67 ± SD = 1.83 years), all elite kayakers. Another kayaker was an actor who helped enhance the credibility of the information. The children completed 2‐min kayak ergometer sprints in counterbalanced control and placebo conditions. The measures included heart rate (HR), feeling state, perceived arousal, and expected‐ and perceived‐ performances. Pre‐sprint and maximal HR during the sprint and distance completed in 2 minutes were statistically significantly higher (p < 0.005) in the placebo than in the control condition without being affected by order effects. While the expected performance in the placebo session was higher (p = 0.008), perceived performances did not differ statistically between the conditions. This study reveals a sport performance‐related objective, but not subjective, placebo effect in children after a short kayak sprint. The findings have practical implications for performance‐related messages children receive from their coaches and others and show how their altered beliefs can influence their performance.
Associations of midlife fitness and obesity profiles with cognitive function
Authors: Tait Jamie L. , Collyer Taya A. , Gall Seana L. , Venn Alison J. , Dwyer Terence , Fraser Brooklyn J. , Moran Chris , Srikanth Velandai K. , Callisaya Michele L.
Published: March 2024

Low fitness and obesity at midlife are individually associated with later‐life decline in cognition and health. However, the relationship between profiles of midlife fitness and obesity with midlife cognition is unclear and was examined by this study. Participants from the third follow‐up of the Childhood Determinants of Adult Health study (2014–2019; aged 36–49 years) were assessed for obesity (body mass index [BMI]), cardiorespiratory (physical work capacity) and muscular fitness (isometric grip and leg strength), and these factors were entered into a latent profile analysis. Psychomotor‐attention, learning–working memory and global cognition composites were derived from z‐scores of individual CogState battery tests. Linear regression analyses examined associations between profiles of fitness and obesity with cognition, adjusting for age, sex, education, alcohol and smoking. Using data from 617 participants [44.4 ± 2.6 (mean ± SD) years, 52% female], we identified 5 mutually exclusive profiles of obesity and fitness. Relative to those with the lowest fitness and highest BMI (5% of sample), those with a profile of (1) highest muscular fitness and average BMI (9%), (2) average muscular fitness and BMI (61%) and (3) highest cardiorespiratory fitness (CRF) and below average BMI (7%) all exhibited better global cognition [at least 0.44 (0.12, 0.77) SD, 95% CI] and psychomotor‐attention performance [at least 0.59 (0.27, 0.91) SD, 95% CI]. Compared with low fitness and unhealthy BMI levels, possessing average or high muscular and CRF and a healthy BMI in midlife was associated with better cognitive performance. Enhancing fitness and reducing obesity in midlife could contribute to improved cognitive performance in middle age.
Surrogate model‐aided global sensitivity analysis framework for seismic consequences estimation in buildings
Authors: Du Jiajun , Wang Wei
Published: March 2024

Seismic consequences estimation for individual buildings is valuable for various stakeholders, including government entities, building owners, and insurers. The robustness of estimation results in the presence of incomplete input information can typically be investigated through sensitivity analysis. However, the estimation process's complexity and the sensitivity analysis's computational burden hinder its practical application, which requires a more efficient procedure to facilitate broader use. This paper proposes a novel framework for sensitivity analysis of seismic consequences estimation to improve the efficiency and reliability of such analysis. The proposed approach encompasses three key components: (1) stochastic ground motion modeling (SGMM)‐based seismic consequences estimation to evaluate the economic, environmental, and social consequences given specific buildings by considering different hazard levels, (2) the training of surrogate model (Gaussian process model) for structural analysis to reduce the computational cost of the evaluation process, and (3) variance‐based global sensitivity analysis to investigate the importance of parameters of concern in the estimation process. The entire procedure is implemented in Python, adhering to object‐oriented programming, and does not rely on external software. Then, the proposed methodology is applied to two distinct three‐story steel moment‐resistant frames (SMRFs) subjected to four different hazard levels to demonstrate its effectiveness. The SGMM method can generate specific ground motions for each hazard level, mitigating the potential for result bias from using ground motions with unrealistic characteristics. Furthermore, the SGMM method is particularly suitable for automated analysis processes reducing the laborious task of screening ground motions from the database. Comparative analysis with surrogate‐free estimation reveals that the surrogate‐based analysis delivers reliable results with significantly reduced computational cost. The results of analyzing different structures under varying hazard levels reflect the variability in sensitivity analysis of consequences estimation, highlighting the necessity of the proposed flexible and efficient framework. Furthermore, the proposed framework's advantages, limitations, and future research needs are discussed.
Nutritional enhancement in black seed (Nigella sativa L.) using bacteria‐based biofertilizers
Authors: Naeem Nayyab , Aftab Arusa , Rizwana Humaira , Aftab Zill‐e‐Huma , Yousaf Zubaida , Maqbool Zainab , Shahzadi Zainab
Published: March 2024

Nigella sativa L. is an aromatic spice, utilized as an original and peculiar flavoring ingredient in a variety of culinary applications and pharmaceuticals. Black seed (Nigella sativa L.) belongs to the family Ranunculaceae. It is an undercultivated crop in Pakistan. The present study was planned keeping in mind sustainable development goals SDG 3 (good health and well‐being) and SDG 15 (life on land). The effects of several rhizospheric bacterial strains and synthetic fertilizers on the development of N. sativa and nutrition were studied using a completely randomized experimental design. For this purpose, plant growth‐promoting effects of different strains (Azospirillum brasilense, Azospirillum lipoferum, and Pantoea agglomerans) and synthetic fertilizers (nitrogen and phosphorus) were assembled to check their effects individually and in combination form. Azospirillum lipoferum and Pantoea agglomerans inoculation significantly enhanced the morphological characteristics of N. sativa, whether applied individually or in combination, with positive effects on seedlings, plant height, number of branches, number of leaves, number of flowers, stamens numbers, follicles number, number of tentacles and seed production. N. sativa plants that were simultaneously inoculated with Azospirillum lipoferum and Pantoea agglomerans showed the highest potential for antioxidant activity, particularly in petroleum ether extracts. In the methanolic extract, a higher amount of radical scavenging was observed as compared to positive and negative control. There was also increase in fat, moisture and carbohydrate contents of the combination inoculated plant. So, from the present study, in Pakistan, the technique is recommended to enhance the yield and nutritional value of N. sativa.
Effect of different reheating processes and conditions on the nutritional, functional, and microbiological properties of cow meat
Authors: Nanje Ombotoh Sabastin , Sylvia Ninying Veshe‐Teh Zemoh , Tonfack Djikeng Fabrice , Azia Morfor Theresia , Achidi Aduni Ufuan
Published: March 2024

The objective of this study was to evaluate the effect of different reheating methods and conditions on the proximate composition, mineral content, oil quality, and functional and microbiological properties of cow meat. For this, a survey was carried out to identify the reheating methods used in the community. For this study, 8.6 kg of raw beef was used and group 1 (500 g) served as raw control. The remaining 8.1 kg was boiled for 30 min in 5 L of water. Four hundred grams of boiled beef was removed and served as cooked control (group 2). The remaining 3688 g was divided into four groups of 922 g, which were, respectively, divided into subgroups of 307 g. The four sets of subgroups were, respectively, reheated by boiling, frying, microwaving and oven roasting for 3 days. Reheating was done three times a day and samples were collected at the end of each day for further analysis. Changes in proximate composition, mineral content, oil quality, functional properties, and microbiological count were evaluated using standard methods. Results showed that frequent reheating of food was the most used preservation method of cooked food, and boiling and steaming were the most used methods. Reheating time significantly reduces the protein, mineral content, and oil quality of cow meat in general. For the functional properties, reheating methods/conditions generally increased the water‐holding capacity, loose and packed bulk densities as well the pH of the meat. Reheating by frying increased the porosity and Hausner ratio of the meat powder while all the reheating treatments reduced the swelling capacity and titratable acidity of cow meat powder. Generally, the reheating methods and duration significantly reduced the bacterial count of cow meat powder. Cow meat should not be reheated for more than 2 days in order to preserve its physiochemical properties.
Construction of a Zygosaccharomyces rouxii strain overexpressing the QOR gene for increased HDMF production
Authors: Wang Yanhong , Wang Xinhui , Jiang Peng , Dai Lingyan , Hu Yijia , Pan Bailing , Li Yueyue , Zhang Jingyu , Zhang Ruoyu , Zhan Shihan , Li Zhijiang
Published: March 2024

4‐Hydroxy‐2,5‐dimethyl‐3(2H)‐furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor‐enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii, and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR. The HDMF production of the ZrQOR strain was significantly higher than that of wild‐type Z. rouxii at 3 and 5 days of culture, with 1.41‐fold and 1.08‐fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii. At 3, 5, and 7 days, QOR gene expression was 4.8‐fold, 3.3‐fold, and 5.6‐fold higher in the ZrQOR strain than in the wild‐type Z. rouxii, respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0–20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis.
Science, technology, and innovation in health for the next twenty years: A survey analysis in Colombia
Authors: Espinosa Oscar , Puentes Gabriela , Rodríguez Jhonathan , Robayo Adriana , Anaya Juan‐Manual
Published: March 2024

Background

Colombia is a Latin American country with a very complex social and political context that has not allowed the allocation of sufficient resources to the fields of science, technology, and innovation (STI). This is particularly worrying for the area of health since not enough resources are allocated for public health, research, or education.

Methods

The so‐called “Great Survey in Health 2019” was administered online through the SurveyMonkey platform to 5298 people in different regions of the country, representing the public, private, and academic sectors. The questionnaire consisted of 46 open and closed questions, including demographic inquiries. Data analysis involved textual analytics and sentiment analysis.

Results

Overall, 56% of those surveyed were women within the adult life cycle. Most respondents had a postgraduate education. Greater participation was observed in the Oriental, Bogotá, and Antioquia regions, which also concentrate the largest number of resources for STI. Among the main recommendations derived from the results, priorities include investing in research, personalised medicine, promoting the social appropriation of knowledge, addressing mental health, regulating research through a statute, promoting undergraduate research, and establishing recertification exams to pursue excellence.

Conclusion

The results of this original study serve as a fundamental input to promote and strengthen the STI processes in life sciences and health. They serve as a guide to generate public policies and actions that guarantee better health and well‐being for the Colombian population, strategically proposing a clear roadmap for the next 20 years.
Barriers and opportunities for health service access among fathers: A review of empirical evidence
Authors: Wynter Karen , Mansour Kayla A. , Forbes Faye , Macdonald Jacqui A.
Published: March 2024

Issue Addressed

Engagement with health supports benefits the whole family, yet few health services report successful engagement of fathers. Our aim was to describe available evidence on barriers and opportunities relevant to health system access for fathers.

Methods

Scoping reviews were conducted seeking empirical evidence from (1) Australian studies and (2) international literature reviews.

Results

A total of 52 Australian studies and 44 international reviews were included. The most commonly reported barriers were at the health service level, related to an exclusionary health service focus on mothers. These included both ‘surface’ factors (e.g., appointment times limited to traditional employment hours) and ‘deep’ factors, in which health service policies perpetuate traditional gender norms of mothers as ‘caregivers’ and fathers as ‘supporters’ or ‘providers’. Such barriers were reported consistently, including but not limited to fathers from First Nations or culturally diverse backgrounds, those at risk of poor mental health, experiencing perinatal loss or other adverse pregnancy and birth events, and caring for children with illness, neurodevelopmental or behavioural problems. Opportunities for father engagement include offering father‐specific resources and support, facilitating health professionals' confidence and training in working with fathers, and ‘gateway consultations’, including engaging fathers via appointments for mothers or infants. Ideally, top‐down policies should support fathers as infant caregivers in a family‐based approach.

Conclusions

Although barriers and opportunities exist at individual and cultural levels, health services hold the key to improved engagement of fathers.

So What?

Evidence‐based, innovative strategies, informed by fathers' needs and healthy masculinities, are needed to engage fathers in health services.
Clinical evaluation of pulmonary quantitative computed tomography parameters for diagnosing eosinophilic chronic obstructive pulmonary disease: Characteristics and diagnostic performance
Authors: Liu Yumeng , Lu Chao , Chen Wenfang , Liu Zhenyu , Wu Songxiong , Ye Hai , Lv Yungang , Peng Zhengkun , Wang Panying , Li Guangyao , Tan Biwen , Wu Guangyao
Published: March 2024

Aims

To investigate the characteristics and diagnostic performance of quantitative computed tomography (QCT) parameters in eosinophilic chronic obstructive pulmonary disease (COPD) patients.

Methods

High‐resolution CT scans of COPD patients were retrospectively analyzed, and various emphysematous parenchyma measurements, including lung volume (LC), lung mean density (LMD), lung standard deviation (LSD), full‐width half maximum (FWHM), and lung relative voxel number (LRVN) were performed. The QCT parameters were compared between eosinophilic and noneosinophilic COPD patients, using a definition of eosinophilic COPD as blood eosinophil values ≥ 300 cells·µL−1 on at least three times. Receiver operating characteristic curves and area under the curve (ROC‐AUC) and python were used to evaluate discriminative efficacy of QCT.

Results

Noneosinophilic COPD patients had a significantly lower TLMD (−846.3 ± 47.9 Hounsfield Unit [HU]) and TFWHM(162.5 ± 30.6 HU) compared to eosinophilic COPD patients (−817.8 ± 54.4, 177.3 ± 33.1 HU, respectively) (p = 0.018, 0.03, respectively). Moreover, the total LC (TLC) and TLSD were significantly lower in eosinophilic COPD group (3234.4 ± 1145.8, 183.8 ± 33.9 HU, respectively) than the noneosinophilic COPD group (5600.2 ± 1248.4, 203.5 ± 20.4 HU, respectively) (p = 0.009, 0.002, respectively). The ROC‐AUC values for TLC, TLMD, TLSD, and TFWHM were 0.91 (95% confidence interval [CI], 0.828–0.936), 0.66 (95% CI, 0.546–0.761), 0.64 (95% CI, 0.524–0.742), and 0.63 (95% CI, 0.511–0.731), respectively. When the TLC value was 4110 mL, the sensitivity was 90.7% (95% CI, 79.7–96.9), specificity was 77.8% (95% CI, 57.7–91.4) and accuracy was 86.4%. Notably, TLC demonstrated the highest discriminative efficiency with an F1 Score of 0.79, diagnostic Odds Ratio of 34.3 and Matthews Correlation Coefficient of 0.69, surpassing TLMD (0.55, 3.66, 0.25), TLSD (0.56, 3.95, 0.26), and TFWHM (0.56, 4.16, 0.33).

Conclusion

Eosinophilic COPD patients exhibit lower levels of emphysema and a more uniform density distribution throughout the lungs compared to noneosinophilic COPD patients. Furthermore, TLC demonstrated the highest diagnostic efficiency and may serve as a valuable diagnostic marker for distinguishing between the two groups.
Autophagy inhibition potentiates energy restriction‐induced cell death in hepatocellular carcinoma cells
Authors: Elgendy Sara M. , Zaher Dana M. , Sarg Nadin H. , Abu Jayab Nour N. , Alhamad Dima W. , Al‐Tel Taleb H. , Omar Hany A.
Published: March 2024

Hepatocellular carcinoma (HCC) significantly contributes to cancer‐related mortality due to the limited response of HCC to current anticancer therapies, thereby necessitating more effective treatment approaches. Energy restriction mimetic agents (ERMAs) have emerged as potential therapies in targeting the Warburg effect, a unique metabolic process in cancer cells. However, ERMAs exhibit limited efficacy when used as monotherapy. Additionally, ERMAs have been found to induce autophagy in cancer cells. The role of autophagy in cancer survival remains a subject of debate. Thus, it is crucial to ascertain whether ERMA‐induced autophagy is a mechanism for cell survival or cell death in HCC. Our study aims to investigate the effect of autophagy inhibition on the survival of HCC cells treated with ERMAs while also examining the potential of combining an autophagy inhibitor such as spautin‐1 with ERMAs to enhance HCC cell death. Our results suggest a cytoprotective role for ERMA‐induced autophagy in HCC cells, as combining the autophagy inhibitor spautin‐1 with ERMAs effectively suppressed ERMA‐induced autophagy and synergistically enhanced their antitumor activity. The treatment combination promoted HCC death through apoptosis, cell cycle arrest, and inhibition of AKT and ERK activation, which are known to play a key role in cellular proliferation. Collectively, our findings highlight a potential strategy to combat HCC by combining energy restriction with autophagy inhibition.
“Bold of them to assume I want to wait until I'm older to do what I love:” One teens' activism and civic engagement online
Authors: McDaniel Dominique Skye
Published: March 2024

This paper explores the social media literacies of Dakari, a 16‐year‐old Black teen reader, writer, and activist, within a broader 3‐month multi‐case study on diverse teens' online literacies. The focus is on Dakari's multimodal literacy practices related to social justice activism and civic engagement. The study highlights how social media platforms empower youth, exemplified by teens like Dakari who utilize these spaces to influence culture, practice critical literacies, and establish civic identities. Examining Dakari's case, three key themes emerge: (1) addressing systemic racism, (2) driving change as a content creator, and (3) challenging the idea that one must wait until adulthood to make a difference. The study highlights the transformative potential of youth of Color's social media literacies, suggesting a reimagining of educators' roles to recognize and respect teens' online literacies while fostering youth identity and political engagement. It is imperative to reshape teaching methods for justice and social change in the digital age. This involves supporting student literacy development and acknowledging the timely language and literacies of youth in social media contexts.
Downregulation of miR‐337‐3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression
Authors: Zhu Lin , Xin Yi‐Juan , He Mu , Bian Jun , Cheng Xiao‐Li , Li Rui , Li Jin‐Jie , Wang Juan , Liu Jia‐Yun , Yang Liu
Published: March 2024

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia‐induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro‐2a cells with hypoxia/reoxygenation (H/R), miR‐337‐3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR‐337‐3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.
Interaction between p21‐activated kinase 4 and β‐catenin as a novel pathway for PTH‐dependent osteoblast activation
Authors: Shen Chen , Oh Ha Ram , Park Young Ran , Chen Jin Hong , Park Byung‐Hyun , Park Ji Hyun
Published: March 2024

Parathyroid hormone (PTH) serves dual roles in bone metabolism, exhibiting both anabolic and catabolic effects. The anabolic properties of PTH have been utilized in the treatment of osteoporosis with proven efficacy in preventing fractures. Despite these benefits, PTH can be administered therapeutically for up to 2 years, and its use in patients with underlying malignancies remains a subject of ongoing debate. These considerations underscore the need for a more comprehensive understanding of the underlying mechanisms. p21‐activated kinase 4 (PAK4) is involved in bone resorption and cancer‐associated osteolysis; however, its role in osteoblast function and PTH action remains unknown. Therefore, in this study, we aimed to clarify the role of PAK4 in osteoblast function and its effects on PTH‐induced anabolic activity. PAK4 enhanced MC3T3‐E1 osteoblast viability and proliferation and upregulated cyclin D1 expression. PAK4 also augmented osteoblast differentiation, as indicated by increased mineralization found by alkaline phosphatase and Alizarin Red staining. Treatment with PTH (1–34), an active PTH fragment, stimulated PAK4 expression and phosphorylation in a protein kinase A‐dependent manner. In addition, bone morphogenetic protein‐2 (which is known to promote bone formation) increased phosphorylated PAK4 (p‐PAK4) and PAK4 levels. PAK4 regulated the expression of both phosphorylated and total β‐catenin, which are critical for osteoblast proliferation and differentiation. Moreover, p‐PAK4 directly interacted with β‐catenin, and disruption of β‐catenin's binding to T‐cell factor impaired PAK4‐ and PTH‐induced osteoblast differentiation. Our findings elucidate the effect of PAK4 on enhancing bone formation in osteoblasts and its pivotal role in the anabolic activity of PTH mediated through its interaction with β‐catenin. These insights improve the understanding of the mechanisms underlying PTH activity and should inform the development of more effective and safer osteoporosis treatments.
Daptomycin Dose Optimization in Pediatric Staphylococcus aureus Bacteremia: A Pharmacokinetic/Pharmacodynamic Investigation
Authors: Olney Katie B. , Howard Joel I. , Burgess David S.
Published: March 2024

Daptomycin is an antibiotic with Gram‐positive activity, including methicillin‐resistant Staphylococcus aureus, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with S. aureus bacteremia. Monte Carlo simulations were performed to determine probability of target attainment (PTA) for six pediatric age cohorts. Area under the curve to minimum inhibitory concentration ratio (AUC0‐24:MIC) ≥666 was used to determine the PTA for efficacy (PTAE). Minimum concentration (Cmin) ≥24.3 mg/L determined the PTA for toxicity (PTAT). Acceptable dosing regimens were those which achieved the combined target of ≥90% PTAE and ≤5% PTAT. Package label dosing of daptomycin yielded insufficient efficacy with only 26.3% PTAE in children 13‐24 months, 39.5% PTAE in children 2‐6 years, 30.1% PTAE in children 7‐11 years, and 50.1% PTAE in adolescents ≥12 years. To achieve the combined efficacy and safety target, doses of 18‐24 mg/kg in children 3‐12 months, 20‐24 mg/kg in children 13‐24 months, 19‐24 mg/kg in children 2‐6 years, 17‐19 mg/kg in children 7‐11 years, and 10‐14 mg/kg in adolescents ≥12 years are necessary. Package label dosing resulted in suboptimal exposure for the majority of pediatric patients in all age groups evaluated. If targeting validated efficacy and safety endpoints, daily daptomycin doses of at least 20 mg/kg in children ≤6 years, 17 mg/kg in children 7‐11 years, and 10 mg/kg in adolescents ≥12 years are necessary. Clinical studies evaluating these higher doses are needed.
Pivotal temperature is not for everyone: Evidence for temperature‐dependent sex determination in three gecko species
Authors: Straková Barbora , Kubička Lukáš , Červenka Jan , Kratochvíl Lukáš
Published: March 2024

The prevalence of environmental sex determination (ESD) in squamate reptiles is often overestimated in the literature. This is surprising because we have reliable data demonstrating ESD in only a few species. The documentation of ESD in three species of geckos presented here has significantly increased our knowledge, given that satisfactory evidence for ESD existed in only eight other gecko species. For the first time, we document the occurrence of ESD in the family Sphaerodactylidae. Our finding of unexpected variability in the shapes of reaction norms among geckos highlights that traditional descriptions using parameters such as pivotal temperature, that is, temperature producing a 50:50 sex ratio, are unsatisfactory. For example, the gecko Pachydactylus tigrinus lacks any pivotal temperature and its sex ratios are strongly female‐biased across the entire range of viable temperatures. We argue for the effective capture of the relationship between temperature and sex ratio using specific nonlinear models rather than using classical simplistic descriptions and classifications of reaction norms.
Seasonal precipitation changes in the western Mediterranean Basin: The case of the Spanish mainland, 1916–2015
Authors: Gonzalez‐Hidalgo José Carlos , Trullenque‐Blanco Víctor , Beguería Santiago , Peña‐Angulo Dhais
Published: March 2024

This study examines the spatial and temporal variations in seasonal precipitation patterns across the Spanish mainland, within the western Mediterranean Basin, spanning the years 1916–2015. Utilizing the recently developed MOPREDAS_century database at a 10 × 10 km grid resolution, our analysis reveals predominantly negative trends in precipitation across the study area over the entire period, primarily driven by declines in spring precipitation, with lesser decreases in summer and winter. Notably, these trends exhibit complexity, manifesting as two distinct pulses occurring roughly at the outset and conclusion of the 20th century. However, upon employing a moving windows analysis, we find that since the mid‐1970s, seasonal precipitation trends have largely been nonsignificant. Spatially, the precipitation regime across 1916–2015 delineates three primary zones: a winter‐maximum zone in the north, an autumn‐maximum zone along the eastern coast, and a transition from winter‐maximum to spring‐maximum towards the western and inland regions. Noteworthy shifts in this spatial distribution are evident over the four 25‐year intervals examined. Initially, during 1916–1940, winter, autumn and spring regimes occupied 44.1%, 24.2% and 31.7% of the land, respectively. Subsequently, in the periods 1941–1965 and 1966–1990, winter dominance expanded to over 50% of the grid area, while spring varied between 34.7% and 25.5%, and autumn decreased notably to 12.4% and 13.5%. Lastly, significant alterations occurred in the final period of 1991–2015, with winter coverage decreasing to 33.7%, spring to 15.8% and autumn expanding to 50.1% of the grid area. In summary, the prevalent winter and spring regimes at the dawn of the 20th century have transitioned towards an autumn‐dominated regime, particularly in much of the central and western Spanish mainland, with these shifts possibly linked to the evolving precipitation trends. These findings contribute novel insights, particularly pre‐1950, and align with published results post‐1950 across the Mediterranean, particularly in its western regions. Furthermore, they suggest a potential connection between changes in the spatial distribution of seasonal precipitation regimes and temporal variations in the primary moisture sources over the study area.