bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsaponifiable Matter from Wheat Bran Cultivated in Korea Inhibits Hepatic Lipogenesis by Activating AMPK Pathway
Authors: An Minju , Heo Huijin , Park Jinhee , Jeong Heon-Sang , Kim Younghwa , Lee Junsoo
Published: November 2023

Unsaponifiable matter (USM) from wheat bran, a by-product obtained from wheat milling, is abundant in health-promoting compounds such as phytosterols, tocopherols, policosanols, and alkylresorcinols. This study aimed to examine the effects of USM from the wheat bran of normal and waxy type wheat, Saekeumkang (SKK) and Shinmichal (SMC), on hepatic lipid accumulation in free fatty acid (FFA)-induced hepatocytes and to investigate the cellular mechanism. The total phytochemical contents were 46.562 g/100 g USM and 38.130 g/100 g USM from SKK and SMC, respectively. FFA treatment increased intracellular lipid accumulation by approximately 260% compared to the control group; however, treatment with USM from SKK and SMC significantly attenuated lipid accumulation in the hepatocytes in a dose-dependent manner. Moreover, USM downregulated the expression of lipogenic factors such as fatty acid synthase and sterol regulatory-element-binding protein 1c by approximately 40% compared to the FFA treatment group. Treatment with USM promoted lipolysis and positively regulated the expression of the proteins involved in β-oxidation, including peroxisome proliferator-activated receptor α and its downstream protein, carnitine palmitoyltransferase 1A. Moreover, the blockade of AMPK activation significantly abolished the inhibitory effects of USM on hepatic lipid accumulation. These results indicated that the USM from both SKK and SMC can alleviate lipid accumulation in hepatocytes in an AMPK-dependent manner. Therefore, USM from wheat bran may be useful as a therapeutic intervention for treating metabolic-dysfunction-associated fatty liver disease.
Association between NTRK2 Polymorphisms, Hippocampal Volumes and Treatment Resistance in Major Depressive Disorder
Authors: Paolini Marco , Fortaner-Uyà Lidia , Lorenzi Cristina , Spadini Sara , Maccario Melania , Zanardi Raffaella , Colombo Cristina , Poletti Sara , Benedetti Francesco
Published: November 2023

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 (NTRK2)-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to BDNF and NTRK2 on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one NTRK2 polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology.
Sentiments about Mental Health on Twitter—Before and during the COVID-19 Pandemic
Authors: Beierle Felix , Pryss Rüdiger , Aizawa Akiko
Published: November 2023

During the COVID-19 pandemic, the novel coronavirus had an impact not only on public health but also on the mental health of the population. Public sentiment on mental health and depression is often captured only in small, survey-based studies, while work based on Twitter data often only looks at the period during the pandemic and does not make comparisons with the pre-pandemic situation. We collected tweets that included the hashtags #MentalHealth and #Depression from before and during the pandemic (8.5 months each). We used LDA (Latent Dirichlet Allocation) for topic modeling and LIWC, VADER, and NRC for sentiment analysis. We used three machine-learning classifiers to seek evidence regarding an automatically detectable change in tweets before vs. during the pandemic: (1) based on TF-IDF values, (2) based on the values from the sentiment libraries, (3) based on tweet content (deep-learning BERT classifier). Topic modeling revealed that Twitter users who explicitly used the hashtags #Depression and especially #MentalHealth did so to raise awareness. We observed an overall positive sentiment, and in tough times such as during the COVID-19 pandemic, tweets with #MentalHealth were often associated with gratitude. Among the three classification approaches, the BERT classifier showed the best performance, with an accuracy of 81% for #MentalHealth and 79% for #Depression. Although the data may have come from users familiar with mental health, these findings can help gauge public sentiment on the topic. The combination of (1) sentiment analysis, (2) topic modeling, and (3) tweet classification with machine learning proved useful in gaining comprehensive insight into public sentiment and could be applied to other data sources and topics.
Contrast-Enhanced Ultrasound Follow-Up for Acute Pyelonephritis Patients
Authors: Boccatonda Andrea , Venerato Stefano , D’Ardes Damiano , Cocco Giulio , Schiavone Cosima , Vicari Susanna
Published: November 2023

Contrast-enhanced ultrasound (CEUS) is increasingly used in clinical practice as the first diagnostic method in patients with suspected pyelonephritis rather than abdominal CT with contrast medium, especially in young subjects. We performed a retrospective analysis on patients in for whom a CEUS examination was utilized as a follow-up method after acute pyelonephritis as normal clinical practice. Through evaluating all patients, in terms duration between CEUS examination and normalization (healing) of the renal disease, we found that the mean duration is 25.9 days. Our ultrasound findings did not induce any therapeutic modifications, not even in the cases in which the examination was repeated several times. Therefore, setting up a CEUS follow-up examination after 25 days from the first diagnosis can reduce the number of repeated tests, benefitting patients and the healthcare system in terms of reducing costs.
Utilization of Proximate Healthcare Facilities and Children’s Wait Times in Senegal: An IV-Tobit Analysis
Authors: Oyekale Abayomi Samuel
Published: November 2023

Universal health coverage (UHC) defines individuals’ timely access to healthcare services without suffering any health-related financial constraints. The Senegalese government has shown commitments towards achievement of UHC as a way of improving access by the population to quality healthcare services. This is very pertinent for promoting some indicators of under-five health in Senegal. Therefore, this study analyzed the factors influencing sick children’s utilization of the nearest healthcare facilities and their wait times in Senegal. The data were from the Service Provision Assessment (SPA) survey, which was conducted in 2018. The instrumental Tobit regression model was used for data analysis. The results showed that 63.50% and 86.01% of the children utilized health posts and publicly owned facilities, respectively. Also, 98.46% of the children utilized urban facilities. The nearest facilities were utilized by 74.55%, and 78.19% spent less than an hour in the facilities. The likelihood of using the nearest healthcare facilities significantly reduced (p < 0.05) with caregivers’ primary education, higher education, residence in some regions (Fatick, Kaokack, Saint Louis, Sediou, and Tambacounda), and use of private/NGO not-for-profit facilities, but increased with not having visited any other providers, residence in the Kaffrie region, vomiting symptoms, use of health centers, and use of health posts. Moreover, treatment wait times significantly increased (p < 0.05) with the use of nearest facilities, residence in some regions (Diourbel, Kaokack, Matam and Saint Louis), use of private for-profit facilities, use of private not-for-profit facilities, and urban residence, but decreased with secondary education, use of health centers, use of health posts, vomiting symptoms, and showing other symptoms. It was concluded that reduction in wait times and utilization of the nearest healthcare facilities are fundamental to achieving UHC in Senegal. Therefore, more efforts should be integrated at promoting regional and sectoral equities through facilitated public and private healthcare investment.
Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies
Authors: van der Voorn Stephanie M. , van Drie Esmée , Proost Virginnio , Dimitrova Kristina ,   Netherlands ACM/PLN Registry, Ernst Robert F. , James Cynthia A. , Tichnell Crystal , Murray Brittney , Calkins Hugh , Saguner Ardan M. , Duru Firat , Ellinor Patrick T. , Bezzina Connie R. , Jurgens Sean J. , van Tintelen J. Peter , van Veen Toon A. B.
Published: November 2023

Inherited forms of arrhythmogenic and dilated cardiomyopathy (ACM and DCM) are characterized by variable disease expression and age-related penetrance. Calcium (Ca2+) is crucially important for proper cardiac function, and dysregulation of Ca2+ homeostasis seems to underly cardiomyopathy etiology. A polymorphism, c.286T>G p.(Ser96Ala), in the gene encoding the histidine-rich Ca2+ binding (HRC) protein, relevant for sarcoplasmic reticulum Ca2+ cycling, has previously been associated with a marked increased risk of life-threatening arrhythmias among idiopathic DCM patients. Following this finding, we investigated whether p.(Ser96Ala) affects major cardiac disease manifestations in carriers of the phospholamban (PLN) c.40_42delAGA; p.(Arg14del) pathogenic variant (cohort 1); patients diagnosed with, or predisposed to, ACM (cohort 2); and DCM patients (cohort 3). We found that the allele frequency of the p.(Ser96Ala) polymorphism was similar across the general European–American population (control cohort, 40.3–42.2%) and the different cardiomyopathy cohorts (cohorts 1–3, 40.9–43.9%). Furthermore, the p.(Ser96Ala) polymorphism was not associated with life-threatening arrhythmias or heart failure-related events across various patient cohorts. We therefore conclude that there is a lack of evidence supporting the important role of the HRC p.(Ser96Ala) polymorphism as a modifier in cardiomyopathy, refuting previous findings. Further research is required to identify bona fide genomic predictors for the stratification of cardiomyopathy patients and their risk for life-threatening outcomes.
Diagnosing X-Linked Adrenoleukodystrophy after Implementation of Newborn Screening: A Reference Laboratory Perspective
Authors: Prinzi Julia , Pasquali Marzia , Hobert Judith A. , Palmquist Rachel , Wong Kristen N. , Francis Stephanie , De Biase Irene
Published: November 2023

Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal β-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013–2016). To date, thirty-five states have implemented newborn screening (NBS) for ALD, and a few programs have reported on the successes and challenges experienced. However, the overall impact of NBS on early detection of ALD has yet to be fully determined. Here, we conducted a retrospective analysis of VLCFA testing performed by our reference laboratory (ARUP Laboratories, Salt Lake City, UT, USA) over 10 years. Rate of detection, age at diagnosis, and male-to-female ratio were evaluated in patients with abnormal results before and after NBS implementation. After NBS inclusion, a significant increase in abnormal results was observed (471/6930, 6.8% vs. 384/11,670, 3.3%; p < 0.0001). Patients with ALDP deficiency identified via NBS were significantly younger (median age: 30 days vs. 21 years; p < 0.0001), and males and females were equally represented. ALD inclusion in NBS programs has increased pre-symptomatic detection of this disease, which is critical in preventing adrenal crisis as well as the severe cerebral form.
Blade Number Effects in Radial Disc Pump Impellers: Overall Performances with Cavitation Sensitivity Analysis
Authors: Jiang Qifeng , Liu Chen , Bois Gérard , Heng Yaguang
Published: November 2023

Straight radial impeller disc pumps are widely used in several industrial applications for hard-to-pump working flow media, such as two-phase inlet conditions, either including non-miscible bubbles or solid particles with a high concentration within the main working flow. Compared with conventional pump designs, these pumps have not been widely studied, because of their particular simple design and low efficiency values that can however reach a maximum value of 0.5 with a good pressure increase in single-phase conditions. Regarding this, no basic analysis has been performed to build one-dimensional design rules considering the relative effects of design parameters proper to these unusual designs like the blade number, blade height and disc spacing. This step is an important one for two-phase flow performance evaluations which are usually derived from single-phase ones as for conventional pumps. Two different disc pump designs with, respectively, 8 and 10 radial blades, are numerically and experimentally investigated. Experimental investigations are performed in an open loop tap water test facility, under various working conditions, combining flow rate and rotational speed variations. The overall pump performances are compared and analyzed, including cavitation onset phenomena that have been found to influence the experimental performances of both pumps. The overall performance modification between both impeller designs is analyzed. Comparisons between CFD and experimental results give reliable results and can be considered to cover a sufficiently wide range of design parameters allowing us to build future adapted design rules for such specific designs.
Simultaneous Utilization of Multiple Radio Access Networks in Ubiquitous 6G Connectivity for Autonomous Ships: Opportunities and Challenges
Authors: Koo Hyounhee , Ryoo Changho , Kim Wooseong
Published: November 2023

The growing significance of ubiquitous 6G connectivity within the maritime sector is a consequence of its evolution into an era characterized by the adoption of autonomous ships. This evolution necessitates the development of adaptable communication capabilities, even in the face of increasing heterogeneity in Radio Access Networks (RANs). This heterogeneity is a consequence of the extended lifespans of maritime communication technologies used by both legacy and emerging ships at sea, in contrast to the generational shift seen in terrestrial communication technologies. This paper undertakes a comprehensive examination and provides an insightful overview of communication technologies within the framework of 3rd Generation Partnership Project (3GPP) standards with the aim of preparing for the forthcoming 6G standardization to enable ubiquitous 6G connectivity in the maritime domain. The primary focus of this paper is the mobile RAN entities (e.g., satellites and uncrewed aerial vehicles (UAVs)) positioned for integration into the 5G and beyond systems. These entities are distinguished by their differences from conventional terrestrial RAN entities, which are typically stationary on land. This integration enables User Equipment (UE) to connect to various RAN entities, including mobile RANs, interconnected with core networks, thereby granting UE secure access to external internets through 5G and beyond systems, enabling them to enjoy a diverse range of application services, even in areas beyond terrestrial coverage, such as at sea. This paper further conducts an in-depth analysis of a transport layer-level solution known as the Access Traffic Steering, Switching, and Splitting (ATSSS) feature enabling a concurrent connection to multiple RANs for data-traffic delivery. Furthermore, this paper explores opportunities and challenges for future research in the realm of forthcoming 6G standardization within 3GPP, especially when combined with the ATSSS features for the success of autonomous ships within the maritime sector. These considerations encompass the concept of autonomous ships as mobile RAN entities, the integration of legacy maritime communications into the 6G framework, and the variability in maritime channel measurements, generally employed as one of the criteria for selecting an appropriate RAN among multiple options, influenced by uncontrollable factors such as climate change.
The Impact of Sluice Construction in the North Branch of the Changjiang Estuary on Saltwater Intrusion and Freshwater Resources
Authors: Yang Yidi , Zhu Jianrong , Chen Zhengbing , Ma Rui
Published: November 2023

Estuarine projects can quickly change the estuarine topography and influence the hydrodynamics and saltwater intrusion. The Changjiang Estuary is a multiple-bifurcation megaestuary, and the outstanding feature of the saltwater intrusion is the saltwater spillover from the North Branch (NB) into the South Branch (SB). In this study, the improved ECOM-si model was adopted to numerically experiment with the impact of the sluices that are planned for construction in the upper, middle, and lower reaches of the NB on the saltwater intrusion and freshwater resources. The simulation results show that, on the one hand, sluice construction can eliminate the saltwater spillover from the NB into the SB; on the other hand, sluice construction makes water enter the NB from the SB, and the runoff discharging into the sea in the SB decreases. The water intake time of the Qingcaosha Reservoir (QCSR) increases by 3.2 days for sluice construction in the upper reaches of the NB and decreases by 0.97 and 0.94 days for sluice construction in the middle and lower reaches of the NB, respectively. Considering the impact of sluice construction in the NB on the saltwater intrusion and freshwater resources, the construction of sluices in the upper reaches of the NB is recommended.
Spatiotemporal Characteristics and Influencing Factors of Urban Heat Island Based on Geographically Weighted Regression Model: A Case Study of Urumqi City
Authors: Ma Yunfei , Mamitimin Yusuyunjiang , Tiemuerbieke Bahejiayinaer , Yimaer Rebiya , Huang Meiling , Chen Han , Tao Tongtong , Guo Xinyi
Published: November 2023

Rapid urbanization threatens the ecological environment and quality of life by significantly altering land use and land cover (LULC) and heat distribution. One of the most significant environmental consequences of urbanization is the urban heat island effect (UHI). This study investigated the spatiotemporal characteristics of the SUHI and its relationship with land use types from 2000 to 2020 in Urumqi City, located in an arid and semi-arid region of northwestern China. Additionally, the ordinary least squares (OLS) and geographically weighted regression (GWR) models were used to quantify the relationship between the land surface temperature (LST) and influencing factors. The results showed that the area of the lower surface temperature classes has decreased significantly. In comparison, the area of the higher surface temperature classes has experienced a steady rise over the last two decades. From 2000 to 2020, the share of the area occupied by the temperature range <30 °C decreased by 67.09%. In addition, the LST varied significantly from one category of land use to another. The average LST of built-up land and unused land was higher than the average LST of other land use types in all years, while the average LST of grassland, forest land, and water bodies was significantly lower. Finally, the results of the GWR model showed that R2 and adjusted R2 of the GWR were 0.75 and 0.73, obviously larger than the 0.58 of the OLS models. The GWR model’s higher R2 and adjusted R2 compared to the OLS model indicates that the relationship between LST and the influencing factors underlying the model may exhibit spatial non-stationarity, and the GWR model performs better than the OLS model. The results of both OLS and GWR models show that the normalized difference vegetation index (NDVI) and slope were negatively correlated with LST, while the urban index (UI) and normalized difference built-up index (NDBI) were positively correlated with LST. The findings of the study indicate that increasing green spaces and limiting the unplanned expansion of urban areas are effective measures to mitigate the UHIs in the study area. The results of the study may provide valuable insights into the spatiotemporal characteristics of the UHI and its drivers. Understanding the spatiotemporal characteristics of the UHI can help urban planners, policymakers, and scientists develop more effective urban cooling strategies and improve the urban thermal environment.
Electronic, Optical, and Vibrational Properties of an AgAlS2 Crystal in a High-Pressure Phase
Authors: Rudysh Myron Ya. , Fedorchuk Anatolii O. , Brik Mikhail G. , Grechenkov Jurij , Bocharov Dmitry , Piskunov Sergei , Popov Anatoli I. , Piasecki Michal
Published: November 2023

The aim of this study is to comprehensively examine the structural composition and properties of the AgAlS2 crystal during its high-pressure phase. This analysis delves into the second coordination environment of the crystal structure and elucidates the distinct transformations it undergoes during the phase transition. The band energy structure was calculated, and the origin of electronic levels was clarified. It is shown that the crystal becomes non-stratified during the phase transition. This study also determined the values of the crystal’s carrier effective masses, underscoring its spatial anisotropy. It was found that the calculated optical functions are similar to the crystal in the chalcopyrite structure, and their differences are shown. Further, this study involved the calculation of the crystal’s phonon spectrum, revealing the spectrum’s transformation during the phase transition. The vibrational frequencies were also obtained, with a symmetrical classification of vibrational modes. Finally, this study derived the infrared and Raman spectra of the AgAlS2 crystal, thereby providing a comprehensive picture of the crystal during its high-pressure phase.
The Effect of Preloaded Compressive Stress and Curvature of Defect on Blast-Induced Fracture Behavior by Caustic and Numerical Models
Authors: Huang Chen , Zhang Zong-Xian , Aladejare Adeyemi , Guan Xianbo , Yu Bingbing , Yang Liyun
Published: November 2023

In this study, the effects of preloaded uniaxial compressive stress and defect (prefabricated by laser cutting) curvature on blast-induced cracks and stress wave propagation were investigated in polymethyl methacrylate (PMMA) specimens using caustics theory. Based on the mathematical relationship between stress and optics, the fracture behavior (the propagation path, dynamic stress intensity factors (DSIFs), propagation velocity, initiation angle of the main crack, and damage degree between the defect and the blasthole) was calculated and analyzed quantitatively. The results show that the preloaded stress could mainly restrain the main crack propagation in the horizontal direction and reduce the initiation angle and damage degree at the defects. Meanwhile, the crack initiation position of the positive curvature defect was not at the end of the defect. In addition, the curvature of the defect significantly affected the blast-induced fracture compared to preloaded stresses. Comparing the main crack with other curvature defects, the DSIFs, velocity, crack arrest time, crack length, and horizontal offset distance of the main crack with negative curvature defect were the largest. The variation in the full stress field in the specimen under blasting and preloaded stress was simulated by a numerical model. The results show that the curvature of the defect has a significant effect on tensile waves at the end of defects, and the tensile stress from high to low was C-25, C0, and C25, in that order.
General Image Manipulation Detection Using Feature Engineering and a Deep Feed-Forward Neural Network
Authors: Ahmed Sajjad , Yoon Byungun , Sharma Sparsh , Singh Saurabh , Islam Saiful
Published: November 2023

Within digital forensics, a notable emphasis is placed on the detection of the application of fundamental image-editing operators, including but not limited to median filters, average filters, contrast enhancement, resampling, and various other operations closely associated with these techniques. When conducting a historical analysis of an image that has potentially undergone various modifications in the past, it is a logical initial approach to search for alterations made by fundamental operators. This paper presents the development of a deep-learning-based system designed for the purpose of detecting fundamental manipulation operations. The research involved training a multilayer perceptron using a feature set of 36 dimensions derived from the gray-level co-occurrence matrix, gray-level run-length matrix, and normalized streak area. The system detected median filtering, mean filtering, the introduction of additive white Gaussian noise, and the application of JPEG compression in digital Images. Our system, which utilizes a multilayer perceptron trained with a 36-feature set, achieved an accuracy of 99.46% and outperformed state-of-the-art deep-learning-based solutions, which achieved an accuracy of 97.89%.
A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
Authors: Mancilla Viviana J. , Braden-Kuhle Paige N. , Brice Kelly N. , Mann Allison E. , Williams Megan T. , Zhang Yan , Chumley Michael J. , Barber Robert C. , White Sabrina N. , Boehm Gary W. , Allen Michael S.
Published: November 2023

The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-α, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.
Metaproteomic and Metagenomic-Coupled Approach to Investigate Microbial Response to Electrochemical Conditions in Microbial Fuel Cells
Authors: Godain Alexiane , Vogel Timothy M. , Monnier Jean-Michel , Paitier Agathe , Haddour Naoufel
Published: November 2023

MFCs represent a promising sustainable biotechnology that enables the direct conversion of organic matter from wastewater into electricity using bacterial biofilms as biocatalysts. A crucial aspect of MFCs is how electroactive bacteria (EAB) behave and their associated mechanisms during extracellular electron transfer to the anode. A critical phase in the MFC start-up process is the initial colonization of the anode by EAB. Two MFCs were operated with an external resistance of 1000 ohms, one with an applied electrical voltage of 500 mV during the initial four days of biofilm formation and the other without any additional applied voltage. After stabilization of electricity production, total DNA and protein were extracted and sequenced from both setups. The combined metaproteomic/metagenomic analysis revealed that the application of voltage during the colonization step predominantly increased direct electron transfer via cytochrome c, mediated primarily by Geobacter sp. Conversely, the absence of applied voltage during colonization resulted in a broader diversity of bacteria, including Pseudomonas and Aeromonas, which participated in electricity production via mediated electron transfer involving flavin family members.
Multidisciplinary Management of Sternal Osteomyelitis Due to Klebsiella aerogenes after Open Heart Surgery in a Patient with Multiple Myeloma: A Case Report and Discussion of the Literature
Authors: Pignatti Marco , Dolci Giampiero , Zamagni Elena , Pascale Renato , Piccin Ottavio , Ammar Alessandro , Zeneli Flavia , Miralles Maria Elisa Lozano , Mancuso Katia , Cipriani Riccardo , Viale Pierluigi , Pacini Davide , Martin-Suàrez Sofia
Published: November 2023

Sternal wound complications following cardiac surgery, including sternal dehiscence, mediastinitis, and osteomyelitis, pose significant challenges in terms of management and patient outcomes. We present a case report highlighting the complex management of a patient who underwent open heart surgery for severe aortic valve stenosis, followed by sternal wound dehiscence and sternum osteomyelitis due to extended spectrum beta lactamase (ESBL) producing Klebsiella aerogenes. A multiple myeloma diagnosis was also suspected at the positron emission tomography (PET) scan and confirmed with bone marrow biopsy. Multidisciplinary evaluation of the case led to a comprehensive treatment plan. To control the sternal osteomyelitis, total sternectomy was performed followed by immediate reconstruction with a bone (tibia) graft from the tissue bank and fixation with the minimal hardware possible. A microsurgical latissimus dorsi free flap was required to reconstruct the soft tissue defect. After 6 weeks of antibiotic treatment with ertapenem and fosfomycin based on a culture of intraoperative material, no clinical, imaging, or laboratory signs of infection were seen. Multiple myeloma treatment was then started. At 1 year of follow up, no recurrence of infection occurred, and the reconstruction was stable and closed. Multiple myeloma is under chronic treatment with novel agent combination, with an excellent haematological response.
Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study
Authors: Toida Tatsunori , Sato Yuji , Komatsu Hiroyuki , Fujimoto Shouichi
Published: November 2023

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI—estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI–all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.
Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer’s Disease: A Narrative Review
Authors: Simão Daiane Oliveira , Vieira Vitoria Silva , Tosatti Jéssica Abdo Gonçalves , Gomes Karina Braga
Published: November 2023

Alzheimer’s Disease (AD) is a multifactorial, progressive, and chronic neurodegenerative disorder associated with the aging process. Memory deficits, cognitive impairment, and motor dysfunction are characteristics of AD. It is estimated that, by 2050, 131.5 million people will have AD. There is evidence that the gastrointestinal microbiome and diet may contribute to the development of AD or act preventively. Communication between the brain and the intestine occurs through immune cells in the mucosa and endocrine cells, or via the vagus nerve. Aging promotes intestinal dysbiosis, characterized by an increase in pro-inflammatory pathogenic bacteria and a reduction in anti-inflammatory response-mediating bacteria, thus contributing to neuroinflammation and neuronal damage, ultimately leading to cognitive decline. Therefore, the microbiota–gut–brain axis has a significant impact on neurodegenerative disorders. Lipids may play a preventive or contributory role in the development of AD. High consumption of saturated and trans fats can increase cortisol release and lead to other chronic diseases associated with AD. Conversely, low levels of omega-3 polyunsaturated fatty acids may be linked to neurodegenerative diseases. Unlike other studies, this review aims to describe, in an integrative way, the interaction between the gastrointestinal microbiome, lipids, and AD, providing valuable insights into how the relationship between these factors affects disease progression, contributing to prevention and treatment strategies.
The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece—A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Zikou Eva , Dovrolis Nikolas , Dimosthenopoulos Charilaos , Gazouli Maria , Makrilakis Konstantinos
Published: November 2023

The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.
Parenteral Nutrition: Current Use, Complications, and Nutrition Delivery in Critically Ill Patients
Authors: Lopez-Delgado Juan Carlos , Grau-Carmona Teodoro , Mor-Marco Esther , Bordeje-Laguna Maria Luisa , Portugal-Rodriguez Esther , Lorencio-Cardenas Carol , Vera-Artazcoz Paula , Macaya-Redin Laura , Llorente-Ruiz Beatriz , Iglesias-Rodriguez Rayden , Monge-Donaire Diana , Martinez-Carmona Juan Francisco , Sanchez-Ales Laura , Sanchez-Miralles Angel , Crespo-Gomez Monica , Leon-Cinto Cristina , Flordelis-Lasierra Jose Luis , Servia-Goixart Lluis ,   on behalf of the ENPIC Study Group
Published: November 2023

Background: Parenteral nutrition (PN) is needed to avoid the development of malnutrition when enteral nutrition (EN) is not possible. Our main aim was to assess the current use, complications, and nutrition delivery associated with PN administration in adult critically ill patients, especially when used early and as the initial route. We also assessed the differences between patients who received only PN and those in whom EN was initiated after PN (PN-EN). Methods: A multicenter (n = 37) prospective observational study was performed. Patient clinical characteristics, outcomes, and nutrition-related variables were recorded. Statistical differences between subgroups were analyzed accordingly. Results: From the entire population (n = 629), 186 (29.6%) patients received PN as initial nutrition therapy. Of these, 74 patients (11.7%) also received EN during their ICU stay (i.e., PN-EN subgroup). PN was administered early (<48 h) in the majority of patients (75.3%; n = 140) and the mean caloric (19.94 ± 6.72 Kcal/kg/day) and protein (1.01 ± 0.41 g/kg/day) delivery was similar to other contemporary studies. PN showed similar nutritional delivery when compared with the enteral route. No significant complications were associated with the use of PN. Thirty-two patients (43.3%) presented with EN-related complications in the PN-EN subgroup but received a higher mean protein delivery (0.95 ± 0.43 vs 1.17 ± 0.36 g/kg/day; p = 0.03) compared with PN alone. Once adjusted for confounding factors, patients who received PN alone had a lower mean protein intake (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.18–0.47; p = 0.001), shorter ICU stay (HR: 0.96; 95% CI: 0.91–0.99; p = 0.008), and fewer days on mechanical ventilation (HR: 0.85; 95% CI: 0.81–0.89; p = 0.001) compared with the PN-EN subgroup. Conclusion: The parenteral route may be safe, even when administered early, and may provide adequate nutrition delivery. Additional EN, when possible, may optimize protein requirements, especially in more severe patients who received initial PN and are expected to have longer ICU stays. NCT Registry: 03634943.
Selenium in Infants and Preschool Children Nutrition: A Literature Review
Authors: Dobrzyńska Małgorzata , Kaczmarek Katarzyna , Przysławski Juliusz , Drzymała-Czyż Sławomira
Published: November 2023

Selenium (Se), an essential trace element, is fundamental to human health, playing an important role in the formation of thyroid hormones, DNA synthesis, the immune response, and fertility. There is a lack of comprehensive epidemiological research, particularly the serum Se concetration in healthy infants and preschool children compared to the estimated dietary Se intake. However, Se deficiencies and exceeding the UL have been observed in infants and preschool children. Despite the observed irregularities in Se intake, there is a lack of nutritional recommendations for infants and preschool children. Therefore, the main objective of this literature review was to summarize what is known to date about Se levels and the risk of deficiency related to regular consumption in infants and preschool children.
Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process
Authors: Hebbink Gerald A. , Janssen Pauline H. M. , Kok Jurjen H. , Menarini Lorenzo , Giatti Federica , Funaro Caterina , Consoli Salvatore Fabrizio , Dickhoff Bastiaan H. J.
Published: November 2023

Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and provides advantages for achieving blend homogeneity. One potential challenge of continuous blending is the risk of over-lubrication. In this study, blending homogeneity and lubricant sensitivity are investigated for both batch and continuous processes. Given their distinct chemical structures and morphologies, anhydrous lactose and granulated lactose are expected to exhibit varying sensitivities to changes in process settings across both technologies. The findings suggest that both lactose grades provide highly stable blends that can be safely utilised in both batch and continuous modes. Optimisation should focus on process variables, such as the quality of loss-in-weight feeders used for dosing low doses of ingredients. The most significant process parameter for lubricant sensitivity was the type of lactose used. Anhydrous lactose produced harder tablets than the more porous granulated lactose but was more sensitive to lubrication at the same settings. The magnesium stearate content and its interaction with the type of lactose are also critical factors, with magnesium stearate having a counterproductive impact on tabletability.
A Physiologically Based Pharmacokinetic Approach to Recommend an Individual Dose of Tacrolimus in Adult Heart Transplant Recipients
Authors: Pei Ling , Li Run , Zhou Hong , Du Wenxin , Gu Yajie , Jiang Yingshuo , Wang Yongqing , Chen Xin , Sun Jianguo , Zhu Junrong
Published: November 2023

Tacrolimus is the principal immunosuppressive drug which is administered after heart transplantation. Managing tacrolimus therapy is challenging due to a narrow therapeutic index and wide pharmacokinetic (PK) variability. We aimed to establish a physiologically based pharmacokinetic (PBPK) model of tacrolimus in adult heart transplant recipients to optimize dose regimens in clinical practice. A 15-compartment full-PBPK model (Simbiology® Simulator, version 5.8.2) was developed using clinical observations from 115 heart transplant recipients. This study detected 20 genotypes associated with tacrolimus metabolism. CYP3A5*3 (rs776746), CYP3A4*18B (rs2242480), and IL-10 G-1082A (rs1800896) were identified as significant genetic covariates in tacrolimus pharmacokinetics. The PBPK model was evaluated using goodness-of-fit (GOF) and external evaluation. The predicted peak blood concentration (Cmax) and area under the drug concentration–time curve (AUC) were all within a two-fold value of the observations (fold error of 0.68–1.22 for Cmax and 0.72–1.16 for AUC). The patients with the CYP3A5*3/*3 genotype had a 1.60-fold increase in predicted AUC compared to the patients with the CYP3A5*1 allele, and the ratio of the AUC with voriconazole to alone was 5.80 when using the PBPK model. Based on the simulation results, the tacrolimus dosing regimen after heart transplantation was optimized. This is the first PBPK model used to predict the PK of tacrolimus in adult heart transplant recipients, and it can serve as a starting point for research on immunosuppressive drug therapy in heart transplant patients.
Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer
Authors: Beljkas Milan , Ilic Aleksandra , Cebzan Alen , Radovic Branko , Djokovic Nemanja , Ruzic Dusan , Nikolic Katarina , Oljacic Slavica
Published: November 2023

Histone deacetylases (HDACs) are the major regulators of the balance of acetylation of histone and non-histone proteins. In contrast to other HDAC isoforms, HDAC6 is mainly involved in maintaining the acetylation balance of many non-histone proteins. Therefore, the overexpression of HDAC6 is associated with tumorigenesis, invasion, migration, survival, apoptosis and growth of various malignancies. As a result, HDAC6 is considered a promising target for cancer treatment. However, none of selective HDAC6 inhibitors are in clinical use, mainly because of the low efficacy and high concentrations used to show anticancer properties, which may lead to off-target effects. Therefore, HDAC6 inhibitors with dual-target capabilities represent a new trend in cancer treatment, aiming to overcome the above problems. In this review, we summarize the advances in tumor treatment with dual-target HDAC6 inhibitors.
Active and Intelligent Packaging: A Review of the Possible Application of Cyclodextrins in Food Storage and Safety Indicators
Authors: Puebla-Duarte Andrés Leobardo , Santos-Sauceda Irela , Rodríguez-Félix Francisco , Iturralde-García Rey David , Fernández-Quiroz Daniel , Pérez-Cabral Ingrid Daniela , Del-Toro-Sánchez Carmen Lizette
Published: November 2023

Natural cyclodextrins (CDs) can be formed by 6, 7, or 8 glucose molecules (α-, β-, and γ-, respectively) linked in a ring, creating a cone shape. Its interior has an affinity for hydrophobic molecules, while the exterior is hydrophilic and can interact with water molecules. This feature has been used to develop active packaging applied to food, interacting with the product or its environment to improve one or more aspects of its quality or safety. It also provides monitoring information when food is optimal for consumption, as intelligent packaging is essential for the consumer and the merchant. Therefore, this review will focus on discerning which packaging is most appropriate for each situation, solubility and toxicological considerations, characterization techniques, effect on the guest properties, and other aspects related to forming the inclusion complex with bioactive molecules applied to packaging.
Development of a DNN Predictive Model for the Optimal Operation of an Ambient Air Vaporizer of LNG
Authors: Shin Jong-Ho , Lim Seung-Kil , Kim Jae-Gon , Lee Geun-Cheol , Bang June-Young
Published: November 2023

In this study, we conducted preliminary research with the objective of leveraging artificial intelligence to optimize the efficiency and safety of the entire Ambient Air Vaporizer (AAV) system for LNG (Liquid Natural Gas). By analyzing a year-long dataset of real operational data, we identified key variables that significantly influence the outlet temperature of Natural Gas (NG). Based on these insights, a Deep Neural Network (DNN) prediction model was developed to forecast the NG outlet temperature. The endeavor to create an effective prediction model faced specific challenges, primarily due to the narrow operational range of fan speeds and safety-focused guidelines. To surmount these obstacles, various learning algorithms were evaluated under multiple conditions. Ultimately, a DNN model exhibiting lower values of both absolute mean error (MAE) and mean square error (MSE) was successfully established.