bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization Design and Pressure Fluctuation Suppression Based on Orthogonal Method for a Centrifugal Compressor
Authors: Zhao Huanxin , Tan Lei , Yang Dangguo , Liu Bing , Fan Honggang , Li Hongshuai
Published: May 2023

An air compressor is the core component of the air supply system of a hydrogen fuel cell, which demands high efficiency and reliable stability in a wide operation region. In this work, a centrifugal air compressor for a hydrogen fuel cell is first designed and then measured experimentally. Furthermore, a test rig for assessing the aerodynamic performance of the centrifugal air compressor is established, which includes a pipeline, gas flowmeter, flow regulating valve, pressure transmitter, centrifugal compressor, controller, DC power supply and computer. Then, the orthogonal method is employed to conduct the aerodynamic performance optimization. Four optimization parameters—including blade number, blade angle at the inlet, blade angle at the outlet and wrap angle—are set with three levels. Nine compressor individuals are designed according to the orthogonal method, and then numerical simulation is implemented to confirm the aerodynamic performance and flow pattern. Results show that the blade number has the greatest influence on the compressor’s performance, and the blade angle at inlet is also very important. The optimal performance of the compressor improves compared to that of the baseline compressor; the efficiencies of the baseline compressor and optimal compressor are 81.3% and 83.8%, respectively, improving by 2.5%. The frequency domain of pressure fluctuation in the centrifugal compressor is related to the stator-rotor interaction. The peak value of pressure fluctuation amplitude occurs at the rotation frequency of 833 Hz and its harmonic frequency. In comparison with the baseline compressor, the pressure fluctuation amplitude of the optimal compressor is obviously reduced, especially near the volute tongue.
Compound Uncertainty Quantification and Aggregation for Reliability Assessment in Industrial Maintenance
Authors: Grenyer Alex , Erkoyuncu John Ahmet , Addepalli Sri , Zhao Yifan
Published: May 2023

The mounting increase in the technological complexity of modern engineering systems requires compound uncertainty quantification, from a quantitative and qualitative perspective. This paper presents a Compound Uncertainty Quantification and Aggregation (CUQA) framework to determine compound outputs along with a determination of the greatest uncertainty contribution via global sensitivity analysis. This was validated in two case studies: a bespoke heat exchanger test rig and a simulated turbofan engine. The results demonstrated the effective measurement of compound uncertainty and the individual impact on system reliability. Further work will derive methods to predict uncertainty in-service and the incorporation of the framework with more complex case studies.
A Mini-Review on Recent Fractional Models for Agri-Food Problems
Authors: Tomasiello Stefania , Macías-Díaz Jorge E.
Published: May 2023

This work aims at providing a concise review of various agri-food models that employ fractional differential operators. In this context, various mathematical models based on fractional differential equations have been used to describe a wide range of problems in agri-food. As a result of this review, we found out that this new area of research is finding increased acceptance in recent years and that some reports have employed fractional operators successfully in order to model real-world data. Our results also show that the most commonly used differential operators in these problems are the Caputo, the Caputo–Fabrizio, the Atangana–Baleanu, and the Riemann–Liouville derivatives. Most of the authors in this field are predominantly from China and India.
Stochastic EM Algorithm for Joint Model of Logistic Regression and Mechanistic Nonlinear Model in Longitudinal Studies
Authors: Zhang Hongbin
Published: May 2023

We study a joint model where logistic regression is applied to binary longitudinal data with a mismeasured time-varying covariate that is modeled using a mechanistic nonlinear model. Multiple random effects are necessary to characterize the trajectories of the covariate and the response variable, leading to a high dimensional integral in the likelihood. To account for the computational challenge, we propose a stochastic expectation-maximization (StEM) algorithm with a Gibbs sampler coupled with Metropolis–Hastings sampling for the inference. In contrast with previous developments, this algorithm uses single imputation of the missing data during the Monte Carlo procedure, substantially increasing the computing speed. Through simulation, we assess the algorithm’s convergence and compare the algorithm with more classical approaches for handling measurement errors. We also conduct a real-world data analysis to gain insights into the association between CD4 count and viral load during HIV treatment.
The Newton–Puiseux Algorithm and Triple Points for Plane Curves
Authors: Canino Stefano , Gimigliano Alessandro , Idà Monica
Published: May 2023

The paper is an introduction to the use of the classical Newton–Puiseux procedure, oriented towards an algorithmic description of it. This procedure allows to obtain polynomial approximations for parameterizations of branches of an algebraic plane curve at a singular point. We look for an approach that can be easily grasped and is almost self-contained. We illustrate the use of the algorithm first in a completely worked out example of a curve with a point of multiplicity 6, and secondly, in the study of triple points on reduced plane curves.
Denoising in Representation Space via Data-Dependent Regularization for Better Representation
Authors: Chen Muyi , Wang Daling , Feng Shi , Zhang Yifei
Published: May 2023

Despite the success of deep learning models, it remains challenging for the over-parameterized model to learn good representation under small-sample-size settings. In this paper, motivated by previous work on out-of-distribution (OoD) generalization, we study the representation learning problem from an OoD perspective to identify the fundamental factors affecting representation quality. We formulate a notion of “out-of-feature subspace (OoFS) noise” for the first time, and we link the OoFS noise in the feature extractor to the OoD performance of the model by proving two theorems that demonstrate that reducing OoFS noise in the feature extractor is beneficial in achieving better representation. Moreover, we identify two causes of OoFS noise and prove that the OoFS noise induced by random initialization can be filtered out via L2 regularization. Finally, we propose a novel data-dependent regularizer that acts on the weights of the fully connected layer to reduce noise in the representations, thus implicitly forcing the feature extractor to focus on informative features and to rely less on noise via back-propagation. Experiments on synthetic datasets show that our method can learn hard-to-learn features; can filter out noise effectively; and outperforms GD, AdaGrad, and KFAC. Furthermore, experiments on the benchmark datasets show that our method achieves the best performance for three tasks among four.
Really Vague? Automatically Identify the Potential False Vagueness within the Context of Documents
Authors: Lian Xiaoli , Huang Dan , Li Xuefeng , Zhao Ziyan , Fan Zhiqiang , Li Min
Published: May 2023

Privacy policies are critical for helping individuals make decisions on the usage of information systems. However, as a common language phenomenon, ambiguity occurs pervasively in privacy policies and largely impedes their usefulness. The existing research focuses on the identification of individual vague words or sentences, without considering the context of documents, which may cause a significant amount of false vagueness. Our goal is to automatically detect the potential false vagueness and the related supporting evidence, which illustrates or explains the vagueness, and therefore probably assist in alleviating the vagueness. We firstly analyze the public manual annotations and define four common patterns of false vagueness and three types of supporting evidence. Then we propose the approach of the F·vague-Detector to automatically detect the supporting evidence and then locate the corresponding potential false vagueness. According to our analysis, about 29–39% of individual vague sentences have at least one clarifying sentence in the documents, and experiments show good performance of our approach, with recall of 66.98–67.95%, precision of 70.59–94.85%, and F1 of 69.24–78.51% on the potential false vagueness detection. Detecting the vagueness of isolated sentences without considering their context within the whole document would bring about one-third potential false vagueness, and our approach can detect this potential false vagueness and the alleviating evidence effectively.
Cleaning and Disinfecting Oval-Shaped Root Canals: Ex Vivo Evaluation of Three Rotary Instrumentation Systems with Passive Ultrasonic Irrigation
Authors: Li Ying , Wang Zhengyang , Bao Pingping , Meng Tingting , Liu Meng , Li Huixu , Shen Ya , Liu Dayong , Jia Zhi , Liu He
Published: May 2023

Background and Objectives: Successful root canal treatment depends on the thorough removal of biofilms through chemomechanical preparation. This study aimed to investigate and compare the cleaning and disinfecting efficiency of oval-shaped root canals using XP-endo Shaper (XPS), ProTaper Next (PTN), and HyFlex CM (HCM) in combination with passive ultrasonic irrigation (PUI). Materials and Methods: Ninety extracted teeth were contaminated and randomly divided into three groups: XPS, PTN, and HCM. Each group was assigned to three subgroups: subgroup A (sterile saline), subgroup B (3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid), and subgroup C (3% sodium hypochlorite, 17% ethylenediaminetetraacetic acid, and PUI). Bacterial sampling was conducted both from baseline samples and samples after chemomechanical preparation. Scanning electron microscopy (SEM) was used to evaluate the residue bacterial biofilms, hard tissue debris, and smear layers on the buccolingual walls of oval-shaped root canals. Results: When combined with sterile saline, XPS demonstrated a higher reduction of bacterial counts and was more effective in eradicating Enterococcus faecalis in the middle third of the canals compared to the other instruments (p < 0.05). Additionally, when used with antimicrobial irrigants, XPS was more effective in disinfecting the coronal third of the canals than the other instruments (p < 0.05). Furthermore, XPS reduced hard tissue debris more effectively in the middle third of canals than in the apical third (p < 0.05). Conclusions: XPS outperforms PTN and HCM in disinfecting oval-shaped root canals. Despite the fact that combining XPS and PUI improves cleaning and disinfecting, removing hard tissue debris from the critical apical area remains challenging.
Secreted Protein Acidic and Rich in Cysteine (SPARC) to Manage Coronavirus Disease-2019 (COVID-19) Pandemic and the Post-COVID-19 Health Crisis
Authors: Ghanemi Abdelaziz , Yoshioka Mayumi , St-Amand Jonny
Published: May 2023

Coronavirus disease-2019 (COVID-19) has had and will have impacts on public health and health system expenses. Indeed, not only it has led to high numbers of confirmed COVID-19 cases and hospitalizations, but its consequences will remain even after the end of the COVID-19 crisis. Therefore, therapeutic options are required to both tackle the COVID-19 crisis and manage its consequences during the post COVID-19 era. Secreted protein acidic and rich in cysteine (SPARC) is a biomolecule that is associated with various properties and functions that situate it as a candidate which may be used to prevent, treat and manage COVID-19 as well as the post-COVID-19-era health problems. This paper highlights how SPARC could be of such therapeutic use.
Study on P-AlGaAs/Al/Au Ohmic Contact Characteristics for Improving Optoelectronic Response of Infrared Light-Emitting Device
Authors: Lee Hyung-Joo , Shim Jae-Sam , Park Jin-Young , Kwac Lee-Ku , Seo Chang-Ho
Published: May 2023

The Al/Au alloy was investigated to improve the ohmic characteristic and light efficiency of reflective infrared light-emitting diodes (IR-LEDs). The Al/Au alloy, which was fabricated by combining 10% aluminum and 90% gold, led to considerably improved conductivity on the top layer of p-AlGaAs of the reflective IR-LEDs. In the wafer bond process required for fabricating the reflective IR-LED, the Al/Au alloy, which has filled the hole patterns in Si3N4 film, was used for improving the reflectivity of the Ag reflector and was bonded directly to the top layer of p-AlGaAs on the epitaxial wafer. Based on current-voltage measurements, it was found that the Al/Au alloyed material has a distinct ohmic characteristic pertaining to the p-AlGaAs layer compared with those of the Au/Be alloy material. Therefore, the Al/Au alloy may constitute one of the favored approaches for overcoming the insulative reflective structures of reflective IR-LEDs. For a current density of 200 mA, a lower forward voltage (1.56 V) was observed from the wafer bond IR-LED chip made with the Al/Au alloy; this voltage was remarkably lower in value than that of the conventional chip made with the Au/Be metal (2.29 V). A higher output power (182 mW) was observed from the reflective IR-LEDs made with the Al/Au alloy, thus displaying an increase of 64% compared with those made with the Au/Be alloy (111 mW).
A High-Reliability Piezoelectric Tile Transducer for Converting Bridge Vibration to Electrical Energy for Smart Transportation
Authors: Pham Thanh Huyen , Bui Thanh Danh , Dao Toan Thanh
Published: May 2023

Piezoelectric energy transducers offer great potential for converting the vibrations of pedestrian footsteps or cars moving on a bridge or road into electricity. However, existing piezoelectric energy-harvesting transducers are limited by their poor durability. In this paper, to enhance this durability, a piezoelectric energy transducer with a flexible piezoelectric sensor is fabricated in a tile protype with indirect touch points and a protective spring. The electrical output of the proposed transducer is examined as a function of pressure, frequency, displacement, and load resistance. The maximum output voltage and maximum output power obtained were 6.8 V and 4.5 mW, respectively, at a pressure of 70 kPa, a displacement of 2.5 mm, and a load resistance of 15 kΩ. The designed structure limits the risk of destroying the piezoelectric sensor during operation. The harvesting tile transducer can work properly even after 1000 cycles. Furthermore, to demonstrate its practical applications, the tile was placed on the floor of an overpass and a walking tunnel. Consequently, it was observed that the electrical energy harvested from the pedestrian footsteps could power an LED light fixture. The findings suggest that the proposed tile offers promise with respect to harvesting energy produced during transportation.
Gut Microbiota and B Cell Receptor (BCR) Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Is Biodiversity Correlated with Clinical Response or Immune-Related Adverse Event Occurrence? A Cross-Sectional Study
Authors: Zuccaro Valentina , Petazzoni Greta , Mileto Irene , Corbella Marta , Asperges Erika , Sacchi Paolo , Rattotti Sara , Varettoni Marzia , Defrancesco Irene , Cambieri Patrizia , Baldanti Fausto , Arcaini Luca , Bruno Raffaele
Published: May 2023

Several studies have strengthened the link between the gut microbiota (GM) and the response to immunotherapy in patients with tumors, highlighting the potential role of GM as a biomarker of response. Targeted therapies including B-cell receptor (BCR) inhibitors (BCRi) represent the newest approach to the treatment of chronic lymphocytic leukemia (CLL); however, not all patients achieve a satisfactory response, and immune-related adverse events (irAEs) can also impact the efficacy. The aim of the study was to compare GM biodiversity in patients with CLL, treated with BCRi for at least 12 months. Twelve patients were enrolled: 10 patients in the responder group (R) and 2 patients in the non-responder group (NR). We identified seven patients (58.3%) who experienced adverse reactions (AE). Although we did not observe a significant difference across the study population in terms of relative abundance and alpha and beta diversity, we found a differing distribution of bacterial taxa between the analyzed groups. We noted a higher level of the class Bacteroidia and the order Bacteroidales in the R group, and an inversion in the Firmicutes and Bacteroidetes ratio in the AE group. No prior studies have focused on linking GM and response to BCRi in these patients. Although the analyses are preliminary, they provide suggestions to guide future research.
Organic Farming Allows Balanced Fungal and Oomycetes Communities
Authors: Nam Bora , Lee Hyo Jung , Choi Young-Joon
Published: May 2023

Conventional and organic farming systems affect soils differently, thereby influencing microbial diversity and composition. Organic farming, which relies on natural processes, biodiversity, and cycles adapted to local conditions, is generally known to improve soil texture and alleviate microbial diversity loss compared with that of conventional farming, which uses synthetic inputs such as chemical fertilisers, pesticides, and herbicides. Although they affect the health and productivity of host plants, the community dynamics of fungi and fungi-like oomycetes (under Chromista) in organic farmland are poorly understood. The present study aimed to determine the differences in the diversity and composition of fungi and oomycetes inhabiting organic and conventional farm soils using culture-based DNA barcoding and culture-independent environmental DNA (eDNA) metabarcoding. Four tomato farms with different farming practices were selected and investigated: mature pure organic (MPO) via non-pesticide and organic fertiliser, mature integrated organic (MIO) via non-pesticide and chemical fertiliser, mature conventional chemical (MCC) via both pesticide and chemical fertiliser, and young conventional chemical (YCC). Culture-based analysis revealed that different genera were dominant on the four farms: Linnemannia in MPO, Mucor in MIO, and Globisporangium in MCC and YCC. eDNA metabarcoding demonstrated that the fungal richness and diversity on the MPO farm were higher than that on other farms. Both conventional farms exhibited simpler fungal and oomycete network structures with lower phylogenetic diversity. Interestingly, a high richness of oomycetes was shown in YCC; in which, Globisporangium, a potential pathogenic group on tomato plants, was abundantly observed. Our findings indicate that organic farming enhances fungal and oomycete diversity, which may provide robust support for maintaining healthy and sustainable agricultural practices. This study contributes to our knowledge on the positive effects of organic farming on crop microbiomes and provides essential information for maintaining biological diversity.
Paleoproterozoic East Pana Layered Intrusion (Kola Peninsula, Russia): Geological Structure, Petrography, Geochemistry and Cu-Ni-PGE Mineralization
Authors: Pripachkin Pavel , Rundkvist Tatiana , Groshev Nikolay
Published: May 2023

The East Pana intrusion is a part of the Paleoproterozoic Fedorova–Pana complex (FPC), which belongs to the group of Fennoscandian layered mafic–ultramafic massifs. This article discusses the magmatic stratification of the East Pana intrusion, as well as Cu-Ni and platinum-group elements (PGE) mineralization (PGE zones A, B and C) in its various parts with a total length of more than 20 km, including the East Chuarvy PGE deposit. Based on the whole-rock data on the distribution of major, trace, and ore-forming elements, it is assumed that PGE zone A belongs to the main ore–magmatic system of the FPC, while PGE zones B and C belong to the minor ore–magmatic systems. At the same time, additional magmatic injection played an important role in the formation of economic Cu-Ni-PGE mineralization (PGE zone B), characterized by high PGE concentrations and moderate palladium enrichment. On the normalized distribution spectra of trace elements, the crystallization products of this injection (Gabbronorite Zone 2) have a positive Zr-Hf anomaly, which distinguishes it from host rocks with an anomaly of the opposite sign (Gabbronorite Zone 1, Gabbro Zone). It is assumed that this portion of magma was intruded as a sill of crystal mush, the fractionation of which at depth led to its enrichment with residual liquid.
Effect of Cation Chloride Concentration on the Dissolution Rates of Basaltic Glass and Labradorite: Application to Subsurface Carbon Storage
Authors: Mesfin Kiflom G. , Wolff-Boenisch Domenik , Gislason Sigurdur R. , Oelkers Eric H.
Published: May 2023

The steady-state dissolution rates of basaltic glass and labradorite were measured in the presence of 10 to 700 × 10−3 mol·kg−1 aqueous NaCl, KCl, CaCl2, and MgCl2 at 25 °C. All rates were measured in mixed flow reactors, and at pH~3.6 by the addition of HCl to the reactive fluids. The steady-state basaltic glass dissolution rates, based on Si release, increased by ~0.3 log units in the presence of 10−3 mol·kg−1 of either CaCl2 or MgCl2 compared to their rates in 10−3 mol·kg−1 of NaCl or KCl. In contrast, the steady-state dissolution rates of labradorite decreased by ~0.4 log units in the presence of 10−3 mol·kg−1 of either CaCl2 or MgCl2 compared to their rates in 10−3 mol·kg−1 of NaCl or KCl. These contrasting behaviours likely reflect the varying effects of these cations on the stability of rate controlling Si-rich activated complexes on the surface of the dissolving solids. On average, the Si release rates of these solids are similar to each other and increase slightly with increasing ionic strength. As the pH of water charged with 10 to 30 bars CO2 is ~3.6, the results of this study indicate that both basaltic glass and labradorite dissolution will likely be effective at increasing the pH and adding Ca to the aqueous phase in saline fluids. This observation supports potential efforts to store carbon through its mineralization in saline aquifers containing Ca-bearing feldspar and in submarine basalts.
Phosphates Induced H-Type or J-Type Aggregation of Cationic Porphyrins with Varied Side Chains
Authors: Li Zhiliang , Zeman Charles J. , Valandro Silvano , Bantang Jose Paolo O. , Schanze Kirk S.
Published: May 2023

Non-covalent interactions have been extensively used to fabricate nanoscale architectures in supramolecular chemistry. However, the biomimetic self-assembly of diverse nanostructures in aqueous solution with reversibility induced by different important biomolecules remains a challenge. Here, we report the synthesis and aqueous self-assembly of two chiral cationic porphyrins substituted with different types of side chains (branched or linear). Helical H-aggregates are induced by pyrophosphate (PPi) as indicated by circular dichroism (CD) measurement, while J-aggregates are formed with adenosine triphosphate (ATP) for the two porphyrins. By modifying the peripheral side chains from linear to a branched structure, more pronounced H- or J-type aggregation was promoted through the interactions between cationic porphyrins and the biological phosphate ions. Moreover, the phosphate-induced self-assembly of the cationic porphyrins is reversible in the presence of the enzyme alkaline phosphatase (ALP) and repeated addition of phosphates.
Ultrasound-Assisted Fermentation to Remove Cadmium from Rice and Its Application
Authors: Yang Xiaotong , Yin Jie , Guo Yahui , Yu Hang , Yuan Shaofeng , Qian He , Yao Weirong , Song Jiangfeng
Published: May 2023

Rice, which is a major part of the daily diet, is becoming more and more contaminated by cadmium (Cd). This study combined low-intensity ultrasonic waves with the Lactobacillus plantarum fermentation method and optimized this technique by a single-factor and response surface experiment, aiming to solve the practical problems that the current Cd removal methods for rice cannot address, due to the fact that they require a long time (nearly 24 h), which prevents meeting the rice production demands. The described technique required a short time (10 h), and the highest Cd removal reached 67.05 ± 1.38%. Further analysis revealed that the maximum adsorption capacity of Lactobacillus plantarum for Cd increased by nearly 75%, and the equilibrium adsorption capacity increased by almost 30% after the ultrasonic intervention. Additionally, a sensory evaluation and other experiments proved that the properties of the rice noodles prepared from Cd-reduced rice obtained by ultrasound-assisted fermentation were comparable to those of traditional rice noodles, indicating that this method can be used in actual rice production.
Exploring the Modulatory Effect of High-Fat Nutrition on Lipopolysaccharide-Induced Acute Lung Injury in Vagotomized Rats and the Role of the Vagus Nerve
Authors: Seesing Maarten F. J. , Janssen Henricus J. B. , Geraedts Tessa C. M. , Weijs Teus J. , van Ark Ingrid , Leusink-Muis Thea , Folkerts Gert , Garssen Johan , Ruurda Jelle P. , Nieuwenhuijzen Grard A. P. , van Hillegersberg Richard , Luyer Misha D. P.
Published: May 2023

During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.
Parent’s Perception of the Types of Support Given to Families with an Infant with Phenylketonuria
Authors: Cassidy Sophie , Evans Sharon , Pinto Alex , Daly Anne , Ashmore Catherine , Ford Suzanne , Buckley Sharon , MacDonald Anita
Published: May 2023

Background: A diagnosis of phenylketonuria (PKU) in an infant is a devastating and overwhelming event for their parents. Providing appropriate information and support is paramount, especially at the beginning of a child’s life. Investigating if parents are receiving the right support is important for continued care. Methodology: An online survey was distributed to explore parents’ perceptions of current support and information provided by their healthcare provider and to rate sources of other support (n = 169 participants). Results: Dietitians received the highest (85%) rate of “very helpful” support. Overall, parents found Facebook to be helpful for support but had mixed reactions when asked if healthcare professionals (HCPs) should provide advice as part of the groups. When rating the most effective learning methods, the top three were 1:1 teaching sessions (n = 109, 70%), picture books (n = 73, 50%), and written handouts (n = 70, 46%). Conclusion: Most parents are happy with the support and information they receive from their dietitian but required more support from other HCPs. Facebook groups provide parents with the social support that HCPs and their family may be unable to offer, suggesting a place for social media in future PKU care.
Long-Term Effects of a Ketogenic Diet for Cancer
Authors: Egashira Ryuichiro , Matsunaga Michiko , Miyake Akimitsu , Hotta Sayaka , Nagai Naoko , Yamaguchi Chise , Takeuchi Mariko , Moriguchi Misaki , Tonari Satoko , Nakano Mai , Saito Hitomi , Hagihara Keisuke
Published: May 2023

A ketogenic diet has been proposed as a potential supportive therapy for cancer patients, although its long-term influence on survival rates remain controversial. In our previous report, we presented promising results for 37 of 55 patients with advanced cancer enrolled between 2013 and 2018 who remained on a ketogenic diet for at least 3 months. We followed all 55 patients until March 2023 and analyzed the data up to March 2022. For the 37 patients with previously reported promising results, the median follow-up period was 25 (range of 3–104) months and 28 patients died. The median overall survival (OS) in this subset of 37 patients was 25.1 months and the 5-year survival rate was 23.9%. We also evaluated the association between the duration of the ketogenic diet and outcome in all 55 patients, except for 2 patients with insufficient data. The patients were divided into two groups: those who followed the diet for ≥12 months (n = 21) and those who followed it for <12 months (n = 32). The median duration of the ketogenic diet was 37 (range of 12–99) months for the ≥12 months group and 3 (range of 0–11) months for the <12 months group. During the follow-up period, 41 patients died (10/21 in the ≥12 months group and 31/32 in the <12 months group). The median OS was 19.9 months (55.1 months in the ≥12 months group and 12 months in the <12 months group). Following the inverse probability of treatment weighting to align the background factors of the two groups and make them comparable, the adjusted log-rank test showed a significantly better OS rate in the group that continued the ketogenic diet for a longer period (p < 0.001, adjusted log-rank test). These results indicate that a longer continuation of the ketogenic diet improved the prognosis of advanced cancer patients.
Sex, Nutrition, and NAFLD: Relevance of Environmental Pollution
Authors: Dolce Arianna , Della Torre Sara
Published: May 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and represents an increasing public health issue given the limited treatment options and its association with several other metabolic and inflammatory disorders. The epidemic, still growing prevalence of NAFLD worldwide cannot be merely explained by changes in diet and lifestyle that occurred in the last few decades, nor from their association with genetic and epigenetic risk factors. It is conceivable that environmental pollutants, which act as endocrine and metabolic disruptors, may contribute to the spreading of this pathology due to their ability to enter the food chain and be ingested through contaminated food and water. Given the strict interplay between nutrients and the regulation of hepatic metabolism and reproductive functions in females, pollutant-induced metabolic dysfunctions may be of particular relevance for the female liver, dampening sex differences in NAFLD prevalence. Dietary intake of environmental pollutants can be particularly detrimental during gestation, when endocrine-disrupting chemicals may interfere with the programming of liver metabolism, accounting for the developmental origin of NAFLD in offspring. This review summarizes cause–effect evidence between environmental pollutants and increased incidence of NAFLD and emphasizes the need for further studies in this field.
Infants Fed Breastmilk or 2′-FL Supplemented Formula Have Similar Systemic Levels of Microbiota-Derived Secondary Bile Acids
Authors: Hill David R. , Buck Rachael H.
Published: May 2023

Human milk represents an optimal source of nutrition during infancy. Milk also serves as a vehicle for the transfer of growth factors, commensal microbes, and prebiotic compounds to the immature gastrointestinal tract. These immunomodulatory and prebiotic functions of milk are increasingly appreciated as critical factors in the development of the infant gut and its associated microbial community. Advances in infant formula composition have sought to recapitulate some of the prebiotic and immunomodulatory functions of milk through human milk oligosaccharide (HMO) fortification, with the aim of promoting healthy development both within the gastrointestinal tract and systemically. Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2′-fucosyllactose (2′-FL) on serum metabolite levels relative to breastfed infants. A prospective, randomized, double-blinded, controlled study of infant formulas (64.3 kcal/dL) fortified with varying levels of 2′-FL and galactooligosaccharides (GOS) was conducted [0.2 g/L 2′-FL + 2.2 g/L GOS; 1.0 g/L 2′-FL + 1.4 g/L GOS]. Healthy singleton infants age 0–5 days and with birth weight > 2490 g were enrolled (n = 201). Mothers chose to either exclusively formula-feed or breastfeed their infant from birth to 4 months of age. Blood samples were drawn from a subset of infants at 6 weeks of age (n = 35–40 per group). Plasma was evaluated by global metabolic profiling and compared to a breastfed reference group (HM) and a control formula (2.4 g/L GOS). Fortification of control infant formula with the HMO 2′-FL resulted in significant increases in serum metabolites derived from microbial activity in the gastrointestinal tract. Most notably, secondary bile acid production was broadly increased in a dose-dependent manner among infants receiving 2′-FL supplemented formula relative to the control formula. 2′-FL supplementation increased secondary bile acid production to levels associated with breastfeeding. Our data indicate that supplementation of infant formula with 2′-FL supports the production of secondary microbial metabolites at levels comparable to breastfed infants. Thus, dietary supplementation of HMO may have broad implications for the function of the gut microbiome in systemic metabolism. This trial was registered at with the U.S. National library of Medicine as NCT01808105.
Positive Association of Serum Vitamin B6 Levels with Intrapulmonary Lymph Node and/or Localized Pleural Metastases in Non-Small Cell Lung Cancer: A Retrospective Study
Authors: Liu Lu , Yu Hang , Bai Jingmin , Xu Qing , Zhang Yong , Zhang Xinsheng , Yu Zhimeng , Liu Yinghua
Published: May 2023

The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B vitamins and intrapulmonary lymph nodes as well as localized pleural metastases in patients with non-small cell lung cancer (NSCLC). This was a retrospective study including patients who underwent lung surgery for suspected NSCLC at our institution from January 2016 to December 2018. Logistic regression models were used to evaluate the associations between serum B vitamin levels and intrapulmonary lymph node and/or localized pleural metastases. Stratified analysis was performed according to different clinical characteristics and tumor types. A total of 1498 patients were included in the analyses. Serum vitamin B6 levels showed a positive association with intrapulmonary metastasis in a multivariate logistic regression (odds ratio (OR) of 1.016, 95% confidence interval (CI) of 1.002–1.031, p = 0.021). After multivariable adjustment, we found a high risk of intrapulmonary metastasis in patients with high serum vitamin B6 levels (fourth quartile (Q4) vs. Q1, OR of 1.676, 95%CI of 1.092 to 2.574, p = 0.018, p for trend of 0.030). Stratified analyses showed that the positive association between serum vitamin B6 and lymph node metastasis appeared to be stronger in females, current smokers, current drinkers, and those with a family history of cancer, squamous cell carcinoma, a tumor of 1–3 cm in diameter, or a solitary tumor. Even though serum vitamin B6 levels were associated with preoperative NSCLC upstaging, B6 did not qualify as a useful biomarker due to weak association and wide confidence intervals. Thus, it would be appropriate to prospectively investigate the relationship between serum vitamin B6 levels and lung cancer further.
A Novel Class of Functionally Tuneable Star-Shaped Molecules for Interaction with Multiple Proteins
Authors: Barik Debashis , Anand Geethanjali , Cheekatla Subba Rao , Porel Mintu
Published: May 2023

Molecules with tuneable properties are well known for their applications in the material and bio-medical fields; nevertheless, the structural and functional tunability makes them more significant in diverse applications. Herein, we designed and synthesized a novel class of star-shaped molecules via incorporating two important functional groups, i.e., triazole and dithiocarbamate (DTC). The rationale behind selecting these two key functional groups is their diverse applications, e.g., DTC having applications for therapeutics, pesticides, and vulcanizing agents, and triazole having applications for anti-cancer, fungicides, anti-microbials, inhibitors, etc. The structure of the molecules was strategically designed in such a way that their overall structures are the same (central tertiary-amine and peripheral hydroxy groups), except the key functional group (DTC and triazole) in the respective molecules was different. Following synthesis and characterization, the influence of DTC and triazole groups on their bioactivity was compared via interacting with the most abundant proteins present in the blood, including serum albumin, trypsin, haemoglobin, and ribonuclease. From both the experimental and molecular docking studies, it was confirmed that the triazole molecule has a higher binding affinity towards these proteins as compared to the DTC molecule. In summary, two star-shaped DTC- and triazole-based molecules were synthesized and their bioactivity was compared via binding with blood plasma proteins.
Network Biology-Inspired Machine Learning Features Predict Cancer Gene Targets and Reveal Target Coordinating Mechanisms
Authors: Weiskittel Taylor M. , Cao Andrew , Meng-Lin Kevin , Lehmann Zachary , Feng Benjamin , Correia Cristina , Zhang Cheng , Wisniewski Philip , Zhu Shizhen , Yong Ung Choong , Li Hu
Published: May 2023

Anticipating and understanding cancers’ need for specific gene activities is key for novel therapeutic development. Here we utilized DepMap, a cancer gene dependency screen, to demonstrate that machine learning combined with network biology can produce robust algorithms that both predict what genes a cancer is dependent on and what network features coordinate such gene dependencies. Using network topology and biological annotations, we constructed four groups of novel engineered machine learning features that produced high accuracies when predicting binary gene dependencies. We found that in all examined cancer types, F1 scores were greater than 0.90, and model accuracy remained robust under multiple hyperparameter tests. We then deconstructed these models to identify tumor type-specific coordinators of gene dependency and identified that in certain cancers, such as thyroid and kidney, tumors’ dependencies are highly predicted by gene connectivity. In contrast, other histologies relied on pathway-based features such as lung, where gene dependencies were highly predictive by associations with cell death pathway genes. In sum, we show that biologically informed network features can be a valuable and robust addition to predictive pharmacology models while simultaneously providing mechanistic insights.
Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism
Authors: Samman Waad A. , Selim Salma M. , El Fayoumi Hassan M. , El-Sayed Norhan M. , Mehanna Eman T. , Hazem Reem M.
Published: May 2023

Alzheimer’s disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the memory impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims to examine the possible mechanisms of the neuroprotective effects of dapagliflozin against aluminum chloride (AlCl3)-induced AD. Rats were distributed into four groups: group 1 received saline, group 2 received AlCl3 (70 mg/kg) daily for 9 weeks, and groups 3 and 4 were administered AlCl3 (70 mg/kg) daily for 5 weeks. Dapagliflozin (1 mg/kg) and dapagliflozin (5 mg/kg) were then given daily with AlCl3 for another 4 weeks. Two behavioral experiments were performed: the Morris Water Maze (MWM) and the Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in the brain, as well as changes in acetylcholinesterase (AChE) and amyloid β (Aβ) peptide activities and oxidative stress (OS) markers, were all evaluated. A western blot analysis was used for the detection of phosphorylated 5’ AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of Rapamycin (p-mTOR) and heme oxygenase-1 (HO-1). Tissue samples were collected for the isolation of glucose transporters (GLUTs) and glycolytic enzymes using PCR analysis, and brain glucose levels were also measured. The current data demonstrate that dapagliflozin represents a possible approach to combat AlCl3-induced AD in rats through inhibiting oxidative stress, enhancing glucose metabolism and activating AMPK signaling.
Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro
Authors: Melander Erik , Eriksson Camilla , Wellens Sara , Hosseini Kimia , Fredriksson Robert , Gosselet Fabien , Culot Maxime , Göransson Ulf , Hammarlund-Udenaes Margareta , Loryan Irena
Published: May 2023

The blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution within the brain to gauge the potential of these two cCPPs as scaffolds for CNS drugs. In a rat model, SFTI-1 exhibited, for a peptide, high extent of BBB transport with a partitioning of unbound SFTI-1 across the BBB, Kp,uu,brain, of 13%, while only 0.5% of kalata B1 equilibrated across the BBB. By contrast, kalata B1, but not SFTI-1, readily entered neural cells. SFTI-1, but not kalata B1, could be a potential CNS delivery scaffold for drugs directed to extracellular targets. These findings indicate that differences between the BBB transport and cellular uptake abilities of CPPs are crucial in the development of peptide scaffolds.
The First Report of In Vitro Antifungal and Antibiofilm Photodynamic Activity of Tetra-Cationic Porphyrins Containing Pt(II) Complexes against Candida albicans for Onychomycosis Treatment
Authors: da Rosa Pinheiro Ticiane , Dantas Gabrielle Aguiar , da Silva Jean Lucas Gutknecht , Leal Daniela Bitencourt Rosa , da Silva Ricardo Barreto , de Lima Burgo Thiago Augusto , Santos Roberto Christ Vianna , Iglesias Bernardo Almeida
Published: May 2023

Onychomycosis is a prevalent nail fungal infection, and Candida albicans is one of the most common microorganisms associated with it. One alternative therapy to the conventional treatment of onychomycosis is antimicrobial photoinactivation. This study aimed to evaluate for the first time the in vitro activity of cationic porphyrins with platinum(II) complexes 4PtTPyP and 3PtTPyP against C. albicans. The minimum inhibitory concentration of porphyrins and reactive oxygen species was evaluated by broth microdilution. The yeast eradication time was evaluated using a time-kill assay, and a checkerboard assay assessed the synergism in combination with commercial treatments. In vitro biofilm formation and destruction were observed using the crystal violet technique. The morphology of the samples was evaluated by atomic force microscopy, and the MTT technique was used to evaluate the cytotoxicity of the studied porphyrins in keratinocyte and fibroblast cell lines. The porphyrin 3PtTPyP showed excellent in vitro antifungal activity against the tested C. albicans strains. After white-light irradiation, 3PtTPyP eradicated fungal growth in 30 and 60 min. The possible mechanism of action was mixed by ROS generation, and the combined treatment with commercial drugs was indifferent. The 3PtTPyP significantly reduced the preformed biofilm in vitro. Lastly, the atomic force microscopy showed cellular damage in the tested samples, and 3PtTPyP did not show cytotoxicity against the tested cell lines. We conclude that 3PtTPyP is an excellent photosensitizer with promising in vitro results against C. albicans strains.
Determination of Sustainable Critical Flux through a Long-Term Membrane Resistance Model
Authors: Xu Rongle , Fan Yaobo , Yang Min , Song Jinqiu
Published: May 2023

A long-term membrane resistance model (LMR) was established to determine the sustainable critical flux, which developed and simulated polymer film fouling successfully in a lab-scale membrane bioreactor (MBR) in this study. The total polymer film fouling resistance in the model was decomposed into the individual components of pore fouling resistance, sludge cake accumulation and cake layer compression resistance. The model effectively simulated the fouling phenomenon in the MBR at different fluxes. Considering the influence of temperature, the model was calibrated by temperature coefficient τ, and a good result was achieved to simulate the polymer film fouling at 25 and 15 °C. The relationship between flux and operation time was simulated and discussed through the model. The results indicated that there was an exponential correlation between flux and operation time, and the exponential curve could be divided into two parts. By fitting the two parts to two straight lines, respectively, the intersection of the two straight lines was regarded as the sustainable critical flux value. The sustainable critical flux obtained in this study was just 67% of the critical flux. The model in this study was proven to be in good agreement with the measurements under different fluxes and different temperatures. In addition, the sustainable critical flux was first proposed and calculated in this study, and it was shown that the model could be used to predict the sustainable operation time and sustainable critical flux, which provide more practical information for designing MBRs. This study is applicable to polymer films used in a wide variety of applications, and it is helpful for maintaining the long-term stable operation of polymer film modules and improving the efficiency of polymer film modules.