bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Computations on Prime Numbers
Authors: Vega Frank
Published: January 2024

Let $\Psi(n) = n \cdot \prod_{q \mid n} \left(1 + \frac{1}{q} \right)$ denote the Dedekind $\Psi$ function where $q \mid n$ means the prime $q$ divides $n$. Define, for $n \geq 3$; the ratio $R(n) = \frac{\Psi(n)}{n \cdot \log \log n}$ where $\log$ is the natural logarithm. Let $N_{n} = 2 \cdot \ldots \cdot q_{n}$ be the primorial of order $n$. We state that if the inequality $R(N_{n+1}) < R(N_{n})$ holds for all primes $q_{n}$ (greater than some threshold), then the Riemann hypothesis is true and the Cram{\'e}r's conjecture is false. In this note, we prove that the previous inequality always holds for all sufficiently large primes $q_{n}$. This manuscript was based on numerical computations which confirm and support the truthfulness of this mathematical result.
Two Major Conjectures on Prime Numbers
Authors: Vega Frank
Published: January 2024

Let $\Psi(n) = n \cdot \prod_{q \mid n} \left(1 + \frac{1}{q} \right)$ denote the Dedekind $\Psi$ function where $q \mid n$ means the prime $q$ divides $n$. Define, for $n \geq 3$; the ratio $R(n) = \frac{\Psi(n)}{n \cdot \log \log n}$ where $\log$ is the natural logarithm. Let $N_{n} = 2 \cdot \ldots \cdot q_{n}$ be the primorial of order $n$. We state that if the inequality $R(N_{n+1}) < R(N_{n})$ holds for all primes $q_{n}$ (greater than some threshold), then the Riemann hypothesis is true and the Cram{\'e}r's conjecture is false. In this note, we prove that the previous inequality always holds for all sufficiently large primes $q_{n}$.
Blivande lärares kunskap om neuropsykiatriska funktionsnedsättningar.
Authors: Littmarck Sofia , Hallberg Mathilda
Published: January 2024

Under hösten 2020 meddelade regeringen att ett tillägg om neuropsykiatriska svårigheter hade införts i examensmålen för lärarutbildningarna. Syftet var att stärka lärares kunskaper om neuropsykiatriska svårigheter med målet att öka likvärdigheten i förskola och skola. Beslutet föregicks av ett förslag på tillägg till examensmålen som skickades ut på remiss till bland annat högskolor och universitet. Under remisstiden svarade flera lärosäten att de var kritiska mot tillägget. Analysen av remissvaren och förslaget till ändring av examensordningen visar en spänning mellan olika sätt att se på vilka perspektiv som ska råda i lärarutbildningens undervisning om elevers olikheter. Att lyfta fram en särskild grupp elever i examensmålen ansågs motverka snarare än stärka likvärdigheten i förskola och skola.
Case Report: A family history of peanut allergy and hereditary alpha-tryptasemia
Authors: Chantran Yannick , Renaudin Hélène , Arock Michel , Guiddir Tamazoust , Nemni Ariane
Published: January 2024

Context

Hereditary alpha-tryptasemia (HαT) is associated with elevated basal serum tryptase (bST) and is associated with a higher risk of severe anaphylactic reactions in patients with clonal mast cell disorders or IgE-mediated Hymenoptera venom-induced anaphylaxis. The consequence of this genetic trait remains to be determined in other allergic diseases and food allergy in particular.

Objectives

Here, we describe three cases of peanut allergy among siblings from a single family of four: two of them were associated with HαT, and the third one was associated with the tryptase wild-type genotype.

Methods

TPSAB1/TPSB2 genotypes were determined by digital PCR. After the case description, we provided a review of the literature regarding bST levels and tryptase genotypes in anaphylaxis, with a particular focus on food allergy.

Results

Compared to the sibling with the conventional tryptase genotype, the two siblings with HαT presented a lower peanut threshold at the initial oral food challenge, higher peanut skin prick test reactivity, higher levels of specific IgE to peanut, Ara h 2, and Ara h 6, and a lower IgG4/IgE ratio after 10 years of oral immunotherapy.

Conclusion

The tryptase genotype and HαT status might modify the clinical presentation and biological features of food allergy.
Annexin A7 mediates lysosome repair independently of ESCRT-III
Authors: Ebstrup Malene Laage , Sønder Stine Lauritzen , Fogde Ditte Louise , Heitmann Anne Sofie Busk , Dietrich Tiina Naumanen , Dias Catarina , Jäättelä Marja , Maeda Kenji , Nylandsted Jesper
Published: January 2024

Lysosomes are crucial organelles essential for various cellular processes, and any damage to them can severely compromise cell viability. This study uncovers a previously unrecognized function of the calcium- and phospholipid-binding protein Annexin A7 in lysosome repair, which operates independently of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Our research reveals that Annexin A7 plays a role in repairing damaged lysosomes, different from its role in repairing the plasma membrane, where it facilitates repair through the recruitment of ESCRT-III components. Notably, our findings strongly suggest that Annexin A7, like the ESCRT machinery, is dispensable for membrane contact site formation within the newly discovered phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway. Instead, we speculate that Annexin A7 is recruited to damaged lysosomes and promotes repair through its membrane curvature and cross-linking capabilities. Our findings provide new insights into the diverse mechanisms underlying lysosomal membrane repair and highlight the multifunctional role of Annexin A7 in membrane repair.
Endothelial anthrax toxin receptor 2 plays a protective role in liver fibrosis
Authors: Huang Xiaojuan , Zhang Liyin , Luo Wei , Zeng Yu , Li Xiaoxue , Yang Nan , Huang Wenwen , Ding Bi-Sen
Published: January 2024

Hepatocellular carcinoma is one of the leading cancers worldwide and is a potential consequence of fibrosis. Therefore, the identification of key cellular and molecular mechanisms involved in liver fibrosis is an important goal for the development of new strategies to control liver-related diseases. Here, single-cell RNA sequencing data (GSE136103 and GES181483) of clinical liver non-parenchymal cells were analyzed to identify cellular and molecular mechanisms of liver fibrosis. The proportion of endothelial subpopulations in cirrhotic livers was significantly higher than that in healthy livers. Gene ontology and gene set enrichment analysis of differentially expressed genes in the endothelial subgroups revealed that extracellular matrix (ECM)-related pathways were significantly enriched. Since anthrax toxin receptor 2 (ANTXR2) interacts with the ECM, the expression of ANTXR2 in the liver endothelium was analyzed. ANTXR2 expression in the liver endothelium of wild-type (WT) mice significantly decreased after a 4-time sequential injection of carbon tetrachloride (CCl4) to induce liver fibrosis. Next, conditional knockout mice selectively lacking Antxr2 in endothelial cells were generated. After endothelial-specific Antxr2 knockout mice were subjected to the CCl4 model, the degree of liver fibrosis in the knockout group was significantly more severe than that in the control group. In addition, ANTXR2 in human umbilical vein endothelial cells promoted matrix metalloproteinase 2 (MMP2) activation to degrade the ECM in vitro. Finally, endothelial-specific overexpression of Antxr2 alleviated the development of liver fibrosis following adeno-associated virus treatment. Collectively, these results suggested that endothelial ANTXR2 plays a protective role in liver fibrosis. This function of ANTXR2 may be achieved by promoting MMP2 activation to degrade the ECM.
Impact of solar-driven heating strategies on the phase change thermal storage performance of erythritol
Authors: Deng Yuxuan , Zhen Yu , Zhu Xiaojuan , Li Yanna , Xu Jing
Published: January 2024

With escalating energy demands, solar power stands out for its abundance and renewable advantages, presenting a paramount sustainable solution. Herein, we tactically incorporate phase change material (PCM) into solar energy systems, resulting in substantial enhancements in energy storage and utilization. Through numerical simulations, the thermal dynamics and phase change processes associated with various heating methodologies are investigated, aiming to achieve optimal thermal performance and energy efficiency. Detailed analysis of temperature dynamics within the PCM under two distinct heating methods reveals pivotal thermal fluctuations in both the PCM and water during heat release. The results indicate that bottom heating promptly induces rayleigh convection, resulting in a uniform temperature and a stable phase interface, which are desirable for heat transfer. In contrast, central tube heating concentrates heat transfer in the upper PCM layer, leading to an uneven phase interface and thermal stratification. Configurations with two horizontally aligned heating tubes result in a 36% reduction in melting duration compared to the single central tube setup, highlighting enhanced efficiency. Additionally, the bottom heating approach demonstrates improved energy storage efficiency in both the initial and second heating cycles. These findings highlight the potential of PCM-integrated combined heating systems for solar energy capture, confirming their efficiency and practicality in addressing modern household energy demands.
State-of-the-art multimodal scanning hard X-ray imaging and tomography sheds light at multiple length-scales on biomineralization related processes
Authors: Medjoubi K. , Benzerara K. , Debrie J. , Tang E. , Bazin D. , Letavernier E. , Desjardins K. , Somogyi A.
Published: January 2024

Biomineralization is a widespread process among living organisms, playing a significant role in the formation and preservation of geological structures, biogeochemical cycles, regulation of ocean chemistry, and carbon sequestration. Moreover pathological biomineralization has a huge impact on human health. The growth of biominerals provides a rich area for research at multiple length-scales since they have controlled hierarchical structures from nano-to macroscopic scales. Here, we provide an overview on the potentials of the state-of-the-art scanning hard X-ray imaging and tomography methods developed at the NANOSCOPIUM beamline at Synchrotron Soleil in such studies. Multimodal scanning imaging provides simultaneous information on the elemental composition by X-ray fluorescence (XRF) spectrometry, on the sample morphology by absorption contrast imaging, on the crystalline structure by X-ray diffraction, and on the luminescence characteristics by X-ray Excited Optical Luminescence. As illustrated through diverse research cases about biomineralization in stromatolites and pathological calcification, such a versatile portfolio of X-ray imaging techniques provides unique complementary information to conventional laboratory techniques on biominerals and the underlying mineral precipitation processes.
Causal association between genetically predicted circulating immune cell counts and frailty: a two-sample Mendelian randomization study
Authors: Guo Xiao-Guang , Zhang Ya-Juan , Lu Ya-Xin , Lu Jia-Mei , Zhang Jie , Li Hui-Xin , Chen Chao-Jin , Yang Jian-Jun
Published: January 2024

Background

Despite the recognized link between immune responses and frailty, the association between immune cell counts and frailty based on previous observational studies remains disputed, with uncertain causal nexus. This study aimed to elucidate causal association between genetically predicted circulating immune cell counts and frailty.

Methods

We conducted the two-sample Mendelian randomization (MR) study with independent genetic variants associated with six immune cell subtype counts from genome-wide association studies in 563,946 European individuals. Frailty summary data, assessed via frailty index (FI), was obtained from study comprising 175,226 subjects. Univariate MR, reverse MR and multivariate MR were conducted to comprehensive investigate the association between immune cell counts and FI, with two-step MR analysis for mediation analysis.

Results

Univariate MR evidence indicated that among six leukocyte subtype counts, only elevated eosinophil count was significantly correlated with higher FI (β = 0.059, 95% confidence interval [CI], 0.042–0.078, P=5.63E-11), with no reverse causal relationship identified in reverse MR. In multivariate MR, the causal effect of eosinophil count retained statistical significance (β = 0.063, 95% CI, 0.021–0.104, P = 0.003). Ultimately, the two-step MR analysis demonstrated two mediators in this causal pathway: asthma (β= 0.019, 95% CI, 0.013–0.025, P = 35.84E-10, mediated proportion, 31.732%) and rheumatoid arthritis (β= 0.004, 95% CI, 0.001–0.006, P=1.75E-03, mediated proportion, 6.411%).

Conclusions

Within immune cell subtypes, MR evidence indicated only genetically predicted circulating eosinophil count had irreversible and independent causal effect on frailty, with asthma and rheumatoid arthritis possibly serving as partial mediators. The finding stressed the need for further exploring physiological functions of eosinophils in order to develop effective strategies against frailty.
Poor prognostic factors of pharmacokinetic origin predict outcomes in inflammatory bowel disease patients treated with anti-tumor necrosis factor-α
Authors: Spencer Elizabeth A. , Dubinsky Marla C. , Kamm Michael A. , Chaparro Maria , Gionchetti Paolo , Rizzello Fernando , Gisbert Javier P. , Wright Emily K. , Schulberg Julien D. , Hamilton Amy L. , McGovern Dermot P. B. , Dervieux Thierry
Published: January 2024

Introduction

We evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab.

Methods

Baseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations. HLA DQA1*05 carrier status (rs2097432 A/G or G/G variant) was measured using real time polymerase chain reaction. The outcomes consisted of immune response, clinical and biochemical remission (C-reactive protein<3 mg/L in the absence of symptoms), and endoscopic remission (SES-CD<3). Statistical analysis consisted of logistic regression and nonlinear mixed effect models.

Results and discussion

In 415 patients enrolled from 4 different cohorts (median age 27 [IQR: 15-43] years, 46% females), Clearance>0.326 L/day and HLA DQA1*05 carrier status were 2-fold more likely to have antidrug antibodies (OR=2.3, 95%CI: 1.7-3.4; p<0.001, and OR=1.9, 95%CI: 1.4-2.8; p<0.001, respectively). Overall, each incremental PPF of PK origin resulted in a 2-fold (OR=2.16, 95%CI: 1.7-2.7; p<0.01) higher likelihood of antidrug antibody formation. The presence of both PPF of PK origin resulted in higher rates of antidrug antibodies (p<0.01) and lower clinical and biochemical remission (p<0.01). Each incremental increase in PPF of PK origin associated with lower likelihood of endoscopic remission (OR=0.4, 95%CI: 0.2-0.7; p<0.001). Prior biologic experience heightened the negative impact of PPF of PK origin on clinical and biochemical remission (p<0.01). Implementation of proactive therapeutic drug monitoring reduced it, particularly during maintenance and in the presence of higher drug concentrations (p<0.001). We conclude that PPF of PK origin, including both higher Clearance and carriage of HLA DQA1*05, impact outcomes in patients with IBD.
Vertical stratification of phytoplankton biomass in a deep estuary site: implications for satellite-based net primary productivity
Authors: Gall Mark , Zeldis John , Safi Karl , Wood Simon , Pinkerton Matthew
Published: January 2024

The accuracy of satellite estimates for water column net primary productivity (NPP) are contingent upon the reliability of surface phytoplankton biomass, specifically chlorophyll a (Chl.a) and carbon (Cphyt), as indicators of euphotic biomass and photosynthetic rate. We assessed patterns in water column biomass at a deep estuary site (~40 m) in the Firth of Thames, Hauraki Gulf, New Zealand, using ten years (2005-2015) of in situ sampling (40 seasonal voyages and moored instrumentation). Seasonal biomass stratification coincided with physical and chemical stratification and exhibited a reasonable predictability based on surface Chl.a measures from mooring timeseries. High Chl.a (but not Cphyt) accumulated from late-spring (Nov.) in the lower portion of the water column, under nutrient deficient, clear surface water with deep euphotic zone conditions, peaking in mid-summer (Jan.) and ending by early autumn (Mar.). Satellite (MODIS-Aqua) NPP (2002-2018), was estimated with and without correction for deep biomass in two vertically generalized production models (Chl.a-VGPM and Cphyt-CbPM). Mean annual NPP (220-161 g C m-2 y-1, VGPM and CbPM respectively) increased 5-18% after accounting for euphotic zone deep biomass with a mid-summer maxim (Jan.: 30-33%). Interannual anomalies in biomass and NPP (about -10% to 10%) were an order of magnitude greater than small decreasing trends (<< 1% y-1). We discuss the impacts of observational factors on biomass and NPP estimation. We offer contextual insights into seasonal patterns by considering previous observations of biomass trends and nutrient enrichment in the Firth of Thames region. We propose future directions in accounting for deep biomass variations from shallow coastal areas to deeper continental shelf waters.
Modeling a domain wall network in BiFeO3 with stochastic geometry and entropy-based similarity measure
Authors: Cipollini Davide , Swierstra Andele , Schomaker Lambert
Published: January 2024

A compact and tractable two-dimensional model to generate the topological network structure of domain walls in BiFeO3 thin films is presented in this study. Our method combines the stochastic geometry parametric model of the centroidal Voronoi tessellation optimized using the von Neumann entropy, a novel information-theoretic tool for networks. The former permits the generation of image-based stochastic artificial samples of domain wall networks, from which the network structure is subsequently extracted and converted to the graph-based representation. The von Neumann entropy, which reflects information diffusion across multiple spatiotemporal scales in heterogeneous networks, plays a central role in defining a fitness function. It allows the use of the network as a whole rather than using a subset of network descriptors to search for optimal model parameters. The optimization of the parameters is carried out by a genetic algorithm through the maximization of the fitness function and results in the desired graph-based network connectivity structure. Ground truth empirical networks are defined, and a dataset of network connectivity structures of domain walls in BiFeO3 thin films is undertaken through manual annotation. Both a versatile tool for manual network annotation of noisy images and a new automatic network extraction method for high-quality images are developed.
Finite element analysis of female pelvic organ prolapse mechanism: current landscape and future opportunities
Authors: Yang Miyang , Chen Chujie , Wang Zhaochu , Long Jiaye , Huang Runyu , Qi Wan , Shi Rong
Published: January 2024

The prevalence of pelvic organ prolapse (POP) has been steadily increasing over the years, rendering it a pressing global health concern that significantly impacts women’s physical and mental wellbeing as well as their overall quality of life. With the advancement of three-dimensional reconstruction and computer simulation techniques for pelvic floor structures, research on POP has progressively shifted toward a biomechanical focus. Finite element (FE) analysis is an established tool to analyze the biomechanics of complex systems. With the advancement of computer technology, an increasing number of researchers are now employing FE analysis to investigate the pathogenesis of POP in women. There is a considerable number of research on the female pelvic FE analysis and to date there has been less review of this technique. In this review article, we summarized the current research status of FE analysis in various types of POP diseases and provided a detailed explanation of the issues and future development in pelvic floor disorders. Currently, the application of FE analysis in POP is still in its exploratory stage and has inherent limitations. Through continuous development and optimization of various technologies, this technique can be employed with greater accuracy to depict the true functional state of the pelvic floor, thereby enhancing the supplementation of the POP mechanism from the perspective of computer biomechanics.
Driving forces shaping the microbial ecology in meat packing plants
Authors: Yang Xianqin , Narvaez-Bravo Claudia , Zhang Peipei
Published: January 2024

Meat production is a complex system, continually receiving animals, water, air, and workers, all of which serve as carriers of bacteria. Selective pressures involved in different meat processing stages such as antimicrobial interventions and low temperatures, may promote the accumulation of certain residential microbiota in meat cutting facilities. Bacteria including human pathogens from all these sources can contaminate meat surfaces. While significant advancements have been made in enhancing hygienic standards and pathogen control measures in meat plants, resulting in a notable reduction in STEC recalls and clinical cases, STEC still stands as a predominant contributor to foodborne illnesses associated with beef and occasionally with pork. The second-and third-generation sequencing technology has become popular in microbiota related studies and provided a better image of the microbial community in the meat processing environments. In this article, we reviewed the potential factors influencing the microbial ecology in commercial meat processing facilities and conducted a meta-analysis on the microbiota data published in the last 10 years. In addition, the mechanisms by which bacteria persist in meat production environments have been discussed with a focus on the significant human pathogen E. coli O157:H7 and generic E. coli, an indicator often used for the hygienic condition in food production.
Gut microbiota and its therapeutic implications in tumor microenvironment interactions
Authors: Feng Pengya , Xue Xia , Bukhari Ihtisham , Qiu Chunjing , Li Yingying , Zheng Pengyuan , Mi Yang
Published: January 2024

The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.
Rapid and simultaneous multiepitope antigen-based detection of Enterococcus by microscale thermophoresis and immunomagnetic separation
Authors: Liu Yan , Wang Ziyan , Wang Ze , Zhou Jun , Han Jiaojiao , Lu Chenyang , Liu Bing , Yu Rongxian , Sun Xiaoling , Zhang Zhen , Wang Rixin , Su Xiurong
Published: January 2024

Background

Generally, enterococci bacteria cause nosocomial infections and are major indicators of bacterial contamination in marine bathing beach. However, a method for the rapid and simultaneous detection of multiple pathogenic enterococci has not been developed on account of the wide variety of pathogenic enterococci and their existence in complex matrices.

Methods

Immunoinformatics tools were used to design a multi-epitope antigen for the detection of various pathogenic enterococci by using the sequence of dltD gene on enterococci lipoteichoic acid (LTA) surface, which is associated with toxicological effects. The multi-epitopes included enterococci such as Enterococcus faecalis, E. gallinarum, E. raffinosus, E. durans, E. faecium, E. hirae, E. thailandicus, E. casseliflavus, E. avium, E. mundtii, E. lactis, E. solitarius, E. pseudoavium, and E. malodoratum. Microscale thermophoresis (MST) and western blot were carried out to detect the affinity between multi-epitope antigens and antibodies and between multi-epitope antibodies and bacteria. Furthermore, the detection of pathogenic enterococci was carried out by using immunomagnetic beads (IMBs) and immune chromatographic test strip (ICTS).

Results

The multi-epitope antibody had a satisfactory affinity to the antigen and enterococci. IMBs and ICTS were detected with a minimum of 101 CFU/mL and showed incompatibility for Vibrio parahemolyticus, V. vulnifcus, V. harveyi, V. anguillarum, and Edwardsiella tarda.

Implication

The present study demonstrated that the multi-epitope antigens exhibited excellent specificity and sensitivity, making them highly suitable for efficient on-site screening of enterococci bacteria in marine bathing beaches.
Rapid discrimination between clinical Clostridioides difficile infection and colonization by quantitative detection of TcdB toxin using a real-time cell analysis system
Authors: Shen Yuhang , Lin Shan , You Peijun , Chen Yu , Luo Yun , Song Xiaojun , Chen Yunbo , Jin Dazhi
Published: January 2024

Objectives

It is important to accurately discriminate between clinical Clostridioides difficile infection (CDI) and colonization (CDC) for effective antimicrobial treatment.

Methods

In this study, 37 stool samples were collected from 17 CDC and 20 CDI cases, and each sample were tested in parallel through the real-time cell analysis (RTCA) system, real-time PCR assay (PCR), and enzyme-linked immunosorbent assay (ELISA).

Results

RTCA-measured functional and toxical C. difficile toxin B (TcdB) concentrations in the CDI group (302.58 ± 119.15 ng/mL) were significantly higher than those in the CDC group (18.15 ± 11.81 ng/mL) (p = 0.0008). Conversely, ELISA results revealed no significant disparities in TcdB concentrations between the CDC (26.21 ± 3.57 ng/mL) and the CDI group (17.07 ± 3.10 ng/mL) (p = 0.064). PCR results indicated no significant differences in tcdB gene copies between the CDC (774.54 ± 357.89 copies/μL) and the CDI group (4,667.69 ± 3,069.87 copies/μL) (p = 0.407). Additionally, the functional and toxical TcdB concentrations secreted from C. difficile isolates were measured by the RTCA. The results from the CDC (490.00 ± 133.29 ng/mL) and the CDI group (439.82 ± 114.66 ng/mL) showed no significant difference (p = 0.448). Notably, RTCA-measured functional and toxical TcdB concentration was significantly decreased when mixed with pooled CDC samples supernatant (p = 0.030).

Conclusion

This study explored the novel application of the RTCA assay in effectively discerning clinical CDI from CDC cases.
Maternal diet and human milk composition: an updated systematic review
Authors: Petersohn Inga , Hellinga Anneke H. , van Lee Linde , Keukens Nicole , Bont Louis , Hettinga Kasper A. , Feskens Edith J. M. , Brouwer-Brolsma Elske M.
Published: January 2024

Context

Exclusive breastfeeding for 6 months after birth provides infants with the best start for life. A review by Bravi et al. summarized the importance of maternal diet as a determinant of human milk composition based on data up to 2015, but evidence on nutrient intake level was limited.

Objective

We updated the review by Bravi et al., critically assessed differences in study designs and sampling methods, and graphically visualized trends and associations.

Data sources

PubMed was systematically searched for articles published between January 2015 and March 2021.

Data extraction

Article screening, selection, and data extraction was done by two independent researchers, including a risk of bias assessment based on 11 criteria. Articles were eligible when including: quantitative information, commonly used effect estimates, healthy mother-infant dyads.

Results

Twenty seven observational and five intervention studies were identified (n = 7,138) and combined with results of Bravi et al. Fatty acids were still the most studied human milk components in relation to maternal diet (n = 17 studies) with maternal fish intake being predominantly positively associated with milk ALA (r = 0.28–0.42), DHA (r = 0.24–0.46), and EPA (r = 0.25–0.28) content. PUFAs from diet were generally positively correlated with their concentrations in milk, while SFA intake was negatively associated with several fatty acids in milk. Studies on associations with maternal diet and milk carbohydrates, proteins, vitamins and minerals were limited in number and varied in methods and results.

Conclusion

This updated review shows that evidence on the association between maternal diet and human milk fatty acids is rapidly increasing, but still diversified in methodology and results. Further studies, preferably intervention studies, assessing diet and milk carbohydrates, proteins, vitamins and minerals are needed to be able draw conclusions on the importance of maternal diet for human milk composition as a whole.
Study of amino acids absorption and gut microbiome on consumption of pea protein blended with enzymes-probiotics supplement
Authors: Rathi Abhijit , Gaonkar Tejal , Dhar Debojyoti , Kallapura Gopalakrishna , Jadhav Swati
Published: January 2024

The current randomized, double-blind, crossover clinical trial was conducted to evaluate changes in the amino acid absorption and gut microbiota on consumption of pea protein supplemented with an enzymes-probiotics blend (Pepzyme Pro). A total of 15 healthy subjects were instructed to take test (pea protein + Pepzyme Pro) or placebo (pea protein + maltodextrin) for 15 days with a 30-day washout period. Blood samples were analyzed for plasma-free amino acids, insulin, and C-reactive protein (CRP). Additionally, nitrogen levels in urine and feces, along with the composition of gut microbiota, were evaluated. On day 15, the test arm showed a tendency to increase the rate of absorption and total absorption (AUC) of amino acids compared with the placebo arm, though the increase was statistically insignificant. In addition, 15-day test supplementation showed a tendency to reduce Tmax of all the amino acids (statistically insignificant except alanine, p = 0.021 and glycine, p = 0.023) in comparison with the placebo supplementation. There were no changes in urine and fecal nitrogen levels as well as serum CRP levels in the test and placebo arm. The increase in serum insulin level after 4 h was statistically significant in both arms, whereas the insulin level of the placebo and test arm at 4 h was not statistically different. Supplementation showed changes with respect to Archaea and few uncharacterized species but did not show statistically significant variations in microbiome profile at the higher taxonomic levels. A study with large sample size and detailed gut microbiome analysis is warranted to confirm the results statistically as well as to characterize altered species. However, the current study could provide an inkling of a positive alteration in protein digestibility, amino acid absorption, and gut microbiome with regular consumption of protein and enzymes-probiotics blend.

Clinical Trial Registration:clinicaltrials.gov/; identifier [CTRI/2021/10/037072].
A bibliometric analysis of the Fasting-Mimicking Diet
Authors: Lin Xiaoxiao , Gao Yue
Published: January 2024

The Fasting-Mimicking Diet (FMD) is a nutritional strategy that involves significantly reducing calorie intake for a specific period to mimic the physiological effects of fasting while still providing the body with nutrition. Our study aimed to conduct a bibliometric study to explore the latest publishing trends and areas of intense activity within the sphere of FMD. We extracted data on FMD publications from the Web of Science Core Collection (WOSCC) database. The bibliometric analysis was conducted by WOSCC Online Analysis Platform and VOSviewer 1.6.16. In total, there were 169 publications by 945 authors from 342 organizations and 25 countries/regions, and published in 111 journals. The most productive country, organization, author, and journal were the United States, the University of Southern California, Valter D. Longo, and Nutrients, respectively. The first high-cited document was published in Ageing Research Reviews and authored by Mattson et al. In this study, they discuss the various health benefits of FMD including improved metabolic health, weight management, and even potential effects on delaying aging processes and reducing the risk of chronic diseases. In conclusion, our study is the first bibliometric analysis of the FMD. The main research hotspots and frontiers were FMD for cancer, FMD for metabolic-related diseases, and FMD for cognitive improvement. FMD may have some potential benefits for multiple diseases which should be further investigated.
Effectiveness and safety of the bevacizumab and erlotinib combination versus erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis
Authors: Motta-Guerrero Rodrigo , Leon Garrido-Lecca Alejandro , Failoc-Rojas Virgilio E. , Calle-Villavicencio Ana , Villacorta-Carranza Robert , Huerta-Collado Yesenia , Torres-Mera Alicia , Valladares-Garrido Mario J. , Rivera-Francia Víctor , Carracedo Carlos , Raez Luis
Published: January 2024

Background

The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC.

Methods

Using eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis.

Results

The bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54–0.73, p < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64–0.97, p = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78–1.10, p = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76–6.88, p = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs.

Conclusions

The bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.
Community implementation of a brief parent mediated intervention for toddlers with probable or confirmed autism spectrum disorder: feasibility, acceptability, and drivers of success (IE Drmic et al.)
Authors: Drmic Irene , Brian Jessica , Roncadin Caroline , Shaver Chantelle , Pase Marlene , Rugajs Natalie , Tofano Kristina , Dowds Erin , Zwaigenbaum Lonnie , Smith Isabel M. , Bryson Susan E.
Published: January 2024

Background

Social ABCs is a caregiver-mediated Naturalistic Developmental Behavioral Intervention for toddlers with confirmed/suspected Autism Spectrum Disorder (ASD), with evidence in controlled research settings. Information is lacking on implementation in community settings. We reported on the treatment effectiveness of this program within a community setting, and the current paper describes the implementation phase of this work. Distinguishing between treatment and implementation effectiveness is critical for transporting interventions from laboratory to community.

Objectives

Describe the implementation of Social ABCs through a large public autism service, supported by a research-community partnership.

Methods

We describe this project through the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as it focuses on implementation of evidence-based practices in publicly funded services. We apply this framework to the reporting stage. This project took place in the context of a 3-year government-funded pilot at a hospital-based publicly funded autism service. Participants: Program developers; Autism Service team; toddlers with suspected/confirmed ASD aged 14–34 months (M = 25.18 months) and their caregivers. Training/supervision: Provided by program developers at tapering intensity. Evaluation: Caregivers completed the Caregiver Diary and satisfaction surveys. We explored training processes, intervention uptake, acceptability, adaptations to fit community context, appropriateness, perceived impact, and facilitators/barriers.

Results

Six coaches were trained to fidelity, and three of these were further trained as Site Trainers. 183 clinically referred families enrolled and 89.4% completed the 12-week program. Caregivers reported increases in adherence and competence, high satisfaction and perceived benefits for their children. Coaches reported high satisfaction. Toddlers were appropriately identified to receive the intervention. Referral processes improved, including decreased referral age, and increased family readiness for diagnostic assessment and subsequent services.

Conclusions

Social ABCs was successfully implemented in a community service through a research-community partnership. The program was feasible, acceptable, and appropriate within a community context. Drivers of success included funding, institutional support, shared decision-making, adaptations to fit context, leadership support, perceived positive impact, and commitment to evaluation.
Unravelling the role of Sildenafil and SB204741 in suppressing fibrotic potential of peritoneal fibroblasts obtained from PD patients
Authors: Chaturvedi Saurabh , Singh Harshit , Agarwal Vikas , Jaiswal Akhilesh , Prasad Narayan
Published: January 2024

Introduction: Peritoneal fibrosis (PF) results in technique failure in peritoneal dialysis (PD) patients. Peritoneal fibroblasts are characterized by increase in the ACTA2 gene, responsible for alpha smooth muscle actin (α−SΜΑ), extracellular matrix (ECM) production, and inflammatory cytokines production, which are the are key mediators in the pathogenesis of PF. 5-hydroxytryptamine (5-HT; serotonin) induces ECM synthesis in fibroblasts in a transforming growth factor-beta 1 (TGF-β1) dependent manner. The purpose of our study was to identify the potential mechanism and role of sildenafil and 5HT2B receptor inhibitor (SB204741) combination in attenuating PD-associated peritoneal fibrosis.

Methods: Studies were performed to determine the effect of TGF-β1, sildenafil, and SB204741 on human peritoneal fibroblasts (HPFBs) isolated from the parietal peritoneum of patients in long-term PD patients (n = 6) and controls (n = 6). HPFBs were incubated with TGF-β1 (10 ng/mL) for 1 h and later with TGF-β1 (10 ng/mL)/[sildenafil (10 µM) or SB204741 (1 µM)] and their combination for 24 h (post-treatment strategy). In the pre-treatment strategy, HPFBs were pre-treated with sildenafil (10 µM) or SB204741 (1 µM) and a combination of the two for 1 h and later with only TGF-β1 (10 ng/mL) for 24 h.

Results: The anti-fibrotic effects of the combination of sildenafil and SB204741 were greater than that of each drug alone. In TGF-β1-stimulated HPFBs, pro-fibrotic genes (COL1A1, COL1A2, ACTA2, CTGF, FN1, and TGFB1) exhibited higher expression than in controls, which are crucial targets of sildenafil and SB204741 against peritoneal fibrosis. The synergistic approach played an anti-fibrotic role by regulating the pro- and anti-fibrotic gene responses as well as inflammatory cytokine responses. The combination treatment significantly attenuated peritoneal fibrosis, as evident by the almost complete amelioration of ACTA2 expression, restoration of anti-fibrotic genes (MMP2/TIMP1), and, at least, by reducing the expression of pro-inflammatory cytokines (IFN-γ, IL-4, IL-17, IL-1β, IL-6, TNF-α, and TGF-β1) along with an increase in IL-10 levels.

Discussion: Taken together, the above research evidences that the combination of sildenafil and SB204741 may have therapeutic potential in suppressing peritoneal fibrosis due to peritoneal dialysis.
The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model
Authors: Xu Nan , Ijaz Muhammad , Shu Yishuo , Wang Peng , Ma Lei , Wang Ping , Ding Hailing , Shahbaz Muhammad , Shi Haiyan
Published: January 2024

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients’ clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia.

Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice.

Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect.

Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD’s maximal therapeutic response, there existed a hysteresis. WDD’s effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats.

Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.
Effectiveness and economic evaluation of rhTPO and rhIL-11 in the treatment of cancer therapy induced thrombocytopenia based on real-world research
Authors: Gong Fa-Min , Liu Fu-Yue , Ma Xue , Ma Song-Tao , Xiao Hong-Tao , Jiang Gang , Qi Ting-Ting
Published: January 2024

Objective: Based on real-world research, we aimed to evaluate the effectiveness and economy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin 11 (rhIL-11) in the treatment of cancer therapy induced thrombocytopenia (CTIT).

Methods: We retrospectively collected clinical data of patients with CTIT who were treated with rhTPO or rhIL-11 in a single cancer hospital from January 2020 to December 2021. Propensity score matching (PSM) was applied to eliminate confounding factors. The measurements of effectiveness analysis were the platelet compliance rate, days of medication, days of compliance, highest platelet count after medication, platelet count elevation before and after medication, and the lowest platelet count after next-cycle cancer therapy. The economic evaluation was performed according to the results of the effectiveness evaluation. At the same time, patients were stratified according to type of tumor and grade of thrombocytopenia for subgroup analysis.

Results: A total of 262 patients were collected and 174 patients were enrolled after PSM, 87 in the rhTPO group and 87 in the rhIL-11 group. In all patients, there were no significant differences in the platelet compliance rate, mean days of medication, median days of compliance, median highest platelet count after medication, and the median platelet count elevation before and after medication between the two groups (p > 0.05), but the median lowest platelet count after next-cycle cancer therapy in the rhTPO group was lower than that in the rhIL-11 group (p = 0.014). The subgroup analysis showed that the rhTPO group had longer mean days of medication than the rhIL-11 group in patients with hematological malignancies (p = 0.042), and a lower median lowest platelet count after next-cycle cancer therapy in patients with grade I/II thrombocytopenia than rhIL-11 group (p = 0.022), with no significant difference in other outcome indicators (p > 0.05). As there was no statistically significant difference in platelet compliance rate between the two groups, the cost-minimization analysis showed that the rhIL-11 group had lower treatment costs than the rhTPO group.

Conclusion: RhTPO and rhIL-11 showed similar effectiveness in the treatment of CTIT, but rhIL-11 was more advantageous in economic cost.