bluuebunny/crossref_metadata_2025 huggingface dataset:
A missense mutation in Ehd1 associated with defective spermatogenesis and male infertility
Authors: Meindl Katrin , Issler Naomi , Afonso Sara , Cebrian-Serrano Alberto , Müller Karin , Sterner Christina , Othmen Helga , Tegtmeier Ines , Witzgall Ralph , Klootwijk Enriko , Davies Benjamin , Kleta Robert , Warth Richard
Published: October 2023

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.R398W) of EHD1 in patients who had low molecular weight proteinuria (0.7–2.1 g/d) and high-frequency hearing loss. It was already known from Ehd1 knockout mice that inactivation of Ehd1 can lead to male infertility. However, the exact role of the EHD1 protein and its p.R398W mutant during spermatogenesis remained still unclear. Here, we report the testicular phenotype of a knockin mouse model carrying the p.R398W mutation in the EHD1 protein. Male homozygous knockin mice were infertile, whereas the mutation had no effect on female fertility. Testes and epididymes were significantly reduced in size and weight. The testicular epithelium appeared profoundly damaged and had a disorganized architecture. The composition of developing cell types was altered. Malformed acrosomes covered underdeveloped and misshaped sperm heads. In the sperm tail, midpieces were largely missing indicating disturbed assembly of the sperm tail. Defective structures, i.e., nuclei, acrosomes, and sperm tail midpieces, were observed in large vacuoles scattered throughout the epithelium. Interestingly, cilia formation itself did not appear to be affected, as the axoneme and other parts of the sperm tails except the midpieces appeared to be intact. In wildtype mice, EHD1 co-localized with acrosomal granules on round spermatids, suggesting a role of the EHD1 protein during acrosomal development. Wildtype EHD1 also co-localized with the VPS35 component of the retromer complex, whereas the p.R398W mutant did not. The testicular pathologies appeared very early during the first spermatogenic wave in young mice (starting at 14 dpp) and tubular destruction worsened with age. Taken together, EHD1 plays an important and probably multifaceted role in spermatogenesis in mice. Therefore, EHD1 may also be a hitherto underestimated infertility gene in humans.
High-pressure reactions between the pnictogens: the rediscovery of BiN
Authors: Glazyrin K. , Aslandukov A. , Aslandukova A. , Fedotenko T. , Khandarkhaeva S. , Laniel D. , Bykov M. , Dubrovinsky L.
Published: October 2023

We explore chemical reactions within pnictogens with an example of bismuth and nitrogen under extreme conditions. Understanding chemical reactions between Bi and N, elements representing the first and the last stable elements of the nitrogen group, and the physical properties of their compounds under ambient and high pressure is far from being complete. Here, we report the high-pressure high-temperature synthesis of orthorhombic Pbcn BiN (S.G. #60) from Bi and N2 precursors at pressures above 40 GPa. Using synchrotron single-crystal X-ray diffraction on the polycrystalline sample, we solved and refined the compound’s structure and studied its behavior and compressibility on decompression to ambient pressure. We confirm the stability of Pbcn BiN to pressures as low as 12.5(4) GPa. Below that pressure value, a group–subgroup phase transformation occurs, resulting in the formation of a non-centrosymmetric BiN solid with a space group Pca21 (S.G. #29). We use ab initio calculations to characterize the polymorphs of BiN. They also provide support and explanation for our experimental observations, in particular those corresponding to peculiar Bi–N bond evolution under pressure, resulting in a change in the coordination numbers of Bi and N as a function of pressure within the explored stability field of Pbcn BiN.
Characteristics of the pulmonary microbiota in patients with mild and severe pulmonary infection
Authors: Zhan Danting , Li Dan , Yuan Ke , Sun Yihua , He Lijuan , Zhong Jiacheng , Wang Lingwei
Published: October 2023

Background

Lung infection is a global health problem associated with high morbidity and mortality and increasing rates of hospitalization. The correlation between pulmonary microecology and infection severity remains unclear. Therefore, the purpose of this study was to investigate the differences in lung microecology and potential biomarkers in patients with mild and severe pulmonary infection.

Method

Patients with pulmonary infection or suspected infection were divided into the mild group (140 cases) and the severe group (80 cases) according to pneomonia severity index (PSI) scores. Here, we used metagenomic next-generation sequencing (mNGS) to detect DNA mainly from bronchoalveolar lavage fluid (BALF) collected from patients to analyze changes in the lung microbiome of patients with different disease severity.

Result

We used the mNGS to analyze the pulmonary microecological composition in patients with pulmonary infection. The results of alpha diversity and beta diversity analysis showed that the microbial composition between mild and severe groups was similar on the whole. The dominant bacteria were Acinetobacter, Bacillus, Mycobacterium, Staphylococcus, and Prevotella, among others. Linear discriminant analysis effect size (LEfSe) results showed that there were significant differences in virus composition between the mild and severe patients, especially Simplexvirus and Cytomegalovirus, which were prominent in the severe group. The random forest model screened 14 kinds of pulmonary infection-related pathogens including Corynebacterium, Mycobacterium, Streptococcus, Klebsiella, and Acinetobacter. In addition, it was found that Rothia was negatively correlated with Acinetobacter, Mycobacterium, Bacillus, Enterococcus, and Klebsiella in the mild group through co-occurrence network, while no significant correlation was found in the severe group.

Conclusion

Here, we describe the composition and diversity of the pulmonary microbiome in patients with pulmonary infection. A significant increase in viral replication was found in the severe group, as well as a significant difference in microbial interactions between patients with mild and severe lung infections, particularly the association between the common pathogenic bacteria and Rothia. This suggests that both pathogen co-viral infection and microbial interactions may influence the course of disease. Of course, more research is needed to further explore the specific mechanisms by which microbial interactions influence disease severity.
Reactive oxidant species induced by antifungal drugs: identity, origins, functions, and connection to stress-induced cell death
Authors: Gonzalez-Jimenez Irene , Perlin David S. , Shor Erika
Published: October 2023

Reactive oxidant species (ROS) are unstable, highly reactive molecules that are produced by cells either as byproducts of metabolism or synthesized by specialized enzymes. ROS can be detrimental, e.g., by damaging cellular macromolecules, or beneficial, e.g., by participating in signaling. An increasing body of evidence shows that various fungal species, including both yeasts and molds, increase ROS production upon exposure to the antifungal drugs currently used in the clinic: azoles, polyenes, and echinocandins. However, the implications of these findings are still largely unclear due to gaps in knowledge regarding the chemical nature, molecular origins, and functional consequences of these ROS. Because the detection of ROS in fungal cells has largely relied on fluorescent probes that lack specificity, the chemical nature of the ROS is not known, and it may vary depending on the specific fungus-drug combination. In several instances, the origin of antifungal drug-induced ROS has been identified as the mitochondria, but further experiments are necessary to strengthen this conclusion and to investigate other potential cellular ROS sources, such as the ER, peroxisomes, and ROS-producing enzymes. With respect to the function of the ROS, several studies have shown that they contribute to the drugs’ fungicidal activities and may be part of drug-induced programmed cell death (PCD). However, whether these “pro-death” ROS are a primary consequence of the antifungal mechanism of action or a secondary consequence of drug-induced PCD remains unclear. Finally, several recent studies have raised the possibility that ROS induction can serve an adaptive role, promoting antifungal drug tolerance and the evolution of drug resistance. Filling these gaps in knowledge will reveal a new aspect of fungal biology and may identify new ways to potentiate antifungal drug activity or prevent the evolution of antifungal drug resistance.
Maternal beliefs about infant-directed speech misalign with interactions with their infants
Authors: Ramirez Alexus G. , Herbst Elana , Golinkoff Roberta Michnick
Published: October 2023

Introduction

Infant-directed speech (IDS) refers to how people in many societies talk with young children. Compared to speech directed to an adult (ADS), IDS includes a slower rate, fewer words per utterance, higher-than-average pitch, and elongated vowels. Although many benefits are associated with using IDS, there is little information on what parents think about IDS. The current study asked: (1) How do mothers conceptualize IDS; (2) Is there an alignment between mothers' IDS beliefs and their speech register when teaching a new word to their child; and (3) How do mothers' IDS beliefs associate with children's expressive language and performance on a word learning task?

Methods

Fifty-three mothers and their 15- to 21-month-old monolingual English-reared infants (Mage = 17.92, SD = 1.99, 23 males) participated. Mothers were asked to teach their child a novel word and to complete the Parent Language Belief Questionnaire (PLBQ). Mothers' IDS was recorded as they taught their child a novel word and was compared to their ADS from interacting with the experimenter.

Results

Findings revealed that mothers had mixed beliefs about their use of IDS. Yet, most mothers used IDS as they taught their child a novel word. Lastly, mothers' IDS beliefs did not predict children's language skills or word learning at test.

Discussion

The current study is the first to explore whether mothers' beliefs about their use of infant-directed speech align with their actual use of IDS. As the positive benefits between IDS and children's language development have been documented, identifying the barriers surrounding why parents may not use IDS with their children is essential.
Construction of a deltaic strandplain during the Roman period in the Tavoliere di Puglia plain and palaeoclimatic implications
Authors: De Santis Vincenzo , Scicchitano Giovanni , Scardino Giovanni , Mele Daniela , Sulpizio Roberto , Colangelo Giuseppe , Zingaro Marina , Antonino Natasha Luigia , Tomaselli Valeria , Caldara Massimo
Published: October 2023

In response to the accidental exhumation of three ancient trees by farmers, we conducted a multidisciplinary study based on the stratigraphic analysis of boreholes, carbon-14 dating, aerial photo interpretation, and analysis of palaeobotanical and archaeological evidences. We reconstructed the formation and evolution during Roman times of a first “continuous” and then “discontinuous” deltaic strandplain at the mouth of the Carapelle Stream in the Tavoliere di Puglia Plain—the second-largest plain in Italy. Ttwo main phases can be recognised in the evolution of the Carapelle deltaic strandplain: 1) a first phase, lasted until ca. the birth of Christ, was characterised by a regular and continuous construction of sand ridges one leaning against the other; 2) a second phase, lasted more or less from the birth of Christ to the termination of the construction of the deltaic strandplain, was characterised by the discontinuous construction of sand ridges/coastal barriers with the isolation of lagoons/ponds, and by evidences of alluvial events. The most probable climatic–environmental scenario to have formed the Roman-period deltaic strandplain implied that: 1) the first phase was triggered by a higher total amount of precipitations, but with less extreme alluvial events; 2) the second phase was triggered by a total amount of precipitation lower than the previous period, but with higher occurrence of extreme alluvial events and/or by extreme alluvial events separated by longer period of low precipitations. This second phase was enhanced by the opening of vegetation. The passage between the first and second phase of the Carapelle deltaic strandplain coincides with the passage from overall negative NAO index to an overall positive NAO index.
Biology in a social context: a comprehensive analysis of humanization in introductory biology textbooks
Authors: Meuler Madison , Lee Jiae , Foutch Katherine , Al-Khayat Noor , Boukouzis Katerina , Christensen Priya , Crooks Carmella , Hassanain Lubna M. , Karimi Parnian , Kim Galina V. , Randall Alyssa , Redford Ingrid K. , Socko Rita , Theobald Elli J.
Published: October 2023

To grapple with the sterility and Whiteness of Western science, scholars have proposed a pedagogical shift to culturally relevant and/or culturally sustaining pedagogy. A key tenet of culturally relevant pedagogy is a focus on developing students’ ability to use the knowledge they obtain to identify, analyze, and solve real-world problems. Thus, the ability to foster this consciousness among students and make justice/injustice visible within biology curricula is an act of humanization. Here, we characterize and quantify the extent to which six prominent introductory biology US-based textbooks include humanizing content. First, we built consensus on what it means to humanize biology in a textbook by iteratively revising a coding protocol until we achieved a continuum of humanization. Our continuum evaluates the quantity, location, and the nature of the humanizing element within the textbook. Then, we used the continuum to collect data through qualitative coding: each chapter of each textbook was coded by two coders who came to consensus on the humanizing elements within. We find that in general, the inclusion of humanizing content in introductory biology textbooks is rare: of the 9,670 pages of textbooks that we analyzed, we found 1,352 humanizing passages but the vast majority of these were discussed in a single sentence (23%) or multiple sentences (61%), rarely multiple paragraphs (13%) or entire sections (2%). Similarly, of the 9,262 questions in the books (e.g., in section or chapter summaries), only 2.5% of them were humanizing and of those, only (64%) provided an answer, and of the ones that provided an answer, we only coded 42% of the answers as humanizing. In addition to quantifying the amount of humanization, we also describe the ways in which the passages were presented. For example, only about 9% of the humanizing passages included nuance, 5% discussed equity/inequity, and only 4% positioned biology as a means to accomplish justice. In all, we present what we believe is the most comprehensive assessment of humanizing elements in introductory biology textbooks and pair that with specific guidance to instructors who seek to include humanizing elements in their classes.
Genetic predisposition of the gastrointestinal microbiome and primary biliary cholangitis: a bi-directional, two-sample Mendelian randomization analysis
Authors: Luo Xin , You Xin
Published: October 2023

Background

The gut-liver axis indicates a close relationship between the gastrointestinal microbiome (GM) and primary biliary cholangitis (PBC). However, the causality of this relationship remains unknown. This study investigates the causal relationship between the GM and PBC using a bidirectional, two-sample Mendelian randomization (MR) analysis.

Methods

Genome-wide association data for GM and PBC were obtained from public databases. The inverse-variance weighted method was the primary method used for MR analysis. Sensitivity analyses were conducted to assess the stability of the MR results. A reverse MR analysis was performed to investigate the possibility of reverse causality.

Results

Three bacterial taxa were found to be causally related to PBC. Class Coriobacteriia (odds ratio (OR) = 2.18, 95% confidence interval (CI): 1.295-3.661, P< 0.05) and order Coriobacteriales (OR = 2.18, 95% CI: 1.295-3.661, P<0.05) were associated with a higher risk of PBC. Class Deltaproteobacteria (OR = 0.52, 95% CI: 0.362–0.742, P< 0.05) had a protective effect on PBC. There was no evidence of reverse causality between PBC and the identified bacterial taxa.

Conclusion

Previously unrecognized taxa that may be involved in the pathogenesis of PBC were identified in this study, confirming the causality between the GM and PBC. These results provide novel microbial targets for the prevention and treatment of PBC.
Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol
Authors: Chen Fei , Matsuda Aiko , Budinger G. R. Scott , Sporn Peter H. S. , Casalino-Matsuda S. Marina
Published: October 2023

Patients with chronic lung disease, obesity, and other co-morbid conditions are at increased risk of severe illness and death when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hypercapnia, the elevation of CO2 in blood and tissue, commonly occurs in patients with severe acute and chronic lung disease, including those with pulmonary infections, and is also associated with high mortality risk. We previously reported that hypercapnia increases viral replication and mortality of influenza A virus infection in mice. We have also shown that culture in elevated CO2 upregulates expression of cholesterol synthesis genes in primary human bronchial epithelial cells. Interestingly, factors that increase the cholesterol content of lipid rafts and lipid droplets, platforms for viral entry and assembly, enhance SARS-CoV-2 infection. In the current study, we investigated the effects of hypercapnia on ACE2 expression and entry of SARS-CoV-2 pseudovirus (p-SARS-CoV-2) into airway epithelial cells. We found that hypercapnia increased ACE2 expression and p-SARS-CoV-2 uptake by airway epithelium in mice, and in cultured VERO and human bronchial epithelial cells. Hypercapnia also increased total cellular and lipid raft-associated cholesterol in epithelial cells. Moreover, reducing cholesterol synthesis with inhibitors of sterol regulatory element binding protein 2 (SREBP2) or statins, and depletion of cellular cholesterol, each blocked the hypercapnia-induced increases in ACE2 expression and p-SARS-CoV-2 entry into epithelial cells. Cigarette smoke extract (CSE) also increased ACE2 expression, p-SARS-CoV-2 entry and cholesterol accumulation in epithelial cells, an effect not additive to that of hypercapnia, but also inhibited by statins. These findings reveal a mechanism that may account, in part, for poor clinical outcomes of SARS-CoV-2 infection in patients with advanced lung disease and hypercapnia, and in those who smoke cigarettes. Further, our results suggest the possibility that cholesterol-lowering therapies may be of particular benefit in patients with hypercapnia when exposed to or infected with SARS-CoV-2.
Dysregulation of circulating T follicular helper cell subsets and their potential role in the pathogenesis of syphilis
Authors: Shen Fuping , Shen Yuhuan , Xu Yuni , Zhao Jiwei , Zhao Zhao , Liu Jinlin , Ge Yumei
Published: October 2023

Introduction

The role of the host immune response could be critical in the development of Treponema pallidum (Tp) infection in individuals with latent syphilis. This study aims to investigate the alterations in T follicular helper T (Tfh) cell balance among patients with secondary syphilis and latent syphilis.

Methods

30 healthy controls (HCs), 24 secondary syphilis patients and 41 latent syphilis patients were enrolled. The percentages of total Tfh, ICOS+ Tfh, PD-1+ Tfh, resting Tfh, effector Tfh, naïve Tfh, effector memory Tfh, central memory Tfh,Tfh1, Tfh2, and Tfh17 cells in the peripheral blood were all determined by flow cytometry.

Results

The percentage of total Tfh cells was significantly higher in secondary syphilis patients compared to HCs across various subsets, including ICOS+ Tfh, PD-1+ Tfh, resting Tfh, effector Tfh, naïve Tfh, effector memory Tfh, central memory Tfh, Tfh1, Tfh2, and Tfh17 cells. However, only the percentages of ICOS+ Tfh and effector memory Tfh cells showed significant increases in secondary syphilis patients and decreases in latent syphilis patients. Furthermore, the PD-1+ Tfh cells, central memory Tfh cells, and Tfh2 cells showed significant increases in latent syphilis patients, whereas naïve Tfh cells and Tfh1 cells exhibited significant decreases in secondary syphilis patients when compared to the HCs. However, no significant change was found in resting Tfh and effector Tfh in HCs and secondary syphilis patients or latent syphilis patients.

Discussion

Dysregulated ICOS+ Tfh or effector memory Tfh cells may play an important role in immune evasion in latent syphilis patients.
Case Report: The many faces of bullous pemphigoid
Authors: Rechtien Laura , Sollfrank Lukas , Foerster Yannick , Berking Carola , Sticherling Michael
Published: October 2023

The pemphigoid group comprises a number of bullous skin diseases with autoantibodies against different constituents of the basement membrane zone that result in subepidermal detachment and clinically characteristic tense blisters, erosions, urticarial erythema, and itching. Apart from the most frequent type of bullous pemphigoid with antibodies against BP180, which is found predominantly in elderly patients, the disease may present at other ages and different pathogenic conditions. Here, four cases are presented of young age (3 months and 25, 34, and 46 years) and in association with vaccination, pregnancy, or metastatic cancer. Though anti-BP180 was found in all cases, a different pathogenic background may be found in any of them, resulting in characteristic clinical manifestation, yet demanding specifically adapted therapeutic approaches.
Cellular immune response to SARS-CoV-2 in patients with primary antibody deficiencies
Authors: Mizera Dorota , Dziedzic Radosław , Drynda Anna , Gradzikiewicz Ada , Jakieła Bogdan , Celińska-Löwenhoff Magdalena , Padjas Agnieszka , Matyja-Bednarczyk Aleksandra , Zaręba Lech , Bazan-Socha Stanisława
Published: October 2023

Introduction

Primary antibody deficiencies (PAD) are inborn defects of the immune system that result in increased susceptibility to infections. Despite the reduced response to vaccination, PAD patients still benefit from it by reducing the risk of severe infections and complications. SARS-CoV-2 vaccines are recommended in PAD patients, but their immune effects are poorly studied. Here, we analyze virus-specific T-cell responses in PAD patients after booster vaccination against SARS-CoV-2.

Patients and methods

The study included 57 adult PAD patients on long-term immunoglobulin replacement therapy (IgRT) diagnosed with X-linked agammaglobulinemia (XLA; n = 4), common variable immunodeficiency (CVID; n = 33), isotype defects or IgG subclass deficiency (n = 6), and unclassified IgG deficiency (n = 14). Of those, 49 patients (86%) received vaccination against SARS-CoV-2 using mRNA vaccine (Pfizer-BioNTech). T-cell responses were assessed at a median of 21 (13 – 30) weeks after the booster dose (mainly the third dose) using commercially available interferon-gamma release assay (IGRA) with recombinant SARS-CoV-2 spike S1 protein.

Results

Vaccinated PAD patients showed an increased (3.8-fold, p = 0.004) release of IFN-γ upon S1 stimulation. In this group, we also documented higher serum levels of anti-SARS-CoV-2 IgG (4.1-fold, p = 0.01), although they were not associated with IGRA results. Further subgroup analysis revealed very similar IGRA responses in CVID and unclassified IgG deficiencies that were 2.4-fold increased compared to XLA and 5.4-fold increased compared to patients with isotype defects or IgG subclass deficiencies (e.g., vs. CVID: p = 0.016). As expected, CVID and XLA patients showed decreased serum titers of anti-SARS-CoV-2 antibodies compared to other studied groups (e.g., CVID vs. unclassified IgG deficiency: 4.4-fold, p = 0.006). The results did not depend directly on IgRT mode or dose, number of vaccine doses and time from the last booster dose, and clinical manifestations of PAD. Interestingly, anti-SARS-CoV-2 titers were positively correlated with serum immunoglobulin levels before IgRT (e.g., for IgA: r = 0.45, p<0.001; for IgG: r = 0.34, p = 0.009) and the percentage of peripheral blood NK cells (r = 0.48, p<0.001).

Conclusions

Our results documented satisfactory in vitro cellular immune response in PAD patients after booster SARS-CoV-2 vaccination. Therefore, even patients with agammaglobulinemia should benefit from vaccination due to the apparent induction of cell-mediated immunity, which, together with IgRT, grants comprehensive protection against the pathogen.
Synthesis strategies of iron nitrides at carbon cloth as battery-like electrode for hybrid supercapacitors
Authors: Kordek-Khalil Karolina , Moyseowicz Adam , Moyseowicz Agata K.
Published: October 2023

In recent years, hybrid supercapacitors (HSCs) or supercapatteries which combine a capacitor-type electrode with an electrode based on materials exhibiting a Faradaic (battery-like) response have been intensively investigated for next-generation energy storage applications. HSCs attracted great attention due to a significant increase of maximum energy density stored while providing stable long-term performance and good rate capability. However, the electrochemical performance of the device is closely related to the inherent properties of the electrode material, including morphology and structure. In this paper, we present synthesis protocols for iron oxide/hydrophilic carbon cloth (Fe2O3@hCC) composite electrodes and their electrochemical performance as a negative electrode operating in an alkaline electrolyte. Two environmentally friendly, scalable and facile synthesis approaches were applied, including hydrothermal treatment and direct electrodeposition. Next, the Fe2O3@hCC electrodes were treated to convert iron oxide to iron nitride (Fe2N). The results showed that the synthesis of the precursor for iron nitride has a direct impact on morphology, crystalline structure and electrochemical performance. Furthermore, the amorphous Fe2N obtained from electrodeposition exhibited significantly better Faradaic behavior, achieving a specific capacity up to 186 mAh g-1, 66% higher than the composite electrode with Fe2N from the hydrothermal approach.
Section optimization design of UHPC beam bridges based on improved particle swarm optimization
Authors: Li Beian , Li Yongsi , Liu Xiang , Liu Xianlin , Zhu Siwen , Ke Lu
Published: October 2023

Ultra-high performance concrete has excellent mechanical properties such as ultra-high strength and high durability, and has a broad application prospect in the field of bridge engineering. To make full use of the superior mechanical properties of UHPC and reduce the cost of the bridge, the particle swarm optimization algorithm is used to optimize the structural design of the UHPC beam bridge; Aiming at the problem that the traditional particle swarm optimization algorithm is easy to fall into local optimum, the nonlinear adaptive weight update method is used to improve the particle swarm optimization algorithm. Based on the above-mentioned improved particle swarm optimization algorithm, the optimal design method of ordinary reinforced UHPC beams and prestressed UHPC beams with commonly used highway spans is studied. The reliability of the optimized structural limit state is analyzed by Monte Carlo (MC) importance sampling method. The results show that compared with the traditional particle swarm optimization algorithm, the improved particle swarm optimization algorithm has higher convergence speed and convergence accuracy. The optimal height-span ratio of ordinary reinforced UHPC beams decreases with the increase of the span, and the construction cost gradually increases; The optimal height-span ratio of the prestressed beam decreases first and then increases with the increase of the span, and the construction cost gradually increases. The calculation results of load capacity reliability indexes of optimization results are all higher than the target reliability indexes of similar components stipulated in China’s “Uniform Standard for Structural Reliability Design of Highway Engineering”.
The protective performance of rubber pads for penetration fuze
Authors: Ding Libo , Zhang An , Peng Junwei , Li Changsheng
Published: October 2023

To ensure the reliable functioning of hard target-penetration fuze on the battlefield, this study focuses on research related to fuze protective pads. The main factors causing fuze functional failure are summarized, and a simplified model of projectile penetration into target plates is established. The design conditions for the yield stress parameter of the fuze casing material are derived based on stress wave propagation theory. Modal analysis of the projectile is conducted using dynamic simulation software ANSYS to determine its vibration modes and low-pass filtering frequency. Static compression experiments are performed on different rubber materials (nitrile rubber, fluorine rubber, silicone rubber, and natural rubber) to obtain stress–strain curves and constitutive model parameters. Marshall hammer tests were carried out on rubber pads of different materials and thicknesses, confirming the validity of the simulation results and the feasibility of rubber filtering. The study indicates that when using a 2 mm thick rubber pad for protection, natural rubber provides the best protection. When using a 6 mm thick rubber pad, nitrile rubber shows the best protective performance. Under a 13-tooth tooling impact load, the best protection is achieved using a 2 mm thick natural rubber pad. When using a 6 mm thick pad, silicone rubber provides the best protection. Under a 15-tooth tooling impact load, fluorine rubber provides the best protection when using a 2 mm thick pad, while silicone rubber offers the best protection when using a 6 mm thick pad. Under a 17-tooth tooling impact load, natural rubber offers the best protection when using a 2 mm thick pad, and fluorine rubber demonstrates the best protection when using a 6 mm thick pad. The obtained research results provide a reference for protective methods of hard target-penetration fuze.
Principles, applications, and future of artificial intelligence in dermatology
Authors: Omiye Jesutofunmi A. , Gui Haiwen , Daneshjou Roxana , Cai Zhuo Ran , Muralidharan Vijaytha
Published: October 2023

This paper provides an overview of artificial-intelligence (AI), as applied to dermatology. We focus our discussion on methodology, AI applications for various skin diseases, limitations, and future opportunities. We review how the current image-based models are being implemented in dermatology across disease subsets, and highlight the challenges facing widespread adoption. Additionally, we discuss how the future of AI in dermatology might evolve and the emerging paradigm of large language, and multi-modal models to emphasize the importance of developing responsible, fair, and equitable models in dermatology.
A di-electrophoretic simulation procedure of iron-oxide micro-particle drug attachment system for leukemia treatment using COMSOL software: a potential treatment reference for LMICs
Authors: Kiwumulo Henry Fenekansi , Muwonge Haruna , Ibingira Charles , Lubwama Michael , Kirabira John Baptist , Ssekitoleko Robert Tamale
Published: October 2023

Background

Leukemia encompasses various subtypes, each with unique characteristics and treatment approaches. The challenge lies in developing targeted therapies that can effectively address the specific genetic mutations or abnormalities associated with each subtype. Some leukemia cases may become resistant to existing treatments over time making them less susceptible to chemotherapy or other standard therapies.

Objective

Developing new treatment strategies to overcome resistance is an ongoing challenge particularly in Low and Middle Income Countries (LMICs). Computational studies using COMSOL software could provide an economical, fast and resourceful approach to the treatment of complicated cancers like leukemia.

Methods

Using COMSOL Multiphysics software, a continuous flow microfluidic device capable of delivering anti-leukemia drugs to early-stage leukemia cells has been computationally modeled using dielectrophoresis (DEP).

Results

The cell size difference enabled the micro-particle drug attachment to the leukemia cells using hydrodynamic focusing from the dielectrophoretic force. This point of care application produced a low voltage from numerically calculated electrical field and flow speed simulations.

Conclusion

Therefore, such a dielectrophoretic low voltage application model can be used as a computational treatment reference for early-stage leukemia cells with an approximate size of 5 μm.
Effects of nutrient injection on the Xinjiang oil field microbial community studied in a long core flooding simulation device
Authors: Cheng Wei , Fan Huiqiang , Yun Yuan , Zhao Xueqing , Su Zhaoying , Tian Xuefeng , Liu Dakun , Ma Ting , Li Guoqiang
Published: October 2023

Microbial Enhanced Oil Recovery (MEOR) is an option for recovering oil from depleted reservoirs. Numerous field trials of MEOR have confirmed distinct microbial community structure in diverse production wells within the same block. The variance in the reservoir microbial communities, however, remains ambiguously documented. In this study, an 8 m long core microbial flooding simulation device was built on a laboratory scale to study the dynamic changes of the indigenous microbial community structure in the Qizhong Block, Xinjiang oil field. During the MEOR, there was an approximate 34% upswing in oil extraction. Based on the 16S rRNA gene high-throughput sequencing, our results indicated that nutrition was one of the factors affecting the microbial communities in oil reservoirs. After the introduction of nutrients, hydrocarbon oxidizing bacteria became active, followed by the sequential activation of facultative anaerobes and anaerobic fermenting bacteria. This was consistent with the hypothesized succession of a microbial ecological “food chain” in the reservoir, which preliminarily supported the two-step activation theory for reservoir microbes transitioning from aerobic to anaerobic states. Furthermore, metagenomic results indicated that reservoir microorganisms had potential functions of hydrocarbon degradation, gas production and surfactant production. Understanding reservoir microbial communities and improving oil recovery are both aided by this work.
Adaptive laboratory evolution of a thermophile toward a reduced growth temperature optimum
Authors: Lehmann Maria , Prohaska Christoph , Zeldes Benjamin , Poehlein Anja , Daniel Rolf , Basen Mirko
Published: October 2023

Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as adaptations, somewhat implying that they evolved from a non-thermophilic background and that thermophiles, i.e., organisms with growth temperature optima (TOPT) above 45°C, evolved from mesophilic organisms (TOPT 25–45°C). On the contrary, it has also been argued that LUCA, the last universal common ancestor of Bacteria and Archaea, may have been a thermophile, and mesophily is the derived trait. In this study, we took an experimental approach toward the evolution of a mesophile from a thermophile. We selected the acetogenic bacterium T. kivui (TOPT 66°C) since acetogenesis is considered ancient physiology and cultivated it at suboptimal low temperatures. We found that the lowest possible growth temperature (TMIN) under the chosen conditions was 39°C. The bacterium was subsequently subjected to adaptive laboratory evolution (ALE) by serial transfer at 45°C. Interestingly, after 67 transfers (approximately 180 generations), the adapted strain Adpt45_67 did not grow better at 45°C, but a shift in the TOPT to 60°C was observed. Growth at 45°C was accompanied by a change in the morphology as shorter, thicker cells were observed that partially occurred in chains. While the proportion of short-chain fatty acids increased at 50°C vs. 66°C in both strains, Adpt45_67 also showed a significantly increased proportion of plasmalogens. The genome analysis revealed 67 SNPs compared to the type strain, among these mutations in transcriptional regulators and in the cAMP binding protein. Ultimately, the molecular basis of the adaptation of T. kivui to a lower TOPT remains to be elucidated. The observed change in phenotype is the first experimental step toward the evolution of thermophiles growing at colder temperatures and toward a better understanding of the cold adaptation of thermophiles on early Earth.
Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population
Authors: Kim Bo-Hyun , Lee HyunWoo , Ham Hongki , Kim Hee Jin , Jang Hyemin , Kim Jun Pyo , Park Yu Hyun , Kim Mansu , Seo Sang Won
Published: October 2023

Amyloid-beta (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). We aimed to identify genes related to Aβ uptake in the Korean population and investigate the effects of these novel genes on clinical outcomes, including neurodegeneration and cognitive impairments. We recruited a total of 759 Korean participants who underwent neuropsychological tests, brain magnetic resonance imaging, 18F-flutemetamol positron emission tomography, and microarray genotyping data. We performed gene-based association analysis, and also performed expression quantitative trait loci and network analysis. In genome-wide association studies, no single nucleotide polymorphism (SNP) passed the genome-wide significance threshold. In gene-based association analysis, six genes (LCMT1, SCRN2, LRRC46, MRPL10, SP6, and OSBPL7) were significantly associated with Aβ standardised uptake value ratio in the brain. The three most significant SNPs (rs4787307, rs9903904, and rs11079797) on these genes are associated with the regulation of the LCMT1, OSBPL7, and SCRN2 genes, respectively. These SNPs are involved in decreasing hippocampal volume and cognitive scores by mediating Aβ uptake. The 19 enriched gene sets identified by pathway analysis included axon and chemokine activity. Our findings suggest novel susceptibility genes associated with the uptake of Aβ, which in turn leads to worse clinical outcomes. Our findings might lead to the discovery of new AD treatment targets.
The AMPK activator metformin improves recovery from demyelination by shifting oligodendrocyte bioenergetics and accelerating OPC differentiation
Authors: Narine Mohanlall , Azmi Maryam A. , Umali Martin , Volz Ashley , Colognato Holly
Published: October 2023

Multiple Sclerosis (MS) is a chronic disease characterized by immune-mediated destruction of myelinating oligodendroglia in the central nervous system. Loss of myelin leads to neurological dysfunction and, if myelin repair fails, neurodegeneration of the denuded axons. Virtually all treatments for MS act by suppressing immune function, but do not alter myelin repair outcomes or long-term disability. Excitingly, the diabetes drug metformin, a potent activator of the cellular “energy sensor” AMPK complex, has recently been reported to enhance recovery from demyelination. In aged mice, metformin can restore responsiveness of oligodendrocyte progenitor cells (OPCs) to pro-differentiation cues, enhancing their ability to differentiate and thus repair myelin. However, metformin’s influence on young oligodendroglia remains poorly understood. Here we investigated metformin’s effect on the temporal dynamics of differentiation and metabolism in young, healthy oligodendroglia and in oligodendroglia following myelin damage in young adult mice. Our findings reveal that metformin accelerates early stages of myelin repair following cuprizone-induced myelin damage. Metformin treatment of both isolated OPCs and oligodendrocytes altered cellular bioenergetics, but in distinct ways, suppressing oxidative phosphorylation and enhancing glycolysis in OPCs, but enhancing oxidative phosphorylation and glycolysis in both immature and mature oligodendrocytes. In addition, metformin accelerated the differentiation of OPCs to oligodendrocytes in an AMPK-dependent manner that was also dependent on metformin’s ability to modulate cell metabolism. In summary, metformin dramatically alters metabolism and accelerates oligodendroglial differentiation both in health and following myelin damage. This finding broadens our knowledge of metformin’s potential to promote myelin repair in MS and in other diseases with myelin loss or altered myelination dynamics.
Usability and utility of a remote monitoring system to support physiotherapy for people with Parkinson's disease
Authors: van den Bergh Robin , Evers Luc J. W. , de Vries Nienke M. , Silva de Lima Ana L. , Bloem Bastiaan R. , Valenti Giulio , Meinders Marjan J.
Published: October 2023

Background

Physiotherapy for persons with Parkinson's disease (PwPD) could benefit from objective and continuous tracking of physical activity and falls in daily life.

Objectives

We designed a remote monitoring system for this purpose and describe the experiences of PwPD and physiotherapists who used the system in daily clinical practice.

Methods

Twenty-one PwPD (15 men) wore a sensor necklace to passively record physical activity and falls for 6 weeks. They also used a smartphone app to self-report daily activities, (near-)falls and medication intake. They discussed those data with their PD-specialized physiotherapist (n= 9) during three regular treatment sessions. User experiences and aspects to be improved were gathered through interviews with PwPD and physiotherapists, resulting in system updates. The system was evaluated in a second pilot with 25 new PwPD (17 men) and eight physiotherapists.

Results

We applied thematic analysis to the interview data resulting in two main themes: usability and utility. First, the usability of the system was rated positively, with the necklace being easy to use. However, some PwPD with limited digital literacy or cognitive impairments found the app unclear. Second, the perceived utility of the system varied among PwPD. While many PwPD were motivated to increase their activity level, others were not additionally motivated because they perceived their activity level as high. Physiotherapists appreciated the objective recording of physical activity at home and used the monitoring of falls to enlarge awareness of the importance of falls for PwPD. Based on the interview data of all participants, we drafted three user profiles for PwPD regarding the benefits of remote monitoring for physiotherapy: for profile 1, a monitoring system could act as a flagging dashboard to signal the need for renewed treatment; for profile 2, a monitoring system could be a motivational tool to maintain physical activity; for profile 3, a monitoring system could passively track physical activity and falls at home. Finally, for a subgroup of PwPD the burdens of monitoring will outweigh the benefits.

Conclusions

Overall, both PwPD and physiotherapists underline the potential of a remote monitoring system to support physiotherapy by targeting physical activity and (near-)falls. Our findings emphasize the importance of personalization in remote monitoring technology, as illustrated by our user profiles.
Feasibility of common, enjoyable game play for assessing daily cognitive functioning in older adults
Authors: Schwab Nadine , Wu Chao-Yi , Galler Jake , DeRamus Thomas , Ford Abaigeal , Gerber Jessica , Kitchen Robert , Rashid Barnaly , Riley Misha , Sather Lauren , Wang Xifeng , Young Cathrine , Yang Liuqing , Dodge Hiroko H. , Arnold Steven E.
Published: October 2023

Background

Frequent digital monitoring of cognition is a promising approach for assessing endpoints in prevention and treatment trials of Alzheimer’s disease and related dementias (ADRD). This study evaluated the feasibility of the MIND GamePack© for recurrent semi-passive assessment of cognition across a longitudinal interval.

Methods

The MIND GamePack consists of four iPad-based games selected to be both familiar and enjoyable: Word Scramble, Block Drop, FreeCell, and Memory Match. Participants were asked to play 20 min/day for 5 days (100 min) for 4 months. Feasibility of use by older adults was assessed by measuring gameplay time and game performance. We also evaluated compliance through semi-structured surveys. A linear generalized estimating equation (GEE) model was used to analyze changes in gameplay time, and a regression tree model was employed to estimate the days it took for game performance to plateau. Subjective and environmental factors associated with gameplay time and performance were examined, including daily self-reported questions of memory and thinking ability, mood, sleep, energy, current location, and distractions prior to gameplay.

Results

Twenty-six cognitively-unimpaired older adults participated (mean age ± SD = 71.9 ± 8.6; 73% female). Gameplay time remained stable throughout the 4-months, with an average compliance rate of 91% ± 11% (1946 days of data across all participants) and weekly average playtime of 210 ± 132 min per participant. We observed an initial learning curve of improving game performance which on average, plateaued after 22–39 days, depending on the game. Higher levels of self-reported memory and thinking ability were associated with more gameplay time and sessions.

Conclusion

MIND GamePack is a feasible and well-designed semi-passive cognitive assessment platform which may provide complementary data to traditional neuropsychological testing in research on aging and dementia.
Greater hemodynamic stresses initiate aneurysms on major cerebral arterial bifurcations
Authors: Guo Hao , Liu Jian-Feng , Li Cong-Hui , Wang Ji-Wei , Li Hui , Gao Bu-Lang
Published: October 2023

Objective

To retrospectively investigate the hemodynamic stresses in initiating aneurysm formation on major cerebral arterial bifurcations with computational fluid dynamics (CFD) analysis.

Methods

The cerebral 3D angiographic data of major cerebral arterial bifurcations of the internal carotid, middle cerebral, anterior cerebral, and basilar arteries in 80 patients harboring bifurcation aneurysms and 80 control subjects with no aneurysms were retrospectively collected for the CFD analysis of hemodynamic stresses associated with aneurysm formation.

Results

Bifurcation angles at major bifurcations in all patients were significantly positively (P < 0.001) correlated with the age. At the center of direct flow impingement (CDFI) on the bifurcation wall, total pressure was the highest but dropped rapidly toward the branches. Wall shear stress, dynamic pressure, strain rate, and vorticity were lowest at the CDFI but they increased quickly toward the branches. The bifurcation angle was significantly (P < 0.001) enlarged in patients with bifurcation aneurysms than those without them, for all major arterial bifurcations. Most aneurysms leaned toward the smaller arterial branch or the arterial branch that formed a smaller angle with the parent artery, where the hemodynamic stresses increased significantly (P < 0.05), compared with those on the contralateral arterial branch forming a larger angle with the parent artery. Following the aneurysm development, all the hemodynamic stresses on the aneurysm dome decreased significantly (P < 0.001) compared with those at the initiation site on the bifurcation wall after virtual aneurysm removal. With the decrease of bifurcation angles, all the hemodynamic stresses decreased.

Conclusion

The formation of intracranial aneurysms on major intracranial arterial bifurcations is significantly associated with locally abnormally augmented hemodynamic stresses, which must be reduced.