bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: associations with neonatal white matter microstructure
Authors: Sanders Ashley F. P. , Tirado Brian , Seider Nicole A. , Triplett Regina L. , Lean Rachel E. , Neil Jeffrey J. , Miller J. Philip , Tillman Rebecca , Smyser Tara A. , Barch Deanna M. , Luby Joan L. , Rogers Cynthia E. , Smyser Christopher D. , Warner Barbara B. , Chen Edith , Miller Gregory E.
Published: February 2024

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation’s effects on white matter development diverge depending on the availability of foundational resources in utero.
MFSD7c functions as a transporter of choline at the blood–brain barrier
Authors: Nguyen Xuan Thi Anh , Le Thanh Nha Uyen , Nguyen Toan Q. , Thi Thuy Ha Hoa , Artati Anna , Leong Nancy C. P. , Nguyen Dat T. , Lim Pei Yen , Susanto Adelia Vicanatalita , Huang Qianhui , Fam Ling , Leong Lo Ngah , Bonne Isabelle , Lee Angela , Granadillo Jorge L. , Gooch Catherine , Yu Dejie , Huang Hua , Soong Tuck Wah , Chang Matthew Wook , Wenk Markus R. , Adamski Jerzy , Cazenave-Gassiot Amaury , Nguyen Long N.
Published: February 2024

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c–/–) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood–brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c–/–embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c–/– embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.
A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle
Authors: Park Junsun , Kim Hyunmin , Gestaut Daniel , Lim Seyeon , Opoku-Nsiah Kwadwo A. , Leitner Alexander , Frydman Judith , Roh Soung-Hun
Published: February 2024

Proper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate folding of essential eukaryotic proteins. Using cryoEM and biochemical analyses, we determine the ATP-driven cycle of TRiC-PFD-PhLP2A interaction. PhLP2A binds to open apo-TRiC through polyvalent domain-specific contacts with its chamber’s equatorial and apical regions. PhLP2A N-terminal H3-domain binding to subunits CCT3/4 apical domains displace PFD from TRiC. ATP-induced TRiC closure rearranges the contacts of PhLP2A domains within the closed chamber. In the presence of substrate, actin and PhLP2A segregate into opposing chambers, each binding to positively charged inner surface residues from CCT1/3/6/8. Notably, actin induces a conformational change in PhLP2A, causing its N-terminal helices to extend across the inter-ring interface to directly contact a hydrophobic groove in actin. Our findings reveal an ATP-driven PhLP2A structural rearrangement cycle within the TRiC chamber to facilitate folding.
Molecular-level architecture of Chlamydomonas reinhardtii’s glycoprotein-rich cell wall
Authors: Poulhazan Alexandre , Arnold Alexandre A. , Mentink-Vigier Frederic , Muszyński Artur , Azadi Parastoo , Halim Adnan , Vakhrushev Sergey Y. , Joshi Hiren Jitendra , Wang Tuo , Warschawski Dror E. , Marcotte Isabelle
Published: February 2024

Microalgae are a renewable and promising biomass for large-scale biofuel, food and nutrient production. However, their efficient exploitation depends on our knowledge of the cell wall composition and organization as it can limit access to high-value molecules. Here we provide an atomic-level model of the non-crystalline and water-insoluble glycoprotein-rich cell wall of Chlamydomonas reinhardtii. Using in situ solid-state and sensitivity-enhanced nuclear magnetic resonance, we reveal unprecedented details on the protein and carbohydrate composition and their nanoscale heterogeneity, as well as the presence of spatially segregated protein- and glycan-rich regions with different dynamics and hydration levels. We show that mannose-rich lower-molecular-weight proteins likely contribute to the cell wall cohesion by binding to high-molecular weight protein components, and that water provides plasticity to the cell-wall architecture. The structural insight exemplifies strategies used by nature to form cell walls devoid of cellulose or other glycan polymers.
Understanding the AIE phenomenon of nonconjugated rhodamine derivatives via aggregation-induced molecular conformation change
Authors: Yang Lin-Lin , Wang Haoran , Zhang Jianyu , Wu Bo , Li Qiyao , Chen Jie-Ying , Tang A-Ling , Lam Jacky W. Y. , Zhao Zheng , Yang Song , Tang Ben Zhong
Published: February 2024

The bottom-up molecular science research paradigm has greatly propelled the advancement of materials science. However, some organic molecules can exhibit markedly different properties upon aggregation. Understanding the emergence of these properties and structure-property relationship has become a new research hotspot. In this work, by taking the unique closed-form rhodamines-based aggregation-induced emission (AIE) system as model compounds, we investigated their luminescent properties and the underlying mechanism deeply from a top-down viewpoint. Interestingly, the closed-form rhodamine-based AIE system did not display the expected emission behavior under high-viscosity or low-temperature conditions. Alternatively, we finally found that the molecular conformation change upon aggregation induced intramolecular charge transfer emission and played a significant role for the AIE phenomenon of these closed-form rhodamine derivatives. The application of these closed-form rhodamine-based AIE probe in food spoilage detection was also explored.
Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma
Authors: Zeng Ling-Hui , Tang Chao , Yao Minli , He Qiangqiang , Qv Meiyu , Ren Qianlei , Xu Yana , Shen Tingyu , Gu Weizhong , Xu Chengyun , Zou Chaochun , Ji Xing , Wu Ximei , Wang Jirong
Published: February 2024

Aberrant activation of sonic hedgehog (SHH) signaling and its effector transcriptional factor GLI1 are essential for oncogenesis of SHH-dependent medulloblastoma (MBSHH) and basal cell carcinoma (BCC). Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1’s proteasomal degradation and negates the transcription of SHH signaling. As a result, Gli1S941E loss-of-function knock-in significantly reduces the incidence and severity of smoothened-M2 transgene-induced spontaneous MBSHH, whereas Gli1S941A gain-of-function knock-in phenocopies Gli1 transgene in causing BCC-like proliferation in skin. Correspondingly, phospho-Ser937-GLI1, a destabilized form of GLI1, positively correlates to the overall survival rate of children with MBSHH. Together, these findings indicate that SHH-induced p38α inactivation and subsequent GLI1 dephosphorylation and stabilization in controlling SHH signaling and may provide avenues for future interventions of MBSHH and BCC.
Distribution of Pt single atom coordination environments on anatase TiO2 supports controls reactivity
Authors: Zang Wenjie , Lee Jaeha , Tieu Peter , Yan Xingxu , Graham George W. , Tran Ich C. , Wang Peikui , Christopher Phillip , Pan Xiaoqing
Published: February 2024

Single-atom catalysts (SACs) offer efficient metal utilization and distinct reactivity compared to supported metal nanoparticles. Structure-function relationships for SACs often assume that active sites have uniform coordination environments at particular binding sites on support surfaces. Here, we investigate the distribution of coordination environments of Pt SAs dispersed on shape-controlled anatase TiO2 supports specifically exposing (001) and (101) surfaces. Pt SAs on (101) are found on the surface, consistent with existing structural models, whereas those on (001) are beneath the surface after calcination. Pt SAs under (001) surfaces exhibit lower reactivity for CO oxidation than those on (101) surfaces due to their limited accessibility to gas phase species. Pt SAs deposited on commercial-TiO2 are found both at the surface and in the bulk, posing challenges to structure-function relationship development. This study highlights heterogeneity in SA coordination environments on oxide supports, emphasizing a previously overlooked consideration in the design of SACs.
Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a)
Authors: Marlęga-Linert Joanna , Gąsecka Aleksandra , van der Pol Edwin , Kuchta Agnieszka , Filipiak Krzysztof J. , Fijałkowski Marcin , Gruchała Marcin , Nieuwland Rienk , Mickiewicz Agnieszka
Published: February 2024

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter >  ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% – 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8–54.7); p = 0.005], 42.6% [(29.7–54.1); p = 0.030] and 26.7% [(1.0–62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.
Towards Room Temperature Thermochromic Coatings with controllable NIR-IR modulation for solar heat management & smart windows applications
Authors: Khanyile B. S. , Numan N. , Simo A. , Nkosi M. , Mtshali C. B. , Khumalo Z. , Madiba I. G. , Mabakachaba B. , Swart H. , Coetsee-Hugo E. , Duvenhage Mart-Mari , Lee E. , Henini M. , Gibaud A. , Chaker M. , Rezaee P. , Lethole N. , Akbari M. , Morad R. , Maaza M.
Published: February 2024

Solar heat management & green air-conditioning are among the major technologies that could mitigate heat islands phenomenon while minimizing significantly the CO2 global foot-print within the building & automotive sectors. Chromogenic materials in general, and thermochromic smart coatings especially are promising candidates that consent a noteworthy dynamic solar radiation Infrared (NIR-IR) regulation and hence an efficient solar heat management especially with the expected increase of the global seasonal temperature. Within this contribution, two major challenging bottlenecks in vanadium oxide based smart coatings were addressed. It is validated for the first time that the NIR-IR modulation of the optical transmission (∆TTRANS = T(T〈TMIT) − T(T〉TMIT) of Vanadium oxide based smart coatings can be controlled & tuned. This upmost challenging bottle-neck controllability/tunability is confirmed via a genuine approach alongside to a simultaneous drastic reduction of the phase transition temperature TMIT from 68.8 °C to nearly room temperature. More precisely, a substantial thermochromism in multilayered V2O5/V/V2O5 stacks equivalent to that of standard pure VO2 thin films but with a far lower transition temperature, is reported. Such a multilayered V2O5/V/V2O5 thermochromic system exhibited a net control & tunability of the optical transmission modulation in the NIR-IR (∆TTRANS) via the nano-scaled thickness’ control of the intermediate Vanadium layer. In addition, the control of ∆TTRANS is accompanied by a tremendous diminution of the thermochromic transition temperature from the elevated bulk value of 68.8 °C to the range of 27.5–37.5 ºC. The observed remarkable and reversible thermochromism in such multilayered nano-scaled system of V2O5/V/V2O5 is likely to be ascribed to a noteworthy interfacial diffusion, and an indirect doping by alkaline ions diffusing from the borosilicate substrate. It is hoped that the current findings would contribute in advancing thermochromic smart window technology and their applications for solar heat management in glass windows in general, skyscraper especially & in the automotive industry. If so, this would open a path to a sustainable green air-conditioning with zero-energy input.
A comprehensive DNA barcoding of Indian freshwater fishes of the Indus River system, Beas
Authors: Modeel Sonakshi , Negi Ram Krishan , Sharma Monika , Dolkar Padma , Yadav Sheetal , Siwach Sneha , Yadav Pankaj , Negi Tarana
Published: February 2024

The Beas River is one of the important rivers of the Indus River system located in Himachal Pradesh, India, that harbors a diverse range of freshwater fish species. The present study employed COI gene to investigate the ichthyofaunal diversity of river Beas. Through the sequencing of 203 specimens from Beas River, we identified 43 species, belonging to 31 genera, 16 families, and 10 orders. To analyze the genetic divergence and phylogeny of identified species, 485 sequences of Indian origin were retrieved from BOLD, resulting in a dataset of 688 sequences. Our findings consistently revealed a hierarchical increase in the mean K2P genetic divergence within species (0.80%), genus (9.06%), and families (15.35%). Automated Barcode Gap discovery, Neighbour Joining, and Bayesian inference consensus tree methodologies were employed to determine the putative species and their phylogeny, successfully delimiting most of the species with only a few exceptions. The results unveiled six species exhibiting high intra-species divergence (> 2%), suggesting the presence of sibling species and falsely identified sequences on online databases. The present study established the first DNA barcoding-based inventory of freshwater fish species in the Beas River providing comprehensive insights into economically exploited endangered and vulnerable species. In order to ensure the sustainable use of aquatic resources in the Beas River, we recommend the implementation of species measures to protect biodiversity and genetic resources.
Integration of Swin UNETR and statistical shape modeling for a semi-automated segmentation of the knee and biomechanical modeling of articular cartilage
Authors: Kakavand Reza , Palizi Mehrdad , Tahghighi Peyman , Ahmadi Reza , Gianchandani Neha , Adeeb Samer , Souza Roberto , Edwards W. Brent , Komeili Amin
Published: February 2024

Simulation studies, such as finite element (FE) modeling, provide insight into knee joint mechanics without patient involvement. Generic FE models mimic the biomechanical behavior of the tissue, but overlook variations in geometry, loading, and material properties of a population. Conversely, subject-specific models include these factors, resulting in enhanced predictive precision, but are laborious and time intensive. The present study aimed to enhance subject-specific knee joint FE modeling by incorporating a semi-automated segmentation algorithm using a 3D Swin UNETR for an initial segmentation of the femur and tibia, followed by a statistical shape model (SSM) adjustment to improve surface roughness and continuity. For comparison, a manual FE model was developed through manual segmentation (i.e., the de-facto standard approach). Both FE models were subjected to gait loading and the predicted mechanical response was compared. The semi-automated segmentation achieved a Dice similarity coefficient (DSC) of over 98% for both the femur and tibia. Hausdorff distance (mm) between the semi-automated and manual segmentation was 1.4 mm. The mechanical results (max principal stress and strain, fluid pressure, fibril strain, and contact area) showed no significant differences between the manual and semi-automated FE models, indicating the effectiveness of the proposed semi-automated segmentation in creating accurate knee joint FE models. We have made our semi-automated models publicly accessible to support and facilitate biomechanical modeling and medical image segmentation efforts (https://data.mendeley.com/datasets/k5hdc9cz7w/1).
A novel iterative detection method based on a lattice reduction-aided algorithm for MIMO OFDM systems
Authors: Liu Haitao , Cheng Xuchao , Li Wenqing , Feng Fan , Wang Liguo , Xiao Ying , Fu Shiqi
Published: February 2024

The lattice reduction-aided algorithm has received broad attention from researchers since it operates as a maximum likelihood receiver with better system performance for multiple-input multiple-output orthogonal frequency division multiplexing systems and contains a full diversity. A novel iterative detection algorithm canceling parallel iterations that employ the lattice reduction-aided approach is proposed. Soft information is exchanged through the detector itself. Its iteration occurs inside the detector, which reduces much of the exchange cost between the multiple-input multiple-output orthogonal frequency division multiplexing detector and the turbo decoder. Since the parallel interference cancellation algorithm is constrained by the accuracy of the initial value of the detection, it is easy to form error propagation after several iterations. Due to the lattice reduction-aided algorithm, its performance is approximated with the maximum likelihood algorithm. Therefore, the lattice reduction-aided algorithm is introduced into the parallel interference cancellation algorithm to make its detection algorithm more accurate and overcome the effect of error propagation in the manuscript. Simulation results indicate that the proposed algorithm leads to an improvement of 0.8–2 dB when the bit error rate is set to 10–4 when compared to other algorithms.
Zinc oxide resveratrol nanoparticles ameliorate testicular dysfunction due to levofloxacin-induced oxidative stress in rats
Authors: Zaki Naglaa F. , Orabi Sahar H. , Abdel-Bar Hend Mohamed , Elbaz Hamed T. , Korany Reda M. S. , Ismail Ayman K. , Daoush Walid M. , Abduljabbar Maram H. , Alosaimi Manal E. , Alnemari Reem M. , Mahboub Heba H. , Ahmed Mohamed M.
Published: February 2024

The present work is aimed to assess the protective influence of zinc oxide resveratrol nanoparticles against oxidative stress-associated testicular dysfunction. The number of 50 male albino rats were randomly separated into five groups (n = 10): Group I, control: rats gavage distilled water orally; Group II, Levofloxacin: rats that administered Levofloxacin (LFX) softened in distilled water at a dosage of 40 mg/kg−1 BW orally every other day; Group III, Zn-RSV: rats administered with Zn-RSV (zinc oxide resveratrol in distilled water at a dose 20 mg/kg−1 BW orally every other day; Group IV, (LFX + Zn-RSV): rats that were administered with Levofloxacin along with Zn-RSV nPs; Group V, Levofloxacin + Zn: rats were administered with Levofloxacin and Zno at a dose of 20 mg/kg−1 BW orally every other day as mentioned before. This study lasted for 2 months. Sera were collected to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone values. Testicular tissues were utilized to evaluate levels of superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and catalase (CAT). Semen samples were utilized to measure their quality (motility, concentration, and vitality). Histopathological and immune histochemical techniques investigated the morphological changes in the testis. Rats treated with Levofloxacin showed significantly lower levels of serum LH, testosterone, FSH, testicular enzymatic NO, catalase, SOD, BAX, and BCL-2 immune reactivity and sperm quality but significantly greater testicular malondialdehyde and caspase-3 immuno-reactivity Compared to both control and zinc oxide resveratrol treatment. Zinc oxide resveratrol nanoparticles ameliorated the harmful side effects of Levofloxacin. Improvements were more pronounced in the co-treatment (LFX + Zn-RSV) Zinc oxide resveratrol group than in the co-treatment (LFX + Zno) Zinc oxide group. Zinc oxide resveratrol nanoparticles could be a possible solution for levofloxacin oxidative stress-induced fertility problems.
Utilization and associated factors of cervical cancer screening service among eligible women attending maternal health services at Adare General Hospital, Hawassa city, Southern Ethiopia
Authors: Assefa Abiyu Ayalew , Feleke Tihun , G/Tsadik Sintayehu Assefa , Degela Fekadu , Zenebe Andualem , Abera Geleta
Published: February 2024

This particular study aimed to assess the magnitude of cervical cancer screening service utilization and associated factors among eligible women attending maternal health services at Adare General Hospital, Hawassa city, Southern Ethiopia, 2022. Institution-based cross-sectional study was conducted using a systematic random sampling technique among 299 eligible women from March 1- to April 30, 2022. Data was collected through face-to-face interviews using a pretested structured questionnaire. Data was also entered into Epi-data version 3.1 and exported to SPSS version 25.0 for analysis. Both bivariable and multi-variable logistic regression model was fitted and the presence of association was declared at a p value of less than 0.05. The strenth of association was determined using adjusted odd ratios together with a 95% confidence interval. Among interviewed women, 19.8% (95% CI 15.5%, 24.0%) of them had screened for cervical cancer at least once within the past five years. Place of residence (AOR = 0.37; 95% CI 0.14–0.96), modern contraception use (AOR = 2.49; 95% CI 1.04–5.96), discussion about cervical cancer with healthcare providers (AOR = 2.34; 95% CI 1.08–5.07), and comprehensive knowledge about cervical cancer (AOR = 0.25; 95% CI 0.10–0.62) were independently associated with cervical cancer screening service utilization. The study depicted relatively low utilization of cervical cancer screening services. The women were more likely to utilize the service if they are dwellers of urban residences, used modern contraception, had discussion about cervical cancer with healthcare providers, and had good comprehensive knowledge about cervical cancer. Thus, women living in rural areas should get more emphasis on cervical cancer prevention strategies, and improving consistent discussion about cervical cancer with clients visiting for maternal health services by healthcare providers in health facilities also be recommended.
Comparing a common clavicle maturation-based age estimation method to ordinary regression analyses with quadratic and sex-specific interaction terms in adolescents
Authors: Reder Sebastian R. , Fritzen Isabel , Brockmann Marc A. , Hardt Jochen , Elsner Katrin , Petrowski Katja , Bjelopavlovic Monika
Published: February 2024

Established methods of age estimation are based on correlating defined maturation stages of bony structures with tables representing the observed range of biological ages in the majority of cases. In this retrospective monocentric study in southwestern Germany, common age estimation methodology was assessed in n = 198 subjects at the age of 25 or younger by analyzing the influence of age, quadratic age, biological sex and age-sex interaction on the ossification stages of the medial epiphysis fugue. Three readers (ICC ≥ 0.81 for left/right side) evaluated routine care computed tomography images of the clavicle with a slice thickness of 1 mm. By using least square regression analyses, to determine the real biological age a quadratic function was determined corrected for the age estimated by established methods and sex (R2 = 0.6 each side), reducing the mean absolute error and root mean squared error in the age estimation of women (2.57 and 3.19) and men (2.57 and 3.47) to 1.54 and 1.82 for women, and 1.54 and 2.25 for men. In women, the medial clavicle epiphysis seem to fuse faster, which was particularly observable from approximately 18 years of age. Before that age, the estimation method was relatively close to the ideal correlation between assessed and real age. To conclude, the presented new method enables more precise age estimation in individuals and facilitates the determination and quantification of additional variables, quantifying their influence on the maturation of the medial clavicle epiphysis based on the established ossification stages.
Profiling the antibody response of humans protected by immunization with Plasmodium vivax radiation-attenuated sporozoites
Authors: Lopez-Perez Mary , Jain Aarti , Davies D. Huw , Vásquez-Jiménez Juan M. , Herrera Sonia M. , Oñate José , Felgner Philip L. , Herrera Sócrates , Arévalo-Herrera Myriam
Published: February 2024

Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the RTS, S and R21Matrix-M vaccines. Similar advances in P. vivax (Pv) vaccination have been elusive. We previously reported 42% (5/12) of sterile protection in malaria-unexposed, Duffy-positive (Fy +) volunteers immunized with PvRAS followed by a controlled human malaria infection (CHMI). Using a custom protein microarray displaying 515 Pv antigens, we found a significantly higher reactivity to PvCSP and one hypothetical protein (PVX_089630) in volunteers protected against P. vivax infection. In mock-vaccinated Fy + volunteers, a strong antibody response to CHMI was also observed. Although the Fy- volunteers immunized with non-irradiated Pv-infected mosquitoes (live sporozoites) did not develop malaria after CHMI, they recognized a high number of antigens, indicating the temporary presence of asexual parasites in peripheral blood. Together, our findings contribute to the understanding of the antibody response to P. vivax infection and allow the identification of novel parasite antigens as vaccine candidates.

Trial registration: ClinicalTrials.gov number: NCT 01082341.
Non-invasive 3D imaging of human melanocytic lesions by combined ultrasound and photoacoustic tomography: a pilot study
Authors: Kukk Anatoly Fedorov , Scheling Felix , Panzer Rüdiger , Emmert Steffen , Roth Bernhard
Published: February 2024

The accurate determination of the size and depth of infiltration is critical to the treatment and excision of melanoma and other skin cancers. However, current techniques, such as skin biopsy and histological examination, pose invasiveness, time-consumption, and have limitations in measuring at the deepest level. Non-invasive imaging techniques like dermoscopy and confocal microscopy also present limitations in accurately capturing contrast and depth information for various skin types and lesion locations. Thus, there is a pressing need for non-invasive devices capable of obtaining high-resolution 3D images of skin lesions. In this study, we introduce a novel device that combines 18 MHz ultrasound and photoacoustic tomography into a single unit, enabling the acquisition of colocalized 3D images of skin lesions. We performed in vivo measurements on 25 suspicious human skin nevi that were promptly excised following measurements. The combined ultrasound/photoacoustic tomography imaging technique exhibited a strong correlation with histological Breslow thickness between 0.2 and 3 mm, achieving a coefficient of determination (R$$^2$$2) of 0.93, which is superior to the coefficients from the individual modalities. The results procured in our study underscore the potential of combined ultrasound and photoacoustic tomography as a promising non-invasive 3D imaging approach for evaluating human nevi and other skin lesions. Furthermore, the system allows for integration of other optical modalities such as optical coherence tomography, microscopy, or Raman spectroscopy in future applications.
Comparison of preparation methods of rat kidney single-cell suspensions
Authors: Wang Tiantian , Shen Wanjun , Li Lin , Wang Haoran , Zhang Min , Chen Xiangmei
Published: February 2024

Preparation of kidney tissue single-cell suspensions is the basis of single-cell sequencing, flow cytometry and primary cell culture, but it is difficult to prepare high quality whole kidney single-cell suspensions because of the complex structure of the kidney. We explored a technique called stepwise enzymatic digestion (StE) method for preparing a single-cell suspension of rat whole kidney tissue which contained three main steps. The first step is to cut the kidney into a homogenate. The second step is the digestion of renal tubules using Multi Tissue Dissociation Kit 2 and the last step is the digestion of glomeruli using type IV collagenase. We also compared it with two previous techniques, mechanical grinding method and simple enzymatic digestion method. The StE method had the advantages of high intrinsic glomerular cells and immune cells harvest rate, high singlets rate and high cell viability compared with the other two techniques. In conclusion, the StE method is feasible, highly efficient, and worthy of further research and development.
Machine learning enables non-Gaussian investigation of changes to peripheral nerves related to electrical stimulation
Authors: Morales Andres W. , Du Jinze , Warren David J. , Fernández-Jover Eduardo , Martinez-Navarrete Gema , Bouteiller Jean-Marie C. , McCreery Douglas C. , Lazzi Gianluca
Published: February 2024

Electrical stimulation of the peripheral nervous system (PNS) is becoming increasingly important for the therapeutic treatment of numerous disorders. Thus, as peripheral nerves are increasingly the target of electrical stimulation, it is critical to determine how, and when, electrical stimulation results in anatomical changes in neural tissue. We introduce here a convolutional neural network and support vector machines for cell segmentation and analysis of histological samples of the sciatic nerve of rats stimulated with varying current intensities. We describe the methodologies and present results that highlight the validity of the approach: machine learning enabled highly efficient nerve measurement collection, while multivariate analysis revealed notable changes to nerves’ anatomy, even when subjected to levels of stimulation thought to be safe according to the Shannon current limits.
Potential benefits of climate change on navigation in the northern sea route by 2050
Authors: Mahmoud Mohamed Rami , Roushdi Mahmoud , Aboelkhear Mostafa
Published: February 2024

Climate change has been inducing a continuous increase in temperatures within the Arctic region, consequently leading to an escalation in the rates of Arctic ice depletion. These changes have profound implications for navigation along the Arctic Northern Sea Route (NSR). However, access to the NSR is constrained to specific temporal intervals when the sea ice thickness reaches a threshold that permits safe passage of ships. This research employs climate change model simulations and the Polar Operational Limit Assessment Risk Indexing System framework to investigate the navigational feasibility of diverse ship types along NSR during the calendar years 2030, 2040, and 2050, under SSP2-4.5 and SSP5-8.5 scenarios. Different ship categories were analyzed within the context of these two scenarios. Results indicate considerable variation in the navigability of different ship categories across different scenarios and years. In general, polar ships demonstrate a higher navigational potential throughout most of the year, while pleasure crafts are constrained to specific periods. These findings bear significant implications for the future of shipping along the NSR. As Arctic ice continues to melt, NSR is anticipated to become more accessible to ships, albeit with navigational availability remaining contingent on the ship category and seasonal considerations.
Determination of biomarker candidates for the placenta accreta spectrum by plasma proteomic analysis
Authors: Melekoglu Rauf , Yasar Seyma , Colak Cemil , Kasap Murat , Dogan Umran Karabulut , Yologlu Saim , Yilmaz Ercan , Shazly Sherif
Published: February 2024

Placenta accreta spectrum (PAS) presents a significant obstetric challenge, associated with considerable maternal and fetal-neonatal morbidity and mortality. Nevertheless, it is imperative to acknowledge that a noteworthy subset of PAS cases remains undetected until the time of delivery, thereby contributing to an augmented incidence of morbidity among the affected individuals. The delayed identification of PAS not only hinders timely intervention but also exacerbates the associated health risks for both the maternal and fetal outcomes. This underscores the urgency to innovate strategies for early PAS diagnosis. In this study, we aimed to explore plasma proteins as potential diagnostic biomarkers for PAS. Integrated transcriptome and proteomic analyses were conducted to establish a novel diagnostic approach. A cohort of 15 pregnant women diagnosed with PAS and delivering at Inonu University Faculty of Medicine between 01/04/2021 and 01/01/2023, along with a matched control group of 15 pregnant women without PAS complications, were enrolled. Plasma protein identification utilized enzymatic digestion and liquid chromatography-tandem mass spectrometry techniques. Proteomic analysis identified 228 plasma proteins, of which 85 showed significant differences (P < 0.001) between PAS and control cases. We refined this to a set of 20 proteins for model construction, resulting in a highly accurate classification model (96.9% accuracy). Notable associations were observed for proteins encoded by P01859 (Immunoglobulin heavy constant gamma 2), P02538 (Keratin type II cytoskeletal 6A), P29622 [Kallistatin (also known as Serpin A4)], P17900 (Ganglioside GM2 activator Calmodulin-like protein 5), and P01619 (Immunoglobulin kappa variable 3–20), with fold changes indicating their relevance in distinguishing PAS from control groups. In conclusion, our study has identified novel plasma proteins that could serve as potential biomarkers for early diagnosis of PAS in pregnant women. Further research and validation in larger PAS cohorts are necessary to determine the clinical utility and reliability of these proteomic biomarkers for diagnosing PAS.
The effect of periodic resistance training on obese patients with type 2 diabetic nephropathy
Authors: Li Sumei , Yuan Shouping , Zhang Jintian , Xu Feipeng , Zhu Feng
Published: February 2024

Resistance training is an exercise against resistance designed to train the endurance and strength of muscle. To observe the effect of intervention of periodic resistance training on obese patients with type 2 diabetic nephropathy. A total of 60 obese patients with type 2 diabetic nephropathy were randomized into resistance training group and aerobic exercise group (30 patients each group) for observing the changes of blood glucose, body weight, blood lipid, insulin resistance, serum creatinine (Scr), urinary microalbumin, urinary albumin excretion rate (UAER) calculated by urinary creatinine, and glomerular filtration rate (GFR) after 12 weeks of intervention, and relevant significance as well. The number of patients with hypoglycemia during the intervention was also recorded. After 12 weeks of intervention, the weight, Body mass index (BMI), Waist, Triglyceride (TG), Cholesterol (TC), Low-density lipoprotein cholesterol (LDL), Fasting glucose (FBG), Fasting insulin (FINS), Glycosylated hemoglobin (HbA1c) and urine Albumin–Creatinine Ratio (uACR) were decreased and GFR was increased in both groups (P < 0.05), but the effect was more significant in the resistance training group. GFR was increased from 92.21 ± 10.67 mL/(min·1.73 m2) to 100.13 ± 12.99 mL/(min·1.73 m2) in resistance training group (P < 0.05). In the aerobic exercise group, GFR was increased from 89.98 ± 9.48 mL/(min·1.73 m2) to 92.51 ± 11.35 mL/(min·1.73 m2) (P > 0.05). Periodic resistance training can not only control the weight, blood sugar and blood lipid of obese patients with type 2 diabetic nephropathy, but also improve the urinary albumin excretion rate and glomerular filtration rate of early obese patients with type 2 diabetic nephropathy, and delay the progression of diabetic nephropathy. It is an effective non-drug intervention.
Use of stable isotopes to reveal trophic relationships and transmission of a food-borne pathogen
Authors: Bouchard Émilie , Bonin Michaël , Sharma Rajnish , Hernández-Ortiz Adrián , Gouin Géraldine-G. , Simon Audrey , Leighton Patrick , Jenkins Emily
Published: February 2024

Predators in food webs are valuable sentinel species for zoonotic and multi-host pathogens such as Toxoplasma gondii. This protozoan parasite is ubiquitous in warm-blooded vertebrates, and can have serious adverse effects in immunocompromised hosts and foetuses. In northern ecosystems, T. gondii is disproportionately prevalent in Inuit people and wildlife, in part due to multiple routes of transmission. We combined data on T. gondii infection in foxes from Nunavik (northern Québec, Canada) with stable isotope data tracking trophic relationships between foxes and several of their main prey species. Red (Vulpes vulpes) and Arctic fox (Vulpes lagopus) carcasses were collected by local trappers from 2015 to 2019. We used magnetic capture PCR to detect DNA of T. gondii in heart and brain tissues, and enzyme-linked immunosorbent assay to detect antibodies in blood. By linking infection status with diet composition, we showed that infected foxes had a higher probability of consuming aquatic prey and migratory geese, suggesting that these may be important sources of T. gondii transmission in the Arctic. This use of stable isotopes to reveal parasite transmission pathways can be applied more broadly to other foodborne pathogens, and provides evidence to assess and mitigate potential human and animal health risks associated with T. gondii in northern ecosystems.
Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study
Authors: Nishioki Toshihiko , Sato Tadashi , Okajima Akifumi , Motomura Hiroaki , Takeshige Tomohito , Watanabe Junko , Yae Toshifumi , Koyama Ryo , Kido Kenji , Takahashi Kazuhisa
Published: February 2024

Various infection control measures implemented during the coronavirus disease (COVID-19) pandemic have reduced the number of respiratory infections, which are the most common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Here, we investigated whether infectious disease prevention during the COVID-19 pandemic reduced COPD exacerbations and the characteristics of patients exhibiting exacerbations before and during the COVID-19 pandemic. We included outpatients and inpatients with moderate or severe COPD exacerbations who required systemic steroids between April 1, 2018 and March 31, 2022. Their medical records were retrospectively compared and analyzed in 2-year intervals (before and during the COVID-19 pandemic). During the 4-year observation period, 70,847 outpatients and 2,772 inpatients were enrolled; 55 COPD exacerbations were recorded. The number of COPD exacerbations decreased from 36 before to 19 during the COVID-19 pandemic. Regarding the characteristics of patients with exacerbations, the % forced expiratory volume in one second (52.3% vs. 38.6%, P = 0.0224) and body mass index (BMI) (22.5 vs. 19.3, P = 0.0127) were significantly lower during the COVID-19 pandemic than before the pandemic. The number of COPD exacerbations during the pandemic decreased. Additionally, the tendency for a reduction in COPD exacerbation was greatest in patients with preserved lung function or above-standard BMI patients.
Relationship between residual visual field and full-field stimulus testing in patients with late-stage retinal degenerative diseases
Authors: Sakai Daiki , Maeda Tadao , Yamamoto Midori , Yokota Satoshi , Maeda Akiko , Hirami Yasuhiko , Nakamura Makoto , Kurimoto Yasuo , Mandai Michiko
Published: February 2024

This study aimed to investigate how the extent and central/peripheral location of the residual visual field (VF) in patients with late-stage inherited retinal diseases (IRDs) are related to retinal sensitivity detected using full-field stimulus testing (FST). We reviewed the results of Goldmann perimetry and FST from the medical records of patients with IRDs whose VF represents central (within 10°) and/or peripheral islands, or undetectable. In total, 19 patients (19 eyes) were analyzed in this study. The median value of residual VF area was 1.38%. The median values of rod and cone sensitivities were  − 14.9 dB and 7.4 dB, respectively. Patients with only the peripheral island (− 33.9 dB) had better median rod sensitivity than other groups (only central,  − 18.9 dB; both,  − 3.6 dB). VF area significantly correlated with rod sensitivity (r = − 0.943, p = 0.005) in patients with only peripheral island, but not with cone sensitivity. Peripheral VF islands were significant contributors to FST results, especially rod sensitivity. With reduced or loss of central vision, the extent of residual peripheral VF significantly affected rod sensitivity, suggesting that FST can be useful in quantitatively estimating the overall remaining vision in patients with late-stage IRD.
ATP-dependent conformational dynamics in a photoactivated adenylate cyclase revealed by fluorescence spectroscopy and small-angle X-ray scattering
Authors: Ujfalusi-Pozsonyi K. , Bódis E. , Nyitrai M. , Kengyel A. , Telek E. , Pécsi I. , Fekete Z. , Varnyuné Kis-Bicskei N. , Mas C. , Moussaoui D. , Pernot P. , Tully M. D. , Weik M. , Schirò G. , Kapetanaki S. M. , Lukács A.
Published: February 2024

Structural insights into the photoactivated adenylate cyclases can be used to develop new ways of controlling cellular cyclic adenosine monophosphate (cAMP) levels for optogenetic and other applications. In this work, we use an integrative approach that combines biophysical and structural biology methods to provide insight on the interaction of adenosine triphosphate (ATP) with the dark-adapted state of the photoactivated adenylate cyclase from the cyanobacterium Oscillatoria acuminata (OaPAC). A moderate affinity of the nucleotide for the enzyme was calculated and the thermodynamic parameters of the interaction have been obtained. Stopped-flow fluorescence spectroscopy and small-angle solution scattering have revealed significant conformational changes in the enzyme, presumably in the adenylate cyclase (AC) domain during the allosteric mechanism of ATP binding to OaPAC with small and large-scale movements observed to the best of our knowledge for the first time in the enzyme in solution upon ATP binding. These results are in line with previously reported drastic conformational changes taking place in several class III AC domains upon nucleotide binding.
Mn-promoted MoS2 catalysts for CO2 hydrogenation: enhanced methanol selectivity due to MoS2/MnOx interfaces
Authors: Alves Gustavo A. S. , Pacholik Gernot , Pollitt Stephan , Wagner Tobias , Rameshan Raffael , Rameshan Christoph , Föttinger Karin
Published: February 2024

Considering the alarming scenario of climate change, CO2 hydrogenation to methanol is considered a key process for phasing out fossil fuels by means of CO2 utilization.
Interconversion between multicomponent slider-on-deck and palladium capsule: regulation of catalysis and encapsulation
Authors: Valiyev Isa , Paul Indrajit , Li Yi-Fan , Elramadi Emad , Schmittel Michael
Published: February 2024

The full interconversion of a multicomponent slider-on-deck and a palladium(ii) capsule is used to establish the up/down regulation of a copper(i)-catalyzed aza Hopf cyclization that is reported by characteristic fluorescence changes.
Microporous transport layers facilitating low iridium loadings in polymer electrolyte water electrolysis
Authors: Weber Carl Cesar , De Angelis Salvatore , Meinert Robin , Appel Christian , Holler Mirko , Guizar-Sicairos Manuel , Gubler Lorenz , Büchi Felix N.
Published: February 2024

The 3D structure of the anodic catalyst layer in polymer electrolyte water electrolysis is characterized and its shown that Pt-coated microporous transport layers help to reduce iridium loadings by maximizing catalyst utilization.