bluuebunny/crossref_metadata_2025 huggingface dataset:
The Resistance of Soybean Variety Heinong 84 to Apple Latent Spherical Virus Is Controlled by Two Genetic Loci
Authors: Ma Tingshuai , Zhang Ying , Li Yong , Zhao Yu , Attiogbe Kekely Bruno , Fan Xinyue , Fan Wenqian , Sun Jiaxing , Luo Yalou , Yu Xinwei , Ji Weiqin , Cheng Xiaofei , Wu Xiaoyun
Published: February 2024

Apple latent spherical virus (ALSV) is widely used as a virus-induced gene silencing (VIGS) vector for function genome study. However, the application of ALSV to soybeans is limited by the resistance of many varieties. In this study, the genetic locus linked to the resistance of a resistant soybean variety Heinong 84 was mapped by high-throughput sequencing-based bulk segregation analysis (HTS–BSA) using a hybrid population crossed from Heinong 84 and a susceptible variety, Zhonghuang 13. The results showed that the resistance of Heinong 84 to ALSV is controlled by two genetic loci located on chromosomes 2 and 11, respectively. Cleaved amplified polymorphic sequence (CAPS) markers were developed for identification and genotyping. Inheritance and biochemical analyses suggest that the resistance locus on chromosome 2 plays a dominant dose-dependent role, while the other locus contributes a secondary role in resisting ALSV. The resistance locus on chromosome 2 might encode a protein that can directly inhibit viral proliferation, while the secondary resistance locus on chromosome 11 may encode a host factor required for viral proliferation. Together, these data reveal novel insights on the resistance mechanism of Heinong 84 to ALSV, which will benefit the application of ALSV as a VIGS vector.
Metabolite Biomarkers for Early Ischemic–Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model
Authors: Shevtsova Yulia , Starodubtseva Natalia , Tokareva Alisa , Goryunov Kirill , Sadekova Alsu , Vedikhina Irina , Ivanetz Tatiana , Ionov Oleg , Frankevich Vladimir , Plotnikov Egor , Sukhikh Gennady , Zorov Dmitry , Silachev Denis
Published: February 2024

Hypoxic–ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice–Vannucci model of HIE in rats. We evaluated the diagnostic fidelity of this approach in a range between 3 and 6 h after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 h of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.
Does Telotristat Have a Role in Preventing Carcinoid Heart Disease?
Authors: Herrera-Martínez Aura D. , Fuentes-Fayos Antonio C. , Sanchez-Sanchez Rafael , Montero Antonio J. , Sarmento-Cabral André , Gálvez-Moreno María A. , Gahete Manuel D. , Luque Raúl M.
Published: February 2024

Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin production. Telotristat use in patients with carcinoid syndrome and uncontrollable diarrhea under somatostatin analogs is approved, but its specific role in patients with CHD is still not clear. IN this context, we aimed to explore the effect of telotristat in heart fibrosis using a mouse model of serotonin-secreting metastasized neuroendocrine neoplasm (NEN). To this aim, four treatment groups (n = 10/group) were evaluated: control, monthly octreotide, telotristat alone, and telotristat combined with octreotide. Plasma serotonin and NT-proBNP levels were determined. Heart fibrosis was histologically evaluated after 6 weeks of treatment or when an individual mouse’s condition was close to being terminal. Heart fibrosis was observed in all groups. Non-significant reductions in primary tumor growth were observed in all of the treated groups. Feces volume was increased in all groups. A non-significant decrease in feces volume was observed in the octreotide or telotristat-treated groups, while it was significantly reduced with the combined treatment at the end of the study compared with octreotide (52 g reduction; p < 0.01) and the control (44.5 g reduction; p = 0.05). Additionally, plasma NT-proBNP decreased in a non-significant, but clinically relevant, manner in the octreotide (28.2% reduction), telotristat (45.9% reduction), and the octreotide + telotristat (54.1% reduction) treatment groups. No significant changes were observed in plasma serotonin levels. A similar non-significant decrease in heart valve fibrosis was observed in the three treated groups. In conclusion, Telotristat alone and especially in combination with octreotide decreases NT-proBNP levels in a mouse model of serotonin-secreting metastasized NEN, when compared with the control and octreotide, but its effect on heart valve fibrosis (alone and in combination) was not superior to octreotide in monotherapy.
Synthesis and Investigations of the Antitumor Effects of First-Row Transition Metal(II) Complexes Supported by Two Fluorinated and Non-Fluorinated β-Diketonates
Authors: Pellei Maura , Del Gobbo Jo’ , Caviglia Miriam , Gandin Valentina , Marzano Cristina , Karade Deepika V. , Noonikara Poyil Anurag , Dias H. V. Rasika , Santini Carlo
Published: February 2024

The 3d transition metal (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes, supported by anions of sterically demanding β-diketones, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), were synthesized and evaluated for their antitumor activity. To assess the biological effects of substituents on phenyl moieties, we also synthesized and investigated the analogous metal(II) complexes of the anion of the less bulky 1,3-diphenylpropane-1,3-dione (HLPh) ligand. The compounds [Cu(LCF3)2], [Cu(LMes)2] and ([Zn(LMes)2]) were characterized by X-ray crystallography. The [Cu(LCF3)2] crystallizes with an apical molecule of solvent (THF) and features a rare square pyramidal geometry at the Cu(II) center. The copper(II) and zinc(II) complexes of diketonate ligands, derived from the deprotonated 1,3-dimesitylpropane-1,3-dione (HLMes), adopt a square planar or a tetrahedral geometry at the metal, respectively. We evaluated the antitumor properties of the newly synthesized (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes against a series of human tumor cell lines derived from different solid tumors. Except for iron derivatives, cellular studies revealed noteworthy antitumor properties, even towards cancer cells endowed with poor sensitivity to the reference drug cisplatin.
Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs
Authors: Nistor Marius , Schmidt Martin , Klingner Carsten , Klingner Caroline , Matziolis Georg , Shayganfar Sascha , Schiffner René
Published: February 2024

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2–5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.
Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma
Authors: Ageenko Alisa , Vasileva Natalia , Richter Vladimir , Kuligina Elena
Published: February 2024

Glioblastoma is one of the most malignant and aggressive tumors of the central nervous system. Despite the standard therapy consisting of maximal surgical resection and chemo- and radiotherapy, the median survival of patients with this diagnosis is about 15 months. Oncolytic virus therapy is one of the promising areas for the treatment of malignant neoplasms. In this review, we have focused on emphasizing recent achievements in virotherapy, both as a monotherapy and in combination with other therapeutic schemes to improve survival rate and quality of life among patients with glioblastoma.
Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design
Authors: Botnari Marina , Tchertanov Luba
Published: February 2024

The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme transforming vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents delivered by its redox partner through thiol-disulfide exchange reactions. The luminal loop (L-loop) is the principal mediator of hVKORC1 activation, and it is a region frequently harbouring numerous missense mutations. Four L-loop hVKORC1 mutants, suggested in vitro as either resistant (A41S, H68Y) or completely inactive (S52W, W59R), were studied in the oxidised state by numerical approaches (in silico). The DYNASOME and POCKETOME of each mutant were characterised and compared to the native protein, recently described as a modular protein composed of the structurally stable transmembrane domain (TMD) and the intrinsically disordered L-loop, exhibiting quasi-independent dynamics. The DYNASOME of mutants revealed that L-loop missense point mutations impact not only its folding and dynamics, but also those of the TMD, highlighting a strong mutation-specific interdependence between these domains. Another consequence of the mutation-induced effects manifests in the global changes (geometric, topological, and probabilistic) of the newly detected cryptic pockets and the alternation of the recognition properties of the L-loop with its redox protein. Based on our results, we postulate that (i) intra-protein allosteric regulation and (ii) the inherent allosteric regulation and cryptic pockets of each mutant depend on its DYNASOME; and (iii) the recognition of the redox protein by hVKORC1 (INTERACTOME) depend on their DYNASOME. This multifaceted description of proteins produces “omics” data sets, crucial for understanding the physiological processes of proteins and the pathologies caused by alteration of the protein properties at various “omics” levels. Additionally, such characterisation opens novel perspectives for the development of “allo-network drugs” essential for the treatment of blood disorders.
Populus euphratica GRP2 Interacts with Target mRNAs to Negatively Regulate Salt Tolerance by Interfering with Photosynthesis, Na+, and ROS Homeostasis
Authors: Li Jing , Zhao Rui , Liu Jian , Yao Jun , Ma Siyuan , Yin Kexin , Zhang Ying , Liu Zhe , Yan Caixia , Zhao Nan , Zhou Xiaoyang , Chen Shaoliang
Published: February 2024

The transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in the roots and shoots of Populus euphratica (a salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba ‘717-1B4’ (P. × canescens) increased its salt sensitivity, which was reflected in the plant’s growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich the target mRNAs that physically interacted with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in this transgenic poplar. Specifically, PeGRP2 negatively affected the stability of the target mRNAs encoding the photosynthetic proteins PETC and RBCMT; antioxidant enzymes SOD[Mn], CDSP32, and CYB1-2; ATPases AHA11, ACA8, and ACA9; and the Na+/H+ antiporter NHA1. This resulted in (i) a greater reduction in Fv/Fm, YII, ETR, and Pn; (ii) less pronounced activation of antioxidative enzymes; and (iii) a reduced ability to maintain Na+ homeostasis in the transgenic poplars during long-term salt stress, leading to their lowered ability to tolerate salinity stress.
Anti-Idiotypic Nanobodies Mimicking an Epitope of the Needle Protein of the Chlamydial Type III Secretion System for Targeted Immune Stimulation
Authors: Koroleva Ekaterina A. , Goryainova Oksana S. , Ivanova Tatiana I. , Rutovskaya Marina V. , Zigangirova Naylia A. , Tillib Sergei V.
Published: February 2024

The development of new approaches and drugs for effective control of the chronic and complicated forms of urogenital chlamydia caused by Chlamydia trachomatis, which is suspected to be one of the main causes of infertility in both women and men, is an urgent task. We used the technology of single-domain antibody (nanobody) generation both for the production of targeting anti-chlamydia molecules and for the subsequent acquisition of anti-idiotypic nanobodies (ai-Nbs) mimicking the structure of a given epitope of the pathogen (the epitope of the Chlamydial Type III Secretion System Needle Protein). In a mouse model, we have shown that the obtained ai-Nbs are able to induce a narrowly specific humoral immune response in the host, leading to the generation of intrinsic anti-Chlamydia antibodies, potentially therapeutic, specifically recognizing a given antigenic epitope of Chlamydia. The immune sera derived from mice immunized with ai-Nbs are able to suppress chlamydial infection in vitro. We hypothesize that the proposed method of the creation and use of ai-Nbs, which mimic and present to the host immune system exactly the desired region of the antigen, create a fundamentally new universal approach to generating molecular structures as a part of specific vaccine for the targeted induction of immune response, especially useful in cases where it is difficult to prepare an antigen preserving the desired epitope in its native conformation.
Human Pulmonary Artery Endothelial Cells Increased Glycolysis and Decreased Nitric Oxide Synthase O-GlcNAcylation in Pulmonary Arterial Hypertension
Authors: Basehore Sarah E. , Clyne Alisa Morss
Published: February 2024

Pulmonary arterial hypertension (PAH) is a fatal disease that primarily affects women. In PAH, endothelial cells become dysfunctional, reducing production of the vasodilator nitric oxide while increasing proliferation. Other studies suggest altered glucose metabolism in PAH. Our recent study showed that increased endothelial glucose metabolism in disturbed flow increased O-GlcNAcylation of endothelial nitric oxide synthase (eNOS), the enzyme that makes nitric oxide, which then reduced nitric oxide production. We therefore hypothesized that elevated endothelial glycolytic activity in PAH endothelial cells would reduce nitric oxide production by increasing eNOS O-GlcNAcylation. We cultured human pulmonary artery endothelial cells (HPAECs) from failed lung transplant (“non-PAH”) and idiopathic PAH patients (“PAH”) and quantified glycolytic activity, nitric oxide production, and eNOS O-GlcNAcylation in each cell type. Our data show that PAH HPAECs had higher glucose uptake and glycolytic metabolites, as well as decreased nitric oxide production, compared to non-PAH HPAECs. However, PAH HPAECs had lower eNOS O-GlcNAcylation and UDP-GlcNAc, the substrate for O-GlcNAcylation. Interestingly, both glucose uptake and eNOS O-GlcNAcylation were higher in female as compared to male HPAECs. These data suggest that although endothelial glycolytic metabolism is altered in PAH, eNOS O-GlcNAcylation is not connected to decreased nitric oxide. In addition, differences in glucose metabolism and protein O-GlcNAcylation in HPAECs from male and female donors could relate to PAH sexual dimorphism.
Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa
Authors: Chen Rene , Guo Robyn , Petty Amy J. , Jaleel Tarannum
Published: February 2024

Hidradenitis Suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune system. A hallmark of HS pathophysiology is dysregulation of both the innate and adaptive immune system. The role of immune system dysregulation in HS development has motivated researchers to explore the utility of biologic immunomodulators. In 2015, adalimumab, a tumor necrosis factor-α inhibitor, was approved by the Food and Drug Administration (FDA) for treatment of moderate-to-severe HS in the US. In 2023, secukinumab, an interleukin-17A (IL-17A) inhibitor, was approved by the European Medicines Agency for treatment of moderate-to-severe HS in Europe. Ongoing clinical trials have shown promising clinical responses to targeted therapies against other pro-inflammatory cytokines including IL-17, IL-12, IL-1, IL-36, IL-6, IL-10, interferon γ, C5a, and Janus kinase (JAK). We provide an update on the efficacy and clinical usage of targeted biologics in HS treatment.
An Update on Current Therapeutic Options in IgA Nephropathy
Authors: Lim Regina Shaoying , Yeo See Cheng , Barratt Jonathan , Rizk Dana V.
Published: February 2024

Immunoglobulin A nephropathy (IgAN) remains the leading cause of primary glomerular disease worldwide. Outcomes are poor with high rates of progressive chronic kidney disease and kidney failure, which contributes to global healthcare costs. Although this disease entity has been described, there were no disease-specific treatments until recently, with the current standard of care focusing on optimal supportive measures including lifestyle modifications and optimization of the renin-angiotensin-aldosterone blockade. However, with significant advances in the understanding of the pathogenesis of IgAN in the past decade, and the acceptance of surrogate outcomes for accelerated drug approval, there have been many new investigational agents tested to target this disease. As these agents become available, we envision a multi-pronged treatment strategy that simultaneously targets the consequences of ongoing nephron loss, stopping any glomerular inflammation, inhibiting pro-fibrotic signals in the glomerulus and tubulo-interstitium, and inhibiting the production of pathogenic IgA molecules. This review is an update on a previous review published in 2021, and we aim to summarize the developments and updates in therapeutic strategies in IgAN and highlight the promising discoveries that are likely to add to our armamentarium.
A Novel Scoring System Predicting Red Blood Cell Transfusion Requirements in Patients Undergoing Invasive Spine Surgery
Authors: Schenk Alina , Ende Jonas , Hoch Jochen , Güresir Erdem , Grabert Josefin , Coburn Mark , Schmid Matthias , Velten Markus
Published: February 2024

Background: Access to blood products is crucial for patient safety during the perioperative course. However, reduced donations and seasonally occurring blood shortages pose a significant challenge to the healthcare system, with surgeries being postponed. The German Blood Transfusion act requires that RBC packages become assigned to an individual patient, resulting in a significant reduction in the available blood products, further aggravating shortages. We aimed to develop a scoring system predicting transfusion probability in patients undergoing spine surgery to reduce assignment and, thus, increase the availability of blood products. Methods: The medical records of 252 patients who underwent spine surgery were evaluated and 18 potential predictors for RBC transfusion were tested to construct a logistic-regression-based predictive scoring system for blood transfusion in patients undergoing spine surgery. Results: The variables found to be the most important included the type of surgery, vertebral body replacement, number of stages, and pre-operative Hb concentration, indicating that surgical specification and the extent of the surgical procedure were more influential than the pre-existing patient condition and medication. Conclusions: Our model showed a good discrimination ability with an average AUC [min, max] of 0.87 [0.6, 0.97] and internal validation with a similar AUC of 0.84 [0.66, 0.97]. In summary, we developed a scoring system to forecast patients’ perioperative transfusion needs when undergoing spine surgery using pre-operative predictors, potentially reducing the need for RBC allocation and, thus, resulting in an increased availability of this valuable resource.
Concentrations of Cobalt, Chromium and Titanium and Immunological Changes after Primary Total Knee Arthroplasty—A Cohort Study with an 18-Year Follow-Up
Authors: Brüggemann Anders , Hailer Nils P.
Published: February 2024

Background: Total knee arthroplasty (TKA) generates elevated metal ion concentrations, but long-term changes in the concentrations of cobalt (Co), chromium (Cr) and titanium (Ti) after primary TKA and potential subsequent immune system activation—not limited to the joint but systemically—are not known. Patients and Methods: We conducted a cohort study on 26 patients with TKA (19 women; 16 with metal-backed and 10 with all-polyethylene tibial components) 18.3 years (min. 16.7, max. 20.5) after index TKA. A total of 69% of patients additionally underwent subsequent arthroplasty of the contralateral knee or either hip after the index surgery. Blood samples were analysed by inductively coupled plasma–mass spectrometry, and leukocytes were characterised by flow cytometry. Patients were clinically assessed using the Knee Society score and by plain radiography of the knee. Results: The median metal ion concentrations were 0.7 (0.1–13.0) µg/L for Co, 0.9 (0.4–5.0) µg/L for Cr, and 1.0 (0.2–13.0) µg/L for Ti. There was no relevant difference in systemic metal ion concentrations between patients exposed to single and multiple arthroplasties. The absolute count and proportion of CD3+CD4+CD8+ T cells was inversely correlated with both Co (rho −0.55, p = 0.003) and Cr concentrations (rho −0.59, p = 0.001). Conclusions: Between the first and second decades after primary TKA, in most patients, the concentrations of Co, Cr and Ti in blood samples were below the thresholds that are considered alarming. The negative correlation of Co and Cr concentrations with a subset of lymphocytes that commonly increases during immune activation is reassuring. This represents a worst-case scenario, underscoring that the investigated metal ions remain within reasonable ranges, even after additional hardware exposure.
Late Post-Dissection Dynamic Intermittent Malperfusion of the Aortic Arch in Association with a Rare Heterogenous LOX Gene Variation
Authors: Leclercq Barbara , Bertolino Julien , Rossillon Alexandre , Gariboldi Vlad , El Harake Sarah , Silhol François , Bartoli Michel , Vaisse Bernard , Bartoli Axel , Sarlon-Bartoli Gabrielle
Published: February 2024

Late ischaemic consequences of type A aortic dissection are rare. We present a 6-year late complication of type A aortic dissection treated by Bentall surgery in a 41-year-old patient. The patient presented with several episodes of lipothymia associated with hypertensive attacks with anisotension, cervicalgia, hemicranial headache, abdominal pain and lower limb slipping initially on exertion and later at rest. On dynamic examination, we diagnosed an intermittent dynamic occlusion of the aortic arch and rare LOX gene variation, which is considered to be associated with aneurysm or dissection of the ascending aorta in young patients. Surgical treatment by replacement of the ascending aorta and the aortic arch with reimplantation of the brachiocephalic trunk (BcTr) allowed the symptoms to resolve.
Detection of Alpha-1 Antitrypsin Levels in Chronic Obstructive Pulmonary Disease in Respiratory Clinics in Spain: Results of the EPOCONSUL 2021 Audit
Authors: Calle Rubio Myriam , Miravitlles Marc , López-Campos José Luis , Soler-Cataluña Juan J. , Alcazar Navarrete Bernardino , Fuentes-Ferrer Manuel E. , Rodriguez Hermosa Juan Luis
Published: February 2024

Background: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021–2022, as well as to compare with a previous audit conducted in 2014–2015. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. Results: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. Conclusions: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.
Phenolic Compounds of Therapeutic Interest in Neuroprotection
Authors: Nájera-Maldonado José Manuel , Salazar Ricardo , Alvarez-Fitz Patricia , Acevedo-Quiroz Macdiel , Flores-Alfaro Eugenia , Hernández-Sotelo Daniel , Espinoza-Rojo Mónica , Ramírez Mónica
Published: February 2024

The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood–brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemia, and traumatic brain injury (TBI).
Persistent Organic Pollutants in Austrian Human Breast Milk Collected between 2013 and 2016
Authors: Hartmann Christina , Kaiser Andreas-Marius , Moche Wolfgang , Weiss Stefan , Raffesberg Wolfgang , Scharf Sigrid , Graf-Rohrmeister Klaudia , Thanhaeuser Margarita , Haiden Nadja , Uhl Maria
Published: February 2024

Breast milk holds an immense nutritional value as it contains health-promoting substances in a unique, optimal form. Additionally, breast milk’s significance extends to health and environmental protection, as it serves as an indicator of both maternal and infant exposure. In this study, breast milk samples collected in 2013 and in 2014–2016 from mothers in Vienna (Austria) were analysed for polybrominated diphenyl ethers (PBDE) and per- and polyfluoroalkyl substances (PFAS), as well as further substances which have been listed under the Stockholm Convention on Persistent Organic Pollutants (POPs) due to their persistent, bioaccumulative and toxic properties. The total concentration of the PBDE congeners in the samples (n = 18, sampled 2013) ranged from 0.055 to 52 ng/g lipid, and from 0.002 to 2.5 ng/g breast milk. In the pooled sample, the sum of PBDEs was detected at a level of 4.4 ng/g lipid. Based on the 2014–2016 study population, certain PFAS were detected in all samples (n = 40). Exposure to the sum of four specific PFAS including perfluorooctanesulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluoro-n-nonanoic acid (PFNA) and perfluoro-1-hexanesulfonate (PFHxS) ranged between 0.014 and 0.12 ng/L breast milk. In the pooled sample, PFOS and PFOA were found in concentrations of 0.025 ng/g and of 0.045 ng/g, respectively. In addition, the first generation of POPs, mainly organochlorine compounds, was measured in a pooled sample of breast milk from participants sampled in 2014–2016 as part of the WHO/UNEP breast milk monitoring program and compared to the POPs measured in pooled samples collected in 1987/1988 and 1992/1993, respectively. Therefore, this paper demonstrates the effectiveness of the Stockholm Convention on POPs by comparing the Austrian results from the WHO/UNEP global breast milk study from 1987 to 2016. However, the data also show that, despite these reductions, health-relevant levels are still being reached, particularly in terms of children’s health when the presence of the new generation of POPs, such as PBDEs and PFAS, in human breast milk is taken into account.
Clinical Outcome of Multiple Platelet-Rich Plasma Injection and Correlation with PDGF-BB in the Treatment of Knee Osteoarthritis
Authors: Partan Radiyati Umi , Putra Khoirun Mukhsinin , Hafizzanovian Hafizzanovian , Darma Surya , Reagan Muhammad , Muthia Putri , Radiandina Afifah Salshabila , Rahmawati Eny
Published: February 2024

(1) Background: Current treatments for knee osteoarthritis (KOA), such as intra-articular corticosteroids or hyaluronic acid (HA) injections, are controversial due to their ineffectiveness in preventing disease progression. Platelet-rich plasma (PRP) has become a promising and possible treatment for KOA. It is thought to enhance articular cartilage regeneration and reduce OA-related impairment. PRP contains growth factors such as PDGF-BB, which stimulates growth and inhibits joint damage. Based on numerous studies, after a certain amount of time, it was found that multiple PRP treatments reduced pain more than a single injection. This study evaluates the efficacy of multiple PRP (m-PRP) injections compared to multiple HA (m-HA) injections for KOA treatment, focusing on their correlation with PDGF-BB levels. (2) Methods: In this single-center, open-label, randomized, comparative clinical trial, 30 KOA patients received m-PRP and m-HA injections. VAS and WOMAC were used to evaluate clinical outcomes and PDGF-BB concentrations. (3) Results: The study analysis revealed a statistically significant reduction in pain indices. In both the m-PRP and m-HA groups after 12 weeks, m-PRP showed superior results. PDGF-BB concentrations also increased, with a strong negative correlation and statistical significance using Spearman’s rho. (4) Conclusions: Multiple PRP injections are safe and associated with elevated PDGF-BB, reduced VAS and WOMAC scores, providing the potential for articular cartilage regeneration and inhibiting knee osteoarthritis progression.
Advancements and Challenges in High-Capacity Ni-Rich Cathode Materials for Lithium-Ion Batteries
Authors: Ahangari Mehdi , Szalai Benedek , Lujan Josue , Zhou Meng , Luo Hongmei
Published: February 2024

Nowadays, lithium-ion batteries are undoubtedly known as the most promising rechargeable batteries. However, these batteries face some big challenges, like not having enough energy and not lasting long enough, that should be addressed. Ternary Ni-rich Li[NixCoyMnz]O2 and Li[NixCoyAlz]O2 cathode materials stand as the ideal candidate for a cathode active material to achieve high capacity and energy density, low manufacturing cost, and high operating voltage. However, capacity gain from Ni enrichment is nullified by the concurrent fast capacity fading because of issues such as gas evolution, microcracks propagation and pulverization, phase transition, electrolyte decomposition, cation mixing, and dissolution of transition metals at high operating voltage, which hinders their commercialization. In order to tackle these problems, researchers conducted many strategies, including elemental doping, surface coating, and particle engineering. This review paper mainly talks about origins of problems and their mechanisms leading to electrochemical performance deterioration for Ni-rich cathode materials and modification approaches to address the problems.
Research on the Influence of Deep-Water Drilling Risers on Drillstring Motion Trajectory and Vibration Characteristics
Authors: Hai Weiguo , He Yingming , Xue Qilong
Published: February 2024

The swing of the riser in deep-water drilling can significantly impact the drill string. In this study, we establish a riser model that considers the combined disturbance of periodic dynamic wind and wave loads. By coupling it with the drill string model, we develop a dynamic model for deep-water drilling systems. Through analyzing multiple sets of different drilling parameters, we examine displacements and impact forces at various positions along the drill string system. Specifically, our focus lies on velocity, acceleration, and rotational speed information of BHA. We investigate how WOB and rotational speed influence motion trajectory and vibration characteristics of the drill string within the dynamic model of deep-water drilling systems. Simulation results reveal slight differences in whirling trajectories between inside the riser and below mud line for the drill string. Rotational speed has a greater impact on the drill string compared to WOB; higher rotational speeds lead to increased collision forces between the drill string system and both riser and wellbore. Our findings identify specific combinations of WOB and rotational speed parameters that can stabilize drilling operations within dynamic models for deep-water drilling systems. These research results provide valuable insights for adjusting WOB and rotational speed parameters in deep-water drilling.
Z-Numbers-Based MCDM Approach for Personnel Selection at Institutions of Higher Education for Transportation
Authors: Gottwald Dalibor , Chocholáč Jan , Kayacı Çodur Merve , Čubranić-Dobrodolac Marjana , Yazir Kubra
Published: February 2024

Personnel evaluation and selection is an essential part of modern business. Appropriate candidate selection can significantly contribute to companies in terms of increased profit, good culture, reputation, reduced costs, etc. This paper addresses the personnel evaluation and selection problem at the University of Pardubice, Faculty of Transport Engineering (UPCE). Since this is a typical ranking alternative problem where multiple criteria affect the decision, the Z-numbers-based Alternative Ranking Order Method Accounting for the two-step Normalization (AROMAN) is applied. Four Ph.D. candidates are assessed, and the most appropriate is selected to be employed by the UPCE. The Z-numbers fuzzy AROMAN method ranks Ph.D. candidate number four as the most appropriate alternative. To investigate the stability and sensitivity of the Z-numbers fuzzy AROMAN method, the values of parameters β and λ used in the mathematical calculations of the method were changed. The results of sensitivity analysis revealed that the obtained solution is stable. To confirm the robustness of the proposed approach, a comparative analysis is performed. Simple Additive Weighting (SAW), Weighted Product Model (WPM), and Z-number fuzzy TOPSIS were applied. Besides, we applied the fuzzy inferior ratio method as well. The results confirm the high robustness of the proposed Z-numbers fuzzy AROMAN method.
Regularized Discrete Optimal Transport for Class-Imbalanced Classifications
Authors: Chen Jiqiang , Wan Jie , Ma Litao
Published: February 2024

Imbalanced class data are commonly observed in pattern analysis, machine learning, and various real-world applications. Conventional approaches often resort to resampling techniques in order to address the imbalance, which inevitably alter the original data distribution. This paper proposes a novel classification method that leverages optimal transport for handling imbalanced data. Specifically, we establish a transport plan between training and testing data without modifying the original data distribution, drawing upon the principles of optimal transport theory. Additionally, we introduce a non-convex interclass regularization term to establish connections between testing samples and training samples with the same class labels. This regularization term forms the basis of a regularized discrete optimal transport model, which is employed to address imbalanced classification scenarios. Subsequently, in line with the concept of maximum minimization, a maximum minimization algorithm is introduced for regularized discrete optimal transport. Subsequent experiments on 17 Keel datasets with varying levels of imbalance demonstrate the superior performance of the proposed approach compared to 11 other widely used techniques for class-imbalanced classification. Additionally, the application of the proposed approach to water quality evaluation confirms its effectiveness.
Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain
Authors: Bonanno Mirjam , Papa Davide , Cerasa Antonio , Maggio Maria Grazia , Calabrò Rocco Salvatore
Published: February 2024

Chronic stress and chronic pain share neuro-anatomical, endocrinological, and biological features. However, stress prepares the body for challenging situations or mitigates tissue damage, while pain is an unpleasant sensation due to nociceptive receptor stimulation. When pain is chronic, it might lead to an allostatic overload in the body and brain due to the chronic dysregulation of the physiological systems that are normally involved in adapting to environmental challenges. Managing stress and chronic pain (CP) in neurorehabilitation presents a significant challenge for healthcare professionals and researchers, as there is no definitive and effective solution for these issues. Patients suffering from neurological disorders often complain of CP, which significantly reduces their quality of life. The aim of this narrative review is to examine the correlation between stress and pain and their potential negative impact on the rehabilitation process. Moreover, we described the most relevant interventions used to manage stress and pain in the neurological population. In conclusion, this review sheds light on the connection between chronic stress and chronic pain and their impact on the neurorehabilitation pathway. Our results emphasize the need for tailored rehabilitation protocols to effectively manage pain, improve treatment adherence, and ensure comprehensive patient care.
Unraveling the Mechanism of Toughness Fluctuation in Ultra-High-Strength Casing from the Perspective of Crystallography
Authors: Gao Zhan , Dong Xiaoming , Yu Jieru , Tang Junjie , Yu Yishuang , Wei Liangliang , Liu Shilong , Jin Xuejun
Published: February 2024

The microstructure and impact toughness in an ultra-high-strength casing were investigated, attempting to reveal the reason for toughness fluctuations along the casing in terms of crystallography. The morphological structures at the head of the casing are lath bainite, while those at the end are granular bainite and lath bainite. The head exhibits a higher density of high-angle grain boundaries dominated by block boundaries and a higher impact toughness than the end, showing an inhomogeneous microstructure and causing toughness fluctuations in the casing. The higher density of block boundaries in the head resulted from weaker variant selection because of its higher cooling rate than the end. Therefore, the underlying reason for the toughness fluctuations lies in the varying densities of the block boundaries along the casing triggered by uneven cooling.
Batch Fine Magnetic Pattern Transfer Method on Permanent Magnets Using Coercivity Change during Heating for Magnetic MEMS
Authors: Nagai Keita , Sugita Naohiro , Shinshi Tadahiko
Published: February 2024

In magnetic microelectromechanical systems (MEMSs), permanent magnets in the form of a thick film or thin plate are used for structural and manufacturing purposes. However, the geometric shape induces a strong self-demagnetization field during thickness–direction magnetization, limiting the surface magnetic flux density and output power. The magnets must be segmented or magnetized in a fine and multi-pole manner to weaken the self-demagnetization field. Few studies have been performed on fine multi-pole magnetization techniques that can generate a higher surface magnetic flux density than segmented magnets and are suitable for mass production. This paper proposes a batch fine multi-pole magnetic pattern transfer (MPT) method for the magnets of MEMS devices. The proposed method uses two master magnets with identical magnetic patterns to sandwich a target magnet. Subsequently, the coercivity of the target magnet is reduced via heating, and the master magnet’s magnetic pattern is transferred to the target magnet. Stripe, checkerboard, and concentric circle patterns with a pole pitch of 0.3 mm are magnetized on the NdFeB master magnets N38EH with high intrinsic coercivity via laser-assisted heating magnetization. The MPT yields the highest surface magnetic flux density at 160 °C, reaching 39.7–66.1% of the ideal magnetization pattern on the NdFeB target magnet N35.
Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
Authors: Saupe Mario , Wiedemeier Stefan , Gastrock Gunter , Römer Robert , Lemke Karen
Published: February 2024

Although the enormous potential of droplet-based microfluidics has been successfully demonstrated in the past two decades for medical, pharmaceutical, and academic applications, its inherent potential has not been fully exploited until now. Nevertheless, the cultivation of biological cells and 3D cell structures like spheroids and organoids, located in serially arranged droplets in micro-channels, has a range of benefits compared to established cultivation techniques based on, e.g., microplates and microchips. To exploit the enormous potential of the droplet-based cell cultivation technique, a number of basic functions have to be fulfilled. In this paper, we describe microfluidic modules to realize the following basic functions with high precision: (i) droplet generation, (ii) mixing of cell suspensions and cell culture media in the droplets, (iii) droplet content detection, and (iv) active fluid injection into serially arranged droplets. The robustness of the functionality of the Two-Fluid Probe is further investigated regarding its droplet generation using different flow rates. Advantages and disadvantages in comparison to chip-based solutions are discussed. New chip-based modules like the gradient, the piezo valve-based conditioning, the analysis, and the microscopy module are characterized in detail and their high-precision functionalities are demonstrated. These microfluidic modules are micro-machined, and as the surfaces of their micro-channels are plasma-treated, we are able to perform cell cultivation experiments using any kind of cell culture media, but without needing to use surfactants. This is even more considerable when droplets are used to investigate cell cultures like stem cells or cancer cells as cell suspensions, as 3D cell structures, or as tissue fragments over days or even weeks for versatile applications.
Assessment of the Possibility of Using Bacterial Strains and Bacteriophages for Epidemiological Studies in the Bioaerosol Environment
Authors: Wróbel Radosław , Andrych-Zalewska Monika , Matla Jędrzej , Molska Justyna , Sierzputowski Gustaw , Szulak Agnieszka , Włostowski Radosław , Włóka Adriana , Rutkowska-Gorczyca Małgorzata
Published: February 2024

During the COVID-19 pandemic, microbiological controls neglected the spread of viruses through the air. Techniques to identify this threat required additional research to enable control measures to be introduced to protect against the spread of disease through this route. Due to the very high level of risk occurring during research on the COVID-19 and SARS-CoV-2 viruses, it seems necessary to use analogous microorganisms that will allow, through an experiment, to validate or challenge a method that stops the spread of infectious microorganisms, without unnecessary risk to research staff. The presented work was carried out to assess the possibility of using airborne microorganisms that are safe for humans for this type of research. The work presents the selection process of bacteria and viruses (bacteriophages) that have the greatest potential for use in experimental studies on airborne-droplet transmission indoors, especially in hospital facilities. In the study, it was assumed that determining the survival rates of groups of organisms would allow them to be used as a proxy for studying more dangerous bacteria and viruses. Survival studies of selected microorganisms were carried out, and the paper selected microorganisms with the highest survival rate in a given environment.
The Science of Shiga Toxin-Producing (Verotoxin-Producing) Escherichia coli (STEC): An Ongoing One Health Journey toward Improved Health and Food Safety—Editorial Summary
Authors: Thomas Krysty D. , McAllister Tim A.
Published: February 2024

Verotoxigenic Escherichia coli (VTEC), also termed Shiga toxin-producing Escherichia coli (STEC), is a human pathogen transmitted by food, water, animals, and their environment, and from one person to another [...]