bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Molecular Mechanisms Involved in Viral Infection Progression Based on Text Mining: Case Study for HIV Infection
Authors: Tarasova Olga , Biziukova Nadezhda , Shemshura Andrey , Filimonov Dmitry , Kireev Dmitry , Pokrovskaya Anastasia , Poroikov Vladimir V.
Published: January 2023

Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life. While highly active antiretroviral therapy may decrease the viral load and the velocity of HIV infection progression, some individual peculiarities may affect viral load control or the progression of T-cell malfunction induced by HIV. Our study is aimed at the text-based identification of molecular mechanisms that may be involved in viral infection progression, using HIV as a case study. Specifically, we identified human proteins and genes which commonly occurred, overexpressed or underexpressed, in the collections of publications relevant to (i) HIV infection progression and (ii) acute and chronic stages of HIV infection. Then, we considered biological processes that are controlled by the identified protein and genes. We verified the impact of the identified molecules in the associated clinical study.
Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity
Authors: Lazewski Dawid , Kucinska Malgorzata , Potapskiy Edward , Kuzminska Joanna , Popenda Lukasz , Tezyk Artur , Goslinski Tomasz , Wierzchowski Marcin , Murias Marek
Published: January 2023

Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF2 moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure–activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.
The Distinct Effects of the Mitochondria-Targeted STAT3 Inhibitors Mitocur-1 and Mitocur-3 on Mast Cell and Mitochondrial Functions
Authors: Pavlyuchenkova Anastasia N. , Chelombitko Maria A. , Fedorov Artem V. , Kuznetsova Maria K. , Zinovkin Roman A. , Razin Ehud
Published: January 2023

There is accumulating evidence that mitochondria and mitochondrial STAT3 are involved in the activation of mast cells. The mitochondria-targeted curcuminoids Mitocur-1 and Mitocur-3 have been suggested to reduce antigen-dependent mast cell activation by inhibiting mitochondrial STAT3. The aim of the current work was to investigate the mechanisms of action of these mitocurcuminoids on mast cells and mitochondrial functions. The pretreatment of rat basophilic leukemia cells RBL-2H3 with Mitocur-1 and Mitocur-3 decreased antigen-dependent degranulation but did not affect spontaneous degranulation. Both compounds caused mitochondrial fragmentation and increased mitochondrial ROS. Inhibition of Drp1 prevented mitochondrial fragmentation induced by Mitocur-3 but not by Mitocur-1. The antioxidant N-acetylcysteine inhibited mitochondrial fission induced by Mitocur-1 but not Mitocur-3. Mitochondrial fragmentation caused by Mitocur-3 but not Mitocur-1 was accompanied by activation of Drp1 and AMPK. These data suggest a distinct mechanism of action of mitocurcuminoids on the mitochondria of RBL-2H3 cells: Mitocur-3 stimulated AMPK and caused Drp1-dependent mitochondrial fragmentation, while Mitocur-1-induced mitochondrial fission was ROS-dependent. This difference may contribute to the higher toxicity of Mitocur-3 compared to Mitocur-1. The findings contribute to further drug development for inflammatory and allergic diseases.
Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact
Authors: Mrozikiewicz-Rakowska Beata , Szabłowska-Gadomska Ilona , Cysewski Dominik , Rudziński Stefan , Płoski Rafał , Gasperowicz Piotr , Konarzewska Magdalena , Zieliński Jakub , Mieczkowski Mateusz , Sieńko Damian , Grzela Tomasz , Noszczyk Maria , Paleska Barbara , Czupryniak Leszek , Lewandowska-Szumiel Malgorzata
Published: January 2023

Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing—a step toward the development of cell-based therapies.
Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFβ-Induced EMT in Human Non-Small Cell Lung Cancer
Authors: Andreucci Elena , Bugatti Kelly , Peppicelli Silvia , Ruzzolini Jessica , Lulli Matteo , Calorini Lido , Battistini Lucia , Zanardi Franca , Sartori Andrea , Bianchini Francesca
Published: January 2023

Growth factors and cytokines released in the lung cancer microenvironment promote an epithelial-to-mesenchymal transition (EMT) that sustains the progression of neoplastic diseases. TGFβ is one of the most powerful inducers of this transition, as it induces overexpression of the fibronectin receptor, αvβ6 integrin, in cancer cells which, in turn, is strongly associated with EMT. Thus, αvβ6 integrin receptors may be exploited as a target for the selective delivery of anti-tumor agents. We introduce three novel synthesized conjugates, in which a selective αvβ6 receptor ligand is linked to nintedanib, a potent kinase inhibitor used to treat advanced adenocarcinoma lung cancer in clinics. The αvβ6 integrin ligand directs nintedanib activity to the target cells of the tumor microenvironment, avoiding the onset of negative side effects in normal cells. We found that the three conjugates inhibit the adhesion of cancer cells to fibronectin in a concentration-dependent manner and that αvβ6-expressing cells internalized the conjugated compounds, thus permitting nintedanib to inhibit 2D and 3D cancer cell growth and suppress the clonogenic ability of the EMT phenotype as well as intervening in other aspects associated with the EMT transition. These results highlight αvβ6 receptors as privileged access points for dual-targeting molecular conjugates engaged in an efficient and precise strategy against non-small cell lung cancer.
Genome-Wide Comparative Analysis of the Fasciclin-like Arabinogalactan Proteins (FLAs) in Salicacea and Identification of Secondary Tissue Development-Related Genes
Authors: Zhang Yingying , Zhou Fangwei , Wang Hui , Chen Yingnan , Yin Tongming , Wu Huaitong
Published: January 2023

Fasciclin-like arabinogalactan proteins (FLAs) are a subclass of arabinogalactan proteins (AGPs) containing both AGP-like glycated domains and fasciclin (FAS) domains, which are involved in plant growth and development and synthesis of the cell wall. However, these proteins have not been identified or analyzed in willow, Salix, the sister genus of Populus. In this study, we performed a whole genome study of the FLA gene family of Salix suchowensis and compared it with the FLA gene family of Populus deltoides. The results showed the presence of 40 and 46 FLA genes in P. deltoides and S. suchowensis, distributed on 17 and 16 chromosomes, respectively. Four pairs of tandem repeat genes were found in willow, while poplar had no tandem repeat genes. Twelve and thirteen pairs of duplicated gene fragments were identified in poplar and willow, respectively. The multispecies phylogenetic tree showed that the FLA gene family could be divided into four groups (I–IV), with Group 1 showing significant expansion in woody plants. A gene expression analysis showed that PdeFLA19/27 in Group I of poplar was highly expressed, specifically during the secondary growth period of the stem and the rapid elongation of seed hairs. In the Group I genes of S. suchowensis, SsuFLA25/26/28 was also highly expressed during the secondary growth period, whereas increased expression of SsuFLA35 was associated with seed hair tissue. These results provide important clues about the differences in the FLA gene family during the evolution of herbs and woody plants, and suggest that the FLA gene family may play an essential role in regulating the secondary growth of woody plants. It also provides a reference for further studies on the regulation of secondary growth and seed hair development by FLA genes in poplar and willow.
mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
Authors: Cilleros-Holgado Paula , Gómez-Fernández David , Piñero-Pérez Rocío , Reche-López Diana , Álvarez-Córdoba Mónica , Munuera-Cabeza Manuel , Talaverón-Rey Marta , Povea-Cabello Suleva , Suárez-Carrillo Alejandra , Romero-González Ana , Suárez-Rivero Juan Miguel , Romero-Domínguez Jose Manuel , Sánchez-Alcázar Jose Antonio
Published: January 2023

Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.
Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn’s Disease Adult Patients
Authors: Rizzello Fernando , Gionchetti Paolo , Spisni Enzo , Saracino Ilaria Maria , Bellocchio Irene , Spigarelli Renato , Collini Noemi , Imbesi Veronica , Dervieux Thierry , Alvisi Patrizia , Valerii Maria Chiara
Published: January 2023

Wrong dietary habits, such as the Western-style diet, are considered important risk factors for the development of Inflammatory Bowel Diseases (IBDs). Nevertheless, the role of dietary patterns in the clinical management of IBD patients has not been fully investigated yet. Fifty-four patients diagnosed with active Crohn’s disease (CD) were enrolled and subjected to nutritional intake analysis through a weekly food diary. Nutritional patterns were analyzed, and nutrient intake was compared with those of 30 healthy subjects (HS). Blood levels of cholesterol, folic acid, minerals (K, Mg, Fe) and amino acids, were measured in CD patients to assess the presence of nutritional deficiencies. CD patients, with respect to HS, consumed significantly lower amounts of fiber, vitamins (A, E, C, B6, folic acid) and β-carotene. Their calcium, potassium, phosphorus, iron, magnesium, copper and iodine intake were also found to be significantly lower. In blood, CD patients had significantly lower concentrations of total cholesterol, potassium, iron, and amino acids. Active CD patient diet was significantly different from those of HS and may contribute to the establishment of nutritional deficiencies. Intestinal malabsorption was evidenced in these patients. Correction of the diet with specific nutritional plans is a necessary therapeutic step for these patients. ClinicalTrials.gov: NCT02580864.
Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids
Authors: Mom Robin , Réty Stéphane , Auguin Daniel
Published: January 2023

Aquaporins (AQPs) are water channels widely distributed in living organisms and involved in many pathophysiologies as well as in cell volume regulations (CVR). In the present study, based on the structural homology existing between mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), cholesterol consensus motif (CCM) and the extra-cellular vestibules of AQPs, we investigated the binding of corticosteroids on the AQP family through in silico molecular dynamics simulations of AQP2 interactions with cortisol. We propose, for the first time, a putative AQPs corticosteroid binding site (ACBS) and discussed its conservation through structural alignment. Corticosteroids can mediate non-genomic effects; nonetheless, the transduction pathways involved are still misunderstood. Moreover, a growing body of evidence is pointing toward the existence of a novel membrane receptor mediating part of these rapid corticosteroids’ effects. Our results suggest that the naturally produced glucocorticoid cortisol inhibits channel water permeability. Based on these results, we propose a detailed description of a putative underlying molecular mechanism. In this process, we also bring new insights on the regulatory function of AQPs extra-cellular loops and on the role of ions in tuning the water permeability. Altogether, this work brings new insights into the non-genomic effects of corticosteroids through the proposition of AQPs as the membrane receptor of this family of regulatory molecules. This original result is the starting point for future investigations to define more in-depth and in vivo the validity of this functional model.
WT1 Pulsed Human CD141+ Dendritic Cell Vaccine Has High Potential in Solid Tumor-Targeted Immunotherapy
Authors: Cho Sung Yoon , Jeong Seong Mun , Jeon Young Joo , Yang Sun Ja , Hwang Ju Eun , Yoo Byung Moo , Kim Hyun Soo
Published: January 2023

Dendritic cells (DC) are powerful cells that play critical roles in anti-tumor immunity, and their use in cancer immunotherapy unlocks hidden capabilities as an effective therapeutic. In order to maximize the full potential of DC, we developed a DC vaccine named CellgramDC-WT1 (CDW). CDW was pulsed with WT1, an antigen commonly expressed in solid tumors, and induced with zoledronate to aid DC maturation. Although our previous study focused on using Rg3 as an inducer of DC maturation, problems with quality control and access led us to choose zoledronate as a better alternative. Furthermore, CDW secreted IL-12 and IFN-γ, which induced the differentiation of naïve T cells to active CD8+ T cells and elicited cytotoxic T lymphocyte (CTL) response against cancer cells with WT1 antigens. By confirming the identity and function of CDW, we believe CDW is an improved DC vaccine and holds promising potential in the field of cancer immunotherapy.
Downregulation of CDC25C in NPCs Disturbed Cortical Neurogenesis
Authors: Zhou Xiaokun , Lu Danping , Yi Wenxiang , Xu Dan
Published: January 2023

Cell division regulators play a vital role in neural progenitor cell (NPC) proliferation and differentiation. Cell division cycle 25C (CDC25C) is a member of the CDC25 family of phosphatases which positively regulate cell division by activating cyclin-dependent protein kinases (CDKs). However, mice with the Cdc25c gene knocked out were shown to be viable and lacked the apparent phenotype due to genetic compensation by Cdc25a and/or Cdc25b. Here, we investigate the function of Cdc25c in developing rat brains by knocking down Cdc25c in NPCs using in utero electroporation. Our results indicate that Cdc25c plays an essential role in maintaining the proliferative state of NPCs during cortical development. The knockdown of Cdc25c causes early cell cycle exit and the premature differentiation of NPCs. Our study uncovers a novel role of CDC25C in NPC division and cell fate determination. In addition, our study presents a functional approach to studying the role of genes, which elicit genetic compensation with knockout, in cortical neurogenesis by knocking down in vivo.
Pure Platelet and Leukocyte–Platelet-Rich Plasma for Regenerative Medicine in Orthopedics—Time- and Preparation-Dependent Release of Growth Factors and Effects on Synovial Fibroblasts: A Comparative Analysis
Authors: Mariani Erminia , Pulsatelli Lia , Cattini Luca , Dolzani Paolo , Assirelli Elisa , Cenacchi Annarita , Di Martino Alessandro , Arciola Carla Renata , Filardo Giuseppe
Published: January 2023

Intra-articular injections of autologous platelet concentrates are considered capable to enhance the healing of cartilage lesions, alleviate joint inflammation, and relieve other musculoskeletal pathological conditions. The aim of this study was to analyze the soluble fractions obtained from platelet-rich plasma (pure- and leukocyte-PRP) to compare time- and preparation-dependent modifications of growth factor concentrations and the supporting activity of the two preparations on synovial fibroblast growth and hyaluronic acid (HA) production in vitro. The release kinetics of FGF-2, SDF-1, VEGF, HGF, EGF, PD GF-AB/BB, IGF-1, VCAM-1, and TGF-β isoforms were followed up to 168 h after PRP activation, and their amounts were determined by multiplex-beads immunoassay. Synovial cell growth and supernatant HA production were respectively analyzed by Alamar Blue assay and ELISA. Time-dependent modifications grouped molecules in three peculiar patterns: one reaching the highest concentrations within 18 h and decreasing afterwards, another progressively increasing up to 168 h, and the last peaking at the central time points. Synovial fibroblast growth in response to L-PRP and P-PRP revealed differences over time and among added concentrations. Both preparations displayed a preserved supporting capacity of HA synthesis.
Influence of Ranunculus acris Flower Extract on Allium cepa Root Meristem
Authors: Smirnova Maria V. , Koygerova Alena A. , Tsvetov Nikita S.
Published: January 2023

The plant Ranunculus acris (L.) is widespread. It is used in folk medicine. The use of herbal medicines can have adverse effects on humans and requires studies of herbal raw materials for genotoxicity. The goals of the study were to examine the toxic and genotoxic effects of aqueous solutions of R. acris flowers at concentrations of 0.625%, 1.25%, 2.5%, 5% and 10% using the Allium test and to determine the numbers of flavonoids and polyphenols and the antioxidant activity of the extracts. It has been shown that aqueous solutions of buttercup flower extract have a depressing effect on mitosis in the cells of the root meristem of Allium cepa (L.) and cause chromosomal abnormalities (chromosomal stickiness, chromosome lagging, nuclear buds and bridges in anaphase).
Post-Stroke Rehabilitation: Challenges and New Perspectives
Authors: Morone Giovanni , Pichiorri Floriana
Published: January 2023

A stroke is determined by insufficient blood supply to the brain due to vessel occlusion (ischemic stroke) or rupture (hemorrhagic stroke), resulting in immediate neurological impairment to differing degrees [...]
The Footprint of Type 1 Diabetes on Red Blood Cells: A Metabolomic and Lipidomic Study
Authors: Herance José Raul , Ciudin Andreea , Lamas-Domingo Rubén , Aparicio-Gómez Carolina , Hernández Cristina , Simó Rafael , Palomino-Schätzlein Martina
Published: January 2023

The prevalence of diabetes type 1 (T1D) in the world populations is continuously growing. Although treatment methods are improving, the diagnostic is still symptom-based and sometimes far after onset of the disease. In this context, the aim of the study was the search of new biomarkers of the disease in red blood cells (RBCs), until now unexplored. The metabolomic and the lipidomic profile of RBCs from T1D patients and matched healthy controls was determined by NMR spectroscopy, and different multivariate discrimination models were built to select the metabolites and lipids that change most significantly. Relevant metabolites were further confirmed by univariate statistical analysis. Robust separation in the metabolomic and lipidomic profiles of RBCs from patients and controls was confirmed by orthogonal projection on latent structure discriminant analysis (OPLS-DA), random forest analysis, and significance analysis of metabolites (SAM). The main changes were detected in the levels of amino acids, organic acids, creatine and phosphocreatine, lipid change length, and choline derivatives, demonstrating changes in glycolysis, BCAA metabolism, and phospholipid metabolism. Our study proves that robust differences exist in the metabolic and lipidomic profile of RBCs from T1D patients, in comparison with matched healthy individuals. Some changes were similar to alterations found already in RBCs of T2D patients, but others seemed to be specific for type 1 diabetes. Thus, many of the metabolic differences found could be biomarker candidates for an earlier diagnosis or monitoring of patients with T1D.
The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case–Control Study
Authors: Giannouli Aikaterini , Efthymiou Vasiliki , Konidari Marianna , Mani Iliana , Aravantinos Leon , Dourakis Spyridon P. , Antoniou Aristeidis , Deligeoroglou Efthymios , Bacopoulou Flora
Published: January 2023

The aim of this case–control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3–20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (β = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD.
Comparison of Mid-Term Outcomes between Microhook ab Interno Trabeculotomy and Goniotomy with the Kahook Dual Blade
Authors: Okada Naoki , Hirooka Kazuyuki , Onoe Hiromitsu , Okumichi Hideaki , Kiuchi Yoshiaki
Published: January 2023

This study retrospectively examined the mid-term surgical outcomes between microhook ab interno trabeculotomy (μLOT) and goniotomy when one was using the Kahook Dual Blade (KDB) in combination with phacoemulsification in primary open-angle glaucoma and exfoliation glaucoma patients. Between December 2016 and December 2020, the current study examined 47 μLOT and 52 KDB eyes that underwent surgery. When there was a < 20% reduction in the preoperative intraocular pressure (IOP) or when the IOP was > 18 mmHg (criterion A), the IOP was > 14 mmHg (criterion B) at two consecutive follow-up visits, or when there was a requirement for reoperation, these were all considered to indicate that the surgery failed. A genetic algorithm that used the preoperative IOP was used to determine the score matching. After score matching, a total of 27 eyes were evaluated. In the μLOT and KDB groups, the mean postoperative follow-up periods were 31.2 ± 13.3 and 37.2 ± 16.3 months, respectively. The results for both of the groups show there were significant postoperative reductions in the IOP (p < 0.05) and medication scores (p < 0.05) at 6, 12, 24 and 36 months. At 12, 24, and 36 months, the probabilities of success in the μLOT and KDB groups for criterion A were 70.4% and 48.2%, 61.9% and 48.2%, and 55.0% and 48.2% (p = 0.32; log-rank test), respectively. For criterion B, the results for the two groups were 55.6% and 33.3%, 44.4% and 33.3%, and 44.4% and 33.3% (p = 0.15; log-rank test), respectively. Similar postoperative complications were found between the groups. Comparable mid-term surgical outcomes were found for the uses of μLOT and KDB.
PFC@O2 Targets HIF-1α to Reverse the Immunosuppressive TME in OSCC
Authors: Lan Zhou , Zou Ke-Long , Cui Hao , Chen Hao , Zhao Yu-Yue , Yu Guang-Tao
Published: January 2023

As a typical hallmark of solid tumors, hypoxia affects the effects of tumor radiotherapy, chemotherapy, and photodynamic therapy. Therefore, targeting the hypoxic tumor microenvironment (TME) is a promising treatment strategy for cancer therapy. Here, we prepared an Albumin Human Serum (HSA)-coated perfluorocarbon (PFC) carrying oxygen (PFC@O2) to minimize OSCC hypoxia. The results showed that PFC@O2 significantly downregulated the expression of HIF-1α and the number of M2-like macrophages in vitro. Furthermore, PFC@O2 effectively inhibited the growth of oral squamous cell carcinoma (OSCC) and reduced the proportion of negative immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and M2-like macrophages of TME in a 4-nitroquinoline N-oxide (4NQO)-induced mouse model. Conversely, the infiltration of CD4+ and CD8+ T cells was significantly increased in TME, suggesting that the anti-tumor immune response was enhanced. However, we also found that hypoxia-relative genes expression was positively correlated with CD68+/CD163+ TAMs in human tissue specimens. In summary, PFC@O2 could effectively inhibit the progression of OSCC by alleviating hypoxia, which provides a practical basis for gas therapy and gas synergistic therapy for OSCC.
Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan
Authors: Tokushige Katsutoshi , Kogiso Tomomi , Egawa Hiroto
Published: January 2023

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure <35 mmHg and pulmonary vascular resistance <400 dyn/s/cm−5 are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT.
Real-World Comparison of Transcatheter Versus Surgical Aortic Valve Replacement in the Era of Current-Generation Devices
Authors: Sa Young Kyoung , Hwang Byung-Hee , Chung Woo-Baek , Lee Kwan Yong , Lee Jungkuk , Kang Dongwoo , Ko Young-Guk , Yu Cheol Woong , Kim Juhan , Choi Seung-Hyuk , Bae Jang-Whan , Chae In-Ho , Choi Yun-Seok , Park Chul Soo , Yoo Ki Dong , Jeon Doo Soo , Kim Hyo-Soo , Chung Wook-Sung , Chang Kiyuk
Published: January 2023

Few studies have reported comparisons of out-of-hospital clinical outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) in the era of current-generation valves that reflect the real-world situation. Data on patients with severe AS aged 65 years or older who underwent TAVR or SAVR between 2015 and 2018 were obtained from the National Health Insurance Service in Korea and clinical event rate was analyzed. The primary endpoint was all-cause death at 1 year. The cohort included a total of 4623 patients over 65 years of age, of whom 1269 (27.4%) were treated with TAVR. After 1:1 propensity score matching, 2120 patients were included in the study. TAVR was associated with reduced 1-year mortality (hazard ratio (HR): 0.55; 95% confidence interval (CI): 0.42–0.70; p < 0.001). There was no difference between the groups in the incidence of ischemic stroke (HR: 0.72, 95% CI: 0.43–1.20; p = 0.21) and intracranial hemorrhage (HR: 1.10; p = 0.74). Permanent pacemaker insertion was observed more frequently in the TAVR cohort (9.4% vs. 2.5%, HR: 3.95, 95% CI: 2.57–6.09; p < 0.001), whereas repeat procedures were rare in both treatments (0.5% vs. 0.3%, p = 0.499). In the nation-wide real-world data analysis, TAVR with current-generation devices showed significantly lower 1-year mortality compared to SAVR in severe AS patients.
Prognostic Potential of Cyclin D1 Expression in Colorectal Cancer
Authors: Jun Sun-Young , Kim Jiyoung , Yoon Nara , Maeng Lee-So , Byun Jae Ho
Published: January 2023

Cyclin D1 is mainly known as an oncogenic driver in cancers, and the dysregulated cyclin D1/cyclin-dependent kinase (CDK) 4/6 axis is considered an attractive target for cancer therapy. Recent studies have reported that tumors respond to therapeutic interventions targeting altered cyclin D1 expression via application of the CDK4/6 inhibitor. However, the prognostic and therapeutic contributions of cyclin D1 to colorectal cancer (CRC) remain controversial. Herein, we assessed the associations between cyclin D1 expression and clinicopathological factors, including patients’ overall survival (OS) and recurrence-free survival (RFS), in 495 surgically resected primary CRCs. We also examined previous studies for cyclin D1 in CRCs. High expressions of cyclin D1 (cyclin D1High) was observed in 389 CRC cases (78.6%). Cyclin D1High consistently predicted better patient OS and RFS in CRCs. Based on multivariate analysis, cyclin D1High and young age of patients remained as independent prognosticators of higher OS rate, whereas cyclin D1High, females, chemotherapy, absence of nodal metastasis, and lower T-category remained as independent prognosticators of better RFS. Cyclin D1 is commonly overexpressed in CRCs, and its expression can be used as a favorable prognostic indicator in patients with CRCs; this may be important for predicting responses to subsequent CDK4/6 inhibitors.
Coping Strategies and Posttraumatic Growth Following Transient Ischemic Attack: A Qualitative Study
Authors: Kindermann David , Grosse-Holz Veronika Maria , Andermann Martin , Ringleb Peter Arthur , Friederich Hans-Christoph , Rizos Timolaos , Nikendei Christoph
Published: January 2023

A transient ischemic attack (TIA) is defined as a temporary neurological dysfunction due to focal brain ischemia. We aimed to identify common coping strategies and the possible occurrence of posttraumatic growth in TIA patients. Semistructured interviews were conducted with TIA patients three months after TIA. We asked the participants about possible changes in the aftermath of their TIA and their way of coping with said changes. All interviews were tape-recorded and subsequently transcribed verbatim. Thematic content analysis was performed to identify main categories and themes. Seventeen patients with a median age of 66 years completed the semistructured interviews. Qualitative content analysis revealed 332 single codes, from which the three main categories “impairments as a consequence of TIA”, “coping strategies” and “posttraumatic growth” were generated. The main categories were further subdivided into seven categories and thirty-six themes. TIA patients may suffer from various physical impairments, which also involve medication side effects. Activating resources on the one hand, and avoiding negative thoughts and feelings on the other hand, were identified to be the relevant coping strategies in TIA patients. Posttraumatic growth seems to be a common phenomenon after TIA, which may have important implications for treatment and rehabilitation.
Spring Plates as a Valid Additional Fixation in Comminuted Posterior Wall Acetabular Fractures: A Retrospective Multicenter Study
Authors: De Mauro Domenico , Rovere Giuseppe , Are Lorenzo , Smakaj Amarildo , Aprato Alessandro , Mezzadri Umberto , Bove Federico , Casiraghi Alessandro , Marino Silvia , Ciolli Gianluca , Cerciello Simone , Maccagnano Giuseppe , Noia Giovanni , Massè Alessandro , Maccauro Giulio , Liuzza Francesco
Published: January 2023

Background: The posterior wall fracture is the most frequent pattern of acetabular fractures. Many techniques of fixation have been described in the literature and involve plates, screws, or a combination of both. This study aims to investigate the clinical and radiological outcomes of spring plates in the treatment of comminuted posterior wall acetabular fractures. (2) Methods: A retrospective multicenter (four level I trauma centers) observational study was performed. Patients with a comminuted posterior wall acetabular fracture treated with a spring plate (DePuy Synthes, West Chester, PA) were included. Diagnosis was made according to the Judet and Letournel classification. Diagnosis was confirmed with plain radiographs in an antero-posterior view and Judet views, iliac and obturator oblique views, and thin-slice CT with multiplanar reconstructions. (3) Results: Forty-six patients (34 males and 12 females) with a mean age of 51.7 years (range 19–73) were included. The most common mechanism of injury was motor vehicle accident (34 cases). In all cases, spring plates were placed under an overlapping reconstruction plate. The mean follow-up was 33.4 months (range 24–48). The mean period without weight-bearing was 4.9 weeks (range 4–7), and full weight-bearing was allowed at an average of 8.2 weeks (range 7–11) after surgery. (4) Conclusions: According to the present data, spring plates can be considered a viable additional fixation of the posterior wall acetabular fractures.
Leishmania Infection during Ruxolitinib Treatment: The Cytokines-Based Immune Response in the Setting of Immunocompromised Patients
Authors: Duminuco Andrea , Scarso Salvatore , Cupri Alessandra , Parrinello Nunziatina Laura , Villari Loredana , Scuderi Grazia , Giunta Giuliana , Leotta Salvatore , Milone Giulio Antonio , Giuffrida Giulia , Palumbo Giuseppe Alberto , Milone Giuseppe
Published: January 2023

Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis. Leishmania is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-Leishmania antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient.
Is Thrombocytopenia an In-Hospital Mortality Risk Factor among Patients with Acute Ischemic Stroke? A Propensity Score-Matched Analysis from the MIMIC-IV Database
Authors: Wang Yan-Ru , Yang Li-Yu , Lee Cho-Hao , Chang Shu-Hao , Chen Po-Huang , Jhou Hong-Jie
Published: January 2023

(1) Background: We aimed to evaluate the aspect of thrombocytopenia in patients with acute ischemic stroke (AIS); (2) Methods: Patients with AIS were recruited in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The thrombocytopenia was defined as a platelet blood count of less than 150 K/µL. We compared the patient characteristics and clinical outcomes using propensity score matching (PSM); (3) Results: Thrombocytopenia affected 151 out of the 1236 patients (12.2%). Patients with thrombocytopenia were older (70.5 ± 12.8 vs. 68.4 ± 14.4; SMD = 0.154) and had a higher Charlson comorbidity index (7.3 ± 2.5 vs. 6.7 ± 2.7; SMD = 0.228) and acute physiology score III (44.8 ± 21.0 vs. 38.2 ± 19.1; SMD = 0.328) than those without thrombocytopenia. The risk of in-hospital mortality did not increase linearly or nonlinearly with a lower platelet count (overall p value = 0.794; nonlinear p value = 0.646). After PSM, 147 pairs remained. Thrombocytopenia was not linked with in-hospital mortality (HR: 1.06, 95% CIs: 0.60–1.88); (4) Conclusions: We described the clinical characteristics of patients admitted for thrombocytopenia and AIS who did not receive reperfusion therapy; additionally, we found that thrombocytopenia was not an independent short-term risk factor of in-hospital mortality.
“A Different Ride”: A Qualitative Interview Study of Parents’ Experience with Early Diagnosis and Goals, Activity, Motor Enrichment (GAME) Intervention for Infants with Cerebral Palsy
Authors: Morgan Catherine , Badawi Nadia , Novak Iona
Published: January 2023

Cerebral palsy is the most common physical disability of childhood, and early diagnosis followed by best practice early intervention is important for optimizing child and family outcomes. We investigated parents’ views of an early diagnosis of cerebral palsy (CP), followed by Goals, Activity, Motor Enrichment (GAME) intervention. Semi-structured interviews were conducted within a pilot randomised clinical trial. Transcriptions were analyzed using grounded theory. Participants were nine mothers whose infants had received GAME intervention because they were identified as being at high risk for cerebral palsy early in infancy. The parenting experience was described as a “different ride”. The diagnosis was devastating with many time-consuming challenges, but acceptance ensued. Parents wanted an early diagnosis, prognosis, and early intervention, despite the anxiety and workload, because it meant they could help. Parents perceived that GAME was beneficial because they were taught how to help; it was goal-based and home-based. They believed the collaboration and communication skills of the therapist shaped success. Future research should focus on a broader range of participants to understand parent’s experiences with key aspects of early intervention more fully.
Comparison of the Predictive Accuracy of Intraocular Lens Power Calculations after Phototherapeutic Keratectomy in Granular Corneal Dystrophy Type 2
Authors: Yoon Sook Hyun , Jo Woo Kyung , Kim Tae-im , Seo Kyoung Yul , Choi Jinseok , Jun Ikhyun , Kim Eung Kweon
Published: January 2023

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease affecting vision. Phototherapeutic keratectomy (PTK) is advantageous in removing vision-threatening corneal opacities and postponing keratoplasty; however, it potentially disturbs accurate intraocular lens (IOL) power calculation in cataract surgery. The myopic/hyperopic Haigis-L method with or without the central island has been reported; nevertheless, an optimal method has not yet been established. To compare the predictive accuracy of post-PTK IOL power calculations in GCD2, the retrospective data of 30 eyes from July 2017 to December 2020 were analyzed. All GCD2-affected eyes underwent post-PTK standard cataract surgery using the WaveLight EX500 platform (Alcon Laboratories, Inc., Fort Worth, TX, USA) under a single surgeon. The mean prediction error (MPE) and absolute error (MAE) with the myopic/hyperopic Haigis-L, Barrett Universal II, Barrett True-K, Haigis, and SRK/T by standard keratometry (K) and total keratometry (TK), where possible, were analyzed. Barrett Universal II and SRK/T showed significantly superior MPE, and MAE compared with the myopic/hyperopic Haigis-L method. TK was not significantly superior to K in the same formula. In conclusion, this study suggests that these biometries and formulas, especially Barrett Universal II and SRK/T, are potentially useful in IOL power calculation in GCD2 after PTK.
Mechanical Properties of PLA Specimens Obtained by Additive Manufacturing Process Reinforced with Flax Fibers
Authors: Paulo Ana , Santos Jorge , da Rocha João , Lima Rui , Ribeiro João
Published: January 2023

Although polylactic acid (PLA) is one of the most used materials in additive manufacturing, its mechanical properties are quite limiting for its practical application, therefore, to improve these properties it is frequent to add fibers and, in this way, create a more resistant composite material. In this paper, the authors developed PLA composites reinforced with flax fibers to evaluate the improvement of tensile and flexural strength. The experimental design of experiments was based on the L18 Taguchi array where the control factors were the extruder temperature (three levels), number of strands (three levels), infill percentage of the specimens (three levels), and whether the flax fiber had surface chemical treatment. The tensile and flexural specimens were made on a 3D printing machine and was a mold was developed to fix and align the fiber strands during the printing process. The tensile and flexural experimental tests were performed in agreement with ASTM D638.14 and ISO 14125 standards, respectively. Analyzing the results, it was verified that the surface chemical treatment (NaOH) of the fiber did not show any influence in the mechanical properties of the composites; in contrast, the infill density demonstrated a huge influence for the improvement of mechanical strength. The maximum values of tensile and bending stress were 50 MPa and 73 MPa, respectively. The natural fiber reinforcement can improve the mechanical properties of the PLA composites.
Design, Simulation, and Mechanical Testing of 3D-Printed Titanium Lattice Structures
Authors: Bari Klaudio
Published: January 2023

Lattice structure topology is a rapidly growing area of research facilitated by developments in additive manufacturing. These low-density structures are particularly promising for their medical applications. However, predicting their performance becomes a challenging factor in their use. In this article, four lattice topologies are explored for their suitability as implants for the replacement of segmental bone defects. The study introduces a unit-cell concept for designing and manufacturing four lattice structures, BCC, FCC, AUX, and ORG, using direct melt laser sintering (DMLS). The elastic modulus was assessed using an axial compression strength test and validated using linear static FEA simulation. The outcomes of the simulation revealed the disparity between the unit cell and the entire lattice in the cases of BCC, FCC, and AUX, while the unit-cell concept of the full lattice structure was successful in ORG. Measurements of energy absorption obtained from the compression testing revealed that the ORG lattice had the highest absorbed energy (350 J) compared with the others. The observed failure modes indicated a sudden collapsing pattern during the compression test in the cases of BCC and FCC designs, while our inspired ORG and AUX lattices outperformed the others in terms of their structural integrity under identical loading conditions.
Methods for Measuring Carbon Dioxide Uptake and Permanence: Review and Implications for Macroalgae Aquaculture
Authors: Rose Deborah J. , Hemery Lenaïg G.
Published: January 2023

Carbon dioxide removal (CDR) is gaining recognition as a necessary action in addition to emissions reduction to prevent some of the worst effects of climate change. Macroalgae aquaculture has been identified as a potential CDR strategy and significant research investments have been made in this area. This article reviews current methods for monitoring carbon to assess the potential for application in the context of macroalgae aquaculture as a CDR strategy. In total, 382 papers were included in the review and categorized by carbon uptake methods, carbon permanence methods, and comprehensive frameworks for assessing carbon capture. While methods for measuring carbon uptake are well established, methods to assess the permanence of carbon in the natural life cycle of macroalgae and in products following harvest are lacking. To achieve the full benefit of macroalgae cultivation as a climate solution, monitoring, reporting, and verification standards and improved methods for assessing carbon uptake and permanence need to be developed.