bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary sensory autonomic neuropathy type VI in the age of genetic testing
Authors: Peringassery Sateesh Lekshmi , Chitamanni Pavani , Akinsanmi Danielle , Ghosh Suman , Pavlakis Steven G. , Reznikov Alexandra 
Published: August 2024

AbstractBackgroundHereditary sensory and autonomic neuropathy type VI (HSAN VI) is a rare recessive genetic disorder caused by mutations in the human dystonin (DST) gene. We report a novel homozygous alternate transcript mutation in the DST gene causing a severe neonatal form of HSAN VI.Patient DescriptionThis baby boy was born with severe hypotonia, respiratory distress, dysmorphic features, and bilateral club feet. Imaging, karyotyping, Prader–Willi assay, spinal muscular atrophy genetic panel and myotonic dystrophy genetic panel were all negative. A comprehensive neuropathy panel detected a homozygous pathogenic variant in the DST gene—alternate transcript NM_015546.4:c.1357G>A (p.Trp4525*). Nerve conduction studies revealed mixed axonal and demyelinating sensorimotor neuropathy, suggesting the possibility of motor involvement in severe forms of this rare condition. The infant ultimately developed sepsis and died from cardiorespiratory arrest. Neuropathological findings of focal and mild spinal nerve axonal degeneration were nonspecific.ConclusionCollective analysis of these patients would help to further characterize the spectrum of disease pathology and could provide insight into the neurophysiology and neuropathology of this rare condition.
Kynurenine pathway in type 2 diabetes: Role of metformin
Authors: Al‐Qahtani Zainah , Al‐kuraishy Hayder M. , Ali Naif H. , Elewa Yaser Hosny Ali , Batiha Gaber El‐Saber 
Published: August 2024

AbstractThe Kynurenine pathway (KP) which is involved in the synthesis of nicotinamide adenine dinucleotide (NAD) from tryptophan (Trp) is intricate in the development of insulin resistance (IR) and type 2 diabetes (T2D). Inflammatory reactions in response to cardiometabolic disorders can induce the development of IR through the augmentation of KP. However, kynurenine (KYN), a precursor of kynurenic acid (KA) is increased following physical exercise and involved in the reduction of IR. Consequently, KP metabolites KA and KYN have anti‐diabetogenic effects while other metabolites have diabetogenic effects. KP modulators, either inhibitors or activators, affect glucose homeostasis and insulin sensitivity in T2D in a bidirectional way, either protective or detrimental, that is not related to the KP effect. However, metformin through inhibition of inflammatory signaling pathways can reduce the activation of KP in T2D. These findings indicated a strong controversy regarding the role of KP in T2D. Therefore, the objectives of this mini review were to clarify how KP induces the development of IR and T2D. In addition, this review aimed to find the mechanistic role of antidiabetic drug metformin on the KP, and how KP modulators affect the pathogenesis of T2D.
Bread consumption trends in Poland: A socio‐economic perspective and factors affecting current intake
Authors: Sadowski Adam , Dobrowolska Bogusława , Dziugan Piotr , Motyl Ilona , Liszkowska Wiktoria , Rydlewska‐Liszkowska Izabela , Berłowska Joanna 
Published: August 2024

AbstractFermentation processes have been known since ancient times and are widely used in the production of food, beverages, and other areas. One of the most well‐known fermented products is bread. It plays an important role in human nutrition because of the valuable compounds it contains. The growing population leads to an increase in global bread consumption and other bakery products. Simultaneously, in developed countries, declining consumption trends are observed. Understanding the complex interplay between socio‐economic dynamics, food production policies, and the dietary patterns of society is crucial for shaping effective strategies that align with the principles of a sustainable and resilient food system. The aim of this study was to determine bread consumption trends in Poland. Data were obtained from the Household Budget Surveys carried out by Statistics Poland. The study considered the period from 1978 to 2020 and was performed in three dimensions: socio‐economic groups, the number of people in households, and income quintile groups. A decreasing trend in bread consumption was observed within the analyzed period in all three socio‐economic groups. Based on the analysis of the relationship between bread consumption and income level per capita, the same observation was made. There was no correlation between the amount of bread consumed and the number of people in the household. The obtained data are determined by many factors, including prices of bread, demographic changes, dietary patterns, and education in the field of human nutrition.
Cancer risk among people living with Human Immunodeficiency Virus (HIV) in Rwanda from 2007 to 2018
Authors: Dusingize Jean Claude , Murenzi Gad , Muhoza Benjamin , Businge Lydia , Remera Eric , Uwinkindi Francois , Hagenimana Marc , Rwibasira Gallican , Nsanzimana Sabin , Castle Philip E. , Anastos Kathryn , Clifford Gary M. 
Published: August 2024

AbstractAssessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population‐based cancer registry data were used to identify cancer cases in both PLHIV and HIV‐negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2–36.6), non‐Hodgkin lymphoma (NHL) (1.6, 1.3–2.0), Hodgkin lymphoma (HL) (1.6, 1.1–2.4), cervical (2.3, 2.0–2.7), vulvar (4.0, 2.5–6.5), penile (3.0, 2.0–4.5), and eye cancers (2.2, 1.6–3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0–9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2–4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections.
Therapeutic approaches and novel antifibrotic agents in renal fibrosis: A comprehensive review
Authors: Lahane Ganesh Panditrao , Dhar Arti , Bhat Audesh 
Published: August 2024

AbstractRenal fibrosis (RF) is one of the underlying pathological conditions leading to progressive loss of renal function and end‐stage renal disease (ESRD). Over the years, various therapeutic approaches have been explored to combat RF and prevent ESRD. Despite significant advances in understanding the underlying molecular mechanism(s), effective therapeutic interventions for RF are limited. Current therapeutic strategies primarily target these underlying mechanisms to halt or reverse fibrotic progression. Inhibition of transforming growth factor‐β (TGF‐β) signaling, a pivotal mediator of RF has emerged as a central strategy to manage RF. Small molecules, peptides, and monoclonal antibodies that target TGF‐β receptors or downstream effectors have demonstrated potential in preclinical models. Modulating the renin–angiotensin system and targeting the endothelin system also provide established approaches for controlling fibrosis‐related hemodynamic changes. Complementary to pharmacological strategies, lifestyle modifications, and dietary interventions contribute to holistic management. This comprehensive review aims to summarize the underlying mechanisms of RF and provide an overview of the therapeutic strategies and novel antifibrotic agents that hold promise in its treatment.
CASQ2 alleviates lung cancer by inhibiting M2 tumor‐associated macrophage polarization and JAK/STAT pathway
Authors: Ding Yan , Yuan Xiaoliang , Wang Ying , Yan Jun 
Published: August 2024

AbstractLung cancer (LC) is a major inducer of cancer‐related death. We aim to reveal the effect of Calsequestrin2 (CASQ2) on macrophage polarization and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in LC. Hub genes were determined from protein–protein interaction networks based on GSE21933 and GSE1987 data sets using bioinformatic analysis. Expression of hub genes was verified by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell Counting Kit‐8, 5‐ethynyl‐2'‐deoxyuridine, wound‐healing, colony formation, and transwell assays were performed to assess the impact of CASQ2 on LC cells. A xenograft mouse model was evaluated using hematoxylin–eosin, immunohistochemistry, and terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling staining to investigate the effect of CASQ2 on LC. The role of CASQ2 in regulating macrophage polarization and JAK/STAT pathway was evaluated by western blot andRT‐qPCR. We screened out 155 common differentially expressed genes in GSE21933 and GSE1987 data sets. Myomesin‐2, tyrosine kinase, sex determining region Y‐box 2, platelet and endothelial cell adhesion molecule 1, matrix metallopeptidase 9, claudin‐5, caveolin‐1, CASQ2, recombinant ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2), and ankyrin repeat domain 1 were identified as the hub genes with high prediction value. CASQ2 was selected as a pivotal regulator of LC. In vitro experiments and xenograft models revealed that CASQ2 overexpression suppressed proliferation, colony formation, migration, invasion of LC cells, and tumor growth in vivo. Additionally, overexpression of CASQ2 promoted the expression of M1 macrophage markers (cluster of differentiation 80 [CD80], interleukin [IL]‐12, inducible nitric oxide synthase [iNOS]), while decreasing the expression of M2 macrophage markers (CD163, IL‐10, Arg1) in tumor‐associated macrophages and xenograft tissues. Finally, we found that overexpression of CASQ2 inhibited JAK/STAT pathway. CASQ2 is a novel biomarker, which can alleviate LC via inhibiting M2 tumor‐associated macrophage polarization and JAK/STAT pathway.
Hesperetin‐loaded chitosan nanoparticles ameliorate hyperglycemia by regulating key enzymes of carbohydrate metabolism in a diabetic rat model
Authors: Radhakrishnan Sivamathi Rathna Priya , Mohan Karthik , Natarajan Ashokkumar 
Published: August 2024

AbstractThe study aimed to investigate the potential of hesperetin‐loaded chitosan nanoparticles (HSPCNPs) in alleviating hyperglycemia by modulating key enzymes in diabetic rats. Chitosan nanoparticles loaded with hesperetin were prepared using the ionic gelation method and characterized with Electron microscope (SEM), zeta potential, particle size analysis, Fourier‐transform infrared (FT‐IR), Energy dispersive spectroscopy (EDS) and Encapsulation efficiency and Loading efficiency. To induce diabetes, rats were fed a high‐fat beef tallow diet for 28 days, then given a single dose of streptozotocin (STZ) at 35 mg/kg b.w in 0.1 M citrate buffer (pH 4.0). Rats were treated with HSPCNPs at doses of 10, 20, and 40 mg/kg b.w. The analyzed parameters included body weight, food and water intake, plasma glucose and insulin, liver and skeletal muscle glycogen levels, and carbohydrate metabolism. SEM imaging revealed dimensions between 124.2 and 251.6 nm and a mean particle size of 145.0 nm. FT‐IR analysis confirmed the presence of functional groups in the chitosan nanoparticles, and the zeta potential was 35.5 mV. HSPCNP 40 mg/kg b.w significantly (p < 0.05) reduced blood glucose levels and glycosylated hemoglobin, improving body weight, food intake, and reducing water intake. In diabetic rats, enzymes for carbohydrate metabolism like fructose 1,6‐bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose 6‐phosphatase are evaluated in the liver, while glucose 6 phosphate dehydrogenase and hexokinase activity were significantly lower. Additionally, plasma insulin levels increased, indicating enhanced insulin sensitivity. The results show that HSPCNPs at 40 mg/kg b.w. ameliorate hyperglycemia to provide robust protection against diabetic complications and significantly improve metabolic health.
Calycosin activates Nrf2/Keap1 signaling to ameliorate hydrogen peroxide‐induced spinal cord neuron death and mitochondrial dysfunction
Authors: Ruan Ye , Cai Ziming , Kang Zhengwen , Liang Jinzhu , Tian He , Yu Qinghe , Zhang Qiusheng , Lin Wenping 
Published: August 2024

AbstractOxidative stress is a hallmark of secondary injury of spinal cord injuries. Controlling oxidative stress is crucial for mitigating secondary injury and promoting functional recovery after spinal cord injuries. Calycosin is an O‐methylated isoflavone with antioxidant activity. To evaluate the effect of calycosin on spinal cord neurons under oxidative stress and clarify the molecular mechanism underlying the effect, we tested the neuroprotective activity of calycosin in a primary spinal cord neuron culture model. We found that calycosin protected neurons from H2O2‐induced neuronal death in a dose‐dependent manner. Further experiments revealed that calycosin decreased H2O2‐induced mitochondrial fragmentation and mitochondrial membrane potential loss, and subsequently reduced H2O2‐triggered release of mitochondrial cytochrome c into the cytoplasm. In addition, calycosin inhibited H2O2‐induced reactive oxygen species generation and activation of NF‐κB signaling in spinal cord neurons. Furthermore, the expression of several antioxidant enzymes such as HO‐1, NQO1, GCLC, GCLM, TrxR1, and Trx1 was significantly promoted by calycosin. More importantly, we revealed that the Nrf2/Keap1 signal is crucial for the effect of calycosin, because calycosin increased the amount of nuclear Nrf2 while decreasing the amount of cytoplasmic Nrf2. Nrf2 knockdown with siRNA transfection abolished the neuroprotective effect of calycosin. Taken together, this study disclosed a novel mechanism by which calycosin combats oxidative stress. Our study thus sheds light on the potential clinical application of calycosin in SCI treatment.
A proton channel, Otopetrin 1 (OTOP1) is N‐glycosylated at two asparagine residues in third extracellular loop
Authors: Sasaki Omi , Yano‐Nashimoto Saori , Yamaguchi Soichiro 
Published: August 2024

AbstractA proton (H+) channel, Otopetrin 1 (OTOP1) is an acid sensor in the sour taste receptor cells. Although OTOP1 is known to be activated by extracellular acid, no posttranslational modification of OTOP1 has been reported. As one of the posttranslational modifications, glycosylation is known to modulate many ion channels. In this study, we investigated whether OTOP1 is glycosylated and how the glycosylation affects OTOP1 function. Pharmacological and enzymatic examinations (using an N‐glycosylation inhibitor, tunicamycin and peptide: N‐glycanase F [PNGase F]) revealed that overexpressed mouse OTOP1 was N‐glycosylated. As the N‐glycans were Endoglycosidase H (Endo H)‐sensitive, they were most likely high‐mannose type. A site‐directed mutagenesis approach revealed that both two asparagine residues (N238 and N251) in the third extracellular loop between the fifth transmembrane region and the sixth transmembrane region (L5‐6) were the glycosylation sites. Prevention of the glycosylations by the mutations of the asparagine residues or by tunicamycin treatment diminished the whole‐cell OTOP1 current densities. The results of cell surface biotinylation assay showed that the prevention of the glycosylations reduced the surface expression of OTOP1 at the plasma membrane. These results indicate that mouse OTOP1 is N‐glycosylated at N238 and N251, and that the glycosylations are necessary for OTOP1 to show the maximum degree of H+ current densities at the plasma membrane through promoting its targeting to the plasma membrane. These findings on glycosylations of OTOP1 will be a part of a comprehensive understanding on the regulations of OTOP1 function.
Single‐cell transcriptomic analysis of B cells reveals new insights into atypical memory B cells in COVID‐19
Authors: García‐Vega Melissa , Llamas‐Covarrubias Mara Anais , Loza Martin , Reséndiz‐Sandoval Mónica , Hinojosa‐Trujillo Diana , Melgoza‐González Edgar , Valenzuela Olivia , Mata‐Haro Verónica , Hernández‐Oñate Miguel , Soto‐Gaxiola Alan , Chávez‐Rueda Karina , Nakai Kenta , Hernández Jesús 
Published: August 2024

AbstractHere, we performed single‐cell RNA sequencing of S1 and receptor binding domain protein‐specific B cells from convalescent COVID‐19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID‐19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS‐CoV‐2 and that these genes may contribute to the immune response for COVID‐19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID‐19 and the role of other B cell subsets across different clinical manifestations.
Examining the effects of ChatGPT on tourism and hospitality student responses through integrating technology acceptance model
Authors: Zhu Chris Zhen Gan , Hall C. Michael , Fong Lawrence Hoc Nang , Lin Feifei , Naderi Koupaei Sara 
Published: August 2024

AbstractChatGPT has gained increased attention as an artificial intelligence (AI)‐based tool in the field of tourism and hospitality education in recent years. This study investigates the impact of perceived ease of use, perceived usefulness and authenticity on student attitude and intention to use ChatGPT by incorporating the concept of authenticity into the technology acceptance model (TAM) theoretical framework in tourism and hospitality education. This study found that authenticity had the strongest indirect effect on student intention to use ChatGPT compared with perceived ease of use and perceived usefulness. This study broadens the applicability of TAM theory in ChatGPT and provides practical insights into its application.
Low‐dose ionizing radiation‐induced RET/PTC1 rearrangement via the non‐homologous end joining pathway to drive thyroid cancer
Authors: Liu Yuhao , Zhu Jiaojiao , Zhou Shenghui , Hou Yifan , Yan Ziyan , Ao Xingkun , Wang Ping , Zhou Lin , Chen Huixi , Liang Xinxin , Guan Hua , Gao Shanshan , Xie Dafei , Gu Yongqing , Zhou Ping‐Kun 
Published: August 2024

AbstractThyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled‐coil domain containing 6 [CCDC6]‐rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N‐thy‐ori‐3‐1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low‐dose IR‐induced RET/PTC1 rearrangement in a dose‐dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI‐1, and Olaparib were employed to inhibit non‐homologous end joining (NHEJ), homologous recombination (HR), and microhomology‐mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR‐induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) decreased the efficiency of NHEJ and thus reduced IR‐induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR‐induced RET/PTC1 rearrangement. Targeting DNA‐PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR‐induced RET/PTC1 rearrangement in PTC.
Pyroptosis and the fight against lung cancer
Authors: Wang Jiwei , Su Huiling , Wang Min , Ward Richard , An Su , Xu Tian‐Rui 
Published: August 2024

AbstractPyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage‐associated molecular patterns (DAMPs), leading to the activation of caspase‐1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore‐forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto‐inhibition. Upon caspases mediated cleavage of gasdermins, the pro‐pyroptotic N‐terminal fragment is released from the auto‐inhibition of C‐terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)‐1β, IL‐18, and high‐mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.