bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary cilium participates in radiation‐induced bystander effects through TGF‐β1 signaling
Authors: Qu Pei , Shao Zhiang , Zhang Yanan , He Jinpeng , Lu Dong , Wei Wenjun , Hua Junrui , Wang Wei , Wang Jufang , Ding Nan 
Published: November 2023

AbstractMany studies have indicated that tumor growth factor‐beta (TGF‐β) signaling mediates radiation‐induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF‐β signaling to regulate diverse cellular processes. But whether the PC participates in TGF‐β induced RIBEs remains unclear. The cellular levels of TGF‐β1 were detected by western blot analysis and the secretion of TGF‐β1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0/G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF‐β1 signaling was interfered by LY2109761, a TGF‐β receptor 1 (TβR1) inhibitor, or TGF‐β1 neutral antibody. The DNA damages were induced by TGF‐β1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci. Compared with unirradiated control, both A549 and Beas‐2B cells expressed and secreted more TGF‐β1 after carbon ion beam or X‐ray irradiation. RCM collected from irradiated cells or TGF‐β1 treatment caused an increase of DNA damage in cocultured unirradiated Beas‐2B cells while blockage of TGF‐β signaling by TβR1 inhibitor or TGF‐β1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF‐β1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0/G1 phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF‐β1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.
Physiologically Based Pharmacokinetic Modeling for Maribavir to Inform Dosing in Drug‐Drug Interaction Scenarios with CYP3A4 Inducers and Inhibitors
Authors: Chen Grace , Sun Kefeng , Michon Ingrid , Barter Zoe , Neuhoff Sibylle , Ghosh Lipika , Ilic Katarina , Song Ivy H. 
Published: November 2023

AbstractMaribavir, an orally available antiviral agent, has been approved in multiple countries for the treatment of patients with refractory post‐transplant cytomegalovirus (CMV) infection and/or disease. Maribavir is primarily metabolized by CYP3A4; coadministration with CYP3A4 inducers and inhibitors may significantly alter maribavir exposure, thereby affecting its efficacy and safety. The effect of CYP3A4 inducers and inhibitors on maribavir exposure was evaluated based on a drug‐drug interaction (DDI) study and physiologically‐based pharmacokinetic (PBPK) modeling. The effect of rifampin (a strong inducer of CYP3A4 and moderate inducer of CYP1A2), administered at a 600 mg dose once daily, on maribavir pharmacokinetics was assessed in a clinical phase 1 DDI study in healthy participants. A full PBPK model for maribavir was developed and verified using in vitro and clinical pharmacokinetic data from phase 1 studies. The verified PBPK model was then used to simulate maribavir DDI interactions with various CYP3A4 inducers and inhibitors. The DDI study results showed that coadministration with rifampin decreased the maribavir maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), and trough concentration (Ctrough) by 39%, 60%, and 82%, respectively. Based on the results from the clinical DDI study, the coadministration of maribavir with rifampin is not recommended. The PBPK model did not predict a clinically significant effect of CYP3A4 inhibitors on maribavir exposure; however, it predicted that strong or moderate CYP3A4 inducers, including carbamazepine, efavirenz, phenobarbital, and phenytoin, may reduce maribavir exposure to a clinically significant extent, and may prompt the consideration of a maribavir dosing increase, in accordance with local approved labels and/or regulations.
Intensified capture of recombinant blood coagulation factors by continuous, integrated downstream processing
Authors: Engelmaier Hannah , Dattenböck Christoph , Petrushevska‐Seebach Katerina , Jungbauer Alois , Hammerschmidt Nikolaus 
Published: November 2023

AbstractBACKGROUNDThe biopharmaceutical community has realized the tremendous potential of continuous processing for process intensification. However, to date reports of continuous processes for monoclonal antibodies (mAb) represent the overwhelming majority, while integrated continuous processes for non‐mAb products are rare.RESULTSWe have developed an integrated, continuous process for capture of recombinant blood coagulation factors: Factor VIII (FVIII) and VonWillebrand factor (VWF). Due to their complex and diverse nature, tailored solutions beyond chromatographic separations are required for continuously producing non‐mAb products. Our integrated process consists of three continuous unit operations that include cell removal, product capture by precipitation and precipitate collection with a yield of 33% and 56% for FVIII and VWF, respectively. These unit operations were developed individually and then integrated into a continuous process at laboratory scale. Using prototype equipment, we have demonstrated continuous, integrated capture of recombinant blood coagulation factors over a duration of 24 h.CONCLUSIONThe continuous solutions employed were developed for FVIII and VWF, but may very well be applied to other molecules. These solutions to continuous solid–liquid separation and integration are important parts in the puzzle that is continuous downstream processing of biopharmaceuticals. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Assessing vitamin D as a biomarker in inflammatory bowel disease
Authors: Yeaman Fiona , Nguyen Anke , Abasszade Joshua , Gupta Sanjana , Bell Sally , Moore Gregory 
Published: November 2023

AbstractBackground and AimA reliable serum biomarker for inflammatory bowel disease (IBD) activity is needed. Vitamin D is involved in inflammation and has been demonstrated to be low in IBD patients with active disease. It is routinely measured in IBD patients. Therefore, vitamin D may have a role as a serum biomarker in IBD. This study aims to investigate whether serum vitamin D may be useful as a biomarker in IBD in a real‐world IBD population.MethodsPatients were identified by review of fecal calprotectin (FCP) results, and those who had a clinical review, vitamin D test, and FCP performed within 3 months were included. Clinical scores were calculated from chart review. Nonparametric tests were used to investigate vitamin D and FCP levels, serum biomarkers, and clinical scores.ResultsOf 616 patients identified, 325 episodes of matched vitamin D level and biomarker data were obtained. A statistically significant correlation was found between vitamin D levels and FCP levels for all patients (r = −0.19 [s –0.29 to −0.080], P < 0.001]. This remained true when patients were divided into IBD subsets. Low vitamin D was associated with partial Mayo scores and C‐reactive protein (CRP) to albumin ratio in ulcerative colitis, and CRP and CRP/albumin ratio in Crohn's disease.ConclusionVitamin D level is negatively correlated with FCP and it may be considered as an adjunct biomarker at this stage. A prospective study would be beneficial to investigate further correlations between vitamin D and existing biomarkers of inflammation in IBD.
The efficacy and safety of pure laparoscopic liver resection for hepatocellular carcinoma in super‐elderly patients over 80 years: A multicenter propensity analysis
Authors: Namba Yosuke , Kobayashi Tsuyoshi , Hashimoto Masakazu , Onoe Takashi , Mashima Hiroaki , Oishi Koichi , Honmyo Naruhiko , Abe Tomoyuki , Kuroda Shintaro , Ohdan Hideki 
Published: November 2023

AbstractBackgroundVery few reports have evaluated the safety of laparoscopic liver resection in super‐elderly patients. We assessed the short‐term outcomes of laparoscopic liver resection in patients with hepatocellular carcinoma aged ≥80 years, using propensity score matching.MethodsWe retrospectively analyzed the data of 287 patients (aged ≥80 years) who underwent liver resection for hepatocellular carcinoma at eight hospitals belonging to Hiroshima Surgical study group of Clinical Oncology, between January 2012 and December 2021. The perioperative outcomes were compared between laparoscopic and open liver resection, using propensity score matching.ResultsOf the 287 patients, 83 and 204 were included in the laparoscopic and open liver resection groups, respectively. Propensity score matching was performed, and 52 patients were included in each group. The operation (p = .68) and pringle maneuver (p = .11) time were not different between the groups. There were no significant differences in the incidences of bile leakage or organ failure. The laparoscopic liver resection group had significantly less intraoperative bleeding and a lower incidence of cardiopulmonary complications (both p < .01).ConclusionsLaparoscopic liver resection can be safely performed in elderly patients aged ≥80 years.
Effect of previous heterologous flavivirus vaccinations on human antibody responses in tick‐borne encephalitis and dengue virus infections
Authors: Roßbacher Lena , Malafa Stefan , Huber Kristina , Thaler Melissa , Aberle Stephan W. , Aberle Judith H. , Heinz Franz X. , Stiasny Karin 
Published: November 2023

AbstractArthropod‐borne flaviviruses include a number of medically relevant human pathogens such as the mosquito‐borne dengue (DEN), Zika, and yellow fever (YF) viruses as well as tick‐borne encephalitis virus (TBEV). All flaviviruses are antigenically related and anamnestic responses due to prior immunity can modulate antibody specificities in subsequent infections or vaccinations. In our study, we analyzed the induction of broadly flavivirus cross‐reactive antibodies in tick‐borne encephalitis (TBE) and DEN patients without or with prior flavivirus exposure through TBE and/or YF vaccination, and determined the contribution of these antibodies to TBE and dengue virus (DENV) neutralization. In addition, we investigated the formation of cross‐reactive antibodies in TBE‐vaccination breakthroughs (VBTs). A TBEV infection without prior YF or TBE vaccination induced predominantly type‐specific antibodies. In contrast, high levels of broadly cross‐reactive antibodies were found in samples from TBE patients prevaccinated against YF as well as in DEN patients prevaccinated against TBE and/or YF. While these cross‐reactive antibodies did not neutralize TBEV, they were effective in neutralizing DENV. This discrepancy points to structural differences between the two viruses and indicates that broadly cross‐reactive epitopes are less accessible in TBEV than in DENV. In TBE VBT infections, type‐specific antibodies dominated the antibody response, thus revealing no difference from that of unvaccinated TBE patients. Our results emphasize significant differences in the structural properties of different flaviviruses that have an impact on the induction of broadly cross‐reactive antibodies and their functional activities in virus neutralization.
High sera levels of SARS‐CoV‐2 N antigen are associated with death in hospitalized COVID‐19 patients
Authors: Chenane Houssem Redha , Lingas Guillaume , Menidjel Reyene , Laouenan Cédric , Tubiana Sarah , Descamps Diane , Le Hingrat Quentin , Abel Laurent , Guedj Jérémie , Malhotra Surbhi , Kumar‐Singh Samir , Visseaux Benoit , Ghosn Jade , Charpentier Charlotte , Lebourgeois Samuel ,   the French COVID Cohort Study Group
Published: November 2023

AbstractThe presence of free severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) nucleocapsid‐antigen in sera (N‐antigenemia) has been shown in COVID‐19 patients. However, the link between the quantitative levels of N‐antigenemia and COVID‐19 disease severity is not entirely understood. To assess the dynamics and clinical association of N‐antigen sera levels with disease severity in COVID‐19 patients, we analyzed data from patients included in the French COVID cohort, with at least one sera sample between January and September 2020. We assessed N‐antigenemia levels and anti‐N IgG titers, and patient outcomes was classified in two groups, survival or death. In samples collected within 8 days since symptom onset, we observed that deceased patients had a higher positivity rate (93% vs. 81%; p < 0.001) and higher median levels of predicted N‐antigenemia (2500 vs. 1200 pg/mL; p < 0.001) than surviving patients. Predicted time to N‐antigen clearance in sera was prolonged in deceased patients compared to survivors (23.3 vs 19.3 days; p < 0.0001). In a subset of patients with both sera and nasopharyngeal (NP) swabs, predicted time to N‐antigen clearance in sera was prolonged in deceased patients (p < 0.001), whereas NP viral load clearance did not differ between the groups (p = 0.07). Our results demonstrate a strong relationship between N‐antigenemia levels and COVID‐19 severity on a prospective cohort.
Molecular investigation of some DNA viruses in mucosal melanoma: Case–control study
Authors: Arvia Rosaria , Tanturli Michele , Ugolini Filippo , Vannucchi Margherita , Massi Daniela , Zakrzewska Krystyna 
Published: November 2023

AbstractThe association between viral infections and both cutaneous and mucosal melanoma (MM) has not been fully investigated. Here, we assessed the prevalence of the DNA of a broad range of viruses in 31 MMs and 15 biopsies of healthy mucosa (HM) using molecular methods. The parvoviruses CuV and B19V, herpesviruses HSV1, HSV2, EBV, HHV6, and HHV8, polyomavirus MCPyV, and α‐HPVs were not detected, or rarely found, in MMs, and in HM, of the digestive, respiratory, and female genital tract. The overall prevalence of β‐HPV in MMs was not significantly higher compared to that in HM (70.9% and 53.3% respectively; p = 0.514). However, the number of MMs positive for β‐HPV types belonging to Species 3 and 5 and for some viral types belonging to Species 1, 2, 3, and 5 were significantly higher compared with HM (p < 0.05). Moreover, compared to HM, the MM samples contained a significantly higher number of β‐HPV types, mainly belonging to Species 1, 3, and 5 (p < 0.05). Our data, although suggesting a role for certain β‐HPV types in MM oncogenesis, require additional investigation in larger populations to support this hypothesis.
Isolation, structure characterization and in vitro immune‐enhancing activity of a glucan from the peels of stem lettuce (Lactuca sativa)
Authors: Zou Xianguo , Shen Mingjie , Li Jingjing , Sun Peilong , Zhong Xianfeng , Yang Kai 
Published: November 2023

AbstractBACKGROUNDStem lettuce is a medicinal and edible plant. The peels, accounting for 300–400 g kg−1 raw stem lettuce and containing polysaccharides 200 g kg−1, are discarded as industrial waste, causing environment pollution and resource waste.RESULTSA polysaccharide named PPSL10‐2 was obtained from the peels of stem lettuce after hot water extraction, and gradation with cascade ultrafiltration and purification using DEAE‐Sepharose cellulose. The purity and molecular weight of PPSL10‐2 is 96.10% and 2.2 × 104 Da respectively, as detected by high‐performance gel permeation chromatography. PPSL10‐2 was found to be an α‐(1→4)‐d‐glucan that branched at O‐6 with a terminal 1‐linked α‐d‐Glcp as side chain, and devoid of helix conformation, which was characterized by monosaccharide composition analysis, Fourier‐transform infrared spectroscopy, Congo red test, scanning electron microscopy, methylation analysis and NMR spectroscopy. Furthermore, PPSL10‐2 exhibited potent immune‐enhancing effect by improving proliferation and phagocytosis, promoting the secretion of nitric oxide and cytokines, as well as the expression of related genes in RAW264.7 macrophages.CONCLUSIONThe findings of the present study suggest that peels as an agricultural by‐product of stem lettuce are good sources of polysaccharides, which could be developed as immunopotentiator for improving human health. © 2023 Society of Chemical Industry.
Antibacterial and phytotoxicological properties assessment of Momordica charantia extract‐based ZnO nanoparticles
Authors: Doğaroğlu Zeynep Görkem , Uysal Yağmur , Çaylalı Zehranur , Karakoç Gökçen 
Published: November 2023

AbstractBACKGROUNDUtilizing the fruit extract of bitter melon (Momordica charantia), zinc nanoparticles (ZnO‐NPs) were synthesized through a green approach, a novel endeavor in current literature. The primary objective was to evaluate the phytotoxic and growth‐promoting effects of these ZnO‐NPs on wheat, chosen as a test plant. Structural characterization using X‐ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy revealed the hexagonal wurtzite crystal structure of ZnO‐NPs and identified spherical M. charantia‐produced (MC)‐ZnO‐NPs ranging in size from 48 to 150 nm.RESULTSAt a concentration of 2000 mg L−1, both MC‐ and raw‐ZnO‐NPs augmented wheat germination percentages. Furthermore, raw‐ZnO‐NPs at 4000 mg L−1 demonstrated the highest chlorophyll content. Despite the plant's increased accumulation of MC‐ZnO‐NPs, no statistically significant toxic effects were observed. The antibacterial efficacy of ZnO‐NPs was assessed against Gram‐positive and Gram‐negative microorganisms. MC‐ZnO‐NPs exhibited a 67.9% inhibition zone against Escherichia coli at 0.04 mg L−1, while raw‐ZnO‐NPs exhibited 75.6% inhibition at the same concentration.CONCLUSIONThe study suggests that ZnO‐NPs synthesized from M. charantia exhibit both growth‐promoting effects on wheat without significant phytotoxicity and potent antibacterial properties, particularly against Escherichia coli. However, further investigations are warranted to comprehensively understand the interactions between ZnO‐NPs and plants. Future research should focus on M. charantia, exploring its enhanced effects on plant growth, development and antibacterial attributes. These findings hold promise for potential agricultural applications, emphasizing the need for detailed phytotoxicological assessments of ZnO‐NPs. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Associations of social vulnerability with truncal and extremity melanomas in the United States
Authors: Goyal Ansh , Fei‐Zhang David J. , Pawlik Timothy M. , Bentrem David J. , Wayne Jeffrey D. 
Published: November 2023

AbstractBackgroundPrior studies in social determinants (SDoH) of truncal‐extremity melanomas (TEM) have analyzed race, income, and environmental factors relative to their effect on health disparities. However, they are limited by the narrow scopes of SDoH and study population, while lacking analyses of interrelational contribution of SDoH on TEM disparities.MethodsThis retrospective cohort study of adult TEM patients (1975–2017) assessed linear regression trends in months of survival, as well as logistic regression trends in advanced presenting stage, surgery, and chemotherapy receipt across TEM subtypes with increasing overall social vulnerability and vulnerability in 15 SDoH variables grouped into socioeconomic status (SES), minority‐language status (ML), household composition (HH), and housing‐transportation (HT) themes measured by the SVI. SVI measures are ranked/compared across all US counties for relative vulnerability in a specific SDH and their total composite while accounting for sociodemographic–regional differences.ResultsAcross 325 760 TEM patients, increasing overall social vulnerability demonstrated significant decreases in the survival period for 7/13 TEM histology types (p < 0.001), with relative decreases in the survival period as high as 44.0% (67.0–37.5 months) for epithelioid cell. SES and HH were the highest‐magnitude contributors to these overall trends. For many patients with TEM, increased odds of advanced presenting stage (highest with acral‐lentiginous: odds ratio [OR], −1.18; 95% confidence interval [CI], 1.02–1.36), decreased odds of indicated surgery receipt (lowest with amelanotic, 0.79; 0.71–0.87), and increased odds of indicated chemotherapy (highest with melanoma in giant nevi: 1.50; 1.01–2.44) were observed; SES and ML followed by HH and HT contributed to these trends.ConclusionsThere were detriments in TEM care & prognosis in the United States with increasing social vulnerability. Identifying which SDH quantifiably are associated more with disparities in interrelational, real‐world contexts is important to provide nuance to inform future research and initiatives to address TEM disparity.
Computed Tomographic Evaluations in Patients with Empty Nose Syndrome
Authors: Huang Chien‐Chia , Sun Ping Hsueh , Wu Pei‐Wen , Huang Chi‐Che , Chang Po‐Hung , Fu Chia‐Hsiang , Lee Ta‐Jen 
Published: November 2023

ObjectiveWe aimed to evaluate computed tomography (CT) images of patients with empty nose syndrome (ENS), investigate the impact of reconstruction surgery on sinus inflammation, and identify the optimal airspace diameter after surgery.MethodsWe conducted a retrospective case series analysis, identifying and enrolling patients with ENS with perioperative CT findings. The clinical characteristics of the participants were collected, and the modified Lund‐Mackay (mLM) CT scores were determined. The anterior airspace diameter was evaluated by measuring the distance between the septum and the lateral nasal wall on the coronal plane at the level of the nasolacrimal duct.ResultsTwenty patients with ENS and perioperative CT images were enrolled. The mean total mLM CT score and all subsite scores showed no significant changes after surgery. The Empty Nose Syndrome 6‐item Questionnaire (ENS6Q) score, Sino‐nasal Outcome Test‐25 (SNOT‐25) score, sleep symptoms domain, psychological domain, and empty nose symptoms domain were significantly associated with anterior airspace diameter in the regression analysis.ConclusionThere was no significant difference in sinus inflammation between preoperative and postoperative CT evaluations. The anterior airspace diameters were significantly associated with ENS6Q and SNOT‐25 scores.Level of Evidence4 Laryngoscope, 134:2105–2110, 2024