bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune‐driven demyelination
Authors: Robichon Katharina , Bibi Rabia , Kiernan Mackenzie , Denny Lisa , Prisinzano Thomas E , Kivell Bronwyn M , La Flamme Anne Camille 
Published: December 2023

AbstractObjectivesMultiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease‐modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.MethodsUsing the well‐established murine model for immune‐driven demyelination of MS, experimental autoimmune encephalomyelitis, the effect of KOR agonists in combination with DMTs fingolimod or dimethyl fumarate on disease progression, immune cell infiltration and activation as well as myelination were analysed.ResultsFingolimod in combination with the KOR agonist, nalfurafine, significantly increased each individual beneficial effect as measured by increased recovery of mice and reduced relapses. These beneficial effects correlated with a reduction in immune cell infiltration into the CNS as well as peripheral immune cell alterations including a reduction in autoreactive CD4+ T‐cell cytokine production as well as increased myelination in the spinal cords of co‐treated animals. In contrast, while the use of dimethyl fumarate in combination with nalfurafine did not adversely affect the benefits of nalfurafine, the combination did not significantly enhance those benefits.ConclusionThis study indicates that KOR agonists can be used in combination with fingolimod and dimethyl fumarate with the nalfurafine–fingolimod combination providing enhanced benefits.
FTO up‐regulation induced by MYC suppresses tumour progression in Epstein‒Barr virus‐associated gastric cancer
Authors: Xu Yun‐Yun , Li Ting , Shen Ao , Bao Xiao‐Qiong , Lin Jin‐Fei , Guo Li‐Zhen , Meng Qi , Ruan Dan‐Yun , Zhang Qi‐Hua , Zuo Zhi‐Xiang , Zeng Zhao‐lei 
Published: December 2023

AbstractBackgroundEpstein‒Barr virus‐associated gastric cancer (EBVaGC) is regarded as a distinct molecular subtype of GC, accounting for approximately 9% of all GC cases. Clinically, EBVaGC patients are found to have a significantly lower frequency of lymph node metastasis and better prognosis than uninfected individuals. RNA N6‐methyladenosine (m6A) modification has an indispensable role in modulating tumour progression in various cancer types. However, its impact on EBVaGC remains unclear.MethodsMethylated RNA immunoprecipitation sequencing (MeRIP‐seq) and m6A dot blot were conducted to compare the m6A modification levels between EBVaGC and EBV‐negative GC (EBVnGC) cells. Western blot, real‐time quantitative PCR (RT‐qPCR) and immunohistochemistry were applied to explore the underlying mechanism of the reduced m6A modification in EBVaGC. The biological function of fat mass and obesity‐associated protein (FTO) was determined in vivo and in vitro. The target genes of FTO were screened by MeRIP‐seq, RT‐qPCR and Western blot. The m6A binding proteins of target genes were verified by RNA pulldown and RNA immunoprecipitation assays. Chromatin immunoprecipitation and Luciferase report assays were performed to investigate the mechanism how EBV up‐regulated FTO expression.ResultsM6A demethylase FTO was notably increased in EBVaGC, leading to a reduction in m6A modification, and higher FTO expression was associated with better clinical outcomes. Furthermore, FTO depressed EBVaGC cell metastasis and aggressiveness by reducing the expression of target gene AP‐1 transcription factor subunit (FOS). Methylated FOS mRNA was specifically recognized by the m6A ‘reader’ insulin‐like growth factor 2 mRNA binding protein 1/2 (IGF2BP1/2), which enhanced its transcripts stability. Moreover, MYC activated by EBV in EBVaGC elevated FTO expression by binding to a specific region of the FTO promoter.ConclusionsMechanistically, our work uncovered a crucial suppressive role of FTO in EBVaGC metastasis and invasiveness via an m6A‐FOS‐IGF2BP1/2‐dependent manner, suggesting a promising biomarker panel for GC metastatic prediction and therapy.
Task offloading in an optimized power‐performance manner
Authors: Naseri Rojin , Abdollahi Azgomi Mohammad , Naghash Asadi Ali 
Published: December 2023

SummaryThe cloud computing systems, such as the Internet of Things (IoT), are usually introduced with a three‐layer architecture (IoT‐Fog‐Cloud) for the task offloading that is a solution to compensate for resource constraints in these systems. Offloading at the right location is the most significant challenge in this field. It is more appropriate to offload tasks to fog than to cloud based on power and performance metrics, but its resources are more limited than the resources of the cloud. This paper tries to optimize these factors in the fog by specifying the number of usable servers in the fog. For this purpose, we model a fog computing system using the queueing theory. Furthermore, binary search and reinforcement learning algorithms are proposed to determine the minimum number of servers with the lowest power consumption. We evaluate the cost of the fog in different scenarios. By solving the model, we find that the proposed dispatching policy is very flexible and outperformed the known policies by up to 31% and in no case is it worse than either of them, and the overall offloading cost increases when fog rejects tasks with a high probability. Our offloading method is more effective than running all fog servers simultaneously, based on simulation results. It is evident from the similarities between the simulation results and those derived from the analytical method that the model and results are valid.
Derivation, validation, and comparison of a new prognostic scoring system for acute lower gastrointestinal bleeding
Authors: Smith Christopher , Leggett Gillian , Jayaprakash Anthoor , Khan Mohammed , Thomson John M. , Vijayan Balasubramaniam , Fraser Andrew , Leeds John S. 
Published: December 2023

AbstractObjectivesLower gastrointestinal bleeding is a common presentation with little data concerning risk factors for adverse outcomes. The aim was to derive and validate a scoring system to stratify risk in lower gastrointestinal bleeding and compare it to the Oakland score.MethodsA total of 2385 consecutive patients (mean age 65 years, 1140 males) were used to derive the score using multivariate logistic regression modeling then internally and externally validated. The Oakland score was applied and area under receiver operating characteristic (AUROC) curves were calculated and compared. A score of <1 was compared with an Oakland score of <9 to assess 30‐day rebleeding and mortality rates.ResultsRebleeding was associated with age, inpatient bleeding, syncope, malignancy, tachycardia, hypotension, lower hemoglobin and mortality with age, inpatient bleeding, liver/gastrointestinal disease, tachycardia, and hypotension. The area under the receiver operating characteristic curves was 0.742 for rebleeding and 0.802 for mortality. A score <1 was associated with rebleeding (0.0%–2.2%) and mortality (0%). The Oakland score had a significantly lower area under the receiver operating characteristic curve for rebleeding of 0.687 but not for mortality; 0.757. A score <1 was associated with a lower 30‐day rebleeding risk compared to an Oakland score <9 (4/379 vs. 15/355, p = 0.009) but not mortality (0/365 vs. 1/355, p = 0.493).ConclusionsOur score predicts 30‐day rebleeding and mortality rate with low scores associated with very low risk. The Aberdeen score is superior to the Oakland score for predicting rebleeding. Prospective evaluation of both scores is required.
Carbonylation of Boranes – A Computational Study
Authors: Espinosa Ferao Arturo 
Published: December 2023

AbstractThe classical simple picture of stepwise B‐to‐C migratory insertion of all three alkyl groups in the carbonylation reaction of trialkyl boranes with CO was shown not to be correct, except for the first alkyl group shift affording an acyl borane. The second and third direct alkyl shifts turned out to be kinetically hampered due to the non‐activated character of the B−C bond in electron‐poor B atoms. The latter can only be achieved by either the autocatalytic action of the final alkyl boron oxide or by formation of dimeric species with weakened B‐alkyl bonds at borate centres. Both thermodynamic and several NICS‐related parameters pointed to scarce, even “negative”, aromatic character for boroxines, the final cyclotrimerization products of alkyl‐boron oxides.
Updating stereotypical attributions in light of new information: The attractiveness halo effect changes when attractiveness changes
Authors: Rougier Marine , De Houwer Jan 
Published: December 2023

AbstractIn the attractiveness halo effect, a single known piece of information about a target stimulus (attractiveness of a person) influences assumptions about a host of other attributes about that target (e.g. this person is socially competent or vain). We examined for the first time whether this effect can be updated, that is, whether new information about physical attractiveness (e.g. that someone is not as attractive as initially thought) can undo the effects of earlier information. Across three preregistered experiments (n = 1131), we obtained evidence of a halo‐update effect and showed that updating depended on the extent to which personality traits are stereotypically related to attractiveness (i.e. updating was larger for the traits that are typically influenced by attractiveness information). We also explored potential mediators of the halo‐update effect. By shedding new light on the malleability of stereotypical attributions, our work has both theoretical and practical implications.
Influence of char‐forming lignin in combination with aluminium phosphinate on thermal stability and combustion properties of polyamide 11 blends
Authors: Mandlekar Neeraj , Cayla Aurelie , Rault Francois , Giraud Stephane , Guan Jinping , Salaün Fabien 
Published: December 2023

AbstractPolyamide 11 (PA) blends based on char‐forming industrial lignin and aluminum phosphinate (AlP) were prepared to improve flame retardant (FR) properties using a green and eco‐friendly approach. This study investigates the thermal degradation and combustion behavior of PA blends prepared by using AlP in combination with two different types of industrial lignins (i.e., kraft lignin (DL) and lignosulphonate lignin (LL). Thermogravimetric (TG) analysis showed that ternary blends containing LL and AlP developed higher char residue up to 10.7 wt% upon decomposition in inert atmospheres. The combination of lignin and AlP increases the thermal stability by shifting the initial decomposition temperature (T5%) and temperature at maximum decomposition (Tmax) to a higher temperature range, attributed to the stabilization of decomposition products. Furthermore, combustion behavior studied by cone calorimeter (forced combustion) and pyrolysis combustion flow calorimeter (PCFC) tests presented a significant reduction in the peak of heat release rate (PHRR) and total heat release (THR). It was found that LL and AlP‐containing blends more effectively decreased fire parameters like PHRR and THR than that of DL and AlP‐containing blends. The best interaction with reduced fire‐retardant properties was obtained when 10 wt% loading of lignin (DL/LL) and AlP was used. The reduction in heat release parameters was mainly ascribed to the condensed phase mechanism by forming an efficient protective char layer, which acts as a barrier against heat and mass transfer between the condensed and the gas phases. Raman spectroscopy analysis also confirmed the formation of the protective graphitic layer in the condensed phase.
Dietary diversity practice and its associated factors among pregnant women in Eastern Ethiopia: A community‐based cross‐sectional study
Authors: Geremew Habtamu , Abdisa Samuel , Zerihun Ebisa , Gizaw Yitagesu Kifelew , Kassa Yoseph , Gashu Chalachew , Simegn Mulat Belay 
Published: December 2023

AbstractMicronutrient insufficiencies during pregnancy have a marked impact on the health of the woman and her offspring. Evidence about the dietary practice of pregnant women is limited in Ethiopia, particularly in drought‐prone areas where food insecurity is widely seen. Therefore, this research aimed to assess the dietary diversity practice and associated factors among pregnant women in Chiro district, Eastern Ethiopia. We employed a community‐based cross‐sectional survey in Chiro district, Eastern Ethiopia. The data were collected from 417 randomly selected pregnant women using an interview‐administered structured questionnaire. EpiData‐3.1 and STATA‐14 were used for data entry and analysis, respectively. The binary logistic regression analysis was deployed to assess the association between dietary diversity practice and predictor variables. Out of 420 calculated sample size, 417 pregnant women completed the survey giving a response rate of 99.3%. The overall prevalence of optimal dietary diversity was 38.4% (95% CI: 33.7%, 43.2%). Educational status (adjusted odds ratio [AOR]: 2.71, 95% CI: 1.08, 6.81), meal frequency (AOR: 1.91, 95% CI: 1.11, 3.28), home gardening (AOR: 4.21, 95% CI: 2.48, 7.16), and household food security (AOR: 0.23, 95% CI: 0.13, 0.40) were independent predictors of dietary diversity practice.This study found that a substantial proportion of pregnant women had suboptimal dietary diversity, indicating a fundamental micronutrient inadequacy. Educational status, meal frequency, home gardening practice, and household food security were independent determinants of dietary diversity practice. The findings suggest that promoting maternal education and home gardening practice, and controlling food insecurity might enhance optimal dietary diversity.
Association of hypernatremia with mortality in patients with COVID‐19: A systematic review and meta‐analysis
Authors: Ma Yongzhi , Zhang Panjuan , Hou Ming 
Published: December 2023

AbstractBackgroundThe COVID‐19 pandemic worldwide has caused varying degrees of severity of lung damage in patients, with acute respiratory distress and death in severe cases. However, this is not directly caused by the virus itself, but by the production of inflammasome by monocytes in the body, leading to a systemic inflammatory response, which results in a very poor clinical prognosis for patients with COVID‐19.ObjectiveThe purpose of this meta‐analysis was to look at the relationship between hypernatremia and mortality in COVID‐19 patients.MethodsWe searched the PubMed, Web of Science, Embase, and Cochrane databases for articles published from the inception of the database until August 27, 2022. Three researchers reviewed the literature, retrieved data, and assessed the quality of the literature, respectively. A meta‐analysis was performed using State 17 software to assess the value of the effect of hypernatremia on mortality in patients with new coronavirus pneumonia.ResultsA total of nine publications was finally included in this study, including a total of 11,801 patients with COVID‐19, including 1278 in the hypernatremia group and 10,523 in the normonatremia group. Meta‐analysis showed that hypernatremia was associated with mortality in patients with COVID‐19 [OR = 4.15, 95% CI (2.95–5.84), p = .002, I² = 66.7%] with a sensitivity of 0.36 [0.26, 0.48] and a specificity of 0.88 [0.83, 0.91]. The posterior probability of mortality was 42% in patients with COVID‐19 hypernatremia and 15% in patients who did not have COVID‐19 hypernatremia.ConclusionAccording to available data, hypernatremia is associated with death in patients with COVID‐19.
Connecting the dots: Human papillomavirus vaccination gaps and the upsurge of oral human papillomavirus infection in United States of America
Authors: Farhan Kanza , Imam Syed Irtiza , Tariq Muhammad Burhan , Ahmed Aliza , Suheb Mahammed Khan , Akilimali Aymar 
Published: December 2023

SynopsisThis Editorial calls attention to the worrisome rise in oral HPV infections in the USA, which has been related to an increase in oral sex activity. It emphasizes the need for increased vaccination rates, dispelling myths and addressing disparities in oropharyngeal cancer prevention.
External Evaluation of Population Pharmacokinetic Models for High‐Dose Methotrexate in Adult Patients with Hematological Tumors
Authors: Chen Shengyang , Huang Lifeng , Huang Weikun , Zheng You , Shen Li , Liu Maobai , Chen Wansheng , Wu Xuemei 
Published: December 2023

AbstractCurrently, numerous population pharmacokinetic (popPK) models for methotrexate (MTX) have been published for estimating PK parameters and variability. However, it is unclear whether the accuracy of these models is sufficient for clinical application. The aim of this study is to evaluate published models and assess their predictive performance according to the standards of scientific research. A total of 237 samples from 74 adult patients who underwent high‐dose MTX (HDMTX) treatment at Shanghai Changzheng Hospital were collected. The software package NONMEM was used to perform an external evaluation for each model, including prediction‐based diagnosis, simulation‐based diagnosis, and Bayesian forecasting. The simulation‐based diagnosis includes normalized prediction distribution error (NPDE) and visual predictive check (VPC). Following screening, 7 candidate models suitable for external validation were identified for comparison. However, none of these models exhibited excellent predictive performance. Bayesian simulation results indicated that the prediction precision and accuracy of all models significantly improved when incorporating prior concentration information. The published popPK models for MTX exhibit significant differences in their predictive performance, and none of the models were able to accurately predict MTX concentrations in our data set. Therefore, before adopting any model in clinical practice, extensive evaluation should be conducted.
Pharmacokinetics of Tacrolimus in Pregnant Solid‐Organ Transplant Recipients: A Retrospective Study
Authors: Versluis Jorn , Bourgonje Arno R. , Touw Daan J. , Meinderts Jildau R. , Prins Jelmer R. , de Jong Margriet F. C. , Mian Paola 
Published: December 2023

AbstractData on the pharmacokinetics of tacrolimus during pregnancy are limited. Therefore, the aim of this retrospective study was to characterize the whole‐blood pharmacokinetics of tacrolimus throughout pregnancy. In this single‐center retrospective cohort study, whole‐blood tacrolimus trough concentrations corrected for the dose (concentration‐to‐dose [C/D] ratios) were compared before, monthly during, and after pregnancy in kidney, liver, and lung transplant recipients who became pregnant and gave birth between 2000 and 2022. Descriptive statistics and linear mixed models were used to characterize changes in tacrolimus C/D ratios before, during, and after pregnancy. The total study population included 46 pregnancies (31 pregnant women). Nineteen, 21, and 6 pregnancies were following kidney, liver, and lung transplantation, respectively. Immediate‐release or extended‐release formulations were used in 54.5% and 45.5% of the women, respectively. Tacrolimus C/D ratios significantly (P < .001) decreased (−48%) compared to the prepregnancy state at 7 months of pregnancy. These ratios recovered within 3 months postpartum (P = .002). C/D ratios tended to be lower during treatment with an extended‐release formulation than with an immediate‐release formulation (P = .071). Transplantation type did not significantly affect C/D ratios during pregnancy (P = .873). In conclusion, we found that tacrolimus whole‐blood pharmacokinetics change throughout pregnancy, with the lowest C/D ratios (48% decrease) in the 7th month of pregnancy. In general, the decrease in C/D ratios seems to stabilize from month 4 onward compared to prepregnancy.
Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019–2021
Authors: Viñuela Laura , de Salazar Adolfo , Fuentes Ana , Serrano‐Conde Esther , Falces‐Romero Iker , Pinto Adriana , Portilla Irene , Masiá Mar , Peraire Joaquim , Gómez‐Sirvent Juan Luis , Sanchiz Marta , Iborra Asunción , Baza Begoña , Aguilera Antonio , Olalla Julián , Espinosa Nuria , Iribarren José Antonio , Martínez‐Velasco Marina , Imaz Arkaitz , Montero Marta , Rivero María , Suarez‐García Inés , Maciá María Dolores , Galán Juan Carlos , Perez‐Elias Maria Jesus , García‐Fraile Lucio Jesús , Moreno Cristina , Garcia Federico 
Published: December 2023

AbstractTo evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019–2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in‐depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%–4.6%), 6.1% (95% CI, 5.0%–7.3%) for NNRTI, 0.9% (95% CI, 0.5%–1.4%) for PI, and 0.2% (95% CI, 0.0%–0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%–2.9%), 11.8% for NNRTI, (95% CI, 10.3%–13.5%), 0.2% (95% CI, 0.1%–0.6%) for PI, and 2.5% (95% CI, 1.5%–4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non‐Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019–2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first‐line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first‐line antiretroviral therapy.
The roles of 6K protein on Getah virus replication and pathogenicity
Authors: Meng Hui , Mou Chunxiao , Zhang Liangjiu , Zhou Jingye , Lu Tianyuan , Chen Zhenhai 
Published: December 2023

AbstractAlphavirus is a type of arbovirus that can infect both humans and animals. The amino acid sequence of the 6K protein, being one of the structural proteins of the alphavirus, is not conserved. Deletion of this protein will result in varying effects on different alphaviruses. Our study focuses on the function of the Getah virus (GETV) 6K protein in infected cells and mice. We successfully constructed infectious clone plasmids and created resulting viruses (rGETV and rGETV‐Δ6K). Our comprehensive microscopic analysis revealed that the 6 K protein mainly stays in the endoplasmic reticulum. In addition, rGETV‐Δ6K has lower thermal stability and sensitivity to temperature than GETV. Although the deletion of the 6K protein does not reduce virion production in ST cells, it affects the release of virions from host cells by inhibiting the process of E2 protein transportation to the plasma membrane. Subsequent in vivo testing demonstrated that neonatal mice infected with rGETV‐Δ6K had a lower virus content, less significant pathological changes in tissue slices, and milder disease than those infected with the wild‐type virus. Our results indicate that the 6K protein effectively reduces the viral titer by influencing the release of viral particles. Furthermore, the 6K protein play a role in the clinical manifestation of GETV disease.