bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterising the prevalence of overweight and obese status among adults with sickle cell disease
Authors: Ibemere Stephanie O. , Oyedeji Charity I. , Preiss Liliana , Van Althuis Laura E. , Hankins Jane S. , Azul Melissa , Burns Ebony N. , Glassberg Jeffrey , Hagar Ward , Hussain Faiz , King Allison , Melvin Cathy , Myers John , Snyder Angela , Shah Nirmish , Tanabe Paula ,   Sickle Cell Disease Implementation Consortium
Published: November 2022

SummaryIndividuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient‐reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20–45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9 (21.1–28) kg/m2. In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSβ+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSβ0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p = 0.0003) compared to those with HbSS or HbSβ0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity‐related complications that may impact SCD‐related complications.
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation
Authors: Wang Tianning , Min Lingyuan , Gao Yan , Zhao Mengmeng , Feng Shaojie , Wang Huiyun , Wang Yunshan , Zheng Yan 
Published: November 2022

AbstractTuftelin (TUFT1) is highly expressed in various tumor types and promotes tumor growth and metastasis by activating AKT and other core signaling pathways. However, the effects of post‐translational modifications of TUFT1 on its oncogenic function remain unexplored. In this study, we found that TUFT1 was SUMOylated at K79. SUMOylation deficiency significantly impaired the ability of TUFT1 to promote the proliferation, migration, and invasion of gastric cancer (GC) cells by blocking AKT/mTOR signaling pathway activation. SUMOylation of TUFT1 is mediated by the E3 SUMO ligase tripartite motif‐containing protein 27 (TRIM27), and these two proteins regulate the malignant behavior of GC cells and AKT activation in the same pathway. TUFT1 binds to TRIM27 through its N‐terminus, and decreased binding affinity of TUFT1 to TRIM27 significantly impairs its oncogenic effect. In addition, data collected from GC clinical samples indicated that the combined detection of TUFT1 and TRIM27 expression reflected tumor malignancy and patient survival with higher precision. In addition, we proved that SUMOylated TUFT1 is not only an upstream signal for AKT activation but also directly activates mTOR by forming a complex with Rab GTPase activating protein 1, which further inhibits Rab GTPases and promotes the perinuclear accumulation of mTORC1. Altogether, these data indicate that SUMOylated TUFT1 is the active form that affects GC progression through the AKT/mTOR signaling pathway and might be a promising therapeutic target or biomarker for GC progression.
Derivation of pancreatic acinar cell carcinoma cell line HS‐1 as a patient‐derived tumor organoid
Authors: Hoshi Daisuke , Kita Emiri , Maru Yoshiaki , Kogashi Hiroyuki , Nakamura Yuki , Tatsumi Yasutoshi , Shimozato Osamu , Nakamura Kazuyoshi , Sudo Kentaro , Tsujimoto Akiko , Yokoyama Ryo , Kato Atsushi , Ushiku Tetsuo , Fukayama Masashi , Itami Makiko , Yamaguchi Taketo , Hippo Yoshitaka 
Published: November 2022

AbstractAcinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long‐term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy‐derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS‐1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS‐1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.
LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1‐p53/c‐Myc axis
Authors: Oyang Linda , Ouyang Lei , Yang Lixia , Lin Jinguan , Xia Longzheng , Tan Shiming , Wu Nayiyuan , Han Yaqian , Yang Yiqing , Li Jian , Chen Xiaohui , Tang Yanyan , Su Min , Luo Xia , Li Jinyun , Xiong Wei , Zeng Zhaoyang , Liao Qianjin , Zhou Yujuan 
Published: November 2022

AbstractCancer cells prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can upregulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 overexpression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)‐related protein expression in NPC cells, promoting phosphorylated PHB1 nuclear translocation through 14‐3‐3σ. LPLUNC1 overexpression also increased p53 but decreased c‐Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS‐related protein expression induced by LPLUNC1 overexpression. Finally, we found that treatment with all‐trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis, and increased OXPHOS‐related protein expression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1‐PHB1‐p53/c‐Myc axis decreased glycolysis in NPC cells, and ATRA upregulated LPLUNC1 expression, ATRA maybe a promising drug for the treatment of NPC.
Anti‐cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression
Authors: Miao Yazhou , Deng Yuxuan , Liu Jinqiu , Wang Jing , Hu Boyi , Hao Shuyu , Wang Herui , Zhang Zhe , Jin Zeping , Zhang Yang , Li Chunzhao , Zhang Peng , Wan Hong , Zhang Shaodong , Feng Jie , Ji Nan 
Published: November 2022

AbstractIntroductionGlioblastoma (GBM) is the most malignant form of glioma and has a poor median survival time. Fibroblast activation protein alpha (FAP) is a dual‐specificity serine protease that is strongly associated with the development and progression of human carcinomas. However, relatively little is known about the function of FAP and its potential as a therapeutic target in GBMs.AimsIn this study, we aimed to explore the role of FAP in GBM through a series of experiments and to evaluate the therapeutic effect of PT100, a small molecule inhibitor of FAP, on GBM.ResultsIncreased FAP expression was associated with poor survival in glioma. In vitro, FAP knockdown inhibited the process of EMT and caused a decrease in the number of M2 macrophages. In vivo, PT100 was confirmed to suppress the progression of GBMs significantly.ConclusionsFAP could serve as a biomarker and novel therapeutic target for the treatment of GBM and that PT100 is a promising drug for the treatment of GBM.
Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling
Authors: Jiang Yimin , Lin Yunshi , Tan Yuhang , Shen Xinkai , Liao Meihua , Wang Huan , Lu Nannan , Han Feng , Xu Nenggui , Tang Chunzhi , Song Juxian , Tao Rongrong 
Published: November 2022

AbstractAimsCerebrovascular impairment contributes to the pathogenesis of Alzheimer's disease (AD). However, it still lacks effective intervention in clinical practice. Here, we investigated the efficacy of electroacupuncture (EA) in cerebrovascular repair in 3xTg‐AD mice and its mechanism.Methods3xTg‐AD mice were employed to evaluate the protective effect of EA at ST36 acupoint (EAST36). Behavioral tests were performed to assess neurological disorders. Laser speckle contrast imaging, immunostaining, and Western blot were applied to determine EAST36‐boosted cerebrovascular repair. The mechanism was explored in 3xTg mice and endothelial cell cultures by melatonin signaling modulation.ResultsEAST36 at 20/100 Hz effectively alleviated the olfactory impairment and anxiety behavior and boosted cerebrovascular repair in AD mice. EAST36 attenuated cerebral microvascular degeneration in AD mice by modulating endothelial cell viability and injury. Consequently, the Aβ deposits and neural damage in AD mice were reversed after EAST36. Mechanistically, we revealed that EAST36 restored melatonin levels in AD mice. Melatonin supplement mimicked the EAST36 effect on cerebrovascular protection in AD mice and endothelial cell cultures. Importantly, blockage of melatonin signaling by antagonist blunted EAST36‐induced cerebrovascular recovery and subsequent neurological improvement.ConclusionsThese findings provided strong evidence to support EAST36 as a potential nonpharmacological therapy against cerebrovascular impairment in AD. Further study is necessary to better understand how EAST36 treatment drives melatonin signaling.
Pre‐transplant hypoalbuminemia is not associated with worse short‐term outcomes among kidney transplant recipients
Authors: Breyer Isabel , Astor Brad C. , Srivastava Aniruddha , Aziz Fahad , Garg Neetika , Mohamed Maha A. , Jorgenson Margaret R. , Mandelbrot Didier A. , Parajuli Sandesh 
Published: November 2022

AbstractIntroductionSerum albumin is an indicator of overall health status, but it remains unclear how pre‐transplant hypoalbuminemia is associated with early post‐transplant outcomes.MethodsThis study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001–12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0 g/dL), mild (≥3.5 – < 4.0g/dL), moderate (≥3.0 – < 3.5g/dL), or severe hypoalbuminemia (<3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re‐operation related to post‐transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post‐transplant.ResultsA total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p < 0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37‐0.91; p = 0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07–0.68; p = 0.01) were associated with significantly lower rates of acute rejection within 6 months post‐transplant.ConclusionPatients with pre‐transplant hypoalbuminemia have post‐transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.
Public perception of guilt and deserved punishment in medical cannabis diversion
Authors: Rozmann Nir , Ne'eman‐Haviv Vered 
Published: November 2022

AbstractIntroductionIllegal drug diversion is a well‐documented social problem that has received little research attention, despite the growing use of medical cannabis (MC) worldwide. This study examines public attitudes towards the punishment of MC diversion in Israel.MethodWe used a quantitative method. Participants were 399 Israelis who were given five scenarios of MC diversion to persons with and without a licence, with and without payment, and for personal profit.ResultsRespondents' attitudes differed with respect to the guilt and deserved punishment of the traffickers as a function of whether the recipient did or did not have a licence and did or did not pay for the MC. Transfers to individuals without a licence and for payment were judged more harshly than those to individuals without payment, whether or not they had a licence.Discussion and ConclusionThe discussion addresses the findings with reference to Kohlberg's moral development theory. The findings of the study attest to the importance of public attitudes in shaping legal policy in Israel.
Pharmakologie der Januskinase‐Inhibitoren – Teil 1: Pharmakokinetik
Authors: Eichner Adina , Wohlrab Johannes 
Published: November 2022

ZusammenfassungDer Einsatz von Januskinase‐Inhibitoren zur Therapie chronisch‐entzündlicher Erkrankungen etabliert sich zunehmend als Behandlungsoption in mehreren Indikationen. Um den klinischen Einsatz effizient zu gestalten, sind pharmakologische Kenntnisse zum JAK/STAT‐Signalweg zu den Besonderheiten der Pharmakokinetik der einzelnen Arzneistoffe essenziell. Der JAK/STAT‐Signalweg ist auf mehreren Ebenen (Rezeptor‐, Kinase‐, STAT‐ und SOCS‐Ebene) reguliert, sodass beim Einsatz von Januskinase‐Inhibitoren die klinisch relevante Pharmakodynamik stark vom Dosisregime, der behandelten Indikation, der Komedikation und der Komorbidität abhängt. Für den praktischen Alltag ist es deshalb von großer Bedeutung, zu erkennen, dass die genannten Faktoren relevanten Einfluss auf den therapeutischen Nutzen von Januskinase‐Inhibitoren haben können. Vor diesem Hintergrund ist auf eine zulassungskonforme Anwendung der Januskinase‐Inhibitoren besonderer Wert zu legen.
Extinction risk of Chinese angiosperms varies between woody and herbaceous species
Authors: Chen Yuheng , Wu Yongbin , Dong Yuran , Li Yao , Ge Zhiwei , George Oduro , Feng Gang , Mao Lingfeng 
Published: November 2022

AbstractAimUnderstanding how species' traits and environmental contexts relate to extinction risk is a critical priority for ecology and conservation biology. This study aims to identify and explore factors related to extinction risk between herbaceous and woody angiosperms to facilitate more effective conservation and management strategies and understand the interactions between environmental threats and species' traits.LocationChina.TaxonAngiosperms.MethodsWe obtained a large dataset including five traits, six extrinsic variables, and 796,118 occurrence records for 14,888 Chinese angiosperms. We assessed the phylogenetic signal and used phylogenetic generalized least squares regressions to explore relationships between extinction risk, plant traits, and extrinsic variables in woody and herbaceous angiosperms. We also used phylogenetic path analysis to evaluate causal relationships among traits, climate variables, and extinction risk of different growth forms.ResultsThe phylogenetic signal of extinction risk differed among woody and herbaceous species. Angiosperm extinction risk was mainly affected by growth form, altitude, mean annual temperature, normalized difference vegetation index, and precipitation change from 1901 to 2020. Woody species' extinction risk was strongly affected by height and precipitation, whereas extinction risk for herbaceous species was mainly affected by mean annual temperature rather than plant traits.Main conclusionsWoody species were more likely to have higher extinction risks than herbaceous species under climate change and extinction threat levels varied with both plant traits and extrinsic variables. The relationships we uncovered may help identify and protect threatened plant species and the ecosystems that rely on them.
Developmental effects of constitutive mTORC1 hyperactivity and environmental enrichment on structural synaptic plasticity and behaviour in a rat model of autism spectrum disorder
Authors: Granak Simon , Tuckova Klara , Kutna Viera , Vojtechova Iveta , Bajkova Laura , Petrasek Tomas , Ovsepian Saak V. 
Published: November 2022

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental condition causing a range of social and communication impairments. Although the role of multiple genes and environmental factors has been reported, the effects of the interplay between genes and environment on the onset and progression of the disease remains elusive. We housed wild‐type (Tsc2+/+) and tuberous sclerosis 2 deficient (Tsc2+/−) Eker rats (ASD model) in individually ventilated cages or enriched conditions and conducted a series of behavioural tests followed by the histochemical analysis of dendritic spines and plasticity in three age groups (days 45, 90 and 365). The elevated plus‐maze test revealed a reduction of anxiety by enrichment, whereas the mobility of young and adult Eker rats in the open field was lower compared to the wild type. In the social interaction test, an enriched environment reduced social contact in the youngest group and increased anogenital exploration in 90‐ and 365‐day‐old rats. Self‐grooming was increased by environmental enrichment in young and adult rats and decreased in aged Eker rats. Dendritic spine counts revealed an increased spine density in the cingulate gyrus in adult Ekers irrespective of housing conditions, whereas spine density in hippocampal pyramidal neurons was comparable across all genotypes and groups. Morphometric analysis of dendritic spines revealed age‐related changes in spine morphology and density, which were responsive to animal genotype and environment. Taken together, our findings suggest that under TSC2 haploinsufficiency and mTORC1 hyperactivity, the expression of behavioural signs and neuroplasticity in Eker rats can be differentially influenced by the developmental stage and environment.
CCR5‐Δ32polymorphism—a possible protective factor from gait impairment amongst post‐stroke patients
Authors: Molad Jeremy , Hallevi Hen , Seyman Estelle , Rotschild Ofer , Bornstein Natan M. , Tene Oren , Giladi Nir , Hausdorff Jeffrey M. , Mirelman Anat , Ben Assayag Einor 
Published: November 2022

AbstractBackground and purposeStroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss‐of‐function mutation in the C‐C chemokine receptor 5 gene (CCR5‐Δ32) has recently been reported as a protective factor in post‐stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke.MethodParticipants were 575 survivors of first‐ever, mild–moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi‐professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force‐sensitive insoles.CCR5‐Δ32 status and gait measures were available for 335 patients.ResultsCCR5‐Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non‐carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity.ConclusionsSignificant associations were found between gait measurements andCCR5‐Δ32 loss‐of‐function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long‐term gait function after ischaemic stroke.
First‐line levetiracetam versus enzyme‐inducing antiseizure medication in glioma patients with epilepsy
Authors: van der Meer Pim B. , Maschio Marta , Dirven Linda , Taphoorn Martin J. B. , Koekkoek Johan A. F. ,   Italian League Against Epilepsy Brain Tumor‐Related Epilepsy Study Group
Published: November 2022

AbstractObjectiveThis study aimed to directly compare the effectiveness of first‐line monotherapy levetiracetam (LEV) versus enzyme‐inducing antiseizure medications (EIASMs) in glioma patients.MethodsIn this nationwide retrospective observational cohort study, Grade 2–4 glioma patients were included, with a maximum duration of follow‐up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause‐specific cox proportional hazard models were estimated, adjusting for potential confounders.ResultsIn the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first‐line LEV and 183 glioma patients first‐line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20–2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78–2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89–12.55, p = .001).SignificanceIn this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro‐oncology guideline recommendations to avoid EIASMs in glioma patients.
Surprise, Hope and Gift: A Pneumatological Account of the Unexpected Nature of Vocation
Authors: Lovell Cara F. 
Published: November 2022

AbstractGod's call can be surprising and unexpected. This article evaluates theologies of vocation in light of this potential for surprise. Contemporary Protestant theological interpretations of vocation are critiqued as incomplete due to their tendency to present vocation as the expression and utilisation of innate abilities without giving sufficient account of how an individual might be called to something totally new and surprising. It will be suggested that this arises from a focus on creation as the dominant theological lens for interpreting vocation. An alternative focused on eschatology and pneumatology will be proposed in which both natural talents and new abilities are recognised as gifts of the Spirit given for the purpose of anticipatory proleptic participation in the coming Kingdom of God.