bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse gut microbiota pattern between mild and severe cancer‐related fatigue in lung cancer patients treated with first‐line chemotherapy: A pilot study
Authors: Wei Hao , Xie Lingling , Zhao Yihan , He Jun , Zhu Jiang , Li Mei , Sun Yu 
Published: December 2022

AbstractBackgroundCancer survivors perceive cancer‐related fatigue (CRF) as one of the most common symptoms. However, the potential relationship between CRF and gut microbiota has not been elucidated. Our study aimed to preliminary explore the diverse gut microbiota composition between mild and severe CRF in advanced lung cancer patients undergoing first‐line chemotherapy.MethodsA total of 20 advanced lung patients treated with first‐line chemotherapy were enrolled, 10 with mild CRF and 10 with severe CRF. The self‐reported Piper Fatigue Scale and stool samples were collected from all eligible patients. The 16 S ribosomal ribonucleic acid gene was performed to analyze the intestinal microbiome.ResultsWe identified the significantly diverse gut microbiota composition among patients with mild and severe CRF. The pattern was characterized by the increasing abundance in short‐chain fatty acid‐producing taxa for mild CRF patients (genus Lachnospiraceae‐UCG‐008 and family Lachnospiraceae, p < 0.05), whereas higher abundance in taxa related to inflammation (family Enterobacteriaceae and genus Escherichia‐Shigella, p < 0.05) for severe CRF patients. Significantly different Kyoto Encyclopedia of Genes and Genomes pathways between mild and severe CRF patients were evaluated concerning fatty acid metabolism, nucleotide metabolism, brain function, amino acid metabolism, and so on (p < 0.05).ConclusionsOur study observed a plausible association between different levels of CRF and the diverse gut microbiota composition, with increasing proinflammation taxa in severe CRF patients and anti‐inflammation taxa growing in mild CRF patients. Further studies are warranted to evaluate whether CRF can be improved by modulating the gut microbiota composition.
Characteristics of xylazine‐related deaths in West Virginia—Xylazine‐related deaths
Authors: Sibbesen Julie , Abate Marie A. , Dai Zheng , Smith Gordon S. , Lundstrom Eric , Kraner James C. , Mock Allen R. 
Published: December 2022

AbstractBackground and ObjectivesThe involvement of xylazine, a veterinary drug, in West Virginia (WV) human drug‐related deaths was examined.MethodsWV drug deaths from 2019 (when xylazine was first identified) to mid‐2021. Characteristics including toxicology findings were compared between xylazine and nonxylazine deaths.ResultsOf 3292 drug deaths, 117 involved xylazine, and the proportions of deaths with it have increased (1% [2019] to 5% [mid‐2021)]. Xylazine decedents had more cointoxicants, with fentanyl (98%) predominant followed by methamphetamine. Xylazine decedents had a significantly greater history of drug or alcohol misuse and hepatic disease.Conclusions and Scientific SignificanceIn one of the largest analyses of xylazine‐involved deaths in a predominantly rural state, identification of xylazine was increasing with multiple cointoxicants (especially fentanyl), and was present in a few deaths with only one other substance involved. Health professionals should be aware of possible enhanced toxicity from xylazine ingestion especially since naloxone does not reverse xylazine's adverse effects.
An integrated interpreting service normalizes access to care for culturally and linguistically diverse (CALD) patients with colorectal cancer
Authors: Hodgson Russell , Albatat Batool , Tacey Mark , Zucchi Emiliano , Strugnell Neil , Lee Belinda 
Published: December 2022

AbstractAimTo compare access to the initial management and overall survival with colorectal cancer for limited English proficient (LEP) patients compared with patients from an English background.MethodsAll newly diagnosed patients from 2017 with colorectal cancer from a single health service with a highly multicultural catchment area and a well‐developed and integrated translation and language support (TALS) department were recruited. Time from referral to: biopsy, date seen by a surgeon, oncologist, discussion at a multidisciplinary meeting (MDM), and day of commencement of the first treatment modality, and overall survival were analyzed.ResultsOne hundred sixty‐two patients were analyzed, including 57 LEP patients from 22 countries of birth. Interpreters were present at 687/782 appointments with LEP patients. There were no differences in demographics or cancer staging. There were no differences between English background and LEP patients with regard to times from referral to biopsy (1 vs. 0 days), specialist review (surgical: 4 vs. 6 days, oncological: 45 vs. 57 days), MDM discussion (23 vs. 15 days), or commencement of treatment (32 vs. 28.5 days). There were no differences in treatment for colorectal cancer, although a higher rate of stomas was noted in LEP patients. There was no difference in overall survival between groups.ConclusionTime to critical initial checkpoints and overall survival were similar in LEP and English background patients with colorectal cancer. An integrated TALS department may abrogate the language and cultural barriers that are known to disadvantage LEP patients and may contribute to normalizing care for the culturally and linguistically diverse community.
Effects of compound of hawthorn (Crataegus pinnatifida) and Chinese yam (Dioscorea opposita Thunb.) extracts on growth performance, intestinal health, and immune function in weaned pigs
Authors: Fu Linglong , Sun Mengning , Dong Wenxuan , Zhang Gang , Han Dandan , Zang Jianjun , Liu Hu 
Published: December 2022

AbstractPlant extracts were considered as natural resources to alleviate weaning stress in pig production. A 28‐day study (Phase 1: d 0–14 and Phase 2: d 15–28) was conducted to investigate the effects of compound of hawthorn and yam extracts on growth performance, intestinal health, and immune function in weaned pigs. A total of 144 weaned pigs with average body weight (BW) of 7.89 ± 1.09 kg were assigned to three treatments with six replicates pens by BW and sex. Dietary treatments included negative control (NC), corn‐soybean meal basal diet; positive control (PC), NC + 0.08% enzyme preparations and 0.3% acidifiers; and CHY, NC + 0.3% compound of hawthorn and yam extracts. Compared with NC‐fed pigs, pigs fed CHY had greater (p < 0.05) growth performance in Phase 1. The CHY‐fed pigs had greater (p < 0.05) activities of duodenal lipase, trypsin, and greater (p < 0.05) serum concentrations of total antioxidant capacity and glutathione peroxidase. The CHY‐fed pigs had improved (p < 0.05) jejunal morphology and greater (p < 0.05) ileac valeric acid and colonic propionic acid, isobutyric acid concentrations than NC‐ and PC‐fed pigs. In conclusion, CHY can improve growth performance and is a promising additive in weaned pig diets.
Development of a chatbot for depression: adolescent perceptions and recommendations
Authors: Dosovitsky Gilly , Bunge Eduardo 
Published: December 2022

BackgroundChatbots are a relatively new technology that has shown promising outcomes for mental health symptoms in adults; however, few studies have been done with adolescents or reported adolescent user experiences and recommendations for chatbot development.MethodsTwenty three participants ages 13–18 (Mage = 14.96) engaged in user testing of a chatbot developed to psychoeducate adolescents on depression, teach behavioral activation, and change negative thoughts. Thematic analysis was conducted of participants' responses to user experience questions, impressions, and recommendations.ResultsOver half (56.5%) of the sample completed the full intervention and provided user experience feedback online. The average NPS score was 6.04 (SD = 2.18), and 64.3% (n = 9) said they would use the chatbot in the future. Of all user experience responses, 54.5% were positive. The most common impressions were related to symptom improvement (61.1%) and availability (52.8%) The most frequent recommendations were related to solving technical problems (66%).ConclusionsChatbots for mental health are acceptable to some adolescents, a population that tends to be reluctant to engage with traditional mental health services. Most participants reported positive experiences with the chatbot, believing that it could help with symptom improvement and is highly available. Adolescents highlighted some technical and stylistic problems that developers should consider. More pilot and user testing is needed to develop mental health chatbots that are appealing and relevant to adolescents.
Efficacy of tezepelumab in patients with evidence of severe allergic asthma: Results from the phase 3 NAVIGATOR study
Authors: Corren Jonathan , Ambrose Christopher S. , Griffiths Janet M. , Hellqvist Åsa , Lindsley Andrew W. , Llanos Jean‐Pierre , Colice Gene , Menzies‐Gow Andrew 
Published: December 2022

AbstractBackgroundAllergic asthma is the most common phenotype among patients with severe asthma. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) versus placebo in patients with severe, uncontrolled asthma. This exploratory analysis evaluated the efficacy of tezepelumab in NAVIGATOR participants with evidence of severe allergic asthma.MethodsPatients (12–80 years old) receiving medium‐ or high‐dose inhaled corticosteroids and ≥ 1 additional controller medication, with or without oral corticosteroids, were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks in NAVIGATOR. In this analysis, the AAER, forced expiratory volume in 1 second (FEV1), patient‐reported outcomes (PROs), and type 2 biomarker levels were evaluated in patients grouped by sensitivity to perennial aeroallergens, confirmed symptomatic allergy, and eligibility for omalizumab treatment according to the United States (OMA‐US) and the European Union (OMA‐EU) prescribing information, including subgroups according to baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels.ResultsOf 1059 patients who received treatment in NAVIGATOR, 680 (64%) had perennial aeroallergen sensitivity and 318 (30%) had confirmed symptomatic allergy; 379 (36%) and 359 (34%) patients were OMA‐US‐ and OMA‐EU‐eligible, respectively. Tezepelumab reduced the AAER over 52 weeks versus placebo by 58% (95% confidence interval [CI]: 47–67) to 68% (95% CI: 55–77) across these subgroups. Among omalizumab‐eligible patients, AAERs were reduced in patients across baseline blood eosinophil counts and FeNO levels. Tezepelumab improved FEV1 and PROs, and reduced type 2 biomarkers, versus placebo in patients with and without perennial allergy.ConclusionsTezepelumab was efficacious in patients with severe, uncontrolled asthma with evidence of allergic inflammation, defined by multiple clinically relevant definitions. These findings further support the benefits of tezepelumab in a broad population of patients with severe asthma, including those with severe allergic asthma.
Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis
Authors: Azuri Joseph , Hammerman Ariel , Aboalhasan Enis , Sluckis Ben , Arbel Ronen 
Published: December 2022

AbstractAimsHigher doses of the glucagon‐like peptide‐1 agonist semaglutide and, more recently, tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money.Materials and MethodsWe calculated the cost needed to treat to achieve a 1% reduction in body weight using high‐dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT‐1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022.ResultsUsing tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%‐19.3%) compared with 12.4% (95% CI: 11.5%‐13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908‐$1075) compared with $1845 (95% CI: $1707‐$1989) with semaglutide. Scenario analysis confirmed these findings.ConclusionsTirzepatide provides better value for money than semaglutide for weight reduction.
Dorsal attention network activity during perceptual organization is distinct in schizophrenia and predictive of cognitive disorganization
Authors: Keane Brian P. , Krekelberg Bart , Mill Ravi D. , Silverstein Steven M. , Thompson Judy L. , Serody Megan R. , Barch Deanna M. , Cole Michael W. 
Published: December 2022

AbstractVisual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes, but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether brain network differences in schizophrenia occur in related illnesses or vary with illness features transdiagnostically. To address these topics, we scanned (functional magnetic resonance imaging, fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting‐state connections for shape completion. Illusory/fragmented task activation differences (‘modulations’) in the dorsal attention network (DAN) could distinguish people with schizophrenia from the other groups (AUCs > .85) and could transdiagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except in schizophrenia. The secondary visual network was strongly and similarly modulated in each group. Task modulations were dispersed over more networks in patients compared to controls. In summary, DAN activity during visual perceptual organization is distinct in schizophrenia, symptomatically relevant, and potentially related to improper attention‐related feedback into secondary visual areas.
Increased uptake of the P2X7 receptor radiotracer 18F‐JNJ‐64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice
Authors: Morgan James , Moreno Oscar , Alves Mariana , Baz Zuriñe , Menéndez Méndez Aida , Leister Hanna , Melia Ciara , Smith Jonathon , Visekruna Alexander , Nicke Annette , Bhattacharya Anindya , Ceusters Marc , Henshall David C. , Gómez‐Vallejo Vanessa , Llop Jordi , Engel Tobias 
Published: December 2022

AbstractObjectiveThe P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested 18F‐JNJ‐64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure‐damage and epileptogenesis.MethodsStatus epilepticus was induced via an intra‐amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of 18F‐JNJ‐64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. 18F‐JNJ‐64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy.ResultsP2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi‐ and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control.SignificanceTaken together, our data suggest that P2X7R‐based PET imaging may help to identify seizure‐induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R‐based treatments.
The cytosolic lncRNAdutA affects STATa signaling and developmental commitment in Dictyostelium
Authors: Saga Yukika , Shimoyama Yudai , Yamada Yoko , Morikawa Naoki , Kawata Takefumi 
Published: December 2022

AbstractSTATa is a pivotal transcription factor for Dictyostelium development. dutA is the most abundant RNA transcribed by RNA polymerase II in Dictyostelium, and its functional interplay with STATa has been suggested. This study demonstrates that dutA RNA molecules are distributed as spot‐like structures in the cytoplasm, and that its cell type‐specific expression changes dramatically during development. dutA RNA was exclusively detectable in the prespore region of slugs and then predominantly localized in prestalk cells, including the organizer region, at the Mexican hat stage before most dutA transcripts, excluding those in prestalk O cells, disappeared as culmination proceeded. dutA RNA was not translated into small peptides from any potential open reading frame, which confirmed that it is a cytoplasmic lncRNA. Ectopic expression of dutA RNA in the organizer region of slugs caused a prolonged slug migration period. In addition, buffered suspension‐cultured cells of the strain displayed reduced STATa nuclear translocation and phosphorylation on Tyr702. Analysis of gene expression in various dutA mutants revealed changes in the levels of several STATa‐regulated genes, such as the transcription factors mybC and gtaG, which might affect the phenotype. dutA RNA may regulate several mRNA species, thereby playing an indirect role in STATa activation.
Relaxation degree and defect dipoles‐controlled resistivity and leakage current in BF–BT‐based ceramics
Authors: Li Yang , Zheng Ting , Li Bing , Wu Jiagang 
Published: December 2022

AbstractThe low resistivity and high leakage current of bismuth ferrite–barium titanate‐based ceramics greatly limit its development. In this work, the resistivity and leakage current have been regulated by changing the relaxation degree and defect dipoles. With the introduction of Sb, the ceramics endure from weak relaxors with typically ferroelectric behavior to relaxor ferroelectrics and then to relaxors, where nearly 20 times improved resistivity can be obtained in relaxor ferroelectrics with chemical‐homogeneous grain structure and strip‐shaped/submicron‐sized coexisted domains, whereas deteriorated properties appear in relaxors with core–shell structure and tweed‐like ferroelectric domains. The decreased concentration of oxygen vacancies and Ti3+is responsible for the improved insulation in relaxor‐ferroelectrics, whereas the emergence of core–shell structure leads to electrical inhomogeneity and the conductive channels result in decreased resistivity. In addition, the leakage current mechanism is transformed from Ohmic conduction to space‐charge‐limited current as the electric field increases, which is induced by different domain switchings in ceramics with varied relaxation degrees.
Targeted gene panel analysis of Japanese patients with maturity‐onset diabetes of the young‐like diabetes mellitus: Roles of inactivating variants in the ABCC8 and insulin resistance genes
Authors: Yorifuji Tohru , Watanabe Yoh , Kitayama Kana , Yamada Yuki , Higuchi Shinji , Mori Jun , Kato Masaru , Takahashi Toru , Okuda Tokuko , Aoyama Takane 
Published: December 2022

AbstractAims/IntroductionTo investigate the genetic background of Japanese patients with suspected maturity‐onset diabetes of the young (MODY).Materials and MethodsOn 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A > G analysis and methylation‐specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency <0.001 and Combined Annotation Dependent Depletion score >20 (CS >20) were listed as rare variants of uncertain significance‐CS >20.ResultsA total of 157 pathogenic/likely pathogenic variants and 44 rare variants of uncertain significance‐CS >20 were identified. In the pathogenic/likely pathogenic variants, alterations in the GCK gene were the most common (82, 52.2%) followed by HNF1A (29, 18.5%), HNF4A (13, 8.3%) and HNF1B (13, 8.3%). One patient was a 29.5% mosaic with a truncating INSR variant. In the rare variants of uncertain significance‐CS >20, 20 (45.5%) were in the genes coding for the adenosine triphosphate‐sensitive potassium channel, KCNJ11 or ABCC8, and four were in the genes of the insulin‐signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis.ConclusionsCausative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. ABCC8‐MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY.