bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulated mitochondrial transcription factor A enhances mycoplasma infection to promote the metastasis of hepatocellular carcinoma
Authors: Wang Yinping , Wang Gang , Hong Xin , Zhao Jing , Wu Dan , Chen Lin , Liu Xiaoli , Kong Deyu , Huang Qichao , Xing Jinliang , Wang Nan , Zhao Yilin 
Published: January 2023

AbstractMycoplasma is widespread in various hosts and may cause various diseases in animals. Interestingly, the occurrence of mycoplasma infection was observed in many tumor types. However, the mechanism regulating its infection is far from clear. We unexpectedly found that the knockdown of mitochondrial transcription factor A (TFAM) remarkably enhanced mycoplasma infection in hepatocellular carcinoma (HCC) cells. More importantly, we found that mycoplasma infection facilitated by TFAM knockdown significantly promoted HCC cell metastasis. Mycoplasma infection was further found to be positively correlated with poor prognosis in patients with HCC. Mechanistically, the decreased TFAM expression upregulated the transcription factor Sp1 to increase the expression level of Annexin A2 (ANXA2), which was reported to interact with membrane protein of mycoplasma. Moreover, we found that mycoplasma infection enhanced by the TFAM downregulation promoted HCC migration and invasion by activating the nuclear factor‐κB signaling pathway. The downregulation of TFAM enhanced mycoplasma infection in HCC cells and promoted HCC cell metastasis. Our study contributes to the understanding of the pathological role of mycoplasma infection and provides supporting evidence that targeting TFAM could be a potential strategy for the treatment of HCC with mycoplasma infection.
Association of KMT2C/D loss‐of‐function variants with response to immune checkpoint blockades in colorectal cancer
Authors: Liu Ruiqi , Niu Yanling , Liu Chao , Zhang Xin , Zhang Jinku , Shi Min , Zou Wenbo , Gu Binbin , Zhu Honglin , Wang Danhua , Yuan Hongling , Li Wei , Zhao Dandan , Zheng Qiaosong , Liu Rong , Chen Weiping , Ma Tonghui , Zhang Yanqiao 
Published: January 2023

AbstractImmune checkpoint inhibitors (ICIs) have become important treatment strategies, yet responses vary among patients and predictive biomarkers are urgently needed. Mutations in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/D mutations might be a predictor of immunotherapeutic efficacy. Here, we investigated the associations of KMT2C/D loss‐of‐function (LOF) variants with tumor mutation burden (TMB), MSI‐H, PD‐L1 expression, the levels of tumor‐infiltrating leukocytes (TILs), and clinical response to ICIs. It was found that KMT2C/D LOF variants were associated with higher TMB. Compared with the non‐LOF group, the proportion of patients with MSI‐H tumors was larger in the LOF group. PD‐L1 expression was higher in the LOF group only for colorectal cancer in both the Chinese and The Cancer Genome Atlas cohorts. Importantly, KMT2C/D LOF variants were associated with decreased regulatory T cells and increased levels of CD8+ T cells, activated NK cells, M1 macrophages, and M2 macrophages in colorectal cancer. However, there was no significant association between KMT2C/D LOF and TILs levels in other cancer types. Consistently, the results showed that KMT2C/D LOF variants were associated with prolonged overall survival only in colorectal cancer (p = 0.0485). We also presented that patients with KMT2C/D LOF mutations exhibited a better clinical response to anti‐PD‐1 therapy in a Chinese colorectal cancer cohort (p = 0.002). Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. In addition, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.
Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan
Authors: Kage Hidenori , Shinozaki‐Ushiku Aya , Ishigaki Kazunaga , Sato Yusuke , Tanabe Masahiko , Tanaka Shota , Tanikawa Michihiro , Watanabe Kousuke , Kato Shingo , Akagi Kiwamu , Uchino Keita , Mitani Kinuko , Takahashi Shunji , Miura Yuji , Ikeda Sadakatsu , Kojima Yasushi , Watanabe Kiyotaka , Mochizuki Hitoshi , Yamaguchi Hironori , Kawazoe Yoshimasa , Kashiwabara Kosuke , Kohsaka Shinji , Tatsuno Kenji , Ushiku Tetsuo , Ohe Kazuhiko , Yatomi Yutaka , Seto Yasuyuki , Aburatani Hiroyuki , Mano Hiroyuki , Miyagawa Kiyoshi , Oda Katsutoshi 
Published: January 2023

AbstractComprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA–RNA panel as well as a paired tumor–normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty‐two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).
Genetic variations predicting progression with docetaxel and novel androgen‐receptor pathway inhibitors
Authors: Shiota Masaki , Akamatsu Shusuke , Sekine Yuya , Kimura Hiroko , Narita Shintaro , Fujimoto Naohiro , Terada Naoki , Blas Leandro , Habuchi Tomonori , Kamoto Toshiyuki , Momozawa Yukihide , Eto Masatoshi 
Published: January 2023

AbstractGenetic variations represented by single‐nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration‐resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.
The influence of periodontitis case definition on the association between periodontal disease and glycaemic status
Authors: Alhassani Ahmed A. 
Published: January 2023

AbstractObjectiveThe association between periodontitis and glycaemic control is complex, and often described as ‘bidirectional’. Although epidemiological studies have examined this relationship extensively, a disagreement on periodontitis case definition still exists. This study aimed to assess the influence of case definition on the association between periodontal disease and glycaemic status.MethodsThe study is a secondary analysis of data from the United States National Health and Nutrition Examination Survey (NHANES), 2009–2014 cycles. The association between periodontitis and glycated haemoglobin (HbA1c) was assessed using different periodontitis case definitions: the definition by the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP), Community Periodontal Index (CPI), ≥1 site with ≥3 mm clinical attachment loss (CAL) and ≥4 mm probing depth (PD), ≥1 site with ≥4 mm CAL and ≥4 mm PD, the 5th European Workshop definitions, Machtei et al. ‘established periodontitis’, the 2017 World Workshop classification, and self‐reported periodontitis. The associations between periodontitis and HbA1c were compared across the case definitions.ResultsThere was substantial variability in prevalence estimates of periodontitis, and in the strength of association between periodontitis and HbA1c when different case definitions were applied. The CDC/AAP and stage III/IV periodontitis were consistently significantly associated with elevated HbA1c. For stage III/IV, the adjusted odds ratios of prediabetes and diabetes HbA1c were 1.19 and 1.76, respectively.ConclusionComprehensive periodontitis case definitions that account for CAL and PD, such as the CDC/AAP and the 2017 classification, seem to better detect the association between periodontal disease and HbA1c.
Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study
Authors: Ayalon‐Dangur Irit , Robenshtok Eyal , Duskin‐Bitan Hadar , Tsvetov Gloria , Gorshtein Alex , Akirov Amit , Shimon Ilan 
Published: January 2023

AbstractObjectiveThe treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow‐up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment.Design and patientsRetrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow‐up terminated if the patient underwent surgery, received cabergoline or was lost to follow‐up.MeasurementsData collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm.ResultsThe cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow‐up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty‐three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth.ConclusionObservation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.
When the microbiome helps the brain‐current evidence
Authors: Drljača Jovana , Milošević Nataša , Milanović Maja , Abenavoli Ludovico , Milić Nataša 
Published: January 2023

AbstractThe gut microbiota‐brain axis has been recognized as a network of connections that provides communication between the gut microflora and both central and autonomic nervous system. The gut microbiota alteration has been targeted for therapy in various neurodegenerative and psychiatric disbalances. Psychobiotics are probiotics that contribute beneficially to the brain function and the host mental health as a result of an interaction with the commensal gut bacteria, although their mechanism of action has not been completely revealed. In this state‐of‐art review, the findings about the potential therapeutic effects of the psychobiotics alone or in combination with conventional medicine in the treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, as well as in some psychiatric diseases like depression, schizophrenia, and bipolar disorder, have been summarized. The evidence of the psychobiotics therapeutic outcomes obtained in preclinical and clinical trials have been given respectively for the observed neurodegenerative and psychiatric disorders.
Hydroxychloroquine for treatment of non‐hospitalized adults with COVID‐19: A meta‐analysis of individual participant data of randomized trials
Authors: Mitjà Oriol , Reis Gilmar , Boulware David R. , Spivak Adam M. , Sarwar Ammar , Johnston Christine , Webb Brandon , Hill Michael D. , Smith Davey , Kremsner Peter , Curran Marla , Carter David , Alexander Jim , Corbacho Marc , Lee Todd C. , Hullsiek Katherine Huppler , McDonald Emily G. , Hess Rachel , Hughes Michael , Baeten Jared M. , Schwartz Ilan , Metz Luanne , Richer Lawrence , Chew Kara W. , Daar Eric , Wohl David , Dunne Michael 
Published: January 2023

AbstractHydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID‐19). Conventional meta‐analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID‐19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID‐19. We evaluated the overall treatment group effect by log‐likelihood ratio test (−2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (−2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614–1.610; −2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta‐analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome‐coronavirus 2 viral clearance and COVID‐19 hospitalization did not show a clinical benefit of HCQ. Our meta‐analysis provides evidence to support the interruption in the use of HCQ in mild COVID‐19 outpatients to reduce progression to severe disease.
Concomitant nivolumab‐associated Grover disease and bullous pemphigoid in a patient with metastatic renal cell carcinoma
Authors: Khazaeli Mahyar , Grover Raminder , Pei Susan 
Published: January 2023

AbstractImmune checkpoint inhibitor (ICI)‐induced bullous pemphigoid (BP) and Grover disease (GD) are uncommon, and concomitant GD and BP is rarer still. We report a third case of concomitant BP and GD associated with nivolumab with emphasis on the clinical, histopathologic and immunofluorescence findings as well as differential diagnoses. A 73‐year‐old male with metastatic renal cell carcinoma on nivolumab developed erythematous scaly papules on the trunk with biopsy showing suprabasal acantholysis with dyskeratosis, consistent with GD. Subsequently, he developed widespread lesions on arms, legs, trunk, and scrotum with new vesiculobullae and urticarial lesions. Biopsy of a vesicle showed subepidermal blister with numerous eosinophils and neutrophils, and immunofluorescence and serological studies were supportive of BP. He continued to have clinically apparent GD that was confirmed on repeat biopsy. The patient was diagnosed with concomitant GD and BP induced by nivolumab and successfully treated with dupilumab. The relationship between ICI‐induced GD and BP is not well understood; it has been suggested that T‐cell activation against the BP180 antigen expressed on surface of tumor cells may predispose susceptible individuals to BP. Subsequent ICI‐induced GD may create keratinocyte injury needed to expose additional proteins to reactivated and autoreactive T‐cells, leading to autoimmunity. An important differential diagnosis is bullous GD, which can be distinguished by negative immunofluorescence and serological studies.
Beyond the Genome: Genetically Modified Crops in Africa and the Implications for Genome Editing
Authors: Rock Joeva Sean , Schnurr Matthew A. , Kingiri Ann , Glover Dominic , Stone Glenn Davis , Ely Adrian , Fischer Klara 
Published: January 2023

ABSTRACTGenome editing — a plant‐breeding technology that facilitates the manipulation of genetic traits within living organisms — has captured the imagination of scholars and professionals working on agricultural development in Africa. Echoing the arrival of genetically modified (GM) crops decades ago, genome editing is being heralded as a technology with the potential to revolutionize breeding based on enhanced precision, reduced cost and increased speed. This article makes two interventions. First, it identifies the discursive continuity linking genome editing and the earlier technology of genetic modification. Second, it offers a suite of recommendations regarding how lessons learned from GM crops might be integrated into future breeding programmes focused on genome editing. Ultimately, the authors argue that donors, policy makers and scientists should move beyond the genome towards systems‐level thinking by prioritizing the co‐development of technologies with farmers; using plant material that is unencumbered by intellectual property restrictions and therefore accessible to resource‐poor farmers; and acknowledging that seeds are components of complex and dynamic agroecological production systems. If these lessons are not heeded, genome‐editing projects are in danger of repeating mistakes of the past.
Risk prediction of atrial fibrillation and its complications in the community using hs troponin I
Authors: Börschel Christin S. , Geelhoed Bastiaan , Niiranen Teemu , Camen Stephan , Donati Maria Benedetta , Havulinna Aki S. , Gianfagna Francesco , Palosaari Tarja , Jousilahti Pekka , Kontto Jukka , Vartiainen Erkki , Ojeda Francisco M. , den Ruijter Hester M. , Costanzo Simona , de Gaetano Giovanni , Di Castelnuovo Augusto , Linneberg Allan , Vishram‐Nielsen Julie K. , Løchen Maja‐Lisa , Koenig Wolfgang , Jørgensen Torben , Kuulasmaa Kari , Blankenberg Stefan , Iacoviello Licia , Zeller Tanja , Söderberg Stefan , Salomaa Veikko , Schnabel Renate B. 
Published: January 2023

AbstractAimsAtrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood‐based biomarkers reflecting cardiac injury such as high‐sensitivity troponin I (hsTnI) may help close this gap.MethodsWe investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C‐reactive protein, N‐terminal pro B‐type natriuretic peptide).ResultsDuring a median follow‐up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91‐fold (95% confidence interval (CI) 3.30, 4.63; p < .01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable‐adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p = .03). Inclusion of hsTnI did improve model discrimination (C‐index CVRF 0.811 vs. C‐index CVRF and hsTnI 0.813; p < .01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p < .01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p < .01).ConclusionhsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT‐proBNP. However, it is associated with the AF‐related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment.
Reconfiguration of response‐set in task switching: Event‐related potential evidence
Authors: Xie Liufang , Cao Bihua , Chen Yun , Wu Jianxiao , Li Fuhong 
Published: January 2023

AbstractIn task switching, an interaction between task and response is often observed, with response repetition (RR) benefits in task‐repeat trials and RR costs in task‐switch trials. The theoretical accounts of the RR effect remain controversial, and neuroscience evidence is scarce. The present study utilized the event‐related potentials (ERPs) method to explore the neural mechanism underlying the RR effect by adopting a cued task‐switching paradigm. The ERP results revealed the interaction between task and response in the P3b time window, with a response switch positivity under task‐repetition conditions and an RR positivity under task‐switching conditions. In addition, there were RR positivity in the N2 irrespective of task transition and in the late component (LC, 550–600 ms) that only under the task repetition condition. On the individual level, the RR benefit positively correlated with the RR positivity in the LC, while the RR costs negatively correlated with RR positivity in the N2/P3 component. These results suggest that both response reconfiguration and episodic‐retrieval make contributions to the RR effects, which were also discussed in terms of predictive model for a domain‐general inference and learning of perceptual categories.
Vibration‐based bending fatigue of additively manufactured alloy 718 with varied surface conditions
Authors: Tullis Rachel , Eidt Wesley , Gockel Joy , Klingbeil Nathan , Scott‐Emuakpor Onome 
Published: January 2023

AbstractSurface roughness is a dominating factor in the fatigue failure of structural components. This is especially true in additive manufacturing (AM), wherein as‐printed surfaces are particularly rough. This work uses a vibration bending fatigue method, which determines the fatigue life of metals at resonant frequencies. The fatigue behavior of AM nickel superalloy 718 fabricated using laser powder bed fusion is investigated with varying surface conditions, processing parameters, and an internal channel. The results indicate that as‐printed surface roughness does not strongly affect vibration bending fatigue life when compared to polished specimens. Fracture surface analysis is performed to determine crack initiation locations, highlighting that most failures initiated from the corners of the rectangular specimens. The outcome of this work is an enhanced understanding of fatigue failure in AM parts with as‐printed surfaces, which is an important step in increasing the efficiency and reliability of AM for applications involving fatigue loading conditions.