bluuebunny/crossref_metadata_2025_split huggingface dataset:
DecreasedCD11c‐positive dendritic cells in the tumor microenvironment predict double‐hit/triple‐hit genotype and survival in diffuse large B‐cell lymphoma
Authors: Yuan Chang‐Tsu , Chuang Shih‐Sung , Cheng Pei‐Yuan , Chang Koping , Wang Hsuan , Tsai Jia‐Huei , Liau Jau‐Yu , Chou Wen‐Chien 
Published: June 2022

AbstractDiffuse large B‐cell lymphoma (DLBCL) is the most common type of non‐Hodgkin lymphoma and is a potentially curable disease. However, it is heterogenous, and the prognosis is poor if the tumor cells harbor fusions involvingMYCandBCL2orMYCandBCL6(double‐hit [DH] lymphoma), or fusions involving all three genes (triple‐hit [TH] lymphoma). Fluorescencein situhybridization is currently the gold standard for confirming the presence of DH/TH genotypes. However, the test is laborious and not readily available in some laboratories. Germinal center B (GCB) signatures and dual expression of MYC and BCL2 are commonly used as initial screening markers (traditional model) in clinical practice. Our study proposes immunohistochemical markers for more conveniently and accessibly screening DH/TH genotypes in DLBCL. We retrospectively reviewed the clinical and pathological parameters of patients with DLBCL. We assessed the proliferative index, apoptotic index, and tumor microenvironment (TME), with regard to T cells and CD11c(+) dendritic cells, in formalin‐fixed paraffin‐embedded tissue. We then generated a decision tree as a screening algorithm to predict DH/TH genotypes and employed decision curve analysis to demonstrate the superiority of this new model in prediction. We also assessed the prognostic significance of related parameters. Our study revealed that GCB subtypes, a Ki67 proliferative index higher than 70%, and BCL2 expression were significantly associated with DH/TH genotypes. Decreased CD11c(+) dendritic cells in the TME indicated additional risk. Our proposed screening algorithm outperformed a traditional model in screening for the DH/TH genotypes. In addition, decreased CD11c(+) dendritic cells in the DLBCL TME were an independent unfavorable prognosticator. In conclusion, we provide a convenient, well‐performing model that predicts DH/TH genotypes in DLBCL. The prognostic significance of CD11c(+) dendritic cells in the TME might influence the classification and development of immunotherapy for DLBCL in the future.
Post‐neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage‐ and regression‐grade independent prognostic information in intestinal‐type gastric adenocarcinoma
Authors: Jesinghaus Moritz , Herz Anna‐Lina , Kohlruss Meike , Silva Miguel , Grass Albert , Lange Sebastian , Novotny Alexander , Ott Katja , Schmidt Thomas , Gaida Matthias , Hapfelmeier Alexander , Denkert Carsten , Weichert Wilko , Keller Gisela 
Published: June 2022

AbstractTumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy‐naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post‐neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated TB according to the criteria from the International Tumour Budding Consensus Conference (ITBCC) in 167 post‐neoadjuvant resections of intestinal‐type GC and correlated the results with overall survival (OS) and clinicopathological parameters. GCs were categorised into Bd1 (0–4 buds, low TB), Bd2 (5–9 buds, intermediate TB), and Bd3 (≥10 buds, high TB). Carcinomas with intermediate and high TB were significantly enriched in higher ypTNM stages and strongly associated with reduced 5‐year OS in univariable analyses (p < 0.001). In multivariable analyses including sex, age, resection status, UICC stage, and tumour regression grading, TB remained a stage‐independent predictor of survival (p < 0.001, hazard ratio Bd2: 2.60, Bd3: 4.74). The assessment of TB according to the ITBCC criteria provides valuable prognostic information in the post‐neoadjuvant setting of intestinal‐type GC and may be a considerable substitute for the conventional grading system in GCs after neoadjuvant therapy.
Re‐adjudication of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) with study‐level meta‐analysis of hospitalization for heart failure from cardiovascular outcomes trials with dipeptidyl peptidase‐4 (DPP‐4) inhibitors
Authors: Scirica Benjamin M. , Im KyungAh , Murphy Sabina A. , Kuder Julia F. , Rodriguez Dolly A. , Lopes Renato D. , Green Jennifer B. , Ruff Christian T. , Sabatine Marc S. 
Published: June 2022

AbstractBackgroundTrial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the cardiovascular (CV) safety of sitagliptin versus placebo on CV outcomes in patients with type 2 diabetes and CV disease and found sitagliptin noninferior to placebo. Subsequently, based on feedback from FDA, the Sponsor of the trial, Merck & Co., Inc., engaged a separate academic research organization, the TIMI Study Group, to re‐adjudicate a prespecified set of originally adjudicated events.MethodsTIMI adjudicated in a blinded fashion all potential hospitalization for heart failure (HHF) events, all potential MACE+ events previously adjudicated as not an endpoint event, and a random subset (~10%) of MACE+ events previously adjudicated as an endpoint event. An updated study‐level meta‐analysis of four randomized, placebo‐controlled, CV outcomes trials with dipeptidyl peptidase 4 (DPP‐4) inhibitors was then performed.ResultsAfter re‐adjudication of potential HHF events in the intent‐to‐treat population, there were 224 patients with a confirmed event in the sitagliptin arm (1.05/100 person‐years) and 239 patients in the placebo arm (1.13/100 person‐years), corresponding to a hazard ratio (HR) of 0.94 (95% confidence interval [95% CI]: 0.78–1.13, p = .49). Concordance between the outcome of the original adjudication and the re‐adjudication for HHF events was 82.7%. The meta‐analysis of CV outcomes trials with DPP‐4 inhibitors with placebo and involving 43 522 patients yielded an HR of 1.07 (95% CI: 0.83–1.39), with moderate heterogeneity (p = .45, I2 = 62.07%).ConclusionThe results of this independent re‐adjudication process and analyses of CV outcomes from TECOS were consistent with the original adjudication results and overall study findings. An updated study‐level meta‐analysis showed no overall significant risk for HHF with DPP‐4 inhibitors, but with statistical heterogeneity.
Sex‐specific cannabinoid 1 receptors on GABAergic neurons in the ventrolateral periaqueductal gray mediate analgesia in mice
Authors: Jiang Zhenhua , Wang Qun , Zhao Jianshuai , Wang Jiajia , Li You , Dai Wei , Zhang Xiao , Fang Zongping , Hou Wugang , Xiong Lize 
Published: June 2022

AbstractSex differences in analgesic effects have gradually attracted public attention in preclinical and clinical studies. Both human and animal females are more sensitive to cannabinoid antinociception than males. Expression of the cannabinoid 1 receptor (CB1R) and the function of the endocannabinoid system have been explored in both male and female mice and CB1Rs in the ventrolateral periaqueductal gray (vlPAG) participate in antinociception. However, whether there are cell‐type‐ and sex‐specific patterns of vlPAG CB1R expression that affect analgesia is unknown. In the current study, we either activated or inhibited CB1Rs in the vlPAG and found that female mice produced stronger analgesia or developed more robust mechanical allodynia than males did. Specific deletion of GABAergic CB1Rs in the vlPAG promoted stronger mechanical allodynia in female mice than that in male mice. However, no sex differences in cannabinoid antinociception were found following chemogenetic inhibition of GABAergic neurons. Using fluorescence in situ hybridization, we found that the sex difference in cannabinoid antinociception was due to females having higher expression of GABAergic CB1Rs in the vlPAG than males. Furthermore, activation of CB1Rs in the vlPAG significantly reduced the frequency of GABA‐mediated spontaneous inhibitory postsynaptic currents recorded in vGlut2‐tdTomato positive neurons in both sexes. This effect was greater in females than males and this reduction was closely related to CB1R expression difference between sexes. Our work indicates that vlPAG GABAergic CB1Rs modulate cannabinoid‐mediated analgesia in a sex‐specific manner, which may provide a potential explanation of sex difference found in the analgesic effect of cannabinoids.
Local targets of T‐stellate cells in the ventral cochlear nucleus
Authors: Lin Lin , Campbell Jay , Oertel Donata , Smith Philip H. 
Published: June 2022

AbstractT‐stellate cells in the ventral cochlear nucleus (VCN) are known to have local axon collaterals that terminate in the vicinity of their dendrites and cell bodies within the same isofrequency lamina in parallel with the auditory nerve fibers that innervate them. Excitatory synaptic connections between stellate cells within an isofrequency lamina are hypothesized to be involved in the nitric oxide‐mediated upregulation of T‐stellate responses to their auditory input. This could serve as a mechanism of variable gain control in the enhancement of responses to vowel spectral peaks. Previous studies have provided indirect evidence for these possible synaptic interconnections between T‐stellate cells, but unequivocal identification has yet to be established. Here, we used retrograde neuronal tracing with adeno‐associated viral vector or biotinylated dextran amine injected into the inferior colliculus (IC) to detect the postsynaptic target of T‐stellate cells within the VCN. We show that backfilled T‐stellate cell axons make monosynapatic connections on the labeled cell bodies and dendrites of other labeled T‐stellate cells within an isofrequency lamina. Electron microscopy revealed that T‐stellate terminals can also make synapses on structures not retrogradely labeled from the IC. Glycine antibodies combined with the viral labeling indicated that these nonbackfilled structures that the labeled T‐stellate terminals were synapsing on are most likely the cell bodies and dendrites of two size categories of glycinergic VCN cells, whose sizes and relative numbers indicated they are the D‐ and L‐stellate cells. These cells are known to provide inhibitory inputs back onto T‐stellate cells. Our data indicate that, in addition to their auditory nerve input, T‐stellate cells provide a second modulatable excitatory input to both inhibitory and excitatory cells in a VCN isofrequency lamina and may play a significant role in acoustic information processing.
Lenvatinib in multimodal therapy for unresectable radioactive iodine‐naïve differentiated thyroid cancer: A case report with literature review
Authors: Kim Hugh Andrew Jinwook , Nichols Anthony Charles , Rachakonda Ramanamurthy , Inculet Richard , Sathya Jinka , Rachinsky Irina , Winquist Eric 
Published: June 2022

AbstractBackgroundPatients with unresectable or metastatic differentiated thyroid carcinoma (DTC) are rare and require individualized therapy. This may require approaches not typically used in resectable disease. We report a patient treated with lenvatinib and external beam radiation therapy.CaseAn 87‐year‐old woman presented with cT4N1aM1 papillary thyroid carcinoma with tracheal invasion. She was not a candidate for surgery, radioactive‐iodine, or radiation, so a trial of lenvatinib was offered. Her tumor showed clinical, biochemical, and radiological response after 5 months of lenvatinib, and she subsequently received external beam radiation. She enjoys good quality of life without evidence of cancer progression off therapy 21 months post‐initiation of treatment.ConclusionLenvatinib may be effective in RAI‐naïve advanced DTC patients as a component of individualized multimodal therapy when conventional options are not feasible.
Co‐occurrence of JAK2 V617F‐mutated essential thrombocythemia and chronic lymphocytic leukemia harboring der(8;17)(q10;q10)
Authors: Manabe Masahiro , Tanizawa Nao , Nanno Satoru , Hagiwara Yuuji , Asada Reiko , Koh Ki‐Ryang 
Published: June 2022

AbstractBackground and CaseWe herein present a case of the co‐occurrence of JAK2‐mutated essential thrombocythemia (ET) with chronic lymphocytic leukemia (CLL) harboring the recurrent and rare whole‐arm translocation, der(8;17)(q10;q10). The co‐existence of lymphoproliferative neoplasms and myeloproliferative neoplasms is suggested to be a rare event. Under this condition, the lymphoproliferative disorder presents a clinically indolent course with a low‐risk biological profile. However, the present case showed aggressive disease progression, reflecting a poor prognostic factor; that is, the loss of 17p caused by the whole‐arm der(8;17)(q10;q10) translocation.ConclusionThe present case report emphasizes the importance of considering the involvement of a genetically poor prognostic factor, regardless of the co‐occurrence of CLL and ET.
Multiclass recognition of AD neurological diseases using a bag of deep reduced features coupled with gradient descent optimized twin support vector machine classifier for early diagnosis
Authors: Velliangiri S. , Pandiaraj Shanthini , S Iwin Thanakumar Joseph , Muthubalaji S. 
Published: June 2022

SummaryAlzheimer's disease (AD) is an advanced neurodegenerative disease of the brain that affects the nerve system of brain. Previously, several feature extraction and classification methods were discussed, but that methods provide high over fitting problem, which leads to minimization of detection accuracy. To overcome these issues, the multi class classification of AD diseases using bag of deep feature reduction technique and twin support vector machine classifier (TSVM) optimized with gradient decent optimizer is proposed in this manuscript for classifying the AD disease as severe AD, mild cognitive impairment, healthy control. At first, the input EEG signals are pre‐processed. To decrease the execution time and processing time with feature size, a bag of deep features reduction technique is used. The reduced feature signals are classified by optimized TSVM. The simulation process is implemented in MATLAB environment. The proposed model achieves higher accuracy 33.84%, 28.93%, 33.03%, 27.93%, higher precision 22.87%, 16.97%, 16.97%, and 36.97%, compared with the existing methods, such as piecewise aggregate approximation support vector machine (MCC‐EEG‐PAA‐SVM), convolutional neural network (MCC‐EEG‐CNN), conformal kernel‐based fuzzy support vector machine (MCC‐EEG‐CKF‐SVM), Pearson correlation coefficient‐based feature selection strategy with linear discriminant analysis classifier (MCC‐EEG‐ PCC‐LDA).
Mapping of stem rot resistance in peanut indicates significant effect for plant architecture locus
Authors: Agmon Sarah , Kunta Srinivas , Dafny Yelin Mery , Moy Judit , Ibdah Mwafaq , Harel Arye , Rabinovitch Onn , Levy Yael , Hovav Ran 
Published: June 2022

AbstractStem rot, caused by the Sclerotium rolfsii, imposes severe yield losses in peanuts (Arachis hypogaea L.) worldwide. Breeding for resistance is challenging because not enough is known about mechanisms for resistance. The goals of this study were to (a) evaluate the field resistance of recombinant inbred lines derived from a resistant × susceptible cross, (b) associate quantitative loci (QTLs), and (c) reveal potential mechanisms for resistance. Lines were inspected during 3 yr in field conditions. Plants were manually inoculated and rated for three parameters: disease level, number of damaged plants/center, and disease power. Significant effects were found for the lines and the environment in all three parameters. Heritability and year‐to‐year correlations were highly significant, suggesting a consistent response of the lines to the stem rot pressure. Quantitative trait loci mapping was performed based on a previously constructed genetic map. Overall, 20 significant QTLs were found for the resistance parameters, concentrating in four locations on chromosomes A07, A03, B03, and B05. Out of the four loci, three were reported in previous studies with different genetic backgrounds suggesting a wide effect. The B05 QTL was the strongest, with the phenotypic variation explained of 11.6–21.7%. Interestingly, this QTL is colocalized with a previously identified major locus for branching habit trait. An additional field trial performed on 14 lines found a significant branching habit effect, wherein bunch‐types lines were more resistant than spreading‐types, suggesting that plant architecture can be a possible factor influencing the infection rate of S. rolfsii on the field level.
Do foreign banks disclose corporate social responsibility practices more than their local counterparts? Empirical evidence of an emerging market context
Authors: Lui Tze Kiat , Zainuldin Mohd Haniff 
Published: June 2022

AbstractThis study examines the levels of corporate social responsibility disclosure (CSRD) between foreign and local banks in Malaysia by engaging the reconciliations of the stakeholder theory and resource‐based view. Additionally, independent directors, portrayed as unique internal resources, may affect the CSRD level. Using the panel data of 37 commercial banks retrieved over the period between 2010 and 2017, OLS and robust regressions revealed that the local banks disclosed more CSR information than their foreign banks' counterparts, and the increasing number of independent directors on the board produced lower CSRD. However, the interaction term offered new insight that the independent directors are acting as an effective resource for the foreign banks with a highly concentrated ownership environment. This gives a nuanced understanding of the proposed integrative theory to stimulate foreign banks' more social and environmental performances.
Efficient Catalytic Conversion of 5‐Hydroxymethylfurfural to 2,5‐Furandicarboxylic Acid over Ruthenium Cluster‐Embedded Ni(OH)2 Catalyst
Authors: Chai Xinyu , Jiang Kaiyue , Wang Jianying , Ren Zhouhong , Liu Xi , Chen Liwei , Zhuang Xiaodong , Wang Tianfu 
Published: June 2022

Abstract5‐Hydroxymethylfurfural (HMF) can be oxidized to 2,5‐furandicarboxylic acid (FDCA) for the production of biorenewable plastics to replace fossil resourced polyethylene terephthalate (PET). Development of a highly efficient electrocatalyst using renewable electricity as energy input is highly desired. In this work, Ru cluster‐embedded Ni(OH)2 nanosheets [Ru/Ni(OH)2] were synthesized and exploited as electrochemical catalysts for the conversion of HMF to FDCA. Ru/Ni(OH)2 exhibited significantly improved current density (40 mA cm−2 at 1.41 V vs. reversible hydrogen electrode) of over 7.7 times in comparison with Ni(OH)2, and nearly 100 % conversion degree for HMF and 98.5 % selectivity towards FDCA were obtained. Operando Raman experiments revealed the catalysis was facilitated by the interconversion between Ni3+ and Ni2+. Density functional theory calculations further revealed the effect of Ru clusters of Ni(OH)2, thereby promoting HMF adsorption capacity on Ni sites to boost HMF oxidation activity. This work provides a novel strategy using Ru clusters to modify earth abundant Ni based catalyst for HMF oxidation to obtain high‐value biomass‐derived products.
Improved read/write assist mechanism for 10‐transistor static random access memory cell
Authors: Abbasian Erfan , Gholipour Morteza 
Published: June 2022

AbstractThis paper presents a robust low‐power 10T SRAM cell (RLP10T) with a novel read/write assist mechanism, improving both read static noise margin (RSNM) and write static noise margin (WSNM) simultaneously. To assess its relative strength, we compared the proposed cell with recently published SRAM cells such as WRE8T, 10T‐P1, HFBS10T, WALP11T, and SE11T in 16‐nm CMOS technology node. The RLP10T cell shows 3.55/1.07 times higher/lower RSNM compared to the WRE8T/WALP11T cell and offers at least 1.10 times higher WSNM. Due to the presence of three series‐connected transistors in its read path, which includes a strong pull‐down transistor, the proposed design shows 1.23 times shorter read delay (TRA) than that of 10T‐P1/HFBS10T cell. The proposed cell incurs a penalty of high write delay (TWA) due to its long write path. However, it exhibits the fourth (second)‐best read (write) power, attributed to its single‐ended structure and lower read (write) frequency. It also dissipates acceptable leakage power due to its single‐bitline structure and the presence of stacked transistors in its read path and pull‐down path of one of the inverters in the cell core. Subjected to the severe process, voltage, and temperature variations, the RLP10T cell offers at least 1.31/1.09/1.03 times lower variability in RSNM/WSNM/TRA at VDD = 0.7 V, at the cost of 1.22 times area overhead compared to the WRE8T cell.
Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry
Authors: Fang Hong , Wang Sa A. , Hu Shimin , Konoplev Sergej N. , Mo Huan , Liu Wei , Zuo Zhuang , Xu Jie , Jorgensen Jeffrey L. , Yin C. Cameron , El Hussein Siba , Jelloul Fatima Zahra , Tang Zhenya , Medeiros L. Jeffrey , Wang Wei 
Published: June 2022

AbstractBackgroundPrompt diagnosis of acute promyelocytic leukemia (APL) is critical for patient care. In this study, we aimed to characterize the immunophenotype of APL and explore immunophenotypic difference between APL and its mimics using flow cytometric analysis.MethodsEighty‐five cases were collected, including 47 APL, 26 NPM1‐mutated acute myeloid leukemia (AML) and 12 KMT2A‐rearranged AML with an APL‐like immunophenotype. Immunophenotypes were analyzed using flow cytometric analysis.ResultsAPL showed four distinct patterns (designated a–d) based on CD45/SSC plots. Blasts in patterns a–c showed high side scatter, whereas blasts in pattern d had low side scatter and were located in the traditional blast gate. Compared with patterns a–c, pattern d of APL (APL‐D) was more often positive for CD2 (p = 0.0005) and CD34 (p = 0.0002) in blasts. All NPM1‐mutated AML and KMT2A‐rearranged AML cases with an APL‐like immunophenotype had blasts in the traditional blast gate on CD45/SSC, mimicking APL‐D. In comparison, uniform CD13 and positive CD64 were seen in 100% (n = 13) APL‐D cases and in only 2 of 26 (8%) NPM1‐mutated AML cases (p < 0.0001). In addition, APL‐D cases were more likely to be positive for CD2 and/or CD34 than NPM1‐mutated AML (p < 0.0001 and p = 0.0007, respectively). In comparison with APL‐D, KMT2A‐rearranged AML cases were less often positive for myeloperoxidase (MPO) (p = 0.001), with none being strongly positive. Similar to NPM1‐mutated AML and different from APL‐D, KMT2A‐rearranged AML cases were rarely positive for CD34 and all negative for CD2.ConclusionsAPL and its immunophenotypic mimics share some immunophenotypic similarities but can be distinguished by CD2, CD13, CD34, CD64, and MPO.