bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects
Authors: Ceppi Francesco , Wilson Ashley L. , Annesley Colleen , Kimmerly Gabriella R. , Summers Corinne , Brand Adam , Seidel Kristy , Wu Qian Vicky , Beebe Adam , Brown Christopher , Mgebroff Stephanie , Lindgren Catherine , Rawlings-Rhea Stephanie D. , Huang Wenjun , Pulsipher Michael A. , Wayne Alan S. , Park Julie R. , Jensen Michael C. , Gardner Rebecca A.
Published: May 2022

T cells modified to express a chimeric antigen receptor (CAR) targeting CD19 can induce potent and sustained responses in children with relapsed/refractory acute lymphoblastic leukemia (ALL). The durability of remission is related to the length of time the CAR T cells persist. Efforts to understand differences in persistence have focused on the CAR construct, in particular the costimulatory signaling module of the chimeric receptor. We previously reported a robust intent-to-treat product manufacturing success rate and remission induction rate in children and young adults with recurrent/refractory B-ALL using the SCRI-CAR19v1 product, a second-generation CD19-specific CAR with 4-1BB costimulation coexpressed with the EGFRt cell-surface tag (NCT02028455). Following completion of the phase I study, two changes to CAR T-cell manufacturing were introduced: switching the T-cell activation reagent and omitting midculture EGFRt immunomagnetic selection. We tested the modified manufacturing process and resulting product, designated SCRI-CAR19v2, in a cohort of 21 subjects on the phase II arm of the trial. Here, we describe the unanticipated enhancement in product performance resulting in prolonged persistence and B-cell aplasia and improved leukemia-free survival with SCRI-CAR19v2 as compared with SCRI-CAR19v1.
High Mobility Group Protein B1 Decreases Surface Localization of PD-1 to Augment T-cell Activation
Authors: Gao Qun , Wang Shumin , Li Feng , Lian Jingyao , Cheng Shaoyan , Yue Dongli , Zhang Zhen , Liu Shasha , Ren Feifei , Zhang Daiqun , Wang Shengdian , Wang Liping , Zhang Yi
Published: May 2022

High-mobility group protein B1 (HMGB1) is a danger signaling molecule that has been found to trigger an effective antitumor immune response. However, the mechanisms underlying its antitumor effects are not fully understood. Here, we found that HMGB1 release induced by chemotherapy in patients with non–small cell lung cancer was negatively correlated with PD-1 expression on CD8+ T cells. In vitro analysis indicated that treatment with HMGB1 led to a significant decrease in the level of expression of PD-1 on CD8+ T cells. Further analysis demonstrated that HMGB1 reduced PD-1 expression by inducing dynamin-mediated internalization of the protein, leading to early endocytosis in the cytoplasm, and subsequently degradation in the lysosomes. In a xenograft model, HER2-targeted chimeric antigen receptor (CAR) T cells had enhanced function in the presence of HMGB1. These data identify a role for HMGB1 as a negative regulator of PD-1 signaling in lung cancer and the observed antitumor effect of HMGB1 on CAR T cells may provide a theoretical foundation for a new immunotherapy combination.
Acute Ischemic Stroke Associated with COVID-19 in a Pediatric Patient: A Case Report
Authors: Vrushabhendra Sukanya , Kodavooru Gururaj Aithala , Kashyape Pawan , Pawar Nikhil
Published: May 2022

COVID-19, caused by novel coronavirus SARS-CoV-2, which seemed to have unaffected the children in the initial period of the pandemic, now has targeted the pediatric population with varied clinical manifestations; the pathophysiology is still under exploration. Neurological presentations are being increasingly reported in both adults and children. We present a case of ischemic stroke in a 12-year-old COVID-19 patient with seizure, right hemiparesis, and dysarthria.
Efficacy of Hemoperfusion in Severe and Critical Cases of COVID-19
Authors: Alavi Darazam Ilad , Kazempour Muhanna , Pourhoseingholi Mohamad Amin , Hatami Firouze , Rabiei Mohammad Mahdi , Javandoust Gharehbagh Farid , Amirdosara Mahdi , Hajiesmaeili Mohammadreza , Shabani Minoosh , Shokouhi Shervin , Lotfollahi Legha , Mardani Masoud , Haghighi-Morad Maryam , Nassiri Amir Ahmad , Rangraz Davoud , Falahaty Hassan , Syami Hosein , Irannejad Yaghoob , Fallah Maryam , Zangi Masoud , Shafigh Navid
Published: May 2022

Introduction: Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. Method: We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) and CytoSorb® 300. Result: A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (p value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; p value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; p < 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. Conclusion: Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.
Dos pactos com o Diabo, a Sereia e os Apus: sobre a participação de não-humanos na constituição do corpo dos danzantes de tijeras (Ayacucho, Peru)
Authors: Caballero Indira Viana
Published: May 2022

A danza de tijeras é parte das celebrações da Festa da Água em Andamarca (Departamento de Ayacucho, Peru) no mês de agosto. Durante a festa os danzantes fazem apresentações e competições em praça pública desafiando sua resistência física: perfuram o corpo com pregos e espinhos, cortam-se com cacos de vidros, caminham sobre brasas. Para que tenham êxito ao realizarem tais desafios, os danzantes fazem negociações contínuas através de pactos e pagapas com seres não-humanos, principalmente com o Diabo, a Sereia e os Apus, aqueles que lhes outorgam proteção e poder. Se tais negociações forem ignoradas, tais seres podem lhes hacer daño, propiciando infortúnios e males diversos. Longas caminhadas para alcançar lugares virgens, nunca antes pisados por um humano, são outra forma de tornar-se um bom danzante, de acumular mais força e poder para tornar-se um maestro.Este trabalho destaca aspectos da relação desses dançarinos com seres não-humanos (Apus, Pachamama,Diabo, Sereiaentre outros) e de como seu corpo precisa ser constituído por eles para que seja um corpo completo.
Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure
Authors: Vest Amanda R. , Wong William W. , Chery Joronia , Coston Alex , Telfer Laura , Lawrence Matthew , Celkupa Didjana , Kiernan Michael S. , Couper Gregory , Kawabori Masashi , Saltzman Edward
Published: May 2022

Background:

Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support.

Methods:

We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry imaging was repeated at 3 and 6 months after LVAD implantation, with participation ending after the 6-month visit or heart transplantation, whichever occurred first. Changes in body composition were evaluated using mixed effects linear regression models.

Results:

The cohort was 87% male, with mean age 56±12 (SD) years, and mean body mass index 26.4±5.4 kg/m
2
. Per sarcopenia ALM criteria, 52% of participants had muscle wasting at baseline. At baseline, mean fat free mass and ALM were 56.4±11.7 and 21.0±5.3 kg, respectively. Both measures increased significantly (
P
<0.001) over 6 months of LVAD support: mean fat free mass change at 3 and 6 months: 2.3 kg (95% CI, 1.0–3.5) and 4.2 kg (95% CI, 2.2–6.1); mean ALM change at 3 and 6 months: 1.5 kg (95% CI, 0.7–2.3) and 2.3 kg (95% CI, 0.9–3.6).

Conclusions:

Among LVAD recipients with advanced systolic heart failure and high baseline prevalence of muscle wasting, there were significant gains in skeletal muscle mass, as represented by dual X-ray absorptiometry fat free mass and ALM, over the first 6 months of LVAD support.
Prophylactic Mechanical Circulatory Support Use in Elective Percutaneous Coronary Intervention for Patients With Stable Coronary Artery Disease
Authors: Zeitouni Michel , Marquis-Gravel Guillaume , Smilowitz Nathaniel R. , Zakroysky Pearl , Wojdyla Daniel M. , Amit Amin P. , Rao Sunil V. , Wang Tracy Y.
Published: May 2022

Background:

Mechanical circulatory support (MCS) devices can be used in high-risk percutaneous coronary intervention (PCI). Our objective was to describe trends and outcomes of prophylactic MCS use in elective PCI for patients with stable coronary artery disease in the American College of Cardiology National Cardiovascular Data Registry’s CathPCI registry.

Methods:

Among 2 108 715 consecutive patients with stable coronary artery disease undergoing elective PCI in the CathPCI registry between 2009 and 2018, we examined patterns of prophylactic use of MCS. Propensity score models with inverse probability of treatment weighting compared effectiveness (in-hospital death, cardiogenic shock, or new heart failure) and safety (stroke, tamponade, major bleeding, or vascular complication requiring treatment) between patients treated with intra-aortic balloon pump versus other MCS (Impella or extracorporeal membrane oxygenation).

Results:

Overall, 6905 (0.3%) patients underwent elective PCI with prophylactic MCS. MCS use trended up from 0.2% of elective PCIs in 2009 to 0.6% in 2018 (
P
<0.0001), driven by other MCS (
P
<0.0001), whereas intra-aortic balloon pump use remained low and constant (
P
=0.12). In-hospital major adverse cardiac events and cardiovascular complications occurred in 7.1% and 18.8% of elective PCI patients with prophylactic MCS use and 0.5% and 2.3% of patients without prophylactic MCS use. Intra-aortic balloon pump use was associated with a higher risk of major adverse cardiac events (9.6% versus 6.0%, adjusted odds ratio, 1.59 [95% CI, 1.32–1.91]) but lower risk of complications (18.2% versus 19.1%, adjusted odds ratio, 0.88 [95% CI, 0.77–0.99]) than use of other MCS.

Conclusions:

The use of prophylactic MCS has increased over time for elective PCI in patients with stable coronary artery disease. Intra-aortic balloon pump was associated with higher major adverse cardiac events but lower risk of procedural complications compared with other MCS.
Bidirectional Association Between Kidney Function and Atrial Fibrillation: A Population‐Based Cohort Study
Authors: van der Burgh Anna C. , Geurts Sven , Ikram M. Arfan , Hoorn Ewout J. , Kavousi Maryam , Chaker Layal
Published: May 2022

Background

Consensus lacks concerning a bidirectional association between kidney function and atrial fibrillation (AF), but this is crucial information for prevention/treatment efforts for both chronic kidney disease and AF. Therefore, we investigated the bidirectional association between kidney function and AF.

Methods and Results

This study was a prospective cohort study including 9228 participants (mean age, 64.9 years; 57.2% women) with information on kidney function (estimated glomerular filtration rate [eGFR] based on serum creatinine [eGFRcreat], cystatin C [eGFRcys], or both [eGFRcreat‐cys], and urine albumin‐to‐creatinine ratio) and AF. Reduced kidney function was defined as eGFRcreat <60 mL/min per 1.73 m
2
. Cox proportional‐hazards, logistic regression, linear mixed, and joint models were used to investigate the association of kidney function with AF and vice versa. During follow‐up (median of 8.0 years), 780 events of incident AF occurred. Lower eGFRcys and eGFRcreat‐cys were associated with increased AF risk (hazard ratio [HR], 1.08 [95% CI, 1.03–1.14] and HR, 1.07 [95% CI, 1.01–1.14], respectively, per 10 mL/min per 1.73 m
2
eGFR decrease). For eGFRcys and eGFRcreat‐cys, 10‐year cumulative incidence of AF was 16% (eGFR <60) and 6% (eGFR ≥60). Prevalent AF (versus no prevalent AF) was associated with 2.85 mL/min per 1.73 m
2
lower eGFRcreat and with a faster decline of eGFRcreat with age. Prevalent AF was associated with a 1.3‐fold increased risk of incident reduced kidney function.

Conclusions

Kidney function, especially eGFRcys, and AF are bidirectionally associated. There are currently no targeted prevention efforts for AF in patients with mild chronic kidney disease and vice versa. Our results could provide the first step to improve prediction/prevention of both conditions.
Visual Distraction Disrupts Category-tuned Attentional Filters in Ventral Visual Cortex
Authors: Dube Blaire , Pidaparthi Lasyapriya , Golomb Julie D.
Published: May 2022

Our behavioral goals shape how we process information via attentional filters that prioritize goal-relevant information, dictating both where we attend and what we attend to. When something unexpected or salient appears in the environment, it captures our spatial attention. Extensive research has focused on the spatiotemporal aspects of attentional capture, but what happens to concurrent nonspatial filters during visual distraction? Here, we demonstrate a novel, broader consequence of distraction: widespread disruption to filters that regulate category-specific object processing. We recorded fMRI while participants viewed arrays of face/house hybrid images. On distractor-absent trials, we found robust evidence for the standard signature of category-tuned attentional filtering: greater BOLD activation in fusiform face area during attend-faces blocks and in parahippocampal place area during attend-houses blocks. However, on trials where a salient distractor (white rectangle) flashed abruptly around a nontarget location, not only was spatial attention captured, but the concurrent category-tuned attentional filter was disrupted, revealing a boost in activation for the to-be-ignored category. This disruption was robust, resulting in errant processing—and early on, prioritization—of goal-inconsistent information. These findings provide a direct test of the filter disruption theory: that in addition to disrupting spatial attention, distraction also disrupts nonspatial attentional filters tuned to goal-relevant information. Moreover, these results reveal that, under certain circumstances, the filter disruption may be so profound as to induce a full reversal of the attentional control settings, which carries novel implications for both theory and real-world perception.
It’s not Rocket Science: Interpreting Figurative Language in Narratives
Authors: Chakrabarty Tuhin , Choi Yejin , Shwartz Vered
Published: May 2022

Figurative language is ubiquitous in English. Yet, the vast majority of NLP research focuses on literal language. Existing text representations by design rely on compositionality, while figurative language is often non- compositional. In this paper, we study the interpretation of two non-compositional figurative languages (idioms and similes). We collected datasets of fictional narratives containing a figurative expression along with crowd-sourced plausible and implausible continuations relying on the correct interpretation of the expression. We then trained models to choose or generate the plausible continuation. Our experiments show that models based solely on pre-trained language models perform substantially worse than humans on these tasks. We additionally propose knowledge-enhanced models, adopting human strategies for interpreting figurative language types: inferring meaning from the context and relying on the constituent words’ literal meanings. The knowledge-enhanced models improve the performance on both the discriminative and generative tasks, further bridging the gap from human performance.
Ultra-fine Entity Typing with Indirect Supervision from Natural Language Inference
Authors: Li Bangzheng , Yin Wenpeng , Chen Muhao
Published: May 2022

The task of ultra-fine entity typing (UFET) seeks to predict diverse and free-form words or phrases that describe the appropriate types of entities mentioned in sentences. A key challenge for this task lies in the large number of types and the scarcity of annotated data per type. Existing systems formulate the task as a multi-way classification problem and train directly or distantly supervised classifiers. This causes two issues: (i) the classifiers do not capture the type semantics because types are often converted into indices; (ii) systems developed in this way are limited to predicting within a pre-defined type set, and often fall short of generalizing to types that are rarely seen or unseen in training.

This work presents LITE🍻, a new approach that formulates entity typing as a natural language inference (NLI) problem, making use of (i) the indirect supervision from NLI to infer type information meaningfully represented as textual hypotheses and alleviate the data scarcity issue, as well as (ii) a learning-to-rank objective to avoid the pre-defining of a type set. Experiments show that, with limited training data, LITE obtains state-of-the-art performance on the UFET task. In addition, LITE demonstrates its strong generalizability by not only yielding best results on other fine-grained entity typing benchmarks, more importantly, a pre-trained LITE system works well on new data containing unseen types.1
Impact of High-Dose Perindopril on Cardiac Function and Angiotensin Converting Enzyme 2/Ang-(1-9)/Ang-(1-7) in Rabbits with Ischemic Cardiac Dysfunction
Authors: Li Shuren , Hao Xiao , Yuan Kexin , Zhang Feifei , Xun Liying , Hao Qingqing , Zhang Qianhui , Xie Yuetao
Published: May 2022

Aim: To investigate the impact of high-dose of perindopril on cardiac function and ACE2/AT2R pathway in rabbits with ischemic cardiac dysfunction. Methods: The thirty rabbits with ischemic cardiac dysfunction were divided into high-dose group (Perindopril, 2 mg/kg/d),
low-dose group (Perindopril, 0.66 mg/kg/d), and control groups (Saline, 2 ml/kg/d) by a random number table. After four weeks, we measured the cardiac function, The level of Ang-(1-7) and Ang-(1-9), mRNA expression level of ACE2 and AT2R. Results: The results showed that high dose and
low dose of perindopril could improve cardiac function (p < 0.001), and high-dose perindopril had more significant improvement (p = 0.041). After treatment, in high-dose group, mRNA level of ACE2, AT2R in myocardium (p < 0.001) and Ang-(1-9) level in serum (p = 0.012)
were higher than low-dose group, while Ang-(1-7) levels in serum didn’t show a significant difference (p = 0.829). LVEF and serum Ang-(1-9) were significantly correlated (p = 0.002), LVEF and ACE2 (p = 0.001), LVEF and AT2R (p = 0.007); however, it was no
correlation between LVEF and serum Ang-(1-7) (p = 0.067). Conclusion: A high-dose of perindopril could improve ischemic cardiac dysfunction by ACE2/Ang-(1-9)/Ang-(1-7) pathway.
Bone Marrow Mesenchymal Stem Cells (BMSCs) Promote the Metastasis of Thyroid Papillary Cancer by Inhibiting Poly-Pyrimidine Tract Binding Protein 1 (PTBP1)
Authors: Gong Yifei , Zhu Xiaoyu , Wang Qun , Li Jialei , Wang Xiaoping
Published: May 2022

We aimed to explore the mechanism underlying the role of bone marrow mesenchymal stem cells (BMSCs) in the invasion of papillary thyroid cancer (PTC) cells. BMSCs were co-cultured with PTC cells WRO or normal thyroid follicular epithelial cells T3TD followed by analysis of cell migration
and proliferation by Transwell assay and MTT assay. Cells were transfected with shRNA or overexpression of PTBP1, followed by measuring cell proliferation and invasion and PTBP1 expression by RT-qPCR and Western blot. Co-cultivation with MSC promoted the malignant transformation of WRO, inhibited
the RNA-binding protein PTBP1 and activation of GS3Kβ/Akt. In addition, silencing of PTBP1 accelerated cell invason and induced overexpression of EMT proteins, while overexpression of PTBP1 inhibited cell proliferation and migration. In conclusion, BMSCs might promote PTC invasion
and metastasis by inhibiting PTBP1 expression, providing a novel insight into the treatment of PTC.
Regulation of Autophagy and Inflammation Improves the Corneal Injury in the Model of Rats with Xerophthalmia
Authors: Wang Rui , Yuan Jing
Published: May 2022

This study assessed the mechanism of regulation of autophagy and inflammation on corneal injury in the model of rats with xerophthalmia. The level of inducer and inhibitor of autophagy in the model of rats with xerophthalmia was detected and cell proliferation was evaluated by MTT assay
together with analysis of colony formation, cell apoptosis and cycle by FCM. The effect of inducer on the corneal injury and inflammation was assessed. The level of autophagy marker LC3 was elevated significantly after treatment with autophagy inducer along with increased cell proliferation
and migration and strengthened sensibility of corneal epithelial cells on corneal injury and inflammation and autophagy rate. In addition, cells in the established model was blocked at G2/M phase. Moreover, autophagy inducer significantly upregulated MMP-10 expression. Furthermore, there was
a target relationship between LC3 and P62. In conclusion, the cell migration, growth and autophagy is induced with autophagy inducer in the model of rats with xerophthalmia, indicating that autophagy inducer might be a brand-new therapeutic target spot for the treatment of xerophthalmia.
Effect of lncRNA00511 on Non-Small Cell Lung Cancer by Regulating miR-29b-3p
Authors: Li Chunlin , Li Zhenyu , Yi Hua , Liu Zhidong
Published: May 2022

This study assessed the effect of LINC00511 on NSCLC cells through regulating miR-29b-3p/DRAM1 axis. LINC00511 expression in NSCLC tissue and para-carcinoma tissue was analyzed and its correlation with TNM stage was assessed. Lung carcinoma cells as A549 cells were cultivatedin vitroand transfected with LINC00511 siRNA or plasmid with DRAM1 overexpression followed by analysis of LINC00511 and miR-184 expression by RT-PCR, cell proliferation and invasion, Bcl-2, Bax and DRAM1 expression by Western Blot. LINC00511 was significantly upregulated in NSCLC tissue and positively correlated with the TNM staging. However, miR-29b-3p was significantly downregulated in NSCLC tissue. The miR-29b-3p was a target of LINC00511. The DRAM1 was a target of miR-29b-3p. Downregulation of LINC00511 restrained proliferation and invasion of A549 cells and promoted cell apoptosis. The development of NSCLC could be prompted by increasing the presentation of LINC00511 through increasing presentation of DRAM1 and being targeted with miR-29b-3p. It could be restrained through reducing the presentation of LINC00511.
A Computer Aided Breast Cancer Detection Using Unit-Linking Pulse Coupled Neural Network & Multiphase Level Set Method
Authors: Begum A. Sumaiya , Kalaiselvi T. , Rahimunnisa K.
Published: May 2022

Breast cancer is one of the lethal diseases with high mortality rates among women. An early detection and diagnosis of the disease can help increase the survival rate. Distinguishing a normal breast tissue from a cancerous one proves to be ambiguous for a Radiologist. A computer aided
system can help a radiologist in better and efficient diagnosis. This paper aims at detection and classification of benign and malignant mammogram images with Unit-linking Pulse Coupled Neural Network combined with Multiphase level set Method. While Unit linking Pulse Coupled Neural Network
(PCNN) helps in coarse feature extraction, Multi phase Level Set method helps in extracting minute details and hence, better classification. The proposed method is tested with images from MIAS open-source database. Performance of the proposed method is measured using sensitivity, accuracy,
specificity and false positive rate. Experiments show that the proposed method gives satisfactory results when compared to the state-of-art methods. The sensitivity obtained by the proposed method is 95.16%, an accuracy of 96.76%, the False Positive Rate (FPR) is as less as 0.85% and specificity
of 97.12%.
Activating Hypoxia-Inducible Factor-1α Reduces Myocardial Ischemia-Reperfusion Injury in Mice Through Hexokinase II
Authors: Huang Yidan , Wang Jiang , Wu Jianjiang , Gu Tai Wan , Ti Tai Lai , Chen Siyu
Published: May 2022

To verify that HIF-1α/HKII pathway is the key mechanism to alleviate myocardial ischemiareperfusion (IR) injury in aged mice through HIF-1α and HKII inhibitors. A mouse I/R model was carried out in young and old C57BL/6 mice for 60 min and reperfusion for 120
min. Mice were injected intraperitoneally with AAV-9 virus to introduce HIF-1α 24 h before ischemia. After 2 h of reperfusion, the mitochondrial ultrastructure, ATP content, membrane potential, and protein expression of HIF-1α, LC3, Bax, Bcl-2, Caspese-9, Caspase-3,
and Cyt-3 were detected. After 24 h, the myocardial infarction area and cardiac ability were evaluated. Young mice and old mice have different protective effects after acute ischemia/reperfusion injury. After the introduction of HIF-1α by AAV-9 virus, the expression of the downstream
target gene HKII can be up-regulated. At the same time, it reduces the expression of key proteins LC3, Bax, Caspese-9, and Caspase-3. Stabilize the membrane potential, ultimately reduce the area of myocardial infarction and improve heart function. Young mice and old mice have different protective
effects after acute ischemia/reperfusion injury. The I/R in the older is caused by HIF-1α. HIF-1α inhibits the opening of mPTP by up-regulating HKII, stabilizes mitochondrial membrane potential, protects mitochondrial integrity, and reduces myocardial ischemia-reperfusion
damage to the myocardium of elderly mice.
Carrier Mobility Analysis of Parallel Gated Junctionless Field Effect Transistor
Authors: Raibaruah Apurba Kumar , Deva Sarma Kaushik Chandra
Published: May 2022

The paper reports analysis of carrier mobility in a Parallel Gated Junctionless Field Effect Transistor. Fully analytical mathematical models for electron and hole mobilities are developed. The mobility models are developed using empirical relation between mobility and transverse and
longitudinal electric field. The Quantum confinement effect has also been considered in the models. In the model electric field dependence on classical and quantum mechanical effects are formulated separately. The total electric field is the summation of the two. The models are compared with
Technology Computer-Aided Design simulation results. The simulation results show that the parallel gated structure exhibits higher electron as well as hole mobility compared to that of a conventional Junctionless Field Effect Transistor. It can also be seen that the carrier mobility enhances
with longer gap length due to reduced longitudinal electric field. As the models are analytical in nature and agree reasonably with numerical simulation results obtained from TCAD the models are suitable for compact modeling.
Photonic Filter-Free Scheme for D-Band mm-Wave Signal Generation with Frequency 12-Tupling Only via One Integrated In-Phase and Quadrature Modulator
Authors: Wang Dong-Fei , Shan Li-Ting , Wang Lei
Published: May 2022

In this work, we have proposed a new scheme of generating continuously tunable and filter-less D-band millimeter-wave (mm-wave) signal with frequency 12-tupling only via one integrated in-phase and quadrature (I/Q) modulator. The two sub-MZMs in the I/Q modulator, biased at peak point,
are applied to eliminate odd order optical tones. By controlling the phase and amplitude of RF driving signals, I/Q modulator bias point, and the optical phase shifter embed in the lower arm of I/Q modulator, a frequency 12-tupling signal can be obtained through the beat frequency in the photodetector.
Employing 10 GHz RF drive signal, 120 GHz millimeter wave signal can be realized by detailed mathematical formula derivation and simulation, and optical sideband suppression ratio (OSSR) can reach 37.65 dB and radio frequency sideband suppression ratio (RFSSR) can reach 32.08 dB.
Study on the Air-Tightness Detection System for Pipetting in the Automated Aptamer Selection Instrument
Authors: Ji Minjie , Wang Chao , Liu Yuan , Chen Zhu , Chen Hui , Deng Yan , Li Song , Wang Zunliang , Zhang Yuanying , He Nongyue
Published: May 2022

Aptamers are a new kind of nano-probes for bioassays and drug delivery, etc. The good air-tightness is important for pipetting to achieve the purpose of the quantitative liquid distribution in the automated aptamer selection instrument. The pipette tip will be worn and torn after the
long-term use, which may result in the leakage, reduction in liquid volume or even pipetting failure. The goal of this study is to constantly detect whether the gas path in the automated aptamer selection instrument leaks during pipetting. The air-tightness detection system is designed according
to the change of the air pressure when sucking and discharging liquid. In this study, a hardware system was built to detect air pressure in the gas path of the instrument during the pipetting process, and data processing algorithm was designed to judge if the air pressure curve was normal
which included differential processing and detection of extreme points within the threshold. The air-tightness detection model can accurately detect the air-tightness in the pipette during the suction and discharge process to ensure the stable operation of the aptamer selection. This system
can also be used for air-tightness detection of other equipment.
Implementation of Field Programmable Gate Array (FPGA) Based Distributed Arithmetic Gated Current Unit to Achieve High ECG Diagnosis Rate
Authors: Varadharajan Senthil Kumaran , Nallasamy Viswanathan
Published: May 2022

Nowadays, the diagnosis of different dreadful diseases are more important to save human livings by using fast growing Machine Learning and Deep Learning frameworks. Many algorithms such as Convolutional Neural Networks (CNN), Long Short Term Memory (LSTM), and Recurrent Neural networks
(RNN) are playing the pivotal role in the diseases diagnosis particularly in detecting heart arrhythmias. But integrating these networks in the real time hardware remains to be daunting challenge among the researchers since it requires more hardware components and in-efficient methods of solving
the larger datasets. To solve the aforementioned problem, this paper proposes the novel Distributed Arithmetic (DA) based Gated Recurrent Units (GRU) for achieving the better hardware efficiency and high diagnosis rate. GRU is considered to be simplified structure of the LSTM with reduced
computational overhead. The paper also implements the Distributed Arithmetic (DA) operation for implementing the GRU’s hardware components to consume the less energy and delay. The extensive experimentation is carried out using ZYNQ-7000 SoC using hardware and software codesign methodology
and tested with ECG datasets from UCI respiratory and performance boundaries such as accuracy, precision, recall, specificity, F1-score, power, delay and area are calculated and evaluated. Finally the validation and comparative analysis is done for the proposed framework. The outcomes proves
that, the proposed DA based GRU framework provides promising solutions for the disease diagnosis and significantly utilized the resources during the experimentation.
The Influence of the Diurnal Cycle in Wind Shear and Thermodynamics on Squall Lines in the West African Monsoon
Authors: Bickle Megan , Marsham John H. , Griffiths Stephen D. , Ross Andrew N. , Crook Julia
Published: May 2022

The West African monsoon has a clear diurnal cycle in boundary layer properties, synoptic flow, and moist convection. A nocturnal low-level jet (LLJ) brings cool, moist air into the continent and we hypothesize that it may support storms by providing vertical wind shear and a source of moisture. We use idealized simulations to investigate how the mean diurnal cycle in temperature and humidity compared with that of the wind shear impacts on mature squall lines. Thermodynamic diurnal changes dominate those of the winds, although when isolated the LLJ wind is favorable for more intense systems. Bulk characteristics of the storms, including in-cloud upward mass flux and—if precipitation evaporation is accounted for—total surface rain rates, correlate well with the system-relative inflow of convectively unstable air and moisture into the storms. Mean updraft speeds and mean rainfall rates over the storms do not correlate as well with system-relative inflows due to variations in storm morphology such as cold pool intensity. We note that storms tend to move near the speed of the African easterly jet and so maximize the inflow of convectively unstable air. Our results explain the observed diurnal cycle in organized moist convection, with the hours from 1800 to 0000 UTC being the most favorable. Storms are more likely to die after this, despite the LLJ supporting them, with the environment becoming more favorable again by midday.

Significance Statement

Large organized storms dominate rainfall in the West African Sahel, but models struggle to predict them at the correct time of day and the underlying mechanisms that control their timings are not well understood. Using idealized simulations, we show that the temperature and humidity of the late evening are favorable for such storms whereas inflow from the low-level jet supports storms overnight. Storm inflows of available energy and moisture predict upward mass transport and total rainfall rates, whereas the strength of the storm’s cold pool is important for storm structure and intensity. Our results demonstrate how the environmental wind profile (which varies throughout the day) interacts with internal storm dynamics, posing a major challenge to parameterized models.
Observation and Simulation of Low-Level Jet Impacts on 3D Urban Heat Islands in Beijing: A Case Study
Authors: Lin Yi , Wang Chenggang , Yan Jiade , Li Ju , He Songwei
Published: May 2022

In this study, we focused on the impacts of the planetary boundary layer (PBL) low-level jet (LLJ) on the horizontal distribution, vertical development, and 3D structure of urban heat island (UHI). Observational datasets were collected from 224 automatic weather stations (AWSs), and an intensive sounding experiment was conducted in Beijing from 28 August to 2 September 2016. Three-dimensional simulations were operated by the Weather Research and Forecasting (WRF) Model. The results show the following: Ri was smaller than 0.25 at both urban and suburban stations near the surface when the LLJ was present. Through turbulent mixing, the LLJ extended the horizontal distribution of the canopy UHI downwind and increased the total UHI area by approximately 1 × 103 km2. The temperature lapse rate in the urban area was 0.7°C (100 m)−1 with the LLJ, twice that in the absence of an LLJ. The jet enhanced the vertical mixing above the urban area, accompanied by a near-surface TKE up to 0.52 m2 s−2, elevating the vertical UHI development height to 200 m. The LLJ is capable of increasing the temperature of the downwind urban area by a maximum of 8.5°C h−1 through warm advection. The temperature advection in the upper air caused by the LLJ also tilted the 3D UHI structure as a plume. Results reproduced the process by which the LLJ affect the 3D UHI structure through turbulence and advection, and could also provide ideas regarding the influence of the LLJ in other PBL processes.
Comparison between Weather Signal Simulation in Frequency and Time Domain
Authors: Ivić Igor R.
Published: May 2022

Simulated weather time series are often used in engineering and research practice to assess radar systems behavior and/or to evaluate the performance of novel techniques. There are two main approaches to simulating weather time series. One is based on summing individual returns from a large number of distributed weather particles to create a cumulative return. The other is aimed at creating simulated random signals based on the predetermined values of radar observables and is of interest herein. So far, several methods to simulate weather time series, using the latter approach, have been proposed. All of these methods are based on applying the inverse discrete Fourier transform to the spectral model with added random fluctuations. To meet the desired simulation accuracy, such an approach typically requires generating the number of samples that is larger than the base sample number due to the discrete Fourier transform properties. In that regard, a novel method to determine simulation length is proposed. It is based on a detailed theoretical development that demonstrates the exact source of errors incurred by this approach. Furthermore, a simple method for time series simulation that is based on the autocorrelation matrix exists. This method neither involves manipulations in the spectral domain nor requires generating the number of samples larger than the base sample number. Herein, this method is suggested for weather time series simulation and its accuracy and efficiency are analyzed and compared to the spectral-based approach.

Significance Statement

All research articles published so far on the topic of weather time series simulation propose the use of inverse discrete Fourier transform (IDFT) when based on the desired Doppler moment values. Herein, a detailed theoretical development that demonstrates the exact source of errors incurred by this approach is presented. Also, a novel method to determine the simulation length that is based on the theoretical error computation is proposed. As an alternative, a computationally efficient general method (not using IDFT) previously developed for the simulation of sequences with desired properties is suggested for weather time series simulation. It is demonstrated that the latter method produces accurate results within overall shorter computational times. Moreover, it is shown that the use of graphics processing unit (GPU), ubiquitous in modern computers, significantly reduces computational times compared to the sole use of central processing unit (CPU) for all simulation-related calculations.
THE ANTIBODY-DRUG CONJUGATE LONCASTUXIMAB TESIRINE FOR THE TREATMENT OF DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Calabretta Eleonora , Hamadani Mehdi , Carlo-Stella Carmelo
Published: May 2022

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous subtype of non-Hodgkin lymphoma. Relapsed/refractory disease represents remains an unmet medical need, despite the introduction of novel cellular and targeted therapies. Loncastuximab tesirine is a CD19-targeting antibody-drug conjugate approved by the US Food and Drug Administration for relapsed DLBCL after two lines of systemic therapy based on a trial showing a 48.3% overall response rate. The spectrum of its clinical applications is expanding and is now being tested in other B-cell malignancies.
Daratumumab in first-line therapy is cost-effective in transplant-eligible patients with newly diagnosed myeloma
Authors: Yamamoto Chihiro , Minakata Daisuke , Koyama Shunsuke , Sekiguchi Kaoru , Fukui Yuta , Murahashi Rui , Nakashima Hirotomo , Matsuoka Sae , Ikeda Takashi , Kawaguchi Shin-ichiro , Toda Yumiko , Ito Shoko , Nagayama Takashi , Umino Kento , Nakano Hirofumi , Morita Kaoru , Yamasaki Ryoko , Ashizawa Masahiro , Ueda Masuzu , Hatano Kaoru , Sato Kazuya , Ohmine Ken , Fujiwara Shin-ichiro , Kanda Yoshinobu
Published: May 2022

Triplet regimens, such as lenalidomide, bortezomib, and dexamethasone (RVd) or thalidomide, bortezomib, and dexamethasone (VTd), are standard induction therapies for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab to RVd and VTd has been investigated in the GRIFFIN and CASSIOPEIA trials, respectively, resulting in improvement in the rate of minimal residual disease (MRD) negativity. In this study, we conducted a cost-effectiveness analysis with a 10-year time horizon to compare first-line and second-line use of daratumumab for transplant-eligible patients with NDMM. Because long-term follow-up data for these clinical trials are not yet available, we developed a Markov model that uses MRD status to predict progression-free survival. Daratumumab was used either in the first-line setting in combination with RVd or VTd or in the second-line setting with carfilzomib plus dexamethasone (Kd). Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were calculated from a Japanese and US payer perspective. In the Japanese analysis, D-RVd showed higher QALYs (5.43 vs 5.18) and lower costs (¥64 479,793 vs ¥71  287 569) compared with RVd, and D-VTd showed higher QALYs (5.67 vs 5.42) and lower costs (¥43  600 310 vs ¥49 471,941) compared with VTd. Similarly, the US analysis demonstrated dominance of a strategy incorporating daratumumab in first-line treatment regimens. Given that overall costs are reduced and outcomes are improved when daratumumab is used as part of a first-line regimen, the economic analysis indicates that addition of daratumumab to first-line RVd and VTd regimens is a dominant strategy compared with reserving its use for the second-line setting.
Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia
Authors: Moskop Amy , Pommert Lauren , Baggott Christina , Prabhu Snehit , Pacenta Holly L. , Phillips Christine L. , Rossoff Jenna , Stefanski Heather E. , Talano Julie-An , Margossian Steve P. , Verneris Michael R. , Myers G. Doug , Karras Nicole A. , Brown Patrick A. , Qayed Muna , Hermiston Michelle L. , Satwani Prakash , Krupski Christa , Keating Amy K. , Wilcox Rachel , Rabik Cara A. , Fabrizio Vanessa A. , Chinnabhandar Vasant , Goksenin A. Yasemin , Curran Kevin J. , Mackall Crystal L. , Laetsch Theodore W. , Guest Erin M. , Breese Erin H. , Schultz Liora M.
Published: May 2022

Infants with B-cell acute lymphoblastic leukemia (B-ALL) have poor outcomes because of chemotherapy resistance leading to high relapse rates. Tisagenlecleucel, a CD19-directed chimeric antigen receptor T-cell (CART) therapy, is US Food and Drug Administration approved for relapsed or refractory B-ALL in patients ≤25 years; however, the safety and efficacy of this therapy in young patients is largely unknown because children <3 years of age were excluded from licensing studies. We retrospectively evaluated data from the Pediatric Real-World CAR Consortium to examine outcomes of patients with infant B-ALL who received tisagenlecleucel between 2017 and 2020 (n = 14). Sixty-four percent of patients (n = 9) achieved minimal residual disease-negative remission after CART and 50% of patients remain in remission at last follow-up. All patients with high disease burden at time of CART infusion (>M1 marrow) were refractory to this therapy (n = 5). Overall, tisagenlecleucel was tolerable in this population, with only 3 patients experiencing ≥grade 3 cytokine release syndrome. No neurotoxicity was reported. This is the largest report of tisagenlecleucel use in infant B-ALL and shows that this therapy is safe and can be effective in this population. Incorporating this novel immunotherapy into the treatment of infant B-ALL offers a promising therapy for a highly aggressive leukemia.
Relative hypercoagulation induced by suppressed fibrinolysis after tisagenlecleucel infusion in malignant lymphoma
Authors: Yamasaki-Morita Makiko , Arai Yasuyuki , Ishihara Takashi , Onishi Tomoko , Shimo Hanako , Nakanishi Kayoko , Nishiyama Yukiko , Jo Tomoyasu , Hiramatsu Hidefumi , Mitsuyoshi Takaya , Mizumoto Chisaki , Kanda Junya , Nishikori Momoko , Kitawaki Toshio , Nogami Keiji , Takaori-Kondo Akifumi , Nagao Miki , Adachi Souichi
Published: May 2022

Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has facilitated progress in treatment of refractory/relapsed diffuse large B-cell lymphoma (DLBCL). A well-known adverse event after CAR-T therapy is cytokine release syndrome(CRS). However, the etiology and pathophysiology of CRS-related coagulopathy remain unknown. Therefore, we conducted a prospective cohort study to comprehensively analyze coagulation/ fibrinolysis parameters present in peripheral blood of adult DLBCL patients treated with tisagenlecleucel in a single institution. Samples were collected from 25 patients at 3 time points: before lymphocyte-depletion chemotherapy and on days 3 and 13 after CAR-T infusion. After infusion, all patients except 1 experienced CRS, and 13 required the administration of tocilizumab. A significant elevation in the plasma level of total plasminogen activator inhibitor 1 (PAI-1), which promotes the initial step of coagulopathy (mean, 22.5 ng/mL before lymphocyte-depletion and 41.0 on day 3, P = .02), was observed at the onset of CRS. Moreover, this suppressed fibrinolysis-induced relatively hypercoagulable state was gradually resolved after CRS remission with normalization of total PAI-1 to preinfusion levels without any organ damage (mean values of soluble fibrin: 3.16 µg/mL at baseline, 8.04 on day 3, and 9.16 on day 13, P < .01; and mean PAI-1: 25.1 ng/mL on day 13). In conclusion, a hypofibrinolytic and relatively hypercoagulable state concomitant with significant total PAI-1 elevation was observed at the onset of CRS even in DLBCL patients with mild CRS. Our results will facilitate understanding of CRS-related coagulopathy, and they emphasize the importance of monitoring sequential coagulation/fibrinolysis parameters during CAR-T therapy.