bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological evaluation following development of new and persistent left bundle branch block after transcatheter aortic valve replacement: A single center pilot study
Authors: Patel Hiren , Tsai Christina , Atallah Issam , Ahmad Ali , Bedi Rohil , Golemi Lolita , Mikhail Salwa , Karickal Jissmaria , Azrak Elie , Bishara Sam , Harjai Kishore , Bauer Christopher , Hussein Ahmed , Gopinathannair Rakesh , Mar Philip L
Published: July 2023

Introduction

New and persistent left bundle branch block (NP‐LBBB) following Transcatheter Aortic Valve Replacement (TAVR) is an ongoing concern with incidence ranging from as low as 4% to up to 65% (varying for different types of valves). Such patients are at risk of developing high‐grade atrioventricular block (HAVB) warranting permanent pacemaker (PPM) implantation. However, currently, there are no consensus guidelines or large prospective studies to risk stratify these patients for safer discharge after TAVR.

Objectives

To provide insight from a single center study on using modified electrophysiology (EP) study to risk stratify post‐TAVR patients to outpatient monitoring for low‐risk versus pacemaker implantation for high‐risk patients.

Methods and Results

Between June 2020 and March 2023, all patients who underwent a TAVR procedure (324 patients) at our institution were screened for development of NP‐LBBB post‐operatively. Out of 26 patients who developed NP‐LBBB, after a pre‐specified period of observation, 18 patients were deemed eligible for a modified EP study to assess His‐Ventricular (HV) interval. 11 out of 18 patients (61.1%) had normal HV interval (HV < 55 ms). Three out of 18 patients (16.7%) had HV prolongation (55 ms < HV < 70 ms) without significant HV prolongation (defined as an increase in HV interval > 30%) with intra‐procedural procainamide challenge. Four out of 18 patients (22.2%) had significant HV prolongation (HV > 70 ms) warranting PPM implantation based on a multidisciplinary approach and shared decision‐making with the patients. Total of 50% of patients discharged with PPM (two out of four patients) were noted to be pacemaker dependent based on serial device interrogations. All patients who did not receive PPM were discharged with ambulatory monitoring with 30‐day event monitor and did not develop HAVB on serial follow‐up.

Conclusion

Normal HV interval up to 55 ms on modified EP study after TAVR and development of NP‐LBBB can be utilized as a threshold for risk stratification to facilitate safe discharge. The optimal upper limit of HV interval threshold remains unclear in determining appropriate candidacy for PPM.
Closed system production of serum eye drops using dockable saline
Authors: Kirwan Susy , Kwan Patrick S. L. , So Ronald , Tuinukuafe Alice
Published: July 2023

Background and Objectives

A fully closed system solution to manufacture serum eye drops using diluted serum has remained elusive, necessitating production steps to mitigate bacterial contamination risks in a clean suite environment, hampering production efficiency amid growing demand. We describe our recent implementation of a fully closed manufacturing process at New Zealand Blood Service.

Materials and Methods

A dockable format for sterile saline manufactured to custom specifications configured with a 15‐cm tubing to enable sterile connections was sourced from a local pharmaceutical manufacturer.

Results

From a total of 30,168 eye drop vials manufactured since implementation, the average production time was reduced by up to 45% performed in the general laboratory environment, attributed to eliminating processes performed in a clean suite. No bacterial contamination was observed, demonstrating robust sterile connections.

Conclusion

Dockable saline takes serum eye drops manufactured from a functionally closed system to a fully closed system, thereby enhancing patient safety, significantly reducing manufacturing time and cost and transforming production from a highly restrictive process into a portable workflow that is simple, practical and effective.
Intrafusal cross‐bridge dynamics shape history‐dependent muscle spindle responses to stretch
Authors: Simha Surabhi N. , Ting Lena H.
Published: July 2023

Computational models can be critical to linking complex properties of muscle spindle organs to the sensory information that they encode during behaviours such as postural sway and locomotion where few muscle spindle recordings exist. Here, we augment a biophysical muscle spindle model to predict the muscle spindle sensory signal. Muscle spindles comprise several intrafusal muscle fibres with varied myosin expression and are innervated by sensory neurons that fire during muscle stretch. We demonstrate how cross‐bridge dynamics from thick and thin filament interactions affect the sensory receptor potential at the spike initiating region. Equivalent to the Ia afferent's instantaneous firing rate, the receptor potential is modelled as a linear sum of the force and rate change of force (yank) of a dynamic bag1 fibre and the force of a static bag2/chain fibre. We show the importance of inter‐filament interactions in (i) generating large changes in force at stretch onset that drive initial bursts and (ii) faster recovery of bag fibre force and receptor potential following a shortening. We show how myosin attachment and detachment rates qualitatively alter the receptor potential. Finally, we show the effect of faster recovery of receptor potential on cyclic stretch–shorten cycles. Specifically, the model predicts history‐dependence in muscle spindle receptor potentials as a function of inter‐stretch interval (ISI), pre‐stretch amplitude and the amplitude of sinusoidal stretches. This model provides a computational platform for predicting muscle spindle response in behaviourally relevant stretches and can link myosin expression seen in healthy and diseased intrafusal muscle fibres to muscle spindle function.
Failure Analysis of Once-Through Steam Generator (OTSG) Tube
Authors: Tina Wahida , Donaldson Elizabeth , Dickinson Thomas E. , Schmidt William Hal
Published: July 2023

The once-through steam generator (OTSG) produces superheated steam using purified feed water. The plant-specific water quality, steam quality, high temperature, and pressure operations lead to the leakage of the OTSG tubes with economic, safety, and environmental consequences. Tube leakage is one of the most frequent causes of OTSG tube failure. A leaking tube was discovered within the OTSG unit of the 110 MW cogeneration plant. The failed section of the tube was removed from the steam generator. Several metallurgical examinations of this tube segment were performed to identify the failure mode and cause. A portion of the tube was analyzed using optical emission spectroscopy (OES) to determine the alloy composition. The results confirmed that the tubing was fabricated from a material consistent with chemical specifications for ASME Specification SB 407 Inconel Alloy 800 (UNS N08800). Glass bead blasting was used to determine the deposit-weight-density (DWD). The DWD value was a maximum of 5.1 g/ft2. The maximum internal deposit thickness was 0.002 in. No evidence of overheating was observed. Scanning electron microscope-energy-dispersive x-ray analysis (SEM-EDXA) was used to determine the elemental composition of the internal deposits. The results indicated that the internal gray deposits primarily comprised iron, chromium, and nickel compounds. There were also fewer amounts of sodium, silicon, aluminum, potassium, and calcium species. The subject tube failure involved a through-wall crack that occurred as stress corrosion cracking (SCC). Additions of caustic solution used in OTSG water treatment practices potentially induced corrosive substances into the tube.
Thermodynamic and Thermo-Economic Analysis of a Solar-Integrated Double-Turbine Kalina Cycle for Varying Solar Flux Conditions
Authors: Parvathy S. Devi , Varghese James
Published: July 2023

Kalina cycle is established as a reliable low-grade energy cycle working on solar, geothermal, and other waste heat recovery sources. This work aims to develop a novel methodology for optimizing a Kalina cycle according to the solar irradiation. A comprehensive analysis of performance is conducted by varying the parameters of the Kalina system, modeled with high- and low-pressure turbines. The present work implements and analyzes the performance of a multi turbine Kalina cycle with cylindrical parabolic collectors for energy input at different time, on a particular day, for a location. The proposed cycle is modeled to simulate the working. The dependency of parameters—separator pressure, concentration of ammonia in boiler, intermediate separator temperature and vapor fraction at condenser side turbine exit—on the system performance is investigated. Optimization is conducted using genetic algorithm with net power as objective function for different solar irradiations. The optimized power values are 282.62, 246.75, 222.31, and 180.0 kW for solar influxes 507.7, 461.8, 413.9, and 321.0 W/m2 respectively. The results show that the proposed model can be adopted for better performance. A thermo-economic analysis of an optimized output is conducted to conclude on capital investment and operation cost for sustainable power production. The analysis yields highest cost rate of exergy destruction of 58936.41$/year for the boiler. The investment cost of the turbines together is 89% of the total capital investment, and hence, thermo-economic factor is highest for these components.
Accuracy of Expired BinaxNOW Rapid Antigen Tests
Authors: Vaeth Mary Jane E. , Abdullah Omar , Cheema Minahil , Sun Kristie , Elhabashy Maryam , Mitchell Asia , Foyez Maisha , Talla Mahita , Cheema Aamna , Locke Charles , Kantsiper Melinda , Pekosz Andrew , Mostafa Heba H. , Siddiqui Zishan K.
Published: July 2023

The study examining the reliability of expired antigen testing kits in the context of COVID-19 has significant real-world implications. By demonstrating that these expired kits retain their sensitivity in detecting the virus, this work provides evidence that expired kits can still be utilized, reducing waste and optimizing resources in health care systems.
Higher habitual lying time is inversely associated with vagal-related heart rate variability outcomes in younger adults
Authors: O'Brien Myles W. , Schwartz Beverly D. , Shivgulam Madeline E. , Daley W. Seth , Frayne Ryan J. , Kimmerly Derek S.
Published: July 2023

Heart rate variability (HRV) is a well-established noninvasive marker of autonomic cardiac control. We test whether time spent sitting (negatively) versus lying (positively) influences vagal HRV outcomes. HRV (10 min supine electrocardiogram) and free-living postures (dual-accelerometer configuration, 7 days) were measured in 31 young healthy adults (15♀, age: 23 ± 3 years). Habitual lying (66 ± 61 min/day), but not sitting time (558 ± 109 min/day), total sedentary time (623 ± 132 min/day), nor step counts (10 752 ± 3200 steps/day; all, p > 0.090), was associated with root mean square of successive cardiac interval differences (ρ = −0.409, p = 0.022) and normalized high-frequency HRV (ρ = −0.361, p = 0.046). These findings document a paradoxical negative impact of waking lying time on cardioautonomic function.

 

Take home message

Using a multi-accelerometer configuration, we demonstrated that more habitual waking time lying, but not sitting or total sedentary time, was associated with worse vagally mediated cardiac control.
Linear and nonlinear mechanical responses of cell monolayers under crowding
Authors: Guan Qing-Ling , Dong Li-Quan , Hao Qun
Published: July 2023

Epithelial monolayers play an important role in a broad range of physiological and pathological processes, such as embryonic development and wound healing. Epithelial monolayers become crowded during cell proliferation and growth, however, their mechanical properties entities remain obscure. This paper presents a novel and efficient method utilizing the structural stiffness matrix-based computational method (SMM) to investigate the mechanical characteristics of an epithelial monolayer as it undergoes varying degrees of crowding. Both D1-type extrusion, representing the extrusion of live cells, and D2-type extrusion, describing the extrusion of apoptotic cells, are examined. Our simulations reveal that the epithelial monolayer exhibits linear elastic behavior under slight crowding and nonlinear elastic behavior in response to overcrowding. These mechanical properties are significantly influenced by the strength of cellular cytoskeleton and the mode of cell extrusion. Moreover, our analysis indicates that the linear deformation of these monolayers is predominantly born by the variation in cell orientation, while the nonlinear deformation originates from the existence of the microtubules. This study further deepens our understanding of the relationship between the mechanical properties of cytoskeleton, individual cells and their monolayers, and may shed light on linking cell behavior to the patterning and morphogenesis of tissues.
Long-range entanglement between spin qubits in quantum dots by virtual photon process
Authors: Hu Ye-Bin , Chen Rong , Yan Guo-Qing , Zhu Xing-Yu
Published: July 2023

Electron spin qubits in silicon quantum dots are an attractive candidate for large-scalable quantum computation. An essential step for quantum information processing based on spin qubits is to realize the spatially separated two-qubit gate and entanglement with high fidelity. Here, we consider two spin qubits coupled to a common superconducting resonator in circuit quantum electrodynamics. We investigate the long-range two-qubit iSWAP gate mediated by virtual microwave photons using a Gaussian smoothing pulse. We show that the entangling gate fidelity can reach [Formula: see text] under realistic experimental conditions and analyze the factors limiting gate fidelity. Moreover, we numerically demonstrate the generation of remote Bell entangled states of spin qubits with high fidelity. In addition, this spin–resonator architecture can be used to implement quantum algorithms using our scheme. These results pave the way for quantum information processing with spin qubits.
Tuning structural and electronic properties of single wall AlN nanotubes
Authors: Hosseini Razieh , Movlarooy Tayebeh , Vatankhahan Adeleh
Published: July 2023

The electronic and structural characteristics of the armchair and zigzag single-walled AlN nanotubes (SWAlNNTs) have been considered by using density functional theory (DFT). The effects of tube diameter on the Al–N bond length, the buckling separation, tube lengths, valence band maximum (VBM), conduction band minimum (CBM), Fermi energy, strain energy, and bandgap have been studied. The strain energy calculation revealed that higher-diameter nanotubes are more stable than those with smaller diameters consequently at the same chirality armchair AlNNTs are more stable than zigzag types. It revealed a correlation between the bandgap and buckling: the smaller the bandgap, the higher the buckling, and the buckling separation increases by decreasing tube diameter. The 2p-orbitals of Al and N atoms have the most contribution to CBM and VBM, respectively. All zigzag and armchair AlNNTs are semiconductors having direct and indirect bandgap, respectively. It is also found that for both zigzag and armchair AlNNTs, with increasing nanotube diameter, the bandgap increased. The conclusions of this study can definitely be useful in future experimental works on optoelectronic devices.
Modular structural elements incorporating decommissioned flexible flowlines and geopolymer concrete
Authors: Aslani Farhad , Zhang Yifan , Valizadeh Afsaneh , Philip Lendyn
Published: July 2023

This study proposes the design of modular structural geopolymer concrete elements incorporating decommissioned flexible flowlines. To evaluate and assess the feasibility of the proposed modular structural elements, this study aims to investigate its feasibility from the perspectives of sustainability including cost analysis, circular economy (CE) analysis and CO2 emission estimate. Moreover, a series of numerical analyses using finite element modelling (FEM) is conducted to provide insight into the mechanical behaviour of such modular columns and beams. Apart from the cost-saving, CE and social impact benefits of the proposed elements, the results indicate that modular structural elements incorporating flowline have shown very high axial, shear and flexural capacities, which make them suitable to be used in high-rising buildings, bridges, etc. The proposed elements can be a solution to decommission and reuse the flexible flowline on a large scale in construction.
Modulation of red blood cell nitric oxide synthase phosphorylation in the quiescent and exercising human forearm
Authors: Leo Jeffrey A. , Sabapathy Surendran , Kuck Lennart , Simmonds Michael J.
Published: July 2023

In vitro investigations demonstrate that human erythrocytes synthesize nitric oxide via a functional isoform of endothelial nitric oxide synthase (NOS) (RBC-NOS). We tested the hypothesis that phosphorylation of RBC-NOS at serine residue 1177 (RBC-NOS1177) would be amplified in blood draining-active skeletal muscle. Furthermore, given hypoxemia modulates local blood flow and thus shear stress, and nitric oxide availability, we performed duplicate experiments under normoxia and hypoxia. Nine healthy volunteers performed rhythmic handgrip exercise at 60% of individualized maximal workload for 3.5 min while breathing room air (normoxia) and after being titrated to an arterial oxygen saturation ≈80% (hypoxemia). We measured brachial artery blood flow by high-resolution duplex ultrasound, while continuously monitoring vascular conductance and mean arterial pressure using finger photoplethysmography. Blood was sampled during the final 30 s of each stage from an indwelling cannula. Blood viscosity was measured to facilitate calculation of accurate shear stresses. Erythrocytes were assessed for levels of phosphorylated RBC-NOS1177 and cellular deformability from blood collected at rest and during exercise. Forearm exercise increased blood flow, vascular conductance, and vascular shear stress, which coincided with a 2.7 ± 0.6-fold increase in RBC-NOS1177 phosphorylation ( P < 0.0001) and increased cellular deformability ( P < 0.0001) under normoxia. When compared with normoxia, hypoxemia elevated vascular conductance and shear stress ( P < 0.05) at rest, while cellular deformability ( P < 0.01) and RBC-NOS1177 phosphorylation ( P < 0.01) increased. Hypoxemic exercise elicited further increases in vascular conductance, shear stress, and cell deformability ( P < 0.0001), although a subject-specific response in RBC-NOS1177 phosphorylation was observed. Our data yield novel insights into the manner that hemodynamic force and oxygen tension modulate RBC-NOS in vivo.
Using an Efficient Detection Method to Prevent Personal Data Leakage for Web-Based Smart City Platforms
Authors: Chiu Chih-Chieh , Tsai Pang-Wei , Yang Chu-Sing
Published: July 2023

Many Internet of Things and information exchange technologies bring convenience, cost-efficiency, and sustainability to smart city solutions. These changes have improved our day-to-day quality of life, with impacts on: (a) lifestyle (e.g., automation and robotic reaction), (b) infrastructure (efficient energy consumption), and (c) data-driven management (data sensing, collection, and investigation). It is common to integrate Web-based interfaces and such solutions for developing platforms. When software and hardware components store, retrieve, and transfer such information, people may suffer from personal data leakage. This paper introduces a privacy information detection method, using a data weighting mechanism to save time and cost in finding personal information leaks over Web services. According to an initial evaluation, the proposed method can reduce time by 62.19% when processing 8,000 crawled files, and roll-back verification shows that it maintains 90.08% accuracy for finding marked content.
A Reduced Order Model Based on ANN-POD Algorithm for Steady-State Neutronics and Thermal-Hydraulics Coupling Problem
Authors: Liu Hanxing , Zhang Han
Published: July 2023

The neutronics and thermal-hydraulics (N/TH) coupling behavior analysis is a key issue for nuclear power plant design and safety analysis. Due to the high-dimensional partial differential equations (PDEs) derived from the N/TH system, it is usually time consuming to solve such a large-scale nonlinear equation by the traditional numerical solution method of PDEs. To solve this problem, this work develops a reduced order model based on the proper orthogonal decomposition (POD) and artificial neural networks (ANNs) to simulate the N/TH coupling system. In detail, the POD method is used to extract the POD modes and corresponding coefficients from a set of full-order model results under different boundary conditions. Then, the backpropagation neural network (BPNN) is utilized to map the relationship between the boundary conditions and POD coefficients. Therefore, the physical fields under the new boundary conditions could be calculated by the predicated POD coefficients from ANN and POD modes from snapshot. In order to assess the performance of an ANN-POD-based reduced order method, a simplified pressurized water reactor model under different inlet coolant temperatures and inlet coolant velocities is utilized. The results show that the new reduced order model can accurately predict the distribution of the physical fields, as well as the effective multiplication factor in the N/TH coupling nuclear system, whose relative errors are within 1%.
Beyond Neoantigens: Antigens Derived from Tumor Drivers as Cancer Vaccine Targets
Authors: Crosby Erika J. , Hartman Zachary C. , Lyerly H. Kim
Published: July 2023

A vaccine targeting HER2, a nonmutated but overexpressed tumor antigen, readily primed T cells for ex vivo expansion and adoptive transfer with minimal toxicity. This regimen led to intramolecular epitope spreading in a majority of patients and offers a treatment modality that may improve outcomes for patients with metastatic breast cancer expressing HER2.

See related article by Disis et al., p. 3362
Supplementary Table 1 from The MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study
Authors: LoRusso Patricia , Yamamoto Noboru , Patel Manish R. , Laurie Scott A. , Bauer Todd M. , Geng Junxian , Davenport Teffany , Teufel Michael , Li Jian , Lahmar Mehdi , Gounder Mrinal M.
Published: July 2023

Study representativeness table
Supplementary Figure 1 from The MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study
Authors: LoRusso Patricia , Yamamoto Noboru , Patel Manish R. , Laurie Scott A. , Bauer Todd M. , Geng Junxian , Davenport Teffany , Teufel Michael , Li Jian , Lahmar Mehdi , Gounder Mrinal M.
Published: July 2023

GDF-15 fold change from baseline for dose-escalation cohorts receiving BI 907828 D1q3wand BI 907828 D1D8q4w
Supplemental Table 2 from Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies
Authors: Zhu Iowis , Piraner Dan I. , Roybal Kole T.
Published: July 2023

Functional synNotch circuits.
Supplemental Table 1 from Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies
Authors: Zhu Iowis , Piraner Dan I. , Roybal Kole T.
Published: July 2023

Summary of chimeric immune receptors designed to incorporate multiple intracellular signaling domains distributed among discrete polypeptide chains.
Supplementary Figure Legends from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: July 2023

Supplementary Figure Legends
Figure S5 from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: July 2023

Disruption of WNT gradient in normal intestinal villi reduces gamma delta T cells
Figure S4 from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: July 2023

Correlation between gut-specific transcription factors, gamma delta T cell density and BTNL genes in human tumors
Figure S3 from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: July 2023

Knockdown of Cdx1, Cdx2 and Hnf4a fails to influence organoid morphology or expression of Btnl genes
Figure S1 from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B.
Published: July 2023

WNT expression is independent of BTN3A1 and BTN2A1
Data from Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies
Authors: Zhu Iowis , Piraner Dan I. , Roybal Kole T.
Published: July 2023

Abstract
The immune system includes an array of specialized cells that keep us healthy by responding to pathogenic cues. Investigations into the mechanisms behind immune cell behavior have led to the development of powerful immunotherapies, including chimeric-antigen receptor (CAR) T cells. Although CAR T cells have demonstrated efficacy in treating blood cancers, issues regarding their safety and potency have hindered the use of immunotherapies in a wider spectrum of diseases. Efforts to integrate developments in synthetic biology into immunotherapy have led to several advancements with the potential to expand the range of treatable diseases, fine-tune the desired immune response, and improve therapeutic cell potency. Here, we examine current synthetic biology advances that aim to improve on existing technologies and discuss the promise of the next generation of engineered immune cell therapies.
Supplementary Figure S8 from Immunologic assessment of tumors from a race-matched military cohort identifies mast cell depletion as a marker of prostate cancer progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y , Song Yingjie , Sesterhenn Isabell A , Chesnut Gregory T , Tan Shyh-Han
Published: July 2023

Supplementary Figure S8 shows non-significant relative cell type scores by Dx Age Group.
Supplementary Figure S11 from Immunologic assessment of tumors from a race-matched military cohort identifies mast cell depletion as a marker of prostate cancer progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y , Song Yingjie , Sesterhenn Isabell A , Chesnut Gregory T , Tan Shyh-Han
Published: July 2023

Supplementary Figure S11 shows BCR-free and Metastasis-free survival for cell types dichotomized by median cutoffs.
Supplementary Figure S10 from Immunologic assessment of tumors from a race-matched military cohort identifies mast cell depletion as a marker of prostate cancer progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y , Song Yingjie , Sesterhenn Isabell A , Chesnut Gregory T , Tan Shyh-Han
Published: July 2023

Supplementary Figure S10 shows BCR-free and Metastasis-free survival for top differentially expressed genes in AA tumors dichotomized by median cutoffs.
Supplementary Table 3 from Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib
Authors: Ida Hanae , Shimizu Toshio , Nishino Makoto , Nakamura Yoshiaki , Yazaki Shu , Katsuya Yuki , Sato Jun , Koyama Takafumi , Iwasa Satoru , Sudo Kazuki , Kondo Shunsuke , Yonemori Kan , Shitara Kohei , Shiono Satoshi , Matsuoka Daiko , Yasuda Keisuke , Otake Yohei , Suzuki Takuya , Takase Takao , Takashima Shuya , Yamaguchi Kohei , Semba Taro , Yamamoto Noboru
Published: July 2023

Supplementary Table 3. Safety Summary by E7389-LF Dose
Supplementary Figure 3 from Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib
Authors: Ida Hanae , Shimizu Toshio , Nishino Makoto , Nakamura Yoshiaki , Yazaki Shu , Katsuya Yuki , Sato Jun , Koyama Takafumi , Iwasa Satoru , Sudo Kazuki , Kondo Shunsuke , Yonemori Kan , Shitara Kohei , Shiono Satoshi , Matsuoka Daiko , Yasuda Keisuke , Otake Yohei , Suzuki Takuya , Takase Takao , Takashima Shuya , Yamaguchi Kohei , Semba Taro , Yamamoto Noboru
Published: July 2023

S3. Imaging of 2 Patients with Cholangiocarcinoma During Treatment.
FIGURE 2 from Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib
Authors: Ida Hanae , Shimizu Toshio , Nishino Makoto , Nakamura Yoshiaki , Yazaki Shu , Katsuya Yuki , Sato Jun , Koyama Takafumi , Iwasa Satoru , Sudo Kazuki , Kondo Shunsuke , Yonemori Kan , Shitara Kohei , Shiono Satoshi , Matsuoka Daiko , Yasuda Keisuke , Otake Yohei , Suzuki Takuya , Takase Takao , Takashima Shuya , Yamaguchi Kohei , Semba Taro , Yamamoto Noboru
Published: July 2023

Percentage changes from baseline in sums of target lesion diameters over time per RECIST v1.1 by investigator assessment. Tumor types of patients with at least a 30% reduction at any timepoint are listed. aPlus nivolumab 360 mg every 3 weeks; bplus nivolumab 240 mg every 2 weeks. Q#W, every # weeks; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1.
Data from Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y. , Song Yingjie , Sesterhenn Isabell A. , Chesnut Gregory T. , Tan Shyh-Han
Published: July 2023

Elucidating the cellular immune components underlying aggressive prostate cancer, especially among African American (AA) men who are disproportionately affected by this disease compared with Caucasian American (CA) men, will support more inclusive precision medicine treatment strategies. We aimed to evaluate which immune-related genes and cell types are differentially expressed in AA tumors and how immunobiology impacts prostate cancer progression.

We purified nucleic acid from tumor biopsies, obtained following radical prostatectomy, from 51 patients (AA = 26, CA = 25). Gene expression was measured using the NanoString platform from which we estimated immune cell abundances and assessed differences between groups based on clinicopathologic data. Product-limit estimates determined associations with biochemical recurrence (BCR)-free and metastasis-free survival.

DVL2 and KLRC2 were significantly upregulated in CA tumors and were also associated with worse disease progression. No significant differences in immune cell abundances by race were observed. Highly significant reductions in abundances of mast cells versus tumor-infiltrating lymphocytes (TIL) were found in men with high-grade pathologies and in men who later developed metastases. Low ratios of mast cells versus TILs were associated with worse BCR-free survival and metastasis-free survival.

Although estimated immune cell abundances were not different by race, we identified genes involved in metabolism and natural killer cell functions that were differentially expressed between AA and CA tumors. Among the entire cohort, depletion of mast cells within prostatectomy tumors was characteristic of advanced disease and susceptibility to disease progression.
Significance:
Our findings demonstrate that there are immune-related genes and pathways that differ by race. Impaired intratumoral cellular immune composition, especially for TIL-normalized mast cells, may be vital in predicting and contributing to prostate cancer disease progression.
A Mild Skeletal Dysplasia Caused by a Biallelic Missense Variant in the SLC35D1 Gene
Authors: Esen Tuna Eren , Uzun Özlem Ünal , Ceylan Ahmet Cevdet
Published: July 2023

Introduction: Biallelic variants in the SCL35D1 gene have been originally associated with a severe skeletal dysplasia called “Schneckenbecken dysplasia” because of the resemblance of the pelvic shape to a snail. More recently, SLC35D1 variants have been associated with much milder phenotypes of skeletal dysplasia. Our report describes one such individual with a novel SLC35D1 variant. Case Presentation: A 17-year-old male with a coarse face and short stature was referred to our clinic. On his radiographic imaging, shortness of the long bones and metaphyseal flaring were detected. Using a clinical exome panel, we discovered a novel homozygous missense variant in the SLC35D1 gene, c.899G>T (p.Gly300Val). Conclusions: We identified a biallelic variant that was causative for a mild skeletal dysplasia and showed its phenotypic effects. Our observation confirms the existence of nonlethal skeletal dysplasias associated with biallelic SLC35D1 variants and suggests the existence of a phenotypic spectrum.
CETICISMO ACADÊMICO NAS "RÈGLES POUR LA DIRECTION DE L'ESPRIT (I, II, III, IV) DE DESCARTES
Authors: Oliveira Marcelo de
Published: July 2023

O ceticismo acadêmico se encontra utilizado na formulação dos preceitos epistêmicos para a reformulação da ciência, nas Règles Pour La Direction De L’Esprit (1701, Amsterdam, texto póstumo e inacabado). O probabilismo de Carnéades, compreendido como o principal vetor do ceticismo acadêmico na modernidade, fundamenta a certeza. Outras teses para a correção epistêmica do espírito parecem advir da tradição acadêmica, como a definição de science como sagesse, por exemplo (Règle I). Desse modo, a busca da verdade (coordenada principal das Règles, como nos evidencia a Règle IV) não abdica do ceticismo. Tratar-se-á, neste artigo, de compreender que o probabilismo acadêmico aparece no projeto de busca da verdade das Règles de modo negativo, pois Descartes ataca a modalidade do provável. Outros tópicos acadêmicos aparecem em questão, como a busca de sabedoria, a mitigação da dúvida, a disciplina do assentimento pela recusa do provável e a verdade do fideísmo. Estes tópicos se resumem ao método acadêmico, definido pela recursividade epistêmica.
ESTADO ENTRE A HISTÓRIA E A ETERNIDADE
Authors: Pina Albano
Published: July 2023

A dissolução (ou morte) estatal é uma preocupação comum a todos os autores contratualistas. Na sua maioria, eles consideram o estado um corpo mortal que, bem ou mal constituído, está inevitavelmente condenando a dissolver- se. E quanto a Espinosa? Acaso pensa o autor que o corpo político, tal como o corpo humano, tem uma morte certa, inevitável; ou julga, pelo contrário, que o estado pode ser eterno? Esta é a questão a que aqui se procura responder, analisando, para isso, várias passagens dispersas do Tratado Teológico-Político e do Tratado Político em que o assunto é (direta ou indiretamente) tratado. Da interpretação que apresentamos, deverá resultar claro que o problema da morte estatal não tem apenas um interesse teórico, mas está relacionada com aqueles que são, para Espinosa, os limites práticos da ciência política.
LEITURA ESPINOSANA DE "A NÁUSEA": A MELANCOLIA DE ROQUENTIN
Authors: Cavallari Ágatha
Published: July 2023

Este artigo pretende analisar a noção de melancolia tal como apresentada na caracterização de Roquentin, protagonista do romance sartriano A náusea, à luz da análise espinosana sobre os afetos, nas partes III e IV da Ética. No livro de Sartre, podemos observar sugestões constantes sobre a peculiar tristeza do personagem, baseadas em sua relação com a descoberta da contingência. Por outro lado, de acordo com a necessidade ontológica, as considerações de Espinosa sobre os afetos afirmam a impotência do melancólico e apontam a servidão daquele que crê ser conduzido pela fortuna. Portanto, nesta dinâmica, indicaremos Roquentin como o exemplo do homem que não é senhor de si, nos termos espinosanos.
CONCEITO DE BEATITUDE EM FICHTE E ESPINOSA: IMPLICAÇÕES MORAIS E POLÍTICAS DO IDEALISMO E DO DOGMATISMO
Authors: Scarfia Lucas Damián
Published: July 2023

Neste artigo procuro expor a forma pela qual aparece o conceito de beatitude (Seligkeit-beatitudo) no pensamento de Fichte e de Espinosa. Tendo isso em vista, ressalto a importância de considerar os fundamentos metafísicos dos seus sistemas filosóficos para poder compreender suas implicações práticas - em particular as morais e políticas - a respeito do sentido que aquele conceito adota. Assim, pretendo analisar a metafísica fichteana do ansiar (Sehnen) como base da sua concepção da beatitude em um sentido moral, ao mesmo tempo que buscarei, em um sentido filosófico-histórico, confrontar essa perspectiva com a ideia espinosana de uma beatitudo, que, deixando de lado a moralidade, uma vez que para ele a política assume um papel primário na existência humana, de um ponto de vista fichteano só poderia ser considerada como irracional e dogmática. O confronto entre ambos os pensadores pretende favorecer a compreensão tanto de suas posições sobre o tema como dos seus sistemas filosóficos per se.
Application of Medical Image Detection Technology Based on Deep Learning in Pneumoconiosis Diagnosis
Authors: Peng Shengguang
Published: July 2023

Pneumoconiosis is a disease characterized by pulmonary tissue deposition caused by dust exposure in the workplace. In China, due to the large number and wide distribution of pneumoconiosis patients, there is a high demand for the case data of lung biopsy during the diagnosis of pneumoconiosis. This text studied the application of medical image detection technology in pneumoconiosis diagnosis based on deep learning (DL). A medical image detection and convolution neural network (CNN) based on DL was analyzed, and the application of DL medical image technology in pneumoconiosis diagnosis was researched. The experimental results in this paper showed that in the last round of testing, the accuracy of ResNet model including deconvolution structure reached 95.2%. The area under curve (AUC) value of the working characteristics of the subject is 0.987. The sensitivity was 99.66%, and the specificity was 88.61%. The non staging diagnosis of pneumoconiosis improved the diagnostic sensitivity while ensuring high specificity. At the same time, Delong test method was used to conduct AUC analysis on the three models, and the results showed that model C was more effective than model A and model B. There is no significant difference between model A and model B, and there is no significant difference in diagnostic efficiency. In a word, the diagnosis of the model has high sensitivity and low probability of missed diagnosis, which can greatly reduce the working pressure of diagnostic doctors and effectively improve the efficiency of diagnosis.
Science as a Collective Effort: Collaboration at the Zoophysiological Laboratory 1911–1945
Authors: Lyngs Allan
Published: July 2023

This paper will address scientific collaboration at the Zoophysiological Laboratory during the 1911–1945 directorship of Nobel Prize winner August Krogh. Using authorship information and acknowledgments from the laboratory’s publications, this paper maps the many researchers involved in the work. In total, 193 different people contributed to the work at the Zoophysiological Laboratory. The paper further analyzes what labor, materials, ideas, and knowledge were exchanged between the individuals in the laboratory. While science has become more collaborative throughout the twentieth century, this paper underlines that collaboration was very much part of the research process in the early twentieth century.
IL-33/ST2 axis of human amnion fibroblasts participates in inflammatory reactions at parturition
Authors: Lei Wen-jia , Zhang Fan , Lin Yi-kai , Li Meng-die , Pan Fan , Sun Kang , Wang Wang-sheng
Published: July 2023

Background

Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition.

Methods

The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition.

Results

Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice.

Conclusion

IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.
Influencing factors and prognostic value of left ventricular systolic dysfunction in patients with complete occlusion of the left anterior descending artery reperfused by primary percutaneous coronary intervention
Authors: Jing Yongle , Lu Chengzhi , Guo Suzhen , Chen Bingwei , Ye Xuying , He Qiang , Xia Wei , Xin Ting
Published: July 2023

Background

The aim of this study was to perform a retrospective analysis of patients with acute anterior wall ST-segment elevation myocardial infarction (AAW-STEMI) whose left anterior descending (LAD) artery was completely occluded and reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influencing factors and prognostic value of left ventricular systolic dysfunction (LVSD) in the acute phase of acute myocardial infarction (AMI).

Methods

A total of 304 patients with AAW-STEMI were selected. The selected patients were divided into two groups: the preserved left ventricular ejection fraction (pLVEF) group (LVEF ≥ 50%, n = 185) and the reduced left ventricular ejection fraction (rLVEF) group (LVEF < 50%, n = 119). The influencing factors of LVSD and their predictive value for LVSD were analyzed. Patients were followed up by examining outpatient records and via telephone. The predictive value of LVSD for the cardiovascular mortality of patients with AAW-STEMI was analyzed.

Results

Age, heart rate (HR) at admission, number of ST-segment elevation leads (STELs), peak creatine kinase (CK) and symptom to wire-crossing (STW) time were independent risk factors for LVSD (P < 0.05). The receiver operating characteristic (ROC) analysis showed that the peak CK had the strongest predictive value for LVSD, with an area under the curve (AUC) of 0.742 (CI, 0.687 to 0.797) as the outcome. At a median follow-up of 47 months (interquartile range, 27 to 64 months), the Kaplan‒Meier survival curves up to 6-year follow-up revealed a total of 8 patients succumbed to cardiovascular disease, with 7 (6.54%) in the rLVEF group and 1 (0.56%) in the pLVEF group, respectively (hazard ratio: 12.11, [P = 0.02]). Univariate and multivariate Cox proportional hazards regression analysis demonstrated that rLVEF was an independent risk predictor of cardiovascular death in patients with AAW-STEMI discharged after PPCI (P < 0.01).

Conclusions

Age, HR at admission, number of STELs, peak CK, and STW time may be used to identify patients with a high risk of heart failure (HF) in a timely manner and initiate early standard therapy for incident LVSD in the acute phase of AAW-STEMI reperfused by PPCI. A trend toward increased cardiovascular mortality at follow-up was significantly linked to LVSD.
Research to develop a diagnostic ultrasound nomogram to predict benign or malignant lymph nodes in HIV-infected patients
Authors: Huang Chen , Shi Xia , Ma Xin , Liu Jianjian , Huang Jingjing , Deng Li , Cao Ye , Zhao Mingkun
Published: July 2023

Background

This study aimed to establish an effective ultrasound diagnostic nomogram for benign or malignant lymph nodes in HIV-infected patients.

Methods

The nomogram is based on a retrospective study of 131 HIV-infected patients who underwent ultrasound assess at the Shanghai Public Health Clinical Center from December 2017 to July 2022. The nomogram’s predictive accuracy and discriminative ability were determined by concordance index (C-index) and calibration curve analysis. A nomogram combining the lymph node US characteristics were generated based on the multivariate logistic regression results.

Results

Predictors contained in the ultrasound diagnostic nomogram included age (OR 1.044 95%CI: 1.014–1.074 P = 0.004), number of enlarged lymph node regions (OR 5.445 95%CI: 1.139–26.029 P = 0.034), and color Doppler flow imaging (CDFI) grades (OR 9.614 95%CI: 1.889–48.930 P = 0.006). The model displayed good discrimination with a C (ROC) of 0.775 and good calibration.

Conclusions

The proposed nomogram may result in more-accurate diagnostic predictions for benign or malignant lymph nodes in patients with HIV infection.