bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Experiment Based Evaluation of the Thermal Performance of a Flipchip Electronic Assembly
Authors: Mithal Pankaj
Published: July 2023

A finite element method based design of experiment (DOE) study was conducted to evaluate the thermal performance of an automotive electronic assembly. The assembly design consists of a flipchip IC mounted on a thin FR-4 PCB bonded to an aluminum backplate. The study captures the influence of the number of thermal vias present in the substrate, the thermal conductivity and thickness of the epoxy layer between the substrate and the backplate, the IC active area, thermal conductivity of the underfill marterial and the power dissipation of the IC, on the thermal performance of the assembly. Single factor analysis of various design parameters indicates that the thermal conductivity and thickness of the epoxy layer are the most critical parameters of the design from a thermal performance viewpoint.
DYNA3D Simulations of Pendulum Impact Tests on Steel Guardrails
Authors: Bank Lawrence C. , Gentry T. Russell , Yin Jiansheng , Lamtenzan J. Daniel
Published: July 2023

The response of a G4(1S) strong post steel w-beam guardrail system to dynamic impact has been investigated in a series of full-size physical tests and in simulated experiments using LLNL-DYNA3D. The physical tests were conducted at the Federal Outdoor Impact Laboratory (FOIL) at the Turner Fairbank Highway Research Center of the Federal Highway Administration (FHWA) in McLean, Virginia using a pendulum. In the pendulum tests, an 880 kg mass was used to strike the rail perpendicular to its face. The rail section was attached to steel posts and blockouts and supported in a specially designed fixture. Initial velocities of the pendulum at impact were 9.25, 20, 30 and 35 km/h. From acceleration data taken during the testing, acceleration, force, velocity and displacement histories of the impact event were calculated. Data from the LLNL-DYNA3D simulations of the impact tests compared well with the data obtained from the full-scale testing. Animations of the deformed shapes of the rails at 25 msec intervals compared favorably with high speed film images. Force versus displacement histories showed good agreement with those obtained from quasi-static experiments.
Study of CVD Coated and Uncoated INCO 718 Exposed to Particulate Flow
Authors: Shanov Vesselin , Tabakoff Widen , Gunaraj J. A.
Published: July 2023

The major problem confronting developers of coal burning boilers, fluidized beds, and gas and steam turbines, is the serious erosion of the systems’ components by the suspension of fly ash or other solid particles in the flow. A permanent loss of performance is associated with surface erosion, which is caused by particle surface impacts. To improve the resistance of hot erosion and corrosion, new alloys and coatings are investigated. The objective of this research work is to investigate the basic erosion process and fluid mechanics associated with material degradation in coated and uncoated INCO 718. This nickel-based superalloy is frequently used for manufacturing of jet engine and rocket components. Chemical vapor deposition (CVD) technique is used to apply a ceramic coating (TiC) to the INCO 718 superalloy. The erosive wear of the samples is investigated experimentally by exposing them to chromite particle laden flow at velocities from 180 to 305 m/s and temperatures from ambient to 538°C in a specially designed erosion wind tunnel. In addition, the eroded surface is examined by scanning electron microscopy (SEM). The obtained results show the effect of the impingement angle, temperature and velocity on the erosion rate. The cumulative effects of the impacting particles mass on the weight loss and the erosion rate of the coating are also investigated. This study demonstrates that the tested CVD titanium carbide is a perfect high temperature erosion resistant coating for INCO 718.
Dynamic Response and Fatigue Characterization of Aluminum Boron Carbide Ceramic Composite Materials for Disk Drive Actuator Applications
Authors: Perettie D. J. , Fox R. T. , Pyzik A. J. , Han C. , Macioce P. , Nashif A.
Published: July 2023

Use of alternate materials has been suggested as a means of achieving improvements in disk drive performance, with actuator support components representing one area where such a change could prove beneficial. Increases in specific stiffness along the head support structure/assembly serve to increase the frequencies at which resonance is observed, ultimately translating to a potential reduction in off-track error due to the onset of uncontrolled vibration observed at the head-disk interface. Additional benefits projected to be attributable to these structural stiffness influences include improvement of both access times and usable areal density. Aluminum-Boron Carbide ceramic composites possess favorable material property combinations which readily lend themselves to this application. Components fabricated to designs developed for this purpose were tested for dynamic response when subjected to both cyclic temperature exposure (−40°C to 100°C) and controlled humidity (85% at 85°C) conditions. These results, combined with cyclic fatigue characterization suggest that Aluminum-Boron Carbide can function as a feasible, higher performance alternative to the conventional stainless steel, aluminum, and magnesium metals currently used for this purpose.
Suture-Induced Intramural Stresses and Intimal Hyperplasia
Authors: Ballyk Peter D. , Ojha Matadial , Walsh Colin , Butany Jagdish
Published: July 2023

Intimal hyperplasia is a major cause of outflow stenosis and thrombosis of prosthetic bypass grafts. In an end-to-side graft-artery anastomosis, the thickness of the early cellular lesion is greatest at the suture-line, where the distribution is roughly uniform around the junction (Bassiouny et al., 1992; Trubel et al., 1994). This distribution is difficult to explain on the basis of either hemodynamic or compliance mismatch factors alone since these effects are not uniformly distributed (Ojha, 1994; Ballyk et al., 1995).
Computational Simulation of Magnetic Resonance Angiograms in Stenotic Vessels: Effect of Stenosis Severity
Authors: Bergman Harris L. , Siegel John M. , Oshinski John N. , Pettigrew Roderic I. , Ku David N.
Published: July 2023

Post stenotic signal loss limits the widespread use of magnetic resonance (MR) angiography. The signal loss causes ambiguity when determining the degree of stenosis and when assessing patency. Thus it is important to devise strategies for reducing signal loss associated with stenoses.
Modeling Contact in Biological Joints Using Penalty and Augmented Lagrangian Methods
Authors: Weiss Jeffrey A. , Schauer Dale A. , Gardiner John C.
Published: July 2023

Contact is inherent in biological joints. Examples include contact between articulating surfaces of joints and between soft tissues and bone. To accurately simulate the mechanics of joints using the finite element method, a robust treatment of contact is essential. The objective of this study was to compare the performance of standard penalty methods to the augmented Lagrangian (AL) method for enforcing contact in a model of joint mechanics, using both computational cost and accuracy for the comparisons. Comparisons were carried out using a representative problem from finite element simulations of joint mechanics.
The Effect of Strain Rate on the Axial Stress-Strain Response of the Human Annulus Fibrosus in Tension and Compression: Experiment and Poroelastic Finite Element Predictions
Authors: Duncan Neil A. , Ashford Frank A. , Lotz Jeffrey C.
Published: July 2023

We investigated the effect of strain rate on the axial tension and compression response of the annulus fibrosus. In compression, the stress-strain response of the annulus stiffened by 800% when loaded at physiologic loading rates compared to quasi-static rates, whereas in tension the annulus stiffened by only 100%. We also developed a nonlinear poroelastic FEM to predict the axial tension and compression response of the annulus. The model was unable to predict the significant effect of strain rate on the axial stress-strain response we observed experimentally, though excellant agreemant was found at quasi-static strain rates.
Wall Shear Stress Gradient Measurements Within the Distal Anastomosis of Vascular Bypass Grafts: An In Vivo Model Study
Authors: Keynton Robert S. , Evancho Mary M. , Sims Rick L. , Rodway Nancy V. , Li Qun , Mallugari Nagesh , Rittgers Stanley E.
Published: July 2023

There has long been a debate in the bioengineering community as to the role of hemodynamics in the development of cardiovascular diseases. Several researchers [1,2] have hypothesized that the Wall Shear Stress Gradient (WSSG) is directly related to the development of intimal hyperplasia [IH] within vascular bypass grafts. Unfortunately, this hypothesis is based on results from numerical [1,2] studies and not direct in vivo measurements. Therefore, it is the purpose of this paper to determine the relationship between the wall shear stress gradient and the development of IH at the distal anastomosis of vascular bypass grafts in an in vivo model.
Infrared Photodetection in the Picowatt Range Using Uncooled Micromechanical Sensors
Authors: Lai J. , Perazzo T. , Shi Z. , Majumdar A.
Published: July 2023

Bi-material microcantilever beams have been used to photothermally detect infrared and visible radiation with 10 pW resolution for power and 3 fJ for energy, while operating at room temperature. The resolution was improved by an order of magnitude by optimizing the thickness ratio of the two beam materials, as well as by modulating the input radiation at sufficiently high frequency to be in the thermal white-noise limit of the cantilever. Noise-equivalent radiative power was detected with a noise-spectral density of 100 pW/Hz and a detectivity, D*, higher than 108cmHz/W.
Optimal Design of a Microfabricated Diffusion-Based Extraction Device
Authors: Holl Mark R. , Galambos Paul , Forster Fred K. , Brody James P. , Yager Paul
Published: July 2023

The miniaturization of micro-fluidic chemical assays of fluid mixtures containing particles such as biological molecules and cells is a technically and commercially significant objective. Successful automation of chemical analysis of small samples requires seamless integration of several subsystems that perform tasks routinely carried out by a skilled technician. In this paper is presented a methodology for the optimal design of a novel micro-flow diffusion-based constituent extraction device based on parallel fluid flow through a microchannel. The streamwise distance required for the constituent being extracted to achieve an average concentration across the micro-channel that is a fixed percentage of the equilibrium concentration is defined as the equilibration length. The constituent concentration within the micro-channel is calculated using a 1-D analytical diffusion model. The equilibration length is used to construct a family of process space design curves specific to the extracted constituent. An optimization objective function is specified to identify the design that maximizes the volume flow rate of product stream.

The methodology is applied to the design of a device for the extraction of albumin (a protein present in blood) from a carrier sample stream with viscosity approximately that of water. The device is specified for a length sufficient for the mean albumin concentration in the product stream to reach a value that is 99% of the equilibrium concentration of albumin for an infinite length device. This process sensitivity information provides design requirements for upstream and downstream fluidic components, and is essential for integration of the device into a “lab on a chip” chemical analysis system.
A Bimetallic Thermally Actuated Micropump
Authors: Yang Yue , Zhou Zhaoying , Ye Xiongying , Jiang Xiaoning
Published: July 2023

In this paper a bimetallic thermally-actuated membrane micropump is presented. The micropump have been fabricated using silicon micromachining technique. The pump consists of two chips and comprises a pump chamber, two bimetallic actuators and two check valves integrated on the same structure. The size of the pump chamber is about 3mm × 3mm × 0.7mm, and that of microvalve outlet is 100 μm × 100 μm. Flow characteristics of the pump and its main components are tested and discussed. The maximum flow rate of the pump is approximately 43 μl/min, under the driving voltage of 16V and frequency of 0.9 Hz.
Dynamic Fracture via Molecular Dynamics and Cohesive Finite Element Method
Authors: Xu X.-P.
Published: July 2023

Dynamic fracture is investigated using molecular dynamics and cohesive finite element approaches. The molecular dynamics technique is based on the motion of a given number of atoms governed by their mutual interatomic interactions that are described by interatomic potentials. Using million atom systems, many recent laboratory findings occur in our simulation experiments. With every atomistic degree of freedom being accounted for, microscopic processes are identified. The continuum formulation involves specifying a set of cohesive surfaces. Each cohesive surface is described by a traction-displacement relation that allows for the creation of new free surface. The solid under consideration has inhomogeneities randomly distributed. Results for crack growth and branching are in accord with experimental observations. Some discussion on coupling continuum finite element and molecular dynamics is also presented.
Relaxed specificity of BcpB transporters mediates interactions between
Burkholderia cepacia
complex contact-dependent growth inhibition systems
Authors: Elery Zaria K. , Myers-Morales Tanya , Phillips Erica D. , Garcia Erin C.
Published: July 2023

Belonging to the two-partner secretion family of proteins, contact-dependent growth inhibition (CDI) systems mediate interbacterial antagonism among closely related Gram-negative bacteria. The toxic portion of a large surface protein, BcpA/CdiA, is delivered to the cytoplasm of neighboring cells where it inhibits growth. Translocation of the antibacterial polypeptide out of the producing cell requires an associated outer membrane transporter, BcpB/CdiB. Some bacteria, including many
Burkholderia
species, encode multiple distinct CDI systems, but whether there is interaction between these systems is largely unknown. Using
Burkholderia cepacia
complex species as a model, here we show that related BcpB transporters exhibit considerable secretion flexibility and can secrete both cognate and non-cognate BcpA substrates. We also identified an additional unique
Burkholderia dolosa
CDI system capable of mediating interbacterial competition and demonstrated that its BcpB transporter has similar relaxed substrate specificity. Our results showed that two BcpB transporters (BcpB-2 and BcpB-3) were able to secrete all four of the
B. dolosa
BcpA toxins, while one transporter (BcpB-1) appeared unable to secrete even its cognate BcpA substrate under the tested conditions. This flexibility provided a competitive advantage, as strains lacking the full repertoire of BcpB proteins had decreased CDI activity. Similar results were obtained in
Burkholderia multivorans
, suggesting that secretion flexibility may be a conserved feature of
Burkholderia
CDI systems. Together these findings suggest that the interaction between distinct CDI systems enhances the efficiency of bacterial antagonism.

IMPORTANCE

The
Burkholderia cepacia
complex (Bcc) is a group of related opportunistic bacterial pathogens that occupy a diverse range of ecological niches and exacerbate disease in patients with underlying conditions. Contact-dependent growth inhibition (CDI) system proteins, produced by Gram-negative bacteria, contain antagonistic properties that allow for intoxication of closely related neighboring bacteria via a secreted protein, BcpA. Multiple unique CDI systems can be found in the same bacterial strain, and here we show that these distinct systems interact in several Bcc species. Our findings suggest that the interaction between CDI system proteins is important for interbacterial toxicity. Understanding the mechanism of interplay between CDI systems provides further insight into the complexity of bacterial antagonism. Moreover, since many bacterial species are predicted to encode multiple CDI systems, this study suggests that interactions between these distinct systems likely contribute to the overall competitive fitness of these species.
Effects on global warming by microbial methanogenesis in alkaline lakes during the Late Paleozoic Ice Age (LPIA)
Authors: Xia Liuwen , Cao Jian , Hu Wenxuan , Stüeken Eva E. , Wang Xiaolin , Yao Suping , Zhi Dongming , Tang Yong , Xiang Baoli , He Wenjun
Published: July 2023

Methane (CH4) is an important greenhouse gas, but its behavior and influencing factors over geological time scales are not sufficiently clear. This study investigated the Late Paleozoic Ice Age (LPIA), which is thought to have experienced an interval of rapid warming at ca. 304 Ma, that may have been analogous to modern warming. To explore possible causes of this warming event, we investigated ancient alkaline lakes in the Junggar Basin, northwestern China. Results show that microbial CH4 cycling here was strong, as evidenced by carbonate δ13C (δ13Ccarb) values of >5‰, ~+0.6‰ offsets between pristane δ13C (δ13CPr) and phytane δ13C (δ13CPh) values, a 3β-methylhopane index of 9.5% ± 3.0%, and highly negative δ13C values of hopanes (–44‰ to –61‰). Low sulfate concentrations in the alkaline lakes made methanogenic archaea more competitive than sulfate-reducing bacteria, and the elevated levels of dissolved inorganic carbon promoted methanogenesis. Biogenic CH4 emissions from alkaline lakes, in addition to CO2, may have contributed to rapid climate warming.
Co-occurring IPMN and pancreatic cancer: the same or different? An overview from histology to molecular pathology
Authors: Omori Yuko , Furukawa Toru , Scarpa Aldo , Luchini Claudio
Published: July 2023

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of the most well-established precursors of pancreatic cancer. Its progression to acquire invasiveness is a complex process, based on the accumulation of morphological and genetic alterations. Recent advances in DNA sequencing also showed that co-occurring IPMNs and pancreatic cancers could be totally independent, further complicating our understanding of this complex scenario. The distinction between IPMN and related pancreatic cancer vs IPMN and co-occurring—but not related—pancreatic cancer is a challenging task in routine diagnostic activity, but may have important implications for precision oncology. Of note, recent multiregional sequencing-based studies focused not only on IPMN multi-step tumourigenesis, but also on the divergent intratumoural heterogeneity of this neoplasm. Globally considered, there are three different situations in which co-occurring IPMNs and invasive carcinomas can be found in the same pancreata, indicated with different terminologies: (1) IPMN-associated carcinoma: this definition indicates a carcinoma arising from an IPMN and can be also defined as IPMN-derived carcinoma, sequential or likely related; (2) independent IPMN and invasive carcinoma: the two lesions are not related, and this situation is defined as concomitant, de novo or likely independent; (3) branch-off pathway, where an invasive carcinoma and an adjacent IPMN develop divergently in a forked fashion from a common ancestral clone. In this review, we aim at clarifying the most important nomenclature/definitions of these different situations, also providing an overview of the molecular state-of-the-art and of the clinical implications of this complex landscape.
Return-to-work interventions for sick-listed employees with burnout: a systematic review
Authors: Lambreghts Charlotte , Vandenbroeck Sofie , Goorts Kaat , Godderis Lode
Published: July 2023

Burnout is a work-related mental health problem that often causes long-term sickness absence. Return-to-work (RTW) interventions for burned-out sick-listed employees aim to prevent long-term work disability. This systematic review addresses two questions: (1) Which interventions for burned-out sick-listed employees have been studied?; (2) What is the effect of these interventions on RTW?

We performed a systematic literature review and searched PubMed, Cochrane Central Register of Controlled Trials, Embase, CINAHL and Web of Science from 1 January 2000 to 31 December 2022. We searched for articles of interventions for burned-out sick-listed employees. We conducted the review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Outcome was RTW.

We identified 2160 articles after removal of all duplicates. Eight studies met inclusion criteria. RTW outcomes were number of sick-leave days, sick-leave rates, median period of RTW and worked hours per week. Five studies described person-directed interventions, one described a workplace-directed intervention, one described a combination of both intervention types and one study described all three types of intervention. Only the workplace-directed intervention showed a significant improvement in RTW compared with the comparator group: at 18-month follow-up, 89% of the intervention group had returned to work compared with 73% of the comparator group.

Only a limited number of studies have explored interventions specifically focused on burned-out sick-listed employees and the effect on RTW. Due to heterogeneity and moderate to high risk of bias of these studies, no firm conclusions can be drawn on the described interventions and their effect on RTW.

The study was registered with the International prospective register of systematic reviews (PROSPERO, registration number: CRD42018089155).
Elasto-plastic and post-yield weakening jointed rockmass response in a comparison of equivalent-continuum and explicit structural models
Authors: Fischer Caitlin P. , Diederichs Mark S.
Published: July 2023

The strength and stiffness of a composite rockmass (intact material, defects, joints, bedding, etc.) are primary inputs for the engineering analysis of rock slopes and underground excavations. The Geological Strength Index (GSI) has served rock engineering for three decades as a rockmass assessment system based on the blockiness of the rockmass and discontinuity condition. GSI is used to factor the Hoek–Brown strength envelope for intact rock to represent jointed rockmasses in conventional equivalent-continuum numerical modelling. Modern numerical tools can represent networks of discrete (explicit) structure with assigned discontinuity properties. This provides an opportunity to compare explicit structural modelling with the conventional implicit equivalent-continuum approach. In this paper, explicit structural models are developed using elasto-plastic (constant-strength) constitutive models for intact rock and realistic parametric ranges for explicit structure properties. Explicit model results are compared to equivalent-continuum results, validating the classical implicit approach while also identifying key limitations. Explicit models with post-yield weakening of the intact and structural elements are then developed and compared to post-yield weakening implicit models that use post-yield dilation and empirical relationships between peak and residual GSI. The results provide guidance for practical modelling in strain-weakening rockmasses, including recommendations for post-yield dilation in the traditional implicit approach.
Picea × darwyniana Björk & Goward: an invalid taxonomic name
Authors: Strong W.L
Published: July 2023

Picea ×  darwyniana Björk & Goward was recently proposed to replace Picea albertiana S. Brown as the representative taxon for the hybrid offspring of Picea glauca (Moench) Voss and Picea engelmannii Parry ex Engelm., but should be considered invalid for three reasons. First, the proponents failed to document in any way that the P. albertiana isotypes were Picea glauca ×  mariana Little & Pauley hybrids, as they claimed. Secondly, the P. albertiana isotypes lacked pubescent twigs, purple markings on their seed cones, and denticulate cone-scale margins, which are characteristics of P. glauca ×  mariana. This indicates a misinterpretation of the P. albertiana parentage. Lastly, P. × darwyniana appears to be an example of P. albertiana ssp. ogilviei Strong & Hills. As the latter is an earlier and validly published name, P. × darwyniana is an illegitimate replacement for plants within the P. glauca ×  engelmannii (= P.a. ssp. albertiana) and P. engelmannii ×  glauca (= P.a. ssp. ogilviei) circumscriptions based on naming priority.
Elder-oriented Active Learning for Adaptation of Perception Intelligence in Home Service Robots
Authors: Wang Qi , He Yan , Sheng Weihua , Zhang Senlin , Liu Meiqin , Chen Badong
Published: July 2023

Active learning is a special case of machine learning in which a learning algorithm can interactively query a user to label new data points with the desired outputs. In robotics, active learning allows a robot to adapt its perception intelligence to a new environment with users’ help. This paper presents a new active learning method for elderly care robots to select data that is not only useful for learning but also easy for the elderly user to label. First, a series of image properties related to annotation difficulty are determined based on existing medical researches in human vision in elderly population. Based on that, a user study is conducted to determine the ground truth of annotation difficulty of images for the older adults. Second, a robust annotation difficulty predictor is developed using the results of the user study, and the difficulty prediction of an image is combined with three other active learning criteria to form an annotation difficulty-aware active learning metric, which facilitates the query data selection as the robot adapts its perception intelligence in a home environment. Third, we present an ablation study of the proposed active learning method through a simulation experiment. The experimental results validate the advantages of the proposed method.
Bifidobacteria Encapsulation and Viability of Probiotic Culture during Oral Delivery in a Milk Drink Matrix
Authors: Voblikova Tatiana , Laricheva Kristina
Published: July 2023

The use of an alginate hydrogel exclusively for the immobilization of bifidobacteria during oral delivery led to a decrease in the total number of bifidobacteria to 4.0 lg CFU/ml in pH gradients in models of the stomach and intestines, which required clarification of the composition of the protective coating. The introduction of resistant starch into the composition of the microcapsule contributed to the preservation of the viability of immobilized bifidobacteria up to 87% of the initial concentration when passing through the model environment simulating the human digestion system. The introduction of sodium carboxymethylcellulose into the composition of the hydrogel contributed to the regulation of the degradation of the polymer matrix and the controlled release of bifidobacteria. The use of sodium carboxymethylcellulose 0.5% in the formation of a polymer microcapsule provided the maximum encapsulation efficiency of 93.2% and the maximum decay rate of bacteria-loaded microcapsules of 95.7%. The modified alginate matrix contributes to maintaining the level of viable cells of probiotic microorganisms (Bifidobacterium bifidum 791) of at least 108 CFU/g when stored for three weeks. As a result of the research, a system for oral delivery of immobilized bifidobacteria in the structure of microparticles with a closed surface in the matrix of a milk drink has been developed, which increases the effectiveness of probiotics for human health in the composition of food products.
Supplementary Data 1 from HLA-I Evolutionary Divergence Confers Response to PD-1 Blockade plus Chemotherapy in Untreated Advanced Non–Small Cell Lung Cancer
Authors: Jiang Tao , Jin Qiqi , Wang Jiahao , Wu Fengying , Chen Jian , Chen Gongyan , Huang Yunchao , Chen Jianhua , Cheng Ying , Wang QiMing , Pan Yueyin , Zhou Jianying , Shi Jianhua , Xu Xingxiang , Lin LiZhu , Zhang Wei , Zhang Yiping , Liu Yunpeng , Fang Yong , Feng Jifeng , Wang Zhehai , Hu Sheng , Fang Jian , Shu Yongqian , Cui Jiuwei , Hu Yi , Yao Wenxiu , Li Xingya , Lin Xiaoyan , Wang Rui , Wang Yongsheng , Shi Wei , Feng Gaohua , Ni Jun , Mao Beibei , Ren Dandan , Sun Huaibo , Zhang Henghui , Chen Luonan , Zhou Caicun , Ren Shengxiang
Published: July 2023

Supplementary Materials
Supplementary Figure S19 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Subasumstat initiates cell death and cytotoxic T cell activity
Data from Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment
Authors: Roschewski Mark , Patel Manish R. , Reagan Patrick M. , Saba Nakhle S. , Collins Graham P. , Arkenau Hendrik-Tobias , de Vos Sven , Nuttall Barrett , Acar Melih , Burke Kathleen , White Rafael D. , Udriste Maria , Sharma Shringi , Dougherty Brian , Stetson Daniel , Jenkins David , Mortlock Andrew , Forcina Alessandra , Munugalavadla Veerendra , Flinn Ian
Published: July 2023

AbstractBackground:
Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL.
Methods:
Final results of the phase I study of acalabrutinib plus STAT3 inhibitor (danvatirsen; AZD9150) in patients with R/R DLBCL are reported. Danvatirsen 200 mg intravenous infusion [Days 1, 3, 5 (Cycle 1); weekly infusions starting Day 8, Cycle 1] was administered in combination with oral acalabrutinib 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.
Results:
Seventeen patients received combination treatment. One dose-limiting toxicity (Grade 3 liver transaminase) occurred in 1 patient. The most common reason for treatment discontinuation was PD (65%). In evaluable patients (n = 17), objective response rate was 24%; median duration of response was 1.9 months. All responders with available DLBCL cell-of-origin data were either activated B-cell or nongerminal center B-cell like subtype. Genetic subtype did not correlate with response. Baseline and longitudinal plasma cell-free DNA (cfDNA) concentrations were mostly higher in nonresponding patients. cfDNA changes were generally concordant with imaging. Pretreatment circulating B-cell levels were higher in responders versus nonresponders.
Conclusions:
Targeting both STAT3 and BTK in combination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.
Data from A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Pook David , Geynisman Daniel M. , Carles Joan , de Braud Filippo , Joshua Anthony M. , Pérez-Gracia José Luis , Llácer Pérez Casilda , Shin Sang Joon , Fang Bruno , Barve Minal , Maruzzo Marco , Bracarda Sergio , Kim Miso , Kerloeguen Yannick , Gallo Jorge Daniel , Maund Sophia L. , Harris Adam , Huang Kuan-Chieh , Poon Victor , Sutaria Dhruvitkumar S. , Gurney Howard
Published: July 2023

AbstractPurpose:
To report the safety and efficacy of ipatasertib (AKT inhibitor) combined with rucaparib (PARP inhibitor) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with second-generation androgen receptor inhibitors.
Patients and Methods:
In this two-part phase Ib trial (NCT03840200), patients with advanced prostate, breast, or ovarian cancer received ipatasertib (300 or 400 mg daily) plus rucaparib (400 or 600 mg twice daily) to assess safety and identify a recommended phase II dose (RP2D). A part 1 dose-escalation phase was followed by a part 2 dose-expansion phase in which only patients with mCRPC received the RP2D. The primary efficacy endpoint was prostate-specific antigen (PSA) response (≥50% reduction) in patients with mCRPC. Patients were not selected on the basis of tumor mutational status.
Results:
Fifty-one patients were enrolled (part 1 = 21; part 2 = 30). Ipatasertib 400 mg daily plus rucaparib 400 mg twice daily was the selected RP2D, received by 37 patients with mCRPC. Grade 3/4 adverse events occurred in 46% (17/37) of patients, with one grade 4 adverse event (anemia, deemed related to rucaparib) and no deaths. Adverse events leading to treatment modification occurred in 70% (26/37). The PSA response rate was 26% (9/35), and the objective response rate per Response Criteria in Solid Tumors (RECIST) 1.1 was 10% (2/21). Median radiographic progression-free survival per Prostate Cancer Working Group 3 criteria was 5.8 months [95% confidence interval (CI), 4.0–8.1], and median overall survival was 13.3 months (95% CI, 10.9–not evaluable).
Conclusions:
Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC.
Data from FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Authors: Wilde Blake R. , Chakraborty Nishma , Matulionis Nedas , Hernandez Stephanie , Ueno Daiki , Gee Michayla E. , Esplin Edward D. , Ouyang Karen , Nykamp Keith , Shuch Brian , Christofk Heather R.
Published: July 2023

Abstract
Fumarate accumulation due to loss of fumarate hydratase (FH) drives cellular transformation. Germline FH alterations lead to hereditary leiomyomatosis and renal cell cancer (HLRCC) where patients are predisposed to an aggressive form of kidney cancer. There is an unmet need to classify FH variants by cancer-associated risk. We quantified catalytic efficiencies of 74 variants of uncertain significance. Over half were enzymatically inactive, which is strong evidence of pathogenicity. We next generated a panel of HLRCC cell lines expressing FH variants with a range of catalytic activities, then correlated fumarate levels with metabolic features. We found that fumarate accumulation blocks de novo purine biosynthesis, rendering FH-deficient cells reliant on purine salvage for proliferation. Genetic or pharmacologic inhibition of the purine salvage pathway reduced HLRCC tumor growth in vivo. These findings suggest the pathogenicity of patient-associated FH variants and reveal purine salvage as a targetable vulnerability in FH-deficient tumors.
Significance:
This study functionally characterizes patient-associated FH variants with unknown significance for pathogenicity. This study also reveals nucleotide salvage pathways as a targetable feature of FH-deficient cancers, which are shown to be sensitive to the purine salvage pathway inhibitor 6-mercaptopurine. This presents a new rapidly translatable treatment strategy for FH-deficient cancers.
A "leda e triste" Inês de Castro: a figuração da vítima coletiva na epopeia camoniana
Authors: Queiroz José Francisco da Silva
Published: July 2023

Transposta das crônicas historiográficas para o suporte ficcional, a história de Inês de Castro assumiu a condição atemporal e mitológica que hoje a sustém como heroína entre heroínas da literatura universal. Na epopeia camoniana, embora não seja a primeira a mimetizar o fato histórico, tivemos a ordenação das estruturas narrativas que tornaram famoso o acontecimento histórico. Mas para além do infausto amor interrompido por razões palacianas, algo mais terrível se esconde na “paixão” de Inês de Castro. O que propomos neste artigo consiste no reconhecimento das “marcas vitimárias” que levaram a esposa póstuma do príncipe D. Pedro a se tornar o “bode expiatório” da “violência coletiva” cujo relato épico se ampara em um exemplo mitológico plasmado por Ovídio nas Metamorfoses. Ao contrapormos o sacrifício de Políxena à execução coletiva de Inês, mostraremos como uma mesma estrutura vicária se repete permitindo que o horror do fato histórico se encobrisse pela rede de analogias e alegorias do discurso poético.
Posso te beijar no tempo
Authors: Munizo Raeltom Santos
Published: July 2023

Outros Desassossegos.
Global, Regional, and National Economic Consequences of Stroke
Authors: Gerstl Jakob V.E. , Blitz Sarah E. , Qu Qing Rui , Yearley Alexander G. , Lassarén Philipp , Lindberg Rebecca , Gupta Saksham , Kappel Ari D. , Vicenty-Padilla Juan C. , Gaude Edoardo , Atchaneeyasakul Kunakorn C. , Desai Shashvat M. , Yavagal Dileep R. , Peruzzotti-Jametti Luca , Patel Nirav J. , Aziz-Sultan Mohammed A. , Du Rose , Smith Timothy R. , Bernstock Joshua D.
Published: July 2023

BACKGROUND:

An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries.

METHODS:

Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP.

RESULTS:

Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%).

CONCLUSIONS:

The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.
Entoloma sicoense, a new species in the subgenus Cyanula (Entolomataceae)
Authors: FACHADA VASCO , PEDREIRO HELDER , RAIMUNDO SUSETE , NOORDELOOS MACHIEL , DIMA BÁLINT , MARQUES GUILHERMINA
Published: July 2023

Entoloma sicoense, a bluish gray mushroom species belonging to section Poliopodes, is described as a new addition to the subgenus Cyanula. This study presents the phylogeny, taxonomy, and ecological significance of Entoloma sicoense, which inhabits mossy broad-leaved forests in the eastern North Atlantic region. The discovery of this new species expands our understanding of fungal diversity and highlights the ecological significance of the subgenus Cyanula in Serra de Sicó. Entoloma sicoense exhibits specific morphological characteristics, such as slate gray basidiomata, a smooth concolorous stipe, and a sterile gill edge rich in brilliant granules. This research underscores the importance of documenting and describing new species in Serra de Sico´ for comprehensive cataloging, conservation efforts, and further exploration of its ecological role within the local ecosystem. The new species is presented with morphological, illustrated description as well as molecular work and comparison with similar species.
The identity of Celonites montanus Mocsáry, 1906 (Hymenoptera: Vespidae: Masarinae) and its first record from Kazakhstan
Authors: FATERYGA ALEXANDER V. , FADEEV KIRILL I.
Published: July 2023

Celonites montanus Mocsáry, 1906, described from the Alai Range in Kyrgyzstan, is synonymized with C. kostylevi Panfilov, 1961, syn. nov. and C. haemorrhoidalis Gusenleitner, 2012, syn. nov. (both also described from Kyrgyzstan). The species is reported from Kazakhstan (Almaty Province) for the first time. It was collected at nototribic flowers of Lagochilus platyacanthus Rupr. (Lamiaceae). Trophic relationships between C. montanus and its forage plant are discussed.
First report of two braconid genera Syntretus Foerster and Xynobius Foerster from India with description of one new species
Authors: GUPTA ANKITA , ACHTERBERG CORNELIS VAN , PATTAR ROHIT , H.M. HEMANTH KUMAR
Published: July 2023

Two genera, namely Syntretus Foerster (Braconidae: Euphorinae) and Xynobius Foerster (Braconidae: Opiinae), are reported for the first time from India. One new species, Syntretus curvatus Gupta, van Achterberg & Pattar, sp. nov. is described and illustrated from southern India. Xynobius chrysops Wu, van Achterberg, Sheng & Chen, 2018, described from Vietnam, is reported newly from India.
A Retrospective Report on Simple Febrile Seizure Management in a Pediatric Emergency Department
Authors: VanDerhoef Katlin F. , Bergmann Kelly , Kaila Rahul , Shanley Ryan , Louie Jeffrey P.
Published: July 2023

Objective:

To determine whether pediatric emergency medicine physicians are compliant with the 9-year-old simple febrile seizure guideline created by the American Academy of Pediatrics (AAP).

Methods:

A retrospective chart review of patients, ages 6 to 60 months, who presented to the emergency department between May 2011 and December 2019. Key variables abstracted were urine, blood, nasal viral swab, and radiographic results.

Results:

The retrospective cohort of 285 children met inclusion criteria. Among 285 children, 342 studies were performed with a median of 1.2 studies per patient. There were 77 urine cultures obtained with 6 bacterial pathogens. Nasal viral swabs were performed on 65 children with 9 positive results. Blood cultures were obtained for 28 children and none were positive. Chest radiographs were performed on 37 children with 4 showing pneumonia.

Conclusion:

The study results reflect areas of opportunity to update guidelines with a focus to consider obtaining urine studies, viral sampling, and chest x-rays.
Choice and solidarity in Viola Ardone's Oliva Denaro
Authors: Donadey Anne
Published: July 2023

Contemporary Italian writer Viola Ardone's most recent novel, Oliva Denaro (2021), fictionalizes the story of Franca Viola, a young Sicilian woman whose refusal to marry her rapist in the 1960s was the first such situation to become highly publicized. In 1981, the law supporting so-called “reparatory marriages” was repealed in Italy, and Viola's case is widely seen as having been the impetus for the change. This article first places the novel in its historical context. It discusses afterlives of Viola’ story, which was important in the Italian public sphere in the mid-1960s and has enjoyed renewed popularity since 2012. This article argues that the running thread of choice in Ardone's novel should not be read as a liberal feminist version of one individual woman defying an entire society and becoming a fully autonomous self in the process, but as a situation that applies to every character in the text. It demonstrates that, unlike the way in which Viola's story is often framed, Ardone views feminist social justice change as a collective endeavor—a gathering of many individual choices that contribute to a collective end and require institutional backing—rather than a sole individual's trajectory.
Trust in Supervisor and Employee Creativity: The Mediating Role of Information Sharing
Authors: Cai Jincheng , Zheng Lei , Zhuang Fangyan , Yang Siyu , Wang Zhiwei
Published: July 2023

Creativity is modern era productivity. Many efforts have been made to enhance employee creativity. This study adopted the social exchange model of creativity to understand in-depth the integrated effect of affective and cognitive trust in supervisor (ATS/CTS) on employee creativity. We recruited 528 subordinates who completed a three-wave survey at one-month intervals. Multilevel modeling results showed that ATS and CTS were positively related to employee creativity. Moreover, information sharing served as a mediator for the relationship between CTS and employee creativity, but not between ATS and employee creativity. In addition, the mediation effect of information sharing on ATS-employee creativity was significant for employees with high levels of CTS but not for those with low levels of CTS. Our results suggested an integrated effect of ATS and CTS in information sharing and its consequences on employee creativity. We have confirmed and extended the social exchange model by examining the integrated effect of ATS and CTS on employee creativity. CTS seems to be a threshold in the relationship between ATS and employee information sharing. Our findings clarify ways to develop human resource training to promote ATS and CTS to foster employee creativity.
The Effect of Reality Therapy on Resilience and Self-Efficacy of Prisoners: A Randomized Controlled Trial Study
Authors: Malekzadeh Mohammad , Zoladl Mohammad , Movahedi Hamed
Published: July 2023

This study aimed to determine the effect of reality therapy training on self-efficacy and resilience in male prisoners. To this end, a randomized controlled trial was conducted with a pre-test, post-test, and a control group. The research questionnaires including the Scherer self-efficacy questionnaire and the Connor-Davidson resilience questionnaire were administered to 300 prisoners. Of them, 78 prisoners who met the inclusion criteria were selected and randomly assigned to the intervention and control groups. The intervention group attended ten 90-min sessions on reality therapy training per week. At the end of the training period, the study groups were required to attend the post-test. The data were analyzed with the SPSS software version 23 and through an independent t-test and a paired t-test. The results at the post-test phase showed a significant increase of self-efficacy and resilience in the experimental group, as compared to the control group ( p < .01). Therefore, it is recommended for authorities to improve the self-efficacy and resilience of prisoners through reality therapy trainings.
COVID-19, Diffuse Anxiety, and Public (Mis)Trust in Government: Empirical Insights and Implications for Crime and Justice
Authors: Reid Jonathan C. , Brown Samantha J. , Dmello Jared
Published: July 2023

Given that trust in government is a critical feature of a well-functioning democracy, research into its determinants has long been a priority among public opinion scholars. The consensus in the literature is that short-term factors drive the ebbs and flows of public trust, and a climate of mistrust has significant consequences on the government's ability to deliver on policies and enforce the law. Despite decades of extensive research on public trust, changing circumstances related to the COVID-19 pandemic support the need to investigate the factors shaping trust in this distinct period. This article, using data from the American National Election Study, explores how economic, social, and political anxieties pervasive throughout the pandemic influence trust in the United States government. Findings from ordered logistic regression analyses indicate that public trust in government is associated with views of the government's COVID-19 response, beliefs about the state of the country and government corruption, economic anxieties, and concerns about election fraud and the status of American democracy. Findings also reveal that sentiments toward institutions—including the police and the Center for Disease Control—contribute to variability in public trust. The implications of these findings for criminal justice research and policy are also considered.