bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteria-Induced Calcite Precipitation for Engineering and Environmental Applications
Authors: Baidya Purnima , Dahal Bhim Kumar , Pandit Archana , Joshi Dev Raj
Published: June 2023

Numerous engineering and environmental issues can be resolved using the bacterial-induced calcite precipitation (BCP), which has the potential to be environmentally friendly, sustainable, and economical. In BCP, bacterial enzymes used substrates and divalent cations to bind negatively charged ions to the bacterial surface and produce biocementation. Various metabolic pathways involved in the calcite precipitation and ureolysis are the principal bacterial pathways that have been illustrated by most bacteria including Sporosarcina pasteurii, Bacillus subtilis, and Pseudomonas putida. Ammonia is produced by these bacteria, which is toxic and should be eliminated. Therefore, BCP via carbonic anhydrase could be a preferred option because the end-products are not toxic. The growing global requirement of ground improvement boosted the demand for biostabilization because of its numerous benefits, including environmental issues. Dust suppression, remediated soil contaminants, polychlorinated biphenyl calcium ions, and CO2 sequestration, proving that BCP is environmentally friendly and sustainable. Furthermore, for fine-grained soils having pores smaller than 0.5 μm, the enzyme-induced calcite that uses enzymes instead of bacteria is more suitable to stabilize the soil by precipitating the calcite. The use of BCP as binders for soil stability and strengthening, innovative construction materials, subsurface barriers, and impermeable crusts is an emerging field. Calcite precipitated in the pores increases strength more than 20 times, resulting in a significant reduction in compressibility. Similarly, reduced soil permeability to up to 99% broadens its applicability. This review argues that BCP can be induced by multiple approaches, including urease expressing bacteria and carbonic anhydrase expressing bacteria as well as free enzymes.
Prevalence of Primary Dysmenorrhoea and Its Impact on Academic Performance among Croatian Students during the COVID-19 Pandemic
Authors: Horvat Marta , Pavan Jukić Doroteja , Marinović Lovro , Bursać Dina , Ribić Rosana , Neuberg Marijana , Bursać Danijel
Published: June 2023

Background. Dysmenorrhoea is one of the most common gynaecological problems. Therefore, it is important to investigate its impact during the COVID-19 pandemic which has a great impact on the lives of menstruating people all over the world. Aim. To determine the prevalence and impact of primary dysmenorrhoea on academic performance among students during the pandemic. Materials and Methods. This cross-sectional study was conducted in April 2021. All data were collected by an anonymous self-assessed web‐based questionnaire. Due to voluntary participation in the study, 1210 responses were received, but 956 were left for analysis after exclusion criteria were applied. Descriptive quantitative analysis was performed and Kendall rank correlation coefficient was used. Results. The prevalence of primary dysmenorrhoea was 90.1%. Menstrual pain was mild in 7.4% of cases, moderate in 28.8%, and severe in 63.8%. The study found that primary dysmenorrhoea has a great perceived impact on all included aspects of academic performance. Most affected were concentration in class in 810 (94.1%) and doing homework and learning in 809 (94.0%) female students. There is also a correlation between menstrual pain intensity and its impact on academic performance (

p
<
0.001

). Conclusions. Our study found that the prevalence of primary dysmenorrhoea among students at the University of Zagreb is high. Painful menstruation greatly impacts academic performance and therefore it is important to do more research on this topic.
The Association between Neutrophil-to-Lymphocyte Ratio and Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Adane Tiruneh , Melku Mulugeta , Worku Yilkal Belete , Fasil Alebachew , Aynalem Melak , Kelem Amanuel , Getawa Solomon
Published: June 2023

Background. Glycated hemoglobin (HbA1c) is a commonly used clinical marker to monitor the control of type 2 diabetes mellitus patients (T2DM). However, it is unable to identify the ongoing inflammatory changes in the body. These factors could be easily identified and monitored by the neutrophil-to-lymphocyte ratio (NLR). Therefore, this study is aimed at investigating the relationship between NLR and glycemic control in T2DM. Method. A comprehensive search of eligible studies was performed in various databases published until July 2021. A random effect model was used to estimate the standardized mean difference (SMD). A metaregression, subgroup, and sensitivity analysis were conducted to search for potential sources of heterogeneity. Result. A total of 13 studies were included in this study. Accordingly, the SMD of the NLR values between the poor and good glycemic control groups was 0.79 (95% CI, 0.46-1.12). Our study also showed that high NLR was significantly associated with poor glycemic control in T2DM patients (

OR
=
1.50

, 95% CI: 1.30-1.93). Conclusion. The results of this study suggest an association between high NLR values and an elevated HbA1C in T2DM patients. Therefore, NLR should be considered a marker of glycemic control in addition to HbA1c in T2DM patients.
Urinary Tract Infection and Associated Factors among Pregnant Women Receiving Antenatal Care at a Primary Health Care Facility in the Northern Region of Ghana
Authors: Vicar Ezekiel K. , Acquah Samuel E. K. , Wallana Williams , Kuugbee Eugene D. , Osbutey Emmanuel K. , Aidoo Abigail , Acheampong Emmanuel , Mensah Gloria Ivy
Published: June 2023

Urinary tract infection (UTI) is frequently encountered during pregnancy and is associated with adverse maternal, fetal, and neonatal effects. However, very little information is available on the prevalence of UTI among pregnant women in the northern part of Ghana, a region with a high birth rate. This study employed a cross-sectional analysis of the prevalence, antimicrobial profile, and risk factors associated with UTI in 560 pregnant women attending primary care for antenatal check-ups. Sociodemographic obstetrical history and personal hygiene information were obtained using a well-structured questionnaire. Afterward, clean catch mid-stream urine samples were collected from all participants and subjected to routine microscopy examination and culture. Of 560 pregnant women, 223 cases (39.8%) were positive for UTI. There was a statistically significant association between sociodemographic, obstetric, and personal hygiene variables and UTI (

p
<
0.0001

). Escherichia coli (27.8%) was the commonest bacterial isolate followed by CoNS (13.5%) and Proteus species (12.6%). These isolates exhibited greater resistance to ampicillin (70.1–97.3%) and cotrimoxazole (48.1–89.7%) but were fairly susceptible to gentamycin and ciprofloxacin. Gram-negative resistance to meropenem was up to 25.0%, and Gram positives resistance to cefoxitin and vancomycin was up to 33.3% and 71.4% respectively. The current findings extend our knowledge of the high frequency of UTIs and associated risk factors in pregnant women with E. Coli being the predominant and usual isolate. Variation existed in the resistance pattern of isolates to various drugs, underscoring the need to perform urine culture and susceptibility before treatment.
A Single DC Source Generalized Switched Capacitors Multilevel Inverter with Minimal Component Count
Authors: Jena Kasinath , Kumar Dhananjay , Kumar B. Hemanth , Janardhan K. , Singh Arvind R. , Naidoo Raj , Bansal Ramesh C.
Published: June 2023

This paper presents a new single-source switched capacitor- (SC-) based multilevel inverter (MLI) design with a boosting potential of three times the supply voltage. To produce a waveform with seven output voltage levels, the suggested switching capacitor inverter consists of eight switches, single diode, and two capacitors. Because capacitors are inherently balanced, there is no need for a balancing circuit or sensor. The structure can be expanded using the provided generalized equations. In addition, the technique for switching control and loss analyses is explored. A fair comparison with the most recent SCMLI topologies has been conducted to demonstrate the merits of the proposed work. Furthermore, the proposed topology is evaluated using the MATLAB/SIMULINK tool, and experiments under both transient and steady-state situations are performed to demonstrate its feasibility. At dynamic-loaded situations, the performance of the proposed SCMLI with dynamic modulation index and switching frequency is tested.
Benefit of Panoramic Radiography in the Detection of Carotid Calcifications: Clinical Case Reports and Review of the Literature
Authors: Zaghden Olfa , Jaziri Rawia , Kammoun Rym , Chaabani Imen , Alaya Touhami Ben
Published: June 2023

Atherosclerotic lesions in the common carotid artery are one of the most frequent causes of ischemic stroke. They are usually diagnosed by cardiologists and are managed following complementary examinations. In dental practice, panoramic radiograph is a basic examination frequently performed in first line. On this radiography, possible unilateral or bilateral opacities projecting to the latero-cervical regions can be visualized, raising suspicion of carotid calcifications. The aim of this study was to present, through three cases and a review of the literature, the benefit of PR in the diagnosis of carotid calcifications and the approaches to be followed in case of such suspicious images. This would contribute, in some cases, to an early diagnosis and management, thus avoiding the evolution towards cerebral vascular accidents.
Predicting the Adsorption Efficiency Using Machine Learning Framework on a Carbon-Activated Nanomaterial
Authors: Prasad Kalapala , Ravi Kumar V. , Kumar R. Suresh , Rajesh A. S. , Rai Anjani Kumar , Al-Ammar Essam A. , Wabaidur Saikh Mohammad , Iqbal Amjad , Kefyalew Dawit
Published: June 2023

Due to the excessive use of paracetamol (PCM), a significant amount of its metabolite has been released into the surroundings, and its removal from the surroundings must happen quickly and sustainably. Multicomponent adsorption modelling is difficult because it is challenging to anticipate the relationships among the adsorbates in this artificial intelligence-based modelling, a choice among different algorithms. Utilizing various algorithms, many studies assessed the single and binary adsorption of paracetamol on activated carbon. The present study implements that the effectiveness of PCM adsorption on a carbon-activated nanomaterial was predicted using an artificial neural network, a machine learning technology. As a factor of adsorbent particle size, adsorbent dosage, training time, and starting concentrations, the adsorption capacity for each medicinal ingredient was examined. SEM was used to analyze a nanomaterial that had been chemically altered with orthophosphoric acid (FTIR). To determine the residual proportion of PCM in solvent, batch adsorption of PCM was then carried out at various operation conditions, including contact time, temperatures, and initial dosage. The adsorption effectiveness of paracetamol on carbon-activated nanoparticle was calculated using experimental results. Thus, by using machine learning framework, the adsorption efficiency of paracetamol on a carbon-activated nanomaterial was predicted.
Incidental Diagnosis of Oligosymptomatic Bilateral Perirenal Erdheim–Chester Disease during Emergency Investigation for COVID-19 Infection
Authors: Vargas Juliano Cordova , Cardozo Caio , Stanzione Renata , Fiore Lucas , D'Almeida Costa Felipe , Fonseca Abreu Rodrigo , Hamerschlak Nelson , Perini Guilherme
Published: June 2023

Erdheim–Chester disease (ECD), a rare form of non-Langerhans histiocytosis, is a multisystem disorder. The case reported here refers to a 49-year-old man presenting at the emergency room with respiratory symptoms. While undergoing diagnostic tests for COVID-19 infection, tomography revealed asymptomatic bilateral perirenal tumors, while renal function remained unaltered. ECD was suggested as an incidental diagnosis and confirmed by core needle biopsy. This report provides a brief description of the clinical, laboratory, and imaging findings in this case of ECD. This diagnosis, albeit rare, should be taken into consideration in the context of incidental findings of abdominal tumors to ensure that treatment, when required, is instituted early.
Numerical Simulations of Carbon Dioxide Storage Efficiency in Heterogeneous Reservoir Models
Authors: Myshakin Evgeniy M. , Haeri Foad , Moore Johnathan , Crandall Dustin , Goodman Angela L.
Published: June 2023

The U.S. Department of Energy’s National Energy Technology Laboratory (DOE-NETL) has been developing methods and tools (the online Carbon Dioxide Storage prospeCtive Resource Estimation Excel aNalysis (CO2-SCREEN) tool) to estimate carbon dioxide (CO2) storage potential in subsurface reservoirs. The CO2 storage efficiency terms are input in the tool to calculate storage potential in targeted reservoirs. In this effort, two CO2 storage efficiency terms were evaluated: volumetric displacement (

E

V

) and microscopic displacement (

E

d

). The first term deals with efficiency of CO2 propagation into an accessible reservoir volume, while the second term evaluates effectiveness of native fluid displacement with CO2. The interpreted well logs and core sample measurements were applied to create the heterogeneous reservoir models including geostatistical realizations of porosity and intrinsic permeability fields. Supercritical CO2 was injected over the course of 30 years into brine-saturated reservoir models for clastics, limestone, and dolomite lithologies and deltaic fluvial, aeolian, shallow marine, and reef depositional environments by means of varying reservoir parameters and injection scenarios. The reservoir models providing vertically heterogeneous petrophysical properties and designated as “layered reservoir models” (with homogeneous parameters along each layer of the model) were not determined to be a transition between the homogeneous and heterogeneous models in respect to storage efficiency. Another finding shows that high-efficiency factors do not necessarily mean increased CO2 storage; they rather indicate that the available volume and pore space are more fully utilized. The CO2 storage efficiency factors were evaluated dynamically at the select time points using

P

10

‐

P

50

‐

P

90

percentiles. The results of this study show that the

P

10

‐

P

90

distribution for volumetric efficiency is wider when compared to the microscopic efficiency. It was found that where dominant buoyancy forces drive the plume to the top of a target formation, the volumetric efficiency is low. Tighter sandstone and carbonate formations show prevalence of capillary forces and better utilization of reservoir volume.
A Low-Overhead Auditing Protocol for Dynamic Cloud Storage Based on Algebra
Authors: Ding Fudong , Wu Libing , Zhang Zhuangzhuang , Wu Xianfeng , Ma Chao , Liu Qin
Published: June 2023

With the widespread adoption of cloud storage, ensuring the integrity of outsourced data has become increasingly important. Various cloud storage auditing protocols based on public key cryptography have been proposed. However, all of them require complex cryptographic operations and incur significant storage and communication costs. To address the issues of significant storage overhead for data tags, high computational complexity of cryptographic algorithms, and limited efficiency of dynamic data algorithms in signature algorithm-based cloud storage outsourcing data integrity verification protocols, we propose a dynamic auditing protocol called AB-DPDP, which is based on algebra. Our protocol reduces the computational complexity of tag generation by utilizing basic algebraic operations instead of the traditional cryptographic method used in most current auditing protocols. To reduce storage overhead and protect private data, our protocol stores only tags, allowing for data to be restored through these tags, as opposed to storing both tags and data on the cloud server. To accommodate for more frequent and efficient data dynamics, we propose the dynamic index skip table data structure. Furthermore, the security of our proposed protocol is thoroughly proven based on the security definition of secure cloud storage. Finally, through theoretical analysis and experimental evaluation, we demonstrate the advantages of our scheme in terms of data privacy, storage overhead, communication overhead, computation overhead, and data dynamic efficiency.
Effects of Antioxidant Supplementation on Graves’ Disease: A Meta-Analysis
Authors: Song Qi , Ji Xiaoxue , Xie Ying
Published: June 2023

Objective. The main objective of this study is to evaluate the clinical efficacy of antithyroid drugs combined with antioxidant supplementation represented by selenium in the treatment of Graves’ disease. Methods. Relevant randomized controlled trials (RCTs) were searched in PubMed, MEDLINE, Embase, the Cochrane Library databases, and the Chinese Medical Association. The search was conducted from the time of library construction to December 20, 2022. Three writers gradually examined, evaluated, and graded the literature and then used RevMan 5.3 to analyze the data and develop conclusions. Results. A total of seven papers were screened according to the search requirements. The results showed that free triiodothyronine (FT3) (WMD = −2.29, 95% CI: −3.55 to −1.02,

P
=
0.0004

), free thyroxine (FT4) (WMD = −0.62, 95% CI: −1.05 to −0.18,

P
=
0.0005

), thyrotropin receptor antibody (TRAb) (WMD = −1.31, 95% CI: −1.63 to −0.99,

P
<
0.00001

), and thyroid peroxidase antibody (TPOAb) (WMD = −9.8, 95% CI: −16.57 to −3.03,

P
=
0.005

) in the observation group (selenium supplementation combined with antithyroid drugs) were significantly lower than those in the control group (antithyroid drugs combined with or without placebo). In addition, selenium supplementation can increase serum selenium (WMD = 33.29, 95% CI: 30.7 to 35.87,

P
<
0.00001

), selenoprotein levels (WMD = 1.3, 95% CI: 0.8 to 1.8,

P
<
0.00001

), and blood lipid levels (WMD = 32.3, 95% CI: 17.87 to 46.74,

P
<
0.0001

). It cannot be excluded that the process of selenium supplementation treatment will affect the patient’s lipid levels. Conclusion. Selenium is a trace mineral that is crucial for human health. In patients with Graves’ disease, the use of antithyroid medications along with selenium supplementation can considerably enhance thyroid function. It has the potential to drastically lower TPOAb and TRAb levels as well as FT3 and FT4 levels, which is crucial for the treatment, recovery, and prognosis of hyperthyroid patients. Further research is required to determine whether the impact of antioxidant supplementation on blood lipids will restrict the use of this medication.
Measurement Technique and Result Analysis of Helicopter Rotor Blade Structural Vibration Load
Authors: Zhang Honglin , Wang Zefeng , Xia Pinqi
Published: June 2023

The measurement of helicopter rotor blade structural load amid flight has always been the difficulty in flight test. In this paper, the principle of the existing blade structural load measurement method (electrical measurement method) was analyzed, and the problem of physical decoupling in the use of this method was expounded. As a weak signal measurement, the electrical measurement method also has electromagnetic interference problems, which will affect the flight test period of blade structural load measurement. Therefore, a numerical decoupling measurement method based on fiber Bragg grating (FBG) was proposed. Then, the new method was applied and verified in the load equation modeling test and the flight test under the real atmospheric environment was carried out. Through comparing and analyzing the measured data of the new method and the electrical measurement one, the correctness of the FBG data decoupling method was validated. The results indicate that the method proposed in this paper can effectively improve the efficiency of blade load equation modeling engineering and has good application value.
A Hybrid Convolutional Neural Network and Support Vector Machine‐Based Credit Card Fraud Detection Model
Authors: Berhane Tesfahun , Melese Tamiru , Walelign Assaye , Mohammed Abdu
Published: June 2023

Credit card fraud is a common occurrence in today’s society because the majority of us use credit cards as a form of payment more frequently. This is the outcome of developments in technology and an increase in online transactions, which have given rise to frauds that have caused significant financial losses. In order to detect fraud in credit card transactions, efficient and effective approaches are needed. In this study, we developed a hybrid CNN‐SVM model for detecting fraud in credit card transactions. The effectiveness of our suggested hybrid CNN‐SVM model for detecting fraud in credit card transactions was tested using real‐world public credit card transaction data. The architecture of our hybrid CNN‐SVM model was developed by replacing the final output layer of the CNN model with an SVM classifier. The first classifier is a fully connected layer with softmax that is trained using an end‐to‐end approach, whereas the second classifier is a support vector machine that is piled on top by deleting the final fully connected and softmax layer. According to experimental results, our hybrid CNN‐SVM model produced classification performances with accuracy, precision, recall, F1‐score, and AUC of 91.08%, 90.50%, 90.34%, 90.41, and 91.05%, respectively.
Pulsed Electromagnetic Field Promotes Bone Anabolism in Postmenopausal Osteoporosis through the miR-6976/BMP/Smad4 Axis
Authors: Huang Jinming , Li Yi , Zhu Siyi , Wang Liqiong , Pei Hongliang , Wang Xiangxiu , Bao Tianjie , Jiang Zhiyuan , Yang Lin , He Chengqi
Published: June 2023

Background. Insufficient bone formation is the key reason for the imbalance of bone metabolism and one of the main mechanisms for the occurrence and deterioration of postmenopausal osteoporosis (PMOP). Accumulating evidence has demonstrated that pulsed electromagnetic field (PEMF), as a physiotherapy, can treat osteoporosis by promoting osteogenic differentiation in osteoblasts. However, little is known about its mechanisms. Methods. In vivo, ovariectomized mice were administered PEMF for 4 weeks, and skeletal analysis was conducted. In vitro, hydrogen peroxide-treated mouse osteoblast precursor cells with or without PEMF intervention were subjected to osteogenic differentiation testing and miRNA microarrays. The potential target miRNAs were validated, followed by gene expression assays to further clarify their regulatory relationships with target pathways. Results. We found that PEMF reduced bone loss in ovariectomized mice and promoted osteogenic differentiation of hydrogen peroxide-treated osteoblast precursor cells via downregulation of miR-6976-5p. Mechanistically, reduced miR-6976-5p enhanced the nuclear transport of phosphorylated Smad1/5/9 by upregulating Smad4, thereby activating the BMP/Smad pathway. Additionally, the administration of miR-6976-5p inhibitors successfully promoted osteogenic differentiation in vitro, and its antagomirs protected bone mass in vivo. miR-6976-5p mimics and agomirs acted in the opposite way. Conclusion. These results provide evidence that PEMF alleviates estrogen deficiency-induced bone loss by activating osteoblastic progenitor cells and maintaining their osteogenic differentiation and shed light on the mechanisms involved, which may provide a potential option for the clinical application of PEMF in PMOP.
Comparison of Derivative-Free Optimization: Energy Optimization of Steam Methane Reforming Process
Authors: Kim Minsu , Han Areum , Lee Jaewon , Cho Sunghyun , Moon Il , Na Jonggeol
Published: June 2023

In modern chemical engineering, various derivative-free optimization (DFO) studies have been conducted to identify operating conditions that maximize energy efficiency for efficient operation of processes. Although DFO algorithm selection is an essential task that leads to successful designs, it is a nonintuitive task because of the uncertain performance of the algorithms. In particular, when the system evaluation cost or computational load is high (e.g., density functional theory and computational fluid dynamics), selecting an algorithm that quickly converges to the near-global optimum at the early stage of optimization is more important. In this study, we compare the optimization performance in the early stage of 12 algorithms. The performance of deterministic global search algorithms, global model-based search algorithms, metaheuristic algorithms, and Bayesian optimization is compared by applying benchmark problems and analyzed based on the problem types and number of variables. Furthermore, we apply all algorithms to the energy process optimization that maximizes the thermal efficiency of the steam methane reforming (SMR) process for hydrogen production. In this application, we have identified a hidden constraint based on real-world operations, and we are addressing it by using a penalty function. Bayesian optimizations explore the design space most efficiently by training infeasible regions. As a result, we have observed a substantial improvement in thermal efficiency of 12.9% compared to the base case and 7% improvement when compared to the lowest performing algorithm.
Successful Non-Surgical Root Canal Treatment on Auto-Transplanted Maxillary Premolar with Apical Periodontitis
Authors: Naglieri Christopher M. , Bash Ellie , Karunanayake Glen A. , Camargo Carlos H. R. , Komabayashi Takashi
Published: June 2023

Auto-transplantation is a procedure that replaces traumatized or congenitally missing teeth. While most auto-transplanted teeth are successfully integrated into recipient sites, the donor tooth may develop apical periodontitis, causing early failure. In the present case report, the periodontic resident performed the procedure on a 15-year-old male by selecting donor teeth #4 and #13 and transplanting them at recipient sites #29 and #20, respectively. After 6 weeks, the patient was referred to the endodontic resident for evaluation of tooth #20 due to symptom development. While one auto-transplanted tooth (donor tooth #4, recipient site #29) was successfully integrated, the other (donor tooth #13, recipient site #20) was unsuccessful: the patient was diagnosed with pulp necrosis and a chronic apical abscess. Because of the patient’s age, collaboration among periodontic, endodontic, and orthodontic residents/specialists informed the clinical decision to pursue non-surgical root canal treatment (NSRCT) rather than extraction. The canal was cleaned and shaped to a size #80 using copious irrigation of 2.5% sodium hypochlorite (NaOCl), followed by 17% ethylenediaminetetraacetic acid (EDTA) via the EndoVac Negative Pressure Irrigation system. The tooth was dried with paper points, and then calcium hydroxide was mixed with 2.5% NaOCl and placed with an amalgam carrier 2 mm from the radiographic apex. The tooth was next temporized with Teflon tape and Fuji TRIAGE. Four weeks later, after confirming the patient was asymptomatic and tooth mobility had decreased, the canal was obturated using EndoSequence Bioceramic Root Repair Material Fast Set Putty in 2 mm incremental layers to achieve a three-dimensional fill and create an apical plug to prevent gutta-percha extrusion, then backfilled in incremental layers of gutta-percha to the cementoenamel junction (CEJ). At the 8-month follow-up, the patient was asymptomatic, and the periodontal ligament (PDL) had no signs of periapical pathology. When teeth undergoing auto-transplantation procedures develop apical periodontitis, NSRCT can be implemented.
Solitary Plasmacytoma of the Breast: A Case of an Uncommon Breast Neoplasm
Authors: McCormack Sean , Hamad Eyad , Hamad Amar
Published: June 2023

Plasmacytoma is a rare cancer that originates from a single plasma cell and is characterized by the abnormal proliferation of monoclonal plasma cells. It is typically localized in a single area of the body, most commonly in the bone or soft tissue. Solitary plasmacytoma can be further classified as either solitary plasmacytoma of bone (SPB) or solitary extramedullary plasmacytoma (SEP or EMP). Diagnosis may be delayed in symptomatically silent plasmacytomas, but early diagnosis and prompt treatment are crucial for the management of this disease. The mean age for patients with plasmacytoma varies depending on the specific type of plasmacytoma, but generally, it is more common in older adults. Soft tissue plasmacytomas are uncommon, and plasmacytomas manifesting within the breast are extremely rare, especially when they are not a manifestation of multiple myeloma (MM). This report presents a case of SEP of the breast in a 79-year-old female patient. This rare disease needs to be studied further in terms of long-term survival and disease progression to MM. By raising awareness and understanding of plasmacytoma, we aim to improve outcomes and quality of life for patients affected by this disease.
Table S9 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 9: Sources of antibodies
Table S8 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 8: Comparison of clinical safety data for SHP2 inhibitors
Table S5 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 5: Plasma and brain tissue concentrations, brain-to-plasma ratios, and brain concentration over IC50 values for PF-07284892 and TNO155 at dose levels preferred for concomitant administration
Table S4 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 4: Pharmacokinetics of PF-07284892 in preclinical species
Table S2 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 2: Phosphatase Profiling of PF-07284892
Table S1 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Table 1: X-ray crystallography data collection and refinement statistics
Figure S2 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Figure 2: Intermittent dosing of PF-07284892 preserves efficacy and improves tolerability preclinically
Figure S1 from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Supplementary Figure 1: Comparison of the structures of PF-07284892, RMC445507, TNO155 bound to SHP2
Data from SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy
Authors: Drilon Alexander , Sharma Manish R. , Johnson Melissa L. , Yap Timothy A. , Gadgeel Shirish , Nepert Dale , Feng Gang , Reddy Micaela B. , Harney Allison S. , Elsayed Mohamed , Cook Adam W. , Wong Christina E. , Hinklin Ronald J. , Jiang Yutong , Brown Eric N. , Neitzel Nickolas A. , Laird Ellen R. , Wu Wen-I , Singh Anurag , Wei Ping , Ching Keith A. , Gaudino John J. , Lee Patrice A. , Hartley Dylan P. , Rothenberg S. Michael
Published: June 2023

Abstract
Rationally targeted therapies have transformed cancer treatment, but many patients develop resistance through bypass signaling pathway activation. PF-07284892 (ARRY-558) is an allosteric SHP2 inhibitor designed to overcome bypass-signaling-mediated resistance when combined with inhibitors of various oncogenic drivers. Activity in this setting was confirmed in diverse tumor models. Patients with ALK fusion–positive lung cancer, BRAFV600E-mutant colorectal cancer, KRASG12D-mutant ovarian cancer, and ROS1 fusion–positive pancreatic cancer who previously developed targeted therapy resistance were treated with PF-07284892 on the first dose level of a first-in-human clinical trial. After progression on PF-07284892 monotherapy, a novel study design allowed the addition of oncogene-directed targeted therapy that had previously failed. Combination therapy led to rapid tumor and circulating tumor DNA (ctDNA) responses and extended the duration of overall clinical benefit.
Significance:
PF-07284892–targeted therapy combinations overcame bypass-signaling-mediated resistance in a clinical setting in which neither component was active on its own. This provides proof of concept of the utility of SHP2 inhibitors in overcoming resistance to diverse targeted therapies and provides a paradigm for accelerated testing of novel drug combinations early in clinical development.

See related commentary by Hernando-Calvo and Garralda, p. 1762.

This article is highlighted in the In This Issue feature, p. 1749
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: June 2023

Brigimadlin (BI 907828) is an oral MDM2–p53 antagonist that has shown encouraging antitumor activity in vivo. We present phase Ia results from an open-label, first-in-human, phase Ia/Ib study investigating brigimadlin in patients with advanced solid tumors (NCT03449381). Fifty-four patients received escalating doses of brigimadlin on day 1 of 21-day cycles (D1q3w) or days 1 and 8 of 28-day cycles (D1D8q4w). Based on dose-limiting toxicities during cycle 1, the maximum tolerated dose was selected as 60 mg for D1q3w and 45 mg for D1D8q4w. The most common treatment-related adverse events (TRAE) were nausea (74.1%) and vomiting (51.9%); the most common grade ≥3 TRAEs were thrombocytopenia (25.9%) and neutropenia (24.1%). As evidence of target engagement, time- and dose-dependent increases in growth differentiation factor 15 levels were seen. Preliminary efficacy was encouraging (11.1% overall response and 74.1% disease control rates), particularly in patients with well-differentiated or dedifferentiated liposarcoma (100% and 75% disease control rates, respectively).

Significance:

We report phase Ia data indicating that the oral MDM2–p53 antagonist brigimadlin has a manageable safety profile and shows encouraging signs of efficacy in patients with solid tumors, particularly those with MDM2-amplified advanced/metastatic well-differentiated or dedifferentiated liposarcoma. Further clinical investigation of brigimadlin is ongoing.

See related commentary by Italiano, p. 1765.

This article is highlighted in the In This Issue feature, p. 1749
Versions of Local Time
Authors: Michon John A.
Published: June 2023

In the interdisciplinary study of time we see a shift from a physicalistic paradigm, as we know it from Julius T. Fraser’s work, to a rather more cognitive-theoretical approach, as advanced, for instance, by Allen Newell, who takes mental activity to consist of a complex, active search through a problem space. In this article, I compare some recent efforts of physically oriented researchers Prigogine and Barbour with the cognitive approach taken by chronopsychologists Lakoff, Gibson, Jones, Leyton and others. It stipulates that the classical notion of temporality as an absolute property of the universe has in fact been replaced by versions of local time. Recent examples of timing on the basis of local time include temporal information processing according to the demands of metaphor, scripts, dynamic attention, and more. The common ground appears to be that time is a derived entity, based on embodied (inborn) as well as situated (acquired) processing activity.
The Temporal Challenge of Hope
Authors: Ostovich Steve
Published: June 2023

Hope informs and inspires our actions. We look to succeed at achieving what we hope for, and this orients our hope towards the future in which time is conceived linearly. The connection between hope as success and linear time creates several difficulties when we seek to defend our hope. This is especially the case regarding past hopes and the dead, who can no longer hope for themselves. J. T. Fraser’s hierarchical theory of time’s conflicts is a complex theory of time that makes possible thinking through hope more critically.
Towards an Interdisciplinary Approach to Time in Fiction
Authors: Ksenofontova Alexandra
Published: June 2023

The paper surveys five major perspectives on studying time in fiction: narratology, history of temporal regimes, temporal pluralism, aesthetics of time, and politics of time. It argues that these approaches have so far remained largely unintegrated, leading to a separation between areas of literary criticism that are in reality closely linked. In particular, some approaches separate time as subject from time as the principal element of narratives. Some approaches disregard the transhistorical plurality of temporal experiences, while others turn a blind eye to larger historical changes in the perception of time. Finally, some scholars choose to focus only on temporal aesthetics, while others explore only the fictional politics of time. Scrutinizing these three schisms of studying time in literary criticism, the paper argues for a re-integrated approach that accommodates insights from various disciplines and adopts a broader perspective on time and temporality in fiction.
Time, Conflicts and Chance
Authors: Lestienne Rémy
Published: June 2023

After having briefly introduced the circumstances by which J. T. Fraser was led to build his theory of Time as Conflicts and the way this notion takes consistency through several levels, according to the abilities of the inert or living beings that populate the world, I try to analyze and comment upon them. At each of these levels, the complexity of time is manifested by concepts that oppose each other: permanence and change, movement and rest, divisibility and atomicity, chance and irreversibility, increasing entropy and local decreases, etc. In Fraser’s view, as in mine, the most important issues concern the division of time into past, present, and future, and the irreversibility of the world’s course. Fraser writes that these concepts become consistent only with the appearance of life, because only living beings (and even more so the human race) perceive these things in their Umwelt. Without disagreeing with him on this point, I emphasize the dominant role that Chance plays in the evolution of the world, at all levels considered by Fraser (except atemporality), even if living systems learned, sooner and better than any others, how to take advantage of their position as thermodynamically open systems. I use this argument to suggest, after Alfred North Whitehead, that next to the time of the living we must posit the existence of an objective motor of the world, restoring the ontology of the division of events into past, present, and future, as well as the specificity of the present.
A Different Cup of Time
Authors: Turner Frederick
Published: June 2023

This essay provides a poetic picture of the author’s experience of the International Society for the Study of Time, of which he has been a member since the 1970s. It includes excerpts from the author’s poetry, including from “Turn Again,” an unpublished work of “semantic autobiography” that charts the process by which the meanings of words emerge and deepen over a lifetime. The word “Time,” especially as characterized by the founder of the Society, J. T. Fraser, is the central actor in the Society’s social and intellectual drama.
Obstetric Violence: Sterilisation without Consent. The Case of Y.P. v. Russian Federation
Authors: den Exter André
Published: June 2023

On 20 September 2022, the European Court of Human Rights (ECtHR) delivered its judgment in a remarkable case on sterilisation without the patient’s consent, Y.P. v Russian Federation (ECtHR, application no. 43399/13, 20 September 2022). According to the Court, there is no inhuman and degrading treatment, but it was a justified medical procedure. However, the Court did conclude a violation of the right to private life, under Article 8 ECHR. This outcome is at odds with an earlier sterilisation case without consent, V.C. v Slovakia (V.C. v. Slovakia, ECtHR application no. 18968/07, 8 November 2011). The question is how both rulings can be understood, especially the legal consideration regarding the prohibition of torture. After all, both cases lacked the patient’s consent.
Bringing Together the Criminologies of Atrocity and Serious Economic Crimes
Authors: Aydın-Aitchison Andy
Published: June 2023

The paper reflects on the value of linking criminological research on atrocity with that on serious economic crime. The two areas of criminological research are outlined briefly, before common challenges around complexity and interdependence are set out. An example of a criminal career encompassing both atrocity and serious economic criminality is put forward to support claims that atrocity and economic crime can usefully be studied together. Three further examples of research are discussed to show the possible merits of bringing together two criminological strands. Ultimately, studying the two forms of criminality together would respect the lived experience of victims, who see firsthand how atrocity and serious economic crime go hand in hand.
How many co-authors had Perpetua and Saturus?
Authors: Braginskaya Nina V. , Lebedev Pavel N.
Published: June 2023

The early Christian work “The Passion of Saints Perpetua and Felicity” consists of different parts combined into a single book. Three parts are generally accepted: 1) Perpetua’s Notes, 2) Saturus’s Vision, 3) the Eyewitness story and the Prologue and Epilogue written by the same author. We argue that the Prologue plus Epilogue and the Eyewitness story had different authors and there was one more person, who was neither a participant nor a contemporary of the Carthaginian martyrdom. The results of his activity can be found in short sentences connecting the parts, as well as in violations of the structure of the narrative and a serious mistake made in the enumeration of the arrested catechumens. The authors claim also that this kind of collection as in The Passion had no analogues in ancient classical literature and followed the model of the New Testament.
Muslims’ Experience with Islamophobia in Slovakia
Authors: Kosárová Dominika
Published: June 2023

In several European countries, Slovakia included, Islamophobia has been shaped by the challenges faced by Europe (an influx of refugees, terrorism, rise of the far right) since circa 2015. Anti-Muslim narratives have penetrated politics as well as the media and are shared by a significant part of the Slovak population. This article aims at contributing to the existing research on Islamophobia in Slovakia through an exploratory case study focusing on a different perspective, Muslims themselves. The main objective of the research is to identify the magnitude and character of Islamophobia experienced by Muslims in Slovakia since 2015. Data were gathered using an online survey. The findings revealed not only the extent but also the most common features of Islamophobia experienced by Muslims, including the type of incidents, the places of their occurrence, and the nexus between Islamophobic incidents and origin of respondents (Slovak or foreign), external manifestation of their faith, and sex.
Franz Brentano’s Conception of the Object and its Intentional Inexistence
Authors: Antonelli Mauro
Published: June 2023

In line with earlier works, this article argues for a “continuist” interpretation of Brentano’s conception of intentionality. It maintains that Brentano’s conception of intentionality rests on a complex set of notions, which are reduced to a minimal core or applied more fully depending on the complexity of the mental phenomenon under consideration and perspective from which it is analyzed. The article positions this conceptual structure in relation to theories of objects developed within the framework of late- and Neo-Scholastic philosophy where, since the psychic act can relate to its object in different ways, the different types and roles of objects must be distinguished. This theory of objects enables Brentano to reinterpret Aristoteles’s idea of the intentionality of mental phenomena in light of the commentaries and interpretations of Thomas Aquinas while also giving space to other medieval texts.