bluuebunny/crossref_metadata_2025 huggingface dataset:
Semi-Permanent Stuck-At Fault injection attacks on Elephant and GIFT lightweight ciphers
Authors: Joshi Priyanka , Mazumdar Bodhisatwa
Published: April 2024

Fault attacks pose a potent threat to modern cryptographic implementations, particularly those used in physically approachable embedded devices in IoT environments. Information security in such resource-constrained devices is ensured using lightweight ciphers, where combinational circuit implementations of SBox are preferable over look-up tables as they are more efficient regarding area, power, and memory requirements. Most existing fault analysis techniques focus on fault injection in memory cells and registers. Recently, a novel fault model and analysis technique, namelySemi-Permanent Stuck-At(SPSA) fault analysis, has been proposed to evaluate the security of ciphers with combinational circuit implementation ofSubstitution layerelements, SBox. In this work, we propose optimized techniques to recover the key in a minimum number of ciphertexts in such implementations of lightweight ciphers. Based on the proposed techniques, a key recovery attack on the NIST lightweight cryptography (NIST-LWC) standardization process finalist,ElephantAEAD, has been proposed. The proposed key recovery attack is validated on two versions ofElephantcipher. The proposed fault analysis approach recovered the secret key within 85–240 ciphertexts, calculated over 1,000 attack instances. To the best of our knowledge, this is the first work on fault analysis attacks on theElephantscheme. Furthermore, an optimized combinational circuit implementation ofSpongentSBox (SBox used inElephantcipher) is proposed, having a smaller gate count than the optimized implementation reported in the literature. The proposed fault analysis techniques are validated on primary and optimized versions ofSpongentSBox through Verilog simulations. Further, we pinpoint SPSA hotspots in the lightweightGIFTcipher SBox architecture. We observe thatGIFTSBox exhibits resilience toward the proposed SPSA fault analysis technique under the single fault adversarial model. However,eightSPSA fault patterns reduce the nonlinearity of the SBox to zero, rendering it vulnerable to linear cryptanalysis. Conclusively, SPSA faults may adversely affect the cryptographic properties of an SBox, thereby leading to trivial key recovery. TheGIFTcipher is used as an example to focus on two aspects: (i) its SBox construction is resilient to the proposed SPSA analysis and therefore characterizing such constructions for SPSA resilience and (ii) an SBox even though resilient to the proposed SPSA analysis, may exhibit vulnerabilities toward other classical analysis techniques when subjected to SPSA faults. Our work reports new vulnerabilities in fault analysis in the combinational circuit implementations of cryptographic protocols.
The Role of Zinc Triflate Additive for Improved Electrochemical Performance of Nickel-Rich Layered Oxide Lithium Battery Cathode via Suppression of Interfacial Parasitic Reactions
Authors: Akella Sri Harsha , Blanga Shalev , Zysler Melina , Radovsky Gal , Noked Malachi
Published: April 2024

Nickel-rich layered oxide cathode materials with low cobalt content, such as LiNi0.90Mn0.05Co0.05O2 (NMC90), have the potential to enable cost-effective, high-energy-density lithium-metal batteries. However, NMC90 cathode materials are prone to severe parasitic reactions at higher voltages during prolonged cycling. The addition of small percentages of electrolyte additives to the neat commercial electrolyte can significantly enhance the overall electrochemical performance of lithium-metal batteries. This study investigates the effects of zinc triflate (Zn(Otf)2) as an electrolyte additive on the enhancement of the electrochemical performances of lithium-metal batteries comprising nickel-rich layered oxide cathode materials. X-ray photoelectron spectroscopy analysis revealed that Zn(Otf)2 decomposition leads to enhanced fluorination at the interfacial layers, which contributes to improved chemical stability. Utilizing operando electrochemical mass spectroscopy, we demonstrate that Zn(Otf)2 additives effectively suppress the electrolyte degradation, which is otherwise detrimental to electrochemical performance. Electrochemical studies show that the inclusion of only ∼1% Zn(Otf)2 as additive in neat commercial electrolyte enhances the electrochemical performance indicated by a 10% improvement in discharge capacity after 150 cycles. This study paves the way for researchers to develop novel fluorinated triflate based electrolyte additives aimed at enhancing the stabilization of interfaces for lithium ion, and potentially also Li-metal batteries.
Review—Electrochemical Sensing of Uric Acid: Methods and Recent Materials
Authors: Dhinasekaran Durgalakshmi , John Josfel Flora , Subashchandran Shanthi
Published: April 2024

Uric acid (UA) is an important biomarker in blood to diagnosis diseases linked with hyperuricemia. Although several detection methods exist for UA sensing, electrochemical method has emerged as a promising alternative. For effective performance of a biosensor, the choice of electroactive material plays a crucial role. The developed electrodes are enzymatic and non-enzymatic with modified nano-structures of metal oxides, ferrites and carbon-based materials. Several combinations of nanocomposites using metal oxides with carbon-based compounds show promising results for biosensor applications. This is attributed to its functional groups, higher surface area and porous nature that can improve the sensing performance as it requires only quick-time processing with inexpensive and direct detection methods. The electrochemical method uses anodic peak current which is the analytical signal to sense the electrochemical oxidation of UA. This technique paves a new way to make electrodes for point-of-detection devices in near future. It could be the next generation of non-invasive analysis for food hygiene as well as biomedical and clinical applications. This review focuses on materials used in electrochemical sensing of UA and discusses on the application of different electrochemical techniques in UA detection.
Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance
Authors: Medow Marvin S. , Stewart Julian M.
Published: April 2024

We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.
Paraganglioma of the Neck: A Rare Case With Spinal Metastasis
Authors: McCormack Sean , Hamad Eyad , Hamad Amar
Published: April 2024

Paragangliomas are rare neuroendocrine tumors that arise from the paraganglia, which are clusters of neuroendocrine cells associated with the autonomic nervous system. These tumors are commonly found in the adrenal medulla but can also occur in other locations outside the adrenal gland. Here, we present a case report of a slow-growing paraganglioma in the left neck with spinal metastasis in a 60-year-old man. This case highlights the importance of considering paraganglion tumors in the differential diagnosis of neck masses and the need for early diagnosis and management to prevent potential complications. Importantly, both the clinical picture and anatomical location of these tumors is important when determining treatment plans.
Eccentric Compression Performance of Core‐Steel Tube with T‐Shaped Steel Reinforced Concrete Column
Authors: Gao Liang , Wang Peng , You Xuehui
Published: April 2024

This paper introduces a novel steel–concrete composite column referred to as the core‐steel tube with T‐shaped steel reinforced concrete (CSTRC) column, which is composed of a core steel tube with T‐shaped steel embedded in a reinforced concrete column. To investigate the mechanical performance of the CSTRC column under eccentric compressive load, the load–deformation response, stress, and strain distribution of CSTRC columns under eccentric load are analyzed by finite element software. Furthermore, the effects of slenderness ratio, concrete and steel strength on the eccentric compression performance of CSTRC columns are also discussed. Finally, a set of formulas for predicting the ultimate strength of the CSTRC columns is proposed. The study results reveal that: (1) The established finite element model accurately predicts bearing capacity and strain development. (2) When the eccentricity is 0.2, the specimen exhibits characteristics indicative of small eccentricity failure. Conversely, when the eccentricity is 0.8, the specimen demonstrates traits associated with large eccentricity failure. Furthermore, as the eccentricity increases, there is a notable decrease in the bearing capacity of the specimen. (3) The slenderness ratio affects the failure mode of the CSTRC columns, with consideration for second‐order effects necessary when the ratio exceeds 22. (4) Increasing the concrete strength, steel strength, and steel ratio significantly enhances the ultimate load values of the CSTRC columns. (5) A comparison between calculated and simulated values demonstrates good agreement, validating the accuracy of the proposed method.
Experimental and Numerical Studies on the Vibration of Hybrid Composite with an Edge Crack
Authors: Alemneh Adimass Solomon , Gebrekidan Koricho Ermias , Paramasivam Velmurugan , Krishnan Vignesh
Published: April 2024

The hybrid composite plate is increasingly used in marine, robotic arm, and other applications. Edge crack is the greatest common fault in the structural systems during its working time. In this research, the successful fabrications of a hybrid composite of epoxy‐based composites reinforced with bamboo and glass fibers have been done to examine the vibration characteristics under free vibration. First‐order shear deformation theory is used to study the fundamental natural frequencies of asymmetrically hybrid composite beam with edge cracks for cantilever beam boundary conditions. Both numerical (FEM) using ABAQUS software and experimental investigations are done for the vibration analysis of unidirectional bamboo/glass fiber epoxy hybrid composite (BGHC) beam with edge cracks using fracture mechanics theory. It is observed that implications edge crack with different crack depth and various fiber weight ratio parameters have a major effect on vibration analysis. Also, it is clear that the natural frequencies of the hybrid composite are significantly affected due to the fiber weight ratio and crack depth of the hybrid composite materials. So, crack lengths are playing a vital role in the dynamic or vibration characteristics of the hybrid composite materials. The results of natural frequencies have been shown that they are decreased with an increase in crack depth and an increase in the bamboo fiber weight. Thus, BGHC‐2 made from 30% bamboo and 10% glass fiber can be a viable candidate for applications that will produce good vibration properties. Generally, the first‐third natural frequency of the hybrid composite beam decreases within the increase of bamboo fiber and decreases in glass fiber. The composite materials having 60% of epoxy with 20% bamboo and 20% glass fiber, and 60% of epoxy with 10% glass and 30% bamboo fibers, are observed with a gradual decrease in the values of natural frequencies with respect to increasing in crack depth. A fine agreement was accomplished between the simulation and experimental results. Therefore, the present approach can be used to identify cracks for mechanical health monitoring by linking the variation in natural frequencies of the hybrid composite beams.
PV Power Forecasting in the Hexi Region of Gansu Province Based on AP Clustering and LSTNet
Authors: Li Xujiong , Yang Guoming , Gou Jun
Published: April 2024

Accurate PV power forecasting is becoming a mandatory task to integrate the PV system into the power grid, schedule it, and ensure the safety of the power grid. In this paper, a novel model for PV power prediction using AP-LSTNet has been proposed. It consists of a combination of affinity propagation clustering and long-term and short-term time series network models. First, the affinity propagation algorithm is used to divide the regionally distributed photovoltaic station clusters into different seasons. The Pearson correlation coefficient is used to determine the strong correlation between meteorological factors of photovoltaic power, and the bilinear interpolation method is used to encrypt the meteorological data of the corresponding photovoltaic station cluster. Furthermore, LSTNet is used to mine the long-term and short-term temporal and spatial dependence of photovoltaic power, and meteorological factor series and linear components of auto-regression are superimposed to realize the simultaneous prediction of multiple photovoltaic stations in the group. Finally, PV power plants in five cities, Wuwei, Jinchang, Zhangye, Jiuquan, and Jiayuguan in the Hexi region of Gansu Province, China, will be selected to test the proposed model. The experimental comparison shows that the prediction model achieves high prediction accuracy and robustness.
Effects of Mechanical and Electrical Topologies on Piezoelectric Stacked Energy Harvesting in Vehicle Suspensions
Authors: Li Yang , Wang Ruoyu , Wan Zhao , Chen Ming , Liang Guijie
Published: April 2024

The choice of mechanical and electrical topologies can affect piezoelectric energy harvesting efficiency, but the problem of achieving high‐efficiency energy conversion in energy harvesters stacked as cantilevers has not been perfectly solved. This study focuses on the topology of piezoelectric elements in a stacked vehicle suspension vibration energy harvesting device. Through theoretical analysis, the stress expressions of the excited and driven elements are derived. The stress of the piezoelectric elements is affected by the positions of the connection and excitation points. A stress model was established for a four‐piece piezoelectric element connected by a thin light rod in ANASYS. The simulation results show that the average stress in the piezoelectric bending element model is maximum when the excitation and connection points are located at both ends of the free end. Compared with the middle position of the free end of the piezoelectric element, the average stress of the model is increased by 92.904%. Considering the difference in voltage generated by piezoelectric elements, four kinds of electrical topology are designed and analyzed experimentally. When the driven elements are connected in parallel and then connected in series with the excited element, the output power varied the least with the change of load resistance. The system produces a high power and offers a wide selection of load resistors. When the load is 26 kΩ, a single set of four piezoelectric elements produces 86.407 mW of output power.
Evaluating the Influence of Artificial Intelligence on Scholarly Research: A Study Focused on Academics
Authors: Ekundayo Tosin , Khan Zafarullah , Nuzhat Sabiha
Published: April 2024

This study is aimed at exploring the impact of artificial intelligence (AI) on academic research by conducting a focus group research strategy. The focus group consists of individuals who are actively involved in academic research and have experience working with AI technologies. The purpose of the focus group is to gather in‐depth insights into how AI has influenced research methodologies, findings, and overall knowledge creation. The study will begin by identifying seven participants through purposive sampling, with an aim of recruiting a diverse group of individuals from various academic disciplines. Purposive sampling, also known as selective sampling, enhances the study’s validity by ensuring that the sample consists of individuals with a high level of expertise in the subject matter. Seven is large enough to generate a diverse range of perspectives and experiences and small enough to ensure that every participating academic researcher has a chance to contribute to the conversation. The focus group is conducted using a Zoom video conferencing to gather academics from different institutions across the world. It also eliminates distance issue required for conducting an in‐person session. This provides opportunity to cover a wide array research specialization representation. Data analysis is conducted using a thematic analysis approach, with a focus on identifying key themes and patterns that emerge from the data. The findings of this study contribute to a better understanding of the impact of AI on academic research and provide insights into the potential future direction of AI in academic research. While the study is aimed at providing practical recommendations for researchers who are interested in incorporating AI into their research practices, it also ignites the conversation on future incorporation of technologies into academic research activity.
Microbial‐ and Plant‐Derived Bioactive Peptides and Their Applications against Foodborne Pathogens: Current Status and Future Prospects
Authors: Parvez Anowar Khasru , Jubyda Fatema Tuz , Ayaz Mohammed , Sarker Amily , Haque Nabila , Khan Md. Shahriar , Mou Taslin Jahan , Rahman Md. Atikur , Huq Md. Amdadul
Published: April 2024

Bioactive peptides (BAPs) obtained from plants and microbes have been thoroughly explored and studied due to their prophylactic properties. The use of BAPs seems to be a promising substitute for several currently available antibiotics because of their antimicrobial properties against foodborne pathogens. BAPs have several other useful properties including antitumor, antihypertensive, antioxidant, antiobesity, and antidiabetic activities. Nowadays, scientists have attempted to recombinantly synthesize bioactive peptides to study their characteristics and potential uses, since BAPs are not found in large quantities in nature. Many pathogenic microorganisms including foodborne pathogens are becoming resistant to various antibiotics. To combat these pathogens, scientists are working to find novel, innovative, and safe antimicrobial agents. Plant‐ and microbe‐based BAPs have demonstrated noteworthy antimicrobial activity against a wide range of pathogenic microorganisms, including foodborne pathogens. BAPs can kill pathogenic microorganisms by disrupting membrane integrity, inhibiting DNA and RNA synthesis, preventing protein synthesis, blocking protein activity, or interacting with certain intracellular targets. In addition, the positive effect of BAP consumption extends to gut microbiota modulation and affects the equilibrium of reactive oxygen species in the gut. This article discusses recombinant BAPs, BAPs generated from plants and microbes, and their antimicrobial applications and modes of action for controlling foodborne pathogens.
Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients
Authors: Nief Corrine A. , Hammer Phoebe M. , Wang Aihui , Charu Vivek , Tanweer Amina , Litkouhi Babak , Kidd Elizabeth , Gentles Andrew J. , Howitt Brooke E.
Published: April 2024

Purpose:

Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing.

Experimental Design:

We collected a 105-patient case-control cohort of stage I EEC comprising 45 patients who experienced recurrence less than 6 years after excision, and 60 Fédération Internationale de Gynécologie et d'Obstétrique grade-matched controls without recurrence. We first utilized two RNA-based, previously validated machine learning approaches, namely, EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI), which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 patients with stage I EEC.

Results:

EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI, 4.1–23.8; P < 0.001).

Conclusions:

Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.
Cell-Free Human Papillomavirus DNA Is a Sensitive Biomarker for Prognosis and for Early Detection of Relapse in Locally Advanced Cervical Cancer
Authors: Sivars Lars , Jylhä Cecilia , Crona Guterstam Ylva , Zupancic Mark , Lindqvist Britta , Nordenskjöld Magnus , Tham Emma , Hellman Kristina
Published: April 2024

Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC).

Experimental Design: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type–specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics.

Results: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1–2 months after end-of-treatment), or tumor evaluation (3–4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time.

Conclusions: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.
Evaluating the Efficacy of AI Chatbots as Tutors in Urology: A Comparative Analysis of Responses to the 2022 In-Service Assessment of the European Board of Urology
Authors: May Matthias , Körner-Riffard Katharina , Kollitsch Lisa , Burger Maximilian , Brookman-May Sabine D. , Rauchenwald Michael , Marszalek Martin , Eredics Klaus
Published: April 2024

Introduction: This study assessed the potential of large language models (LLMs) as educational tools by evaluating their accuracy in answering questions across urological subtopics. Methods: Three LLMs (ChatGPT-3.5, ChatGPT-4, and Bing AI) were examined in two testing rounds, separated by 48 h, using 100 Multiple-Choice Questions (MCQs) from the 2022 European Board of Urology (EBU) In-Service Assessment (ISA), covering five different subtopics. The correct answer was defined as “formal accuracy” (FA) representing the designated single best answer (SBA) among four options. Alternative answers selected from LLMs, which may not necessarily be the SBA but are still deemed correct, were labeled as “extended accuracy” (EA). Their capacity to enhance the overall accuracy rate when combined with FA was examined. Results: In two rounds of testing, the FA scores were achieved as follows: ChatGPT-3.5: 58% and 62%, ChatGPT-4: 63% and 77%, and BING AI: 81% and 73%. The incorporation of EA did not yield a significant enhancement in overall performance. The achieved gains for ChatGPT-3.5, ChatGPT-4, and BING AI were as a result 7% and 5%, 5% and 2%, and 3% and 1%, respectively (p > 0.3). Within urological subtopics, LLMs showcased best performance in Pediatrics/Congenital and comparatively less effectiveness in Functional/BPS/Incontinence. Conclusion: LLMs exhibit suboptimal urology knowledge and unsatisfactory proficiency for educational purposes. The overall accuracy did not significantly improve when combining EA to FA. The error rates remained high ranging from 16 to 35%. Proficiency levels vary substantially across subtopics. Further development of medicine-specific LLMs is required before integration into urological training programs.
Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings
Authors: King Cole , Mali Ivina , Strating Hunter , Fangman Elizabeth , Neyhard Jenna , Payne Macy , Bossmann Stefan H. , Plakke Bethany
Published: April 2024

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females. Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.
Experiences of People with Aphasia Receiving Enhanced Community-Based Speech-Language Pathology Provided by Speech-Language Pathology Students
Authors: Gibbons Nicola , Cook Kate J. , Sutherland Dean , Tillard Gina
Published: April 2024

Introduction: Treatment intensity for people with aphasia (PWA) is a significant factor in enhancing recovery. Personal factors such as fatigue, physical endurance, and motivation as well as clinician availability have been described as barriers to increased intensity. The use of student therapists has been shown to assist with addressing service gaps. Methods: The aim of the study was to explore the experiences of PWA who received enhanced community-based treatment delivered by speech-language pathology (SLP) students. Enhanced community-based treatment was defined as three or more treatment sessions per week targeting communication. Semi-structured interviews were conducted with 10 PWA living in New Zealand. Interview data were analysed with reflexive thematic analysis. Results: Two themes and six sub-themes were developed. Theme 1 related to intensity and included more treatment is better than less (sub-theme 1), there’s a “right time” for more intensive treatment (sub-theme 2), the hard work is worth the effort (sub-theme 3). Theme 2 related to working with SLP students; it didn’t feel like they were students (sub-theme 4), we just got on so well (sub-theme 5), and they listened to what I wanted (sub-theme 6). Conclusions: The findings confirm that PWA value access to more intensive treatment and desire involvement in decisions about flexible treatment schedules. PWA have positive experiences when treatment is provided by SLP students. Implications for clinical practice and future research directions are discussed.
Molekulare Pathologie bei Brustkrankheiten: diagnostische, prognostische und therapeutische Instrumente
Authors: Varga Zsuzsanna , Maccio Umberto
Published: April 2024

Molekulare Tests bei Brustkrebs haben zunehmend an Aufmerksamkeit und Bedeutung gewonnen, da spezifische molekulare Ergebnisse nicht nur onkologische Entscheidungen zum systemischen adjuvanten oder neoadjuvanten Setting oder zum metastasierten Setting mitbestimmen können, sondern zunehmend in diagnostischen histopathologischen Routinediensten zur Unterscheidung zwischen morphologisch überlappenden oder mehrdeutigen histologischen Bildern dienen. Die Diagnosewerkzeuge umfassen in den meisten Fällen ein breites Spektrum an immunhistochemischen Panels, gefolgt von entitätsspezifischen In-situ-Hybridisierungssonden und, in bestimmten Fällen, von Next-Generation-Sequenzierung. Der Ablauf, welche Methodik angewandt wird und in welcher Reihenfolge, hängt von der spezifischen Entität bzw. von der jeweiligen Differenzialdiagnose ab. In Bezug auf prognostische/prädiktive molekulare Tests basieren die Auswahl des Assays und der Arbeitsablauf auf klinischen Algorithmen und auf dem Nachweis gezielter Therapien je nach den molekularen Veränderungen. In dieser Übersichtsarbeit möchten wir den Einsatz molekularer Techniken 1) im histologischen diagnostischen Setting (wie Subtypisierung von invasiven Karzinomen/malignen Spindelzelltumoren und Sarkomen und einigen B3-Läsionen) und 2) im Zusammenhang mit adjuvanten, neoadjuvanten oder anderen klinischen Settings mit besonderem Schwerpunkt auf gezielten Therapien ansprechen.
Bladder Stones in Renal Transplant Patients: Presentation, Management, and Follow-up
Authors: Sandberg Maxwell , Cohen Adam , Escott Megan , Temple Davis , Marie-Costa Claudia , Rodriguez Rainer , Gordon Alex , Rong Anita , Andres-Robusto Brian , Roebuck Emily H. , Whitman Wyatt , Webb Christopher J. , Stratta Robert J. , Assimos Dean , Wood Kyle , Mirzazadeh Maajid
Published: April 2024

Introduction: The study aim was to analyze the presentation, management, and follow-up of renal transplant patients developing bladder calculi. Methods: Patients who underwent renal transplant with postoperative follow-up at our institution were retrospectively analyzed (1984–2023) to assess for the development of posttransplant bladder stones. All bladder stones were identified by computerized tomography imaging and stone size was measured using this imaging modality. Results: The prevalence of bladder calculi post-renal transplantation during the study window was 0.22% (N = 20/8,835) with a median time to bladder stone diagnosis of 13 years posttransplant. Of all bladder stone patients, 6 (30%) received deceased donor and 14 (70%) living donor transplants. There were 11 patients with known bladder stone composition available; the most common being calcium oxalate (N = 6). Eleven (55%) patients had clinical signs or symptoms (most commonly microhematuria). Fourteen of the bladder stone cohort patients (70%) underwent treatment including cystolitholapaxy in 12 subjects. Of these 14 patients, 9 (64%) were found to have nonabsorbable suture used for their ureteroneocystostomy closure. Conclusions: The prevalence of bladder stones post-renal transplant is low. The utilization of nonabsorbable suture for ureteral implantation was the main risk factor identified in our series. This technique is no longer used at our institution. Other factors contributing to bladder stone formation in this population warrant identification.
O drama refratado em arte do ator
Authors: Portich Ana
Published: April 2024

In the 18th Century authors such as Luigi and François Roccoboni, Rémond de Saint- Albine and Diderot have attempted to define the actor’s art from the perspective of the actor’s posture concerning sensibility.
Fídias ou Da criação
Authors: Petrônio Rodrigo
Published: April 2024

This dialogue is a reflection on the act of creation, with a socratic structure, and Giacomo Leopardi's dialogues, obviouslly whitout their brillancy, are some thems which Socrates and Fidias talk about in this text.
New distribution record of Alstonia sebusii (Van Heurck & Müll. Arg.) Monach. from Manipur, India
Authors: Kazhuhrii Eshuo
Published: April 2024

The genus Alstonia belonging to the Apocyanaceae family is represented by 44 species distributed worldwide. In India, the taxon is represented by eight species, reported from Andaman & Nicobar Islands, Western Ghats, Eastern Ghats, western Himalaya, and northeastern regions. The present study reported the occurrence of Alstonia sebusii from Pudunamei village, Mao, a new addition to the flora of Manipur. Detailed morphological descriptions and measurements were recorded based on living plant specimens. The plant is locally called ‘Topfiira Koso Pro’ having ethno-medicinal properties and widely been used by local people of the state to treat various ailments. The plant is rare and found to occur at specific location at Pudunamei village.
Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults
Authors: Fayol Antoine , Schiele François , Ferrières Jean , Puymirat Etienne , Bataille Vincent , Tea Victoria , Chamandi Chekrallah , Albert Franck , Lemesle Gilles , Cayla Guillaume , Weizman Orianne , Simon Tabassome , Danchin Nicolas ,   on behalf of the FAST-MI Investigators
Published: April 2024

BACKGROUND:

Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed.

METHODS:

The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences.

RESULTS:

Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66–0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80–1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62–0.98]).

CONCLUSIONS:

In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.
Long‐Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model
Authors: Balaji Poornima , Barry Michael A. , Tran Vu Toan , Marschner Simone , Lu Juntang , Nguyen Duc Minh , Mina Ashraf , Bandodkar Sushil , Alvarez Shirley , James Virginia , Ronquillo John , Varikatt Winny , Kovoor Pramesh , McEwan Alistair , Thiagalingam Aravinda , Thomas Stuart P. , Qian Pierre C.
Published: April 2024

Background

Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long‐term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation.

Methods and Results

Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80–120 W for 240 s–480 s) and 12 to 16 radiofrequency ablations (180 s–240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0–343.4) mm
2
versus 50.1 (IQR, 32.0–74.6) mm
2
,
P
<0.001; depth 16.4 (IQR, 13.9–18.9) mm versus 7.5 (IQR, 6.0–8.9) mm
P
<0.001] and 5.5 months [area 20.0 (IQR, 3.4–31.8) mm
2
versus 5.0 (IQR, 1.4–7.3) mm
2
,
P
=0.025; depth 5.9 (IQR, 1.9–8.8) mm versus 3.1 (IQR, 1.2–4.1) mm,
P
=0.005] using mixed models. Renal denervation resulted in significant long‐term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (
P
=0.01) and 45% reduction with radiofrequency (
P
=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (
P
<0.001) and 72.9% reduction with radiofrequency (
P
<0.001)] at 5.5 months compared with undenervated controls.

Conclusions

Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.
Finding Pattern in the Noise: Persistent Implicit Statistical Knowledge Impacts the Processing of Unpredictable Stimuli
Authors: Kóbor Andrea , Janacsek Karolina , Hermann Petra , Zavecz Zsófia , Varga Vera , Csépe Valéria , Vidnyánszky Zoltán , Kovács Gyula , Nemeth Dezso
Published: April 2024

Humans can extract statistical regularities of the environment to predict upcoming events. Previous research recognized that implicitly acquired statistical knowledge remained persistent and continued to influence behavior even when the regularities were no longer present in the environment. Here, in an fMRI experiment, we investigated how the persistence of statistical knowledge is represented in the brain. Participants (n = 32) completed a visual, four-choice, RT task consisting of statistical regularities. Two types of blocks constantly alternated with one another throughout the task: predictable statistical regularities in one block type and unpredictable ones in the other. Participants were unaware of the statistical regularities and their changing distribution across the blocks. Yet, they acquired the statistical regularities and showed significant statistical knowledge at the behavioral level not only in the predictable blocks but also in the unpredictable ones, albeit to a smaller extent. Brain activity in a range of cortical and subcortical areas, including early visual cortex, the insula, the right inferior frontal gyrus, and the right globus pallidus/putamen contributed to the acquisition of statistical regularities. The right insula, inferior frontal gyrus, and hippocampus as well as the bilateral angular gyrus seemed to play a role in maintaining this statistical knowledge. The results altogether suggest that statistical knowledge could be exploited in a relevant, predictable context as well as transmitted to and retrieved in an irrelevant context without a predictable structure.
T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia
Authors: Roessner Philipp M. , Seufert Isabelle , Chapaprieta Vicente , Jayabalan Ruparoshni , Briesch Hannah , Massoni-Badosa Ramon , Boskovic Pavle , Benckendorff Julian , Roider Tobias , Arseni Lavinia , Coelho Mariana , Chakraborty Supriya , Vaca Alicia M. , Sivina Mariela , Muckenhuber Markus , Rodriguez-Rodriguez Sonia , Bonato Alice , Herbst Sophie A. , Zapatka Marc , Sun Clare , Kretzmer Helene , Naake Thomas , Bruch Peter-Martin , Czernilofsky Felix , ten Hacken Elisa , Schneider Martin , Helm Dominic , Yosifov Deyan Y. , Kauer Joseph , Danilov Alexey V. , Bewarder Moritz , Heyne Kristina , Schneider Christof , Stilgenbauer Stephan , Wiestner Adrian , Mallm Jan-Philipp , Burger Jan A. , Efremov Dimitar G. , Lichter Peter , Dietrich Sascha , Martin-Subero José I. , Rippe Karsten , Seiffert Martina
Published: April 2024

The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of Tbx21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity, induced by inflammatory signals provided by the microenvironment, triggered T-bet expression, which affected promoter-proximal and distal chromatin coaccessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regulation of interferon signaling and negative control of proliferation by T-bet. In line, we showed that T-bet represses cell cycling and is associated with longer overall survival of patients with CLL. Our study uncovered a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling, which has implications for the stratification and therapy of patients with CLL. Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in the inflammatory signaling pathways in CLL.
HA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation
Authors: Krakow Elizabeth F. , Brault Michelle , Summers Corinne , Cunningham Tanya M. , Biernacki Melinda A. , Black R. Graeme , Woodward Kyle B. , Vartanian Nicole , Kanaan Sami B. , Yeh Albert C. , Dossa Robson G. , Bar Merav , Cassaday Ryan D. , Dahlberg Ann , Till Brian G. , Denker Andrew E. , Yeung Cecilia C. S. , Gooley Ted A. , Maloney David G. , Riddell Stanley R. , Greenberg Philip D. , Chapuis Aude G. , Newell Evan W. , Furlan Scott N. , Bleakley Marie
Published: April 2024

Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective antileukemic effect post-HCT. We conducted a phase 1 clinical trial using a novel TCR-T product targeting the minor H antigen, HA-1, to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms. The primary objective was to evaluate the feasibility and safety of administration of HA-1 TCR-T after HCT. CD8+ and CD4+ T cells expressing the HA-1 TCR and a CD8 coreceptor were successfully manufactured from HA-1–disparate HCT donors. One or more infusions of HA-1 TCR-T following lymphodepleting chemotherapy were administered to 9 HCT recipients who had developed disease recurrence after HCT. TCR-T cells expanded and persisted in vivo after adoptive transfer. No dose-limiting toxicities occurred. Although the study was not designed to assess efficacy, 4 patients achieved or maintained complete remissions following lymphodepletion and HA-1 TCR-T, with 1 patient still in remission at >2 years. Single-cell RNA sequencing of relapsing/progressive leukemia after TCR-T therapy identified upregulated molecules associated with T-cell dysfunction or cancer cell survival. HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial was registered at ClinicalTrials.gov as #NCT03326921.
High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention
Authors: Holtzman Noa G. , Curtis Lauren M. , Salit Rachel B. , Shaffer Brian C. , Pirsl Filip , Ostojic Alen , Steinberg Seth M. , Schulz Eduard , Wilder Jennifer S. , Hughes Thomas E. , Rose Jeremy , Memon Sarfraz , Korngold Robert , Gea-Banacloche Juan C. , Fowler Daniel H. , Hakim Frances T. , Gress Ronald E. , Bishop Michael R. , Pavletic Steven Z.
Published: April 2024

Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130.