bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between the effects of Hamiltonian and Liouvillian exceptional points on the Leggett-Garg inequality and no-signaling-in-time conditions
Authors: Zhou Kun-Jie , Zou Jian , 徐 宝明 , Shao Bin
Published: February 2025

In this paper we investigate the effect of exceptional points (EPs) on the violation of Leggett–Garg inequality (LGI) and no-signaling-in-time (NSIT) conditions, and compare the different effects between the Hamiltonian EP (HEP) and Liouvillian EP (LEP) on those violations. We consider an open system consisting of two coupled qubits and each qubit is contacted with a thermal bath at different temperature. In the case of omitting of quantum jumps, we find that the system exhibits a second order HEP, which separates the parameter space into an overdamped regime and an underdamped regime. In this situation, the LGI and NSIT conditions can be violated in both regimes, and not violated at the HEP. In the case of without omitting of quantum jumps, we find that the system exhibits a third order LEP, which also separates the parameter space into an overdamped regime and an underdamped regime. In this situation, the LGI can only be violated in the underdamped regime with large coupling strength between the qubits. Conversely, the NSIT conditions can be violated in both regimes, as well as at the LEP, except in the overdamped regime with small coupling strength between the qubits. Comparing the violations of the LGI and NSIT conditions with HEP and LEP, we find that the quantum jumps would reduce the generation of coherence and enhance the decoherence and lead to narrower parameter regimes that the LGI and NSIT conditions can be violated. Furthermore, in both cases, the NSIT conditions can be violated in a wider parameter regime than the LGI.
Neurophysiology
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter details how electrical activity in the brain affects behavior, using Deidre's experience with epilepsy as an example. After wires were implanted in her brain to pinpoint the source of her seizures, doctors stimulated specific areas, triggering changes in her behavior, such as uncontrollable laughter. This response demonstrated that even complex mental processes, like humor, are the products of electrical activity in the brain. The chapter further delves into neurophysiology, explaining how neurons process information through electrical signals and neurotransmitters. It explores how these electrical signals propagate along neurons and play a critical role in controlling behaviors, thoughts, and sensations.
Vision
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter explores the complexities of vision and how the visual system processes light to construct perception of the world. It begins with the basic physics of light entering the eye and describes the structures involved, such as the retina, which transduces light into neuronal activity. It also examines the six types of retinal neurons and their roles in encoding light as neural signals, including the differences between photoreceptors that enable scotopic and photopic visual systems. The chapter reviews the evolutionary adaptations of vision in various species and how the human brain devotes a significant portion of the cerebral cortex to visual analysis. By following the path of light through the eye to its neural processing, it underscores the remarkable mechanisms that allow humans to perceive, interpret, and respond to the visual world.
Motor Control and Plasticity
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter focuses on the motor system, emphasizing the intricate connection between sensory input and motor behavior, as demonstrated by Ian Waterman's unique case. Ian lost his body senses as a result of nerve damage, leaving him unable to feel light touch or sense muscle activity and body position. Remarkably, he adapted by using vision to guide his movements, highlighting how sensory feedback is essential for even basic motor tasks. The chapter examines motor functions from both behavioral and neuroscience perspectives, exploring reflexes, motor planning, and the trade-off between accuracy and speed in motor control. By analyzing hierarchical control mechanisms in the spinal cord and brain, the chapter explains the complexity of seemingly effortless actions, such as walking or grasping, while introducing the concept of motor plans that guide and fine-tune behavior.
The First Steps in Vision: From Light to Neural Signals
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter explores the initial stages of vision, beginning with the fundamental physics of light and its dual nature existing both as waves and photons. It delves into the structure and function of the human eye, focusing on how the cornea, lens, and retina collaborate to capture and process light. The chapter also examines key mechanisms of adaptation to varying brightness levels, including pupil adjustments and the distinct roles of rods and cones in the duplex retina. It highlights the retina's complexity, detailing photoreceptor types, neural pathways, and processes like dark and light adaptation that enable effective vision under diverse lighting. Through these elements, the retina translates light into neural signals, initiating the intricate journey of visual perception.
Neurophysiology
Authors: Watson Neil V. , Breedlove S. Marc
Published: February 2025

This chapter explores the intricate processes of neurophysiology, emphasizing how neurons communicate using electrical signals as their fundamental language. It explains the sequence of synaptic transmission, where action potentials trigger neurotransmitter release, altering postsynaptic membrane potentials to either excite or inhibit neuronal activity. The chapter also highlights the utility of electroencephalograms (EEGs), which measure collective electrical activity in the brain to study behavioral states, epilepsy, and sensory processing. It describes multiple sclerosis (MS) as a condition where demyelination disrupts saltatory conduction, causing diverse motor and sensory issues. Finally, it examines Wilder Penfield's groundbreaking brain mapping during surgeries, where electrical stimulation of the brain revealed a consistent and organized representation of the body, linking specific cortical regions to sensations, movements, and even memories.
The Sensorimotor System
Authors: Watson Neil V. , Breedlove S. Marc
Published: February 2025

This chapter explores the interplay between sensory processing, motor control, and pain systems in the human body, revealing how these systems enable perception and movement while signaling distress. The somatosensory system translates environmental stimuli into electrical signals via specialized receptors, such as Pacinian corpuscles and nociceptors, which detect touch and pain, emphasizing survival-critical stimuli while filtering extraneous inputs. Pain operates as an emergency alert system, prompting withdrawal or recuperation behaviors and involving intricate pathways from nociceptors to the brain, with emotional and sensory components. Motor systems utilize sensory feedback to plan and execute movements, relying on a hierarchical structure from the spinal cord to the cortex and involving proprioceptors like muscle spindles and Golgi tendon organs for precise control. The chapter also highlights the role of mirror neurons in the premotor cortex in understanding others' actions, suggesting they may underpin empathy and imitation, though their exact functions remain debated.
Psychopathology
Authors: Watson Neil V. , Breedlove S. Marc
Published: February 2025

This chapter explores the profound impact and diverse challenges of psychiatric disorders, emphasizing their widespread prevalence and biological roots. Stress increases the risk of schizophrenia, a disorder characterized by hallucinations, delusions, and cognitive deficits, shaped by a complex interplay of genetic and environmental factors. Antipsychotic drugs revolutionized treatment but present limitations, including long-term movement effects and high relapse rates. Mood disorders, the most common psychopathologies, include depression and bipolar disorder, with treatments such as selective serotonin reuptake inhibitors (SSRIs) and lithium, which researchers discovered serendipitously. Anxiety disorders, trauma-related conditions like posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder involve severe disruptions to daily life, with treatments like SSRIs and cognitive-behavioral therapy addressing symptoms while research continues to refine interventions. Finally, Tourette's syndrome stands out with its distinctive symptoms and links to related neuropsychiatric conditions.
Suggested solutions for Chapter 6
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 6 of Clayden, Greeves & Warren Organic Chemistry, second edition, on nucleophilic addition to the carbonyl group.
Suggested solutions for Chapter 20
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 20 of Clayden, Greeves & Warren Organic Chemistry, second edition, on formation and reactions of enols and enolates.
Suggested solutions for Chapter 21
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 21 of Clayden, Greeves & Warren Organic Chemistry, second edition, on electrophilic aromatic substitution.
Suggested solutions for Chapter 30
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 30 of Clayden, Greeves & Warren Organic Chemistry, second edition, on aromatic Heterocycles 2: synthesis.
Suggested solutions for Chapter 38
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 38 of Clayden, Greeves & Warren Organic Chemistry, second edition, on synthesis and reactions of carbenes.
Suggested solutions for Chapter 39
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 39 of Clayden, Greeves & Warren Organic Chemistry, second edition, on determining reaction mechanisms.
Cognitive Neuroscience
Authors: Chun Marvin M. , Most Steven B.
Published: February 2025

This chapter introduces the neural basis of cognition, exploring how brain activity underpins our thoughts, emotions, and behaviours, firmly rooting the mind in materialism rather than dualism. It outlines the brain's intricate structure, describing how its 100 billion neurons form a network of specialised regions, such as the fusiform gyrus for face recognition, while emphasising functional specialisation and hemispheric coordination. It examines cognitive neuroscience methods, such as neuropsychology, electrophysiology, and advanced imaging like functional magnetic resonance imaging (fMRI), each offering unique strengths and limitations in spatial, temporal, and invasive precision. Techniques such as electroencephalography (EEG) and transcranial magnetic stimulation (TMS) demonstrate how researchers measure or manipulate neural activity to infer causation and enhance our understanding of brain-behaviour relationships. The chapter highlights the integration of these methods to decode the brain's role in cognition, paving the way for scientific advances and practical applications in treating neural disorders.
Everyday Memory
Authors: Chun Marvin M. , Most Steven B.
Published: February 2025

This chapter explores the complexities of human memory, defining it as a system that encodes, stores, and retrieves information, with distinct processes for short-term and long-term memory. It highlights the ‘memory paradox’, showing how memory demonstrates immense storage potential while remaining fallible, as seen in cases of wrongful eyewitness identifications. The chapter explains how people can improve memory through encoding techniques, spacing study sessions, and retrieval practice, while recognising that these strategies often fail to strengthen autobiographical memory, which depends on personal narratives and cultural influences. It also examines how memory failures arise from interference, blocking, and suggestibility, emphasising that recalling memories involves active reconstruction, which often leads to distortion. Finally, the chapter warns against over-relying on memory in legal contexts, stressing the risks of treating it as a factual and infallible record.
Language and Communication
Authors: Chun Marvin M. , Most Steven B.
Published: February 2025

This chapter explores the nature of language, emphasising its defining characteristics, development, and its relationship with thought. Language, distinct from other forms of communication, is communicative, referential, structured, and endlessly creative, allowing humans to produce novel expressions. Children exhibit a language instinct, rapidly acquiring it through innate cognitive structures and sensitive periods for learning. From sounds to meaning, language comprehension involves phonemes, morphemes, and complex mental processes, while its production relies on intricate planning and coordination of linguistic units. Finally, the chapter examines how language influences thought, addressing debates such as the Sapir-Whorf hypothesis, and highlights both the interplay and limits of language in shaping human cognition.
Enhancing HBV Vaccine Uptake and Immunity through Long-acting Antiretroviral Therapy Programmatic Synergy in the U.S. South
Authors: Ochieng Eudiah , Robinson Vickie , Anderson Erica , Niles-Carnes Larisa , Smith Bradley L , Armstrong Wendy S , Lora Meredith , Colasanti Jonathan A , Collins Lauren F
Published: February 2025

We leveraged a long-acting antiretroviral therapy (ART) program infrastructure in the U.S. South to vaccinate 32/39 (82%) of eligible persons with HIV against hepatitis B virus (HBV). Novel interprofessional programmatic synergy may facilitate HBV vaccine uptake in a population uniquely at risk in the era of two-drug and injectable ART.
Zero energy modes with gaussian, exponential, or polynomial decay: Exact solutions in hermitian and nonhermitian regimes
Authors: Marra Pasquale , Nigro Angela
Published: February 2025

Topological zero modes in topological insulators or superconductors are exponentially localized at the phase transition between a topologically trivial and nontrivial phase. These modes are solutions of a Jackiw-Rebbi equation modified with an additional term which is quadratic in the momentum. Moreover, localized fermionic modes can also be induced by harmonic potentials in superfluids and superconductors or in atomic nuclei. Here, by using inverse methods, we consider in the same framework exponentially-localized zero modes, as well as gaussian modes induced by harmonic potentials (with superexponential decay) and polynomially decaying modes (with subexponential decay), and derive the explicit and analytical form of the modified Jackiw-Rebbi equation (and of the SchrÃ¶dinger equation) which admits these modes as solutions. We find that the asymptotic behavior of the mass term is crucial in determining the decay properties of the modes. Furthermore, these considerations naturally extend to the nonhermitian regime. These findings allow us to classify and understand topological and nontopological boundary modes in topological insulators and superconductors.
Performance, carcass, and pork traits in barrows and gilts slaughtered over 130 kg: insights from a Brazilian perspective
Authors: Alves Laya Kannan Silva , Carnino Bruno Braga , Muro Bruno Bracco Donatelli , Pairis-Garcia Monique Danielle , Dipold Carolina Carvalho , dos Santos Fernanda Mariane , Lo Buono José Enrico Monteiro , Garbossa Pollyana Leite Matioli , Silva Júnior Fabiano Vaquero , Garbossa Cesar Augusto Pospissil
Published: February 2025

Brazil is a major pork producer, with increasing market demands driving heavier slaughter weights. Sexual condition is a well stablished factor influencing pig performance, carcass composition, and pork quality, with previous studies focusing primarily on lighter pigs. This study compared the performance, carcass characteristics, and pork traits of heavy-slaughtered barrows and gilts. A total of 144 pigs (72 barrows; 72 gilts), with an average weight of 55.68 ±6.48 kg, were utilized in a randomized complete block design. They were allocated into 48 pens based on sex and body weight. Each pen (three pigs of the same sex) was considered the experimental unit for performance evaluation across the growing, finishing 1, and finishing 2 phases, with ad libitum access to water and feed. After a 63-day trial, one pig per pen (n = 48; 24 barrows, 24 gilts) was slaughtered for carcass and pork trait analysis. Data analysis was conducted using SAS (SAS Institute Inc., Cary, NC), and the effects of sexual condition were analyzed by ANOVA. Data were presented as least squares means, with differences deemed statistically significant at P<0.05. Throughout the study, barrows exhibited higher average daily gain (1.306 kg vs. 1.206 kg, +8.25%, P = 0.0004) and feed intake (3.378 kg vs. 2.957 kg, +14.24%, P < 0.0001), while gilts showed superior feed efficiency (0.409 vs. 0.387, +5.74%, P = 0.009). Although hot and chilled carcass weights did not differ (P>0.05), gilts had greater hot carcass yield (+2.83%) and chilled carcass yield (+3.08%) than barrows (P<0.0001). Gilts also exhibited lower initial pH (-3.28%, P=0.006) and initial temperature (-4.46%, P=0.01), with no differences in final temperature. No differences were found in L* and a* color indices, but gilts had lower b* (-3.98%, P=0.004) and Chroma (-4.06%, P=0.008) values compared to barrows. These results suggest that increasing slaughter weight above 130 kg leads to minimal practical differences between barrows and gilts in performance, carcass traits, and pork quality, reinforcing the suitability of both sexes for heavier slaughter weights in Brazilian production systems.
Light-resistant target detection improvement algorithm for overexposed environments
Authors: Zheng Chen , Li Zhiwei , Liu Hui , Huang Sha , Zhao Yanjia
Published: February 2025

In strong light environments, images often appear overexposed, which seriously impacts the accuracy of target detection. Most existing researches, however, require additional modules to assist in detection, which affects the timeliness of the detection process. To address the issues of reduced target detection accuracy and timeliness in overexposed environments, this paper proposes a real-time anti-light target detection improvement algorithm based on you only look once (YOLO) v8n, focusing on enhancing the model's ability to extract features from overexposed images without the need for additional modules. Firstly, online overexposure enhancement technology is integrated into model training to simulate overexposed images produced in overexposed environments, enhancing the model's robustness in detecting overexposed environments. Deformable convolution networks v2 (DCNv2) is used to improve the cross stage partial bottleneck with 2 convolutions (C2F) layer, addressing the issue of traditional convolution's poor feature extraction performance for overexposed images, thereby aiding the model in capturing targets with weakened or missing features and enhancing the model's ability to construct the geometric shape of targets. Secondly, large separable kernel attention (LSKA) is introduced to enhance the spatial pyramid pooling fast (SPPF) layer, strengthening the model's overall connectivity for targets with missing features. Finally, distance intersection over union (DIoU) is utilized to optimize the detection accuracy of overlapping targets in overexposed environments. The experimental results show that, compared to the original model, the mAP50 and mAP50-95 of the model designed in this paper are improved by 23.2% and 15.7%, respectively, and the model size only increases by 0.3M. While improving detection accuracy, the lightweight requirements for actual deployment are also met.
Field evaluation of peanut cultivars to early leaf spot, late leaf spot, and southern blight at Verona, MS, 2023
Authors: Tripathi Subina , Wilkerson Tessie , Jimenez Madrid Alejandra Maria , Solomon Walter , Burgess Brad
Published: February 2025

Early and late leaf spot and southern blight , caused by the fungal pathogens Passalora arachidicola, Nothopassalora personata and Athelia rolfsii, respectively, are among the important diseases in peanut production regions of the United States. Leaf spot symptoms include lesions on leaves, petioles and stems often with a yellow halo in the case of early leaf spot, while southern blight symptoms include wilting and plant death. This report evaluates disease susceptibility within the Mississippi State Official Peanut Variety Trial located in Verona, MS during 2023. Results from these trials will assist U.S. peanut producers in selecting management options for these diseases.
Field evaluation of Orondis Gold for controlling pink rot of potato in Maine, 2024
Authors: Teng Lijie , Fan Xiaowei , Askarizadeh Mandana , Morris Shayli , Zhang Xiuyan , Hynes Georgia , Chim Bee , Hao Jianjun
Published: February 2025

Potato pink rot, caused by Phytophthora erythroseptica, is a significant soilborne disease affecting potato production. Symptoms include tuber rot with a characteristic salmon-pink discoloration when exposed to air. To evaluate the efficacy of chemicals for controlling pink rot in potatoes, a field trial was conducted in 2024 at the Aroostook Research Farm in Presque Isle, ME, using the susceptible cultivar ‘Kennebec’. This study evaluates the performance of four fungicides applied as seed and soil treatments under field conditions, providing valuable insights for improving disease management strategies for potato growers.
Associations Between Social Economic Determinants and Long-Term Outcomes of Critically Ill Patients
Authors: van Sleeuwen Dries , van de Laar Floris A. , Simons Koen S. , van Bommel Daniëlle , Burgers-Bonthuis Dominique , Koeter Julia , Bisschops Laurens L.A. , Janssen Inge , Rettig Thijs C.D. , van der Hoeven Johannes G. , van den Boogaard Mark , Zegers Marieke
Published: February 2025

Objective:

Differences in socioeconomic status (SES) may influence long-term physical, psychological, and cognitive health outcomes of ICU survivors. However, the relationship between SES and these three long-term health outcomes is rarely studied. The aim of this study was to investigate associations between SES and the occurrence of long-term outcomes 1-year post-ICU.

Design:

Prospective cohort study.

Setting:

Seven Dutch ICUs.

Patients:

Patients 16 years old or older and admitted for greater than or equal to 12 hours to the ICU between July 2016 and March 2020 completed questionnaires, or relatives if patients could not complete them themselves, at ICU admission and 1 year after ICU admission.

Interventions:

None.

Measurements and Main Results:

Validated scales were used for the outcomes: physical problems (fatigue or ≥ 3 new physical symptoms), psychological problems (anxiety, depression, or post-traumatic stress), cognitive impairment, and a composite score. Occurrence of outcomes were calculated for: origin, education level, employment status, income, and household structure. Adjusted odds ratios (aORs) were calculated with covariates age, gender, admission type, severity-of-illness, and pre-ICU health status. Of the 6555 patients included, 3246 (49.5%) completed the questionnaires at admission and after 1 year. Low education level increased the risk of having health problems in the composite score 1-year post-ICU (aOR 1.84; 95% CI, 1.39–2.44; p < 0.001). Pre-ICU unemployment increased the risk of having physical problems (aOR 1.98; 95% CI, 1.31–3.01; p = 0.001). Migrants and low income was associated with more psychological problems (aOR 2.03; 95% CI, 1.25–3.24; p < 0.01; aOR 1.54; 95% CI, 1.10–2.16; p = 0.01, respectively), and unpaid work with less psychological (aOR 0.26; 95% CI, 0.08–0.73; p = 0.02) and cognitive (aOR 0.11; 95% CI, 0.01–0.59; p = 0.04) problems.

Conclusions:

Indicators of lower SES, including low education level, low income, unemployment and migrants were associated with an increased risk of post-ICU health problems. Gaining insight into the complex relationship between SES and long-term health problems is necessary to decrease disparities in healthcare.
Health Literacy–Based Heart Failure Self-care (H2Lit) Application
Authors: Cajita Mia , Doorenbos Ardith Z. , Vuckovic Karen M. , Tintle Nathan , Dunn Susan L.
Published: February 2025

The purpose of this study was to describe the development of a health literacy–focused heart failure self-care intervention (H2Lit Web-based app) and assess its usability using an online testing platform. We used an iterative approach, wherein participants evaluated more refined versions of H2Lit over four rounds of testing. Healthy participants were recruited for the earlier rounds of testing, and participants with heart failure were recruited for the final round. A total of 44 participants (10 participants with heart failure) were enrolled in the study. The participants had a mean age of 47.6 years, 57% were female, 70% identified as White, 70% were college-educated, and 34% had low health literacy. Using the System Usability Scale (score range of 0 to 100), the participants gave H2Lit a mean usability score of 74.1 in round 1, 54.3 in round 2, 85.3 in round 3, and 82.5 in round 4. H2Lit's usability score did not significantly differ between participants with adequate health literacy and those with low health literacy after controlling for age, sex, education level, and computer use duration. Further research is needed to determine the effect of the H2Lit intervention on heart failure self-care and heart failure–related outcomes.
Relationship between Central Corneal Thickness and Inter-eye Disease Severity in Primary Angle Closure Glaucoma
Authors: Prasad Shimna C. , Umapathi Ruthra M. , Hlaing Tin Nwe , Atalay Eray , Girard Michael J. , Aung Tin , Nongpiur Monisha E.
Published: February 2025

Precis:

Inter-ocular comparison of primary angle closure glaucoma subjects with asymmetrical and symmetrical visual field loss, revealed significantly thinner central corneal thickness and higher presenting intraocular pressure in the worse eye of the asymmetrical group.

Purpose:

To compare the inter-ocular clinical and biometric parameters of primary angle-closure glaucoma (PACG) with asymmetrical and symmetrical visual-field loss at presentation.

Patient and Methods:

Retrospective study in which the following clinical data were extracted: presenting intraocular pressure (IOP), gonioscopy, visual-field mean deviation (MD), central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL). Asymmetrical PACG was defined as the inter-eye visual-field MD difference >6 dB, symmetrical PACG <3 dB, and those with inter-eye difference between 3-6 dB were excluded. Linear mixed effects model was used to adjust for the interdependence of the right and left eyes.

Results:

Of 243 PACG subjects, 122 (50.3%) presented with asymmetrical, and 69 (28.4%) with symmetrical disease. The worse eyes in subjects with asymmetrical PACG had significantly higher presenting IOP (P<0.001), narrower angles (P<0.001), more myopic refraction (P<0.001) and thinner CCT (529.2±36.1 μm vs. 535.8±38.5 μm; P<0.001) compared to the fellow eyes; but no inter-eye differences were observed for AL (P=0.93) and ACD (P=0.53). In symmetric PACG, no significant inter-eye differences were observed for CCT (532.3±33.1 vs. 533.1±34.6 μm, P=0.67), AL (P=0.85) and ACD (P=0.18), but the relatively worse eye had higher presenting IOP (P=0.003). In the stepwise multiple linear regression analysis in the asymmetrical group, CCT was the only significant variable (P=0.006), explaining 12% of the variability of the visual-field MD of the worse eye.

Conclusions:

In asymmetrical PACG, worse eyes have thinner CCT and higher presenting IOP. Difference in CCT could either be inherent or acquired, and more tests would be needed to tease that out.
BRAF Gene Fusions in Melanoma
Authors: Odintsov Igor , Davis Dale , Pissaloux Daniel , Tirode Franck , de la Fouchardiere Arnaud , Hanna John
Published: February 2025

BRAF gene fusions have been well-described in Spitzoid melanocytic lesions but can also occur uncommonly in conventional melanomas. Here we report a series of 17 melanomas harboring BRAF gene fusions as their putative primary genetic driver. All but one of these tumors occurred in adults (age range 13 to 96) with a relatively even sex distribution (41% female) and a broad distribution of anatomic sites. None of the tumors showed typical Spitzoid histomorphologic features. Molecular analysis identified the first example of BRAF kinase domain duplication in melanoma, which raises interesting questions regarding the mechanism of fusion-induced BRAF activation. Although we did not identify histomorphologic features that could distinguish BRAF-fused melanomas from more conventional melanomas, we did observe a generally low tumor mutational burden and a lower rate of UV-associated mutational signatures (3/17; 18%), suggesting that BRAF-fused melanomas are molecularly and mechanistically distinct from conventional cutaneous melanomas. We report detailed treatment information and clinical outcomes for this series, with most patients having shown disease progression on systemic immunotherapy (8/12; 67%). Our results highlight the need for continued molecular subclassification to yield a comprehensive understanding of melanoma pathogenesis and have potential implications for therapeutic selection in BRAF-fused and perhaps other unconventional forms of melanoma.
Primary effusion lymphoma in people with and without HIV infection in the United States
Authors: Volesky-Avellaneda Karena D. , Luo Qianlai , Amaswami Ramya R. , Lurain Kathryn , Song Joo Y. , Horner Marie-Josèphe , Cohen Colby , Shiels Meredith S. , Engels Eric A.
Published: February 2025

Objective:

Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma (NHL) subtype caused by Kaposi sarcoma (KS) herpesvirus. We describe PEL incidence and survival in people with HIV (PWH) and people without HIV in the US.

Design:

Retrospective cohort study of PEL people with and without HIV.

Methods:

PEL cases were identified in the HIV/AIDS Cancer Match (HACM) Study, a linkage of population-based cancer and HIV registries in 14 US regions. PEL incidence was examined using negative binomial regression and compared with the general population using a standardized incidence ratio. Survival was evaluated using Cox proportional hazard regression.

Results:

During 2001–2019, 53% of 174 PEL cases identified in HACM data were among PWH. PWH had >700-fold higher PEL incidence than the general population. Compared to PEL cases without HIV, PWH were younger (median age: 44.8 vs. 77.7 years). Among PWH, prior KS was associated with 59-fold higher PEL incidence versus those without an AIDS diagnosis. PEL comprised 1.15% of the 8010 NHLs diagnosed among PWH in HACM during 2001–2019. HIV was not associated with mortality among PEL cases. Among PWH, Burkitt lymphoma and diffuse large B-cell lymphoma exhibited similar mortality to PEL but central nervous system lymphoma mortality was worse.

Conclusions:

There are two distinct subgroups of PEL cases in the US: younger patients with HIV and older patients without HIV. The proportion of PEL cases among PWH is highly disproportionate to the size of the HIV population, reflecting the greatly elevated incidence of PEL among PWH.
The Effect of Concomitant Hysterectomy Route on Robotic Sacrocolpopexy Outcomes
Authors: Swallow Christina , Imamoglu Metehan , Imamoglu Aysegul Gizem , Xu Xiao , Harmanli Oz
Published: February 2025

Importance

Sacrocolpopexy is essential in the surgical management of advanced pelvic organ prolapse, and selecting the appropriate route for concomitant hysterectomy is critical.

Objectives

The aim of this study was to evaluate the effect of the hysterectomy route at the time of robot-assisted laparoscopic sacrocolpopexy (RA-SCP) on mesh exposure. Secondary outcomes were perioperative complications and prolapse recurrence.

Study Design

This was a retrospective cohort study of 405 patients who underwent an RA-SCP at our institution from January 2013 to July 2019 with at least 6 month follow-up; the patients were grouped with respect to hysterectomy route as robot-assisted supracervical hysterectomy (SCH), total vaginal hysterectomy (VH), and posthysterectomy (PH). The primary outcome measure was mesh exposure. Short-term complications and anatomic failure were also analyzed.

Results

Two hundred three of our patients (50.1%) had a concomitant SCH, 93 (23.0%) had a concomitant VH, and 109 (26.9%) were PH at the time of their robotic sacrocolpopexy. Sacrocolpopexy mesh exposure occurred in 4 patients (1%), with an additional 6 patients (1.5%) with midurethral sling mesh exposure. Mesh exposure rates did not differ significantly between groups. At 6 months after surgery, anatomic failure rates did not differ significantly between groups (P = 0.69).

Intraoperative and postoperative complication rates were low (bowel obstruction, 2.0%; bladder injury, 1.2%, after excluding those caused by sling trocars; venous thromboembolism, 0.7%; transfusion, 0.5%). Postoperative infection and readmission rates did not differ significantly between groups.

Conclusions

Patients with different routes of hysterectomy at the time of RA-SCP have similar mesh exposure and prolapse recurrence rates. Serious complications are rare in all groups.
Simultaneous single-cell CRISPR, RNA, and ATAC-seq enables multiomic CRISPR screens to identify gene regulatory relationships
Authors: Shevade Kaivalya , Yang Yeqing Angela , Feng Kevin , Mader Karl , Sevim Volkan , Parsons Jacob , Arora Gunisha , Elfawy Hasnaa , Mace Rachel , Federman Scot , Esanov Rustam , Shafer Shawn , Chow Eric D , Przybyla Laralynne
Published: February 2025

The ability to identify gene functions and interactions in specific cellular contexts has been greatly enabled by functional genomics technologies. CRISPR-based genetic screens have proven invaluable in elucidating gene function in mammalian cells. Single-cell functional genomics methods, such as Perturb-seq and Spear-ATAC, have made it possible to achieve high-throughput mapping of the functional effects of gene perturbations by profiling transcriptomes and DNA accessibility, respectively. Combining single-cell chromatin accessibility and transcriptomic data via multiomic approaches has facilitated the discovery of novel cis and gene regulatory interactions. However, pseudobulk readouts from cell populations can often cloud the interpretation of results due to a heterogeneous response from cells receiving the same genetic perturbation, which could be mitigated by using transcriptional profiles of single cells to subset the ATAC-seq data. Existing methods to capture CRISPR guide RNAs to simultaneously assess the impact of genetic perturbations on RNA and ATAC profiles require either cloning of gRNA libraries in specialized vectors or implementing complex protocols with multiple rounds of barcoding. Here, we introduce CAT-ATAC, a technique that adds CRISPR gRNA capture to the existing 10X Genomics Multiome assay, generating paired transcriptome, chromatin accessibility and perturbation identity data from the same individual cells. We demonstrate up to 77% guide capture efficiency for both arrayed and pooled delivery of lentiviral gRNAs in induced pluripotent stem cells (iPSCs) and cancer cell lines. This capability allows us to construct gene regulatory networks (GRNs) in cells under drug and genetic perturbations. By applying CAT-ATAC, we were able to identify a GRN associated with dasatinib resistance, indirectly activated by the HIC2 gene. Using loss of function experiments, we further validated that the gene, ZFPM2, a component of the predicted GRN, also contributes to dasatinib resistance. CAT-ATAC can thus be used to generate high-content multidimensional genotype-phenotype maps to reveal novel gene and cellular interactions and functions.
A randomized double-blind placebo-controlled Phase 1 trial of PXS-6302, a topical lysyl oxidase inhibitor, in mature scars
Authors: Morellini Natalie , Gong Peijun , Rea Suzanne , Douglas Helen , Ho Phuoc Hao , Cense Barry , Kennedy Brendan F. , Jarolimek Wolfgang , Charlton Brett , Findlay Alison , Leadbetter Joanna , Wood Fiona M. , Fear Mark W.
Published: February 2025

Skin scars are a significant clinical challenge, with poor appearance and increased tissue stiffness affecting both physical and psychological wellbeing. Lysyl oxidases are a family of enzymes that catalyze collagen crosslinking, a key factor in scar pathophysiology. Here we report a randomized, double-blind, placebo-controlled Phase 1 clinical trial to assess the safety and tolerability of PXS-6302, a topical pan-lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants with scars were enrolled and PXS-6302 or placebo cream applied to a 10 cm2area for three months. No severe adverse events were reported. All treatment-related adverse events (AEs) were localized skin reactions. Treatment with PXS-6302 significantly inhibited lysyl oxidase activity (66%). Hydroxyproline (a marker for collagen) and total protein concentration in the scar were significantly reduced in the PXS-6302 treatment group compared to placebo. Optical coherence tomography (OCT) was used to measure vascularity and attenuation (a marker of extracellular matrix composition). PXS-6302 treatment significantly increased vessel density at 3 months compared to baseline. Tissue attenuation was also significantly increased in PXS-6302 treated participants compared to baseline, suggesting extracellular matrix was becoming increasingly similar to normal skin. No significant differences between placebo and PXS-6302 treatment groups were observed in Patient Observer Scar Assessment Scale (POSAS) scores at study conclusion. To our knowledge, this study represents the first demonstration of a safe and effective pharmaceutical intervention that significantly improves the molecular composition of established scar extracellular matrix in humans. Pan-lysyl oxidase inhibition therefore represents a potential paradigm shift for the amelioration of scarring.

One Sentence Summary

Mature scars remodeled after treatment with a topical cream for three months.
Knowledge, attitude, and willingness to Perform On-Site Cardiopulmonary Resuscitation Among Individuals Trained in Public CPR: A Cross-Sectional Survey
Authors: Cui ShaoMei , Ye DanJuan , Yang Heng , Zhang LiYan , Chen Lixia
Published: February 2025

Objectives

In China, the rescue rate by first responders who have received public Cardiopulmonary resuscitation (CPR) training remains low. While CPR training boosts emergency knowledge and skills among the public, the degree to which this knowledge is retained, along with attitudes and willingness to perform CPR after training, remains elusive. Thus, this study aimed to investigate factors influencing individuals’ retention of knowledge, attitude toward CPR, and willingness to perform on-site CPR following training.

Methods

This cross-sectional study targeted 190 participants from various regions of China who had undergone public CPR training. They completed a questionnaire via online survey between January and February 2024, following CPR training courses.

Results

Out of 190 distributed questionnaires, 186 were returned and deemed valid, yielding a response rate of 97.9%. Among the respondents, 110 (59.1%) and 76 (40.9%) were female and male, respectively. The correct response rate for CPR knowledge was merely 39.2%. Notably, the majority of respondents held a positive attitude towards performing CPR on-site, with 86.0% strongly agreeing that “timely administration of CPR can save many lives.” Regarding willingness to perform CPR on-site, 95.7% were willing to administer CPR to a family member, whereas only 58.6% were willing to perform CPR for strangers. Legal protection for first responders was cited by 84.4% of respondents as influencing their willingness to perform CPR on-site. According to univariate statistical analysis, factors such as having personal experience in performing CPR on-site, witnessing a cardiac arrest, frequency of CPR training attended in the past 12 months, and educational level significantly influenced (P<0.05) the mastery of CPR knowledge. Similarly, these factors, as well as having family members at high risk of cardiogenic sudden death, significantly affected the attitude towards performing CPR on-site (p<0.05).

Conclusions

The proficiency level in cardiopulmonary resuscitation knowledge remains suboptimal. Although most participants displayed a positive attitude towards performing CPR on-site, their willingness was limited and influenced by various factors. Therefore, organizations offering public CPR training are recommended to implement regular refresher courses, scenario-based simulations, and interactive discussions to mitigate apprehensions and enhance the willingness of trainees for intervention.
A standard scoring method for measuring white cast of mineral sunscreens and improving user compliance across diverse skin tones
Authors: Maldonado López Alexandra M. , Gallagher Emily , Curry Aiden , Sahloff Kylie Q. , da Silva Souza Ivan Domicio
Published: February 2025

Using broad-spectrum sunscreen is an effective practice for preventing skin cancers caused by ultraviolet (UV) radiation. Mineral sunscreens containing zinc oxide (ZnO) and titanium dioxide (TiO2) as physical UV filters are suitable for individuals with sensitive skin or allergies to chemical UV filters. Consumer compliance with sunscreen application depends largely on its cosmetic elegance, especially regarding white cast. Despite this, there is no official method to quantify white cast and help design sunscreens for diverse skin tones. To address this gap, we developed validated white cast scoring protocols that combine 1) subjective consumer feedback on formulations containing ZnO concentrations ranging from 0–30% with 2) objective L* measurements (whiteness) determined after sunscreen application. Our findings demonstrate a strong correlation between increasing ZnO percentages and higher L* values, resulting in a more visible white cast. White cast scores for the ZnO formulations were substantially consistent across both in vivo and in vitro methodologies, with higher ZnO concentrations producing unacceptable levels of white cast. This study provides a white cast scoring system as a quantitative tool for evaluating and refining mineral sunscreen formulations, contributing to the development of more cosmetically elegant sunscreens suitable for a wide range of skin tones.
The Proportional Treatment Effect: A Metric That Empowers and Connects
Authors: Wang Guoqiao , Liao Yijie , Li Caiyan , Jin Kun , Li Yan , Cutter Gary
Published: February 2025

Clinical trials with continuous endpoints, evaluate efficacy by comparing the difference in mean changes from baseline between groups. However, clinicians often interpret results in terms of a proportional reduction rather than an absolute difference. An alternative approach is to reparametrize this difference as a proportional treatment effect, calculated by dividing the difference by the placebo mean change. We demonstrate that, in theory, the proportional treatment effect can be more powerful than the simple difference in means while still controlling the type I error rate. This is achieved using the delta method as implemented in well-established computational tools like the R package ‘msm’ and the SAS procedure ‘NLMIXED’. By analyzing data from phase III trials, we illustrate how a proportional treatment effect connects treatment outcomes across various endpoints and different presentation formats. The availability of these well-established statistical tools for estimating proportional treatment effects, combined with this theoretical demonstration, suggests an alternative test statistic for clinical trials with continuous endpoints.
High-frequency gravitational waves detection with the BabyIAXO haloscopes
Authors: Reina-Valero José , Navarro-Madrid Jose R. , Blas Diego , Díaz-Morcillo Alejandro , Irastorza Igor García , Gimeno Benito , Monzó-Cabrera Juan
Published: February 2025

We present the first analysis using RADES-BabyIAXO cavities as detectors of high-frequency gravitational waves (HFGWs). In particular, we discuss two configurations for distinct frequency ranges of HFGWs: cavity 1, mostly sensitive at a frequency range of 252.8–333.2 MHz, and cavity 2, at 2.504–3.402 GHz, which is a scaled down version of cavity 1. We find that cavity 1 will reach sensitivity to strains of the HFGWs of order h1∼10−21, while cavity 2 will reach h2∼10−20. These represent the best estimations of the RADES-BabyIAXO cavities as HFGW detectors, showing how this setup can produce groundbreaking results in axion physics and HFGWs simultaneously.

Published by the American Physical Society
2025
Chatbot research in the fields of business and information systems: a systematic review and bibliometric analysis
Authors: Li Zhenyan , Wu Chuanhui , Li Jiaxuan , Yuan Qinjian
Published: February 2025

Purpose

Chatbots are increasingly embodied in business and IS contexts to enhance customer and user experience. Despite wide interest in chatbots among business and IS academics, surprisingly, there are no current comprehensive reviews to reveal the knowledge structure of chatbot research in such areas.

Design/methodology/approach

This study employed a mixed-method approach that combines systematic review and bibliometric analysis to provide a comprehensive synthesis of chatbot research. The sample was obtained in December 2023 after searching across six databases: EBSCOhost, PsycINFO, Web of Science, Scopus, ACM Digital Library and IEEE Computer Society Digital Library.

Findings

This study reveals the major trend in publication trends, countries, article performance and cluster distribution of chatbot research. We also identify the key themes of chatbot research, which mainly focus on how users interact with chatbots and their consequences, such as users’ cognition and behavior. Moreover, several important research agendas have been discussed to address some limitations in the current chatbot research in business and IS fields.

Originality/value

The present review is one of the first attempts to systematically reveal the ongoing knowledge map of chatbots in business and IS fields, which makes important contributions and provides useful resources for future chatbot research and practice.