bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural insights into the unexpected agonism of tetracyclic antidepressants at serotonin receptors 5-HT
1e
R and 5-HT
1F
R
Authors: Zilberg Gregory , Parpounas Alexandra K. , Warren Audrey L. , Fiorillo Bianca , Provasi Davide , Filizola Marta , Wacker Daniel
Published: April 2024

Serotonin [5-hydroxytryptamine (5-HT)] acts via 13 different receptors in humans. Of these receptor subtypes, all but 5-HT
1e
R have confirmed roles in native tissue and are validated drug targets. Despite 5-HT
1e
R’s therapeutic potential and plausible druggability, the mechanisms of its activation remain elusive. To illuminate 5-HT
1e
R’s pharmacology in relation to the highly homologous 5-HT
1F
R, we screened a library of aminergic receptor ligands at both receptors and observe 5-HT
1e
R/5-HT
1F
R agonism by multicyclic drugs described as pan-antagonists at 5-HT receptors. Potent agonism by tetracyclic antidepressants mianserin, setiptiline, and mirtazapine suggests a mechanism for their clinically observed antimigraine properties. Using cryo-EM and mutagenesis studies, we uncover and characterize unique agonist-like binding poses of mianserin and setiptiline at 5-HT
1e
R distinct from similar drug scaffolds in inactive-state 5-HTR structures. Together with computational studies, our data suggest that these binding poses alongside receptor-specific allosteric coupling in 5-HT
1e
R and 5-HT
1F
R contribute to the agonist activity of these antidepressants.
Optical control of 4
f
orbital state in rare-earth metals
Authors: Thielemann-Kühn Nele , Amrhein Tim , Bronsch Wibke , Jana Somnath , Pontius Niko , Engel Robin Y. , Miedema Piter S. , Legut Dominik , Carva Karel , Atxitia Unai , van Kuiken Benjamin E. , Teichmann Martin , Carley Robert E. , Mercadier Laurent , Yaroslavtsev Alexander , Mercurio Giuseppe , Le Guyader Loïc , Agarwal Naman , Gort Rafael , Scherz Andres , Dziarzhytski Siarhei , Brenner Günter , Pressacco Federico , Wang Ru-Pan , Schunck Jan O. , Sinha Mangalika , Beye Martin , Chiuzbăian Gheorghe S. , Oppeneer Peter M. , Weinelt Martin , Schüßler-Langeheine Christian
Published: April 2024

A change of orbital state alters the coupling between ions and their surroundings drastically. Orbital excitations are hence key to understand and control interaction of ions. Rare-earth elements with strong magneto-crystalline anisotropy (MCA) are important ingredients for magnetic devices. Thus, control of their localized 4
f
magnetic moments and anisotropy is one major challenge in ultrafast spin physics. With time-resolved x-ray absorption and resonant inelastic scattering experiments, we show for Tb metal that 4
f
-electronic excitations out of the ground-state multiplet occur after optical pumping. These excitations are driven by inelastic 5
d
-4
f
-electron scattering, altering the 4
f
-orbital state and consequently the MCA with important implications for magnetization dynamics in 4
f
-metals and more general for the excitation of localized electronic states in correlated materials.
A macroevolutionary role for chromosomal fusion and fission in
Erebia
butterflies
Authors: Augustijnen Hannah , Bätscher Livio , Cesanek Martin , Chkhartishvili Tinatin , Dincă Vlad , Iankoshvili Giorgi , Ogawa Kota , Vila Roger , Klopfstein Seraina , de Vos Jurriaan M. , Lucek Kay
Published: April 2024

The impact of large-scale chromosomal rearrangements, such as fusions and fissions, on speciation is a long-standing conundrum. We assessed whether bursts of change in chromosome numbers resulting from chromosomal fusion or fission are related to increased speciation rates in
Erebia
, one of the most species-rich and karyotypically variable butterfly groups. We established a genome-based phylogeny and used state-dependent birth-death models to infer trajectories of karyotype evolution. We demonstrated that rates of anagenetic chromosomal changes (i.e., along phylogenetic branches) exceed cladogenetic changes (i.e., at speciation events), but, when cladogenetic changes occur, they are mostly associated with chromosomal fissions rather than fusions. We found that the relative importance of fusion and fission differs among
Erebia
clades of different ages and that especially in younger, more karyotypically diverse clades, speciation is more frequently associated with cladogenetic chromosomal changes. Overall, our results imply that chromosomal fusions and fissions have contrasting macroevolutionary roles and that large-scale chromosomal rearrangements are associated with bursts of species diversification.
Bacterial community profiles of select tributaries of Laguna Lake in the Philippines
Authors: Castro Arizaldo E. , Montecillo Andrew D. , Villanueva Ren Mark D. , Obusan Marie Christine M.
Published: April 2024

Laguna Lake is known for its ecological, economic, and cultural importance. Effects of urbanization and accumulation of emerging pollutants have been associated with its water quality; however, the microbial ecology of its tributaries remains to be explored. We report bacterial community profiles from shotgun metagenomes of its select tributary waters.
Long-term cognitive effects of COVID-19 studied with repeated neuropsychological testing
Authors: Matthews Beverly , Datey Chakrabarty Ashima , Chakrabarty Arindam
Published: April 2024

COVID-19 has a wide range of clinical manifestations. Apart from respiratory symptoms, neurological manifestations and cognitive impairment are commonly seen. Due to lack of a clear consensus on the definition of long COVID a pragmatic approach of assessing change from neurological baseline has become prevalent. We present the case of a high functioning woman in her late 40s who had a mild course of acute illness but developed cognitive difficulties. No organic causes for her cognitive difficulties were found. Neuropsychological testing showed impairment in right frontal lobe functioning. The patient showed a response to empirical treatment with Attention deficit hyperactivity disorder (ADHD) medications. Repeat neuropsychological testing 1 year later showed continued dysfunction in executive functioning. We present the details of her test findings and discuss the proposed pathophysiology behind neurocognitive effects of long COVID.
Prevalence of work-related musculoskeletal disorders and associated factors affecting emergency medical services professionals in Jordan: a cross-sectional study
Authors: Nazzal Mohammad S , Oteir Alaa O , Alrawashdeh Ahmad , Alwidyan Mahmoud T , Obiedat Qussai , Almhdawi Khader A , Ismael Noor T , Williams Brett
Published: April 2024

Objectives

Emergency medical services (EMSs) personnel are at high risk for developing work-related musculoskeletal disorders (WMSDs). However, no studies have yet investigated the prevalence and effect of these disorders on the Jordanian EMS personnel. Therefore, this study aimed to determine the prevalence of WMSDs among Jordanian EMS personnel and its associated factors.

Design

This study used a cross-sectional design. Participants were asked to complete a self-administrated and validated questionnaire to measure the WMSDs, including a demographic survey and the Nordic Musculoskeletal Questionnaire. Descriptive and multivariable regression analyses were used.

Setting

The Jordanian Civil Defence stations in the main cities of Jordan.

Participants

The sample consisted of 435 EMS workers which were obtained across the country of Jordan. A total of 79.0% of the participants were male, with a mean age of 27.9 (±4.3 SD) years.

Results

The pain in the lower back (308, 70.8%) and neck (252, 57.9%) were the most reported in the last 12 months. Furthermore, about half of the participants reported having pain in their upper back (234, 53.8%), knee (227, 52.2%) and shoulder (226, 52.0%) pain in the last 12 months. Overall, WMSDs in at least one body part were significantly associated with age, experience, being a male, increased body mass index and lower educational level.

Conclusions

There is a high prevalence of musculoskeletal complaints among EMS personnel. Multiple variables may be incorporated into a national prevention campaign and professional development programme to educate EMS personnel on avoiding WMSDs.
Effects of different exercise interventions on chemotherapy-related cognitive impairment in patients with breast cancer: a study protocol for systematic review and network meta-analysis
Authors: Dong Yu , Huang Hao , Wang Aiping
Published: April 2024

Introduction

Breast cancer stands as the most prevalent type of cancer affecting women globally, and chemotherapy plays a pivotal role in its treatment by diminishing tumour recurrence and enhancing the survival rates of patients. However, chemotherapy-related cognitive impairment (CRCI) often occurs in patients undergoing treatment. Although multiple clinical trials have indicated that exercise therapy can improve CRCI in patients with breast cancer, there are variations in the types of exercise interventions and their effectiveness. We aim to perform a pioneering network meta-analysis (NMA) to assess and prioritise the effectiveness of various exercise interventions in enhancing cognitive function in patients with breast cancer undergoing chemotherapy.

Methods and analysis

We will search multiple databases, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Sinomed databases, from their inception to May 2023. The main outcome is the cognitive function changes in patients with breast cancer, including subjective and objective results. We will specifically include randomised controlled trials reported in English and Chinese languages, whose primary outcome consists of an assessment of the cognitive function of patients with breast cancer using standardised and validated assessment tools, encompassing both subjective and objective outcomes. The quality of all the trials included will be evaluated based on ‘Version 2 of the Cochrane tool for assessing the risk of bias in randomized controlled trials (RoB2)’. We will conduct a Bayesian NMA to thoroughly evaluate and compare the effectiveness of different exercise interventions. We will use cumulative ranking probability plots to estimate the ranking of the best interventions for various exercises. Network plots and funnel plots will be employed to display the study sizes and participants of each exercise intervention, as well as potential publication biases.

Ethics and dissemination

The study findings will be shared via peer-reviewed journals to ensure the highest quality and credibility of the research. As the reporting will not include any private patient data, there are no ethical considerations associated with this protocol.

PROSPERO registration number

CRD42023406597.
Linking genetic counseling communication skills to patient outcomes and experiences using a community-engagement and provider-engagement approach: research protocol for the GC-PRO mixed methods sequential explanatory study
Authors: Fisher Elena R , Cragun Deborah , Dedrick Robert F , Lumpkins Crystal Y , Ramírez Mariana , Kaphingst Kimberly A , Petersen Ashley , MacFarlane Ian M , Redlinger-Grosse Krista , Shire Abdirashid , Culhane-Pera Kathleen A , Zierhut Heather A
Published: April 2024

Introduction

In over 50 years since the genetic counseling (GC) profession began, a systematic study of GC communication skills and patient-reported outcomes in actual sessions across multiple clinical specialties has never been conducted. To optimize GC quality and improve efficiency of care, the field must first be able to comprehensively measure GC skills and determine which skills are most critical to achieving positive patient experiences and outcomes. This study aims to characterise GC communication skills using a novel and pragmatic measure and link variations in communication skills to patient-reported outcomes, across clinical specialties and with patients from diverse backgrounds in the USA. Our community-engagement and provider-engagement approach is crucial to develop recommendations for quality, culturally informed GC care, which are greatly needed to improve GC practice.

Methods and analysis

A mixed methods, sequential explanatory design will be used to collect and analyze: audio-recorded GC sessions in cancer, cardiac, and prenatal/reproductive genetic indications; pre-visit and post-visit quantitative surveys capturing patient experiences and outcomes and post-visit qualitative interview data. A novel, practical checklist will measure GC communication skills. Coincidence analysis will identify patterns of GC skills that are consistent with high scores on patient-reported measures. Two-level, multilevel models will be used to evaluate how GC communication skills and other session/patient characteristics predict patient-reported outcomes. Four community advisory boards (CABs) and a genetic counselor advisory board will inform the study design and analysis.

Ethics and dissemination

This study has been approved by the single Institutional Review Board of the University of Minnesota. This research poses no greater than minimal risk to participants. Results from this study will be shared through national and international conferences and through community-based dissemination as guided by the study’s CABs. A lay summary will also be disseminated to all participants.
General practitioners’ risk literacy and real-world prescribing of potentially hazardous drugs: a cross-sectional study
Authors: Wegwarth Odette , Hoffmann Tammy C , Goldacre Ben , Spies Claudia , Giese Helge A
Published: April 2024

Background

Overuse of medical care is a pervasive problem. Studies using hypothetical scenarios suggest that physicians’ risk literacy influences medical decisions; real-world correlations, however, are lacking. We sought to determine the association between physicians’ risk literacy and their real-world prescriptions of potentially hazardous drugs, accounting for conflicts of interest and perceptions of benefit–harm ratios in low-value prescribing scenarios.

Setting and sample

Cross-sectional study—conducted online between June and October 2023 via field panels of Sermo (Hamburg, Germany)—with a convenience sample of 304 English general practitioners (GPs).

Methods

GPs’ survey responses on their treatment-related risk literacy, conflicts of interest and perceptions of the benefit–harm ratio in low-value prescribing scenarios were matched to their UK National Health Service records of prescribing volumes for antibiotics, opioids, gabapentin and benzodiazepines and analysed for differences.

Results

204 GPs (67.1%) worked in practices with ≥6 practising GPs and 226 (76.0%) reported 10–39 years of experience. Compared with GPs demonstrating low risk literacy, GPs with high literacy prescribed fewer opioids (mean (M): 60.60 vs 43.88 prescribed volumes/1000 patients/6 months, p=0.016), less gabapentin (M: 23.84 vs 18.34 prescribed volumes/1000 patients/6 months, p=0.023), and fewer benzodiazepines (M: 17.23 vs 13.58 prescribed volumes/1000 patients/6 months, p=0.037), but comparable volumes of antibiotics (M: 48.84 vs 40.61 prescribed volumes/1000 patients/6 months, p=0.076). High-risk literacy was associated with lower conflicts of interest (ϕ = 0.12, p=0.031) and higher perception of harms outweighing benefits in low-value prescribing scenarios (p=0.007). Conflicts of interest and benefit–harm perceptions were not independently associated with prescribing behaviour (all ps >0.05).

Conclusions and relevance

The observed association between GPs with higher risk literacy and the prescription of fewer hazardous drugs suggests the importance of risk literacy in enhancing patient safety and quality of care.
B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors
Authors: Flippot Ronan , Teixeira Marcus , Rey-Cardenas Macarena , Carril-Ajuria Lucia , Rainho Larissa , Naoun Natacha , Jouniaux Jean-Mehdi , Boselli Lisa , Naigeon Marie , Danlos Francois-Xavier , Escudier Bernard , Scoazec Jean-Yves , Cassard Lydie , Albiges Laurence , Chaput Nathalie
Published: April 2024

Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition is plateauing, and biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures. Mechanisms of B cell response include antibody-dependent cellular cytotoxicity and phagocytosis, promotion of CD4+ and CD8+ T cell activation, maintenance of antitumor immune memory. In several solid tumor types, higher levels of B cells, specific B cell subpopulations, or the presence of tertiary lymphoid structures have been associated with improved outcomes on immune checkpoint inhibitors. The fate of B cell subpopulations may be widely influenced by the cytokine milieu, with versatile roles for B-specific cytokines B cell activating factor and B cell attracting chemokine-1/CXCL13, and a master regulatory role for IL-10. Roles of B cell-specific immune checkpoints such as TIM-1 are emerging and could represent potential therapeutic targets. Overall, the expanding field of B cells in solid tumors of holds promise for the improvement of current immunotherapy strategies and patient selection.
Hospice and palliative care utilization in 16 004 232 medicare claims: comparing trauma to surgical and medical inpatients
Authors: Fakhry Samir M , Carrick Matthew M , Hoffman Melissa Red , Shen Yan , Garland Jeneva M , Wyse Ransom J , Watts Dorraine D
Published: April 2024

Background

Hospice and palliative care (PC) utilization is increasing in geriatric inpatients, but limited research exists comparing rates among trauma, surgical and medical specialties. The goal of this study was to determine whether there are differences among these three groups in rates of hospice and PC utilization.

Methods

Patients from Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files for 2016–2020 aged ≥65 years were analyzed. Patients with a National Trauma Data Standard-qualifying ICD-10 injury code with abbreviated injury score ≥2 were classified as ‘trauma’; the rest as ‘surgical’ or ‘medical’ using CMS MS-DRG definitions. Patients were classified as having PC if they had an ICD-10 diagnosis code for PC (Z51.5) and as hospice discharge (HD) if their hospital disposition was ‘hospice’ (home or inpatient). Use proportions for specialties were compared by group and by subgroups with increasing risk of poor outcome.

Results

There were 16M hospitalizations from 1024 hospitals (9.3% trauma, 26.3% surgical and 64.4% medical) with 53.7% women, 84.5% white and 38.7% >80 years. Overall, 6.2% received PC and 4.1% a HD. Both rates were higher in trauma patients (HD: 3.6%, PC: 6.3%) versus surgical patients (HD: 1.5%, PC: 3.0%), but lower than in medical patients (HD: 5.2%, PC: 7.5%). PC rates increased in higher risk patient subgroups and were highest for inpatient HD.

Conclusions

In this large study of Medicare patients, HD and PC rates varied significantly among specialties. Trauma patients had higher HD and PC utilization rates than surgical, but lower than medical. The presence of comorbidities, frailty and/or severe traumatic brain injury (in addition to advanced age) may be valuable criteria in selection of trauma patients for hospice and PC services. Further studies are needed to inform the most efficient use of hospice and PC resources, with particular focus on both timing and selection of subgroups most likely to benefit from these valuable yet limited resources.

Level of evidence

Level III, therapeutic/care management.
Recent advances in graphene oxide-based electrochemical sensors
Authors: Ramirez Carlos A. , Thiruppathi Antony R. , Ozoemena Okoroike , Chen Aicheng
Published: April 2024

Graphene oxide-based nanomaterials are garnering significant attention from various fields due to their unique physical and chemical properties, which make them attractive for myriad applications. This feature article stems from Dr. Aicheng Chen’s Lecture for the 2023 Ricardo Aroca Award of the Canadian Society for Chemistry and focuses primarily on the synthesis and applications of graphene oxide-based nanomaterials for electrochemical sensing. Graphene oxide (GO), reduced graphene oxide, and functionalized and doped GO-based nanomaterials are emerging as promising enablers of broad applications in electrochemical sensors. This is due to their distinctive functional groups and novel properties, which include high electrical conductivities, large surface areas, and enhanced catalytic activities. Several strategies for the synthesis of these nanomaterials are described in this feature article, encompassing the modified Hummers method, electrochemical, thermal, and microwave reactor methods. The characterization of these GO-based nanomaterials is highlighted, employing techniques such as scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman, and X-ray photoelectron spectroscopy to study their morphologies, structures, and chemical compositions. The development of GO-based electrochemical sensors and their pharmaceutical, medical, environmental, and food safety applications are discussed. Further, the effects of these GO-based nanomaterials and different electrochemical techniques (e.g., cyclic voltammetry, square wave voltammetry, linear sweep voltammetry, and differential pulse voltammetry) on the performance of various electrochemical sensors are addressed.
Alpha-like correlations in "Equation missing" Ne, comparison of quartetting wave function and THSR approaches
Authors: Röpke G. , Xu C. , Zhou B. , Ren Z. Z. , Funaki Y. , Horiuchi H. , Lyu M. , Tohsaki A. , Yamada T.
Published: April 2024

$$^{20}$$

20

Ne can be considered as a double-magic $$^{16}$$

16

O core nucleus surrounded by four nucleons, the constituents of an $$\alpha $$
α
-like quartet. Similar to other nuclei ($$^{212}$$

212

Po, $$^{104}$$

104

Ti, etc.) with a quartet on top of a double-magic core nucleus, significant $$\alpha $$
α
-like correlations are expected. Correlations in the ground state of $$^{20}$$

20

Ne are investigated using different approaches. The quartetting wave function approach (QWFA) predicts a large $$\alpha $$
α
-like cluster contribution near the surface of the nuclei. The Tohsaki-Horiuchi-Schuck-Röpke (THSR) approach describes $$\alpha $$
α
-like clustering in nuclear systems. The results of the QWFA in the Thomas-Fermi and shell-model approximation are compared with THSR calculations for the container model. Results for the $$\alpha $$
α
formation probability and the rms radii are shown.
Field redefinition invariant Lagrange multiplier formalism with gauge symmetries
Authors: McKeon D. G. C. , Brandt F. T. , Martins-Filho S.
Published: April 2024

It has been shown that by using a Lagrange multiplier field to ensure that the classical equations of motion are satisfied, radiative effects beyond one-loop order are eliminated. It has also been shown that through the contribution of some additional ghost fields, the effective action becomes form invariant under a redefinition of field variables, and furthermore, the usual one-loop results coincide with the quantum corrections obtained from this effective action. In this paper, we consider the consequences of a gauge invariance being present in the classical action. The resulting gauge transformations for the Lagrange multiplier field as well as for the additional ghost fields are found. These gauge transformations result in a set of Faddeev–Popov ghost fields arising in the effective action. If the gauge algebra is closed, we find the Becci–Rouet–Stora–Tyutin (BRST) transformations that leave the effective action invariant.
TEMPLATE-ENGINEERED TRIVALENT IRON AND CHROMIUM CONTAINING MACROCYCLIC COMPLEXES: CHARACTERIZATION AND IN VITRO STUDIES
Authors: KUMAR JAI , KUMAR RAMESH , JANGRA ARTI , SINGH DEVENDER , KUMAR HARISH , KUMAR SURESH , KUMAR PARVIN , KHANNA RADHIKA
Published: April 2024

A novel series of tetraaza macrocyclic complexes of biological importance was synthesized by “in situ” template reaction between triethylenetetramine and dibenzoylmethane in the presence of trivalent Fe and Cr metal salts in 1:1:1 molar ratio. These complexes are represented by molecular formula [M(C[Formula: see text]H[Formula: see text]N[Formula: see text]X]X2; [Formula: see text](III) and Cr(III); [Formula: see text], NO[Formula: see text], −OAc; C[Formula: see text]H[Formula: see text]N[Formula: see text] ligand. The reported complexes were characterized by using various physicochemical and spectroscopic techniques including elemental analyses, molar conductance, thermo-gravimetric analysis, FTIR, UV–Visible and mass spectral studies. The results obtained from analytical techniques and spectroscopic techniques together suggested the complexes have a square pyramidal geometry. Various computational studies were performed including molecular docking and modeling. Further, macrocyclic complexes were also screened for their “in vitro” antimicrobial activity against selected bacterial and fungal strains. The antioxidant activity of these complexes was also evaluated. Some of the complexes were found to possess remarkable antimicrobial activity and antioxidant activity. However, complex [Fe(C[Formula: see text]H[Formula: see text]N[Formula: see text](NO[Formula: see text]](NO[Formula: see text] was found to be most potent against selected bacterial and fungal strains. On the other hand, complex [Cr(C[Formula: see text]H[Formula: see text]N[Formula: see text](NO[Formula: see text]](NO[Formula: see text] was found to show best antioxidant activity with lowest value of IC[Formula: see text].
ShennongMGS: An LLM-based Chinese Medication Guidance System
Authors: Dou Yutao , Huang Yuwei , Zhao Xiongjun , Zou Haitao , Shang Jiandong , Lu Ying , Yang Xiaolin , Xiao Jian , Peng Shaoliang
Published: April 2024

The rapidly evolving field of Large Language Models (LLMs) holds immense promise for healthcare, particularly in medication guidance and adverse drug reaction prediction. Despite their potential, existing LLMs face challenges in dealing with complex polypharmacy scenarios and often grapple with data lag issues. To address these limitations, we introduce an LLM-based Chinese medication guidance system, called ShennongMGS, specifically tailored for robust medication guidance and adverse drug reaction predictions. Our system transforms multi-source heterogeneous medication information into a knowledge graph and employs a two-stage training strategy to construct a specialised LLM (ShennongGPT). This method enables the simulation of professional pharmacists’ decision-making processes and incorporates the capability for knowledge self-updating, thereby significantly enhancing drug safety and the overall quality of medical services. Rigorously evaluated by medical professionals and artificial intelligence experts, our method demonstrates superiority, outperforming existing general and specialised LLMs in performance.
ReHarvest: An ADC Resource-Harvesting Crossbar Architecture for ReRAM-Based DNN Accelerators
Authors: Xu Jiahong , Liu Haikun , Duan Zhuohui , Liao Xiaofei , Jin Hai , Yang Xiaokang , Li Huize , Liu Cong , Mao Fubing , Zhang Yu
Published: April 2024

ReRAM-based
Processing-In-Memory
(PIM) architectures have been increasingly explored to accelerate various
Deep Neural Network
(DNN) applications because they can achieve extremely high performance and energy-efficiency for in-situ analog
Matrix-Vector Multiplication
(MVM) operations. However, since ReRAM crossbar arrays’ peripheral circuits–
analog-to-digital converters
(ADCs) often feature high latency and low area efficiency, AD conversion has become a performance bottleneck of in-situ analog MVMs. Moreover, since each crossbar array is tightly coupled with very limited ADCs in current ReRAM-based PIM architectures, the scarce ADC resource is often underutilized.

In this article, we propose ReHarvest, an ADC-crossbar decoupled architecture to improve the utilization of ADC resource. Particularly, we design a many-to-many mapping structure between crossbars and ADCs to share all ADCs in a tile as a resource pool, and thus one crossbar array can harvest much more ADCs to parallelize the AD conversion for each MVM operation. Moreover, we propose a
multi-tile matrix mapping
(MTMM) scheme to further improve the ADC utilization across multiple tiles by enhancing data parallelism. To support fine-grained data dispatching for the MTMM, we also design a bus-based interconnection network to multicast input vectors among multiple tiles, and thus eliminate data redundancy and potential network congestion during multicasting. Extensive experimental results show that ReHarvest can improve the ADC utilization by 3.2×, and achieve 3.5× performance speedup while reducing the ReRAM resource consumption by 3.1× on average compared with the state-of-the-art PIM architecture–FORMS.
Deceived by Immersion: A Systematic Analysis of Deceptive Design in Extended Reality
Authors: Hadan Hilda , Choong Lydia , Zhang-Kennedy Leah , Nacke Lennart E.
Published: April 2024

The well-established deceptive design literature has focused on conventional user interfaces. With the rise of extended reality (XR), understanding deceptive design’s unique manifestations in this immersive domain is crucial. However, existing research lacks a full, cross-disciplinary analysis that analyzes how XR technologies enable new forms of deceptive design. Our study reviews the literature on deceptive design in XR environments. We use thematic synthesis to identify key themes. We found that XR’s immersive capabilities and extensive data collection enable subtle and powerful manipulation strategies. We identified eight themes outlining these strategies and discussed existing countermeasures. Our findings show the unique risks of deceptive design in XR, highlighting implications for researchers, designers, and policymakers. We propose future research directions that explore unintentional deceptive design, data-driven manipulation solutions, user education, and the link between ethical design and policy regulations.
Designing an Open-Source Flow Battery Kit: Workshop Presentation Given at Flow4U Conference
Authors: Smith Kirk , Pinto Daniel Fernández , Hauser Josh , Faez Sanli
Published: April 2024

These slides were presented at the Flow4U conference held at Eindhoven University on April 9, 2024. They detail the early efforts of a project to develop an open-source flow battery for research and educational use. An online version of the slides, including videos, is available at https://fbrc.codeberg.page/flow4u-slides/ . The project and documentation are still works in progress and should not be taken as instructions for building a battery or a cell for non-experts.
Mechanisms of spinophilin-dependent pancreas dysregulation in obesity
Authors: Stickel Kaitlyn C. , Shah Nikhil R. , Claeboe Emily T. , Orr Kara S. , Mosley Amber L. , Doud Emma H. , Belecky-Adams Teri L. , Baucum Anthony J.
Published: April 2024

To our knowledge, these data are the first to demonstrate that obesity impacts spinophilin protein interactions in the pancreas and identify spinophilin specifically in pancreatic β cells as a modulator of whole body glucose tolerance.
M2 receptors are required for spatiotemporal sequence learning in mouse primary visual cortex
Authors: Sarkar Susrita , Martinez Reyes Catalina , Jensen Cambria M. , Gavornik Jeffrey P.
Published: April 2024

Muscarinic acetylcholine receptors are required for multiple forms of plasticity in the brain and support perceptual functions, but the precise role of the five subtypes (M1–M5) are unclear. Here we show that the M2 receptor is specifically required to encode experience-dependent representations of spatiotemporal relationships in both monocular and binocular regions of mouse V1. This work identifies a novel functional role for M2 receptors in coding temporal information into cortical circuits.
Magnitude of Thrombocytopenia and Associated Factors among Pregnant Women Attending the Antenatal Care Service Unit of Wachemo University Nigist Ellen Mohammed Comprehensive Specialized Hospital Hosanna, Southern Ethiopia
Authors: Tirago Dembelo , Yemane Tilahun , Tadasa Edosa
Published: April 2024

Background. Thrombocytopenia is the second most common hematological disorder in pregnancy after anemia worldwide and affects 7‐8% of all pregnancies. Pregnant women with thrombocytopenia have complications of excessive bleeding during or after childbirth, exudation at the cesarean section, and neonatal thrombocytopenia. Therefore, the main aim of this study was to assess the magnitude of thrombocytopenia and its associated factors among pregnant women attending the Antenatal Care Service Unit of Wachemo University Nigist Ellen Mohammed Comprehensive Specialized Hospital Hosanna, Southern Ethiopia. Materials and Methods. A cross‐sectional study was conducted from June 1 to August 30, 2022, involving 209 consecutive pregnant women who came to the hospital during the study period for antenatal care follow‐up. Sociodemographic, reproductive, and other clinical data were collected using a structured questionnaire. A four‐milliliter venous blood specimen was collected for complete blood analysis and peripheral blood smear. The data were analyzed by using SPSS version 25. Descriptive statistical analysis and bivariate and multivariate logistic regression analyses were performed. A P value ≤0.05 was considered to indicate statistical significance. Results. The overall magnitude of thrombocytopenia among pregnant women was 14.8% (95% CI: 10, 19.6). The prevalence of mild, moderate, and severe thrombocytopenia was 77.4%, 16.1%, and 6.5%, respectively. Multivariate logistic regression revealed that rural residence (AOR = 2.6 and 95% CI = 1.02, 7.12), cigarette smoking (AOR = 8.4 and 95% CI = 1.86, 38), anemia (AOR = 8.3 and 95% CI = 2.7, 25.6), and alcohol consumption (AOR = 8.2 and 95% CI = 2.17–31) were significantly independent factors associated with the development of thrombocytopenia. Conclusion. The magnitude of thrombocytopenia in this study was 14.8%. Rural residence, cigarette smoking, alcohol consumption, and anemia were significantly associated with thrombocytopenia. Therefore, the platelet count should be routinely determined during antenatal care visits for proper diagnosis and to minimize bleeding during and/or after childbirth.
Facts and Hopes on Cancer Immunotherapy for Small Cell Lung Cancer
Authors: Zugazagoitia Jon , Osma Handerson , Baena Javier , Ucero Alvaro C. , Paz-Ares Luis
Published: April 2024

Platinum-based chemotherapy plus PD1 axis blockade is the standard of care in the first-line treatment of extensive-stage small cell lung cancer (SCLC). Despite the robust and consistent increase in long-term survival with PD1 axis inhibition, the magnitude of the benefit from immunotherapy seems lower than that for other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including T-cell exclusion, downregulation of components of the MHC class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints, among others. New immunotherapies aiming to target some of these dominant immune suppressive features are being intensively evaluated preclinically and clinically in SCLC. They include strategies to enhance the efficacy and/or reverse features that promote intrinsic resistance to PD1 axis inhibition (e.g., restoring MHC class I deficiency and targeting DNA damage response) and novel immunomodulatory agents beyond T-cell checkpoint blockers (e.g., T cell–redirecting strategies, antibody–drug conjugates, or macrophage checkpoint blockers). Among them, delta-like ligand 3–targeted bispecific T-cell engagers have shown the most compelling preliminary evidence of clinical efficacy and hold promise as therapies that might contribute to further improve patient outcomes in this disease. In this study, we first provide a brief overview of key tumor microenvironment features of human SCLC. Then, we update the current clinical evidence with immune checkpoint blockade and review other emerging immunotherapy strategies that are gaining increasing attention in SCLC. We finally summarize our future perspective on immunotherapy and precision oncology for this disease.
Monitoring Hepatocellular Carcinoma Using Tumor Content in Circulating Cell-Free DNA
Authors: Lian Shifeng , Lu Chenyu , Li Fugui , Yu Xia , Ai Limei , Wu Biaohua , Gong Xueyi , Zhou Wenjing , Liang Xuejun , Zhan Jiyun , Yuan Yong , Fang Fang , Liu Zhiwei , Ji Mingfang , Zheng Zongli
Published: April 2024

Purpose:

The objective of the study was to evaluate the use of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.

Experimental Design:

We included 67 patients with hepatitis B virus–related HCC, of whom 17 had paired pre- and posttreatment samples, and 90 controls. Additionally, in a prospective cohort with hepatitis B virus surface antigen–positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA.

Results:

High tumor content was associated with advanced tumor stage (P < 0.001) and poor survival after HCC diagnosis [HR = 12.35; 95% confidence interval (CI) = 1.413–107.9; P = 0.023]. Tumor content turned negative after surgery (P = 0.027), whereas it remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95% CI = 92.2%–99.7%). In pre-HCC samples, the tumor content increased from 0.014 at 4 years before diagnosis to 0.026 at 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95% CI = 11.5%–37.8%) within 1 year before diagnosis to 30.4% (95% CI = 13.2%–52.9%) at the Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 81.8% (95% CI = 59.7%–94.8%) at stage B, and 95.5% (95% CI = 77.2%–99.9%) at stage C.

Conclusions:

The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC 1 yearearlier than clinical diagnosis and in predicting patient prognosis.
Hydrogen peroxide is responsible for the cytotoxic effects of Streptococcus pneumoniae on primary microglia in the absence of pneumolysin
Authors: Jennert Franziska , Schaaf Désirée , Nau Roland , Kohler Thomas P. , Hammerschmidt Sven , Häusler Darius , Valentin-Weigand Peter , Seele Jana
Published: April 2024

Introduction: Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants, among them hydrogen peroxide (H2O2) and pneumolysin (Ply), which contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone marrow-derived macrophages (BMDM).
Methods: Microglia and BMDM were co-incubated with S. pneumoniae D39 to analyze survival of phagocytes by fluorescence microscopy, bacterial growth by quantitative plating, and phagocytosis by an antibiotic protection assay. Ply was detected by hemolysis assay and Western blot analysis.
Results: We found that microglia were killed during pneumococcal infection with a wild-type and an isogenic ply-deficient mutant, whereas viability of BMDM was not affected by pneumococci. Treatment with recombinant Ply showed a dose-dependent cytotoxic effect on microglia and BMDM. However, high concentrations of recombinant Ply were required and under the chosen experimental conditions, Ply was not detectable in the supernatant during infection of microglia. Inactivation of H2O2 by exogenously added catalase abolished its cytotoxic effect. Consequently, infection of microglia with pneumococci deficient for the pyruvate oxidase SpxB, primarily producing H2O2, resulted in reduced killing of microglia.
Conclusion: Taken together, in the absence of Ply, H2O2 caused cell death in primary phagocytes in concentrations produced by pneumococci.
Efficacy, Safety, and Quality of Life of Pegcetacoplan in Japanese Patients with Paroxysmal Nocturnal Hemoglobinuria Treated within the Phase 3 PEGASUS Trial
Authors: Nishimori Hisakazu , Nakazawa Hideyuki , Tamura Shinobu , Uchida Toshiki , Usuki Kensuke , Szamosi Johan , de Latour Régis Peffault , Röth Alexander , Panse Jens
Published: April 2024

Introduction: Pegcetacoplan, the first approved proximal complement C3 inhibitor, showed superiority to eculizumab in improving hemoglobin levels and clinical outcomes in the phase 3 PEGASUS study in patients with paroxysmal nocturnal hemoglobinuria (PNH) and inadequate response to eculizumab. Methods: This analysis evaluates the efficacy and safety of pegcetacoplan for Japanese patients in PEGASUS, as they are known for different clinicopathologic features compared to non-Asian patients. Ten Japanese patients were enrolled to receive pegcetacoplan (n = 5) or eculizumab (n = 5) during the 16-week randomized controlled period. All patients received pegcetacoplan monotherapy during the open-label period until week 48. Results: Treatment with pegcetacoplan improved hemoglobin with a mean change from baseline of 2.4 g/dL at week 16, which was sustained through 48 weeks. Pegcetacoplan-treated Japanese patients experienced sustained improvements in key secondary efficacy endpoints, including freedom from transfusion, lactate dehydrogenase level, reticulocyte count, and FACIT-Fatigue score. The safety profile was consistent with previously reported data from pegcetacoplan studies. No events of hemolysis, meningococcal infection, or thrombosis were reported in the Japanese population and all Japanese patients remained on treatment throughout the study. Conclusion: These data suggest that Japanese patients with PNH can be effectively and safely managed with pegcetacoplan.
Hypothalamic GABAergic Neurons Expressing Cellular Retinoic Acid Binding Protein 1 (CRABP1) Are Sensitive to Metabolic Status and Liraglutide in Male Mice
Authors: Lavoie Olivier , Turmel Audrey , Mattoon Paige , Desrosiers William James , Plamondon Julie , Michael Natalie Jane , Caron Alexandre
Published: April 2024

Introduction: Owing to their privileged anatomical location, neurons of the arcuate nucleus of the hypothalamus (ARC) play critical roles in sensing and responding to metabolic signals such as leptin and glucagon-like peptide 1 (GLP-1). In addition to the well-known proopiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons, subpopulations of GABAergic neurons are emerging as key regulators of energy balance. However, the precise identity of these metabolic neurons is still elusive. Here, we identified and characterized the molecular signature of a novel population of GABAergic neurons of the ARC expressing Cellular retinoic acid binding protein 1 (Crabp1). Methods: Using a combination of immunohistochemistry and in situ hybridization techniques, we investigated the expression of Crabp1 across the mouse brain and characterized the molecular identity of Crabp1ARC neurons. We also determined whether Crabp1ARC neurons are sensitive to fasting, leptin, and GLP1R agonism by assessing cFOS immunoreactivity as a marker of neuronal activity. Results: Crabp1ARC neurons represent a novel GABAergic neuronal population robustly enriched in the ARC and are distinct from the prototypical melanocortin neurons. Crabp1ARC neurons overlap with three subpopulations of yet uncharacterized ARC neurons expressing Htr3b, Tbx19, and Tmem215. Notably, Crabp1ARC neurons express receptors for metabolic hormones and their activity is modulated by the nutritional state and GLP1R agonism. Conclusion: Crabp1ARC neurons represent a novel heterogeneous population of GABAergic neurons sensitive to metabolic status.
Current Surgical Methods in Local Rectal Excision
Authors: Šemanjski Kristina , Lužaić Karla , Brkić Jure
Published: April 2024

Background: The treatment of rectal cancer has evolved with the advancement of surgical techniques. Less invasive approaches are becoming more accepted as the primary treatment method. Summary: Such methods as transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery can reduce morbidity and mortality rates. However, not all patients are suitable candidates for these procedures, and proper diagnostics are necessary to establish indications. Compared to total mesorectal excision, transanal excision techniques have been shown to have fewer complications and comorbidities while still being able to remove cancerous tissue entirely. Transanal excision is the simplest method, where the operator removes visible rectal lesions. The basic principle of transanal endoscopic microsurgery is to dilate the rectum mechanically and by air insufflation and then use special surgical instruments to remove suspicious lesions under the vision of a telescope. Transanal minimally invasive surgery combines transanal endoscopic microsurgery and single-incision laparoscopic surgery, making the hard-to-reach proximal rectum accessible to classic laparoscopic instruments. Key Message: Local excision techniques, when used as a monotherapy for treating patients with rectal cancer, have established themselves as a curative and less radical treatment for strictly selected patients with early rectal carcinoma, leading to improved quality of life. When combined with other modalities such as neoadjuvant chemoradiotherapy, total neoadjuvant therapy, and immunotherapy, transanal surgery can be offered to patients with locally advanced rectal cancer as part of the organ preservation strategy. This review will discuss the patient selection and technical aspects of transanal surgery, showcasing its current role in treating rectal carcinoma.
Sustentabilidade e consumo na imprensa
Authors: Britto Ana Carolina Milo
Published: April 2024

Boa parte das discussões em torno da questão ambiental surgem da necessidade de evidenciar a importância da sustentabilidade na sociedade contemporânea, como alternativa aos recursos limitados do planeta. Surge então, uma nova forma de encarar o consumo, que será explorado sob a perspectiva da mídia e do papel do jornalismo na produção de conteúdo, além dos aspetos cotidianos.
A criação de um sistema de coleta de informações de jornais
Authors: Kühl Júlio Cesar Assis , Lorenzetti Silvana , Fanganiello Vera Lígia
Published: April 2024

(1º parágrafo do artigo)

O Projeto Leviathan desenvolveu em uma primeira etapa, uma técnica de coleta de informações históricas aplicada aos Anais do Parlamento Brasileiro; a partir de margo de 1975 vem atuando em atividades paralelas no setor do jornalismo, tendo como objetivo básico o estudo dos aspectos importantes de um jornal — visto como uma unidade de informacöes a serem cadastradas e conservadas em um banco de dados.
O Juízo Divino na História: a História de Israel em Ez. 20, 1-44.
Authors: Mota Jorge Cesar
Published: April 2024

Resenha do livro:

GARMUS, O. F. M. (Frei Ludovico). — O Juízo Divino na História. A História de Israel em Ez. 20, 1-44. Editora Vozes, Petrópolis, 1975, 108 págs.
O negro no mundo dos brancos
Authors: Oliveira Lúcia Maria de
Published: April 2024

Resenha do livro:

FERNANDES, Florestan. O negro no mundo dos brancos. Difusäo Europeia do Livro. Säo Paulo, 1972. 283 päg.