bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating and Mitigating Limitations of Large Language Models in Clinical Decision Making
Authors: Hager Paul , Jungmann Friederike , Bhagat Kunal , Hubrecht Inga , Knauer Manuel , Vielhauer Jakob , Holland Robbie , Braren Rickmer , Makowski Marcus , Kaisis Georgios , Rueckert Daniel
Published: January 2024

Clinical decision making is one of the most impactful parts of a physician’s responsibilities and stands to benefit greatly from AI solutions and large language models (LLMs) in particular. However, while LLMs have achieved excellent performance on medical licensing exams, these tests fail to assess many skills that are necessary for deployment in a realistic clinical decision making environment, including gathering information, adhering to established guidelines, and integrating into clinical workflows. To understand how useful LLMs are in real-world settings, we must evaluate themin the wild, i.e. on real-world data under realistic conditions. Here we have created a curated dataset based on the MIMIC-IV database spanning 2400 real patient cases and four common abdominal pathologies as well as a framework to simulate a realistic clinical setting. We show that current state-of-the-art LLMs do not accurately diagnose patients across all pathologies (performing significantly worse than physicians on average), follow neither diagnostic nor treatment guidelines, and cannot interpret laboratory results, thus posing a serious risk to the health of patients. Furthermore, we move beyond diagnostic accuracy and demonstrate that they cannot be easily integrated into existing workflows because they often fail to follow instructions and are sensitive to both the quantity and order of information. Overall, our analysis reveals that LLMs are currently not ready for clinical deployment while providing a dataset and framework to guide future studies.
Modulation of circadian rhythms in articular cartilage by heat pulses
Authors: Gonçalves Cátia F. , Dudek Michal , Pathiranage Dharshika RJ , Paszek Anna , El-Houni Zeyad , Li Shiyang , Tawy Gwenllian , Biant Leela , Hoyland Judith A. , Meng Qing-Jun
Published: January 2024

Objective

Prior studies have shown that disruption of the circadian clock leads to cartilage degeneration in mice while shift work is associated with higher risk of osteoarthritis (OA) in humans. In this study we investigated the potential of heat pulses to restore dampened circadian rhythms in articular cartilage.

Methods

Femoral head cartilage explants and primary chondrocytes were isolated from PER2::LUC mice. Human femoral condyle cartilage was obtained from osteoarthritic patients undergoing total knee replacement. Tissues and cells were exposed to heat shock at various temperatures (37-43 °C) and incubation lengths. Bioluminescence from explants and cells was recorded in real-time. RNA sequencing and qPCR were used to assess gene expression changes in response to heat.

Results

We established that a 60-min pulse at 43 °C was sufficient to restore dampened PER2::LUC rhythms in mouse cartilage explants or in primary chondrocytes. Transcriptome analysis in mouse articular cartilage showed an up-regulation of genes encoding heat shock proteins and collagens, and a transient down-regulation ofSox9,Runx2,Per1,ClockandCry2. Heat induced the expression of circadian clock genes in human osteoarthritic knee cartilage. Mechanistically, inhibition of HSP90 activity or perturbation of F-actin polymerisation blocked the heat-induced resynchronisation of circadian rhythms.

Conclusion

Together, these data have contributed to a greater understanding of the multifaceted nature of the connections between circadian timekeeping, heat stress responses and homeostasis in articular cartilage. These findings also suggest that time-prescribed temperature increases could be developed into a non-invasive intervention to slow down tissue ageing and restore homeostasis in osteoarthritic joints by improving circadian oscillations of cartilage rhythmic pathways.
Integration of fear learning and fear expression across the dorsoventral axis of the hippocampus
Authors: Pompili Marco N. , Hamou Noé , Wiener Sidney I.
Published: January 2024

Classically, the dorsal and ventral hippocampus are thought to play distinct roles in fear conditioning, with the dorsal hippocampus primarily handling information about environmental cues and contexts, and the ventral hippocampus more involved in emotional processing. Both functions are essential for the learning and expression of conditioned fear responses, but how these processes are integrated remains largely unexplored. In this study, we simultaneously recorded single-unit activity from the dorsal and ventral hippocampus during fear conditioning to identify the neural dynamics that may underlie these processes and their integration. As fear expression emerged, shifts in neural firing patterns were observed in both regions, with a stronger shift in ventral hippocampal activity, as expected. However, contrary to the prevailing view of the ventral hippocampus as central to anxiety and fear regulation, fear expression-related neuronal responses were surprisingly more predominant in the dorsal hippocampus. In contrast, ventral hippocampal neuronal activity was more closely linked with the acquisition of conditioned fear. These features were combined in cell assemblies that emerged during fear conditioning, composed of both dorsal fear expression-responsive neurons and ventral fear learning-responsive cells. These multifactorial engrams, distributed along the hippocampal dorso-ventral axis, provide a potential substrate for integrating fear acquisition and expression, thereby coordinating associative learning.
Core-corona procedure and microcanonical hadronization to understand strangeness enhancement in proton-proton and heavy ion collisions in the EPOS4 framework
Authors: Werner K.
Published: January 2024

The multiplicity dependence of multistrange hadron yields in proton-proton and lead-lead collisions at several TeV allows one to study the transition from very big to very small systems, in particular, concerning collective effects. I investigate this, employing a core-corona approach based on new microcanonical hadronization procedures in the 4 framework, as well as new methods allowing one to transform energy-momentum flow through freeze-out surfaces into invariant-mass elements. I try to disentangle effects due to “canonical suppression” and “core-corona separation”, which will both lead to a reduction of the yields at low multiplicity.

Published by the American Physical Society
2024
Precursory Cooper flow in ultralow-temperature superconductors
Authors: Hou Pengcheng , Cai Xiansheng , Wang Tao , Deng Youjin , Prokof'ev Nikolay V. , Svistunov Boris V. , Chen Kun
Published: January 2024

Superconductivity at low temperature—observed in lithium and bismuth, as well as in various low-density superconductors—calls for the development of reliable theoretical and experimental tools for predicting ultralow critical temperatures Tc of Cooper instability in a system demonstrating simply normal Fermi liquid behavior in a broad range of temperatures below the Fermi energy TF. Equally important are controlled predictions of stability in a given Cooper channel. We identify such a protocol within the paradigm of precursory Cooper flow—a universal ansatz describing logarithmically slow temperature evolution of the linear response of the normal state to the pair-creating perturbation. Applying this framework to the two-dimensional uniform electron gas, we reveal a series of exotic superconducting states, pushing controlled theoretical predictions of Tc to the unprecedentedly low scale of 10−100TF.

Published by the American Physical Society
2024
Cavity optomechanical detection of persistent currents and solitons in a bosonic ring condensate
Authors: Pradhan Nalinikanta , Kumar Pardeep , Kanamoto Rina , Dey Tarak Nath , Bhattacharya M. , Mishra Pankaj Kumar
Published: January 2024

We present numerical simulations of the cavity optomechanical detection of persistent currents and bright solitons in an atomic Bose-Einstein condensate confined in a ring trap. This paper describes a technique that measures condensate rotation , in real time, and with minimal destruction, in contrast to currently used methods, all of which destroy the condensate completely. For weakly repulsive interatomic interactions, the analysis of persistent currents extends our previous few-mode treatment of the condensate [P. Kumar ] to a stochastic Gross-Pitaevskii simulation. For weakly attractive atomic interactions, we present the first analysis of optomechanical detection of matter-wave soliton motion. We provide optical cavity transmission spectra containing signatures of the condensate rotation, sensitivity as a function of the system response frequency, and atomic density profiles quantifying the effect of the measurement backaction on the condensate. We treat the atoms at a mean-field level and the optical field classically, account for damping and noise in both degrees of freedom, and investigate the linear as well as nonlinear response of the configuration. Our results are consequential for the characterization of rotating matter waves in studies of atomtronics, superfluid hydrodynamics, and matter-wave soliton interferometry.

Published by the American Physical Society
2024
Deformed Fredkin model for the
ν=5/2
Moore-Read state on thin cylinders
Authors: Voinea Cristian , Pu Songyang , Kirmani Ammar , Ghaemi Pouyan , Rahmani Armin , Papić Zlatko
Published: January 2024

We propose a frustration-free model for the Moore-Read quantum Hall state on sufficiently thin cylinders with circumferences ≲7 magnetic lengths. While the Moore-Read Hamiltonian involves complicated long-range interactions between triplets of electrons in a Landau level, our effective model is a simpler one-dimensional chain of qubits with deformed Fredkin gates. We show that the ground state of the Fredkin model has high overlap with the Moore-Read wave function and accurately reproduces the latter's entanglement properties. Moreover, we demonstrate that the model captures the dynamical response of the Moore-Read state to a geometric quench, induced by suddenly changing the anisotropy of the system. We elucidate the underlying mechanism of the quench dynamics and show that it coincides with the linearized bimetric field theory. The minimal model introduced here can be directly implemented as a first step towards quantum simulation of the Moore-Read state, as we demonstrate by deriving an efficient circuit approximation to the ground state and implementing it on an IBM quantum processor.

Published by the American Physical Society
2024
Calculating the many-body density of states on a digital quantum computer
Authors: Summer Alessandro , Chiaracane Cecilia , Mitchison Mark T. , Goold John
Published: January 2024

Quantum statistical mechanics allows us to extract thermodynamic information from a microscopic description of a many-body system. A key step is the calculation of the density of states, from which the partition function and all finite-temperature equilibrium thermodynamic quantities can be calculated. In this work, we devise and implement a quantum algorithm to perform an estimation of the density of states on a digital quantum computer which is inspired by the kernel polynomial method. Classically, the kernel polynomial method allows us to sample spectral functions via a Chebyshev polynomial expansion. Our algorithm computes moments of the expansion on quantum hardware using a combination of random-state preparation for stochastic trace evaluation and a controlled unitary operator. We use our algorithm to estimate the density of states of a nonintegrable Hamiltonian on the Quantinuum H1-1 trapped ion chip for a controlled register of 18 qubits. This not only represents a state-of-the-art calculation of thermal properties of a many-body system on quantum hardware, but also exploits the controlled unitary evolution of a many-qubit register on an unprecedented scale.

Published by the American Physical Society
2024
Hyperoptimized Approximate Contraction of Tensor Networks with Arbitrary Geometry
Authors: Gray Johnnie , Chan Garnet Kin-Lic
Published: January 2024

Tensor network contraction is central to problems ranging from many-body physics to computer science. We describe how to approximate tensor network contraction through bond compression on arbitrary graphs. In particular, we introduce a hyperoptimization over the compression and contraction strategy itself to minimize error and cost. We demonstrate that our protocol outperforms both handcrafted contraction strategies in the literature as well as recently proposed general contraction algorithms on a variety of synthetic and physical problems on regular lattices and random regular graphs. We further showcase the power of the approach by demonstrating approximate contraction of tensor networks for frustrated three-dimensional lattice partition functions, dimer counting on random regular graphs, and to access the hardness transition of random tensor network models, in graphs with many thousands of tensors.

Published by the American Physical Society
2024
Time-resolved AUSAXS at BL28XU at SPring-8
Authors: Nakanishi Yohei , Fujinami So , Shibata Motoki , Miyazaki Tsukasa , Yamamoto Katsuhiro , Takenaka Mikihito
Published: January 2024

An anomalous ultra-small-angle X-ray scattering (AUSAXS) system has been constructed at BL28XU at SPring-8 for time-resolved AUSAXS experiments. The path length was extended to 9.1 m and a minimum of q = 0.0069 nm−1 was attained. Scattering profiles at 0.0069 to 0.3 nm−1 were successfully obtained at 17 different X-ray energies in 30 s using the BL28XU optical setup, which enables adjustment of the energy of the incident X-rays quickly without the beam position drifting. Time-resolved measurements were conducted to investigate changes in the structure of zinc compounds in poly(styrene-ran-butadiene) rubber during vulcanization. A change in energy dependence of the scattered intensity with time was found during vulcanization, suggesting the transformation of zinc in the reaction.
Crystal structures of the alkali aluminoboracites A
4B4Al3O12Cl (A = Li, Na)
Authors: Yoshino Sho , Arima Hidechika , Ishijima Masanao , Kajihara Koichi
Published: January 2024

Single crystals of alkali aluminoboracites, A
4B4Al3O12Cl (A = Li, Na), were grown using the self-flux method, and their isotypic cubic crystal structures were determined by single-crystal X-ray diffraction. Na4B4Al3O12Cl is the first reported sodium boracite, and its lattice parameter [13.5904 (1) Å] is the largest among the boracites consisting of a cation–oxygen framework reported so far. For both crystals, structure models refined in the cubic space group F\overline{4}3c, which assume that all cubic octant subcells in the unit cell are equivalent, converged with R1 factors of ∼0.03. However, the presence of weak hhl reflections with odd h and l values indicates that refinements in the space group F23, which presume a checkerboard-like ordering of two types of subcells with slightly different atomic positions, are more appropriate.
(E)-N,N-Diethyl-4-{[(4-methoxyphenyl)imino]methyl}aniline: crystal structure, Hirshfeld surface analysis and energy framework
Authors: Subashini A. , Kumaravel R. , Tharmalingam B. , Ramamurthi K. , Crochet Aurélien , Stoeckli-Evans Helen
Published: January 2024

In the title benzylideneaniline Schiff base, C18H22N2O, the aromatic rings are inclined to each other by 46.01 (6)°, while the Car—N= C—Car torsion angle is 176.9 (1)°. In the crystal, the only identifiable directional interaction is a weak C—H...π hydrogen bond, which generates inversion dimers that stack along the a-axis direction.
Electrifying the future: analysing the determinants of electric vehicle adoption
Authors: Pandita Deepika , Bhatt Vimal , Kumar V. V. Ravi , Fatma Anam , Vapiwala Fatima
Published: January 2024

Purpose

This study aims to emphasize green energy-driven solutions to address environmental sustainability issues, particularly to promote the uptake of electric vehicles (EVs). This study intends to investigate user adoption of EVs as the existing predicament of converting car owners to EV buyers, demanding a push to create a facilitating environment for EV uptake.

Design/methodology/approach

A survey-based quantitative study involving 330 car owners and potential buyers was conducted involving four predictors, i.e. financial benefits, social influence, charging infrastructure and range consciousness. Environmental concerns and socio-demographic factors such as age, family income and gender were considered as moderators between these predictors and EV adoption intention. Partial least square structural equation modelling was used to analyse the proposed relationships.

Findings

The findings indicated that financial benefits (ß = 0.169, t = 3.930), social influence (ß = 0.099, t = 2.605), range consciousness (ß = 0.239, t = 3.983) and charging infrastructure (ß = 0.142, t = 4.8) significantly impact EV adoption. Family income was the most significant moderator with a large effect size (F square = 0.224), followed by environmental concern (F square = 0.182) and age (F square = 0.042) having a medium moderation effect and, subsequently, gender (F square = 0.010) as a mild moderator.

Originality/value

By analysing environmental concerns as a moderator, this study fosters a novel understanding of how environmental concerns impact EV adoption, which has not been explored. Additionally, the empirical assessment of the socio-economic and socio-demographic factors of EV adoption helps to offer a consumer perspective to the government and policymakers in undertaking initiatives to promote EV adoption.
Artificial intelligence: threat or asset to academic integrity? A bibliometric analysis
Authors: Rodrigues Margarida , Silva Rui , Borges Ana Pinto , Franco Mário , Oliveira Cidália
Published: January 2024

Purpose

This study aims to address a systematic literature review (SLR) using bibliometrics on the relationship between academic integrity and artificial intelligence (AI), to bridge the scattering of literature on this topic, given the challenge and opportunity for the educational and academic community.

Design/methodology/approach

This review highlights the enormous social influence of COVID-19 by mapping the extensive yet distinct and fragmented literature in AI and academic integrity fields. Based on 163 publications from the Web of Science, this paper offers a framework summarising the balance between AI and academic integrity.

Findings

With the rapid advancement of technology, AI tools have exponentially developed that threaten to destroy students' academic integrity in higher education. Despite this significant interest, there is a dearth of academic literature on how AI can help in academic integrity. Therefore, this paper distinguishes two significant thematical patterns: academic integrity and negative predictors of academic integrity.

Practical implications

This study also presents several contributions by showing that tools associated with AI can act as detectors of students who plagiarise. That is, they can be useful in identifying students with fraudulent behaviour. Therefore, it will require a combined effort of public, private academic and educational institutions and the society with affordable policies.

Originality/value

This study proposes a new, innovative framework summarising the balance between AI and academic integrity.
‘We welcome migrants and the tourists come’: postmodern hospitality in Palermo, Sicily
Authors: Neil Margaret
Published: January 2024

In Palermo, Sicily, actors use the metaphor of hospitality to profess cosmopolitan attitudes towards ‘migrants’. This raises a conceptual puzzle: hospitality and cosmopolitanism represent contradictory models of social ethics. But an ethnography of one social enterprise reveals that the hospitality in use is not traditional hospitality. Rather, employing what I call ‘postmodern hospitality’ shows a contemporary, reimagined form of hospitality that is compatible with the ‘Mediterranean cosmopolitanism’ invoked. Actors can thus declare sociopolitical aims of including ‘migrants’ while saving their ‘dying’ city. But this politics blurs with economic aims of attracting tourists. Following ‘postmodern hospitality’ shows how local actors use idealized images of Sicily to appeal to outsiders while attempting to subvert engrained ideas of Sicily as ‘backwards’. The risk is that they participate in the European spectacle of migration, and the commodification of notions of ‘Mediterraneanness’ and ‘Southernness’.
Truth clashes: caste atrocities, false cases, and the limits of hate crime law in North India
Authors: Fuchs Sandhya
Published: January 2024

This article brings together theories of truth in legal anthropology and the anthropology of religion to highlight how legal institutions can co‐opt hate crime laws and reproduce patterns of sociopolitical oppression. Drawing on extensive ethnographic research on the social life of India's only hate crime law – the 1989 Prevention of Atrocities Act (PoA), which punishes violence against Dalit (ex‐untouchable) communities – the article argues that hate crime cases involve a clash between three different truth logics: attributive truth or credibility; formal juridical truth regimes defined by evidentiary technicalities; and a distinct mode of experiential‐discriminatory truth, which is defined by its processual character. As Indian police and judiciary conflate these truth logics in practice, they publicly and legally erase realities of caste discrimination and (re)construct marginalized communities like Dalits as greedy and unreliable narrators.
Revising the Logic Model Behind Health Care's Social Care Investments
Authors: GOTTLIEB LAURA M. , HESSLER DANIELLE , WING HOLLY , GONZALEZ‐ROCHA ALEJANDRA , CARTIER YURI , FICHTENBERG CAROLINE
Published: January 2024

Policy Points

This article summarizes recent evidence on how increased awareness of patients’ social conditions in the health care sector may influence health and health care utilization outcomes.

Using this evidence, we propose a more expansive logic model to explain the impacts of social care programs and inform future social care program investments and evaluations.
Ameliorating effects of Acanthopanax koreanum extract and components on nicotine dependence and withdrawal symptoms
Authors: Lee Hyun Jun , Ortiz Darlene Mae , Sayson Leandro Val , Kim Mikyung , Cheong Jae Hoon , Kim Hee Jin
Published: January 2024

Tobacco smoking is a serious health problem in society. While smoking rates are declining, smoking remains a serious risk to national health. Currently, there are several medications available to aid in smoking cessation. However, these medications have the disadvantages of low success rates in smoking cessation and various side effects. Therefore, natural‐based smoking cessation aids are being suggested as a good alternative due to their accessibility and minimal side effects. The roots and stems of Acanthopanax koreanum (AK) Nakai, a plant that is native to Jeju Island, South Korea, have traditionally been used as tonic and sedatives. Moreover, eleutheroside B and chlorogenic acid are the main components of AK stem extract. In the present study, we investigated the effect of 70% ethanol AK extract and its components on ameliorating nicotine dependence and withdrawal symptoms by using behavioural tests in mice. In addition, alterations in the dopaminergic and DRD1‐EPAC‐ERK‐CREB pathways were observed using dopamine ELISA and western blotting using mouse brains. Our findings demonstrate that the AK extract and its components effectively mitigated the effects of nicotine treatment in behavioural tests. Furthermore, it normalized the dopamine concentration and the expression level of nicotine acetylcholine receptor α7. Additionally, it was observed that AK extract and its components led to the normalization of DRD1, ERK and CREB expression levels. These results indicate that AK extract exhibits effects in ameliorating nicotine dependence behaviour and alleviating withdrawal symptoms. Moreover, EB and CGA are considered potential marker components of AK extract.
Assessing the sub‐lethal impacts of insecticides on aphid parasitoids through laboratory‐based studies
Authors: McDougall Robert , Mata Luis , Ward Samantha , Hoffmann Ary , Umina Paul A.
Published: January 2024

Aphids are a major pest of cropping systems throughout the world. In most cases, crop aphids are controlled with broad‐spectrum insecticides; although generally very effective at preventing yield loss, this approach risks non‐target damage to beneficial organisms. In the last 20 years, a number of selective insecticides have become available to control aphids while minimising harm to other arthropods. Previous studies have found that two such insecticides, flonicamid and afidopyropen, cause only low‐level acute mortality impacts on aphid parasitoids in Australian grain crops. However, little research has examined the sub‐lethal effects of these chemicals, which could induce various physiological changes that impact pest control. We hypothesised that both flonicamid and afidopyropen have negative effects that extend beyond the immediate acute mortality previously published. To test this hypothesis, we undertook a series of experiments to determine the effects of flonicamid and afidopyropen, along with the synthetic pyrethroid gamma‐cyhalothrin, on aphid parasitism (mummification) rate, emergence rate of the next generation and the next generation sex ratio in three important aphid parasitoids,Aphidius colemani(Viereck),Diaeretiella rapae(M'Intosh) andAphelinus abdominalis(Dalman). Analogous with previous research, our acute toxicity bioassays showed that all three insecticides had low (<30%) mortality impacts. Although sub‐lethal impacts could not be assessed forD. rapaedue to the low level of aphid parasitism by that species, our findings showed negative impacts on fecundity in survivingA. abdominalisandA. colemani. Of particular note is the increase in International Organisation for Biological Control ratings to moderate (30%–80% mortality and/or reproductive reduction) when mortality and reduced fecundity effects were combined to determine overall fitness impacts. Gamma‐cyhalothrin typically resulted in higher negative impacts onA.abdominalisandA.colemani(compared with flonicamid and afidopyropen); however, quite surprisingly, these impacts were not rated as highly toxic. Taken together, our results suggest that, even when sub‐lethal impacts are considered, flonicamid and afidopyropen are useful tools for farmers targeting aphid populations while minimising the non‐target impacts on parasitoids. We recommend semi‐field and/or field trials to further assess the impacts of these insecticides on aphid parasitoid populations.
A cross‐sectional study exploring the characteristics of female survivors of sexual violence living with HIV/AIDS in the eastern region of Democratic Republic of Congo
Authors: Nyakio Olivier , Kibukila Fabrice , Mukwege Denis , Bwani Joyeux , Tambwe Albert , Bhattacharjee Priyadarshini , Bandyopadhyay Soham , Akilimali Aymar , Kakudji Prosper , Kakoma Jean Baptiste
Published: January 2024

Background

Sexual violence remains a persistent and devastating issue in eastern Democratic Republic of Congo (DRC).

Aim

To elucidate the sociodemographic, sexual, and obstetrical characteristics associated with the experiences of victims of sexual violence (VSV) among women in the region.

Materials and Methods

A cross‐sectional study was conducted involving 625 women from eastern DRC. Participants provided self‐reported data, collected through interviews conducted by trained female interviewers in secure environments. Associations between VSV and various sociodemographic and reproductive health factors were examined.

Results

Of the respondents, 26.1% reported experiences of sexual violence. VSV were predominantly younger, with 56.44% aged between 15 and 24 years. Single women comprised 57.67% of VSV, and 37.42% identified as farmers. There were 33.13% of VSV who were illiterate, and 81.60% belonged to the low socio‐economic stratum. Early physiological and reproductive milestones characterised VSV: 52.15% experienced menarche at or before 13 years, 34.97% initiated sexual intercourse before age 15, and 18.70% reported their first pregnancy before age 15. Higher nulliparity was observed in VSV (29.45%) compared to non‐VSV (9.31%). A lower prevalence of HIV infection was found among VSV (11.04%) relative to non‐VSV (25.76%).

Conclusion

Sexual violence in the eastern DRC exhibits multifactorial associations. Younger women, those in certain occupations, and those with specific reproductive histories appear more vulnerable. The findings underscore the urgency for targeted interventions, enhanced access to education, and improved reproductive health services. Addressing these pressing issues should remain a primary focus in both societal and public health spheres.
3‐Hydroxy‐3‐methylglutaryl‐CoA synthase 2 facilitates erectile dysfunction via inhibiting autophagy by enhancing the mammalian target of rapamycin pathway in type 1 diabetic mellitus rats
Authors: Dai Zhiqiang , Zeng Yang , Tan Xiao , Zhou Tao , Li Xiong , Deng Qingfu
Published: January 2024

Background

The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood.

Objectives

To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs).

Materials and methods

First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p‐mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p‐eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot.

Results

The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p‐mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone.

Discussion and conclusion

HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function.
Review of clinical pharmacokinetics and pharmacodynamics of clonidine as an adjunct to opioids in palliative care
Authors: Amna Sarwat , Øhlenschlæger Thomas , Sædder Eva Aggerholm , Sigaard Jarl Voss , Bergmann Troels Korshøj
Published: January 2024

Clonidine is an α‐adrenoceptor agonist acting on receptors in the brain and peripheral tissues, leading to a reduction in sympathetic outflow and release of certain neurotransmitters. Clonidine has multiple uses across various medical conditions. One of its uses is as adjuvant to anaesthetic and analgesic agents specially opioids, mostly administered through intravenous and epidural routes. The opioids, effective in cancer pain management, are associated with various side effects such as sedation, pruritus, constipation, nausea, respiratory depression, tolerance and dependence. Combination of clonidine with opioids seems to help to achieve better pain management and less need of opioids. Use of clonidine in palliative care has been less common, but it is gradually gaining recognition for its potential benefits in managing symptoms like cancer pain and agitation. This combination approach has been explored in palliative care settings, including cancer pain and agitation, where patients experience complex and refractory symptoms. It seems to be well tolerated and gives better symptom relief. The available literature on clonidine's use in cancer pain and agitation management, especially in subcutaneous form, is limited and outdated. Therefore, the optimal dosing, safety profile and overall effectiveness of subcutaneous clonidine requires further exploration through prospective research studies.
Patient survey on cancer genomic medicine in Japan under the national health insurance system
Authors: Kage Hidenori , Akiyama Nana , Chang Hyangri , Shinozaki‐Ushiku Aya , Ka Mirei , Kawata Junichi , Muto Manabu , Okuma Yusuke , Okita Natsuko , Tsuchihara Katsuya , Kikuchi Junko , Shirota Hidekazu , Hayashi Hideyuki , Kokuryo Toshio , Yachida Shinichi , Hirasawa Akira , Kubo Makoto , Kenmotsu Hirotsugu , Tanabe Masahiko , Ushiku Tetsuo , Muto Kaori , Seto Yasuyuki , Oda Katsutoshi
Published: January 2024

In Japan, comprehensive genomic profiling (CGP) tests have been reimbursed under the national health care system for solid cancer patients who have finished standard treatment. More than 50,000 patients have taken the test since June 2019. We performed a nation‐wide questionnaire survey between March 2021 and July 2022. Questionnaires were sent to 80 designated Cancer Genomic Medicine Hospitals. Of the 933 responses received, 370 (39.7%) were web based and 563 (60.3%) were paper based. Most patients (784, 84%) first learned about CGP tests from healthcare professionals, and 775 (83.1%) gave informed consent to their treating physician. At the time of informed consent, they were most worried about test results not leading to novel treatment (536, 57.4%). On a scale of 0–10, 702 respondents (75.2%) felt that the explanations of the test result were easy to understand (7 or higher). Ninety‐one patients (9.8%) started their recommended treatment. Many patients could not receive recommended treatment because no approved drugs or clinical trials were available (102/177, 57.6%). Ninety‐eight patients (10.5%) did not wish their findings to be disclosed. Overall satisfaction with the CGP test process was high, with 602 respondents (64.5%) giving a score of 7–10. The major reason for choosing 0–6 was that the CGP test result did not lead to new treatment (217/277, 78.3%). In conclusion, satisfaction with the CGP test process was high. Patients and family members need better access to information. More patients need to be treated with genomically matched therapy.
Pyramidalis muscle formation during human embryonic and early fetal periods
Authors: Iwasa Yui , Kanahashi Toru , Imai Hirohiko , Otani Hiroki , Yamada Shigehito , Takakuwa Tetsuya
Published: January 2024

The pyramidalis muscle (PM) is a paired small triangular muscle of the anterior abdominal wall; however, its physiological significance is unclear. Recent studies have failed to detect this muscle during embryonic period. Hence, the present study aimed to determine the time when PM is emerging and reveal its features using high‐resolution magnetic resonance imaging. Fourteen embryos between Carnegie stage (CS)18 and CS23 and 59 fetuses (crown‐rump length: 39.5–185.0 mm) were selected for this study. The PM was first detected in one of the three samples at CS20. It was detected in five of the seven samples (71.4%) between CS21 and CS23. Forty‐eight samples (81.4%) at early fetal period had PMs on both the right and left sides, and 3 (5.1%) had it only on the right side. Eight samples (13.6%) had no PMs. No side‐differences or sexual dimorphisms were detected. The PM length was larger than the width in most samples, although the length/width ratio varied among the samples. The PM/rectus abdominis muscle length and PM/umbilicus‐pubic symphysis length ratios were almost constant, irrespective of the crown‐rump length. The PM was located ventrally inferior to the rectus abdominis and closer to the medial muscle groups of the lower limb than the rectus abdominis. The present study demonstrated that PM formation occurred in the late embryonic period, and that the frequency, side differences, sex dimorphism, and spatial position of the PM in the early fetal period were similar to those in adults.
The role of glucagon‐like peptide 1 receptor agonists for weight control in individuals with acquired hypothalamic obesity—A systematic review
Authors: Ng Victoria Wen Wei , Gerard Gheslynn , Koh Jonathan Jin Kai , Loke Kah Yin , Lee Yung Seng , Ng Nicholas Beng Hui
Published: January 2024

Hypothalamic obesity does not respond well to conventional interventions for obesity. GLP‐1 receptor agonists have mechanisms independent of the hypothalamus which may be potentially beneficial for managing hypothalamic obesity. This systematic review summarizes the efficacy and safety of GLP‐1 receptor agonists use in hypothalamic obesity. A PRISMA‐compliant systematic review was performed. Data was extracted from included studies and analysed based on change in weight, body mass index, glycaemic control, satiety, and safety profile with GLP‐1 receptor agonist use. Ten studies comprising 5 case reports, 4 case series and 1 randomized‐controlled trial included 54 patients (24 males, 30 females) with mean age of 25.2 (range 13–71) years with hypothalamic obesity who had received GLP‐1 receptor agonists (exenatide = 48, liraglutide = 5 and dulaglutide = 1) over a mean duration of treatment of 12 (range 3–51) months. Mean weight reduction of 7.4 (SD 7.92) kg was observed in patients in whom weight was reported, with 85.7% of patients experiencing weight loss. All patients on liraglutide had weight reduction post‐therapy. The sole trial had reported a non‐significant reduction in BMI post‐exenatide. Glycaemic control had either improved/maintained in all patients in whom this was measured. The main side effects of GLP‐1 receptor agonist in individuals with hypothalamic obesity were nausea and vomiting; there were no major safety concerns. Based on limited published experience, GLP‐1RA may be effective and safe for weight control in hypothalamic obesity, with the added benefit of improved glycaemic control in those with concurrent diabetes mellitus.
From ejection fraction, to myocardial strain, and myocardial work in echocardiography: Clinical impact and controversies
Authors: Dell'Angela Luca , Nicolosi Gian Luigi
Published: January 2024

Enhancing an echocardiographic tool, aimed to detect even subtle left ventricular (LV) systolic function abnormalities, capable of obtaining both early diagnosis and risk prediction of heart disease, represents an ambitious, attractive, and arduous purpose in the modern era of cardiovascular imaging. Ideally, that tool should be simple, reliable, and reproducible, in order to be concretely applied in routine clinical practice. Importantly, that technique should be physiologically plausible and useful both at the population‐level, as well as in the individual subject. For a long time, LV ejection fraction (EF) has been considered the first‐line parameter for assessing LV global systolic function, strictly related to the prognosis, at least in some settings. However, LV EF limitations are well‐known, even though frequently overemphasized, including its load‐dependency. Therefore, myocardial strain techniques have been proposed, deemed able to disclose even subtle early LV function anomalies. Nevertheless, many disadvantages of myocardial strain have been reported as well. More recently, myocardial work (MW) analysis has been introduced as a new echocardiographic tool for the evaluation of LV global systolic function, attempting to overcome EF and strain disadvantages. However, MW has shown many limits as well. Notwithstanding, LV EF still remains a landmark functional classification marker for heart failure and cardiac oncology, allowing reliable fast reassessment of LV function changes during patient management, in order to guide treatment in individual cases as well. Notably, global longitudinal strain and MW parameters seem to show better meaningful results at the population‐level, but controversial clinical impact, major limitations, wide cut‐offs spread and overlap, when the single value needs to be applied to the single case. Taking into account the recent literature‐based evidence, the scope of the present narrative critical review is trying to delineate the different types of information given by the described LV global systolic function parameters, both at the population‐level and in the individual case, in order to trace a comparative analysis of advantages and limitations in clinical practice.
Observing an expert's action swapped with an observer's face increases corticospinal excitability during combined action observation and motor imagery
Authors: Watanabe Hironori , Washino Sohei , Ogoh Shigehiko , Miyamoto Naokazu , Kanehisa Hiroaki , Kato Hirokazu , Yoshitake Yasuhide
Published: January 2024

This study aimed to examine whether observing an expert's action swapped with an observer's face increases corticospinal excitability during combined action observation and motor imagery (AOMI). Twelve young males performed motor imagery of motor tasks with different difficulties while observing the actions of an expert performer and an expert performer with a swapped face. Motor tasks included bilateral wrist dorsiflexion (EASY) and unilateral two‐ball rotating motions (DIFF). During the AOMI of EASY and DIFF, single‐pulse transcranial magnetic stimulation was delivered to the left primary motor cortex, and motor‐evoked potentials (MEPs) were obtained from the extensor carpi ulnaris and first dorsal interosseous muscles of the right upper limb, respectively. Visual analogue scale (VAS) assessed the subjective similarity of the expert performer with the swapped face in the EASY and DIFF to the participants themselves. The MEP amplitude in DIFF was larger in the observation of the expert performer with the swapped face than that of the expert performer (P = 0.012); however, the corresponding difference was not observed in EASY (P = 1.000). The relative change in the MEP amplitude from observing the action of the expert performer to that of the expert performer with the swapped face was positively correlated with VAS only in DIFF (r = 0.644, P = 0.024). These results indicate that observing the action of an expert performer with the observer's face enhances corticospinal excitability during AOMI, depending on the task difficulty and subjective similarity between the expert performer being observed and the observer.
Crosstalk between inflammasome sensors and DNA damage response pathways
Authors: Burlet Delphine , Huber Anne‐Laure , Tissier Agnès , Petrilli Virginie
Published: January 2024

Eukaryotic cells encounter diverse threats jeopardizing their integrity, prompting the development of defense mechanisms against these stressors. Among these mechanisms, inflammasomes are well‐known for their roles in coordinating the inflammatory response against infections. Extensive research has unveiled their multifaceted involvement in cellular processes beyond inflammation. Recent studies emphasize the intricate relationship between the inflammasome and the DNA damage response (DDR). They highlight how the DDR participates in inflammasome activation and the reciprocal impact of inflammasome on DDR and genome integrity preservation. Moreover, novel functions of inflammasome sensors in DDR pathways have emerged, broadening our understanding of their roles. Finally, this review delves into identifying common signals that drive the activation of inflammasome sensors alongside activation cues for the DNA damage response, offering potential insights into shared regulatory pathways between these critical cellular processes.
Anchoring of hyaluronan glycocalyx to CD44 reduces sensitivity of HER2‐positive gastric cancer cells to trastuzumab
Authors: Chen Si , Zhang Guoliang , Liu Yiwen , Yang Cuixia , He Yiqing , Guo Qian , Du Yan , Gao Feng
Published: January 2024

Trastuzumab is widely used in human epidermal growth factor receptor 2 (HER2)‐positive gastric cancer (GC) therapy, but ubiquitous resistance limits its clinical application. In this study, we first showed that CD44 antigen is a significant predictor of overall survival for patients with HER2‐positive GC. Next, we found that CD44 could be co‐immunoprecipitated and co‐localized with HER2 on the membrane of GC cells. By analyzing the interaction between CD44 and HER2, we identified that CD44 could upregulate HER2 protein by inhibiting its proteasome degradation. Notably, the overexpression of CD44 could decrease the sensitivity of HER2‐positive GC cells to trastuzumab. Further mechanistic study showed that CD44 upregulation could induce its ligand, hyaluronan (HA), to deposit on the cancer cell surface, resulting in covering up the binding sites of trastuzumab to HER2. Removing the HA glycocalyx restored sensitivity of the cells to trastuzumab. Collectively, our findings suggested a role for CD44 in regulating trastuzumab sensitivity and provided novel insights into HER2‐targeted therapy.
Corporate social responsibility and investor relationship management
Authors: Jiao Jie , Wang Yanyang , Yan An
Published: January 2024

Following the Fukushima Daiichi nuclear disaster, utilities firms increase their commitments to corporate social responsibility (CSR), emphasizing on addressing environmental concerns over non‐environmental ones. The intensified focus on CSR is especially significant in utilities firms with substantial institutional ownerships. Concurrent to the increase in CSR, utilities firms also exhibit a decline in advertising expenditures, a trend more pronounced in firms facing more financial constraints. Our findings suggest that utilities firms substitute CSR for advertising following the Fukushima accident. This shift appears driven by investors’ heightened focus on environmental issues in the aftermath of the accident.