bluuebunny/crossref_metadata_2025 huggingface dataset:
A case for activating producers’ rights in discussions on conservation of biodiversity through Geographical Indications
Authors: Saxena Devanshi , Frison Christine
Published: February 2024

Geographical Indications (GIs) are collective rights granted to a group of producers in a limited geographical area. One of the rationales of GI protection is biodiversity conservation which is rapidly being advanced. However, if the GI fails to value the terroir associated with it, it can risk erosion of bio(cultural)diversity. In this paper, taking lessons from such experiences, we argue for activating producers’ rights in discussions on biodiversity conservation through GIs and for the systematic inclusion of environmental law, which is considered relevant by the producers, in the GI specification. The rationale of sustainability and sustainable development and the integration of the capabilities approach to IP governance is part of our theoretical underpinnings for such an argument. Given the relationship between these concepts, we first explain biodiversity conservation and then situate the role of GIs in this context. Finally, we also differentiate between third-party certifications and eco-labels and GIs. The role of the former can be useful but limited as GIs offer a better opportunity to include producers’ own views. We support our arguments throughout the paper using various examples from secondary empirical research. In practice, we argue for making GI laws, including designing of GI specifications, in a manner that producers’ participation is included by design. Considerations of bio(cultural)diversity should be, by design, a part of GIs to increase their efficiency in fulfilling this rationale of protection. This calls for more interdisciplinary and intradisciplinary engagement from GI scholars as well.
Default property rules for same-gender marriages: equivalence over equality?
Authors: Thijs Hannelore , Verbeke Alain-Laurent
Published: February 2024

More and more jurisdictions accept that marriage should be open for all couples, both different and same gender. While this identical application of marriage as an institution is not open for debate, differences between same-gender couples and different-gender couples may have some value as to the precise content of marital property rules. Existing research finds that same-gender couples better represent the modern-day relationship model of equal role distribution, as they pursue a more egalitarian division of household labour and a greater individualization of finances than different-gender couples. Nevertheless, marital property rules have exclusively been shaped by the perspective of and inequalities experienced by (traditional) different-gender couples. The resulting heteronormative rules impose a degree of solidarity and protection that same-gender couples may not desire or need. Through 12 interviews, we carry out a first step in exploring the patrimonial wishes and needs of same-gender couples. We find that multiple interviewees prefer more autonomy during their relationship, while there is a preference to share assets upon a break-up or divorce. Consequently, we argue that a separation-based regime with a participation in the assets accumulated during the relationships offers a more appropriate property regime for same-gender couples than a community-based regime. While additional research is essential, the current findings could already offer arguments in further refining the current default regime for all married couples.
Strategies for optimal sky subtraction in the low surface brightness regime
Authors: Watkins Aaron E , Kaviraj Sugata , Collins Chris C , Knapen Johan H , Kelvin Lee S , Duc Pierre-Alain , Román Javier , Mihos J Christopher
Published: February 2024

The low surface brightness (LSB) regime (μg  ≳  26 mag arcsec−2) comprises a vast, mostly unexplored discovery space, from dwarf galaxies to the diffuse interstellar medium. Accessing this regime requires precisely removing instrumental signatures and light contamination, including, most critically, night sky emission. This is not trivial, as faint astrophysical and instrumental contamination can bias sky models at the precision needed to characterize LSB structures. Using idealized synthetic images, we assess how this bias impacts two common LSB-oriented sky-estimation algorithms: (1) masking and parametric modelling, and (2) stacking and smoothing dithered exposures. Undetected flux limits both methods by imposing a pedestal offset to all derived sky models. Careful, deep masking of fixed sources can mitigate this, but source density always imposes a fundamental limit. Stellar scattered light can contribute ∼28–29 mag arcsec−2 of background flux even in low-density fields; its removal is critical prior to sky estimation. For complex skies, image combining is an effective non-parametric approach, although it strongly depends on observing strategy and adds noise to images on the smoothing kernel scale. Preemptive subtraction of fixed sources may be the only practical approach for robust sky estimation. We thus tested a third algorithm, subtracting a preliminary sky-subtracted coadd from exposures to isolate sky emission. Unfortunately, initial errors in sky estimation propagate through all subsequent sky models, making the method impractical. For large-scale surveys like Legacy Survey of Space and Time, where key science goals constrain observing strategy, masking and modelling remain the optimal sky estimation approach, assuming stellar scattered light is removed first.
Stark broadening data for ultraviolet lines of Ni v
Authors: Hamdi Rafik , Sahal-Bréchot Sylvie , Dimitrijević Milan S , Elabidi Haykel
Published: February 2024

We provide in this work Stark broadening data (widths and shifts) for 120 ultraviolet spectral lines of Ni v ion. Our calculations are performed using the semiclassical perturbation method. For energy levels and oscillator strength calculations, we use the multiconfiguration Hatree–Fock approach. Stark shifts and widths are calculated for collisions with electrons and with the positive ions: H+, He+, and He++, allowing us to take into account the important perturbers in stellar atmospheres. We compare our Stark widths with estimations obtained using the Cowley formula. Our electron impact Stark widths are also fitted with temperature using a logarithmic formula. Finally, our obtained Stark widths are used to investigate the influence of Stark broadening in the atmospheric conditions of hot DA white dwarfs. Despite the importance of ultraviolet lines of Ni v ion for modelling white dwarf atmospheres and also for investigations of variation of fundamental constants with gravitational potential, we did not find Stark broadening data previously calculated or measured for Ni v ion. The objective of this work is to give the missed data.
Simulations of spin-driven AGN jets in gas-rich galaxy mergers
Authors: Talbot Rosie Y , Sijacki Debora , Bourne Martin A
Published: February 2024

In this work, we use hydrodynamical simulations to explore the effects of kinetic active galactic nuclei (AGN) jet feedback on the progression and outcome of the major merger of two isolated, gas-rich galaxies. We present simulations that use the moving-mesh code arepo to follow the progression of the merger through the first passage and up to the final coalescence, modelling the black holes at the centres of both of the merging galaxies using our prescription for black hole accretion via an α-disc and feedback in the form of a spin-driven jet. We find that the jets drive large-scale, multiphase outflows which launch large quantities of cold gas out to distances greater than 100 kpc and with velocities that reach $\sim 2500 \, {\rm km \, s^{-1}}$. Gas in the outflows that decelerates, cools, and falls back on the galaxies can provide a rich source of fuel for the black hole, leading to intense episodes of jet activity in which the jet can become significantly misaligned. The presence of AGN jets affects the growth of the stellar component: star formation is moderately suppressed at all times during the merger and the peak of the star formation rate, attained during the final coalescence of the galaxies, is reduced by a factor of ∼2. Analysis of simulations such as these will play a central role in making precise predictions for multimessenger investigations of dual radio-AGN, which next-generation observational facilities such as LISA, Athena and SKA will make possible.
What if GW190425 did not produce a black hole promptly?
Authors: Radice David , Ricigliano Giacomo , Bhattacharya Mukul , Perego Albino , Fattoyev Farrukh J , Murase Kohta
Published: February 2024

It is widely believed that the binary neutron star merger GW190425 produced a black hole promptly upon merger. Motivated by the potential association with the fast radio burst FRB 20190425A, which took place 2.5 h after the merger, we revisit the question of the outcome of GW190425 by means of numerical relativity simulations. We show that current laboratory and astrophysical constraints on the equation of state of dense matter do not rule out the formation of a long-lived remnant. However, the formation of a stable remnant would have produced a bright kilonova, in tension with upper limits by ZTF at the location and time of FRB 20190425A. Moreover, the ejecta would have been optically thick to radio emission for days to months, preventing a putative FRB from propagating out. The predicted dispersion measure is also several orders of magnitude larger than that observed for FRB 20190425A. Our results indicate that FRB 20190425A and GW190425 are not associated. However, we cannot completely rule out the formation of a long-lived remnant, due to the incomplete coverage of the relevant sky regions. More observations of GW190425-like events, including potential upper limit, have the potential to constrain nuclear physics. To this aim, it is important that follow-up observational campaigns of gravitational wave events are informed by the properties of the source, such as their chirp mass, and we urge the LIGO-Virgo-KAGRA collaboration to promptly release them publicly.
Minute-Cadence Observations of the LAMOST Fields with the TMTS: V. Machine Learning Classification of TMTS Catalogues of Periodic Variable Stars
Authors: Guo Fangzhou , Lin Jie , Wang Xiaofeng , Chen Xiaodian , Li Tanda , Chen Liyang , Xia Qiqi , Mo Jun , Xi Gaobo , Zhang Jicheng , Liu Qichun , Jiang Xiaojun , Yan Shengyu , Peng Haowei , Liu Jialian , Li Wenxiong , Lin Weili , Xiang Danfeng , Ma Xiaoran , Cai Yongzhi
Published: February 2024

Periodic variables are always of great scientific interest in astrophysics. Thanks to the rapid advancement of modern large-scale time-domain surveys, the number of reported variable stars has experienced substantial growth for several decades, which significantly deepened our comprehension of stellar structure and binary evolution. The Tsinghua University-Ma Huateng Telescopes for Survey (TMTS) has started to monitor the LAMOST sky areas since 2020, with a cadence of 1 minute. During the period from 2020 to 2022, this survey has resulted in densely sampled light curves for ~30,000 variables of the maximum powers in the Lomb-Scargle periodogram above the 5σ threshold. In this paper, we classified 11,638 variable stars into 6 main types using XGBoost and Random Forest classifiers with accuracies of 98.83% and 98.73%, respectively. Among them, 5301 (45.55%) variables are newly discovered, primarily consisting of δ Scuti stars, demonstrating the capability of TMTS in searching for short-period variables. We cross-matched the catalogue with Gaia’s second Data Release (DR2) and LAMOST’s seventh Data Release (DR7) to obtain important physical parameters of the variables. We identified 5504 δ Scuti stars (including 4876 typical δ Scuti stars and 628 high-amplitude δ Scuti stars), 5899 eclipsing binaries (including EA-, EB- and EW-type) and 226 candidates of RS Canum Venaticorum. Leveraging the metal abundance data provided by LAMOST and the Galactic latitude, we discovered 8 candidates of SX Phe stars within the class of ”δ Scuti stars”. Moreover, with the help of Gaia color-magnitude diagram, we identified 9 ZZ ceti stars.
Variability in the white spot: a new genus and species of Discodorididae (Nudibranchia) from the central and western Pacific Ocean
Authors: Donohoo Samantha A , Gosliner Terrence M
Published: February 2024

In this paper, a new genus in the nudibranch family Discodorididae, Avaldesia n. gen., is established for Avaldesia albomacula (Chan & Gosliner, 2007) and Avaldesia tahala (Chan & Gosliner, 2007), originally assigned to the genus Thordisa Bergh, 1877, and a new species, Avaldesia tamatoa n. sp., described here from the central Pacific. To establish species relationships within Avaldesia, as well as the placement of Avaldesia within Discodorididae, we utilized four molecular markers (cytochrome c oxidase subunit I, 16S rRNA, histone H3 and 28S rRNA) in our Bayesian inference and maximum likelihood analyses. Four species delimitation methods were complemented by morphological dissections and scanning electron microscopy. Our results reveal a clear separation between Avaldesia and Thordisa and suggest that Avaldesia is more closely related to the genera Hoplodoris Bergh, 1880 and Asteronotus Ehrenberg, 1831. The most characteristic features of Avaldesia include a radula with increasing denticulation towards the fimbriate outermost laterals and a reproductive system with a lobate vestibular gland, occasional hollow vestibular spine and a penis armed with one or more penial spines. All species of Avaldesia are found in shallow water (5–10 m depth) on rocky reefs, sandy sediments and algal fields with distributions across the Indo-Pacific.
Keep your eyes healthy: eat organic food
Authors: Finsterer Josef , Beltramim Larissa , Bombardi Larissa M , de Almeida Antonio-Carlos G , Scorza Fulvio A
Published: February 2024

This letter is a comment on the 2023 article entitled “Effect of xanthophyll-rich food and supplement intake on visual outcomes in healthy adults and those with eye disease: a systematic review, meta-analysis, and meta-regression of randomized controlled trials,” recently published in Nutrition Reviews, by Hu et al.
Hepatitis Delta Virus Reporting Requirements in the United States and Territories: A Systematic Review
Authors: Assadi-Rad Milaveh , Acosta Brenda E , Hesterman Matthew C , Fallon Braden S , Hill Rachel L , Farnsworth Ethan W , Barbeau Bree , Vilven Dede , Lynch Keisa M , Weller Melodie L
Published: February 2024

Hepatitis D virus (HDV) is a rare coinfection with hepatitis B virus. Currently, HDV is not a nationally notifiable disease in the United States. Only 55% of states and territories require HDV reporting, and most lack defined case definitions. Standardization of reporting requirements is crucial for monitoring HDV epidemiology.
Identity and Extensionality in Boffa Set Theory
Authors: Maia Nuno , Nizzardo Matteo
Published: February 2024

Boffa non-well-founded set theory allows for several distinct sets equal to their respective singletons, the so-called ‘Quine atoms’. Rieger contends that this theory cannot be a faithful description of set-theoretic reality. He argues that, even after granting that there are non-well-founded sets, ‘the extensional nature of sets’ precludes numerically distinct Quine atoms. In this paper we uncover important similarities between Rieger’s argument and how non-rigid structures are conceived within mathematical structuralism. This opens the way for an objection against Rieger, whilst affording the theoretical resources for a defence of Boffa set theory as a faithful description of set-theoretic reality.
Biologically generated turbulent energy flux in shear flow depends on tensor geometry
Authors: Si Xinyu , Fang Lei
Published: February 2024

It has been proposed that biologically generated turbulence plays an important role in material transport and ocean mixing. Both experimental and numerical studies have reported evidence of the nonnegligible mixing by moderate Reynolds number swimmers, such as zooplankton, in quiescent water, especially at aggregation scales. However, the interaction between biologically generated agitation and the background flow, as a key factor in biologically generated turbulence that could reshape our previous knowledge of biologically generated turbulence, has long been ignored. Here, we show that the geometry between the biologically generated agitation and the background hydrodynamic shear can determine both the intensity and direction of biologically generated turbulent energy flux. Measuring the migration of a centimeter-scale swimmer—as represented by the brine shrimp Artemia salina—in a shear flow and verifying through an analog experiment with an artificial jet revealed that different geometries between the biologically generated agitation and the background shear can result in spectral energy transferring toward larger or smaller scales, which consequently intensifies or attenuates the large-scale hydrodynamic shear. Our results suggest that the long ignored geometry between the biologically generated agitation and the background flow field is an important factor that should be taken into consideration in future studies of biologically generated turbulence.
Loss of synaptopodin impairs mGluR5 and protein synthesis–dependent mGluR-LTD at CA3-CA1 synapses
Authors: Wu Pei You , Ji Linjia , De Sanctis Claudia , Francesconi Anna , Inglebert Yanis , McKinney R Anne
Published: February 2024

Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the central nervous system and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD. A subset of dendritic spines containing synaptopodin (SP), an actin-associated protein is critical for mGluR-LTD and protects spines from elimination through mGluR1 activity. The precise cellular function of SP is still enigmatic and it is still unclear how SP contributes to the functional aspect of mGluR-LTD despite its modulation of the structural plasticity. In this study, we show that the lack of SP impairs mGluR-LTD by negatively affecting the mGluR5-dependent activity. Such impairment of mGluR5 activity is accompanied by a significant decrease of surface mGluR5 level in SP knockout (SPKO) mice. Intriguingly, the remaining mGluR-LTD becomes a protein synthesis-independent process in the SPKO and is mediated instead by endocannabinoid signaling. These data indicate that the postsynaptic protein SP can regulate the locus of expression of mGluR-LTD and provide insight into our understanding of spine/synapse-specific plasticity.
Relation Between Pole and Running Masses of Heavy Quarks Using the Principle of Maximum Conformality
Authors: Salinas-Arizmendi Daniel , Schmidt Iván
Published: February 2024

The relation of the pole and running heavy quark masses of the order of $\mathcal {O}\left(\alpha _s^4\right)$ in perturbative quantum chromodynamics (pQCD) can be obtained using the principle of maximum conformality (PMC), a formalism that provides a rigorous method for eliminating renormalization scale and scheme ambiguities for observables in pQCD. Using PMC, optimal renormalization scale for the heavy quark mass ratio is determined, independent of the renormalization scale and scheme up to order $\alpha _s^4$. Precise values are then obtained for the PMC pole masses of the heavy quarks $M_b^{\text{PMC}}=4.86^{+0.03}_{-0.02}$ GeV, $M_t^{\text{PMC}}=172.3\pm 0.6$ GeV, and the running mass $\overline{m}_t^{\text{PMC}}=162.6\pm 0.7$ GeV at the PMC scale.
Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial
Authors: Husain Muhammad Omair , Chaudhry Imran Bashir , Khoso Ameer B , Husain Muhammad Ishrat , Ansari Moin Ahmed , Mehmood Nasir , Naqvi Haider A , Nizami Asad Tamizuddin , Talib Uroosa , Rajput Aatir H , Bassett Paul , Foussias George , Deakin Bill , Husain Nusrat
Published: February 2024

Background and Hypothesis

Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia.

Study Design

A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed.

Study Results

We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes.

Conclusions

We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge.

Trial Registration

ClinicalTrials.gov: NCT03510741.
EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder
Authors: Jeong El , Woo Shin Yong , Byun Jung-Ick , Sunwoo Jun-Sang , Roascio Monica , Mattioli Pietro , Giorgetti Laura , Famà Francesco , Arnulfo Gabriele , Arnaldi Dario , Kim Han-Joon , Jung Ki-Young
Published: February 2024

Study Objectives

Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies and eventually phenoconverts to overt neurodegenerative diseases including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Associations of baseline resting-state electroencephalography (EEG) with phenoconversion have been reported. In this study, we aimed to develop machine learning models to predict phenoconversion time and subtype using baseline EEG features in patients with iRBD.

Methods

At baseline, resting-state EEG and neurological assessments were performed on patients with iRBD. Calculated EEG features included spectral power, weighted phase lag index, and Shannon entropy. Three models were used for survival prediction, and four models were used for α-synucleinopathy subtype prediction. The models were externally validated using data from a different institution.

Results

A total of 236 iRBD patients were followed up for up to 8 years (mean 3.5 years), and 31 patients converted to α-synucleinopathies (16 PD, 9 DLB, 6 MSA). The best model for survival prediction was the random survival forest model with an integrated Brier score of 0.114 and a concordance index of 0.775. The K-nearest neighbor model was the best model for subtype prediction with an area under the receiver operating characteristic curve of 0.901. Slowing of the EEG was an important feature for both models.

Conclusions

Machine learning models using baseline EEG features can be used to predict phenoconversion time and its subtype in patients with iRBD. Further research including large sample data from many countries is needed to make a more robust model.
Heme oxygenase‐1 alleviates allergic airway inflammation by suppressing NF‐κB‐mediated pyroptosis of bronchial epithelial cells
Authors: Lv Jiajia , Zhou Yao , Wang Jing , Wu Yujiao , Yu Qianying , Zhang Meng , Su Wen , Tang Zhiwei , Wu Qun , Wu Min , Xia Zhenwei
Published: February 2024

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase‐1 (HO‐1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO‐1‐mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)‐induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO‐1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO‐1 restrained GSDMD‐mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor‐Kappa B (NF‐κB) p65 RHD domain and thus controlling NF‐κB‐dependent pyroptosis. These data provide new therapeutic indications for purposing HO‐1 to counteract inflammation, which contributes to allergic inflammation control.
Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study
Authors: Polo Friz Melisa , Rezoagli Emanuele , Safaee Fakhr Bijan , Florio Gaetano , Carlesso Eleonora , Giudici Riccardo , Forlini Clarissa , Tardini Francesca , Langer Thomas , Laratta Matteo , Casella Giampaolo , Forastieri Molinari Andrea , Protti Alessandro , Cecconi Maurizio , Cabrini Luca , Biagioni Emanuela , Berselli Angela , Mirabella Lucia , Tonetti Tommaso , De Robertis Edoardo , Grieco Domenico Luca , Antonelli Massimo , Citerio Giuseppe , Fumagalli Roberto , Foti Giuseppe , Zanella Alberto , Grasselli Giacomo , Bellani Giacomo ,   for the COVID-19 Lombardy ICU Network
Published: February 2024

OBJECTIVES:

In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes.

DESIGN:

Retrospective observational cohort study.

SETTING:

Twenty-four Italian ICUs from February 2020 to May 2020.

PATIENTS:

Mechanically ventilated ICU patients with COVID-19-induced respiratory failure.

INTERVENTION:

The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours.

MEASUREMENTS AND MAIN RESULTS:

Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao
2/Fio
2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao
2/Fio
2, Paco
2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04).

CONCLUSIONS:

Our study emphasizes that the Pao
2/Fio
2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.
Association of Epigenetic Age and Outcome in Critically Ill Patients
Authors: Sharma-Oates Archana , Sullivan Jack , Pestana Daniel , dos Santos Claudia C. , Binnie Alexandra , Lord Janet M.
Published: February 2024

OBJECTIVES:

DNA methylation can be used to determine an individual’s biological age, as opposed to chronological age, an indicator of underlying health status. This study aimed to assess epigenetic age in critically ill patients with and without sepsis to determine if higher epigenetic age is associated with admission diagnosis or mortality.

DESIGN:

Secondary analysis of whole blood DNA methylation data generated from a nested case–control study of critically ill septic and nonseptic patients.

SETTING:

Four tertiary care hospitals in Canada.

INTERVENTIONS:

None.

PATIENTS:

Critically ill patients with and without sepsis.

MEASUREMENTS AND MAIN RESULTS:

Epigenetic age was derived from DNA methylation data using the Hannum and PhenoAge algorithms and deviation from the patient’s chronological age in years was determined. Of the 66 patients with sepsis, 34 were male (51.5%), the mean age was 65.03 years and 25 patients (37.8%) died before discharge. Of the 68 nonseptic patients, 47 were male (69.1%), the mean age was 64.92 years and 25 (36.7%) died before discharge. Epigenetic age calculated using the PhenoAge algorithm showed a significant age acceleration of 4.97 years in septic patients (p = 0.045), but no significant acceleration in nonseptic patients. Epigenetic age calculated using the Hannum algorithm showed no significant acceleration in the septic or nonseptic patients. Similarly, in the combined septic and nonseptic cohorts, nonsurvivors showed an epigenetic age acceleration of 7.62 years (p = 0.004) using the PhenoAge algorithm while survivors showed no significant age acceleration. Survivor status was not associated with age acceleration using the Hannum algorithm.

CONCLUSIONS:

In critically ill patients, epigenetic age acceleration, as calculated by the PhenoAge algorithm, was associated with sepsis diagnosis and mortality.
Relevance of detection of RAF fusion transcripts in pan-negative melanoma in routine practice
Authors: Delzenne Guillaume , Boileau Marie , Jamme Philippe , Farchi Olivier , Mortier Laurent
Published: February 2024

Background

Pan-negative melanomas account for 30% of melanomas. In case of immunotherapy failure, therapeutic options are limited. Oncogene fusions represent a target of interest in many solid cancers. In melanoma, the frequency of oncogene fusion is not well documented and not routinely investigated.

Methods

We conducted a single-center retrospective study. The objective was to determine the frequency of oncogene fusion detected by RNA sequencing, in patients with advanced or metastatic pan-negative melanoma. In parallel, an extended molecular alteration search was performed using extended targeted next-generation sequencing.

Results

We identified 59 patients with advanced pan-negative melanoma between January 2021 and January 2023. It was a cutaneous melanoma in 71.1% of the cases, a mucous melanoma in 15.2% of the cases. We identified nine patients with a RAF fusion, including seven BRAF gene fusion and two RAF1 fusion. Of the other molecular alterations, NF1 mutation was the most frequent molecular alteration identified. Among the nine patients with RAF fusions, all the patients initially received treatment with anti-PD1 ± anti-CTLA4 immunotherapy. After immunotherapy failure, five patients benefited from second-line targeted therapy (two with BRAF and MEK inhibitors combination, three MEK inhibitors alone). The response rate was 20%.

Conclusion

In a population of pan-negative melanoma, we detected 15.2% of RAF fusion. Fusion detection allowed the introduction of a second line of targeted therapy, in the absence of a validated therapeutic option in 55.5% of cases. This study suggests the relevance of detecting RAF fusion in a selected population.
Neonatal cutaneous melanoma with cutaneous metastasis: a case report and review of literature
Authors: Ercan Alp , Yalçin Can Ege
Published: February 2024

Malignant melanoma, a rare skin cancer in children, primarily affects individuals over 10 years old. Giant congenital nevi, found in about 1% of newborns, increases the risk. However, the development of melanoma from a pre-existing giant congenital nevus diagnosed during the neonatal period is exceptionally rare. We present a case of congenital melanoma in a newborn, where nodules grew on an existing nevus on the baby’s back. Literature on managing such cases was reviewed. This case highlights the importance of considering malignant transformation in congenital nevi and the challenges in their management. Due to limited reported cases over 80 years, conclusive findings on survival and treatment options are difficult to provide. Clinicians should report outcomes to develop a management algorithm for neonatal melanoma. Further studies are needed to enhance understanding of causes and treatment for patients with congenital giant hairy nevi and associated melanoma.
A Comparison of Non–COVID-19 Hospital Mortality Rates During COVID-19 Surges Compared With Prepandemic Periods
Authors: Yun Adrienne , Zacharias Virginia , Szpunar Susan , Saravolatz Louis Donald
Published: February 2024

A retrospective chart review comparing non–COVID-19–related diseases during the pandemic and prepandemic periods found no difference in the hospital mortality rate during the initial COVID-19 surge compared with pre–COVID-19 baseline. This difference from the literature may be because of assigning more physicians to the hospital during the COVID-19 surge.
Implications of endoplasmic reticulum stress and beta-cell loss in immunodeficient diabetic NRG-Akita mice for understanding monogenic diabetes
Authors: Rashwan Ahmed M. , Abumandour Mohamed M. A. , Kandyel Ramadan , Choudhary Om P. , Soliman Rofaida M. , El Sharaby Ashraf , Nomir Ahmed G.
Published: February 2024

Background:

Immunodeficient mice models have become increasingly important as in vivo models engrafted with human cells or tissues for research. The NOD-Rag1null Ins2Akita Il2r

null (NRG-Akita) mice is a model combined with immunodeficient NRG and monogenic diabetes Akita mice that develop spontaneous hyperglycemia with progressive loss of pancreatic insulin-producing beta-cells with age. This model is one of the monogenic diabetic models, which has been providing a powerful platform for transplantation experiments of stem cells-generated human β-cells. This research aimed to provide insights into the mechanisms underlying this monogenic diabetes, which remains incompletely understood.

Methods:

Histological and immunofluorescence analyses were conducted on endocrine pancreatic islets to compare NRG wild-type (Wt) controls with NRG-Akita mice. Our investigation focused on assessing the expression of endocrine hormones, transcription factors, proliferation, ER stress, and apoptosis.

Results:

Histological analyses on NRG-Akita mice revealed smaller islets at 6-weeks-old, due to fewer β-cells in the islets, compared to NRG-Wt controls, which further progressed with age. The proliferation rate decreased, and apoptosis was abundant in β-cells in NRG-Akita mice. Interestingly, our mechanistic analyses revealed that β-cells in NRG-Akita mice progressively accumulated the endoplasmic reticulum (ER) stresses, leading to a decreased expression of pivotal β-cell transcriptional factor PDX1.

Conclusions:

Altogether, our mechanistic insight into β-cell loss in this model could shed light on essential links between ER stress, proliferation, and cell identity, which might open the door to new therapeutic strategies for various diseases since ER stress is one of the most common features not only in diabetes but also in other degenerative diseases.
Medical thoracoscopy with cryobiopsy as diagnostic tool for pleural metastatic in cutaneous squamous cell carcinoma: a rare case report
Authors: Tanamas Jimmy , Chionardes Melissa Angela , Handoyo Thomas , Kholis Fathur Nur , Farida  , Wibisono Banteng Hanang , Suryanto Agus , Tenda Eric Daniel , Singh Gurmeet , Pangarsa Eko Adhi , Satoto Bambang , Septarina Faiza Rizky , Puspasari Dik
Published: February 2024

Introduction:

Distance metastasis of cutaneous squamous cell carcinoma (cSCC) to pleural is rarely reported, and meets difficulties in diagnosing due to quality of pleural biopsy sample. This case presented a novel technique by using cryobiopsy to obtain adequate sample and was first conducted in our hospital.

Case presentation:

A 62-years-old man admitted to hospital with dyspnoea due to massive right pleural effusion. Lung multi-sliced computed tomography showed right lung pleural effusion with compression atelectasis as well as collapse of medial lobe and upper lobe, multiple solitary nodules on mediastinal, costal antero-posterior and right diaphragm pleural part. Medical thoracoscopy was performed to obtain pleural samples by using cryobiopsy and forceps biopsy. Pathological analysis with Immunohistochemistry (IHC) revealed metastatic squamous cell carcinoma.

Discussion:

Recurrence rate of cSCC remains high even after treatment, with worse prognosis. Distant metastasis to pleural is rarely reported. Clinical approach for malignant pleural effusion by using medical thoracoscopy has 80% sensitivity with minimal complication. Pleural cryobiopsy is a novel technique used for obtaining sample from pleural biopsy with significant larger size of the specimen, less crush artefacts, fragmented and better tissue integrity, although the diagnostic yield and bleeding severity between cryobiopsy and conventional forceps biopsy are not significant

Conclusion:

Medical thoracoscopy with cryobiopsy should be considered as a preferrable diagnostic tool for obtaining better sample specimen, especially for pleural metastatic.
Musculoskeletal disorders in healthcare workers
Authors: Conti Alessio , Albanesi Beatrice , Clari Marco
Published: February 2024

Purpose of review

Musculoskeletal disorders are one of the most relevant occupational problem. The highest prevalence of musculoskeletal disorders is found among healthcare workers, with potential adverse consequences for the provision of care and public health. The objective of this study is to identify and synthesize the most recent literature on musculoskeletal disorders in healthcare workers. This could be useful for healthcare decision makers in translating effective interventions into practice.

Recent findings

The prevalence of musculoskeletal disorders is high among healthcare workers. The most studied population are nurses, surgeons, dental professionals, and physiotherapists. The prevalence of musculoskeletal disorders in these professionals is high, especially in the low-back, neck, and shoulders body areas. Physical and technological interventions are effective in reducing the prevalence of musculoskeletal pain in the aforementioned body areas.

Research on musculoskeletal disorders in healthcare workers is growing, even if mostly descriptive and assessing the point prevalence of this issue. Musculoskeletal disorders represent major public health problems that should be reduced through feasible, cost-effective technological and physical interventions. Future longitudinal and qualitative studies could be valuable in improving knowledge on this complex phenomenon.
Relationships between plasma neurofilament light chain protein, cognition, and brain aging in people with HIV
Authors: Cooley Sarah A. , Petersen Kalen J. , Tice Caitlin , Langford Dianne , Burdo Tricia H. , Roman June , Ances Beau M.
Published: February 2024

Objective:

Neurofilament light chain protein (NfL) is a marker of neuronal injury and neurodegeneration. Typically assessed in cerebrospinal fluid, recent advances have allowed this biomarker to be more easily measured in plasma. This study assesses plasma NfL in people with HIV (PWH) compared with people without HIV (PWoH), and its relationship with cognitive impairment, cardiovascular risk, and a neuroimaging metric of brain aging [brain-age gap (BAG)].

Design:

One hundred and four PWH (HIV RNA <50 copies/ml) and 42 PWoH provided blood samples and completed a cardiovascular risk score calculator, neuroimaging, and cognitive testing.

Method:

Plasma NfL was compared between PWoH and PWH and assessed for relationships with age, HIV clinical markers, cardiovascular disease risk, cognition, and BAG (difference between a brain-predicted age and chronological age).

Results:

Plasma NfL was not significantly different between PWoH and PWH. Higher NfL related to increasing age in both groups. Plasma NfL was not associated with typical HIV disease variables. Within PWH, NfL was higher with higher cardiovascular risk, cognitive impairment and a greater BAG.

Conclusion:

Virally suppressed PWH who are cognitively normal likely do not have significant ongoing neurodegeneration, as evidenced by similar plasma NfL compared with PWoH. However, NfL may represent a biomarker of cognitive impairment and brain aging in PWH. Further research examining NfL with longitudinal cognitive decline is needed to understand this relationship more fully.
Magnetic Resonance Imaging in Preterm Infant: A Systematic Review on Clinical Procedure Safety
Authors: Falsaperla Raffaele , Marino Silvia , Ganci Noemi , Leone Guido , Romano Catia , Tropea Angela , Romeo Placido , Mailo Janette , Ruggieri Martino
Published: February 2024

Background:

Currently, there is no evidence that MRI produces harmful effects on premature newborns, as well as short-term and long-term safety issues regarding radiofrequency fields and loud acoustic environment, while the examination that is being performed has not been clearly investigated. MRI of the brain conducted on preterm infants should be part of the diagnostic workup, when necessary. This article is intended to evaluate the short-term safety of MRI performed in preterm infants, when required, by analyzing all vital parameters available before, during, and after the MRI procedures.

Methods:

We conducted a systematic review of the literature on electronic medical databases (PubMed and ClinicalTrials.gov) following the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all preterm infants who underwent MRI whose clinical, hemodynamic, and respiratory parameters were reported. The quality of the included articles was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool.

Results:

Six studies were included with a total of 311 preterm infants. No severe adverse event, such as death, occurred during MRI procedures. Vital signs remained stable in about two-thirds of all patients.

Conclusions:

Given the general clinical safety of MRI, we suggest it as a tool to be used in preterm infants in Neonatal Intensive Care Units, when necessary. We further suggest the development of standard protocols to guide the use of MRI in preterm infants to maximize the clinical safety of the procedure.
The Equipoise Ruler
Authors: Zychowski Karlie L. , Stalter Lily N. , Erb Bethany M. , Hanlon Bret M. , Bushaw Kyle J. , Buffington Anne , Bradley Taylor , Arnold Robert M. , Clapp Justin , Kruser Jacqueline M. , Schwarze Margaret L.
Published: February 2024

Objective:

To understand professional norms regarding the value of surgery.

Background:

Agreed-upon professional norms may improve surgical decision-making by contextualizing the nature of surgical treatment for patients. However, the extent to which these norms exist among surgeons practicing in the United States is not known.

Methods:

We administered a survey with 30 exemplar cases asking surgeons to use their best judgment to place each case on a scale ranging from “definitely would do this surgery” to “definitely would not do this surgery.” We then asked surgeons to repeat their assessments after providing responses from the first survey. We interviewed respondents to characterize their rationale.

Results:

We received 580 responses, a response rate of 28.5%. For 19 of 30 cases, there was consensus (≥60% agreement) about the value of surgery (range: 63% to 99%). There was little within-case variation when the mode was for surgery and more variation when the mode was against surgery or equipoise. Exposure to peer response increased the number of cases with consensus. Women were more likely to endorse a nonoperative approach when treatment had high mortality. Specialists were less likely to operate for salvage procedures. Surgeons noted their clinical practice was to withhold judgment and let patients decide despite their assessment.

Conclusions:

Professional judgment about the value of surgery exists along a continuum. While there is less variation in judgment for cases that are highly beneficial, consensus can be improved by exposure to the assessments of peers.
The desensitization of the transient receptor potential vanilloid 1 by nonpungent agonists and its resensitization by bradykinin
Authors: Alsalem Mohammad , Aldossary Sara A. , Haddad Mansour , Altarifi Ahmad , Kalbouneh Heba , Azab Belal , Mustafa Ayman G. , Jaffal Sahar M. , El-Salem Khalid
Published: February 2024

Transient receptor potential vanilloid type-1 (TRPV1) channels have crucial roles in inflammatory hyperalgesia. Different inflammatory mediators can modulate TRPV1 sensitization. Bradykinin is an algogenic substance released at the site of inflammation. The aim of the present study is to investigate the desensitization of TRPV1 receptor by nonpungent agonists and to determine how bradykinin and prostaglandin E2 receptors (EP3 and EP4) modulate the resensitization of TRPV1 receptor after being desensitized by nonpungent agonists. Tail flick test was used to investigate capsaicin-induced thermal hyperalgesia and the desensitization of TRPV1 by the nonpungent agonists (olvanil and arvanil) in male BALB/c mice weighed (22–25 g). Resensitization of TRPV1 by bradykinin and the role of prostaglandin receptors in mediating sensitization of TRPV1 were also investigated. Intraplantar injection of capsaicin (0.3 µg) produced a robust thermal hyperalgesia in mice, while olvanil (0.3 µg) or arvanil (0.3 µg) produced no hyperalgesia, emphasizing their lack of pungency. Olvanil and arvanil significantly attenuated capsaicin-induced thermal hyperalgesia in mice. Bradykinin significantly reversed the desensitizing effects of arvanil, but not olvanil. EP4 but not EP3 receptors mediate the sensitization of TRPV1 By bradykinin in vivo. The present study provides evidence for a novel signaling pathway through which bradykinin can regulate the TRPV1 ion channel function via EP4 receptor.