bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevating labor concerns in small-scale fisheries: challenges to decent work in Peru’s jumbo flying squid fishery
Authors: Lozano Alejandro Garcia , Shibata Jesica Pino , Jeri Juan Carlos , Kittinger John N.
Published: May 2024

Despite growing attention on severe labor abuses in seafood production, questions remain about the broader range of challenges to decent work in the sector. Small-scale fisheries (SSFs) in particular have received relatively little attention from a labor-focused perspective. Motivated by this gap, this study elaborates a methodology to assess working conditions in SSFs across multiple dimensions of decent work, specifically through a case study of the artisanal jumbo squid fishery in Peru, a socially and economically important fishery in which working conditions are poorly understood. The findings highlight key decent work deficits in this fishery, including: inadequate coverage and lack of social protections; remuneration occasionally below the minimum wage; excessive working hours; increasingly longer trips in vessels that often lack adequate occupational safety and health features; informal employment relations and high turnover of crew, which are linked to safety issues (i.e., crew sometimes lack skills for this difficult work at sea); and fragmented fishing organizations with limited capacities for social dialogue. Many of the problems are rooted in or exacerbated by the broader governance context, especially widespread informality. The primary policy solutions being pursued are not labor-specific and are unlikely to address decent work deficits. Addressing these complex problems will require involving fishers—importantly, crew members—in efforts to drive improvements in the fishery and enhancing their capacities to lead in the development of solutions to the problems that affect them. More work is necessary to refine indicators and assess working conditions, but this work contributes towards advancing methodologies and highlighting the importance of studying labor in SSFs.
Faked speech detection with zero prior knowledge
Authors: Al Ajmi Sahar Abdullah , Hayat Khizar , Al Obaidi Alaa Mohammed , Kumar Naresh , Najim AL-Din Munaf Salim , Magnier Baptiste
Published: May 2024

Audio is one of the most used ways of human communication, but at the same time it can be easily misused to trick people. With the revolution of AI, the related technologies are now accessible to almost everyone, thus making it simple for the criminals to commit crimes and forgeries. In this work, we introduce a neural network method to develop a classifier that will blindly classify an input audio as real or mimicked; the word ‘blindly’ refers to the ability to detect mimicked audio without references or real sources. We propose a deep neural network following a sequential model that comprises three hidden layers, with alternating dense and drop out layers. The proposed model was trained on a set of 26 important features extracted from a large dataset of audios to get a classifier that was tested on the same set of features from different audios. The data was extracted from two raw datasets, especially composed for this work; an all English dataset and a mixed dataset (Arabic plus English). For the purpose of comparison, the audios were also classified through human inspection with the subjects being the native speakers. The ensued results were interesting and exhibited formidable accuracy, as we were able to get at least $$94\%$$

94
%

correct classification of the test cases, as against the $$85\%$$

85
%

accuracy in the case of human observers.
Predictors of HIV Viral Load Suppression After Enhanced Adherence Counseling, Nekemte, Ethiopia
Authors: Mosisa Yohannis , Ewunetu Adisu , Duftu Kitesa Biresa , Biru Bayise , Diriba Debelo , Shama Adisu Tafari , Lemi Melese , Fetensa Getahun , Feyisa Bikila Regassa
Published: May 2024

Background

Enhanced adherence counseling refers to the counseling intervention for Human Immunodeficiency Virus (HIV) patients with an elevated viral load result, a viral load of > 1000 copies/ml, on a routine or need-based viral load test. The Federal Ministry of Health, Ethiopia, has launched routine viral load testing and enhanced adherence counseling since 2016 for high-viral load people living with HIV, which is applicable throughout the country for all health facilities providing HIV care and treatment. Our study aimed to assess viral load suppression after enhanced adherence counseling and its predictors among high viral load people living with HIV who were on antiretroviral therapy.

Method

We conducted a health facility-based retrospective follow-up study among 352 HIV-infected high-viral load people enrolled in enhanced adherence counseling from July 2018 to June 2021 in Nekemte town public health facilities. Cox proportional hazard analysis was used to identify independent predictors.

Results

The overall 65.1% of 352 persons on antiretroviral treatment achieved HIV viral load suppression after enhanced adherence counseling, (15.01 per 100 person months (95% CI13.02-16.99)). The median time to viral load suppression was 5 months. Age ≥ 15 years (AHR = 1.99, 95% CI: 1.11–3.57), no history of opportunistic infection (AHR = 2.01, 95% CI: 1.18–3.41), and not using substances (AHR = 2.48, 95% CI: 1.19–5.14) were more likely to have viral load suppressed, while having an initial viral load count greater than 50,000 RNA copies/ml (AHR = 0.56, 95% CI: 0.37–0.85) were less likely to have viral load suppressed after enhanced adherence counseling.

Conclusion

Age, history of opportunistic infections, substance use, and an initial viral load count > 50,000 RNA copies/mL were significant predictors of viral load suppression. Enrolling all high-viral-load patients in enhanced adherence counseling is recommended for viral load suppression.
The Regulatory Environment for the Safety of the Internet of Medical Devices Users in the European Union and the United States
Authors: Biczysko-Pudełko Katarzyna
Published: May 2024

The Internet of Medical Things (IoMT) devices, as well as the Internet of Things phenomenon itself, are gaining a new group of customers every day, for whom it is almost a matter of course to use a wide range of devices, such as Internet-connected complex life support equipment or “smart” watches monitoring basic life parameters. With the growing popularity of such devices, however, questions about the safety of their users begin to arise, because almost in proportion to the number of benefits associated with the use of these products, the number of risks associated with them increases – eg improper functioning of Internet-connected life support equipment, in addition to threatening the life or health of its user, may affect the physical security of the product itself, the security of both personal and technical (eg non-personal) data processed by the specific product, or finally the cyber-security of the product. While the issues related to the protection of personal data and privacy, in general, have been discussed many times by the doctrine, the issues related to the protection of users of these devices under consumer law have not been considered much.

In this context, the question arises whether the current legal regulations provide an adequate and sufficient level of protection for IoMT users. In particular, whether the average IoMT user can actually exercise their rights under the provisions of consumer law and whether the protection afforded to him – both in terms of the scope of their rights and the scope of obligations and liability of manufacturers and suppliers of these devices – is not only illusory? In order to answer the above questions, the author will evaluate the prevailing market practices – still focused around the doctrine of “caveat emptor” or “let the buyer beware” – and compare them with these regulations and juxtapose them with relevant legal regulations. However, given the lack of geographical borders in the field of cyber security and privacy, the author will not only analyse EU cyber security legislation, but also US legislation in a comparative legal analysis. The choice of jurisdictions to be compared is also related to the size and importance of both the US and the EU for the global IoMT market. It should be noted that the United States has a dominant position in the IoMT, while the European Union is estimated to have the second largest IoMT market globally. At the same time, however, there are differences in legal systems between the two economic areas. An analysis carried out in this way will make it possible not only to answer the question posed above, but also to possibly identify those areas of regulation that need to be changed or adapted to the realities of IoMT.
The use of personal therapy by psychiatrists and psychiatry trainees: a systematic review
Authors: Aubry R.E. , Morgan M. , Donohue G.
Published: May 2024

Background:

It is widely acknowledged that personal therapy positively contributes to the continued personal well-being and ongoing professional development of mental health professionals, including psychiatrists. As a result, most training bodies continue to recommend personal therapy to their trainees. Given its reported value and benefits, one might hypothesize that a high proportion of psychiatrists avail of personal therapy. This systematic review seeks to investigate whether this is the case.

Aim:

To identify and evaluate the findings derived from all available survey-based studies reporting quantitative data regarding psychiatrists’ and psychiatry trainees’ engagement in personal therapy.

Method:

A systematic search for survey-based studies about the use of personal therapy by psychiatric practitioners was conducted in four databases and platforms (PubMed, Scopus, Embase and EbscoHost) from inception to May 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for quality using the quality assessment checklist for survey studies in psychology (Q-SSP) and findings summarized using narrative synthesis.

Results:

The proportion of trainees who engaged in personal therapy ranged from a low of 13.4% in a recent UK based study to a high of 65.3% among Israeli residents. The proportion of fully qualified psychiatrists who engaged in personal therapy varied from 32.1% in South Korea to 89% in New Zealand.

Conclusion:

This review represents the first known attempt to collect and synthesize data aimed at providing insights into the past and current trends in psychiatrists’ use of personal therapy across different geographic regions and career stages.
DIAMOND ON LADDER SYSTEMS AND COUNTABLY METACOMPACT TOPOLOGICAL SPACES
Authors: CARVALHO RODRIGO , INAMDAR TANMAY , RINOT ASSAF
Published: May 2024

The property of countable metacompactness of a topological space gets its importance from Dowker’s 1951 theorem that the product of a normal space X with the unit interval

$[0,1]$

is again normal iff X is countably metacompact. In a recent paper, Leiderman and Szeptycki studied

$\Delta $

-spaces, which is a superclass of the class of countably metacompact spaces. They proved that a single Cohen real introduces a ladder system

$ L$

over the first uncountable cardinal for which the corresponding space

$X_{ L}$

is not a

$\Delta $

-space, and asked whether there is a ZFC example of a ladder system

$ L$

over some cardinal

$\kappa $

for which

$X_{ L}$

is not countably metacompact, in particular, not a

$\Delta $

-space. We prove that an affirmative answer holds for the cardinal

$\kappa =\operatorname {\mathrm {cf}}(\beth _{\omega +1})$

. Assuming

$\beth _\omega =\aleph _\omega $

, we get an example at a much lower cardinal, namely

$\kappa =2^{2^{2^{\aleph _0}}}$

, and our ladder system L is moreover

$\omega $

-bounded.
Bad Subjects of Good Freedoms
Authors: Anjaria Ulka
Published: May 2024

In Mukti Lakhi Mangharam’s book, Freedom Inc.: Gendered Capitalism in New Indian Literature and Culture, she identifies “Freedom Inc.” as a neoliberal celebration of individual empowerment that contrasts with the multiple ways people have imagined freedom in a longer history of Indian literature and philosophy, which are much more open to collective empowerment and political transformation. This critique is certainly valid, but where in it is there the space for “bad” subjects, erotic desires, or for men and women who disobey, who flaunt rules and whose visions of freedom exceed those framed by respectable behavior or collective uplift? This article gives a few examples of what those alternative freedoms would look like, suggesting that in addition to fundamental rights, Indians might need the freedom to be naughty as well.
Civic associations, populism, and (un-)civic behavior: evidence from Germany
Authors: Popescu Bogdan G. , Jugl Marlene
Published: May 2024

Civic associations are expected to foster civic, pro-social behavior, but this optimistic view is increasingly contested. We argue that populist radical right parties can strategically target and infiltrate associations to diffuse anti-establishment rhetoric and anti-democratic attitudes. We illustrate this phenomenon by examining the relationship between civic associations and compliance with government rules during Germany's first Covid-19 lockdown with a difference-in-differences design. Results show that areas with denser sport, nature, and culture clubs recorded higher mobility under lockdown. We document the infiltration mechanism and the spreading of anti-democratic attitudes within associations, using survey and election data and qualitative evidence including interviews. In doing so, we shed light on a negative effect of social networks and an understudied strategy of challenger populist parties.
The effects of party labels on vote choice with realistic candidate differentiation
Authors: Titelman Noam , Lauderdale Benjamin E.
Published: May 2024

In this paper we test how much party labels influence vote choices between candidates when voters have access to realistically distributed information about candidate positions and demographics. We do not seek to adjudicate a long-running debate about the role of party labels, but present some nuances on the two archetypal theoretical views on vote choices. We use data from the Representative Audit of Britain (RAB) and the British Elections Study (BES) to generate electoral match-ups between randomly selected Conservative versus Labour candidates, with only half of respondents seeing party labels in addition to candidates’ positions and demographics. For our experiment fielded in October 2021, we find negligible to moderate effects of party labels on vote choices. Our results suggest the information on candidate positions and party labels largely act as substitutes for one another, with only modest changes when party labels are made explicit.
HELOTS AT THERMOPYLAE: THE GREEK DEAD AT HERODOTUS 8.25
Authors: Clements Thomas
Published: May 2024

This article argues for a more diverse approach to the appearance of enslaved persons in Greek historiography through an analysis of the Persian navy's battlefield tour of Thermopylae in Book 8 of Herodotus’ Histories. Previous approaches to slavery in Greek historiography have rightly commented on the cultural awkwardness to Greek authors of slaves’ extensive involvement in ancient warfare. However, this is only one aspect of how slaves featured in historiographical narrative. Herodotus continually problematizes the methods of enquiry and many characters within his work engage in enquiry-like activities. Book 8 itself is no different, with much of the action involving errors in human perception. The appearance of helots amongst the heroic dead at Thermopylae is intended both as a narrative reveal, since their presence has not previously been known to the reader, and as a comment on the contestation of Greek identity, which is framed at the start of Book 8 with a series of direct addresses to different groups of Greeks, all of whom take a different approach to their participation in the Persian Wars. Hence what appears to be an incidental detail can in fact be understood in the wider, thematic context of the Histories and especially that of the books concerning the Persian Wars.
First record of sand crab, Jonas kalpakkamensis Barathkumar, Das & Satpathy, 2016 (Decapoda, Brachyura, Corystidae) from the Western Indian Ocean with a key to the genus Jonas
Authors: Sureandiran B. , Dave T. H. , Suyani N. K. , Karuppasamy K.
Published: May 2024

A total of five specimens of sand crab, Jonas kalpakkamensis Barathkumar, Das & Satpathy, 2016 were recorded for the first time from the Western Indian Ocean. The sand crab specimens were collected from the bycatch of the commercial demersal trawler targeting crustaceans at a depth of 15–50 m operated along the western region of the Gujarat coastal waters. The collected specimen consists of 3 males and 2 females and it was identified by comparing with holotype and paratype specimens. Previously, J. kalpakkamensis was reported from the Eastern Indian Ocean in the Bay of Bengal region but there is no report or distribution of this sand crab in the Western Indian Ocean. The detailed taxonomic diagnostic character of the sand crab, J. kalpakkamensis and the key for all species under the genus Jonas reported globally is provided in the current study.
Quantile-based information generating functions and their properties and uses
Authors: Kayal Suchandan , Balakrishnan N.
Published: May 2024

Information generating functions (IGFs) have been of great interest to researchers due to their ability to generate various information measures. The IGF of an absolutely continuous random variable (see Golomb, S. (1966). The information generating function of a probability distribution. IEEE Transactions in Information Theory, 12(1), 75–77) depends on its density function. But, there are several models with intractable cumulative distribution functions, but do have explicit quantile functions. For this reason, in this work, we propose quantile version of the IGF, and then explore some of its properties. Effect of increasing transformations on it is then studied. Bounds are also obtained. The proposed generating function is studied especially for escort and generalized escort distributions. Some connections between the quantile-based IGF (Q-IGF) order and well-known stochastic orders are established. Finally, the proposed Q-IGF is extended for residual and past lifetimes as well. Several examples are presented through out to illustrate the theoretical results established here. An inferential application of the proposed methodology is also discussed
Device closure of residual aortopulmonary window using Konar-MF occluder device: an attractive new option
Authors: Qureshi Ahmad Usaid , Kazmi Tehmina , Sadiq Masood
Published: May 2024

We report a case of a residual aortopulmonary window where a new Konar-MF occluder device was used to close the defect. This device has a low profile and conforms to the anatomy of aortopulmonary window very nicely without unnecessary protrusion on either side. This report highlights the advantage of Konar-MF occluder device for closure of such defects.
Waiting for Somebody to Show Up
Authors: Lee Juseob , Jex Steve M.
Published: May 2024

Abstract: We investigate the effects of college student job applicants’ waiting experience during an employment selection procedure (“applicant waiting”) using experimental vignettes. Drawing on the literature on signaling theory, we propose that applicant waiting signals future mistreatment from the organization, resulting in lower organizational attraction. General self-efficacy was examined for its moderating effects. A sample of 171 US undergraduate students with at least one in-person job interview experience (94.4%) participated in the study. Hypotheses were tested by using moderated regression analysis. The results demonstrate that applicant waiting was negatively associated with organizational attraction, and general self-efficacy moderated the relationship. Contrary to our initial expectation, those with higher general self-efficacy reacted more negatively to applicant waiting conditions than those with lower general self-efficacy.
2.5‐D Local Hybrid Simulations of Discontinuity‐Driven Compressional Boundaries Under Various Magnetic Field Geometries
Authors: Vu Andrew , Liu Terry Z. , Angelopoulos Vassilis , Zhang Hui
Published: May 2024

In the ion foreshock, there are many foreshock transients driven by back streaming foreshock ions. When the foreshock ions interact with tangential discontinuities (TDs), hot flow anomalies form if the foreshock ion‐driven current decreases field strength at TDs, but the opposite situation has been paid little attention. Using 2.5‐D local hybrid simulations, we show that a compressional boundary with enhanced field strength and density can form. We examine how the foreshock ions interact with TDs under various magnetic field geometries to drive currents that lead to compressional boundaries. The current driven by the foreshock ions should peak on its initial side of a TD so that the enhanced field strength at the TD in turn increases this current by keeping more foreshock ions on their initial side. Which side the current peaks can be determined by whether the foreshock ions initially cross the TD and/or how their velocity is projected into the local perpendicular direction. Additionally, the foreshock ion‐driven currents from two sides could compete, and whether a compressional boundary forms is determined by the net current profile. Because such compressive structures in the foreshock can drive magneto sheath jets and cause many geoeffects, it is necessary to fully understand their formation.
Compartmentalization of Axial Seamount's Magma Reservoir Inferred by Analytical and Numerical Deformation Modeling With Realistic Geometry
Authors: Slead S. R. , Wei M. , Nooner S. L. , Chadwick W. W. , Caress D. W. , Beeson J.
Published: May 2024

Axial Seamount is a submarine volcano on the Juan de Fuca Ridge with enhanced magma supply from the Cobb hotspot. We compare several deformation model configurations to explore how the spatial component of Axial's deformation time series relates to magma reservoir geometry imaged by multi‐channel seismic (MCS) surveys. To constrain the models, we use vertical displacements from seafloor pressure sensors and repeat autonomous underwater vehicle (AUV) bathymetric surveys between 2016 and 2020. We show that implementing the MCS‐derived 3D main magma reservoir (MMR) geometry with uniform pressure in a finite element model with uniform elastic host rock properties poorly fits the geodetic data. To test the hypothesis that there is compartmentalization within the MMR that results in heterogeneous pressure distribution, we compare analytical models using various horizontal sill configurations constrained by the MMR geometry. Using distributed pressure sources significantly improves the Root Mean Square Error (RMSE) between the inflation data and the models by an order of magnitude. The RMSE between the AUV data and the models is not improved as much, likely due to larger uncertainty of the AUV data. The models estimate the volume change for the 2016–2020 inter‐eruptive inflation period to be between 0.054 and 0.060 km3 and suggest that the MMR is compartmentalized, with most magma accumulating in sill‐like bodies embedded in crystal mush along the western‐central edge of the MMR. The results reveal the complexity of Axial's plumbing system and demonstrate the utility of integrating geodetic data and seismic imagery to gain insights into magma storage at active volcanoes.
Modeling Interactive Effects of Manganese Bioavailability, Nitrogen Deposition, and Warming on Soil Carbon Storage
Authors: Sulman Benjamin N. , Herndon Elizabeth M.
Published: May 2024

Manganese (Mn) is a redox‐active micronutrient that has been shown to accelerate plant litter decomposition; however, the effect of Mn‐promoted decomposition on soil C storage is unclear. We present a novel biogeochemical model simulating how Mn bioavailability influences soil organic C (SOC) stocks in a soil profile (<50 cm) within a temperate forest. In our model, foliar Mn increased in response to increasing soluble Mn released through Mn‐oxide (birnessite) dissolution in mineral soil layers. The ensuing Mn enrichment in leaf litter redistributed Mn to the surface forest floor layer, promoted enzymatic oxidation of lignin, and decreased SOC stocks. Total SOC loss was partially mitigated by accumulation of lignin‐oxidation products as mineral‐associated organic C. We also explored how Mn‐driven changes to C storage interacted with effects of N deposition and warming. Nitrogen enrichment inhibited Mn‐dependent lignin degradation, increasing SOC stocks and weakening their dependence on Mn bioavailability. Warming stimulated decomposition and reduced C stocks but was less effective at low Mn bioavailability. Our model results suggest that SOC stocks are sensitive to Mn bioavailability because increased plant uptake redistributes Mn to surface soils where it can enhance litter decomposition. Based on our simulations, we predict that Mn becomes limiting to litter decomposition where Mn is poorly soluble. Depletion of bioavailable Mn or other cofactors that are critical to decomposition could limit the response of organic C stocks to warming over time, but quantitative projections of the role of Mn bioavailability in regulating decomposition requires additional measurements to constrain model uncertainties.
Dipolarizing Flux Bundles and Magnetic Flux Transport
Authors: Lui A. T. Y.
Published: May 2024

An important feature intimately related to substorm process is the development of dipolarization in the near‐Earth region. A common concept is that it arises from magnetic flux transported by dipolarizing flux bundles generated by magnetic reconnection in the mid‐tail region. This concept is based on assuming the validity of the frozen‐in‐field condition for dipolarizing flux bundles. The frozen‐in‐field condition of this structure is critically evaluated from observations and by theoretical consideration. It is shown that this structure cannot transport sufficient magnetic flux to the near‐Earth region that is required from observations for substorms.
Spatial Features of the Delayed Ionospheric Response During Low and High Solar Activity
Authors: Schmölter Erik , Dühnen Hanna , Berdermann Jens , Vaishnav Rajesh , Jacobi Christoph
Published: May 2024

The ionospheric response to solar 27‐day signatures has complex temporal and spatial variations, which are driven by short‐ and long‐term changes of the solar activity among other processes (e.g., geomagnetic activity). A delay between these solar and ionospheric signatures occurs due to accumulation of plasma, which depends on the rates of photoionization, photodissociation and recombination in the upper atmosphere. The balance of these processes changes significantly at different solar activity levels. Therefore the present study investigates the delayed ionospheric response during low and high solar activity. For that purpose, global as well as latitude‐ and longitude‐dependent total electron content (TEC) is analyzed via superposed epoch analysis (SEA). Different results based on the solar proxy F10.7 and solar extreme ultraviolet (EUV) irradiance measurements are presented to discuss findings of preceding studies and to provide a first wavelength‐dependent analysis of the spatial features. The SEA shows a good correlation between solar activity level and delayed ionospheric response with particular strong enhancements of the delay at mid‐latitudes. Increased delays are also observed for morning and evening hours. Thus, the present study confirms the correlation of delayed ionospheric response and solar activity level as indicated in preceding studies, and also quantifies the temporal and spatial variations with commonly used data sets. This in turn allows a better understanding of the processes that cause the delayed ionospheric response.
Timing and risk factors associated with acute kidney injury in infants with necrotizing enterocolitis
Authors: Lingasubramanian Geethanjali , Hum Christina Eva , Hunter Krystal , Mehta Rajeev , Bhandari Vineet
Published: May 2024

Objective

To evaluate the prevalence, onset, risk factors, and mortality associated with acute kidney injury (AKI) in infants with necrotizing enterocolitis (NEC).

Design/Methods

Retrospective study at 2 centers in infants with NEC, with/without AKI. AKI assessed by serum creatinine and urine output. Statistical tests used included t, Mann-Whitney U, Chi-square, and Fisher Exact tests.

Results

Among 80 eligible infants with NEC, 56 (70%) had AKI. Median onset of NEC was day 15, with median AKI onset two days (IQR, –5.75 to 0) prior to NEC onset. Vasopressors were significantly more likely to be used in infants with NEC and AKI (p = 0.009). Increased mortality (p = 0.01) was noted in infants with NEC and AKI.

Conclusions

The onset of AKI mostly precedes NEC onset, with moderate to severe AKI more prevalent than the milder form in infants with NEC. These infants are significantly more likely to be hemodynamically unstable and have increased mortality.
Shorter long-term post-transplant life expectancy may be due to prior chemotherapy for the underlying disease: analysis of 3012 patients with acute myeloid leukemia enrolled on 9 consecutive ECOG-ACRIN trials
Authors: Ganzel C. , Wang Y. , Roopcharan K. , Sun Z. , Rowe J. M. , Fernandez H. F. , Paietta E. M. , Luger S. M. , Lazarus H. M. , Cripe L. D. , Douer D. , Wiernik P. H. , Tallman M. S. , Litzow M. R.
Published: May 2024

Several studies reported that patients with acute myeloid leukemia (AML) who remain in long-term remission after allogeneic or autologous transplant have a shorter life expectancy, compared to the general population. However, little is known about the life expectancy of adult long-term survivors of AML who were treated with chemotherapy alone without a transplant and there have been no comparisons with survival among the general population. The current study indicates that the life expectancy of AML patients who achieved and maintained CR for at least 3 years is shorter than expected for age in the US population. This was observed also in patients who did not undergo a transplant including those who have not relapsed during the entire long follow-up period. Thus, late relapse does not explain why patients without transplants have a shortened life expectancy. Taken together, these data strongly suggest that prior chemotherapy for the underlying AML is at least a major contributing factor for the known shortened life expectancy post-transplant.
The OGT–c-Myc–PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth
Authors: Wang Huijuan , Sun Jie , Sun Haofan , Wang Yifei , Lin Bingyi , Wu Liming , Qin Weijie , Zhu Qiang , Yi Wen
Published: May 2024

Deregulated glucose metabolism termed the “Warburg effect” is a fundamental feature of cancers, including the colorectal cancer. This is typically characterized with an increased rate of glycolysis, and a concomitant reduced rate of the tricarboxylic acid (TCA) cycle metabolism as compared to the normal cells. How the TCA cycle is manipulated in cancer cells remains unknown. Here, we show that O-linked N-acetylglucosamine (O-GlcNAc) regulates the TCA cycle in colorectal cancer cells. Depletion of OGT, the sole transferase of O-GlcNAc, significantly increases the TCA cycle metabolism in colorectal cancer cells. Mechanistically, OGT-catalyzed O-GlcNAc modification of c-Myc at serine 415 (S415) increases c-Myc stability, which transcriptionally upregulates the expression of pyruvate dehydrogenase kinase 2 (PDK2). PDK2 phosphorylates pyruvate dehydrogenase (PDH) to inhibit the activity of mitochondrial pyruvate dehydrogenase complex, which reduces mitochondrial pyruvate metabolism, suppresses reactive oxygen species production, and promotes xenograft tumor growth. Furthermore, c-Myc S415 glycosylation levels positively correlate with PDK2 expression levels in clinical colorectal tumor tissues. This study highlights the OGT–c-Myc–PDK2 axis as a key mechanism linking oncoprotein activation with deregulated glucose metabolism in colorectal cancer.
How do I manage functional visual loss
Authors: Ramsay Neil , McKee Justin , Al-Ani Gillian , Stone Jon
Published: May 2024

Functional visual loss is a subtype of functional neurological disorder (FND) and is a common cause of visual impairment seen in both general and neuro-ophthalmological practice. Ophthalmologists can generally diagnose functional visual loss reasonably confidently but often find it harder to know what to say to the patient, how to approach, or even whether to attempt, treatment. There is little evidence-based treatment despite studies showing up to 60% of adults having impactful symptoms on long-term follow-up. The last 20 years has seen large changes in how we understand, approach, and manage FND more widely. In this article, we set out our practical approach to managing functional visual loss which includes : 1) Make a positive diagnosis based on investigations that demonstrate normal vision in the presence of subjectively impaired vision, not just because tests or ocular exam is normal; 2) Explain and label the condition with an emphasis on these positive diagnostic features, not reassurance; 3) Consider eye or brain comorbidities such as migraine, idiopathic intracranial hypertension or amblyopia; 4) Consider working with an orthoptist using diagnostic tests in a positive way to highlight the possibility of better vision; 5) Develop simple treatment strategies for photophobia; 6) Consider psychological factors and comorbidity as part of assessment and therapy, but keep a broader view of aetiology and don’t use this to make a diagnosis; 7) Other treatment modalities including hypnotherapy, transcranial magnetic stimulation and more advanced forms of visual feedback are promising candidates for functional visual loss treatment in the future.
Distinct µ-opioid ensembles trigger positive and negative fentanyl reinforcement
Authors: Chaudun Fabrice , Python Laurena , Liu Yu , Hiver Agnes , Cand Jennifer , Kieffer Brigitte L. , Valjent Emmanuel , Lüscher Christian
Published: May 2024

Fentanyl is a powerful painkiller that elicits euphoria and positive reinforcement1. Fentanyl also leads to dependence, defined by the aversive withdrawal syndrome, which fuels negative reinforcement2,3 (that is, individuals retake the drug to avoid withdrawal). Positive and negative reinforcement maintain opioid consumption, which leads to addiction in one-fourth of users, the largest fraction for all addictive drugs4. Among the opioid receptors, µ-opioid receptors have a key role5, yet the induction loci of circuit adaptations that eventually lead to addiction remain unknown. Here we injected mice with fentanyl to acutely inhibit γ-aminobutyric acid-expressing neurons in the ventral tegmental area (VTA), causing disinhibition of dopamine neurons, which eventually increased dopamine in the nucleus accumbens. Knockdown of µ-opioid receptors in VTA abolished dopamine transients and positive reinforcement, but withdrawal remained unchanged. We identified neurons expressing µ-opioid receptors in the central amygdala (CeA) whose activity was enhanced during withdrawal. Knockdown of µ-opioid receptors in CeA eliminated aversive symptoms, suggesting that they mediate negative reinforcement. Thus, optogenetic stimulation caused place aversion, and mice readily learned to press a lever to pause optogenetic stimulation of CeA neurons that express µ-opioid receptors. Our study parses the neuronal populations that trigger positive and negative reinforcement in VTA and CeA, respectively. We lay out the circuit organization to develop interventions for reducing fentanyl addiction and facilitating rehabilitation.
Molecular mechanism of choline and ethanolamine transport in humans
Authors: Ri Keiken , Weng Tsai-Hsuan , Claveras Cabezudo Ainara , Jösting Wiebke , Zhang Yu , Bazzone Andre , Leong Nancy C. P. , Welsch Sonja , Doty Raymond T. , Gursu Gonca , Lim Tiffany Jia Ying , Schmidt Sarah Luise , Abkowitz Janis L. , Hummer Gerhard , Wu Di , Nguyen Long N. , Safarian Schara
Published: May 2024

Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2–7. Earlier studies concluded that FLVCR1 may function as a haem exporter8–12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14–16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation–π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.
Kainate receptor channel opening and gating mechanism
Authors: Gangwar Shanti Pal , Yelshanskaya Maria V. , Nadezhdin Kirill D. , Yen Laura Y. , Newton Thomas P. , Aktolun Muhammed , Kurnikova Maria G. , Sobolevsky Alexander I.
Published: May 2024

Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission1–4. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism5–11. Although structures of kainate receptor domains and subunit assemblies are available12–18, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders.
Merging adoption of natural climate solutions in agriculture with climatic and non-climatic risks within an (intra)gendered framework
Authors: Antwi Kwabena
Published: May 2024

The extant research on climate variability shares significant theoretical contributions to vulnerability and risks. However, the literature mostly focuses on technical solutions to climate extremes which undermines efforts to identify and solve the dynamics within gender groups in using agricultural-based natural climate solutions (NCS) to address climatic and non-climatic risks. With this in mind, this study implements both quantitative and qualitative approaches including household surveys, key informant interviews, and focus group discussions to investigate the adoption of NCS within gender groups to address climatic and non-climatic risks in three selected communities (Katanga, Dakio, and Zonno) in the Bolgatanga East District of Upper East Region of Ghana. The Relative Importance Index (RII) was used to rank the key climatic and non-climatic risks confronting smallholder farmers in the district. Male and female smallholder farmers affirmed that there has been variation in the climate compared to their childhood. The results indicated climate change-induced erosion (RII = 0.268) as the highest climatic risk among male smallholder farmers. Increased bushfire (RII = 0.263) was the highest climatic risk affecting female smallholder farmers. The findings show that the high cost of farm inputs (RII = 0.505) is the highest non-climatic risk among the male smallholder farmers whereas inadequate credit facilities (RII = 0.295) affected most of the female smallholder farmers. In adapting to the climatic risks, both male and female smallholder farmers with no formal education plant early maturing crop varieties and cover crops on their farmland. Others engage in traditional non-farm activities such as weaving by using renewable materials with reduced ecological footprints to address non-climatic risks. The male and female smallholder farmers with post-secondary education typically resort to temporal migration during the dry season to work on non-farm jobs. Acknowledging the intra-gendered adoption of NCS among marginalized farming households; not only protects against maladaptation but also improves local-level resilience and climate risk management in Ghana.
KAT8 compound inhibition inhibits the initial steps of PINK1-dependant mitophagy
Authors: de Talhouët Capucine , Esteras Noemi , Soutar Marc P. M. , O’Callaghan Benjamin , Plun-Favreau Helene
Published: May 2024

It has recently been shown that KAT8, a genome-wide association study candidate risk gene for Parkinson’s Disease, is involved in PINK1/Parkin-dependant mitophagy. The KAT8 gene encodes a lysine acetyltransferase and represents the catalytically active subunit of the non-specific lethal epigenetic remodelling complex. In the current study, we show that contrary to KAT5 inhibition, dual inhibition of KAT5 and KAT8 via the MG149 compound inhibits the initial steps of the PINK1-dependant mitophagy process. More specifically, our study shows that following mitochondrial depolarisation induced by mitochondrial toxins, MG149 treatment inhibits PINK1-dependant mitophagy initiation by impairing PINK1 activation, and subsequent phosphorylation of Parkin and ubiquitin. While this inhibitory effect of MG149 on PINK1-activation is potent, MG149 treatment in the absence of mitochondrial toxins is sufficient to depolarise the mitochondrial membrane, recruit PINK1 and promote partial downstream recruitment of the autophagy receptor p62, leading to an increase in mitochondrial delivery to the lysosomes. Altogether, our study provides additional support for KAT8 as a regulator of mitophagy and autophagy processes.
Dihydroartemisinin-driven selective anti-lung cancer proliferation by binding to EGFR and inhibition of NRAS signaling pathway-induced DNA damage
Authors: Li Liu-Gen , Peng Xing-Chun , Yang Zi-Yi , Han Ning , Gou Chang-Long , Shi Jun , Yu Li-Li , Chen Nan-Nan , Yu Ting-Ting , Li Tong-Fei , Li Xian-Yu , Hu Jun
Published: May 2024

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.
Contact lenses as novel tear fluid sampling vehicles for total RNA isolation, precipitation, and amplification
Authors: Boychev Nikolay , Lee Seokjoo , Yeung Vincent , Ross Amy E. , Kuang Liangju , Chen Lin , Dana Reza , Ciolino Joseph B.
Published: May 2024

The tear fluid is a readily accessible, potential source for biomarkers of disease and could be used to monitor the ocular response to contact lens (CL) wear or ophthalmic pathologies treated by therapeutic CLs. However, the tear fluid remains largely unexplored as a biomarker source for RNA-based molecular analyses. Using a rabbit model, this study sought to determine whether RNA could be collected from commercial CLs and whether the duration of CL wear would impact RNA recovery. The results were referenced to standardized strips of filtered paper (e.g., Shirmer Strips) placed in the inferior fornix. By performing total RNA isolation, precipitation, and amplification with commercial kits and RT-PCR methods, CLs were found to have no significant differences in RNA concentration and purity compared to Schirmer Strips. The study also identified genes that could be used to normalize RNA levels between tear samples. Of the potential control genes or housekeeping genes, GAPDH was the most stable. This study, which to our knowledge has never been done before, provides a methodology for the detection of RNA and gene expression changes from tear fluid that could be used to monitor or study eye diseases.
Exploring grandiose narcissism among surgeons: a comparative analysis
Authors: Moellmann Henriette L. , Rana Majeed , Daseking Monika , Petersohn Hendric , Rana Madiha
Published: May 2024

The concept of narcissism encompasses various personality traits, including cognitive, emotional and behavioural characteristics, which often lead to difficulties in maintaining a healthy self-esteem. This study examines the prevalence of narcissism traits (Admiration and Rivalry) in the surgical profession and their association with age, gender and professional experience. A total of 1390 participants (408 women, 982 men) took part in an online survey. The results show that female participants have significantly lower levels of rivalry than male colleagues. Additionally, age was found to be inversely correlated with both facets of narcissism, demonstrating that levels of narcissism decrease as age increases. Participants who are still in education tend to show higher levels of both facets. These results improve our understanding of personality traits in surgery and provide valuable insights for researchers and practitioners.