bluuebunny/crossref_metadata_2025 huggingface dataset:
United States–Cuba Relations
Authors: McKercher Asa
Published: February 2024

Since the Cuban Revolution of 1959, relations between Cuba and the United States have been marked by intense mutual hostility. This antagonism is a measure of the historically close ties between the two countries, extending back several centuries and the product of geographic proximity. Much of this long history has been marked by American efforts to control Cuba—often cast as being in Cubans’ best interests—and consequent Cuban resistance. At the same time, some Cubans have welcomed close ties with the United States, economically, culturally, and politically. Moreover, there has been considerable interchange between Americans and Cubans, from tourists looking for excitement to exiles seeking shelter north of the Florida Straits. Given the long shadow the United States has cast over Cuban history and Cuba’s place in several seminal events in US foreign policy, understanding these historical ties is vital for contextualizing the bitterness that has characterized their bilateral relationship for over half a century.
Technology and Religion in Ancient Greece and Rome
Authors: Bur Tatiana
Published: February 2024

Coupling together “technology” and “religion” might, to the modern mind, sound rather antithetical. The former, as we know it, is based in scientific knowledge and produces tangible results; the latter is phenomenological and spiritual. Yet this does not do justice to the full character of ancient science, or of ancient religion. Technologies in Greco-Roman antiquity could, and did, help create and sustain a sense of the divine, whether this was in the context of sanctuary space, or as part of religious occasions or rituals, for example. The kinds of evidence available to unearth the realities of the relation between technology and religion in ancient Greece and Rome span literature, material culture, and, importantly, ancient technical manuals. This final genre tends not to be as familiar to students of the Greco-Roman world in general and especially to students of ancient religion. Yet by combining these dry, and at times abstruse, texts with anecdotal evidence, technical realities and issues of viewership which surround the use of technology in ancient religious contexts can be better understood.

One of the more familiar instances of religious technologies from ancient Greece is that of the theatrical crane (mēchanē). There, epiphanies of gods were fabricated using a conspicuous mechanical construction which speaks to the fundamentally mediated nature of ancient epiphany. The sense of sacred presence within ancient temples in the Greco-Roman world was enhanced using various technical methods including catoptrics—the science of reflection. Religious processions in antiquity involved parading a vast array of objects through the cityscape and technologies of automation began, in the Hellenistic period onward, to feature as part of this conspicuous display of the marvelous. Various other rituals which formed the very basis of Greek religious life, such as divination and dedication, relied on technical, including mechanical, expertise to create, enhance, or authenticate connection with the divine.

Traces of the intersection between religion and technology in Greco-Roman antiquity can be found not only from the Classical institution of the theater but even earlier, including in the Homeric epics. Yet the formalization of the discipline of mechanics in the Hellenistic period gave new shape and vigor to the relation between religion and technology. Subsequently, the Roman period saw increased meta-discourse on the phenomenon, especially thanks to the culturally vibrant “Second Sophistic,” as well as the rise of Christianity, where the word (logos) of god was privileged above anything material.
A Review of Alternative Water Supply Systems in ASEAN
Authors: Tortajada Cecilia , Hartley Kris , Ong Corinne , Arora Ojasvee
Published: February 2024

Climate change, water scarcity and pollution, and growing water demand across all sectors are stressing existing water supply systems, highlighting the need for alternative water supply (AWS) systems. AWS systems are those that have not typically existed in the traditional supply portfolio of a given service area but may be used to reduce the pressure on traditional water resources and potentially improve the system’s resilience. AWS systems have been used for decades, often where traditional systems are unable to maintain sufficient quantity and quality of water supply. Simpler forms of AWS systems, like rainwater harvesting, have been used for centuries. As human population and water demand have increased, AWS systems now play a larger role in the broader supply portfolio, but these systems alone are not able to fully resolve the increasingly complex mix of problems contributing to water stress. Entrenched challenges that go beyond technical issues include low institutional capacity for developing, operating, and maintaining AWS systems; monitoring water quality; more efficiently using available resources; and establishing clear responsibilities among governments, service providers, and property owners. Like traditional water supply systems, AWS systems should be developed within a sustainability-focused framework that incorporates scenario planning to account for evolving natural and institutional conditions. In ASEAN, the adoption of AWS systems varies among countries and provides context-specific lessons for water management around the world. This article provides an overview of AWS systems in the region, including rainwater harvesting, graywater recycling, wastewater reclamation, desalination, and stormwater harvesting.
Ceremonial and Subsistence Water Use
Authors: Whittington Dale , Hanemann Michael
Published: February 2024

Water for cultural and religious purposes, referred to as ceremonial and subsistence (C&S) use, is a distinctive feature of many Indigenous and other communities. Whether this constitutes a legitimate claim for water for an American Indian Tribe in the United States was litigated in the context of a trial to determine the federal government’s obligation to reserve water for Indian Tribes whom it had settled on reservations during the 19th century. Following a U.S. Supreme Court ruling in 1963, the amount of water the federal government was obligated to provide was defined as the quantity of water that could be used to grow crops profitably on the reservation. In 2001, the Arizona Supreme Court adopted a new definition, for Arizona, namely the amount of water that ensured the reservation would be a permanent homeland. However, parts of this 2001 ruling were contradictory and seemed to support the profitable irrigation standard. What the Arizona Supreme Court actually meant was not put to the test until the Hopi water rights trial in 2020. The Hopi Tribe’s water rights claims included a claim for new water to replace diminishing local water supplies in order for the Tribe to continue cultivating traditional varietals of corn and other crops. Hopi agricultural practices date back at least a millennium and are a central part of Hopi culture and religion. The crops are used in cultural and religious ceremonies and are not sold commercially. The Hopi claim for water for irrigation to support C&S cultivation was opposed by the other parties to the case and was rejected by the court.
Racial Perspectives on Facelifts: Evaluating Techniques and Outcomes Across Diverse Populations
Authors: McCleary Sean Patrick , Nirbhay Jain , Moghadam Shahrzad , Le Christina , Roostaeian Jason
Published: February 2024

Background

Facial aesthetic surgery is one of plastic and reconstructive surgery's most sought-after and evolving areas. The growing diversity in both local and worldwide populations compels us to reevaluate our previous approaches and underscores the significance of departing from a singular aesthetic standard. Thankfully, the historical practice of stereotypical racial profiling has become less prevalent in the literature. Regrettably, however, the comparative terminology persists, characterizing non-Caucasian races as deviating from the “norm,” which typically refers to the White or Caucasian race. Additionally, there is a lack of contemporary literature comparing the distinctive considerations relevant to rhytidectomy across multiple racial populations.

Objectives

The aim of this study was to succinctly outline the current body of literature examining the impact of race on facial aging and rhytidectomy, laying the groundwork for subsequent discussion on the relationship between race and facial aesthetic surgery.

Methods

A comprehensive literature review was conducted using PubMed (National Institutes of Health, Bethesda, MD), identifying all studies published before 2023 discussing facial aging and rhytidectomy, specifically in non-Caucasian patients.

Results

A total of 22 publications was identified. Asians were the most described group, with 12 publications, followed by Black/African with 5 and Hispanic/Latinx with 4.

Conclusions

In today's context, the aesthetic surgeon must possess the knowledge and readiness to provide culturally sensitive, patient-centered care guided by subtle anatomical nuances, informed by anecdotal recommendations, and ultimately, aimed at effectively addressing aging concerns within diverse populations.

Level of Evidence: 3
Spatial structure imposes sex-specific costs but does not reduce interlocus sexual conflict
Authors: Halder Subhasish , Kar Shramana , Sethi Simran , Tewari Swadha , Verma Tanya , Nandy Bodhisatta
Published: February 2024

Spatial structure is a common feature of all naturally occurring populations. Theoretically, spatial structuring of a habitat could modulate the intensity of interlocus sexual conflict (ISC) in a population, possibly by modulating intersexual encounter rate. We tested this theory using laboratory populations of Drosophila melanogaster by measuring male-induced decline in female fitness in three-patch habitat systems with two alternative habitat types: structured–interconnected and unstructured. Our results on reproductive and survival costs in females suggested significant costs attributable to male presence (i.e. ISC) and to living on structured habitat. However, there was only weak evidence supporting the theory of modulation of ISC by habitat structuring only. Through a follow-up experiment, we also showed that the effect of habitat on ISC is robust to the alteration of female conditions. Therefore, it appears that spatial structuring per se is unlikely to modulate ISC but can impose additional survival costs. We also showed that this survival cost could be sex specific, possibly reflecting female-biased spontaneous dispersal.
Colonial Confessions: An Autoethnography of Writing Criminology in the New South Africa
Authors: Dixon Bill
Published: February 2024

This article is an autoethnographic account of a 20-year engagement with South African criminology. It is written from the perspective of someone from the Global North, a beneficiary of Britain’s colonial past and the present dominance of northern ways of thinking and being. The aim is to encourage other criminologists from a similar background to reflect on their histories and the impact of their work in the present, and to be open to ideas from outside the Euro-American mainstream of the discipline. The evolution of South African criminology, and its gradual adoption of a more southern or decolonial sensibility, is traced in the work of the author and others.
How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?
Authors: Odierna G Lorenzo , Vucic Steve , Dyer Marcus , Dickson Tracey , Woodhouse Adele , Blizzard Catherine
Published: February 2024

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the ‘dying forward’ excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the ‘dying forward’ excitotoxicity hypothesis and the failure of therapies that target neuronal activation.

One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the ‘dying forward’ excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis.

We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.
Cortical microstructural imaging from diffusion MRI: towards sensitive biomarkers for clinical trials
Authors: Rodriguez-Vieitez Elena , Vannini Patrizia , Montal Victor , Graff Caroline
Published: February 2024

This scientific commentary refers to ‘Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer’s disease’ by Spotorno et al. (https://doi.org/10.1093/brain/awad428).
A severe presentation of ulcers throughout the limbs
Authors: Tsai Joshua T , Alexander Helen , Bailey Clare , Wilsher Mark , Jones Isabel , Markeson Daniel
Published: February 2024

Skin swabs revealed herpes simplex virus (HSV) 1 infection. Despite treatment with aciclovir, large ulcers on each medial thigh continued to progress, requiring surgical debridement and split-thickness skin autografting. Our case highlights the potential need for skin autografts in managing atypical, nonhealing herpetic ulcers despite maximum medical intervention and the importance of testing for HSV in skin ulceration.
A predictive model for medication adherence in older adults with heart failure
Authors: Oh Eun Ha , Kim Chun-Ja , Schlenk Elizabeth A
Published: February 2024

Aims

Although many studies have examined the predictors of medication adherence (MA), further empirical research is required to clarify the best model for predicting MA for older adults with heart failure (HF). Thus, we hypothesized a model in which information (knowledge), motivation (social support and depressive symptoms), and behavioural skills (barriers to self-efficacy) would be associated with MA in patients with HF.

Methods and results

Using a cross-sectional survey, 153 adults aged ≥ 65 years taking medication for HF were recruited from a university hospital in Korea. Data were collected based on the information–motivation–behavioural skills (IMB) model constructs and MA. In the hypothesized path model, self-efficacy was directly related to MA (β = −0.335, P = 0.006), whereas social support was indirectly related to MA through self-efficacy (β = −0.078, P = 0.027). Depressive symptoms were directly related to MA (β = 0.359, P = 0.004) and indirectly related to MA through self-efficacy (β = 0.141, P = 0.004). The hypothesized MA model showed a good fit for the data. Knowledge, social support, and depressive symptoms accounted for 44.3% of the variance in self-efficacy (P = 0.004). Left ventricular ejection fraction, knowledge, social support, depressive symptoms, and self-efficacy explained 64.4% of the variance in MA (P = 0.004).

Conclusion

These results confirmed the IMB model’s suitability for predicting MA in older adults with HF. These findings may guide and inform intervention programmes designed to alleviate depressive symptoms in older adults with HF and enhance their HF knowledge, social support, and self-efficacy, with the ultimate goal of improving their MA.
More than Putin: managed pluralism in Russia's foreign policy
Authors: Strycharz Damian
Published: February 2024

The Russian full-scale invasion of Ukraine took most experts by surprise, but before the war, there were numerous voices in the Russian public debate calling for much tougher policies towards Ukraine and the West than the ones pursued by the government. This article challenges explanations that prioritize external factors or focus solely on President Putin and shows that examining opposition, state media and government discourses is necessary to understand Russia's foreign policy properly. The article contends that the concept of managed pluralism (defined by Harley Balzer in 2003), which has not yet been used in the analysis of Moscow's international behaviour, is a useful tool that can address the gap in the literature and shed light on important mechanisms behind Russia's foreign policy-making. Consequently, the article reveals mechanisms that, by allowing certain voices while eliminating others, steer Russia's foreign policy in a specific direction, which in this case made the invasion of Ukraine possible. Finally, it indicates that observing actors admitted to the public debate and their propositions may be a clue to the direction of Russia's future foreign policy. More broadly, this article points to policy implications and theoretical benefits of managed pluralism for our understanding of other states' foreign policies.
Populism, Collective Narcissism, and Support for War
Authors: Zhai Yida
Published: February 2024

People’s pro-war attitudes provide an important lens for understanding the various conflicts and wars taking place around the globe. The present research bridges the social psychological insights on ingroup identity with the macro realism theory of international relations studies. It examines the association of populism and collective narcissism with support for war under the conditions of offensive and defensive realist foreign policies. The research comprises two studies. Study 1 shows that populism is linked with offensive realism, whereas collective narcissism is associated with defensive realism. Study 2 further demonstrates that the perceptions of threat mediate the relationship between collective narcissism and support for war, rather than mediating the relationship between populism and support for war. Both populism and collective narcissism are related to authoritarianism. This research contributes to a theoretical understanding of the effects of populism and collective narcissism on resorting to military actions in international politics.
The One Step Malliavin scheme: new discretization of BSDEs implemented with deep learning regressions
Authors: Negyesi Balint , Andersson Kristoffer , Oosterlee Cornelis W
Published: February 2024

A novel discretization is presented for decoupled forward–backward stochastic differential equations (FBSDE) with differentiable coefficients, simultaneously solving the BSDE and its Malliavin sensitivity problem. The control process is estimated by the corresponding linear BSDE driving the trajectories of the Malliavin derivatives of the solution pair, which implies the need to provide accurate $\varGamma $ estimates. The approximation is based on a merged formulation given by the Feynman–Kac formulae and the Malliavin chain rule. The continuous time dynamics is discretized with a theta-scheme. In order to allow for an efficient numerical solution of the arising semidiscrete conditional expectations in possibly high dimensions, it is fundamental that the chosen approach admits to differentiable estimates. Two fully-implementable schemes are considered: the BCOS method as a reference in the one-dimensional framework and neural network Monte Carlo regressions in case of high-dimensional problems, similarly to the recently emerging class of Deep BSDE methods (Han et al. (2018 Solving high-dimensional partial differential equations using deep learning. Proc. Natl. Acad. Sci., 115, 8505–8510); Huré et al. (2020 Deep backward schemes for high-dimensional nonlinear PDEs. Math. Comp., 89, 1547–1579)). An error analysis is carried out to show $\mathbb{L}^2$ convergence of order $1/2$, under standard Lipschitz assumptions and additive noise in the forward diffusion. Numerical experiments are provided for a range of different semilinear equations up to $50$ dimensions, demonstrating that the proposed scheme yields a significant improvement in the control estimations.
Operator Space Complexification Transfigured
Authors: Blecher David P , Kalantar Mehrdad
Published: February 2024

Given a finite group $G$, a central subgroup $H$ of $G$, and an operator space $X$ equipped with an action of $H$ by complete isometries, we construct an operator space $X_{G}$ equipped with an action of $G$ that is unique under a “reasonable” condition. This generalizes the operator space complexification $X_{c}$ of $X$. As a linear space $X_{G}$ is the space obtained from inducing the representation of $H$ to $G$ (in the sense of Frobenius). Indeed a main achievement of our paper is the induced representation construction in the category of operator spaces. This has been hitherto elusive even for Banach spaces since it is not clear how to norm the induced space. We show that for a large class of group actions the induced space has a unique operator space norm.
Distribution of quetiapine between serum and whole blood in therapeutic drug-monitoring specimens
Authors: Breivik Håvard , Tunset Mette Elise , Schou Morten Brix , Frost Joachim
Published: February 2024

Quetiapine use is on the rise, leading to a corresponding increase in acute intoxications, some of which have fatal outcomes. When assessing whole-blood quetiapine concentrations during forensic autopsies, interpretations are primarily based on toxicity data from studies of serum concentrations. To our knowledge, there are only two previous studies that have attempted to establish the ratio between whole blood and serum quetiapine concentrations with limited populations and high variability of results. Paired specimens of whole blood and serum from 16 quetiapine users recruited from the Psychiatric Clinic, St. Olav University Hospital were analyzed using LC–MS-MS. Quetiapine concentrations in both matrices were determined and compared. The mean blood:serum ratio of quetiapine was 0.74 (standard deviation (SD) = 0.05, 95% confidence interval (CI) 0.71–0.76, P < 0.001), range 0.66–0.85. Simple linear regression showed strong linear correlation between quetiapine concentrations in the two matrices (B = 0.774, P > 0.001, r = 0.999). Our results imply that quetiapine occurs at lower concentrations within erythrocytes than in plasma. This is most likely due to a high degree of plasma protein binding. Other factors which may influence the distribution of quetiapine between these compartments are solubility, metabolism and passive or active efflux mechanisms. We did not observe any covariation between blood:serum ratios and serum concentrations. Quetiapine was consistently present at lower concentrations in whole blood than in serum. If so inclined to, a conversion factor of ∼0.7 may be considered for extrapolation of concentrations from serum to whole blood, at least in cases with therapeutic quetiapine concentration levels.
Analysis of homemade cannabis edibles by UHPLC–HRMS after standard addition method
Authors: Thiebot Pauline , Magny Romain , Langrand Jérôme , Dufayet Laurène , Houze Pascal , Labat Laurence
Published: February 2024

With recent evolution of cannabis legalization around the world, cannabis edibles are booming, and determining their concentration in Δ9-tetrahydrocannabinol (Δ9-THC), the regulated psychoactive substance, remains a challenge for toxicology laboratories, which must prove whether the product has legal status or not. Cannabinoids are a large family of structurally similar and lipophilic molecules, requiring dedicated pre-analytical methods, as well as efficient chromatographic separation to differentiate cannabinoid isomers which are distinguished by their psychoactive properties and their legal status. Here, we present two independent cases of cannabis edibles, for which we performed analysis of homemade cannabis chocolate cakes and of the resins and herbs used for cooking. Quantitation was carried out with a new developed standard addition method, to avoid matrix effects and matrix-dependent calibration. Extraction by QuEChERs method, followed by targeted and non-targeted analysis by ultra-high performance liquid chromatography hyphenated to high resolution mass spectrometry (UHPLC–HRMS) allowed the identification of several phytocannabinoids, mainly Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and their acid precursors Δ9-THC acid (THCA) and CBD acid (CBDA). Δ9-THC was identified in significant concentrations (mg/g) in both edibles, even though one was prepared with CBD herb. This work highlights the need to analyze cannabis edibles, as well as the resins and herbs used in their preparation if it is homemade, and it proposes a reliable analytical method for toxicology laboratories.
Understanding the onion aphid Neotoxoptera formosana’s (Hemiptera: Aphididae) interaction with Allium (Asparagales: Amaryllidaceae) crops: a comprehensive study of feeding patterns and life history traits
Authors: Zhang Long , Zhang Haiyan , Zhang Keshi , Qin Yaoguo , Yang Maofa , Liu Jianfeng
Published: February 2024

The onion aphid, Neotoxoptera formosana, poses a significant threat to Allium crops worldwide, causing considerable economic losses and quality degradation. To develop effective pest management strategies, it is crucial to understand the feeding behavior and life history of this pest on different Allium crops. In this study, the electrical penetration graph (EPG) technique was used to monitor the thorn-feeding behavior of the onion aphid on 4 Allium crops: leek, chive, garlic, and shallot. The EPG data revealed distinct feeding patterns, with garlic and shallots being more preferred hosts than chives. Additionally, the aphids primarily fed on the phloem in garlic and shallots. Analysis of life history trait showed that chives provided the most favorable conditions for aphid development and reproduction, while leek exhibited relatively unfavorable conditions. Examination of leaf histology also revealed differences among the crops, which may influence aphid feeding behavior. This study provides valuable insights into the interaction between the onion aphid and different Allium crops, aiding in the development of comprehensive pest control strategies to minimize crop damage and economic losses. The use of advanced techniques like EPG contributes to a more detailed understanding of aphid behavior and shows promise for improving pest management in other plant-pest interactions.
The Aarhus Convention and the Latent Right to a Healthy Environment
Authors: Barritt Emily
Published: February 2024

The Aarhus Convention is an ambitious environmental agreement that recognises the right to a healthy environment in its opening article. However, the ambiguous language surrounding this right gives the impression that it is ornamentation and not something requiring serious legal attention. At the same time, the procedural environmental rights which are the centrepiece of the Convention are being eroded, either by design on the part of Contracting Parties or because of a broader malaise about the value of public participation in environmental decision-making. This contribution suggests that closer attention to the legal significance of the substantive right contained in the Convention can help to reinvigorate the procedural Aarhus rights. In so doing, it draws attention to the radical vision of the Aarhus Convention to protect the right of present and future generations to live in an environment adequate to human health and well-being.
Life-history traits of Aedes aegypti (Linnaeus) distributed across a latitudinal range of 23 °N–6 °S
Authors: Neoh Kok-Boon , Bong Lee-Jin , Silalahi Christina Natalina , Panthawong Amonrat , Chareonviriyaphap Theeraphap , Ahmad Intan
Published: February 2024

The growth and associated traits of Aedes aegypti (L.) mosquitoes may adapt and evolve in response to the costs associated with body size in relation to latitudinal variation. We analyzed the life-history traits and energy reserves of field-collected mosquitoes from Taiwan, Thailand, and Indonesia along a latitudinal range spanning from 23°N to 6°S. A U-shaped relationship between body size and latitude was observed. Our study demonstrated the role of latitudinal temperature variations in determining the body size patterns of Ae. aegypti. Notably, the body size of the northern populations (from Taiwan) was significantly larger than those of the tropical populations from Thailand and Indonesia. Models have demonstrated that regional precipitation levels may contribute to body trait variations in certain high-latitude populations in Thailand. However, Indonesian populations have high development rates and large body sizes, indicating the involvement of other physiological traits in determining mosquito body size. The reproductive output of the adult females in this study was positively correlated with body size, but our measure of longevity did not covary significantly with the body size. By contrast, the reproductive output of mosquito-tested populations was in inverse proportion to longevity. Additionally, the mean teneral glycogen levels in the Indonesian and Thai populations were 2.5 times higher than those in the Taiwanese populations. The Indonesian and Thai populations had low mean generation and doubling times, resulting in a high intrinsic rate of increase compared with that of the Taiwanese populations, despite the Taiwanese populations having the highest net reproduction rate.
A custom next-generation sequencing panel for 1p/19q codeletion and mutational analysis in gliomas
Authors: Qi Peng , Yao Qian-Lan , Lao I Weng , Ren Min , Bai Qian-Ming , Cai Xu , Xue Tian , Wei Ran , Zhou Xiao-Yan
Published: February 2024

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.
Skin nerve phosphorylated α-synuclein in the elderly
Authors: Donadio Vincenzo , Fadda Laura , Incensi Alex , Furia Alessandro , Parisini Sara , Colaci Francesco , Defazio Giovanni , Liguori Rocco
Published: February 2024

To determine the incidence of phosphorylated α-synuclein (p-syn) in skin nerves in very old subjects who are prone to developing incidental Lewy bodies, we prospectively performed skin biopsies on 33 elderly subjects, including 13 (>85 years old) and 20 patients (>70 years) suspected of having an acquired small fiber neuropathy. All subjects underwent neurological examination prior to the biopsy. Two screened female subjects (ages 102 and 98 years) were excluded from the study because they showed evidence of a slight bradykinetic-rigid extrapyramidal disorder on neurological examination and were not considered healthy; both showed p-syn in skin nerves. We did not identify p-syn in skin nerves in the remaining 31 subjects. A PubMed analysis of publications from 2013 to 2023 disclosed 490 healthy subjects tested for skin p-syn; one study reported p-syn in 4 healthy subjects, but the remaining subjects tested negative. Our data underscore the virtual absence of p-syn in skin nerves of healthy controls, including those who are very elderly. These data support skin biopsy as a highly specific tool for identifying an underlying synucleinopathy in patients in vivo.
Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity
Authors: Aithal Rakesh , Nangalia Kuldeep , Spirek Mario , Chen Doris , Klein Franz , Krejci Lumir
Published: February 2024

Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.
The jet-like chromatin structure defines active secondary metabolism in fungi
Authors: Shao Wenyong , Wang Jingrui , Zhang Yueqi , Zhang Chaofan , Chen Jie , Chen Yun , Fei Zhangjun , Ma Zhonghua , Sun Xuepeng , Jiao Chen
Published: February 2024

Eukaryotic genomes are spatially organized within the nucleus in a nonrandom manner. However, fungal genome arrangement and its function in development and adaptation remain largely unexplored. Here, we show that the high-order chromosome structure of Fusarium graminearum is sculpted by both H3K27me3 modification and ancient genome rearrangements. Active secondary metabolic gene clusters form a structure resembling chromatin jets. We demonstrate that these jet-like domains, which can propagate symmetrically for 54 kb, are prevalent in the genome and correlate with active gene transcription and histone acetylation. Deletion of GCN5, which encodes a core and functionally conserved histone acetyltransferase, blocks the formation of the domains. Insertion of an exogenous gene within the jet-like domain significantly augments its transcription. These findings uncover an interesting link between alterations in chromatin structure and the activation of fungal secondary metabolism, which could be a general mechanism for fungi to rapidly respond to environmental cues, and highlight the utility of leveraging three-dimensional genome organization in improving gene transcription in eukaryotes.
Balancing the benefits of vaccination: An envy-free strategy
Authors: Ribeiro de Almeida Pedro , Hirata Sanches Vitor , Goldman Carla
Published: February 2024

The Covid-19 pandemic revealed the difficulties of vaccinating a population under the circumstances marked by urgency and limited availability of doses while balancing benefits associated with distinct guidelines satisfying specific ethical criteria. We offer a vaccination strategy that may be useful in this regard. It relies on the mathematical concept of envy-freeness. We consider finding balance by allocating the resource among individuals that seem heterogeneous concerning the direct and indirect benefits of vaccination, depending on age. The proposed strategy adapts a constructive approach in the literature based on Sperner’s Lemma to point out an approximate division of doses guaranteeing that both benefits are optimized each time a batch becomes available. Applications using data about population age distributions from diverse countries suggest that, among other features, this strategy maintains the desired balance, throughout the entire vaccination period. We discuss complementary aspects of the method in the context of epidemiological models of age-stratified Susceptible - Infected - Recovered (SIR) type.
Polyethylenimine-modified graphene quantum dots promote endothelial cell proliferation
Authors: Xu Qirong , Li Chen , Meng Xiangyan , Duo Xinghong , Feng Yakai
Published: February 2024

Endothelial cell proliferation plays an important role in angiogenesis and treatment of related diseases. The aim of this study was to evaluate the effect of polyethylenimine (PEI)-modified graphene quantum dots (GQDs) gene vectors on endothelial cell proliferation. The GQDs-cationic polymer gene vectors were synthesized by amidation reaction, and used to deliver pZNF580 gene to Human umbilical vein endothelial cells (HUVECs) for promoting their proliferation. The chemical modification of GQDs can adjust gene vectors’ surface properties and charge distribution, thereby enhancing their interaction with gene molecules, which could effectively compress the pZNF580 gene. The CCK-8 assay showed that the cell viability was higher than 80% at higher vector concentration (40 μg/mL), demonstrating that the GQDs-cationic polymer gene vectors and their gene complex nanoparticles (NPs) having low cytotoxicity. The results of the live/dead cell double staining assay were consistent with those of the CCK-8 assay, in which the cell viability of the A-GQDs/pZNF580 (94.38 ± 6.39%), C-GQDs-PEI- polylactic acid-co-polyacetic acid (PLGA)/pZNF580 (98.65 ± 6.60%) and N-GQDs-PEI-PLGA/pZNF580 (90.08 ± 1.60%) groups was significantly higher than that of the Lipofectamine 2000/pZNF580 (71.98 ± 3.53%) positive treatment group. The results of transfection and western blot experiments showed that the vector significantly enhanced the delivery of plasmid to HUVECs and increased the expression of pZNF580 in HUVECs. In addition, the gene NPs better promote endothelial cell migration and proliferation. The cell migration rate and proliferation ability of C-GQDs-PEI-PLGA/pZNF580 and N-GQDs-PEI-PLGA/pZNF580 treatment groups were higher than those of Lipofectamine 2000/pDNA treatment group. Modified GQDs possess the potential to serve as efficient gene carriers. They tightly bind gene molecules through charge and other non-covalent interactions, significantly improving the efficiency of gene delivery and ensuring the smooth release of genes within the cell. This innovative strategy provides a powerful means to promote endothelial cell proliferation.
Comparing clinical features between males and females with VEXAS syndrome: data from literature analysis of patient reports
Authors: Echerbault Robin , Bourguiba Rim , Georgin-Lavialle Sophie , Lavigne Christian , Ravaiau Camille , Lacombe Valentin
Published: February 2024

Objectives

VEXAS syndrome is an autoinflammatory disease associated with a somatic mutation of the X-linked UBA1 gene in haematopoietic progenitor cells. This disorder was originally described as a disease affecting men, but rare cases of VEXAS syndrome in women have since been reported. The theoretical existence of phenotypic sex differences in this X-linked disease is debated. We compared the features of VEXAS syndrome between males and females to better understand this disorder and to improve its diagnostic accuracy in females.

Methods

From previously published clinical descriptions of VEXAS syndrome, we included studies that described patients with precise, individual VEXAS-related features. We formed a literature-based cohort of patients by collecting their clinical and biological data and compared the characteristics of male and female patients.

Results

We gathered 224 patient descriptions from 104 articles: 9 women and 215 men. Among the women, 1 had a constitutional 45,X karyotype and 4 had an acquired X monosomy in the bone marrow karyotype, while the marrow karyotype was not provided for the others. No difference was observed in the clinical or biological features according to sex. We also observed no difference in the type of UBA1 mutation or the association with myelodysplastic syndrome.

Conclusions

Our results supported the hypothesis that the UBA1 mutation should be sought under the same conditions in both sexes. As UBA1 is not subject to X-chromosome inactivation, VEXAS syndrome in females requires both UBA1 mutation and X monosomy, thus explaining the similarity between male and female VEXAS-related features and the lower prevalence of VEXAS syndrome in females.
Clarifying Cognitive Control Deficits in Psychosis via Drift Diffusion Modeling and Attractor Dynamics
Authors: Shen Chen , Calvin Olivia L , Rawls Eric , Redish A David , Sponheim Scott R
Published: February 2024

Background and Hypothesis

Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals—potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis.

Study Design

People with psychosis (PwP; N = 122), their first-degree biological relatives (N = 78), and controls (N = 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control.

Study Results

PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits.

Conclusions

Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity.
Ethical Principles Do Not Support Mandatory Preanesthesia Pregnancy Screening Tests: A Narrative Review
Authors: Jackson S. , Hunter J. , Van Norman G.A.
Published: February 2024

(Anesth Analg. October 6, 2023. doi: 10.1213/ANE.0000000000006669. Online ahead of print)

The process of informed consent upholds the principle of patient autonomy, rooted in US constitutional principles of privacy and noninterference. It has been legally required in the United States since 1914, ensuring that individuals have the right to determine what happens to their bodies, as Schloendorff v. New York Society Hospital ruled. The recent US Supreme Court decision on abortion has raised concerns about maternal-fetal conflicts and the rights of pregnant patients to undergo elective anesthesia and surgery. Ethical and legal requirements for informed consent in medical testing vary, with challenges in addressing routine laboratory testing. Not all medical tests carry the same ethical implications, but they should all consider beneficence, nonmaleficence, and patient autonomy. Focusing on the need for preanesthesia pregnancy testing remains a concern in anesthesia and surgery practices. The primary premise is preventing harm to the fetus, but this must be supported by medical evidence and adhere to ethical standards. No study conclusively demonstrates that anesthetic agents significantly increase rates of early human fetal loss or malformations. There is no evidence that anesthetic drugs are generally teratogenic or pose a significant risk of harm to the fetus. While such risks are small, they cannot be guaranteed to be absent.
The Limits of Viability
Authors: Pettker C.M. , Turrentine M.A. , Simhan H.N.
Published: February 2024

(Obstet Gynecol. 2023;142(3):725–726)

The conversation surrounding the “viability” of a pregnancy or fetus is fraught with disagreement in political, legal, religious, philosophical, and scientific settings. Ambiguity in the use of the term has contributed significantly to confusion and misinformation, especially when it is appropriated in a nonmedical context. This article presents a perspective on the term viability, its definition and usage, and how confusion and misinformation surrounding it should be addressed. The focus of this perspective is the use of terminology, not personal opinions, at the beginning of life.
Defining the Neurologic Consequences of Preterm Birth
Authors: Inder T. , Volpe J. , Anderson P.
Published: February 2024

(N Engl J Med. 2023; 389:441–53)

Approximately 15 million babies are born prematurely (before 37 wk gestation) each year, making prematurity the leading cause of neonatal deaths. Despite advancements in perinatal health care, preterm survivors still face a high risk of long-term issues, especially neurological and developmental disabilities. While severe cerebral palsy rates have decreased in the past 2 decades, cognitive impairment and social-emotional challenges among preterm children and young adults remain prevalent. Very preterm children (born <32 wk) typically exhibit lower intelligence quotient scores, with more significant deficits in those born before 26 weeks. The variability in outcomes reflects the extent of brain injury and dysmaturation, with earlier births carrying a risk that is more significant. New insights from advanced neuroimaging and developmental neuroscience emphasize that both brain injury and impaired brain development contribute to adverse neurodevelopmental outcomes. This review explores the major forms of brain injury, subsequent dysmaturation, mediating factors, and their impact on preterm infant neurodevelopment and aims to guide neonatal clinicians in implementing future neuroprotective strategies for better long-term outcomes.
Staged Treatment of the Placenta Accreta Spectrum: A Combined Surgical and Radiologic Approach
Authors: West S. , Martin A. , Copping R. , Gard G. , Maher R. , Seeho S.
Published: February 2024

(Aust N Z J Obstet Gynaecol. 2023; 63: 372–377)

The placenta accreta spectrum (PAS) is defined by aberrant placental invasion into the uterine myometrium. Globally, the prevalence of PAS is rising, which affects maternal health outcomes. The depth of invasion into the uterus determines how it is classified, with placenta accreta (villi connecting to the muscle layer), placenta increta (myometrial invasion), and placenta percreta (transmural invasion beyond the serosa) being the most severe. This study evaluated maternal and neonatal outcomes following a combined surgical and interventional radiology (IR) approach for managing the PAS.