bluuebunny/crossref_metadata_2025 huggingface dataset:
A systems framework for investigating the roles of multiple transporters and their impact on drug resistance
Authors: di San Germano Manfredi , Krishnan J
Published: March 2024

Efflux transporters are a fundamental component of both prokaryotic and eukaryotic cells, play a crucial role in maintaining cellular homeostasis, and represent a key bridge between single cell and population levels. From a biomedical perspective, they play a crucial role in drug resistance (and especially multi-drug resistance, MDR) in a range of systems spanning bacteria and human cancer cells. Typically, multiple efflux transporters are present in these cells, and the efflux transporters transport a range of substrates (with partially overlapping substrates between transporters). Furthermore, in the context of drug resistance, the levels of transporters may be elevated either due to extra or intracellular factors (feedforward regulation) or due to the drug itself (feedback regulation). As a consequence, there is a real need for a transparent systems-level understanding of the collective functioning of a set of transporters and their response to one or more drugs. We develop a systems framework for this purpose and examine the functioning of sets of transporters, their interplay with one or more drugs and their regulation (both feedforward and feedback). Using computational and analytical work, we obtain transparent insights into the systems level functioning of a set of transporters arising from the interplay between the multiplicity of drugs and transporters, different drug–transporter interaction parameters, sequestration and feedback and feedforward regulation. These insights transparently arising from the most basic consideration of a multiplicity of transporters have broad relevance in natural biology, biomedical engineering and synthetic biology.

Insight, Innovation, Integration: Innovation: creating a structured systems framework for evaluating the impact of multiple transporters on drug efflux and drug resistance. Systematic analysis allows us to evaluate the effect of multiple transporters on one/more drugs, and dissect associated resistance mechanisms. Integration allows for elucidation of key cause-and-effect relationships and a transparent systems-level understanding of the collective functioning of transporters and their impact on resistance, revealing the interplay of key underlying factors. Systems-level insights include the essentially different behaviour of transporters as part of a group; unintuitive effects of influx; effects of elevated transporter-levels by feedforward and drug-induced mechanisms. Relevance: a systems understanding of efflux, their role in MDR, providing a framework/platform for use in designing treatment, and in synthetic biology design.
Quantifying microbial guilds
Authors: Rivas-Santisteban Juan , Yubero Pablo , Robaina-Estévez Semidán , González José M , Tamames Javier , Pedrós-Alió Carlos
Published: March 2024

The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we identify and distinguish functional implementations, which are sequence spaces that have different ways of carrying out the function. In contrast, we found that orthology delineation did not consistently align with ecologically (or functionally) distinct implementations of the function. We demonstrate the value of our approach with two case studies: the ammonia oxidation and polyamine uptake guilds from the Malaspina circumnavigation cruise, revealing novel ecological dynamics of the latter in marine ecosystems. Thus, the quantification of guilds helps us to assess the functional role of different taxonomic groups with profound implications on the study of microbial communities.
Predicting bacterial interaction outcomes from monoculture growth and supernatant assays
Authors: Schmitz Désirée A , Wechsler Tobias , Mignot Ingrid , Kümmerli Rolf
Published: March 2024

How to derive principles of community dynamics and stability is a central question in microbial ecology. Bottom-up experiments, in which a small number of bacterial species are mixed, have become popular to address it. However, experimental setups are typically limited because co-culture experiments are labor-intensive and species are difficult to distinguish. Here, we use a four-species bacterial community to show that information from monoculture growth and inhibitory effects induced by secreted compounds can be combined to predict the competitive rank order in the community. Specifically, integrative monoculture growth parameters allow building a preliminary competitive rank order, which is then adjusted using inhibitory effects from supernatant assays. While our procedure worked for two different media, we observed differences in species rank orders between media. We then parameterized computer simulations with our empirical data to show that higher order species interactions largely follow the dynamics predicted from pairwise interactions with one important exception. The impact of inhibitory compounds was reduced in higher order communities because their negative effects were spread across multiple target species. Altogether, we formulated three simple rules of how monoculture growth and supernatant assay data can be combined to establish a competitive species rank order in an experimental four-species community.
Implications for nitrogen and sulphur cycles: phylogeny and niche-range of Nitrospirota in terrestrial aquifers
Authors: Mosley Olivia E , Gios Emilie , Handley Kim M
Published: March 2024

Increasing evidence suggests Nitrospirota are important contributors to aquatic and subsurface nitrogen and sulphur cycles. We determined the phylogenetic and ecological niche associations of Nitrospirota colonizing terrestrial aquifers. Nitrospirota compositions were determined across 59 groundwater wells. Distributions were strongly influenced by oxygen availability in groundwater, marked by a trade-off between aerobic (Nitrospira, Leptospirillum) and anaerobic (Thermodesulfovibrionia, unclassified) lineages. Seven Nitrospirota metagenome-assembled genomes (MAGs), or populations, were recovered from a subset of wells, including three from the recently designated class 9FT-COMBO-42-15. Most were relatively more abundant and transcriptionally active in dysoxic groundwater. These MAGs were analysed with 743 other Nitrospirota genomes. Results illustrate the predominance of certain lineages in aquifers (e.g. non-nitrifying Nitrospiria, classes 9FT-COMBO-42-15 and UBA9217, and Thermodesulfovibrionales family UBA1546). These lineages are characterized by mechanisms for nitrate reduction and sulphur cycling, and, excluding Nitrospiria, the Wood–Ljungdahl pathway, consistent with carbon-limited, low-oxygen, and sulphur-rich aquifer conditions. Class 9FT-COMBO-42-15 is a sister clade of Nitrospiria and comprises two families spanning a transition in carbon fixation approaches: f_HDB-SIOIB13 encodes rTCA (like Nitrospiria) and f_9FT-COMBO-42-15 encodes Wood–Ljungdahl CO dehydrogenase (like Thermodesulfovibrionia and UBA9217). The 9FT-COMBO-42-15 family is further differentiated by its capacity for sulphur oxidation (via DsrABEFH and SoxXAYZB) and dissimilatory nitrate reduction to ammonium, and gene transcription indicated active coupling of nitrogen and sulphur cycles by f_9FT-COMBO-42-15 in dysoxic groundwater. Overall, results indicate that Nitrospirota are widely distributed in groundwater and that oxygen availability drives the spatial differentiation of lineages with ecologically distinct roles related to nitrogen and sulphur metabolism.
The impact of European Cohesion Policy: a spatial perspective
Authors: Amendolagine Vito , Prota Francesco , Serlenga Laura
Published: March 2024

Cohesion Policy is one of the core policy areas of the European Union and one of the largest expenditure items in its budget. Its impact is the subject of intense academic and policy debate, but its effectiveness is an empirical question still open. This article contributes to this debate by performing a region-specific investigation of the direct and indirect impact of Structural Funds expenditure. We employ a heterogeneous panel data model, which accommodates the spatial dependence in a heterogeneous setting and measures heterogeneous spatial spillover effects, both inward and outward. We also consider different channels of spatial spillovers with respect to standard geographical closeness. In particular, the introduction of new measures of proximity that explicitly consider economic linkages between regions is a novel contribution to the literature. The results clearly indicate that the impact of the Cohesion Policy, while positive overall, is highly heterogeneous and the Structural Funds expenditure generates substantial heterogeneous spatial spillovers: the positive effects do not remain confined to the target regions. Finally, strong spillover effects are channelled by value-added trade connections, particularly in regions belonging to the so-called ‘Central European Manufacturing Core’.
From Bauddha Deśa to Śākta Pīṭha: Re/Locating the Hindu Goddess Tārā
Authors: Bordeaux Joel
Published: March 2024

The incorporation of the goddess Tārā into the Hindu pantheon appears to have begun around the turn of the first millennium, a couple of centuries after her first mentions in Buddhist sources. The earliest Hindu texts concerned with Tārā tend to acknowledge this through a narrative wherein the Vedic sage Vasiṣṭha must travel to ‘Greater China’ to learn from the Buddha how to propitiate the goddess properly through the violation of brāhmaṇical purity codes for which Indian tantric traditions are infamous. Over time her ‘foreign’ associations faded, narratives linking Tārā to sites in Assam and Bengal became more prominent, and her worship drew closer to regional Hindu orthopraxy. This essay tracks the latter stages of that process especially through a reading of early modern ritual manuals in Sanskrit before considering a more recent revival of interest in the Hindu Tārā’s Buddhist connections as shown in Bengali sources and fieldwork.
Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups
Authors: Nakamura Kenichi , Takeda Koji , Saito Akiko M , Kato Miho , Sato Shinya , Nakagawa Satoshi , Kawamoto Yasuyuki , Oki Eiji , Okamoto Isamu , Okamoto Hiroaki , Katayama Hiroshi , Mizusawa Junki , Kaba Harumi , Shibata Taro , Fukuda Haruhiko
Published: March 2024

Objective

large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown.

Methods

a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023.

Results

the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects.

Conclusion

the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act’s enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.
Sex and landscape influence spatial genetic variation in a large fossorial mammal, the Bare-nosed Wombat (Vombatus ursinus)
Authors: Tan Woei Jiun , Carver Scott , Martin Alynn M , Fountain-Jones Nicholas M , Proft Kirstin M , Burridge Christopher P
Published: March 2024

Dispersal is an important process that is widely studied across species, and it can be influenced by intrinsic and extrinsic factors. Intrinsic factors commonly assessed include the sex and age of individuals, while landscape features are frequently-tested extrinsic factors. Here, we investigated the effects of both sex and landscape composition and configuration on genetic distances among bare-nosed wombats (Vombatus ursinus)—one of the largest fossorial mammals in the world and subject to habitat fragmentation, threats from disease, and human persecution including culling as an agricultural pest. We analyzed a data set comprising 74 Tasmanian individuals (30 males and 44 females), genotyped for 9,064 single-nucleotide polymorphisms. We tested for sex-biased dispersal and the influence of landscape features on genetic distances including land use, water, vegetation, elevation, and topographic ruggedness. We detected significant female-biased dispersal, which may be related to females donating burrows to their offspring due to the energetic cost of excavation, given their large body sizes. Land use, waterbodies, and elevation appeared to be significant landscape predictors of genetic distance. Land use potentially reflects land clearing and persecution over the last 200 years. If our findings based on a limited sample size are valid, retention and restoration of nonanthropogenic landscapes in which wombats can move and burrow may be important for gene flow and maintenance of genetic diversity.
Financial-legal navigation reduces financial toxicity of pediatric, adolescent, and young adult cancers
Authors: Edward Jean , Northrip Kimberly D , Rayens Mary Kay , Welker Andrea , O’Farrell Rachel , Knuf Jennifer , Fariduddin Haafsah , Costich Julia , D’Orazio John
Published: March 2024

Background

Pediatric, adolescent, and young adult patients with cancer and their caregivers are at high risk of financial toxicity, and few evidence-based oncology financial and legal navigation programs exist to address it. We tested the feasibility, acceptability, and preliminary effectiveness of Financial and Insurance Navigation Assistance, a novel interdisciplinary financial and legal navigation intervention for pediatric, adolescent and young adult patients and their caregivers.

Methods

We used a single-arm feasibility and acceptability trial design in a pediatric hematology and oncology clinic and collected preintervention and postintervention surveys to assess changes in financial toxicity (3 domains: psychological response/Comprehensive Score for Financial Toxicity [COST], material conditions, and coping behaviors); health-related quality of life (Patient-Reported Outcomes Measurement Information System Physical and Mental Health, Anxiety, Depression, and Parent Proxy scales); and perceived feasibility, acceptability, and appropriateness.

Results

In total, 45 participants received financial navigation, 6 received legal navigation, and 10 received both. Among 15 adult patients, significant improvements in FACIT-COST (P = .041) and physical health (P = .036) were noted. Among 46 caregivers, significant improvements were noted for FACIT-COST (P < .001), the total financial toxicity score (P = .001), and the parent proxy global health score (P = .0037). We were able to secure roughly $335 323 in financial benefits for 48 participants. The intervention was rated highly for feasibility, acceptability, and appropriateness.

Conclusions

Integrating financial and legal navigation through Financial and Insurance Navigation Assistance was feasible and acceptable and underscores the benefit of a multidisciplinary approach to addressing financial toxicity.

ClinicalTrials.gov registration

NCT05876325
Laparoscopic deroofing for a giant hepatic cyst with biliary communication: a case report
Authors: Ikeda Taro , Okazaki Taro , Manabe Yu , Nakanishi Rintaro , Kagiyama Hiroki , Owada Yoshiyuki , Hosono Masayoshi , Sendo Hiroyoshi
Published: March 2024

Previous reports describing laparoscopic deroofing as a management modality for a hepatic cyst with biliary communication remain limited. We present the case of a 76-year-old woman who was monitored for 4 years for a giant hepatic cyst in the right lobe of the liver. She presented to our department with a chief complaint of abdominal distension. Moreover, imaging revealed a 24-cm giant hepatic cyst. During laparoscopic deroofing, minimal bile leakage from the intra-cyst wall was observed, which was laparoscopically closed with sutures. No bile leakage or cyst recurrence was observed 18 months postoperative. This highlights that laparoscopic surgery may be used in managing hepatic cysts with biliary communication. Intraoperative findings may reveal biliary communication, which requires careful observation of the cyst wall after deroofing.
(O-03) DORSAL VENOUS LEAK LIGATION IN PATIENTS WITH ERECTILE DYSFUNCTION. REPORT OF 60 PATIENTS WITH 12-MONTH FOLLOW-UP
Authors: Uribe J F
Published: March 2024

Objective

Penile dorsal venocclusive dysfunction is recognized as a cause of erectile dysfunction in some young patients with no other risk factors. The objective of this study is to report the results of a surgical technique in patients who presented ED before the age of 40, with follow-up up to 12 months after treatment.

Materials and Methods

A descriptive study was carried out in a retrospective cohort of medical records with 60 patients who met the inclusion criteria, evaluated, and underwent standardized ligature surgery by the same surgeon between 01/2014 and 04/2022. The group underwent a symptom score (International Index of Erectile Function-5), before surgery, 3, 6 and 12 months after. The results of the IIFE-5 before and after surgery were related to the different degrees of erectile dysfunction (severe, moderate, and mild); additionally they were divided into three groups according to criteria defined by the IIFE-5 as successful, moderate, and poor. The diagnosis of venous leaks was made by penile Doppler ultrasound, recording venous leaks and degree of penile fibrosis. The study protocol was approved by the Research Committee of the Pablo Tobon Uribe Hospital in Medellín.

Results

The age of onset of erectile dysfunction was between 14-39 years, mean 23.9; the mean age of the patients who consulted was 31.5 years. The time of evolution of the disease before attempting surgery varied between 2 months and 21 years (average 9.5 years). The result of the preoperative IIFE-5 was: Severe ED: n=6 (10%) and moderate ED: n=54 (90%), there were no preoperative mild ones. Postoperative outcomes at 12 months were: moderate ED n=13 (21.6%); mild ED n=25 (41.6%) and without ED n=22 (36.6%), after the intervention. Additionally, according to the internal analysis of IIFE-5: n=39 (65%) was successful; n=9 (15%) moderate and n=12 (20%) poor.

Conclusions

Ligation of penile dorsal venous leaks has good medium and long-term results in terms of erection quality and patient satisfaction.

Financing

No conflicto.
(PM-23) YOGA PRACTICE INTERVENTION AS A COMPLEMENTARY AND INTEGRATIVE TREATMENT FOR COMPULSIVE SEXUAL BEHAVIOR DISORDER: A PILOT STUDY
Authors: Costa E M , Takeda O H , Fernandes R Y , Branco W B C , Cruz MVPd , Guirado A G , Vidal RNdF , Ferreira BdO , Scanavino MdT
Published: March 2024

Objective

Investigate the feasibility of a Yoga Practice intervention (YPI) as an integrative treatment for adult men with compulsive sexual behavior disorder (CSBD) explored through the attendance and adherence treatment protocol, and the functionality of data collection mechanisms.

Methods

For this study, twelve men diagnosed with CSBD and that did not present substance-use, paraphilic, psychotic, current manic or hypomanic, neurocognitive disorders, gender dysphoria, physical limitations, already practiced yoga or started psychotherapy more than six months ago were randomized in a 2-arm, double-blind clinical trial, comparing a Kundalini YPI with a supervised muscle stretching 12-week program. Participants submitted their applications online on baseline, times 1 (4 weeks), 2 (8 weeks) and time 3 (12 weeks) and the proportion of treatment and protocol adherence, teacher adherence, and allocation concealment were estimated.

Results

The age range was 24 to 47 years old. 58% were single or widower, 41% married or common-law; 75% were caucasians and 25% afro-descendants. The minimum schooling was elementary, (50% finished college). Average family income was $ 1130. There was no statistically significant association between sociodemographic and intervention groups. The patient attendance was 58%, patient adherence to the protocol 30%, professors' adherence to the protocol reached 100%, and the allocation concealment for the double-blind method ensured 100%. The answers of the self-responsive online questionnaires on psychopathologic variables reached 87% of the requested answers, and the daily practices at home 45%.

Conclusions

Although the YPI evaluated for CSBD was acceptable and functional, this pilot indicates changes in procedures to improve attendance and adherence of patients.

Financing

No conflict.
More than a photoreceptor: aureochromes are intrinsic to the diatom light-regulated transcriptional network
Authors: Coesel Sacha N
Published: March 2024

This article comments on:

Im SH, Lepetit B, Mosesso N, Shrestha S, Weiss L, Nymark M, Roellig R, Wilhelm C, Isono E, Kroth PG. 2024. Identification of promoter targets by Aureochrome 1a in the diatom Phaeodactylum tricornutum. Journal of Experimental Botany 75, 1834–1851.
NEATmap: a high-efficiency deep learning approach for whole mouse brain neuronal activity trace mapping
Authors: Zheng Weijie , Mu Huawei , Chen Zhiyi , Liu Jiajun , Xia Debin , Cheng Yuxiao , Jing Qi , Lau Pak-Ming , Tang Jin , Bi Guo-Qiang , Wu Feng , Wang Hao
Published: March 2024

Quantitative analysis of activated neurons in mouse brains by a specific stimulation is usually a primary step to locate the responsive neurons throughout the brain. However, it is challenging to comprehensively and consistently analyze the neuronal activity trace in whole brains of a large cohort of mice from many terabytes of volumetric imaging data. Here, we introduce NEATmap, a deep learning–based high-efficiency, high-precision and user-friendly software for whole-brain neuronal activity trace mapping by automated segmentation and quantitative analysis of immunofluorescence labeled c-Fos+ neurons. We applied NEATmap to study the brain-wide differentiated neuronal activation in response to physical and psychological stressors in cohorts of mice.
A panel discussion on AI for science: the opportunities, challenges and reflections
Authors: Zhao Weijie
Published: March 2024

Artificial intelligence (AI) tools are changing the way we do science. AlphaFold basically solved the conundrum of protein structure prediction; DeepMD greatly improved the efficiency and accuracy of molecular simulations; and the emerging large language models such as ChatGPT are opening up more possibilities for scientific applications. In this panel, five experts from China and the US discussed the concept, development, bottlenecks and opportunities of AI for Science (AI4S), as well as their understanding of the relationship between AI and science.

Roberto Car

Professor at Department of Chemistry, Princeton University, USA

Weinan E

Professor at School of Mathematical Sciences, Peking University, China; AI for Science Institute, Beijing, China

David Srolovitz

Professor at Department of Mechanical Engineering, University of Hong Kong, China

Han Wang

Professor at the Institute of Applied Physics and Computational Mathematics, Chinese Academy of Sciences, China

Linfeng Zhang (Chair)

Chief scientific officer of DP Technology, China; AI for Science Institute, Beijing, China
Structural constraints of pyocin S2 import through the ferripyoverdine receptor FpvAI
Authors: Goult Jonathan D , Van Daniel C L , Taylor Yasmin V , Inns Patrick G , Kaminska Renata , Vesely Martin , Kleanthous Colin , Paci Emanuele
Published: March 2024

TonB-dependent transporters (TBDTs) mediate energized transport of essential nutrients into gram-negative bacteria. TBDTs are increasingly being exploited for the delivery of antibiotics to drug-resistant bacteria. While much is known about ground state complexes of TBDTs, few details have emerged about the transport process itself. In this study, we exploit bacteriocin parasitization of a TBDT to probe the mechanics of transport. Previous work has shown that the N-terminal domain of Pseudomonas aeruginosa–specific bacteriocin pyocin S2 (PyoS2NTD) is imported through the pyoverdine receptor FpvAI. PyoS2NTD transport follows the opening of a proton-motive force-dependent pore through FpvAI and the delivery of its own TonB box that engages TonB. We use molecular models and simulations to formulate a complete translocation pathway for PyoS2NTD that we validate using protein engineering and cytotoxicity measurements. We show that following partial removal of the FpvAI plug domain which occludes the channel, the pyocin's N-terminus enters the channel by electrostatic steering and ratchets to the periplasm. Application of force, mimicking that exerted by TonB, leads to unraveling of PyoS2NTD as it squeezes through the channel. Remarkably, while some parts of PyoS2NTD must unfold, complete unfolding is not required for transport, a result we confirmed by disulfide bond engineering. Moreover, the section of the FpvAI plug that remains embedded in the channel appears to serve as a buttress against which PyoS2NTD is pushed to destabilize the domain. Our study reveals the limits of structural deformation that accompanies import through a TBDT and the role the TBDT itself plays in accommodating transport.
Nonlinear social evolution and the emergence of collective action
Authors: Allen Benjamin , Khwaja Abdur-Rahman , Donahue James L , Kelly Theodore J , Hyacinthe Sasha R , Proulx Jacob , Lattanzio Cassidy , Dementieva Yulia A , Sample Christine
Published: March 2024

Organisms from microbes to humans engage in a variety of social behaviors, which affect fitness in complex, often nonlinear ways. The question of how these behaviors evolve has consequences ranging from antibiotic resistance to human origins. However, evolution with nonlinear social interactions is challenging to model mathematically, especially in combination with spatial, group, and/or kin assortment. We derive a mathematical condition for natural selection with synergistic interactions among any number of individuals. This result applies to populations with arbitrary (but fixed) spatial or network structure, group subdivision, and/or mating patterns. In this condition, nonlinear fitness effects are ascribed to collectives, and weighted by a new measure of collective relatedness. For weak selection, this condition can be systematically evaluated by computing branch lengths of ancestral trees. We apply this condition to pairwise games between diploid relatives, and to dilemmas of collective help or harm among siblings and on spatial networks. Our work provides a rigorous basis for extending the notion of “actor”, in the study of social evolution, from individuals to collectives.
Charged Spherical Solution in Torsion and Matter Coupling Gravity and Influence of Torsion Parameter and Electric Charge on Compact Stars in Lower Mass Gap
Authors: Maurya S K , Errehymy Abdelghani , Mustafa G , Donmez Orhan , Nisar Kottakkaran Sooppy , Abdel-Aty Abdel-Haleem
Published: March 2024

In this study, we explore a new exact solution for a charged spherical model as well as the astrophysical implications of the torsion parameter χ1 and electric charge Q on compact stars in lower mass gaps in the $f(\mathcal {T})$ gravity framework. Commencing with the field equations that describe anisotropic matter distributions, we select a well-behaved ansatz for the radial component of the metric function, along with an appropriate formulation for the electric field. The resulting model undergoes rigorous testing to ensure its qualification as a physically viable compact object within the $f(\mathcal {T})$ gravity background. We extensively investigate two factors: χ1 and Q, carefully analyzing their impacts on the mass, radius, and stability of the star. Our analyses demonstrate that our models exhibit well-behaved behavior, free from singularities, and can successfully explain the existence of a wide range of observed compact objects. These objects have masses ranging from $0.85^{+0.15}_{-0.15}$ to 2.67 M⊙, with the upper value falling within the mass gap regime observed in gravitational events like GW190814. A notable finding of this study has two aspects: we observe significant effects on the maximum mass (Mmax) and the corresponding radii of these objects. Increasing values of χ1 lead to higher Mmax (approximately $2.64^{+0.13}_{-0.14}$) and smaller radii (approximately $10.40^{+0.16}_{-0.60}$), suggesting the possibility of the existence of massive neutron stars within the system. Conversely, increasing values of Q result in a decrease in Mmax (approximately $1.70^{+0.05}_{-0.03}$) and larger radii (approximately $13.71^{+0.19}_{-0.20}$). Furthermore, an intriguing observation arises from comparing the results: for all values of χ1, nonrotating stars possess higher masses compared to slow-rotating stars, whereas this trend is reversed when adjusting Q.
Boundaries and Disgust in The Duchess of Malfi
Authors: Irish Bradley J
Published: March 2024

Developing recent research on emotion in early modern literature, this essay argues that disgust is the primary emotional mode of Webster’s classic tragedy The Duchess of Malfi. According to modern affective science, disgust is the emotion designed to protect the physical body from material contaminants and protect the social body from symbolic contaminants; as such, it is intimately concerned with the preservation of boundaries. I argue that Malfi stages the thematic collapse of key existential boundaries of the human experiences—boundaries of social class, boundaries of kinship, boundaries between species, and boundaries between life and death—and the result is a compensatory atmosphere of disgust that pervades the play.
Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study
Authors: Denissoff Alexander , Taipale Heidi , Tiihonen Jari , Di Forti Marta , Mittendorfer-Rutz Ellenor , Tanskanen Antti , Mustonen Antti , Niemelä Solja
Published: March 2024

Background and Hypothesis

There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD.

Study Design

We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations.

Study Results

Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60–0.75). Clozapine (0.43; 0.29–0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22–0.71), aripiprazole (0.42; 0.27–0.65), and paliperidone (0.46; 0.30–0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35–1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05–0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45–0.83).

Conclusions

These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD.
Systematic Review of the Link Between Social Cognition and Suicidal Ideation and Behavior in People With Serious Mental Illness
Authors: Parrish Emma M , Steenkamp Lisa , Chalker Samantha A , Moore Raeanne C , Pinkham Amy , Depp Colin A
Published: March 2024

Background and Hypothesis

People with serious mental illness (SMI; psychotic and affective disorders with psychosis) are at an increased risk of suicide, yet there is limited research on the correlates of suicide in SMI. Social cognitive impairments are common among people with SMI and several studies have examined social cognition and suicidal ideation (SI) and behavior. This systematic review aims to evaluate the links between various domains of social cognition, SI, and suicidal behavior in SMI.

Study Design

Electronic databases (PubMed and PsycInfo) were searched through June 2023. Records obtained through this search (N = 618) were screened by 2 independent reviewers according to inclusion criteria. Relevant data were extracted, and study quality was assessed.

Study Results

Studies (N = 16) from 12 independent samples were included in the systematic review (N = 2631, sample sizes ranged from N = 20 to N = 593). Assessments of social cognition and SI and behavior varied widely between studies. Broadly, effects were mixed. Better emotion recognition of negative affect was linked to SI and a history of suicide attempts, though there is little consistent evidence for the relationship of emotion recognition and SI or behavior. On the other hand, better theory of mind ability was linked to SI and a history of suicide attempts. Furthermore, negative attributional bias was linked to current SI, but not a history of SI or attempt.

Conclusions

This review suggests mixed associations between social cognition, SI, and behavior in SMI. Future research should evaluate additional mediators and moderators of social cognition and suicide, employing prospective designs.
Circadian photoentrainment varies by season and depressed state: associations between light sensitivity and sleep and circadian timing
Authors: Wescott Delainey L , Hasler Brant P , Franzen Peter L , Taylor Maddison L , Klevens Alison M , Gamlin Paul , Siegle Greg J , Roecklein Kathryn A
Published: March 2024

Study Objectives

Altered light sensitivity may be an underlying vulnerability for disrupted circadian photoentrainment. The photic information necessary for circadian photoentrainment is sent to the circadian clock from melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The current study tested whether the responsivity of ipRGCs measured using the post-illumination pupil response (PIPR) was associated with circadian phase, sleep timing, and circadian alignment, and if these relationships varied by season or depression severity.

Methods

Adult participants (N = 323, agem = 40.5, agesd = 13.5) with varying depression severity were recruited during the summer (n = 154) and winter (n = 169) months. Light sensitivity was measured using the PIPR. Circadian phase was assessed using Dim Light Melatonin Onset (DLMO) on Friday evenings. Midsleep was measured using actigraphy. Circadian alignment was calculated as the DLMO-midsleep phase angle. Multilevel regression models covaried for age, gender, and time since wake of PIPR assessment.

Results

Greater light sensitivity was associated with later circadian phase in summer but not in winter (β = 0.23; p = 0.03). Greater light sensitivity was associated with shorter DLMO-midsleep phase angles (β = 0.20; p = 0.03) in minimal depression but not in moderate depression (SIGHSAD < 6.6; Johnson-Neyman region of significance).

Conclusions

Light sensitivity measured by the PIPR was associated with circadian phase during the summer but not in winter, suggesting ipRGC functioning in humans may affect circadian entrainment when external zeitgebers are robust. Light sensitivity was associated with circadian alignment only in participants with minimal depression, suggesting circadian photoentrainment, a possible driver of mood, may be decreased in depression year-round, similar to decreased photoentrainment in winter.
Automated detection and classification of polioviruses from nanopore sequencing reads using piranha
Authors: O’Toole Áine , Colquhoun Rachel , Ansley Corey , Troman Catherine , Maloney Daniel , Vance Zoe , Akello Joyce , Bujaki Erika , Majumdar Manasi , Khurshid Adnan , Arshad Yasir , Alam Muhammad Masroor , Martin Javier , Shaw Alexander G , Grassly Nicholas C , Rambaut Andrew
Published: March 2024

Widespread surveillance, rapid detection, and appropriate intervention will be critical for successful eradication of poliovirus. Using deployable next-generation sequencing (NGS) approaches, such as Oxford Nanopore Technologies’ MinION, the time from sample to result can be significantly reduced compared to cell culture and Sanger sequencing. We developed piranha (poliovirus investigation resource automating nanopore haplotype analysis), a ‘sequencing reads-to-report’ solution to aid routine poliovirus testing of both stool and environmental samples and alleviate the bioinformatic bottleneck that often exists for laboratories adopting novel NGS approaches. Piranha can be used for efficient intratypic differentiation of poliovirus serotypes, for classification of Sabin-like polioviruses, and for detection of wild-type and vaccine-derived polioviruses. It produces interactive, distributable reports, as well as summary comma-separated values files and consensus poliovirus FASTA sequences. Piranha optionally provides phylogenetic analysis, with the ability to incorporate a local database, processing from raw sequencing reads to an interactive, annotated phylogeny in a single step. The reports describe each nanopore sequencing run with interpretable plots, enabling researchers to easily detect the presence of poliovirus in samples and quickly disseminate their results. Poliovirus eradication efforts are hindered by the lack of real-time detection and reporting, and piranha can be used to complement direct detection sequencing approaches.
Fusarium amaranthi sp. nov. from Amaranth Is an Emergent Species Closely Related to F. circinatum
Authors: Hassan Oliul , Ryu Hyunjoo , Lee Sang-Yeob , Choi Hyo-Won
Published: March 2024

Amaranth (Amaranthus spp. L) is not native to South Korea but is cultivated in small scales for ornamental purposes as well as leafy vegetables and pseudo cereals. In this study, a new species within the genus Fusarium was isolated from amaranth, showing stem rot symptoms from a farmer field in Hwaseong, South Korea. The disease is characterized by dark-brown spots with black borders, leading to withering. Phylogenetic analysis-based concatenated sequences of translation elongation factor 1-alpha (TEF1), beta-tubulin (tub2), calmodulin (cmdA), RNA polymerase largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) genes revealed that the obtained isolates formed a distinct clad within the Fusarium fujikuroi species complex and is closely related to F. circinatum. Cultural and morphological characteristics and pathogenicity on healthy amaranth plants (stem and leaves) were examined. The isolates readily differentiated from F. circinatum based on one- to five-septate macroconidia and the absence of sterile hyphae. Based on molecular and morphological characteristics, this fungus is demonstrated to be a new species and is described here as F. amaranthi, the causal agent of stem rot of amaranth in South Korea.
Effective, Consistent, and Rapid Noncontact Application Methods for Seedling Basal Stem Infection by Sclerotinia sclerotiorum
Authors: Han Viet-Cuong , Michael Pippa J. , Crockett Rachael , Swift Bec , Bennett Sarita Jane
Published: March 2024

Sclerotinia sclerotiorum (Lib.) de Bary, an economically devastating soilborne fungal pathogen known to cause disease across a wide range of plants, produces long-term inoculum called sclerotia that can germinate either carpogenically by ascospores infecting aboveground plant parts or myceliogenically to infect stem base and roots. Typically, for research purposes, S. sclerotiorum diseases are initiated by direct contact methods, using S. sclerotiorum mycelium agar plugs wrapped around the stem or sclerotia placed directly beneath root mass. However, reproducible noncontact methods leading to basal stem infection are not currently available. Therefore, the objective of this study was to develop effective noncontact protocols that consistently generate basal plant stem infection from S. sclerotiorum in the soil. Using three host plant species (canola, lupin, and lettuce), we determined two methods that reliably produced basal stem infection. The first method, where mycelial agar plugs were positioned just below the soil surface at a distance of 5 mm from each seedling, led to 100% infection in all plants. The second method used pathogen-infested soil by mixing the soil with dry inoculum in the form of a powder prepared from mycelium-colonized organic substrates. Four substrates consistently produced 100% seedling infection at 4 days after inoculation (DAI): wheat bran, wheat grain, red rice, and hulled millet. In contrast, chia, canary, sesame, and ryegrass seed substrates resulted in less than 50% seedling infection at 10 DAI, and infection levels did not progress further. The two soil inoculation methods outlined in this study will enhance future research on the progression of S. sclerotiorum diseases, with the potential to screen disease-resistant host genotypes to basal S. sclerotiorum infection and, in particular, to test the effectiveness of soil applications of fungicides or biocontrol agents against S. sclerotiorum basal infection.
Effects of an Early Intensive Blood Pressure–lowering Strategy Using Remifentanil and Dexmedetomidine in Patients with Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial
Authors: Dong Rui , Li Fen , Li Bin , Chen Qiming , Huang Xianjian , Zhang Jiehua , Huang Qibing , Zhang Zeli , Cao Yunxing , Yang Mingbiao , Li Jianwei , Li Zhanfu , Li Cuiyu , Liu Guohua , Zhong Shu , Feng Guang , Zhang Ming , Xiao Yumei , Lin Kangyue , Shen Yunlong , Shao Huanzhang , Shi Yuan , Yu Xiangyou , Li Xiaopeng , Yao Lan , Du Xinyu , Xu Ying , Kang Pei , Gao Guoyi , Ouyang Bin , Chen Wenjin , Zeng Zhenhua , Chen Pingyan , Chen Chunbo , Yang Hong
Published: March 2024

Background

Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure–lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure–lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage.

Methods

In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure–lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes.

Results

A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group.

Conclusions

Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine–based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.

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What We Already Know about This Topic

What This Article Tells Us That Is New
A Mechanistic and Preclinical Assessment of BioRestore Bioactive Glass as a Synthetic Bone Graft Extender and Substitute for Osteoinduction and Spine Fusion
Authors: Fred Elianna J. , Minardi Silvia , Goodwin Alyssa M. , Nandurkar Tejas S. , Plantz Mark A. , Lyons Joseph G. , Paul Jonathan T. , Foley James P. , Wintring Allison J. , Furman Andrew A. , Jeong Soyeon , Yun Chawon , Stock Stuart R. , Hsu Wellington K. , Hsu Erin L.
Published: March 2024

Study Design:

Preclinical animal study.

Objective:

Evaluate the osteoinductivity and bone regenerative capacity of BioRestore bioactive glass.

Summary of Background Data:

BioRestore is a Food and Drug Administration (FDA)-approved bone void filler that has not yet been evaluated as a bone graft extender or substitute for spine fusion.

Methods:

In vitro and in vivo methods were used to compare BioRestore with other biomaterials for the capacity to promote osteodifferentiation and spinal fusion. The materials evaluated (1) absorbable collagen sponge (ACS), (2) allograft, (3) BioRestore, (4) Human Demineralized Bone Matrix (DBM), and (5) MasterGraft. For in vitro studies, rat bone marrow–derived stem cells (BMSC) were cultured on the materials in either standard or osteogenic media (SM, OM), followed by quantification of osteogenic marker genes (Runx2, Osx, Alpl, Bglap, Spp1) and alkaline phosphatase (ALP) activity. Sixty female Fischer rats underwent L4-5 posterolateral fusion (PLF) with placement of 1 of 5 implants: (1) ICBG from syngeneic rats; (2) ICBG+BioRestore; (3) BioRestore alone; (4) ICBG+Allograft; or (5) ICBG+MasterGraft. Spines were harvested 8 weeks postoperatively and evaluated for bone formation and fusion via radiography, blinded manual palpation, microCT, and histology.

Results:

After culture for 1 week, BioRestore promoted similar expression levels of Runx2 and Osx to cells grown on DBM. At the 2-week timepoint, the relative ALP activity for BioRestore-OM was significantly higher (P<0.001) than that of ACS-OM and DBM-OM (P<0.01) and statistically equivalent to cells grown on allograft-OM. In vivo, radiographic and microCT evaluation showed some degree of bridging bone formation in all groups tested, with the exception of BioRestore alone, which did not produce successful fusions.

Conclusions:

This study demonstrates the capacity of BioRestore to promote osteoinductivity in vitro. In vivo, BioRestore performed similarly to commercially available bone graft extender materials but was incapable of producing fusion as a bone graft substitute.

Level of Evidence:

Level V.