bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Structure of Transdiagnostic Dimensions of Emotional Disorders in Adolescents With Subthreshold Anxiety and Depression: Links With Psychopathology and Socio‐Emotional Adjustment
Authors: Ródenas‐Perea Gabriel , Pérez‐Esteban Alfonso , Pérez‐Albéniz Alicia , Al‐Halabí Susana , Fonseca‐Pedrero Eduardo
Published: December 2024

Background

The transdiagnostic and network model approaches to psychopathology have emerged as an alternative to taxonomic systems. The main goal was to examine the network structure of the transdiagnostic dimensions of emotional disorders in adolescents with subclinical emotional symptoms. In addition, cross‐sectional network analyses were conducted to investigate the relationships between transdiagnostic dimensions, psychopathology, and socio‐emotional adjustment.

Method

The sample consisted of a total of 476 adolescents from 85 schools from different provinces in Spain with subthreshold anxiety and depression. The mean age was 13.77 years (SD = 1.43, range: 10–18 years), 73.9% were female. Several questionnaires assessing transdiagnostic dimensions of emotional disorders, mental health difficulties, self‐esteem, perceived social support, sense of belonging at school, and prosocial behaviour were used.

Results

A strong interrelation was found between the transdiagnostic variables, except with the positive temperament dimension. The dimensions with the greatest weight were those of traumatic re‐experiencing, intrusive cognitions, avoidance, neuroticism, and depressed mood. Negative relationships were found between the transdiagnostic dimensions of emotional disorders and the protective factors included in the study. Stability analyses indicated that the networks were accurately estimated.

Conclusion

The present paper points to the value of conceptualising emotional disorders from a transdiagnostic and network model perspective. In addition, the work provides new insights into the nature of the relationships between transdiagnostic dimensions of emotional disorders, and the role played by risk and protective factors.
Hope or Despair Revisited: Assessing Progress and New Challenges in Global Fisheries
Authors: Cheung William W. L. , Pauly Daniel , Sumaila U. Rashid
Published: December 2024

Marine fisheries are crucial to the economy, livelihood, food security and culture of coastal nations and communities, significantly contributing to the United Nations Sustainable Development Goals. A decade ago, T. J. Pitcher and W. W. L. Cheung highlighted the dichotomy in the perception of fisheries' status, concluding that long‐term sustainability and benefits to people were threatened by overexploitation, climate change, pollution, habitat change and other human stressors. They advocated for a fundamental shift towards ecosystem‐based management, better enforcement of existing regulations and more inclusive and equitable management practices. In this paper, we provide an updated review of the status of global fisheries, reflecting on policy actions, key assessments and research findings over the past decade. While there is a growing recognition of the need for sustainable fisheries management and ocean protection, the overall status of fisheries has not improved. Despite progress in international and national policies addressing direct and indirect drivers such as climate change and harmful practices, these trends have not been reversed. Many challenges identified by Pitcher and Cheung and others persist. Additionally, new and emerging issues such as deep‐sea mining, plastic pollution, unhealthy aquaculture development, increasing social inequity and the rapidly increasing push for the acceleration of the blue economy exacerbate the complexity of achieving fisheries and other ocean management goals. Debating whether there is more hope or despair in global fisheries has become irrelevant. Pathways to ‘bend the curve’ for fisheries are clear, and effective actions are now urgently needed to achieve desirable and sustainable fisheries.
Using Energy‐Dispersive Laue Diffraction to Study Dislocation Arrangements in Materials Showing Wavy and Planar Slip Behavior
Authors: Leidigkeit Carolin , Shokr Mohammad , Tosson Amir , Cakir Cafer Tufan , Radtke Martin , Pietsch Ullrich , Christ Hans‐Jürgen
Published: December 2024

The present work shows an approach to monitor the evolution of the dislocation arrangement of a metallic material caused by cyclic plastic strain using white X‐ray radiation in combination with an energy‐dispersive detector. The method is demonstrated by single‐shot experiments performed on polycrystalline nickel and α‐brass, representing the pure wavy and the pure planar dislocation slip behavior. To correlate the resulting diffraction patterns with various dislocation arrangements of both metals, fatigue tests were carried out up to certain numbers of cycles and at predetermined plastic strain amplitudes. The differences in dislocation microstructure and internal stress distributions give rise to an appreciable change in the peak shape of Laue reflections, leading to unique characteristics in the respective diffraction patterns. Nickel reflections are elongated due to the high amount of cell structures leading to bending and misorientation of the lattice, whereas the present stacking faults in α‐brass result in powder‐like diffraction.
Winners and Losers From Climate Change: An Analysis of Climate Thresholds for Tree Growth and Survival for Roughly 150 Species Across the Contiguous United States
Authors: Clark Christopher M. , Coughlin Justin G. , Phelan Jennifer , Martin Gray , Austin Kemen , Salem Marwa , Sabo Robert D. , Horn Kevin , Thomas R. Quinn , Dalton Rebecca M.
Published: December 2024

Changes in temperature and precipitation are already influencing US forests and that will continue in the future even as we mitigate climate change. Using spatiotemporally matched data for mean annual temperature (MAT) and mean annual precipitation (MAP), we used simulated annealing to estimate critical thresholds for changes in the growth and survival of roughly 150 tree species (153 spp. for growth, 159 spp. for survival) across the conterminous United States (CONUS). We found that growth of nearly one‐third of tree species assessed (44 spp.) decreased with any increase in MAT (42–49 species), whereas fewer responded negatively to projected regional trends in MAP (< 20 species each in the east and west). Hypothetical increases in temperature (+1°C, +2°C) increased average annual growth in the Central East and Pacific Northwest and decreased growth over large areas of the Rockies and Southeast, while decadal survival generally decreased with temperature. Average annual growth and decadal survival had unfavorable associations with projected precipitation, generally decreasing with wetter conditions (+25%) in the east and decreasing with drier conditions (−25%) in the west. Beyond these averages, there were species that positively and negatively responded nearly everywhere across the CONUS, suggesting changes in forest composition are underway. We identified only eight species out of ~150 assessed that were tolerant to increases in temperature, and 24 species in the east and seven in the west were tolerant to regionally specific trends in precipitation (increases in the east and decreases in the west). We assessed confidence on a 5‐point scale (1–5) for five aspects of uncertainty. Average confidence scores were generally high, though some species and metrics had low confidence scores especially for survival. These findings have significant implications for the future national forest carbon sink and for conservation efforts in the face of climate change.
Kidney transplant outcomes of Māori and Pasifika people receiving transplantation in Australia: an Australia and New Zealand Dialysis and Transplant Registry study
Authors: De Souza Laura , Jegatheesan Dev , Chang‐Wai Kuinileti , Johnson David W. , Campbell Scott B. , Viecelli Andrea K. , Cho Yeoungjee , Gately Ryan , Isbel Nicole
Published: December 2024

Background

The numbers of Māori and Pasifika peoples with kidney failure living in Australia are rising. However, data describing outcomes of those proceeding to transplantation are limited. This study describes clinical outcomes of Māori and Pasifika peoples who received a kidney transplant in Australia.

Aims

This study describes clinical outcomes of Maori and Pasifika peoples who received a kidney transplant in Australia.

Methods

A retrospective review was conducted of kidney transplant recipients aged ≥18 years receiving their first graft between 1 January 2002 and 31 December 2021, as recorded in the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was death‐censored graft survival. Secondary outcomes included delayed graft function (DGF), rejection and patient survival.

Results

Of 12 543 transplant recipients, mean age was 50 years and the majority identified as male sex. A total of 89 patients identified as Māori and 313 as Pasifika. Māori and Pasifika patients were more likely to have diabetic kidney disease or obesity at time of transplantation (body mass index > 30 kg/m2) and be current or former smokers compared to other ethnicities. Times to graft loss were shorter for Māori (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.36–3.11) and Pasifika (adjusted HR 1.78, 95% CI 1.39–2.029, P < 0.001) people compared to other ethnicities. The incidences of DGF were significantly higher in the Māori (30%) and Pasifika groups (28%) compared with 22% for other ethnicities (P < 0.005). Overall patient survival was comparable (Māori HR 0.93, 95% CI 0.57–1.49, P = 0.75; Pasifika HR 1.18, Cl 0.88–1.60, P = 0.26).

Conclusions

Times to graft loss for Māori and Pasifika kidney transplant patients were shorter than for other ethnicities.
Bayesian Recursive and Structural Equation Models to Infer Causal Links Among Gait Visual Scores on Campolina Horses
Authors: Bussiman Fernando , Richter Jennifer , Hidalgo Jorge , Silva Fabyano Fonseca e , Ventura Ricardo Vieira , Carvalho Rachel Santos Bueno , Mattos Elisângela Chicaroni , Ferraz José Bento Sterman , Eler Joanir Pereira , de Carvalho Balieiro Júlio Cesar
Published: December 2024

Gait visual scores are widely applied to horse breeding because they are a fast and easy phenotyping strategy, allowing the numeric interpretation of a complex biological process such as gait quality. However, they may suffer from subjectivity or high environmental influence. We aimed to investigate potential causal relationships among six visual gait scores in Campolina horses. The data included 5475 horses with records for at least one of the following traits: Dissociation (Di), Comfort (C), Style (S), Regularity (R), Development (De), and Gait total Scores (GtS). The pedigree comprised three generations with 14,079 horses in the additive relationship matrix. Under a Bayesian framework, (co)variance components were estimated through a multitrait animal model (MTM). Then, the inductive causation algorithm (IC) was applied to the residual (co)variance matrix samples. The resulting undirected graph from IC was directed in 6 possible causal structures, each fitted by a structural equation model. The final causal structure was chosen based on deviance information criteria (DIC). It was found that S significantly impacts the causal network of gait, directly and indirectly affecting C. The indirect causal effect of S on C was through the direct effect of S on De, then the direct effect of De on R, and finally, the direct effect of R on C. Di was caused by S, which is the reason for the genetic correlation between Di and GtS, due to causal effects being added to the model, they absorb the genetic correlation between Di and GtS. Those paths have biological meaning to horse movements and can help breeders and researchers better understand horses' complex causal network of gait.
The Value of a Tooth for Alveolar Ridge Management; Strategies to Manage Ankylosed Maxillary Anterior Teeth in Young Patients
Authors: Janakievski Jim
Published: December 2024

Objective

In the young and growing patient, tooth ankylosis impedes alveolar growth and presents a serious dilemma regarding the best treatment approach. Two common treatment approaches, extraction of the ankylosed tooth or a “wait and see” will result in a compromised alveolar ridge that can affect future prosthetic rehabilitation. The purpose of this article is to discuss five treatment strategies that can be utilized in the management of tooth ankylosis in the growing patient: (1) extraction, (2) decoronation or root submergence, (3) socket shield (partial extraction), (4) segmental osteotomy and (5) replacement with tooth autotransplantation.

Overview

It is important to understand the biologic sequelae of ankylosis and the value of the tooth for alveolar ridge management. Strategies will be discussed with an emphasis on alveolar ridge management using a natural tooth and root. With an interdisciplinary team, treatment options can then be developed, to achieve more favorable long‐term outcomes.

Conclusions

An understanding of each of these procedures and the proper time for implementation will help the clinician achieve the most optimal long‐term outcomes for these growing patients.

Clinical Significance

There are several treatment options for traumatized ankylosed incisors in growing patients. This article will describe the details of these treatment strategies, emphasize the value of the tooth for ridge management and present guidelines about selecting the most optimal strategy based on age, rate of growth, condition of the traumatized tooth, and the definitive prosthetic plan.
Chronic in vivo sequelae of repetitive acute mfb‐DBS on accumbal dopamine and midbrain neuronal activity
Authors: Miguel Telega Lidia , Ashouri Vajari Danesh , Ramanathan Chockalingam , Coenen Volker A. , Döbrössy Máté D.
Published: December 2024

Medial Forebrain Bundle Deep Brain Stimulation (MFB‐DBS) can have rapid and long lasting antidepressant effects in Treatment Resistant Depression (TRD) patients. The mechanisms are not well understood, but one hypothesis stipulates that modulation of the dopaminergic (DAergic) fibers contribute to the therapeutic outcome. Acute DBS effects on DA release have been studied; however, longitudinal studies with acute‐repetitive DBS are lacking. Long‐Evans accumbal DA release and Ventral Tegmental Area (VTA) calcium tonic and phasic signaling to different mfb‐DBS parameters were measured using fiber photometry over 8 weeks, following acute and repetitive stimulation in behaving and non‐behaving animals. DBS‐induced release was observed in both targets, with increased frequency and DBS duration. 130 Hz stimulation increased phasic and tonic DA response over time, with the latter being a potential mechanism for its long‐term clinical effectiveness. VTA calcium transients decreased, while phasic activity increased with frequency. Pulse width (PW)‐mediated differential peak release timing also suggests potential parallel activation of diverse fiber types. Additionally, decreased DA transients rate during Elevated Plus Maze (EPM) suggests context and stimulation duration‐dependent DA release. The data confirm chronic antidromic/orthodromic DAergic responses with stimulation parameter dependent variability, providing novel insights into temporal adaptations, connectivity and fiber recruitment on mfb DBS.

image
Integrative single‐cell RNA‐seq and ATAC‐seq analysis of the evolutionary trajectory features of adipose‐derived stem cells induced into astrocytes
Authors: Long Qingxi , Yuan Yi , Ou Ya , Li Wen , Yan Qi , Zhang Pingshu , Yuan Xiaodong
Published: December 2024

This study employs single‐cell RNA sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin with high‐throughput sequencing technologies (scATAC‐seq) to perform joint sequencing on cells at various time points during the induction of adipose‐derived stem cells (ADSCs) into astrocytes. We applied bioinformatics approaches to investigate the differentiation trajectories of ADSCs during their induced differentiation into astrocytes. Pseudotemporal analysis was used to infer differentiation trajectories. Additionally, we assessed chromatin accessibility patterns during the differentiation process. Key transcription factors driving the differentiation of ADSCs into astrocytes were identified using motif and footprint methods. Our analysis revealed significant shifts in gene expression during the induction process, with astrocyte‐related genes upregulated and stem cell‐related genes downregulated. ADSCs first differentiated into neural stem cell‐like cells with high plasticity, which further matured into astrocytes via two distinct pathways. Marked changes in chromatin accessibility were observed during ADSC‐induced differentiation, affecting transcription regulation and cell function. Transcription factors analysis identified NFIA/B/C/X and CEBPA/B/D as key regulators in ADSCs differentiation into astrocytes. We observed a correlation between chromatin accessibility and gene expression, with ADSCs exhibiting broad chromatin accessibility prior to lineage commitment, where chromatin opening precedes transcription initiation. In summary, we found that ADSCs first enter a neural stem cell‐like state before differentiating into astrocytes. ADSCs also display extensive chromatin accessibility prior to astrocyte differentiation, although transcription has not yet been initiated. These findings offer a theoretical framework for understanding the molecular mechanisms underlying this process.

image
On Time‐Inconsistency in Mean‐Field Games
Authors: Bayraktar Erhan , Wang Zhenhua
Published: December 2024

We investigate an infinite‐horizon time‐inconsistent mean‐field game (MFG) in a discrete time setting. We first present a classic equilibrium for the MFG and its associated existence result. This classic equilibrium aligns with the conventional equilibrium concept studied in MFG literature when the context is time‐consistent. Then we demonstrate that while this equilibrium produces an approximate optimal strategy when applied to the related ‐agent games, it does so solely in a precommitment sense. Therefore, it cannot function as a genuinely approximate equilibrium strategy from the perspective of a sophisticated agent within the ‐agent game. To address this limitation, we propose a new consistent equilibrium concept in both the MFG and the ‐agent game. We show that a consistent equilibrium in the MFG can indeed function as an approximate consistent equilibrium in the ‐agent game. Additionally, we analyze the convergence of consistent equilibria for ‐agent games toward a consistent MFG equilibrium as tends to infinity.
Knockdown of OsPHP1 Leads to Improved Yield Under Salinity and Drought in Rice via Regulating the Complex Set of TCS Members and Cytokinin Signalling
Authors: Yadav Chhaya , Rawat Nishtha , Singla‐Pareek Sneh L. , Pareek Ashwani
Published: December 2024

Plant two‐component system (TCS) is crucial for phytohormone signalling, stress response, and circadian rhythms, yet the precise role of most of the family members in rice remain poorly understood. In this study, we investigated the function of OsPHP1, a pseudo‐histidine phosphotransfer protein in rice, using a functional genomics approach. OsPHP1 is localised in the nucleus and cytosol, and it exhibits strong interactions with all sensory histidine kinase proteins (OsHK1‐6) and cytokinin catabolism genes. Our results demonstrate that OsPHP1 functions as a negative regulator of cytokinin signalling. Knockdown of OsPHP1 enhanced the expression of positive cytokinin signalling regulators, such as OsHKs and OsAHPs (authentic phosphotransfer proteins), while downregulating negative regulators, such as type‐A response regulators (OsRRs) and cytokinin catabolism genes (CKXs). Furthermore, OsPHP1 negatively influences abiotic stress tolerance, as evidenced by the increased sensitivity of OsPHP1‐OE (overexpression) lines to salinity and drought. In contrast, OsPHP1‐KD (knockdown) lines showed enhanced stress resilience, with better photosynthesis, increased tiller and panicle production, higher spikelet fertility, and grain filling. The study demonstrates that OsPHP1 suppresses antioxidant and stress‐responsive genes, exacerbating ion toxicity and reducing osmolyte accumulation, thereby impairing plant growth and yield under stress conditions. These findings highlight OsPHP1 as a critical modulator of plant responses to abiotic stress and suggest potential genetic targets for enhancing crop stress tolerance.
Suicide prevention inpatient group treatment—A treatment development and feasibility study
Authors: Holoshitz Yael , Mehta Haitisha , Itzhaky Liat , Cid Ariana , DeSilva Ravi , Gilbert Sarah , Kaufmann Cassie , Labouliere Christa D. , Brodsky Beth , Stanley Barbara
Published: December 2024

Background

One mainstay of psychiatric treatment for suicidal crises is inpatient psychiatric hospitalization. Despite the need to secure immediate safety and stabilization, inpatient treatment for acutely suicidal patients remains diagnosis‐specific, which may fail to directly target and adequately manage suicidal behavior as a symptom and reason for admission or treatment. The post‐discharge period is a high‐risk period for repeat suicide attempts or death by suicide, but overburdened workforce and high patient turnover make it difficult to provide suicide‐specific treatment.

Methods

In response to this need, we developed the Suicide Prevention Inpatient Group Treatment (SPIGT), a four‐module, group‐based intervention, which provides evidence‐supported concrete tools and psychoeducation to directly address suicidality. To assess feasibility and acceptability of implementation, the SPIGT was piloted on an inpatient psychiatric unit starting in 2016. Group participants were given optional, anonymous surveys after each module. Unit clinicians also completed optional, anonymous surveys to assess their attitudes towards the intervention.

Results

Results indicate that participants responded very favorably to each module, and that unit clinicians felt that the implementation of this intervention was feasible and acceptable.

Conclusion

The SPIGT shows promise as a scalable suicide‐specific, brief intervention, which addresses an unmet and critical need in suicide prevention.
Flexible Tooling Enabled by the Electromagnetics With Discrete Blank Holding Force: Short-Time Pulse Control and Forming Validation
Authors: Li Lei , Hu Guozeng , Jin Rui , Du Hai , Huang Haihong
Published: December 2024

The increasing demand for higher precision in complex surface forming has highlighted the significance of utilizing variable blank holding force (VBHF) in segmented blank holding. However, applying electromagnetic blank holding in such segmented systems remains unexplored, presenting a critical challenge in continuous forming processes. This study proposed an innovative, flexible tooling system driven by an electrically controlled permanent magnet, enabling discrete control of blank holders. An equivalent magnetic circuit for a single magnetic pole was developed alongside a model to characterize variations in electromagnetic force. The discrete VBHF control with a short-time pulse leverages the operating point migration law of the magnet, elucidating the control mechanism of discrete electromagnetic forces. An electrical-magnetic-mechanical coupling simulation model was established using Simulink, Simplorer, and Maxwell. The simulation results reveal that the control error of electromagnetic force across different blank holding areas under varying currents ranges from 0.1% to 1.7%, with a steady-state control error under any electromagnetic force curve remaining within 5%. Electromagnetic blank holding experiments on a car-door prototype demonstrated that the control error of discrete electromagnetic forces is between −50 N and 20 N. Applying short-time pulse current in VBHF loading also ensures forming quality while reducing continuous current consumption by 14.03% and decreasing hydraulic press tonnage demand by 14%. This study provides theoretical and methodological support for designing equipment that enables low-tonnage, high-precision continuous forming of complex surfaces.
Cellular RNA interacts with MAVS to promote antiviral signaling
Authors: Gokhale Nandan S. , Sam Russell K. , Somfleth Kim , Thompson Matthew G. , Marciniak Daphnée M. , Smith Julian R. , Genoyer Emmanuelle , Eggenberger Julie , Chu Lan H. , Park Moonhee , Dvorkin Steve , Oberst Andrew , Horner Stacy M. , Ong Shao-En , Gale Michael , Savan Ram
Published: December 2024

Antiviral signaling downstream of RIG-I–like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides or scaffolds. We hypothesized that RNA plays a role in organizing MAVS signaling platforms. We found that MAVS, through its central intrinsically disordered domain, directly interacted with the 3′ untranslated regions of cellular messenger RNAs. Elimination of RNA by ribonuclease treatment disrupted the MAVS signalosome, including RNA-modulated MAVS interactors that regulate RLR signaling and viral restriction, and inhibited phosphorylation of transcription factors that induce interferons. This work uncovered a function for cellular RNA in promoting signaling through MAVS and highlights generalizable principles of RNA regulatory control of immune signaling complexes.
Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice
Authors: Li Wenwen , Li Jiarui , Li Jing , Wei Chen , Laviv Tal , Dong Meiyi , Lin Jingran , Calubag Mariah , Colgan Lesley A , Jin Kai , Zhou Bing , Shen Ying , Li Haohong , Cui Yihui , Gao Zhihua , Li Tao , Hu Hailan , Yasuda Ryohei , Ma Huan
Published: December 2024

Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TC
mito
), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC
nuc
). We demonstrated that E-TC
mito
repurposes molecules traditionally associated with E-TC
nuc
to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC
mito
weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC
mito
in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.
Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA–mediated silencing
Authors: Lee Seungjae , Lee Sangmi , Desnick Robert , Yasuda Makiko , Lai Eric C.
Published: December 2024

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1—but not other heme biosynthesis enzymes—limits the assembly and activity of Argonaute complexes under heme-replete conditions. This involves a cytoplasmic role for ALAS1, previously considered inactive outside of mitochondria. Moreover, conditional depletion of ALAS activity from mouse hepatocytes increases miRNAs and enhances siRNA-mediated knockdown. Notably, because
ALAS1
is the target of a Food and Drug Administration–approved siRNA drug, agents that suppress ALAS may serve as adjuvants for siRNA therapies.
A cellulose synthase–like protein governs the biosynthesis of
Solanum
alkaloids
Authors: Jozwiak Adam , Panda Sayantan , Akiyama Ryota , Yoneda Ayano , Umemoto Naoyuki , Saito Kazuki , Yasumoto Shuhei , Muranaka Toshiya , Gharat Sachin A. , Kazachkova Yana , Dong Yonghui , Arava Shlomy , Goliand Inna , Nevo Reinat , Rogachev Ilana , Meir Sagit , Mizutani Masaharu , Aharoni Asaph
Published: December 2024

Decades of research on the infamous antinutritional steroidal glycoalkaloids (SGAs) in Solanaceae plants have provided deep insights into their metabolism and roles. However, engineering SGAs in heterologous hosts has remained a challenge. We discovered that a protein evolved from the machinery involved in building plant cell walls is the crucial link in the biosynthesis of SGAs. We show that cellulose synthase–like M [GLYCOALKALOID METABOLISM15 (GAME15)] functions both as a cholesterol glucuronosyltransferase and a scaffold protein. Silencing
GAME15
depletes SGAs, which makes plants more vulnerable to pests. Our findings illuminate plant evolutionary adaptations that balance chemical defense and self-toxicity and open possibilities for producing steroidal compounds in heterologous systems for food, cosmetics, and pharmaceuticals.
Dismay greets possible ban on Chinese drones
Authors: Zhao Celina
Published: December 2024

U.S. scientists studying forests, whales, and more largely rely on devices made in China
Population pharmacokinetics of piperacillin-tazobactam in the plasma and cerebrospinal fluid of critically ill patients
Authors: Kumta Nilesh , Heffernan Aaron J. , Cotta Menino Osbert , Liu Xin , Parker Suzanne , Wallis Steven , Livermore Amelia , Starr Therese , Wong Wai Tat , Joynt Gavin M. , Lipman Jeffrey , Roberts Jason A.
Published: December 2024

Ventriculitis in neurocritical care patients leads to significant morbidity and mortality. Antibiotic dose optimization targeting pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with improved bacterial killing may improve therapeutic outcomes. We sought to develop and apply a population PK model in infected critically ill patients to determine optimal piperacillin-tazobactam (PTZ) dosing regimens to achieve target cerebrospinal fluid (CSF) exposures. Neurosurgical patients with external ventricular drains and receiving PTZ treatment were recruited and had plasma and CSF samples collected and assayed. A population PK model was developed using plasma and CSF piperacillin and tazobactam concentrations. Eight patients were recruited. Median age was 59 years, median weight was 70 kg, and five patients were female. The median creatinine clearance was 84 mL/min/1.73 m
2
(range 52–163). Substantial inter-individual PK variability was apparent, particularly in CSF. Piperacillin penetration into CSF had a median of 3.73% (range 0.73%–7.66%), and tazobactam CSF penetration was not predictable. Dosing recommendations to optimize CSF exposures for the treatment of ventriculitis were not possible due to substantial PK variability and very low drug penetration. High plasma PTZ exposures may not translate to effective exposures in CSF.
SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants
Authors: Rodriguez Lauren , Lee Hery W. , Li Jiani , Martin Ross , Han Dong , Xu Simin , Moshiri Jasmine , Peinovich Nadine , Camus Gregory , Perry Jason K. , Hyland Robert H. , Porter Danielle P. , Abdelghany Mazin , Götte Matthias , Hedskog Charlotte
Published: December 2024

Remdesivir inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; Nsp12). Here, we conducted viral resistance analyses from the Phase 3 PINETREE trial of remdesivir in nonhospitalized participants at risk of severe COVID-19. Nasopharyngeal swabs (collected at baseline [Day 1], Days 2, 3, 7, and 14) were eligible for analysis if their viral load was above the lower limit of quantification for the RT-qPCR assay (2228 copies/mL). The SARS-CoV-2 genome was sequenced for all remdesivir participants and 50% of placebo participants (baseline, Days 3, 7, and 14) and for participants who progressed to COVID-19-related hospitalization or all-cause death (all time points). Emergent substitutions in Nsp12 and other replication complex proteins were phenotyped using site-directed mutagenesis in a SARS-CoV-2 subgenomic replicon system. Overall, emergent Nsp12 substitutions were detected in 8/115 (7.0%) remdesivir participants and 7/129 (5.4%) placebo participants (1 substitution overlap between groups). Based on a structural analysis, none of the emergent Nsp12 substitutions were in direct contact with the incoming nucleoside triphosphate substrate, the RNA, or the RNA template 5′ overhang. One substitution (A376V) showed reduced susceptibility to remdesivir (12.6-fold change in remdesivir half-maximal concentration [EC
50
]); it also showed reduced fitness when introduced in the SARS-CoV-2 replicon and virus
in vitro
. Other substitutions had <1.1-fold change in remdesivir EC
50
. None of the emergent substitutions in Nsp8, Nsp10, Nsp13, or Nsp14 (remdesivir, 10/115 [8.7%]; placebo, 10/129 [7.8%]) showed reduced remdesivir susceptibility. In conclusion, emergent substitutions in the SARS-CoV-2 RdRp complex with reduced remdesivir susceptibility were uncommon, indicating a high barrier to remdesivir resistance.

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT04501952

.
Impact of the inoculum size on the
in vivo
activity of the aztreonam-avibactam combination in a murine model of peritonitis due to
Escherichia coli
expressing CTX-M-15 and NDM-1
Authors: Amoura Ariane , Benchetrit Laura , Magréault Sophie , Chosidow Samuel , Le Menestrel Alice , Jullien Vincent , de Lastours Victoire , Chau Françoise , Dion Sara , Massias Laurent , Fantin Bruno , Lefort Agnès
Published: December 2024

The combination of aztreonam (ATM) and avibactam (AVI) is an attractive option to treat infections caused by extended spectrum β-lactamase plus NDM-1-producing
Enterobacteriaceae
. Since ATM activity was shown to be severely impacted by an increase in the inoculum size
in vitro
, we wondered whether ATM-AVI activity could be impaired in high-inoculum infections. We analyzed the impact of the inoculum size on ATM-AVI activity
in vitro
and in a murine model of peritonitis due to susceptible
Escherichia coli
CFT073-pTOPO and its isogenic derivatives producing NDM-1 (
E. coli
CFT073-NDM1) and CTX-M-15 plus NDM-1 (
E. coli
CFT073-CTXM15-NDM1). The impact of the inoculum size on bacterial morphology was studied by microscopic examination.
In vitro
, at standard (10
5
) inoculum,
E. coli
CFT073-CTXM15-NDM1 was resistant to ATM but susceptible to the ATM-AVI combination. At high (10
7
) inoculum, MICs of ATM alone and of the ATM-AVI combination reached >512 and 64 mg/L, respectively, against all tested strains. ATM led to bacterial filamentation when active against the bacteria, i.e., in monotherapy or in combination with AVI against susceptible
E. coli
CFT073-pTOPO and only in combination with AVI against
E. coli
CFT073-CTXM15-NDM1.
In vivo
, increase in the inoculum led to a drastic decrease in the activity of ATM alone against
E. coli
CFT073-pTOPO and ATM-AVI against
E. coli
CFT073-CTXM15-NDM1. Our results suggest a high
in vivo
impact of the inoculum increase on the activity of ATM alone against ATM-susceptible
E. coli
and of ATM-AVI against CTX-M-15 plus NDM-1 producing
E. coli
. Clinicians must be aware of the risk of failures when using ATM-AVI in high-inoculum infections.
Antibiotic resistance genes profile of selected drinking water treatment plants in South Africa as impacted by different treatment stages
Authors: Kalu Chimdi Mang , Mudau Khuthadzo L. , Ntobeng Lesoka Reneiloe , Masindi Vhahangwele , Tekere Memory
Published: December 2024

Water treatment plants treat raw water making it suitable for consumption. Treatment stages are linked to the quality status of the treatment. The classes of antibiotic resistance genes as impacted by treatment stages remain under explored. We report the classes of antibiotic resistance genes (ARGs) from shotgun metagenomes as influenced by treatment stages.
Complete genome sequence of
Salmonella enterica
bacteriophage SeKF_80, isolated from wastewater in British Columbia
Authors: Guy Thomas , Harlton Colleen , Wang Siyun , Fong Karen
Published: December 2024

Salmonella enterica
is a Gram-negative inhabitant of the gastrointestinal tract of warm-blooded animals and commonly implicated in foodborne illness. Here, we describe the isolation of
Salmonella enterica
phage SeKF_80. The 89,965 bp genome contains 174 predicted coding sequences with 44 predicted functions. Phage SeKF_80 shares species-level similarity with
Salmonella
phages 7–11.
Secular Trends of Fast‐Food Consumption Among Adolescents Aged 12–15 Years: A Global Analysis Including 18 Countries
Authors: Smith Lee , López Sánchez Guillermo F. , Tully Mark A. , Rahmati Masoud , Butler Laurie , Barnett Yvonne , Keyes Helen , Kostev Karel , Oh Hans , Shin Jae Il , Koyanagi Ai
Published: December 2024

Consumption of fast‐food in adolescence is detrimental to mental and physical health. However, data on the temporal trends of fast‐food consumption in this population are scarce, particularly from non‐Western or non‐high‐income settings. Therefore, we aimed to examine this trend in representative samples of school‐going adolescents aged 12–15 years from 18 countries in Africa, Asia, and the Americas, which were predominantly low‐ and middle‐income countries (LMICs). Data from the Global School–based Student Health Survey (GHSH) 2009–2017 were analyzed. Fast‐food consumption referred to eating from a fast‐food restaurant at least once in the past 7 days. The prevalence of fast‐food consumption was calculated for each survey, and crude linear trends within each country were examined by linear regression models. Data on 74,055 students aged 12–15 years were analyzed (mean (standard deviation (SD)) age: 13.9 (1.0) years; 49.2% boys). The mean prevalence of fast‐food consumption was 52.7%. Of the 18 countries included in the study, significant increasing, decreasing, and stable trends were observed in 5, 2, and 11 countries, respectively. The most drastic increases were observed in Morocco between 2010 (44.2%) and 2016 (62.2%) and Lebanon between 2011 (64.6%) and 2017 (77.1%). Significant decreasing trends were observed in Kuwait between 2011 (90.5%) and 2015 (75.1%) and Samoa between 2011 (78.9%) and 2017 (67.3%). The prevalence of fast‐food consumption is overwhelmingly high among adolescents globally. Decreasing trends were only observed in two countries (Kuwait and Samoa). These data suggest that global strategies to tackle fast‐food consumption among adolescents are urgently required.
Initial Experience of Contact Laser Vaporization of the Prostate (CVP) for Benign Prostate Hyperplasia Patients With Hemorrhagic Risk
Authors: Araki Yushi , Kawahara Takashi , Takeshima Teppei , Makiyama Kazuhide , Uemura Hiroji
Published: December 2024

Introduction: Since contact laser vaporization of the prostate (CVP) was approved by the Japanese insurance system in 2016, the use of a 980 nm diode laser system for CVP has become widespread for treating benign prostate hyperplasia (BPH) patients. Our institute has been implementing CVP for BPH since 2018, treating a total of 93 patients, including 28 with a risk of hemorrhage. This study examines the safety and efficacy of CVP treatment for BPH patients with a hemorrhagic risk.

Patient and Methods: A total of 93 BPH patients with lower urinary tract symptoms (LUTS) underwent CVP between February 2018 and September 2022. All patients were on medications for BPH and were refractory to these medications. The median (mean ± SD) age was 72 (72.9±6.27), and the prostate volume was 64 (68.9±32.5). IPSS, QOL index, and OABSS scores for patients not requiring catheterization were 22 (22.1±6.38), 5 (5.24±0.74), and 6 (7±3.29), respectively. The CVP treatment was performed using a 980 nm diode laser. Of the 93 patients, 28 (30.1%) had a hemorrhage risk. This group included 13 (14.0%) who were continuously receiving anticoagulant and/or antiplatelet agents, 13 (14.0%) who temporarily stopped these medications, and 2 (2.1%) who had a hemorrhage risk due to low platelet counts (< 5.0 × 104/μL).

Results: Postoperatively, 15 (16.1%) patients, including 11 who were catheterized preoperatively, needed temporary catheterization after CVP treatment. Of these, 14 had their catheters successfully removed. The IPSS score significantly decreased from 22 (22.1±6.38) to 8 (9.02±6.07) (p < 0.0001). In patients with hemorrhagic risk on anticoagulant and/or antiplatelet agents, the change in hemoglobin level before and after surgery was 0.6 g/dL, a difference that was not significant. Two of the 15 patients with hemorrhagic risk experienced hemorrhage 23 and 26 days postoperatively and underwent transurethral coagulation. Other perioperative complications classified as Clavien–Dindo Grade 2 or higher occurred in 4 (4.3%) patients.

Conclusion: CVP treatment appears to be acceptable for BPH patients with hemorrhagic risk. In this study, late‐onset hemorrhage occurred approximately 1 month postoperatively. Close postoperative follow‐up is required.
Beyond Bottles: Exploring Consumer Perceptions and Preferences for Bag‐in‐Box Wine Packaging
Authors: Scozzafava Gabriele , Dominici Andrea , Canuti Valentina , Casini Leonardo , Boncinelli Fabio
Published: December 2024

The change in consumption habits, the need for product differentiation and the transition to eco‐sustainable wine production have led to the adoption of alternative packaging solutions, moving beyond the traditional glass bottle. This study employs experimental auctions with a sample of 100 participants to assess consumer willingness to pay for both bag‐in‐box and traditional glass bottle packaging. Using statistical tests and regression analysis, we find that consumer preferences for wine packaging formats significantly influence purchasing decisions and perceptions of product quality. Notably, consumers show a lower willingness to pay for the same wine when packaged in a bag‐in‐box than a bottle, and taste does not influence the willingness to pay. Moreover, the preference for bottled wine seems to be socially influenced. This study enriches the understanding of consumer behaviour regarding packaging preferences and provides actionable insights for the wine industry, retailers, policymakers and consumers.
Modification of Asphalt Concrete With Sulfur‐Containing Waste
Authors: Gunka Volodymyr , Sidun Iurii , Helesh Andriy , Demchuk Yuriy , Poliak Olha , Vytrykush Nataliya
Published: December 2024

The expediency of involving large‐tonnage sulfur production waste from Rozdil Mining and Chemical Enterprise Sirka (Ukraine) in road surface production has been substantiated theoretically and practically. In particular, the possibility of using waste from sulfur ores flotation enrichment and sulfur filtration purification from ash and organic impurities and their mixtures in the production of modified hot mix asphalt were investigated. It was found that sulfur content changes in bitumen can influence its operational properties: at sulfur concentrations of 5 wt. %, it acts as a plasticizer and at sulfur content ≥ 20 wt. %, it behaves as a filler. There are reasons to state that it is most effective to introduce sulfur into asphalt concrete (AC) as filler aggregate directly in the preparation process of sulfur asphalt mixes in an asphalt mixer. It is shown that the strength of sulfur AC grows over time and reaches maximum values within 15 days. It has been established experimentally that the use of highly sulfur‐concentrated filler aggregates instead of traditional limestone minerals significantly improves the main operational characteristics of AC, in particular: strength at a temperature of 20°C and at a temperature of 50°C; heat resistance; bitumen content to achieve regulated residual porosity is reduced. It was demonstrated that increasing the sulfur content in filler aggregate makes it possible to reduce the bitumen content in AC. Pilot construction of road pavements was conducted, which confirmed that sulfur AC has better operational characteristics compared with regular AC.
Cholinesterase Inhibitory Activity of Paeoniflorin: Molecular Dynamics Simulation, and In Vitro Mechanistic Investigation
Authors: Abdalla Mohnad , Khalid Asaad , Hedayati Jasmine , Ghayur Muhammad Nabeel
Published: December 2024

Alzheimer’s disease (AD), a neurological disorder, is one of the major reasons for memory loss in the world. AD is characterized by a sequela of cognitive and functional decline caused by brain cell degeneration. Paeoniflorin is a monoterpenoid glycoside found in plants of the Paeoniaceae family, which are known for their medicinal properties including dementia. In this project, we report actions of paeoniflorin on the two related cholinesterases (ChE): acetylChE (AChE) and butyrylChE (BuChE). Paeoniflorin, in a dose‐dependent (maximum inhibition at 1 mg/mL) manner, inhibited both AChE (0.06–1 mg/mL) and BuChE (0.007–1 mg/mL) enzymes with maximum inhibition of AChE enzyme at 90.3 ± 1.4%, while 99.4 ± 0.3% for BuChE enzyme. The EC50 value for the inhibitory effect of the compound against AChE was 0.52 mg/mL (0.18–1.52), while against BuChE was 0.13 mg/mL (0.08–0.21). The observed ani‐ChE action was like an effect also mediated by the known ChE blocker physostigmine. Molecular interactions between paeoniflorin and both ChE enzymes were additionally sought via molecular docking and molecular dynamics simulations for 100 ns, that showed paeoniflorin interacted with the active‐site gorge of AChE and BuChE via hydrogen bonds and water bridging with the many amino acids of the AChE and BuChE enzymes. This study presents the ChE inhibitory potential of paeoniflorin against both AChE and BuChE enzymes. With this kind of inhibitory activity, the chemical can potentially increase ACh levels and may have use in the treatment of dementia of AD.
The Effect of Fuzheng Yiai Decoction on the Transdifferentiation of Lung Adenocarcinoma in EGFR‐TKI‐Resistant Mice
Authors: Sun Jianfeng , Luo Danqing , Li Hui , Zhang Di , Liu Yesha , Jin Song , Guo Hong , He Chengshi , Wu Zhipeng
Published: December 2024

This study aimed to investigate the effect of Fuzheng Yiai Decoction (FZYA) on epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) drug resistance in lung adenosquamous carcinoma (ASC). The expression of thyroid transcription factor 1 (TTF1) and p63 in tumor cells was observed by immunofluorescence staining. Meanwhile, 25 nude mice successfully inoculated with the human lung ASC cell line NCI‐H596 were randomly divided into five groups, namely, the model, gefitinib, low‐, medium‐, and high‐dose FZYA with gefitinib groups. After four weeks of daily intragastric administration of the various treatments, the tumor weight and volume inhibition rates were calculated. The positive expression rate and protein expression of TTF1 and p63 in mouse tumor tissues were evaluated by immunohistochemistry and western blot assays. The results showed that the adenocarcinoma part and the squamous cell carcinoma part of the lung tissue were not either one or the other, and each had unique biological behavior patterns. In terms of the tumor volume and weight, gefitinib treatment along with FZYA reduced the acquired resistance of EGFR‐TKIs in lung ASC, and its inhibitory effect was superior to EGFR‐TKI (gefitinib) treatment alone. Moreover, it was discovered that FZYA inhibited the pedigree transformation among cancer subtypes due to EGFR‐TKI treatment. In conclusion, the application of FZYA inhibited the pedigree transformation among lung cancer subtypes, thus increasing the tumor inhibitory effect and decreasing the EGFR‐TKI drug resistance of tumor cells.