bluuebunny/crossref_metadata_2025 huggingface dataset:
In-hospital prognosis of acute ST-elevation myocardial infarction in patients with recent recreational drug use
Authors: Clement Arthur , Dillinger Jean-Guillaume , Ramonatxo Arthur , Roule Vincent , Picard Fabien , Thevenet Eugenie , Swedzky Federico , Hauguel-Moreau Marie , Sulman David , Stevenard Mathilde , Amri Nabil , Martinez David , Maitre-Ballesteros Laura , Landemaine Thomas , Coppens Alexandre , Bouali Nabil , Guiraud-Chaumeil Paul , Gall Emmanuel , Lequipar Antoine , Henry Patrick , Pezel Theo
Published: February 2024

Aims

Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study.

Methods and results

From 7–22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4–54.6).

Conclusion

In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia.

Trial registration

URL: https://clinicaltrials.gov/ct2/show/NCT05063097.
A novel zinc-chelating compound has antifungal activity against a wide range of Candida species, including multidrug-resistant Candida auris
Authors: Shinohara Takayuki , Wada Akira , Abe Masahiro , Nakayama Nobuko , Nagi Minoru , Miyazaki Yoshitsugu
Published: February 2024

Objectives

In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals.

Methods

The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe.

Results

A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris. We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo. APC6 disrupted the biofilms formed by Candida species.

Conclusions

This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis.
Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity
Authors: Migotsky Nicole , Kumar Surabhi , Shuster John T , Coulombe Jennifer C , Senwar Bhavya , Gestos Adrian A , Farber Charles R , Ferguson Virginia L , Silva Matthew J
Published: February 2024

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from 2 populations of genetic diversity. Additionally, we compared how intrabone relationships varied in the 2 populations. Our first population of genetic diversity included 72 females and 72 males from the 8 inbred founder strains used to create the Diversity Outbred (DO) population. These 8 strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the 2 populations of genetic diversity, we show that each DO mouse does not resemble a single inbred founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intrabone relationships (eg, ultimate force vs. cortical area) were mainly conserved in our 2 populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.
Industrial defective chips detection using deep convolutional neural network with inverse feature matching mechanism
Authors: Ullah Waseem , Khan Samee Ullah , Kim Min Je , Hussain Altaf , Munsif Muhammad , Lee Mi Young , Seo Daeho , Baik Sung Wook
Published: February 2024

The growing demand for high-quality industrial products has led to a significant emphasis on image anomaly detection (AD). AD in industrial goods presents a formidable research challenge that demands the application of sophisticated techniques to identify and address deviations from the expected norm accurately. Manufacturers increasingly recognize the significance of employing intelligent systems to detect flaws and defects in product parts. However, industrial settings pose several challenges: diverse categories, limited abnormal samples and vagueness. Hence, there is a growing demand for advanced image AD techniques within industrial product manufacturing. In this paper, an intelligent industrial defective chips detection framework is proposed which mainly consists of three core components. First, the convolutional features of the efficient backbone model is effectively utilized to balance the computational complexity and performance of industrial resource-constrained devices. Secondly, a novel inverse feature matching followed by masking method is proposed to enhance the explanability that localizes the abnormal regions of the abnormal chips. Finally, to evaluate our proposed method a comprehensive ablation study is conducted, where different machine learning and deep learning algorithms are analysed to claim the superiority of our method. Furthermore, to help the research community, a benchmark dataset is collected from real-world industry manufacturing for defective chip detection. The empirical results from the dataset demonstrate the strength and effectiveness of the proposed model compared to the other models.
Evaluating Acheta domesticus (Orthoptera: Gryllidae) for the reduction of fumonisin B1 levels in livestock feed
Authors: Paulk Ryan T , Abbas Hamed K , Rojas M Guadalupe , Morales-Ramos Juan , Busman Mark , Little Nathan , Shier W Thomas
Published: February 2024

Mycotoxins that contaminate grain can cause the devaluation of agricultural products and create health risks for the consumer. Fumonisins are one such mycotoxin. Produced primarily by Fusarium verticillioides (Hypocreales: Nectriaceae) (Nirenberg, 1976) on corn, fumonisins’ economic impact can be significant by causing various diseases in livestock if contaminated corn is not monitored and removed from animal feed. Finding safe alternatives to the destruction and waste of contaminated grain and restoring its economic value is needed for a sustainable future. Safe reintroduction into the farm food web may be possible through a consumable intermediary such as insects. This study demonstrates the suitability of the house cricket, Acheta domesticus L., as an alternative protein source in domestic animal feed by quantifying fumonisin B1 (FB1) levels in their subsequent insect meal and frass. Small colonies of 2nd instar A. domesticus were reared to 5th instar adults on nutrient-optimized corn-based diets treated with 4 levels of FB1 from 0 to 20 ppm. Increasing levels of FB1 had no adverse effects on the survivorship or growth of A. domesticus. Insect meals prepared from A. domesticus had significantly lower levels of FB1, at 3%–5% of their respective diets, while frass did not differ significantly from their diet. The successful rearing to adulthood of A. domesticus on fumonisin-contaminated diet paired with lower levels of FB1 in their processed insect meal supports the idea that more sustainable agricultural practices can be developed through remediation of low-value mycotoxin-contaminated grain with safer, higher-value insects as livestock feed components.
Round-up of China trade marks in 2023
Authors: Ferrante Michele
Published: February 2024

2023 was a challenging year globally, but China has continued to be attractive to foreign investors, due to its committment to the removal of restrictions on foreign investment and an emphasis on strengthening intellectual property laws so that they are favourable to right holders rather than infringers. The 2023 round-up focuses on the Draft 5th Amendment to the Trademark Law of China, which was published in January 2023. This article analyses the highlights of the Draft Amendment, which includes strengthened provisions relating to bad faith filings and an increased emphasis on the requirement that registered trademarks are actually used. The Draft, if implemented in full, will ensure that repeated filings of trademark applications will no longer be permitted, as well as providing greater protection for well-known marks and changes to procedural rules. The round-up will conclude that the Draft 5th Amendment will enhance the exisiting Trademark Law and further encourage brands to ionvest their business in China.
In vitro comparison of two food choice methodologies for necrophagous species of the genus Thanatophilus (Coleoptera: Staphylinidae: Silphinae)
Authors: Kadlec Jakub , Jakubec Pavel , Šípek Petr
Published: February 2024

To accurately model the food webs, we need to acquire precise data on food ecology of the interacting species. This allows better understanding of the trophic interactions and for the necrophagous species this information could be used in medico-legal investigations. For this reason, we recently proposed standardized laboratory methodology to assess the foraging strategies based on parallel testing of 2 food items (meat, dead larvae) (Jakubec et al. 2021). The original methodology had 2 shortcomings. It was not suited for testing living larvae, which could prove predatory behavior of the species. The methodology was also based on parallel experimental design, where the food items are tested together, which could underestimate the maximum consumption of the tested subject for some items. To test if these concerns are valid, we improved original methodology allowing testing living larvae as well as a new sequential experimental setup, where consumption of each item is tested individually in a random order, thus theoretically giving an unbiased maximum consumption estimate. These methodologies were tested head-to-head on 3 forensically relevant species from the genus Thanatophilus (Thanatophilus micans (Fabricius 1794)(Fabricius 1794), Thanatophilus rugosus (Linnaeus, 1758), and Thanatophilus sinuatus(Fabricius, 1775)). The experiments have confirmed that all 3 species are almost strictly necrophagous, although they were capable of predation, despite the presence of preferred food (meat). The comparison also showed that the sequential design has indeed improved capability to quantify the maximal consumption of the given food item. Thus, we suggest following this methodology in future studies.
The challenge of boredom in education: Kevin Hood Gary’s Why Boredom Matters
Authors: Scribner Campbell F
Published: February 2024

This essay explores the relationship between boredom, leisure, selfhood, and education in Kevin Hood Gary’s book, Why Boredom Matters, paying particular attention to connections between Aristotelian and existentialist approaches to the subject. Following Gary, the essay argues that schools force students to endure boredom or try to stimulate them with distractions, rather than helping them focus on enduring sources of meaning or cultivate stronger senses of self.
Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
Authors: Camprubí-Ferrer Daniel , Tomazatos Alexandru , Balerdi-Sarasola Leire , Cobuccio Ludovico G , Van Den Broucke Steven , Horváth Balázs , Van Esbroeck Marjan , Martinez Miguel J , Gandasegui Javier , Subirà Carme , Saloni Meritxell , Genton Blaise , Bottieau Emmanuel , Cadar Dániel , Muñoz Jose
Published: February 2024

Background

Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited.

Methods

Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM).

Results

Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.

Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.

Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications.

Discussion

mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.
First detection and modelling of spatially resolved Lyα in TW Hya
Authors: Chang Seok-Jun , Arulanantham Nicole , Gronke Max , Herczeg Gregory J , Bergin Edwin A
Published: February 2024

Lyman-α (Lyα) is the strongest emission line in the accretion-generated ultraviolet spectra from T Tauri stars and, as such, plays a critical role in regulating chemistry within the surrounding protoplanetary discs. Due to its resonant nature, the scattering of Lyα photons along the line of sight encodes information about the physical properties of the intervening H i medium. In this work, we present the first spatially resolved spectral images of Lyα emission across a protoplanetary disc in the iconic face-on T Tauri star TW Hya, observed with HST-STIS at spatial offsets 0, ±0.2, and ±0.4 arcsec. To comprehensively interpret these Lyα spectra, we utilize a 3D Monte Carlo Lyα radiative transfer simulation considering the H i wind and protoplanetary disc. From the simulation, we constrain the wind’s properties: the H i column density $\sim 10^{20} {\rm \, cm^{-2}}$ and the outflow velocity $\sim 200 {\rm \, km\, s^{-1}}$. Our findings indicate that successfully interpreting the observed spectra necessitates scattering contributions in the H i layer within the disc. Furthermore, to explore the effect of Lyα radiative transfer on protoplanetary disc chemistry, we compute the radiation field within the scattering medium and reveal that the wind reflection causes more Lyα photons to penetrate the disc. Our results show the necessity of spatially resolved Lyα observations of a broad range of targets, which will decode the complex interactions between the winds, protoplanetary discs, and surrounding environments.
A uGMRT search for radio emission from planets around evolved stars
Authors: Narang Mayank , Puravankara M , Chandra C H Ishwara , Banerjee Bihan , Tyagi Himanshu , Tamura Motohide , Henning Thomas , Mathew Blesson , Lazio Joseph , Surya Arun , Nayak Prasanta K
Published: February 2024

In this work, we present the results from a study using the Giant Meterwave Radio Telescope (GMRT) to search for radio emission from planets around three evolved stars namely α Tau, β UMi, and β Gem. Both α Tau and β UMi host massive ∼ 6 MJ mass planets at about ∼1.4 au from the central star, while β Gem is host to a 2.9 MJ mass planet at 1.7 au from the host star. We observe α Tau and β UMi at two upgraded GMRT bands: band 3 (250–500 MHz) and band 4 (550–900 MHz). We also analysed the archival observations from β Gem at 150 MHz from GMRT. We did not detect any radio signals from these systems. At 400 MHz, the 3σ upper limit is 87 μJy beam−1 for α Tau b and 77.4 μJy beam−1 for β UMi b. From our observations at 650 MHz, we place a 3σ upper limit of 28.2 μJy beam−1 for α Tau b and 33.6 μJy beam−1 for β UMi b. For β Gem b, at 150 MHz, we place an upper limit of 2.5 mJy. At 400 and 650 MHz, our observations are the deepest radio images for any exoplanetary system.
Dynamically coupled kinetic chemistry in brown dwarf atmospheres – II. Cloud and chemistry connections in directly imaged sub-Jupiter exoplanets
Authors: Lee Elspeth K H , Tan Xianyu , Tsai Shang-Min
Published: February 2024

With JWST slated to gain high-fidelity time-dependent data on brown dwarf atmospheres, it is highly anticipated to do the same for directly imaged, sub-Jupiter exoplanets. With this new capability, the need for a full three-dimensional (3D) understanding to explain spectral features and their time dependence is becoming a vital aspect for consideration. To examine the atmospheric properties of directly imaged sub-Jupiter exoplanets, we use the 3D Exo-FMS general circulation model to simulate a metal-enhanced generic young sub-Jupiter object. We couple Exo-FMS to a kinetic chemistry scheme, a tracer-based cloud formation scheme and a spectral radiative-transfer model to take into account the chemical and cloud feedback on the atmospheric thermochemical and dynamical properties. Our results show a highly complex feedback between clouds and chemistry on to the 3D temperature structure of the atmosphere, bringing about latitudinal differences and inducing time-dependent stormy features at photospheric pressures. This suggests a strong connection and feedback between the spatial cloud coverage and chemical composition of the atmosphere, with the temperature changes and dynamical motions induced by cloud opacity and triggered convection feedback driving chemical species behaviour. In addition, we also produce synthetic latitude-dependent and time-dependent spectra of our model to investigate atmospheric variability and periodicity in commonly used photometric bands. Overall, our efforts put the included physics in 3D simulations of exoplanets on par with contemporary 1D radiative-convective equilibrium modelling.
CDBProm: the Comprehensive Directory of Bacterial Promoters
Authors: Martinez Gustavo Sganzerla , Perez-Rueda Ernesto , Kumar Anuj , Dutt Mansi , Maya Cinthia Rodríguez , Ledesma-Dominguez Leonardo , Casa Pedro Lenz , Kumar Aditya , de Avila e Silva Scheila , Kelvin David J
Published: February 2024

The decreasing cost of whole genome sequencing has produced high volumes of genomic information that require annotation. The experimental identification of promoter sequences, pivotal for regulating gene expression, is a laborious and cost-prohibitive task. To expedite this, we introduce the Comprehensive Directory of Bacterial Promoters (CDBProm), a directory of in-silico predicted bacterial promoter sequences. We first identified that an Extreme Gradient Boosting (XGBoost) algorithm would distinguish promoters from random downstream regions with an accuracy of 87%. To capture distinctive promoter signals, we generated a second XGBoost classifier trained on the instances misclassified in our first classifier. The predictor of CDBProm is then fed with over 55 million upstream regions from more than 6000 bacterial genomes. Upon finding potential promoter sequences in upstream regions, each promoter is mapped to the genomic data of the organism, linking the predicted promoter with its coding DNA sequence, and identifying the function of the gene regulated by the promoter. The collection of bacterial promoters available in CDBProm enables the quantitative analysis of a plethora of bacterial promoters. Our collection with over 24 million promoters is publicly available at https://aw.iimas.unam.mx/cdbprom/
Anaplastic Lymphoma Kinase (ALK) Inhibitors Show Activity in Colorectal Cancer With ALK Rearrangements: Case Series and Literature Review
Authors: Hu Tingting , Zhan Jinbo , Li Li , He Yan , Lin Yun , Wang Jingru , Yu Haiming , Xiong Jianping , Fang Ziling , Deng Jun , Huang Shanshan , Xiang Xiaojun
Published: February 2024

Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene detected in approximately 5% of non–small cell lung cancer. However, ALK rearrangement is much less frequent in other solid tumors outside the lungs, such as colorectal cancer (CRC); thus, the optimal management of CRC with ALK rearrangements has yet to be established. In this report, we describe 2 cases of ALK-positive CRC, both of which benefited from ALK tyrosine kinase inhibitor (ALK-TKI) therapy. Case 1 was a postoperative patient with poorly differentiated colon adenocarcinoma, who was diagnosed with metastatic relapse shortly after surgery. Both fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab combined with 5-fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) proved ineffective against the disease. The patient was then treated with ensartinib, as the CAD-ALK fusion gene was detected by genomic analysis. The patient was initially treated with ensartinib monotherapy for 9 months, then with ensartinib combined with local radiotherapy and fruquintinib for another 4 months for isolated hilar hepatic lymph node metastasis. The patient experienced disease progression with an acquired ALK G1202R resistance mutation that responded well to lorlatinib. Case 2 involved a 72-year-old man with advanced colon cancer (pT4bN2aM1b, stage IV) harboring an EML4-ALK fusion. The patient underwent resection of the right colon tumor due to intestinal obstruction, but the disease continued to progress after 12 courses of FOLFIRI and bevacizumab chemotherapy. However, the patient responded remarkably well to alectinib. Our report emphasizes the importance of gene detection in the treatment of malignant tumors, and the significance of ALK mutations in CRC.
Adrenocortical Carcinomas: Molecular Pathogenesis, Treatment Options, and Emerging Immunotherapy and Targeted Therapy Approaches
Authors: Chukkalore Divya , MacDougall Kira , Master Viraj , Bilen Mehmet Asim , Nazha Bassel
Published: February 2024

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy in the advanced setting with poor prognosis. This narrative review provides an overview of the epidemiology of ACC and its molecular pathogenesis with a summary of the main involved signaling pathways. We then provide an update on the clinical presentation, diagnosis, and current management strategies of both localized and metastatic disease from a multidisciplinary perspective. We highlight the debate around the use of mitotane in the adjuvant setting and review the use of combination chemotherapy with etoposide, doxorubicin, and cisplatin. The review also focuses on emerging data providing hope for the use of immune checkpoint inhibitors and targeted therapies in ACC with a summary of ongoing trials.
An auxin research odyssey: 1989–2023
Authors: Cohen Jerry D , Strader Lucia C
Published: February 2024

The phytohormone auxin is at times called the master regulator of plant processes and has been shown to be a central player in embryo development, the establishment of the polar axis, early aspects of seedling growth, as well as growth and organ formation during later stages of plant development. The Plant Cell has been key, since the inception of the journal, to developing an understanding of auxin biology. Auxin-regulated plant growth control is accomplished by both changes in the levels of active hormones and the sensitivity of plant tissues to these concentration changes. In this historical review, we chart auxin research as it has progressed in key areas and highlight the role The Plant Cell played in these scientific developments. We focus on understanding auxin-responsive genes, transcription factors, reporter constructs, perception, and signal transduction processes. Auxin metabolism is discussed from the development of tryptophan auxotrophic mutants, the molecular biology of conjugate formation and hydrolysis, indole-3-butyric acid metabolism and transport, and key steps in indole-3-acetic acid biosynthesis, catabolism, and transport. This progress leads to an expectation of a more comprehensive understanding of the systems biology of auxin and the spatial and temporal regulation of cellular growth and development.
Not so hidden anymore: Advances and challenges in understanding root growth under water deficits
Authors: Voothuluru Priya , Wu Yajun , Sharp Robert E
Published: February 2024

Limited water availability is a major environmental factor constraining plant development and crop yields. One of the prominent adaptations of plants to water deficits is the maintenance of root growth that enables sustained access to soil water. Despite early recognition of the adaptive significance of root growth maintenance under water deficits, progress in understanding has been hampered by the inherent complexity of root systems and their interactions with the soil environment. We highlight selected milestones in the understanding of root growth responses to water deficits, with emphasis on founding studies that have shaped current knowledge and set the stage for further investigation. We revisit the concept of integrated biophysical and metabolic regulation of plant growth and use this framework to review central growth-regulatory processes occurring within root growth zones under water stress at subcellular to organ scales. Key topics include the primary processes of modifications of cell wall–yielding properties and osmotic adjustment, as well as regulatory roles of abscisic acid and its interactions with other hormones. We include consideration of long-recognized responses for which detailed mechanistic understanding has been elusive until recently, for example hydrotropism, and identify gaps in knowledge, ongoing challenges, and opportunities for future research.
Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis
Authors: Hum Christine , Tahir Usama , Mei Shirley H J , Champagne Josee , Fergusson Dean A , Lalu Manoj , Stewart Duncan J , Walley Keith , Marshall John , dos Santos Claudia C , Winston Brent W , Mendelson Asher A , Dave Chintan , McIntyre Lauralyn
Published: February 2024

Background

In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.

Objective

To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.

Methods

A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool.

Results

Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains.

Conclusions

These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.
Within-host evolution of SARS-CoV-2: how often are de novo mutations transmitted from symptomatic infections?
Authors: Korosec Chapin S , Wahl Lindi M , Heffernan Jane M
Published: February 2024

Despite a relatively low mutation rate, the large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has allowed for substantial genetic change, leading to a multitude of emerging variants. Using a recently determined mutation rate (per site replication), as well as within-host parameter estimates for symptomatic SARS-CoV-2 infection, we apply a stochastic transmission-bottleneck model to describe the survival probability of de novo SARS-CoV-2 mutations as a function of bottleneck size and selection coefficient. For narrow bottlenecks, we find that mutations affecting per-target-cell attachment rate (with phenotypes associated with fusogenicity and ACE2 binding) have similar transmission probabilities to mutations affecting viral load clearance (with phenotypes associated with humoral evasion). We further find that mutations affecting the eclipse rate (with phenotypes associated with reorganization of cellular metabolic processes and synthesis of viral budding precursor material) are highly favoured relative to all other traits examined. We find that mutations leading to reduced removal rates of infected cells (with phenotypes associated with innate immune evasion) have limited transmission advantage relative to mutations leading to humoral evasion. Predicted transmission probabilities, however, for mutations affecting innate immune evasion are more consistent with the range of clinically estimated household transmission probabilities for de novo mutations. This result suggests that although mutations affecting humoral evasion are more easily transmitted when they occur, mutations affecting innate immune evasion may occur more readily. We examine our predictions in the context of a number of previously characterized mutations in circulating strains of SARS-CoV-2. Our work offers both a null model for SARS-CoV-2 mutation rates and predicts which aspects of viral life history are most likely to successfully evolve, despite low mutation rates and repeated transmission bottlenecks.
The hidden world of fossil larvae: description and morphological insights of an immature scorpionfly (Mecoptera: Panorpidae) from the Baltic amber
Authors: Szpila Krzysztof , van de Kamp Thomas , Sontag Elżbieta , Krzemiński Wiesław , Kopeć Katarzyna , Soszyńska Agnieszka
Published: February 2024

So far, there has been no information of the pre-imaginal stages in the well-preserved fossil record of the Mecoptera. The first and well-preserved mecopteran larva was discovered in Eocene Baltic amber. The application of synchrotron X-ray microtomography enabled the reconstruction of the body structure with high accuracy, providing a comprehensive set of morphological data that classical stereoscopic microscopy could not capture. The larva is eruciform, with distinct segmentation of the body. All the most important morphological structures are documented, including the chaetotaxy system. Shape of antenna and annulated processes on the abdominal segments point to the third/four stage of development. There is no doubt that the larva belongs to Panorpidae, the most abundant family of extant Mecoptera. The morphological characters point to the closest affinity to larvae of Cerapanorpa and Panorpa but the fossil larva cannot be assigned to any extant genus of Panorpidae. Based on the results of synchrotron X-ray microtomography, it is possible to discuss the assignement of this larva to a lower systematic level than the family, and draw conclusions about the nature of the habitat preferences of Eocene panorpid.
Suppression of Hop Downy Mildew as Influenced by the Timing of Selected Fungicides
Authors: Richardson Briana J. , Gent David H.
Published: February 2024

Downy mildew of hop is a disease that is controlled by the implementation of cultural practices along with the application of fungicides, as there are few cultivars with high levels of resistance to this disease. We conducted studies in western Oregon to elucidate the effect of using synthetic fungicides of various modes of action early versus late in disease management programs when rotated with a copper-based fungicide. When analyzed over the 4 years of this study, there were independent effects from both the specific fungicide mode of action and application timing on disease control. The use of cymoxanil + copper hydroxide or mandipropamid in a program reduced the area under the disease progress curve by 66.3 or 59.7 units (17.7 or 19.6%), respectively, as compared with phosphorous acid. Using synthetic fungicides in the first two applications in a program provided better disease control than using the same fungicides in the third and fourth applications, reducing the area under the disease progress curve by 47.8 units (14.4%). By simply applying modes of action found to be more efficacious earlier in the growing season, the severity of downy mildew was reduced as much as 32% without increasing the total number of applications made.
μ-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats
Authors: Pereira-Silva Raquel , Teixeira-Pinto Armando , Neto Fani L. , Martins Isabel
Published: February 2024

Background

The dorsal reticular nucleus is a pain facilitatory area involved in diffuse noxious inhibitory control (DNIC) through opioidergic mechanisms that are poorly understood. The hypothesis was that signaling of μ-opioid receptors is altered in this area with prolonged chronic inflammatory pain and that this accounts for the loss of DNICs occurring in this condition.

Methods

Monoarthritis was induced in male Wistar rats (n = 5 to 9/group) by tibiotarsal injection of complete Freund’s adjuvant. The immunolabeling of µ-opioid receptors and the phosphorylated forms of µ-opioid receptors and cAMP response element binding protein was quantified. Pharmacologic manipulation of μ-opioid receptors at the dorsal reticular nucleus was assessed in DNIC using the Randall–Selitto test.

Results

At 42 days of monoarthritis, μ-opioid receptor labeling decreased at the dorsal reticular nucleus, while its phosphorylated form and the phosphorylated cAMP response element binding protein increased. [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate (DAMGO) enhanced DNIC analgesia in normal animals (means ± SD: pre-DNIC: 126.9 ± 7.0 g; DNIC − DAMGO: 147.5 ± 8.0 g vs. DNIC + DAMGO: 198.1 ± 19.3 g; P < 0.001), whereas it produced hyperalgesia in monoarthritis (pre-DNIC: 67.8 ± 7.5 g; DNIC − DAMGO: 70.6 ± 7.7 g vs. DNIC + DAMGO: 32.2 ± 2.6 g; P < 0.001). An ultra-low dose of naloxone, which prevents the excitatory signaling of the μ-opioid receptor, restored DNIC analgesia in monoarthritis (DNIC − naloxone: 60.0 ± 6.1 g vs. DNIC + naloxone: 98.0 ± 13.5 g; P < 0.001), compared to saline (DNIC − saline: 62.5 ± 5.2 g vs. DNIC + saline: 64.2 ± 3.8 g). When injected before DAMGO, it restored DNIC analgesia and decreased the phosphorylated cAMP response element binding protein in monoarthritis.

Conclusions

The dorsal reticular nucleus is likely involved in a facilitatory pathway responsible for DNIC hyperalgesia. The shift of μ-opioid receptor signaling to excitatory in this pathway likely accounts for the loss of DNIC analgesia in monoarthritis.

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Angioembolization Has Similar Efficacy and Lower Total Charges than Preperitoneal Pelvic Packing in Patients with Pelvic Ring or Acetabulum Fractures
Authors: Singh Aaron , Kotzur Travis , Koslosky Ezekial , Gonuguntla Rishi , Canseco Lorenzo , Momtaz David , Seifi Ali , Martin Case
Published: February 2024

OBJECTIVES:

To compare cost, hospital related outcomes, and mortality between angioembolization (AE) and preperitoneal pelvic packing (PPP) in the setting of pelvic ring or acetabulum fractures.

METHODS:

Design: Retrospective database review.

Setting:

The National Inpatient Sample, years 2016-2020.

Patient Selection Criteria:

Hospitalized adult patients who underwent AE or PPP in the setting of a pelvic ring or acetabulum fracture.

Outcome Measures and Comparisons: Mortality, and hospital associated outcomes, including total charges following AE versus PPP in the setting of pelvic ring or acetabulum fractures.

RESULTS:

A total of 3,780 patients, 3,620 undergoing angioembolization and 160 undergoing PPP were included. No significant differences in mortality, LOS, time to procedure, or discharge disposition were found (p>0.05); however, PPP was associated with significantly greater charges than angioembolization (p=0.04). Patients who underwent angioembolization had a mean total charge of $250,062.88, while those undergoing PPP had a mean of total charge of $369,137.16.

CONCLUSIONS:

Despite equivalent clinical efficacy in terms of mortality and hospital related outcomes, preperitoneal pelvic packing was associated with significantly greater charges than angioembolization in the setting of pelvic ring or acetabulum fractures. This data information can inform clinical management of these patients and assist trauma centers in resource allocation.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
External Validation of Deep Learning-Based Cardiac Arrest Risk Management System for Predicting In-Hospital Cardiac Arrest in Patients Admitted to General Wards Based on Rapid Response System Operating and Nonoperating Periods: A Single-Center Study
Authors: Cho Kyung-Jae , Kim Kwan Hyung , Choi Jaewoo , Yoo Dongjoon , Kim Jeongmin
Published: February 2024

OBJECTIVES:

The limitations of current early warning scores have prompted the development of deep learning-based systems, such as deep learning-based cardiac arrest risk management systems (DeepCARS). Unfortunately, in South Korea, only two institutions operate 24-hour Rapid Response System (RRS), whereas most hospitals have part-time or no RRS coverage at all. This study validated the predictive performance of DeepCARS during RRS operation and nonoperation periods and explored its potential beyond RRS operating hours.

DESIGN:

Retrospective cohort study.

SETTING:

In this 1-year retrospective study conducted at Yonsei University Health System Severance Hospital in South Korea, DeepCARS was compared with conventional early warning systems for predicting in-hospital cardiac arrest (IHCA). The study focused on adult patients admitted to the general ward, with the primary outcome being IHCA-prediction performance within 24 hours of the alarm.

PATIENTS:

We analyzed the data records of adult patients admitted to a general ward from September 1, 2019, to August 31, 2020.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Performance evaluation was conducted separately for the operational and nonoperational periods of the RRS, using the area under the receiver operating characteristic curve (AUROC) as the metric. DeepCARS demonstrated a superior AUROC as compared with the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), both during RRS operating and nonoperating hours. Although the MEWS and NEWS exhibited varying performance across the two periods, DeepCARS showed consistent performance.

CONCLUSIONS:

The accuracy and efficiency for predicting IHCA of DeepCARS were superior to that of conventional methods, regardless of whether the RRS was in operation. These findings emphasize that DeepCARS is an effective screening tool suitable for hospitals with full-time RRS, part-time RRS, and even those without any RRS.
Measuring Early Relational Health Using PediaTracTM in a Diverse Sample of Infant-Caregiver Dyads
Authors: Huth-Bocks Alissa , Franz Shannon , Berglund Patricia A. , Schroeder Heather M. , Staples Angela D. , Raghunathan Trivellore , Warschausky Seth , Taylor H. Gerry , LeDoux Gabrielle , Dieter Lesa , Rosenblum Katherine , Lajiness-O'Neill Renee ,   on behalf of The PediaTrac Consortiuma
Published: February 2024

Objective:

Early relational health (ERH) is a key developmental predictor and outcome in infancy and early childhood that reflects social-emotional well-being and promotes resilience throughout childhood. Currently, there is no gold-standard developmental screening tool for ERH in pediatric care settings. This study examined the psychometric properties of items assessing ERH that are part of a web-based, caregiver-report screening tool called PediaTracTM. It was hypothesized that ERH could be reliably estimated and that second-order factors would be revealed within the latent construct ERH.

Method:

Participants included 571 caregivers of term (n = 331; ≥37 weeks) and preterm (n = 240; <37 weeks) infants recruited shortly after birth from several academic medical centers and a community health clinic. Caregivers completed PediaTrac modules at birth and 2, 4, 6, 9, 12, 15, and 18 months; data for this study are from the newborn through 12-month periods.

Results:

Results from Item Response Theory Graded Response Modeling revealed excellent reliability for the PediaTrac ERH domain at all time points, ranging from 0.96 to 0.98. Exploratory factor analyses revealed 4 to 5 second-order factors, representing Parent-Child Relationship, Parent Distress, Parenting Stress, Parenting Efficacy, Sensitivity, and Perceptions of Child, depending on period.

Conclusion:

The caregiver-report developmental screening tool, PediaTrac, reliably measures ERH during the first year of life. The measure has promising clinical utility in pediatric clinic settings for tracking ERH over time to ensure early social-emotional well-being and to identify concerns as early as possible.
Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study
Authors: Walker Trent D. , Liao Yi-Tin , Nikahd Melica , Hyer Madison , Shahwan Kathryn T. , Carr David R.
Published: February 2024

BACKGROUND

Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage.

OBJECTIVE

To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC.

MATERIALS AND METHODS

A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome.

RESULTS

There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group.

CONCLUSION

Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.