bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic discovery of DNA-binding tandem repeat proteins
Authors: Hu Xiaoxuan , Zhang Xuechun , Sun Wen , Liu Chunhong , Deng Pujuan , Cao Yuanwei , Zhang Chenze , Xu Ning , Zhang Tongtong , Zhang Yong E , Liu Jun-Jie Gogo , Wang Haoyi
Published: August 2024

Tandem repeat proteins (TRPs) are widely distributed and bind to a wide variety of ligands. DNA-binding TRPs such as zinc finger (ZNF) and transcription activator-like effector (TALE) play important roles in biology and biotechnology. In this study, we first conducted an extensive analysis of TRPs in public databases, and found that the enormous diversity of TRPs is largely unexplored. We then focused our efforts on identifying novel TRPs possessing DNA-binding capabilities. We established a protein language model for DNA-binding protein prediction (PLM-DBPPred), and predicted a large number of DNA-binding TRPs. A subset was then selected for experimental screening, leading to the identification of 11 novel DNA-binding TRPs, with six showing sequence specificity. Notably, members of the STAR (Short TALE-like Repeat proteins) family can be programmed to target specific 9 bp DNA sequences with high affinity. Leveraging this property, we generated artificial transcription factors using reprogrammed STAR proteins and achieved targeted activation of endogenous gene sets. Furthermore, the members of novel families such as MOON (Marine Organism-Originated DNA binding protein) and pTERF (prokaryotic mTERF-like protein) exhibit unique features and distinct DNA-binding characteristics, revealing interesting biological clues. Our study expands the diversity of DNA-binding TRPs, and demonstrates that a systematic approach greatly enhances the discovery of new biological insights and tools.
Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors
Authors: Mindel Vladimir , Brodsky Sagie , Yung Hadas , Manadre Wajd , Barkai Naama
Published: August 2024

Activation domains (ADs) within transcription factors (TFs) induce gene expression by recruiting coactivators such as the Mediator complex. Coactivators lack DNA binding domains (DBDs) and are assumed to passively follow their recruiting TFs. This is supported by direct AD-coactivator interactions seen in vitro but has not yet been tested in living cells. To examine that, we targeted two Med15-recruiting ADs to a range of budding yeast promoters through fusion with different DBDs. The DBD-AD fusions localized to hundreds of genomic sites but recruited Med15 and induced transcription in only a subset of bound promoters, characterized by a fuzzy-nucleosome architecture. Direct DBD-Med15 fusions shifted DBD localization towards fuzzy-nucleosome promoters, including promoters devoid of the endogenous Mediator. We propose that Med15, and perhaps other coactivators, possess inherent promoter preference and thus actively contribute to the selection of TF-induced genes.
Cryo-EM structure of DNA polymerase of African swine fever virus
Authors: Kuai Lu , Sun Junqing , Peng Qi , Zhao Xuejin , Yuan Bin , Liu Sheng , Bi Yuhai , Shi Yi
Published: August 2024

African swine fever virus (ASFV) is one of the most important causative agents of animal diseases and can cause highly fatal diseases in swine. ASFV DNA polymerase (DNAPol) is responsible for genome replication and highly conserved in all viral genotypes showing an ideal target for drug development. Here, we systematically determined the structures of ASFV DNAPol in apo, replicating and editing states. Structural analysis revealed that ASFV DNAPol had a classical right-handed structure and showed the highest similarity to the structure of human polymerase delta. Intriguingly, ASFV DNAPol has a much longer fingers subdomain, and the thumb and palm subdomain form a unique interaction that has never been seen. Mutagenesis work revealed that the loss of this unique interaction decreased the enzymatic activity. We also found that the β-hairpin of ASFV DNAPol is located below the template strand in the editing state, which is different from the editing structures of other known B family DNAPols with the β-hairpin above the template strand. It suggests that B family DNAPols have evolved two ways to facilitate the dsDNA unwinding during the transition from replicating into editing state. These findings figured out the working mechanism of ASFV DNAPol and will provide a critical structural basis for the development of antiviral drugs.
Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach
Authors: Griffin Daniel O
Published: August 2024

While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after the acute period. Postviral fatigue syndromes are recognized with other viral infections and are described after coronavirus disease 2019 (COVID-19). We have a growing number of individuals with symptoms that persist for weeks, months, and years. Here, we share the evidence regarding the abnormalities associated with postacute sequelae of COVID-19 (PASC) and therapeutics. We describe physiological and biochemical abnormalities seen in individuals reporting PASC. We describe the several evidence-based interventions to offer patients. It is expected that this growing understanding of the mechanisms driving PASC and the benefits seen with certain therapeutics may not only lead to better outcomes for those with PASC but may also have the potential for understanding and treating other postinfectious sequelae.
Characteristics of Streptococcal Toxic Shock Syndrome Caused by Different Beta-hemolytic Streptococci Species: A Single-center Retrospective Study
Authors: Inada Makoto , Iwamoto Noriko , Nomoto Hidetoshi , Tsuzuki Shinya , Takemoto Norihiko , Fuwa Noriko , Moriya Ataru , Ohmagari Norio
Published: August 2024

Background

Streptococcal toxic shock syndrome (STSS) is a life-threatening condition caused by beta-hemolytic streptococci (BHS). Streptococcus pyogenes is the main causative agent of this disease; other BHS such as Streptococcus agalactiae or Streptococcus dysgalactiae could also cause STSS. However, the clinical characteristics of STSS caused by other types of BHS remain poorly understood. In this study, we evaluated the likelihood of STSS development in various streptococcal species.

Methods

We conducted a retrospective observational study using adult medical records of patients with invasive BHS in a tertiary care institution from 2002 to 2022 and classified them into STSS or non-STSS groups. Multivariable analysis of bacterial species adjusted for age and diabetes mellitus was conducted. S pyogenes cases were propensity-matched (1:4) to non-pyogenes BHS cases.

Results

A total of 43 STSS and 285 non-STSS cases were identified. S pyogenes, S agalactiae, and S dysgalactiae accounted for 17, 13, and 13 STSS cases, respectively. The crude mortality of STSS was approximately 35% in all groups. A multivariable analysis suggested that STSS was less frequent in S agalactiae and S dysgalactiae cases with odds ratio 0.24 (95% confidence interval [CI], 0.10–0.54; P < .001) and 0.23 (95% CI, .10–.55; P < .001), respectively. Propensity score matching showed that S pyogenes caused STSS more frequently than other BHS cases with an odds ratio of 3.28 (95% CI 1.21–8.77; P = .010).

Conclusions

This study described and compared the clinical characteristics of STSS caused by different BHS. We demonstrated that S pyogenes caused STSS more often than other BHS.
Evolution of Laboratory Diagnostics for Cryptococcosis and Missing Links to Optimize Diagnosis and Outcomes in Resource-Constrained Settings
Authors: Kwizera Richard , Kiiza Tadeo K , Akampurira Andrew , Kimuda Sarah , Mugabi Timothy , Meya David B
Published: August 2024

Cryptococcal meningitis is one of the leading causes of death in sub-Saharan Africa among patients with advanced HIV disease. Early diagnosis is crucial in improving treatment outcomes. Despite advances and the availability of modern and point-of-care diagnostics for cryptococcosis, gaps still exist in resource-constrained settings, leading to unfavorable treatment outcomes. Here, we review the current outstanding issues or missing links that need to be filled to optimize the diagnosis of cryptococcosis in resource-constrained settings to improve treatment outcomes. We highlight the evolution of cryptococcosis diagnostics; the roles of early fungicidal activity, cryptococcal antigen titers, antifungal susceptibility testing, and therapeutic drug monitoring; and the missing links to optimize diagnosis and outcomes, including practical recommendations.
Colo-colonic intussusception secondary to Burkitt lymphoma with concurrent malignant small bowel mesh adhesion
Authors: Ho Mei Jing , Syed Faisal , Wielebinski Wieslawa Mary , Galketiya Kamal
Published: August 2024

Intussusception is a rare presentation in adult population and usually occurs secondary to an underlying pathology. We report an unusual case of a 28-year-old female who developed a colo-colonic intussusception secondary to Burkitt lymphoma which was managed with an extended right hemicolectomy. The case was further complicated by a segment of small bowel with malignant adhesion to a prosthetic mesh requiring resection of the involved segment of small bowel. We have discussed the significance of this case as well as general considerations in the surgical management of adult intussusception.
Giant molecular clouds and their type classification in M 74: Toward understanding star formation and cloud evolution
Authors: Demachi Fumika , Fukui Yasuo , Yamada Rin I , Tachihara Kengo , Hayakawa Takahiro , Tokuda Kazuki , Fujita Shinji , Kobayashi Masato I N , Muraoka Kazuyuki , Konishi Ayu , Tsuge Kisetsu , Onishi Toshikazu , Kawamura Akiko
Published: August 2024

We investigated the giant molecular clouds (GMCs) in M 74 (NGC 628), using data obtained from the PHANGS (Physics at High Angular resolution in Nearby GalaxieS) project. We applied GMC types according to the activity of star formation: Type I without star formation, Type II with H$\alpha$ luminosity ($L_{\mathrm{H\alpha }}$) less than $10^{37.5}\ \rm{erg\ s ^{-1}}$, and Type III with $L_{\mathrm{H\alpha }}$ greater than $10^{37.5}\ \rm{erg\ s^{-1}}$. A total of 432 GMCs were identified, with 59, 201, and 172 GMCs, for Types I, II, and III, respectively. The size and mass of the GMCs range from 23 to 238 pc and $10^{4.9}$ to $10^{7.1}\, M_{\odot }$, indicating that the mass and radius increase from Types I to III. Clusters younger than 4 Myr and H ii regions are concentrated within 150 pc of a GMC, indicating a tight association between these young objects and GMCs. The virial ratio decreases from Type I to Type III, indicating that Type III GMCs are the most gravitationally relaxed among the three. We interpret that the GMCs evolve from Type I to Type III, as previously observed in the Large Magellanic Cloud. Based on a steady-state assumption, the estimated evolutionary timescales of Types I, II, and III are 1, 5, and 4 Myr, respectively. We assume that the timescale of Type III is equal to the age of the associated clusters, indicating a GMC lifetime of 10 Myr or longer. Although Chevance et al. (2020, MNRAS, 493, 2872) investigated GMCs using the same PHANGS dataset of M 74, they did not define a GMC, reaching an evolutionary picture with a 20 Myr duration of the non-star-forming phase, which is five times longer than 4 Myr. We compare the present results with those of Chevance et al. (2020, MNRAS, 493, 2872) and argue that defining individual GMCs is essential for understanding GMC evolution.
TaCAMTA4 negatively regulates H2O2-dependent wheat leaf rust resistance by activating catalase 1 expression
Authors: Sun Tianjie , Ma Nan , Jiao Yuanyuan , Wang Qian , Wang Qipeng , Liu Na , Chen Yan , Han Shengfang , Hou Chunyan , Wang Rongna , Wang Dongmei
Published: August 2024

Leaf rust, caused by Puccinia triticina Erikss. (Pt), is a serious disease threatening wheat (Triticum aestivum L.) production worldwide. Hydrogen peroxide (H2O2) triggered by Pt infection in resistant wheat cultivars cause oxidative damage directly to biomolecules or is activated by calcium signaling and mediates the hypersensitive response. Calmodulin-binding transcriptional activator 4 (TaCAMTA4) has been reported to negatively regulate wheat resistance to Pt. In this study, we found that TaCAMTA4 was induced by Pt race 165 in its compatible host harboring the Pt-resistant locus Lr26, TcLr26, and silencing of TaCAMTA4 increased local H2O2 accumulation and Pt resistance. Subcellular localization and autoactivation tests revealed that TaCAMTA4 is a nucleus-localized transcriptional activator. Furthermore, 4 DNA motifs recognized by TaCAMTA4 were identified by transcription factor-centered Y1H. Through analyzing the transcriptome database, 4 gene clusters were identified, each containing a different DNA motif on each promoter. Among them, the expression of catalase 1 (TaCAT1) with motif-1 was highly induced in the compatible interaction and was decreased when TaCAMTA4 was silenced. The results of electrophoretic mobility shift assay, ChIP-qPCR, and RT-qPCR further showed that TaCAMTA4 directly bound motif-1 in the TaCAT1 promoter. Furthermore, silencing of TaCAT1 resulted in enhanced resistance to Pt and increased local H2O2 accumulation in wheat, which is consistent with that of TaCAMTA4. Since calmodulin-binding transcription activators are Ca2+ sensors and catalases catalyze the decomposition of H2O2, we hypothesize that Ca2+ regulates the plant immune networks that are controlled by H2O2 and implicate a potential mechanism for Pt to suppress resistance by inducing the expression of the TaCAMTA4-TaCAT1 module, which consequently enhances H2O2 scavenging and attenuates H2O2-dependent resistance.
How can event attribution science underpin financial decisions on Loss and Damage?
Authors: Coumou Dim , Arias Paola A , Bastos Ana , Gonzales Charlotte Kendra Gotangco , Hegerl Gabriele C , Hope Pandora , Jack Christopher , Otto Friederike , Saeed Fahad , Serdeczny Olivia , Shepherd Theodore G , Vautard Robert
Published: August 2024

With climate extremes hitting nations across the globe, disproportionately burdening vulnerable developing countries, the prompt operation of the Loss and Damage fund is of paramount importance. As decisions on resource disbursement at the international level, and investment strategies at the national level, loom, the climate science community's role in providing fair and effective evidence is crucial. Attribution science can provide useful information for decision makers, but both ethical implications and deep uncertainty cannot be ignored. Considering these aspects, we articulate a vision that integrates established attribution methods and multiple lines of evidence within a coherent logical framework.
Predicting and understanding photocatalytic CO2 reduction reaction with IR spectroscopy-based interpretable machine learning framework
Authors: Wang Yanxia , Sun Yanjuan , Liu Xinyan , Dong Fan
Published: August 2024

The highly selective conversion of carbon dioxide into value-added products is extremely valuable. However, even with the aid of in situ characterization techniques, it remains challenging to directly correlate extensive spectral data carrying microscopic information with macroscopic performance. Herein, we adopted advanced machine learning (ML) approaches to establish an accurate and interpretable relationship between vibrational spectral signals and catalytic performances to uncover hidden physical insights. Focusing on photocatalytic CO2 reduction, our model is shown to effectively and accurately predict the CO production activity and selectivity based solely on the infrared (IR) spectral signals, the generalizability of which is additionally demonstrated with a new Bi5O7I photocatalytic system. More importantly, further model analysis has revealed a novel strategy to steer CO selectivity, the physical sanity of which is verified by a detailed reaction mechanism analysis. This work demonstrates the tremendous potential of machine-learned spectroscopy to efficiently identify reaction control factors, which can further lay the foundation for targeted optimization and reverse design.
Beyond monopole electrostatics in regulating conformations of intrinsically disordered proteins
Authors: Phillips Michael , Muthukumar Murugappan , Ghosh Kingshuk
Published: August 2024

Conformations and dynamics of an intrinsically disordered protein (IDP) depend on its composition of charged and uncharged amino acids, and their specific placement in the protein sequence. In general, the charge (positive or negative) on an amino acid residue in the protein is not a fixed quantity. Each of the ionizable groups can exist in an equilibrated distribution of fully ionized state (monopole) and an ion-pair (dipole) state formed between the ionizing group and its counterion from the background electrolyte solution. The dipole formation (counterion condensation) depends on the protein conformation, which in turn depends on the distribution of charges and dipoles on the molecule. Consequently, effective charges of ionizable groups in the IDP backbone may differ from their chemical charges in isolation—a phenomenon termed charge-regulation. Accounting for the inevitable dipolar interactions, that have so far been ignored, and using a self-consistent procedure, we present a theory of charge-regulation as a function of sequence, temperature, and ionic strength. The theory quantitatively agrees with both charge reduction and salt-dependent conformation data of Prothymosin-alpha and makes several testable predictions. We predict charged groups are less ionized in sequences where opposite charges are well mixed compared to sequences where they are strongly segregated. Emergence of dipolar interactions from charge-regulation allows spontaneous coexistence of two phases having different conformations and charge states, sensitively depending on the charge patterning. These findings highlight sequence dependent charge-regulation and its potential exploitation by biological regulators such as phosphorylation and mutations in controlling protein conformation and function.
Antibiotics in inflammatory arthritis and background population one year before and after diagnosis: a nationwide drug utilization study
Authors: Kragsnaes Maja S , Risbo Nickolaj , Pedersen Jens Kristian , Obel Niels , Finckh Axel , Pedersen Alma B , Ellingsen Torkell
Published: August 2024

Objectives

To describe antibiotic use in patients with inflammatory arthritis (IA) and in the background population (BP) within one year before and after IA diagnosis.

Methods

Using data from Danish nationwide registries, we identified all adults with a first-time diagnosis of RA, PsA, or AS/spondyloarthritis (AS/SpA) from 2010 through 2018. For each IA patient, we randomly sampled 10 persons from the BP, matched on sex and birthdate. We calculated the prevalence (n [%]) of any antibiotic dispensing and the total antibiotic dispensing in the year before and after diagnosis.

Results

We identified 28 504 new-onset IA patients (RA, n = 16 130; PsA, n = 5988; AS/SpA, n = 6386) and 285 040 BP individuals. Within one year before diagnosis, the total amount of dispensed antibiotics was higher in both RA, PsA and As/SpA compared with the BP (prevalence rate ratios [PRR], 1.48 [1.46; 1.51]; 1.67 [1.62; 1.72]; 1.52 [1.47; 1.56], respectively). The amount increased with 22% in IA patients three months before diagnosis compared with the preceding three-month period.  Although the prevalence of any antibiotic dispensing in IA patients decreased in the year following the diagnosis (IA; 40.6%), the total one-year antibiotic dispensing remained constant in RA (PRR 0.99 [0.97; 1.01]), decreased in PsA (0.91 [0.87; 0.94]) and increased in AS/SpA (1.08 [1.04; 1.12]) patients after diagnosis compared with before.

Conclusion

Antibiotics are more frequently dispensed to individuals developing IA compared with the BP. Antibiotic utilization patterns change after IA diagnosis with marked differences among IA subgroups.
Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians
Authors: Song Yingchao , Li Linzehao , Jiang Yue , Peng Bichen , Jiang Hengxuan , Chao Zhen , Chang Xiao
Published: August 2024

Background and Hypothesis

While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited.

Study Design

To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via a multitrait genome-wide association study. Global and local genetic correlations were estimated by LDSC and ρ-HESS. Pleiotropic loci were identified by the multitrait analysis of GWAS (MTAG).

Study Results

Besides the significant correlation between depression and SCZ, our analysis revealed genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Further multitrait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ.

Conclusions

Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.
Effects of Plant Health-Protecting Product Applications on the Root-Associated Microbiota of Apple Saplings and Strawberries
Authors: Becker Maximilian F. , Deichmann Marion , Klueken A. Michael , Knief Claudia
Published: August 2024

The root-associated microbiome has been of keen research interest due to its large potential for increasing plant performance. In agricultural systems, the use of plant health-protecting products (PHPPs) is essential for obtaining high yields and quality. Knowledge about the impact of PHPP applications on the root-associated microbiome remains limited, especially when applied aboveground. We hypothesized that PHPP application leads to specific plant-mediated responses in the rhizosphere microbiota. We applied different PHPPs on greenhouse-grown apple and strawberry plants, cultivated in different soils. The effects of aboveground PHPP applications on the root-associated microbiota were analyzed by 16S rRNA gene amplicon sequencing. No consistent effects were observed across three experimental trials, although alpha diversity tended to be decreased after PHPP application. In some cases, shifts in community composition (PERMANOVA R2 = 0.192, P = 0.001) or increases in dispersion (PERMDISP Padj  = 0.040) became evident. Movento treatments caused, in part, deterministic shifts in community assembly, whereas Serenade ASO treatments caused rather stochastic shifts. Effects were concluded to be probably transient and to disappear without continuous product application. These rather heterogenous temporary responses are in line with the concept of the “Anna Karenina principle,” under which terms PHPP applications can act as mild stress factors and slightly and transiently alter the belowground bacterial community. These findings indicate that aboveground PHPP applications can have product-specific implications for the root-associated microbiome, which should be considered in the context of microbiome management strategies.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Effect of Barley Yellow Dwarf Virus (BYDV) on Barley: A Precise Assessment of Reductions in Yield Components Under Variable Disease Severities
Authors: Zhao Chenchen , Zhou Meixue
Published: August 2024

Understanding the effects of barley yellow dwarf virus (BYDV) on crop agronomic traits and yield performance helps breeders balance their selection criteria and farmers decide if pesticides should be applied to control aphids that distribute the virus. To precisely assess the deterioration of different agronomic traits and yield components caused by different levels of BYDV infection, seeds of a BYDV-sensitive barley cultivar RGT Planet were space sown in a field plot with 10 cm between seeds and 20 cm between rows under two consecutive years. When BYDV symptoms were shown, plants with different levels (0 to 5) of BYDV infection were tagged. For accurate comparisons, the neighboring non/less-infected plants were also tagged. At maturity, different agronomic traits and yield components were measured on those tagged plants. Results showed a strong linear correlation between BYDV severity and the performance of agronomic traits and yield components. The yield reductions ranged from 30% for the least affected (score of 1) to 90% for the severely affected (score of 5). Our research confirmed previous findings that BYDV seriously affects crop yield and the prediction of yield loss due to BYDV infection should use the percentage of plants with different BYDV symptoms.
Penicillium Species Associated with Postharvest Blue Mold Rots of Garlic in Serbia
Authors: Stošić Stefan , Ristić Danijela , Trkulja Nenad , Živković Svetlana
Published: August 2024

Garlic (Allium sativum L.) is an important plant because of its medicinal and gastronomical benefits. The host can be affected by different plant pathogens, among which Penicillium species are one of the most important rot agents of stored garlic and other stored food products. This research resolves the etiology of blue mold rots associated with garlic in Serbia. Penicillium-like isolates were collected (2016 to 2022) from diseased stored garlic bulbs in Serbia and identified using a polyphasic approach. Detailed characterization of the obtained cultures was performed using three solid media, three incubation temperatures, molecular and phylogenetic analyses of four molecular loci (internal transcribed spacer [ITS], beta-tubulin [BenA], calmodulin [CaM], and DNA-dependent RNA polymerase II second largest subunit [RPB2]), and the pathogenicity assay. Five Penicillium species, that is, P. allii, P. glabrum, P. italicum, P. polonicum, and P. psychrotrophicum, were identified and confirmed as postharvest pathogens of garlic. Herein, we report for the first time the pathogenicity of P. psychrotrophicum and P. italicum on garlic. Findings from this study provide insights into the previously unknown diversity of Penicillium fungi responsible for garlic bulb decay in Serbia and will help in the assessment of the phytosanitary status of this crop, as well as the creation and application of effective disease management strategies.
Progression of Gummy Stem Blight Epidemics on Watermelon With and Without Fungicide Inputs
Authors: Keinath Anthony P. , Anco Daniel J.
Published: August 2024

Gummy stem blight (GSB), caused primarily by the fungus Stagonosporopsis citrulli in the Southeastern United States, affects cucurbits and is particularly destructive on watermelon. Previous epidemiological models of GSB constructed for greenhouse cucumber showed leaf wetness and temperature were the primary and secondary environmental factors, respectively, that explained epidemic progress. The objective of this study was to construct a model that predicted GSB severity on field-grown watermelon based on environmental factors. Disease and weather data from six fungicide experiments in Charleston, South Carolina, in the spring and fall of 1997 and the fall seasons of 2017, 2018, 2019, and 2022 were used as inputs. Fungicide treatments were grouped into nonsprayed, protectant (chlorothalonil and mancozeb), and GSB-specific (cyprodinil, difenoconazole, and fludioxonil) applications. Cumulative hours of leaf wetness were the primary explanatory variable that modeled the increase in proportion GSB severity ≥2% across all epidemics. Incorporation of temperature or other environmental variables did not improve the model. Fit of the overall model was evaluated with k-fold cross-validation, where individual experiments were each excluded from the model-fitting process. Slopes of predicted disease progress curves were lowered significantly compared with the nonsprayed treatments by applications of protectant fungicides. Applying GSB-specific fungicides alternated with chlorothalonil further reduced slope values. The model successfully predicted progress of GSB epidemics under different weather patterns and fungicide applications.
Searching for Laurel Wilt Resistance in Avocados of Mexican and Mexican-Guatemalan Ancestry
Authors: Navia-Urrutia Monica , Sendoya-Corrales Carlos A. , Espindola-Barquera Maria C. , Barrientos-Priego Alejandro F. , Ochoa-Ascencio Salvador , Crane Jonnathan H. , Gazis Romina
Published: August 2024

Laurel wilt (LW), a lethal vascular disease caused by the ambrosia fungus Harringtonia lauricola, has severely reduced avocado (Persea americana Mill.) production in Florida and decimated populations of native lauraceous trees across 12 U.S. states. All commercial avocado cultivars evaluated to date succumb to the disease, but the speed at which the tree declines varies. Cultivars with West Indian (WI) genetic background develop severe symptoms faster than those with Mexican (M) and Guatemalan (G) pedigree. Genetic resistance to LW is urgently needed, because management relies on costly cultural practices. We screened noncommercial open-pollinated progenies from 19 M and 6 M × G accessions, and 2 G × WI cultivars recognized as tolerant by growers. From the five disease response parameters evaluated, the final disease intensity index and disease severity on the last evaluation day were used to classify genotypes. A wide variability of responses was observed within and among families. Symptomatic plants were present in all families, although some individuals within the 15 families remained asymptomatic. The ‘Colín V-33’ (M × G) family was identified as tolerant, and the Libres 3 (M), Bladimiro M-06 (M), ‘Colinmex’ (M × G), ‘Collinson’ (G × WI), Libres 5 (M), and Rag-13 (M) families were classified as moderately tolerant. This is the first time tolerance to LW in avocado is formally reported, although the surviving material needs to be propagated for response validation and field testing. Identifying tolerant accessions can help understand the underlying mechanisms and provide breeders with genetic resources for the future incorporation of resistance genes into commercial cultivars.
Diffusible Signal Factor-Mediated Quorum Sensing Modulates Swarming in Xanthomonas albilineans
Authors: Li Meilin , Bao Yixue , Chen Wenhan , Li Yisha , Du Jinxia , Khan Abdullah , Khan Muhammad Tahir , Powell Charles A. , Chen Baoshan , Zhang Muqing
Published: August 2024

Xanthomonas spp. are plant pathogens known for significantly impacting crop yields. Among them, Xanthomonas albilineans ( Xal) is notable for colonizing the xylem and causing sugarcane leaf scald disease. This study employed homologous recombination to mutate quorum sensing regulatory genes ( rpf) to investigate their role in Xal pathogenicity. Deletions of rpfF (Δ rpfF), rpfC (Δ rpfC), and rpfG (Δ rpfG) led to reduced swarming, growth, and virulence. However, diffusible signal factor (DSF) supplementation restored swarming and growth in the Δ rpfF mutant. Deleting rpfC, rpfG, and rpfF also reduced twitching motility and affected type IV pilus expression. Transcriptomic analysis revealed that Δ rpfF positively regulates flagellar genes. DSF supplementation in Δ rpfF (Δ rpfF-DSF) modulated the expression of flagellar, chemotaxis, and type IV pilus genes. These findings elucidate the DSF-mediated swarming pathway in Xal and provide valuable insights into its regulatory mechanisms.
Lipomatous hypertrophy of the interatrial septum
Authors: Rullo Christine
Published: August 2024

Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare but benign cardiac tumor that can be found on cardiac imaging such as echocardiogram, or during surgery or an autopsy. Cardiac MRI is the best imaging modality to determine the borders of the tumor and its extension into the intraventricular septum and ventricular free wall. Patients require close monitoring because LHIS may cause right or left outflow tract obstruction or superior vena cava obstruction, requiring cardiac surgical intervention. This article describes a patient with LHIS who underwent cardiac surgery because of her increasing symptomatology.
Training and Sustaining: Training and Learning Collaborative Outcomes Across a Statewide Network for Early Autism Diagnosis
Authors: McNally Keehn Rebecca , Paxton Angela , Delaney Mary , Ciccarelli Mary
Published: August 2024

Objective:

The objective of this study was to describe the development of a primary care professional (PCP) autism diagnosis training model and to report on outcomes related to PCP training and sustained engagement in a longitudinal learning collaborative.

Methods:

We developed Accelerating the Diagnosis of Autism with Primary care Training (ADAPT), a training program to prepare PCPs to develop independent competency in evaluation of autism in children aged 14 to 48 months. ADAPT includes didactic and case-based modules and practice-based coaching delivered by an expert diagnostic specialist; after training, PCPs participate in a longitudinal learning collaborative. Aligned with competency-based medical education standards, measures of autism evaluation knowledge and diagnostic competency are collected.

Results:

From 2021 to 2023, 13 PCPs completed ADAPT didactic and practicum training to reach competency in independent autism evaluation. Clinicians demonstrated significant improvement in total autism knowledge after didactic training (p = 0.02). Scoring agreement on an autism observational assessment tool between clinicians and expert diagnosticians improved over case observations and practicum evaluations. Similarly, PCPs demonstrated improved evaluation competence, moving on average from Advanced Beginner to Competent Performer as rated by expert diagnosticians. After training, PCPs attended 57% of monthly learning collaborative sessions.

Conclusion:

Training PCPs to deliver autism evaluations for young children as part of tiered community-based models of care is a promising solution to address access and waitlist challenges. ADAPT is an intensive, standardized PCP training model that results in achievement of independent competency and sustained engagement in autism evaluation. Effectiveness-implementation studies are needed to ensure scalability and sustainability of training models.
The level of glucose in pancreatic cyst fluid is more accurate than carcinoembryonic antigen to identify mucinous tumors: A French multicenter study
Authors: Williet Nicolas , Caillol Fabrice , Karsenti David , Abou-Ali Einas , Camus Marine , Belle Arthur , Chaput Ulriikka , Levy Jonathan , Ratone Jean-Philippe , Tournier Quentin , Grange Rémi , Le Roy Bertrand , Becq Aymeric , Phelip Jean-Marc
Published: August 2024

Background and Objectives

Pancreatic cyst fluid level of glucose is a promising marker to identify mucinous from nonmucinous tumors, but the glucose assay has not yet been recommended. The objective of this study is to compare the diagnostic performances of pancreatic cyst fluid level of glucose and carcinoembryonic antigen (CEA).

Methods

In this French multicenter study, data of consecutive patients who underwent fine-needle aspiration of pancreatic cyst with intracyst glucose assay between 2018 and 2022 were retrospectively reviewed. The area under the receiver operating characteristic curve (AUROC) of glucose and corresponding sensitivity (Se), specificity (Sp), accuracy (Acc), positive predictive value (PPV), and negative predictive value (NPV) were calculated and compared with those of CEA. The best threshold of glucose was identified using the Youden index.

Results

Of the 121 patients identified, 81 had a definitive diagnosis (46 mucinous, 35 nonmucinous tumors) and were included for analysis. An intracystic glucose level <41.8 mg/dL allowed identification of mucinous tumors with better diagnostic performances (AUROC, 93.6%; 95% confidence interval, 87.2%–100%; Se, 95.3%; Sp, 91.2%; Acc, 93.5%; PPV, 93.2%; NPV, 93.9%) compared with CEA level >192 ng/mL (AUROC, 81.2%; 95% confidence interval, 71.3%–91.1%; Se, 41.7%; Sp, 96.9%; Acc, 67.6%; PPV, 93.8%; NPV, 59.6%) (P = 0.035). Combining values of glucose and CEA did not offer additional benefit in terms of diagnosis.

Conclusion

Our results confirm previously published data and support the use of pancreatic cyst fluid glucose for the identification of mucinous tumors when the definitive diagnosis remains uncertain.
Female and male factors that impact on frequency of sexual intercourse in aging couples: a cross-sectional study
Authors: Pio Janaina , Valadares Ana Lucia , Costa Paiva Lúcia
Published: August 2024

Objectives

To assess the prevalence and factors associated with dyspareunia and the lack of sexual intercourse in women between 50 and 70 years cohabiting with their partners.

Methods

This is a descriptive and exploratory cross-sectional study using the snowball technique with prospective data collection using a structured questionnaire to describe multiple aspects of health and sexuality among 266 cohabiting Brazilian couples aged 50 to 70.

Results

The prevalence of lack of sexual activity was 20%. Factors associated with sexual inactivity were female sexual dysfunction (OR: 9.87, 95% CI: 3.24‐30.10, P < 0.001), female dissatisfaction with the partner as a lover (OR: 5.86, 95% CI: 2.03‐16.88, P = 0.001), male sexual dysfunction (OR: 4.51, 95% CI: 1.60‐12.70, P = 0.004), and poor self-rated male health (OR: 3.66, 95% CI: 1.29‐10.40, P = 0.015). The prevalence of dyspareunia was 42.3% in the sample of sexually active women. Factors associated with dyspareunia were female sexual dysfunction (OR: 2.7, 95%, CI: 1.26‐5.77, P = 0.010), moderate/severe vaginal dryness (OR: 4.67, 95% CI: 2.21‐9.87, P < 0.001), and vaginal discomfort (OR: 4.03, 95% CI: 1.77‐9.17, P < 0.001).

Conclusions

The results showed that male, female, and dyadic factors were associated with a lack of sexual activity. On the other hand, only female factors were associated with dyspareunia among sexually active couples.
Human-induced pluripotent stem cell–based hepatic modeling of lipid metabolism–associated TM6SF2-E167K variant
Authors: Faccioli Lanuza A.P. , Sun Yiyue , Animasahun Olamide , Motomura Takashi , Liu Zhenghao , Kurihara Takeshi , Hu Zhiping , Yang Bo , Cetin Zeliha , Baratta Annalisa M. , Shankaran Ajay , Nenwani Minal , Altay Leyla Nurcihan , Huang Linqi , Meurs Noah , Franks Jonathan , Stolz Donna , Gavlock Dillon C. , Miedel Mark T. , Ostrowska Alina , Florentino Rodrigo M. , Fox Ira J. , Nagrath Deepak , Soto-Gutierrez Alejandro
Published: August 2024

Background and Aims:

TM6SF2 rs58542926 (E167K) is related to an increased prevalence of metabolic dysfunction–associated steatotic liver disease. Conflicting mouse study results highlight the need for a human model to understand this mutation’s impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies.

Approach and Results:

We used gene editing on human-induced pluripotent stem cells from a healthy individual to create cells with the TM6SF2-E167K mutation. After hepatocyte-directed differentiation, we observed decreased TM6SF2 protein expression, increased intracellular lipid droplets, and total cholesterol, in addition to reduced VLDL secretion. Transcriptomics revealed the upregulation of genes involved in lipid, fatty acid, and cholesterol transport, flux, and oxidation. Global lipidomics showed increased lipid classes associated with endoplasmic reticulum (ER) stress, mitochondrial dysfunction, apoptosis, and lipid metabolism. In addition, the TM6SF2-E167K mutation conferred a proinflammatory phenotype with signs of mitochondria and ER stress. Importantly, by facilitating protein folding within the ER of hepatocytes carrying TM6SF2-E167K mutation, VLDL secretion and ER stress markers improved.

Conclusions:

Our findings indicate that induced hepatocytes generated from human-induced pluripotent stem cells carrying the TM6SF2-E167K recapitulate the effects observed in human hepatocytes from individuals with the TM6SF2 mutation. This study characterizes an in vitro model that can be used as a platform to identify potential clinical targets and highlights the therapeutic potential of targeting protein misfolding to alleviate ER stress and mitigate the detrimental effects of the TM6SF2-E167K mutation on hepatic lipid metabolism.
Long-term Visual Acuity Outcomes of Deep Sclerectomy in Pediatric Glaucoma
Authors: Alkhalifah Muhannad I. , Mousa Ahmed , Al Obeidan Saleh A.
Published: August 2024

Précis:

This study provides evidence of the long-term efficacy and safety of deep sclerectomy as a successful surgical intervention option in cases with childhood glaucoma.

Objectives:

The primary objective was to evaluate the long-term visual acuity outcomes of deep sclerectomy in pediatric glaucoma and identify factors predicting poor prognosis. The secondary objective was to evaluate the long-term success rate of deep sclerectomy in controlling intraocular pressure (IOP).

Methods:

A retrospective review was conducted of all pediatric patients who underwent deep sclerectomy at King Abdulaziz University Hospital (KAUH) between 2001 and 2016. We included all patients who had valid visual acuity tests. The preoperative findings and long-term visual and IOP outcomes were analyzed.

Results:

A total of 83 eyes of 68 patients were included. The mean (SD) age of participants was 11.1 (4.0) years (range: 5–25 y). The mean age at surgery was 5.9 months, and the mean follow-up period was 10.75 years. The majority of cases (83.1%) were primary congenital glaucoma. Visual acuity was ≥20/40 in 56.6% of cases, ranged between 20/40 and 20/200 in 18.1%, and was ≤20/200 in 25.3% of the operated eyes. Complete success rate (IOP ≤21 mm Hg without medications) after one surgery was achieved in 53 eyes (63.86%). Qualified success rate (IOP ≤21 mm Hg with medications) was achieved in 8 eyes (9.6%), while 22 eyes (26.5%) failed to achieve the target IOP of ≤21 mm Hg or needed additional surgery to achieve it. Nine eyes (10.74%) had postoperative complications.

Conclusion:

Deep sclerectomy is a reasonable option for pediatric glaucoma that can provide good long-term visual outcomes and IOP control with a lower risk of surgical complications.
Caregiving Ability of Mothers of Children With Cancer: Qualitative Content Analysis
Authors: Abbasnezhad Masoomeh , Rassouli Maryam , Nasrabadi Tahereh , Nasrollah Sepideh
Published: August 2024

Background

Childhood cancer confronts the child and the parents with considerable degrees of stress. Because caring for the child is mainly the role of the mother in most families, her ability to take care of the affected child is very important.

Objective

To explore the caregiving ability of Iranian mothers who have children diagnosed with cancer.

Methods

In this present study, which was conducted using the Directed Qualitative Content Analysis Method, 11 parents having children diagnosed with cancer and 5 professional caregivers working at the Department of Hematology and Oncology of Mofid Children Hospital in Tehran, Iran, were selected using purposeful sampling method. Data were collected through semistructured interviews. Data analysis was performed simultaneously with data collection using the Directed Content Analysis Approach.

Results

Five main categories emerged, namely, care exhaustion, care confusion, spiritual conflict, care competence, and care preparedness that represent the beneficiaries’ perception of the caring ability of Iranian mothers of cancer-afflicted children.

Conclusion

Study results revealed that the caregiving capacity of mothers nurturing cancer-stricken children can be evaluated across 5 domains, encompassing a spectrum of maternal requirements in child care. Improving these domains can elevate maternal caregiving proficiency, fostering self-care and enhancing care for the ailing child.

Implication for Practice

A program can be developed based on the findings of the present study, in order to improve the caring ability of mothers of cancer-afflicted children, which results in improving the mother’s care for her cancer-afflicted child.
Comparison of the BIG Score and Pediatric Trauma Score for Predicting Mortality
Authors: Az Adem , Dogan Yunus , Sogut Ozgur , Akdemir Tarik
Published: August 2024

Objectives

The BIG score (base deficit + [2.5 × international normalized ratio] + [15 – Glasgow Coma Score]) was compared with the Pediatric Trauma Score (PTS) for predicting mortality in pediatric patients with multiple trauma.

Methods

This retrospective, single-center study included 318 consecutive pediatric patients (aged 1–18 years) with multiple trauma who were admitted to the emergency department between January 1, 2021, and December 31, 2023. The demographic characteristics, clinical characteristics, and trauma scores (BIG score and PTS) were compared between survivors and nonsurvivors to identify factors associated with mortality.

Results

A PTS of 7 had 100% sensitivity and 81.03% specificity for predicting mortality, with an area under the curve of 0.97 (95% confidence interval 0.9–0.99). Although the positive predictive value (PPV) was low (33.7%), the negative predictive value (NPV) was 100%. A BIG score of 13.7 was identified as the cutoff for mortality, with 92.86% sensitivity and 95.52% specificity (area under the curve 0.98, 95% confidence interval 0.96–0.99). The PPV was 66.7% and the NPV was 99.3%.

Conclusions

Both the PTS and the BIG score were strong predictors of mortality in pediatric patients with multiple trauma. The BIG score had a higher specificity and PPV, whereas a PTS of 7 had 100% sensitivity and a higher NPV.