bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of a novel parahenipavirus from northern short-tailed shrews (Blarina brevicauda[Say, 1823])
Authors: Imai Sakiho , Kishimoto Mai , Horie Masayuki
Published: October 2024

Parahenipaviruses (genusParahenipavirus) are non-segmented negative strand RNA viruses belonging to the familyParamyxoviridaeof the orderMononegavirales. Parahenipaviruses have been detected from shrews and rodents, some of which have been reported to be associated with human diseases. Although many parahenipaviruses have been identified thus far, there still exist large phylogenetic gaps in parahenipaviruses, suggesting the existence of yet-to-be-identified parahenipaviruses. In this study, we analyzed public RNA-seq data and identified a novel parahenipavirus from northern short-tailed shrews (Blarina brevicauda[Say, 1823]), tentatively named Blarina brevicauda virus (BbV). Based on sequence comparisons between BbV and its most closely related viruses, which meet the International Committee on Taxonomy of Viruses species demarcation criteria, we propose that BbV is a novel species of virus in the genusParahenipavirus. Furthermore, mapping analysis using RNA-seq data derived from multiple tissues of northern short-tailed shrews suggested that BbV is kidney-tropic. This study provides novel insights into the diversity of parahenipaviruses, which would contribute to a deeper understanding of their evolution and control of infectious diseases.
Cytomegalovirus Restricts the Innate Immune Response by Nuclear Export of Host Restriction Factor DDX41
Authors: Baruah Vargab , O’Connor Christine M.
Published: October 2024

The innate immune response is the first line of defense against invading pathogens, including the betaherpesvirus, human cytomegalovirus (CMV). The host’s innate response acts as the first line of defense, and CMV, like other viruses, has consequently evolved multiple mechanisms to manipulate host interferon (IFN) responses. DEAD-box Helicase 41 (DDX41) is an intracellular dsDNA sensor that, upon activation by Bruton’s tyrosine kinase (BTK), triggers type I IFN production through the Stimulator of Interferon Genes (STING) signaling pathway. Here, we show the activation of this signaling pathway during lytic CMV infection, wherein BTK, DDX41, and STING are activated through tyrosine phosphorylation, and both DDX41 and BTK interact with STING. Further, CMV infection re-localizes DDX41 from the nucleus to the cytoplasm, where it localizes to the perinuclear virus assembly compartment (vAC). Here, DDX41 phosphorylation is attenuated, suggesting cytoplasmic redistribution leads to a less active or inactive form. Additionally, DDX41 co-localizes in the vAC with the CMV tegument proteins, pp65 and pp71, each of which interact with DDX41 in immunoprecipitation assays. We further demonstrate the protective role of this signaling pathway, as treatment with the BTK inhibitor, orelabrutinib, attenuates DDX41 phosphorylation/activation and supports increased expression of viral proteins and virus replication. In sum, our work highlights the important role of BTK-DDX41-STING signaling in the innate immune response against CMV, which the virus subverts by attenuating its cytoplasmic activity, thereby diverting it from its typically protective function.

Importance

Human cytomegalovirus (CMV) is a ubiquitous pathogen that poses a significant threat to immunocompromised individuals, highlighting the critical role of innate immunity in controlling this viral infection. Despite extensive research, the complex mechanisms underlying innate immunity against CMV and the virus’s strategies for evading immune detection remain only partially understood. This study identifies the activation of the cellular BTK-DDX41-STING innate signaling axis during lytic CMV infection, which ultimately results in protective interferon responses. Our findings show that CMV infection triggers the cytoplasmic redistribution of the cellular protein, DDX41, leading to reduced phosphorylation and activity, thereby undermining its protective function. Additionally, pharmacological inhibition of BTK enhances viral protein expression and replication, highlighting the importance of this pathway in immune defense. Our work identifies BTK- and DDX41-dependent STING signaling as important for innate immune responses against CMV and further advances our understanding of CMV’s manipulation of these responses.
Secreted spermidine synthase reveals a paracrine role for PGC1α-induced growth suppression in prostate cancer
Authors: Schaub-Clerigué Ariane , Hermanova Ivana , Pintor-Rial Ainara , Macchia Alice , Valcarcel-Jimenez Lorea , Lectez Benoit , Garcia-Longarte Saioa , Fagoaga-Eugui Maider , Zabala-Letona Amaia , Pujana-Vaquerizo Mikel , Royo Félix , Azkargorta Mikel , Berra Edurne , Sutherland James D. , Peinado Héctor , Falcón-Perez Juan Manuel , Elortza Félix , Carracedo Arkaitz , Torrano Verónica
Published: October 2024

Prostate cancer is the fifth cause of death by cancer worldwide, second in incidence in the male population. The definition of the molecular basis of its development and the oncogenic signals driving lethality continue to be important objectives in prostate cancer research. Prior work from others and us has demonstrated that loss of PGC1α expression results in a metabolic, signaling and transcriptional reprogramming that supports the development of metastatic disease. However, we do not fully understand the spectrum of tumor suppressive effects regulated by this co-regulator. Here we show that PGC1α governs non-cell autonomous paracrine tumor suppression in prostate cancer. A systematic analysis of the transcriptional landscapes associated to PGC1α loss of expression revealed that PGC1α alters the expression of genes encoding for secreted proteins. Cell secretome studies corroborated that PGC1α-dependent ERRα regulation in prostate cancer cells suppresses the growth of tumor cells exposed to their conditioned media. The integration ofin vitroandin vivosecretomics data and genetic perturbation assays revealed spermidine synthase as a transcriptional target of PGC1α and mediator of a paracrine metabolic growth suppressive effect. Moreover, the activity of the regulatory axis PGC1α-ERRα-SRM was reflected in patients and had prognostic value. Altogether, this work provides unprecedented evidence of the non-cell autonomous tumor suppression role of PGC1α, which broadens the view of this co-regulator as a multifactorial tumor suppressor in prostate cancer.
Aphis craccivora (Hemiptera: Aphididae) synthesizes juvenile hormone III via a pathway involving epoxidation followed by esterification, potentially providing an epoxidation active site for the synthesis of juvenile hormone SB3
Authors: Li Haolin , Kong Xue , Fang Yan , Hou Jiangan , Zhang Wenjie , Zhang Yongheng , Wei Jiguang , Li Xuesheng
Published: October 2024

Juvenile hormones (JHs) play a crucial role in regulating development and reproduction in insects. Most insects predominantly synthesize JH III, which typically involves esterification followed by epoxidation, lepidopteran insects use a pathway of epoxidation followed by esterification. Although hemipteran insects have JH III and JH skipped bisepoxide III (JH SB3), the synthesis pathway and key epoxidases remain unclear. This study was conducted on Aphis craccivora, and demonstrated that corpora allata, microsomes, Ac‐CYP15C1, and Ac‐JHAMT catalyze JH III production in vitro, establishing the pathway of epoxidation followed by esterification. These findings were further confirmed through RNA interference and molecular docking. The presence of JH III and JH SB3 in A. craccivora was identified, and their synthesis pathway was elucidated as follows: Ac‐CYP15C1 oxidizes farnesic acid to JH A, followed by methylation to JH III by Ac‐JHAMT, possibly providing an epoxidation site on the second carbon for JH SB3. This alteration may significantly contribute to the differentiation and functional diversification of JH types in insects.
Glucagon‐like peptide‐1 receptor agonists and kidney outcomes
Authors: MacIsaac Richard J. , Trevella Philippa , Ekinci Elif I.
Published: October 2024

Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney‐protective effect of the GLP‐1RA class of medications has been derived from kidney‐related outcomes reported from cardiovascular outcome trials (CVOTs). GLP‐1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney‐protective effects of GLP‐1RAs are thought to be attributed to their anti‐inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP‐RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP‐1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP‐1RA class of medication and briefly describe kidney outcomes from other major GLP‐1RAs trials. We also discuss a potential role of the dual GLP‐1/glucose‐dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney‐protective agent.

image
Managing climate change impacts on crops: The influence of soil tillage on a triticale crop under water stress conditions
Authors: Madejón Paula , Fernández‐Boy Elena , Madejón Engracia , Morales‐Salmerón Laura , Domínguez María Teresa
Published: October 2024

Water limitations for agriculture will likely become crucial in the next decades in some regions such as the Mediterranean basin with the current climate change projections. In this context, recent evidence suggests that the application of conservation agriculture, which reduces the frequency and intensity of soil tillage, could confer a higher stability of agricultural systems against climate variability. However, not many experiments have addressed the interaction between tillage type and the resistance to drought in rainfed crops. In this work, we evaluated the resistance to drought of triticale (Triticale hexaploide L.) crops managed with different tillage systems: traditional tillage (TT), reduced tillage (RT) and no tillage (NT). A rainfall exclusion experiment was carried out in a typical wheat/legume Mediterranean rotation in SW Spain, in a long‐term experiment established in 2008 comparing the three tillage systems. Grain yield and different variables related to plant ecophysiology, root development, biomass allocation and colonisation by arbuscular mycorrhizal fungi (AMF) were evaluated over one crop cycle. Tillage type had a significant influence on soil water storage (SWS), such that soils under NT had, on average, a 16% greater SWS than soils under RT or TT. Grain yield was significantly reduced by rainfall exclusion, in particular in the TT, where drought reduced grain yield by 31%. Gas exchange data also showed that plants in the TT system were more sensitive to drought, such that maximum photosynthesis rates were reduced by 25% because of rainfall exclusion in this tillage system. Drought had a negative impact on root biomass across the three tillage systems, especially in the RT, where a reduction in the root:shoot ratio was observed. The effect of tillage on mycorrhizal colonisation was more evident than the effect of drought; in general, conservation tillage systems (RT and NT) tended to have higher values for all AMF traits compared to the TT. In summary, the NT system tended to exhibit more favourable performance in terms of soil water retention, grain yield stability under drought conditions and mycorrhizal symbiosis, which suggests enhanced resource use efficiency in this system.
The current attitudes and practices of dentists in Australia towards composite repair: A cross‐sectional survey study
Authors: Khanna R , Han J , Liang E , Lee CY , Manakil J
Published: October 2024

Background

Whether to replace or repair a composite restoration is controversial and varies among clinicians. This study was designed to collect information on the attitudes and practices of Australian dentists towards composite repair.

Methods

An electronic 16‐item questionnaire was distributed online on Australian clinicians’ dental forum with a URL address and instructions on completing the survey. The questionnaire remained accessible for 2 months. The data collected were analysed statistically using descriptive, average rank, Pearson chi‐square and Kruskal–Wallis tests at α = 0.05.

Results

Repair of composite restorations was a widely accepted treatment modality among surveyed dentists. Despite this, approximately half of clinicians reported the prognosis of repaired restorations to be worse when compared to replacement. The most cited indications for repair were partial loss or fracture of the restoration, while the most common reason for repair was because this treatment modality was more conservative in terms of tooth structure removal. Most important patient factor influencing decision to repair composite restoration was caries risk of the patient (n = 50). Most significant situational factor to consider in decision whether to repair was previous (failed) attempts to repair (n = 74). The most important tooth level factor was the proximity of restoration to pulp (mean statistic rank 2.22). The most common composite surface treatment employed by participants bonding to old composite was acid etching (n = 87), and the main reason participants employed their chosen surface treatment was based on personal experience (n = 72).

Conclusion

The repair of composite restorations was a commonly performed procedure that is well accepted but may still be viewed as an inferior treatment to replacement by many Australian dentists. Most dentists agreed on indications for repair restorations and surface conditioning techniques, but there was wide variation in opinions overall. Due to the lack of high‐quality evidence regarding composite repair techniques, dentists tend to rely on personal experience to guide their clinical decisions.
hACE2 upregulation and participation of macrophages and clear cells in the immune response of epididymis to SARS‐CoV‐2 in K18‐hACE2 mice
Authors: da Silva André Acácio Souza , de Oliveira Salmo Azambuja , Battistone Maria Agustina , Hinton Barry Thomas , Cerri Paulo Sérgio , Sasso‐Cerri Estela
Published: October 2024

Background

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus caused the coronavirus disease 2019 pandemic, and the prevalence of deaths among men is higher than among women. The epididymis, divided into caput, corpus, and cauda, shows a region‐specific immunity. The K18‐hACE2 mouse expresses human angiotensin‐converting enzyme 2 (hACE2), the receptor that allows SARS‐CoV‐2 infection. However, studies using this transgenic mouse to evaluate the impact of this viral infection in epididymis have not yet been performed.

Objectives

We evaluated the expression of hACE2 in the epididymis of SARS‐CoV‐2‐infected K18‐hACE2 mice, and assessed the epididymal immune response, focusing on F4/80+ mononuclear phagocytes and tumor necrosis factor‐alpha expression.

Materials and methods

The following analyses were performed in the epididymal sections of infected mice: epithelial height and duct diameter, birefringent collagen, Terminal deoxynucleotidyl Transferase‐mediated dUTP Nick End Labelling, immunoreactions for detection of hACE2, spike, FGF, V‐ATPase, F4/80, tumor necrosis factor‐alpha, and iNOS. Viral particles were identified under electron microscopy. hACE2, Rigi, Tgfb1 and Tnfa expression were also evaluated by real‐time quantitative polymerase chain reaction.

Results

All epididymal regions expressed hACE2, which increased in all epididymal regions in the infected mice. However, the caput appeared to be the most infected region. Despite this, the caput region showed minimal changes while the cauda showed significant epithelial changes associated with increased iNOS immunoexpression. The F4/80+ mononuclear phagocyte area increased significantly in both stroma and epithelium. In addition to the epithelial and stromal mononuclear phagocytes, tumor necrosis factor‐alpha was also detected in clear cells, whose cytoplasm showed a significant increase of this cytokine in the infected animals.

Discussion and conclusion

The K18‐hACE2 mouse is a useful model for evaluating the impact of SARS‐CoV‐2 infection in the epididymis. The infection induced hACE2 upregulation, favoring the virulence in the epididymis. The epididymal regions responded differentially to infection, and the activation of F4/80+ mononuclear phagocytes associated with the increased tumor necrosis factor‐alpha immunolabeling in clear cells indicates a role of clear cells/mononuclear phagocytes immunoregulatory mechanisms in the epididymal immune response to SARS‐CoV‐2 infection.
Reproductive outcomes after antenatal corticosteroids: Secondary analysis of 50‐year follow‐up of the Auckland steroid randomized trial
Authors: St Clair Sophie L. , Walters Anthony G. B. , Crowther Caroline A. , Dalziel Stuart R. , Eagleton Carl , Gamble Gregory D. , McKinlay Christopher J. D. , Milne Barry J. , Harding Jane E. ,   for the ANCHOR Study Group
Published: October 2024

Introduction

Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long‐term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data.

Material and Methods

This is a secondary cohort analysis of the 50‐year follow‐up of the Auckland Steroid Trial (1969–1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo‐controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation).

Results

Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo‐exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03–0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring‐related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term.

Conclusions

Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.
Metastasis‐free survival of uveal melanoma by tumour size category based on The Cancer Genome Atlas (TCGA) classification in 1001 cases
Authors: Bansal Rolika , Sener Hidayet , Ganguly Arupa , Shields Jerry A. , Shields Carol L.
Published: October 2024

Background

Uveal melanoma (UM) can be classified by tumour size category and by The Cancer Genome Atlas (TCGA) groups (cytogenetic‐based, 4‐category prognostic classification into Groups A‐D). This study was conducted to assess impact on metastasis‐free survival (MFS) in UM by tumour size category based on correlation with TCGA classification.

Methods

Retrospective analysis of 1001 cases categorised as small (0.0–3.0 mm), medium (3.1–8.0 mm) and large (≥8.1 mm), grouped by TCGA classification.

Results

Of 1001 cases, TCGA Groups (A/B/C/D) included small (n = 270, 75%/11%/13%/1%), medium (n = 503, 46%/14%/27%/13%) and large (n = 228, 23%/19%/38%/20%) UM. The 5‐and 10‐year Kaplan–Meier MFS for small UM revealed Group A (98%, 98%), Group B (100%, 100%), Group C (86%, NA) and Group D (100%, NA). For medium UM, the values dropped with Group A (95%, 93%), Group B (90%, 90%), Group C (68%, 38%), and Group D (44%, NA). For large UM, the values dropped further with Group A (94%, 86%), Group B (85%, NA), Group C (40%, 28%), and Group D (23%, NA). Additionally, a comparison (small vs. medium vs. large tumour size category) revealed TCGA low‐risk grouping (Groups A or B) in 86% vs. 60% vs. 58% cases with UM.

Conclusion

By tumour size category, favourable cytogenetics (Groups A or B) is found in 86% of small tumours, 60% of medium tumours, and 58% of large tumours. The MFS at 10 years for favourable cytogenetics was 98% for small tumours, 92% for medium tumours, and 54% for large tumours. Tumour size category can serve as a surrogate for TCGA.
The L‐type calcium channel CaV1.3: A potential target for cancer therapy
Authors: Liu Xuerun , Shen Boqiang , Zhou Jingyi , Hao Juan , Wang Jianliu
Published: October 2024

Cancer remains a prominent cause to life expectancy, and targeted cancer therapy stands as a pivotal approach in contemporary therapy. Calcium (Ca2+) signalling plays a multifaceted role in cancer progression, such as proliferation, invasion and distant metastasis. Otherwise, it also exerts an important influence on the efficacy of clinical treatment, including cancer therapy resistance. In this review we discuss the role of the L‐type calcium channel CaV1.3 (calcium voltage‐gated channel subunit alpha1 D) in different types of cancers, highlighting its potential as a therapeutic target for certain cancer types. The development of selective blockers of the CaV1.3 channel has been of great interest and is expected to be a new option for the treatment of cancers such as prostate cancer and endometrial cancer. We present the pharmacological properties of CaV1.3 and the current status of selective blocker development, and analyse the challenges and possible directions for breakthroughs in the development of tailored medicines.
KDELR2 is necessary for chronic obstructive pulmonary disease airway Mucin5AC hypersecretion via an IRE1α/XBP‐1s‐dependent mechanism
Authors: Wu Xiaojuan , Du Fawang , Zhang Aijie , Zhang Guoyue , Xu Rui , Du Xianzhi
Published: October 2024

Airway mucus hypersecretion, a crucial pathological feature of chronic obstructive pulmonary disease (COPD), contributes to the initiation, progression, and exacerbation of this disease. As a macromolecular mucin, the secretory behaviour of Mucin5AC (MUC5AC) is highly dependent on a series of modifying and folding processes that occur in the endoplasmic reticulum (ER). In this study, we focused on the ER quality control protein KDEL receptor (KDELR) and demonstrated that KDELR2 and MUC5AC were colocalized in the airway epithelium of COPD patients and COPD model rats. In addition, knockdown of KDELR2 markedly reduced the expression of MUC5AC both in vivo and in vitro and knockdown of ATF6 further decreased the levels of KDELR2. Furthermore, pretreatment with 4μ8C, an IRE1α inhibitor, led to a partial reduction in the expression of KDELR2 and MUC5AC both in vivo and in vitro, which indicated the involvement of IRE1α/XBP‐1s in the upstream signalling cascade. Our study revealed that KDELR2 plays a crucial role in airway MUC5AC hypersecretion in COPD, which might be dependent on ATF6 and IRE1α/XBP‐1s upstream signalling.
PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS/STING activation
Authors: Li Cheng , Qiao Lingyan , Ge Juan , Hu Sicui , Yang Hongxiu , Hu Conghui , Li Tang
Published: October 2024

Pancreatic β‐cell damage mediated by apoptosis is believed to be a main trigger of type 1 diabetes mellitus (T1DM), which is proposed as an organ‐specific autoimmune disease mediated by T cells. Nonetheless, the fundamental origins of T1DM remain uncertain. Here, we illustrate that an increase in PLAGL1 expression induces β‐cell apoptosis, as evidenced by mitochondrial membrane impairment and nucleolar degradation. The gene expression levels from cDNA samples were determined using qRT‐PCR method. Western blot and Co‐immunoprecipitation were applied for protein expression and interactions, respectively. Flow cytometry and TUNEL assay were used to detect pancreatic β cell apoptosis. Female NOD/LtJ mice with recent‐onset T1DM has been used in in vivo studies. Glucose‐stimulated insulin secretion (GSIS) and glucose tolerance test (GTT) method is used for islet function assessment. Haematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) were performed to evalute histological improvement of islet beta. Subsequent cytoplasmic DNA accumulation triggers DNA senser, the cyclic guanosine monophosphate‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway. STING activation further stimulates downstream IRF3 and NF‐kB pathways, thus boost type‐I interferon signalling and NF‐kB mediated inflammation. These findings elucidate a molecular mechanism linking PLAGL1 induced cell apoptosis to type‐I interferon signalling and suggest a potential benefit for targeting cGAS/STING in T1DM treatment.
A Fundamental Difference in the Nature of Personal Values and Personality Traits Revealed Through Different Patterns of Stability Across Their Distributions
Authors: Lake Joshua , Bardi Anat , Sneddon Joanne , Lee Julie A.
Published: October 2024

Objective

Personal values and personality traits are both important aspects of personality, but much is still unknown about the fundamental differences between the constructs, including how their patterns of temporal stability compare. This paper investigated patterns of intra‐individual stability in both values and traits.

Method

Quantile correlations were estimated between each of the 20 refined personal values and the same values 2 years later in a large longitudinal sample of Australian adults (N = 2875). The same was done for each of the 15 Five‐Factor Model trait facets in a subsample of these participants (n = 2424).

Results

It was observed that more important values tended to remain more stable over time, while traits retained a similar stability regardless of trait strength, and frequently showed small decreases in stability at extreme levels.

Conclusions

Findings indicate that highly prioritized values may be a more central aspect of the self, and a more reliable element for predicting future outcomes, than less highly prioritized values, but in contrast, traits do not function in a way that is dependent on trait strength.
Notable range extension of the genus Biramus Oswald, 1993 (Neuroptera: Hemerobiidae) and first record in Colombia
Authors: Castillo-Avila Camilo , Castillo-Figueroa Dennis
Published: October 2024

Biramus Oswald, 1993 is a hemerobiid genus (Neuroptera) distinguished by forewing morphological traits. This genus is distributed in Venezuela, Panama, Costa Rica, and Mexico. Here, we report Biramus in Colombia for the first time, based on a single female specimen collected in an upper Andean tropical mountain forest at an altitude above 3 000 m, in Guasca - Cundinamarca. This new record extends the genus’ distribution by 440 km in the northwestern region of South America and represents its highest altitudinal record, expanding its elevational distribution by 1373 m.
Moderate embryonic delay of paternal mitochondrial elimination impairs mating and cognition and alters behaviors of adult animals
Authors: Zhang Hu , Zhu Yunan , Xue Ding
Published: October 2024

Rapid elimination of paternal mitochondria following fertilization is a conserved event in most animals, but its physiological significance remains unclear. We find that modest delay of paternal mitochondrial elimination (PME) in
Caenorhabditis elegans
embryos unexpectedly impairs mating and cognition of adult animals and alters their locomotion behaviors. Delayed PME causes decreased adenosine triphosphate (ATP) levels in early embryos, which lead to impaired physiological functions of adult animals through an energy-sensing pathway mediated by an adenosine monophosphate (AMP)–activated protein kinase, AAK-2, and a forkhead box class O (FOXO) transcription factor, DAF-16. Treatment of PME-delayed animals with MK-4, a subtype of vitamin K
2
that can improve mitochondrial ATP production, restores ATP levels in early embryos, and rescues physiological defects of adult animals. Our results suggest that moderate PME delay during embryo development adversely affects crucial physiological functions in adults, which could be evolutionarily disadvantageous. These observations provide mechanistic explanations for the need to swiftly remove paternal mitochondria early during embryo development.
Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions
Authors: Flickinger Kyle M. , Wilson Kelli M. , Rossiter Nicholas J. , Hunger Andrea L. , Vishwasrao Paresh V. , Lee Tobie D. , Mellado Fritz Carlos A. , Richards Rebecca M. , Hall Matthew D. , Cantor Jason R.
Published: October 2024

Chemical screens across hundreds of cell lines have shown that the drug sensitivities of human cancers can vary by genotype or lineage. However, most drug discovery studies have relied on culture media that poorly reflect metabolite levels in human blood. Here, we perform drug screens in traditional and Human Plasma–Like Medium (HPLM). Sets of compounds that show conditional anticancer activity span different phases of global development and include non-oncology drugs. Comparisons of the synthetic and serum-derived components that comprise typical media trace sets of conditional phenotypes to nucleotide synthesis substrates. We also characterize a unique dual mechanism for brivudine, a compound approved for antiviral use. Brivudine selectively impairs cell growth in low folate conditions by targeting two enzymes involved in one-carbon metabolism. Cataloged gene essentiality data further suggest that conditional phenotypes for other compounds are linked to off-target effects. Our findings establish general strategies for identifying drug-nutrient interactions and mechanisms of action by exploiting conditional lethality in cancer cells.
Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4
+
T cell response
Authors: Chudnovskiy Aleksey , Castro Tiago B. R. , Nakandakari-Higa Sandra , Cui Ang , Lin Chia-Hao , Sade-Feldman Moshe , Phillips Brooke K. , Pae Juhee , Mesin Luka , Bortolatto Juliana , Schweitzer Lawrence D. , Pasqual Giulia , Lu Li-Fan , Hacohen Nir , Victora Gabriel D.
Published: October 2024

Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)–based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4
+
T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4
+
and CD8
+
tumor–specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.
Tricky Ts play possum to propagate autoimmune disease
Authors: Panicker Anjali J. , O’Connor Kevin C.
Published: October 2024

Patients with autoimmune disease have exhausted antigen-specific T cells that remain capable of B cell support.
Supplemental Material: Seismic evidence of an extremely thin crust along a 70 Ma slow-spreading crustal segment in the equatorial Atlantic Ocean
Authors: Dhabaria Nirmit , Singh Satish C.
Published: October 2024

 A brief description of methods (data processing, inversions, synthetic tests, and thermal modeling) and supplementary Figures S1–S22 and associated references.  
Supplemental Material: The South Purulia Shear Zone, eastern India: Its anatomy and implication for timing the Rodinia-age collision in the eastern part of the Central Indian Tectonic Zone
Authors: Banerjee Anwesa , Sequeira Nicole , al. et
Published: October 2024

Figure S1: Field photo in southern North Singhbhum Mobile Belt showing fabric relations in mica schists interleaved with quartzite and south-down shear sense during D3 deformation. Text S1: Summary of instrumentation and analytical details for whole-rock geochemistry, laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) U-Pb zircon dating, and electron probe micro-analysis monazite chemical dating. Table S1: Data table for LA-ICP-MS U-Pb zircon analyses. Text S2: Lithological description and textural characteristics of monazite with dates in Ma. Table S2: Chemical compositions of monazites and spot dates. Figure S2: Probability density plots of monazite dates (<10% error) in individual samples.
Seasonal movement and habitat use of Bull Trout (Salvelinus confluentus) near the northern geographic range extent
Authors: Mochnacz Neil J. , Guzzo Matthew M. , Suitor Michael J. , Barth Cameron C. , Ledee Elodie , Chapelsky Andrew J. , Cooke Steven J. , Tate Douglas P. , Gutowsky Lee F.G.
Published: October 2024

The movement ecology of Bull Trout ( Salvelinus confluentus) in watersheds at the northern geographic range extent is not well understood. We implanted 54 Bull Trout with acoustic transmitters in the Prairie Creek watershed, Northwest Territories, Canada and tracked fish from July 2011 to October 2012 using 19 stationary hydrophones. Bull Trout movement patterns generally corresponded to two groups, as a result of individual variation within and across seasons. The first group exhibited seasonal variations in movement and habitat use, moving most (range 11.7–115.9 km) and occupying the largest home ranges in summer and autumn, while exhibiting little movement during winter and spring. The second group made negligible movements within seasons and resided in localized areas. Restricted movement in winter resulted in a severe range contraction. The average distance moved within a season was 11.5 km (range 0.3–64.9 km per fish). The unusually high prevalence of stationarity in this watershed suggest fish can complete all life processes (spawning, feeding, and rearing) in short reaches (<10 km) of Prairie Creek and tributaries. We encourage researchers to replicate our work in other northern watersheds to determine if the life history we describe represents a regional divergence from more southerly populations.
Unusual Presentation of Craniopharyngioma Pituitary Mass in a 71‐Year‐Old Female: A Case Report
Authors: Faust Taylor F. , Reddy Punuru , Weiss Jillian , Steadman Michael , Morizio Connie , Cail Garrett
Published: October 2024

In this report, we present the case of a 71‐year‐old African‐American woman experiencing 2 months of intermittent headaches and episodes of blurred vision. Despite a comprehensive medical history that revealed chronic conditions and previous unrelated surgeries, the initial evaluation appeared to be unremarkable. Following the discovery of a mass on an imaging and a subsequent biopsy, the diagnosis of craniopharyngioma (WHO grade I) was confirmed. However, a brain mass was identified after additional ophthalmologic examination and MRI. This case explores the significance of recognizing atypical presentations of a brain injury that required a specific approach for diagnosis, surgical intervention and treatment, and postoperative care. This case contributes to the constantly evolving understanding of atypical manifestations of tumor characteristics and their complexities, along with the need to develop appropriate patient management strategies and provide optimal outcomes.
Triple‐Negative Breast Cancer: Tumor Immunogenicity and Beyond
Authors: Ibrahim Elio , Diab Ernest , Hayek Rony , Hoyek Karim , Kourie Hampig
Published: October 2024

Triple‐negative breast cancer (TNBC) is a breast malignancy with a poor prognosis and limited therapeutic options. Many studies show that TNBC exhibits heterogeneity across clinical, histopathological, and molecular levels. In this review, we discuss the immunogenic features of TNBC with a focus on immunotherapy and the current standard of care in the neoadjuvant, adjuvant, and metastatic setting. In addition, we address the ongoing research on immunotherapy, antibody‐drug conjugates (ADCs), poly ADP‐ribose polymerase (PARP) inhibitors, and future challenges in the treatment of this entity.
Two Rare Cases of Feline Toxic Epidermal Necrolysis: A Novel Therapeutic Approach With Medical‐Grade Honey
Authors: Peteoacă Alexandra , Cremers Niels A. J. , Peters Linsey J. F.
Published: October 2024

Toxic epidermal necrolysis (TEN) is an acute and life‐threatening dermatological condition that is drug‐induced and characterized by extensive epidermal detachment. These lesions should be protected from infection using a product that has a low risk of reactivity. Medical‐grade honey (MGH) exerts antimicrobial and wound‐healing effects while posing a low risk of exacerbating TEN. In this case report, we are the first to describe the use of MGH for wound management in two feline TEN patients. Case 1 involved a 1‐year‐old female British shorthair cat, while Case 2 featured a 1‐year‐old female mixed‐breed cat. Both patients presented to the hospital with various symptoms, including fever, tongue lesions, and lesions in the abdominal area following ovariohysterectomy surgery. TEN was confirmed via histopathological examination. The suspected cause of TEN in both cases was the iodine present in the surgical scrub. Tongue lesions were addressed with a liquid diet, and all xenobiotics were immediately withdrawn as a precaution. MGH products supplemented with vitamins were applied to the abdominal wounds following a wound lavage with Ringer’s lactate. Daily dressing changes were performed without discomfort, pain, or any adverse reactions. In both cases, debridement became evident after just 1 day, and the patients fully recovered after 12 days of MGH therapy. This case report demonstrates for the first time the successful use of supplemented MGH for wound management in veterinary patients with TEN. The patients did not have any adverse reactions to the treatment, while MGH dressings provided antimicrobial protection and wound‐healing effects. Furthermore, these cases highlight the importance of rapid diagnosis and immediate drug withdrawal to increase the survival rate. Overall, supplemented MGH is a safe and effective method to treat TEN‐related lesions in feline patients.
Late Relapse of Previous Pulmonary Cryptococcosis With Symptoms Resembling Cerebral Infarction: A Case Report
Authors: Pinchuk Anatoli , Geginat Gernot , Rickerts Volker , Neyazi Belal , Stein Klaus Peter , Mawrin Christian , Sandalcioglu I. Erol , Rashidi Ali
Published: October 2024

Cryptococcosis, an infection caused by Cryptococcus neoformans and Cryptococcus gattii, predominantly targets the central nervous system (CNS) in patients with AIDS but is not limited to this group. The disease can also occur in individuals with various immunosuppressive conditions, frequently involving the brain or lungs. Cryptococcal meningitis (CM) is the most common form of fungal meningoencephalitis, leading to intracerebral infections, cerebral infarction, or hydrocephalus. The clinical presentation of CM is nonspecific, and imaging features can vary significantly. This case report presents a patient with cerebral infarction, who was HIV‐negative but had been on long‐term cortisone therapy. Notably, the patient had a history of pulmonary cryptococcosis 15 years prior to cerebral involvement. When initially at our clinic, histology and culture results from brain biopsies were negative and the earlier pulmonary cryptococcosis history was unknown. Subsequently, cryptococcal antigen was detected in both serum and cerebrospinal fluid (CSF), and C. neoformans was cultivated from CSF. This case highlights the critical importance of maintaining a high index of suspicion for CM, particularly in patients with a history of previous cryptococcal infections, and it also demonstrates the possibility of false‐negative brain biopsy results due to secondary vascular events associated with CM.
Elevated SH3 and Multiple Ankyrin Repeat Domains 2 Expression Correlates With Improved Glioma Prognosis
Authors: Li Wenlin , Shi Haiping , He Jimin
Published: October 2024

This study investigates the prognostic significance of SH3 and multiple ankyrin repeat domains 2 (SHANK2) gene expression in glioma patients, using data from The Cancer Genome Atlas (TCGA), the Genotype‐Tissue Expression (GTEx) project, and the Gene Expression Omnibus (GEO). Through comprehensive analysis, we found a significant association between higher SHANK2 expression and improved survival outcomes across various glioma subtypes. To further validate the clinical relevance of SHANK2, we conducted cellular experiments involving siRNA‐mediated knockdown of SHANK2 in U87 and A172 glioma cell lines. Quantitative real‐time PCR (qPCR) and Western blot analyses confirmed the successful knockdown of SHANK2, and subsequent MTT assays revealed that silencing SHANK2 significantly promoted glioma cell proliferation. These findings underscore the potential role of SHANK2 as a tumor suppressor in glioma. The study also introduces a multivariate prognostic model incorporating SHANK2, providing a novel perspective on glioma prognosis. While the retrospective nature of the study presents limitations, our results suggest that SHANK2 expression could serve as a valuable biomarker for glioma prognosis and inform future therapeutic strategies.
A Comparison of the Outcomes of COVID‐19 Vaccinated and Nonvaccinated Patients Admitted to an Intensive Care Unit in a Low‐Middle‐Income Country
Authors: Ghaffar Waleed Bin , Faisal Khan Muhammad , Abdul Ghaffar Moeed Bin , Sohaib Muhammad , Rayani Asma , Mehmood Alam Muhammad , Sibtain Syed Talha , Cheema Zahra , Latif Asad
Published: October 2024

Patients critically afflicted with coronavirus disease 2019 (COVID‐19) often need intensive care unit (ICU) admission, despite comprehensive vaccination campaigns. The challenges faced by healthcare systems in low‐middle‐income countries, including limited infrastructure and resources, play a pivotal role in shaping the outcomes for these patients. This study aimed to meticulously compare outcomes between COVID‐19 vaccinated and nonvaccinated patients admitted to the ICU. In addition, demographic factors and the ICU course influencing mortality were also assessed. A retrospective review of records from the COVID‐ICU of Aga Khan University Hospital spanning July 2021–March 2022 included 133 patients. Statistical analyses, encompassing the Mann–Whitney U‐test and chi‐square/Fisher exact test, discerned quantitative and qualitative differences. Stepwise multivariable logistic regression models with forward selection identified factors associated with hospital mortality. Results revealed comparable cohorts: vaccinated (48.13%) and nonvaccinated (51.87%). Vaccinated individuals, characterized by advanced age and higher Charlson Comorbidity Index, exhibited more critical disease (89.1%; p value: 0.06), acute respiratory distress syndrome (96.9%; p value: 0.013) and elevated inflammatory markers. Despite these differences, both cohorts exhibited similar overall outcomes. Factors such as decreased PaO2/FiO2 ratio on admission and complications during ICU stay were significantly associated with in‐hospital mortality. In conclusion, despite advanced age and increased frailty among vaccinated patients, their mortality rate remained comparable to nonvaccinated counterparts. These findings underscore the pivotal role of vaccination in mitigating severe outcomes within this vulnerable population.
Table S1, Figure S1,Table S2, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6, Figure S7, Figure S8, Figure S9 from Combining Neratinib with CDK4/6, mTOR, and MEK Inhibitors in Models of HER2-positive Cancer
Authors: Zhao Ming , Scott Stephen , Evans Kurt W. , Yuca Erkan , Saridogan Turcin , Zheng Xiaofeng , Wang Heping , Korkut Anil , Cruz Pico Christian X. , Demirhan Mehmet , Kirby Bryce , Kopetz Scott , Diala Irmina , Lalani Alshad S. , Piha-Paul Sarina , Meric-Bernstam Funda
Published: October 2024

Table S1, Figure S1,Table S2, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6, Figure S7, Figure S8, Figure S9
Supplementary Figure S3 from Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer
Authors: van de Haar Joris , Mankor Joanne M. , Hummelink Karlijn , Monkhorst Kim , Smit Egbert F. , Wessels Lodewyk F.A. , Cuppen Edwin , Aerts Joachim G.J.V. , Voest Emile E.
Published: October 2024

STK11/KEAP1/EGFR alterations and survival of TMB-based subgroups in the discovery cohort.
Supplementary Figure S1 from Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer
Authors: van de Haar Joris , Mankor Joanne M. , Hummelink Karlijn , Monkhorst Kim , Smit Egbert F. , Wessels Lodewyk F.A. , Cuppen Edwin , Aerts Joachim G.J.V. , Voest Emile E.
Published: October 2024

The cTMB and outcome of ICB monotherapy in the discovery cohort.
Table 1 from Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy
Authors: Heath Elisabeth , Dyson Gregory , Ribeiro Jennifer R. , Xiu Joanne , Poorman Kelsey , Mamdani Hirva , Al-Hallak Mohammed N. , Shields Anthony F. , Elayoubi Jailan A. , Winer Ira S. , Cackowski Frank C. , Puckrein Gary A. , Lopes Gilberto de Lima , Jones Nathaniel , Hauke Ralph J. , Kareff Samuel A. , Radovich Milan , Sledge George W. , Spetzler David B. , Vidal Gregory A. , Marshall John L.
Published: October 2024

Cohort demographics
Supplementary Table S1 from Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy
Authors: Heath Elisabeth , Dyson Gregory , Ribeiro Jennifer R. , Xiu Joanne , Poorman Kelsey , Mamdani Hirva , Al-Hallak Mohammed N. , Shields Anthony F. , Elayoubi Jailan A. , Winer Ira S. , Cackowski Frank C. , Puckrein Gary A. , Lopes Gilberto de Lima , Jones Nathaniel , Hauke Ralph J. , Kareff Samuel A. , Radovich Milan , Sledge George W. , Spetzler David B. , Vidal Gregory A. , Marshall John L.
Published: October 2024

Description of rural-urban commuting area (RUCA) codes
Supplementary Fiugre S4 from Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy
Authors: Heath Elisabeth , Dyson Gregory , Ribeiro Jennifer R. , Xiu Joanne , Poorman Kelsey , Mamdani Hirva , Al-Hallak Mohammed N. , Shields Anthony F. , Elayoubi Jailan A. , Winer Ira S. , Cackowski Frank C. , Puckrein Gary A. , Lopes Gilberto de Lima , Jones Nathaniel , Hauke Ralph J. , Kareff Samuel A. , Radovich Milan , Sledge George W. , Spetzler David B. , Vidal Gregory A. , Marshall John L.
Published: October 2024

Overall survival by RUCA code and poverty