bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinase polymerase amplification - lateral flow dipstick for rapid and visual detection of Blastocystis spp.
Authors: Mei Xuefang , Su Changwei , Xin Jiahui , Jia Luwei , Zhang Shanrui , Yang Zhenke , Xiaowei Tian , Zhang Zhenchao , Wang Shuai
Published: May 2024

Blastocystis spp. is a ubiquitous protozoon in the intestinal tract of human and many animals. Microscopic examination is the main method of clinical diagnosis for Blastocystis spp., which is prone to false negative. A simple and rapid diagnosis of Blastocystis spp. infection is an important step to prevent and control blastocystosis. Here, a recombinase polymerase amplification-lateral flow dipstick (RPA-LFD) assay was developed for rapid visual detection of Blastocystis spp. DNA amplification could be performed within 18 min at 37°C. The minimum DNA detection limit was 1 pg/μL, and there was no cross-reactivity with 12 other non-target pathogens, which was consistent with the sensitivity of conventional PCR (cPCR). Furthermore, 56 fecal samples from the Third Affiliated Hospital of Xinxiang Medical University were tested using RPA and cPCR methods respectively, and the results were completely consistent. The results show that RPA-LFD method has high accuracy and visual results, which provides a new choice for the differential diagnosis and rapid field detection of Blastocystis spp.
Impact of the COVID-19 pandemic on hospital admission rates for arterial hypertension and coronary heart disease: a German database study
Authors: Sasko Benjamin , Matiakis Marios , Seibert Felix S. , Pagonas Nikolaos , Hippe Hans-Jörg , Babel Nina , Ukena Christian , Westhoff Timm H.
Published: May 2024

Background

During the SARS-CoV-2 pandemic it was speculated that the virus might be associated with a persistent increase of cardiovascular risk. The present study compares pre- and post-pandemic hospital admission rates for hypertension and coronary artery disease.

Methods

Systematic multicentric retrospective cohort analysis of 57.795 hospital admissions in an urban region in Germany during two different periods (pre-pandemic 01–06/2019 vs. post-pandemic era 01–06/2023). Information on hospital admissions for arterial hypertension, chronic coronary syndrome, unstable angina pectoris and acute myocardial infarction were extracted from the hospitals data systems. Additionally, six comorbidities and performed coronary interventions were monitored.

Results

Compared to the pre-pandemic era, there was no increase in hospitalizations for arterial hypertension (516 vs. 483, −6.8%, p = 0.07) or myocardial infarction (487 vs. 349, −23.8%, p < 0.001), but the total number of patient admissions with chest pain as the presenting symptom increased (chronic coronary syndrome: 759 vs. 943, +24.2%, p < 0.001; unstable angina pectoris: 270 vs. 451, +67.0%, p < 0.001). At the same time, the number of performed coronary angiographies increased, but less patients underwent percutaneous interventions. Patients admitted with chest pain in the post-pandemic era were in general healthier with less comorbidities.

Conclusion

The present multicenter cohort study found no evidence for an increase in hospitalizations for arterial hypertension or coronary artery disease after the end of the pandemic. However, further studies with larger sample sizes are needed to confirm our results.
Soluble suppression of tumorigenicity 2 associated with major adverse cardiac events in children with myocarditis
Authors: Shi Tongtong , Ge Jing , Li Shan , Zhang Yali
Published: May 2024

Objective

Soluble suppression of tumorigenicity 2 (sST2) is associated with the prognosis of some cardiac diseases, but studies on sST2 and the prognosis of patients with myocarditis are rare. This study investigated the relationship between major adverse cardiovascular events (MACEs) and sST2 during hospitalization in pediatric patients with myocarditis.

Methods

This was a single-center retrospective cohort study. A total of 252 patients aged ≤14 years diagnosed with myocarditis were enrolled. Events during the hospitalization were defined as MACEs (all-cause death > new heart failure > ventricular arrhythmia).

Results

A total of 25 people had MACEs during their hospital stay. The mortality during hospitalization was 6/23 (26%) in patients with heart failure and 3/10 (30%) in patients with ventricular arrhythmias. After including these risk factors in a multivariate logistic regression analysis, NT-proBNP (OR 4.323; 95% CI, 2.433–7.679; p < 0.001) and sST2 (OR 1.020; 95% CI, 1.003–1.037; p = 0.022) remained statistically significant and were independent risk factors for MACEs during hospitalization in pediatric myocarditis patients.

Conclusions

Elevated levels of NT-proBNP and sST2 were independently associated with major adverse cardiovascular events during hospitalization in children with myocarditis, and both showed good predictive efficacy.
Birds of a feather age together: telomere dynamics and social behavior predict life span in female Japanese quail (Coturnix japonica)
Authors: McCollum Shannon E. , Canter Olivia , Fasanello Vincent J. , Gronsky Sarah , Haussmann Mark F.
Published: May 2024

Social support is vital for mental and physical health and is linked to lower rates of disease and early mortality. Conversely, anti-social behavior can increase mortality risks, both for the initiator and target of the behavior. Chronic stress, which also can increase mortality, may serve as an important link between social behavior and healthy lifespan. There is a growing body of literature in both humans, and model organisms, that chronic social stress can result in more rapid telomere shortening, a measure of biological aging. Here we examine the role of anti-social behavior and social support on physiological markers of stress and aging in the social Japanese quail, Coturnix Japonica. Birds were maintained in groups for their entire lifespan, and longitudinal measures of antisocial behavior (aggressive agonistic behavior), social support (affiliative behavior), baseline corticosterone, change in telomere length, and lifespan were measured. We found quail in affiliative relationships both committed less and were the targets of less aggression compared to birds who were not in these relationships. In addition, birds displaying affiliative behavior had longer telomeres, and longer lifespans. Our work suggests a novel pathway by which social support may buffer against damage at the cellular level resulting in telomere protection and subsequent longer lifespans.
Associations of serum vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults
Authors: Zhao Jiao , Lu Qi , Zhang Xianfeng
Published: May 2024

Introduction

The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults.

Methods

The data from the National Health and Nutrition Examination Survey 2001–2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health.

Results

Serum vitamin B12 level was positively correlated with the total and appendicular lean mass (β = 584.83, P = 0.044; β = 291.65, P = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all P < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (β = -12.75, P = 0.019; β = -0.06, P <0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (β = -0.01, P = 0.018; β = -0.01, P = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (β = -0.01, P = 0.048; β = -0.01, P = 0.025; β = -7.53, P = 0.015).

Conclusions

Vitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.
Elevated AIP is associated with the prevalence of MAFLD in the US adults: evidence from NHANES 2017–2018
Authors: Chen Yan , Lu Chuan , Ju Haonan , Zhou Qingzhi , Zhao Xin
Published: May 2024

Background

Atherogenic Index of plasma (AIP) is closely related to metabolic abnormalities. But as of now, there is no definitive conclusion on the dose-response relationship pattern between AIP and metabolic associated fatty liver disease (MAFLD).

Objective

The objective of this study was to provide a fresh insight for understanding the intrinsic link between AIP and the prevalence of MAFLD by exploring the dose-response pattern between AIP and MAFLD.

Methods

A total of 9254 participants received the survey and 1090 participants were finally included according to the screening criteria. To evaluate the association between AIP and the prevalence of MAFLD based on weighted multivariate logistic regression. Sensitivity analysis of the association between AIP and MAFLD was performed using propensity score matching (PSM). Restrictive cubic splines (RCS) were used to identify patterns of dose-response relationships between AIP and MAFLD, and receiver operator characteristic (ROC) curves were used to evaluate the predictive ability of AIP and traditional lipid parameters for MAFLD.

Results

In this study, a total of 563 participants were found to have MAFLD. The results of weighted multivariate logistic regression analysis demonstrated that, after adjusting for sex and age, participants in the highest quartile (Q4) of AIP had a significantly increased risk of developing MAFLD compared to those in the lowest quartile (Q1) (Model 2: OR = 9.03, 95% CI 4.75–17.17). A similar trend was observed in the fully adjusted model (Model 3: OR = 3.85, 95% CI 1.55–9.52). The RCS analysis revealed a linear dose-response association between AIP and MAFLD(P for crude non-linearity = 0.087). This association remained significant after accounting for potential confounding variables(P for adjusted non-linearity = 0.663). The ROC curve results suggest that AIP performs better than traditional lipid indicators in predicting MAFLD (AUC = 0.732, 95%CI 0.705–0.758).

Conclusion

A linear dose-response relationship exists between AIP and MAFLD, suggesting that as AIP increases, so does the risk of developing MAFLD.
Characterization of the bee community and pollination network in a southeastern U.S. pine savanna
Authors: Ulyshen Michael D. , Robertson Kevin , Horn Scott , Dixon Cinnamon
Published: May 2024

Although the fire-maintained pine savannas of the southeastern U.S. Coastal Plain are recognized for their plant diversity, pollinators associated with these ecosystems remain comparatively understudied. Here we present the results from a season-long effort to record bee-flower interactions at a single site in Florida. We collected 93 bee species (out of an estimated 117) from 79 flower species, with a total of 446 unique interactions. Bee richness and the number of interactions exhibited a bimodal pattern, dipping in mid-summer before an estimated peak in October. The most important floral resources changed throughout the season as did the composition of bees, with the spring and fall periods being particularly distinct. We found that pollen specialists (that collect pollen from a single family of plants) and pollen generalists accounted for a similar proportion of bee species over the entire season. However, pollen generalists outnumbered pollen specialists in the spring and summer before reversing in the fall. Pollen specialists visited significantly fewer plant species and families than pollen generalists and many were collected exclusively from their host family. This was particularly the case for aster specialists active only during the fall. We estimate that between 18.3-25.8% of the local bee fauna depends directly on the overstory trees for nesting habitat including dead wood and resin. Two management recommendations can be made based on these results. First, because fall is the period of peak floral abundance and bee richness, including many late-season aster specialists, it is probably the least favorable time for prescribed fire. Second, considering that a significant proportion of native bees depend on dead wood for nesting, it is important to retain standing dead trees and fallen wood whenever possible.
Bronchom assuages airway hyperresponsiveness in house dust mite-induced mouse model of allergic asthma and moderates goblet cell metaplasia, sub-epithelial fibrosis along with changes in Th2 cytokines and chemokines
Authors: Balkrishna Acharya , Sinha Sandeep , Karumuri Shadrakbabu , Maity Madhulina , Dev Rishabh , Varshney Anurag
Published: May 2024

Background

Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma.

Methods

Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers.

Results

Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels.

Conclusion

Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.
The 4AT scale for rapid detection of delirium in emergency department triage
Authors: Soler-Sanchis Angela , Martínez-Arnau Francisco Miguel , Sánchez-Frutos José , Pérez-Ros Pilar
Published: May 2024

Aims

To assess the diagnostic accuracy and time impact of the 4AT scale in emergency department triage.

Methods

A Prospective diagnostic accuracy study was carried out. People aged ≥65 years presenting to the emergency department from 1 November 2021 to 30 June 2022 were included. Nurses opportunistically screened eligible patients using the 4AT scale during triage according to the Manchester Triage System Francesc de Borja Hospital emergency department, Gandía (Spain). Accuracy was compared with medical diagnosis of delirium. Time (seconds) spent in triage with and without screening was assessed.

Results

The study included 370 patients (55.1% men, mean age 81.8 years), of whom 58.4% (n = 216) were screened. A final diagnosis of delirium was made in 41.4% of those screened. The most frequently used presentational flow charts and discriminators were ‘behaving strangely’ (15%) and ‘rapid onset’ (33.3%). The highest accuracy was obtained for a score of 3 points or more (sensitivity 85.1%; specificity 66.9%; positive predictive value 52.8%; negative predictive value 71.7%). No significant differences were found in the time spent in triage according to the performance of screening.

Conclusion

A score of 3 points or more on the 4AT scale enables rapid detection of delirium in emergency department triage, without consuming more time than conventional triage.
Exploring regulatory flexibility to create novel incentives to optimize drug discovery
Authors: Sullivan Jacqueline A. , Gold E. Richard
Published: May 2024

Efforts by governments, firms, and patients to deliver pioneering drugs for critical health needs face a challenge of diminishing efficiency in developing those medicines. While multi-sectoral collaborations involving firms, researchers, patients, and policymakers are widely recognized as crucial for countering this decline, existing incentives to engage in drug development predominantly target drug manufacturers and thereby do little to stimulate collaborative innovation. In this mini review, we consider the unexplored potential within pharmaceutical regulations to create novel incentives to encourage a diverse set of actors from the public and private spheres to engage in the kind of collaborative knowledge exchange requisite for fostering enhanced innovation in early drug development.
Circulating microRNAs as promising diagnostic biomarkers for hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Alemayehu Ermiyas , Fasil Alebachew , Ebrahim Hussen , Mulatie Zewudu , Bambo Getachew Mesfin , Gedefie Alemu , Teshome Mulugeta , Worede Abebaw , Belete Melaku Ashagrie
Published: May 2024

Introduction: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a major global health problem, ranking as the third leading cause of cancer-related death worldwide. Early identification and diagnosis of HCC requires the discovery of reliable biomarkers. Therefore, the study aimed to assess the diagnostic accuracy of miRNAs for HCC. The protocol was registered on PROSPERO website with the registration number CRD42023417494.

Method: A literature search was conducted in PubMed, Scopus, Embase, Wiley Online Library, and Science Direct databases to identify pertinent articles published between 2018 and 30 July 2023. Stata 17.0 software was employed to determine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC) for evaluating the accuracy of miRNAs in diagnosing HCC. The assessment of heterogeneity among studies involved the use of the Cochran-Q test and I2 statistic tests. Due to the observed significant heterogeneity, the random-effect model was chosen. Subgroup analysis and meta-regression analysis were also undertaken to explore potential sources contributing to heterogeneity. Deeks’ funnel plot was used to assess publication bias. In addition, Fagan’s nomogram and likelihood ratio scattergram were utilized to assess the clinical validity of miRNAs for HCC.

Result: Twenty-four articles were included, involving 1,668 individuals diagnosed with HCC and 1,236 healthy individuals. The findings revealed pooled sensitivity of 0.84 (95% CI: 0.80–0.88), specificity of 0.81 (95% CI: 0.77–0.84), PLR of 4.36 (95% CI: 3.59–5.30), NLR of 0.19 (95% CI: 0.15–0.25), DOR of 22.47 (95% CI: 14.47–32.64), and an AUC of 0.89 (95% CI: 0.86–0.91) for the diagnosis of HCC using miRNAs. Furthermore, results from the subgroup analysis demonstrated that superior diagnostic performance was observed when utilizing plasma miRNAs, a large sample size (≥100), and miRNA panels.

Conclusion: Hence, circulating miRNAs demonstrate substantial diagnostic utility for HCC and can serve as effective non-invasive biomarkers for the condition. Additionally, miRNA panels, miRNAs derived from plasma, and miRNAs evaluated in larger sample sizes (≥100) demonstrate enhanced diagnostic efficacy for HCC diagnosis. Nevertheless, a large pool of prospective studies and multi-center research will be required to confirm our findings in the near future.
Case report: Unveiling a less severe congenital nephrotic syndrome in a Rapa Nui patient with a NPHS1 Maori founder variant
Authors: Krall Paola , Rojo Angélica , Plaza Anita , Canals Sofia , Ceballos María Luisa , Cano Francisco , Guerrero José Luis
Published: May 2024

Background

Congenital nephrotic syndrome (CNS) is a severe kidney disorder characterized by edema, massive proteinuria, and hypoalbuminemia that manifests in utero or within three months after birth. CNS affects 1-3 per 100,000 children, primarily associated with genetic variants and occasionally with infections. Genetic analysis is the first-line method for diagnosis. The most common founder variants have been identified in European populations, often resulting in end-stage kidney disease by 1-2 years of age.

Case-diagnosis/treatment

A female full-term neonate, without prenatal signs of kidney disease, was admitted to Rapa Nui (Eastern Island) Hospital at the age of 2 months due to bronchial obstruction. She presented fever, oliguria, edema, urine protein-to-creatinine ratio (UPCR) 433.33, and hypoalbuminemia (0.9 g/dL). She was transferred to a mainland Chilean hospital following CNS diagnosis. Viral screening detected cytomegalovirus (CMV) positivity in both blood and urine. A kidney biopsy revealed interstitial nephritis and diffuse podocyte damage and the tissue PCR resulted negative for CMV. Interviews with the parents revealed consanguinity, suggestive of hereditary CNS. Genetic analysis identified the Maori founder variant, NPHS1 c.2131C>A (p.R711S), in homozygosis. The patient received albumin infusions and antiviral therapy, being discharged when she was 5 months old, with improved laboratory parameters evidenced by UPCR 28.55, albumin 2.5 g/dL, and cholesterol 190 mg/dL. Subsequent clinical monitoring was conducted through virtual and in-person consultations. At her last follow-up at 4 years 2 months old, she presented UPCR 16.1, albumin 3.3 g/dl and cholesterol 220 mg/dL, maintaining normal kidney function and adequate growth.

Conclusions

To our knowledge, this represents the first case of CNS in Chile carrying a NPHS1 variant associated with prolonged kidney survival. As described in the Maori population, the patient exhibited a less severe clinical course compared to classical NPHS1 patients. Genetic testing for the Maori founder variant in CNS patients related to the New Zealand population, could impact management decisions and potentially prevent the need for nephrectomies.
Genetic deletion of zinc transporter ZnT3 induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism
Authors: Zong Rui , Zhang Xiaoding , Dong Xiaohui , Liu Guan , Zhang Jieyao , Gao Yiting , Zhang Zhongyang , Ma Yiming , Gao Haixia , Gamper Nikita
Published: May 2024

Zinc transporter 3 (ZnT3) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT3 knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT3 deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT3 deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT3 knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT3 knockout mice. We hypothesize that the ZnT3 deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.
Small but mighty: the rise of microprotein biology in neuroscience
Authors: Duffy Erin E. , Assad Elena G. , Kalish Brian T. , Greenberg Michael E.
Published: May 2024

The mammalian central nervous system coordinates a network of signaling pathways and cellular interactions, which enable a myriad of complex cognitive and physiological functions. While traditional efforts to understand the molecular basis of brain function have focused on well-characterized proteins, recent advances in high-throughput translatome profiling have revealed a staggering number of proteins translated from non-canonical open reading frames (ncORFs) such as 5′ and 3′ untranslated regions of annotated proteins, out-of-frame internal ORFs, and previously annotated non-coding RNAs. Of note, microproteins < 100 amino acids (AA) that are translated from such ncORFs have often been neglected due to computational and biochemical challenges. Thousands of putative microproteins have been identified in cell lines and tissues including the brain, with some serving critical biological functions. In this perspective, we highlight the recent discovery of microproteins in the brain and describe several hypotheses that have emerged concerning microprotein function in the developing and mature nervous system.
PARP inhibitor synthetic lethality in ATM biallelic mutant cancer cell lines is associated with BRCA1/2 and RAD51 downregulation
Authors: Muvaffak Asli , Coleman Kevin G.
Published: May 2024

Background

Ataxia telangiectasia-mutated (ATM) kinase is a central regulator of the DNA damage response (DDR) signaling pathway, and its function is critical for the maintenance of genomic stability in cells that coordinate a network of cellular processes, including DNA replication, DNA repair, and cell cycle progression. ATM is frequently mutated in human cancers, and approximately 3% of lung cancers have biallelic mutations in ATM, i.e., including 3.5% of lung adenocarcinomas (LUAD) and 1.4% of lung squamous cell carcinomas (LUSC).

Methods

We investigated the potential of targeting the DDR pathway in lung cancer as a potential therapeutic approach. In this context, we examined whether ATM loss is synthetically lethal with niraparib monotherapy. This exploration involved the use of hATM knockout (KO) isogenic cell lines containing hATM homozygous (-/-) and heterozygous (+/-) generated via CRISPR/Cas9 gene knockout technology in DLD-1, a human colorectal adenocarcinoma cell line. Subsequently, we extended our investigation to non-small cell lung cancer (NSCLC) patient derived xenograft (PDX) models for further validation of poly ADP-ribose polymerase inhibitor (PARPi) synthetic lethality in ATM mutant NSCLC models.

Results

Here, we demonstared that biallelic hATM deletion (-/-) in DLD-1 impairs homologous recombination (HR) repair function and sensitizes cells to the PARPi, niraparib. Niraparib also caused significant tumor regression in one-third of the NSCLC PDX models harboring deleterious biallelic ATM mutations. Loss of hATM (−/−) was concomitantly associated with low BRCA1 and BRCA2 protein expression in both the hATM (−/−) DLD-1 cell line and PARPi-sensitive ATM mutant NSCLC PDX models, suggesting a downstream effect on the impairment of HR-mediated DNA checkpoint signaling. Further analysis revealed that loss of ATM led to inhibition of phosphorylation of MRN (Mre11-Rad50-NBS1) complex proteins, which are required for ATM-mediated downstream phosphorylation of p53, BRCA1, and CHK2.

Conclusions

Taken together, our findings highlight that the synthetic lethality of niraparib in ATM-deficient tumors can be regulated through a subsequent effect on the modulation of BRCA1/2 expression and its effect on HR function.
Vacuum-assisted excision: a safe minimally invasive option for benign phyllodes tumor diagnosis and treatment—a systematic review and meta-analysis
Authors: Gil Maria Luísa Braga Vieira , Coelho Bertha Andrade , Couto Henrique Lima , Silva Henrique Moraes Salvador , Pessoa Eduardo Carvalho , Sharma Nisha , Mann Ritse , McIntosh Stuart A. , Diniz Paulo Henrique Costa , Cantidio Farley Soares , Gil Gabriel Oliveira Bernardes , Salvador Anna Dias , de Almeida Júnior Waldeir José , Avelar José Tadeu Campos , Laranjeira Cláudia Lourdes Soares , Silva Filho Agnaldo Lopes
Published: May 2024

Synopsis

This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint.

Objective

To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision.

Method

A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence.

Results

Five comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29).

Conclusion

This meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.
Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer
Authors: Muñoz-Medel Matías , Pinto Mauricio P. , Goralsky Lauren , Cáceres Mónica , Villarroel-Espíndola Franz , Manque Patricio , Pinto Andrés , Garcia-Bloj Benjamin , de Mayo Tomas , Godoy Juan A. , Garrido Marcelo , Retamal Ignacio N.
Published: May 2024

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis’ virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.
Post-COVID-19 headache- NDPH phenotype: a systematic review of case reports
Authors: Dhiman Neetu Rani , Joshi Deepika , Singh Royana , Gyanpuri vyom , Kumar Anand
Published: May 2024

Background and objectives

Post-acute COVID-19 syndrome or “long COVID” affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection.

Methods

Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis.

Results

Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review.

Conclusion

NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted.

Trial Registration Information

The review is registered in Prospero with no. Identifier (CRD42022354912).

Systematic Review Registration

https://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).
Structure-guided design and cloning of peptide inhibitors targeting CDK9/cyclin T1 protein-protein interaction
Authors: Taghizadeh Mohammad Sadegh , Taherishirazi Mohsen , Niazi Ali , Afsharifar Alireza , Moghadam Ali
Published: May 2024

CDK9 (cyclin-dependent kinase 9) plays a significant role in numerous pathological conditions, such as HIV-1 infection and cancer. The interaction between CDK9 and cyclin T1 is crucial for maintaining the kinase’s active state. Therefore, targeting this protein-protein interaction offers a promising strategy for inhibiting CDK9. In this study, we aimed to design and characterize a library of mutant peptides based on the binding region of cyclin T1 to CDK9. Using Osprey software, a total of 7,776 mutant peptides were generated. After conducting a comprehensive analysis, three peptides, namely, mp3 (RAADVEGQRKRRE), mp20 (RAATVEGQRKRRE), and mp29 (RAADVEGQDKRRE), were identified as promising inhibitors that possess the ability to bind to CDK9 with high affinity and exhibit low free binding energy. These peptides exhibited favorable safety profiles and displayed promising dynamic behaviors. Notably, our findings revealed that the mp3 and mp29 peptides interacted with a conserved sequence in CDK9 (residues 60–66). In addition, by designing the structure of potential peptides in the plasmid vector pET28a (+), we have been able to pave the way for facilitating the process of their recombinant production in an Escherichia coli expression system in future studies. Predictions indicated good solubility upon overexpression, further supporting their potential for downstream applications. While these results demonstrate the promise of the designed peptides as blockers of CDK9 with high affinity, additional experimental studies are required to validate their biological activity and assess their selectivity. Such investigations will provide valuable insights into their therapeutic potential and pave the way for the future development of peptide-based inhibitors targeting the CDK9-cyclin T1 complex.
The metabolism of amino acids, AsA and abscisic acid induced by strigolactone participates in chilling tolerance in postharvest zucchini fruit
Authors: Wang Lei , Liu Li , Huang Anqi , Zhang Hua , Zheng Yonghua
Published: May 2024

Zucchini fruit are notably susceptible to chilling injury when stored at low temperatures. The purpose of this experimental investigation was to assess the influence of strigolactone (ST) (5 μmol L-1) on mitigating chilling injury and the metabolic changes in amino acids, ascorbic acid, and abscisic acid in zucchini fruit stored at 4°C. Research findings demonstrated that ST-treated zucchini fruit displayed a significantly higher tolerance to chilling stress compared to the control group. Postharvest ST treatment led to a decrease in weight loss, accompanied by reduced levels of malondialdehyde and relative ion leakage compared to the untreated group. ST immersion significantly boosted the metabolic pathways associated with proline and arginine, affecting both the enzymatic reactions and gene expressions, thus cumulatively increasing the internal concentrations of these amino acids in zucchini fruit. Zucchini treated with ST exhibited an increased concentration of γ-aminobutyric acid (GABA) as a result of augmented activities and elevated transcriptional levels of glutamate decarboxylase (GAD), GABA transaminase (GAT), and succinate semialdehyde dehydrogenase (SSD). In the ST-treated sample, the elevated enzymatic activities and enhanced gene expressions within the ascorbic acid (AsA) biosynthesis pathway worked together to sustain AsA accumulation. The application of ST resulted in a rise in abscisic acid (ABA) concentration, which correspondingly correlated with the induction of both activities and gene expression levels of crucial enzymes involved in ABA metabolism. Our findings revealed that submerging zucchini fruit in ST could be a highly effective strategy for boosting their chilling tolerance. The alleviation in chilling injury induced by ST may be attributed to the modulation of proline, arginine, GABA, AsA and ABA metabolism.
Artificial intelligence, human cognition, and conscious supremacy
Authors: Mogi Ken
Published: May 2024

The computational significance of consciousness is an important and potentially more tractable research theme than the hard problem of consciousness, as one could look at the correlation of consciousness and computational capacities through, e.g., algorithmic or complexity analyses. In the literature, consciousness is defined as what it is like to be an agent (i.e., a human or a bat), with phenomenal properties, such as qualia, intentionality, and self-awareness. The absence of these properties would be termed “unconscious.” The recent success of large language models (LLMs), such as ChatGPT, has raised new questions about the computational significance of human conscious processing. Although instances from biological systems would typically suggest a robust correlation between intelligence and consciousness, certain states of consciousness seem to exist without manifest existence of intelligence. On the other hand, AI systems seem to exhibit intelligence without consciousness. These instances seem to suggest possible dissociations between consciousness and intelligence in natural and artificial systems. Here, I review some salient ideas about the computational significance of human conscious processes and identify several cognitive domains potentially unique to consciousness, such as flexible attention modulation, robust handling of new contexts, choice and decision making, cognition reflecting a wide spectrum of sensory information in an integrated manner, and finally embodied cognition, which might involve unconscious processes as well. Compared to such cognitive tasks, characterized by flexible and ad hoc judgments and choices, adequately acquired knowledge and skills are typically processed unconsciously in humans, consistent with the view that computation exhibited by LLMs, which are pretrained on a large dataset, could in principle be processed without consciousness, although conversations in humans are typically done consciously, with awareness of auditory qualia as well as the semantics of what are being said. I discuss the theoretically and practically important issue of separating computations, which need to be conducted consciously from those which could be done unconsciously, in areas, such as perception, language, and driving. I propose conscious supremacy as a concept analogous to quantum supremacy, which would help identify computations possibly unique to consciousness in biologically practical time and resource limits. I explore possible mechanisms supporting the hypothetical conscious supremacy. Finally, I discuss the relevance of issues covered here for AI alignment, where computations of AI and humans need to be aligned.
Alterations in brain network connectivity and subjective experience induced by psychedelics: a scoping review
Authors: Yu Zijia , Burback Lisa , Winkler Olga , Xu Lujie , Dennett Liz , Vermetten Eric , Greenshaw Andrew , Li Xin-Min , Milne Michaela , Wang Fei , Cao Bo , Winship Ian R. , Zhang Yanbo , Chan Allen W.
Published: May 2024

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics’ neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics.
Assessing the time variability of GIEMS-2 satellite-derived surface water extent over 30 years
Authors: Bernard Juliette , Prigent Catherine , Jimenez Carlos , Frappart Frédéric , Normandin Cassandra , Zeiger Pierre , Xi Yi , Peng Shushi
Published: May 2024

Inland waters, especially wetlands, play a crucial role in biodiversity, water resources and climate, and contribute significantly to global methane emissions. This study investigates the seasonal and inter-annual variability of the 0.25° × 0.25° surface water extent (SWE) from the Global Inundation Extent from Multi-Satellites (GIEMS-2) extended to a 30-year time series (1992–2020). Comparison with MODIS-derived SWE, CYGNSS-derived SWE and the Global Lakes and Wetlands Database (GLWD) shows consistent spatial patterns globally and over 10 different basins, although there are discrepancies in extent, partly due to different resolutions of the initial satellite observations. Strong cross-correlation (>0.8) in seasonal variability is observed when comparing GIEMS-2 with MODIS, CYGNSS and river discharge in most of the basins studied. Encouraging similarities were found in the inter-annual variability in most basins (cross-correlation >0.6) between GIEMS-2 and MODIS over 20 years, and between GIEMS-2 and river discharge over long time series, including over the Amazon and the Congo basins. These results highlight the reliability of GIEMS-2 in detecting changes in SWE in different environments, especially under dense vegetation, making it a valuable resource for calibrating hydrological models and studying global methane emissions.
The High-Energy X-ray Probe (HEX-P): the circum-nuclear environment of growing supermassive black holes
Authors: Boorman P. G. , Torres-Albà N. , Annuar A. , Marchesi S. , Pfeifle R. W. , Stern D. , Civano F. , Baloković M. , Buchner J. , Ricci C. , Alexander D. M. , Brandt W. N. , Brightman M. , Chen C. T. , Creech S. , Gandhi P. , García J. A. , Harrison F. , Hickox R. , Kammoun E. , LaMassa S. , Lanzuisi G. , Marcotulli L. , Madsen K. , Matt G. , Matzeu G. , Nardini E. , Piotrowska J. M. , Pizzetti A. , Puccetti S. , Sicilian D. , Silver R. , Walton D. J. , Wilkins D. R. , Zhao X. ,   The HEX-P Collaboration
Published: May 2024

Ever since the discovery of the first active galactic nuclei (AGN), substantial observational and theoretical effort has been invested into understanding how massive black holes have evolved across cosmic time. Circum-nuclear obscuration is now established as a crucial component, with almost every AGN observed known to display signatures of some level of obscuration in their X-ray spectra. However, despite more than six decades of effort, substantial open questions remain: how does the accretion power impact the structure of the circum-nuclear obscurer? What are the dynamical properties of the obscurer? Can dense circum-nuclear obscuration exist around intrinsically weak AGN? How many intermediate mass black holes occupy the centers of dwarf galaxies? In this paper, we showcase a number of next-generation prospects attainable with the High-Energy X-ray Probe (HEX-P1) to contribute toward solving these questions in the 2030s. The uniquely broad (0.2–80 keV) and strictly simultaneous X-ray passband of HEX-P makes it ideally suited for studying the temporal co-evolution between the central engine and circum-nuclear obscurer. Improved sensitivities and reduced background will enable the development of spectroscopic models complemented by current and future multi-wavelength observations. We show that the angular resolution of HEX-P both below and above 10 keV will enable the discovery and confirmation of accreting massive black holes at both low accretion power and low black hole masses even when concealed by thick obscuration. In combination with other next-generation observations of the dusty hearts of nearby galaxies, HEX-P will be pivotal in paving the way toward a complete picture of black hole growth and galaxy co-evolution.