bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive exploration of twist1 to identify a biomarker for tumor immunity and prognosis in pan-cancer
Authors: Wang Yue , Li Chunhao , Jiang Tianjiao , Yin Yiqiang , Wang Yaowen , Zhao Hui , Yu Liang
Published: April 2024

Twist1 has been identified as a critical gene in tumor, but current study of this gene remains limitative. This study aims to investigate its roles and potential mechanisms across pan-cancer. The study used various databases and computational techniques to analyze twist’s RNA expression, clinical data, gene mutations, tumor stemness, tumor microenvironment, immune regulation. Furthermore, the experimental method of fluorescence staining was carried out to identify twist1 expression in various tumor masses. After analyzing the protein-protein interaction of TWIST, enrichment analysis and predictive potential drugs were performed, and molecular docking was conducted to validate. We found that twist1 expression was significantly higher in various types of cancer and associated with tumor stage, grade, and poor prognosis in multiple cancers. Differential expression of twist1 was linked to gene mutation, RNA modifications, and tumor stemness. Additionally, twist1 expression was positively associated with tumor immunoregulation and immune checkpoint. Salinomycin, klugline, isocephaelince, manassantin B, and pimonidazole are predictive potential drugs targeting TWIST1. This study revealed that twist1 plays an important role in tumor, and might be a curial marker in tumor diagnose and prognosis. The study also highlighted twist1 as a promising therapeutic target for cancer treatment and provided a foundation for future research.
Bibliometric analysis: Hot spots and frontiers in acupuncture treatment of cerebral infarction
Authors: Han Yutong , Liu Chang , Yang Xinming , Zhou Jiaxiao , Shi Weiping , Gao Huasong , Zhang Huixue , Ran Dawei , Shi Lei
Published: April 2024

Objective:

CiteSpace6.1.R2 is used to analyze the research status of acupuncture in the treatment of cerebral infarction, and to find relevant hot spots and frontiers.

Methods:

The researchers searched the Web of Science Core Collection database. The search date is from the establishment of the database to August 31, 2023. The search terms and expressions are: (“Cerebral Infarction” OR “Ischemic stroke”) AND (“Acupuncture” OR “fire needle”). The researchers used CiteSpace software to draw a knowledge map to explore the hot spots and frontiers of acupuncture in treating cerebral infarction.

Results:

We screened 414 articles in the Web of Science Core Collection database. China is the country with the largest number of publications, with a total of 343 papers published. China’s institutions cooperate most closely, and cooperation between countries is less and more scattered. The author with the highest number of published articles is Chen L, with a total of 31 published articles. The research focus mainly revolves around the mechanism of acupuncture treatment of cerebral infarction and electroacupuncture treatment of cerebral infarction. Among them, acupuncture treatment of cerebral infarction is the most.

Conclusion:

According to CiteSpace’s analysis results, China is at the forefront of this research field, while other countries have less research in this field and little cooperation among countries. At present, the mainstream aspect of research is the mechanism of acupuncture treatment of cerebral infarction electroacupuncture and acupuncture points. Therefore, in future research, we should pay more attention to the treatment of cerebral infarction mechanism of acupuncture, problems with the type of acupuncture used, and acupuncture points.
Application research of radiomics in colorectal cancer: A bibliometric study
Authors: Yang Lihong , Wang Binjie , Shi Xiaoying , Li Bairu , Xie Jiaqiang , Wang Changfu
Published: April 2024

Background:

Radiomics has shown great potential in the clinical field of colorectal cancer (CRC). However, few bibliometric studies have systematically analyzed existing research in this field. The purpose of this study is to understand the current research status and future development directions of CRC.

Methods:

Search the English documents on the application of radiomics in the field of CRC research included in the Web of Science Core Collection from its establishment to October 2023. VOSviewer and CiteSpace software were used to conduct bibliometric and visual analysis of online publications related to countries/regions, authors, journals, references, and keywords in this field.

Results:

A total of 735 relevant documents published from Web of Science Core Collection to October 2023 were retrieved, and a total of 419 documents were obtained based on the screening criteria, including 376 articles and 43 reviews. The number of publications is increasing year by year. Among them, China publishes the most relevant documents (n = 238), which is much higher than Italy (n = 69) and the United States (n = 63). Tian Jie is the author with the most publications and citations (n = 17, citations = 2128), GE Healthcare is the most productive institution (n = 26), Frontiers in Oncology is the journal with the most publications (n = 60), and European Radiology is the most cited journal (n = 776). Hot spots for the application of radiomics in CRC include magnetic resonance, neoadjuvant chemoradiotherapy, survival, texture analysis, and machine learning. These directions are the current hot spots for the application of radiomics research in CRC and may be the direction of continued development in the future.

Conclusion:

Through bibliometric analysis, the application of radiomics in CRC has been increasing year by year. The application of radiomics improves the accuracy of preoperative diagnosis, prediction, and prognosis of CRC. The results of bibliometrics analysis provide a valuable reference for the research direction of radiomics. However, radiomics still faces many challenges in the future, such as the single nature of the data source which may affect the comprehensiveness of the results. Future studies can further expand the data sources and build a multicenter public database to more comprehensively reflect the research status and development trend of CRC radiomics.
Relationship between cervical lordotic angle and cervical segmental motion during craniocervical flexion test: A cross-sectional study
Authors: Lee Jae-hyun , Hwang Ui-jae , Kwon Oh-yun
Published: April 2024

The craniocervical flexion test (CCFT) is commonly used for assessing the performance and function of the deep cervical flexor muscles; however, objective measurements of cervical segmental motion during craniocervical flexion (CCF) are lacking. Therefore, the purpose of this study aimed to investigate cervical segmental motions during CCFT and determine the relationship between changes of cervical segmental motions and the cervical lordotic angle. A cross-sectional study of prospectively collected data. Twenty healthy participants without neck pain underwent standing cervical radiography (lateral view) to measure the cervical lordotic angle, followed by radiography in supine position during the CCFT. The occipito-atlantal (OA) joint angle, atlantoaxial (AA) joint angle, and cervical spinous process posterior displacement (CSPPD) of the C1–C6 vertebrae were measured using lateral cervical radiographs taken during the initial (20 mm Hg) and low-stage (24 mm Hg) CCFT conditions. The CCF motion during the low-stage CCFT was characterized by a significantly increased OA joint angle, decreased AA joint angle, and increased C1–C6 CSPPD compared with the initial stage (P < .05). The change in the value of C1–C6 CSPPD at low-stage CCFT showed a significant positive correlation with the cervical lordotic angle. These results indicate that the cervical lordotic angle is important in minimizing CSPPD and performing appropriately-isolated CCF motion during CCFT.
High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial
Authors: Li Wenwen , Zhao Ranran , Liu Shanshan , Ma Chengming , Wan Xianyao
Published: April 2024

Background:

The effects of vitamin C supplementation on patients with septic shock remain controversial. We aimed to evaluate the effects of different vitamin C dosages on norepinephrine (NE) synthesis in adult patients with septic shock.

Methods:

A total of 58 patients with septic shock admitted to our intensive care unit (ICU) between July 2021 and December 2022 were included. Patients were randomly divided into 3 groups: high-dose vitamin C (150 mg/kg/d, group A), low-dose vitamin C (50 mg/kg/d, group B), and placebo (group C). NE synthesis-related indicators (dopamine-β-hydroxylase [DβH], tyrosine hydroxylase [TH], tetrahydrobiopterin [BH4], and dopamine [DA]), plasma NE, and vitamin C levels were measured every 24 hours and analyzed. All-cause mortality within 28 days and other clinical outcomes (including Acute Physiology and Chronic Health Evaluation [APACHE], Sequential Organ Failure Assessment [SOFA], and Multiple-Organ Dysfunction Syndrome [MODS] scores) were compared.

Results:

Changes in TH, BH4, and DβH levels at 96 hours in groups A and B were greater than those in group C. These differences became more pronounced over the course of the intravenous vitamin C administration. Significant differences between groups A and C were detected at 96-hours TH, 72-hours BH4, 96-hours BH4, 96-hours DA, and DβH levels every 24 hours. The 96-hours TH, 96-hours BH4, and 48-hours DβH in group B were significantly higher than those in group C. The NE levels every 24 hours in groups A and B were higher than those in group C, group A and group C had a statistically significant difference. The 96-hours exogenous NE dosage in groups A and B was significantly lower than that in group C. No significant reductions in APACHE, SOFA, or MODS scores were observed in the vitamin C group, including the duration of ICU stay and mechanical ventilation. The 28-days mortality was lower in groups A and B than in group C (0%, 10%, and 16.67%,P = .187), but the difference was not significant.

Conclusion:

For patients with septic shock, treatment with vitamin C significantly increased TH, BH4, and DβH levels and reduced the exogenous NE dosage, but did not significantly improve clinical outcomes.
Serotonin syndrome treated with cyproheptadine using NPi from a digital pupillometer as a therapeutic indicator: A case report
Authors: Sugaya Kazuki , Misawa Tomotaka , Onodera Makoto , Iseki Ken
Published: April 2024

Rationale:

Serotonin syndrome is a potentially life-threatening condition resulting from the use of antidepressants, their interactions with other serotonergic medications, or poisoning. It presents with a triad of psychiatric, dysautonomic, and neurological symptoms and is sometimes fatal. While cyproheptadine is a specific treatment option, the optimal duration of its administration remains unclear. The purpose of this report is to quantitatively assess the endpoints of serotonin syndrome treatment. Based on the hypothesis that neurological pupil index (NPi) on a digital pupil recorder would correlate with the severity of the serotonin syndrome, we administered cyproheptadine using NPi as an indicator.

Patient concerns:

A patient with a history of depression was brought to our hospital after he overdosed on 251 tablets of serotonin and noradrenaline reuptake inhibitors.

Diagnoses:

On day 3, the patient was diagnosed with serotonin syndrome.

Interventions:

Cyproheptadine syrup was administered at 4 mg every 4 hours. The NPi of the automated pupillometer was simultaneously measured. On day 5, the NPi exceeded 3.0 cyproheptadine was discontinued.

Outcomes:

The patient was discharged on day 7.

Lessons:

The lack of considerable improvement during the treatment period suggests that the patient may have improved on his own. In this case, the relationship between NPi and the severity of serotonin syndrome could not be determined.
Discovering an uncommon site of angioleiomyoma origin: a rare case report
Authors: Zahid Khan Tariq , Bashir Afeera , Javeria Malik , Mehfooz Sana , Ahmed Zeba , Raja Sandesh , Ali Azzam , Raja Adarsh , Khanal Anuva
Published: April 2024

Background:

Angioleiomyoma, a benign tumour of the smooth muscles of blood vessels, primarily affects individuals aged 30–50 years, with a higher incidence in females. While it commonly affects the lower extremities, it can also develop in the head and neck. However, hypopharyngeal angioleiomyomas are extremely rare, with only one documented case in world literature.

Methods:

The authors present a rare case of a 70-year-old male with symptoms of voice change and deglutition discomfort. Imaging studies indicated a hypopharyngeal mass. Direct laryngoscopy showed a well-defined mass originating from the left lateral pharyngeal wall, obstructing the left vallecula and pyriform sinus. The patient underwent anterolateral pharyngotomy with mass excision.

Results:

After a successful anterolateral pharyngotomy, the patient experienced significant improvement in symptoms.

Conclusion:

Diagnosing and managing hypopharyngeal angioleiomyoma is challenging due to its unusual location. Its rarity emphasizes the importance of considering it as a possible differential when evaluating hypopharyngeal masses.
Utility of perioperative ultrasonography and fine-needle aspiration cytology in differentiation between benign and malignant cervical lymphadenopathy: a retrospective cohort study
Authors: Ghabisha Saif , Al-wageeh Saleh , Al-yousofy Fayed , Ahmed Faisal , Al-Mwald Taha , Altam Abdulfattah , Badheeb Mohamed
Published: April 2024

Background:

The preoperative differentiation of benign form malignant cervical lymphadenopathy (CLA) is crucial in determining the need for surgical intervention. This study aims to assess the diagnostic performance of ultrasonography (US), fine-needle aspiration cytology (FNAC), and their combination with the postoperative histopathological diagnoses of CLA.

Method:

In a retrospective study between April 2021 and May 2023, 214 patients with CLA were assessed with preoperative US and FNAC. The morphological parameters, including tissue margins, vascularity, and fatty hilum echogenicity, were collected and analyzed retrospectively. The diagnostic efficacies of US, FNAC, and their combined use were compared to the postoperative histopathological findings.

Result:

In the final histopathological examination, 185 cases (86.4%) were found to be benign, while 29 cases (13.6%) were determined to be malignant. The US features of fatty hilum, echogenicity, and vascularity pattern had the highest diagnostic accuracy in characterizing CLA patterns, with values of 88.3%, 85.5%, and 85.0%, respectively. The receiver operating characteristic (ROC) curve showed a significantly higher area under the curve (AUC) value of 0.883 (95% CI: 0.832–0.923; P<0.0001) for the combined use of all US parameters with better sensitivity (93.10%) and specificity (68.65%) than individual parameters. The overall sensitivity, specificity, and accuracy of FNAC were 97.3%, 82.8%, and 95.3%, respectively. Additionally, US parameters and FNAC together showed a significantly higher AUC value of 0.924 (95% CI: 0.880–0.956; P<0.0001) and achieved a sensitivity of 86.21% and specificity of 88.65%.

Conclusions:

The combined use of US and FNAC provides high sensitivity, specificity, and diagnostic accuracy in characterizing CLA patterns. In limited-resources settings, this approach is feasible, less invasive, and cost-effective, thereby enabling clear management strategies and avoiding additional surgical interventions.
Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer
Authors: Habib Joseph R. , Rompen Ingmar F. , Kaslow Sarah R. , Grewal Mahip , Andel Paul C. M. , Zhang Shuang , Hewitt D. Brock , Cohen Steven M. , van Santvoort Hjalmar C. , Besselink Marc G. , Molenaar I. Quintus , He Jin , Wolfgang Christopher L. , Javed Ammar A. , Daamen Lois A.
Published: April 2024

Objective:

To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value.

Background:

Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC.

Methods:

Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI).

Results:

In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2 mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008).

Conclusion:

In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs.
Research protocol for an observational health data analysis to assess the applicability of randomized controlled trials focusing on newly diagnosed metastatic prostate cancer using real-world data: PIONEER IMI’s “big data for better outcomes” program
Authors: Gandaglia Giorgio , Pellegrino Francesco , De Meulder Bertrand , Hijazy Ayman , Abbott Thomas , Golozar Asieh , Nicoletti Rossella , Gomez-Rivas Juan , Steinbeisser Carl , Evans-Axelsson Susan , Briganti Alberto , N’Dow James
Published: April 2024

Background:

Metastatic prostate cancer (PCa) constitutes ~5% of all new PCa diagnoses in Western countries. For most cases, primary consideration should be given to systemic therapies as the first-line approach based on evidence from randomized controlled trials (RCTs). Despite the importance of RCTs as the pinnacle of evidence in modern medicine, concerns have been raised about their applicability to real-life scenarios. These trials often feature participants who are younger with better performance statuses and prognoses compared to their real-world counterparts. The PIONEER project falls under the Innovative Medicine Initiative’s (IMI) “Big Data for Better Outcomes” initiative, aimed at revolutionizing PCa care in Europe. The central focus lies in improving cancer-related outcomes, enhancing health system efficiency, and elevating the quality of health and social care. This study endeavours to evaluate the generalizability of RCT findings concerning newly diagnosed metastatic PCa.

Methods:

A systematic review of the literature will be conducted to compile patient characteristics from RCTs addressing this subject within the past decade. To create a real-world benchmark, patients with recently diagnosed metastatic PCa from a network of population-based databases will serve as a comparison group. The objective is to assess the applicability of RCT results in two ways. First, a comparison will be made between the characteristics of patients with newly diagnosed metastatic PCa enroled in RCTs and those with the same condition included in our databases which might represent the real-world setting. Second, an evaluation will be undertaken to determine the proportion of real-world patients with newly diagnosed metastatic PCa who meet the criteria for RCT enrolment. This study will rely on extensive observational data, primarily sourced from population-based registries, electronic health records, and insurance claims data. The study cohort is established upon routinely gathered healthcare data, meticulously mapped to the Observational Medical Outcomes Partnership Common Data Model.
The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer’s disease: a meta-analysis
Authors: Kress Gavin T. , Popa Emily S. , Merrill David A. , Bramen Jennifer E. , Siddarth Prabha
Published: April 2024

Physical activity (PA) is a promising therapeutic for Alzheimer’s disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges’ g funnel plots, and Egger’s test were used to assess unbiasedness and visualize intervention effects, and Tau2, Cochran’s Q, and I2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger’s test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.
Scaling approaches and macroecology provide a foundation for assessing ecological resilience in the Anthropocene
Authors: Enquist Brian J. , Erwin Doug , Savage Van , Marquet Pablo A.
Published: April 2024

In the Anthropocene, intensifying ecological disturbances pose significant challenges to our predictive capabilities for ecosystem responses. Macroecology—which focuses on emergent statistical patterns in ecological systems—unveils consistent regularities in the organization of biodiversity and ecosystems. These regularities appear in terms of abundance, body size, geographical range, species interaction networks, or the flux of matter and energy. This paper argues for moving beyond qualitative resilience metaphors, such as the ‘ball and cup’, towards a more quantitative macroecological framework. We suggest a conceptual and theoretical basis for ecological resilience that integrates macroecology with a stochastic diffusion approximation constrained by principles of biological symmetry. This approach provides an alternative novel framework for studying ecological resilience in the Anthropocene. We demonstrate how our framework can effectively quantify the impacts of major disturbances and their extensive ecological ramifications. We further show how biological scaling insights can help quantify the consequences of major disturbances, emphasizing their cascading ecological impacts. The nature of these impacts prompts a re-evaluation of our understanding of resilience. Emphasis on regularities of ecological assemblages can help illuminate resilience dynamics and offer a novel basis to predict and manage the impacts of disturbance in the Anthropocene more efficiently.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
The human side of biodiversity: coevolution of the human niche, palaeo-synanthropy and ecosystem complexity in the deep human past
Authors: Hussain Shumon T. , Baumann Chris
Published: April 2024

Today's biodiversity crisis fundamentally threatens the habitability of the planet, thus ranking among the primary human challenges of our time. Much emphasis is currently placed on the loss of biodiversity in the Anthropocene, yet these debates often portray biodiversity as a purely natural phenomenon without much consideration of its human dimensions and frequently lack long-term vistas. This paper offers a deep-time perspective on the key role of the evolving human niche in ecosystem functioning and biodiversity dynamics. We summarize research on past hunter–gatherer ecosystem contributions and argue that human–environment feedback systems with important biodiversity consequences are probably a recurrent feature of the Late Pleistocene, perhaps with even deeper roots. We update current understandings of the human niche in this light and suggest that the formation of palaeo-synanthropic niches in other animals proffers a powerful model system to investigate recursive interactions of foragers and ecosystems. Archaeology holds important knowledge here and shows that ecosystem contributions vary greatly in relation to different human lifeways, some of which are lost today. We therefore recommend paying more attention to the intricate relationship between biodiversity and cultural diversity, contending that promotion of the former depends on fostering the latter.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Unravelling the functional and phylogenetic dimensions of novel ecosystem assemblages
Authors: Ordonez Alejandro , Gill Jacquelyn L.
Published: April 2024

Human activities are causing taxonomic rearrangements across ecosystems that often result in the emergence of novel communities (assemblies with no historical representative). It is commonly assumed that these changes in the taxonomic makeup of ecosystems also inevitably lead to changes in other aspects of biodiversity, namely functional and phylogenetic diversity. However, this assumption is not always valid, as the changes in functional and phylogenetic composition resulting from taxonomic shifts depend on the level of redundancy in the evaluated community. Therefore, we need improved theoretical frameworks to predict when we can expect coordinated or decoupled responses among these three facets of biodiversity. To advance this understanding, we discuss the conceptual and methodological issues that complicate establishing a link between taxonomic rearrangements driven by human activities and the associated functional and phylogenetic changes. Here, we show that is crucial to consider the expected changes in functional and phylogenetic composition as communities are reshaped owing to human drivers of biodiversity loss to forecast the impacts of novel assemblages on ecosystem functions and the services they provide to humanity.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use
Authors: Weng Yihe , Kruschwitz Johann , Rueda-Delgado Laura M. , Ruddy Kathy , Boyle Rory , Franzen Luisa , Serin Emin , Nweze Tochukwu , Hanson Jamie , Smyth Alannah , Farnan Tom , Banaschewski Tobias , Bokde Arun L.W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , McGrath Jane , Nees Frauke , Papadopoulos Orfanos Dimitri , Paus Tomáš , Poustka Luise , Holz Nathalie , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Schumann Gunter , Walter Henrik , Whelan Robert ,   IMAGEN Consortium
Published: April 2024

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance-use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants. Behaviours and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

Teaser

A robust brain network for sustained attention at age 14 predicts cigarette and cannabis use from ages 14 to 23.
The “abominable mystery” of Schenck: the polymorphism ofSerjania piscatoriaand its implications for the evolution of vascular variants in Paullinieae (Sapindaceae)
Authors: Marques Natália F. , Cunha Neto Israel L. , Brito Lilian A. , Somner Genise V.
Published: April 2024

Serjaniais the only genus of Paullinieae that exhibits all types of vascular variants in stems and includesS. piscatoriawith a complex vascular structure that has intrigued botanists for centuries. Here, we analyzed the stem development ofS. piscatoriain an evolutionary context and determined its phylogenetic position within the genus. We studied four individuals using standardized anatomical techniques and employed DNA sequencing and phylogenetic analysis to determine the species’ phylogenetic position. Additionally, we employed ancestral state reconstruction to explore the pattern of evolution of vascular variants. We find that the stem development inS. piscatoriais determined by various ontogenetic processes that result in vascular variants that occur through modifications during primary and/or secondary growth, or ectopic cambia formation. These various patterns are classified into distinct categories of vascular variants, highlighting the lability of vascular meristems and the polymorphism within the species, which manifests across different individuals.Serjania piscatoriabelongs to a clade composed of species with compound stems, from which the fissured stems observed in the species would have evolved. The findings provide evidence for the diverse stem vasculature inSerjania, and the importance of studying vascular variant diversity from a developmental and evolutionary perspective.
DNA replication in primary hepatocytes without the six-subunit ORC
Authors: Przanowska Róża K. , Chen Yuechuan , Uchida Takayuki-Okano , Shibata Etsuko , Hao Xiaoxiao , Rueda Isaac Segura , Jensen Kate , Przanowski Piotr , Trimboli Anthony , Shibata Yoshiyuki , Leone Gustavo , Dutta Anindya
Published: April 2024

The six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2, which does not have a homolog. Although mouse embryo fibroblasts require ORC2 for proliferation, mouse hepatocytes synthesize DNA in cell culture and endo-reduplicatein vivowithout ORC2. Mouse livers endo-reduplicate after simultaneous deletion of ORC1 and ORC2 both during normal development and after partial hepatectomy. Since endo-reduplication initiates DNA synthesis like normal S phase replication these results unequivocally indicate that primary cells, like cancer cell lines, can load MCM2-7 and initiate replication without ORC.
NovoLign: metaproteomics by sequence alignment
Authors: Kleikamp Hugo B.C. , van der Zwaan Ramon , van Valderen Ramon , van Ede Jitske M. , Pronk Mario , Schaasberg Pim , Allaart Maximilienne T. , van Loosdrecht Mark C.M. , Pabst Martin
Published: April 2024

Tremendous advances in mass spectrometric and bioinformatic approaches have expanded proteomics into the field of microbial ecology. The commonly used spectral annotation method for metaproteomics data relies on database searching, which requires sample-specific databases obtained from whole metagenome sequencing experiments. However, creating these databases is complex, time-consuming, and prone to errors, potentially biasing experimental outcomes and conclusions. This asks for alternative approaches that can provide rapid and orthogonal insights into metaproteomics data. Here we present NovoLign, ade novometaproteomics pipeline that performs sequence alignment ofde novosequences from complete metaproteomics experiments. The pipeline enables rapid taxonomic profiling of complex communities and evaluates the taxonomic coverage of metaproteomics outcomes obtained from database searches. Furthermore, the NovoLign pipeline supports the creation of reference sequence databases for database searching to ensure comprehensive coverage. The NovoLign pipeline is publicly available via:https://github.com/hbckleikamp/NovoLign.
To be browsed or not to be browsed: differences in nutritional characteristics of blackthornPrunus spinosasubject to the long-term pressure of herbivores
Authors: Facciolati Veronica , Zarek Marcin , Błońska Ewa , Lasota Jarosław , Orman Olga , Ciach Michał
Published: April 2024

The impact of ungulates on temperate forest vegetation has been investigated for a long time. Numerous studies on food selection have identified the palatable plant species preferred by large European herbivores. However, intra-specific food selection and the question why particular plants of a given species are ignored during foraging have been neglected in the literature. In central Europe, BlackthornsPrunus spinosagrowing in abandoned pastures are an important component of the red deer’sCervus elaphusdiet. In areas densely populated by deer, annual shoot browsing produces dwarf shrubby forms of blackthorns. However, some blackthorns are not browsed by ungulates and tend to adopt a tree-like form. The existence of distinct, browsing-dependent growth forms of blackthorns raises the question of inter-individual differences in the nutritional composition of plants. Based on factor analysis, we discovered differences in nutritional composition between browsed and unbrowsed blackthorns that might explain the individual plant-related drivers of red deer food preferences. The leaves of browsed blackthorns contained higher concentrations of C, N, P and Cu but lower levels of Ca and Mg than unbrowsed ones. Moreover, browsed blackthorns had a higher water content and higher concentrations of insoluble proteins, chlorophylls and carotenoids. We highlight the fact that the nutritional characteristics of an individual plant may explain the observed food selection pattern, leading to the unhindered growth of a fraction of the blackthorn population, in spite of severe pressure on the part of ungulate herbivores. The results of this study underline the important role of herbivores in the dynamics of plant communities, in which ungulates may mediate the persistence of certain individuals of a given species.

Highlights

Browsing by ungulates leads to the formation of dwarf shrubby forms in blackthorns

Some blackthorns are unbrowsed and adopt a tree-like form

Browsed blackthorns differ in chemical composition from unbrowsed ones

The nutritional profile of a given plant may influence food selection by ungulates
Influence of Incorporating Full-Fat Black Soldier Fly Larvae Meal (BSFLM) in Meat Type Chicken Diets on the Lower Gut Short Chain Fatty Acids profile, Gut Morphology and Intestinal Lesion Score
Authors: Bhattacharyya Jayanta , Chatterjee PareshNath , Chatterjee Jayanta Kumar , Pal Aruna
Published: April 2024

Though protein demand is increasing day by day but the animal protein industry on a global scale is facing the biggest challenge of replacing antibiotic growth promoters (AGP) to raise broiler chickens. Using AGP is a long-standing practice to include in poultry diets for improving the intestinal health and subsequent performance of the broiler chicken. Due to increased restrictions and bans on the usage of antibiotics, the poultry-producing community is in search of a suitable and sustainable alternative to AGPs. The present study was aimed at to evaluate and analyte the potential impacts and consequences associated with the inclusion of black soldier fly larvae meal (BSFLM) in a commercially available meat type chicken when compared to diets that either contained or lacked the presence of antibiotic growth promoters, specifically enramycin at a concentration of 8% and chlortetracycline at a concentration of 15%. Our study also assessed the influence of inclusion of BSFLM on cecal short chain fatty acids (SCFAs), and the gut health. 180 male day-old Vencobb430Y chicks (mean BW 42.52 g) (P > 0.05) were randomly allocated into isonitrogenous and isoenergetic dietary treatments in three equal groups. BSFLM group has exhibited significant higher concentration of short chain fatty acids in cecum like acetate, isobutyrate, butyrate, and total SCFAs compared to both the AGP and CONTROL groups (P<0.05). The villi height of duodenum and jejunum remained significantly higher in BSFLM supplemented birds as compared to the AGP group (P<0.05). From the analysis of frequency plots depicting the severity of intestinal lesions, it was observed that the presence of serosa and mucosa congestion in the anterior sections of the gastrointestinal tract was within the expected range for both the CONTROL and AGP groups, thus indicating that this particular physiological condition can be considered as normal in these experimental groups. In the duodenal part, incorporating BSFL meal showed significantly higher villi height and crypt depth compared with CONTROL and AGP (P<0.05). Inclusion of full-fat BSF has improved overall intestinal health and lower lesion scores compared to the CONTROL and AGP groups. The present investigation explored thepotential of incorporating full-fat black soldier fly larvae (BSFL) meal into the dietary regimens of broilers for sgnificantly bolstering the health and functionality of their gastrointestinal tract, particularly in instances where the inclusion of antimicrobial growth promoters (AGP) is deliberately omitted from said diets.
Protoxylem microtubule patterning requires ROP pattern co-alignment, realistic microtubule-based nucleation, and moderate microtubule flexibility
Authors: Jacobs Bas , Saltini Marco , Molenaar Jaap , Filion Laura , Deinum Eva E.
Published: April 2024

The development of the water transporting xylem tissue in plants involves an intricate interplay of Rho-of-Plants (ROP) proteins and cortical microtubules to generate highly functional secondary cell wall patterns, such as the ringed or spiral patterns in early-developing protoxylem. We study the requirements of protoxylem microtubule band formation with simulations in CorticalSim, extended to include finite microtubule persistence length and a novel algorithm for microtubule-based nucleation. We find that microtubule flexibility is required to facilitate pattern formation for all realistic degrees of mismatch between array and pattern orientation. At the same time, flexibility leads to more density loss, both from collisions and the microtubule-hostile gap regions, making it harder to maintain microtubule bands. Microtubule-dependent nucleation helps to counteract this effect by gradually shifting nucleation from the gap regions to the bands as microtubules disappear from the gaps. Our results reveal the main mechanisms required for efficient protoxylem band formation.
Interleukin-6 induces nascent protein synthesis in human DRG nociceptors via MNK-eIF4E signaling
Authors: Mitchell Molly E. , Torrijos Gema , Cook Lauren F. , Mwirigi Juliet M. , He Lucy , Shiers Stephanie , Price Theodore J.
Published: April 2024

Plasticity of dorsal root ganglion (DRG) nociceptors in the peripheral nervous system requires new protein synthesis. This plasticity is believed to be responsible for the physiological changes seen in DRG nociceptors in animal models of chronic pain. Experiments in human DRG (hDRG) neurons also support this hypothesis, but a direct observation of nascent protein synthesis in response to a pain promoting substance, like interleukin-6 (IL-6), has not been measured in these neurons. To fill this gap in knowledge, we used acutely prepared human DRG explants from organ donors. These explants provide a physiologically relevant microenvironment, closer toin vivoconditions, allowing for the examination of functional alterations in DRG neurons reflective of human neuropathophysiology. Using this newly developed assay, we demonstrate upregulation of the target of the MNK1/2 kinases, phosphorylated eIF4E (p-eIF4E), and nascently synthesized proteins in a substantial subset of hDRG neurons following exposure to IL-6. To pinpoint the specific molecular mechanisms driving this IL-6- driven increase in nascent proteins, we used the specific MNK1/2 inhibitor eFT508. Treatment with eFT508 resulted in the inhibition of IL-6-induced increases in p-eIF4E and nascent proteins. Additionally, using TRPV1 as a marker for nociceptors, we found that these effects occurred in a large number of human nociceptors. Our findings provide clear evidence that IL-6 drives nascent protein synthesis in human TRPV1+ nociceptors via MNK1/2-eIF4E signaling. The work links animal findings to human nociception, creates a framework for additional hDRG signaling experiments, and substantiates the continued development of MNK inhibitors for pain.
Complete loss ofSLC30A8in humans improves glucose metabolism and beta cell function
Authors: Lamarche Lindsey B. , Koch Christopher , Khalid Shareef , Zaman Maleeha , Zessis Richard , Clement Matthew E. , Denning Daniel P. , Goldfine Allison B. , Abbasi Ali , Harrow Jennifer L , Underwood Christina , Tsunoyama Kazuhisa , Asaumi Makoto , Kou Ikuyo , Rodriguez-Flores Juan L , Shuldiner Alan R. , Rasheed Asif , Jahanzaib Muhammad , Mian Muhammad Rehan , Liaqat Muhammad Bilal , Abdulsalam Usman , Sultana Riffat , Jalal Anjum , Saeed Muhammad Hamid , Abbas Shahid , Memon Fazal Rehman , Ishaq Muhammad , Gurtan Allan M. , Dominy John E. , Saleheen Danish
Published: April 2024

Genetic association studies have demonstrated that partial loss ofSLC30A8function protects against type 2 diabetes (T2D) in humans, but the impact of complete loss ofSLC30A8function remains unknown. From whole-exome and genome sequencing of 100,814 participants in the Pakistan Genome Resource, we identified fifteenSLC30A8knockouts, including homozygotes for a variant enriched in South Asians (Gln174Ter) and 615 heterozygotes for loss-of-function (LoF) variants. T2D risk was lower inSLC30A8LoF hetero- and homozygotes, and the protective effect strengthens in a gene dose-dependent manner (ORadditive=0.63 [0.53-0.78, p=7.5E-07], ORrecessive=0.27 [0.09-0.80, p=0.018]). Recall-by-genotype ofSLC30A8LoF hetero- and homozygotes and their family members with oral glucose tolerance tests showed a gene dose-dependent reduction in glucose levels coupled with elevated insulin. Corrected Insulin Response, Disposition Index, and Insulin Sensitivity Index in LoF hetero- and homozygotes indicated higher glucose-stimulated insulin secretion with preserved beta cell function. These data suggest that therapeutic knockdown ofSLC30A8, up to and including complete knockout, may treat T2D safely and effectively.
Real-world evaluation of deep learning algorithms to classify functional pathogenic germline variants
Authors: Chow Ryan D. , Parikh Ravi B. , Nathanson Katherine L.
Published: April 2024

Deep learning models for variant pathogenicity prediction can recapitulate expert-curated annotations, but their performance remains unexplored on actual disease phenotypes in a real-world setting. Here, we apply three state-of-the-art pathogenicity prediction models to classify hereditary breast cancer gene variants in the UK Biobank. Predicted pathogenic variants inBRCA1, BRCA2andPALB2, but notATMandCHEK2, were associated with increased breast cancer risk. We explored gene-specific score thresholds for variant pathogenicity, finding that they could improve model performance. However, when specifically tasked with classifying variants of uncertain significance, the deep learning models were generally of limited clinical utility.
ROS-Induced Stress Promotes Enrichment and Emergence of Antibiotic Resistance in Conventional Activated Sludge Processes
Authors: Manna Bharat , Zhou Xueyang , Singhal Naresh
Published: April 2024

Since the Great Oxidation Event 2.4 billion years ago, microorganisms have evolved sophisticated responses to oxidative stress. These ancient adaptations remain relevant in modern engineered systems, particularly in conventional activated sludge (CAS) processes, which serve as significant reservoirs of antibiotic resistance genes (ARGs). While ROS-induced stress responses are known to promote ARG enrichment/emergence in pure cultures, their impact on ARG dynamics in wastewater treatment processes remains unexplored. Shotgun-metagenomics analysis of two hospital wastewater treatment plants showed that only 35-53% of hospital effluent resistome was retained in final effluent. Despite this reduction, approximately 30% of ARGs in CAS showed higher abundance than upstream stages, of which 22% emerged de novo. Beta-lactamases and efflux pumps constituted nearly 50% of these enriched ARGs. These ARGs exhibited significant correlations (p < 0.05) with ROS stress response genes (oxyR, soxR, sodAB, katG and ahpCF). The CAS resistome determined 58-75% of the effluent ARG profiles, indicating treatment processes outweigh influent composition in shaping final resistome. Proof-of-concept batch reactor experiments confirmed increased ROS and ARG levels under high dissolved oxygen (8 mg/L) compared to low oxygen (2 mg/L). Untargeted metaproteomics revealed higher expression of resistant proteins (e.g., OXA-184, OXA-576, PME-1, RpoB2, Tet(W/32/O)) under elevated ROS levels. Our findings demonstrate that CAS processes actively shape effluent resistome through ROS-mediated selection, indicating that treatment processes, rather than initial wastewater composition, determine final ARG profiles. This study indicates that the emergence of ARGs needs to be considered as an integral aspect of wastewater treatment design and operation to prevent antibiotic resistance dissemination.