bluuebunny/crossref_metadata_2025 huggingface dataset:
United States-Based Colorectal Cancer Surgical Trials Lack Representation and Adequate Reporting of Racially and Ethnically Diverse Participants: Systematic Review and Regression Analysis
Authors: Ore Ana Sofia , Arean-Sanz Rodrigo , Liu Betty , Arndt Kevin , Hernandez Angelica , Ponce Cristina , Bain Paul , Messaris Evangelos
Published: January 2024

BACKGROUND:

Despite the established National Institute of Health Revitalization Act, which aims to include ethnic and racial minority representation in surgical trials, racial and ethnic enrollment disparities persist.

OBJECTIVE:

To assess the proportion of patients from minority races and ethnicities that are included in colorectal cancer surgical trials and reporting characteristics.

DATA SOURCES:

Search was performed using MEDLINE (Ovid), Embase, Web of Science, and Cochrane Central

STUDY SELECTION:

Inclusion criteria included (1) trials performed in the United States between January 1, 2000, and May 30, 2022; (2) patients with colorectal cancer diagnosis; and (3) surgical intervention, technique, or postoperative outcome. Trials evaluating chemotherapy, radiotherapy or other nonsurgical interventions were excluded.

INTERVENTIONS:

Pooled proportion and regression analysis was performed to identify proportion of patients by race and ethnicity included in surgical trials, and association of year of publication and funding source.

MAIN OUTCOME MEASURES:

Proportion of trials reporting race and reporting ethnicity, and proportion of participants by race and ethnicity included in surgical trials.

RESULTS:

We screened 10,673 unique publications, of which 80 were examined in full-text. 15 studies met our inclusion criteria. 66.7% (10) of trials did not report race, three reported races as proportion of White participants only, and three reported 3 or more races. There was no description of ethnicity in 73.3% (11) of trials, with two describing “non-Caucasian” as ethnicity, and two describing only Hispanic ethnicity. Pooled proportion of White participants was 81.3%, 6.2% for Black participants, 3.6% for Asian and 3.5% for Hispanic participants.

LIMITATIONS:

A small number of studies where identified that reported racial or ethnic characteristics of their participants.

CONCLUSIONS:

Both race and ethnicity are severely underreported in colorectal cancer surgical trials. To improve outcomes and ensure the inclusion of vulnerable populations in innovative technologies and novel treatments, reporting must be closely monitored.
Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages
Authors: Tseng Huan-Chin , Hsu Teh-Fu , Lin Yi-Ying , Lai Wei-Yi , Liu Yu-Hao , Yang Yi-Ping , Chen Cheng-Fong , Wang Chien-Ying
Published: January 2024

Background:

Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs).

Methods:

To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations.

Results:

Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential.

Conclusion:

In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.
Real-World Effectiveness of High-Dose Olanzapine and Clozapine for Treatment-Resistant Schizophrenia in Japan
Authors: Watanabe Maiko , Misawa Fuminari , Takeuchi Hiroyoshi
Published: January 2024

Background

Clozapine is considered the gold standard medication for treatment-resistant schizophrenia (TRS). However, given that clozapine treatment is associated with the burden of regular blood monitoring and the risk of life-threatening adverse effects, high-dose olanzapine can serve as an alternative treatment. We conducted a bidirectional mirror-image study to evaluate the effectiveness of high-dose olanzapine compared with clozapine.

Methods

We included patients with TRS who switched from olanzapine to clozapine or switched from clozapine to olanzapine, and received high-dose (>20 mg/d) olanzapine treatment for ≥4 weeks at Yamanashi Prefectural Kita Hospital. We obtained data on hospitalization, seclusion, and modified electroconvulsive therapy (mECT) during the clozapine phase and the olanzapine phase.

Results

A total of 44 patients were included. When patients switched from high-dose olanzapine to clozapine (n = 32), significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once. When patients switched from clozapine to high-dose olanzapine (n = 12), a significant reduction was found in the number of patients who received mECT at least once. When data from both directions of treatment were combined, significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once in favor of clozapine.

Conclusions

Findings suggest that high-dose olanzapine may not be as effective as clozapine for patients with TRS in real-world practice. However, it should be noted that there are unique circumstances that restrict the use of clozapine in Japan.
microRNAs and thrombo-inflammation: relationship in sight
Authors: Águila Sonia , González-Conejero Rocío , Martínez Constantino
Published: January 2024

Purpose of review

Thrombo-inflammation is a multifaceted pathologic process involving various cells such as platelets, neutrophils, and monocytes. In recent years, microRNAs have been consistently implicated as regulators of these cells.

Recent findings

MicroRNAs play a regulatory role in several platelet receptors that have recently been identified as contributing to thrombo-inflammation and neutrophil extracellular trap (NET) formation. In addition, a growing body of evidence has shown that several intracellular and extracellular microRNAs directly promote NET formation.

Targeting microRNAs is a promising therapeutic approach to control thrombosis in patients with both infectious and noninfectious inflammatory diseases. Future research efforts should focus on elucidating the specific roles of microRNAs in thrombo-inflammation and translating these findings into tangible benefits for patients.
Impact of Preoperative Diabetes Mellitus on Postoperative Outcomes in Elective Pancreatic Surgery and Its Implications for Prehabilitation Practice
Authors: Wijma Allard G. , Driessens Heleen , Nijkamp Maarten W. , Hoogwater Frederik J.H. , van Dijk Peter R. , Klaase Joost M.
Published: January 2024

Objectives

Patients with pancreatic disease(s) have a high risk of developing diabetes mellitus (DM). Diabetes mellitus is associated with adverse postoperative outcomes. This study aimed to investigate the prevalence and effects of DM on postoperative outcomes in pancreatic surgery.

Methods

Subgroup analysis of a prospective cohort study conducted at an academic hospital. Patients undergoing pancreatoduodenectomy between January 2019 and November 2022 were included and screened for DM preoperatively using glycated hemoglobin (HbA1c). New-onset DM was diagnosed based on HbA1c ≥ 6.5% (48 mmol/mol). Postoperative outcomes were compared between patients with and without DM.

Results

From 117 patients, 29 (24.8%) were given a diagnosis of DM, and of those, 5 (17.2%) were diagnosed with new-onset DM, and 15 (51.8%) displayed poorly controlled preoperative DM (HbA1c ≥ 7% [53 mmol/mol]). The incidence of surgical site infections (48.3% vs 27.3% in the non-DM group; P = 0.04) was higher for patients with DM. This association remained significant after adjusting for confounders (odds ratio, 2.60 [95% confidence interval, 1.03–6.66]; P = 0.04).

Conclusions

One-quarter of the patients scheduled for pancreatoduodenectomy had DM; over half of them had poor glycemic control. The association between DM status and surgical site infections revealed in this study emphasizes the importance of adequate preoperative glycemic control.
Cell of Origin of Pancreatic cancer
Authors: Zheng Chenlei , Wang Jianing , Wang Junli , Zhang Qi , Liang Tingbo
Published: January 2024

Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal diseases globally, boasting a grim 5-year survival prognosis. The origin cell and the molecular signaling pathways that drive PDAC progression are not entirely understood. This review comprehensively outlines the categorization of PDAC and its precursor lesions, expounds on the creation and utility of genetically engineered mouse models used in PDAC research, compiles a roster of commonly used markers for pancreatic progenitors, duct cells, and acinar cells, and briefly addresses the mechanisms involved in the progression of PDAC. We acknowledge the value of precise markers and suitable tracing tools to discern the cell of origin, as it can facilitate the creation of more effective models for PDAC exploration. These conclusions shed light on our existing understanding of foundational genetically engineered mouse models and focus on the origin and development of PDAC.
Exploring strategies for building a sustainable healthcare system in Africa: lessons from Japan and Switzerland
Authors: Muili Abdulbasit Opeyemi , Tangmi Adrien , Shariff Sanobar , Awad Farah , Oseili Taha
Published: January 2024

Strengthening healthcare infrastructure is an important strategy for building a sustainable healthcare system in Africa. This involves investing in facilities, equipment, and supplies, as well as training and retaining skilled healthcare workers. Additionally, improving healthcare infrastructure and investing in healthcare education and training can lead to significant improvements in health outcomes, such as reducing maternal and child mortality. This is critical for building a sustainable healthcare system. Through a literature review, we assessed the approaches to building a sustainable healthcare system in Africa from the perspectives of Japan’s and Switzerland’s healthcare systems. It was discovered that Japan currently has the highest life expectancy, which can be attributed to insurance policies, healthcare policies, and the integration of emerging technologies and clinical research into their healthcare system. Lessons that Africa must emulate from the Japanese healthcare system include ensuring universal healthcare coverage, improving the workforce, improving primary healthcare, prioritizing the aging population, and investing in technology, infrastructure, and research. Japans healthcare system is also sustainable thanks to its stable workforce and primary healthcare. Switzerland also has an exceptional healthcare system globally, with technical and socioeconomic advancements leading to increased life expectancy and population aging through a worldwide health policy approach, programs tackling professional responsibilities and interprofessional cooperation, and initiatives to support family medicine. By learning from Japan’s and Switzerland’s approaches, Africa will gradually achieve the Sustainable Development Goals and build a sustainable healthcare system.
Front-of-Pack Nutrition Labels
Authors: Drewnowski Adam
Published: January 2024

Front-of-pack nutrition labels that reflect and convey a food's nutritional value have a dual purpose. The first one is to promote consumer demand for more nutrient-rich foods. The second one is to motivate manufacturers to improve the quality of product portfolios by removing excess calories, fat, sugar, and salt. Whether front-of-pack nutrition labels can help shape food supply or food demand is a complex question that needs to be evaluated more closely.
Comparison of dolutegravir and efavirenz on depression, anxiety and sleep disorders in pregnant and postpartum women living with HIV
Authors: van der Wekken-Pas Lena , Nassiwa Sylvia , Malaba Thokozile , Lamorde Mohammed , Myer Landon , Waitt Catriona , Reynolds Helen , Khoo Saye , He Nengjie , van Leeuwen Liesbeth , Burger David , Wang Duolao , Colbers Angela
Published: January 2024

Background:

Both dolutegravir and efavirenz are known to be effective in pregnancy and postpartum to prevent vertical transmission of HIV and to maintain maternal health. Both drugs have also been associated with neuropsychiatric symptoms. To what extent, these symptoms occur in pregnant and postpartum women, however, is not yet known.

Methods:

This was a secondary analysis of the DolPHIN2 study, a multicentre randomized trial among women presenting late in pregnancy with untreated HIV – who received either a dolutegravir-containing or efavirenz-containing regimen. Longitudinal measures of depression, anxiety and sleep quality were analysed during pregnancy and up to 48 weeks postpartum.

Results:

Among 268 women, median (IQR) Edinburgh Post Natal Depression Score (EPDS) scores were 8 (3–11) and highest at enrolment. In the dolutegravir and efavirenz arm, respectively, 23.7 and 25.6% had an EPDS score above 9, indicating possible or probable depression. Abnormal Hospital Anxiety Depression scores (HADS) (above 11) were seen at least once during follow-up in 42 of patients (15.7%), although no differences were seen between treatment arms. No association was found between EPDS, suicidality and HADS scores and the assigned regimen (P = 0.93, 0.97 and 0.18 respectively). Median (IQR) Pittsburgh Sleep Quality index (PSQI) scores for dolutegravir and efavirenz were 6 (5–7) and 5 (5–6.5), respectively, P = 0.70.

Conclusion:

No statistically significant differences were observed between efavirenz-containing or dolutegravir-containing regimens. Rates of depression were high, but decreased over the course of time and confirm the need for psychological support after initial HIV diagnosis in pregnancy.
Rescreening on RBANS Delayed Memory Index? Forget About It!
Authors: Sabbagh Marwan N. , Michalak Wojciech , Thim Hansen Charlotte , Ahmad Wichmann Christian , Clark Alice
Published: January 2024

Objective:

To assess the value of rescreening patients with Alzheimer’s disease who do not meet the inclusion criteria for the Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) at the initial assessment.

Patients and Methods:

Participants (aged 50–85 years, without dementia, Mini-Mental State Examination score ≥22, valid Clinical Dementia Rating [CDR] global score, and amyloid status at baseline) were identified in the European Prevention of Alzheimer’s Dementia database. Changes from baseline in RBANS DMI were estimated using a mixed model for repeated measurements. Logistic regressions were used to estimate the probability of participants with baseline RBANS DMI 86–95 having RBANS DMI ≤85, CDR global score ≥0.5, and amyloid positivity at 6 and 12 months.

Results:

There was significant variability in the change in RBANS DMI scores over time (median change at 6 months: 2.0). An estimated 15% of participants with RBANS DMI 86–95 at baseline progressed to ≤85 at 6 months; 8% also achieved CDR global score ≥0.5 and 5% were also amyloid positive.

Conclusions:

The results from our analysis indicate that there is limited value in rescreening patients based on their initial RBANS DMI score.
The Therapeutic Role of Intermittent Theta Burst Stimulation in Schizophrenia
Authors: Salabat Dorsa , Pourebrahimi Amirali , Mayeli Mahsa , Cattarinussi Giulia
Published: January 2024

Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores (k = 6, P = 0.07), and a significant difference in PANSS total scores (k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores (k = 5, standardized mean difference = −0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.
Polymer-extracted structure of the mechanosensitive channel MscS reveals the role of protein-lipid interactions in the gating cycle
Authors: Moller Elissa , Britt Madolyn , Zhou Fei , Yang Hyojik , Anshkin Andriy , Ernst Robert , Sukharev Sergei , Matthies Doreen
Published: January 2024

Membrane protein structure determination is not only technically challenging but is further complicated by the removal or displacement of lipids, which can result in non-native conformations or a strong preference for certain states at the exclusion of others. This is especially applicable to mechanosensitive channels (MSC’s) that evolved to gate in response to subtle changes in membrane tension transmitted through the lipid bilayer.E. coliMscS, a model bacterial system, is an ancestral member of the large family of MSCs found across all phyla of walled organisms. As a tension sensor, MscS is very sensitive and highly adaptive; it readily opens under super-threshold tension and closes under no tension, but under lower tensions, it slowly inactivates and can only recover when tension is released. However, existing cryo-EM structures do not explain the entire functional gating cycle of open, closed, and inactivated states. A central question in the field has been the assignment of the frequently observed non-conductive conformation to either a closed or inactivated state. Here, we present a 3 Å MscS structure in native nanodiscs obtained with Glyco-DIBMA polymer extraction, eliminating the lipid removal step that is common to all previous structures. Besides the protein in the non-conductive conformation, we observe well-resolved densities of four endogenous phospholipid molecules intercalating between the lipid-facing and pore-lining helices in preferred orientations. Mutations of positively charged residues coordinating these lipids inhibit MscS inactivation, whereas removal of a negative charge near the lipid-filled crevice increases inactivation. The functional data allows us to assign this class of structures to the inactivated state. This structure reveals preserved lipids in their native locations, and the functional effects of their destabilization illustrate a novel inactivation mechanism based on an uncoupling of the peripheral tension-sensing helices from the gate.
Dose range-finding toxicity study in rats with recombinant human lactoferrin produced inKomagataella phaffii
Authors: Peterson Ross , Crawford Robert B. , Blevins Lance K. , Kaminski Norbert E. , Sass June S. , Ferraro Bryce , Vishwanath-Deutsch Roma , Clark Anthony J. , Malinczak Carrie-Anne
Published: January 2024

The oral toxicity of recombinant human lactoferrin (Helaina rhLF, Effera™) produced inKomagataella phaffiiwas investigated in adult Sprague-Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer and the test groups received daily doses of 200, 1000 and 2000 mg of rhLF per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to inform dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 400x Helaina’s intended commercial use, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.
Bridging DNA contacts allow Dps fromE. colito condense DNA
Authors: Shahu Sneha , Vtyurina Natalia , Das Moumita , Meyer Anne S. , Ganji Mahipal , Abbondanzieri Elio A.
Published: January 2024

The DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNAin vitro. However, the mechanism that allows these complexes to nucleate on DNA remains unclear. Here, we examine how DNA topology influences the formation of Dps-DNA complexes. We find that DNA supercoils offer the most preferred template for the nucleation of condensed Dps structures. More generally, bridging contacts between different regions of DNA can facilitate the nucleation of condensed Dps structures. In contrast, Dps shows little affinity for stretched linear DNA before it is relaxed. Once DNA is condensed, Dps forms a stable complex that can form inter-strand contacts with nearby DNA, even without free Dps present in solution. Taken together, our results establish the important role played by bridging contacts between DNA strands in nucleating and stabilizing Dps complexes.

Graphical Abstract

Graphical Abstract.

Working model of nucleation and formation of Dps-DNA complex.

Regions of supercoiled or stochastically bent DNA act as nucleation points for the formation of Dps-DNA complexes by allowing Dps to form bridging contacts. Dps does not readily bind to straight stretches of DNA in isolation. Once Dps-DNA complexes are formed they can form bridging contacts to bind additional DNA.
Jointly benchmarking small and structural variant calls with vcfdist
Authors: Dunn Tim , Zook Justin M. , Holt James M. , Narayanasamy Satish
Published: January 2024

In this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (−28.9%), INDELs (−19.3%), and SVs (−52.4%) across three datasets. Next, we correct a common flaw in phasing evaluations, reducing measured flip errors by over 50%. Lastly, we show that vcfdist is more accurate than previously published works and on par with the newest approaches, but with improved result interpretability.
Large language models overcome the challenges of unstructured text data in ecology
Authors: Castro Andry , Pinto João , Reino Luís , Pipek Pavel , Capinha César
Published: January 2024

The vast volume of currently available unstructured text data, such as research papers, news, and technical report data, shows great potential for ecological research. However, manual processing of such data is labour-intensive, posing a significant challenge. In this study, we aimed to assess the application of three state-of-the-art prompt-based large language models (LLMs), GPT 3.5, GPT 4, and LLaMA-2-70B, to automate the identification, interpretation, extraction, and structuring of relevant ecological information from unstructured textual sources. We focused on species distribution data from two sources: news outlets and research papers. We assessed the LLMs for four key tasks: classification of documents with species distribution data, identification of regions where species are recorded, generation of geographical coordinates for these regions, and supply of results in a structured format. GPT 4 consistently outperformed the other models, demonstrating a high capacity to interpret textual data and extract relevant information, with the percentage of correct outputs often exceeding 90% (average accuracy across tasks: 87–100%). Its performance also depended on the data source type and task, with better results achieved with news reports, in the identification of regions with species reports and presentation of structured output. Its predecessor, GPT 3.5, exhibited reasonably low accuracy across all tasks and data sources (average accuracy across tasks: 81–97%), whereas LLaMA-2-70B showed the worst performance (37– 73%). These results demonstrate the potential benefit of integrating prompt-based LLMs into ecological data assimilation workflows as essential tools to efficiently process large volumes of textual data.
Selection of different parameters to study epistatic effect between heat shock and slightly deleterious mutations in the most fragile stage of embryogenesisCyprinus carpioL
Authors: Kuzmin Aleksandr , Skripskaya Viktoria , Lobanova Valeria , Brodovaya Polina , Tarasova Alina , Popadin Konstantin , Mikhailova Alina G. , Kozenkova Elena , Mugue Nikolai , Vinogradov Evgenii , Balashov Dmitrii
Published: January 2024

The primary genetic challenge encountered in artificial populations lies in the strong genetic drift, which leads to the accumulation of numerous slightly deleterious mutations across the genome. Such mutations diminish the adaptability of the entire population. The objective of this project involves the investigation and implementation of genetic selection methods within cultivated fish populations suchCyprinus carpio L. In order to maintain a high level of genome quality in productive species, we conducted a proof-of-principle experiment employing stress-induced strong purifying selection. This selection process is based on negative epistasis and effectively eliminates organisms carrying an excess of deleterious variants. The first step involves the creation of mutant and intact groups of fish. To obtain mutant groups, we treated male gametes with the ENU mutagen, which primarily induces single-nucleotide substitutions uniformly throughout the genome, thereby imitating natural mutations. This methodology is paramount for the accurate interpretation of experimental outcomes. Notably, temperature stands as a pivotal factor influencing the embryonic development of fish. Therefore, we subjected the embryos to a diverse range of temperatures and varied the duration of exposure during critical stages of embryogenesis. Through meticulous examination, we ascertained that the stage most susceptible to screening purposes is the 22-somite pair stage, occurring at a temperature of 38°C, with a 40-minute exposure period. We suppose, this comprehensive approach can be applied to improve the quality of the gene pool within domestic fish populations, ultimately enhancing the economic efficacy of fish farms. The future prospects of this method encompass its potential application to various species.
Shear flow as a tool to distinguish microscopic activities of molecular machines in a chromatin loop
Authors: Kumar Sandeep , Padinhateeri Ranjith , Thakur Snigdha
Published: January 2024

Several types of molecular machines move along biopolymers like chromatin. However, the details about the microscopic activity of these machines and how to distinguish their modes of action are not well understood. We propose that the activity of such machines can be classified by studying looped chromatin under shear flow. Our simulations show that a chromatin-like polymer with two types of activities (constant or local curvature-dependent tangential forces) exhibits very different behavior under shear flow. We show that one can distinguish both activities by measuring the nature of a globule-to-extended coil transition, tank treading, and tumbling dynamics.
Unravelled proteins form blobs during translocation across nanopores
Authors: Sauciuc Adina , Whittaker Jacob , Tadema Matthijs , Tych Kasia , Guskov Albert , Maglia Giovanni
Published: January 2024

The electroosmotic-driven transport of unravelled proteins across nanopores is an important biological process that is now under investigation for the rapid analysis and sequencing of proteins. For this approach to work, however, it is crucial that the polymer is threaded in single file. Here we found that, contrary to the electrophoretic transport of charged polymers such as DNA, during polypeptide translocation blob-like structures typically form inside nanopores. Comparisons between different nanopore sizes, shapes and surface chemistries showed that under electroosmotic-dominated regimes single-file transport of polypeptides can be achieved using nanopores that simultaneously have an entry and an internal diameter that is smaller than the persistence length of the polymer, have a uniform non-sticky (i.e. non-aromatic) nanopore inner surface, and using moderate translocation velocities.
Relationship between extreme species richness and Holocene persistence of forest-steppe grasslands in Transylvania, Romania
Authors: Novák Jan , Šamonil Pavel , Roleček Jan
Published: January 2024

The most species-rich grasslands worldwide are known from the Carpathian Mts and their periphery in East-Central Europe. They occur in forest-steppe regions, transitional between temperate forest and arid steppe biomes. Their climate, largely suitable for forests, raises questions about the origin of these grasslands. Have they been forested in the past, or locally maintained through a disturbance regime? We addressed these questions to contribute to the broader understanding of Holocene dynamics of open habitats in temperate Europe. We employed soil charcoal analysis and soil morphology to reconstruct past representation of woody species with fine spatial resolution. Our study area was Romanian Transylvania, a region renowned for a well-developed forest-steppe. Six soil profiles along a climatic gradient were assessed: four in forest-steppe grasslands, two in grasslands in adjacent forest region. The results revealed profound differences between forest-steppe and forest grasslands. Forest-steppe profiles showed Phaeozems with low specific anthracomass and continuous dominance byJuniperus, suggesting a long-term presence of grasslands. Forest profiles showed Luvisols with higher anthracomass and abundant charcoal of broad-leaved trees, indicating establishment after deforestation. The high radiocarbon ages of charcoals in basal soil horizons point to a glacial origin of soils and the link of forest-steppe grasslands to glacial forests. Siberian hemiboreal forests and related grasslands may be modern analogues of the reconstructed ecosystems, sharing many species with present day forest-steppe. We highlight the role of disturbances such as fire, herbivore grazing, and human activities in shaping the forest-steppe over time, contributing to the formation of today’s richest grasslands.
Fundamental constraints on the evolution of vertebrate life histories
Authors: Brooks George C. , Uyeda Josef C. , Bone Nicholas , Conrad Hailey M. , Mull Christopher G. , Kindsvater Holly K.
Published: January 2024

Vertebrate life histories evolve in response to selection imposed by abiotic and biotic environmental conditions while being limited by genetic, developmental, physiological, demographic, and phylogenetic processes that constrain adaptation. Despite the well-recognized shifts in selective pressures accompanying transitions among environments, identifying the conditions driving innovation and the consequences for life-history evolution remain an outstanding question. Here, we compare the traits of aquatic and terrestrial vertebrates to infer shifts in demographic and evolutionary constraints that explain differences in life-history optimization. Specifically, our results emphasize the reduced potential for life-history diversification on land, especially that of reproductive strategies. Moreover, our study reveals differences between the evolution of viviparity in the two realms. Transitions from egg laying to live birth represents a major shift across life-history space for aquatic organisms, whereas terrestrial egg-laying organisms evolve live birth without drastic changes in life-history strategy. Whilst trade-offs in the allocation of resources place fundamental constraints on the way life histories can vary, ecological setting influences the position of species within the viable phenotypic space available for adaptive evolution.
The Gut Microbiome Controls Liver Tumors via the Vagus Nerve
Authors: Bauer Kylynda C. , Trehan Rajiv , Ruf Benjamin , Myojin Yuta , Benmebarek Mohamed-Reda , Ma Chi , Seifert Matthias , Nur Amran , Qi Jonathan , Huang Patrick , Soliman Marlaine , Green Benjamin L. , Wabitsch Simon , Springer Danielle A. , Rodriguez-Matos Francisco J. , Ghabra Shadin , Gregory Stephanie N. , Matta Jennifer , Dawson Brian , Golino Jihye , Xie Changqing , Dzutsev Amiran , Trinchieri Giorgio , Korangy Firouzeh , Greten Tim F.
Published: January 2024

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion ofChrm3on CD8+T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.
Minimization of proteome reallocation explains metabolic transition in hierarchical utilization of carbon sources
Authors: Liu Zhihao , Chen Minghao , Hu Jingmin , Wang Yonghong , Chen Yu
Published: January 2024

Cells choose between alternative pathways in metabolic networks under diverse environmental conditions, but the principles governing the choice are insufficiently understood, especially in response to dynamically changing conditions. Here we observed that a lactic acid bacteriumBacillus coagulansdisplayed homolactic fermentation on glucose or trehalose as the sole carbon source, but transitioned from homolactic to heterolactic fermentation during the hierarchical utilization of glucose and trehalose when growing on the mixture. We simulated the observation by dynamic minimization of reallocation of proteome (dMORP) using an enzyme-constrained genome-scale metabolic model ofB. coagulans, which coincided with our omics data. Moreover, we evolved strains to co-utilize mixed carbon sources and repress the choice of heterolactic fermentation, and the dynamics after co-utilization of carbon sources could also be captured by dMORP. Altogether, the findings suggest that upon rapid environmental changes bacteria tend to minimize proteome reallocation and accordingly adjust metabolism, and dMORP would be useful in simulating and understanding cellular dynamics.
CACIMAR: Cross-species Analysis of Cell Identities, Markers, Regulations and Interactions Using Single-cell RNA Sequencing Data
Authors: Jiang Junyao , Li Jinlian , Xu Xueli , Huang Sunan , Jiang Fan , Liang Yanran , Wang Jie
Published: January 2024

Transcriptomic analysis across species is increasingly used to reveal conserved gene regulations which implicate crucial regulators. Cross-species analysis of single-cell RNA sequencing (scRNA-seq) data provides new opportunities to identify the cellular and molecular conservations especially for cell types and cell type-specific gene regulations. However, few methods have been developed to analyze cross-species scRNA-seq data to uncover both molecular and cellular conservation patterns. Here, we built a tool called CACIMAR, which can perform cross-species analysis of cell identities, markers, regulations and interactions using scRNA-seq profiles. Based on the weighted sum models of the conserved features, we developed different conservation scores to measure the conservation of cell types, regulatory networks and intercellular interactions. Using publicly available scRNA-seq data on retinal regeneration in mice and zebrafish, we demonstrated four main functions of CACIMAR. First, CACIMAR allows to identify evolutionarily conserved cell types, including poorly conserved cell types. Second, the tool facilitates the identification of evolutionarily conserved or species-specific marker genes. Third, CACIMAR enables the identification of conserved intracellular regulations, including cell type-specific regulatory subnetworks and regulators. Lastly, CACIMAR provides a unique feature on the identification of conserved intercellular interactions. Overall, CACIMAR facilitates the identification of evolutionarily conserved cell types, marker genes, intracellular regulations and intercellular interactions, providing insights on the cellular and molecular mechanisms of species evolution.
IDENTIFICATION OF KEY GENES ASSOCIATED WITH PCOS (POLY CYSTIC OVARIAN SYNDROME) AND ENDOMETRIAL/OVARIAN CANCER THROUGH BIOINFORMATICS
Authors: Raulo Karishma , Qazi Sahar
Published: January 2024

Background

PCOS, a common endocrine disorder, is linked to increased risks of endometrial cancer (EC) and ovarian cancer (OC). Our study utilizes bioinformatics analysis to identify shared gene signatures and elucidate biological processes between EC/OC and PCOS.

Materials and Methods

Gene expression profiles for PCOS (GSE199225), endometrial cancer (GSE215413), and ovarian cancer (GSE174670) were obtained from the GEO database. Hub genes were identified through functional enrichment analysis and protein-protein interaction. Drug identification analyses were employed to find drugs targeting the hub genes.

Result

Key hub genes linking PCOS and EC includes RECQL4, RAD54L, ATR, CHTF18, WDHD1, CDT1, PLK1, PKMYT1, RAD18, and RPL3; for PCOS and OC, they include HMOX1, TXNRD1, NQO1, GCLC, GSTP1, PRDX1, SOD1, GPX3, BOP1, and BYSL.

Gene Ontology analysis revealed DNA Metabolic Processes in PCOS and EC, while in PCOS and OC, it identified the Removal of Superoxide Radicals. KEGG Pathway analysis highlighted Cell cycle in PCOS and EC and Hepatocellular carcinoma in PCOS and OC. Potential drugs for PCOS and EC include quercetin, calcitriol, and testosterone; for PCOS and OC, eugenol and 1-chloro-2,4-dinitrobenzene are identified.

Conclusion

These findings offer insights into potential therapeutic targets and pathways linking PCOS with EC and OC, enhancing our understanding of the molecular mechanisms involved in these associations.
A comparison of knowledge-based dose prediction approaches to assessing head and neck radiotherapy plan quality
Authors: Leone Alexandra O. , Gronberg Mary , Gay Skylar S. , Govyadinov Pavel A. , Beadle Beth M. , Lim Tze Y. , Whitaker Thomas J. , Hoffman Karen , Court Laurence E. , Cao Wenhua
Published: January 2024

PURPOSE

Recent studies demonstrate deep learning dose prediction algorithms may produce results like those of traditional knowledge-based planning tools. In this exploratory study, we compared 2D DVH-based knowledge-based planning tools and 3D deep learning-based approaches to assessing radiotherapy plan quality.

METHODS

Pre-validated 2D and 3D dose prediction models were applied to 58 patients with head and neck cancer treated under RTOG 0522 obtained from The Cancer Imaging Archive (TCIA). The 2D model was used to predict dose-volume histogram bands for seven organs at risk (OARs; brainstem, spinal cord, oral cavity, larynx, mandible, right parotid, and left parotid). A 3D dose prediction model was used to predict 3D dose distributions, based on computed tomography images, OAR contours, planning target volumes and prescriptions. The mean and D1% to the seven OARs for the 2D and 3D dose prediction models were compared. Further post predictive analysis was done to quantify the predicted 3D dose sparing for all normal tissues.

RESULTS

The two models predicted similar dose sparing to the OARs, with a mean difference of 1.4±5.5 Gy across all evaluated dose metrics. When looking at the sparing of non-OAR normal tissue regions, the 3D model predicted a mean dose reduction to normal tissue regions of 6.4±3.0 Gy when compared with the clinical dose.

CONCLUSION

2D and 3D dose predictions are comparable at predicting dose reductions to OARs. The 3D approach allows for dose visualization, which may support further sparing of normal tissues not typically drawn as OARs on head and neck plans.
An Open-label Clinical Study of Brief Submaximal Cardiopulmonary Testing in Pre-surgical Evaluation: Feasibility of implementation
Authors: Carr Zyad J. , Agarkov Daniel , Li Judy , Charchaflieh Jean , Brenes-Bastos Andres , Freund Jonah , Zafar Jill , Schonberger Robert B. , Heerdt Paul
Published: January 2024

Objectives

We tested the logistic feasibility of integrating brief submaximal cardiopulmonary exercise testing (smCPET) in a pre-surgical evaluation (PSE) clinic.

Design

Prospective open-label clinical device trial.

Setting

Pre-surgical evaluation clinic.

Participants

43 participants who met criteria of i) age>60 years old, ii) revised cardiac risk index of<2, iii) self-reported metabolic equivalents (METs) of>4.6 (i.e. ability to climb 2 flights of stairs), and iv) presenting for noncardiac surgery.

Interventions

Pre-intervention self-reported METs, Duke Activity Status Index (DASI) surveys, smCPET trial, Borg survey of perceived exertion, and post-intervention survey.Measurements: Feasibility endpoints were 1) operational efficiency as measured by length of time of experimental session<20 minutes, 2) no more than moderate perceived physical exertion as quantified by a modified Borg survey of perceived exertion of<7 in the absence of observed complications, 3) high participant satisfaction with smCPET task execution, represented as a score of>8, and 4) high patient satisfaction with scheduling of smCPET testing, represented as a score of>8.

Results

Session time was 16.9 minutes (±6.8). Post-test modified Borg survey was 5.35 (±1.8), corresponding to moderate perceived exertion. Satisfaction [on a scale of 1 (worst) to 10 (best)] regarding ease of smCPET tasks was 9.6 (±0.7) and mean patient satisfaction with smCPET scheduling was 9.5 (±1.5). Operational efficiency was achieved after 10-15 experimental sessions.

Conclusions

Our findings suggest that smCPET integration in a PSE clinic; 1) is time efficient 2) shows high participant satisfaction with task, and 3) rapidly achieved operational efficiency.

Trial Registration

ClinicalTrials.govRegistration: #NCT05743673. Principal Investigator: Zyad J. Carr, M.D. Date of Registration: 5-12-2023.

Strengths and limitations of this study

We examined patient-and logistic-centered acceptance of study procedures within the environment of a high-volume preoperative surgical evaluation clinic.

Study procedures were well tolerated, and participants readily accepted submaximal cardiopulmonary exercise testing with high satisfaction with device use, scheduling, and perceived exertion.

User operational efficiency developed over 10-15 sessions of use.

This feasibility study met our proposed endpoints but is comprised of a small sample of participants, limiting its generalizability to larger populations.