bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of the Efficacy and Safety of Tranexamic Acid in Facelift Surgery
Authors: Al-Hashimi Mustafa , Kaur Pawandeep , Charles Walton , Bhasta Mhafrin , Nahai Foad , Khajuria Ankur
Published: July 2023

Tranexamic acid (TXA) has become widely utilized in different specialities including facelift surgery. The aim of this review was to robustly evaluate the quality of available evidence on the efficacy and safety of TXA use in facelift surgery. We searched the MEDLINE (National Institutes of Health, Bethesda, MD), Embase (Elsevier, Amsterdam, the Netherlands), CINAHL (EBSCO Information Services, Ipswich, MA), Cochrane Central Register of Controlled Trials (CENTRAL; Wiley, Hoboken, NJ), Google Scholar (Alphabet Inc. Mountain View, CA), Science Citation Index (Clarivate, London, UK), and Latin American and Caribbean Center on Health Sciences Information (LILACS; São Paulo, Brazil) databases for randomized controlled trials (RCTs) and observational studies. Primary outcomes were blood loss, postoperative hematoma, ecchymosis, and swelling, in addition to technical considerations and complications. We assessed review quality with the AMSTAR 2 tool, study quality with Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE) tool, and the risk of bias with Cochrane's RoB 2.0 tool for RCTs and ROBINS-I for nonrandomized studies. Of the 368 articles, a total of 3 studies including 150 patients met the inclusion criteria. The RCT reported a significant reduction in postoperative serosanguineous collections in the TXA group (P < .01), and in surgeon-rated postoperative ecchymosis and bruising. The prospective cohort study reported reduced drainage output in first 24 hours in the TXA group (P < .01). The retrospective cohort study reported lower intraoperative blood loss, mean postoperative day 1 drain output, percentage of drain removal on postoperative day 1, and number of days to drain removal in the TXA group (all P < .01). The quality of studies was moderate, and this review was the highest rated compared to previous reviews, as per the AMSTAR 2 tool. Based on limited literature, TXA improves clinical outcomes regardless of the route of administration. Topical TXA is an emerging route, expediting drain removal and reducing blood loss. Future Level I high-quality studies are required.
Gibberellin metabolism and signaling
Authors: Ueguchi-Tanaka Miyako
Published: July 2023

Gibberellins (GAs) are plant hormones with a tetracyclic diterpenoid structure that are involved in various important developmental processes. Two GA-deficient mutants were isolated: a semidwarf mutant “sd1”, which was found to have a defective GA20ox2 gene and was introduced to the world in a green revolution cultivar, and a severe dwarf allele of “d18”, with a defective GA3ox2 gene. Based on the phenotypic similarity of d18, rice dwarf mutants were screened, further classifying them into GA-sensitive and GA-insensitive by applying exogenous GA3. Finally, GA-deficient rice mutants at 6 different loci and 3 GA signaling mutants (gid1, gid2, and slr1) were isolated. The GID1 gene encodes a GA nuclear receptor, and the GID1–DELLA (SLR1) system for GA perception is widely used in vascular plants. The structural characteristics of GID1 and GA metabolic enzymes have also been reviewed.
Difference in the ligand affinity among redundant plant hormone receptors of rice OsCOI1a/1b/2-OsJAZs
Authors: Okumura Taichi , Kitajima Tsumugi , Kaji Takuya , Urano Haruyuki , Matsumoto Kotaro , Inagaki Hideo , Miyamoto Koji , Okada Kazunori , Ueda Minoru
Published: July 2023

(3R, 7S)-jasmonoyl-L-isoleucine (JA-Ile) is a lipid-derived plant hormone that regulates plant responses, including biotic/abiotic stress adaptation. In the plant cells, JA-Ile is perceived by COI1-JAZ co-receptor by causing protein-protein interaction between COI1 and JAZ proteins to trigger gene expressions. In this study, we focused on Oryza sativa, a model monocot and an important crop, with 45 possible OsCOI-OsJAZ co-receptor pairs composed of three OsCOI homologs (OsCOI1a, OsCOI1b, and OsCOI2) and 15 OsJAZ homologs. We performed fluorescein anisotropy and pull-down assays to examine the affinity between JA-Ile and OsCOI1a/1b/2-OsJAZ1-15 co-receptor pairs. The results revealed a remarkable difference in the modes of ligand perception by OsCOI1a/1b and OsCOI2. Recently, the unique function of OsCOI2 in some of the JA-responses were revealed. Our current results will lead to the possible development of OsCOI2-selective synthetic ligand.
iDRPro-SC: identifying DNA-binding proteins and RNA-binding proteins based on subfunction classifiers
Authors: Yan Ke , Feng Jiawei , Huang Jing , Wu Hao
Published: July 2023

Nucleic acid-binding proteins are proteins that interact with DNA and RNA to regulate gene expression and transcriptional control. The pathogenesis of many human diseases is related to abnormal gene expression. Therefore, recognizing nucleic acid-binding proteins accurately and efficiently has important implications for disease research. To address this question, some scientists have proposed the method of using sequence information to identify nucleic acid-binding proteins. However, different types of nucleic acid-binding proteins have different subfunctions, and these methods ignore their internal differences, so the performance of the predictor can be further improved. In this study, we proposed a new method, called iDRPro-SC, to predict the type of nucleic acid-binding proteins based on the sequence information. iDRPro-SC considers the internal differences of nucleic acid-binding proteins and combines their subfunctions to build a complete dataset. Additionally, we used an ensemble learning to characterize and predict nucleic acid-binding proteins. The results of the test dataset showed that iDRPro-SC achieved the best prediction performance and was superior to the other existing nucleic acid-binding protein prediction methods. We have established a web server that can be accessed online: http://bliulab.net/iDRPro-SC.
MSFP: undergraduate ‘collaborate-from-home’ research in macromolecular structure and function
Authors: Jeffery Constance J
Published: July 2023

When the COVID-19 crisis shut down most undergraduate research opportunities, the Macromolecular Structure and Function Research Experiences for Undergraduates Program provided a mentored research experience on the topic of Macromolecular Structure and Function and training in professional skills to assist the participants in pursuing a degree and a future career in STEM. The fully online, remote, computer-based program was funded by the USA National Science Foundation. It involved faculty at four geographically distributed institutions specializing in diverse but complementary approaches to study macromolecular structure and function. Importantly, its online ‘collaborate-from-home’ format made it accessible to students during the pandemic to participate fully in the research, professional development and other activities of the program. This project can also serve as an example for future remote, online projects that would especially be helpful for students who do not have access to similar programs at their universities, cannot travel to attend a summer program, have physical challenges that make it difficult for them to work in a lab or students whose research opportunities are limited due to the war in Ukraine. The lessons learned with the Macromolecular Structure and Function REU program can provide helpful information for ISCB members to set up similar programs to serve additional students.

Availability and implementation

More information and resources are available on the project web site http://jefferylab.moonlightingproteins.org.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
COVRECON: automated integration of genome- and metabolome-scale network reconstruction and data-driven inverse modeling of metabolic interaction networks
Authors: Li Jiahang , Waldherr Steffen , Weckwerth Wolfram
Published: July 2023

Motivation

One central goal of systems biology is to infer biochemical regulations from large-scale OMICS data. Many aspects of cellular physiology and organismal phenotypes can be understood as results of metabolic interaction network dynamics. Previously, we have proposed a convenient mathematical method, which addresses this problem using metabolomics data for the inverse calculation of biochemical Jacobian matrices revealing regulatory checkpoints of biochemical regulations. The proposed algorithms for this inference are limited by two issues: they rely on structural network information that needs to be assembled manually, and they are numerically unstable due to ill-conditioned regression problems for large-scale metabolic networks.

Results

To address these problems, we developed a novel regression loss-based inverse Jacobian algorithm, combining metabolomics COVariance and genome-scale metabolic RECONstruction, which allows for a fully automated, algorithmic implementation of the COVRECON workflow. It consists of two parts: (i) Sim-Network and (ii) inverse differential Jacobian evaluation. Sim-Network automatically generates an organism-specific enzyme and reaction dataset from Bigg and KEGG databases, which is then used to reconstruct the Jacobian’s structure for a specific metabolomics dataset. Instead of directly solving a regression problem as in the previous workflow, the new inverse differential Jacobian is based on a substantially more robust approach and rates the biochemical interactions according to their relevance from large-scale metabolomics data. The approach is illustrated by in silico stochastic analysis with differently sized metabolic networks from the BioModels database and applied to a real-world example. The characteristics of the COVRECON implementation are that (i) it automatically reconstructs a data-driven superpathway model; (ii) more general network structures can be investigated, and (iii) the new inverse algorithm improves stability, decreases computation time, and extends to large-scale models.

Availability and implementation

The code is available in the website https://bitbucket.org/mosys-univie/covrecon.
The origin and fate of fungal mitochondrial horizontal gene transferred sequences in orchids (Orchidaceae)
Authors: Valencia-D Janice , Neubig Kurt M , Clark David P
Published: July 2023

The transfer of DNA among distantly related organisms is relatively common in bacteria but less prevalent in eukaryotes. Among fungi and plants, few of these events have been reported. Two segments of fungal mitochondrial DNA have been recently discovered in the mitogenome of orchids. Here, we build on that work to understand the timing of those transfer events, which orchids retain the fungal DNA and the fate of the foreign DNA during orchid evolution. We update the content of the large DNA fragment and establish that it was transferred to the most recent common ancestor of a highly diverse clade of epidendroid orchids that lived ~28–43 Mya. Also, we present hypotheses of the origin of the small transferred fragment. Our findings deepen the knowledge of these interesting DNA transfers among organelles and we formulate a probable mechanism for these horizontal gene transfer events.
Women in cardiovascular imaging: a call for action to address ongoing challenges
Authors: Joshi Shruti S , Kadavath Sabeeda , Mandoli Giulia Elena , Gimelli Alessia , Gulati Martha , Thamman Ritu , Lundberg Gina , Mehran Roxana , Mulvagh Sharon L , Sade Leyla Elif , Shivalkar Bharati , Shaw Leslee J , Hristova Krasimira , Dweck Marc R , Almeida Ana G , Grapsa Julia
Published: July 2023

Aims

The EACVI Scientific Initiatives Committee and the EACVI women’s taskforce conducted a global survey to evaluate the barriers faced by women in cardiovascular imaging (WICVi).

Methods and results

In a prospective international survey, we assessed the barriers faced at work by WICVi. Three hundred fourteen participants from 53 countries responded. The majority were married (77%) and had children (68%), but most reported no flexibility in their work schedule during their pregnancy or after their maternity leave. More than half of the women reported experiencing unconscious bias (68%), verbal harassment (59%), conscious bias (51%), anxiety (70%), lack of motivation (60%), imposter syndrome (54%), and burnout (61%) at work. Furthermore, one in five respondents had experienced sexual harassment, although this was rarely reported formally. The majority reported availability of mentorship (73%), which was mostly rated as ‘good’ or ‘very good’. While more than two-thirds of respondents (69%) now reported being well trained and qualified to take on leadership roles in their departments, only one-third had been afforded that opportunity. Despite the issues highlighted by this survey, >80% of the participating WICVi would still choose cardiovascular imaging if they could restart their career.

Conclusion

The survey has highlighted important issues faced by WICVi. While progress has been made in areas such as mentorship and training, other issues including bullying, bias, and sexual harassment are still widely prevalent requiring urgent action by the global cardiovascular imaging community to collectively address and resolve these challenges.
Periplasmic methionine sulfoxide reductase (MsrP)—a secondary factor in stress survival and virulence of Salmonella Typhimurium
Authors: Chandra Hari Balaji , Shome Arijit , Sahoo Raj , Apoorva S , Bhure Sanjeev Kumar , Mahawar Manish
Published: July 2023

Among others, methionine residues are highly susceptible to host-generated oxidants. Repair of oxidized methionine (Met-SO) residues to methionine (Met) by methionine sulfoxide reductases (Msrs) play a chief role in stress survival of bacterial pathogens, including Salmonella Typhimurium. Periplasmic proteins, involved in many important cellular functions, are highly susceptible to host-generated oxidants. According to location in cell, two types of Msrs, cytoplasmic and periplasmic are present in S. Typhimurium. Owing to its localization, periplasmic Msr (MsrP) might play a crucial role in defending the host-generated oxidants. Here, we have assessed the role of MsrP in combating oxidative stress and colonization of S. Typhimurium. ΔmsrP (mutant strain) grew normally in in-vitro media. In comparison to S. Typhimurium (wild type), mutant strain showed mild hypersensitivity to HOCl and chloramine-T (ChT). Following exposure to HOCl, mutant strain showed almost similar protein carbonyl levels (a marker of protein oxidation) as compared to S. Typhimurium strain. Additionally, ΔmsrP strain showed higher susceptibility to neutrophils than the parent strain. Further, the mutant strain showed very mild defects in survival in mice spleen and liver as compared to wild-type strain. In a nutshell, our results indicate that MsrP plays only a secondary role in combating oxidative stress and colonization of S. Typhimurium.
Chlamydia pneumoniae-immunoglobulin E antibody responses in serum from children with asthma
Authors: Smith-Norowitz Tamar A , Shulman Anastasiya , Abdelmajid Haram , Hammerschlag Margaret R , Joks Rauno , Weaver Diana , Kohlhoff Stephan
Published: July 2023

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infections in humans. An association between persistent C. pneumoniae infection and asthma pathogenesis has been described. It is unknown whether specific immunoglobulin E (IgE) is a marker of persistent immune activation responses. Therefore, the association between C. pneumoniae-specific-IgE antibodies (Abs) and interferon (IFN)-gamma produced by C. pneumoniae-stimulated peripheral blood mononuclear cells (PBMC) was examined. Blood was collected and serum separated. PBMC from 63 children with or without stable asthma (N = 45 and 18, respectively) were infected or not infected with C. pneumoniae AR-39 and cultured for up to 7 days. Supernatants were collected, and IFN-gamma levels measured (ELISA). Serum C. pneumoniae-IgE Abs were detected by immunoblotting. C. pneumoniae-IgE Abs were detected in asthmatics (27%), compared with non-asthmatics (11%) (P = NS). IFN-gamma responses were more prevalent among asthmatics who had positive C. pneumoniae-IgE Abs (60%) compared with asthmatics without C. pneumoniae-IgE Abs (20%) (P = 0.1432). IFN-gamma responses in C. pneumoniae-stimulated PBMC from children with asthma were more frequent in children who had specific anti-C. pneumoniae-IgE Abs compared to those who did not. This immune response may reflect persistent infection, which may contribute to ongoing asthma symptoms.
Yeast population dynamics in Brazilian bioethanol production
Authors: Rego-Costa Artur , Huang I Ting , Desai Michael M , Gombert Andreas K
Published: July 2023

The large-scale and nonaseptic fermentation of sugarcane feedstocks into fuel ethanol in biorefineries represents a unique ecological niche, in which the yeast Saccharomyces cerevisiae is the predominant organism. Several factors, such as sugarcane variety, process design, and operating and weather conditions, make each of the ∼400 industrial units currently operating in Brazil a unique ecosystem. Here, we track yeast population dynamics in 2 different biorefineries through 2 production seasons (April to November of 2018 and 2019), using a novel statistical framework on a combination of metagenomic and clonal sequencing data. We find that variation from season to season in 1 biorefinery is small compared to the differences between the 2 units. In 1 biorefinery, all lineages present during the entire production period derive from 1 of the starter strains, while in the other, invading lineages took over the population and displaced the starter strain. However, despite the presence of invading lineages and the nonaseptic nature of the process, all yeast clones we isolated are phylogenetically related to other previously sequenced bioethanol yeast strains, indicating a common origin from this industrial niche. Despite the substantial changes observed in yeast populations through time in each biorefinery, key process indicators remained quite stable through both production seasons, suggesting that the process is robust to the details of these population dynamics.
Conjecture 𝒪 for Projective Complete Intersections
Authors: Ke Hua-Zhong
Published: July 2023

Conjecture ${{\mathcal{O}}}$ and Gamma conjectures for quantum cohomology of Fano manifolds were proposed by Galkin, Golyshev, and Iritani [ 16]. We prove Conjecture ${{\mathcal{O}}}$ for Fano complete intersections in projective spaces. The main tools to compute relevant genus-zero Gromov–Witten invariants with primitive insertions are the genus-one topological recursion relation and Zinger’s standard-versus-reduced formula. We also prove a related conjecture of Galkin [ 15] for projective Fano complete intersections.
Applying anti-racist approaches to informatics: a new lens on traditional frames
Authors: Platt Jodyn , Nong Paige , Merid Beza , Raj Minakshi , Cope Elizabeth , Kardia Sharon , Creary Melissa
Published: July 2023

Health organizations and systems rely on increasingly sophisticated informatics infrastructure. Without anti-racist expertise, the field risks reifying and entrenching racism in information systems. We consider ways the informatics field can recognize institutional, systemic, and structural racism and propose the use of the Public Health Critical Race Praxis (PHCRP) to mitigate and dismantle racism in digital forms. We enumerate guiding questions for stakeholders along with a PHCRP-Informatics framework. By focusing on (1) critical self-reflection, (2) following the expertise of well-established scholars of racism, (3) centering the voices of affected individuals and communities, and (4) critically evaluating practice resulting from informatics systems, stakeholders can work to minimize the impacts of racism. Informatics, informed and guided by this proposed framework, will help realize the vision of health systems that are more fair, just, and equitable.
Feeding 3-nitrooxypropanol reduces methane emissions by feedlot cattle on tropical conditions
Authors: Araújo Tiago L R , Rabelo Carlos H S , Cardoso Abmael S , Carvalho Victor V , Acedo Tiago S , Tamassia Luis F M , Vasconcelos Guilherme S F M , Duval Stephane M , Kindermann Maik , Gouvea Vinicius N , Fernandes Marcia H M R , Reis Ricardo A
Published: July 2023

Our objective was to evaluate the effects of feeding 3-nitrooxypropanol (3-NOP; Bovaer, DSM Nutritional Products) at two levels on methane emissions, nitrogen balance, and performance by feedlot cattle. In experiment 1, a total of 138 Nellore bulls (initial body weight, 360 ± 37.3 kg) were housed in pens (27 pens with either 4 or 5 bulls per pen) and fed a high-concentrate diet for 96 d, containing 1) no addition of 3-NOP (control), 2) inclusion of 3-NOP at 100 mg/kg dry matter (DM), and 3) inclusion of 3-NOP at 150 mg/kg DM. No adverse effects of 3-NOP were observed on DM intake (DMI), animal performance, and gain:feed (P > 0.05). In addition, there was no effect (P > 0.05) of 3-NOP on carcass characteristics (subcutaneous fat thickness and rib eye area). In experiment 2, 24 bulls (initial BW, 366 ± 39.6 kg) housed in 12 pens (2 bulls/pen) from experiment 1 were used for CH4 measurements and nitrogen balance. Irrespective of the level, 3-NOP consistently decreased (P < 0.001) animals’ CH4 emissions (g/d; ~49.3%), CH4 yield (CH4/DMI; ~40.7%) and CH4 intensity (CH4/average daily gain; ~38.6%). Moreover, 3-NOP significantly reduced the gross energy intake lost as CH4 by 42.5% (P < 0.001). The N retention: N intake ratio was not affected by 3-NOP (P = 0.19). We conclude that feeding 3-NOP is an effective strategy to reduce methane emissions, with no impairment on feedlot cattle performance.
Data-driven intelligent computational design for products: method, techniques, and applications
Authors: Yang Maolin , Jiang Pingyu , Zang Tianshuo , Liu Yuhao
Published: July 2023

Data-driven intelligent computational design (DICD) is a research hotspot that emerged under fast-developing artificial intelligence. It emphasizes utilizing deep learning algorithms to extract and represent the design features hidden in historical or fabricated design process data and then learn the combination and mapping patterns of these design features for design solution retrieval, generation, optimization, evaluation, etc. Due to its capability of automatically and efficiently generating design solutions and thus supporting human-in-the-loop intelligent and innovative design activities, DICD has drawn the attention of both academic and industrial fields. However, as an emerging research subject, many unexplored issues still limit the development and application of DICD, such as specific dataset building, engineering design-related feature engineering, systematic methods and techniques for DICD implementation in the entire product design process, etc. In this regard, a systematic and operable road map for DICD implementation from a full-process perspective is established, including a general workflow for DICD project planning, an overall framework for DICD project implementation, the common mechanisms and calculation principles during DICD, key enabling technologies for detailed DICD implementation, and three case scenarios of DICD application. The road map can help academic researchers to locate their specific research directions for the further development of DICD and provide operable guidance for the engineers in their specific DICD applications.
Mechanisms and roles of the first stage of nodule formation in lepidopteran insects
Authors: Sato Ryoichi
Published: July 2023

Nodule formation is a process of cellular immunity in insects and other arthropods with open circulatory systems. Based on histological observations, nodule formation occurs in 2 stages. The first stage occurs immediately after microbial inoculation and includes aggregate formation by granulocytes. The second stage occurs approximately 2–6 h later and involves the attachment of plasmatocytes to melanized aggregates produced during the first stage. The first stage response is thought to play a major role in the rapid capture of invading microorganisms. However, little is known regarding how granulocytes in the hemolymph form aggregates, or how the first stage of the immunological response protects against invading microorganisms. Since the late 1990s, our understanding of the molecules and immune pathways that contribute to nodule formation has improved. The first stage of nodule formation involves a hemocyte-induced response that is triggered by pathogen-associated molecular pattern (PAMP) recognition proteins in the hemolymph regulated by a serine proteinase cascade and cytokine (Spätzle) and Toll signaling pathways. Hemocyte agglutination proceeds through stepwise release of biogenic amine, 5-HT, and eicosanoids that act downstream of the Toll pathway. The first stage of nodule formation is closely linked to melanization and antimicrobial peptide (AMP) production, which is critical for insect humoral immunity. Nodule formation in response to artificial inoculation with millions of microorganisms has long been studied. It has recently been suggested that this system is the original natural immune system, and enables insects to respond to a single invading microorganism in the hemocoel.
ATF2 orchestrates macrophage differentiation and activation to promote antibacterial responses
Authors: Rajabalee Nusrah , Siushansian Hannah , Weerapura Milani , Berton Stefania , Berbatovci Fjolla , Hooks Breana , Geoffrion Michele , Yang Dabo , Harper Mary-Ellen , Rayner Katey , Blais Alexandre , Sun Jim
Published: July 2023

The differentiation and activation of macrophages are critical regulatory programs that are central to host inflammation and pathogen defense. However, the transcriptional regulatory pathways involved in these programs are not well understood. Herein, we demonstrate that the activity and expression of the transcription factor ATF2 is precisely regulated during primary human monocyte-to-macrophage differentiation and that its activation is linked to M1 polarization and antibacterial responses. Genetic perturbation experiments demonstrated that deletion of ATF2 (THP-ΔATF2) resulted in irregular and abnormal macrophage morphology, whereas macrophages overexpressing ATF2 (THP-ATF2) developed round and pancake-like morphology, resembling classically activated (M1) macrophages. Mechanistically, we show that ATF2 binds to the core promoter of PPM1A, a phosphatase that regulates monocyte-to-macrophage differentiation, to regulate its expression. Functionally, overexpression of ATF2 sensitized macrophages to M1 polarization, resulting in increased production of major histocompatibility complex class II, IL-1β, and IP-10; improved phagocytic capacity; and enhanced control of the intracellular pathogen Mycobacterium tuberculosis. Gene expression profiling revealed that overexpression of ATF2 reprogramed macrophages to promote antibacterial pathways enriched in chemokine signaling, metabolism, and antigen presentation. Consistent with pathways analysis, metabolic profiling revealed that genetic overexpression or stimuli-induced activation of ATF2 alters the metabolic capacity of macrophages and primes these cells for glycolytic metabolism during M1 polarization or bacterial infection. Our findings reveal that ATF2 plays a central role during macrophage differentiation and M1 polarization to enhance the functional capacities of macrophages.
Closing the gap between murine neutrophils and neutrophil-like cell lines
Authors: Allen Lee-Ann H
Published: July 2023

Advantages of cloned Hoxb8 neutrophil-like cells are discussed and contrasted with weaknesses of human HL-60 and PLB-985 neutrophil-like cell lines, and shared and distinct features of primary murine and human neutrophils are summarized.
A new species of bat in the genus Nyctinomops Miller, 1902 (Chiroptera: Molossidae) from Misiones, Argentina
Authors: Barquez Rubén M , Tomasco Ivanna H , Sánchez R Tatiana , Boero Lourdes , Rodriguez Alejandro Daniel , Díaz M Mónica
Published: July 2023

As currently understood, the genus Nyctinomops contains four species: N. aurispinosus (Peale, 1849), N. femorosaccus (Merriam, 1889), N. laticaudatus (É. Geoffroy St.-Hilaire, 1805), and N. macrotis (Gray, 1840). Only N. macrotis and N. laticaudatus have been recorded from Argentina. We found that specimens of Nyctinomops captured in the province of Misiones, Argentina did not correspond to the characters of either species known from Argentina, and did not match characters of any other known species. Morphological, morphometric, and molecular analyses of these specimens revealed that they represent a new species, which we describe herein.
Total neoadjuvant therapy with or without aflibercept in rectal cancer: 3-year results of GEMCAD-1402
Authors: Pesántez David , ten Hoorn Sanne , Machado Isidro , García-Albéniz Xabier , Rodríguez-Salas Nuria , Heredia-Soto Victoria , Viñal David , Pericay Carles , García-Carbonero Rocio , Losa Ferran , Alonso Vicente , Vera Ruth , Feliu Batlle Jaime , Gallego Javier , Salud Antonieta , Nogué Miquel , Layos Laura , Montagut Clara , Capdevila Jaume , Vermeulen Louis , Maurel Joan , Fernandez-Martos Carlos
Published: July 2023

Background

The results of the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD)-1402 phase II randomized trial suggested that adding aflibercept to modified fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) induction, followed by chemoradiation and surgery, could increase the pathological complete response (pCR) rate in patients with high-risk, locally advanced rectal cancer. Here we update results up to 3 years of follow-up and evaluate the predictive value of consensus molecular subtypes identified with immunohistochemistry (IHC).

Methods

Patients with magnetic resonance imaging–defined T3c-d and/or T4 and/or N2 rectal adenocarcinoma in the middle or distal third were randomly assigned to mFOLFOX6 induction, with aflibercept (mF+A; n = 115) or without aflibercept (mF; n = 65), followed by capecitabine plus radiotherapy and surgery. The risk local relapse, distant metastases, disease-free survival (DFS), and overall survival (OS) were estimated at 3 years. Selected samples were classified via IHC into immune-infiltrate, epithelial, or mesenchymal subtypes.

Results

mF+A and mF had 3-year DFS of 75.2% (95% confidence interval [CI] = 66.1% to 82.2%) and 81.5% (95% CI = 69.8% to 89.1%), respectively; 3-year OS of 89.3% (95% CI = 82.0% to 93.8%) and 90.7% (95% CI = 80.6% to 95.7%), respectively; 3-year cumulative local relapse incidences of 5.2% (95% CI = 1.9% to 11.0%) and 6.1% (95% CI = 1.7% to 15.0%), respectively; and 3-year cumulative distant metastases rates of 17.3% (95% CI = 10.9% to 25.5%) and 16.9% (95% CI = 8.7% to 28.2%), respectively. pCRs were achieved in 27.5% (n = 22 of 80) and 0% (n = 0 of 10) of patients with epithelial and mesenchymal subtypes, respectively.

Conclusion

Adding aflibercept to mFOLFOX6 induction was not associated with improved DFS or OS. Our findings suggested that consensus molecular subtypes identified with IHC subtypes could be predictive of pCR with this treatment.
Vitamin D alleviates neuronal injury in cerebral ischemia-reperfusion via enhancing the Nrf2/HO-1 antioxidant pathway to counteract NLRP3-mediated pyroptosis
Authors: Qiao Jinling , Ma Huizhi , Chen Meirong , Bai Jie
Published: July 2023

Vitamin D supplementation is reported to have anti-inflammatory and neuroprotective effects during cerebral ischemia-reperfusion injury (CIRI), but the protective mechanism has not been fully elucidated. In this study, rats were given prior administrations of 1,25-vitamin D3 (1,25-VitD3) for a week and subjected to 2 hours of middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Supplementation with 1,25-VitD3 significantly reduced neurological deficit scores and cerebral infarction areas, and increased surviving neurons. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced rat cortical neuron cells (RN-C) were subjected to 1,25-VitD3 treatment. Administration of 1,25-VitD3 improved cell viability and inhibited lactate dehydrogenase (LDH) activity and cell apoptosis in OGD/R-stimulated RN-C, as assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) assay, LDH activity assays and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively. Notably, western blot assay showed that 1,25-VitD3 upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) to alleviate oxidative stress, but reduced proteins and inflammatory cytokines related to NLR pyrin domain containing 3 (NLRP3)-mediated pyroptosis, resulting in decreased pyroptosis and neuroinflammation in vivo and in vitro. Transfection of pcDNA-Nrf2 in RN-C also inhibited pyroptosis and OGD/R-induced cell death whereas breakdown of Nrf2 signals destroyed the protective effect of 1,25-VitD3 on OGD/R-stimulated RN-C. In conclusion, 1,25-VitD3 protects neurons against CIRI through activating the antioxidant Nrf2/HO-1 pathway to restrain NLRP3-mediated pyroptosis.
A network pharmacology approach to investigate dehydrocostus lactone inhibits the proliferation and epithelial-mesenchymal transition of human gastric cancer cells via regulating the PI3K/Akt and extracellular signal-regulated kinases/mitogen-activated protein kinase signalling pathways
Authors: Wan Meiqi , Dai Jun , Gan Anna , Wang Jinyu , Lin Fei , Zhang Xiaoying , Lv Xinyan , Wu Bo , Yan Tingxu , Jia Ying
Published: July 2023

Objectives

Dehydrocostus lactone (DHE), a sesquiterpene lactone, has been proven the significant inhibition of multiple cancer cells. However, there are limited reports on the activity of DHE in gastric cancer (GC). In this research, Network pharmacology predicted the anti-GC mechanism of DHE, and the prediction was verified by in-vitro experiments.

Methods

Network pharmacology confirmed the major effect signalling pathway of DHE in treating GC. Cell viability assay, colony formation assay, wound healing assay, cell migration and invasion assay, apoptosis assay, western blot and real-time quantitative polymerase chain reaction verified the mechanism of DHE in GC cell lines.

Key findings

The results showed that DHE inhibited the growth and metastasis of MGC803 and AGS GC cells. Mechanistically, the analysis results indicated that DHE significantly induced the apoptosis process by suppressing the PI3K/protein kinase B (Akt) signalling pathway, and inhibited epithelial-mesenchymal transition by suppressing the extracellular signal-regulated kinases (ERK)/MAPK signalling pathway. The Akt activator (SC79) inhibited DHE induced apoptosis, and DHE had similar effects with the ERK inhibitor (FR180204).

Conclusions

All results suggested that DHE was a potential natural chemotherapeutic drug in GC treatment.
Deep Learning-Based TEM Image Analysis for Fully Automated Detection of Gold Nanoparticles Internalized Within Tumor Cell
Authors: Kaphle Amrit , Jayarathna Sandun , Moktan Hem , Aliru Maureen , Raghuram Subhiksha , Krishnan Sunil , Cho Sang Hyun
Published: July 2023

Transmission electron microscopy (TEM) imaging can be used for detection/localization of gold nanoparticles (GNPs) within tumor cells. However, quantitative analysis of GNP-containing cellular TEM images typically relies on conventional/thresholding-based methods, which are manual, time-consuming, and prone to human errors. In this study, therefore, deep learning (DL)–based methods were developed for fully automated detection of GNPs from cellular TEM images. Several models of “you only look once (YOLO)” v5 were implemented, with a few adjustments to enhance the model’s performance by applying the transfer learning approach, adjusting the size of the input image, and choosing the best optimization algorithm. Seventy-eight original (12,040 augmented) TEM images of GNP-laden tumor cells were used for model implementation and validation. A maximum F1 score (harmonic mean of the precision and recall) of 0.982 was achieved by the best-trained models, while mean average precision was 0.989 and 0.843 at 0.50 and 0.50–0.95 intersection over union threshold, respectively. These results suggested the developed DL-based approach was capable of precisely estimating the number/position of internalized GNPs from cellular TEM images. A novel DL-based TEM image analysis tool from this study will benefit research/development efforts on GNP-based cancer therapeutics, for example, by enabling the modeling of GNP-laden tumor cells using nanometer-resolution TEM images.
The Experience of Living With Polycystic Ovary Syndrome in the Military
Authors: Hopkins Dawnkimberly , Walker Samantha C , Wilson Candy , Siaki Leilani , Phillips Angela K , Wallen Gwenyth R
Published: July 2023

Introduction

Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrinopathy in women, ranging from 5% to 26% depending on diagnostic criteria applied. Common manifestations of PCOS include overweight and obesity, abnormal menstrual cycles, pelvic pain, increased facial and body hair, acne, and infertility. These abnormalities and associated complications have significant military operational and readiness implications. There is a large gap in research regarding active duty servicewomen (ADW) with PCOS. Therefore, the purpose of this study is to describe ADW’s experience of living with PCOS and to describe the service-branch-specific differences among these women.

Materials and Methods

Moderator’s guide, audiotapes, transcripts, and field notes. This was a qualitative descriptive study using focus groups and individual interviews. The David Grant Medical Center Institutional Review Board at Travis AFB, CA, USA, approved the study protocol. Women with PCOS were recruited from U.S. Air Force, Army, and Navy locations. Data were analyzed using constant comparative content analysis.

Results

Twenty-three servicewomen from 19 occupations across the Army, Navy, Air Force, and Marine Corps participated. Three overarching categories emerged: (1) challenges managing PCOS symptoms, (2) navigating the military health care system, and (3) navigating PCOS as a service member.

Conclusions

Servicewomen may have significant career consequences related to PCOS sequelae, such as overweight, obesity, uncontrolled menstrual cycle, and pain. Managing the myriad of symptoms can distract women while deployed, in austere conditions, or at their home stations. As one of the most common cardiometabolic, reproductive endocrinologic conditions in women, PCOS has not received the attention, awareness, education, or research necessary to sufficiently support ADW with this condition. It is imperative that evidence-based strategies are developed to inform relevant and high-quality care for these warfighters. Future qualitative studies are needed to further describe specific stressors and needs of ADW with PCOS. Future intervention studies are also needed to evaluate effective management options for ADW with PCOS.
Conditional Collapse
Authors: Carter Sam
Published: July 2023

Indicative and subjunctive conditionals are in non-complimentary distribution: there are conversational contexts at which both are licensed (Stalnaker 1975; Karttunen and Peters 1979; von Fintel 1998). This means we can ask an important, but under-explored, question: in contexts which license both, what relations hold between the two? In this paper, I’ll argue for an initially surprising conclusion: when attention is restricted to the relevant contexts, indicatives and subjunctives are co-entailing. §1 introduces the indicative/subjunctive distinction, along with a discussion of the relevant notion of entailment; §2 presents the main argument of the paper, and §3 considers some of the philosophical implications of the argument in §2. Finally, §4 argues that we can reconcile the equivalence of indicatives and subjunctives with apparently conflicting judgements.
Whole-genome Duplications and the Long-term Evolution of Gene Regulatory Networks in Angiosperms
Authors: Almeida-Silva Fabricio , Van de Peer Yves
Published: July 2023

Angiosperms have a complex history of whole-genome duplications (WGDs), with varying numbers and ages of WGD events across clades. These WGDs have greatly affected the composition of plant genomes due to the biased retention of genes belonging to certain functional categories following their duplication. In particular, regulatory genes and genes encoding proteins that act in multiprotein complexes have been retained in excess following WGD. Here, we inferred protein–protein interaction (PPI) networks and gene regulatory networks (GRNs) for seven well-characterized angiosperm species and explored the impact of both WGD and small-scale duplications (SSDs) in network topology by analyzing changes in frequency of network motifs. We found that PPI networks are enriched in WGD-derived genes associated with dosage-sensitive intricate systems, and strong selection pressures constrain the divergence of WGD-derived genes at the sequence and PPI levels. WGD-derived genes in network motifs are mostly associated with dosage-sensitive processes, such as regulation of transcription and cell cycle, translation, photosynthesis, and carbon metabolism, whereas SSD-derived genes in motifs are associated with response to biotic and abiotic stress. Recent polyploids have higher motif frequencies than ancient polyploids, whereas WGD-derived network motifs tend to be disrupted on the longer term. Our findings demonstrate that both WGD and SSD have contributed to the evolution of angiosperm GRNs, but in different ways, with WGD events likely having a more significant impact on the short-term evolution of polyploids.
Whole-genome Analyses Reveal Past Population Fluctuations and Low Genetic Diversities of the North Pacific Albatrosses
Authors: Huynh Stella , Cloutier Alison , Chen Guoling , Chan David Tsz Chung , Lam Derek Kong , Huyvaert Kathryn P , Sato Fumio , Edwards Scott V , Sin Simon Yung Wa
Published: July 2023

Throughout the Plio-Pleistocene, climate change has impacted tropical marine ecosystems substantially, with even more severe impacts predicted in the Anthropocene. Although many studies have clarified demographic histories of seabirds in polar regions, the history of keystone seabirds of the tropics is unclear, despite the prominence of albatrosses (Diomedeidae, Procellariiformes) as the largest and most threatened group of oceanic seabirds. To understand the impact of climate change on tropical albatrosses, we investigated the evolutionary and demographic histories of all four North Pacific albatrosses and their prey using whole-genome analyses. We report a striking concordance in demographic histories among the four species, with a notable dip in effective population size at the beginning of the Pleistocene and a population expansion in the Last Glacial Period when sea levels were low, which resulted in increased potential coastal breeding sites. Abundance of the black-footed albatross dropped again during the Last Glacial Maximum, potentially linked to climate-driven loss of breeding sites and concordant genome-derived decreases in its major prey. We find very low genome-wide (π < 0.001) and adaptative genetic diversities across the albatrosses, with genes of the major histocompatibility complex close to monomorphic. We also identify recent selective sweeps at genes associated with hyperosmotic adaptation, longevity, and cognition and memory. Our study has shed light on the evolutionary and demographic histories of the largest tropical oceanic seabirds and provides evidence for their large population fluctuations and alarmingly low genetic diversities.
Six-month safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in Japan: Interim analysis of post-marketing surveillance
Authors: Kuwana Masataka , Sugiyama Naonobu , Momohara Shigeki , Atsumi Tatsuya , Takei Syuji , Tamura Naoto , Harigai Masayoshi , Fujii Takao , Matsuno Hiroaki , Takeuchi Tsutomu , Yamamoto Kazuhiko , Takasaki Yoshinari , Tanigawa Miki , Endo Yutaka , Hirose Tomohiro , Morishima Yosuke , Yoshii Noritoshi , Mimori Tsuneyo , Takagi Michiaki
Published: July 2023

Objectives

We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study.

Methods

This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses.

Results

Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker’s stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection.

Conclusions

In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months.

Study identifier

NCT01932372.
Fertilization, reproductive system, and pregnancy in familial Mediterranean fever: Clinical state of art
Authors: Er Ozan , Ugurlu Serdal
Published: July 2023

Systemic autoinflammatory diseases have always been one of the most striking and challenging aspects of the art of medicine. Among this fascinating constellation of diseases, familial Mediterranean fever (FMF) is the most common. FMF involves the reproductive system and may cause fertility problems. With the start of the interleukin (IL)-1 inhibitors era, there is a need to reorganize our knowledge on FMF management, particularly in pregnant patients and those experiencing fertilization problems. The primary aim of this review is to gather recent information on the effects of FMF on fertilization and the reproductive system, as well as to shed light on the management of pregnancy in FMF patients.
The fission yeast methyl phosphate capping enzyme Bmc1 guides 2′-O-methylation of the U6 snRNA
Authors: Porat Jennifer , Slat Viktor A , Rader Stephen D , Bayfield Mark A
Published: July 2023

Splicing requires the tight coordination of dynamic spliceosomal RNAs and proteins. U6 is the only spliceosomal RNA transcribed by RNA Polymerase III and undergoes an extensive maturation process. In humans and fission yeast, this includes addition of a 5′ γ-monomethyl phosphate cap by members of the Bin3/MePCE family as well as snoRNA guided 2′-O-methylation. Previously, we have shown that the Bin3/MePCE homolog Bmc1 is recruited to the S. pombe telomerase holoenzyme by the LARP7 family protein Pof8, where it acts in a catalytic-independent manner to protect the telomerase RNA and facilitate holoenzyme assembly. Here, we show that Bmc1 and Pof8 are required for the formation of a distinct U6 snRNP that promotes 2′-O-methylation of U6, and identify a non-canonical snoRNA that guides this methylation. We also show that the 5′ γ-monomethyl phosphate capping activity of Bmc1 is not required for its role in promoting snoRNA guided 2′-O-methylation, and that this role relies on different regions of Pof8 from those required for Pof8 function in telomerase. Our results are consistent with a novel role for Bmc1/MePCE family members in stimulating 2′-O-methylation and a more general role for Bmc1 and Pof8 in guiding noncoding RNP assembly beyond the telomerase RNP.