bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms and roles of the first stage of nodule formation in lepidopteran insects
Authors: Sato Ryoichi 
Published: July 2023

AbstractNodule 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

Abstract
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.
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

Abstract
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

Abstract

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

Abstract
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

Abstract

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

AbstractTransmission 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

ABSTRACT

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

AbstractIndicative 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

Abstract
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

Abstract
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 &lt; 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

ABSTRACT

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

ABSTRACT
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.