bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Machine Learning and miRNA for the Diagnosis of Esophageal Cancer
Authors: Aravind Vishnu A , Kouznetsova Valentina L , Kesari Santosh , Tsigelny Igor F
Published: May 2024

Background

Esophageal cancer (EC) remains a global health challenge, often diagnosed at advanced stages, leading to high mortality rates. Current diagnostic tools for EC are limited in their efficacy. This study aims to harness the potential of microRNAs (miRNAs) as novel, noninvasive diagnostic biomarkers for EC. Our objective was to determine the diagnostic accuracy of miRNAs, particularly in distinguishing miRNAs associated with EC from control miRNAs.

Methods

We applied machine learning (ML) techniques in WEKA (Waikato Environment for Knowledge Analysis) and TensorFlow Keras to a dataset of miRNA sequences and gene targets, assessing the predictive power of several classifiers: naïve Bayes, multilayer perceptron, Hoeffding tree, random forest, and random tree. The data were further subjected to InfoGain feature selection to identify the most informative miRNA sequence and gene target descriptors. The ML models’ abilities to distinguish between miRNA implicated in EC and control group miRNA was then tested.

Results

Of the tested WEKA classifiers, the top 3 performing ones were random forest, Hoeffding tree, and naïve Bayes. The TensorFlow Keras neural network model was subsequently trained and tested, the model’s predictive power was further validated using an independent dataset. The TensorFlow Keras gave an accuracy 0.91. The WEKA best algorithm (naïve Bayes) model yielded an accuracy of 0.94.

Conclusions

The results demonstrate the potential of ML-based miRNA classifiers in diagnosing EC. However, further studies are necessary to validate these findings and explore the full clinical potential of this approach.
Soybean molasses increases subcutaneous fat deposition while reducing lipid oxidation in the meat of castrated lambs
Authors: Pereira-Junior Sérgio A G , Costa Rayanne V , Rodrigues Julia L , Torrecilhas Juliana A , Chiaratti Marcos R , Lanna Dante P D , das Chagas Julia C , Nociti Ricardo P , Meirelles Flavio V , Ferraz José Bento S , Fernandes Márcia H M R , Almeida Marco Túlio C , Ezequiel Jane M B
Published: May 2024

This study aimed to evaluate the effect of including soybean molasses (SM) on performance, blood parameters, carcass traits, meat quality, fatty acid, and muscle (longissimus thoracis) transcriptomic profiles of castrated lambs. Twenty Dorper × Santa Inês lambs (20.06 ± 0.76 kg body weight [BW]) were assigned to a randomized block design, stratified by BW, with the following treatments: CON: 0 g/kg of SM and SM20: 200 g/kg of SM on dry matter basis, allocated in individual pens. The diet consisted of 840 g/kg concentrate and 160 g/kg corn silage for 76 d, with the first 12 d as an adaptation period and the remaining 64 d on the finishing diet. The SM20 diet increased blood urea concentration (P = 0.03) while reduced glucose concentration (P = 0.04). Lambs fed SM showed higher subcutaneous fat deposition (P = 0.04) and higher subcutaneous adipocyte diameter (P < 0.01), in addition to reduced meat lipid oxidation (P < 0.01). SM reduced the quantity of branched-chain fatty acids in longissimus thoracis (P = 0.05) and increased the quantity of saturated fatty acids (P = 0.01). In the transcriptomic analysis, 294 genes were identified as differentially expressed, which belong to pathways such as oxidative phosphorylation, citric acid cycle, and monosaccharide metabolic process. In conclusion, diet with SM increased carcass fat deposition, reduced lipid oxidation, and changed the energy metabolism, supporting its use in ruminant nutrition.
Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity
Authors: Khalid Anam , Huang Zhengxuan , Khan Ibrar Muhammad , Khalid Fatima , Nassar Nourhan , Jiang Xinyu , Cheng Maoji , Zhan Kai , Wang Zaigui
Published: May 2024

Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy “Wannan Yellow Chicken line” was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at−80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.
Monarch butterfly optimization-based genetic algorithm operators for nonlinear constrained optimization and design of engineering problems
Authors: El-Shorbagy M A , Alhadbani Taghreed Hamdi
Published: May 2024

This paper aims to present a hybrid method to solve nonlinear constrained optimization problems and engineering design problems (EDPs). The hybrid method is a combination of monarch butterfly optimization (MBO) with the cross-over and mutation operators of the genetic algorithm (GA). It is called a hybrid monarch butterfly optimization with genetic algorithm operators (MBO-GAO). Combining MBO and GA operators is meant to overcome the drawbacks of both algorithms while merging their advantages. The self-adaptive cross-over and the real-valued mutation are the GA operators that are used in MBO-GAO. These operators are merged in a distinctive way within MBO processes to improve the variety of solutions in the later stages of the search process, speed up the convergence process, keep the search from getting stuck in local optima, and achieve a balance between the tendencies of exploration and exploitation. In addition, the greedy approach is presented in both the migration operator and the butterfly adjusting operator, which can only accept offspring of the monarch butterfly groups who are fitter than their parents. Finally, popular test problems, including a set of 19 benchmark problems, are used to test the proposed hybrid algorithm, MBO-GAO. The findings obtained provide evidence supporting the higher performance of MBO-GAO compared with other search techniques. Additionally, the performance of the MBO-GAO is examined for several EDPs. The computational results show that the MBO-GAO method exhibits competitiveness and superiority over other optimization algorithms employed for the resolution of EDPs.
International knowledge connectivity and the increasing concentration of innovation in major global cities
Authors: Cantwell John , Zaman Salma
Published: May 2024

We argue that trans-local knowledge connections positively impact local epistemic inventor communities in global cities, using patent citations as an indicator of global knowledge connectivity. Patented inventions have become more concentrated in the most internationally connected global cities, increasing inter-regional inequality. We identify two dimensions of knowledge connectivity: the compatibility of connections between similar profiles of technological knowledge, and the geographical diversity of knowledge connections between differently specialized global cities. We suggest that interaction between local and international inventor epistemic communities is now a vital driver of local innovation in global cities, and interregional inequality between these and other cities.
Functions of N6-methyladenosine (m6A) RNA modifications in acute myeloid leukemia
Authors: Fang Zehao , Ding Hanyi , Han Jiongping , Fu Leihua , Jin Jing , Feng Weiying
Published: May 2024

N6-methyladenosine is the most common modification of eukaryotic RNA. N6-methyladenosine participates in RNA splicing, nuclear export, translation, and degradation through regulation by methyltransferases, methylation readers, and demethylases, affecting messenger RNA stability and translation efficiency. Through the dynamic and reversible regulatory network composed of “writers, erasers, and readers,” N6-methyladenosine modification plays a unique role in the process of hematopoiesis. Acute myeloid leukemia is a heterogeneous disease characterized by malignant proliferation of hematopoietic stem cells/progenitor cells. Many studies have shown that N6-methyladenosine–related proteins are abnormally expressed in acute myeloid leukemia and play an important role in the occurrence and development of acute myeloid leukemia, acting as carcinogenic or anticancer factors. Here, we describe the mechanisms of action of reversing N6-methyladenosine modification in hematopoiesis and acute myeloid leukemia occurrence and progression to provide a basis for further research on the role of N6-methyladenosine methylation and its regulatory factors in normal hematopoiesis and acute myeloid leukemia, to ultimately estimate its potential clinical value.
Co-design and usability of an interactive web-based fertility decision aid for transgender youth and young adults
Authors: Chen Diane , Shen Elaine , Kolbuck Victoria D , Sajwani Afiya , Finlayson Courtney , Gordon Elisa J
Published: May 2024

Objective

To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design.

Method

TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale).

Results

Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores.

Conclusions

We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.
Technical report: clinical feasibility of augmented reality-navigated chronic subdural hematoma evacuation
Authors: Olexa Joshua , Trang Annie , Chryssikos Timothy , Schwartzbauer Gary , Aarabi Bizhan
Published: May 2024

Management of chronic subdural hematoma (cSDH) poses unique challenges and can be fraught with complications. Understanding the spatial relationships of cSDH to adjacent brain tissue and skull topography is critical for successful surgical treatment. The aim of this report is to highlight the feasibility and efficacy of a novel augmented reality (AR) overlay tool for surgical planning with technical description of two surgical cases using AR for surgical management of cSDH. This report describes a fiducial-less AR system for surgical planning of surgical evacuation of cSDH. The AR system was used to superimpose 3D anatomy onto the patients head to provide image guidance during two cases of evacuation. Imaging demonstrated convexity cSDH. A 3D model of the patient’s anatomy was created and registered onto the patients’ heads using a novel AR system. Surgical evacuation of the cSDH was completed in each case with surgical planning assisted by AR overlay.
Clinical and radiographic outcomes of a novel technique for socket healing: a protocol for a split-mouth randomized controlled trial
Authors: Albash Ziad
Published: May 2024

Tooth extraction is one of the most common routine procedures in the dental clinic. Tooth extraction is followed by an inevitable bone resorption that leads to alveolar ridge reduction in the horizontal and vertical directions. The dimensions of alveolar ridge after socket healing are the result of a balance between the resorption and remodeling mechanisms that occur naturally after tooth extraction. The aim of this study is to evaluate the clinical and radiographic outcomes of the socket decortication technique for socket healing through a split-mouth randomized controlled trial. The proposed research protocol will investigate the effectiveness of this technique in promoting optimal healing and reducing bone loss following tooth extraction. By comparing radiographic data from the intervention side with the control side within the same individual, the study seeks to provide valuable insights into the potential benefits of the novel approach. The findings of this study have the potential to advance current knowledge in the field of dentistry and contribute to improved clinical practices for socket healing.
Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial
Authors: Boeri Luca , De Lorenzis Elisa , Lucignani Gianpaolo , Turetti Matteo , Silvani Carlo , Zanetti Stefano Paolo , Longo Fabrizio , Albo Giancarlo , Salonia Andrea , Montanari Emanuele
Published: May 2024

Background

Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated.

Aim

To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI.

Methods

In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment.

Outcomes

Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS.

Results

Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders.

Clinical Implications

Combination treatment with HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C is effective if started immediately or even after a few months from symptoms in participants with rUTI.

Strengths and Limitations

The main limitation is the lack of long-term follow-up.

Conclusion

The oral formulation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C could be an effective therapy against urinary and sexual distress in participants with rUTI (NCT06268483; ClinicalTrials.gov).
Stem cell quiescence and dormancy in plant meristems
Authors: Eljebbawi Ali , Dolata Anika , Strotmann Vivien I , Stahl Yvonne
Published: May 2024

Plants exhibit opportunistic developmental patterns, alternating between growth and dormancy in response to external cues. Moreover, quiescence plays a critical role in proper plant growth and development, particularly within the root apical meristem and the shoot apical meristem. In these meristematic tissues, cells with relatively slower mitotic activity are present in the quiescent center and the central zone, respectively. These centers form long-term reservoirs of stem cells maintaining the meristematic stem cell niche, and thus sustaining continuous plant development and adaptation to changing environments. This review explores early observations, structural characteristics, functions, and gene regulatory networks of the root and shoot apical meristems. It also highlights the intricate mechanism of dormancy within the shoot apical meristem. The aim is to contribute to a holistic understanding of quiescence in plants, which is fundamental for the proper growth and environmental response of plants.
Description of a pathogenic strain ofAeromonas dhakensisisolated fromAncherythroculter nigrocaudain an inland region of China
Authors: Xu Xiandong , Fu Huiyun , Ouyang Min , Du Jinhui , Zhang Yujie , Chen Yangyang , Huang Jiangfeng , Zhou Zhiyong , Hu Baoqing , Yang Gang , Wen Chungen
Published: May 2024

Aeromonas dhakensis is reported as an emerging pathogenic species within the genus Aeromonas and is widely distributed in tropical coastal areas. This study provided a detailed description and characterization of a strain of A. dhakensis (202108B1) isolated from diseased Ancherythroculter nigrocauda in an inland region of China. Biochemical tests identified the isolate at the genus level, and the further molecular analysis of concatenated housekeeping gene sequences revealed that the strain belonged to the species A. dhakensis. The isolated A. dhakensis strain was resistant to five antibiotics, namely, penicillin, ampicillin, clindamycin, cephalexin, and imipenem, while it was susceptible to or showed intermediate resistance to most of the other 15 tested antibiotics. The isolated strain of A. dhakensis caused acute hemorrhagic septicemia and tissue damage in artificially infected A. nigrocauda, with a median lethal dose of 7.76 × 104 CFU/fish. The genome size of strain 202108B1 was 5 043 286 bp, including 1 chromosome and 4 plasmids. This is the first detailed report of the occurrence of infection caused by an A. dhakensis strain causing infection in an aquaculture system in inland China, providing important epidemiological data on this potential pathogenic species.
Money matters: a critique of ‘informed financial consent’
Authors: Attinger Sara A , Kerridge Ian , Stewart Cameron , Karpin Isabel , Gallagher Siun , Norman Robert J , Lipworth Wendy
Published: May 2024

In recent years, concerns about the financial burdens of health care and growing recognition of the relevance of cost to decision making and patient experience have increasingly focused attention on financial ‘transparency’ and disclosure of costs to patients. In some jurisdictions, there have been calls not only for timely disclosure of costs information, but also for ‘informed financial consent’. However, simply putting the ‘financial’ into ‘informed consent’ and invoking an informed consent standard for cost information encounters several ethical, legal, and practical difficulties. This article will examine the viability and desirability of ‘informed financial consent’, and whether it is possible to derive ideas from traditional informed consent that may improve decision making and the patient experience. We argue that, while there are important legal, ethical, and practical challenges to consider, some of the principles of informed consent to treatment can usefully guide financial communication. We also argue that, while medical practitioners (and their delegates) have an important role to play in bridging the gap between disclosure and enabling informed (financial) decision making, this must be part of a multi-faceted approach to financial communication that acknowledges the influence of non-clinical providers and other structural forces on discharging such obligations.
Pectoralis Major Tendon Reconstruction With Achilles Tendon Allografts Utilizing Combined Pulvertaft Weave and Onlay Techniques
Authors: Wary J Nickolas , Bottoni Craig R , Zhou Liang
Published: May 2024

Surgical treatment of chronic pectoralis major tears presents a technical challenge, as injury chronicity may preclude the ability to perform a direct repair. Many techniques have been described to repair an acute pectoralis tendon rupture, including utilization of unicortical buttons within the humeral footprint. In the chronic setting when direct repair is not possible, reconstruction with allograft tissue can restore strength, improve cosmesis, and yield high functional outcomes; however, literature is limited to small case series. We describe a combined Pulvertaft Weave and onlay technique with dual Achilles tendon allograft in the management of an active duty infantryman with a chronic pectoralis major injury.
Simultaneous Presentation of Swimming-Induced Pulmonary Edema in a Set of Monozygotic Twin Elite Maritime Warfare Candidates: A Novel Case Report
Authors: Matthew A. Tovar , Boswell Gilbert , Sebreros Benjamin
Published: May 2024

Swimming-induced pulmonary edema (SIPE) is an incompletely understood condition that is often seen in U.S. special operations candidates participating in maritime qualification training courses. We present a case of two monozygotic twins with the simultaneous onset of acute respiratory distress during a crucible event of a maritime assessment and selection course. Subsequent pulmonary ultrasonography in both candidates showed wedge-shaped hyperechoic lines (B-lines) extending from the pleural interface into the interstitium. Chest radiography of both candidates revealed bilateral asymmetric hazy opacities consistent with SIPE. Both candidates recovered with supportive measures but were medically removed from training. Given the near-identical exposures of the candidates to the same ambient and water temperatures, duration of water submersion, magnitude of physical stressors, and viral colonization, this case study suggests that there may be underlying genetic factors, in addition to environmental factors, that predispose individuals to developing SIPE. Further benchtop and clinical research must be performed to identify potential genetic polymorphisms that contribute to the development of SIPE and to investigate safe interventions that address the underlying etiologies of SIPE pathophysiology.
The ultraviolet continuum slopes of high-redshift galaxies: evidence for the emergence of dust-free stellar populations at z > 10
Authors: Cullen F , McLeod D J , McLure R J , Dunlop J S , Donnan C T , Carnall A C , Keating L C , Magee D , Arellano-Cordova K Z , Bowler R A A , Begley R , Flury S R , Hamadouche M L , Stanton T M
Published: May 2024

We present an analysis of the ultraviolet (UV) continuum slopes (β) for a sample of 172 galaxy candidates at 8 < zphot < 16 selected from a combination of JWST NIRCam imaging and COSMOS/UltraVISTA ground-based near-infrared imaging. Focusing primarily on a new sample of 121 galaxies at 〈z〉 ≃ 11 selected from ≃ 320 arcmin2 of public JWST imaging data across 15 independent data sets, we investigate the evolution of β in the galaxy population at z ≥ 9. We find a significant trend between β and redshift, with the inverse-variance weighted mean UV slope evolving from 〈β〉 = −2.17 ± 0.06 at z = 9.5 to 〈β〉 = −2.59 ± 0.06 at z = 11.5. Based on a comparison with stellar population models including nebular continuum emission, we find that at z > 10.5 the average UV continuum slope is consistent with the intrinsic blue limit of dust-free stellar populations (βint ≃ −2.6). These results suggest that the moderately dust-reddened galaxy population at z < 10 was essentially unattenuated at z ≃ 11. The extremely blue galaxies being uncovered at z > 10 place important constraints on dust attenuation in galaxies in the early Universe, and imply that the already observed galaxy population is likely supplying an ionizing photon budget capable of maintaining ionized intergalactic medium fractions of ≳ 5 per cent at z ≃ 11.
Challenges nurses face in providing care for patients with juvenile idiopathic arthritis
Authors: Fusama Mie , Nakahara Hideko , Miyamae Takako , Mori Masaaki , Urata Yukitomo , Kawahata Kimito , Kawahito Yutaka , Kojima Masayo , Sugihara Takahiko , Hashimoto Motomu , Murashima Atsuko , Yajima Nobuyuki , Matsui Toshihiro
Published: May 2024

Objectives

This study aimed at identifying challenges nurses face in caring for patients with juvenile idiopathic arthritis (JIA) in Japan.

Methods

Nurses certified by the Japan Rheumatism Foundation were asked to describe their challenges in caring for JIA patients. Data were analysed using qualitative content analysis.

Results

Responses were collected from 89 participants. Fifty-eight issues were identified from 40 participants with experience in caring for JIA patients. Sixteen categories emerged, which were grouped into five challenges: communication, understanding, expertise, system, and collaboration. Care for JIA patients included different challenges from adult patients with rheumatoid arthritis, such as complicated patient–parent relationships, inadequate patient independence, and insufficient patient information. Moreover, 76 issues from 49 participants with no experience were identified. Seven categories emerged, which were grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience in caring for JIA patients, nurses recognized the importance of acquiring knowledge.

Conclusions

This is the first study in Japan regarding the difficulties nurses face in caring for JIA patients. Multidisciplinary team care and a comprehensive understanding of the patient journey, including relationships with guardians, acquaintances, and healthcare providers, are crucial to improve treatment outcome and overall patient quality of life.
Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent cell survival
Authors: Rossi Martina , Banskota Nirad , Shin Chang Hoon , Anerillas Carlos , Tsitsipatis Dimitrios , Yang Jen-Hao , Munk Rachel , Martindale Jennifer L , Yang Xiaoling , Piao Yulan , Mazan-Mamczarz Krystyna , Fan Jinshui , Lehrmann Elin , Lam Kwan-Wood Gabriel , De Supriyo , Abdelmohsen Kotb , Gorospe Myriam
Published: May 2024

RNA modifications, including N6-methyladenosine (m6A), critically modulate protein expression programs in a range of cellular processes. Although the transcriptomes of cells undergoing senescence are strongly regulated, the landscape and impact of m6A modifications during senescence are poorly understood. Here, we report a robust m6A modification of PTCHD4 mRNA, encoding Patched Domain-Containing Protein 4, in senescent cells. The METTL3/METTL14 complex was found to incorporate the m6A modification on PTCHD4 mRNA; addition of m6A rendered PTCHD4 mRNA more stable and increased PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as responsible for the stabilization and increased abundance of m6A-modified PTCHD4 mRNA. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells and sensitized them to senolysis and apoptosis. Our results indicate that m6A modification of PTCHD4 mRNA increases the production of PTCHD4, a protein associated with senescent cell survival, supporting the notion that regulating m6A modification on specific mRNAs could be exploited to eliminate senescent cells for therapeutic benefit.
Skipping events impose repeated binding attempts: profound kinetic implications of protein–DNA conformational changes
Authors: Rogoulenko Elena , Levy Yaakov
Published: May 2024

The kinetics of protein–DNA recognition, along with its thermodynamic properties, including affinity and specificity, play a central role in shaping biological function. Protein–DNA recognition kinetics are characterized by two key elements: the time taken to locate the target site amid various nonspecific alternatives; and the kinetics involved in the recognition process, which may necessitate overcoming an energetic barrier. In this study, we developed a coarse-grained (CG) model to investigate interactions between a transcription factor called the sex-determining region Y (SRY) protein and DNA, in order to probe how DNA conformational changes affect SRY–DNA recognition and binding kinetics. We find that, not only does a requirement for such a conformational DNA transition correspond to a higher energetic barrier for binding and therefore slower kinetics, it may further impede the recognition kinetics by increasing unsuccessful binding events (skipping events) where the protein partially binds its DNA target site but fails to form the specific protein–DNA complex. Such skipping events impose the need for additional cycles protein search of nonspecific DNA sites, thus significantly extending the overall recognition time. Our results highlight a trade-off between the speed with which the protein scans nonspecific DNA and the rate at which the protein recognizes its specific target site. Finally, we examine molecular approaches potentially adopted by natural systems to enhance protein–DNA recognition despite its intrinsically slow kinetics.
SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells
Authors: Li Mengdie , Zhang Zhixiang , He Liuguijie , Wang Xiefeng , Yin Jianxing , Wang Xiuxing , You Yongping , Qian Xu , Ge Xin , Shi Zhumei
Published: May 2024

Background

The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients.

Methods

SMYD2-induced PGC1α methylation and followed nuclear export are confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis are validated by oxygen consumption rate, ECAR, and intracranial glioma model.

Results

PGC1α methylation causes the disabled mitochondrial function to maintain the stemness, thereby enhancing the radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival.

Conclusions

These findings unveil a novel regulatory pathway involving mitochondria that govern stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.
The Brazilian international patient summary initiative
Authors: de Faria Leao Beatriz , Costa Italo Macedo do Amaral , Machado Joice , de Assis Molla Monalisa , Zamarro Aline Rodrigues , Motter Fabiane Raquel , Oliveira Gabriel Gausmann , Costa Karla L de A Calvette , de Mello Blanda Helena , Souza Elivan Silva , Neves Gabriella Nunes , de Melo Matos Robson Willian , dos Santos Paula Xavier , de Oliveira José Eduardo Bueno , Gadenz Sabrina Dalbosco
Published: May 2024

This paper describes the development of the Brazilian version of the International Patient Summary (IPS). A joint technical team is developing the project from Syrian-Lebanese Hospital, São Paulo, and the Coordination of Innovation and Informatics in Health, Secretariat of Information and Digital Health, Brazilian Ministry of Health. The five-phased approach used in the development of Brazil IPS starts with the identification of the Brazilian Ministry of Health national terminologies used to represent concepts for problems, diagnosis and procedures, their upload in a terminology server and mapping to IPS ValueSets, the Fast Healthcare Interoperability Resources profiles customization and, finally, the complete Brazil IPS Implementation Guide is described.
2023 Record marine heat waves: coral reef bleaching HotSpot maps reveal global sea surface temperature extremes, coral mortality, and ocean circulation changes
Authors: Goreau Thomas J F , Hayes Raymond L
Published: May 2024

Coral reefs, the most sensitive ecosystem to high temperature, are on the precipice of mass extinction from global warming [1, 2]. 2023 was the hottest year in recorded history on land and in the sea, with dramatic and unexpected temperature increases [3, 4]. Coral Reef Bleaching HotSpot maps provide unique insight into global ocean circulation changes in response to greenhouse gas (GHG) forcing that caused dramatic global temperature rises [1, 2]. The highest excess daily air temperatures recorded in 175 countries, as well as the most prolonged excessive sea surface temperatures, were centered around Jamaica. 2023 marked the worst coral reef bleaching yet in the Northern Hemisphere, with the Southern Hemisphere poised to follow in early 2024. The HotSpot maps strongly suggest accelerated ocean poleward heat transport, slowdown in upwelling, and decreased deep water formation linked to sharply increased 2023 anomalous sea surface and air temperatures. The 2023 distribution of severe heat and bleaching follows both spatial patterns and temporal trends first shown from a baseline 1982–2001 global SST trend analysis [5]. Increased warming of both hot and cold ocean currents shows that horizontal mixing of tropical heat to the poles is accelerating, and that vertical mixing with cold deep water is slowing down, leading to increased ocean stratification, which will cause sea temperature to increase more rapidly and CO2 mixing with the deep ocean to decrease.
An Integrated, Process Oriented Multilevel Theory of Team Adaptation
Authors: Misisco Anthony T. , Kozlowski Steve W. J.
Published: May 2024

Uncertainty is inherent to the team adaptation process. Stereotypically, team adaptation is operationalized as a response to a negative, external environmental occurrence. This chapter establishes the foundation for a more expansive and integrated multilevel theory of team adaptation to uncertainty. The authors suggest that uncertainty can be created and increased cognizantly by individual actors, can emerge endogenously, and can be positively valent. These principles undergird a process-oriented multilevel theory of team adaptation. First, the authors discuss the implications of teams engaging in deliberate, positive, internal uncertainty creation processes for the long-term development of team-level adaptive capabilities. Next, the authors propose a model of uncertainty that addresses the compilational process through which team members respond to adaptive performance episodes. Conceptualizing the team adaptation process occurring through compilational, patterned networks of interaction advances a model of adaptation that advances theory beyond simplistic compositional models that do not adequately capture the multilevel nature of adaptation.
Physics of nova outbursts: Theoretical models of classical nova outbursts with optically thick winds on 1.2 M⊙ and 1.3 M⊙ white dwarfs
Authors: Kato Mariko , Saio Hideyuki , Hachisu Izumi
Published: May 2024

We present time-dependent nova outburst models with optically thick winds for 1.2 and 1.35$\, M_{\odot }$ white dwarfs (WDs) with a mass-accretion rate of $5 \times 10^{-9}\, M_{\odot }$ yr−1 and for a 1.3$\, M_{\odot }$ WD with $2 \times 10^{-9}\, M_{\odot }$ yr−1. The X-ray flash occurs 11 d before the optical peak of the 1.2$\, M_{\odot }$ WD and 2.5 d before the peak of the 1.3$\, M_{\odot }$ WD. The wind mass-loss rate of the 1.2$\, M_{\odot }$ WD (1.3$\, M_{\odot }$ WD) reaches a peak of $6.4 \times 10^{-5}\, M_{\odot }$ yr−1 ($7.4 \times 10^{-5}\, M_{\odot }$ yr−1) at the epoch of the maximum photospheric expansion with the lowest photospheric temperature of log Tph (K) = 4.33 (4.35). The nuclear energy generated during the outburst is lost in the form of radiation (61% for the 1.2$\, M_{\odot }$ WD; 47% for the 1.3$\, M_{\odot }$ WD), gravitational energy of ejecta (39%; 52%), and kinetic energy of the wind (0.28%; 0.29%). We found an empirical relation for fast novae between the time to optical maximum from the outburst tpeak and the expansion timescale τexp. With this relation, we are able to predict the time to optical maximum tpeak from the ignition model (at t = 0) without following a time-consuming nova wind evolution.
Evaluation of thoracic sympathetic ganglion block as a predictor for response to ketamine infusion therapy and spinal cord stimulation in patients with chronic upper extremity pain
Authors: Kim Jeongsoo , Kim Hangaram , Kim Jae Eun , Yoo Yongjae , Moon Jee Youn
Published: May 2024

Objective

To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS).

Design

Retrospective

Setting

Tertiary hospital single-center

Subjects

Patients who underwent TSGB receiving KIT or SCS within a 3-year window.

Methods

Positive TSGB outcomes were defined as ≥2 0–10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2–4 weeks post-KIT and ≥4 NRS score reduction at 2–4 weeks post-SCS implantation, respectively.

Results

Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n = 20) reported a ≥ 2 0–10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n = 14) KIT responders, significantly higher than that in 30.8% (n = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26–39.02). Among 32 patients who underwent SCS implantation, 68.8% (n = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS.

Conclusions

A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS.
Toward Realistic Models in T2/ℤ2 Flux Compactification
Authors: Imai Hiroki , Maru Nobuhito
Published: May 2024

We consider a six-dimensional gauge theory compactified on $T^2/\mathbb {Z}_2$ with magnetic flux. The configurations of models are classified by winding numbers at the fixed points. Requiring the existence of generation numbers and Yukawa coupling, we see that allowed and forbidden configurations are described by geometry of winding numbers.
The role of thematic specialization in international scientific collaboration: the case of Chagas research
Authors: López Emanuel , Arza Valeria
Published: May 2024

Scientists are increasingly specializing to manage the vast knowledge bases within their domains, making knowledge-sharing strategies essential for scientific progress. Among these strategies, international scientific collaboration has increased markedly. We analyse the role of thematic specialization as one of its drivers in the context of Chagas research, a neglected disease. Since there is a strong research tradition in Latin America on this topic, it is an interesting context to study centre-periphery research dynamics. Using a novel bibliometric database on Chagas research during 1990–2019, we exploit its panel structure in a gravity-type econometric model. The findings show that the degree of specialization and its proximity among partners boost joint publications. Both effects are particularly important for country dyads involving authors from the periphery linked to authors in the centre. This paper is the first empirical study to assess the role of specialization as a driver of international scientific collaboration.
The risk of sexual dysfunction in Chinese women with recurrent pregnancy loss and the associated factors: a multicenter cross-sectional study
Authors: Liu Chuanjiao , Zhang Yiduo , Xu Qian , Yang Chen , Tang Yuanting , Zhang Qiong , Liu Xiumei , Yue Yangang , Yu Fan
Published: May 2024

Background

Recurrent pregnancy loss (RPL) is a severe traumatic event for women of childbearing age. However, the association between RPL and female sexual dysfunction was unknown.

Aim

The study sought to investigate the association between RPL and sexual dysfunction, and to explore the risk factors of sexual dysfunction for RPL patients.

Methods

A multicenter cross-sectional study involving both RPL patients and healthy women was performed in 3 different hospitals in West China from May 2021 to January 2023. Baseline information including sociodemographic data and disease histories were collected. The Female Sexual Function Index (FSFI) was used to assess the sexual function of participants.

Outcomes

The main outcome was the proportion of women at increased risk of sexual dysfunction (total FSFI scores <26.55), and the secondary outcome was risk factors of sexual dysfunction in RPL patients.

Results

A total of 233 RPL patients and 185 healthy women were included in this study. RPL patients had significantly lower total FSFI scores (median 31.7 [interquartile range, 26.6-33.5] vs 33.0 [interquartile range, 31.2-34.1]; P < .001) and a significantly higher risk of sexual dysfunction than healthy women (24.9% vs 8.6%; P < .001). Body mass index >24 kg/m2 (adjusted odds ratio [OR], 4.132; 95% confidence interval [CI], 1.902-8.976, P < .001), working >8 h/d (adjusted OR, 2.111; 95% CI, 1.020-4.369, P = .044), and unexplained RPL (adjusted OR, 3.785; 95% CI, 1.967-7.280, P < .001) were independent risk factors of sexual dysfunction for RPL patients.

Clinical Implications

RPL patients, especially those patients with the previously mentioned risk factors, should be focused on the risk of sexual dysfunction, and appropriate preventions could be applied.

Strength and Limitations

We explored the association between RPL and sexual dysfunction and explored the risk factors of sexual dysfunction among RPL patients for the first time, and the multicenter data increased the generalizability of results. However, the cross-sectional design did not provide an exact causal relationship between RPL and sexual dysfunction, and potential risk factors related to mental health were not investigated.

Conclusion

RPL patients were at an increased risk of sexual dysfunction. Overweight, fatigue caused by work, and unexplained RPL were risk factors of sexual dysfunction for RPL patients.
Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-β1/Smad2/3 pathways: the role of Isochlorogenic acid a
Authors: Guo Jun-Tao , Li Han-Yu , Cheng Chao , Shi Jia-Xue , Ruan Hai-Nan , Li Jun , Liu Chan-Min
Published: May 2024

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor β1 (TGF-β1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-β1/Smad2/3 pathways.