bluuebunny/crossref_metadata_2025 huggingface dataset:
Avaliação da sexualidade de pacientes obesos antes e após a cirurgia bariátrica: uma revisão integrativa
Authors: Lima Elizânia Santos de , Silva Thiago Bruno da , Farias Camilla Ribeiro Lima de
Published: May 2023

Introdução: A obesidade é considerada uma epidemia global, devido ao seu rápido crescimento, sendo um problema de saúde pública que afeta a saúde física e psicológica do indivíduo. Nesse contexto, se insere as alterações na função sexual e reprodutiva, uma vez que a obesidade passa a ser um difilcultador para o indivíduo ter reconhecido o seu papel social como um sujeito, especialmente na vivência da sexualidade. Objetivos: Avaliar a sexualidade de obesos antes e após acirurgia bariátrica. Métodos: Trata-se de uma revisão integrativa da literatura, de caráter descritivo e analítico, realizada entre os meses de abril e maio de 2022. Resultados: Dos 17 artigos selecionados, observou-se que, a maioria dos pacientes relatou melhora do desempenho sexual após a cirurgia bariátrica, identificado pelo aumento da energia/ânimo/menos cansaço, elevação do desempenho sexual e libido, interferência da diminuição do peso e aumento da duração do ato sexual, assim como melhora dos fatores psicossociais, como mais auto-estima, vontade/interesse e menos vergonha. Observou-se que foram realizados mais estudos em mulheres do que em homens, e que a expressão de comportamento e função sexual entre os gêneros se diferem, tanto do ponto de vista biológico quanto psico-relacional. Conclusão: Considerando que a sexualidade é um fator importante que influencia na qualidade de vida do indivíduo, a sua melhora após a CB gera repercussões positivas de ordem física e emocional, não podendo ser subestimados na prática clínica.
Factors affecting formula compliance of infants with IgE mediated cow's milk protein allergy during the pandemic
Authors: Uygun Dilara Kocacik , Karaatmaca Betul , Topal Erdem , Arga Mustafa , Sancakli Ozlem , Ozcan Dilek , Igde Mahir , Cekic Sukru , Bingol Gulbin , Buyuktiryaki Betul , Sackesen Cansin , Sursal Alihan , Ozdener Fatih , Bingol Aysen
Published: May 2023

Introduction

Cow's milk protein allergy (CMPA) is the most commonly encountered food allergy in the world, usually seen in infants under the age of 2 years. This study aims to determine the factors including COVID-19 affecting formula compliance of CMPA patients.

Methods

This study is a prospective, observational study based on 10 different Paediatric Allergy-Immunology clinics in Turkey. Patients aged between 6 months and 2 years, who were followed up with IgE-mediated CMPA treatment or newly diagnosed and using breast milk and/or formula were included in the study. The sociodemographic characteristics of the patients, their symptoms, the treatments they received, and the effects of the COVID-19 pandemic on adherence to formula were evaluated with a questionnaire administered to the parents.

Results

The compliance rate for formula-based treatment was 30.8% (IQR: 28.3, SD: 21.86). The number of patients with a single and multiple food allergy was 127 (51.6%) and 71 (28.9%), respectively. Breastfeeding duration, daily amount of prescribed formula and addition of sweetener to the formula were found to reduce compliance (p = 0.010, p = 0.003, and p = 0.004, respectively). However, it was determined that the patient's height, weight, age at diagnosis, and age of formula onset did not have a significant effect on compliance.

Conclusion

It was found that the duration of breastfeeding, the increase in the daily amount of formula requirement, and the addition of sweeteners had adverse effects on formula compliance. There was no significant correlation between the formula adherence of CMPA patients and the pandemic.
A novel three dimensional-printed biomechanically evaluated patient-specific sacral implant in spinopelvic reconstruction after total en bloc sacrectomy
Authors: Lv Zhaorui , Li Jianmin , Yang Zhiping , Li Xin , Yang Qiang , Li Zhenfeng
Published: May 2023

Background: Reconstruction after a total sacrectomy is a challenge due to the special anatomical and biomechanical factors. Conventional techniques of spinal-pelvic reconstruction do not reconstruct satisfactorily. We describe a novel three-dimensional-printed patient-specific sacral implant in spinopelvic reconstruction after total en bloc sacrectomy.

Methods: We performed a retrospective cohort study including 12 patients with primary malignant sacral tumors, including 5 men and 7 women with a mean age of 58.25 years (range 20–66 years), undergoing total en bloc sacrectomy with 3D printed implant reconstruction from 2016 to 2021. There were 7 cases of chordoma, 3 cases of osteosarcoma, 1 case of chondrosarcoma and 1 case of undifferentiated pleomorphic sarcoma. We use CAD technology to determine surgical resection boundaries, design cutting guides, and individualized prostheses, and perform surgical simulations before surgery. The implant design was biomechanically evaluated by finite element analysis. Operative data, oncological and functional outcomes, complications, and implant osseointegration status of 12 consecutive patients were reviewed.

Results: The implants were implanted successfully in 12 cases without death or severe complications during the perioperative period. Resection margins were wide in 11 patients and marginal in one patient. The average blood loss was 3875 mL (range, 2000–5,000 mL). The average surgical time was 520 min (range, 380–735 min). The mean follow-up was 38.5 months. Nine patients were alive with no evidence of disease, two patients died due to pulmonary metastases, and one patient survived with disease due to local recurrence. Overall survival was 83.33% at 24 months. The Mean VAS was 1.5 (range, 0–2). The mean MSTS score was 21 (range, 17–24). Wound complications occurred in 2 cases. A deep infection occurred in one patient and the implant was removed. No implant mechanical failure was identified. Satisfactory osseointegration was found in all patients, with a mean fusion time of 5 months (range 3–6 months).

Conclusion: The 3D-printed custom sacral prosthesis has been effective in reconstructing spinal-pelvic stability after total en bloc sacrectomy with satisfactory clinical outcomes, excellent osseointegration, and excellent durability.
Biomechanics in liver regeneration after partial hepatectomy
Authors: Wu Yi , Li Ning , Shu Xinyu , Li Wang , Zhang Xiaoyu , Lü Dongyuan , Long Mian
Published: May 2023

The liver is a complicated organ within the body that performs wide-ranging and vital functions and also has a unique regenerative capacity after hepatic tissue injury and cell loss. Liver regeneration from acute injury is always beneficial and has been extensively studied. Experimental models including partial hepatectomy (PHx) reveal that extracellular and intracellular signaling pathways can help the liver recover to its equivalent size and weight prior to an injury. In this process, mechanical cues possess immediate and drastic changes in liver regeneration after PHx and also serve as main triggering factors and significant driving forces. This review summarized the biomechanics progress in liver regeneration after PHx, mainly focusing on PHx-based hemodynamics changes in liver regeneration and the decoupling of mechanical forces in hepatic sinusoids including shear stress, mechanical stretch, blood pressure, and tissue stiffness. Also discussed were the potential mechanosensors, mechanotransductive pathways, and mechanocrine responses under varied mechanical loading in vitro. Further elucidating these mechanical concepts in liver regeneration helps establish a comprehensive understanding of the biochemical factors and mechanical cues in this process. Proper adjustment of mechanical loading within the liver might preserve and restore liver functions in clinical settings, serving as an effective therapy for liver injury and diseases.
Polydopamine surface-modified hyperbranched polymeric nanoparticles for synergistic chemo/photothermal therapy of oral cancer
Authors: Yin Xingyong , Li Zimu , Zhang Yi , Zeng Xiaowei , Wang Qiuxu , Liang Zhigang
Published: May 2023

A novel drug delivery system for the treatment of oral cancer was developed using a facile polydopamine (PDA)-based surface modification and a binding mechanism linking folic acid-targeting ligands. The system was able to achieve the following objectives: loading of chemotherapeutic agents, active targeting, pH responsiveness, and prolonged in vivo blood circulation. DOX-loaded polymeric nanoparticles (DOX/H20-PLA@PDA NPs) were functionalized with amino-poly (ethylene glycol)-folic acid (H2N-PEG-FA) after coating them with PDA to form the targeting combination, DOX/H20-PLA@PDA-PEG-FA NPs. The novel NPs exhibited drug delivery characteristics similar to DOX/H20-PLA@ PDA NPs. Meanwhile, the incorporated H2N-PEG-FA contributed to active targeting, as illustrated in cellular uptake assays and animal studies. In vitro cytotoxicity and in vivo anti-tumor studies have shown that the novel nanoplatforms exhibit extremely effective therapeutic effects. In conclusion, the multifunctional PDA-modified H20-PLA@PDA-PEG-FA NPs offer a promising chemotherapeutic strategy to improve the treatment of oral cancer.
In vivo functions of miRNAs in mammalian spermatogenesis
Authors: Chen Jian , Han Chunsheng
Published: May 2023

MicroRNAs (miRNAs) are believed to play important roles in mammalian spermatogenesis mainly because spermatogenesis is more or less disrupted when genes encoding key enzymes for miRNA biogenesis are mutated. However, it is challenging to study the functions of individual miRNAs due to their family-wise high sequence similarities and the clustered genomic distributions of their genes, both of which expose difficulties in using genetic methods. Accumulating evidence shows that a number of miRNAs indeed play important roles in mammalian spermatogenesis and the underlying mechanisms start to be understood. In this mini review, we focus on highlighting the roles of miRNAs in mammalian spermatogenesis elucidated mainly by using in vivo genetic methods and on discussing the underlying mechanisms. We propose that studies on the roles of miRNAs in spermatogenesis should and can be conducted in a more fruitful way given the progress in traditional methods and the birth of new technologies.
Metabolite abundance in bovine preovulatory follicular fluid is influenced by follicle developmental progression post estrous onset in cattle
Authors: Hessock Emma A. , Edwards J. Lannett , Schrick F. Neal , Payton Rebecca R. , Campagna Shawn R. , Pollock Abigayle B. , Clark Hannah M. , Stokes Allyson E. , Klabnik Jessica L. , Hill Kennedy S. , Roberts Samantha R. , Hinson Meredith G. , Moorey Sarah E.
Published: May 2023

Introduction: Preovulatory follicle response to the luteinizing hormone (LH) surge leads to metabolic, molecular, and functional changes in the oocyte and somatic follicular cells from the onset of estrus to ovulation. Follicular fluid contains metabolites, miRNAs, proteins, and hormones that are byproducts of follicular metabolism and support cellular processes of oocyte, cumulus, and granulosa constituents. Numerous studies have highlighted the importance of follicular fluid composition to support fertility, but critical gaps exist toward understanding dynamic modifications in the follicular fluid metabolome from estrous onset to ovulation. The hypothesis was that abundance of follicular fluid metabolites is dependent on follicle progression post LH surge and variability in follicular fluid metabolome profiles indicate key processes required for preparation of the follicle and oocyte for optimal fertility. The objective was to generate preovulatory follicular fluid metabolome profiles and discern differences in the metabolome of preovulatory follicular fluid samples collected at onset of estrus, 11 h post estrous onset, and 18 h post estrous onset.

Methods: Estrus was synchronized in non-lactating Jersey cows (n=40) and follicular fluid was collected immediately after the first observed standing mount (hr 0) or at approximately h 11 or 18 after the first standing mount. Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry was performed on preovulatory follicular fluid samples (n = 9 collected at hr 0, 9 at h 11, and 10 at h 18) and a multiple linear model was performed to determine if time post estrous onset impacted metabolite abundance.

Results: Metabolites influenced by time post estrous onset were tested for enrichment in KEGG pathways. Ninety metabolites were identified in follicular fluid samples. Twenty metabolites differed in abundance among timepoints post estrous onset (p ≤ 0.05). Pathways corresponding to amino acid and energy metabolism were enriched with metabolites impacted by time post estrous onset (FDR ≤ 0.10).

Discussion: Results from the current study indicate early response to the LH surge to increase bioavailability of amino acids and metabolites used by the cumulus and granulosa cells for energy production and shuttled into the oocyte to support meiotic maturation. Such metabolites may later be used by the ovulatory follicle for protein production.
Biochemical, structural characterization and in-vitro evaluation of antioxidant, antibacterial, cytotoxic, and antidiabetic activities of nanosuspensions of Cinnamomum zeylanicum bark extract
Authors: Nawaz Aqsa , Ali Tayyab , Naeem Muhammad , Hussain Fatma , Li Zhiye , Nasir Abdul
Published: May 2023

Cinnamomum zeylanicum is a traditional medicinal plant known for its anti-inflammatory, antidiabetic, antimicrobial, anticancer, and antioxidant properties. Its therapeutic efficacy using nanosuspensions is still unclear for treating infectious diseases. This study was designed to evaluate the bioactivities, biochemical characterization, and bioavailability of freshly prepared nanosuspensions of C. zeylanicum. Structural and biochemical characterization of C. zeylanicum and its biological activities, such as antioxidants, antimicrobials, antiglycation, α-amylase inhibition, and cytotoxicity was performed using Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC). C. zeylanicum extract and nanosuspensions showed TPCs values of 341.88 and 39.51 mg GAE/100 g while showing TFCs as 429.19 and 239.26 mg CE/100g, respectively. DPPH inhibition potential of C. zeylanicum extract and nanosuspension was 27.3% and 10.6%, respectively. Biofilm inhibition activity revealed that bark extract and nanosuspension showed excessive growth restraint against Escherichia coli, reaching 67.11% and 66.09%, respectively. The α-amylase inhibition assay of extract and nanosuspension was 39.3% and 6.3%, while the antiglycation activity of nanosuspension and extract was 42.14% and 53.76%, respectively. Extracts and nanosuspensions showed maximum hemolysis at 54.78% and 19.89%, respectively. Results indicated that nanosuspensions possessed antidiabetic, antimicrobial, anticancer, and antioxidant properties. Further study, however, is needed to assess the clinical studies for the therapeutic use of nanosuspensions.
Chemical-imaging-guided optical manipulation of biomolecules
Authors: Clark Matthew G. , Ma Seohee , Mahapatra Shivam , Mohn Karsten J. , Zhang Chi
Published: May 2023

Chemical imaging via advanced optical microscopy technologies has revealed remarkable details of biomolecules in living specimens. However, the ways to control chemical processes in biological samples remain preliminary. The lack of appropriate methods to spatially regulate chemical reactions in live cells in real-time prevents investigation of site-specific molecular behaviors and biological functions. Chemical- and site-specific control of biomolecules requires the detection of chemicals with high specificity and spatially precise modulation of chemical reactions. Laser-scanning optical microscopes offer great platforms for high-speed chemical detection. A closed-loop feedback control system, when paired with a laser scanning microscope, allows real-time precision opto-control (RPOC) of chemical processes for dynamic molecular targets in live cells. In this perspective, we briefly review recent advancements in chemical imaging based on laser scanning microscopy, summarize methods developed for precise optical manipulation, and highlight a recently developed RPOC technology. Furthermore, we discuss future directions of precision opto-control of biomolecules.
Snowpack and avalanche characterization over the 2021–2022 winter season in Sisimiut, West Greenland
Authors: Mariani Alberto , Abrahamsen A. B. , Bridle D. , Ingeman-Nielsen T. , Cicoira A. , Monti F. , Marcer M.
Published: May 2023

In Greenland, snow avalanches have been recognized as a significant hazard and a risk to communities for decades. However, prior to this study, no formal avalanche database nor avalanche forecasting service existed in Greenland. This study was conducted over the 2021–2022 snow season to advance snow science research in Greenland and provide the town of Sisimiut with an avalanche bulletin service based on snowpack stability, weather conditions, and avalanche activity monitoring data within the Sisimiut backcountry. Snowpack stratigraphies were assessed and stability tests were performed periodically using standardized methods, and the results were linked with daily weather monitoring and avalanche event characterization. The observed avalanche activity was dominated by slab avalanches, accounting for 96% of the registered events. Instabilities were mainly driven by specific temperature patterns, strong winds, and rain episodes. During cold and calm periods, slow kinetic growth of snow crystals in low-density layers was observed. Abrupt thermal increases were recurrent, resulting in softening of superficial slabs with consequent reactivation of buried weak layers, thus reducing snowpack stability. On the other hand, prolonged warmer temperatures lowered the thermal gradient within the snowpack, leading to rounding and bonding of weak layer grains, thus recovering the snowpack stability. As observed on three occasions, rain events caused the formation of persistent weak layers and should be considered a warning for future snowpack instability. As a result of this study, we retroactively linked local weather patterns with snowpack instability and provided the first periodical avalanche bulletin service for Sisimiut.
Microbial traces found in microdolomite associated with seep-related shallow gas hydrate
Authors: Shiraishi Fumito , Akimoto Takayuki , Tomioka Naotaka , Takahashi Yoshio , Matsumoto Ryo , Snyder Glen T.
Published: May 2023

Recently, microdolomite grains with a diameter of about 30–150 μm were discovered within seep-related shallow gas hydrate in the eastern margin of the Japan Sea, and the preliminary assumption has been that their formation is mediated by microbially secreted extracellular polymeric substances (EPS). To verify this interpretation, the present study investigates the characteristics of minerals and organic matter inside the microdolomite grains. Observation by polarizing microscopy reveals that the microdolomite grains generally consist of combinations of distinct cores and external cements. The cores are mostly dark or cloudy and their abundance does not show clear depth dependence, while the external cements are generally isopachous in the shallow part and polygonal in the deeper portions. To further clarify the characteristics of these cores and external cements, thin-foil sections were prepared from two major types of microdolomite, one with a dark core and polygonal external cement, and one with a cloudy core and isopachous external cement. These thin-foil sections were then analyzed by scanning transmission X-ray microscopy (STXM) and transmission electron microscopy (TEM). In the dark core, fibriform pores of about 100 nm diameter were observed to be closely related with amorphous calcium carbonate (ACC) and carboxy groups, likely created by heterogeneous nucleation on microbial EPS surfaces. The polygonal external cement is composed of monocrystalline dolomite, representing slow crystal growth in the deeper part where hydrate formation is less active. On the other hand, the observed cloudy core and the isopachous external cement are, respectively, composed of scattered and accumulated rhombohedral dolomite crystals, presumably resulting from homogeneous nucleation in saline pockets of rapidly growing hydrate and subsequent crystal accumulation on the surface of spherical oil films.
Science and inquiry-based teaching and learning: a systematic review
Authors: Urdanivia Alarcon Diego Antonio , Talavera-Mendoza Fabiola , Rucano Paucar Fabian Hugo , Cayani Caceres Karina Sandra , Machaca Viza Rina
Published: May 2023

The use of the inquiry-based instructional approach allows the development of research skills and construction of scientific knowledge. When coupled with effective teaching strategies, this approach allows for the modeling of the world's laws and theories with reality, thereby making science more accessible. The objective is to analyze the instructional models, subject areas, and developmental areas implemented by secondary school teachers in science education. After a systematic review of Web of Science, Scopus, and ERIC databases from 2013 to 2022, 51 articles were selected, which include qualitative, experimental, and descriptive works. The results indicate that teaching science has a tendency to achieve learning using scientific reasoning, with high expectations based on evidence, and a predisposition to the use of constructivism instructional models. The need for continuous teacher training to understand scientific knowledge and to master strategies for implementing open inquiry is emphasized. It is concluded that all studies focus on IBL, which encourages new ways of conducting science while considering the cyclic application processes. Similarly, the trend toward technology-based serious games, such as video, audio, and digital platforms, is becoming increasingly evident in current education, as is the drive to develop STEM methodologies.
Large-scale measurement of urban streets’ space health based on the spatial disorder theory—A case study on the old urban area of Daoli District of Harbin City
Authors: Wan Ting , Wang Mingxue
Published: May 2023

As an essential part of urban public space, the basic framework of urban pattern, and the human landscape of the city and street space is of great significance to urban development. From the perspective of urban living safety, the demand for urban space for health has been considered in depth again. Therefore, with emerging new issues in the post-urbanization period such as the development of public health and slow traffic transportation, street space becomes disordered, and the health of street space has drawn great attention. This paper takes the old urban area of Daoli District of Harbin City as an example. The degree of spatial disorder of different streets in the old urban area of Daoli District of Harbin City is derived by using the off-site built environment audit method and mean square weight analysis and other technical methods with multi-source data such as Baidu map API. In this paper, the spatial health measurement of streets with different properties of land usage in the old urban area of Daoli District of Harbin City is classified, and the classification strategies are proposed based on the calculation results. Based on the theory of spatial disorder, a large-scale measurement of street space health provides insights and references for practical urban management in the future. In terms of theoretical research, this paper attempts to fill the gap in urban geospatial disorder research in China.
Emission reduction with hybrid mechanisms in civil aviation: An evolutionary game approach
Authors: Zhang Peiwen , Ding Rui , Wang Yu , Zhang Qiaoyan , Zhao Lianzheng
Published: May 2023

With the rapid growth of the aviation industry, the issue of carbon emissions has become a substantial challenge for governments and airlines. This paper proposes a hybrid carbon emission reduction mechanism, including major airlines in the emission trading systems and implementing carbon tax for small and medium-sized airlines. First, a tripartite evolutionary game model is constructed to study strategic behaviors. Second, four scenarios of evolutionarily stable strategies (ESSs) are analyzed. Finally, the influencing parameters of players’ strategy choices are analyzed through simulations. The results show that: 1) the steady development scenarios (1, 1, 1) can be reached under the appropriate conditions; 2) the parameters such as carbon allowances and carbon tax prices significantly influence the evolutionary trend of stakeholders’ dynamic choices; 3) the implementation of a hybrid mechanism by the government could facilitate the choice of low carbon operation strategies for both types of airlines. Accordingly, a series of policy recommendations are proposed to promote carbon emission reduction in civil aviation. This study combines evolutionary game and scenario analysis methods in an attempt to provide a new perspective on carbon emission reduction governance, thereby promoting the effective development of carbon emission reduction in civil aviation in the future.
Impacts of environmental uncertainty on degree of enterprise financialization and the moderating role of executive incentives
Authors: Chen Dong , Zhu Yating , Zhou Na , Xing Mu
Published: May 2023

This study takes the panel data of China’s A-share listed companies from 2016 to 2020 as the sample to empirically analyze the impact of environmental uncertainty on the degree of corporate financialization, and the moderating role of executive incentive in affecting the relationship between environmental uncertainty and the degree of corporate financialization. It is found that the rise of environmental uncertainty aggravates the degree of enterprise financialization. Executive equity incentives alleviate the degree of corporate financialization and significantly hedge the effect of environmental uncertainty on the degree of corporate financialization. In contrast, executive compensation incentives exacerbate the degree of corporate financialization and do not observably hedge the effect of environmental uncertainty on the degree of corporate financialization. Subgroup regressions indicate that the moderating effect of equity incentives on the relationship between environmental uncertainty and corporate financialization mainly occurs in non-state-owned firms. The findings of this study provide a theoretical base for firms to develop reasonable and practical incentive mechanisms to cope with environmental uncertainty.
Functional mapping of microRNA promoters with dCas9 fused to transcriptional regulators
Authors: Kumar Pradeep , Courtes Mathilde , Lemmers Céline , Le Digarcher Anne , Coku Ilda , Monteil Arnaud , Hong Charles , Varrault Annie , Liu Runhua , Wang Lizhong , Bouschet Tristan
Published: May 2023

MicroRNAs are small non-coding RNAs that control gene expression during development, physiology, and disease. Transcription is a key factor in microRNA abundance and tissue-specific expression. Many databases predict the location of microRNA transcription start sites and promoters. However, these candidate regions require functional validation. Here, dCas9 fused to transcriptional activators or repressors - CRISPR activation (CRISPRa) and inhibition (CRISPRi)- were targeted to the candidate promoters of two intronic microRNAs, mmu-miR-335 and hsa-miR-3662, including the promoters of their respective host genes Mest and HBS1L. We report that in mouse embryonic stem cells and brain organoids, miR-335 was downregulated upon CRISPRi of its host gene Mest. Reciprocally, CRISPRa of Mest promoter upregulated miR-335. By contrast, CRISPRa of the predicted miR-335-specific promoter (located in an intron of Mest) did not affect miR-335 levels. Thus, the expression of miR-335 only depends on the promoter activity of its host gene Mest. By contrast, miR-3662 was CRISPR activatable both by the promoter of its host gene HBS1L and an intronic sequence in HEK-293T cells. Thus, CRISPRa and CRISPRi are powerful tools to evaluate the relevance of endogenous regulatory sequences involved in microRNA transcription in defined cell types.
Calculation of the pharmacogenomics benefit score for patients with medication-related problems
Authors: Polasek Thomas M.
Published: May 2023

Unexpected poor efficacy and intolerable adverse effects are medication-related problems that may result from genetic variation in genes encoding key proteins involved in pharmacokinetics or pharmacodynamics. Pharmacogenomic (PGx) testing can be used in medical practice “pre-emptively” to avoid future patient harm from medications and “reactively” to diagnose medication-related problems following their occurrence. A structured approach to PGx consulting is proposed to calculate the pharmacogenomics benefit score (PGxBS), a patient-centered objective measure of congruency between medication-related problems and patient genotypes. An example case of poor efficacy with multiple medications is presented, together with comments on the potential benefits and limitations of using the PGxBS in medical practice.
Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab
Authors: De Biasi Sara , Mattioli Marco , Meschiari Marianna , Lo Tartaro Domenico , Paolini Annamaria , Borella Rebecca , Neroni Anita , Fidanza Lucia , Busani Stefano , Girardis Massimo , Coppi Francesca , Mattioli Anna Vittoria , Guaraldi Giovanni , Mussini Cristina , Cossarizza Andrea , Gibellini Lara
Published: May 2023

Introduction

A growing number of evidences suggest that the combination of hyperinflammation, dysregulated T and B cell response and cytokine storm play a major role in the immunopathogenesis of severe COVID-19. IL-6 is one of the main pro-inflammatory cytokines and its levels are increased during SARS-CoV-2 infection. Several observational and randomized studies demonstrated that tocilizumab, an IL-6R blocker, improves survival in critically ill patients both in infectious disease and intensive care units. However, despite transforming the treatment options for COVID-19, IL-6R inhibition is still ineffective in a fraction of patients.

Methods

In the present study, we investigated the impact of two doses of tocilizumab in patients with severe COVID-19 who responded or not to the treatment by analyzing a panel of cytokines, chemokines and other soluble factors, along with the composition of peripheral immune cells, paying a particular attention to T and B lymphocytes.

Results

We observed that, in comparison with non-responders, those who responded to tocilizumab had different levels of several cytokines and different T and B cells proportions before starting therapy. Moreover, in these patients, tocilizumab was further able to modify the landscape of the aforementioned soluble molecules and cellular markers.

Conclusions

We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.
The role of circadian clock-controlled mitochondrial dynamics in diabetic cardiomyopathy
Authors: Jin Zhenshuai , Ji Yanwei , Su Wating , Zhou Lu , Wu Xiaojing , Gao Lei , Guo Junfan , Liu Yutong , Zhang Yuefu , Wen Xinyu , Xia Zhong-Yuan , Xia Zhengyuan , Lei Shaoqing
Published: May 2023

Diabetes mellitus is a metabolic disease with a high prevalence worldwide, and cardiovascular complications are the leading cause of mortality in patients with diabetes. Diabetic cardiomyopathy (DCM), which is prone to heart failure with preserved ejection fraction, is defined as a cardiac dysfunction without conventional cardiac risk factors such as coronary heart disease and hypertension. Mitochondria are the centers of energy metabolism that are very important for maintaining the function of the heart. They are highly dynamic in response to environmental changes through mitochondrial dynamics. The disruption of mitochondrial dynamics is closely related to the occurrence and development of DCM. Mitochondrial dynamics are controlled by circadian clock and show oscillation rhythm. This rhythm enables mitochondria to respond to changing energy demands in different environments, but it is disordered in diabetes. In this review, we summarize the significant role of circadian clock-controlled mitochondrial dynamics in the etiology of DCM and hope to play a certain enlightening role in the treatment of DCM.
Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension
Authors: Ye Yi , Xu Qiying , Wuren Tana
Published: May 2023

Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.
Targeted CD7 CAR T-cells for treatment of T-Lymphocyte leukemia and lymphoma and acute myeloid leukemia: recent advances
Authors: Liu Jile , Zhang Yi , Guo Ruiting , Zhao Yifan , Sun Rui , Guo Shujing , Lu Wenyi , Zhao Mingfeng
Published: May 2023

The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunction with recent advances in the 64th annual meeting of the American Society of Hematology (ASH), provides a summary of the meaningful achievements in CD7 CAR T-cell generations and clinical trials over the last few years.
Epigenetic dysregulation of autophagy in sepsis-induced acute kidney injury: the underlying mechanisms for renoprotection
Authors: Zhao Shankun , Liao Jian , Shen Maolei , Li Xin , Wu Mei
Published: May 2023

Sepsis-induced acute kidney injury (SI-AKI), a common critically ill, represents one of the leading causes of global death. Emerging evidence reveals autophagy as a pivotal modulator of SI-AKI. Autophagy affects the cellular processes of renal lesions, including cell death, inflammation, and immune responses. Herein, we conducted a systematic and comprehensive review on the topic of the proposed roles of autophagy in SI-AKI. Forty-one relevant studies were finally included and further summarized and analyzed. This review revealed that a majority of included studies (24/41, 58.5%) showed an elevation of the autophagy level during SI-AKI, while 22% and 19.5% of the included studies reported an inhibition and an elevation at the early stage but a declination of renal autophagy in SI-AKI, respectively. Multiple intracellular signaling molecules and pathways targeting autophagy (e.g. mTOR, non-coding RNA, Sirtuins family, mitophagy, AMPK, ROS, NF-Kb, and Parkin) involved in the process of SI-AKI, exerting multiple biological effects on the kidney. Multiple treatment modalities (e.g. small molecule inhibitors, temsirolimus, rapamycin, polydatin, ascorbate, recombinant human erythropoietin, stem cells, Procyanidin B2, and dexmedetomidine) have been found to improve renal function, which may be attributed to the elevation of the autophagy level in SI-AKI. Though the exact roles of autophagy in SI-AKI have not been well elucidated, it may be implicated in preventing SI-AKI through various molecular pathways. Targeting the autophagy-associated proteins and pathways may hint towards a new prospective in the treatment of critically ill patients with SI-AKI, but more preclinical studies are still warranted to validate this hypothesis.
Changes in the microbiome of the sea anemone Exaiptasia diaphana during bleaching from short-term thermal elevation
Authors: Sydnor Jamison R. , Lopez Jaime , Wolfe Gordon V. , Ott Lisa , Tran Cawa
Published: May 2023

We examined the response of microbial communities in the model sea anemone Exaiptasia diaphana (Aiptasia) to short-term thermal elevation. Through 16S rRNA gene sequencing, we characterized the microbiomes of symbiotic (with algal symbionts) and aposymbiotic (bleached) anemones under ambient (27°C) and heat-stressed (34°C) conditions for 8-10 days, using both replicated endpoint and non-replicated time-course approaches. Consistent with prior studies, we observed a stable abundance of bacteria from the families Alteromonadaceae and Rhodobacteraceae, though with wide variation among individual anemones. We observed that symbiotic state conferred a larger impact on the microbiome than heat stress, implying the microbiome may play a metabolic role in the maintenance of cnidarian-dinoflagellate symbiosis. In particular, Pelobacter, an anaerobic sulfate reducer that is also a potential nitrogen fixer, was present only in symbiotic anemones, and its abundance decreased with initial exposure to 34°C, but recovered after 7 days. In aposymbiotic anemones, the added heat stress appeared to result in a large increase of rare bacterial taxa, which included potential pathogens such as Vibrio following bleaching. We also observed several archaea, the first reported for this model, but only in the seawater surrounding aposymbiotic Aiptasia, where abundance increased dramatically following heat stress. We further explored the diazotrophic (nitrogen fixation) potential of diverse bacteria associated with symbiotic and aposymbiotic Aiptasia, under both ambient and heat-stressed conditions, using nifH-PCR and qPCR and the acetylene reduction assay (ARA). In contrast to some stony corals, nifH was barely expressed in both anemone types, and under ambient conditions, diazotrophic activity was not detectable via ARA. Thus, although this research contributes to the growing knowledge of the bacterial community associated with a prominent model used in coral-symbiosis research, our results also suggest using caution when making direct comparisons between Aiptasia and different coral species in microbiome studies.
Biologically Important Areas II for cetaceans within U.S. and adjacent waters – Gulf of Alaska Region
Authors: Wild Lauren A. , Riley Heather E. , Pearson Heidi C. , Gabriele Christine M. , Neilson Janet L. , Szabo Andy , Moran John , Straley Janice M. , DeLand Sarah
Published: May 2023

We delineated and scored Biologically Important Areas (BIAs) for cetacean species in the Gulf of Alaska region. BIAs represent areas and times in which cetaceans are known to concentrate for activities related to reproduction, feeding, and migration, and also the known ranges of small and resident populations. This National Oceanic and Atmospheric Association (NOAA)-led effort uses structured expert elicitation principles to build upon the first version of NOAA’s BIAs for cetaceans. Supporting evidence for these BIAs came from aerial-, land-, and vessel-based surveys; satellite-tagging data; passive acoustic monitoring; Indigenous knowledge; photo-identification data; and/or prey studies. A total of 20 BIAs were identified, delineated, and scored for six species: beluga whale (Delphinapterus leucas), fin whale (Balaenoptera physalus), gray whale (Eschrichtius robustus), humpback whale (Megaptera novaeangliae), North Pacific right whale (Eubalaena japonica), and sperm whale (Physeter macrocephalus). Of the 20 total BIAs, there were two small and resident populations, one migratory, and 17 feeding areas; no reproductive BIAs were identified. An additional five watch list areas were identified, a new feature to the second version of BIAs. In addition to more comprehensive narratives and maps, the BIA II products improve upon the first version by creating metadata tables and incorporating a scoring and labeling system which improves quantification and standardization of BIAs within and across regions. BIAs are compilations of the best available science and have no inherent regulatory authority. They have been used by NOAA, other federal agencies, and the public to support planning and marine mammal impact assessments, and to inform the development of conservation measures for cetaceans.
Assessment of the establishment success of surfgrass Phyllospadix iwatensis from shoots in a leaf trimming method: implications for large-scale restoration
Authors: Sun Jie , Luo Fan-Shu , Yu Guo-Xu , Zhang Hong-Yu , Li Wen-Tao , Zhang Pei-Dong
Published: May 2023

Phyllospadix spp. play a crucial role in the supply of ecosystem services in rocky shores, but they have been rapidly reduced because of natural and anthropogenic causes. Since Phyllospadix spp. are attached to rocks in the surf zone with a strong hydrodynamic condition, their transplanted shoots easily disappear due to the high current velocity, resulting in the failure of transplantation. We described a leaf trimming method for transplanting shoots of surfgrass Phyllospadix iwatensis and evaluated the method’s establishment success for potential use in large-scale restoration projects. A 30-day laboratory experiment was conducted to determine the effect of leaf trimming on shoot survival, growth, and physiology. Successful establishment of new patches from shoots transplanted with the leaf trimming method was assessed through a shoot-transplanting field experiment over 15 months. The survival of P. iwatensis shoots was not significantly affected by the leaf trimming proportion of 10%–60%. The leaf elongation rate and total leaf area of the shoots exposed to 10%–50% leaf trimming reached or exceeded those of the control at the end of the laboratory experiment; however, the growth of the shoots under 60% leaf trimming was significantly lower than those under the control (p < 0.05). The soluble sugar and starch contents of the shoots also displayed a similar trend to the growth, with the lowest values attained at 60% of leaf trimming. The survival rate of shoots exposed to 50% leaf trimming treatment was 70% after 15 months following transplantation, which was 1.23 times higher than that of shoots in the control (p < 0.05). The shoot height in the 50% leaf trimming treatment was 1.02 times higher than that of shoots in the control at the end of the field experiment. There were no significant differences in photosynthetic pigment contents of P. iwatensis shoots between the leaf trimming treatment and the control (p > 0.05). Our study suggested that the leaf trimming method is an efficient restoration technique for the transplantation of P. iwatensis shoots, and is potentially useful in facilitating large-scale restoration projects.
Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation
Authors: Itano Andrea , Maslin Douglas , Ramani Kritika , Mehraei Golbarg , Carpenter Nancy , Cormack Taylor , Saghari Mahdi , Moerland Matthijs , Troy Erin , Caffry Will , Wardwell-Scott Leslie , Abel Stuart , McHale Duncan , Bodmer Mark
Published: May 2023

Introduction

EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body.

Methods

Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model.

Results

Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation.

Discussion

This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation.

Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.