bluuebunny/crossref_metadata_2025 huggingface dataset:
Focused ultrasound for the remote modulation of nitric oxide release from injectable PEG-fibrinogen hydrogels for tendon repair
Authors: Meyers Kaylee M. , Simon Alex , Khan Zerin M. , Rajachar Rupak M. , Vlaisavljevich Eli
Published: April 2023

Introduction: Tendon disorders such as tendinosis, the degradation of collagen in tendon, or tendonitis, inflammation of tendon tissue, contribute to 30% of musculoskeletal complaints. To address the limitations of currently available treatments for tendon repair, an injectable polyethylene glycol (PEG)-fibrinogen hydrogel encompassing nitric oxide (NO) releasing µ-particles was generated. The release of nitric oxide, a therapeutic molecule that modulates many wound healing processes, from the hydrogel can be modified with thermal and mechanical stimulus. To achieve remote control over NO release from hydrogels after deployment, focused ultrasound (FUS) was explored as it provides highly controlled thermal and mechanical stimulus non-invasively.

Methods: In this work, the ability of FUS to remotely elicit on-demand NO generation from acoustically active composite hydrogels via thermal and/or mechanical stimulus was explored. Specifically, the temperature and time-dependent release of NO was simulated and characterized when applying FUS to composite hydrogels.

Results: Results from acoustic simulations as well as thermocouple heating studies indicated that high spatial and temporal control over hydrogel warming could be achieved non-invasively with a 3.5 MHz FUS transducer. FUS was also able to remotely control NO release from hydrogels with various thermal magnitudes and durations. Additionally, no apparent changes in the mechanical properties of hydrogels were observed with FUS treatment.

Discussion: Utilizing FUS thermal and mechanical stimulus provides a potential method of remotely controlling NO release from hydrogels at a wound site to aid in tendon repair.
Improved social functioning and role functioning in rheumatic patients using a non-verbal communication tool: Results from a randomized, double-blind, controlled pilot-study
Authors: Karnik Julia , Riedl David , Schirmer Michael
Published: April 2023

Introduction

Pain is a leading symptom in patients with rheumatic diseases, limiting not only physical functioning but also social well-being. This study studied the practicability of colored wristbands as non-verbal communication tools and the effects of these tools on social and role functioning in rheumatic patients.

Methods

This prospective, double-blind, randomized controlled pilot study recruited 110 patients. Practicability of colored silicon wristbands as non-verbal communication tools was assessed by questionnaires. The control group received written information on the rheumatic diseases and their management in general. Social functioning and role functioning were assessed using two subscales from the EORTC QLQ-C30.

Results

A significant overall improvement of social functioning (p = 0.005) and role functioning (p = 0.001) with medium to large effect size were reported by patients both in the intervention and the control group. Post hoc analyses revealed a significant change in the mean social functioning (p = 0.007) and role functioning scores with medium effect size, while no such effect was found in the control group for neither variable (p = 0.006 and p = 0.06–0.21, respectively). 42.9% of the patients will continue to use a non-verbal communication tool in the future. Practicability of the wristbands was limited by small size of the wristbands in 17.6% and uncomfortable wearing of the wristbands and skin irritation each in 4.4% of the patients.

Discussion

This study shows first promising results for the use of a non-verbal communication tool in about 50.0% of the patients with rheumatic diseases, to improve their social functioning and role functioning.
Coupled Effects of Pore Water Velocity and Soil Heterogeneity on Bacterial Transport: Intact vs. Repacked Soils
Authors: Chen Jing , Yang Liqiong , Chen Xijuan , Ripp Steven , Zhuang Jie
Published: April 2023

Graphical Abstract

Depth profile of pore water velocity effect in differently structured soils.
Structurally Various Sorbicillinoids From an Endophytic Fungus Acremonium citrinum SS-g13
Authors: Peng Xiao-Ping , Li Gang , Wang Li-Mei , Wang Qi , Wang Cong , Ji Li-Xia , Cao Chen-Xi , Lin Guo-Feng , Jiang Zu-Yang , He Zhuo-qian , Wang Pei , Lou Hong-Xiang
Published: April 2023

Three new sorbicillinoids, including trimer trisorbicillinone E (1), acremosorbicillinoids A and B (2 and 3), and a new alkaloid acremokaloid A (4), and a new natural product 2S,3S-acetyl-β-methyltryptophan (5), were isolated from an endophytic fungus Acremonium citrinum SS-g13, which is found in Fructus mori plant root. In addition, eight known sorbicillinoids (6–13) were also obtained. The new compound structures were established using NMR, HRESIMS spectra, and reported spectroscopic data. The absolute configurations of compounds 1–5, were determined by spectroscopic analysis, Snatzke’s method, and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compound 11 exhibited significant cholesterol efflux enhancing activity. A plausible biosynthesis pathway for the sorbicillinoids is discussed.
Antidepressants amitriptyline, fluoxetine, and traditional Chinese medicine Xiaoyaosan caused alterations in gut DNA virome composition and function in rats exposed chronic unpredictable mild stress
Authors: Li Jialin , Qu Wan , Hu Chengcheng , Liu Zongbao , Yan He
Published: April 2023

Background

In clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear.

Methods

In this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing.

Results

The results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem.

Conclusion

Our study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.
Pathophysiology and mechanisms of hearing impairment related to neonatal infection diseases
Authors: Capra Daniela , DosSantos Marcos F. , Sanz Carolina K. , Acosta Filha Lionete Gall , Nunes Priscila , Heringer Manoela , Ximenes-da-Silva Adriana , Pessoa Luciana , de Mattos Coelho-Aguiar Juliana , da Fonseca Anna Carolina Carvalho , Mendes Carmelita Bastos , da Rocha Lanni Sarmento , Devalle Sylvie , Niemeyer Soares Filho Paulo , Moura-Neto Vivaldo
Published: April 2023

The inner ear, the organ of equilibrium and hearing, has an extraordinarily complex and intricate arrangement. It contains highly specialized structures meticulously tailored to permit auditory processing. However, hearing also relies on both peripheral and central pathways responsible for the neuronal transmission of auditory information from the cochlea to the corresponding cortical regions. Understanding the anatomy and physiology of all components forming the auditory system is key to better comprehending the pathophysiology of each disease that causes hearing impairment. In this narrative review, the authors focus on the pathophysiology as well as on cellular and molecular mechanisms that lead to hearing loss in different neonatal infectious diseases. To accomplish this objective, the morphology and function of the main structures responsible for auditory processing and the immune response leading to hearing loss were explored. Altogether, this information permits the proper understanding of each infectious disease discussed.
Identification of microbial community in the urban environment: The concordance between conventional culture and nanopore 16S rRNA sequencing
Authors: Lee Annie Wing-Tung , Chan Chloe Toi-Mei , Wong Lily Lok-Yee , Yip Cheuk-Yi , Lui Wing-Tung , Cheng Kai-Chun , Leung Jake Siu-Lun , Lee Lam-Kwong , Wong Ivan Tak-Fai , Ng Timothy Ting-Leung , Lao Hiu-Yin , Siu Gilman Kit-Hang
Published: April 2023

Introduction

Microbes in the built environment have been implicated as a source of infectious diseases. Bacterial culture is the standard method for assessing the risk of exposure to pathogens in urban environments, but this method only accounts for <1% of the diversity of bacteria. Recently, full-length 16S rRNA gene analysis using nanopore sequencing has been applied for microbial evaluations, resulting in a rise in the development of long-read taxonomic tools for species-level classification. Regarding their comparative performance, there is, however, a lack of information.

Methods

Here, we aim to analyze the concordance of the microbial community in the urban environment inferred by multiple taxonomic classifiers, including ARGpore2, Emu, Kraken2/Bracken and NanoCLUST, using our 16S-nanopore dataset generated by MegaBLAST, as well as assess their abilities to identify culturable species based on the conventional culture results.

Results

According to our results, NanoCLUST was preferred for 16S microbial profiling because it had a high concordance of dominant species and a similar microbial profile to MegaBLAST, whereas Kraken2/Bracken, which had similar clustering results as NanoCLUST, was also desirable. Second, for culturable species identification, Emu with the highest accuracy (81.2%) and F1 score (29%) for the detection of culturable species was suggested.

Discussion

In addition to generating datasets in complex communities for future benchmarking studies, our comprehensive evaluation of the taxonomic classifiers offers recommendations for ongoing microbial community research, particularly for complex communities using nanopore 16S rRNA sequencing.
Dynamic variation of bacterial community assemblage and functional profiles during rice straw degradation
Authors: Sun Ruibo , Wang Xin , Alhaj Hamoud Yousef , Lu Mengxing , Shaghaleh Hiba , Zhang Wenjie , Zhang Chaochun , Ma Chao
Published: April 2023

Bacteria is one of the most important drivers of straw degradation. However, the changes in bacterial community assemblage and straw-decomposing profiles during straw decomposition are not well understood. Based on cultivation-dependent and independent technologies, this study revealed that the “common species” greatly contributed to the dynamic variation of bacterial community during straw decomposition. Twenty-three functional strains involved in straw decomposition were isolated, but only seven were detected in the high-throughput sequencing data. The straw decomposers, including the isolated strains and the agents determined by functional prediction, constituted only 0.024% (on average) of the total bacterial community. The ecological network showed that most of the identified decomposers were self-existent without associations with other species. These results showed that during straw composition, community assembly might be greatly determined by the majority, but straw decomposition functions might be largely determined by the minority and emphasized the importance of the rare species in community-specific functions.
Antibiofilm effects of punicalagin against Staphylococcus aureus in vitro
Authors: Xu Yunfeng , Guo Weiping , Luo Denglin , Li Peiyan , Xiang Jinle , Chen Junliang , Xia Xiaodong , Xie Qinggang
Published: April 2023

Staphylococcus aureus is a common foodborne pathogen which can form biofilms to help them resist to antimicrobials. It brings great harm to human health. Punicalagin has good antimicrobial activities against S. aureus, but its effect on biofilm formation has not been clearly illustrated. The aim of this study was to explore the antibiofilm effects of punicalagin against S. aureus. Results showed that punicalagin did not significantly interfere with the growth of S. aureus at the concentrations of 1/64 MIC to 1/16 MIC. The biomass and metabolic activity of biofilms were significantly reduced when exposed to sub-inhibitory concentrations of punicalagin. The number of viable cells in the biofilms was also decreased after punicalagin treatment. Scanning electron microscopy and confocal laser scanning microscopy images confirmed that punicalagin damaged the structure of biofilms. The antibiofilm mechanism was partly due to the modification of the cell surface which led to the reduction of cell surface hydrophobicity. These findings suggest that punicalagin has the potential to be developed as an alternative to control S. aureus biofilms.
Neuroinflammation aggravated by traumatic brain injury at high altitude is reversed by L-serine via NFAT1-mediated microglial polarization
Authors: Liu Jinchun , Peng Shunhua , Ye Lisha , Sun Yechao , Zhao Qiong , Wei Hua , Luo Qianqian , He Min , Wang Guohua
Published: April 2023

Traumatic brain injury (TBI) is one of the main causes of disability and death, especially in plateau areas, where the degree of injury is often more serious than in plain areas. It is likely that high altitude (HA) aggravates neuroinflammation; however, prior studies are limited. This study was designed to evaluate the effects of HA on the degree of TBI and the neuroprotective effects and underlying mechanisms of L-serine against TBI at HA (HA-TBI). In in vivo experiments, wild-type mice and mice with Nfat1 (Nfat1−/−) deficiency in the C57BL/6 background were kept in a hypobaric chamber for 3 days under simulated conditions of 4,000 m, 6,000 m and 8,000 m above sea level. After leaving the chamber, the standardized TBI model was established immediately. Mice were then intraperitoneally injected with L-serine (342 mg.kg−1) 2 h after TBI and then daily for 5 days. Behavioral tests and histological analysis were assessed at different time points post TBI induction. In vitro, we applied primary cultured microglia for hypoxia treatment (1% O2 for 24 h). The major findings include the following: (1) with increasing altitude, the neurological function of TBI mice decreased, and the damage to cerebral gray matter and white matter became more significant, (2) L-serine significantly improved the sensorimotor function of mice, reversed the increase in brain lesion volume, and promoted the renovation of brain tissue after HA-TBI, (3) L-serine significantly decreased the activation of microglia and promoted microglia polarization toward the protective M2 phenotype both in vivo and in vitro, (4) L-serine significantly suppressed the expression of NFAT1 in mice after HA-TBI and inhibited NFAT1 expression in primary microglia after hypoxia, and (5) knockout of Nfat1 inhibited the inflammatory reaction caused by excessive activation of microglia, and L-serine lost its neuroprotective effect in Nfat1 knockout mice. The present study suggests that HA aggravates brain damage after TBI and that the damage also increases with increasing altitude. As an endogenous amino acid, L-serine may be a neuroprotective agent against HA-TBI, and suppression of NFAT1 in microglia is a potential therapy for neuroinflammation in the future.
Bicarbonate boosts flash response amplitude to augment absolute sensitivity and extend dynamic range in murine retinal rods
Authors: Adhikari Rajan D. , Kossoff Amanda M. , Cornwall M. Carter , Makino Clint L.
Published: April 2023

Rod photoreceptors in the retina adjust their responsiveness and sensitivity so that they can continue to provide meaningful information over a wide range of light intensities. By stimulating membrane guanylate cyclases in the outer segment to synthesize cGMP at a faster rate in a Ca2+-dependent fashion, bicarbonate increases the circulating “dark” current and accelerates flash response kinetics in amphibian rods. Compared to amphibian rods, mammalian rods are smaller in size, operate at a higher temperature, and express visual cascade proteins with somewhat different biochemical properties. Here, we evaluated the role of bicarbonate in rods of cpfl3 mice. These mice are deficient in their expression of functional cone transducin, Gnat2, making cones very insensitive to light, so the rod response to light could be observed in isolation in electroretinogram recordings. Bicarbonate increased the dark current and absolute sensitivity and quickened flash response recovery in mouse rods to a greater extent than in amphibian rods. In addition, bicarbonate enabled mouse rods to respond over a range that extended to dimmer flashes. Larger flash responses may have resulted in part from a bicarbonate-induced elevation in intracellular pH. However, high pH alone had little effect on flash response recovery kinetics and even suppressed the accelerating effect of bicarbonate, consistent with a direct, modulatory action of bicarbonate on Ca2+- dependent, membrane guanylate cyclase activity.
MicroRNA 3′ ends shorten during adolescent brain maturation
Authors: Thomas Kristen T. , Vermare Anaïs , Egleston Suzannah O. , Wang Yong-Dong , Mishra Ashutosh , Lin Tong , Peng Junmin , Zakharenko Stanislav S.
Published: April 2023

MicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics remain poorly understood during adolescent and early adult brain maturation, when symptoms often first appear. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early-, mid-, and late-adolescent and adult mice. Furthermore, we use quantitative proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects. We found that ~25% of miRNAs’ 3′ ends shorten with age due to increased 3′ trimming and decreased U tailing. Particularly, shorter but functionally competent isoforms (isomiRs) of miR-338-3p increase up to 10-fold during adolescence and only in brain. MiRNAs that undergo 3′ shortening exhibit stronger negative correlations with targets that decrease with age and stronger positive correlations with targets that increase with age, than miRNAs with stable 3′ ends. Increased 3′ shortening with age was also observed in available mouse and human miRNA-seq data sets, and stronger correlations between miRNAs that undergo shortening and their mRNA targets were observed in two of the three available data sets. We conclude that age-associated miRNA 3′ shortening is a well-conserved feature of postnatal brain maturation.
Machine learning algorithms assist early evaluation of enteral nutrition in ICU patients
Authors: Wang Ya-Xi , Li Xun-Liang , Zhang Ling-Hui , Li Hai-Na , Liu Xiao-Min , Song Wen , Pang Xu-Feng
Published: April 2023

Background

This study applied machine learning (ML) algorithms to construct a model for predicting EN initiation for patients in the intensive care unit (ICU) and identifying populations in need of EN at an early stage.

Methods

This study collected patient information from the Medical Information Mart for Intensive Care IV database. All patients enrolled were split randomly into a training set and a validation set. Six ML models were established to evaluate the initiation of EN, and the best model was determined according to the area under curve (AUC) and accuracy. The best model was interpreted using the Local Interpretable Model-Agnostic Explanations (LIME) algorithm and SHapley Additive exPlanation (SHAP) values.

Results

A total of 53,150 patients participated in the study. They were divided into a training set (42,520, 80%) and a validation set (10,630, 20%). In the validation set, XGBoost had the optimal prediction performance with an AUC of 0.895. The SHAP values revealed that sepsis, sequential organ failure assessment score, and acute kidney injury were the three most important factors affecting EN initiation. The individualized forecasts were displayed using the LIME algorithm.

Conclusion

The XGBoost model was established and validated for early prediction of EN initiation in ICU patients.
Consumer perception of “artificial meat” in the educated young and urban population of Africa
Authors: Kombolo Ngah Moïse , Chriki Sghaier , Ellies-Oury Marie-Pierre , Liu Jingjing , Hocquette Jean-François
Published: April 2023

African’s population is expected to grow especially in cities to reach about 2.5 billion in 2050. This will create an unprecedented boom in the demand for animal products over the coming years which will need to be managed properly. Industry stakeholders worldwide have been touting the potential benefits of “artificial meat” in recent years as a more sustainable way of producing animal protein. “Artificial meat” is therefore moving into the global spotlight and this study aimed to investigate how African meat consumers of the coming generations perceive it, i.e., the urban, more educated and younger consumers. Three surveys were conducted with more than 12,000 respondents in total. The respondents came from 12 different countries (Cameroon, Congo, -DRC Democratic Republic of Congo, Ghana, Ivory Coast, Kenya, Morocco, Nigeria, Senegal South Africa, Tanzania and Tunisia). Respondents in this survey prefered the term “artificial meat”. This term was therefore used throughout the survey. “Artificial meat” proved to be fairly well known in the surveyed countries as about 64% the respondents had already heard of “artificial meat.” Only 8.9% were definitely willing to try “artificial meat” (score of 5 on a scale of 1–5) mostly males between 31 and 50 years of age. Furthermore, 31.2% strongly agreed that “artificial meat” will have a negative impact on the rural life (score of 5 on a scale of 1–5) and 32.9% were not prepared to accept “artificial meat” as a viable alternative in the future but were still prepared to eat meat alternatives. Of all the results, we observed significant differences in responses between respondents’ countries of origin, age and education level with interactions between these factors for willingness to try. For instance, the richest and most educated countries that were surveyed tended to be more willing to try “artificial meat.” A similar pattern was observed for willingness to pay, except that gender had no significant effect and age had only a small effect. One major observation is that a large majority of respondents are not willing to pay more for “artificial meat” than for meat from livestock.
Evaluating dried salted cod amino acid signature for nutritional quality assessment and discriminant analysis
Authors: Quaresma M. A. G. , Pereira G. , Nunes M. L. , Sponda C. , Jardim A. , Gonçalves H. , Santos C. , Roseiro L. C.
Published: April 2023

Aim

Thus, the aim of this study was to answer three scientific questions: (1) Are the protein content and amino acid profile of dried salted cod influenced by species (Gadus morhua and Gadus macrocephalus)? (2) Are the protein content and amino acid profile of dried salted cod influenced by the geographical area of capture (Iceland and Norway)? and (3) Does the amino acid profile have the potential to be used as a discriminator of species and geographical areas of capture?

Methods

A total of 45 dried salted cods (2–3 kg of dry weight; n = 15 samples/origin) were used in this study. The Atlantic cod was fished in the Atlantic northeast (FAO 27 area) within the Exclusive Economic zones (EEZ) of Norway (n = 15) and Iceland (n = 15), while the Pacific cod was caught in the Pacific northeast (FAO 67 area) within the Alaska EEZ (n = 15). Total protein content was determined by the Kjeldahl method, in accordance with the AOAC procedures. The amino acid profile was analyzed by HPLC with fluorescence detection (at excitation and emission wavelengths of 338 and 425 nm, respectively).

Results

The Atlantic cod presented higher contents of total protein (33.90 versus 33.10 g/100 g of cod edible portion; p = 0.017) and total amino acid contents (32.52 versus 32.04 g/100 g of cod edible portion; p = 0.015) but displayed lower percentage of indispensable amino acids (32.16 versus 32.83 g/100 g of protein; p < 0.001) than Pacific cod. Among the Atlantic cod harvesting locations, the Norwegian cod displayed higher total amino acid contents (96.91 versus 96.81 g/100 g of protein; p = 0.012) and higher percentage of indispensable amino acids (35.38 versus 28.94 g/100 g of protein; p = 0.042) than the Icelandic counterpart. A correct classification of 100% was obtained for the Pacific and Icelandic cod varieties, but the classification accuracy in the Norwegian cod was of just 86.67%, since 2 samples out of 15 were incorrectly classified as Icelandic.

Conclusion

The comparison of cod species showed that the Atlantic cod had a significantly lower EAAI than the Pacific cod (p < 0.001; 88.23 versus 88.61). On the other hand, the comparison of the two origins in the Atlantic cod, showed that Norwegian cod displayed a significantly higher EAAI than the Icelandic cod (99.15 versus 77.32). The assessment of the EAAI allows the classification of the protein’s nutritional quality, allowing us to classify both cod species as a good protein source to human diet. However, within the Atlantic cod, the Norwegian cod’s protein is classified as high quality, while the Icelandic cod attain the classification of useful quality. Regarding the amino acid profile discriminatory potential to classify cod samples. The results show that the AA profile has 100% accuracy in the separation of cod species, but was not globally efficient in the differentiation of the Norwegian from the Icelandic cod.
Emerging trends of BCG immunotherapy for bladder cancer in last decade: a bibliometric and visualization analysis
Authors: Chen Xingfeng , He Fang , Zhang Wenjin , Fu Yao , Cao Zhiqin
Published: April 2023

Background

One of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection.

Methods

We searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization.

Results

A total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years.

Conclusion

The results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.
Designing, analyzing, and interpreting observational studies of physical activity and cancer outcomes from a clinical oncology perspective
Authors: Courneya Kerry S. , Friedenreich Christine M.
Published: April 2023

Observational studies may play an important role in evaluating physical activity (PA) as a cancer treatment; however, few studies have been designed, analyzed, or interpreted from a clinical oncology perspective. The purpose of the present paper is to apply the Exercise as Cancer Treatment (EXACT) Framework to assess current observational studies of PA and cancer outcomes from a clinical oncology perspective and provide recommendations to improve their clinical utility. Recent systematic reviews and meta-analyses of over 130 observational studies have concluded that higher prediagnosis and postdiagnosis PA are associated with lower risks of cancer-specific and all-cause mortality. Most of these studies, however, have: (a) included cancer patients receiving heterogeneous treatment protocols, (b) provided minimal details about those cancer treatments, (c) assessed PA prediagnosis and/or postdiagnosis without reference to those cancer treatments, (d) reported mainly mortality outcomes, and (e) examined subgroups based on demographic and disease variables but not cancer treatments. As a result, current observational studies on PA and cancer outcomes have played a modest role in informing clinical exercise trials and clinical oncology practice. To improve their clinical utility, we recommend that future observational studies of PA and cancer outcomes: (a) recruit cancer patients receiving the same or similar first-line treatment protocols, (b) collect detailed data on all planned and unplanned cancer treatments beyond whether or not cancer treatments were received, (c) assess PA in relation to cancer treatments (i.e., before, during, between, after) rather than in relation to the cancer diagnosis (i.e., various time periods before and after diagnosis), (d) collect data on cancer-specific outcomes (e.g., disease response, progression, recurrence) in addition to mortality, (e) conduct subgroup analyses based on cancer treatments received in addition to demographic and disease variables, and (f) interpret mechanisms for any associations between PA and cancer-specific outcomes based on the clinical oncology scenario that is recapitulated rather than referencing generic mechanisms or discordant preclinical models. In conclusion, observational studies are well-suited to contribute important knowledge regarding the role of PA as a cancer treatment; however, modifications to study design and analysis are necessary if they are to inform clinical research and practice.
Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population
Authors: Zhang Ningning , Xiang Yimei , Shao Qing , Wu Jing , Liu Yumin , Long Hua , Tao Dan , Zeng Xiaohua
Published: April 2023

Purpose

The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.

Materials and methods

Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan–Meier method.

Results

In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively.

Conclusions

De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.
Therapeutic mammoplasty: a “wise” oncoplastic choice—lessons from the largest single-center cohort from Asia
Authors: Koppiker Chaitanyanand , Joshi Sneha , Mishra Rupa , Kelkar Devaki A. , Chigurupati Pragnya , Joshi Anjali , John Jisha , Kadu Shweta , Bagdia Amitkumar , Thakkar Deepti , Deshmukh Chetan , Allampati Harikiran , Sharan Gautam , Dhar Upendra , Nare Smeeta , Nagarkar Sanket , Busheri Laleh , Varghese Beenu , Pai Mugdha
Published: April 2023

Introduction

The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM.

Methods

All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures.

Results

The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1–pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains.

Conclusion

We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.
Cardiotoxicity of lung cancer-related immunotherapy versus chemotherapy: a systematic review and network meta-analysis of randomized controlled trials
Authors: Jin Chengwei , Qi Jia , Wang Qilei , Pu Chenwei , Tan Mingming
Published: April 2023

Background

Previous clinical randomized controlled trials (RCTs) have demonstrated that immune checkpoint inhibitors (ICIs) cause various toxicities during cancer treatment, but the effects of different inhibitors in combination with chemotherapy for cardiotoxicity remain controversial. The aim of the present study was to assess cardiotoxicity caused by programmed cell death protein 1 (PD-1), programmed cell death-Ligand 1 (PD-L1), and cytotoxic T lymphocyte associate protein-4 (CTLA-4) in combination with chemotherapy to treat lung cancer.

Methods

The following ICIs were included in the present study: durvalumab, avelumab, ipilimumab, atezolizumab, pembrolizumab, cemiplimab, and nivolumab. The relevant information was extracted using a predefined data extraction table, and the risk of bias was assessed in randomized controlled trials using the Cochrane Bias Risk tool. The main outcomes were hypertension, heart failure, pericardial effusion, and other adverse cardiac events. The random effects model was used to conduct a paired meta-analysis, and a random effects network meta-analysis was then performed within a Bayesian framework.

Results

In total, 17 RCTs were included in the present study. There were 11,063 individuals in the experimental and control groups, with an average age greater than 60 years. Based on the evaluation of all drug classes in RCTs, CTLA-4+chemotherapy (RR, -0.69 [95% CI, 2.91-1.52] and PD-L1 (RR, -0.21 [95% CI, -1.03-0.60]) were less cardiotoxic than the control arm, which indicated they were safer options for adverse cardiac events. PD-L1 alone was less cardiotoxic than PD-1 alone (RR, -0.57 [95% CI, -1.96-0.82]). Further, the dual immunotarget inhibitor, PD-1+CTLA-4, had the lowest SUCRA value and had the highest cardiotoxicity (SUCRA=9).

Conclusion

When classified according to drug type, CTLA-4+chemotherapy is associated with fewer cardiac adverse events compared to other treatments. Dual immunotarget inhibitors are more likely to have adverse cardiac reactions. Therefore, clinicians should consider this evidence when developing an ICI immunotherapy regimen for lung cancer.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42023360931.
Case Report: PD-L1-negative advanced bladder cancer effectively treated with anlotinib and tislelizumab: A report of two cases
Authors: Li Teng , Hu Wuyun , Jin Lan , Yin Xianghua , Kang Dongxu , Piao Longzhen
Published: April 2023

Second-line treatment for metastatic or locally advanced urothelial cancer (UC) is limited. Immunotherapy is approved as a second-line treatment for metastatic UC. Its use as a first-line agent is limited to patients who are ineligible for cisplatin-based treatments. The fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, can be applied as a third-line approach after the failure of these prior treatments in eligible patients. Therefore, it is especially important to combine limited drugs for second-line treatment of advanced or metastatic UC. Anlotinib is a multiple tyrosine kinase inhibitor agent with both anti-angiogenic and FGFR inhibitory effects. For two patients with advanced and metastatic UC, we combined anlotinib and tislelizumab therapy even though there is no indication of its use. We describe two patients with programmed death ligand-1 (PD-L1)-negative advanced bladder cancer, one with FGFR3 mutation and another with FGFR3 wild type. Both patients had progressed after first-line chemotherapy with gemcitabine and cisplatin. We selected anlotinib in combination with tislelizumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, for second-line treatment. Responses were evaluated as partial remission in both cases, who achieved up to 12 months of progression-free survival with no significant adverse events. Two patients with PD-L1-negative UC underwent second-line therapy using tislelizumab in combination with anlotinib, and the efficacy was better than that of tislelizumab alone. These results suggest that anlotinib may act synergistically with tislelizumab in the treatment of UC.
Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy
Authors: Sun Huiyan , Chen Dandan , Xin Wenjing , Ren Lixue , LI Qiang , Han Xuchen
Published: April 2023

Cardiomyopathies are a clinically heterogeneous group of cardiac diseases characterized by heart muscle damage, resulting in myocardium disorders, diminished cardiac function, heart failure, and even sudden cardiac death. The molecular mechanisms underlying the damage to cardiomyocytes remain unclear. Emerging studies have demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by iron dyshomeostasis and lipid peroxidation, contributes to the development of ischemic cardiomyopathy, diabetic cardiomyopathy, doxorubicin-induced cardiomyopathy, and septic cardiomyopathy. Numerous compounds have exerted potential therapeutic effects on cardiomyopathies by inhibiting ferroptosis. In this review, we summarize the core mechanism by which ferroptosis leads to the development of these cardiomyopathies. We emphasize the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial effects in treating cardiomyopathies. This review suggests that inhibiting ferroptosis pharmacologically may be a potential therapeutic strategy for cardiomyopathy treatment.
Energy metabolism disturbance in migraine: From a mitochondrial point of view
Authors: Wang Yicheng , Wang Yongli , Yue Guangxin , Zhao Yonglie
Published: April 2023

Migraine is a serious central nervous system disease with a high incidence rate. Its pathogenesis is very complex, which brings great difficulties for clinical treatment. Recently, many studies have revealed that mitochondrial dysfunction may play a key role in migraine, which affects the hyperosmotic of Ca2+, the excessive production of free radicals, the decrease of mitochondrial membrane potential, the imbalance of mPTP opening and closing, and the decrease of oxidative phosphorylation level, which leads to neuronal energy exhaustion and apoptosis, and finally lessens the pain threshold and migraine attack. This article mainly introduces cortical spreading depression, a pathogenesis of migraine, and then damages the related function of mitochondria, which leads to migraine. Oxidative phosphorylation and the tricarboxylic acid cycle are the main ways to provide energy for the body. 95 percent of the energy needed for cell survival is provided by the mitochondrial respiratory chain. At the same time, hypoxia can lead to cell death and migraine. The pathological opening of the mitochondrial permeability transition pore can promote the interaction between pro-apoptotic protein and mitochondrial, destroy the structure of mPTP, and further lead to cell death. The increase of mPTP permeability can promote the accumulation of reactive oxygen species, which leads to a series of changes in the expression of proteins related to energy metabolism. Both Nitric oxide and Calcitonin gene-related peptide are closely related to the attack of migraine. Recent studies have shown that changes in their contents can also affect the energy metabolism of the body, so this paper reviews the above mechanisms and discusses the mechanism of brain energy metabolism of migraine, to provide new strategies for the prevention and treatment of migraine and promote the development of individualized and accurate treatment of migraine.
A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain
Authors: Bhatt Manan , Gauthier-Manuel Laure , Lazzarin Erika , Zerlotti Rocco , Ziegler Christine , Bazzone Andre , Stockner Thomas , Bossi Elena
Published: April 2023

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). Its homeostasis is maintained by neuronal and glial GABA transporters (GATs). The four GATs identified in humans are GAT1 (SLC6A1), GAT2 (SLC6A13), GAT3 (SLC6A11), and betaine/GABA transporter-1 BGT-1 (SLC6A12) which are all members of the solute carrier 6 (SLC6) family of sodium-dependent transporters. While GAT1 has been investigated extensively, the other GABA transporters are less studied and their role in CNS is not clearly defined. Altered GABAergic neurotransmission is involved in different diseases, but the importance of the different transporters remained understudied and limits drug targeting. In this review, the well-studied GABA transporter GAT1 is compared with the less-studied BGT-1 with the aim to leverage the knowledge on GAT1 to shed new light on the open questions concerning BGT-1. The most recent knowledge on transporter structure, functions, expression, and localization is discussed along with their specific role as drug targets for neurological and neurodegenerative disorders. We review and discuss data on the binding sites for Na+, Cl−, substrates, and inhibitors by building on the recent cryo-EM structure of GAT1 to highlight specific molecular determinants of transporter functions. The role of the two proteins in GABA homeostasis is investigated by looking at the transport coupling mechanism, as well as structural and kinetic transport models. Furthermore, we review information on selective inhibitors together with the pharmacophore hypothesis of transporter substrates.