bluuebunny/crossref_metadata_2025 huggingface dataset:
Alejo Carpentier e o barroco americano
Authors: Kovalski Josoel
Published: August 2023

O escritor cubano Alejo Carpentier conseguiu, a partir de uma prática escriturária emancipatória em relação aos escritos tradicionalmente aceitos, estabelecer uma releitura da práxis americana de narrar. Esforçando-se para reinserir o insólito como evento movimentador de narrativas, debruçou-se nos acontecimentos relatados pela vivência americana, tendo como conceito operatório o real maravilhoso, termo chave na invocação de uma América barroca, um barroco espacial e telúrico, a-histórico e plural. Polígrafo, e habitante esporádico da Ilha cubana, Alejo Carpentier retoma a América Latina como um local barroquizado, de uma latência sempre apta a reafirmar os discursos da abundância que fizeram muitas vezes o continente americano ser visto como exótico e bárbaro pelo olhar europeu. Este artigo busca salientar a práxis literária de Carpentier, informando vivência artística, sobretudo a literária, a partir dos conceitos que desenvolveu para se reler a América. Sua literatura, portanto, sob o signo do real maravilhoso é um projeto barroco de leitura da maravilha americana, cuja razão de ser essencial difere dos movimentos vanguardistas que o cooptaram, mas por outro lado o fizeram, juntamente com o periodismo que marcou toda sua carreira, buscar a vertente venal barroca como expressão de uma América Latina cósmica. Procuramos tecer o principal viés de Alejo Carpentier, o barroco-maravilhoso, enfocando suas opções políticas, artísticas e literárias como procedimentos multifários de um homem ensejado por um barroco plural, telúrico, próprio.
Surgical treatment of familial adenomatous polyposis in children: cross-sectional study
Authors: Khabibullina L. R. , Razumovsky A. Yu. , Sherbakova O. V.
Published: August 2023

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by the APC gene mutation, characterized by colon adenomas and colorectal cancer, including in children. The issue of timing and indications for surgical treatment of FAP in childhood remains debatable.

AIM: to identify predictors of surgery for FAP in pediatric patients.

PATIENTS AND METHODS: a retrospective case-control study was conducted. The results of treatment of 50 children with FAP who were in the surgical department of the Russian Children's Clinical Hospital from January 2000 to April 2023 were analyzed. Two groups were formed: patients who underwent surgery of FAP under the age of 18 (case), and patients who did not undergo surgery at this age (control). We analyzed potential predictors: the age of manifestation, the clinical, the characteristics of adenomas, the anemia and family history, polyposis of the upper gastrointestinal tract.

RESULTS: in the surgical group, the proportion of patients with more than 100 adenomas was higher (23 (88%) versus 11 (45%) (p=0.002)). It was revealed that the number of adenomas was more than 100 at the time of the first colonoscopy (OR 12 (95% CI (3–80), p=0.02) and the presence of colon bleeding (OR 5.8 (95% CI 1–35, p=0 .03) are independent predictors of colproctectomy in children.

CONCLUSION: the number of adenomas over 100 and colon bleeding are independent predictors of colproctectomy in childhood.
Crohn’s disease penetrating form. Difficulties of diagnostics and preoperative planning (clinical case)
Authors: Belikovа M. Ya. , Gorshenin T. L. , Borovik I. K. , Sizov Yu.  A.
Published: August 2023

AIM: to demonstrate the difficulties of differential diagnosis of the penetrating variant of Crohn’s disease and malignant neoplasm of the intestine.

PATIENTS AND METHODS: a clinical case of a patient of an older age group with the onset of a penetrating variant of Crohn’s disease is presented.

RESULTS: according to the results of an urgent check-up on the day of admission, the patient had an abdominal mass in the right iliac region, involving the intestinal wall, anterior abdominal wall, complicated by acute intestinal obstruction. Preliminary diagnosis: colon tumor complicated by inflammation and acute intestinal obstruction. The patient’s condition and two life-threatening complications required an urgent surgical intervention — extended right-sided hemicolectomy. The primary histological examination also did not allow us to exclude the tumor nature, but a second revision of histology with immunohistochemical analysis made it possible to establish the diagnosis of Crohn’s disease.

CONCLUSION: Crohn’s disease can debut at any age, including complicated forms. This requires the inclusion of this pathology in the differential diagnosis with malignant neoplasms of the intestine, especially when the changes are located in the right iliac region. This will help to optimize the surgical approach.
Methemoglobinemia in the postoperative period against the background of taking Almagel (clinical case)
Authors: Volkov Artem V. , Polovinkin V. V.
Published: August 2023

Methemoglobinemia were recorded in two patients with intestinal paresis and gastrostasis in the early postoperative period and unauthorized intake of Almagel by patients for the relief of heartburn.

In the presented cases, drugs that can cause methemoglobinemia were used in the treatment: ropivacaine, metoclopramide, ketoprofen. Nevertheless, taking into account the pairing of the presented cases, it is impossible to exclude the effect of the drug Almagel on methemoglobin genesis.

CONCLUSION: the presented cases demonstrate manifestations of rare and poorly recognized drug methemoglobinemia, probably as a result of taking the antacid drug Almagel. Timely diagnosis and treatment of this condition ensures the rapid reversibility of a complex multifactorial biochemical process.
Early outcomes of chronic anal fissure treatment using the lateral internal sphincterotomy method without excision (randomized trial NCT05117697)
Authors: Goloktionov N. A. , Titov A. Yu. , Ponomarenko A. A. , Sagidova K. I. , Lebedeva E. Yu. , Mudrov A.  A. , Zharkov E. E.
Published: August 2023

PURPOSE OF THE STUDY: improvement of the treatment of chronic anal fissure results.

PATIENTS AND METHODS: the study included 70 patients randomized by random number generation into 2 groups: 30 patients underwent lateral internal sphincterotomy (main group, LIS), and 40 patients underwent LIS in combination with the excision of the fissure (EF) (control group, LIS + EF).

RESULTS: the pain intensity both after stool and during the daytime in the main group (LIS) has been significantly lower than in the control group (LIS + EF) (p < 0.05). The median duration of the patients’ temporary disability in the LIS group was 6 (4; 9) days, in the LIS + EF group — 17 (9; 23.5) days (p = 0.04). On day 15, the defect has epithelialized in 12/30 (40%) patients of the main group (LIS) and none (0/40) in the control group (LIS + EF) (p = 0.00001), on day 30 — in 22/30 (73.3%) and 2/40 (5%) (p = 0.00001), on day 45 — in 26/30 (87%) and 20/40 (50%) (p = 0.002), and on day 60 — in 28/30 (93.3%) and 38/40 (95%) (p = 1.0), respectively. On the day 30 after surgery, 3/30 (10%) patients of the main group and 15/40 (37.5%) of the control group had complaints regarding passing gas (p = 0.01), on day 60 — anal sphincter insufficiency (ASI) persisted in 1/30 (3%) patients in the LIS group and in 3/40 (7.5%) patients in the LIS + EF group (p = 0.63). Excision of the fissure in 5.4 (1.4–20.9) times increases the chance of developing ASI on day 30 of the postoperative period (p = 0.015) and 52 (10.2; 268.3) times increases the chance of non-healing of the defect during this period (p = 0.000002) and 6.5 (1.9; 22) times on the day 45 (p = 0.003), in comparison with the LIS only.

CONCLUSION: refusal to excise the anal fissure during its surgical treatment and perform the lateral internal sphincterotomy only can reduce the intensity of postoperative pain syndrome, the rate of postoperative complications and reduce the time of epithelialization of the anoderm defect.
Endoscopic injections of autoplasma rich in platelets in the treatment of postradiation ulcers of the rectum
Authors: Leontev Alexander V. , Grishina Elena A. , Danilov Mikhail A. , Nadina Irina V. , Shishin Kirill V.
Published: August 2023

AIM: to develop a technique and evaluate the effectiveness of endoscopic injections of autoplasma rich in platelets (PRP) in patients with post-radiation rectal ulcers.

PATIENTS AND METHODS: 41 patients with post-radiation rectal ulcer underwent endoscopic injections of APBT to epithelialize the ulcer.

RESULTS: The average number of injections for epithelialization of a post-radiation ulcer is 5. 31(75.6%) patients during the manipulation of the sermon pain syndrome, the severity of full strength on the scale of the analog-analogue scale. In 39 (95.1%) patients, complete healing of the post-radiation ulcer of the rectum was diagnosed after endoscopic injections of PRP.

CONCLUSION: PRP endoscopic injections are a technically feasible, safe and effective method in the treatment of patients with post-radiation rectal ulcers.
Characteristics of the intestinal microbiota in patients with colorectal cancer
Authors: Sukhina M. A. , Stavtsev M. H. , Achkasov S. I. , Yudin S. M.
Published: August 2023

AIM: to study the intestinal microbiota and identify its characteristic features in patients with colorectal cancer.

PATIENTS AND METHODS: in this study, the composition of the intestinal microbiota in patients with colorectal cancer was analyzed, while the comparison group consisted of patients with non-inflammatory bowel diseases.

RESULTS: previous studies have shown the possible role of enterococci and some types of clostridia in stimulating oncogenic processes and, on the contrary, the vital role of lactobacilli and bifidobacteria in intestinal homeostasis maintaining. The aim of this study was to compare the gut microbiota composition in colorectal cancer patients and non-inflammatory bowel diseases patients gut microbita. The proportion of enterococci was increased in patients with colorectal cancer (12.7% in the study group and 7.6% in the control group) on the contrary the proportion of bifidobacteria and obligate anaerobes was decreased (1.5% in the study group and 4% in the control groups) and (3.3 % of the study group and 9.7% in the control group) respectively. Decrease of the microbiota biodiversity was observed for the patients with colorectal cancer that was calculated by the Shannon diversity Index (4.46 in the study group and 4.8 in the control group), also two-fold increase of Pseudomonas aeruginosa share (2.2% in the study group and 1.1% in the control group) was found for this cohort, Clostridium septicum was isolated only from patients with colorectal cancer.

CONCLUSION: this study results suggest the diagnostic significance of the species diversity of the intestinal microbiota.
Environmental spatial mapping within equine indoor arenas
Authors: McGill Staci , Coleman Robert , Jackson Josh , Tumlin Kimberly , Stanton Victoria , Hayes Morgan
Published: August 2023

Equine indoor arenas are unique infrastructure investments found at equine farms and facilities. Environmental concerns within these facilities (temperature, respirable dust, moisture, and air movement) have been identified through surveys and small research studies. Thirty-seven indoor arenas at equine facilities within 160 km (100 miles) of Lexington, KY, were visited from August 2018 to August 2021. Semi-structured interviews were conducted to gather more information regarding the environment within the indoor arena and information about the equine facility. Site assessments were also conducted and temperatures (footing or ground level, air at 1.37 m above the footing, and roof), air speeds at 1.37 m above the footing, and light levels at 1.37 m above the footing across the indoor arena spaces were measured, in addition to the total number of horses at the facilities and daily average and maximum use of the indoor arenas. Spatial mapping was conducted using ArcMap 10.7 (Esri; Redlands, California), with kriging being used for the interpolation. The created maps were used to determine the variability of the temperatures, air speed, and lighting within the indoor arenas. These variabilities were examined for the statistical significance for variables of the indoor arenas that were determined by structural and design aspects and for facility usage information gathered from the semi-structured interviews. The variables that were statistically significant were roof ventilation for roof temperature variability, roof insulation for footing temperature variability, building enclosure for lighting variability, total number of horses at the facility for lighting variability, and total daily number of horses in the indoor arena for the ambient air temperature variability. One of the most significant results was the lack of air movement observed in the majority of the indoor arenas. Over 80% of the indoor arenas were experiencing still air speed conditions (< 0.51 m/s) during the site assessment. There is a need for more research on the environmental conditions within indoor arenas, the potential health impacts to the humans and horses in the spaces, and how design changes to the facilities could improve these environments.
Global research trends of nanotechnology for pain management
Authors: Zhu Yi , Yao Yiyi , Kuang Riyu , Chen Zheng , Du Zhen , Qu Shuangquan
Published: August 2023

Background: Nanotechnology has been increasingly used in healthcare during recent years. However, the systematic evaluation of research on nanotechnology for pain management is lacking. In this study, we employed a bibliometric approach to examine the status of the research and global trends of nanotechnology in relation to pain management.

Methods: We selected relevant papers published in the Web of Science Core Collection database between 2013 and 2022 using search terms related to nanotechnology and pain management. Subsequently, the following bibliographic information was collected: publication year, originating country/region, affiliated authors and institutions, published journal, references cited, citation frequency, and keywords. The bibliometric software programs VOSViewer and CiteSpace were employed to obtain bibliometric statistics and perform visual analysis.

Results: A total of 2680 papers were retrieved. The number of publications in the field of nanotechnology for pain management has been increasing annually since 2013. China had the highest number of published papers, whereas the United States led in total citations. The Chinese Academy of Sciences was the most prolific institution, while the Tehran University of Medical Sciences had the highest overall citations. Furthermore, De Paula was the most prolific author. Papers associated with nanotechnology for pain management were mainly published in the International Journal of Pharmaceutics, Pharmaceutics, and the International Journal of Nanomedicine. Keyword analysis showed that “in-vitro” and “drug-delivery” appeared most frequently, with the top 10 common keywords comprising nanoparticles, pain, in-vitro, drug-delivery, delivery, release, inflammation, neuropathic pain, formulation, and expression. Lastly, the latest emerging keyword was “electrochemical sensor”.

Conclusion: Research on applying nanotechnology for pain management is growing steadily. China is the top country in terms of number of publications, with institutions under the Chinese Academy of Sciences making significant contributions to this field. “In-vitro” and “drug-delivery” are the current hotspots in this area, with “electrochemical sensor” as the latest topic at the research forefront. However, national and inter-institutional collaborations should be strengthened to enable patients with pain disorders to benefit from nanotechnology implementation in pain management.
Antibacterial mechanism of areca nut essential oils against Streptococcus mutans by targeting the biofilm and the cell membrane
Authors: Liu Shuwei , Zhang Tiantian , Li Zhijin , Wang Yan , Liu Lei , Song Zhenbo
Published: August 2023

Introduction

Dental caries is one of the most common and costly biofilm-dependent oral diseases in the world. Streptococcus mutans is the major cariogenic pathogen of dental caries. S. mutans synthesizes extracellular polysaccharides by autologous glucosyltransferases, which then promotes bacterial adhesion and cariogenic biofilm formation. The S. mutans biofilm is the principal target for caries treatment. This study was designed to explore the antibacterial activity and mechanisms of areca nut essential oil (ANEO) against S. mutans.

Methods

The ANEOs were separated by negative pressure hydro-distillation. The Kirby-Bauer method and broth microdilution method were carried out to evaluate the antibacterial activity of different ANEOs. The antibacterial mechanism was revealed by crystal violet staining, XTT reduction, microbial adhesion to hydrocarbon test, extracellular polysaccharide production assay, glucosyltransferase activity assay, lactate dehydrogenase leaking, propidium iodide staining and scanning electron microscopy (SEM). The cytotoxicity of ANEOs was determine by MTT assay.

Results

The ANEOs separated at different temperatures exhibited different levels of antibacterial activity against S. mutans, and the ANEO separated at 70°C showed the most prominent bacteriostatic activity. Anti-biofilm experiments showed that the ANEOs attenuated the adhesion ability of S. mutans by decreasing the surface hydrophobicity of the bacteria, prevented S. mutans biofilm formation by inhibiting glucosyltransferase activity, reducing extracellular polysaccharide synthesis, and reducing the total biofilm biomass and activity. SEM further demonstrated the destructive effects of the ANEOs on the S. mutans biofilm. Cell membrane-related experiments indicated that the ANEOs destroyed the integrity of the cell membrane, resulting in the leakage of lactic dehydrogenase and nucleic acids. SEM imaging of S. mutans cell showed the disruption of the cellular morphology by the ANEOs. The cytotoxicity assay suggested that ANEO was non-toxic towards normal oral epithelial cells.

Discussion

This study displayed that ANEOs exerted antibacterial activity against S. mutans primarily by affecting the biofilm and disrupting the integrity of the cell membrane. ANEOs has the potential to be developed as an antibacterial agent for preventing dental caries. Additionally, a new method for the separation of essential oil components is presented.
Influence of the Yucatan earthquake event
Authors: Li Changcheng
Published: August 2023

In recent years, seismic wave effects caused by meteorite impacts have been widely observed. The meteorite impact event that occurred 66 million years ago is one of the most famous impact events in Earth’s history. The influences of the seismic wave field generated by this collision event on the solid Earth itself is worth exploring. Therefore, this study initially estimated the seismic source parameter information based on the multiring structure of the meteorite crater, and then simulates the seismic event. The results of this study provide a possible explanation for the formation of the Earth’s tectonic plates. The findings of this study suggest that the seismic wave field generated by the meteorite impact event 66 million years ago may have caused the destruction of the Solid Earth, leading to the formation of the boundary between the Indian Ocean and the Pacific Plate. Simultaneously, this study has important significance for inspiring the development of new geoscientific methods.
Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review
Authors: Xie Zeyu , Hu Jia , Gu Hangye , Li Mengting , Chen Jisheng
Published: August 2023

Purpose

This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.

Methods

Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.

Results

34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.

Conclusion

This study’s results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.
Impact of high standard farmland construction policy on chemical fertilizer reduction: a case study of China
Authors: Liu Yang , Liao Wenmei , Zhang Xu , Qiu Hailan
Published: August 2023

Promoting chemical fertilizer (CF) reduction is an inevitable requirement for achieving high-quality agricultural development, and high standard farmland construction (HSFC) provides a new path for promoting CF reduction. Takes the implementation of HSFC policy as the starting point, this paper uses the provincial panel data of China from 2005 to 2017 to analyze the impact of HSFC policy on CF reduction and its mechanism of action by using the continuous difference-in-difference (DID) model and mediating model. The baseline regression results show that implementing the HSFC policy has reduced the amount of CF per unit area by 8.9 % on average, which has a significant policy effect. The mechanism analysis shows that the HSFC policy can promote CF reduction by improving the agricultural mechanization level and expanding the scale of operations in agriculture. The results of heterogeneity analysis show that in the natural geographical location dimension, the effect of HSFC policy on CF reduction in the eastern and central regions is more obvious; In the dimension of functional areas of grain production, the impact of HSFC policy on CF reduction in major grain-producing regions is more obvious. Therefore, in the future, it is necessary to continue to vigorously promote the HSFC and give full play to the effective role of HSFC in CF reduction. China should vigorously promote the development level of agricultural mechanization and the large-scale operation of agriculture and further strengthen the HSFC in the western region and non-major grain-producing areas.
UAV-based thermography reveals spatial and temporal variability of evapotranspiration from a tropical rainforest
Authors: Bulusu Medha , Ellsäßer Florian , Stiegler Christian , Ahongshangbam Joyson , Marques Isa , Hendrayanto Hendrayanto , Röll Alexander , Hölscher Dirk
Published: August 2023

Evapotranspiration (ET) from tropical forests plays a significant role in regulating the climate system. Forests are diverse ecosystems, encompass heterogeneous site conditions and experience seasonal fluctuations of rainfall. Our objectives were to quantify ET from a tropical rainforest using high-resolution thermal images and a simple modeling framework. In lowland Sumatra, thermal infrared (TIR) images were taken from an uncrewed aerial vehicle (UAV) of upland and riparian sites during both dry and wet seasons. We predicted ET from land surface temperature data retrieved from the TIR images by applying the DATTUTDUT energy balance model. We further compared the ET estimates to ground-based sap flux measurements for selected trees and assessed the plot-level spatial and temporal variability of ET across sites and seasons. Average ET across sites and seasons was 0.48 mm h–1, which is comparable to ET from a nearby commercial oil palm plantation where this method has been validated against eddy covariance measurements. For given trees, a positive correlation was found between UAV-based ET and tree transpiration derived from ground-based sap flux measurements, thereby corroborating the observed spatial patterns. Evapotranspiration at upland sites was 11% higher than at riparian sites across all seasons. The heterogeneity of ET was lower at upland sites than at riparian sites, and increased from the dry season to the wet season. This seasonally enhanced ET variability can be an effect of local site conditions including partial flooding and diverse responses of tree species to moisture conditions. These results improve our understanding of forest-water interactions in tropical forests and can aid the further development of vegetation-atmosphere models. Further, we found that UAV-based thermography using a simple, energy balance modeling scheme is a promising method for ET assessments of natural (forest) ecosystems, notably in data scarce regions of the world.
Investigating Doxorubicin’s mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives
Authors: Huang Zhuo , Jing Huining , Lv Juanjuan , Chen Yan , Huang YuanQiong , Sun Shuwen
Published: August 2023

Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood.

Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer.

Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration.

Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin’s therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.
The influence of anti-cancer therapies on lymphocyte subpopulations of lung cancer patients
Authors: Gessner Philipp , Tessema Belay , Scholz Markus , Sack Ulrich , Boldt Andreas , Kühnapfel Andreas , Gessner Christian
Published: August 2023

Introduction

There are limited data on the influence of different anti-cancer therapies on lymphocyte subpopulations and their relationships to survival of non-small cell lung cancer (NSCLC) patients. This study aimed to assess the effect of immunotherapy, chemotherapy, immunochemotherapy, adjuvant chemotherapy after surgery, and antibodies against Vascular Endothelial Growth Factors (VEGF) on B cell, T cell, and NK cell subpopulations, and the survival time of NSCLC patients.

Methods

A total of 32 consecutive NSCLC patients were recruited at Pulmonology Clinic, Leipzig from January 2018 to March 2020 and enrolled in this study. Immunophenotyping was done using a FACS Canto II flow cytometer (BD Biosciences) before the administration of the planned therapy and during therapy with up to 7 observational windows for each patient targeting 130 immunologic parameters.

Results

Absolute transitional B cells was significantly increased after immunotherapy (p = 0.032), immunochemotherapy (p = 0.030), and antibodies against VEGF (p = 0.024). Similarly, absolute counts and percentage of B cells were significantly increased after adjuvant chemotherapy (p = 0.023). However, absolute counts and percentage of transitional B cells are significantly decreased after chemotherapy (p = 0.001). Activated cytotoxic T cells were significantly increased after immunotherapy (p = 0.031) and immunochemotherapy (p = 0.030). The overall survival rate of NSCLC patients was 31%.

Conclusions

In conclusion, this study suggests that different types of anti-cancer therapies affect lymphocyte subpopulations of NSCLC patients. Further large-scale and multicentre studies are required to confirm our results and to evaluate the prognostic value of lymphocyte subpopulations.
Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array
Authors: Kuzumi Ai , Norimatsu Yuta , Matsuda Kazuki M. , Ono Chihiro , Okumura Taishi , Kogo Emi , Goshima Naoki , Fukasawa Takemichi , Fushida Natsumi , Horii Motoki , Yamashita Takashi , Yoshizaki-Ogawa Asako , Yamaguchi Kei , Matsushita Takashi , Sato Shinichi , Yoshizaki Ayumi
Published: August 2023

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.
Unusually high clarithromycin resistance in Mycobacterium abscessus subsp. abscessus isolated from human gastric epithelium
Authors: Chouhan Deepak , Retnakumar R. J. , Devi T. Barani , Dharmaseelan Sanjai , Alexander Sneha Mary , Devadas Krishnadas , Chattopadhyay Santanu , Nair Gopinath Balakrish , Pillai Madhavan Radhakrishna
Published: August 2023

Mycobacterium abscessus subsp. abscessus is a rapidly growing facultative intracellular pathogen that usually infects human lung and skin epithelium. Recently, we and another group have shown that it also has the potential to colonize human gastric epithelium, but its significance with respect to gastric diseases remains unclear. Although Helicobacter pylori still remains the only definite gastric pathogen, recent studies have shown that M. abscessus subsp. abscessus also has the potential to colonize human gastric epithelium. M. abscessus subsp. abscessus is known to exhibit multidrug resistance and clarithromycin has been used as the drug of choice. We aimed to determine the clarithromycin resistance profile of 117 (74 rough and 43 smooth) gastric M. abscessus subsp. abscessus strains and to detect the point mutations in rrl and erm (41) genes conferring the resistance. Our data showed 79.48% (19 smooth and 74 rough) of M. abscessus subsp. abscessus strains were resistant to clarithromycin (MIC90 ≤ 512 μg/mL), while 20.51% (24 smooth) were susceptible (MIC90 ≤ 8 μg/mL). Nucleotide sequence analysis of the rrl gene with reference strains of M. abscessus subsp. abscessus did not show any mutation that is relevant to the clarithromycin resistance. However, analysis of erm (41) gene showed that M. abscessus subsp. abscessus strains, which were susceptible to clarithromycin had C, C, G, and C at their nucleotide positions 28, 159, 238, and 330, respectively, while the resistant strains showed T, T, A, and A at the same positions. Based on antibiogram and sequence analysis data we recommend further studies involving genomic analysis to identify the other genes involved in high clarithromycin resistance in gastric M. abscessus subsp. abscessus along with the mechanisms involved.
Multi-approach methods to predict cryptic carbapenem resistance mechanisms in Klebsiella pneumoniae detected in Central Italy
Authors: Cornacchia Alessandra , Janowicz Anna , Centorotola Gabriella , Saletti Maria Antonietta , Ranieri Sofia Chiatamone , Ancora Massimo , Ripà Paola , Cammà Cesare , Pomilio Francesco , Chiaverini Alexandra
Published: August 2023

The rapid emergence of carbapenem-resistant Klebsiella pneumoniae (Kp) strains in diverse environmental niches, even outside of the clinical setting, poses a challenge for the detection and the real-time monitoring of novel antimicrobial resistance trends using molecular and whole genome sequencing-based methods. The aim of our study was to understand cryptic resistance determinants responsible for the phenotypic carbapenem resistance observed in strains circulating in Italy by using a combined approach involving whole genome sequencing (WGS) and genome-wide association study (GWAS). In this study, we collected 303 Kp strains from inside and outside clinical settings between 2018–2022 in the Abruzzo region of Italy. The antimicrobial resistance profile of all isolates was assessed using both phenotypic and bioinformatic methods. We identified 11 strains resistant to carbapenems, which did not carry any known genetic determinants explaining their phenotype. The GWAS results showed that incongruent carbapenem-resistant phenotype was associated specifically with strains with two capsular types, KL13 and KL116 including genes involved in the capsule synthesis, encoding proteins involved in the assembly of the capsule biosynthesis apparatus, capsule-specific sugar synthesis, processing and export, polysaccharide pyruvyl transferase, and lipopolysaccharide biosynthesis protein. These preliminary results confirmed the potential of GWAS in identifying genetic variants present in KL13 and KL116 that could be associated with carbapenem resistance traits in Kp. The implementation of advanced methods, such as GWAS with increased antimicrobial resistance surveillance will potentially improve Kp infection treatment and patient outcomes.
Concentrate supplementation improves cold-season environmental fitness of grazing yaks: responsive changes in the rumen microbiota and metabolome
Authors: Yi Simeng , Wu Hao , Liu Yue , Dai Dongwen , Meng Qingxiang , Chai Shatuo , Liu Shujie , Zhou Zhenming
Published: August 2023

Yak (Bos grunniens) is an important economic animal species on the Qinghai-Tibet Plateau. Yaks grazed in the cold season often suffer from nutritional stress, resulting in low production performance. This situation can be improved by properly feeding the grazing yaks in the cold season; however, there is still little information about the effect of different feeding levels on the intestinal microflora and metabolites of yaks. Therefore, this study aimed to explore the effect of feeding different doses of concentrate supplements on rumen bacterial communities and metabolites in grazing yaks during the cold season. Feed concentrate supplementation significantly improved the production performance and rumen fermentation status of grazing yaks during the cold season, and switched the type of ruminal fermentation from acetic acid fermentation to propionic acid fermentation. Ruminal fermentation parameters and ruminal bacterial abundance correlated strongly. At the phylum level, the abundance of Firmicutes increased with increasing concentrate supplementation, while the opposite was true for Bacteroidota. At the genus level, the abundance of Christensenellaceae_R-7_group, NK4A214_group, Ruminococcus, norank_f__Eubacterium_coprostanoligenes_group, norank_f__norank_o__ Clostridia_UCG-014, Lachnospiraceae_NK3A20_group, Acetitomaculum, and Family_XIII_AD3011_group increased with increasing concentrate supplementation, while the abundance of Rikenellaceae_RC9_gut_ group decreased. Dietary concentrate supplementation altered the concentration and metabolic mode of metabolites in the rumen, significantly affecting the concentration of metabolites involved in amino acid and derivative metabolism (e.g., L-aspartic acid, L-glutamate, and L-histidine), purine metabolism (e.g., guanine, guanosine, and hypoxanthine), and glycerophospholipid metabolism (e.g., phosphatidate, phosphatidylcholine, and phosphocholine), and other metabolic pathways. The strong correlation between yak rumen microorganisms and metabolites provided a more comprehensive understanding of microbial community composition and function. This study showed significant changes in the composition and abundance of bacteria and metabolites in the rumen of cool season grazing yaks fed with concentrate supplements. Changes in ruminal fermentation parameters and metabolite concentration also showed a strong correlation with ruminal bacterial communities. These findings will be helpful to formulate supplementary feeding strategies for grazing yaks in the cold season from the perspective of intestinal microorganisms.
Genomic characterization of an NDM-9-producing Acinetobacter baumannii clinical isolate and role of Glu152Lys substitution in the enhanced cefiderocol hydrolysis of NDM-9
Authors: Gaillot Susie , Oueslati Saoussen , Vuillemenot Jean-Baptiste , Bour Maxime , Iorga Bogdan I. , Triponney Pauline , Plésiat Patrick , Bonnin Rémy A. , Naas Thierry , Jeannot Katy , Potron Anaïs
Published: August 2023

Here, we characterized the first French NDM-9-producing Acinetobacter baumannii isolate. A. baumannii 13A297, which belonged to the STPas25 (international clone IC7), was highly resistant to β-lactams including cefiderocol (MIC >32 mg/L). Whole genome sequencing (WGS) using both Illumina and Oxford Nanopore technologies revealed a 166-kb non-conjugative plasmid harboring a blaNDM-9 gene embedded in a Tn125 composite transposon. Complementation of E. coli DH5α and A. baumannii CIP70.10 strains with the pABEC plasmid carrying the blaNDM-1 or blaNDM-9 gene, respectively, resulted in a significant increase in cefiderocol MIC values (16 to >256-fold), particularly in the NDM-9 transformants. Interestingly, steady-state kinetic parameters, measured using purified NDM-1 and NDM-9 (Glu152Lys) enzymes, revealed that the affinity for cefiderocol was 3-fold higher for NDM-9 (Km = 53 μM) than for NDM-1 (Km = 161 μM), leading to a 2-fold increase in catalytic efficiency for NDM-9 (0.13 and 0.069 μM−1.s−1, for NDM-9 and NDM-1, respectively). Finally, we showed by molecular docking experiments that the residue 152 of NDM-like enzymes plays a key role in cefiderocol binding and resistance, by allowing a strong ionic interaction between the Lys152 residue of NDM-9 with both the Asp223 residue of NDM-9 and the carboxylate group of the R1 substituent of cefiderocol.
Optimization of a small molecule inhibitor of secondary nucleation in α-synuclein aggregation
Authors: Staats Roxine , Brotzakis Z. Faidon , Chia Sean , Horne Robert I. , Vendruscolo Michele
Published: August 2023

Parkinson’s disease is characterised by the deposition in the brain of amyloid aggregates of α-synuclein. The surfaces of these amyloid aggregates can catalyse the formation of new aggregates, giving rise to a positive feedback mechanism responsible for the rapid proliferation of α-synuclein deposits. We report a procedure to enhance the potency of a small molecule to inhibit the aggregate proliferation process using a combination of in silico and in vitro methods. The optimized small molecule shows potency already at a compound:protein stoichiometry of 1:20. These results illustrate a strategy to accelerate the optimisation of small molecules against α-synuclein aggregation by targeting secondary nucleation.
Tissue clearing applications in memory engram research
Authors: Yip Kwok Yui Tony , Gräff Johannes
Published: August 2023

A memory engram is thought to be the physical substrate of the memory trace within the brain, which is generally depicted as a neuronal ensemble activated by learning to fire together during encoding and retrieval. It has been postulated that engram cell ensembles are functionally interconnected across multiple brain regions to store a single memory as an “engram complex”, but visualizing this engram complex across the whole brain has for long been hindered by technical limitations. With the recent development of tissue clearing techniques, advanced light-sheet microscopy, and automated 3D image analysis, it has now become possible to generate a brain-wide map of engram cells and thereby to visualize the “engram complex”. In this review, we first provide a comprehensive summary of brain-wide engram mapping studies to date. We then compile a guide on implementing the optimal tissue clearing technique for engram tagging approaches, paying particular attention to visualize engram reactivation as a critical mnemonic property, for which whole-brain multiplexed immunostaining becomes a challenging prerequisite. Finally, we highlight the potential of tissue clearing to simultaneously shed light on both the circuit connectivity and molecular underpinnings of engram cells in a single snapshot. In doing so, novel brain regions and circuits can be identified for subsequent functional manipulation, thus providing an opportunity to robustly examine the “engram complex” underlying memory storage.
Effects of physical activity in child and adolescent depression and anxiety: role of inflammatory cytokines and stress-related peptide hormones
Authors: Hu Shaojuan , Li Xinyuan , Yang Luodan
Published: August 2023

Depression and anxiety are the most common mental illnesses affecting children and adolescents, significantly harming their well-being. Research has shown that regular physical activity can promote cognitive, emotional, fundamental movement skills, and motor coordination, as a preventative measure for depression while reducing the suicide rate. However, little is known about the potential role of physical activity in adolescent depression and anxiety. The studies reviewed in this paper suggest that exercise can be an effective adjunctive treatment to improve depressive and anxiety symptoms in adolescents, although research on its neurobiological effects remains limited.
PTCH1 and CTNNB1 emerge as pivotal predictors of resistance to neoadjuvant chemotherapy in ER+/HER2- breast cancer
Authors: Ozcan Gulnihal
Published: August 2023

Introduction

Endeavors in the molecular characterization of breast cancer opened the doors to endocrine therapies in ER+/HER2- breast cancer, increasing response rates substantially. Despite that, taxane-based neoadjuvant chemotherapy is still a cornerstone for achieving breast-conserving surgery and complete tumor resection in locally advanced cancers with high recurrence risk. Nonetheless, the rate of chemoresistance is high, and deselecting patients who will not benefit from chemotherapy is a significant task to prevent futile toxicities. Several multigene assays are being used to guide decisions on chemotherapy. However, their development as prognostic assays but not predictive assays limits predictive strength, leading to discordant results. Moreover, high costs impediment their use in developing countries. For global health equity, robust predictors that can be cost-effectively incorporated into routine clinical management are essential.

Methods

In this study, we comprehensively analyzed 5 GEO datasets, 2 validation sets, and The Cancer Genome Atlas breast cancer data to identify predictors of resistance to taxane-based neoadjuvant therapy in ER+/HER2- breast cancer using efficient bioinformatics algorithms.

Results

Gene expression and gene set enrichment analysis of 5 GEO datasets revealed the upregulation of 63 genes and the enrichment of CTNNB1-related oncogenic signatures in non-responsive patients. We validated the upregulation and predictive strength of 18 genes associated with resistance in the validation cohort, all exhibiting higher predictive powers for residual disease and higher specificities for ER+/HER2- breast cancers compared to one of the benchmark multi-gene assays. Cox Proportional Hazards Regression in three different treatment arms (neoadjuvant chemotherapy, endocrine therapy, and no systemic treatment) in a second comprehensive validation cohort strengthened the significance of PTCH1 and CTNNB1 as key predictors, with hazard ratios over 1.5, and 1.6 respectively in the univariate and multivariate models.

Discussion

Our results strongly suggest that PTCH1 and CTNNB1 can be used as robust and cost-effective predictors in developing countries to guide decisions on chemotherapy in ER +/HER2- breast cancer patients with a high risk of recurrence. The dual function of PTCH1 as a multidrug efflux pump and a hedgehog receptor, and the active involvement of CTNNB1 in breast cancer strongly indicate that PTCH1 and CTNNB1 can be potential drug targets to overcome chemoresistance in ER +/HER2- breast cancer patients.