bluuebunny/crossref_metadata_2025 huggingface dataset:
In sickness and in health: the dynamics of the fruit bat gut microbiota under a bacterial antigen challenge and its association with the immune response
Authors: Berman Tali S. , Weinberg Maya , Moreno Kelsey R. , Czirják Gábor Á. , Yovel Yossi
Published: April 2023

Introduction

Interactions between the gut microbiome (GM) and the immune system influence host health and fitness. However, few studies have investigated this link and GM dynamics during disease in wild species. Bats (Mammalia: Chiroptera) have an exceptional ability to cope with intracellular pathogens and a unique GM adapted to powered flight. Yet, the contribution of the GM to bat health, especially immunity, or how it is affected by disease, remains unknown.

Methods

Here, we examined the dynamics of the Egyptian fruit bats’ (Rousettus aegyptiacus) GM during health and disease. We provoked an inflammatory response in bats using lipopolysaccharides (LPS), an endotoxin of Gram-negative bacteria. We then measured the inflammatory marker haptoglobin, a major acute phase protein in bats, and analyzed the GM (anal swabs) of control and challenged bats using high-throughput 16S rRNA sequencing, before the challenge, 24h and 48h post challenge.

Results

We revealed that the antigen challenge causes a shift in the composition of the bat GM (e.g., Weissella, Escherichia, Streptococcus). This shift was significantly correlated with haptoglobin concentration, but more strongly with sampling time. Eleven bacterial sequences were correlated with haptoglobin concentration and nine were found to be potential predictors of the strength of the immune response, and implicit of infection severity, notably Weissella and Escherichia. The bat GM showed high resilience, regaining the colony’s group GM composition rapidly, as bats resumed foraging and social activities.

Conclusion

Our results demonstrate a tight link between bat immune response and changes in their GM, and emphasize the importance of integrating microbial ecology in ecoimmunological studies of wild species. The resilience of the GM may provide this species with an adaptive advantage to cope with infections and maintain colony health.
SARS-CoV-2 Spike protein alters microglial purinergic signaling
Authors: Alves Vinícius Santos , Santos Stephanie Alexia Cristina Silva , Leite-Aguiar Raíssa , Paiva-Pereira Elaine , Reis Renata Rodrigues dos , Calazans Mariana L. , Fernandes Gabriel Gripp , Antônio Leticia Silva , de Lima Emanuelle V. , Kurtenbach Eleonora , Silva Jerson Lima , Fontes-Dantas Fabricia Lima , Passos Giselle Fazzioni , Figueiredo Cláudia Pinto , Coutinho-Silva Robson , Savio Luiz Eduardo Baggio
Published: April 2023

Despite long-term sequelae of COVID-19 are emerging as a substantial public health concern, the mechanism underlying these processes still unclear. Evidence demonstrates that SARS-CoV-2 Spike protein can reach different brain regions, irrespective of viral brain replication resulting in activation of pattern recognition receptors (PRRs) and neuroinflammation. Considering that microglia dysfunction, which is regulated by a whole array of purinergic receptors, may be a central event in COVID-19 neuropathology, we investigated the impact of SARS-CoV-2 Spike protein on microglial purinergic signaling. Here, we demonstrate that cultured microglial cells (BV2 line) exposed to Spike protein induce ATP secretion and upregulation of P2Y6, P2Y12, NTPDase2 and NTPDase3 transcripts. Also, immunocytochemistry analysis shows that spike protein increases the expression of P2X7, P2Y1, P2Y6, and P2Y12 in BV2 cells. Additional, hippocampal tissue of Spike infused animals (6,5ug/site, i.c.v.) presents increased mRNA levels of P2X7, P2Y1, P2Y6, P2Y12, NTPDase1, and NTPDase2. Immunohistochemistry experiments confirmed high expression of the P2X7 receptor in microglial cells in CA3/DG hippocampal regions after spike infusion. These findings suggest that SARS-CoV-2 Spike protein modulates microglial purinergic signaling and opens new avenues for investigating the potential of purinergic receptors to mitigate COVID-19 consequences.
Camrelizumab plus platinum-irinotecan followed by maintenance camrelizumab plus apatinib in untreated extensive-stage small-cell lung cancer: a nonrandomized clinical trial
Authors: Ni Jun , Si Xiaoyan , Wang Hanping , Zhang Xiaotong , Zhang Li
Published: April 2023

Background

Programmed cell death-ligand 1 (PD-L1) inhibitors plus chemotherapy have made substantial progress in extensive-stage small-cell lung cancer (ES-SCLC), but the survival benefit is still limited. This study aimed to evaluate the preliminary efficacy and safety of camrelizumab plus platinum-irinotecan (IP/IC) followed by maintenance camrelizumab plus apatinib in patients with untreated ES-SCLC.

Methods

In this non-randomized clinical trial (NCT04453930), eligible patients with untreated ES-SCLC received 4-6 cycles of camrelizumab plus IP/IC, followed by maintenance with camrelizumab plus apatinib until disease progression or unmanageable toxicity. The primary endpoint was progression-free survival (PFS). Patients who received PD-L1 inhibitors (atezolizumab or durvalumab) plus platinum-etoposide (EP/EC) were selected as the historical control.

Results

Nineteen patients received IP/IC plus camrelizumab and 34 patients received EP/EC plus PD-L1 inhibitor. At a median follow-up time of 12.1 months, the median PFS was 10.25 months (95% CI: 9.40-NA) in the IP/IC plus camrelizumab group and 7.10 months (95% CI 5.79-8.40) in the EP/EC plus PD-L1 inhibitor group, respectively (HR=0.58, 95% CI 0.42-0.81). The objective response rate of IP/IC plus camrelizumab and EP/EC plus PD-L1 inhibitor was 89.6% and 82.4%, respectively. The most common treatment-related adverse events in the IP/IC plus camrelizumab group was neutropenia, followed by reactive cutaneous capillary endothelial proliferation (RCCEP) and diarrhea. The occurrence of immune-related adverse event was found to be associated with a prolonged PFS (HR=4.64, 95% CI 1.92-11.18).

Conclusions

IP/IC plus camrelizumab followed by maintenance camrelizumab plus apatinib showed preliminary efficacy and acceptable safety profile in patients with untreated ES-SCLC.
Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease
Authors: Lenti Marco Vincenzo , Scribano Maria Lia , Biancone Livia , Ciccocioppo Rachele , Pugliese Daniela , Pastorelli Luca , Fiorino Gionata , Savarino Edoardo , Caprioli Flavio Andrea , Ardizzone Sandro , Fantini Massimo Claudio , Tontini Gian Eugenio , Orlando Ambrogio , Sampietro Gianluca Matteo , Sturniolo Giacomo Carlo , Monteleone Giovanni , Vecchi Maurizio , Kohn Anna , Daperno Marco , D’Incà Renata , Corazza Gino Roberto , Di Sabatino Antonio
Published: April 2023

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.
Post-LASIK dry eye disease: A comprehensive review of management and current treatment options
Authors: Tamimi Atena , Sheikhzadeh Farzad , Ezabadi Sajjad Ghane , Islampanah Muhammad , Parhiz Peyman , Fathabadi Amirhossein , Poudineh Mohadeseh , Khanjani Zahra , Pourmontaseri Hossein , Orandi Shirin , Mehrabani Reyhaneh , Rahmanian Mohammad , Deravi Niloofar
Published: April 2023

Laser-assisted in situ keratomileusis (LASIK) is a unique corneal stromal laser ablation method that uses an excimer laser to reach beneath corneal dome-shaped tissues. In contrast, surface ablation methods, such as photorefractive keratectomy, include removing epithelium and cutting off the Bowman’s layer and the stromal tissue of the anterior corneal surface. Dry eye disease (DED) is the most common complication after LASIK. DED is a typical multi-factor disorder of the tear function and ocular surface that occurs when the eyes fail to produce efficient or adequate volumes of tears to moisturize the eyes. DED influences quality of life and visual perception, as symptoms often interfere with daily activities such as reading, writing, or using video display monitors. Generally, DED brings about discomfort, symptoms of visual disturbance, focal or global tear film instability with possible harm to the ocular surface, the increased osmolarity of the tear film, and subacute inflammation of the ocular surface. Almost all patients develop a degree of dryness in the postoperative period. Detection of preoperative DED and committed examination and treatment in the preoperative period, and continuing treatments postoperatively lead to rapid healing, fewer complications, and improved visual outcomes. To improve patient comfort and surgical outcomes, early treatment is required. Therefore, in this study, we aim to comprehensively review studies on the management and current treatment options for post-LASIK DED.
Streptomyces RNases – Function and impact on antibiotic synthesis
Authors: Jones George H.
Published: April 2023

Streptomyces are soil dwelling bacteria that are notable for their ability to sporulate and to produce antibiotics and other secondary metabolites. Antibiotic biosynthesis is controlled by a variety of complex regulatory networks, involving activators, repressors, signaling molecules and other regulatory elements. One group of enzymes that affects antibiotic synthesis in Streptomyces is the ribonucleases. In this review, the function of five ribonucleases, RNase E, RNase J, polynucleotide phosphorylase, RNase III and oligoribonuclease, and their impact on antibiotic production will be discussed. Mechanisms for the effects of RNase action on antibiotic synthesis are proposed.
Facilitative interaction networks in experimental microbial community dynamics
Authors: Fujita Hiroaki , Ushio Masayuki , Suzuki Kenta , Abe Masato S. , Yamamichi Masato , Okazaki Yusuke , Canarini Alberto , Hayashi Ibuki , Fukushima Keitaro , Fukuda Shinji , Kiers E. Toby , Toju Hirokazu
Published: April 2023

Facilitative interactions between microbial species are ubiquitous in various types of ecosystems on the Earth. Therefore, inferring how entangled webs of interspecific interactions shift through time in microbial ecosystems is an essential step for understanding ecological processes driving microbiome dynamics. By compiling shotgun metagenomic sequencing data of an experimental microbial community, we examined how the architectural features of facilitative interaction networks could change through time. A metabolic modeling approach for estimating dependence between microbial genomes (species) allowed us to infer the network structure of potential facilitative interactions at 13 time points through the 110-day monitoring of experimental microbiomes. We then found that positive feedback loops, which were theoretically predicted to promote cascade breakdown of ecological communities, existed within the inferred networks of metabolic interactions prior to the drastic community-compositional shift observed in the microbiome time-series. We further applied “directed-graph” analyses to pinpoint potential keystone species located at the “upper stream” positions of such feedback loops. These analyses on facilitative interactions will help us understand key mechanisms causing catastrophic shifts in microbial community structure.
Concept development of a mainstream deammonification and comparison with conventional process in terms of energy, performance and economical construction perspectives
Authors: Cheenakula Dheeraja , Griebel Kai , Montag David , Grömping Markus
Published: April 2023

Deammonification for nitrogen removal in municipal wastewater in temperate and cold climate zones is currently limited to the side stream of municipal wastewater treatment plants (MWWTP). This study developed a conceptual model of a mainstream deammonification plant, designed for 30,000 P.E., considering possible solutions corresponding to the challenging mainstream conditions in Germany. In addition, the energy-saving potential, nitrogen elimination performance and construction-related costs of mainstream deammonification were compared to a conventional plant model, having a single-stage activated sludge process with upstream denitrification. The results revealed that an additional treatment step by combining chemical precipitation and ultra-fine screening is advantageous prior the mainstream deammonification. Hereby chemical oxygen demand (COD) can be reduced by 80% so that the COD:N ratio can be reduced from 12 to 2.5. Laboratory experiments testing mainstream conditions of temperature (8–20°C), pH (6–9) and COD:N ratio (1–6) showed an achievable volumetric nitrogen removal rate (VNRR) of at least 50 gN/(m3∙d) for various deammonifying sludges from side stream deammonification systems in the state of North Rhine-Westphalia, Germany, where m3 denotes reactor volume. Assuming a retained Norganic content of 0.0035 kgNorg./(P.E.∙d) from the daily loads of N at carbon removal stage and a VNRR of 50 gN/(m3∙d) under mainstream conditions, a resident-specific reactor volume of 0.115 m3/(P.E.) is required for mainstream deammonification. This is in the same order of magnitude as the conventional activated sludge process, i.e., 0.173 m3/(P.E.) for an MWWTP of size class of 4. The conventional plant model yielded a total specific electricity demand of 35 kWh/(P.E.∙a) for the operation of the whole MWWTP and an energy recovery potential of 15.8 kWh/(P.E.∙a) through anaerobic digestion. In contrast, the developed mainstream deammonification model plant would require only a 21.5 kWh/(P.E.∙a) energy demand and result in 24 kWh/(P.E.∙a) energy recovery potential, enabling the mainstream deammonification model plant to be self-sufficient. The retrofitting costs for the implementation of mainstream deammonification in existing conventional MWWTPs are nearly negligible as the existing units like activated sludge reactors, aerators and monitoring technology are reusable. However, the mainstream deammonification must meet the performance requirement of VNRR of about 50 gN/(m3∙d) in this case.
Qihuang needle therapy in senile cervical spondylotic radiculopathy
Authors: Yang Juan , Huang Hongfang , Shi Jinshan , He Cheng , Zhang Kun , Chen Zhenhu , Zeng Rui , Liu Jia
Published: April 2023

Background

Neurogenic cervical spondylosis [cervical spondylotic radiculopathy (CSR)] accounts for ~50–60% of all types of cervical spondylosis, and its incidence is the highest among all types of cervical spondylosis.

Objective

The present study aimed to investigate the clinical efficacy of the Qihuang needle in the treatment of senile cervical radiculopathy.

Methods

A total of 55 elderly patients with neurogenic cervical spondylosis were randomly divided into the general acupuncture group (27 cases) and the Qihuang acupuncture group (28 cases). The treatment given to these patients lasted for three sessions. The VAS scores and the Tanaka Yasuhisa Scale scores were compared before the treatment, after the first treatment, after the first session, and at the end of the session.

Results

The basic data of the two groups before the treatment showed no difference. The VAS scores in the mackerel acupuncture group decreased significantly, whereas in the Tanaka Kangjiu Scale scores, the efficiency rates of the first and second courses of treatment increased significantly.

Conclusion

The Qihuang needle therapy is recommended for the treatment of cervical spondylosis of the nerve root type. The said therapy is characterized by selection of fewer acupoints, a quick operation time, and no needle retention.
Case report: Cortico-ocular interaction networks in NBA2K
Authors: Stamatis Andreas , Garcia-Retortillo Sergi , Morgan Grant B. , Sanchez-Moreno Ana
Published: April 2023

The sport industry has never seen growth such as eSports’. Using synchronized monitoring of two biological processes on a 25-year-old gamer, we investigated how his brain (via EEG) and eyes (via pupil dilation) interacted dynamically over time as an integrated network during NBA2K playing time. After the spectral decomposition of the different Brain and Eye signals into seven frequency bands, we calculated the bivariate equal-time Pearson’s cross-correlation between each pair of EEG/Eye spectral power time series. On average, our results show a reorganization of the cortico-muscular network across three sessions (e.g., new interactions, hemispheric asymmetry). These preliminary findings highlight the potential need for individualized, specific, adaptive, and periodized interventions and encourage the continuation of this line of research for the creation of general theories of networks in eSports gaming. Future studies should recruit larger samples, investigate different games, and explore cross-frequency coordination among other key organ systems.
High prevalence of abdominal aortic aneurysm in older men with cerebrovascular disease: Evaluation of a local screening program
Authors: Loban M. , Gratama J. W. C. , Klemm P. L. , Van Leeuwen Roeland B. , Vriesema H. , Bienfait Henri Paul
Published: April 2023

Introduction

Patients with cerebrovascular disease may suffer from other vascular morbidities, such as abdominal aortic aneurysm (AAA). Previously, a high prevalence of AAA has been demonstrated in men 60 years of age and older who have experienced TIA or stroke. This report evaluates the results of a decade's operation of a local screening program for AAA in this selected neurologic population.

Methods

Men aged ≥60 years and admitted to the neurology ward of a community-based hospital in the Netherlands from 2006 to 2017 with a diagnosis of TIA or stroke were selected for screening. The diameter of the abdominal aorta was assessed by abdominal ultrasonography. Patients with detected AAA were referred for evaluation by a vascular surgeon.

Results

AAA was detected in 72 of 1,035 screened patients (6.9%). AAAs with a diameter of 3.0–3.9 cm accounted for 61.1% of the total aneurysms found; AAAs with a diameter of 4.0–5.4 cm accounted for 20.8% of the total; and large aneurysms with a diameter of ≥5.5 cm accounted for 18.1% of all aneurysms discovered. A total of 18 patients (1.7%) underwent elective aneurysm repair.

Discussion

The detection rate of AAA in older men with cerebrovascular disease was roughly 5-fold the detection rate in known European screening programs in older men from the general population. The proportion of large AAAs (≥5.5 cm) was also substantially higher. These findings reveal a previously unknown co-morbidity in patients with cerebrovascular disease and may be helpful for cardiovascular management of this large group of neurologic patients. Current and future AAA screening programs may also benefit from this knowledge.
LiNbO3 dynamic memristors for reservoir computing
Authors: Zhao Yuanxi , Duan Wenrui , Wang Chen , Xiao Shanpeng , Li Yuan , Li Yizheng , An Junwei , Li Huanglong
Published: April 2023

Information in conventional digital computing platforms is encoded in the steady states of transistors and processed in a quasi-static way. Memristors are a class of emerging devices that naturally embody dynamics through their internal electrophyiscal processes, enabling nonconventional computing paradigms with enhanced capability and energy efficiency, such as reservoir computing. Here, we report on a dynamic memristor based on LiNbO3. The device has nonlinear I-V characteristics and exhibits short-term memory, suitable for application in reservoir computing. By time multiplexing, a single device can serve as a reservoir with rich dynamics which used to require a large number of interconnected nodes. The collective states of five memristors after the application of trains of pulses to the respective memristors are unique for each combination of pulse patterns, which is suitable for sequence data classification, as demonstrated in a 5 × 4 digit image recognition task. This work broadens the spectrum of memristive materials for neuromorphic computing.
Pathogenesis of cerebral amyloid angiopathy caused by chaotic glymphatics—Mini-review
Authors: Lui Forshing , Alcaide Jessa , Knowlton Stella , Ysit Michael , Zhong Ning
Published: April 2023

Cerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage in the elderly. It is also associated pathologically with Alzheimer’s disease (AD). Both CAA and AD share similar pathology of deposition amyloid beta fibrils (Aβ). Aβ is deposited mainly in the neurites in AD and vascular walls in CAA. Aβ is formed inside the brain parenchyma from the amyloid precursor protein. It is easier to understand how Aβ is deposited in the cerebral neurites in AD. However, the pathogenesis of CAA is still largely unknown. It is difficult to understand or visualize how Aβ fibrils formed inside the brain can be deposited against the cerebral perfusion pressure to be deposited in the cerebral and meningeal arterial walls. We encountered an unusual clinical case of acute aneurysmal subarachnoid hemorrhage which was followed after a few years with localized CAA involving mainly the sites of the subarachnoid hemorrhage. We reviewed the formation of Aβ and postulated how the Aβ fibrils are transported retrogradely toward the cerebral arteries and deposited in the arterial walls resulting in the final pathology of CAA. There is a clear disturbance of the glymphatic system, the aquaporin-4 channel, and the parenchymal border macrophages.
Engaging distributed cortical and cerebellar networks through motor execution, observation, and imagery
Authors: Henschke Julia U. , Pakan Janelle M. P.
Published: April 2023

When we interact with the environment around us, we are sometimes active participants, making directed physical motor movements and other times only mentally engaging with our environment, taking in sensory information and internally planning our next move without directed physical movement. Traditionally, cortical motor regions and key subcortical structures such as the cerebellum have been tightly linked to motor initiation, coordination, and directed motor behavior. However, recent neuroimaging studies have noted the activation of the cerebellum and wider cortical networks specifically during various forms of motor processing, including the observations of actions and mental rehearsal of movements through motor imagery. This phenomenon of cognitive engagement of traditional motor networks raises the question of how these brain regions are involved in the initiation of movement without physical motor output. Here, we will review evidence for distributed brain network activation during motor execution, observation, and imagery in human neuroimaging studies as well as the potential for cerebellar involvement specifically in motor-related cognition. Converging evidence suggests that a common global brain network is involved in both movement execution and motor observation or imagery, with specific task-dependent shifts in these global activation patterns. We will further discuss underlying cross-species anatomical support for these cognitive motor-related functions as well as the role of cerebrocerebellar communication during action observation and motor imagery.
Associations between adherence to MIND diet and general obesity and lipid profile: A cross-sectional study
Authors: Fateh Hawal Lateef , Muhammad Sarmad S. , Kamari Negin
Published: April 2023

Background

The term “Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)” has recently been coined to describe a new eating pattern. Recent research is looking at how this food pattern affects chronic illnesses. Thus, this study aimed to investigate the association between the use and adherence to the MIND diet with general obesity and blood lipid profile.

Methods

In this cross-sectional study, 1,328 Kurdish adults between the ages of 39 and 53 had their dietary intake evaluated using a valid and reliable 168-item Food Frequency Questionnaire (FFQ). Adherence to the MIND diet was examined based on the components advised in this eating pattern. Each subject’s lipid profiles and anthropometric measurements were documented.

Results

The mean age and BMI in the study population were 46.16 ± 7.87 year and 27.19 ± 4.60 kg/m2, respectively. The chances of having increased serum triglycerides (TG) were 42% lower in those in the third tertile of the MIND diet score compared to those in the first tertile (ORs: 0.58; 95% CI 0.38−0.95; P = 0.001). In the crude model and after adjusting for confounders, lowering high-density lipoprotein cholesterol (HDL-C) (ORs: 0.72; 95% CI 0.55−1.15; P = 0.001).

Conclusion

We found that greater adherence to the MIND diet was associated with the decrease odds of general obesity and lipid profile. Further study is essential owing to the relevance of chronic diseases like MetS and obesity in health status.
Case report: anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma with high level of microsatellite instability response to pembrolizumab
Authors: Shigeta Naoko , Murakami Shuji , Yokose Tomoyuki , Miyagi Yohei , Saito Haruhiro
Published: April 2023

The presence of anaplastic lymphoma kinase (ALK) rearrangement is reported to be related to the lack of efficacy of immune checkpoint inhibitors (ICIs). High levels of microsatellite instability (MSI-high) are important biomarkers of ICIs, particularly in colorectal cancer. The therapeutic effect of ICIs for MSI-high NSCLC is uncertain because of the rarity of these tumors. Here we report a case of ALK rearranged NSCLC with MSI-high. A 48-year-old male was diagnosed with lung adenocarcinoma, cT4N3M1a, stage IVA with ALK rearrangement, high PD-L1 expression with a tumor proportion score (TPS) of 100%, and MSI-high. The patient was treated with alectinib as the first-line therapy but progressed at five months with left atrial invasion re-expansion. The patient discontinued alectinib and was switched to pembrolizumab monotherapy. After two months, left atrial invasion significantly decreased. The patient continued pembrolizumab for a year without noticeable adverse events, and tumor shrinkage persisted. This case supports the efficacy of ICIs for MSI-high NSCLC, even in the presence of ALK rearrangement.
Research trends in endoscopic applications in early gastric cancer: A bibliometric analysis of studies published from 2012 to 2022
Authors: Liu Yuan , Wen Haolang , Wang Qiao , Du Shiyu
Published: April 2023

Background

Endoscopy is the optimal method of diagnosing and treating early gastric cancer (EGC), and it is therefore important to keep up with the rapid development of endoscopic applications in EGC. This study utilized bibliometric analysis to describe the development, current research progress, hotspots, and emerging trends in this field.

Methods

We retrieved publications about endoscopic applications in EGC from 2012 to 2022 from Web of Science™ (Clarivate™, Philadelphia, PA, USA) Core Collection (WoSCC). We mainly used CiteSpace (version 6.1.R3) and VOSviewer (version 1.6.18) to perform the collaboration network analysis, co-cited analysis, co-occurrence analysis, cluster analysis, and burst detection.

Results

A total of 1,333 publications were included. Overall, both the number of publications and the average number of citations per document per year increased annually. Among the 52 countries/regions that were included, Japan contributed the most in terms of publications, citations, and H-index, followed by the Republic of Korea and China. The National Cancer Center, based in both Japan and the Republic of Korea, ranked first among institutions in terms of number of publications, citation impact, and the average number of citations. Yong Chan Lee was the most productive author, and Ichiro Oda had the highest citation impact. In terms of cited authors, Gotoda Takuji had both the highest citation impact and the highest centrality. Among journals, Surgical Endoscopy and Other Interventional Techniques had the most publications, and Gastric Cancer had the highest citation impact and H-index. Among all publications and cited references, a paper by Smyth E C et al., followed by one by Gotoda T et al., had the highest citation impact. Using keywords co-occurrence and cluster analysis, 1,652 author keywords were categorized into 26 clusters, and we then divided the clusters into six groups. The largest and newest clusters were endoscopic submucosal dissection and artificial intelligence (AI), respectively.

Conclusions

Over the last decade, research into endoscopic applications in EGC has gradually increased. Japan and the Republic of Korea have contributed the most, but research in this field in China, from an initially low base, is developing at a striking speed. However, a lack of collaboration among countries, institutions, and authors, is common, and this should be addressed in future. The main focus of research in this field (i.e., the largest cluster) is endoscopic submucosal dissection, and the topic at the frontier (i.e., the newest cluster) is AI. Future research should focus on the application of AI in endoscopy, and its implications for the clinical diagnosis and treatment of EGC.
Clinically relevant glioblastoma patient-derived xenograft models to guide drug development and identify molecular signatures
Authors: Alcaniz Joshua , Winkler Lars , Dahlmann Mathias , Becker Michael , Orthmann Andrea , Haybaeck Johannes , Krassnig Stefanie , Skofler Christina , Kratzsch Tobias , Kuhn Susanne A. , Jödicke Andreas , Linnebacher Michael , Fichtner Iduna , Walther Wolfgang , Hoffmann Jens
Published: April 2023

Glioblastoma (GBM) heterogeneity, aggressiveness and infiltrative growth drastically limit success of current standard of care drugs and efficacy of various new therapeutic approaches. There is a need for new therapies and models reflecting the complex biology of these tumors to analyze the molecular mechanisms of tumor formation and resistance, as well as to identify new therapeutic targets. We established and screened a panel of 26 patient-derived subcutaneous (s.c.) xenograft (PDX) GBM models on immunodeficient mice, of which 15 were also established as orthotopic models. Sensitivity toward a drug panel, selected for their different modes of action, was determined. Best treatment responses were observed for standard of care temozolomide, irinotecan and bevacizumab. Matching orthotopic models frequently show reduced sensitivity, as the blood-brain barrier limits crossing of the drugs to the GBM. Molecular characterization of 23 PDX identified all of them as IDH-wt (R132) with frequent mutations in EGFR, TP53, FAT1, and within the PI3K/Akt/mTOR pathway. Their expression profiles resemble proposed molecular GBM subtypes mesenchymal, proneural and classical, with pronounced clustering for gene sets related to angiogenesis and MAPK signaling. Subsequent gene set enrichment analysis identified hallmark gene sets of hypoxia and mTORC1 signaling as enriched in temozolomide resistant PDX. In models sensitive for mTOR inhibitor everolimus, hypoxia-related gene sets reactive oxygen species pathway and angiogenesis were enriched. Our results highlight how our platform of s.c. GBM PDX can reflect the complex, heterogeneous biology of GBM. Combined with transcriptome analyses, it is a valuable tool in identification of molecular signatures correlating with monitored responses. Available matching orthotopic PDX models can be used to assess the impact of the tumor microenvironment and blood-brain barrier on efficacy. Our GBM PDX panel therefore represents a valuable platform for screening regarding molecular markers and pharmacologically active drugs, as well as optimizing delivery of active drugs to the tumor.
The trend of opioid prescriptions among cancer patients in a tertiary hospital: A multimethod quantitative study
Authors: Limsomwong Pawita , Ingviya Thammasin , Fumaneeshoat Orapan
Published: April 2023

Introduction

Pain is a major symptom in cancer patients. World Health Organization recommends opioids as the main analgesic agent. Few studies have examined the amount of opioid uses in cancer patients in Southeast Asia, however, none of them have examined the factors associated with the amount of opioid uses which were lower than required.

Objectives

To assess the trends and factors associated with opioid prescriptions for cancer patients in Songklanagarind Hospital, the largest referral center in Southern Thailand.

Design

Multi-method quantitative study.

Methods

We reviewed the electronic medical records of 20,192, outpatients aged ≥18 years diagnosed with cancer between 2016 and 2020 who received opiod prescriptions. Oral morphine equivalents (OME) were calculated using the standard conversion factors and the OME trend during the study period was assessed by a generalized additive model. Factors affecting the morphine equivalent daily dose (MEDD) were assessed using multiple linear regression with a generalized estimating equation.

Results

The mean overall MEDD for all study patients was 27.8 ± 21.9 mg per day per patient. The bone and articular cartilage cancer patients had the highest MEDD. For every 5-year increase in the duration of cancer, the MEDD increased by 0.02 (95% confidence interval [CI]: 0.01 - 0.04). Patients with stage 4 cancer received a higher average MEDD of 4.04 (95% CI: 0.30-7.62) as compared to those with stage 1 cancer. Patients with bone metastasis received a average higher MEDD of 4.03 (95% CI: 0.82-7.19) compared to those without. Age was inversely associated with the MEDD. Patients aged 42-58, 59-75 and >76years old received MEDDs of 4.73 (95% CI: 2.31-7.15), 6.12 (95% CI: 3.66-8.59) and 8.59 (95% CI: 6.09-11.09) compared with those aged 18-42 years old. Brain metastasis was inversely associated with MEDD of 4.49 (95% CI: 0.61-8.37) compared to those without.

Conclusion

Opioid use in cancer patients in this study is lower than the average global usage. Promoting opioid prescriptions for pain management through medical education can help doctors overcome opiophobia.
Predictive value of a nomogram model for adverse outcomes in very low birth weight infants with patent ductus arteriosus: A prospective study
Authors: Sun Xuan , Chen Ling , Gao Jinzhi
Published: April 2023

Objective

To establish a nomogram model incorporating markers of echocardiography and N-terminal pro brain natriuretic peptide (NT-proBNP) for predicting adverse outcomes of patent ductus arteriosus (PDAao) in very low birth weight infants and to evaluate the predictive values of the model.

Methods

A prospective study was conducted for very low birth weight infants who were admitted from May 2019 to September 2020. An echocardiogram and blood NT-proBNP test were carried out in the first 48 h after birth, and the arterial duct remained open in all patients. Other data collected included clinical symptoms and infant characteristics. A nomogram model was established to predict the risk of PDAao (including severe BPD, IVH, NEC or death). Internal verifications were performed for the nomogram, and the discrimination and calibration of the model were evaluated by the C-index and calibration curve.

Results

Eighty-two infants were enrolled and divided into an adverse outcome (AO) group and normal outcome (NO) group with 41 patients in each group. PDA diameter, PDA maximum flow velocity, left atrium diameter/aortic diameter (LA/AO) ratio and NT-proBNP level were independent risk factors for PDAao and were included in the nomogram model. The model presented good discrimination with a C-index of 0.917 (95% CI 0.859–0.975). The calibration curves in showed high consistency and indicated good Correspondence: between the event incidence predicted by the nomogram model and the true incidence of PDAao.

Conclusion

The nomogram model incorporating the PDA diameter, PDA maximum flow velocity, LA/AO ratio and NT-proBNP level in the first 48 h could early predict the later occurrence of PDAao in very low birth weight infants.
Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports
Authors: Sedlin E. , Lau S. , von Bernuth H. , Kallinich T. , Mayer B.
Published: April 2023

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient’s blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available.
Trajectory of hearing loss in children with unilateral hearing loss
Authors: Fitzpatrick Elizabeth M. , Nassrallah Flora , Gaboury Isabelle , Whittingham JoAnne , Vos Bénédicte , Coyle Doug , Durieux-Smith Andrée , Pigeon Marie , Olds Janet
Published: April 2023

Introduction

The aim of this study was to quantify the amount of deterioration in hearing and to document the trajectory of hearing loss in early identified children with unilateral hearing loss (UHL). We also examined whether clinical characteristics were associated with the likelihood of having progressive hearing loss.

Methods

As part of the Mild and Unilateral Hearing Loss Study, we followed a population-based cohort of 177 children diagnosed with UHL from 2003 to 2018. We applied linear mixed models to examine hearing trends over time including the average amount of change in hearing. Logistic regression models were used to examine the relationship between age and severity at diagnosis, etiology, and the likelihood of progressive loss and amount of deterioration in hearing.

Results

The median age of the children at diagnosis was 4.1 months (IQR 2.1, 53.9) and follow-up time was 58.9 months (35.6, 92.0). Average hearing loss in the impaired ear was 58.8 dB HL (SD 28.5). Over the 16-year period, 47.5% (84/177) of children showed deterioration in hearing in one or both ears from their initial diagnostic assessment to most recent assessment including 21 (11.9%) who developed bilateral hearing loss. Average deterioration in the impaired ear ranged from 27 to 31 dB with little variation across frequencies. Deterioration resulted in a change in category of severity for 67.5% (52/77) of the children. Analysis for children who were followed for at least 8 years showed that most lost a significant amount of hearing rapidly in the first 4 years, with the decrease stabilizing and showing a plateau in the last 4 years. Age and severity at diagnosis were not significantly associated with progressive/stable loss after adjusting for time since diagnosis. Etiologic factors (ENT external/middle ear anomalies, inner ear anomalies, syndromic hearing loss, hereditary/genetic) were found to be positively associated with stable hearing loss.

Conclusion

Almost half of children with UHL are at risk for deterioration in hearing in one or both ears. Most deterioration occurs within the first 4 years following diagnosis. Most children did not experience sudden “large” drops in hearing but more gradual decrease over time. These results suggest that careful monitoring of UHL especially in the early years is important to ensure optimal benefit from early hearing loss detection.
Biomarkers of post-match recovery in semi-professional and professional football (soccer)
Authors: Pérez-Castillo Íñigo M. , Rueda Ricardo , Bouzamondo Hakim , López-Chicharro José , Mihic Niko
Published: April 2023

High-level football (soccer) players face intense physical demands that result in acute and residual fatigue, impairing their physical performance in subsequent matches. Further, top-class players are frequently exposed to match-congested periods where sufficient recovery times are not achievable. To evaluate training and recovery strategies, the monitoring of players’ recovery profiles is crucial. Along with performance and neuro-mechanical impairments, match-induced fatigue causes metabolic disturbances denoted by changes in chemical analytes that can be quantified in different body fluids such as blood, saliva, and urine, thus acting as biomarkers. The monitoring of these molecules might supplement performance, neuromuscular and cognitive measurements to guide coaches and trainers during the recovery period. The present narrative review aims to comprehensively review the scientific literature on biomarkers of post-match recovery in semi-professional and professional football players as well as provide an outlook on the role that metabolomic studies might play in this field of research. Overall, no single gold-standard biomarker of match-induced fatigue exists, and a range of metabolites are available to assess different aspects of post-match recovery. The use of biomarker panels might be suitable to simultaneously monitoring these broad physiological processes, yet further research on fluctuations of different analytes throughout post-match recovery is warranted. Although important efforts have been made to address the high interindividual heterogeneity of available markers, limitations inherent to these markers might compromise the information they provide to guide recovery protocols. Further research on metabolomics might benefit from evaluating the long-term recovery period from a high-level football match to shed light upon new biomarkers of post-match recovery.
Functional contextual implementation of an evolutionary, entropy-based, and embodied free energy framework: Utilizing Lagrangian mechanics and evolutionary game theory’s truth vs. fitness test of the veridicality of phenomenological experience
Authors: Edwards Darren J.
Published: April 2023

The Bayesian approach of cognitive science largely takes the position that evolution drives perception to produce precepts that are veridical. However, some efforts utilizing evolutionary game theory simulations have shown that perception is more likely based on a fitness function, which promotes survival rather than promoting perceptual truth about the environment. Although these findings do not correspond well with the standard Bayesian approach to cognition, they may correspond with a behavioral functional contextual approach that is ontologically neutral (a-ontological). This approach, formalized through a post-Skinnerian account of behaviorism called relational frame theory (RFT), can, in fact, be shown to correspond well with an evolutionary fitness function, whereby contextual functions form that corresponds to a fitness function interface of the world. This fitness interface approach therefore may help provide a mathematical description for a functional contextual interface of phenomenological experience. Furthermore, this more broadly fits with a neurological active inference approach based on the free-energy principle (FEP) and more broadly with Lagrangian mechanics. These assumptions of how fitness beats truth (FBT) and FEP correspond to RFT are then discussed within a broader multidimensional and evolutionary framework called the extended evolutionary meta-model (EEMM) that has emerged out of the functional contextual behavioral science literature to incorporate principles of cognition, neurobiology, behaviorism, and evolution and are discussed in the context of a novel RFT framework called “Neurobiological and Natural Selection Relational Frame Theory” (N-frame). This framework mathematically connects RFT to FBT, FEP, and EEMM within a single framework that expands into dynamic graph networking. This is then discussed for its implications of empirical work at the non-ergodic process-based idiographic level as applied to individual and societal level dynamic modeling and clinical work. This discussion is framed within the context of individuals that are described as evolutionary adaptive and conscious (observer-self) agents that minimize entropy and can promote a prosocial society through group-level values and psychological flexibility.
Understanding the role of emotion and expertise in psychotherapy: An application of dynamical systems mathematical modeling to an entire course of therapy
Authors: Diaz Patricia , Peluso Paul R. , Freund Robert , Baker Andrew Z. , Peña Gabriel
Published: April 2023

Introduction

The therapeutic relationship continues to be one of the most important factors in therapeutic outcomes. Given the place of emotion in the definition of the therapeutic relationship, as well as the demonstrated positive impact that emotional expression has on therapeutic process and outcome, it stands to reason that studying the emotional exchange between the therapist and client further would be warranted.

Methods

This study used a validated observational coding system--the Specific Affect Coding System (SPAFF) and a theoretical mathematical model to analyze behaviors which make up the therapeutic relationship. Specifically, the researchers used to codify relationship-building behaviors between an expert therapist and his client over the course of six sessions. Dynamical systems mathematical modeling was also employed to create “phase space portraits” depicting the relational dynamics between the master therapist and his client over six sessions.

Results

Statistical analysis was used to compare SPAFF codes and model parameters between the expert therapist and his client. The expert therapist showed stability in affect codes over six sessions while the client’s affect codes appeared to be more flexible over time, though model parameters remained stable across the six sessions. Finally, phase space portraits depicted the evolution of the affective dynamics between the master therapist and his client as the relationship matured.

Discussion

The clinician’s ability to stay emotionally positive and relatively stable across the six sessions (relative to the client) was noteworthy. It formed the basis for a stable base from which she could explore alternative methods to relate to others that she had allowed to dictate her actions, which is in keeping with previous research on the role of therapist facilitation of the therapeutic relationship, emotional expression within the therapeutic relationship, and influence of these on client outcomes. These results provide a valuable foundation for future research on emotional expression as a key component of the therapeutic relationship in psychotherapy.