bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol and e-cigarette damage alveolar-epithelial barrier by activation of P2X7r and provoke brain endothelial injury via extracellular vesicles
Authors: Mekala Naveen , Trivedi Jayshil , Bhoj Priyanka , Togre Namdev , Rom Slava , Sriram Uma , Persidsky Yuri
Published: January 2024

Background

Use of nicotine containing products like electronic cigarettes (e-Cig) and alcohol are associated with mitochondrial membrane depolarization, resulting in the extracellular release of ATP, and mitochondrial DNA (mtDNA), mediating inflammatory responses. While nicotine effects on lungs is well-known, chronic alcohol (ETH) exposure also weakens lung immune responses and cause inflammation. Extracellular ATP (eATP) released by inflammatory/stressed cells stimulate purinergic P2X7 receptors (P2X7r) activation in adjacent cells. We hypothesized that injury caused by alcohol and e-Cig to pulmonary alveolar epithelial cells (hPAEpiC) promote the release of eATP, mtDNA and P2X7r in circulation. This induces a paracrine signaling communication either directly or via EVs to affect brain cells (human brain endothelial cells - hBMVEC).

Methods

We used a model of primary human pulmonary alveolar epithelial cells (hPAEpiC) and exposed the cells to 100 mM ethanol (ETH), 100 µM acetaldehyde (ALD), or e-Cig (1.75 µg/mL of 1.8% or 0% nicotine) conditioned media, and measured the mitochondrial efficiency using Agilent Seahorse machine. Gene expression was measured by Taqman RT-qPCR and digital PCR. hPAEpiC-EVs were extracted from culture supernatant and characterized by flow cytometric analysis. Calcium (Ca2+) and eATP levels were quantified using commercial kits. To study intercellular communication via paracrine signaling or by EVs, we stimulated hBMVECs with hPAEpiC cell culture medium conditioned with ETH, ALD or e-cig or hPAEpiC-EVs and measured Ca2+ levels.

Results

ETH, ALD, or e-Cig (1.8% nicotine) stimulation depleted the mitochondrial spare respiration capacity in hPAEpiC. We observed increased expression of P2X7r and TRPV1 genes (3-6-fold) and increased intracellular Ca2+ accumulation (20-30-fold increase) in hPAEpiC, resulting in greater expression of endoplasmic reticulum (ER) stress markers. hPAEpiC stimulated by ETH, ALD, and e-Cig conditioned media shed more EVs with larger particle sizes, carrying higher amounts of eATP and mtDNA. ETH, ALD and e-Cig (1.8% nicotine) exposure also increased the P2X7r shedding in media and via EVs. hPAEpiC-EVs carrying P2X7r and eATP cargo triggered paracrine signaling in human brain microvascular endothelial cells (BMVECs) and increased Ca2+ levels. P2X7r inhibition by A804598 compound normalized mitochondrial spare respiration, reduced ER stress and diminished EV release, thus protecting the BBB function.

Conclusion

Abusive drugs like ETH and e-Cig promote mitochondrial and endoplasmic reticulum stress in hPAEpiC and disrupts the cell functions via P2X7 receptor signaling. EVs released by lung epithelial cells against ETH/e-cig insults, carry a cargo of secondary messengers that stimulate brain cells via paracrine signals.
Evaluating spatially variable gene detection methods for spatial transcriptomics data
Authors: Chen Carissa , Kim Hani Jieun , Yang Pengyi
Published: January 2024

Background

The identification of genes that vary across spatial domains in tissues and cells is an essential step for spatial transcriptomics data analysis. Given the critical role it serves for downstream data interpretations, various methods for detecting spatially variable genes (SVGs) have been proposed. However, the lack of benchmarking complicates the selection of a suitable method.

Results

Here we systematically evaluate a panel of popular SVG detection methods on a large collection of spatial transcriptomics datasets, covering various tissue types, biotechnologies, and spatial resolutions. We address questions including whether different methods select a similar set of SVGs, how reliable is the reported statistical significance from each method, how accurate and robust is each method in terms of SVG detection, and how well the selected SVGs perform in downstream applications such as clustering of spatial domains. Besides these, practical considerations such as computational time and memory usage are also crucial for deciding which method to use.

Conclusions

Our study evaluates the performance of each method from multiple aspects and highlights the discrepancy among different methods when calling statistically significant SVGs across diverse datasets. Overall, our work provides useful considerations for choosing methods for identifying SVGs and serves as a key reference for the future development of related methods.
Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial
Authors: Yu Liang , Shen Xiao-Juan , Liu He , Zhou Yu-Ting , Zhang Qin , Zhang Zhen-Duo , Shen Shu-Min
Published: January 2024

Background

A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery.

Methods

In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18–80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions.

Discussion

Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial.

Trial registration

Chinese Clinical Trial Registry (https://www.chictr.org.cn/) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.
Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial)
Authors: Maehara Kosuke , Esaki Mitsuru , Sumida Yorinobu , Yamaguchi Daisuke , Nishioka Kei , Homma Hitoshi , Inada Taisuke , Shiotsuki Kazuo , Fukuda Shin-Ichiro , Akiho Hirotada , Nomura Tadahiro , Mizuta Yumi , Ishida Satoshi , Fujimoto Shun , Kimura Shunichiro , Tanaka Yuichiro , Hata Kaori , Shiga Noriko , Iwasa Tsutomu , Kimura Yusuke , Nakamura Norimoto , Suzuki Yusuke , Minoda Yosuke , Hata Yoshitaka , Ogino Haruei , Tagawa Koshiro , Ihara Eikichi , Ogawa Yoshihiro
Published: January 2024

Background

Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD.

Methods

This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study.

Discussion

This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures.

Trial registration

The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.
The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study
Authors: Kreis Lena , Dejaco Christian , Schmidt Wolfgang Andreas , Németh Robert , Venhoff Nils , Schäfer Valentin Sebastian
Published: January 2024

Background

Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases.

Methods

This study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study.

Discussion

This is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug.

Trial registration

ClinicalTrials.gov, NCT05623592. Registered on 21 November 2022.

EU Clinical Trials Register, 2022-501058-12-00.

German Clinical Trials Register DRKS00030571.
Inflammatory responses and barrier disruption in the trachea of chicks following Mycoplasma gallisepticum infection: a focus on the TNF-α-NF-κB/MLCK pathway
Authors: Zhong Lemiao , Wu Chunlin , Zhao Yan , Huang Baoqin , Luo Zhongbao , Wu Yijian
Published: January 2024

Mycoplasma gallisepticum (MG) can induce persistent inflammatory damage to the tracheal mucosa of poultry and cause chronic respiratory diseases in chickens. To further investigate the mechanism of MG-induced injury to the tracheal mucosa, we used chick embryo tracheal organ culture (TOC) as a model to study the invasion and reproduction of MG, the effect of MG on tracheal morphology, and the potential factors that promote MG tissue invasion. The results showed that MG infection significantly damaged the tracheal epithelial structure and weakened tracheal epithelial barrier function; MG also increased the occurrence of bacterial displacement, with a significant (p < 0.05) increase in the bacterial load of the infected TOCs at 5 and 7 days post-infection. In addition, MG significantly (p < 0.05) increased the expression levels of inflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β), and IL-6, and activated the NF-κB signalling pathway, leading to increased nuclear translocation of NF-κB p65. Simultaneously, the map kinase pathway (MAPK) was activated. This activation might be associated with increased myosin light chain (MLC) phosphorylation, which could lead to actin-myosin contraction and disruption of tight junction (TJ) protein function, potentially compromising epithelial barrier integrity and further catalysing MG migration into tissues. Overall, our results contribute to a better understanding of the interaction between MG and the host, provide insight into the mechanisms of damage to the tracheal mucosa induced by MG infection, and provide new insights into the possible pathways involved in Mycoplasma gallisepticum infection in vivo.
Interventions to improve appropriateness of laboratory testing in the intensive care unit: a narrative review
Authors: Devis Luigi , Catry Emilie , Honore Patrick M. , Mansour Alexandre , Lippi Giuseppe , Mullier François , Closset Mélanie
Published: January 2024

Healthcare expenses are increasing, as is the utilization of laboratory resources. Despite this, between 20% and 40% of requested tests are deemed inappropriate. Improper use of laboratory resources leads to unwanted consequences such as hospital-acquired anemia, infections, increased costs, staff workload and patient stress and discomfort. The most unfavorable consequences result from unnecessary follow-up tests and treatments (overuse) and missed or delayed diagnoses (underuse). In this context, several interventions have been carried out to improve the appropriateness of laboratory testing. To date, there have been few published assessments of interventions specific to the intensive care unit. We reviewed the literature for interventions implemented in the ICU to improve the appropriateness of laboratory testing. We searched literature from 2008 to 2023 in PubMed, Embase, Scopus, and Google Scholar databases between April and June 2023. Five intervention categories were identified: education and guidance (E&G), audit and feedback, gatekeeping, computerized physician order entry (including reshaping of ordering panels), and multifaceted interventions (MFI). We included a sixth category exploring the potential role of artificial intelligence and machine learning (AI/ML)-based assisting tools in such interventions. E&G-based interventions and MFI are the most frequently used approaches. MFI is the most effective type of intervention, and shows the strongest persistence of effect over time. AI/ML-based tools may offer valuable assistance to the improvement of appropriate laboratory testing in the near future. Patient safety outcomes are not impaired by interventions to reduce inappropriate testing. The literature focuses mainly on reducing overuse of laboratory tests, with only one intervention mentioning underuse. We highlight an overall poor quality of methodological design and reporting and argue for standardization of intervention methods. Collaboration between clinicians and laboratory staff is key to improve appropriate laboratory utilization. This article offers practical guidance for optimizing the effectiveness of an intervention protocol designed to limit inappropriate use of laboratory resources.
SLA-ORECS: an SLA-oriented framework for reallocating resources in edge-cloud systems
Authors: Lan Shizhan , Duan Zhuoxi , Lu Song , Tan Bin , Chen Shi , Liang Yeyu , Chen Shan
Published: January 2024

The emergence of the Fifth Generation (5G) era has ushered in a new era of diverse business scenarios, primarily characterized by data-intensive and latency-sensitive applications. Edge computing technology integrates the information services environment with cloud computing capabilities at the edge of the network. However, the evolving landscape of business models necessitates a unified edge architecture capable of accommodating diverse requirements, posing substantial challenges for service providers in meeting Service-Level Agreements (SLAs).In response to these challenges, we introduce SLA-ORECS. This innovative framework dynamically allocates dedicated and shared resources within the edge-cloud system to cater to service requests with varying SLAs, thereby facilitating performance isolation. Furthermore, we have developed an optimization algorithm to enhance the efficiency of SLA assurance during request dispatch.The evaluation of SLA-ORECS highlights its noteworthy performance improvements, particularly in terms of system throughput and average time consumption.
Consumer nutrition environment measurements for nutrient-dense food availability and food sustainability: a scoping review
Authors: Baker Katherine , Burd Laura , Figueroa Roger
Published: January 2024

Consumer nutrition environments are defined as places in which consumers interact with the food they eat; these food choices can impact human and planetary health. Assessment measures for consumer nutrition environments are numerous, and vary widely on what, and how, they assess the food environment. The objective of this scoping review was to synthesize existing evidence on nutrition environment measurements and their capacity to assess nutrient-dense food access and food sustainability capacity. Eligibility criteria were developed to capture relevant peer-reviewed literature about auditing measures designed to assess nutrient-dense foods and food sustainability capacity in the consumer nutrition environment. A search strategy was conducted to collect articles published between January 1, 2002-June 4, 2022, using PubMed, Web of Science, Scopus, PsycINFO and the Cochrane library electronic databases. After screening 2457 manuscripts, 58 met inclusion criteria. Study aims, funding source(s), types of retailers assessed, assessment format and name, constructs measured, food categories measured, assessment of validity and/or reliability, and other relevant data were extracted from each manuscript. Results showed that most measures use checklists, surveys, questionnaires or similar methods to assess availability, quality, and price of select food items as assessment constructs. Most do not assess nutrient-dense food availability, and even fewer assess food sustainability. Development of comprehensive, reliable, and valid consumer nutrition environment measures that assess nutrient-dense food availability and food sustainability is important for research, planning, evaluation and advocacy aimed at improving consumer food environments for human and planetary health.
Factors associated with food security among small-holder farming households in Lesotho
Authors: Nkoko Nthabeleng , Cronje Natasha , Swanepoel Jan Willem
Published: January 2024

Background

Food insecurity and malnutrition are persistent challenges worldwide and Lesotho is not an exception. Hunger and poverty have worsened with the dawn of COVID-19 pandemic and on-going Russia–Ukraine war. The study seeks to assess food security and associated socio-economic factors among farming households in Lesotho. Household food security has been assessed using Household Food Access Scale (HFIAS) and Household Dietary Diversity Score (HDDS). Questionnaires were employed to collect data from 236 farming households.

Results

The HFIAS results show that 40% of the farming households were food secure, 18% were mildly food insecure, 32% were moderately food insecure and 10% were severely food secure and severe food insecurity mostly experienced in the highlands. HDDS results indicated that the farming households had consumed 8 to 12 food groups 7 days prior to data collection, the mean HDDS is 9.68. Households that are involved in commercial farming had more (9.98) diverse diets than those in subsistence farming (8.67). Households in the highlands have the lowest diet diversity (9.0) among the four agro-ecological zones. A logistic regression analysis indicated that the socio-economic factors associated with food security were household income, household size, marital status and education status of the respondent.

Conclusions

The findings depict that over half (60%) of the farming households experience varied degrees of food insecurity. Contrary to this, the farming households had consumed highly varied diets in the past 7 days. The socio-economic factors that influence the attainment of food security household food security were household size, household income, education and marital status. The findings suggest that agricultural development interventions must be more sensitive to household food security and nutrition, which includes training farmers on nutrition and food security issues. Furthermore, socio-economic factors must be considered in the development of interventions, since they influence the food security of the farming households.
Molecular characterization of an outbreak-involved Bacillus anthracis strain confirms the spillover of anthrax from West Africa
Authors: Wang Shuchao , Suluku Roland , Jalloh Mohamed B. , Samba Ahmed F. , Jiang Baogui , Xie Yubiao , Harding Doris , Zhang Mengyao , Sahr Foday , Sesay Mahmud E. , Squire James S. , Vandi Mohamed A. , Kallon Moinina N. , Zhang Shoufeng , Hu Rongliang , Zhao Yuee , Mi Zhiqiang
Published: January 2024

Background

Anthrax, a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, remains a major global public health concern, especially in countries with limited resources. Sierra Leone, a West African country historically plagued by anthrax, has almost been out of report on this disease in recent decades. In this study, we described a large-scale anthrax outbreak affecting both animals and humans and attempted to characterize the pathogen using molecular techniques.

Methods

The causative agent of the animal outbreak in Port Loko District, Sierra Leone, between March and May 2022 was identified using the nanopore sequencing technique. A nationwide active surveillance was implemented from May 2022 to June 2023 to monitor the occurrence of anthrax-specific symptoms in humans. Suspected cases were subsequently verified using quantitative polymerase chain reaction. Full-genome sequencing was accomplished by combining long-read and short-read sequencing methods. Subsequent phylogenetic analysis was performed based on the full-chromosome single nucleotide polymorphisms.

Results

The outbreak in Port Loko District, Sierra Leone, led to the death of 233 animals between March 26th and May 16th, 2022. We ruled out the initial suspicion of Anaplasma species and successfully identified B. anthracis as the causative agent of the outbreak. As a result of the government's prompt response, out of the 49 suspected human cases identified during the one-year active surveillance, only 6 human cases tested positive, all within the first month after the official declaration of the outbreak. The phylogenetic analysis indicated that the BaSL2022 isolate responsible for the outbreak was positioned in the A.Br.153 clade within the TransEuroAsian group of B. anthracis.

Conclusions

We successfully identified a large-scale anthrax outbreak in Sierra Leone. The causative isolate of B. anthracis, BaSL2022, phylogenetically bridged other lineages in A.Br.153 clade and neighboring genetic groups, A.Br.144 and A.Br.148, eventually confirming the spillover of anthrax from West Africa. Given the wide dissemination of B. anthracis spores, it is highly advisable to effectively monitor the potential reoccurrence of anthrax outbreaks and to launch campaigns to improve public awareness regarding anthrax in Sierra Leone.

Graphical Abstract
Lipidomics reveals serum lipid metabolism disorders in CTD-induced liver injury
Authors: Li Shan , Duan Xiaotong , Zhang Yixin , Zhao Cancan , Yu Ming , Li Xiaofei , Li Xiaomei , Zhang Jianyong
Published: January 2024

Background

Cantharidin (CTD), the main toxic component of Mylabris, has been extensively used for tumor treatment in recent years. CTD-induced liver toxicity has attracted significant interest in clinic.

Methods

In this study, biochemical parameters and liver pathological changes were analyzed after CTD was administered to mice by gavage. Subsequently, a lipidomic approach was used to investigate serum lipid metabolism disorders, and the mechanism underlying CTD-induced liver injury in mice was explored.

Results

The results showed that the levels of TC and LDL-C were significantly increased after CTD intervention. Besides, pathological results showed inflammatory cell infiltration and hepatocyte necrosis in the liver. Furthermore, lipidomics found that a total of 18 lipid metabolites were increased and 40 were decreased, including LPC(20:4), LPC(20:3), PC(22:6e/2:0), PE(14:0e/21:2), PC(18:2e/22:6), glycerophospholipids, CE(16:0), CE(18:0) Cholesterol esters and TAG(12:0/12:0/22:3), TAG(16:1/16:2/20:4), TAG(18:1/18:1/20:0), TAG(16:2/18:2/18:2), TAG(18:0/18:0/20:0), TAG(13:1/19:0/19:0) glycerolipids. Metabolic pathway analysis found that glycerophospholipid, glycerol ester and glycosylphosphatidylinositol (GPI)-anchored biosynthetic metabolic pathways were dysregulated and the increase in PE caused by glycophoric metabololism and GPI may be the source of lipid metabolism disorders caused by CTD. Overall, the present study provided new insights into the mechanism of CTD-induced liver injury and increased drug safety during clinical application.
The effect of enhanced structure in the posterior segment of clear aligners during anterior retraction: a three-dimensional finite element and experimental model analysis
Authors: Jin Xiaohan , Tian Xue , Lee Zhi Hui Victoria , Zheng Yikan , Song Jinlin , Han Xianglong
Published: January 2024

Background

Mesial tipping of posterior teeth occurs frequently during space closure with clear aligners (CAs). In this study, we proposed a new modification of CA by localized thickening of the aligner to form the enhanced structure and investigate its biomechanical effect during anterior retraction.

Methods

Two methods were employed in this study. First, a finite element (FE) model was constructed, which included alveolar bone, the first premolars extracted maxillary dentition, periodontal ligaments (PDL), attachments and aligners. The second method involved an experimental model—a measuring device using multi-axis transducers and vacuum thermoforming aligners. Two groups were formed: (1) The control group used common CAs and (2) the enhanced structure group used partially thickened CAs.

Results

FE model revealed that the enhanced structure improved the biomechanics during anterior retraction. Specifically, the second premolar, which had a smaller PDL area, experienced a smaller protraction force and moment, making it less likely to tip mesially. In the same vein, the molars could resist movement due to their larger PDL area even though they were applied larger forces. The resultant force of the posterior tooth was closer to the center of resistance, reducing the tipping moment. The canine was applied a larger retraction force and moment, resulting in sufficient retraction of anterior teeth. The experimental model demonstrated a similar trend in force variation as the FE model.

Conclusions

Enhanced structure allowed force distribution more in accordance with optimal principles of biomechanics during the extraction space closure while permitting less mesial tipping and anchorage loss of posterior teeth and better retraction of anterior teeth. Thus, enhanced structure alleviated the roller coaster effect associated with extraction cases and offered a new possibility for anchorage reinforcement in clear aligner therapy.
Combined thoracoscopic and laparoscopic surgery for epiphrenic diverticulum with associated gastroesophageal reflux disease: a case report
Authors: Uchi Yusuke , Ozawa Soji , Ando Tomofumi , Hayashi Koki , Aoki Takuma , Shimazu Motohide
Published: January 2024

Background

Surgery is indicated for symptomatic epiphrenic esophageal diverticula. Based on the features of a case, thoracoscopic or laparoscopic approaches may be used. Epiphrenic diverticula are often associated with esophageal motility disorders, but cases of reflux esophagitis have rarely been reported. In this report, we describe a case of an epiphrenic esophageal diverticulum with reflux esophagitis, which was successfully treated by thoracoscopic diverticulectomy and laparoscopic fundoplication.

Case presentation

A 69-year-old man visited the hospital with a chief complaint of eructation and hiccup. Upper gastrointestinal endoscopy revealed a diverticulum in the left wall of the esophagus, which was 37–45 cm distal to the incisors. High-resolution manometry (HRM) showed no esophageal motility disorders. Due to the large size of the diverticulum, a thoracoscopic resection of the esophageal diverticulum was performed. Additionally, the patient had reflux esophagitis due to a hiatal hernia. The anti-reflux mechanism would be more impaired during the diverticulectomy; therefore, we decided that anti-reflux surgery should be performed simultaneously. Thoracoscopic esophageal diverticulectomy and laparoscopic Dor fundoplication were performed. The patient had an uncomplicated postoperative course and was discharged on the tenth operative day. He has been symptom-free without acid secretion inhibitors for 21 months after the surgery.

Conclusions

We described a rare case of a large epiphrenic diverticulum with reflux esophagitis. A good surgical outcome was achieved by thoracoscopic resection of the diverticulum and laparoscopic Dor fundoplication.
The road forward to incorporate seawater microbes in predictive reef monitoring
Authors: Terzin Marko , Laffy Patrick W. , Robbins Steven , Yeoh Yun Kit , Frade Pedro R. , Glasl Bettina , Webster Nicole S. , Bourne David G.
Published: January 2024

Marine bacterioplankton underpin the health and function of coral reefs and respond in a rapid and sensitive manner to environmental changes that affect reef ecosystem stability. Numerous meta-omics surveys over recent years have documented persistent associations of opportunistic seawater microbial taxa, and their associated functions, with metrics of environmental stress and poor reef health (e.g. elevated temperature, nutrient loads and macroalgae cover). Through positive feedback mechanisms, disturbance-triggered heterotrophic activity of seawater microbes is hypothesised to drive keystone benthic organisms towards the limit of their resilience and translate into shifts in biogeochemical cycles which influence marine food webs, ultimately affecting entire reef ecosystems. However, despite nearly two decades of work in this space, a major limitation to using seawater microbes in reef monitoring is a lack of a unified and focused approach that would move beyond the indicator discovery phase and towards the development of rapid microbial indicator assays for (near) real-time reef management and decision-making. By reviewing the current state of knowledge, we provide a comprehensive framework (defined as five phases of research and innovation) to catalyse a shift from fundamental to applied research, allowing us to move from descriptive to predictive reef monitoring, and from reactive to proactive reef management.
The nexus between the volatility of Bitcoin, gold, and American stock markets during the COVID-19 pandemic: evidence from VAR-DCC-EGARCH and ANN models
Authors: Terraza Virginie , Boru İpek Aslı , Rounaghi Mohammad Mahdi
Published: January 2024

The spread of the coronavirus has reduced the value of stock indexes, depressed energy and metals commodities prices including oil, and caused instability in financial markets around the world. Due to this situation, investors should consider investing in more secure assets, such as real estate property, cash, gold, and crypto assets. In recent years, among secure assets, cryptoassets are gaining more attention than traditional investments. This study compares the Bitcoin market, the gold market, and American stock indexes (S&P500, Nasdaq, and Dow Jones) before and during the COVID-19 pandemic. For this purpose, the dynamic conditional correlation exponential generalized autoregressive conditional heteroskedasticity model was used to estimate the DCC coefficient and compare this model with the artificial neural network approach to predict volatility of these markets. Our empirical findings showed a substantial dynamic conditional correlation between Bitcoin, gold, and stock markets. In particular, we observed that Bitcoin offered better diversification opportunities to reduce risks in key stock markets during the COVID-19 period. This paper provides practical impacts on risk management and portfolio diversification.
Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study
Authors: Chu Jian , Tung Lillian , Attalah Issam , Wei Changli , Cobleigh Melody , Rao Ruta , Feinstein Steven B. , Usha Lydia , Banach Kathrin , Reiser Jochen , Okwuosa Tochukwu M.
Published: January 2024

Background

Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin.

Methods

We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression.

Results

Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05).

Conclusions

In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.
Innovation in humanitarian assistance—a systematic literature review
Authors: Bruder Maximilian , Baar Thomas
Published: January 2024

The promise of innovation in humanitarian contexts has generated an expanding literature, from academics as well as practitioners. However, the field has become characterised by conceptual ambiguity and insular approaches, inhibiting the integration of findings and best practices. Therefore, this paper aims to identify the key concepts, definitions, and themes in humanitarian innovation (HI) research by applying a systematic literature review and content analysis. Based on data from 301 publications, we analyse scholarly and practitioner articles addressing the topic of humanitarian innovation. Our analysis suggests that efforts to reform the humanitarian system by leveraging innovation have been primarily ad hoc, fragmented, and serving miscellaneous separate objectives. This results in the implementation of incremental improvements, rather than transformative change throughout the sector. To bridge the gap between the various conceptualisations of HI, we propose a conceptual framework that provides a system perspective on HI, which includes the institutions, actors, contextual factors, and outputs of the system. The implications of our finding for further research and policy are discussed as well.

Points for practitioners

• Ensure active participation and inclusion of affected populations in innovation agendas and processes.

• Strengthen collaborative efforts among actors (donors, practitioners, private sector, intermediaries, NGOs) in humanitarian sector to increase coordination, knowledge exchange, and bundling of resources for innovation.

• Facilitate evidence-based approaches and data-driven decision-making, for the operationalisation of appropriate innovations.

• Increase the quality and quantity of funding going to innovation actors, and steer funding towards innovations explicitly catering to the needs of affected populations.

Graphical Abstract
Versatile extracellular vesicle-mediated information transfer: intercellular synchronization of differentiation and of cellular phenotypes, and future perspectives
Authors: Minakawa Tomohiro , Yamashita Jun K.
Published: January 2024

In recent years, extracellular vesicles (EVs) have attracted significant attention as carriers in intercellular communication. The vast array of information contained within EVs is critical for various cellular activities, such as proliferation and differentiation of multiple cell types. Moreover, EVs are being employed in disease diagnostics, implicated in disease etiology, and have shown promise in tissue repair. Recently, a phenomenon has been discovered in which cellular phenotypes, including the progression of differentiation, are synchronized among cells via EVs. This synchronization could be prevalent in widespread different situations in embryogenesis and tissue organization and maintenance. Given the increasing research on multi-cellular tissues and organoids, the role of EV-mediated intercellular communication has become increasingly crucial. This review begins with fundamental knowledge of EVs and then discusses recent findings, various modes of information transfer via EVs, and synchronization of cellular phenotypes.
Biochemical and microbial meta-profiling reveal the anti-cancer efficacy of Eu—an endemic traditional brew of the Toto tribe from India
Authors: Bhattacharjee Soumita , Sarkar Indrani , Sarkar Mahima Misti , Roy Swarnendu , Ghosh Chandra , Sen Arnab
Published: January 2024

Background

Eu is a lesser-known and traditional millet-based fermented brew of the Toto tribe from West Bengal, India. The starter culture used in this brew consists of diverse microflora. Identifying those microbes will not only help us gain a deeper understanding of the brew, but also quantify the impacts of this brew on the human system after consumption. Due to the progress in Illumina sequencing technology, the meta-profiling of 16S rRNA has emerged as a valuable resource for exploring the microbiome of any sample. We have utilised this tool (V3–V4 region) to study the microbiome population of Eu.

Results

The microbial diversity present in the brew was mainly constituted of probiotic and fermenting bacteria. The nutrient profiling of Eu estimated the amount of protein, carbohydrate, free amino acid, and free fatty acid. The nutritional substance present in the brew probably supports the growth of the probiotic microflora. Reverse ecology-based network analysis revealed considerable complementary interaction between humans and the microflora present in the Eu. GC–MS outlining enlisted thirteen potent compounds from Eu, and a comprehensive network pharmacological study on those compounds revealed the anti-cancerous properties of Eu, especially against gastrointestinal malignancy, by reducing the proliferation of malignant cells and forming pro-inflammatory cytokines.

Conclusions

The current study focuses on the meta-profiling and nutritional characteristics of Eu, which highlight the beverage’s potential as a probiotic health drink. Reverse ecology analysis demonstrated that the probiotic microflora competes strongly against pathogenic bacteria. Additionally, in silico network pharmacological research identified the drink as a potentially health-promoting and anti-cancer beverage.
Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation: an updated review
Authors: Saidullah Shahab , Ahmad Binish Ayub , Waqas Muhammad Saad , Fatima Anam , Khan Malik Hasnat ul Hassan , Khiyam Umer , Malik Jahanzeb
Published: January 2024

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia affecting millions of individuals worldwide and posing significant challenges to healthcare systems. The growing body of research has uncovered sex-related differences in AF pathophysiology, including the role of fatty acid-binding protein 4 (FABP4) and leptin as potential biomarkers. FABP4 and leptin, key adipokines involved in cardiovascular health, have been linked to inflammation, oxidative stress, and endothelial dysfunction, all of which may contribute to AF development. These adipokines exhibit sex-specific differences in their concentrations, with females generally showing higher FABP4 levels and males displaying distinct leptin profiles. Furthermore, hormonal influences, particularly estrogen, and testosterone, play significant roles in shaping AF risk and atrial remodeling. Estrogen is associated with cardioprotective effects, while testosterone may exert proarrhythmic effects. Understanding these sex-specific mechanisms could lead to more tailored and effective clinical management of AF. The future of AF research holds promise for precision medicine, novel therapeutic targets, artificial intelligence integration, and personalized care approaches. Emphasizing patient-centered care, telemedicine, and multidisciplinary collaboration can further enhance AF management and improve patient outcomes. In conclusion, recognizing and addressing sex-related factors in AF pathophysiology offer opportunities for gender-responsive interventions and advancements in AF management. Implementing these insights may pave the way for targeted therapies and improved quality of life for individuals affected by AF.
Frequency and risk factors of psychological distress among individuals with epilepsy before and during the outbreak of the SARS-CoV-2 Omicron variant in China: an online questionnaire survey
Authors: Hao Xiaoting , Zhang Qi , Zhong Chenxi , Li Enzhi , Jiang Yingqi , Xu Jiajun , Li Yuanyuan , Zhou Dong , Yan Bo
Published: January 2024

Background

The COVID-19 pandemic substantially increases the risk of severe psychological distress among people with epilepsy (PWE), especially those with monthly household income < 5000 RMB or with uncontrolled seizures. Patients with Kessler scores > 12 should consult a psychiatrist, especially during major disasters. This study was aimed to compare the frequency of psychological distress among Chinese PWE before and during the outbreak of the SARS-CoV-2 Omicron variant, and to identify risk factors for such distress.

Methods

In this prospective study, we collected sociodemographic data of PWE aged > 14 years, who were treated at our center during December 1 to 15, 2022. All participants completed the 6-item Kessler Psychological Distress Scale before the outbreak and again during the outbreak. Health visitors who were unrelated to those patients during the outbreak were included as a control. Multivariate logistic regression analysis was performed to identify risk factors of severe psychological distress and its exacerbation.

Results

Of the 223 PWE, 127 were tested positive for SARS-CoV-2, while 174 of 218 controls were positive for SARS-CoV-2. The neurological symptoms were similar between PWE and controls with SARS-CoV-2. The average Kessler score of PWE was significantly higher during the outbreak than before it (9.93 ± 3.98 vs. 8.52 ± 0.23, P < 0.001). The average score of controls during the outbreak (5.146 ± 0.35, P < 0.001) was significantly lower than that of the PWE. We identified three independent predictors for severe psychological distress in PWE during the outbreak, i.e., monthly household income < 5000 RMB (OR = 0.252, 95%CI 0.064–0.998, P = 0.048), severe psychological distress before the outbreak (OR = 0.067, 95%CI 0.026–0.174, P < 0.001), and seizure onset within 30 days before the assessment during the outbreak (OR = 0.356, 95%CI 0.157–0.805, P = 0.013). Of the three predictors, the last one was also an independent predictor for exacerbation of psychological distress during the outbreak (OR = 0.302, 95%CI 0.123–0.741, P = 0.009).

Conclusions

Our analysis suggests that the COVID-19 pandemic has substantially increased psychological distress of individuals with epilepsy, regardless of the viral infection or not. Various neurological symptoms similar to those of “long COVID” appeared for the first time among these individuals during the Omicron outbreak, highlighting the need for clinicians to screen carefully for this condition. Management of epilepsy during the pandemic or a similar major disaster should focus on the control of seizures and maintenance of mental health, especially among those with monthly household incomes below 5000 RMB, suffering uncontrolled seizures and having a history of severe psychological distress.
An initial investigation of the non-isotropic feature of GNSS tropospheric delay
Authors: Xu Ying , Yang Zaozao , Zhou Hongzhan , Zhang Fangzhao
Published: January 2024

Tropospheric delay is a significant error source in Global Navigation Satellite Systems (GNSS) positioning. Slant Path Delay (SPD) is commonly derived by multiplying Zenith Tropospheric Delay (ZTD) with a mapping function. However, mapping functions, assuming atmospheric isotropy, restrict the accuracy of derived SPDs. To improve the accuracy, a horizontal gradient correction is introduced to account for azimuth-dependent SPD variations, treating the atmosphere as anisotropic. This study uncovers that, amidst atmospheric dynamics and spatiotemporal changes in moisture content, the SPD deviates from that based on traditional isotropy or anisotropy assumption. It innovatively introduces the concept that SPD exhibits non-isotropy with respect to azimuth angles. Hypothesis validation involves assessing SPD accuracy using three mapping functions at five International GNSS Service (IGS) stations, referencing the SPD with the ray-tracing method. It subsequently evaluates the SPD accuracy with horizontal gradient correction based on Vienna Mapping Function 3 (VMF3) estimation. Lastly, the non-isotropic of SPD is analyzed through the ray-tracing method. The results indicate the smallest residual (1.1–82.7 mm) between the SPDs with VMF3 and those with the ray-tracing. However, introducing horizontal gradient correction yields no significant improvement of SPD accuracy. Considering potential decimeter-level differences in SPD due to non-isotropic tropospheric delay across azimuth angles, a precise grasp and summary of these variations is pivotal for accurate tropospheric delay modeling. This finding provides vital support for future high-precision tropospheric delay modeling.