bluuebunny/crossref_metadata_2025 huggingface dataset:
Current status and perspectives of the quality system in histocompatibility laboratories in Poland
Authors: Uhrynowska-Tyszkiewicz Izabela , Bogunia-Kubik Katarzyna , Baj-Krzyworzeka Monika , Piątosa Barbara
Published: January 2024

Allogeneic transplantation is a multi-step process involving many clinicians and laboratory personnel working together to achieve a common goal—to maximize the recipients’ chance of survival and to improve their quality of life. One of the key elements of the process is to ensure high quality, accuracy, and reliability of histocompatibility testing. This manuscript presents: the development and organizational principles of the national system of supervision and control of histocompatibility laboratories in Poland, problems faced by these laboratories, availabe proficiency testing schemes, as well as suggestions and prospects for the future raised by members of the Polish histocompatibility community.
Dynamics of humoral and cellular response to three doses of anti-SARS-CoV-2 BNT162b2 vaccine in patients with hematological malignancies and older subjects
Authors: Laquintana Valentina , Mottini Carla , Marchesi Francesco , Marcozzi Benedetta , Terrenato Irene , Sperandio Eleonora , de Latouliere Luisa , Carrieri Francesca , Pimpinelli Fulvia , Pontone Martina , Pellini Raul , Campo Flaminia , Conti Laura , Accetta Celeste , Mandoj Chiara , Petrone Fabrizio , Di Bella Ornella , Vujovic Branka , Morrone Aldo , Compagnone Mirco , Principato Eugenia , Pinto Eleonora , Papa Elena , Falcucci Paolo , La Malfa Antonia , Pallocca Matteo , De Marco Federico , Piaggio Giulia , Ciliberto Gennaro , Mengarelli Andrea , di Martino Simona
Published: January 2024

Background

Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients.

Objective

To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy.

Methods

We measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80–92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D.

Results

An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts.

Conclusion

FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.
Construction of disulfidptosis-based immune response prediction model with artificial intelligence and validation of the pivotal grouping oncogene c-MET in regulating T cell exhaustion
Authors: Li Pengping , Wang Shaowen , Wan Hong , Huang Yuqing , Yin Kexin , Sun Ke , Jin Haigang , Wang Zhenyu
Published: January 2024

Background

Given the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity.

Methods

Based on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET.

Results

The expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells.

Conclusion

To summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.
Dynamic immune signatures of patients with advanced non–small-cell lung cancer for infection prediction after immunotherapy
Authors: Luo Yung-Hung , Shen Chia-I , Chiang Chi-Lu , Huang Hsu-Ching , Chen Yuh-Min
Published: January 2024

Background

Pulmonary infections are a crucial health concern for patients with advanced non–small-cell lung cancer (NSCLC). Whether the clinical outcome of pulmonary infection is influenced by immunotherapy(IO) remains unclear. By evaluating immune signatures, this study investigated the post-immunotherapy risk of pulmonary infection in patients with lung cancer and identified circulating biomarkers that predict post-immunotherapy infection.

Methods

Blood specimens were prospectively collected from patients with NSCLC before and after chemotherapy(C/T) and/or IO to explore dynamic changes in immune signatures. Real-world clinical data were extracted from medical records for outcome evaluation. Mass cytometry and ELISA were employed to analyze immune signatures and cytokine profiles to reveal potential correlations between immune profiles and the risk of infection.

Results

The retrospective cohort included 283 patients with advanced NSCLC. IO was associated with a lower risk of pneumonia (odds ratio=0.46, p=0.012). Patients receiving IO and remained pneumonia-free exhibited the most favorable survival outcomes compared with those who received C/T or developed pneumonia (p<0.001). The prospective cohort enrolled 30 patients. The proportion of circulating NK cells significantly increased after treatment in IO alone (p<0.001) and C/T+IO group (p<0.01). An increase in cell densities of circulating PD-1+CD8+(cytotoxic) T cells (p<0.01) and PD-1+CD4+ T cells (p<0.01) were observed in C/T alone group after treatment. In IO alone group, a decrease in cell densities of TIM-3+ and PD-1+ cytotoxic T cells (p<0.05), and PD-1+CD4+ T cells (p<0.01) were observed after treatment. In C/T alone and C/T+IO groups, cell densities of circulating PD-1+ cytotoxic T cells significantly increased in patients with pneumonia after treatment(p<0.05). However, in IO alone group, cell density of PD-1+ cytotoxic T cells significantly decreased in patients without pneumonia after treatment (p<0.05). TNF-α significantly increased after treatment with IO alone (p<0.05) but decreased after C/T alone (p<0.01).

Conclusions

Our results indicate that the incorporation of immunotherapy into treatment regimens may potentially offer protective effects against pulmonary infection. Protective effects are associated with reduction of exhausted T-cells and augmentation of TNF-α and NK cells. Exhausted T cells, NK cells, and TNF-α may play crucial roles in immune responses against infections. These observations highlight the potential utility of certain circulating biomarkers, particularly exhausted T cells, for predicting post-treatment infections.
Research advances of Zanthoxylum bungeanum Maxim. polyphenols in inflammatory diseases
Authors: Qi Jinxin , Pan Zhaoping , Wang Xiaoyun , Zhang Nan , He Gu , Jiang Xian
Published: January 2024

Zanthoxylum bungeanum Maxim., commonly known as Chinese prickly ash, is a well-known spice and traditional Chinese medicine ingredient with a rich history of use in treating inflammatory conditions. This review provides a comprehensive overview of the botanical classification, traditional applications, and anti-inflammatory effects of Z. bungeanum, with a specific focus on its polyphenolic components. These polyphenols have exhibited considerable promise, as evidenced by preclinical studies in animal models, suggesting their therapeutic potential in human inflammatory diseases such as ulcerative colitis, arthritis, asthma, chronic obstructive pulmonary disease, cardiovascular disease, and neurodegenerative conditions. This positions them as a promising class of natural compounds with the potential to enhance human well-being. However, further research is necessary to fully elucidate their mechanisms of action and develop safe and effective therapeutic applications.
Tree shrews as a new animal model for systemic sclerosis research
Authors: Zheng Leting , Chen Shuyuan , Wu Qiulin , Li Xi , Zeng Wen , Dong Fei , An Weiwei , Qin Fang , Lei Ling , Zhao Cheng
Published: January 2024

Objective

Systemic sclerosis (SSc) is a chronic systemic disease characterized by immune dysregulation and fibrosis for which there is no effective treatment. Animal models are crucial for advancing SSc research. Tree shrews are genetically, anatomically, and immunologically closer to humans than rodents. Thus, the tree shrew model provides a unique opportunity for translational research in SSc.

Methods

In this study, a SSc tree shrew model was constructed by subcutaneous injection of different doses of bleomycin (BLM) for 21 days. We assessed the degree of inflammation and fibrosis in the skin and internal organs, and antibodies in serum. Furthermore, RNA sequencing and a series of bioinformatics analyses were performed to analyze the transcriptome changes, hub genes and immune infiltration in the skin tissues of BLM induced SSc tree shrew models. Multiple sequence alignment was utilized to analyze the conservation of selected target genes across multiple species.

Results

Subcutaneous injection of BLM successfully induced a SSc model in tree shrew. This model exhibited inflammation and fibrosis in skin and lung, and some developed esophageal fibrosis and secrum autoantibodies including antinuclear antibodies and anti-scleroderma-70 antibody. Using RNA sequencing, we compiled skin transcriptome profiles in SSc tree shrew models. 90 differentially expressed genes (DEGs) were identified, which were mainly enriched in the PPAR signaling pathway, tyrosine metabolic pathway, p53 signaling pathway, ECM receptor interaction and glutathione metabolism, all of which are closely associated with SSc. Immune infiltration analysis identified 20 different types of immune cells infiltrating the skin of the BLM-induced SSc tree shrew models and correlations between those immune cells. By constructing a protein-protein interaction (PPI) network, we identified 10 hub genes that were significantly highly expressed in the skin of the SSc models compared to controls. Furthermore, these genes were confirmed to be highly conserved in tree shrews, humans and mice.

Conclusion

This study for the first time comfirmed that tree shrew model of SSc can be used as a novel and promising experimental animal model to study the pathogenesis and translational research in SSc.
Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice
Authors: Więsik-Szewczyk Ewa , Zegadło Arkadiusz , Sobczyńska-Tomaszewska Agnieszka , Korzeniowska Marcelina , Jahnz-Rózyk Karina
Published: January 2024

Lung involvement is not widely recognized as a complication of auto-inflammatory diseases. We present a broad approach to diagnose a severe form of autoinflammatory syndrome in an adult male patient. A 63-year-old Caucasian male presented with recurrent episodes of high fever, interstitial lung infiltration, and pleural effusion. Laboratory tests performed during the flares revealed lymphopenia and increased levels of C-reactive protein and ferritin. Broad diagnostic research on infections, connective tissue diseases, and malignancies yielded negative results. The patient’s symptoms promptly resolved upon the administration of glucocorticoids; however, they reappeared when the prednisone dose was reduced. All attempts to administer immunomodulatory and immunosuppressive medications were ineffective. During follow-up, autoinflammatory syndrome was suspected; however, no pathological variants of monogenic autoinflammatory diseases were identified by genome-exome sequencing. The patient did not respond to interleukin 1 blockade with anakinra. He died due to multi-organ failure, and his condition remained unresolved until the first reported description of vacuole, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS). We describe the diagnostic traps and reasoning process involved in establishing that the patient’s symptoms were autoinflammatory in nature based on clinical symptoms, in addition to the proof of concept gained from genetic reevaluation and identification of pathogenic variants in the UBA1 gene. The aim of this review is to increase the awareness of VEXAS among pulmonologists. Genetic screening for UBA1 should be considered in patients with recurrent pneumonitis of unknown origin with elevated inflammatory markers and signs of cytopenia, especially if they require chronic steroids to control the disease. Respiratory manifestations are part of VEXAS; these may be dominant in the course of the disease and severe at presentation.
Micro-biological degradation and transformation of dissolved organic matter following continuous cropping of tobacco
Authors: Chen Peng , Wang Lei , Li Wei-hua , Zhang Xiu-xia , Gao Huan-huan , Zhou Xian-hong , Zhuang Qian-ying , Li Jian , Li Xing-yue , Zhang An-sheng
Published: January 2024

In recent years, the problems associated with continuous cropping (CC) that cause soil degradation have become increasingly serious. As a key soil quality property, dissolved organic matter (DOM) affects the circulation of carbon and nutrients and the composition of bacterial communities in soil. However, research on the changes in the molecular composition of DOM after CC is limited. In this study, the soil chemical properties, DOM chemical diversity, bacterial community structure, and their interactions are explored in the soil samples from different CC years (CC1Y, CC3Y, CC5Y, and CC7Y) of tobacco. With increasing CC year of tobacco, most of the soil chemical properties, such as total carbon, total nitrogen and organic matter, decreased significantly, while dissolved organic carbon first decreased and then increased. Likewise, the trends of DOM composition differed with changing duration of CC, such as the tannin compounds decreased from 18.13 to 13.95%, aliphatic/proteins increased from 2.73 to 8.85%. After 7 years of CC, the soil preferentially produced compounds with either high H/C ratios (H/C > 1.5), including carbohydrates, lipids, and aliphatic/proteins, or low O/C ratios (O/C < 0.1), such as unsaturated hydrocarbons. Furthermore, core microorganisms, including Nocardioides, wb1-P19, Aquabacterium, Methylobacter, and Thiobacillus, were identified. Network analysis further indicated that in response to CC, Methylobacter and Thiobacillus were correlated with the microbial degradation and transformation of DOM. These findings will improve our understanding of the interactions between microbial community and DOM in continuous cropping soil.
Combined analysis of host IFN-γ, IL-2 and IP-10 as potential LTBI biomarkers in ESAT-6/CFP-10 stimulated blood
Authors: Rapulana Antony M. , Mpotje Thabo , Baiyegunhi Omolara O. , Ndlovu Hlumani , Smit Theresa K. , McHugh Timothy D. , Marakalala Mohlopheni J.
Published: January 2024

Background: Accurate diagnosis of latent tuberculosis infected (LTBI) individuals is important in identifying individuals at risk of developing active tuberculosis. Current diagnosis of LTBI routinely relies on the detection and measurement of immune responses using the Tuberculin Skin Test (TST) and interferon gamma release assays (IGRAs). However, IGRA, which detects Mycobacterium tuberculosis specific IFN-γ, is associated with frequent indeterminate results, particularly in immunosuppressed patients. There is a need to identify more sensitive LTBI point of care diagnostic biomarkers. The aim of this study was to assess the validity of early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) stimulated plasma to identify additional cytokines and chemokines as potential biomarkers of LTBI.

Method: The levels of 27 cytokines and chemokines were measured by Bio-Plex Pro cytokine, chemokine and growth factor assay in ESAT-6 and CFP-10 co-stimulated plasma from 20 LTBI participants with positive IGRA (Quantiferon TB Gold plus) and 20 healthy controls with negative IGRA. Traditional ELISA was used to validate the abundance of the best performing markers in 70 LTBI and 72 healthy participants. All participants were HIV negative.

Results: We found that Interleukin 1 receptor antagonist (IL1ra) (p = 0.0056), Interleukin 2 (IL-2) (p < 0.0001), Interleukin 13 (IL-13) (p < 0.0001), Interferon gamma-induced protein 10 (IP-10) (p < 0.0001), and Macrophage inflammatory protein-1 beta (MIP1b) (p = 0.0010) were significantly higher in stimulated plasma of LTBI compared to healthy individuals. Stimulated plasma IL-2 (cutoff 100 pg/mL), IP-10 (cutoff 300 pg/mL) and IL-13 (5 pg/mL) showed potential in diagnosing LTBI with PPV = 100%, 0.89.4%, and 80.9% and NPV = 86.9%, 0.85.7%, and 84.2%, respectively.

Conclusion: Our data shows that co-stimulating whole blood with ESAT-6 and CFP-10 may help distinguish LTBI from healthy individuals. We also identified IL-2 and IP-10 as potential biomarkers that could be added to the currently used IFN-γ release assays in detection of LTBI.
Dual role of α7 nicotinic acetylcholine receptors in the retrosplenial cortex for aversive memory acquisition and retrieval
Authors: Pastor Verónica , Katche Cynthia
Published: January 2024

In the retrosplenial cortex (RSC), the role of cholinergic modulation via α7 nicotinic receptors and their involvement in memory is unknown. In recent years, the RSC has been shown to deteriorate in the early stages of Alzheimer’s disease (AD). Likewise, the cholinergic system has been postulated as one of those responsible for cognitive impairment in patients with AD. Great interest has arisen in the study of α7 nicotinic receptors as more specific targets for the treatment of this disease. For this reason, we aim to study the role of α7 receptors of the RSC in memory processing. We infused a selective α7 receptor antagonist into the anterior part of the RSC (aRSC) to assess its role in different phases of aversive memory processing using an inhibitory avoidance task. We found that α7 nicotinic receptors are involved in memory acquisition and expression, but not in its consolidation. These results identify aRSC α7 nicotinic receptors as key players in aversive memory processing and highlight their significant potential as therapeutic targets for Alzheimer’s disease.
Is badfiction processed differently by the human brain? An electrophysical study on reading experience
Authors: Weitin Thomas , Fabian Thomas , Glawion Anastasia , Brottrager Judith , Pilz Zsofia
Published: January 2024

Literary reception is a special case of language processing. The judgment of literature reveals deep social patterns with embodied cognition. In this study, we investigate how differences in literary quality resonate in the human brain. Modifying a series of stimuli previously used in studies of the emotional potential of Harry Potter, we alternate passages from the original novels with passages from imitative and intentionally poorly written fanfiction. EEG data shows how the three text types are processed differently by the brain. Comparing the brain activity of the readers for the various text types, we see a difference in the absolute power but not in the relative power of the frequency bands. Reading badfiction evokes the lowest activity. However, the functionality of this activity is the same for all texts since the relative power of the frequency bands does not differ. When comparing the participant groups, we observe the opposite situation. Here, different relative powers of the frequency bands reflect different judgments and reading habits of participants. For example, fans of Harry Potter, regular readers of fantasy texts, and generally frequent readers read the texts more attentively, which is reflected in a pronounced relative activity of the theta and alpha frequency bands. Non-frequent readers and readers who are not devoted to Harry Potter and fantasy in general have increased activity in the delta frequency band. This suggests their saliency detection is more prominent because they are less familiar with reading or the subject matter. To support our findings, we use the EEG data without averaging over stimuli and participants, capturing the participants' responses on the level of individual stimuli. A Kohonen self-organizing map trained on this more extensive data finds reliably detectable differences in the responses to passages from the original Harry Potter novels and fan- and badfiction. Our study allows for an interpretation of an adaptive brain response. Readers who enjoy Harry Potter or have experience with the fantasy genre show different reactions from those who do not. Thus, badfiction appears to be processed differently by the human brain, but not for all readers in the same way.
Detection and evaluation of signals for immune-related adverse events: a nationwide, population-based study
Authors: Kim Eo Jin , Kim Ye-Jee , Heo Ja Yoon , Kim Minju , Lee Soohyeon , Seo Seyoung , Myung Jisun , Oh Ji Seon , Park Sook Ryun
Published: January 2024

Background

Immune checkpoint inhibitors (ICIs) are one of the main pillars of cancer therapy. Since other studies such as clinical trial and retrospective study have limitations for detecting the immune-related adverse events (irAEs) characterized by unpredictable onset, nonspecific symptoms and wide clinical spectrum, we aimed to identify the incidence of irAEs and to detect and evaluate the signals using real-world data.

Methods

Cancer patients treated with anticancer medications were analyzed using the nationwide health insurance claims database of South Korea from 2017 to 2019, and Clinical Data Warehouse (CDW) database of Asan Medical Center (AMC), a tertiary referral hospital, from 2012 to 2019. AEs of ICI users were compared with those of non-ICI anticancer medication users. PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab) were evaluated. We defined an AE as a newly added diagnosis after the ICI prescription using an ICD-10 diagnostic code. A signal was defined as an AE that was detected by any one of the four indices of data mining: hazard ratio (HR), proportional claims ratio (PCR), claims odds ratio (COR), or information component (IC). All detected signals were reviewed and classified into well-known or potential irAEs. Signal verification was performed for targeted AEs using CDW of AMC using diagnostic codes and text mining.

Results

We identified 118 significant signals related to ICI use. We detected 31 well-known irAEs, most of which were endocrine diseases and skin diseases. We also detected 33 potential irAEs related to disorders in the nervous system, eye, circulatory system, digestive system, skin and subcutaneous tissues, and bones. Especially, portal vein thrombosis and bone disorders such as osteoporosis with pathological fracture and fracture of shoulder, upper arm, femur, and lower leg showed high HR in ICI users than in non-ICI users. The signals from hospital database were verified using diagnostic codes and text mining.

Conclusion

This real-world data analysis demonstrated an efficient approach for signal detection and evaluation of ICI use. An effective real-world pharmacovigilance system of the nationwide claims database and the EMR could complement each other in detecting significant AE signals.
Clinical management of intrahepatic cholangiocarcinoma: surgical approaches and systemic therapies
Authors: Ruff Samantha M. , Pawlik Timothy M.
Published: January 2024

Intrahepatic cholangiocarcinoma (ICCA) is a rare and aggressive malignant tumor that arises from the biliary tracts in the liver. Upfront surgery with adjuvant capecitabine in patients with resectable disease is often the standard treatment. Unfortunately, only 20% of patients present with resectable disease and many individuals will develop recurrence or metastatic disease after curative-intent resection. Patients with advanced or metastatic ICCA often require multidisciplinary care with a combination of cytotoxic chemotherapy, targeted therapy, and/or locoregional therapies. Gemcitabine plus cisplatin is currently first line therapy for advanced or metastatic ICCA. In recent years, efforts have been focused to develop more effective targeted therapy, most commonly with FGFR and IDH inhibitors for ICCA. Despite these efforts, ICCA still carries a poor prognosis. We herein review the current clinical management of ICCA focusing on surgical technique and systemic therapies.
Applying the estimand and target trial frameworks to external control analyses using observational data: a case study in the solid tumor setting
Authors: Polito Letizia , Liang Qixing , Pal Navdeep , Mpofu Philani , Sawas Ahmed , Humblet Olivier , Rufibach Kaspar , Heinzmann Dominik
Published: January 2024

Introduction: In causal inference, the correct formulation of the scientific question of interest is a crucial step. The purpose of this study was to apply causal inference principles to external control analysis using observational data and illustrate the process to define the estimand attributes.

Methods: This study compared long-term survival outcomes of a pooled set of three previously reported randomized phase 3 trials studying patients with metastatic non-small cell lung cancer receiving front-line chemotherapy and similar patients treated with front-line chemotherapy as part of routine clinical care. Causal inference frameworks were applied to define the estimand aligned with the research question and select the estimator to estimate the estimand of interest.

Results: The estimand attributes of the ideal trial were defined using the estimand framework. The target trial framework was used to address specific issues in defining the estimand attributes using observational data from a nationwide electronic health record-derived de-identified database. The two frameworks combined allow to clearly define the estimand and the aligned estimator while accounting for key baseline confounders, index date, and receipt of subsequent therapies. The hazard ratio estimate (point estimate with 95% confidence interval) comparing the randomized clinical trial pooled control arm with the external control was close to 1, which is indicative of similar survival between the two arms.

Discussion: The proposed combined framework provides clarity on the causal contrast of interest and the estimator to adopt, and thus facilitates design and interpretation of the analyses.
From antimicrobial to anticancer: unraveling the potential of pleurocidin and pleurocidin-derived peptides in the treatment of cancers
Authors: Piktel Ewelina , Wnorowska Urszula , Gorbacz-Konończuk Joanna , Sienkiewicz Jakub , Głuszek Katarzyna , Okła Sławomir , Bucki Robert
Published: January 2024

Antimicrobial peptides (AMPs), commonly referred to as host defense peptides, are found in a wide range of organisms, including bacteria, plants, and both vertebrate and invertebrate animals. They function as an initial defense mechanism against pathogenic microorganisms, modulate immune responses, and in specific instances, confer protection against the onset of cancer. Pleurocidin (Ple) is a linear antimicrobial peptide with amphipathic α-helical conformation, isolated originally from the winter flounder (Pleuronectes americanus), notable for its wide-ranging effectiveness against both bacteria and fungi. While the majority of research on pleurocidin’s biological characteristics has primarily focused on deciphering its mechanisms of interaction with the biological membranes of pathogenic bacteria and host cells, as well as investigating its modes of killing activities, there is a growing body of evidence suggesting that pleurocidin and pleurocidin-derived analogs might be effectively employed as anti-cancer agents against breast carcinoma and leukemia due to their potent cytotoxic properties and selectivity towards cancer cells. Notably, some characteristics of pleurocidin observed in microbiological investigations of this compound could be effectively applied in examining the anti-cancer capabilities of Ple-like derivatives. This review provides a comprehensive overview of the literature on the biological activities of pleurocidin, pleurocidin-derived peptides, pleurocidin-containing hybrid peptides, and nanosystems. The primary emphasis is on elucidating the range of activities exhibited by these compounds, evaluating their potential therapeutic applications, assessing their safety profile, and identifying any limits observed thus far. This paper will also discuss potential areas for further investigation into the anti-cancer effects of Ple and its derivatives, drawing insights from microbiological research.
Comparative gene co-expression networks show enrichment of brassinosteroid and vitamin B processes in a seagrass under simulated ocean warming and extreme climatic events
Authors: Booth Mitchell W. , Sinclair Elizabeth A. , Jung Elisabeth Maria U. , Austin Rachel , Bayer Philipp E. , Krauss Siegfried L. , Breed Martin F. , Kendrick Gary A.
Published: January 2024

Introduction

Ocean warming combined with extreme climatic events, such as marine heatwaves and flash flooding events, threaten seagrasses globally. How seagrasses cope with these challenges is uncertain, particularly for range-edge populations of species such as Posidonia australis in Shark Bay, Western Australia. Analyzing gene expression while manipulating multiple stressors provides insight into the genetic response and resilience of seagrasses to climate change. We conducted a gene expression study on a polyploid clone of P. australis during an 18-week mesocosm experiment to assess the responses to single and combined future climate change-associated stressors.

Methods

Plants were exposed to (1) future ocean warming temperature (baseline +1.5°C) followed by a simulated marine heat wave (baseline +5.5°C), (2) light deprivation simulating observed marine heatwave driven turbidity (95% shade) at baseline temperatures, or (3) both stressors simultaneously. Basal leaf meristems were sampled for gene expression analysis using RNA-seq at four time points during the experiment. Weighted gene co-expression network analysis, GO term enrichment, and KEGG pathway enrichment analyses were used to identify stress responses.

Results

Shaded plants showed specific gene enrichment for shade avoidance (programmed cell death) after three weeks of stress, and before any heated tanks showed a specific heat response. Shaded plants were positively correlated with programmed cell death and stress-related processes at the end of the experiment. Once ocean warming temperatures (+1.5°C) were in effect, gene enrichment for heat stress (e.g., ROS scavenging and polyamine metabolism) was present. Vitamin B processes, RNA polymerase II processes. and light-related meristematic phase changes were expressed with the addition of simulated MHW. Heated plants showed meristematic growth signatures as well as trehalose and salicylic acid metabolism. Brassinosteroid-related processes were significantly enriched in all stressor treatments at all time points, except for the isolated heat-stressed plants three weeks after stressor initiation.

Discussion

Gene expression responses to the interaction between heat waves and turbidity-induced light reduction support the observed geographical scale mortality in seagrasses observed for P. australis in Shark Bay, suggesting that even this giant polyploid clone will be negatively impacted by more extreme climate change projections.
The association between Long-COVID symptomology, perceived symptom burden and mental health in COVID-19 patients in Shijiazhuang, China: a population-based health survey
Authors: Li Yufei , Lam Lawrence T. , Xiao Ying , Qiu Zhengqi , Zhang Yanming
Published: January 2024

Background

Long-COVID (LC) refers to post-acute COVID-19 symptoms that can last for months or longer after the initial infection, affecting the physical health of infected patients. This study aims to investigate the association between the symptomology of LC and the mental health of patients in China. It also aims to examine the relationship between the perceived symptom burden and mental health of these patients.

Methods

A population-based stratified cluster sample was recruited, using a standard sampling procedure, from a prefecture-level city in Northern China. Participants included patients who had tested positive for COVID-19 after December 2022. LC symptomology was assessed using a LC symptoms checklist where the perceived symptom burden was measured by the included 5-point Likert scales. Mental health of patients was measured using the Depression, Anxiety, and Stress Scale (DASS), the original Connor-Davidson Resilience Scale (CD-RISC), and the Duke-UNC Functional Social Support Questionnaire (DUFSS). Data were analysed using multiple linear regression models.

Results

About 25% of respondents, experienced COVID symptoms lasting longer than two months that could only be explained by the infection. Post-exertional malaise (22.2%) and fatigue (21.2%) were the most common symptoms. After controlling for potential confounding variables, LC symptomology was significantly and positively associated with depression (t=2.09, p=0.037) and anxiety (t=4.51, p<0.001), but not stress. Perceived symptoms burden was also positively and significantly related to depression (β=0.35, p<0.001), anxiety (β=0.54, p<0.001), and stress (β=0.35, p<0.001), suggesting a dose-response relationship between perceived symptom burden and mental ill health.

Conclusion

This study highlights the importance of recognising the risk of LC, patients’ perception of the symptom burden and its potential impact on mental health. Healthcare professionals should be aware of the complexity of psychological comorbidities among infected patients reporting prolonged symptoms, and be able to give advice regarding long-term management of the symptoms.
Spatiotemporal patterns and risk mapping of provincial hand, foot, and mouth disease in mainland China, 2014–2017
Authors: Wei Yuxin , Ma Yue , Zhang Tao , Luo Xuelian , Yin Fei , Shui Tiejun
Published: January 2024

Background

Hand, foot, and mouth disease (HFMD) has remained a serious public health threat since its first outbreak in China. Analyzing the province-level spatiotemporal distribution of HFMD and mapping the relative risk in mainland China will help determine high-risk provinces and periods of infection outbreaks for use in formulating new priority areas for prevention and control of this disease. Furthermore, our study examined the effect of air pollution on HFMD nationwide, which few studies have done thus far.

Methods

Data were collected on the number of provincial monthly HFMD infections, air pollution, meteorological variables, and socioeconomic variables from 2014 to 2017 in mainland China. We used spatial autocorrelation to determine the aggregate distribution of HFMD incidence. Spatiotemporal patterns of HFMD were analyzed, risk maps were developed using the Bayesian spatiotemporal model, and the impact of potential influencing factors on HFMD was assessed.

Results

In our study, from 2014 to 2017, the HFMD annual incidence rate in all provinces of mainland China ranged from 138.80 to 203.15 per 100,000 people, with an average annual incidence rate of 165.86. The temporal risk of HFMD for 31 Chinese provinces exhibited cyclical and seasonal characteristics. The southern and eastern provinces had the highest spatial relative risk (RR > 3) from 2014 to 2017. The HFMD incidence risk in provinces (Hunan, Hubei, and Chongqing) located in central China increased over time. Among the meteorological variables, except for the mean two-minute wind speed (RR 0.6878; 95% CI 0.5841, 0.8042), all other variables were risk factors for HFMD. High GDP per capita (RR 0.9922; 95% CI 0.9841, 0.9999) was a protective factor against HFMD. The higher the birth rate was (RR 1.0657; 95% CI 1.0185, 1.1150), the higher the risk of HFMD. Health workers per 1,000 people (RR 1.2010; 95% CI 1.0443, 1.3771) was positively correlated with HFMD.

Conclusions

From 2014 to 2017, the central provinces (Hunan, Hubei, and Chongqing) gradually became high-risk regions for HFMD. The spatiotemporal pattern of HFMD risk may be partially attributed to meteorological and socioeconomic factors. The prevalence of HFMD in the central provinces requires attention, as prevention control efforts should be strengthened there.
An application of BWM for risk control in reverse logistics of medical waste
Authors: Wang Xiaozhu , Liu Long , Wang Lingyu , Cao Wenjun , Guo Di
Published: January 2024

The pollution posed by medical waste complicate the procedures of medical waste logistics (MWL), and the increasingly frequent occurrence of public health emergencies has magnified the risks posed by it. In this study, the authors established an index of the factors influencing the risks posed by MWL along five dimensions: the logistics business, emergency capacity, equipment, personnel, and management. The best-worst case method was used to identify the critical risk-related factors and rank them by importance. Following this, we assessed the risk posed by MWL in four major cities in China as an example and propose the corresponding measures of risk control. The results showed that the linking of business processes was the most important factor influencing the risk posed by MWL. The other critical risk-related factors included the location of the storage site, the capacity for emergency transportation, measures to manage emergencies, and the safety of packaging. Of the cities considered, Beijing was found to be a high-risk city, and its MWL needed to be improved as soon as possible in light of the relevant critical risks. Shanghai, Guangzhou, and Shenzhen were evaluated as general-risk cities, which meant that the risks of MWL were not a priority in these areas, and the other goals of urban development should be comprehensively considered during the long-term planning for MWL in these municipalities.
Transient comparison of techniques to counter multi-drug resistant bacteria: prime modules in curation of bacterial infections
Authors: Naveed Muhammad , Waseem Muhammad , Mahkdoom Izma , Ali Nouman , Asif Farrukh , Hassan Jawad ul , Jamil Hamza
Published: January 2024

Multidrug-resistant organisms are bacteria that are no longer controlled or killed by specific drugs. One of two methods causes bacteria multidrug resistance (MDR); first, these bacteria may disguise multiple cell genes coding for drug resistance to a single treatment on resistance (R) plasmids. Second, increased expression of genes coding for multidrug efflux pumps, which extrude many drugs, can cause MDR. Antibiotic resistance is a big issue since some bacteria may withstand almost all antibiotics. These bacteria can cause serious sickness, making them a public health threat. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Multidrug resistant Mycobacterium tuberculosis (TB), and CRE are gut bacteria that resist antibiotics. Antimicrobial resistance is rising worldwide, increasing clinical and community morbidity and mortality. Superbugs have made antibiotic resistance in some environmental niches even harder to control. This study introduces new medicinal plants, gene-editing methods, nanomaterials, and bacterial vaccines that will fight MDR bacteria in the future.
Optimizing lower limb rehabilitation: the intersection of machine learning and rehabilitative robotics
Authors: Zhang Xiaoqian , Rong Xiyin , Luo Hanwen
Published: January 2024

Lower limb rehabilitation is essential for recovery post-injury, stroke, or surgery, improving functional mobility and quality of life. Traditional therapy, dependent on therapists' expertise, faces challenges that are addressed by rehabilitation robotics. In the domain of lower limb rehabilitation, machine learning is progressively manifesting its capabilities in high personalization and data-driven approaches, gradually transforming methods of optimizing treatment protocols and predicting rehabilitation outcomes. However, this evolution faces obstacles, including model interpretability, economic hurdles, and regulatory constraints. This review explores the synergy between machine learning and robotic-assisted lower limb rehabilitation, summarizing scientific literature and highlighting various models, data, and domains. Challenges are critically addressed, and future directions proposed for more effective clinical integration. Emphasis is placed on upcoming applications such as Virtual Reality and the potential of deep learning in refining rehabilitation training. This examination aims to provide insights into the evolving landscape, spotlighting the potential of machine learning in rehabilitation robotics and encouraging balanced exploration of current challenges and future opportunities.
Use of video-electroencephalography as a first-line examination in veterinary neurology: development and standardization of electroencephalography in unsedated dogs and cats
Authors: Lyon Elsa , Pochat Hervé , Blot Stéphane , Troupel Thibaut , Van Caenegem Nicolas , Besnard Stéphane , Escriou Catherine
Published: January 2024

Objective

To assess the feasibility and validate the use of video-electroencephalography (EEG) in conscious dogs and cats and to propose guidelines of routine EEG in veterinary clinical practice.

Design

Prospective clinical study.

Data

One hundred and fifty EEG recordings were carried out to validate the clinical adding-value, reproducibility, and guidelines on 140 owned animals. One hundred and one EEGs were performed on dogs and 49 on cats.

Procedures

We compared recordings performed with 8 EEG unwired stud Ag/AgCl electrodes held by elastic straps and 8 EEG wired cup Ag electrodes held by a tailor-made manufactured headset combined with a wired video-EEG device. Electrodes placement was determined according to previously published animal EEG protocols. Physiological sensors, such as electrocardiography, electromyography, and respiratory sensors were added. Stimulation protocols were tested. Quality and interpretability were evaluated.

Results

Headsets and recording procedures appeared suitable for all skull shapes and sizes. Video-EEG recordings were successfully performed without tranquilization or anesthesia except for 9 animals. Median EEG recordings time was 40 min. Impedance remained below 20 kΩ in 99% of dog EEGs and 98% of cat EEGs. Isosynchrony was reported in 6% of the channels. Seventy-five percent of dog EEGs and 83% of cat EEGs were readable for more than 50% (to 100%) of their duration. Successful discrimination of vigilance states from rhythm analysis (wakefulness, drowsiness, and sleepiness) was possible in 99% of dog EEGs and 91% of cat EEGs. Photic driving responses during photic stimulations were observed in 11% of dog EEGs and 85% of cat EEGs. Electroencephalography recordings were directly informative in 32% of the examinations: in 25% EEG abnormalities were associated with clinical signs and 7% concerned EEG abnormalities without clinical symptoms during recording. Thirteen percent of dogs subjected to photic stimulation exhibited epileptic anomalies. Among 9 EEGs with other history-based stimulations, three displayed epileptic graphoelements.

Conclusions

We have developed a standardized unanesthetized video-EEG procedure easily performed and reproducible in dogs and cats. Qualitative and quantitative technical and medical criteria were evaluated and were in accordance with human EEG recommendations. Moreover, we have demonstrated its relevance and accuracy for diagnostic purposes, providing further arguments for the use of EEG as a first-line neurological functional exploration test.
A 4-Phase Combined Adhesion Threshold Algorithm for Wheel Slide Protection Systems in Rail Vehicles
Authors: Ma Tianhe , Tian Chun , Wu Mengling , Weng Jingjing
Published: January 2024

The wheel slide protection control system for rail vehicles plays a crucial role in ensuring a consistent braking performance in all operating environments, making it a vital factor in the safety and efficiency of rail transportation. In this paper, a hybrid approach to wheel slide protection control is presented, which combines the rule-based control strategy and the model-based control methods using adhesion force estimation. Model-based control usually relies on mathematical models to characterize the vehicle dynamics, requiring online estimators to be designed or extra sensors to be added for practical application. Rule-based control operates on predefined rules and thresholds and the available data from vehicles in service. A comparative test was conducted between the traditional rule-based control strategy and the proposed combined control strategy using a semi-physical simulation test bench. The performance differences of the control strategies were analyzed from two perspectives: adhesion utilization and air consumption. It was observed that among the traditional 2-phase, 3-phase, 4-phase and the optimized 4-phase combined control method, the combined control strategy has the best adhesion utilization and the traditional 4-phase control strategy has the least air consumption.