bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal antibodies in idiopathic chronic eosinophilic pneumonia: a scoping review
Authors: Murillo Andrea Dionelly , Castrillon Ana Isabel , Serrano Carlos Daniel , Fernandez-Trujillo Liliana
Published: February 2024

Background

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare disease characterized by pulmonary radiological alterations, peripheral eosinophilia, and demonstrated pulmonary eosinophilia. Oral steroids (OSs) are the standard management, but relapses occur in up to 50% of patients during the decrease or suspension of steroids, usually requiring reinitiation of treatment, exposing patients to secondary events derived from the management. Management with monoclonal antibodies has been proposed in these cases to control the disease and limit the secondary effects. The objective is to describe the extent and type of evidence regarding the use of monoclonal antibodies for ICEP.

Methods

A panoramic review of the literature was performed. Observational and experimental studies of pediatric and adult populations that managed recurrent ICEP with monoclonal antibodies were included. Data search, selection, and extraction were performed by two independent reviewers.

Results

937 studies were found. After applying the inclusion and exclusion criteria, 37 titles remained for the final analysis: a retrospective, observational, real-life study, two case series publications, and 34 case reports published in academic poster sessions and letters to the editor. In general, the use of monoclonal antibodies approved for severe asthma could be useful for the control of ICEP, since most of the results show a good response for clinical and radiological outcomes. Biological drugs seem to be a safer option for controlling relapses in ICEP, allowing lowering/suspension of OSs, and sometimes replacing them in patients intolerant to them, patients with significant comorbidities, and patients who have already developed adverse events.

Conclusion

The extent of the evidence supporting management of ICEP with monoclonal antibodies against IL-5 and IgE (omalizumab) is limited, but it could be promising in patients who present frequent relapses, in cortico-dependent individuals, or in patients in whom the use of steroids is contraindicated. The extent of the evidence for management with dupilumab is more limited. Studies with better design and structure are needed to evaluate quality of life and outcomes during a clear follow-up period. To our knowledge, this is the first scoping review of the literature showing the extent of the evidence for the management of ICEP with monoclonal antibodies.
Collagen type IV alpha 1 chain (COL4A1) expression in the developing human lung
Authors: Markasz Laszlo , Mobini-Far Hamid , Sindelar Richard
Published: February 2024

Background

Collagen type IV alpha 1 chain (COL4A1) in the basement membrane is an important component during lung development, as suggested from animal models where COL4A1 has been shown to regulate alveolarization and angiogenesis. Less is known about its role in human lung development. Our aim was to study COL4A1 expression in preterm infants with different lung maturational and clinical features.

Methods

COL4A1 expression in 115 lung samples from newborn infants (21-41 weeks’ gestational age; 0-228 days’ postnatal age [PNA]) was studied by immunohistochemistry combined with digital image analysis. Cluster analysis was performed to find subgroups according to immunohistologic and clinical data.

Results

Patients were automatically categorized into 4 Groups depending on their COL4A1 expression. Expression of COL4A1 was mainly extracellular in Group 1, low in Group 2, intracellular in Group 3, and both extra- and intracellular in Group 4. Intracellular/extracellular ratio of COL4A1 expression related to PNA showed a distinctive postnatal maturational pattern on days 1-7, where intracellular expression of COL4A1 was overrepresented in extremely preterm infants.

Conclusions

COL4A1 expression seems to be highly dynamic during the postnatal life due to a possible rapid remodeling of the basement membrane. Intracellular accumulation of COL4A1 in the lungs of extremely premature infants occurs more frequently between 1 and 7 postnatal days than during the first 24 hours. In view of the lung arrest described in extremely preterm infants, the pathological and/or developmental role of postnatally increased intracellular COL4A1 as marker for basement membrane turnover, needs to be further investigated.
LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma
Authors: Zhou Xiaofeng , Li Zhizun , Li Moyu
Published: February 2024

Background

This Study investigated the role of WWTR1-AS1 in cervical squamous cell carcinoma (CSCC).

Results

WWTR1-AS1 expression was upregulated in CSCC tissues. WWTR1-AS1 was predicted to interact with miR-136, whereas correlation analysis revealed that there was no close correlation between WWTR1-AS1 and miR-136 across CSCC samples. Moreover, WWTR1-AS1 and miR-136 did not regulate the expression of each other. In addition, overexpression of WWTR1-AS1 increased the expression levels of Notch3, which could be targeted by miR-136. Cell stemness analysis indicated that the overexpression of WWTR1-AS1 and Notch3 increased CSCC cell stemness and the capacity of CSCC cell to grow as spheroids. Overexpression of miR-136 decreased CSCC cell stemness and reversed the effects of overexpression of WWTR1-AS1 on Notch3 in CSCC cells.

Conclusion

Therefore, WWTR1-AS1 may upregulate Notch3 through miR-136 to increase cancer cell stemness in CSCC.
‘I don’t want to be a guinea pig’ - Swedish women’s experiences of breast abscess treatment
Authors: Johansson Margareta , Amir Lisa H.
Published: February 2024

Background

It is well known that breastfeeding plays an important role in the health of women and children. However, women are not always given optimal support and most do not reach their breastfeeding goals. About one in five, breastfeeding women report mastitis and a small proportion of these develop a breast abscess. Our aim was to describe the experiences of a group of Swedish breastfeeding women who developed a breast abscess.

Methods

A qualitative cross-sectional study with 18 study participants was undertaken in Sweden in 2017–2018. Potential participants were identified through electronic medical records at a university hospital and invited to participate in audio-recorded telephone interviews. Women were between 2 and 24 months postpartum at the time of the interview, on average 8 months. We conducted a thematic analysis in six steps according to Braun and Clark.

Results

Our analysis identified two themes: 1) Seeking care and receiving treatment was long and unpleasant, and 2) Importance of adequate professional care. Women who experienced a breast abscess were uncertain about where to ask for professional help. They often had a long wait for the right time to undergo the unpleasant and painful procedure of draining their breast abscess. The women felt it was important to receive professional care with respectful communication, continuity of care, and to receive adequate information, but they did not always receive this level of care.

Conclusions

Women with puerperal breast abscesses often fall between medical specialty areas. No longer under the care of obstetricians and maternity services, their problem is too complicated for general practitioners or emergency departments, but not regarded as serious by breast surgeons. Healthcare professionals urgently need adequate training in order to deal with breastfeeding problems and be able to offer women-centred care.
A survey of barriers and facilitators to the adoption of buprenorphine prescribing after implementation of a New Jersey-wide incentivized DATA-2000 waiver training program
Authors: Nyaku Amesika N. , Zerbo Erin A. , Chen Clement , Milano Nicole , Johnston Barbara , Chadwick Randall , Marcello Stephanie , Baston Kaitlan , Haroz Rachel , Crystal Stephen
Published: February 2024

Background

Opioid-involved overdose deaths continue to rise in the US, despite availability of highly effective treatments for opioid use disorder (OUD), in part due to the insufficient number of treatment providers. Barriers include the need for providers to gain expertise and confidence in providing MOUD to their patients who need these treatments. To mitigate this barrier, New Jersey sponsored a buprenorphine training program with financial incentives for participation, which met the then existing requirement for the DATA-2000 waiver. In a 2019 follow-up survey, participants reported on barriers and facilitators to subsequent buprenorphine prescribing.

Methods

Participants in the training program completed a 10-min electronic survey distributed via email. The survey addressed demographics, practice characteristics, current buprenorphine prescribing, and barriers and facilitators to adoption and/or scale up of buprenorphine prescribing.

Results

Of the 440 attendees with a valid email address, 91 individuals completed the survey for a response rate of 20.6%. Of the 91 respondents, 89 were eligible prescribers and included in the final analysis. Respondents were predominantly female (n = 55, 59.6%) and physicians (n = 55, 61.8%); representing a broad range of specialties and practice sites. 65 (73%) of respondents completed the training and DEA-registration, but only 31 (34.8%) were actively prescribing buprenorphine. The most frequently cited barriers to buprenorphine prescribing were lack of access to support services such as specialists in addiction, behavioral health services, and psychiatry. The most frequently reported potential facilitators were integrated systems with direct access to addiction specialists and psychosocial services, easier referral to behavioral health services, more institutional support, and improved guidance on clinical practice standards for OUD treatment.

Conclusion

More than half (52.3%) of those who completed incentivized training and DEA registration failed to actively prescribe buprenorphine. Results highlight provider perceptions of inadequate availability of support for the complex needs of patients with OUD and suggest that broader adoption of buprenorphine prescribing will require scaling up support to clinicians, including increased availability of specialized addiction and mental health services.
Association between atherogenic index of plasma control level and incident cardiovascular disease in middle-aged and elderly Chinese individuals with abnormal glucose metabolism
Authors: Min Qianqian , Wu Zhigang , Yao Jiangnan , Wang Siyi , Duan Lanzhi , Liu Sijia , Zhang Mei , Luo Yanhong , Ye Dongmei , Huang Yuxu , Chen Lan , Xu Ke , Zhou Jianghua
Published: February 2024

Background

The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism.

Methods

Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis.

Results

398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90–1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99–1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01–2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03–2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables.

Conclusions

In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.
Artificial nighttime lighting impacts Plasmodium falciparum mature stage V gametocytes infectivity in Anopheles stephensi
Authors: Llergo Jose Luis , Garuti Helena , Lopez Celia , Sanchez Julia , Calvo David
Published: February 2024

Background

Malaria is one of the most important vector-borne diseases of humans with an estimated 241 million cases worldwide in 2020. As an urban and periurban mosquito species, Anopheles stephensi is exposed to artificial human stimuli like light that can alter many aspects of mosquito behaviour, physiology and metabolism. Therefore, fluctuations in the light environment may influence the host, parasite and/or mosquito biology and hence modulate risk for disease transmission. In this study, the effect of artifitial light at night on mosquito infectivity by Plasmodium falciparum during the first hours of blood digestion was tested.

Methods

A total of three independent standard membrane feeding assays were performed to artificially fed septic and aseptic mosquitoes with P. falciparum infected blood. After blood feeding, females were transferred to incubators with different photoperiod cycles, so digestion occurred under day artificial light or dark. At 7 and 16 days post blood feeding, mosquitoes were dissected for midguts and salivary glands, respectively. Percentage of mosquitoes fed, percentage of prevalence and P. falciparum oocyst intensity between septic and aseptic mosquitoes in the two different photoperiod regimes, were compared using a Kruskal-Wallis test followed by a Dunn´s multiple comparison test .

Results

The exposition of mosquitoes to light after they took an infected blood meal has a negative effect on the successful progression of P. falciparum in the mosquito midgut. Antibiotic treatment significantly incremented the number of oocysts per midgut. Photophase significantly reduced the median oocyst intensity in both septic and aseptic mosquitoes. The percentage of oocyst reduction, understood as the percentage of reduction in the mean oocyst intensity of the parasite in the mosquito midgut between photophase and scotophase, was 51% in the case of aseptic mosquitoes and 80% for septic mosquitoes, both in the photophase condition.

Conclusion

Although there are still many gaps in the understanding of parasite-mosquito interactions, these results support the idea that light can, not only, influence mosquito biting behaviour but also parasite success in the mosquito midgut. Hence, light can be considered an interesting additional mosquito-control strategy to reduce mosquito-borne diseases.
Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan
Authors: Kobayashi Takao , Sugiura Kazuko , Ojima Toshiyuki , Serizawa Mariko , Hirai Kyuya , Morishita Eriko
Published: February 2024

Background

 We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan.

Methods

We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology.

Results

Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction.

Conclusions

This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications.
Diagnostic potential of NRG1 in benign nerve sheath tumors and its influence on the PI3K-Akt signaling and tumor immunity
Authors: Yan Suwei , Zhao Jingnan , Gao Pengyang , Li Zhaoxu , Li Zhao , Liu Xiaobing , Wang Pengfei
Published: February 2024

Objective

Benign nerve sheath tumors (BNSTs) present diagnostic challenges due to their heterogeneous nature. This study aimed to determine the significance of NRG1 as a novel diagnostic biomarker in BNST, emphasizing its involvement in the PI3K-Akt pathway and tumor immune regulation.

Methods

Differential genes related to BNST were identified from the GEO database. Gene co-expression networks, protein-protein interaction networks, and LASSO regression were utilized to pinpoint key genes. The CIBERSORT algorithm assessed immune cell infiltration differences, and functional enrichment analyses explored BNST signaling pathways. Clinical samples helped establish PDX models, and in vitro cell lines to validate NRG1’s role via the PI3K-Akt pathway.

Results

Nine hundred eighty-two genes were upregulated, and 375 downregulated in BNST samples. WGCNA revealed the brown module with the most significant difference. Top hub genes included NRG1, which was also determined as a pivotal gene in disease characterization. Immune infiltration showed significant variances in neutrophils and M2 macrophages, with NRG1 playing a central role. Functional analyses confirmed NRG1’s involvement in key pathways. Validation experiments using PDX models and cell lines further solidified NRG1’s role in BNST.

Conclusion

NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.
Direct osteosynthesis in the treatment of atlas burst fractures: a systematic review
Authors: Niu He-Gang , Zhang Jing-Jing , Yan Yi-Zhu , Yang Kun , Zhang Yin-Shun
Published: February 2024

Purpose

The treatment of unstable atlas fractures remains a controversial topic. The study aims at assessing the prognosis and efficacy of osteosynthesis for unstable atlas fractures through a review of the current literature and additionally aims to compare outcomes between the transoral and posterior approaches.

Methods

A systematic review of databases including PubMed, EMBASE, Cochrane, Web of Science, CNKI, and Wanfang was conducted. Titles and abstracts were screened by two reviewers to identify studies meeting pre-defined inclusion criteria for comprehensive analysis.

Results

The systematic review included 28 articles, 19 employing the posterior approach and 9 utilizing the transoral approach. It covered osteosynthesis in 297 patients with unstable atlas fractures, comprising 169 treated via the posterior approach and 128 via the transoral approach. Analysis revealed high healing rates and clinical improvement in both approaches, evidenced by improvements in the visual analog scale, range of motion, atlantodens interval, and lateral displacement distance post-surgery.

Conclusion

Osteosynthesis offers effective treatment for unstable atlas fractures. Both transoral and posterior approaches can achieve good clinical outcomes for fracture, and biomechanical studies have confirmed that osteosynthesis can maintain the stability of the occipitocervical region, preserve the motor function of the atlantoaxial and occipito-atlantoaxial joints, and greatly improve the quality of life of patients. However, variations exist in the indications and surgical risks associated with each method, necessitating their selection based on a thorough clinical evaluation of the patient's condition.
Simple and secure thrombectomy without circulatory arrest for acute pulmonary embolism
Authors: Sasaki Hanae , Kowatari Ryosuke , Kondo Norihiro , Minakawa Masahito
Published: February 2024

Background

Surgical pulmonary artery thrombectomy is a well-established emergency treatment for massive pulmonary embolism (PE) in which fibrinolysis or thrombolysis are not effective. However, surgery for massive PE that requires peripheral pulmonary artery thrombus removal remains challenging. We established a simple and secure pulmonary artery thrombectomy method using cardiopulmonary bypass and cardiac arrest. In this procedure, the surgical assistant arm, typically used for coronary artery bypass grafting, is used to obtain a feasible working space during thrombectomy.

Case presentation

We present seven consecutive massive PE cases that were treated with the present surgical method and successfully weaned from cardiopulmonary bypass or extracorporeal membrane oxygenation postoperatively.

Conclusions

This procedure can be used to prevent right ventricular failure after surgery as surgeons can remove the peripheral thrombus with clear vision up to the second branch of the pulmonary artery.
Modified blade: an interventional option in rigid bronchoscopy for non-resectable benign tracheal stenosis
Authors: Messina Gaetana , Di Filippo Vincenzo , Capasso Francesca , Puca Maria Antonietta , Leonardi Beatrice , Grande Mario , Rainone Anna , Leone Francesco , Vicario Giuseppe , De Gregorio Simona , Cerullo Giuseppe , Ponticiello Antonio , Pirozzi Mario , Farese Stefano , Zotta Alessia , Natale Giovanni , Messina Giovanni , Vicidomini Giovanni , Fiorelli Alfonso , Ciardiello Fortunato , Fasano Morena
Published: February 2024

Introduction

Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis.

Materials and methods

The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o’clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure.

Result

We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of ‘Luigi Vanvitelli’ of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis.

Conclusion

Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.
RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling
Authors: Zhou Yu-Jiao , Yang Min-Li , He Xin , Gu Hui-Ying , Ren Ji-Hua , Cheng Sheng-Tao , Fu Zhou , Zhang Zhen-Zhen , Chen Juan
Published: February 2024

Background

Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood.

Methods

By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis.

Results

Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7.

Conclusions

Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.
Molecular insights versus morphological traits: rethinking identification of the closely related Angiostrongylus cantonensis and Angiostrongylus malaysiensis
Authors: Kaenkaew Chanisara , Chan Abigail Hui En , Saralamba Naowarat , Ruangsittichai Jiraporn , Chaisiri Kittipong , Charoennitiwat Vachirapong , Thaenkham Urusa
Published: February 2024

Background

The closely related Angiostrongylus cantonensis and Angiostrongylus malaysiensis have been reported to coexist in Thailand and share similar hosts and life cycles. Recently, in an angiostrongyliasis outbreak in Thailand, both A. cantonensis and A. malaysiensis were found in the cerebrospinal fluid of affected patients. Morphological similarities, overlapping distribution, shared hosts and habitats, and the close genetics of the two Angiostrongylus species can complicate accurate species identification. Addressing these challenges, this study aims to evaluate whether a correlation between the morphological and genetic identities of A. cantonensis and A. malaysiensis can improve species identification accuracy.

Methods

Angiostrongylus spp. specimens from five zoogeographical regions in Thailand were subjected to morphological and molecular identification using the mitochondrial cytochrome b gene and the nuclear internal transcribed spacer 2 region (ITS2). The morphological characters for males and females were then validated using the species identity obtained from the nuclear ITS2 region.

Results

The results revealed that morphological misidentifications between these two closely related species are common due to overlapping morphological characters. Although certain male traits such as body length and width aided species differentiation, female traits were found to be less reliable. Furthermore, hybrid forms (8.2%) were revealed through the ITS2 results, which can further complicate morphological identification. Mito-nuclear discordance was also present in 1.9% of the Angiostrongylus specimens from Thailand, suggesting a complex historical interbreeding between the species.

Conclusions

Based on our findings, we suggest that nuclear ITS2 is a reliable marker for species identification of A. cantonensis and A. malaysiensis, especially in regions where both species coexist. Additionally, the scope and consequences of hybridization between the two closely related Angiostrongylus species should be further investigated in Thailand.

Graphical Abstract
Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg
Authors: Ukalovic Dubravka , Leeb Burkhard F. , Rintelen Bernhard , Eichbauer-Sturm Gabriela , Spellitz Peter , Puchner Rudolf , Herold Manfred , Stetter Miriam , Ferincz Vera , Resch-Passini Johannes , Zwerina Jochen , Zimmermann-Rittereiser Marcus , Fritsch-Stork Ruth
Published: February 2024

Objectives

Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg).

Methods

Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted.

Results

The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54–0.78); adalimumab, 0.70 (95% CI, 0.68–0.74); certolizumab, 0.84 (95% CI, 0.79–0.89); etanercept, 0.68 (95% CI, 0.55–0.87); tocilizumab, 0.72 (95% CI, 0.69–0.77).

The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD.

Conclusion

Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.
Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney
Authors: Sandersfeld Mira , Büttner-Herold Maike , Ferrazzi Fulvia , Amann Kerstin , Benz Kerstin , Daniel Christoph
Published: February 2024

Background

Macrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters.

Methods

Using immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients.

Results

The frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease.

Conclusion

Although M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.
Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report
Authors: Pethő Ákos , Schnabel Karolina , Dézsi László
Published: February 2024

Background

Hemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment.

Case presentation

This report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful.

Conclusion

Numerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here.
The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy
Authors: Ahmed Toka A. , Ahmed Sara M. , Elkhenany Hoda , El-Desouky Mohamed A. , Magdeldin Sameh , Osama Aya , Anwar Ali Mostafa , Mohamed Ihab K. , Abdelgawad Mohamed Essameldin , Hanna Demiana H. , El-Badri Nagwa
Published: February 2024

Background

Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs.

Methods

PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days.

Results

Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-β, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain.

Conclusion

These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Graphical abstract
Diversity of endophytic bacteria isolated from leguminous agroforestry trees in western Kenya
Authors: Emitaro William Omuketi , Kawaka Fanuel , Musyimi David Mutisia , Adienge Asenath
Published: February 2024

Plants have diverse and vast niches colonized by endophytic microorganisms that promote the wellbeing of host plant. These microbes inhabit internal plant tissues with no signs of ill health. Bacterial endophytes from many plants have been isolated and characterized due to their beneficial roles however their diversity in leguminous plants still remain unexploited. Diversity of bacterial endophytes isolated from Sesbania sesban, Leucaena diversifolia and Calliandra calothyrsus was assessed using morphological and molecular characteristics. A total of 27 pure isolates were recovered from C. Calothyrsus, L. diversifolia and S. sesban constituting 44.4%, 33.3% and 22.2% from the leaves, stems and roots respectively. The isolates differentiated into Gram positive and negative with rods and spherical shapes. Analysis of 16S rRNA gene sequences revealed 8 closely related bacterial genera that consisted of Bacillus (33.3%), Staphylococcus (22.2%), Alcaligens (11.1%), Pantoea (11.1%), Xanthomonas,and Sphingomonas (7.4%) each. Others included Acinetobacter, and Pseudomonas at 3.7% each. Bacterial endophytes of genus bacillus were isolated from all the three plants. These results indicate the presence of high diversity of endophytic bacteria associated with the different parts of L. diversifolia, S. sesban and C. salothyrsus growing in western Kenya.
Feeling safe in the context of digitalization in healthcare: a scoping review
Authors: Minartz Peter , Aumann Christine Maria , Vondeberg Carmen , Kuske Silke
Published: February 2024

Background

Digitalization in healthcare and society can be challenging, particularly for people who have limited digital experiences. New digital technologies can influence individuals’ perceived safety and well-being. In this study, we aimed to identify and analyze the literature on needs and influencing factors in the context of emotional and psychological safety and digitalization in healthcare.

Methods

A scoping review was conducted based on the PRISMA-ScR standard. The literature was searched based on the databases Medline via PubMed, PsycINFO via Ovid, and CINAHL via EBSCO. Literature was included after a review of the titles, abstracts, and full texts published in English or German in the last 5 years (October 2017–September 2022). Eligible literature included definitions and descriptions of emotional and/or psychological safety and was related to digitalization in healthcare and was analyzed qualitatively via inductive content analysis. The findings were analyzed from ethical, psychosocial, legal, economic, and political perspectives.

Results

A total of 32 publications were finally included thereof qualitative (n = 20), quantitative (n = 3), and mixed methods (n = 2) studies. Other included publications were systematic integrative reviews, scoping reviews, narrative reviews, white papers, and ethical statements. Of these publications, four qualitative studies focused on emotional or psychological safety in the context of digital technology use in healthcare as a primary research aim. Most literature has shown that perceived safety is influenced by perceived changes in healthcare, digital (health) literacy, the design of digital technology, and need orientation. The needs identified in this context overlap strongly with the influencing factors. A low or high perceived safety has an impact on users’ thoughts and actions.

Conclusion

The importance of emotional safety in the context of digital technologies in healthcare is growing, while psychological safety seems to be underrepresented. The interaction between the influencing factors and the need to feel safe leads to considerations that can affect user behavior and have far-reaching outcomes for the implementation of digital technology in healthcare.

Systematic review registration

Open Science Framework Registries on 16 December 2022 https://doi.org/10.17605/OSF.IO/HVYPT.
Harmfulness metrics in digital twins of social network rumors detection in cloud computing environment
Authors: Li Hao , Yang Wu , Wang Wei , Wang Huanran
Published: February 2024

Social network rumor harm metric is a task to score the harm caused by a rumor by analyzing the spreading range of the rumor, the users affected, the repercussions caused, etc., and then the harm caused by the rumor. Rumor hazard metric models can help rumor detection digital twins to understand and analyze user behaviors and assist social network network managers to make more informed decisions. However, there is a lack of models that can quantify the harm of rumors and automated harm metric models in rumor detection digital twins. To address this issue, this paper proposes an innovative social network rumor harm metric based on rumor propagation knowledge and a large language model (LLM), RSK-T5. The method first completes the joint task of rumor comment stance detection and sentiment analysis to capture critical features of rumor propagation. Then, this knowledge is used in the pre-training process of LLM to improve the model's understanding of rumor propagation patterns. Finally, the fine-tuning phase focuses on the hazard metrics task to improve the generalization energy. We compare with some existing variants of rumor detection methods, and experimental results demonstrate that RSK-T5 achieves the lowest MSE scores on three well-known rumor detection datasets. The ablative learning work demonstrates the effectiveness of RSK-T5's knowledge of two rumor spreads.
Prevalence of dyslipidemia and associated factors in sedentary occupational population from Shanghai: a cross-sectional study
Authors: Gu Dongxing , Wang Dandan , Zhu Qinzhong , Luo Li , Zhang Tiantian
Published: February 2024

Background

Dyslipidemia is a major risk factor for cardiovascular diseases, but its prevalence and determinants among sedentary occupational population are poorly understood. This study aimed to investigate the prevalence and associated factors for dyslipidemia among a sedentary occupational population in Shanghai, China.

Methods

We collected data from 35,950 sedentary occupational workers on their demographics, social, medical, and family history, lifestyle, anthropometry, and biochemistry. We used the 2016 Chinese guideline for the management of dyslipidemia in adults to define dyslipidemia and its subtypes. We performed multivariate logistic regression to examine the factors associated with dyslipidemia.

Results

The prevalence of dyslipidemia was 29.10%, with 15.86% for high triglycerides (TG), 6.43% for high total cholesterol (TC), 5.37% for high low-density lipoprotein cholesterol (LDL-C), and 14.68% for low high-density lipoprotein cholesterol (HDL-C). Men had a significantly higher prevalence of dyslipidemia than women (39.64% vs. 12.43%, P < 0.01). Factors associated with dyslipidemia included older age, being married, longer sedentary time while resting, frequent intake of animal viscera, current smoking, hypertension, diabetes, and obesity. Current drinking was associated with a 1.24 times higher prevalence of high TG (P < 0.01). Current smokers were less likely to have low HDL-C than non-smokers.

Conclusions

Our present study, in a population of 35,950 sedentary occupational workers from Shanghai, demonstrated a prevalence of dyslipidemia, but lower than in other previous studies without the limitation of occupational characteristics. Prevention and control measures for dyslipidemia should take into account the characteristics and related factors for this population group.