bluuebunny/crossref_metadata_2025 huggingface dataset:
Concentrations of selected immunological parameters in the serum and processing fluid of suckling piglets and the serum and colostrum of their mothers
Authors: Augustyniak Agata , Czyżewska-Dors Ewelina , Pomorska-Mól Małgorzata
Published: May 2024

Background

Blood sampling from neonatal piglets is related to multiple disadvantages. Therefore, a new, alternative matrix is required to assess piglets’ early immune status efficiently. The present study aimed to assess the usefulness of processing fluid for determining selected piglets’ immune parameters. 264 pigs − 31 sows, 146 male piglets, and 87 female piglets from commercial indoor farrow-to-finish pig herd were included in this study. 264 serum, 31 colostrum, and 146 processing fluid samples were collected. Serum was collected from all animals, colostrum was collected from sows, and processing fluid was collected from male piglets only. Using commercial ELISA tests, the concentration of various immunoglobulins, cytokines, and acute phase proteins was assessed in each matrix. Statistical analyses were employed to determine differences in the concentration of measured indices between piglets’ serum and processing fluid and correlations in the concentration of tested indices between particular sets of matrices.

Results

Statistical analyses did not reveal significant differences in the IgG, IgA, IL-1β, IL-4, IL-6, and IFN-γ concentration between piglets’ serum and processing fluid (p > 0.05). A positive correlation (p < 0.05) regarding the concentration of some indices between processing fluid and samples collected from sows was also observed.

Conclusions

Processing fluid can be considered a promising alternative to blood for assessing some immunological indices in piglets, such as IgG, IgA, IL-1β, IL-4, IL-6, and IFN-γ, and, possibly, in the indirect assessment of some indices in lactating sows, including IgA, IL-1β, IL-4, IL-6, IL-8, IFN-γ, or Pig-MAP.
A comparative study of the risk assessment and heavy metal contamination of coastal sediments in the Red sea, Egypt, between the cities of El-Quseir and Safaga
Authors: Elgendy Ahmed R. , El Daba Abd El Mohsen S. , El-Sawy Mohamed A. , Alprol Ahmed E. , Zaghloul Ghada Y.
Published: May 2024

This study aimed to assess the influence of pollution on the quality of sediments and the risks associated with El-Qusier and Safaga Cities, Red Sea, Egypt, during 2021, divided into four sectors, using multiple pollution indices. To achieve that, we evaluated the metal pollution index (MPI), contamination factor (Cf), pollution load index (PLI), contamination security index (CSI), and anthropogenicity (Anp%). Moreover, carcinogenic and non-carcinogenic risks are used for human health hazards. Results indicated that Mn and Fe recorded the highest concentrations, whereas Cd had the lowest. El-Quseir City sediments were found the following metal ions: Fe > Mn > Ni > Zn > Cu > Co > Pb > Cd, where the order in the Safaga City was: Fe > Mn > Zn > Ni > Cu > Pb > Co > Cd. MPI > 1, this is alarming in the study area due to heavy metal pollution. In addition, Cf < 1 in all metals except Cd with contamination degree CD ranged from low to considerable contamination in El-Qusier city. In contrast, contamination ranged from significant to very high in Safaga city. PLI < 1 is lower than the reference at all monitored stations. CSI values ranged from relatively low to moderate. Besides Cd, data reflect each element's low environmental danger (EriMe40). This study's risk index (RI) is low to moderate in Sector 1 and high to extremely high in Sector 2. HQ and HI index < 1 means it is safe for human health in order: HI ingestion > HI dermal. CSR for different pathways was recorded as dermal > ingestion, in which total CSR for all paths is considered harmful, and the cancer risk is troublesome and higher than the reference ranges of 1 × 10–6–1 × 10–4. In conclusion, the examined heavy metals provide environmental hazards across the assessed locations.
When the smoke gets in your lungs: short-term effects of Indonesia’s 2015 forest fires on health care use
Authors: Sambodo Novat Pugo , Pradhan Menno , Sparrow Robert , van Doorslaer Eddy
Published: May 2024

Background

The forest fires that ravaged parts of Indonesia in 2015 were the most severely polluting of this century but little is known about their effects on health care utilization of the affected population. We estimate their short-term impact on visit rates to primary and hospital care with particular focus on visits for specific smoke-related conditions (respiratory disease, acute respiratory tract infection (ARTI) and common cold).

Method

We estimate the short-term impact of the 2015 forest fire on visit rates to primary and hospital care by combining satellite data on Aerosol Optical Depth (AOD) with administrative records from Indonesian National Health Insurance Agency (BPJS Kesehatan) from January 2015–April  2016. The 16 months of panel data cover 203 districts in the islands of Sumatra and Kalimantan before, during and after the forest fires. We use the (more efficient) ANCOVA version adaptation of a fixed effects model to compare the trends in healthcare use of affected districts (with AOD value above 0.75) with control districts (AOD value below 0.75). Considering the higher vulnerability of children’s lungs, we do this separately for children under 5 and the rest of the population adults (> 5), and for both urban and rural areas, and for both the period during and after the forest fires.

Results

We find little effects for adults. For young children we estimate positive effects for care related to respiratory problems in primary health care facilities in urban areas. Hospital care visits in general, on the other hand, are negatively affected in rural areas. We argue that these patterns arise because accessibility of care during fires is more restricted for rural than for urban areas.

Conclusion

The severity of the fires and the absence of positive impact on health care utilization for adults and children in rural areas indicate large missed opportunities for receiving necessary care. This is particularly worrisome for children, whose lungs are most vulnerable to the effects. Our findings underscore the need to ensure ongoing access to medical services during forest fires and emphasize the necessity of catching up with essential care for children after the fires, particularly in rural areas.
Ferroptotic therapy in cancer: benefits, side effects, and risks
Authors: Diao Jiandong , Jia Yuanyuan , Dai Enyong , Liu Jiao , Kang Rui , Tang Daolin , Han Leng , Zhong Yingjie , Meng Lingjun
Published: May 2024

Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various cancer types. However, it can lead to side effects, including immune cell death, bone marrow impairment, liver and kidney damage, cachexia (severe weight loss and muscle wasting), and secondary tumorigenesis. In this review, we discuss the advantages and offer an overview of the diverse range of documented side effects. Furthermore, we examine the underlying mechanisms and explore potential strategies for side effect mitigation.
Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options
Authors: Gao Hongli , Xi Zhuo , Dai Jingwei , Xue Jinqi , Guan Xin , Zhao Liang , Chen Zhiguang , Xing Fei
Published: May 2024

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.
Exploring the opinions and potential impact of unflavoured e-liquid on smoking cessation among people who smoke and smoking relapse among people who previously smoked and now use e-cigarettes: findings from a UK-based mixed methods study
Authors: Khouja Jasmine N. , Dyer Maddy L. , Havill Michelle A. , Dockrell Martin J. , Munafò Marcus R. , Attwood Angela S.
Published: May 2024

Background

Although electronic cigarettes (e-cigarettes) appear to be effective in helping people who smoke to stop smoking, concerns about use of e-cigarettes among young people have led to restrictions on non-tobacco flavoured e-liquids in some countries and some US states. These restrictions could reduce the appeal of these products to non-smoking youth but could have negative consequences for people who smoke or use e-cigarettes.

Methods

In this mixed methods study, we recruited UK adults who smoked or used to smoke and subsequently vaped to explore their opinions of unflavoured e-liquids and their beliefs about how they would be impacted by hypothetical e-liquid flavour restrictions. Participants trialled an unflavoured e-liquid instead of their usual nicotine product for four hours and completed a survey and an online interview.

Results

Using Interpretive Phenomenological Analysis and graphically presented data, we found differences in participants’ opinions of unflavoured e-liquid. If only unflavoured, tobacco flavoured, and menthol flavoured e-liquids remained on the UK market, some people who smoke or vape may be unaffected, but some may relapse to smoking or continue smoking. Despite most wanting to prevent young people from initiating vaping, participants had varying opinions on whether flavour restrictions would be an effective method.

Conclusions

The findings highlight that people who smoke and vape could be impacted by flavour restrictions in a range of ways, some of which could have a potential adverse impact on harm reduction efforts in the UK (e.g., by making smoking more appealing than vaping).
Signaling, cancer cell plasticity, and intratumor heterogeneity
Authors: Cordani Marco , Dando Ilaria , Ambrosini Giulia , González-Menéndez Pedro
Published: May 2024

Cancer’s complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in effective cancer management. Variability within a tumor arises from the existence of diverse populations of cancer cells, impacting the progression, spread, and resistance to treatments. At the core of this variability is the concept of cellular plasticity - the intrinsic ability of cancer cells to alter their molecular and cellular identity in reaction to environmental and genetic changes. This adaptability is a cornerstone of cancer’s persistence and progression, making it a formidable target for treatments. Emerging studies have emphasized the critical role of such plasticity in fostering tumor diversity, which in turn influences the course of the disease and the effectiveness of therapeutic strategies. The transformative nature of cancer involves a network of signal transduction pathways, notably those that drive the epithelial-to-mesenchymal transition and metabolic remodeling, shaping the evolutionary path of cancer cells. Despite advancements, our understanding of the precise molecular machinations and signaling networks driving these changes is still evolving, underscoring the necessity for further research. This editorial presents a series entitled “Signaling Cancer Cell Plasticity and Intratumor Heterogeneity” in Cell Communication and Signaling, dedicated to unraveling these complex processes and proposing new avenues for therapeutic intervention.
Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis
Authors: Sharifi Aliabadi Leyla , Azari Mojtaba , Taherian Mohammad Reza , Barkhordar Maryam , Abbas Syed Aon Mehdi , Azari Morteza , Ahmadvand Mohammad , Salehi Zahra , Rouzbahani Shiva , Vaezi Mohammad
Published: May 2024

Background

Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients.

Results

This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn’t respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%.

Conclusion

While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.
Burden of cardiovascular disease attributed to air pollution: a systematic review
Authors: Khoshakhlagh Amir Hossein , Mohammadzadeh Mahdiyeh , Gruszecka-Kosowska Agnieszka , Oikonomou Evangelos
Published: May 2024

Background

Cardiovascular diseases (CVDs) are estimated to be the leading cause of global death. Air pollution is the biggest environmental threat to public health worldwide. It is considered a potentially modifiable environmental risk factor for CVDs because it can be prevented by adopting the right national and international policies. The present study was conducted to synthesize the results of existing studies on the burden of CVDs attributed to air pollution, namely prevalence, hospitalization, disability, mortality, and cost characteristics.

Methods

A systematic search was performed in the Scopus, PubMed, and Web of Science databases to identify studies, without time limitations, up to June 13, 2023. Exclusion criteria included prenatal exposure, exposure to indoor air pollution, review studies, conferences, books, letters to editors, and animal and laboratory studies. The quality of the articles was evaluated based on the Agency for Healthcare Research and Quality Assessment Form, the Newcastle–Ottawa Scale, and Drummond Criteria using a self-established scale. The articles that achieved categories A and B were included in the study.

Results

Of the 566 studies obtained, based on the inclusion/exclusion criteria, 92 studies were defined as eligible in the present systematic review. The results of these investigations supported that chronic exposure to various concentrations of air pollutants, increased the prevalence, hospitalization, disability, mortality, and costs of CVDs attributed to air pollution, even at relatively low levels. According to the results, the main pollutant investigated closely associated with hypertension was PM2.5. Furthermore, the global DALY related to stroke during 2016–2019 has increased by 1.8 times and hospitalization related to CVDs in 2023 has increased by 8.5 times compared to 2014.

Conclusion

Ambient air pollution is an underestimated but significant and modifiable contributor to CVDs burden and public health costs. This should not only be considered an environmental problem but also as an important risk factor for a significant increase in CVD cases and mortality. The findings of the systematic review highlighted the opportunity to apply more preventive measures in the public health sector to reduce the footprint of CVDs in human society.
Factors influencing the posterior cruciate ligament buckling phenomenon—a multiple linear regression analysis of bony and soft tissue structures of the knee joint
Authors: Zhang Jiaying , Huang Tianwen , Jia Zhenyu , Yang Yangyang , Tsai Tsung-Yuan , Li Pingyue
Published: May 2024

Purpose

To determine whether posterior cruciate ligament (PCL) buckling (angular change) is associated with anterior cruciate ligament (ACL) status (intact or ruptured), meniscal bone angle (MBA), anterior tibial translation (ATT), body weight, femoral-tibial rotation (FTR), posterior tibial slope (PTS), PCL length and femoral-tibial distance (FTD) and to identify the factors that have the greatest influence.

Methods

All enrolled participants were scanned with a 3.0 T, 8-channel coil MRI system (Magnetom Verio; Siemens). Bone and soft tissue parameters were measured by MIMICS software for each subject and each measured parameter was correlated with PCL buckling phenomena. The correlated and statistically significant parameters were then analyzed by multiple linear regression to determine the magnitude of the effect of the different parameters on the PCL buckling phenomenon.

Results

A total of 116 subjects (50 ACL ruptured and 66 age, weight and height matched volunteers with uninjured knees) were enrolled. Among all measured parameters, there were 8 parameters that correlated with PCL angle (PCLA), of which ACL status had the strongest correlation with PCLA (r = − 0.67, p =  < 0.001); and 7 parameters that correlated with PCL-posterior femoral cortex angle (PCL-PCA), of which ATT had the strongest correlation with PCL-PCA (r = 0.69, p =  < 0.001). PCLIA was not significantly correlated with any of the measured parameters. Multiple linear regression analyses revealed four parameters can explain PCLA, of which ACL status had the strongest effect on PCLA (absolute value of standardized coefficient Beta was 0.508). Three parameters can explain PCL-PCA, of which ATT had the strongest effect on PCLIA (r = 0.69, p = < 0.001), ATT has the greatest effect on PCL-PCA (absolute value of normalized coefficient Beta is 0.523).

Conclusions

PCLA may be a simple and easily reproducible and important supplement for the diagnosis of ACL injury; PCL-PCA is a simple and easily reproducible and important complementary tool for the detection of ATT. The use of PCLA is more recommended to aid in the diagnosis of ACL injury.
Randomised controlled trial of tourniquet associated pain generated in lower limb after exsanguination by Esmarch bandage versus limb elevation
Authors: Mitrichev Alexander , Maunder John , Jabur Aiden , Singh Prince , Lees Deborah , Morse Levi , Parkinson Benjamin
Published: May 2024

Background

Tourniquets are common adjuncts in the operating theatre but can be associated with post-operative pain. This study was designed to compare what effect pre-tourniquet Esmarch bandage exsanguination has on pain, compared to pre-tourniquet exsanguination by elevation alone.

Methods

52 volunteers (104 lower limbs) were included in this study with each volunteer acting as their own matched control. The primary outcome was patient reported pain, measured in both legs simultaneously using area under curve. Secondary outcomes were pain score during inflation and deflation, cumulative pain score, duration of recovery and blood pressure during testing.

Results

Pain after Esmarch was superior to elevation as measured by area under pain curve (68.9 SD 26.1 vs 77.2 SD 27.3, p = 0.0010), independent of leg dominance. Cumulative pain scores demonstrated the same superiority after inflation (50.7 SD 17.1 vs 52.9 SD 17.0, p = 0.026) but not after deflation (p = 0.59). Blood pressure was not significantly different. Time to full recovery of the lower limb was the same for both groups—7.6 min (SD 2.1 min, p = 0.80).

Conclusion

Previous studies describe a positive effect on pain when Esmarch bandage was used prior to tourniquet inflation for upper limb. Our findings suggest the same benefit from Esmarch when it was used on lower limbs—particularly during inflation of tourniquet. In addition to pain profiles, surgeon preference and patient factors need to be considered when deciding between elevation and Esmarch bandage.
Childhood maltreatment and alcohol and tobacco use trajectories in rural Chinese adolescents
Authors: Niu Li , French Doran C. , Wang Yuyan , Sun Jianing , Lin Danhua
Published: May 2024

Background

There is a high prevalence of childhood maltreatment among Chinese children and adolescents, but little is known about its impact on alcohol and tobacco use trajectories and how positive school and neighborhood environments moderate the associations. The objective of this study was to assess the association between multiple forms of childhood maltreatment and longitudinal alcohol and tobacco use trajectories, and to assess the possibility that perceived connections to school and neighborhood moderate these associations.

Methods

This longitudinal cohort study included 2594 adolescents (9 to 13 years) from a low-income rural area in China. Childhood exposure to abuse and neglect was assessed using the Childhood Trauma Questionnaire. Participants reported past-month alcohol and tobacco use at three time points over 1 year.

Results

Growth curve models revealed that childhood sexual abuse was associated with a higher risk of past-month drinking (OR = 1.53, 95% CI 1.19–2.03, p < 0.001) and smoking (OR = 1.82, 95% CI 1.30–2.55, p < 0.001). Neglect was associated with a higher risk of past-month drinking (OR = 1.52, 95% CI 1.06–1.90, p < 0.05) and smoking (OR = 2.02, 95% CI 1.34–3.02, p < 0.001). None of the maltreatment forms predicted a faster increase in either drinking or smoking. These associations were found independent of personal, family, and contextual characteristics. School and neighborhood connection moderated the association between physical abuse and past-month drinking, such that physical abuse was associated with a greater risk of drinking only for youth who perceived low school or neighborhood connections.

Conclusions

Findings demonstrate the importance of early experiences of childhood maltreatment for adolescent alcohol and tobacco use. Enhancing school and neighborhood connectedness for physically abused youth may help protect them from alcohol use.
Bent ab interno needle goniotomy versus gonioscopy-assisted transluminal trabeculotomy in primary open-angle glaucoma: study protocol of a randomized clinical trial
Authors: Ayub Gabriel , De Francesco Ticiana , Costa Vital Paulino
Published: May 2024

Background

Minimally invasive glaucoma surgery (MIGS) is a new class of surgeries, which combines moderate to high success rates and a high safety profile. Bent Ab interno Needle Goniotomy (BANG) and Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) are two low-cost MIGS procedures that communicate the anterior chamber to Schlemm’s canal. Most of the available publications on MIGS are either case series or retrospective studies, with different study protocols. The aim of this manuscript is to describe a randomized clinical trial (RCT) protocol to compare the long-term intraocular pressure (IOP) control and the safety of both procedures in eyes with primary open-angle glaucoma.

Methods

This is a parallel, double-arm, single-masked RCT that includes pseudophakic primary open-angle glaucoma (POAG) eyes. After inclusion criteria, medications will be washed out to verify baseline IOP before surgery. Patients will be randomized to BANG or GATT using a sealed envelope. Follow-up visits will be 1, 7, 15, 30, 60, 90, 180, 330 and 360 days after surgery. On PO330, a new medication washout will be done. The main outcome is the IOP reduction following the procedures. Complimentary evaluation of functional and structural parameters, safety, and quality of life will be done after 30, 90, 180, and 360 days.

Discussion

Our study was designed to compare the long-term efficacy and safety of two low-cost MIGS. Most of the published studies on this subject are case series or retrospective cohorts, with different study protocols, which included different types and severities of glaucomas, combined with cataract extraction. Our study only included mild to moderate POAG eyes, with previous successful cataract extraction. Moreover, it provides a standardized protocol that could be replicated in future studies investigating various types of MIGS. This would allow comparison between different techniques in terms of efficacy, safety, and patients’ quality of life.

Trial registration

Retrospectively registered at the Registro Brasileiro de Ensaios Clínicos (ReBEC) platform RBR-268ms5y. Registered on July 29, 2023.

The study was approved by the Ethics Committee of the University of Campinas, Brazil.
Two chromatographic methods for determination of cytarabine and dexamethazone; two co-administered drugs for the treatment of leukemia: green analytical perspective
Authors: Magdy Maimana A. , Elgebaly Ahmed M. , Taha Ahmed A. , Ali Nourddin W. , Farid Nehal F.
Published: May 2024

Two sensitive, straightforward and repeatable chromatographic techniques were developed for the determination of Cytarabine HCl and Dexamethazone in their pure form and spiked human plasma without prior separation. The drugs are used co-administered for the treatment of Leukemia, a certain type of blood cancer. Method (A) is an isocratic chromatographic HPLC method; separation was accomplished on C18 column using the eluting mixture of 6.9 g/L Monobasic Sodium Phosphate pH 3: methanol (70:30, v/v) and detection was at 275 nm. Concentrations were in the range of 0.2–15 μg/mL for both CYT and DEX. Method (B) is a HPTLC method in which separation was attained on HPTLC F254 plates using methanol: ethyl acetate: ammonia, (7.8:2:0.2, by volume) as eluting solvents and detection was at 275 nm. Concentrations were in the range of 0.1–4 μg/band for both CYT and DEX. The parameters for system suitability testing were evaluated to determine the effectiveness of the developed chromatographic procedures in terms of performance. The recently developed techniques were applied for the determination of the drugs under investigation in spiked human plasma. Validation parameters were examined in accordance with US-FDA criteria. All results were found to be within the acceptable ranges. To evaluate the greenness characters of the proposed methods to the environment; three greenness assessment tools including eco-scale assessments (ESA), green analytical procedure index (GAPI), and Analytical Greenness calculator (AGREE) were used. Acceptable and satisfying results that demonstrated the greenness characteristics of the suggested methods were attained.
Validated chromatographic methods for determination of teriflunomide and investigation of its intrinsic stability
Authors: Boltia Shereen A. , Mora Mai M. , Ismail Nahla S. , Zaazaa Hala E.
Published: May 2024

Two rapid, precise, and sensitive stability-indicating high performance chromatographic methods for the measurement of Teriflunomide in its degradation products’ existence were developed. These were RP-HPLC and HPTLC using UV detector. HPLC separation was accomplished utilizing Thermo BDS hypercil C18 column (250 × 4.6 mm, 5 μm) and acetonitrile: 0.03 M potassium dihydrogen phosphate: triethylamine (50:50:0.1%, by volume) as mobile phase at flow rate of 1mL/min. The separated peaks were detected at 250.0 nm. The densitometric approach was conducted utilizing HPTLC 60 F254 silica gel plates, and a developing system of benzene: ethanol: acetic acid (7.5:1:0.25, by volume) and detection was done at 250.0 nm. The developed approaches were evaluated regarding the International Conference on Harmonization (ICH) instructions. The calibration curves of both techniques were constructed with linearity ranges of (5-100) µg/mL and (2–10) µg /band, for HPLC and densitometric determination, consecutively. Teriflunomide was exposed to base and acid hydrolysis, oxidation using H2O2 and finally, thermal degradation as stated in ICH guidelines. The degradation product structures’ elucidation was achieved through LC-MS.
Anti-CX3CL1 (fractalkine) monoclonal antibody attenuates lung and skin fibrosis in sclerodermatous graft-versus-host disease mouse model
Authors: Hasegawa Takumi , Utsunomiya Akira , Chino Takenao , Kasamatsu Hiroshi , Shimizu Tomomi , Matsushita Takashi , Obara Takashi , Ishii Naoto , Ogasawara Hideaki , Ikeda Wataru , Imai Toshio , Oyama Noritaka , Hasegawa Minoru
Published: May 2024

Background

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and inflammation, followed by excessive fibrosis of the skin and other internal organs, including the lungs. CX3CL1 (fractalkine), a chemokine expressed on endothelial cells, supports the migration of macrophages and T cells that express its specific receptor CX3CR1 into targeted tissues. We previously reported that anti-CX3CL1 monoclonal antibody (mAb) treatment significantly inhibited transforming growth factor (TGF)-β1-induced expression of type I collagen and fibronectin 1 in human dermal fibroblasts. Additionally, anti-mouse CX3CL1 mAb efficiently suppressed skin inflammation and fibrosis in bleomycin- and growth factor-induced SSc mouse models. However, further studies using different mouse models of the complex immunopathology of SSc are required before the initiation of a clinical trial of CX3CL1 inhibitors for human SSc.

Methods

To assess the preclinical utility and functional mechanism of anti-CX3CL1 mAb therapy in skin and lung fibrosis, a sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) mouse model was analyzed with immunohistochemical staining for characteristic infiltrating cells and RNA sequencing assays.

Results

On day 42 after bone marrow transplantation, Scl-cGVHD mice showed increased serum CX3CL1 level. Intraperitoneal administration of anti-CX3CL1 mAb inhibited the development of fibrosis in the skin and lungs of Scl-cGVHD model, and did not result in any apparent adverse events. The therapeutic effects were correlated with the number of tissue-infiltrating inflammatory cells and α-smooth muscle actin (α-SMA)-positive myofibroblasts. RNA sequencing analysis of the fibrotic skin demonstrated that cGVHD-dependent induction of gene sets associated with macrophage-related inflammation and fibrosis was significantly downregulated by mAb treatment. In the process of fibrosis, mAb treatment reduced cGVHD-induced infiltration of macrophages and T cells in the skin and lungs, especially those expressing CX3CR1.

Conclusions

Together with our previous findings in other SSc mouse models, the current results indicated that anti-CX3CL1 mAb therapy could be a rational therapeutic approach for fibrotic disorders, such as human SSc and Scl-cGVHD.
Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients
Authors: Watanabe Tomoya , Ototake Yasushi , Akita Asami , Suzuki Mao , Kanaoka Miwa , Tamura Jun , Saigusa Yusuke , Yamaguchi Yukie
Published: May 2024

Background

Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren’s syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc.

Methods

A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis.

Results

This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14–6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99–4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23–32.60; P = 0.024).

Conclusions

Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.
A GMP-compliant manufacturing method for Wharton’s jelly-derived mesenchymal stromal cells
Authors: Chu Wanglong , Zhang Fen , Zeng Xiuping , He Fangtao , Shang Guanyan , Guo Tao , Wang Qingfang , Wu Jianfu , Li Tongjing , Zhong Zhen Zhong , Liang Xiao , Hu Junyuan , Liu Muyun
Published: May 2024

Background

Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) hold great therapeutic potential in regenerative medicine. Therefore, it is crucial to establish a Good Manufacturing Practice (GMP)-compliant methodology for the isolation and culture of WJ-MSCs. Through comprehensive research, encompassing laboratory-scale experiments to pilot-scale studies, we aimed to develop standardized protocols ensuring the high yield and quality of WJ-MSCs manufacturing.

Methods

Firstly, optimization of parameters for the enzymatic digestion method used to isolate WJ-MSCs was conducted. These parameters included enzyme concentrations, digestion times, seeding densities, and culture media. Additionally, a comparative analysis between the explant method and the enzymatic digestion method was performed. Subsequently, the consecutive passaging of WJ-MSCs, specifically up to passage 9, was evaluated using the optimized method. Finally, manufacturing processes were developed and scaled up, starting from laboratory-scale flask-based production and progressing to pilot-scale cell factory-based production. Furthermore, a stability study was carried out to assess the storage and use of drug products (DPs).

Results

The optimal parameters for the enzymatic digestion method were a concentration of 0.4 PZ U/mL Collagenase NB6 and a digestion time of 3 h, resulting in a higher yield of P0 WJ-MSCs. In addition, a positive correlation between the weight of umbilical cord tissue and the quantities of P0 WJ-MSCs has been observed. Evaluation of different concentrations of human platelet lysate revealed that 2% and 5% concentrations resulted in similar levels of cell expansion. Comparative analysis revealed that the enzymatic digestion method exhibited faster outgrowth of WJ-MSCs compared to the explant method during the initial passage. Passages 2 to 5 exhibited higher viability and proliferation ability throughout consecutive passaging. Moreover, scalable manufacturing processes from the laboratory scale to the pilot scale were successfully developed, ensuring the production of high-quality WJ-MSCs. Multiple freeze-thaw cycles of the DPs led to reduced cell viability and viable cell concentration. Subsequent thawing and dilution of the DPs resulted in a significant decrease in both metrics, especially when stored at 20–27 °C.

Conclusion

This study offers valuable insights into optimizing the isolation and culture of WJ-MSCs. Our scalable manufacturing processes facilitate the large-scale production of high-quality WJ-MSCs. These findings contribute to the advancement of WJ-MSCs-based therapies in regenerative medicine.
Comparative in vivo characterization of newly discovered myotropic adeno-associated vectors
Authors: Ji Jacqueline , Lefebvre Elise , Laporte Jocelyn
Published: May 2024

Background

Adeno-associated virus (AAV)-based gene therapy is a promising strategy to treat muscle diseases. However, this strategy is currently confronted with challenges, including a lack of transduction efficiency across the entire muscular system and toxicity resulting from off-target tissue effects. Recently, novel myotropic AAVs named MyoAAVs and AAVMYOs have been discovered using a directed evolution approach, all separately demonstrating enhanced muscle transduction efficiency and liver de-targeting effects. However, these newly discovered AAV variants have not yet been compared.

Methods

In this study, we performed a comparative analysis of these various AAV9-derived vectors under the same experimental conditions following different injection time points in two distinct mouse strains.

Results

We highlight differences in transduction efficiency between AAV9, AAVMYO, MyoAAV2A and MyoAAV4A that depend on age at injection, doses and mouse genetic background. In addition, specific AAV serotypes appeared more potent to transduce skeletal muscles including diaphragm and/or to de-target heart or liver.

Conclusions

Our study provides guidance for researchers aiming to establish proof-of-concept approaches for preventive or curative perspectives in mouse models, to ultimately lead to future clinical trials for muscle disorders.
Laparoscopic excision of accessory spleen for recurrent autoimmune hemolytic anemia after splenectomy: a case report
Authors: Kashiwagi Ryosuke , Ishida Masaharu , Onodera Koichi , Aoki Shuichi , Iseki Masahiro , Miura Takayuki , Ohtsuka Hideo , Mizuma Masamichi , Nakagawa Kei , Kamei Takashi , Unno Michiaki
Published: May 2024

Background

Splenectomy is indicated in cases of autoimmune hemolytic anemia (AIHA), which are refractory to medical management. In post-splenectomy, there exists a theoretical risk of AIHA recurrence, especially if an accessory spleen undergoes compensatory hypertrophy. In this context, we present a unique case of recurrent AIHA managed through laparoscopic excision of the accessory spleen (LEAS).

Case presentation

A 60-year-old male underwent laparoscopic splenectomy (LS) for AIHA refractory to standard medical therapies. Following the surgery, there was a marked improvement in hemolytic anemia symptoms, and oral steroid therapy was terminated 7 months post-LS. Nonetheless, a year after the LS, the patient exhibited a marked decline in hemoglobin levels, dropping to a concerning 5.8 g/dl, necessitating the reintroduction of oral steroids. A subsequent contrast-enhanced computed tomography (CT) scan unveiled an enlarged accessory spleen. The patient then underwent LEAS, during which the accessory spleen, obscured within adipose tissue, proved challenging to visualize laparoscopically. This obstacle was surmounted utilizing intraoperative ultrasonography (US), enabling successful excision of the accessory spleen. The post-surgical period progressed without complications, and the steroid dosage was reduced to one-twelfth of its initial preoperative quantity.

Conclusions

Recurrent AIHA can be instigated by post-splenectomy compensatory hypertrophy of the accessory spleen. Ensuring comprehensive splenic tissue excision is crucial in AIHA management to obviate recurrent stemming from hypertrophic remnants. In scenarios of AIHA recurrence tied to an enlarged accessory spleen, LEAS stands as a viable and effective therapeutic modality.
Laparoscopic sigmoid colectomy for transverse colonic varices due to an inferior mesenteric arteriovenous fistula
Authors: Munechika Taro , Shiokawa Keiichi , Takeshita Issei , Shimokobe Hisaaki , Sahara Kurumi , Matsumoto Yoshiko , Aisu Naoya , Yoshimatsu Gumpei , Hasegawa Suguru
Published: May 2024

Background

Colonic varices are a rare gastrointestinal anomaly often associated with portal hypertension. Arteriovenous fistula (AVF) in the inferior mesenteric artery (IMA) region is even rarer. Diagnosis and treatment of these entities present unique challenges, especially when the IMA is involved.

Case presentation

A 48-year-old man with a history of cholecystectomy presented with after a positive fecal occult blood test. Investigations revealed varices from the splenic flexure to the transverse colon and suspected AVF in the IMA region. Given the high risk and low efficacy of endoscopic and radiological interventions, laparoscopic sigmoidectomy was performed. This surgical approach successfully addressed both the AVF and the associated varices.

Conclusion

This case underscores the importance of surgical intervention for AVF and colonic varices in the IMA region, particularly when other treatment options pose high risks and have limited efficacy. The favorable postoperative outcome in this case highlights the effectiveness of carefully chosen surgical methods when managing such complex and rare conditions.
Acetylation proteomics and metabolomics analyses reveal the involvement of starch synthase undergoing acetylation modification during UV-B stress resistance in Rhododendron Chrysanthum Pall
Authors: Liu Meiqi , Sun Li , Cao Yuhang , Xu Hongwei , Zhou Xiaofu
Published: May 2024

Background

Rhododendron chrysanthum Pall. (R. chrysanthum) is a plant that lives in high mountain with strong UV-B radiation, so R. chrysanthum possess resistance to UV-B radiation. The process of stress resistance in plants is closely related to metabolism. Lysine acetylation is an important post-translational modification, and this modification process is involved in a variety of biological processes, and affected the expression of enzymes in metabolic processes. However, little is known about acetylation proteomics during UV-B stress resistance in R. chrysanthum.

Results

In this study, R. chrysanthum OJIP curves indicated that UV-B stress damaged the receptor side of the PSII reaction center, with a decrease in photosynthesis, a decrease in sucrose content and an increase in starch content. A total of 807 differentially expressed proteins, 685 differentially acetylated proteins and 945 acetylation sites were identified by quantitative proteomic and acetylation modification histological analysis. According to COG and subcellular location analyses, DEPs with post-translational modification of proteins and carbohydrate metabolism had important roles in resistance to UV-B stress and DEPs were concentrated in chloroplasts. KEGG analyses showed that DEPs were enriched in starch and sucrose metabolic pathways. Analysis of acetylation modification histology showed that the enzymes in the starch and sucrose metabolic pathways underwent acetylation modification and the modification levels were up-regulated. Further analysis showed that only GBSS and SSGBSS changed to DEPs after undergoing acetylation modification. Metabolomics analyses showed that the metabolite content of starch and sucrose metabolism in R. chrysanthum under UV-B stress.

Conclusions

Decreased photosynthesis in R. chrysanthum under UV-B stress, which in turn affects starch and sucrose metabolism. In starch synthesis, GBSS undergoes acetylation modification and the level is upregulated, promotes starch synthesis, making R. chrysanthum resistant to UV-B stress.
Improving image quality of sparse-view lung tumor CT images with U-Net
Authors: Ries Annika , Dorosti Tina , Thalhammer Johannes , Sasse Daniel , Sauter Andreas , Meurer Felix , Benne Ashley , Lasser Tobias , Pfeiffer Franz , Schaff Florian , Pfeiffer Daniela
Published: May 2024

Background

We aimed to improve the image quality (IQ) of sparse-view computed tomography (CT) images using a U-Net for lung metastasis detection and determine the best tradeoff between number of views, IQ, and diagnostic confidence.

Methods

CT images from 41 subjects aged 62.8 ± 10.6 years (mean ± standard deviation, 23 men), 34 with lung metastasis, 7 healthy, were retrospectively selected (2016–2018) and forward projected onto 2,048-view sinograms. Six corresponding sparse-view CT data subsets at varying levels of undersampling were reconstructed from sinograms using filtered backprojection with 16, 32, 64, 128, 256, and 512 views. A dual-frame U-Net was trained and evaluated for each subsampling level on 8,658 images from 22 diseased subjects. A representative image per scan was selected from 19 subjects (12 diseased, 7 healthy) for a single-blinded multireader study. These slices, for all levels of subsampling, with and without U-Net postprocessing, were presented to three readers. IQ and diagnostic confidence were ranked using predefined scales. Subjective nodule segmentation was evaluated using sensitivity and Dice similarity coefficient (DSC); clustered Wilcoxon signed-rank test was used.

Results

The 64-projection sparse-view images resulted in 0.89 sensitivity and 0.81 DSC, while their counterparts, postprocessed with the U-Net, had improved metrics (0.94 sensitivity and 0.85 DSC) (p = 0.400). Fewer views led to insufficient IQ for diagnosis. For increased views, no substantial discrepancies were noted between sparse-view and postprocessed images.

Conclusions

Projection views can be reduced from 2,048 to 64 while maintaining IQ and the confidence of the radiologists on a satisfactory level.

Relevance statement

Our reader study demonstrates the benefit of U-Net postprocessing for regular CT screenings of patients with lung metastasis to increase the IQ and diagnostic confidence while reducing the dose.

Key points

• Sparse-projection-view streak artifacts reduce the quality and usability of sparse-view CT images.

• U-Net-based postprocessing removes sparse-view artifacts while maintaining diagnostically accurate IQ.

• Postprocessed sparse-view CTs drastically increase radiologists’ confidence in diagnosing lung metastasis.

Graphical Abstract