bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of a macrophage carbamylated proteome reveals a function in post-translational modification crosstalk
Authors: You Youngki , Tsai Chia-Feng , Patel Rishi , Sarkar Soumyadeep , Clair Geremy , Zhou Mowei , Liu Tao , Metz Thomas O. , Das Chittaranjan , Nakayasu Ernesto S.
Published: September 2023

Background

Lysine carbamylation is a biomarker of rheumatoid arthritis and kidney diseases. However, its cellular function is understudied due to the lack of tools for systematic analysis of this post-translational modification (PTM).

Methods

We adapted a method to analyze carbamylated peptides by co-affinity purification with acetylated peptides based on the cross-reactivity of anti-acetyllysine antibodies. We also performed immobilized-metal affinity chromatography to enrich for phosphopeptides, which allowed us to obtain multi-PTM information from the same samples.

Results

By testing the pipeline with RAW 264.7 macrophages treated with bacterial lipopolysaccharide, 7,299, 8,923 and 47,637 acetylated, carbamylated, and phosphorylated peptides were identified, respectively. Our analysis showed that carbamylation occurs on proteins from a variety of functions on sites with similar as well as distinct motifs compared to acetylation. To investigate possible PTM crosstalk, we integrated the carbamylation data with acetylation and phosphorylation data, leading to the identification 1,183 proteins that were modified by all 3 PTMs. Among these proteins, 54 had all 3 PTMs regulated by lipopolysaccharide and were enriched in immune signaling pathways, and in particular, the ubiquitin-proteasome pathway. We found that carbamylation of linear diubiquitin blocks the activity of the anti-inflammatory deubiquitinase OTULIN.

Conclusions

Overall, our data show that anti-acetyllysine antibodies can be used for effective enrichment of carbamylated peptides. Moreover, carbamylation may play a role in PTM crosstalk with acetylation and phosphorylation, and that it is involved in regulating ubiquitination in vitro.

Graphical Abstract
Exo-miR-1290-induced by COX-2 overexpression promotes cancer-associated fibroblasts activation and tumor progression by CUL3-Nrf2 pathway in lung adenocarcinoma
Authors: Bai Xiaoming , Shao Jiaofang , Duan Tinghong , Liu Xue , Wang Min , Li Xuanya , You Qiang , Zhang Zhiyuan , Pan Jinshun
Published: September 2023

Background

Cancer-associated fibroblasts (CAFs) are critically involved in tumor progression by maintaining extracellular mesenchyma (ECM) production and improving tumor development. Cyclooxygenase-2 (COX-2) has been proved to promote ECM formation and tumor progression. However, the mechanisms of COX-2 mediated CAFs activation have not yet been elucidated. Therefore, we conducted this study to identify the effects and mechanisms of COX-2 underlying CAFs activation by tumor-derived exosomal miRNAs in lung adenocarcinoma (LUAD) progression.

Methods

As measures of CAFs activation, the expressions of fibroblasts activated protein-1 (FAP-1) and α-smooth muscle actin (α-SMA), the main CAFs markers, were detected by Western blotting and Immunohistochemistry. And the expression of Fibronectin (FN1) was used to analyze ECM production by CAFs. The exosomes were extracted by ultracentrifugation and exo-miRNAs were detected by qRT-PCR. Herein, we further elucidated the implicated mechanisms using online prediction software, luciferase reporter assays, co-immunoprecipitation, and experimental animal models.

Results

In vivo, a positive correlation was observed between the COX-2 expression levels in parenchyma and α-SMA/FN1 expression levels in mesenchyma in LUAD. However, PGE2, one of major product of COX-2, did not affect CAFs activation directly. COX-2 overexpression increased exo-miR-1290 expression, which promoted CAFs activation. Furthermore, Cullin3 (CUL3), a potential target of miR-1290, was found to suppress COX-2/exo-miR-1290-mediated CAFs activation and ECM production, consequently impeding tumor progression. CUL3 is identified to induce the Nuclear Factor Erythroid 2–Related Factor 2 (NFE2L2, Nrf2) ubiquitination and degradation, while exo-miR-1290 can prevent Nrf2 ubiquitination and increase its protein stability by targeting CUL3. Additionally, we identified that Nrf2 is direcctly bound with promoters of FAP-1 and FN1, which enhanced CAFs activation by promoting FAP-1 and FN1 transcription.

Conclusions

Our data identify a new CAFs activation mechanism by exosomes derived from cancer cells that overexpress COX-2. Specifically, COX-2/exo-miR-1290/CUL3 is suggested as a novel signaling pathway for mediating CAFs activation and tumor progression in LUAD. Consequently, this finding suggests a novel strategy for cancer treatment that may tackle tumor progression in the future.
Screening utility and acceptability of the Kiswahili-pGALS (paediatric Gait, Arms, Legs, Spine) at a tertiary referral hospital in Kenya-A diagnostic accuracy study
Authors: Kawishe Jacqueline E. , Ngugi Anthony , Luchters Stanley , Foster Helen , Migowa Angela
Published: September 2023

Background

Paediatric rheumatic diseases cause considerable disease burden to children and their families (Moorthy LN, Peterson MGE, Hassett AL, et al, Pediatric Rheumatology 8:20, 2010). Delayed diagnosis is a significant determinant of severity and mortality attributed to these conditions (Foster HE, Eltringham MS, Kay LJ, et al, Arthritis Care Res 57(6):921-7, 2007). pGALS is a simple clinical tool used to assess joints and identify musculoskeletal (MSK) conditions in school-going children to enable early referral to paediatric rheumatologists.

Objectives

This study aimed to translate and determine the diagnostic accuracy and acceptability of a Kiswahili version of the pGALS screening tool among Kiswahili-speaking children.

Methods

The pGALS screening questions were translated into Kiswahili according to the World Health Organisation (WHO) standard for translation of a tool. The validity of the Kiswahili PGALS was ascertained and acceptability rated (time taken, discomfort). Using systematic random sampling, we enrolled children aged 5–16 years presenting at the Aga Khan University Hospital’s (AKUH) emergency department in Kenya, who spoke Kiswahili and had symptoms suggestive of an MSK condition. Those already under follow-up at the paediatric rheumatology service at AKUH were excluded. MSK assessment was undertaken by two resident doctors using the newly translated Kiswahili-pGALS and findings were compared with a paediatric rheumatologist examination (‘gold-standard’) on the same day, and who was blinded to the pGALS findings. We analysed demographic details of the participants and determined the diagnostic accuracy by cross tabulation of the index test results by the results of the reference standard.

Results

One hundred children with a median age of nine years (IQR 7–11) were enrolled. The sensitivity and specificity of the Kiswahili-pGALS screening tool were 76.8% (95%CI 63.6–87.0%) and 40.0% (95%CI 23.9–57.9%), respectively. The diagnostic accuracy was 62.7% (95%CI 52.1–72.1%), area under the ROC was 0.58 (95%CI 0.48–0.68). The median time to perform the Kiswahili-pGALS was 5.0 min (IQR 3.5–6.0 min). Ninety percent of the guardians found the practice of Kiswahili-pGALS to have none, or only some discomfort.

Conclusions

The Kiswahili-pGALS’s was found to be a useful screening tool to aid early identification of MSK conditions in Kiswahili-speaking settings. However, the low specificity implies that relatively large number of false positives would still need to be reviewed by a rheumatologist if the tool is adapted for use.
Clinical presentation of human monkeypox virus infection during the 2022 outbreak: descriptive case series from a large italian Research Hospital
Authors: Salvo Pierluigi Francesco , Farinacci Damiano , Lombardi Francesca , Ciccullo Arturo , Tamburrini Enrica , Santangelo Rosaria , Borghetti Alberto , Di Giambenedetto Simona
Published: September 2023

Background

In May 2022, a new case of Monkeypox Virus (MPX) was reported in a non-endemic area, the United Kingdom, and since then, the number of confirmed cases in Europe has been increasing until WHO, on May 10 2023, declared that MPOX is no longer a public health emergency of international concern. We aimed to describe the clinical and microbiological characteristics of sixteen patients with a confirmed diagnosis of MPX followed by a single Italian clinical centre, the Fondazione Policlinico Universitario Agostino Gemelli, between May 20 and August 30.

Materials and methods

A prospective observational study has been conducted, collecting microbiological samples during the time of the infection, as well as epidemiological and clinical data of the patients. All patients provided written informed consent.

Results

During clinical practice, 16 individuals presenting with consistent symptoms tested positive for MPX on a polymerase chain reaction. All patients were men having sex with men (MSM). The most frequent clinical presentation was a vesicular erythematous cutaneous rash, mainly distributed on the genital and perianal area, but also regarding limbs, face, neck, chest and back in some of the patients. Systemic symptoms, such as fever or lymphadenopathy, involved eight patients. The symptom most frequently reported by patients was pruritus in the area of the vesicles. Thirteen patients also reported pain. Nine patients were HIV-1 coinfected, but no significant differences have been observed compared to other cohort patients. The median time between the onset of symptoms and the healing was 19.5 days (IQR 14.0–20.3).

Conclusions

Our cohort of patients presented a mild manifestation of the disease with no complications and no need for antiviral therapy nor hospitalization. This population seems different from the ones reported in the literature during the previous outbreaks in endemic areas in epidemiological data and clinical manifestations but also from a cohort of patients described in the literature from the 2022 outbreak, suggesting the importance for healthcare workers to keep in mind the possibility of an MPX infection in the differential diagnosis of patients presenting with consistent symptoms, even in non-endemic areas, to ensure efficient isolation of the patient for infection control purposes and effective management of the infection preventing the development of MPOX-related complications.
Clinical application of modified hip joint lateral position in femoral neck fracture
Authors: Liu Haitian , Gao Enpeng , Zhong Zhiwei , Wu Wenjuan , Zhang Zuzhuo
Published: September 2023

Background

To show the femoral neck better in hip lateral view of X-ray, we design a modified hip lateral view and then investigate the value in femoral neck fractures.

Methods

CT images of 10 normal hip joints for 3D reconstruction were selected, the Mimics Medical 21.0 was used, and rotating the proximal femur was to find the most suitable angle for showing the femoral neck well, designed the modified lateral view according to this angle. We collected 35 healthy cases and 35 femoral neck fractures as the normal and fracture group. And two groups were all taken hip anteroposterior view, cross-table lateral view and modified lateral view, which were analyzed by two radiologists to score the anatomical structures of the articular surface, femoral head, head neck junction, femoral neck, basal region and intertrochanteric region. Friedman test was used to analyze the score of femoral neck at different angles. T test and Wilcoxon signed-rank test were to compare inter-groups.

Results

The modified lateral view was designed as follows: The subjects were supine, with the sagittal axis biased toward the healthy side at an angle of approximately 20° to the long axis of the examination table, the hip joint flexed at 45°, the lower extremity abducted at 40°, the centerline inclined 45° toward the head and the centerline aligned with the center of the groin. The modified lateral view showed the femoral head, head neck junction and femoral neck more clearly than the cross-table lateral view, but the cross-table lateral view showed the femoral neck basal and intertrochanteric region better. In addition, the time of taking the modified lateral view was significantly less than the cross-table lateral view (normal group: 0.789 min ± 0.223 vs 0.623 min ± 0.207, P < 0.001; fracture group: 1.131 min ± 0.362 vs 0.946 min ± 0.390, P < 0.001).

Conclusions

The modified lateral view can obtain a standard sagittal image of femoral neck, which can show the dislocation and angulation of the sagittal femoral neck fracture clearly, and improve the accuracy of diagnosis. And it is more convenient and easier for patients to cooperate, which is worthy promoting and applying in clinical work.
Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway
Authors: Wang Kewen , Zhang Xianji , Li Xin , Li Dekun , Shan Ziliang , Yao Changfeng
Published: September 2023

Background and Aim

Knee osteoarthritis (KOA) is characterized by joint wear and degeneration. Unfortunately, the medical community currently lacks effective treatment options for this disease. Suspension exercise therapy is considered an effective form of non-weight-bearing exercise for treating KOA. However, its mechanism of intervention in KOA is unclear. Therefore, this study aimed to evaluate the protective effects of non-weight-bearing exercise on rats with KOA and attempted to explore the underlying mechanisms.

Methods

In this study, a papain-induced KOA model was constructed, and the pathological changes in cartilage tissue were observed by hematoxylin and eosin (H&E) staining and scored according to the Mankin scoring principle. The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Reverse transcription–quantitative polymerase chain reaction and Western blotting were used to detect the expression of mRNA and proteins in the TLR4/MyD88/NF-κB signaling pathway.

Results

H&E staining and Mankin score data confirmed that non-weight-bearing exercise significantly improved articular cartilage degradation compared with that in the model group. Further, we observed that non-weight-bearing exercise differentially reduced serum levels of IL-1β, IL-6, and TNF-α. Mechanistically, non-weight-bearing exercise downregulated gene and protein expression of TLR4, MyD88, and NF-κB in cartilage tissue.

Conclusion

Non-weight-bearing exercise resulted in the progression of KOA by modulating the TLR4/MyD88/NF-κB signaling pathway and decreasing the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α to slow down the degeneration of articular cartilage.
Spatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence
Authors: Zhang Shuming , Yuan Long , Danilova Ludmila , Mo Guanglan , Zhu Qingfeng , Deshpande Atul , Bell Alexander T. F. , Elisseeff Jennifer , Popel Aleksander S. , Anders Robert A. , Jaffee Elizabeth M. , Yarchoan Mark , Fertig Elana J. , Kagohara Luciane T.
Published: September 2023

Background

Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within the HCC tumor microenvironment (TME) that underlie responses to modern systemic therapy.

Methods

We applied spatial transcriptomics (ST) profiling to characterize the tumor microenvironment in HCC resection specimens from a prospective clinical trial of neoadjuvant cabozantinib, a multi-tyrosine kinase inhibitor that primarily blocks VEGF, and nivolumab, a PD-1 inhibitor in which 5 out of 15 patients were found to have a pathologic response at the time of resection.

Results

ST profiling demonstrated that the TME of responding tumors was enriched for immune cells and cancer-associated fibroblasts (CAF) with pro-inflammatory signaling relative to the non-responders. The enriched cancer-immune interactions in responding tumors are characterized by activation of the PAX5 module, a known regulator of B cell maturation, which colocalized with spots with increased B cell marker expression suggesting strong activity of these cells. HCC-CAF interactions were also enriched in the responding tumors and were associated with extracellular matrix (ECM) remodeling as there was high activation of FOS and JUN in CAFs adjacent to the tumor. The ECM remodeling is consistent with proliferative fibrosis in association with immune-mediated tumor regression. Among the patients with major pathologic responses, a single patient experienced early HCC recurrence. ST analysis of this clinical outlier demonstrated marked tumor heterogeneity, with a distinctive immune-poor tumor region that resembles the non-responding TME across patients and was characterized by HCC-CAF interactions and expression of cancer stem cell markers, potentially mediating early tumor immune escape and recurrence in this patient.

Conclusions

These data show that responses to modern systemic therapy in HCC are associated with distinctive molecular and cellular landscapes and provide new targets to enhance and prolong responses to systemic therapy in HCC.
The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants—a multi-site prospective cohort study
Authors: Davidson Aimee L. , Dressel Uwe , Norris Sarah , Canson Daffodil M. , Glubb Dylan M. , Fortuno Cristina , Hollway Georgina E. , Parsons Michael T. , Vidgen Miranda E. , Holmes Oliver , Koufariotis Lambros T. , Lakis Vanessa , Leonard Conrad , Wood Scott , Xu Qinying , McCart Reed Amy E. , Pickett Hilda A. , Al-Shinnag Mohammad K. , Austin Rachel L. , Burke Jo , Cops Elisa J. , Nichols Cassandra B. , Goodwin Annabel , Harris Marion T. , Higgins Megan J. , Ip Emilia L. , Kiraly-Borri Catherine , Lau Chiyan , Mansour Julia L. , Millward Michael W. , Monnik Melissa J. , Pachter Nicholas S. , Ragunathan Abiramy , Susman Rachel D. , Townshend Sharron L. , Trainer Alison H. , Troth Simon L. , Tucker Katherine M. , Wallis Mathew J. , Walsh Maie , Williams Rachel A. , Winship Ingrid M. , Newell Felicity , Tudini Emma , Pearson John V. , Poplawski Nicola K. , Mar Fan Helen G. , James Paul A. , Spurdle Amanda B. , Waddell Nicola , Ward Robyn L.
Published: September 2023

Background

Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.

Methods

This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.

Results

Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.

Conclusions

These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.
Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study
Authors: Baraliakos Xenofon , van der Heijde Désirée , Sieper Joachim , Inman Robert D. , Kameda Hideto , Li Yihan , Bu Xianwei , Shmagel Anna , Wung Peter , Song In-Ho , Deodhar Atul
Published: September 2023

Background

Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.

Methods

Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.

Results

Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.

Conclusions

Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.

Trial registration

NCT02049138.
Dynamic access control method for SDP-based network environments
Authors: You Hyunjin , Ko Doochan , Kim Daniel , Wong Richard , Joe Inwhee
Published: September 2023

With online work environments and other distributed computing systems—such as cloud technologies or Internet of Things systems—becoming increasingly popular today due to the COVID-19 pandemic and general technological advances, the question of how to keep them secure has also become a pertinent concern. With this increased dependence on online systems for companies, cyberattacks have also been on the rise. To protect terminal devices, many companies have resorted to implementing a single boundary-defense model. This method has yielded positive results in securing the network from external threats, but it does not effectively protect network from internal security threats. With the vulnerabilities in the internal network security in mind, a dynamic access control method used with a zero-trust software-defined perimeter security model could be a viable solution. This study proposes a dynamic access control method using an engine with a new reward and penalty point-based system (RP Engine) and a dynamic task engine (DT Engine) for a zero-trust SDP security model.
Simcan2Cloud: a discrete-event-based simulator for modelling and simulating cloud computing infrastructures
Authors: Cañizares Pablo C. , Núñez Alberto , Bernal Adrián , Cambronero M. Emilia , Barker Adam
Published: September 2023

Cloud computing is an evolving paradigm whose adoption has been increasing over the last few years. This fact has led to the growth of the cloud computing market, together with fierce competition for the leading market share, with an increase in the number of cloud service providers. Novel techniques are continuously being proposed to increase the cloud service provider’s profitability. However, only those techniques that are proven not to hinder the service agreements are considered for production clouds. Analysing the expected behaviour and performance of the cloud infrastructure is challenging, as the repeatability and reproducibility of experiments on these systems are made difficult by the large number of users concurrently accessing the infrastructure. To this, must be added the complications of using different provisioning policies, managing several workloads, and applying different resource configurations. Therefore, in order to alleviate these issues, we present Simcan2Cloud, a discrete-event-based simulator for modelling and simulating cloud computing environments. Simcan2Cloud focuses on modelling and simulating the behaviour of the cloud provider with a high level of detail, where both the cloud infrastructure and the interactions of the users with the cloud are integrated in the simulated scenarios. For this purpose, Simcan2Cloud supports different resource allocation policies, service level agreements (SLAs), and an intuitive and complete API for including new management policies. Finally, a thorough experimental study to measure the suitability and applicability of Simcan2Cloud, using both real-world traces and synthetic workloads, is presented.
Role of dopamine in the pathophysiology of Parkinson’s disease
Authors: Zhou Zhi Dong , Yi Ling Xiao , Wang Dennis Qing , Lim Tit Meng , Tan Eng King
Published: September 2023

A pathological feature of Parkinson’s disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. DA is the neurotransmitter of dopaminergic neurons. Accumulating evidence suggests that DA interacts with environmental and genetic factors to contribute to PD pathophysiology. Disturbances of DA synthesis, storage, transportation and metabolism have been shown to promote neurodegeneration of dopaminergic neurons in various PD models. DA is unstable and can undergo oxidation and metabolism to produce multiple reactive and toxic by-products, including reactive oxygen species, DA quinones, and 3,4-dihydroxyphenylacetaldehyde. Here we summarize and highlight recent discoveries on DA-linked pathophysiologic pathways, and discuss the potential protective and therapeutic strategies to mitigate the complications associated with DA.
“Good luck, social distance”: rapid decarceration and community care for serious mental illness and substance use disorder during the COVID-19 pandemic
Authors: James Jennifer E. , Dauria Emily F. , Desai Riya , Bell Adelaide , Izenberg Jacob M.
Published: September 2023

The COVID-19 pandemic inspired calls for rapid decarceration of prisons and jails to slow the spread of disease in a high-risk congregate setting. Due to the rarity of intentionally-decarcerative policies, little is known about the effects of rapid decarceration on individuals with serious mental illness (SMI) substance use disorder (SUD), a population who receive many services via the criminal legal system (CLS). We conducted interviews with 13 key informants involved in CLS in San Francisco, CA to better understand the implication of the decarcerative policies put into practice in early 2020. Participants described a tension between the desire to have fewer people incarcerated and the challenges of accessing services and support – especially during the lockdown period of the pandemic – outside of the CLS given the number of services that are only accessible to those who have been arrested, incarcerated, or sentenced. These findings emphasize the need for investing in community social services rather than further expanding the CLS to achieve the goal of supporting individuals with SMI and SUD shrinking the US system of mass incarceration.
A meta-analysis of systematic reviews and meta-analyses to evaluate the psychological consequences of COVID-19
Authors: Sokouti Massoud , Shafiee-Kandjani Ali Reza , Sokouti Mohsen , Sokouti Babak
Published: September 2023

Background

Several meta-analysis studies have been reported in the literature on the incidence of psychopathological conditions resulting from the COVID-19 pandemic. This investigation aims to compile and analyze the findings of previously published meta-analysis research, as shown by the present meta-analysis of previous meta-analysis studies.

Methods

The PubMed and Scopus databases were searched from 1 January 2019 to 30 May 2022. The procedure was carried out according to the PRISMA flow chart and the qualities of the identified studies were analyzed using AMSTAR 2. Heterogeneities and risk of bias were assessed using the Meta-MUMS tool. The corresponding results, forest and funnel plots of the psychological consequences of COVID-19 were synthesized.

Results

Eleven meta-analysis studies were included. Random-effects meta-analysis of anxiety and depression showed (ER = 0.318 p-value < 0.001, ER = 0.295 p-value < 0.001) high heterogeneities (I2 = 99.70%, I2 = 99.75) between studies. Random-effects meta-analyses of sleep difficulties and insomnia were shown (ER = 0.347 p-value < 0.001, ER = 0.265, p-value < 0.001) along with heterogeneities (I2 = 99.89, I2 = 99.64). According to the random meta-analysis of post-traumatic stress syndrome (PTSS) and post-traumatic stress disorder (PTSD) (ER = 0.246, p-value = 0.001, ER = 0.223 p-value < 0.001) with heterogeneities (I2 = 99.75, I2 = 99.17). Random-effects meta-analyses of somatic and fear symptoms have been shown (ER = 0.16 p-value < 0.001, ER = 0.41, p-value = 0.089) with high heterogeneities (I2 = 99.62, I2 = 98.63). Random-effects meta-analysis of obsessive–compulsive symptoms and distress (ER = 0.297 p-value = 0.103; ER = 0.428, p-value = 0.013) with high heterogeneity, as I2 = 99.38%. Subgroup analysis of all symptoms and Egger's tests for detecting publication bias were also assessed.

Conclusion

The data from the current meta-analysis showed different psychological disorders of COVID-19 during the pandemic. Clinicians should be aware of the prevalence with which COVID-19-infected patients experience emotional distress, anxiety, fatigue, and PTSD. About half of the included systematic reviews (SRs)/meta-analyses (MAs) suffered from poorer methodological quality and increased risk of bias, reducing confidence in the findings. There must be more SRs/MAs and high-quality clinical trials conducted to confirm these findings.
Seed nano-priming using silica nanoparticles: effects in seed germination and physiological properties of Stevia Rebaudiana Bertoni
Authors: Hasanaklou Nasibeh Tavakoli , Mohagheghi Vahid , Hasanaklou Hourieh Tavakoli , Ma’mani Leila , Malekmohammadi Marjan , Moradi Foad , Dalvand Yadollah
Published: September 2023

Background

This study aimed to assess the effects of different concentrations of silicon (Si) nutrient sources, including bulk silicon dioxide (bSiO2) and two types of silica nanoparticles, nSiO2 (I) and nSiO2 (II) at different concentrations of 1, 5, 10, 25, 50, and 100 ppm in the germination process of stevia. The priming experiment was conducted using a completely randomized design with three replicates to ensure the reliability of the results.

Results

All stevia seedlings subjected to nano-priming significantly improved the germination parameters. The germination percentage increased by 106%, reaching 68% in nano-primed seedlings. Similarly, the germination rate showed a remarkable increase of 128.12% at 7.3 day−1. Additionally, the root, shoot, and seedling dry weight increased by 283%, 168.9%, and 220% and determined 0.092, 0.078, and 0.17 g plant−1, respectively, compared to the control. Furthermore, seed priming with nSiO2 (I) at a concentration of 10 ppm resulted in an increased catalase (CAT) activity (36.15 Umg−1 protein) and peroxidase (POX) activity (approximately 0.057 U.mg−1 protein). Also, the highest sucrose amount was observed in the root (equal to 160.4 μg g−1 DW) and shoot (equal to 247 μg g−1 DW) of seedlings primed with 10 ppm of nSiO2 (I). However, it should be noted that nano-priming at the highest concentration led to oxidative damage indicated by an increase in H2O2 concentration. Conversely, bSiO2 demonstrated a lesser effect on improving germination, seedling growth, antioxidant activities, and biochemical attributes compared to nSiO2 (I), and nSiO2 (II).

Conclusions

This study established that seed priming with nSiO2 (I) at a concentration of 10 ppm was the most effective in enhancing germination percentage and rate, root/shoot/dry weight, biochemical attributes, and enzyme activities (such as α-amylase, CAT, and POX). The results suggested that seed priming with nSiO2 (I) at the optimal concentration could improve the seed germination by enhancing the antioxidant system, starch metabolism, and ultimately protecting plants from oxidative damage.

Graphical Abstract
Prediction of p53 mutation status in rectal cancer patients based on magnetic resonance imaging-based nomogram: a study of machine learning
Authors: Zhong Xia , Peng Jiaxuan , Shu Zhenyu , Song Qiaowei , Li Dongxue
Published: September 2023

Background

The current study aimed to construct and validate a magnetic resonance imaging (MRI)-based radiomics nomogram to predict tumor protein p53 gene status in rectal cancer patients using machine learning.

Methods

Clinical and imaging data from 300 rectal cancer patients who underwent radical resections were included in this study, and a total of 166 patients with p53 mutations according to pathology reports were included in these patients. These patients were allocated to the training (n = 210) or validation (n = 90) cohorts (7:3 ratio) according to the examination time. Using the training data set, the radiomic features of primary tumor lesions from T2-weighted images (T2WI) of each patient were analyzed by dimensionality reduction. Multivariate logistic regression was used to screen predictive features, which were combined with a radiomics model to construct a nomogram to predict p53 gene status. The accuracy and reliability of the nomograms were assessed in both training and validation data sets using receiver operating characteristic (ROC) curves.

Results

Using the radiomics model with the training and validation cohorts, the diagnostic efficacies were 0.828 and 0.795, the sensitivities were 0.825 and 0.891, and the specificities were 0.722 and 0.659, respectively. Using the nomogram with the training and validation data sets, the diagnostic efficacies were 0.86 and 0.847, the sensitivities were 0.758 and 0.869, and the specificities were 0.833 and 0.75, respectively.

Conclusions

The radiomics nomogram based on machine learning was able to predict p53 gene status and facilitate preoperative molecular-based pathological diagnoses.
Intrahepatic cholangiocarcinoma with extensive intraductal extension of high-grade biliary intraepithelial neoplasia: a case report
Authors: Kubota Haruna , Hashimoto Yasushi , Toyota Kazuhiro , Yano Raita , Kobayashi Hironori , Yokoyama Yujiro , Sakashita Yoshihiro , Taniyama Kiyomi , Miyamoto Katsunari , Murakami Yoshiaki
Published: September 2023

Background

Intrahepatic cholangiocarcinoma (ICC) is frequently associated with precursor lesions, and biliary intraepithelial neoplasia (BilIN) may play a significant role in the development of ICC. However, the exact sequence and progression of these lesions remain to be elucidated. We report a rare case of ICC that exhibited extensive longitudinal intraductal extension of high-grade BilIN in the posterior bile ducts and involved the hepatic hilum and the peripheral hepatic parenchyma.

Case presentation

A 70-year-old female presented with anorexia. Computed tomography (CT) revealed a 15 mm enhancing intrahepatic tumor extending to the right intrahepatic secondary confluence. This was associated with a 7 mm diameter cystic dilatation of the segment 6 bile duct (B6). Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis at the bifurcation of the posterior bile duct branch. Bile cytology confirmed the diagnosis of adenocarcinoma cells. Therefore, the patient was diagnosed with an ICC involving the right glissonean pedicle and underwent a right hepatectomy and lymph node dissection. Histologic examination revealed the tumor consisted of moderately differentiated adenocarcinoma. In connection with this lesion, diffuse intraductal atypical epithelial cells, which were diagnosed as high-grade BilIN, was observed not only in the dilated B6 but in the entire posterior bile ducts, which measured approximately 120 mm in diameter. Furthermore, two distinct foci of adenocarcinomas were identified in the peripheral hepatic parenchyma. A lymph node metastasis was also present. The pathological diagnosis was ICC pT4N1M0 stage IVA. The patient underwent adjuvant chemotherapy and has shown no recurrence 5 years after surgery. Imaging modalities were unable to accurately assess the extent of the intraductal neoplastic lesions due to their low papillary or sessile intraductal tubular growth. No risk factors for BilIN development, which has the potential to predispose to cholangiocarcinoma, were identified in the present case.

Conclusions

We present a case of ICC involving the right hepatic hilum, accompanied by extensive longitudinal extensions of high-grade BilIN and multifocal microscopic invasions in peripheral hepatic parenchyma. Notably, the intraductal lesions involved the entire posterior intrahepatic bile ducts. The presence of biliary neoplasia with extensive intraductal extension, in conjunction with ICC, should be considered as a variant of BilIN.
Nanoarchitectured conjugates targeting angiogenesis: investigating heparin-taurocholate acid conjugates (LHT7) as an advanced anti-angiogenic therapy for brain tumor treatment
Authors: Kim Hyung Shik , Seol Jae Hak , Hwang Hae Hyun , Lee Dong Yun
Published: September 2023

Background

Glioblastoma is a highly malignant brain tumor associated with poor prognosis. Conventional therapeutic approaches have limitations due to their toxic effects on normal tissue and the development of tumor cell resistance. This study aimed to explore alternative mechanisms for glioblastoma treatment by targeting angiogenesis.

Methods

The study investigated the anti-angiogenic properties of heparin in glioblastoma treatment. To overcome the limitations of heparin, a heparin-taurocholate conjugate (LHT7) was synthesized by conjugating heparin to taurocholic acid. The study utilized the U87MG human glioblastoma cell line and human umbilical vein endothelial cells (HUVEC) as experimental models. Cell viability assays and sprouting assays were performed to assess the effects of LHT7. Additionally, phosphorylation of angiogenesis-related proteins, such as phospho-ERK and phospho-VEGFR2, was measured. The anti-angiogenic effects of LHT7 were further evaluated using a glioblastoma orthotopic mouse model.

Results

Treatment with LHT7 resulted in a dose-dependent reduction in cell viability in U87MG human glioblastoma cells. The sprouting of HUVEC cells was significantly decreased upon LHT7 treatment. Furthermore, LHT7 treatment led to a decrease in the phosphorylation of angiogenesis-related proteins, including phospho-ERK and phospho-VEGFR2. In the glioblastoma orthotopic mouse model, LHT7 exhibited anti-angiogenic effects, supporting its potential as a therapeutic agent.

Conclusions

The conjugation of heparin and taurocholic acid to create LHT7 offers several advantages over conventional therapeutic approaches for glioblastoma. LHT7 demonstrated anti-angiogenic properties, as evidenced by the reduction in cell viability and inhibition of endothelial cell sprouting. Moreover, LHT7 modulated the phosphorylation of angiogenesis-related proteins. These findings suggest that LHT7 holds promise as a medication for glioblastoma treatment, offering potential implications for improving patient outcomes.

Graphical Abstract
Evaluation of freshwater heavy metals accumulation effect on oxidative stress, Metallothionein biosynthesis and histopathology of Procambarus clarkii (Girard,1985) collected from three locations in the Delta region, Egypt
Authors: Mona Mahy M. , Younis Mai L. , Atlam Aalaa I.
Published: September 2023

Background

In this study, the effect of heavy metals accumulation influence was evaluated on adult crayfish Procambarus clarkii (Decapoda, Astacidea) collected from three different Governmental locations (Kafr El-Shaikh, El-Menofya, and El-Gharbiya) of the Egyptian Delta. The activity of super oxidase dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) of gills, hepatopancreas, and muscle tissue were measured. SDS Polyacrylamide gel electrophoresis (SDS-PAGE) and West blotting technique were performed to detect MT Protein expression.

Results

The results revealed that Kafr El-Shaikh reflected the highest Superoxide dismutase (SOD), Catalase, and Glutathione S-transferase (GST) activity levels (97.2 u/100 mg, 28.5 u/100 mg, and 8.3 nmol mg (-1) protein min (-1) respectively. Superior protein polymorphism % (30%) remarked collected Freshwater crayfish P. clarkii from Kafr El-Shaikh location. Varied protein polymorphism % was shown between collected crayfish from El-Menofya, and El-Gharbiya locations (5.5 and 6.2 respectively) Increasing Metallothioneins intensity (15.4%) for collected Freshwater crayfish Procambarus clarkii from Kafr El-Shaikh Location.

Conclusion

Heavy metal stress influences antioxidant status and also induces increasing Metallothioneins intensity, especially samples that were collected from the Kafr El-Shaikh area.
Effect of cognitive retraining treatment in mild to moderate depressive disorders
Authors: Gupta Aarzoo , Kumari Santha
Published: September 2023

Background

Cognitive retraining or remediation approaches dispense high levels of stimulation and new learning tasks, leading to an increased neural connections, which facilitate rapid recovery in patients with neurological as well as psychiatric conditions.

Objectives

The current study aimed to investigate the effect of cognitive retraining (CR) in depressive disorders. We assigned 40 patients with mild to moderate depression to two sample groups, with 20 participants each: CR alone and CR with medicine. A 6-week CR module was delivered, and participants’ scores on measures such as the Beck Depression Inventory-II, Metacognition Questionnaire 30, World Health Organization Quality of Life- Brief, and Global Assessment of Functioning were compared.

Results

Analysis using Stata/IC version 16 included descriptive statistics, paired and independent t-tests, analysis of covariance, and propensity score matching. Cohen's d was computed to determine the effect size. Within-group analysis revealed statistically significant differences in pre-post scores of the outcome measures (p < .05) and large effect size (d = 3.41; d = 3.60) in both groups. The difference in scores of outcome measures between the groups was not significant (p > .05) even when covariates were controlled, or nearest neighbor match analysis was carried out. CR is effective in alleviating symptoms and dysfunctional metacognitive beliefs in addition to enhancing functioning and quality of life.

Conclusions

CR-based interventions may be essential mental health services owing to growing research in psychotherapy via virtual modes such as tele- and video-conferencing. These interventions can substantiate both prevention and remedy.
Viscoelastic properties of small bowel mesentery at MR elastography in Crohn’s disease: a prospective cross-sectional exploratory study
Authors: van Schelt Anne-Sophie , Beek Kim Johanna , Wassenaar Nienke Petronella Maria , Schrauben Eric M. , Runge Jurgen H. , Gecse Krisztina Barbara , van der Bilt Jarmila D. W. , Neefjes-Borst E. Andra , Buskens Christianne Johanna , Nederveen Aart J. , Stoker Jaap
Published: September 2023

Background

Creeping fat is a pathological feature of small bowel Crohn’s disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD.

Methods

Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients’ mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann–Whitney U-test). Within CD patients, the affected and “presumably” unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland–Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters.

Results

SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%.

Conclusion

MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection.

Trial registration

Dutch trial register, NL9105, registered 7 December 2020.

Relevance statement

MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn’s disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection.

Key points

• MRE of the mesentery in patients with active CD is feasible.

• Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis.

• MRE provides biomarkers to quantify mesenteric disease activity in active CD.

Graphical Abstract