bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-engaging with arts and cultural activities at the Life Rooms: ‘It’s given me spring’
Authors: Worsley Joanne , Billington Josie , Balabanova Ekaterina
Published: June 2024

Background

Mersey Care NHS Foundation Trust’s Life Rooms initiative is an established and successful model of integrating arts and culture within NHS provision. In the face of COVID-19, the Life Rooms was restructured to provide a full suite of online resources. Following the lifting of restrictions, in-person arts provision returned to the Life Rooms sites. Additional evidence in respect of the impact on mental health and wellbeing of the return to in-person arts and cultural activities provided by the Life Rooms, as well as the relative merits of online and in-person arts and cultural activities, is needed to inform future planning around in-person, online, and/or hybrid provision.

Methods

Interviews with practitioners delivering cultural and creative courses at the Life Rooms (n = 8) and users of the Life Rooms (n = 5) were conducted to explore the impact of the return to in-person arts provision at the Life Rooms, as well as the merits of online and in-person arts provision. Data were analysed using thematic analysis.

Results

Three overarching themes were identified: ‘Provision, access, and reach’; ‘Value of arts and creativity’; and ‘Challenges with the Life Rooms model in the new normal’. The findings demonstrate the critical role of arts and cultural provision in providing stigma-free environments to reconnect the vulnerable and isolated. As re-engagement remained slow, there is a need to be responsive to hesitation around re-engaging in-person. The Life Rooms online learning offer remained vital for those who are vulnerable or otherwise unable to access in-person activities.

Conclusions

As our findings show a demand for maintaining online provision that enables accessibility together with in-person provision that boosts community connectedness, ensuring continued online access alongside in-person delivery should be prioritised. As mental health demands could continue to grow in coming years as the pandemic evolves, in-person arts engagement could have an important role in meeting mental health needs.
Cultural competences among future nurses and midwives: a case of attitudes toward Jehovah’s witnesses’ stance on blood transfusion
Authors: Domaradzki Jan , Głodowska Katarzyna , Doron Einat , Markwitz-Grzyb Natalia , Jabkowski Piotr
Published: June 2024

Background

Transcultural nursing recognises the significance of cultural backgrounds in providing patients with quality care. This study investigates the opinions of master’s students in nursing and midwifery regarding the attitudes of Jehovah’s Witnesses towards refusing blood transfusions.

Methods

349 master’s students in nursing and midwifery participated in a quantitative study and were surveyed via the Web to evaluate their awareness of the stance of Jehovah’s Witnesses on blood transfusions and the ethical and legal dilemmas associated with caring for Jehovah’s Witness (JW) patients.

Results

The study yielded three significant findings. It unequivocally demonstrates that nursing and midwifery students possess inadequate knowledge regarding Jehovah’s Witnesses’ stance on blood transfusions and their acceptance of specific blood products and medical procedures. Despite being cognisant of the ethical and legal dilemmas of caring for JW patients, students lack an understanding of patients’ autonomy to reject blood transfusions and their need for bloodless medicine. Students also articulated educational needs regarding cultural competencies regarding the Jehovah’s Witnesses’ beliefs on blood transfusions and non-blood management techniques.

Conclusions

Healthcare professionals need the knowledge and skills necessary to provide holistic, patient-centred and culturally sensitive care. This study emphasises the urgent need for university curricula and nursing postgraduate training to include modules on transcultural nursing and strategies for minimising blood loss.
Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction
Authors: Shirodkar Diksha , Smithson Sarah Francesca , Keen Richard , Lester Tracy , Banos-Pinero Benito , Burren Christine Pamela
Published: June 2024

Background

Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis.

Case presentation

A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother’s persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition).

Conclusion

This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways.
Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation
Authors: Zhang Fengqin , Yue Huihui , Dong Ruihan , He Jianhan , Zhou Ling , Dou Xinran , Wang lingling , Zheng Pengdou , Mao Zhenyu , Zhu Xiaoyan , Wang Yi , Liu Huiguo , Zhang Huilan
Published: June 2024

Background

Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it’s unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear.

Methods

To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions.

Results

In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts.

Conclusion

In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.
Incident heart failure and the subsequent risk of progression to end stage kidney disease in individuals with type 2 diabetes
Authors: Liu Sylvia , Liu Jian-Jun , Ang Keven , Lee Janus , Chan Clara , Gurung Resham L. , Zheng Huili , Tang Justin , Lim Su Chi
Published: June 2024

Background

Diabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes.

Methods

In this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2–9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first.

Results

180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3–29.5] versus 6.5 [2.3–18.6]).

Conclusion

Incident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis.
Integrated pathway mining and selection of an artificial CYP79-mediated bypass to improve benzylisoquinoline alkaloid biosynthesis
Authors: Takenaka Musashi , Kamasaka Kouhei , Daryong Kim , Tsuchikane Keiko , Miyazawa Seiha , Fujihana Saeko , Hori Yoshimi , Vavricka Christopher J. , Hosoyama Akira , Kawasaki Hiroko , Shirai Tomokazu , Araki Michihiro , Nakagawa Akira , Minami Hiromichi , Kondo Akihiko , Hasunuma Tomohisa
Published: June 2024

Background

Computational mining of useful enzymes and biosynthesis pathways is a powerful strategy for metabolic engineering. Through systematic exploration of all conceivable combinations of enzyme reactions, including both known compounds and those inferred from the chemical structures of established reactions, we can uncover previously undiscovered enzymatic processes. The application of the novel alternative pathways enables us to improve microbial bioproduction by bypassing or reinforcing metabolic bottlenecks. Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant-derived compounds with important pharmaceutical properties. BIA biosynthesis has developed into a prime example of metabolic engineering and microbial bioproduction. The early bottleneck of BIA production in Escherichia coli consists of 3,4-dihydroxyphenylacetaldehyde (DHPAA) production and conversion to tetrahydropapaveroline (THP). Previous studies have selected monoamine oxidase (MAO) and DHPAA synthase (DHPAAS) to produce DHPAA from dopamine and oxygen; however, both of these enzymes produce toxic hydrogen peroxide as a byproduct.

Results

In the current study, in silico pathway design is applied to relieve the bottleneck of DHPAA production in the synthetic BIA pathway. Specifically, the cytochrome P450 enzyme, tyrosine N-monooxygenase (CYP79), is identified to bypass the established MAO- and DHPAAS-mediated pathways in an alternative arylacetaldoxime route to DHPAA with a peroxide-independent mechanism. The application of this pathway is proposed to result in less formation of toxic byproducts, leading to improved production of reticuline (up to 60 mg/L at the flask scale) when compared with that from the conventional MAO pathway.

Conclusions

This study showed improved reticuline production using the bypass pathway predicted by the M-path computational platform. Reticuline production in E. coli exceeded that of the conventional MAO-mediated pathway. The study provides a clear example of the integration of pathway mining and enzyme design in creating artificial metabolic pathways and suggests further potential applications of this strategy in metabolic engineering.
A five years malaria surveillance data analysis of North Shewa zone, Amhara region, Ethiopia: July 2018 to June 2023
Authors: Moltot Tebabere , Bekele Girma , Gebreegziabher Zenebe Abebe , Lemma Tesfansh , Sisay Moges , Silesh Mulualem , Mulugeta Melkam , Demissie Legesse , Kebede Tirusew Nigussie , Taye Birhan Tsegaw
Published: June 2024

Background

Malaria is a critical public health concern in Ethiopia, with significant socioeconomic consequences. Malaria data trend analysis is essential for understanding transmission patterns and adopting evidence-based malaria control measures. The purpose of this study was to determine the 5 year distribution of malaria in North Shewa zone, Amhara region, Ethiopia, in 2023.

Methods

A descriptive cross-sectional study design was employed to analyse the 5 year trend of malaria surveillance data in the North Shewa zone of the Amhara regional, Ethiopia, spanning from July 2018 to June 2023. The malaria indicator data were gathered from the zone’s public health emergency management database. Malaria data from the previous 5 years was collected, compiled, processed, and analysed using Microsoft Excel 2019.

Results

Among a total of 434,110 suspected cases 47,889 (11.03%) cases were confirmed as malaria, with an average annual malaria incidence rate of 4.4 per 1000 population in the Zone. Malaria cases exhibited an increase from Epidemiological Week (Epi week) 37 to Epi week 49 (September to November) and again from Epi week 22 to week 30 (May to July). Individuals aged 15 and above, and all districts in the Zone except Angolela were notably affected by malaria.

Conclusion

Despite implementing various measures to reduce malaria incidence, the disease continues to persist in the zone. Therefore, the Zone Health Department should intensify its preventive and control efforts.
Inhibition of WNT/β-catenin signalling during sex-specific gonadal differentiation is essential for normal human fetal testis development
Authors: Lundgaard Riis Malene , Delpouve Gaspard , Nielsen John E. , Melau Cecilie , Langhoff Thuesen Lea , Juul Hare Kristine , Dreisler Eva , Aaboe Kasper , Tutein Brenøe Pia , Albrethsen Jakob , Frederiksen Hanne , Juul Anders , Giacobini Paolo , Jørgensen Anne
Published: June 2024

Sex-specific gonadal differentiation is directed by complex signalling promoting development in either male or female direction, while simultaneously inhibiting the opposite pathway. In mice, the WNT/β-catenin pathway promotes ovarian development and the importance of actively inhibiting this pathway to ensure normal testis development has been recognised. However, the implications of alterations in the tightly regulated WNT/β-catenin signalling during human fetal gonad development has not yet been examined in detail. Thus, the aim of this study was to examine the consequences of dysregulating the WNT/β-catenin signalling pathway in the supporting cell lineage during sex-specific human fetal gonad development using an established and extensively validated ex vivo culture model. Inhibition of WNT/β-catenin signalling in human fetal ovary cultures resulted in only minor effects, including reduced secretion of RSPO1 and reduced cell proliferation although this was not consistently found in all treatment groups. In contrast, promotion of WNT/β-catenin signalling in testes severely affected development and function. This included disrupted seminiferous cord structures, reduced cell proliferation, reduced expression of SOX9/AMH, reduced secretion of Inhibin B and AMH as well as loss of the germ cell population. Additionally, Leydig cell function was markedly impaired with reduced secretion of testosterone, androstenedione and INSL3. Together, this study suggests that dysregulated WNT/β-catenin signalling during human fetal gonad development severely impairs testicular development and function. Importantly, our study highlights the notion that sufficient inhibition of the opposite pathway during sex-specific gonadal differentiation is essential to ensure normal development and function also applies to human fetal gonads.
Neonatal Chlamydia muridarum respiratory infection causes neuroinflammation within the brainstem during the early postnatal period
Authors: Hedley Kateleen E , Gomez Henry M , Kecelioglu Eda , Carroll Olivia R , Jobling Phillip , Horvat Jay C , Tadros Melissa A
Published: June 2024

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase.
Proportion of early treatment seeking for sexually transmitted infections and associated factors among patients attending youth friendly service in Bahir Dar City health centers, Northwest, Ethiopia
Authors: Zeleke Getachew , Mekonnen Alemtshay , Abuhay Tigist , Agimas Muluken Chanie
Published: June 2024

Background

Sexually transmitted infection is a common public health issue of youths and is characteristically transmitted through sexual intercourse. Even though early treatment for sexually transmitted infection is very important to reduce further complications and economic burden, studies to identify the proportion and the possible factor of early treatment seeking is rare in Ethiopia.

Objective

To assess the proportion of early treatment seeking for sexually transmitted infections and associated factors among patients attending youth friendly service in Bahir Dar city health centers, northwest, Ethiopia 2023.

Method

Institutional based Cross-sectional study was used among 407 participants from April 25 to May 24 /2023. A systematic random sampling technique was used to select the participants. An interview-administered questionnaire was used for data collection, whereas Epi-data version 4.6.0.2 and the statistical package for statistical science version 23 were used for data entry and analysis respectively. A frequency table and bar chart were used for descriptive analysis. Multiple binary logistic regression was employed to identify the factors at p-value of <0.05. The necessary assumption of the model was also checked by the Hosmer and Lemishow test.

Results

The response rate of this study was 391 (96.1%) and the proportion of early treatment for sexually transmitted infection was 108 (27.6%, 95%CI; 23-32). Good knowledge about sexually transmitted infection (AOR=1.98, 95CI%; 1.13-3.47) know about their HIV status (AOR=1.95, 95%CI; 1.13-3.36), perceive severity of sexually transmitted infection (AOR=11.23, 95%CI; 6.15-20.45), and not fear the stigma about being infected with sexually transmitted infection (AOR=2.29, 95%CI; 1.32-3.96) were the significantly associated factors for early treatment of sexually transmitted infection.

Conclusion and recommendation

The proportion of early treatment for sexually transmitted infection in Bahir Dar city was low. Knowledge about STIs, testing/ knowing HIV status, perception of the severity about sexually transmitted infection, and fear of stigma about sexually transmitted infection were the statistically significant factors for early treatment of sexually transmitted infection. So the government better give attention to health education and other health promotion activities to increase the knowledge of youths about sexually transmitted infection and to change their perception of sexually transmitted infection.
The role of corruption in global food systems: a systematic scoping review
Authors: Demeshko Anastassia , Clifford Astbury Chloe , Lee Kirsten M. , Clarke Janielle , Cullerton Katherine , Penney Tarra L.
Published: June 2024

Background

Corruption exists at all levels of our global society and is a potential threat to food security, food safety, equity, and social justice. However, there is a knowledge gap in the role and impact of corruption within the context of the global food system. We aimed to systematically review empirical literature focused on corruption in the global food system to examine how it is characterized, the actors involved, its potential impacts, and the solutions that have been proposed to address corruption in the food system.

Methods

We used a systematic scoping review methodology. Terms combining corruption and the food system were searched in Scopus, PubMed, Web of Science, PsycInfo and Econlit, in October 2021. Two screeners applied a priori selection criteria to screen the articles at the title and abstract and full-text levels. Data was extracted into a charting form and thematically synthesized to describe the types of corruption in the food system, the actors involved, how corruption impacts the food system, and potential solutions. Sankey diagrams and narrative summaries were developed to summarize the included studies and findings.

Results

From the 238 included records, five main types of corruption were identified in the global food system: bureaucratic corruption, fraud, bribery, organized crime, and corporate political activity. These different types of corruption spanned across various food system areas, from policy and governance structures to food environments, and involved a wide range of actors. More powerful actors like those in public and private sectors tended to instigate corruption in the food system, while community members and primary producers tended to be impacted by it. The impacts of corruption were mostly negative and corruption was found to undermine food system governance and regulatory structures; threaten health, safety, and food security; and lead or contribute to environmental degradation, economic loss, erosion of trust, social inequities, and decreased agricultural productivity. While solution-oriented literature was limited, the essential role of strong governance,  use of technology and predictive modelling methods to improve detection of corruption, and organizational approaches to problem solving were identified.

Conclusion

Our review findings provide researchers and policymakers with a comprehensive overview of corruption in the global food system, providing insights to inform a more holistic approach to addressing the issue. Addressing corruption in the food system is an essential element of supporting the transition to a more healthy, equitable and sustainable global food system.
Cell death shapes cancer immunity: spotlighting PANoptosis
Authors: Gao Lixia , Shay Chloe , Teng Yong
Published: June 2024

PANoptosis represents a novel type of programmed cell death (PCD) with distinctive features that incorporate elements of pyroptosis, apoptosis, and necroptosis. PANoptosis is governed by a newly discovered cytoplasmic multimeric protein complex known as the PANoptosome. Unlike each of these PCD types individually, PANoptosis is still in the early stages of research and warrants further exploration of its specific regulatory mechanisms and primary targets. In this review, we provide a brief overview of the conceptual framework and molecular components of PANoptosis. In addition, we highlight recent advances in the understanding of the molecular mechanisms and therapeutic applications of PANoptosis. By elucidating the complex crosstalk between pyroptosis, apoptosis and necroptosis and summarizing the functional consequences of PANoptosis with a special focus on the tumor immune microenvironment, this review aims to provide a theoretical basis for the potential application of PANoptosis in cancer therapy.
Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons
Authors: Makabe Kenta , Okada Hiroyuki , Tachibana Naohiro , Ishikura Hisatoshi , Ito Norihito , Tanaka Masaru , Chijimatsu Ryota , Terashima Asuka , Yano Fumiko , Asaka Meiko , Yanagihara Dai , Taketomi Shuji , Matsumoto Takumi , Tanaka Sakae , Omata Yasunori , Saito Taku
Published: June 2024

Background

Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis.

Methods

We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells.

Results

Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1β and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia–astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells.

Conclusions

Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.
ITC-Net-blend-60: a comprehensive dataset for robust network traffic classification in diverse environments
Authors: Bayat Marziyeh , Garshasbi Javad , Mehdizadeh Mozhgan , Nozari Neda , Rezaei Khesal Abolghasem , Dokhaei Maryam , Teimouri Mehdi
Published: June 2024

Objectives

Recognition of mobile applications within encrypted network traffic holds considerable effects across multiple domains, encompassing network administration, security, and digital marketing. The creation of network traffic classifiers capable of adjusting to dynamic and unforeseeable real-world settings presents a tremendous challenge. Presently available datasets exclusively encompass traffic data obtained from a singular network environment, thereby restricting their utility in evaluating the robustness and compatibility of a given model.

Data description

This dataset was gathered from 60 popular Android applications in five different network scenarios, with the intention of overcoming the limitations of previous datasets. The scenarios were the same in the applications set but differed in terms of Internet service provider (ISP), geographic location, device, application version, and individual users. The traffic was generated through real human interactions on physical devices for 3–15 min. The method used to capture the traffic did not require root privileges on mobile phones and filtered out any background traffic. In total, the collected dataset comprises over 48 million packets, 450K bidirectional flows, and 36 GB of data.
Fetal hemoglobin induction in azacytidine responders enlightens methylation patterns related to blast clearance in higher-risk MDS and CMML
Authors: Chatzilygeroudi Theodora , Chondrou Vasiliki , Boers Ruben , Siamoglou Stavroula , Athanasopoulou Katerina , Verigou Evgenia , Gribnau Joost , Alexis Spyridon , Labropoulou Vassiliki , Kourakli Alexandra , Patrinos George P. , Sgourou Argyro , Symeonidis Argiris
Published: June 2024

Background

As new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indicator for decitabine-treated patients. Although epigenetic mechanisms are assumed, responding patients’ epigenomes have not been thoroughly examined. We aimed to clarify HbF kinetics and prognostic value for azacytidine treated patients, as well as the epigenetic landscape that might influence HbF re-expression and its clinical relevance.

Results

Serial HbF measurements by high-performance liquid chromatography (n = 20) showed induction of HbF only among responders (p = 0.030). Moreover, HbF increase immediately after the first azacytidine cycle demonstrated prognostic value for progression-free survival (PFS) (p = 0.032, HR = 0.19, CI 0.24–1.63). Changes in methylation patterns were revealed with methylated DNA genome-wide sequencing analysis (n = 7) for FOG-1, RCOR-1, ZBTB7A and genes of the NuRD-complex components. Targeted pyrosequencing methodology (n = 28) revealed a strong inverse correlation between the degree of γ-globin gene (HBG2) promoter methylation and baseline HbF levels (p = 0.003, rs =  − 0.663). A potential epigenetic mechanism of HbF re-expression in azacytidine responders was enlightened by targeted methylation analysis, through hypomethylation of site -53 of HBG2 promoter (p = 0.039, rs =  − 0.504), which corresponds to MBD2-NuRD binding site, and to hypermethylation of the CpG326 island of ZBTB7A (p = 0.05, rs = 0.482), a known HbF repressor. These changes were associated to blast cell clearance (pHBG2 = 0.011, rs = 0.480/pZBTB7A = 0.026, rs = 0.427) and showed prognostic value for PFS (pZBTB7A = 0.037, HR = 1.14, CI 0.34–3.8).

Conclusions

Early HbF induction is featured as an accessible prognostic indicator for HMA treatment and the proposed potential epigenetic mechanism of HbF re-expression in azacytidine responders includes hypomethylation of the γ-globin gene promoter region and hypermethylation of the CpG326 island of ZBTB7A. The association of these methylation patterns with blast clearance and their prognostic value for PFS paves the way to discuss in-depth azacytidine epigenetic mechanism of action.

Graphical abstract
Distinct signatures of gut microbiota and metabolites in primary biliary cholangitis with poor biochemical response after ursodeoxycholic acid treatment
Authors: Han Weijia , Song Ting , Huang Zhongyi , Liu Yanmin , Xu Bin , Huang Chunyang
Published: June 2024

Background

About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response.

Methods

This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal.

Results

PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy.

Conclusion

PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.
Ischemic cardio-cerebrovascular disease and all-cause mortality in Chinese elderly patients: a propensity-score matching study
Authors: Yang Qian , Sun Shasha , Cui Long-Biao , Gao Shan , Gu Zhenghui , Fang Zhiyi , Zhang Yingjie , Chen Sijia , Sun Naiyuan , Wang Yabin , Cao Feng
Published: June 2024

Background

Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients.

Methods

This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches.

Results

Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32–2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47–2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16–1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15–1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients.

Conclusions

Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.

Graphical Abstract
Network of doctors for multimorbidity and diabetes — the NOMAD intervention: protocol for feasibility trial of multidisciplinary team conferences for people with diabetes and multimorbidity
Authors: Bugge Stine Jorstad , Henriksen Daniel Pilsgaard , Damkier Per , Rahbek Martin Torp , Schousboe Karoline , Rothmann Mette Juel , Poulsen Marianne Kjær , Hansen Camilla , Nagarajah Subagini , Jensen Per Bruno , Johansson Sofie Lock , Panou Vasiliki , Schneider Ida Ransby , Pedersen Charlotte Gjørup , Andersen Jonas Dahl , Hangaard Jørgen , Zwisler Ann-Dorthe Olsen
Published: June 2024

Background

The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity.

Methods

A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial.

Discussion

A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future.

Administrative information

Protocol version: 01

Trial registration

NCT05913726 — registration date: 21 June 2023
Delayed cold-stored vs. room temperature stored platelet transfusions in bleeding adult cardiac surgery patients—a randomized multicentre pilot study (PLTS-1)
Authors: Bartoszko Justyna , Peer Miki , Grewal Deep , Ansari Saba , Callum Jeannie , Karkouti Keyvan
Published: June 2024

Background

Platelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP.

Methods

This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product).

Discussion

DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study.

Trial registration

NCT 06147531 (clinicaltrials.gov).
A review on the anti-parasitic activity of ruthenium compounds
Authors: Chakraborty Shibam , Ghosh Sumit , Dalui Shauryabrota , Dey Avijit
Published: June 2024

Background

There are many infectious diseases in the world caused by parasites. Among them, toxoplasmosis, American trypanosomiasis, African trypanosomiasis, leishmaniasis, neosporosis and malaria are more common and contribute to a majority of the affected individuals.

Main body

Due to extensive use of antibiotics, antibiotic resistant strain of the parasites has developed. So, we need to develop a new metal ligand complexes which have many configurations, can overcome this drug resistance and also show significant results in elimination of the parasites. A series of anti-parasitic drugs have been formulated and tested for its activity. In this review, we have tried to see the interaction of different ruthenium drugs (arene ruthenium complex, ruthenium clotrimazole complex, etc.) on different parasites associated with the aforementioned diseases.

Conclusion

Combination of ruthenium to any organic ligand shows synergistic effects against parasite either by overcoming the drug resistance of the parasite or by binding with new targets due to the presence of ruthenium ion. The multiple modes of action generate an effective drug exhibiting anti-parasitic activity at low concentration.

Graphical abstract
Clinical outcomes of post-placental insertion of Copper T380A and Multiload 375 contraceptive devices during cesarean section: a randomized clinical trial
Authors: Awaga Hatem Abo Elftooh , Abdel-Mawjud Mahmoud Ahmad , Ismail Mohammed Samir , Ahmed Salah Roshdy
Published: June 2024

Background

To compare two types of intrauterine devices, namely Cu T380A IUD and Multiload 375 IUD, inserted immediately post-placental during cesarean section, with regard to expulsion rates and side effects.

Methods

A randomized comparative clinical trial was carried out over 200 patients with 100 patients in each group. Transabdominal ultrasonography (US) was done on all patients before discharge to ensure the adequate position of the IUD in addition to casco speculum examination to assess the IUD threads, and then women were requested to attend a follow-up appointment at 6 weeks after delivery; gynecological examinations in addition to transvaginal sonography were done to measure the top-fundal distance that reflects the position of the IUD. The participants were instructed to report the pattern of bleeding during the puerperium, fever, or vaginal discharge.

Results

The ultrasonographic assessment of IUD position before patient discharge (1st assessment) revealed that 18% of Cu T380A IUD users were displaced in comparison to 24% of Multiload 375 IUD, and such difference between both groups was not statistically significant (P = 0.3); furthermore, the ultrasonographic assessment of IUD position after 6 weeks (2nd assessment) revealed that 19% of Cu T380A IUD users were displaced in comparison to 30% of Multiload 375 IUD, and such difference between both groups was statistically significant (P = 0.047). In addition, none of the included patients in both groups suffered from fever after IUD insertion.

Conclusion

The present study demonstrated that post-placental insertion of Multiload 375 IUCD results in significantly higher displacement compared to post-placental insertion of Cu T380A IUCD, as well as significantly more bleeding problems with Cu T380A IUCD as compared with Multiload 375 IUCD.

Trial registration

The study was registered prospectively on clinical trial.gov with trial registeration number NCT05624411 (Registered 22-October-2022, https://clinicaltrials.gov/study/NCT05624411).