bluuebunny/crossref_metadata_2025 huggingface dataset:
Sirtuin-dependent reversible lysine acetylation of the
o
-succinylbenzoyl-coenzyme A synthetase of
Bacillus subtilis
Authors: Burckhardt Rachel M. , Escalante-Semerena Jorge C.
Published: October 2024

Reversible lysine acylation (RLA) is a conserved posttranslational modification that cells of all domains of life use to regulate the biological function of proteins, some of which have enzymatic activity. Many AMP-forming organic acid:CoA ligases are regulated
via
acylation in prokaryotes and eukaryotes. Here, we report the acetylation of the
o
-succinylbenzoyl-CoA synthetase (EC 6.2.1.26) of
Bacillus subtilis
(
Bs
MenE) by the GCN5-related acetyltransferase (GNAT) AcuA enzyme of this bacterium.
Bs
MenE is part of the metabolic pathway that assembles menaquinone (MK), an essential component of the electron transport chain in
B. subtilis
. We demonstrate that the active-site lysine 471 (K471) of
Bs
MenE is acetylated specifically by
Bs
AcuA, and that acetylated
Bs
MenE (
Bs
MenE
Ac
) is deacetylated by the NAD
+
-dependent sirtuin (
Bs
SrtN) of this bacterium. The
in vivo
analyses performed in this study were done in an
Escherichia coli
Δ
menE
strain because the enzymatic activity of MenE is essential in
B. subtilis
, but not in
E. coli
. The use of a heterologous system allowed us to assess the effect of acetylation on
Bs
MenE function under MK-dependent growth conditions. Based on our
in vivo
data, we suggest that regulation of
Bs
MenE by RLA reduces MK production, negatively affecting the growth rate and yield of the culture.

IMPORTANCE

Reversible lysine acylation (RLA) is a posttranslational modification used by all cells to rapidly control the biological function of proteins. Herein, we identify an acetyltransferase and deacetylase in the soil bacterium
Bacillus subtilis
that can modify/demodify an enzyme required for the synthesis of menaquinone (MK), an essential electron carrier involved in respiration in cells of all domains of life. Based on our data, we suggest that under some as-yet-undefined physiological conditions,
B. subtilis
modulates MK biosynthesis, which changes the flux of electrons through the electron transport chain of this bacterium. To our knowledge, this is the first example of control of respiration by RLA.
National health and economic impact of a lifestyle program to prevent type 2 diabetes mellitus in Germany: a simulation study
Authors: Ogurtsova Katherine , Laxy Michael , Emmert-Fees Karl , Dintsios Charalabos-Markos , Zhang Ping , Icks Andrea
Published: October 2024

Introduction

To examine the long-term health and economic impact of a lifestyle diabetes prevention program in people with high risk of developing type 2 diabetes in Germany.

Research design and methods

We assessed the lifetime cost-effectiveness of a 2-year pragmatic lifestyle program for preventing type 2 diabetes targeting German adults aged 35–54 and 55–74 years old with hemoglobin A1c (HbA1c) from 6.0% to 6.4%. We used the Centers for Disease Control and Prevention RTI Diabetes Cost-Effectiveness Model to run a simulation on the program effectiveness. We estimated incremental health benefits in quality-adjusted life years (QALYs) and costs using an established simulation model adapted to the German context, from a healthcare system and societal perspective. The cost-effectiveness of the program was measured by incremental cost-effectiveness ratios (ICERs) in cost per QALY. We projected the number of type 2 diabetes cases prevented by participation rate if the program was implemented nationwide.

Results

The lifestyle program would result to more QALYs and higher costs. The lifetime ICERs were 14 690€ (35–54 years old) and 14 372€ (55–74 years old) from a healthcare system perspective and cost saving (ICER=−3805€) and cost-effective (ICER=4579€), respectively, from a societal perspective. A total of 10 527 diabetes cases would be prevented over lifetime if the program was offered to all eligible people nationwide and 25% of those would participate in the program.

Conclusions

Implementing the lifestyle intervention for people with HbA1c from 6.0% to 6.4% could be a cost-effective at standard willingness to pay level strategy for type 2 diabetes prevention. The intervention in the younger cohort could be cost saving from a societal perspective. The successful implementation of a lifestyle-based diabetes prevention program could be an important component of a successful National Diabetes Strategy in Germany.
SoundMind Trial: a study protocol for a randomised controlled trial for online acceptance and commitment therapy and sound therapy for tinnitus
Authors: Huang Xiaoling , Tang Dongmei , Sun Shan , Li Huawei
Published: October 2024

Introduction

Tinnitus is a common ailment that affects 10%–15% of adults worldwide. Comorbidities associated with tinnitus often include hearing loss, emotional distress and sleep disorders, with insomnia being a common issue among patients with tinnitus. Audiological and psychological approaches are typically used to treat chronic subjective tinnitus, with the combination of sound therapy and cognitive–behavioural therapy-based counselling having the strongest evidence for effectiveness. Acceptance and commitment therapy (ACT) has also shown promising effects in reducing the impact of tinnitus when delivered in groups or online. However, there is a lack of evidence on the effects of combining ACT with sound therapy for patients with tinnitus-related insomnia. Therefore, this study aims to compare the efficacy of internet-delivered ACT combined with sound therapy versus sound therapy alone for tinnitus in a superiority, two-arm randomised controlled trial.

Methods and analysis

A total of 164 patients with chronic subjective tinnitus and insomnia will be randomised to receive internet-delivered guided self-help tinnitus treatment based on ACT combined with tailored sound therapy or tailored sound therapy alone. The primary outcome is the variation in Tinnitus Handicap Inventory scores observed 2 months after randomisation between the two study groups. Secondary outcomes will include insomnia severity, sleep parameters, tinnitus loudness, tinnitus acceptance, depression and anxiety. The outcomes will be assessed at 2, 3 and 6 months post randomisation.

Ethics and dissemination

The study is approved by the review board and ethics committee of the Eye and ENT Hospital of Fudan University (approval number: 2023066-1). The findings will be disseminated through presentations at relevant conferences and peer-reviewed publications.

Trial registration number

NCT05963542.
Satisfaction and preference for home delivery pharmaceutical services among patients attending primary care settings in Qatar during COVID-19 pandemic: a cross-sectional study
Authors: Alam Muhammad Tanveer , Veettil Shajitha Thekke , Krishnan Jeyaram Illiayaraja , Alsalmi Reena Ghazi , Jacob Jinsy , Mousa Aly Tamer , Sakallah Samah Auni Mesbah , Mahmood Shafqat , Al Nuaimi Ahmed
Published: October 2024

Objectives

During the COVID-19 epidemic, due to the high risk associated with travel and group gatherings, the Ministry of Public Health in Qatar introduced home delivery of pharmaceutical services. This study aims to investigate the satisfaction and preferences of patients who used the new home delivery services provided by health centres (HCs).

Study design

A cross-sectional study was conducted using an exploratory questionnaire to assess patients’ preferences for pharmaceutical delivery services.

Settings

Primary care.

Participants

A convenient sample of 604 adults who used the pharmaceutical delivery services was recruited. The study tool measured satisfaction with a set of 11 service evaluation criteria on a Likert scale of 5 grades. The score ranged between 1 for highly dissatisfied and 5 for highly satisfied. A quantitative summary satisfaction score was calculated by summing the satisfaction rating for home delivery on the 11 service evaluation criteria. The final score was adjusted to a maximum of 100 for ease of understanding.

Results

Results showed that 45.5% of participants were highly satisfied with the overall quality of the home delivery service. Furthermore, 58.9% were willing to recommend the service to others, while only 30.9% considered the delivery cost to be reasonable. Among the factors associated with satisfaction was nationality, where Qatari nationals had a significantly higher mean satisfaction score (89%) compared with expatriates (79.5%).

Outcome

The satisfaction score exhibited a significant positive trend with age and educational level. Factors such as gender, the time required to access the HCs, frequency of requesting pharmacy service and income categories did not show a significant difference in the satisfaction score.

Conclusion

The home delivery service is a promising addition to primary care. It may play a crucial role in enhancing accessibility for the beneficiaries reducing unnecessary visits to HCs in the future.
The chronic wound characterisation study and biobank: a study protocol for a prospective observational cohort investigation of bacterial community composition, inflammatory responses and wound-healing trajectories in non-healing wounds
Authors: Iversen Anne Kristine Servais , Lichtenberg Mads , Fritz Blaine Gabriel , Díaz-Pinés Cort Isabel , Al-Zoubaidi Dania Firas , Gottlieb Hans , Kirketerp-Møller Klaus , Bjarnsholt Thomas , Jakobsen Tim Holm
Published: October 2024

Introduction

Chronic wounds affect 1%–2% of the global population, with rising incidence due to ageing and lifestyle-related diseases. Bacterial biofilms, found in 80% of chronic wounds, and scattered single-cell bacteria may hinder healing. Microbes are believed to negatively impact healing by exacerbating inflammation and host immune response.

Methods and analysis

The primary objective of the chronic wound characterisation (CWC) study is to investigate chronic wounds through a prospective observational cohort study exploring bacterial community composition, inflammatory responses and the influence of bacteria on wound-healing trajectories. The CWC study will be investigated through two cohorts: thepredictiveandin-depth.

Thepredictive cohortincludes patients with a chronic wound scheduled for mechanical debridement. The debrided material will be collected for dual RNA sequencing and 16s ribosomal RNA gene sequencing, as well as samples for microbial culturing and a photo to assess the wound. Clinical data is recorded, and healing and/or other clinical endpoints are established through medical records.

Thein-depth cohortincludes and follows patients undergoing split-thickness skin grafting. Extensive sampling (ESwabs, biopsies, tape strips, debrided material and a sample of the skin graft) will be performed on surgery and patients will be seen at two follow-up visits. Samples will be analysed through culturing and next-generation sequencing methods. A biobank will be established comprising longitudinal clinical samples and clinical data.

Ethics and dissemination

The study has been approved by the board of health ethics, Capital Region of Denmark, under protocol number H-20032214. The study findings will be disseminated through peer-reviewed publications and showcased at both national and international conferences and meetings within the domains of microbiology, wound healing and infection.
Developing the ‘Life Threads’ approach to support families after traumatic brain injury in UK community settings: protocol for a qualitative prefeasibility study
Authors: Whiffin Charlotte Jane , Ellis-Hill Caroline , Norman Alyson , Lee Morag , Singh Parmjeet Kaur , Clark-Wilson Jo , Daisley Audrey , Felles Natasha Yasmin , Holloway Mark , Rose Sara , Gracey Fergus
Published: October 2024

Introduction

Traumatic brain injury (TBI) brings about inevitable and significant changes for family members. Mental health effects for family members are well documented but there are significant gaps in support options across services. Here, we describe our protocol for a study that seeks to investigate the potential for a narrative, creative approach, the ‘Life Threads’ approach, as a low intensity, accessible means of support that can be applied across service contexts.

Methods

We will recruit 20 family members of someone who sustained a TBI from services in an area of the UK with a diverse demographic. Family members will be provided with the ‘Life Threads’ approach materials and guided in their use. The study is planned to run from March 2023 to July 2024.

Analysis

Collection of data on potential usefulness, feasibility and acceptability will be through focus groups and individual interviews. Transcripts will be analysed using reflexive thematic analysis, conducted within a relativist, constructivist orientation.

Ethics and dissemination

Ethical approvals have been sought and gained (Nottingham 1 Research Ethics Committee, 23/EM/0185, 4 September 2023), and the study has been registered with ISRCTN. As a research team, we are guided by our own personal, professional and research experiences of TBI which we will consider reflexively throughout the research process. Results will be disseminated in collaboration with our patient and public involvement group through open peer-reviewed journal publication and scientific conference, with lay summaries shared via recruitment sites.

Trial registration number

ISRCTN17392794.
Diabetic health literacy and associated factors among patients with diabetes attending follow-up in public hospitals of Northeastern Ethiopia: a multicentre cross-sectional study
Authors: Nigussie Elda Mekonnen , Demeke Mekasha Getnet , Adane Tigist Demssew , Mengistu Bethelehem Taye , Goshu Abel Tibebu , Dessie Yihenew Ayehu , Worku Birhan Getye , Asefa Eyosiyas Yeshialem
Published: October 2024

Objective

To assess the magnitude of diabetic health literacy (DHL) and associated factors among diabetes patients attending follow-up at public hospitals in Northeastern Ethiopia.

Design

An institution-based cross-sectional study was conducted from 24 May to 24 June 2022.

Setting

Diabetic clinics of four public hospitals in Northeastern Ethiopia.

Participants

611 adult diabetes patients who have been undergoing follow-up care for at least 6 months were systematically selected. Patients who were unable to communicate, were critically ill and with gestational diabetes mellitus were excluded from the study.

Outcomes

DHL was assessed using a 15-item tool developed from existing literature.

Results

Of all the participants, 300 (49.1%) had low, 174 (28.5%) moderate and 137 (22.4%) had high DHL levels. The significant factors impacting DHL included age (<40 years old: AOR=3.48, 95% CI=2.11–5.77; 40–60 years: AOR=2.79, 95% CI=1.75–4.46), low education (AOR=0.29, 95% CI=0.16–0.56 for those who can’t read and write; AOR=0.41, 95% CI=0.23–0.74 for those who can read and write; AOR=0.45, 95% CI=0.27–0.76 for primary education), exposure to diabetic education (AOR=1.84, 95% CI=1.31–2.58), having ≥2 information sources (AOR=2.28, 95% CI=1.57–3.32), moderate social support (AOR=1.94, 95% CI=1.32–2.87), strong social support (AOR=2.73, 95% CI=1.75–4.26) and urban residence (AOR=1.65, 95% CI=1.14–2.39).

Conclusion

The study showed that less than a quarter of the patients have high DHL, with almost half having low levels of DHL. Tailoring health education programmes to diverse educational levels, incorporating multiple information sources and fostering social support networks could enhance DHL.
Emerging lessons from experiences at transitions in care among hospitalised patients with cancer with postdischarge frequent emergency department use: a qualitative study using linked clinical and patient-reported interview data from Quebec, Canada
Authors: Kurteva Siyana , Nassar Nabil , Tamblyn Robyn
Published: October 2024

Background

While teamwork is essential to providing high-quality patient-centred care, challenges in interprofessional collaboration and decision-making in hospital settings are common, especially for patients with cancer. The purpose of this qualitative study was to identify emerging themes and potential challenges related to hospital discharge experiences among patients hospitalised for cancer who became frequent emergency department (ED) users postdischarge.

Methods

A cohort of patients with cancer discharged from an academic health centre in Montreal (Canada) between October 2014 and November 2016 was assembled. Using health administrative claims from the provincial universal healthcare programme, frequent ED (FED) users were identified as patients who had a ≥4 ED visits in the year following hospital discharge. Qualitative analysis of transcripts from semistructured telephone interviews conducted with patients 25–30 days’ postdischarge was used for in-depth exploratory analyses to characterise hospital discharge experiences and transition process from the hospital to the community.

Results

Overall, 182 (14.5%) of 1253 patients with cancer who became FED users were included in this study. The mean age was 69.1 (SD=11.5), 59.9% (n=109) were male, and the most frequent cancers were 80 (43.9%) respiratory and 52 (28.6%) upper digestive cancer. Content analyses revealed six emerging themes from the FED patient interviews. Overall, these included (1) incomplete communication of information, (2) hospital discharge planning, (3) coordinating care among team members, (4) follow-up with outpatient providers, (5) monitoring and managing symptoms after discharge and (6) enlisting help of social and community supports.

Conclusions

Using integrated data from clinical, administrative claims and patient interviews, this study provided insights into the challenges related to hospital discharge experiences and transition into community among hospitalised patients with cancer with FED use. Application of our findings could assist in hospital discharge preparation and improvement in healthcare delivery and health outcomes.

Trial registration number

NCT01179867.
Treatments, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China: a retrospective analysis of the Beijing Municipal Medical Insurance Database
Authors: Zeng Yi , Liang SiTing , Wang Hanming , Zeng JiaDong , Luo Ying , Wang Weihao , Qiao JingTao , Fan Jingwen , Zhang Zhen , Guo Lixin
Published: October 2024

Objectives

Diabetes is closely associated with risk of stroke and its adverse sequelae. Approximately 20%–33% of patients with stroke have diabetes. In China, however, it is unclear how stroke affects healthcare utilisation, medications and complications among people with diabetes. This study aimed to analyse the clinical characteristics, treatment options, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China.

Design

A retrospective, multicentre, observational study.

Setting

Beijing Municipal Medical Insurance Database, with data from 2016 to 2018.

Participants

The study included patients with diabetes whose data included 2016–2018 outpatient medication records and who had Beijing medical insurance. Patients who did not have continuous prescription records for more than 2 months were excluded from the analysis. In total, 2 853 036 people with diabetes were included, and patients who had and did not have a stroke were compared.

Results

In our study, 19.75%–22.30% of patients with diabetes suffered from stroke between 2016 and 2018. The average annual medical cost for a patient diagnosed with diabetes is ¥9606.65, and the cost increases to ¥13 428.39 when diabetes was combined with stroke; thus, stroke increases the medical cost for patients with diabetes by 39.78% (p<0.0001). Among patients with diabetes who had a stroke, 4.76 medications were used (1.8 hypoglycaemic drugs and 2.97 non-hypoglycaemic drugs); these numbers were significantly greater than for patients with diabetes who did not have a stroke receiving both hypoglycaemic drugs and non-hypoglycaemic drugs (p<0.0001). Among patients with diabetes who did not have a stroke, 3.58 medications were used (1.66 hypoglycaemic drugs and 1.92 non-hypoglycaemic drugs). Patients with diabetes who had a stroke also had significantly greater incidences of diabetic peripheral neuropathy, diabetic kidney disease, diabetic retinopathy and diabetic angiopathy than those who did not have a stroke (p<0.0001). These drugs and costs increased with the number of complications (p<0.0001). The increased medical costs for each specific complication are also listed. We also analysed the medical costs and medication regimens stratified by sex, age group and complications.

Conclusions

Stroke is associated with a significant increase in complications and medications for patients with diabetes and greatly adds to the economic burden of these patients. Early identification of stroke risk factors in patients with diabetes, as well as targeted poststroke diabetes management, is crucial from a socioeconomic perspective for a comprehensive management and treatment of stroke in patients with diabetes.
Exploring the decision-making experience of elderly diabetes patients regarding their health-seeking behaviour: a descriptive qualitative study
Authors: Du Qiu Hui , Yang Jin Hong , Zhang Zi Chen , Li Shao Bo , Liu Yu Qin , Li Yu Min , Yang You , Jia Hong Hong
Published: October 2024

Background

Diabetes has emerged as a critical global public health issue. The burden of diabetes is escalating in developing countries, including China. For individuals with diabetes, making informed and rational decisions regarding health-seeking behaviour is crucial to prevent or delay the occurrence of complications. However, prevalent irrational health-seeking behaviours among Chinese patients with diabetes have led to a low treatment rate of only 32.2%. In this study, we explore the subjective experiences of elderly patients with diabetes related to their decision-making experience for seeking healthcare, providing valuable insights for targeted intervention, and provide theoretical basis for establishing an efficient medical and health service system.

Methods

A qualitative study using descriptive phenomenology research methodology was adopted to explore the decision-making experience of elderly diabetes patients in seeking healthcare services. A purposive sampling approach, specifically maximum variation sampling, was employed to conduct semistructured in-depth interviews with 11 eligible participants between January and February 2023. Data analysis was carried out using QSR Nvivo 12.0 software and Colaizzi’s seven-step analysis method.

Results

Four themes emerged: ‘lack of disease risk perception and negative coping styles’, ‘ huge medical and economic burden’, ‘lack of family and social support’ and ‘Dissatisfaction with medical services’.

Conclusion

The health-seeking behavioural decision-making level of elderly diabetic patients is relatively low. Medical and healthcare professionals should formulate targeted intervention measures aimed at improving their disease cognition level, changing their coping styles and enhancing their health-seeking behavioural decision-making level to improve their health outcomes. Meanwhile, policymakers should plan and allocate medical resources in a targeted manner based on the needs and expectations of patients.
An expert consensus on the most effective components of integrated motivational interviewing and cognitive behavioural therapy for lifestyle behaviour change: protocol for an online modified Delphi study
Authors: Barrett Stephen , Begg Stephen , Dunford Ashley , O'Halloran Paul , Rodda Kane , Denniss Emily , Breckon Jeff , Kingsley Michael
Published: October 2024

Introduction

Behaviour change interventions are advocated as a key approach to manage behavioural risk factors such as insufficient physical activity, poor diet and smoking. Integrated motivational interviewing and cognitive behavioural therapy (MI-CBT) interventions have become increasingly popular to promote behaviour change; however, there is a lack of agreement as to what constitutes necessary components of MI-CBT interventions for lifestyle behaviour change. The primary objective of this study is to use a consensus method to develop guidelines to design and deliver MI-CBT interventions for lifestyle behaviour change.

Methods

A three-round modified Delphi study will be conducted with an expert, international panel of clinicians and researchers. An online survey will be developed from assessments of key MI-CBT literature and practice guides to identify commonly used components of individually delivered MI and CBT interventions. In each round, participants will rate the extent to which they agree with each component using a Likert scale. Responses from Rounds 1 and 2 will be presented to participants in subsequent rounds. Responses will be represented using bar graphs and include the median and IQR of participants’ responses. To encourage consensus, participants will be asked to consider the group responses before finalising their opinion to the statements. If at least 80% of the experts agree to a statement in Rounds 2 or 3, it will be included in a final list of necessary statements.

Discussion

This modified Delphi process will help transparency in the design and implementation of MI-CBT interventions. The consensus statement will also help reporting and comparability among effectiveness studies for MI-CBT intervention studies, and help inform research, policy and practice.

Ethics and dissemination

Ethical approval has been granted by the La Trobe University Human Research Ethics Committee (approval number HEC24066). The results will be disseminated via peer-reviewed publications, conferences and international professional associations.
Factors affecting patients on antiretroviral therapy lost to follow-up in Asunafo South District of Ahafo Region, Ghana: a cross-sectional study
Authors: Kogi Robert , Krah Theresa , Asampong Emmanuel , Kamau Edward Mberu
Published: October 2024

Introduction

Despite the increased and effective programme coverage for antiretroviral therapy (ART), a considerable proportion of individuals receiving ART discontinue medication at different stages of their treatment pathway. In sub-Saharan Africa, approximately half of individuals who test positive for HIV are lost to follow-up (LTFU). This study was set out to answer the following question ‘What are the factors that affect patients on ART loss to follow-up in Asunafo South District of Ghana?’.

Methods

Cross-sectional study design with systematic random sampling was employed to select 620 HIV patients on ART. Stata V.17.0 was used to analyse the data. A cox-proportional hazard regression was fitted in order to determine the predictor variables. Variables for the multivariable regression model were chosen by entering the outcome variable (LTFU) and explanatory variables into the model. Finally, the association between the explanatory and outcome factors was determined using the adjusted HRs and their associated 95% CI was considered.

Results

A total of 600 respondents were used for the final analysis after data cleaning. Patients who began ART at age 41 years or older had a significantly lower chance of being LTFU than those who began ART at age 35 or less (adjusted HR (aHR)=0.34, 95% CI 0.13 to 0.84). Furthermore, patients who started ART with a primary education had 1.68-fold increased risk of LTFU compared with patients with no education (aHR=1.68; 95% CI 0.83 to 3.43). In addition, patients in rural locations had a 2.65-fold higher likelihood of being LTFU than patients in urban areas (aHR=2.65, 95% CI 1.29 to 5.44). The main reasons for missing ART appointments among patients included walking long distance to clinic, cost of transportation, fear of scolding from clinic staff, stigma and erratic supply of antiretrovirals.

Conclusion

All clinicians should consider the risk factors that have been identified when providing ART services and counselling.
Interferon-induced factor 16 is essential in metastatic melanoma to maintain STING levels and the immune responses upon IFN-γ response pathway activation
Authors: Kobayashi Yuta , Bustos Matias A , Hayashi Yoshinori , Yu Qiang , Hoon Dave
Published: October 2024

Background

Immune checkpoint inhibitor (ICIs)-based therapies are the standard of care treatment for patients with metastatic melanoma (MM). The stimulator of interferon genes (STING) signaling pathway is critical in controlling immune responses to ICIs. Interferon (IFN)-γ-inducible protein 16 (IFI16) is a cytosolic DNA sensor that activates the STING signaling pathway. The link between IFI16 and STING signaling pathway on IFN-γ stimulation and the connection to ICIs response remains not completely understood.

Methods

Deconvolution analyses were performed using the TCGA-SKCM, GSE91061, and PRJEB23709 public RNA sequencing (RNA-seq) data sets that contained RNA-seq for patients with MM. Functional assays combined with cytokine arrays were performed using MM cell lines to validate in silico data. Multiplex immunofluorescence was performed on untreated or pretreatment tumor samples from patients with MM.

Results

Deconvolution analysis showed that high-IFI16levels in melanoma cells were associated with a good prognosis in patients with MM and positively correlated with M1-macrophage infiltration. Functional assays using MM cell lines demonstrated that IFI16 is a key molecule to sense cytosolic DNA and activate STING and nuclear factor kappa B (NF-κB) signaling pathways, independent of cyclic GMP-AMP synthase or absent in melanoma 2, on IFN-γ stimulation. IFI16 knockdown significantly decreased CXCL10 and ICAM1 secretion. EZH2 inhibitor reversed the repressive epigenetic control on IFI16 to promote STING and NF-κB signaling pathways on IFN-γ stimulation. Increased IFI16, ICAM1, and CXCL10 levels in tumor samples from patients with MM were positively correlated with M1-macrophage infiltration and a significantly better response to ICIs.

Conclusions

This study identifies IFI16 as a key sensor during IFN-γ stimulation associated with ICI response, and it proposes the epigenetic EZH2 inhibitor as an alternative treatment strategy to overcome ICI resistance in patients with MM.
The effect of rituximab on patient reported outcomes in the preclinical phase of rheumatoid arthritis: 2 year data from the PRAIRI study
Authors: Frazzei Giulia , Cramer Sophie H M , Landewé Robert B M , Maijer Karen I , Gerlag Danielle M , Tak Paul P , de Vries Niek , van Baarsen Lisa G M , van Vollenhoven Ronald F , Tas Sander W
Published: October 2024

Objectives

Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients’ quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population.

Methods

Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)).

Results

No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=−0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found.

Conclusion

One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development.

Trial registration number

Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).
Combining patient-reported outcome measures to screen for active disease in rheumatoid arthritis and psoriatic arthritis
Authors: Looijen Agnes E M , Snoeck Henkemans Selinde V J , van der Helm-van Mil Annette H M , Welsing Paco M J , Koc Gonul Hazal , Luime Jolanda J , Kok Marc R , Tchetverikov Ilja , Korswagen Lindy-Anne , Baudoin Paul , Vis Marijn , de Jong Pascal H P
Published: October 2024

Objectives

To investigate whether a combination of general health (Visual Analogue Scale (VAS)), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain (VAS/Numerical Rating Scale (NRS)), quality of life (EQ-5D), fatigue (VAS/NRS) and presenteeism (0%–100% productivity loss) could aid as a screening tool to detect active disease in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Methods

RA patients from the tREACH trial and TARA trial (n=683) and PsA patients from the DEPAR cohort (n=525) were included. The association of a deterioration in the aforementioned patient-reported outcome measure (PROM) scores between two consecutive visits and having active disease was assessed. Active disease was defined as a change from disease activity score (DAS) ≤2.4 to DAS >2.4 in RA or Disease Activity Index in Psoriatic Arthritis (DAPSA) ≤14 to DAPSA >14 in PsA. The area under the curve (AUC) of the sum score of deteriorated PROMs was evaluated.

Results

4594 RA and 1154 PsA visits were evaluated and active disease occurred in 358 (8%) RA and 177 (15%) PsA visits. In both RA and PsA, a deterioration in general health (VAS), HAQ-DI, EQ-5D and pain (VAS/NRS) was significantly associated with active disease. The combination of these PROMs showed acceptable to excellent discriminative ability (RA AUC=0.76, PsA AUC=0.85). If a cut-point of ≥1 deteriorated PROMs is used, 40% of the visits in which RA patients have remission or low disease activity are correctly specified (specificity of 40%), while 10% of visits with active disease are overlooked (sensitivity of 90%). In PsA, these percentages are 41% and 4%, respectively.

Conclusion

A combination of general health, HAQ-DI, EQ-5D and pain could aid as a screening tool for active disease in patients with RA and PsA. These data could help facilitate remote monitoring of RA and PsA patients in the future.

Trial registration numbers

ISRCTN26791028, NTR2754.
Understanding external carotid artery collateralisation after cerebral revascularisation in moyamoya disease: insights from quantitative analysis
Authors: Li Wenjie , Zhao Meng , Liu Xingju , Wang Peijiong , Zhu Huan , Zhang Qihang , Zhu Chenyu , Zhang Qian , Ye Xun , Zhao Jizong , Zhang Yan
Published: October 2024

Background

This study aims to quantitatively evaluate collateralisation angiogenesis ratio (CAR) of external carotid artery and intracranial arterial residual volumes (ARV) postcerebral revascularisation in moyamoya disease (MMD) and elucidate the factors influencing external carotid artery collateralisation.

Methods

The study retrospectively analysed 297 patients diagnosed with MMD who underwent cerebral revascularisation at our University’s Hospital, between January 2015 and May 2023. The clinical data, imaging results and surgical specifics for the patients were collected. Using a newly proposed digital subtraction angiography-based evaluation system, the CAR of external carotid artery and the intracranial ARV were evaluated quantitatively following standardised protocols.

Results

The study included 136 male and 161 female patients. The severity of ischaemic (r=−0.297) and haemorrhagic (r=−0.270) MMD, as assessed by the Suzuki stage, demonstrated a significant negative correlation with intracranial ARV (p<0.001). However, no significant correlation was observed between the intracranial ARV and the modified Rankin Scale scores. Patients with fetal-type posterior cerebral arteries exhibited greater intracranial ARV compared with those without (p=0.003). Additionally, a positive correlation was observed between external carotid artery collateralisation and intracranial ARV post-revascularisation (r=0.340, p<0.001). The CAR of external carotid artery following cerebral revascularisation in patients with MMD remained independent correlation of the intracranial ARV (β=0.385, 95% CI (0.921 to 1.669), p<0.001) and Suzuki stage (β=0.211, 95% CI (0.009 to 0.030), p<0.001).

Conclusions

This study showed a complex association between ARV, the Suzuki stage and the collateralisation of the external carotid artery in patients with MMD who are undergoing revascularisation. These findings provide insights into MMD progression and revascularisation outcomes and may guide clinical decision-making to improve patient care.
Assessing climate change vulnerability in Canadian marine conservation networks: implications for conservation planning and resilience
Authors: Keen Laura H. , Stortini Christine H. , Boyce Daniel G. , Stanley Ryan R.E.
Published: October 2024

Marine protected areas (MPAs) are critical in safeguarding biodiversity and ecosystem functions under climate change. The long-term effectiveness of these static conservation measures will depend on how well they represent current and future ocean changes. Here, we use the Climate Risk Index for Biodiversity to assess the vulnerability representation of marine ecosystems within the Canadian marine conservation network (CMCN) under two divergent emissions scenarios. We found that MPAs best represent climate vulnerability in Atlantic Canada (85% representativity overall, and 93% in the Gulf of Saint Lawrence under low emissions), followed by the Pacific (78%) and Arctic (63%; lowest in the Eastern Arctic (41% under high emissions) regions). Notably, MPAs with lower climate vulnerability are proportionally overrepresented in the CMCN. Broad-scale geographic targets employed in the Scotian Shelf-Bay of Fundy network planning process achieve over 90% representativity of climate vulnerabilities, underscoring the importance of ensuring habitat representativity and geographic distribution in conservation planning to enhance climate resilience, even if not explicitly prioritized. Moving towards Canada’s target to protect 30% of its waters by 2030, prioritizing representativity and designation of MPAs in currently underrepresented climate-vulnerable regions may be crucial to enhancing the resilience of the CMCN amidst an ever-changing climate.
Trainability maximization using estimation of distribution algorithms assisted by surrogate modelling for quantum architecture search
Authors: Soloviev Vicente P. , Dunjko Vedran , Bielza Concha , Larrañaga Pedro , Wang Hao
Published: October 2024

Quantum architecture search (QAS) involves optimizing both the quantum parametric circuit configuration but also its parameters for a variational quantum algorithm. Thus, the problem is known to be multi-level as the performance of a given architecture is unknown until its parameters are tuned using classical routines. Moreover, the task becomes even more complicated since well-known trainability issues, e.g., barren plateaus (BPs), can occur. In this paper, we aim to achieve two improvements in QAS: (1) to reduce the number of measurements by an online surrogate model of the evaluation process that aggressively discards architectures of poor performance; (2) to avoid training the circuits when BPs are present. To detect the presence of the BPs, we employed a recently developed metric, information content, which only requires measuring the energy values of a small set of parameters to estimate the magnitude of cost function’s gradient. The main idea of this proposal is to leverage a recently developed metric which can be used to detect the onset of vanishing gradients to ensure the overall search avoids such unfavorable regions. We experimentally validate our proposal for the variational quantum eigensolver and showcase that our algorithm is able to find solutions that have been previously proposed in the literature for the Hamiltonians; but also to outperform the state of the art when initializing the method from the set of architectures proposed in the literature. The results suggest that the proposed methodology could be used in environments where it is desired to improve the trainability of known architectures while maintaining good performance.
Different phase leads to different transport behavior in Pb9Cu(PO4)6O compounds
Authors: Liu Ran , Guo Ting , Lu Jiajun , Ren Junfeng , Ma Tianxing
Published: October 2024

The recent claimed room-temperature superconductivity in Cu-doped lead apatite at ambient pressure is under debate. To identify its physical origin, we conducted a detailed analysis of the crystal structure, band structure, lattice dynamics and magnetic properties of the parent Pb[Formula: see text](PO4)6O compound and the two different phases of Pb9Cu(PO4)6O (LK-99) compound. Our results show that the parent Pb[Formula: see text](PO4)6O compound is an indirect band gap semiconductor, where Cu doping at the 4f site of Pb leads to a semiconducting to half-metallic transition. Two half-filled flat bands spanning the Fermi energy levels are present in the 4f phase of LK-99, which are mainly formed by hybridization of the d orbitals of Cu with the 2p orbitals of O. In addition, 6h phase of LK-99 always has spin polarization at the bottom of the conduction band and at the top of the valence band, making the material a magnetic semiconductor. Our theoretical research reveals recent experimental reports on the different transport properties of LK-99.
Remarks on celestial amplitudes and Liouville theory
Authors: Giribet Gaston
Published: October 2024

The relation between celestial holography and Liouville field theory is investigated. It is shown that the duality relations between different Selberg-type integrals appearing in the Coulomb gas realization of Liouville correlation functions induce a series of relations between celestial amplitudes with shifted values of the operator dimensions [Formula: see text].
THE RELATIONSHIP OF POSTERIOR TIBIAL SLOPE WITH CRUCIATE LIGAMENTS AND MENISCAL INJURIES BASED ON MRI– A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Vijay C. , Santosh M. S. , Shreyas M. J. , Jain Nirav , Adarsh T.
Published: October 2024

Purpose: Various studies show that the disparities in the posterior tibial slope can make native cruciate ligaments and the menisci susceptible to tears. This study is to determine the relationship between posterior tibial slope with the anterior cruciate ligament, posterior cruciate ligament and meniscal injuries.

Methods: A total of 72 subjects between 18 and 60 years having a history of traumatic knee pain were included in the study. All subjects were clinically examined, radiologically investigated, and the posterior tibial slope of the patients was calculated. Incidences of cruciate ligaments and menisci injury were identified.

Results: In our study, the mean medial compartment posterior tibial slope and lateral compartment posterior tibial slope in all the Anterior Cruciate Ligament injured patients are 7.82 ± 2.56 and 10.53 ± 3.46. But in controls, it is 5.91 ± 4.49 and 6.24 ± 5.15, respectively. The differences are statistically significant ([Formula: see text] 10). In cases with increased lateral Posterior Tibial Slope, more degeneration was seen in the lateral meniscus. Less Posterior Tibial Slope is associated with Posterior Cruciate Ligament tears.

Conclusion: Anterior cruciate ligament is more prone to tears with a steeper posterior tibial slope. Lateral Meniscus tear is frequently associated with acute Anterior Cruciate Ligament injury and Medial Meniscus tear is predominantly associated with a chronic Anterior Cruciate Ligament injury. A decreased posterior tibial slope is more often associated with patients with a posterior cruciate ligament injury and is considered a risk factor for native Posterior Cruciate Ligament.
Subsurface Characterization and Revealing Geometry of the Baribis Fault in the Eastern Part of West Java Using Long-Offset Resistivity Tomography
Authors: Nurhandoko Bagus Endar B. , Triyoso Kaswandhi , Wibowo Satryo Agung , Komara Insan Rizal , Guntara Wisnu , Asmawati Diah , Martha Rio K. , Widowati Sri , Supriyanto Eko B. , Suryolaksana Agung , Nefrizal Nefrizal , Nurani Amalia , Endartyanto Aries , Nurhasan Nurhasan
Published: October 2024

The Baribis Fault is an important active fault in West Java, Indonesia. This fault has recently attracted the attention of many parties since some fault segments pass through densely populated areas, raising the risk of shallow earthquakes. The long-offset resistivity tomography method was applied to image the active Baribis Faults. This method clearly showed the subsurface geometry, including the contact characteristics of the Baribis Fault near the subsurface. The long-offset resistivity tomography surveys were acquired using multi-electrodes and multi-nodes, and the data acquisition was wirelessly controlled via a WiFi connection. The pole–dipole resistivity tomography image shows a 35∘ dip overhang structure of the Baribis thrust fault near the Jatigede area in Middle Eastern West Java, with a strike fault segment in a relative East–West direction. However, the other long-offset tomography images in northeastern West Java, near the Conggeang–Sumedang area, show the oblique thrust fault phenomena of the Baribis Fault with a strike in the Northeast–Southwest direction. The stress caused by the Cimandiri–Lembang regional strike–slip fault likely influences the dynamics of the Baribis Fault in the close area of Sumedang.
Design of a playable spherical grip strength detection system based on a PVDF flexible sensor
Authors: Yang Aichao , Song Rui , Wang Xue , Luo Haijun
Published: October 2024

Grip strength is a crucial indicator for assessing individual health and muscle function, reflecting the level of upper limb strength development. Current grip strength detection devices, while able to accurately assess the magnitude of grip strength, do not integrate well into daily life and have certain limitations in unobtrusive detection during individual activities. Inspired by elderly individuals playing with walnuts in their hands to improve hand blood circulation, clear meridians, and prevent cardiovascular diseases, this work designs a playable spherical grip strength detection (PSGD) system based on polyvinylidene fluoride (PVDF) flexible sensor. The PVDF sensor has a vertical pressure sensitivity of 3.955 V/N and can respond to vertical pressures in the 0–15 Hz frequency range, maintaining stable output over more than 2000 cycles. The PSGD system consists of a spherical shell, a PVDF flexible sensor, a data collection and transmission module, and a data reception and display module, enabling effective collection, processing, transmission, display, and storage of grip strength signals during playing. The PSGD system can respond excellently to grip strength signals, with the magnitude of the grip strength positively correlating with the output voltage signal. It can also distinguish the grip strength differences between individuals and has excellent output stability. The PSGD system holds broad application prospects in fields such as rehabilitative medicine and elderly health management.