bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multi-mode Electronic Load Sensing Control Scheme with Power Limitation and Pressure Cut-off for Mobile Machinery
Authors: Cheng Min , Sun Bolin , Ding Ruqi , Xu Bing
Published: February 2023

In mobile machinery, hydro-mechanical pumps are increasingly replaced by electronically controlled pumps to improve the automation level, but diversified control functions (e.g., power limitation and pressure cut-off) are integrated into the electronic controller only from the pump level, leading to the potential instability of the overall system. To solve this problem, a multi-mode electrohydraulic load sensing (MELS) control scheme is proposed especially considering the switching stability from the system level, which includes four working modes of flow control, load sensing, power limitation, and pressure control. Depending on the actual working requirements, the switching rules for the different modes and the switching direction (i.e., the modes can be switched bilaterally or unilaterally) are defined. The priority of different modes is also defined, from high to low: pressure control, power limitation, load sensing, and flow control. When multiple switching rules are satisfied at the same time, the system switches to the control mode with the highest priority. In addition, the switching stability between flow control and pressure control modes is analyzed, and the controller parameters that guarantee the switching stability are obtained. A comparative study is carried out based on a test rig with a 2-ton hydraulic excavator. The results show that the MELS controller can achieve the control functions of proper flow supplement, power limitation, and pressure cut-off, which has good stability performance when switching between different control modes. This research proposes the MELS control method that realizes the stability of multi-mode switching of the hydraulic system of mobile machinery under different working conditions.
White matter hyperintensities and cerebral microbleeds in persistent post-traumatic headache attributed to mild traumatic brain injury: a magnetic resonance imaging study
Authors: Ashina Håkan , Christensen Rune H. , Al-Khazali Haidar Muhsen , Iljazi Afrim , Tolnai Daniel , Eigenbrodt Anna K. , Larsson Henrik B. W. , Schytz Henrik W. , Lindberg Ulrich , Amin Faisal Mohammad
Published: February 2023

Objective

To examine whether white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs) are more prevalent in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI), compared with healthy controls.

Methods

A magnetic resonance imaging (MRI) study of adults with persistent post-traumatic headache attributed to mild TBI and age- and gender-matched healthy controls. A semi-structured interview and validated self-report instruments were used to record data on demographics, clinical characteristics, and comorbidities. Imaging data were obtained on a 3T MRI Scanner using a 32-channel head coil. Participants and controls underwent a single MRI session, in which fluid-attenuated inversion recovery was used to visualize WMHs, and susceptibility-weighted imaging was used to detect CMBs. The primary outcomes were (I) the difference in the mean number of WMHs between participants with persistent post-traumatic headache and healthy controls and (II) the difference in the mean number of CMBs between participants with persistent post-traumatic headache and healthy controls. All images were examined by a certified neuroradiologist who was blinded to the group status of the participants and controls.

Results

A total of 97 participants with persistent post-traumatic headache and 96 age- and gender-matched healthy controls provided imaging data eligible for analyses. Among 97 participants with persistent post-traumatic headache, 43 (44.3%) participants presented with ≥ 1 WMH, and 3 (3.1%) participants presented with ≥ 1 CMB. Compared with controls, no differences were found in the mean number of WMHs (2.7 vs. 2.1, P = 0.58) and the mean number of CMBs (0.03 vs. 0.04, P = 0.98).

Conclusions

WMHs and CMBs were not more prevalent in people with persistent post-traumatic headache than observed in healthy controls. Future studies should focus on other MRI techniques to identify radiologic biomarkers of post-traumatic headache.
Characterizing healthcare utilization patterns in a Danish population with headache: results from the nationwide headache in Denmark (HINDER) panel
Authors: Do Thien Phu , Dømgaard Mikala , Stefansen Simon , Steiner Timothy J. , Ashina Messoud
Published: February 2023

Introduction

Worldwide, far from all of those who would benefit make use of headache services, largely because of clinical, social, and political barriers to access. Identifying the factors contributing to low healthcare utilization can generate evidence to guide health policy. Our purpose here is better to characterize healthcare utilization patterns in Denmark.

Methods

The Headache in Denmark (HINDER) study is a nationwide cross-sectional survey of people with headache, conducted using SurveyXact (Rambøll Group A/S, Copenhagen). Healthcare utilization was assessed in a study sample generated by population screening and recruitment. Data collection occurred over two weeks, from September 23rd until October 4th, 2021. The questions enquired into disease characteristics, management, burden, medication intake and healthcare utilization.

Results

The number of participants included in the HINDER panel was 4,431, with 2,990 (67.5%: 2,522 [84.3%] female, 468 [15.7%] male; mean age 40.9 ± 11.6 years) completing the survey. One quarter of participants (27.7%) disagreed or strongly disagreed that they were able to manage their headache attacks. Most participants (81.7%) agreed or strongly agreed that their headache was a burden in their everyday lives. The most reported acute medications, by 87.2% of participants, were simple analgesics; of note, 8.6% reported using opioids for their headache. One quarter of participants (24.4%) had never consulted a medical doctor for their headache; one in six (16.5%: more than two thirds of the 24.4%) had never done so despite agreeing or strongly agreeing that their headache was a burden in their everyday lives. Two thirds (65.3%) of participants overall, and almost three quarters (72.4%) of those with weekly headache, had tried one or more complementary or alternative therapies outside conventional medical care.

Conclusions

Our findings are indicative of inadequate delivery of headache care in a country that provides free and universal coverage for all its residents. The implications are twofold. First, it is not sufficient merely to make services available: public education and increased awareness are necessary to encourage uptake by those who would benefit. Second, educational interventions in both pre- and postgraduate settings are necessary, but a prerequisite for these is a resetting of policy priorities, properly to reflect the very high population ill-health burden of headache.
Growth, structure, and morphology of van der Waals epitaxy Cr1+δTe2 films
Authors: Wang Xiaodan , Zhou Hua , Bai Lihui , Wang Hui-Qiong
Published: February 2023

The preparation of two-dimensional magnetic materials is a key process to their applications and the study of their structure and morphology plays an important role in the growth of high-quality thin films. Here, the growth, structure, and morphology of Cr1+δTe2 films grown by molecular beam epitaxy on mica with variations of Te/Cr flux ratio, growth temperature, and film thickness have been systematically investigated by scanning tunneling microscopy, reflection high-energy electron diffraction, scanning electron microscope, and X-ray photoelectron spectroscopy. We find that a structural change from multiple phases to a single phase occurs with the increase in growth temperature, irrespective of the Cr/Te flux ratios, which is attributed to the desorption difference of Te atoms at different temperatures, and that the surface morphology of the films grown at relatively high growth temperatures (≥ 300 °C) exhibits a quasi-hexagonal mesh-like structure, which consists of nano-islands with bending surface induced by the screw dislocations, as well as that the films would undergo a growth-mode change from 2D at the initial stage in a small film thickness (2 nm) to 3D at the later stage in thick thicknesses (12 nm and 24 nm). This work provides a general model for the study of pseudo-layered materials grown on flexible layered substrates.
Carboxylated graphene quantum dots-mediated photothermal therapy enhances drug-membrane permeability, ROS production, and the immune system recruitment on 3D glioblastoma models
Authors: Perini Giordano , Palmieri Valentina , Friggeri Ginevra , Augello Alberto , De Spirito Marco , Papi Massimiliano
Published: February 2023

Graphene quantum dots (GQDs) are biocompatible nanoparticles employed in biomedical field, thanks to their size and photophysical properties. GQDs have shown the capability to cross biological barriers, including the blood–brain barrier, which makes them promising agents for brain diseases therapy. It has been shown that surface-functionalized GQDs enhance membrane fluidity and intracellular uptake, exerting a synergistic effect with antitumor drugs at subtherapeutic doses. Here, we tested GQDs effects in combination with chemotherapeutic agents doxorubicin and temozolomide, on a complex 3D spheroid model of glioblastoma. We observed that the capability of GQDs to absorb and convert near-infrared light into heat is a key factor in membrane permeability enhancement on 3D model. This non-invasive therapeutic strategy named photothermal therapy (PTT), combined to chemotherapy at subtherapeutic doses, significantly increased the effect of antitumor drugs by reducing tumor growth and viability. Furthermore, the increase in membrane permeability due to GQDs-mediated PTT enhanced the release of reactive oxygen species with strong migration of the immune system towards irradiated cancer spheroids. Our data indicate that the increase in membrane permeability can enhance the efficacy of antitumor drugs at subtherapeutic doses against glioblastoma, reducing side effects, and directing immune response, ultimately improving quality of life for patients.
Does multi-way, long-range chromatin contact data advance 3D genome reconstruction?
Authors: Olshen Adam B. , Segal Mark R.
Published: February 2023

Background

Methods for inferring the three-dimensional (3D) configuration of chromatin from conformation capture assays that provide strictly pairwise interactions, notably Hi-C, utilize the attendant contact matrix as input. More recent assays, in particular split-pool recognition of interactions by tag extension (SPRITE), capture multi-way interactions instead of solely pairwise contacts. These assays yield contacts that straddle appreciably greater genomic distances than Hi-C, in addition to instances of exceptionally high-order chromatin interaction. Such attributes are anticipated to be consequential with respect to 3D genome reconstruction, a task yet to be undertaken with multi-way contact data. However, performing such 3D reconstruction using distance-based reconstruction techniques requires framing multi-way contacts as (pairwise) distances. Comparing approaches for so doing, and assessing the resultant impact of long-range and multi-way contacts, are the objectives of this study.

Results

We obtained 3D reconstructions via multi-dimensional scaling under a variety of weighting schemes for mapping SPRITE multi-way contacts to pairwise distances. Resultant configurations were compared following Procrustes alignment and relationships were assessed between associated Procrustes root mean square errors and key features such as the extent of multi-way and/or long-range contacts. We found that these features had surprisingly limited influence on 3D reconstruction, a finding we attribute to their influence being diminished by the preponderance of pairwise contacts.

Conclusion

Distance-based 3D genome reconstruction using SPRITE multi-way contact data is not appreciably affected by the weighting scheme used to convert multi-way interactions to pairwise distances.
An age-old problem or an old-age problem? A UK survey of attitudes, historical use and recommendations by healthcare professionals to use healthcare apps
Authors: Chowdhury Sulayman Z. , Stevens Sebastian , Wu Charlotte , Woodward Claire , Andrews Tim , Ashall-Payne Liz , Leigh Simon
Published: February 2023

Background

The coronavirus pandemic has exacerbated barriers to accessing face-to-face care. Consequently, the potential for digital health technologies (DHTs) to address unmet needs has gained traction. DHTs may circumvent several barriers to healthy independent living, resulting in both socioeconomic and clinical benefits. However, previous studies have demonstrated these benefits may be disproportionately realised among younger populations while excluding older people.

Methods

We performed a prospective survey using the One Poll market research platform among 2000 adults from the United Kingdom. To mitigate against self-selection bias, participants were not informed of the topic of the survey until they had completed recruitment. We compared willingness to use and historical use of health-apps, in addition to recommendations to use health-apps from healthcare professionals; comparing outcomes across all age groups, including a reference group (n = 222) of those aged 18-24. Outcomes were analysed using multivariate logistic regression and reported as odds ratios (OR) with respondent age, ethnicity, gender, and location as covariates.

Results

Willingness to use health-apps decreased significantly with age, reaching a minimum (OR = 0.39) among those aged 65 and over compared to the reference group of 18-24 year olds. Despite this, more than 52% of those aged 65 and over were willing to use health-apps. Functions and features most cited as useful by older populations included symptom self-monitoring and surgery recovery assistance. The likelihood of never having used a health-app also increased consistently with age, reaching a maximum among those aged 65 and over (OR = 18.3). Finally, the likelihood of being recommended health-apps by a healthcare professional decreased significantly with age, (OR = 0.09) for those aged 65 and over. In absolute terms, 33.8% of those aged 18-24, and 3.9% of those aged 65 and over were recommended health-apps by their healthcare professionals.

Conclusion

Although absolute utilisation of health-apps decreases with age, the findings of this study suggest that the gap between those willing to use health-apps, and those being recommended health-apps by healthcare professionals increases with age. Given the increasing availability of evidence-based health-apps designed for older populations, this may result in entirely avoidable unmet needs, suggesting that more should be done by healthcare professionals to recommend health-apps to older persons who are generally positive about their use. This may result in considerable improvements in healthy and independent ageing.
Identification of decreased intrinsic capacity: Performance of diagnostic measures of the ICOPE Screening tool in community dwelling older people in the VIMCI study
Authors: Rojano i Luque Xavier , Blancafort-Alias Sergi , Prat Casanovas Susanna , Forné Susanna , Martín Vergara Nuria , Fabregat Povill Pilar , Vila Royo Maria , Serrano Rosa , Sanchez-Rodriguez Dolores , Vílchez Saldaña Montserrat , Martínez Iris , Domínguez López Mariola , Riba Porquet Francesc , Intxaurrondo González Aimar , Salvà Casanovas Antoni
Published: February 2023

Background

The World Health Organization (WHO) has developed the Integrated Care for Older People (ICOPE) strategy to face the challenges of ageing societies. This strategy is focused on person centered care and the assessment intrinsic capacity (IC). Early identification of five domains of IC (cognition, locomotion, vitality, sensory (hearing and vision), and psychological) has been shown to be related with adverse outcomes and can guide actions towards primary prevention and healthy ageing. IC assessment proposed by the WHO ICOPE guidelines is composed by two steps: First, Screening for decreased IC by the ICOPE Screening tool; second, by the reference standard methods. The aim was to assess the performance of diagnostic measures (sensibility, specificity, diagnostic accuracy, and agreement of the ICOPE Screening tool) compared to the reference standard methods in European community-dwelling older adults.

Methods

Cross-sectional analysis of the baseline of the ongoing VIMCI (Validity of an Instrument to Measure Intrinsic Capacity) cohort study, which was carried out in Primary Care centers and outpatient clinics from 5 rural and urban territories in Catalonia (Spain). Participants were 207community dwelling persons ≥ 70-year-old with Barthel $$\ge$$
≥
90, without dementia or advanced chronic conditions who provided their consent to participate. The 5 IC domains were assessed by the ICOPE Screening tool and the reference methods (SPPB, gait speed, MNA, Snellen chart, audiometry, MMSE, GDS5) during patients’ visit. Agreement was assessed with the Gwet AC1 index.

Results

ICOPE Screening tool sensitivity was higher for cognition (0.889) and ranged between 0.438 and 0.569 for most domains. Specificity ranged from 0.682 to 0.96, diagnostic accuracy from 0.627 to 0.879, Youden index from 0.12 to 0.619, and Gwet AC1 from 0.275 to 0.842.

Conclusion

The ICOPE screening tool showed fair performance of diagnostic measures; it was helpful to identify those participants with satisfactory IC and showed a modest ability to identify decreased IC in older people with high degree of autonomy. Since low sensitivities were found, a process of external validation would be recommended to reach better discrimination. Further studies about the ICOPE Screening tool and its performance of diagnostic measures in different populations are urgently required.
Opioid prescribing among aged care residents during the first year of the COVID-19 pandemic: an analysis using general practice health records in Australia
Authors: Dai Zhaoli , Raban Magdalena Z. , Sezgin Gorkem , McGuire Precious , Datta Shirmilla , Wabe Nasir , Pearce Christopher , Woodman Richard , Georgiou Andrew
Published: February 2023

Background

Opioid use is common among adults 65 years and older, while long-term use of opioids remains controversial and poses risks of drug dependence and other adverse events. The acute disease caused by the SARS-CoV-2 (COVID-19) pandemic has created new challenges and barriers to healthcare access, particularly for long-term care residents. Australia had a relatively low incidence and deaths due to COVID-19 during the first year of the pandemic compared to most OECD countries. In this context, we examined opioid prescribing rates and their dosage in residential aged care facilities (RACFs) before (2019) and during the COVID-19 pandemic (2020) from March to December in Australia.

Methods

We conducted a retrospective cohort analysis using general practice electronic health records. This includes 17,304 RACF residents aged 65 years and over from 361 general practices in New South Wales and Victoria. Number of opioid prescriptions and percentage of opioids over 50 mg/day of oral morphine equivalent (OME) were described. Multivariate generalized estimating equations were applied to estimate odds ratios [aORs (95% confidence intervals)] for 1) opioids prescribed per consultation and 2) prescription opioids over 50 mg/day OME.

Results

In 2020 among 11,154 residents, 22.8% of 90,897 total prescriptions were opioids, and of the opioids, 11.3% were over 50 mg/day OME. In 2019 among 10,506 residents, 18.8% of 71,829 total prescriptions were opioids, of which 10.3% were over 50 mg/day OME. Year [2020 vs. 2019: aOR (95% CI):1.50 (1.44, 1.56); 1.29 (1.15, 1.46)] and regionality [rural/regional vs. metropolitan: 1.37 (1.26, 1.49); 1.40 (1.14, 1.71)] were associated with higher odds of prescription opioids and OME > 50 mg/day, respectively. Similar results were found when limited to the same residents (n = 7,340) recorded in both years.

Conclusions

Higher prescription rates of opioids were observed during the COVID-19 pandemic in 2020 than in 2019 in Australian RACFs. The higher odds of prescription opioids and higher dosing in rural/regional than metropolitan areas indicate a widening of the gap in the quality of pain management during the pandemic. Our findings contribute to the limited data that indicate increased opioid prescriptions in long-term care facilities, which is likely to continue while COVID-19 pandemic restrictions remain.
Possibility of mpox viral transmission and control from high-risk to the general population: a modeling study
Authors: Yang Shiting , Guo Xiaohao , Zhao Zeyu , Abudunaibi Buasiyamu , Zhao Yunkang , Rui Jia , Wang Yao , Song Wentao , Wei Hongjie , Chen Tianmu
Published: February 2023

Background

Mpox is an emerging infectious disease that is now a global hazard. The strategies for preventing and controlling mpox should be further investigated in terms of transmission characteristics, infection risk among different populations, and ideal therapeutic approaches.

Methods

A multi-group dynamic model was used to quantify the transmissibility of mpox. We further analyzed the transmission risk from men who have sex with men (MSM) to non-MSM and evaluated the effects of three intervention measures, including community-based prevention, early detection, and vaccination.

Results

The median value of effective reproduction number (Reff) and probability of contact via a single contact (q) among MSM worldwide is 3.11 (interquartile range [IQR]: 2.82–5.57) and 2.15% (IQR: 1.95–3.84%). We found that the cumulative incidence rate of non-MSM is much lower than that of MSM (< 1/2048) when the possibility of infection (including the percentage of high-risk behaviors of contact degree [C] and q) was lowered to less than 1 in 100,000. When comparing the three intervention measures, if we want to control the cumulative incidence rate to 5.96 × 10–8 we need to increase the vaccine coverage to 81% or reduce the transmission rate factor (Cq) to 70% or shorten the transmission period to 74%.

Conclusions

Mpox has high transmissibility in MSM, which required minimize the risk of infection and exposure to high-risk populations. Community prevention and control is the top priority of interventions to contain the spread of mpox.
Safety and efficacy of tuberculosis vaccine candidates in low- and middle-income countries: a systematic review of randomised controlled clinical trials
Authors: Wilson Lydia , Gracie Lara , Kidy Farah , Thomas G. Neil , Nirantharakumar Krishnarajah , Greenfield Sheila , Manaseki-Holland Semira , Ward Derek J. , Gooden Tiffany E.
Published: February 2023

Background

Tuberculosis (TB) remains a leading cause of death worldwide, with 98% of cases occurring in low- and middle-income countries (LMICs). The only vaccine licenced for the prevention of TB has limited protection for adolescents, adults and vulnerable populations. A safe and effective vaccine for all populations at risk is imperative to achieve global elimination of TB. We aimed to systematically review the efficacy and safety of TB vaccine candidates in late-phase clinical trials conducted in LMICs.

Methods

Medline, Embase, CENTRAL, PubMed, Clinicaltrials.gov and Greylit.org were searched in June 2021 to identify phase 2 or later clinical randomised controlled trials that report the efficacy or safety (adverse events) of TB vaccine candidates with participants of any age living in an LMIC. TB vaccine candidates listed in the 2020 WHO Global TB Report were eligible for inclusion aside from BCG revaccination. Trials were excluded if all participants had active TB at baseline. Two reviewers independently assessed papers for eligibility, and for bias and quality using the Risk of Bias 2 tool and GRADE guidelines, respectively. We report efficacy rates and frequencies of adverse events from each included trial where available and qualitatively synthesise the findings.

Results

Thirteen papers representing eleven trials met our inclusion criteria. Seven vaccine candidates were reviewed across seven countries: M72/AS01, RUTI, VPM1002, H56:IC31, MTBVAC, DAR-901 and ID93 + GLA-SE. Two trials reported on efficacy: an efficacy rate of 54% (95% CI 11.5, 76.2) was reported for M72/AS01 in adults with latent TB and 3% (95% CI -13.9, 17.7) for DAR-901 in healthy adolescents. However, the latter trial was underpowered. All vaccine candidates had comparable occurrences of adverse events between treatment arms and demonstrated acceptable safety profiles; though, RUTI resulted in one serious complication in a person living with HIV. M72/AS01 was the only vaccine considered safe across a diverse group of people including people living with HIV or latent TB and healthy infants and adolescents.

Conclusion

Further efficacy trials for M72/AS01 are warranted to include additional populations at risk where safety has been demonstrated. Further safety trials are needed for the remaining vaccine candidates to confirm safety in vulnerable populations.
Risk factors associated with Pneumocystis jirovecii pneumonia in non-HIV immunocompromised patients and co-pathogens analysis by metagenomic next-generation sequencing
Authors: Huang Liping , Xu Shuyun , Huang Zhimin , Chen Yusheng , Xu Nengluan , Xie Baosong
Published: February 2023

Background

Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear.

Methods

Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. 

Results

A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 109/L (OR 6.882, P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV, EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group(p < 0.005). 

Conclusions

Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 109/L. Prophylaxis for PJP cannot rely solely on CD4+ T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.
Human salivary protein-derived peptides specific-salivary SIgA antibodies enhanced by nasal double DNA adjuvant in mice play an essential role in preventing Porphyromonas gingivalis colonization: an in-vitro study
Authors: Koyanagi Kayo , Kataoka Kosuke , Yoshimatsu Hideki , Fujihashi Kohtaro , Miyake Tatsuro
Published: February 2023

Background

We previously showed that fimbriae-bore from Poryphyromonas gingivalis (Pg), one of the putative periodontopathogenic bacteria specifically bound to a peptide domain (stat23, prp21) shared on statherin or acidic proline-rich protein 1 (PRP1) molecule of human salivary proteins (HSPs). Here, we investigated whether the nasal administration of DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 as double DNA adjuvant (dDA) with stat23 and prpr21 induces antigen (Ag)-specific salivary secretory IgA (SIgA) antibodies (Abs) in mice. Further, we examined that stat23- and prpr21-specific salivary SIgA Abs induced by dDA have an impact on Pg-binding to human whole saliva-coated hydroxyapatite beads (wsHAPs).

Material and methods

C57BL/6N mice were nasally immunized with dDA plus sta23 or/and prp21 peptide as Ag four times at weekly intervals. Saliva was collected one week after the final immunization and was subjected to Ag-specific ELISA. To examine the functional applicability of Ag-specific SIgA Abs, SIgA-enriched saliva samples were subjected to Pg binding inhibition assay to wsHAPs.

Results

Significantly elevated levels of salivary SIgA Ab to stat23 or prp21 were seen in mice given nasal stat23 or prp21 with dDA compared to those in mice given Ag alone. Of interest, mice nasally given the mixture of stat23 and prp21 as double Ags plus dDA, resulted in both stat23- and prp21-specific salivary SIgA Ab responses, which are mediated through significantly increased numbers of CD11c+ dendritic cell populations and markedly elevated Th1 and Th2 cytokines production by CD4+ T cells in the mucosal inductive and effector tissues. The SIgA Ab-enriched saliva showed significantly reduced numbers of live Pg cells binding to wsHAPs as compared with those in mice given double Ags without dDA or naïve mice. Additionally, saliva from IgA-deficient mice given nasal double Ags plus dDA indicated no decrease of live Pg binding to wsHAPs.

Conclusion

These findings show that HSP-derived peptides-specific salivary SIgA Abs induced by nasal administration of stat23 and prp21 peptides plus dDA, play an essential role in preventing Pg attachment and colonization on the surface of teeth, suggesting a potency that the SIgA may interrupt and mask fimbriae-binding domains in HSPs on the teeth.
Routine healthcare disruptions: a longitudinal study on changes in self-management behavior during the COVID-19 pandemic
Authors: Menting Juliane , van Schelven Femke , Aussems Claire , Heijmans Monique , Boeije Hennie
Published: February 2023

Background

The outbreak of COVID-19 had a significant impact on routines and continuity of professional care. As frequent users of this professional care, especially for people with chronic diseases this had consequences. Due to barriers in access to healthcare, an even greater appeal was made on the self-management behaviors of this group. In the present study, we aim to investigate the extent to which self-management changed during the recent pandemic, and which factors contributed to these changes.

Methods

The Dutch ‘National Panel of people with Chronic Illness or Disability’ was used to collect self-reported data of people with at least one chronic disease. Self-management was assessed with the Partners in Health questionnaire at two time points: before the crisis in 2018 and during the second wave of crisis in Autumn 2020. Paired t-tests were used to analyze changes in self-management. Potential associating factors on three levels – patient, organization and environment – were assessed in 2020 and their impact on self-management changes was tested with multinomial logistic regression.

Results

Data from 345 panel members was available at two time points. In the majority of people, self-management behaviors were stable (70.7%). About one in seven experienced improved self-management (15.1%), and a similar proportion experienced deteriorated self-management (14.2%). Sex, physical disability, mental health and daily stressors due to COVID-19 (patient level), changes in healthcare access (organization level), and social support (environment level) were significantly associated with experienced changes in self-management.

Conclusions

People with chronic diseases experienced different trajectories of self-management changes during COVID-19. We need to be aware of people who seem to be more vulnerable to a healthcare crisis and report less stable self-management, such as those who experience mental health problems or daily stressors. Continuity of care and social support can buffer the impact of a healthcare crisis on self-management routines of people with chronic diseases.
Detection and characterization of constitutive replication origins defined by DNA polymerase epsilon
Authors: Jaksik Roman , Wheeler David A. , Kimmel Marek
Published: February 2023

Background

Despite the process of DNA replication being mechanistically highly conserved, the location of origins of replication (ORI) may vary from one tissue to the next, or between rounds of replication in eukaryotes, suggesting flexibility in the choice of locations to initiate replication. Lists of human ORI therefore vary widely in number and location, and there are currently no methods available to compare them. Here, we propose a method of detection of ORI based on somatic mutation patterns generated by the mutator phenotype of damaged DNA polymerase epsilon (POLE).

Results

We report the genome-wide localization of constitutive ORI in POLE-mutated human tumors using whole genome sequencing data. Mutations accumulated after many rounds of replication of unsynchronized dividing cell populations in tumors allow to identify constitutive origins, which we show are shared with high fidelity between individuals and tumor types. Using a Smith–Waterman-like dynamic programming approach, we compared replication origin positions obtained from multiple different methods. The comparison allowed us to define a consensus set of replication origins, identified consistently by multiple ORI detection methods. Many DNA features co-localized with the consensus set of ORI, including chromatin loop anchors, G-quadruplexes, S/MARs, and CpGs. Among all features, the H2A.Z histone exhibited the most significant association.

Conclusions

Our results show that mutation-based detection of replication origins is a viable approach to determining their location and associated sequence features.
Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study
Authors: Cao Xingqi , Yang Zhenqing , Li Xueqin , Chen Chen , Hoogendijk Emiel O. , Zhang Jingyun , Yao Nengliang Aaron , Ma Lina , Zhang Yawei , Zhu Yong , Zhang Xuehong , Du Yuxian , Wang Xiaofeng , Wu Xifeng , Gill Thomas M. , Liu Zuyun
Published: February 2023

Background

Comorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors.

Methods

We included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40–69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0–5) and the frailty index (FI_Frailty, range: 0–1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models.

Results

Compared with non-frail participants, those with pre-frailty (FP_Frailty [met 1–2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings.

Conclusions

Frailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.
Management of encephalomyocarditis virus infection in Italian pig farms: a case report
Authors: Scollo A. , Mazzoni C. , Luppi A.
Published: February 2023

Background

Encephalomyocarditis virus (EMCV) has been isolated from many animals, frequently as the cause of fatal myocarditis, but pigs are the most susceptible domestic specie. The virus was isolated in swine farms since 1958 in Panama and Europe from cases of sudden death in young pigs, and the main origin of outbreaks has been assumed to be local rodent populations. There is no treatment for the disease.

Case presentation

The clinical case describes an outbreak of encephalomyocarditis virus in a farrowing (farm A) and a weaning (farm B) site, with mortality that reached 24.2% in suckling piglets and 7.7% in weaners. The farms were located in an endemic Italian area, and the outbreak was characterised by high mortality with sudden death and clinical signs due to heart failure (trembling, dispnea and fever). The rodents control program was the key action in managing the outbreak. However, in the weaning site, the lack of rodent program in some unexplored areas of the barn (false ceiling) was responsible of a longer time of resolution of the outbreak. An unusual support treatment approach from human medicine suggestion was also applied using acetylsalicylic acid for its antiphlogistic and antithrombotic effects.

Conclusions

To control the rodent population in a pig farm is often difficult and requires a deep knowledge also of the rodents habits. Considering the lack of treatment for the disease and the absence of available vaccines in several Countries, acetylsalicylic acid might be of interest for further studies as an important support for pigs’ recovery.
Myeloid deficiency of the intrinsic clock protein BMAL1 accelerates cognitive aging by disrupting microglial synaptic pruning
Authors: Iweka Chinyere Agbaegbu , Seigneur Erica , Hernandez Amira Latif , Paredes Sur Herrera , Cabrera Mica , Blacher Eran , Pasternak Connie Tsai , Longo Frank M. , de Lecea Luis , Andreasson Katrin I.
Published: February 2023

Aging is associated with loss of circadian immune responses and circadian gene transcription in peripheral macrophages. Microglia, the resident macrophages of the brain, also show diurnal rhythmicity in regulating local immune responses and synaptic remodeling. To investigate the interaction between aging and microglial circadian rhythmicity, we examined mice deficient in the core clock transcription factor, BMAL1. Aging Cd11bcre;Bmallox/lox mice demonstrated accelerated cognitive decline in association with suppressed hippocampal long-term potentiation and increases in immature dendritic spines. C1q deposition at synapses and synaptic engulfment were significantly decreased in aging Bmal1-deficient microglia, suggesting that BMAL1 plays a role in regulating synaptic pruning in aging. In addition to accelerated age-associated hippocampal deficits, Cd11bcre;Bmallox/lox mice also showed deficits in the sleep–wake cycle with increased wakefulness across light and dark phases. These results highlight an essential role of microglial BMAL1 in maintenance of synapse homeostasis in the aging brain.
Assessment of the clinical and analytical performance of the Aptima SARS-CoV-2 assay using the VALCOR protocol
Authors: Dhillon Sharonjit K. , Simoens Cindy , Cuypers Lize , Bode Jannes , Bonde Jesper , Corbisier Philippe , Cocuzza Clementina E. , Van Ranst Marc , Arbyn Marc
Published: February 2023

Background

The COVID-19 pandemic highlighted the importance of diagnostic testing against curbing the spread of SARS-CoV-2. The urgent need and scale for diagnostic tools resulted in manufacturers of SARS-CoV-2 assays receiving emergency authorization that lacked robust analytical or clinical evaluation. As it is highly likely that testing for SARS-CoV-2 will continue to play a central role in public health, the performance characteristics of assays should be evaluated to ensure reliable diagnostic outcomes are achieved.

Methods

VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a study protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays. Using clinical samples collated from VALCOR, the performance of Aptima SARS-CoV-2 assay was assessed against a standard comparator assay. Diagnostic test parameters such as sensitivity, specificity and overall per cent agreement were calculated for the clinical performance of Aptima SARS-CoV-2 assay.

Results

A total of 180 clinical samples were tested with an addition of 40 diluted clinical specimens to determine the limit of detection. When compared to the standard comparator assay Aptima had a sensitivity of 100.0% [95% CI 95.9–100.0] and specificity of 96.7% [95% CI 90.8–99.3]. The overall percent agreement was 98.3% with an excellent Cohen’s coefficient of κ = 0.967 [95% CI 0.929–1.000]. For the limit of detection, Aptima was able to detect all of the diluted clinical samples.

Conclusion

In conclusion. validation of Aptima SARS-CoV-2 assay using clinical samples collated through the VALCOR protocol showed excellent test performance. Additionally, Aptima demonstrated high analytical sensitivity by detecting all diluted clinical samples corresponding to a low limit of detection.
Surgical considerations in the resection of solitary fibrous tumors of the pleura
Authors: Ajouz Hana , Sohail Amir Humza , Hashmi Hassan , Martinez Aguilar Myriam , Daoui Sabrina , Tembelis Miltiadis , Aziz Muhammad , Zohourian Tirajeh , Brathwaite Collin E. M. , Cerfolio Robert J.
Published: February 2023

Solitary fibrous tumors (SFTs) are rare mesenchymal pleural neoplasms with an overall good prognosis and low recurrence rate if completely resected and if degree of differentiation is favorable. Within the last decade, advances in research have led to more reliable methods of differentiating SFTs from other soft tissue tumors. Historically, several markers were used to distinguish SFTs from similar tumors, but these markers had poor specificity. Recent evidence showed NAB2-STAT6 fusion gene to be a distinct feature of SFTs with 100% specificity and sensitivity. Surgical resection, with an emphasis on obtaining negative margins, is the mainstay of treatment for SFTs. Preoperative planning with detailed imaging is imperative to delineate the extent of disease and vascular supply. One important radiologic distinction to aid delineation of a pleural-based tumor compared to a pulmonary parenchymal-based tumor is the angle that the tumor forms with the chest wall, which is obtuse for a pleural-based tumor, and acute for tumors of the lung parenchyma. Often, preoperative tissue diagnosis is not available, and surgery is both diagnostic and curative. Intraoperatively, emphasis should be on complete resection with negative margins. SFTs are resected via several approaches: thoracotomy, sternotomy with the option of hemi-clamshell extension, video-assisted thoracoscopic surgery, and robotic approach, which is increasingly being used and is our preference. We recommend a minimally invasive approach for most lesions, and have resected SFTs of the pleura that are up to 12 cm with the robotic approach. However, the current literature often cites 5 cm as the cut off for an open thoracotomy. Nevertheless, even with larger tumors, a minimally invasive robotic approach is our preference and practice. For giant SFTs (> 20 cm), an open approach may be preferable. Multiple thoracotomies and rib resection may be required to gain adequate exposure and ensure complete resection in these tumors. However, it is noteworthy that most of these tumors have a soft consistency and thus, once bagged, can easily be removed minimally invasively, and thus minimally invasive approach should not be completely ruled out. Recurrence in SFTs usually results from incomplete resection and redo surgery may portend a favorable prognosis.
Latent profiles of childhood psychological maltreatment and their links to adult mental health in China and the UK
Authors: Xiao Zhuoni  , Obsuth Ingrid , Meinck Franziska , Murray Aja Louise
Published: February 2023

Background

Though links between childhood maltreatment and mental health have been established, little known about how specific types of childhood maltreatment tend to cluster and how the resulting patterns of exposure impact mental health outcomes.

Method

The current study used latent profile analyses in Chinese (N = 544) and UK (N = 589) samples to identify childhood psychological maltreatment profiles (i.e., profiles of psychological abuse, psychological neglect, and psychological non-support) in different country contexts, and their associations with a range of mental health (i.e., depression, anxiety, anger, physical aggression, verbal aggression, and hostility), and broader well-being (i.e., self-esteem) outcomes. Unadjusted as well as analyses adjusted for adverse childhood experiences (ACEs) were conducted.

Results

Four profiles were identified in both samples, but their nature differed between the Chinese sample (“Psychological Non-support”, “Low-Maltreated”, “High-Maltreated”, and “Severe-Maltreated”) and the UK sample (“Low-Maltreated”, “Moderate-Maltreated”, “High-Maltreated”, and “Severe-Maltreated”). Individuals in the “Psychological Non-support” in China and “Low-Maltreated” class in the UK displayed better mental health outcomes–lower levels of depression, anxiety, and aggression, and higher self-esteem. In contrast, individuals in the “Severe-Maltreated” profiles in both the Chinese and UK samples displayed poorer mental health outcomes–higher depression, anxiety, and aggression, and lower self-esteem. Interventions and prevention efforts are needed for individuals categorized in profiles affected by psychological maltreatment.

Conclusion

This study highlights the importance of using targeted intervention or prevention to prevent psychological maltreatment, as well as improve mental health outcomes in individuals who have experienced psychological maltreatment.