bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suburban Blues: Urbanicity, healthcare service mix and spatial patterns of admissions for depression
Authors: Berger M , Zuba M , Simon J 
Published: October 2023

Abstract

Objectives
Medical practice variation is a key target for policy makers aiming to improve the efficiency of healthcare delivery. Studies point to strong regional variation in healthcare utilization in Austria which seems to be a by-product of institutional rules and healthcare service mix rather than variance in epidemiology.

Methods
We use a set of routine healthcare data on hospital admissions for depressive episodes (ICD-10 F320-F329) of adult Austrian patients from 2009 to 2014 on the municipality level to explore spatial patterns of supply-induced demand by nearby hospitals (“Roemer's law”) in hospital admission rates. The dataset covers 99,844 hospital episodes of 69,555 patients in 2,114 municipalities. We estimate a random effects spatial autoregressive model to regress log hospital admission rates on hospital supply and urbanicity as proxies for the municipalities’ healthcare service mix alongside a set of relevant socio-economic/-demographic characteristics.

Preliminary results
Hospital admission rates per 1,000 inhabitants in the population for depressive episodes vary strongly between municipalities (min=0, max=37.7, mean=1.9, SD = 1.8). We find higher admission rates in the population of suburban municipalities (0.10, 95%-CI: 0.58 - 0.13) and municipalities with hospitals (0.07, 95%-CI: 0.01 - 0.1), regardless of hospital type and size. The spatial structure suggests positive spill-over effects on the hospital admission rates between neighbouring municipalities.

Conclusions
Our results suggest that high admission rates are a seemingly suburban phenomenon and that healthcare service mix is a driving factor for admission rates. Though it is not clear whether the regional variation in medical practice reflects under- or oversupply of hospital care, promoting timely access to primary care and early-stage treatments may reduce the burden of avoidable hospitalizations for patients and public budgets, and close a gap of unmet need for care of vulnerable populations.

Key messages
• Hospital admission rates for depression of adults per 1,000 inhabitants in the population for depressive episodes vary strongly between municipalities.
• Hospital supply and urbanicity are major driving factors of the spatial patterns in regional varation of hospital admissions.
Strengthening Infectious Disease Control and Pandemic Preparedness in The Netherlands
Authors: Versteeg S , De Munter A , Linthorst M 
Published: October 2023

Abstract

The COVID-19 pandemic showed the importance of a strong public health system. During the pandemic, infectious disease control departments of Dutch Regional Public Health Services (RPHSs) reached their limits. In preparation for new large outbreaks and pandemics, investments must be made in strengthening infectious disease control departments at RPHSs. In March-May 2022, the 25 RPHSs established a programme to reinforce their infectious disease control departments in 2023-2024. The programme addresses current vulnerabilities and focuses on five pillars: increasing staff capacity (1), improving cross-regional monitoring and surveillance (2), strengthening public health research infrastructure (3), improving cross-regional collaboration (4) and increasing training opportunities for professionals (5). The Dutch Ministry of Health, Welfare and Sport is funding the two-year (2023-2024) national programme, assisting the 25 RPHSs to address regional and cross-regional vulnerabilities with 75 million euro. The programme started in January 2023 and already resulted in the start of new national consultation structures and the employment of many new infectious disease professionals, whilst considering task rearrangement of medical and non-medical professionals. RPHSs are working together with national partners to strengthen cross-regional monitoring and surveillance. A national consortium, together with infectious disease professionals at RPHS, is currently working on scientific knowledge enhancement and innovation in the public health work field. The programme provides national education opportunities and investigates career prospects of public health professionals. The programme provides insight in regional similarities and differences and identifies strengths and needs to improve infectious disease control. Outcomes of the programme are used by RPHSs and their national partners to determine what is needed for structural strengthening of infectious disease control departments.

Key messages
• The 25 Dutch RPHSs work together to strengthen infectious disease control.
• The programme contributes to reinforcement, innovation and further professionalisation of the infectious disease control.
PEP-flute selfcare in epidemic respiratory infectious diseases – high societal impact at low cost?
Authors: Mollerup A , Henriksen M , Larsen S C , Bennetzen A S , Simonsen M K , Kofod L M , Weis N , Heitmann B L 
Published: October 2023

Abstract

Background
The COVID-19 pandemic has led to worldwide increases in mortality and disrupted healthcare systems. The necessary countermeasures have adversely affected our lives, both mentally and economically. Home-based interventions to help individuals with early COVID-19 overcome the disease with fewer symptoms are needed. This study explored if self-care using positive expiratory pressure (PEP) as airway clearance is effective in reducing respiratory symptoms and, thus hypothetically prevent COVID-19 associated pneumonia.

Methods
This open-label, randomized trial (ClinicalTrials.gov:NCT04530435) recruited community dwelling adults from Capital Region and Region Zealand in Denmark from 6 Oct 2020 to 26 Feb 2021. Eligible participants (verified SARS-CoV-2 infection, COVID-19 symptoms, and able to perform self-care) were randomized to usual care or to PEP-flute self-care (PEP thrice daily) as an add-on to usual care. PEP-flutes were delivered by express mail and instructions given by video-links. The primary outcome was a change (analyzed by repeated measures mixed linear models) in self-reported symptom severity from baseline to day 30, as assessed by the COPD (chronic obstructive pulmonary disease) assessment test (CAT). Another outcome was the perceived effect of PEP-selfcare.

Results
The PEP self-care group (n = 190) had significantly lower symptom severity (group difference -1.2 points (95% confidence interval -2.1 to -0.2; p = 0.017)) at day 30 compared to the usual care group (n = 188). The PEP self-care group reported less chest tightness, less dyspnea, more vigor, and higher level of daily activity. When asked, “How do you describe the PEP-flute effect?”, 30% (n = 56) from the PEP group reported PEP-use to provoke coughing of phlegm. No serious adverse events were reported.

Conclusions
In early COVID-19, PEP-flute self-care was effective in reducing respiratory symptom severity among community dwelling adults and may have a future societal impact at a low cost.

Key messages
• We advocate for more research in self-care interventions to confirm if campaigns and handouts of PEP-flutes to mobilize the citizens’ selfcare are suitable public health responses to the next pandemic.
• More research is needed to establish efficacy of non-drug interventions like PEP-selfcare for airway clearance to prevent pneumonia.
AZD7442 utilization for Pre-Exposure Prophylaxis Against COVID-19 in a French Early Access Program
Authors: Artaud C , Majed L , Fabry-Vendrand C , Taylor S , Ferreira C , Dube S , Thabut G , Suau D , Lahouegue A 
Published: October 2023

Abstract

Background
AZD7442, a combination of 2 neutralizing antibodies, has been shown to reduce symptomatic COVID-19 risk by 83% at 6 months among high-risk individuals in a Phase 3 trial (PROVENT). The French Health Authorities authorized AZD7442 use in immunocompromised patients through Early Access Program (EAP). Eligibility for EAP was serological anti-spike levels of &lt; 260 BAU/ml and very high risk of severe COVID. This abstract aims to describe the AZD7442 eligible population in France and characterize AZD7442 uptake in the EAP.

Methods
This is a retrospective observational database analysis of the EAP data. Demographics, and clinical characteristics of participants are described.

Results
27,782 patients were included in the EAP between 12/15/2021 and 11/30/2022. AZD7442 was mostly prescribed by onco-hematologists (24.2%), followed by nephrologists (19.9%), internal medicine specialists (15.6%), and rheumatologists (6.5%). 50% of participants were over 65 years, 54.7% were male. The majority (96.7%) had received at least three vaccine doses at inclusion. Most common comorbidities were cancer (34.9%), chronic kidney disease (23.7%), hypertension (23.2%), cardiovascular disease (19.4% &gt;2CV factors), and diabetes (9.2%). 6 months follow-up data were available for 2106 patients.

Conclusions
In the EAP, health care professionals prioritized IC patients at the highest risk of severe COVID-19, consistent with the authorization granted in France. However, based on the approved criteria, HCP have the potential to broaden the use of AZD7442 among different IC groups which can lead to more equitable access. The large size of the EAP presents an opportunity to generate evidence regarding the effectiveness of AZD7442. Lack of follow up data highlights the need to enrich the EAP data to study relevant effectiveness endpoints as COVID-19 hospitalizations and mortality. An innovative observational comparative study is planned by combining EAP data and French National Claims database SNDS.

Key messages
• These findings could guide future efforts to implement COVID-19 prophylaxis measures.
• The large size of the EAP presents an opportunity to generate evidence regarding the effectiveness of AZD7442.
Towards SDG30: Fighting HCV with a screening program in Lombardy
Authors: Meloni A , Piccinelli S , Marrocu C , Odone A , Cereda D 
Published: October 2023

Abstract

Background
The third Sustainable Development Goal, specifically in target 3.3, identifies fighting HCV as a priority.
It is estimated that in Italy more than 200.000 patients eligible for HCV treatment are not being treated and 20% are not aware of the infection. Lombardy region to promptly identify and treat patients affected, developed a screening program to be offered to all patients born between 1969 and 1989. Healthcare facilities were divided into first and second-level centers and the campaign was designed in 2 phases: at the first level centres patients were screened with blood tests, if positive they were contacted by second level structures to get a diagnostic test and if confirmed positive to start the therapeutic approach.

Methods
The screening program started in June 2022 and consisted of an opportunistic offer of free testing for serum anti-HCV antibodies in the context of any healthcare performance offered to eligible patients. Data were uploaded and collected on a web database from which second-level centers could obtain data of positive patients to contact them and set appointment for confirmation tests.

Results
As of 31st December 2022 120,193 individuals underwent HCV screening in 75 screening centers in Lombardy. The mean age was 44 years, 65.2% were females, and 83.7% were tested at outpatient blood collection centers. 604 (0.50%) patients tested positive with mean age 47 (±5). HCV-RNA was detectable in 125 out of 441 (28.3%) anti-HCV positive subjects with available HCV-RNA. Patients with active HCV infection were aged 46 (±6) and were mostly males (56.8%). Overall, the prevalence of active infection in the general population was 0.10% and was higher in elderly.

Conclusions
The prevalence of active HCV infection in the general population born between 1969 and 1989 in Lombardy was low. Considering the higher prevalence of active infection in the elderly population, an extension of the screening offer to patients born between 1949-70 could be evaluated.

Key messages
• Prevalence of active HCV infection in screened population is low.
• Extending the screening offer may result in higher number of positive results and more people directed towards treatment.
SARS-CoV-2 incidence and hospitalisation in South Tyrol (Italy): a population-based ecological study
Authors: Cristofor C D , Lorenzon A , Palandri L , Uguzzoni F , Lozza F , Poluzzi R , Rizzi C , Bertoli P , Zerzer F , Righi E 
Published: October 2023

Abstract

Background
Literature associating SARS-CoV-2 spread to environmental variables such as altitude, tourism, vaccination adherence and demographics, is inconclusive and contrasting. This study aimed at studying these relationships during the first unrestricted winter in South Tyrol, a multicultural Italian alpine province.

Methods
An ecological study was performed, based on the 20 districts of the area. Data about incidence and hospitalization between November ’21 and February ’22 was collected and associated to geographical, demographic and health-related characteristics via bivariate analyses.

Results
Incidence (range: 15% - 22%) and hospitalization (range: overall = 0.09% - 0.26%/ intensive care unit (ICU) = 0 - 0.06%) varied widely among districts. Incidence showed positive correlations with average altitude (Rho=0.62, p &lt; 0.001), tourist amount (0.54, p &lt; 0.04) and average family size (0.66, p &lt; 0.005); whereas negative ones with vaccination coverage (-0.62, p &lt; 0.04) and population density (-0.44, p &lt; 0.05). Similar trends were observed for ICU admissions. Incidence was significantly higher in Ladin speaking districts and lower in Italian ones, while ordinary wards admission appeared lowest in Ladin districts and higher in the Italian ones, as well as close to main cities and hospitals.

Conclusions
Living in urban districts, geographically and linguistically closer to the Health Authorities, may have played a protective role against infection and severe disease, through an increased adherence to public health preventive measures. The concomitant higher rate of admissions might be due to the easier access to the structures. By contrast, infection spread was higher in rural and sparsely populated districts, associated with greater winter tourism and family sizes, but also characterized by lower herd immunity and institutional closeness. More attention should be paid to communities with special needs (geographical and cultural) to ensure equitable means for future pandemics.

Key messages
• Living in urban districts may protect against infection spread through increased adherence to public health preventive measures, and facilitate hospitalisations due to easier access to the structures.
• More attention should be paid to communities geographically and culturally distant from Public Health Institutions to ensure equitable means for future pandemics.
Knowledge and attitudes towards dementia care among healthcare workers in Somaliland: a need assessment survey
Authors: Duale Mohamed Abdilahi , Gebremariam Tewelde Tesfaye 
Published: October 2023

AbstractThe present pilot survey assessed the levels of healthcare workers’ knowledge of dementia and attitudes towards dementia care in Somaliland. Between June and July 2023, we administered an adapted online survey with 30 Alzheimer’s disease Knowledge Scale (ADKS) true or false statements and 10 Dementia Care Attitude Scale (DCAS) Likert-scale items. The reliability of the Likert-scale DCAS items was assessed using Cronbach’s alpha. A Chi-square, Mann-Whitney U-test, and independent sample t-test were used to assess the relationship and differences of the outcome variables (knowledge and attitude) across the healthcare workers’ baseline information. The mean ADKS score was 18.7 (SD = 3.1). Out of 107 healthcare workers who completed the survey, 49.5% had high dementia knowledge (score ≥18.7). The participants’ median (IQR) attitude score was 34 (25, 39), and 46.7% (50 of 107) had a positive attitude towards dementia care. In conclusion, health professionals in Somaliland had low levels of knowledge and negative attitudes towards dementia care.
Antibody-conjugating nanogel (Conjugel) with two immune checkpoint inhibitors for enhanced cancer immunotherapy
Authors: Chae Yun Jin , Lee Kang-Gon , Oh Doogie , Lee Su-Kyoung , Park Yongdoo , Kim Jongseong 
Published: October 2023

AbstractCancer immunotherapy by immune checkpoint inhibitors (ICI) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, we show the development of an antibody-conjugating system (Conjugel) that potentiates the efficacy of bispecific immunotherapy that simultaneously targets CTLA-4 and PD-L1. The Conjugel, consisting of highly deformable nanogels and antibody-binding protein, was loaded with two ICI monoclonal antibodies (mAb). Compared with mAb treatment alone, treatment with a bispecific Conjugel loaded with the both ICIs significantly decreased both the survival of MCF-7 and MDA-MB-231 breast cancer cellsin vitroand the size of 4T1-Luc2-derived orthotopic syngeneic tumorsin vivo. Furthermore, the ICI-loaded Conjugel was less toxicin vivothan the combination treatment delivered as a bolus. Our findings have important implications for Conjugel-based immunotherapy, developing the safer and higher efficacy of ICIs to treat breast cancers.
Activation of Complement by Human Fibrin Clots: involvement of C1q and factor H
Authors: Kang Yu-Hoi , Varghese Praveen M. , Pondman Kirsten , Kishore Uday , Sim Robert B. 
Published: October 2023

AbstractThe classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator including immune complexes. Factor H is regarded as the key downregulatory protein of the alternative pathway of complement. However, C1q and factor H both bind to target surfaces via charge distribution patterns. For few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation by such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are reported to recognize “foreign” or altered-self materials. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the classical pathway of complement and whether this is regulated by factor H. We show here that both C1q and factor H bind to fibrin formed in microtitre plates as well as fibrin clots formed underin vitrophysiological conditions. Both C1q and factor H become covalently bound to fibrin clots and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the classical pathway activation induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences.
Simulation of adaptive immune receptors and repertoires with complex immune information to guide the development and benchmarking of AIRR machine learning
Authors: Chernigovskaya Maria , Pavlović Milena , Kanduri Chakravarthi , Gielis Sofie , Robert Philippe A. , Scheffer Lonneke , Slabodkin Andrei , Haff Ingrid Hobæk , Meysman Pieter , Yaari Gur , Sandve Geir Kjetil , Greiff Victor 
Published: October 2023

AbstractMachine learning (ML) has shown great potential in the adaptive immune receptor repertoire (AIRR) field. However, there is a lack of large-scale ground-truth experimental AIRR data suitable for AIRR-ML-based disease diagnostics and therapeutics discovery. Simulated ground-truth AIRR data are required to complement the development and benchmarking of robust and interpretable AIRR-ML methods where experimental data is currently inaccessible or insufficient. The challenge for simulated data to be useful is incorporating key features observed in experimental repertoires. These features, such as antigen or disease-associated immune information, cause AIRR-ML problems to be challenging. Here, we introduce LIgO, a software suite, which simulates AIRR data for the development and benchmarking of AIRR-ML methods. LIgO incorporates different types of immune information both on the receptor and the repertoire level and preserves native-like generation probability distribution. Additionally, LIgO assists users in determining the computational feasibility of their simulations. We show two examples where LIgO supports the development and validation of AIRR-ML methods: (1) how individuals carrying out-of-distribution immune information impacts receptor-level prediction performance and (2) how immune information co-occurring in the same AIRs impacts the performance of conventional receptor-level encoding and repertoire-level classification approaches. LIgO guides the advancement and assessment of interpretable AIRR-ML methods.
Sleep spindle density and temporal clustering are associated with sleep-dependent memory consolidation in Parkinson’s disease
Authors: Lahlou Soraya , Kaminska Marta , Doyon Julien , Carrier Julie , Sharp Madeleine 
Published: October 2023

AbstractSleep is required for successful memory consolidation. Sleep spindles, bursts of oscillatory activity occurring during non-REM sleep, are known to be crucial for this process and, recently, it has been proposed that the temporal organization of spindles into clusters might additionally play a role in memory consolidation. In Parkinson’s disease, spindle activity is reduced, and this reduction has been found to be predictive of cognitive decline. However, it remains unknown whether alterations in sleep spindles in Parkinson’s disease are predictive of sleep-dependent cognitive processes like memory consolidation, leaving open questions about the possible mechanisms linking sleep and more general cognitive state in Parkinson’s patients. The current study sought to fill this gap by recording overnight polysomnography and measuring overnight declarative memory consolidation in a sample of thirty-five Parkinson’s patients. Memory consolidation was measured using a verbal paired-associates task administered before and after the night of recorded sleep. We found that lower sleep spindle density at frontal leads during non-REM stage 3 was associated with worse overnight declarative memory consolidation. We also found that patients who showed less temporal clustering of spindles exhibited worse declarative memory consolidation. These results suggest alterations to sleep spindles, which are known to be a consequence of Parkinson’s disease, might represent a mechanism by which poor sleep leads to worse cognitive function in Parkinson’s patients.Statement of significanceSleep — particularly spindle activity — is critical for memory consolidation, a core cognitive process. Changes to the architecture and oscillations of sleep are well documented in Parkinson’s disease (PD) and have been associated with worse overall cognition. However, whether altered sleep plays a causal role in this relationship, by directly interfering with sleep-dependent cognitive processes, or whether it represents a mere epiphenomenon of advancing disease, remains unknown. Our study is the first to investigate a possible direct relationship between sleep and cognition in PD. We show that sleep spindles and their temporal clustering into ‘trains’ relate to impairments in overnight declarative memory consolidation in patients. These findings are an important first step towards identifying modifiable sources of cognitive impairment in PD.