bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures for the care of people with dementia: a European comparison
Authors: Schmachtenberg Tim , Monsees Jessica , Thyrian Jochen René 
Published: November 2022

Abstract
Background
Dementia is a disease that impacts people with dementia, their families, and the healthcare system. In 2018, the number of people with dementia in the EU, the European Free Trade Association (EFTA), and the UK was estimated to be 9.1 million. National dementia strategies and publications by organisations such as Alzheimer Europe outline how dementia-specific care should be designed. This study aims to provide insights into existing formal care structures, models of good practise, and gaps in dementia-specific care for people with dementia in 17 European countries.

Methods

The research is based on guided interviews with
country-specific care experts. A mixed-methods approach with a combination of
open and closed questions was used. All interviews were
recorded and transcribed verbatim based on the transcription rules of Kuckarts
(2010). For data evaluation, the qualitative content analysis model of Mayring
(2014) was used.

Results
In all 17 countries, efforts for
dementia-friendly care and models of good care practise exist. However, there
are large differences between European countries regarding the spread of
dementia-specific services. In nine countries (Bulgaria, Finland, Italy,
Liechtenstein, Luxembourg, the Netherlands, Norway, Sweden, the UK), there are
already nationwide structures, while in five countries (Belgium, Greece,
Ireland, Portugal, Romania), services are only available in certain regions. In
three countries (Austria, Denmark, Germany) dementia-specific outpatient
services are widespread nationwide, whereas inpatient services are not.
Simultaneously, in all countries, areas with major care gaps exist. Several
European states have an urgent need for action concerning the expansion of the
provision of dementia-specific services, the reduction of regional differences
regarding the provision of care, the elimination of barriers to access to care,
the dementia-friendliness of services, and the participation of people with dementia
and their relatives in care and research.

Conclusions
To reduce the existing structural inequalities
in care between and within European countries, and to establish quality-related
minimum standards in the care of people with dementia, transnational concepts
are needed. The EU, in cooperation with care planners, research institutions,
care providers, and patient organisations, should develop European care
guidelines or dementia plans that contain concrete measures, schedules, and
budgets.
Impact of parasite genomic dynamics on the sensitivity of Plasmodium falciparum isolates to piperaquine and other antimalarial drugs
Authors: Wakoli Dancan M. , Ondigo Bartholomew N. , Ochora Douglas O. , Amwoma Joseph G. , Okore Winnie , Mwakio Edwin W. , Chemwor Gladys , Juma Jackeline , Okoth Raphael , Okudo Charles , Yeda Redemptah , Opot Benjamin H. , Cheruiyot Agnes C. , Juma Dennis , Roth Amanda , Ogutu Benhards R. , Boudreaux Daniel , Andagalu Ben , Akala Hoseah M. 
Published: November 2022

Abstract
Background
Dihydroartemisinin-piperaquine (DHA-PPQ) is an alternative first-line antimalarial to artemether-lumefantrine in Kenya. However, recent reports on the emergence of PPQ resistance in Southeast Asia threaten its continued use in Kenya and Africa. In line with the policy on continued deployment of DHA-PPQ, it is imperative to monitor the susceptibility of Kenyan parasites to PPQ and other antimalarials.

Methods
Parasite isolates collected between 2008 and 2021 from individuals with naturally acquired P. falciparum infections presenting with uncomplicated malaria were tested for in vitro susceptibility to piperaquine, dihydroartemisinin, lumefantrine, artemether, and chloroquine using the malaria SYBR Green I method. A subset of the 2019–2021 samples was further tested for ex vivo susceptibility to PPQ using piperaquine survival assay (PSA). Each isolate was also characterized for mutations associated with antimalarial resistance in Pfcrt, Pfmdr1, Pfpm2/3, Pfdhfr, and Pfdhps genes using real-time PCR and Agena MassARRAY platform. Associations between phenotype and genotype were also determined.

Results
The PPQ median IC50 interquartile range (IQR) remained stable during the study period, 32.70 nM (IQR 20.2–45.6) in 2008 and 27.30 nM (IQR 6.9–52.8) in 2021 (P=0.1615). The median ex vivo piperaquine survival rate (IQR) was 0% (0–5.27) at 95% CI. Five isolates had a PSA survival rate of ≥10%, consistent with the range of PPQ-resistant parasites, though they lacked polymorphisms in Pfmdr1 and Plasmepsin genes. Lumefantrine and artemether median IC50s rose significantly to 62.40 nM (IQR 26.9–100.8) (P = 0.0201); 7.00 nM (IQR 2.4–13.4) (P = 0.0021) in 2021 from 26.30 nM (IQR 5.1–64.3); and 2.70 nM (IQR 1.3–10.4) in 2008, respectively. Conversely, chloroquine median IC50s decreased significantly to 10.30 nM (IQR 7.2–20.9) in 2021 from 15.30 nM (IQR 7.6–30.4) in 2008, coinciding with a decline in the prevalence of Pfcrt 76T allele over time (P = 0.0357). The proportions of piperaquine-resistant markers including Pfpm2/3 and Pfmdr1 did not vary significantly. A significant association was observed between PPQ IC50 and Pfcrt K76T allele (P=0.0026).

Conclusions
Circulating Kenyan parasites have remained sensitive to PPQ and other antimalarials, though the response to artemether (ART) and lumefantrine (LM) is declining. This study forms a baseline for continued surveillance of current antimalarials for timely detection of resistance.
Malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen
Authors: Al-Quhaiti Mona A. A. , Abdul-Ghani Rashad , Mahdy Mohammed A. K. , Assada Methaq A. 
Published: November 2022

Abstract
Background
Malaria burden among under-five children living in endemic areas of Yemen is largely unknown due to the lack of community-based studies. Therefore, this study determined the prevalence and risk factors associated with falciparum malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen.

Methods
This community-based, cross-sectional study recruited 400 under-five children from two rural districts of Al-Mahweet governorate in December 2019. Demographic characteristics (gender, age, education and occupation of the child’s parents, and household size) and risk factors associated with malaria were collected through interviews with children’s caregivers using a structured questionnaire. Finger-prick blood was screened for Plasmodium falciparum and non-falciparum species using rapid diagnostic tests (RDTs), and duplicate Giemsa-stained thick and thin blood films were examined for malaria parasites. The density of asexual P. falciparum stages was also estimated. Data were then analysed, and the agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa index. Statistical significance was set at a P-value of < 0.05.

Results
Plasmodium falciparum was prevalent among 9.8% (95% CI 7.0–13.1) of under-five children in the rural communities of Al-Mahweet, with a median asexual parasite density of 763 ± 2606 parasites/μl of blood (range: 132–4280) and low-to-moderate parasitaemia levels. Approximately one-third of microscopy-confirmed cases were gametocyte carriers. Multivariable logistic regression analysis confirmed that age of three years or older (AOR = 5.6, 95% CI 1.6–19.8; P = 0.007), not sleeping under a mosquito net the previous night of the survey (AOR = 8.0, 95% CI 2.4–27.4; P = 0.001), sleeping outdoors at night (AOR = 4.4, 95% CI 2.0–10.0; P < 0.001), and absence of indoor residual spraying (IRS) during the last year (AOR = 4.2, 95% CI 1.9–9.4; P < 0.001) were the independent predictors of falciparum malaria among under-five children in the rural communities of Al-Mahweet. The observed percentage agreement between thick-film microscopy and RDTs was 98.5%, with a very good agreement (k-index = 0.9) between the two methods for falciparum malaria diagnosis that was statistically significant.

Conclusion
Approximately one in ten under-five children in rural communities of Al-Mahweet is infected with P. falciparum based on microscopy and RDTs. Age of three years or older, not sleeping under mosquito nets, sleeping outdoors at night and absence of IRS can independently predict falciparum malaria among them. The very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria in children supports the usefulness of using RDTs in such resource-limited rural communities.
Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer
Authors: Pang Jianyu , Yu Qian , Chen Yongzhi , Yuan Hongjun , Sheng Miaomiao , Tang Wenru 
Published: November 2022

AbstractNon-small cell lung cancer (NSCLC) is the most widely distributed tumor in the world, and its immunotherapy is not practical. Neutrophil is one of a tumor’s most abundant immune cell groups. This research aimed to investigate the complex communication network in the immune microenvironment (TIME) of NSCLC tumors to clarify the interaction between immune cells and tumors and establish a prognostic risk model that can predict immune response and prognosis of patients by analyzing the characteristics of Neutrophil differentiation. Integrated Single-cell RNA sequencing (scRNA-seq) data from NSCLC samples and Bulk RNA-seq were used for analysis. Twenty-eight main cell clusters were identified, and their interactions were clarified. Next, four subsets of Neutrophils with different differentiation states were found, closely related to immune regulation and metabolic pathways. Based on the ratio of four housekeeping genes (ACTB, GAPDH, TFRC, TUBB), six Neutrophil differentiation-related genes (NDRGs) prognostic risk models, including MS4A7, CXCR2, CSRNP1, RETN, CD177, and LUCAT1, were constructed by Elastic Net and Multivariate Cox regression, and patients’ total survival time and immunotherapy response were successfully predicted and validated in three large cohorts. Finally, the causes of the unfavorable prognosis of NSCLC caused by six prognostic genes were explored, and the small molecular compounds targeted at the anti-tumor effect of prognostic genes were screened. This study clarifies the TIME regulation network in NSCLC and emphasizes the critical role of NDRGs in predicting the prognosis of patients with NSCLC and their potential response to immunotherapy, thus providing a promising therapeutic target for NSCLC.
Circular RNAs in organ injury: recent development
Authors: Wong Ryan , Zhang Yiwen , Zhao Hailin , Ma Daqing 
Published: November 2022

AbstractCircular ribonucleic acids (circRNAs) are a class of long non-coding RNA that were once regarded as non-functional transcription byproducts. However, recent studies suggested that circRNAs may exhibit important regulatory roles in many critical biological pathways and disease pathologies. These studies have identified significantly differential expression profiles of circRNAs upon changes in physiological and pathological conditions of eukaryotic cells. Importantly, a substantial number of studies have suggested that circRNAs may play critical roles in organ injuries. This review aims to provide a summary of recent studies on circRNAs in organ injuries with respect to (1) changes in circRNAs expression patterns, (2) main mechanism axi(e)s, (3) therapeutic implications and (4) future study prospective. With the increasing attention to this research area and the advancement in high-throughput nucleic acid sequencing techniques, our knowledge of circRNAs may bring fruitful outcomes from basic and clinical research.
HNRNPA2B1-mediated m6A modification of TLR4 mRNA promotes progression of multiple myeloma
Authors: Jia Chuiming , Guo Yiwei , Chen Yao , Wang Xinya , Xu Qiuting , Zhang Yu , Quan Lina 
Published: November 2022

Abstract
Background
Multiple myeloma (MM) is a malignancy of plasma cells that remains incurable. Toll-like receptor 4 (TLR4) acts as a stress-responsive signal, protecting mitochondria during proteasome inhibitor (PI) exposure, maintaining mitochondrial metabolism and increasing drug resistance in MM. However, the mechanism of TLR4 regulation remains elusive.

Aims
The purpose of this study was to investigate the methylation pattern of multiple myeloma and its effect on the expression of HNRNPA2B1 and downstream targets.

Methods
The methylation level in MM and normal bone marrow specimens was detected using a colorimetric assay. HNRNPA2B1 gene knockdown was achieved in RPMI 8226 MM cells via adenovirus transfection. CCK8 and flow cytometric assays were used to detect proliferation and apoptosis, respectively. Transcriptome sequencing and m6A methylation MeRIP sequencing were applied, and differentially expressed genes (DEGs) were detected. Three independent NCBI GEO datasets were applied to examine the effects of HNRNPA2B1 and TLR4 expression on MM patient survival.

Results
HNRNPA2B1 promoted MM progression. Clinical data from database revealed that HNRNPA2B1 was adverse prognostic factor for survival among MM patients. Furthermore, transcriptome sequencing and methylation sequencing showed that HNRNPA2B1 recognized and was enriched at the m6A sites of TLR4 and TLR4 was down-regulated of both the m6A level and transcription level in HNRNPA2B1-knockdown MM cells. Moreover, TLR4 was an adverse survival prognostic factor based on database analysis.

Conclusion
Overall, our study implies that the RNA-binding protein HNRNPA2B1 increases cell proliferation and deregulates cell apoptosis in MM through TLR4 signaling. Our study suggests HNRNPA2B1 as a potential therapeutic target for MM.
Hemophagocytic lymphohistocytosis in trisomy 21: successful treatment with interferon inhibition
Authors: Guild Allison , Fritch Jordan , Patel Sachit , Reinhardt Adam , Acquazzino Melissa 
Published: November 2022

Abstract
Background
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation primarily driven by the cytokine interferon gamma. It can be either a genetic or acquired disorder associated with infection, malignancy, and rheumatologic disorders. Trisomy 21 can express a wide range of phenotypes which include immune dysregulation and shares inherent pathophysiology with a group of disorders termed interferonopathies. Knowledge of this overlap in seemingly unrelated conditions could provide a basis for future research, and most importantly, alternative therapeutic interventions in acute life threatening clinical scenarios. Herein, we describe two patients with trisomy 21 presenting with HLH that was refractory to conventional treatment. Both patients were successfully managed with novel interventions targeting the interferon pathway.

Case presentation
We describe a 17-month-old male and 15-month-old female with trisomy 21 presenting with a myriad of signs and symptoms including fever, rash, cytopenias, and hyperferritinemia, both ultimately diagnosed with HLH. Each had relapsing, refractory HLH over time requiring several admissions to the hospital receiving conventional high dose corticosteroids and interleukin-1 inhibition therapy. Successful steroid-free remission was achieved after targeting interferon inhibition with emapalumab induction followed by long-term maintenance on baricitinib.

Conclusion
To our knowledge, these are the first reported cases of relapsed, refractory HLH in patients with trisomy 21 successfully treated with emapalumab and transitioned to a steroid-sparing regimen with oral baricitinib for maintenance therapy. Trisomy 21 autoimmunity and HLH are both thought to be driven by interferon gamma. Targeting therapy toward interferon signaling in both HLH and autoimmunity in trisomy 21 may have potential therapeutic benefits. Further investigation is needed to determine if trisomy 21 may predispose to the development of HLH given this common pathway.
Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer’s disease
Authors: Salasova Alena , Monti Giulia , Andersen Olav M. , Nykjaer Anders 
Published: November 2022

AbstractThe family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer’s disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Intubation first-pass success in a high performing pre-hospital critical care system is not associated with 30-day mortality: a registry study of 4496 intubation attempts
Authors: Ljungqvist Harry , Pirneskoski Jussi , Saviluoto Anssi , Setälä Piritta , Tommila Miretta , Nurmi Jouni 
Published: November 2022

Abstract
Background
Lower intubation first-pass success (FPS) rate is associated with physiological deterioration, and FPS is widely used as a quality indicator of the airway management of a critically ill patient. However, data on FPS’s association with survival is limited. We aimed to investigate if the FPS rate is associated with 30-day mortality or physiological complications in a pre-hospital setting. Furthermore, we wanted to describe the FPS rate in Finnish helicopter emergency medical services.

Methods
This was a retrospective observational study. Data on drug-facilitated intubation attempts by helicopter emergency medical services were gathered from a national database and analysed. Multivariate logistic regression, including known prognostic factors, was performed to assess the association between FPS and 30-day mortality, collected from population registry data.

Results
Of 4496 intubation attempts, 4082 (91%) succeeded on the first attempt. The mortality rates in FPS and non-FPS patients were 34% and 38% (P = 0.21), respectively. The adjusted odds ratio of FPS for 30-day mortality was 0.88 (95% CI 0.66–1.16). Hypoxia after intubation and at the time of handover was more frequent in the non-FPS group (12% vs. 5%, P < 0.001, and 5% vs. 3%, P = 0.01, respectively), but no significant differences were observed regarding other complications.

Conclusion
FPS is not associated with 30-day mortality in pre-hospital critical care delivered by advanced providers. It should therefore be seen more as a process quality indicator instead of a risk factor of poor outcome, at least considering the current limitations of the parameter.
Prevalence and influence of hypouricemia on cardiovascular diseases in patients with rheumatoid arthritis
Authors: Zou Yao-Wei , Li Qian-Hua , Zhu Ying-Ying , Pan Jie , Gao Jing-Wei , Lin Jian-Zi , Wu Tao , Zhang Qian , Zheng Hu-Wei , Mo Ying-Qian , Ma Jian-Da , Dai Lie 
Published: November 2022

Abstract
Background
Serum uric acid (SUA) acts as an antioxidant and abnormally low SUA may raise the risk of developing atherosclerotic disorders. There is a U-shaped association between SUA with cardiovascular diseases (CVDs) in general population. However, the prevalence of hypouricemia and its influence on CVDs in rheumatoid arthritis (RA) remains unclear.

Methods
This cross-sectional study collected clinical data from a Chinese RA cohort. Hypouricemia was defined as SUA ≤ 3.0 mg/dL, and hyperuricemia was defined as SUA ≥ 7.0 mg/dL. CVDs were defined as a history of angina pectoris, myocardial infarction, heart failure, stroke and peripheral arterial disease. Restricted cubic spline regression and logistic regression analysis were conducted to evaluate the associations between SUA levels and CVDs.

Results
Among 1130 RA patients recruited, the mean age was 53.2 years and 79.0% were female. The prevalence of hypouricemia and hyperuricemia were 10.6% and 12.0%, respectively. RA patients with hyperuricemia had a higher rate of CVDs than normouricemic patients (27.9% vs. 7.1%, P < 0.05). Surprisingly, RA patients with hypouricemia also had a higher rate of CVDs (20.7% vs. 7.1%, P < 0.05) even without higher traditional cardiovascular risk factors. A U-shaped association between SUA levels and total CVDs was found (Pnon-linear < 0.001). Multivariate logistic regression analysis revealed that compared with normouricemia, both hypouricemia [adjusted OR (AOR) = 4.707, 95% CI 2.570–8.620] and hyperuricemia (AOR = 3.707, 95% CI 2.174–6.321) were associated with higher risk of CVDs.

Conclusions
Hypouricemia may be a potential risk factor of CVDs in RA patients