bluuebunny/crossref_metadata_2025_split huggingface dataset:
"In their own words": delineating the contours of dyspnea invisibility in patients with advanced chronic obstructive pulmonary disease from quantitative discourse analysis
Authors: Dedonder Jonathan , Gelgon Christelle , Guerder Antoine , Nion Nathalie , Lavault Sophie , Morélot-Panzini Capucine , Gonzalez-Bermejo Jésus , Benoit Laelia , Similowski Thomas , Serresse Laure 
Published: January 2024

AbstractBackgroundDyspnea conveys an upsetting or distressing experience of breathing awareness. It heavily weighs on chronic respiratory disease patients, particularly when it persists despite maximal treatment of causative abnormalities. The physical, psychological and social impacts of persistent dyspnea are ill-appreciated by others. This invisibility constitutes a social barrier and impedes access to care. This study aimed to better understand dyspnea invisibility in patients with chronic obstructive pulmonary disease (COPD) through quantitative discourse analysis.MethodsWe conducted a lexicometric analysis (lemmatization, descending hierarchical classification, multicomponent analysis, similarity analysis) of 11 patients' discourses (6 men, severe COPD; immediate postexacerbation rehabilitation) to identify semantic classes and communities, which we then confronted with themes previously identified using interpretative phenomenological analysis (IPA).ResultsClass#1 ("experience and need for better understanding"; 38.9% of semantic forms, 50% of patients) illustrates the gap that patients perceive between their experience and what others see, confirming the importance of dyspnea invisibility in patients' concerns. Class#2 ("limitations"; 28.7% of forms) and Class#3 (management"; 13.1% of forms) point to the weight of daily limitations in performing basic activities, of the need to accept or adapt to the constraints of the disease. These three classes matched previously identified IPA-derived themes. Class#4 ("hospitalization"; 18.2% of forms) points to the importance of interactions with the hospital, especially during exacerbations, which constitutes novel information.ConclusionsLexicometry confirms the importance of dyspnea invisibility as a burden to COPD patients.
The complement cascade in lung injury and disease
Authors: Detsika M. G. , Palamaris K. , Dimopoulou I. , Kotanidou A. , Orfanos S. E. 
Published: January 2024

Abstract
Background
The complement system is an important arm of immune defense bringing innate and adaptive immunity. Although originally regarded as a major complementary defense mechanism against pathogens, continuously emerging evidence has uncovered a central role of this complex system in several diseases including lung pathologies.

Main body
Complement factors such as anaphylatoxins C3a and C5a, their receptors C3aR, C5aR and C5aR2 as well as complement inhibitory proteins CD55, CD46 and CD59 have been implicated in pathologies such as the acute respiratory distress syndrome, pneumonia, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, and lung cancer. However, the exact mechanisms by which complement factors induce these diseases remain unclear. Several complement-targeting monoclonal antibodies are reported to treat lung diseases.

Conclusions
The complement system contributes to the progression of the acute and chronic lung diseases. Better understanding of the underlying mechanisms will provide groundwork to develop new strategy to target complement factors for treatment of lung diseases.
ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy
Authors: Soumoy Laura , Genbauffe Aline , Mouchart Lena , Sperone Alexandra , Trelcat Anne , Mukeba-Harchies Léa , Wells Mathilde , Blankert Bertrand , Najem Ahmad , Ghanem Ghanem , Saussez Sven , Journe Fabrice 
Published: January 2024

AbstractDespite advancements in treating metastatic melanoma, many patients exhibit resistance to targeted therapies. Our study focuses on ATP1A1, a sodium pump subunit associated with cancer development. We aimed to assess ATP1A1 prognostic value in melanoma patients and examine the impact of its ligand, bufalin, on melanoma cell lines in vitro and in vivo. High ATP1A1 expression (IHC) correlated with reduced overall survival in melanoma patients. Resistance to BRAF inhibitor was linked to elevated ATP1A1 levels in patient biopsies (IHC, qPCR) and cell lines (Western blot, qPCR). Additionally, high ATP1A1 mRNA expression positively correlated with differentiation/pigmentation markers based on data from The Cancer Genome Atlas (TCGA) databases and Verfaillie proliferative gene signature analysis. Bufalin specifically targeted ATP1A1 in caveolae, (proximity ligation assay) and influenced Src phosphorylation (Western blot), thereby disrupting multiple signaling pathways (phosphokinase array). In vitro, bufalin induced apoptosis in melanoma cell lines by acting on ATP1A1 (siRNA experiments) and, in vivo, significantly impeded melanoma growth using a nude mouse xenograft model with continuous bufalin delivery via an osmotic pump. In conclusion, our study demonstrates that ATP1A1 could serve as a prognostic marker for patient survival and a predictive marker for response to BRAF inhibitor therapy. By targeting ATP1A1, bufalin inhibited cell proliferation, induced apoptosis in vitro, and effectively suppressed tumor development in mice. Thus, our findings strongly support ATP1A1 as a promising therapeutic target, with bufalin as a potential agent to disrupt its tumor-promoting activity.
In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes
Authors: Gnondjui Albert A. , Toure Offianan A. , Ako Berenger A. , Koui Tossea S. , Assohoun Stanislas E. , Gbessi Eric A. , N’Guessan Landry T. , Tuo Karim , Beourou Sylvain , Assi Serge-Brice , Yapo Francis A. , Sanogo Ibrahima , Jambou Ronan 
Published: January 2024

AbstractBackgroundDecreased efficacy of artemisinin-based combination therapy (ACT) forPlasmodium falciparummalaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure.MethodsIsolates were collected from patients attending health centres in Abidjan with uncomplicatedP. falciparummalaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay.Results134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism.ConclusionThis study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.
Mosquito control by abatement programmes in the United States: perspectives and lessons for countries in sub-Saharan Africa
Authors: Ochomo Eric , Rund Samuel S. C. , Mthawanji Rosheen S. , Antonio-Nkondjio Christophe , Machani Maxwell , Samake Siriman , Wolie Rosine Z. , Nsango Sandrine , Lown Laurel Anne , Matoke-Muhia Damaris , Kamau Luna , Lukyamuzi Edward , Njeri Jane , Chabi Joseph , Akrofi Otubea Owusu , Ntege Charles , Mero Victor , Mwalimu Charles , Kiware Samson , Bilgo Etienne , Traoré Mohamed Moumine , Afrane Yaw , Hakizimana Emmanuel , Muleba Mbanga , Orefuwa Emma , Chaki Prosper , Juma Elijah Omondi 
Published: January 2024

AbstractAfrica and the United States are both large, heterogeneous geographies with a diverse range of ecologies, climates and mosquito species diversity which contribute to disease transmission and nuisance biting. In the United States, mosquito control is nationally, and regionally coordinated and in so much as the Centers for Disease Control (CDC) provides guidance, the Environmental Protection Agency (EPA) provides pesticide registration, and the states provide legal authority and oversight, the implementation is usually decentralized to the state, county, or city level. Mosquito control operations are organized, in most instances, into fully independent mosquito abatement districts, public works departments, local health departments. In some cases, municipalities engage independent private contractors to undertake mosquito control within their jurisdictions. In sub–Saharan Africa (SSA), where most vector-borne disease endemic countries lie, mosquito control is organized centrally at the national level. In this model, the disease control programmes (national malaria control programmes or national malaria elimination programmes (NMCP/NMEP)) are embedded within the central governments’ ministries of health (MoHs) and drive vector control policy development and implementation. Because of the high disease burden and limited resources, the primary endpoint of mosquito control in these settings is reduction of mosquito borne diseases, primarily, malaria. In the United States, however, the endpoint is mosquito control, therefore, significant (or even greater) emphasis is laid on nuisance mosquitoes as much as disease vectors. The authors detail experiences and learnings gathered by the delegation of African vector control professionals that participated in a formal exchange programme initiated by the Pan-African Mosquito Control Association (PAMCA), the University of Notre Dame, and members of the American Mosquito Control Association (AMCA), in the United States between the year 2021 and 2022. The authors highlight the key components of mosquito control operations in the United States and compare them to mosquito control programmes in SSA countries endemic for vector-borne diseases, deriving important lessons that could be useful for vector control in SSA.
Social inequalities in early childhood language development during the COVID-19 pandemic: a descriptive study with data from three consecutive school entry surveys in Germany
Authors: Hoffmann Stephanie , Tschorn Mira , Spallek Jacob 
Published: January 2024

Abstract
Background
Social health inequalities are still of great public health importance in modern societies. The COVID-19 pandemic may have affected social inequalities in people's health due to containment measures. As these measures particularly affected children, they might have been particularly vulnerable to increased social inequalities. The aim of the study was to describe health inequalities during the pandemic based on language delay (LD) in children in order to inform public health interventions for a population at risk of long-term health and education inequalities.

Methods
Data of 5–7 year old children from three consecutive school entry surveys in the German federal state of Brandenburg were used, including data compulsorily collected before the pandemic (2018/2019: n = 19,299), at the beginning of the pandemic (2019/2020: n = 19,916) and during the pandemic (2020/2021: n = 19,698). Bivariate and multivariate binary regression analyses [OR, 95% CI] cross-sectionally examined the relationship between the prevalence of LD [yes/no] and social inequalities, operationalized by family socioeconomic position [SEP low/middle/high], migration background [native-German language/non-native German language] and length of kindergarten attendance [< 4 years/ ≥ 4 years]. Factors contributing to inequality in LD were examined by socioeconomic stratification.

Results
Cross-sectionally, LD prevalence has decreased overall (2018/2019: 21.1%, 2019/2020: 19.2%, 2020/2021: 18.8%), and among children from both high SEP and native German-speaking families. As LD prevalence increased among children from families with low SEP and remained stable among non-native German speakers, social inequalities in LD prevalence increased slightly during the pandemic i) by low SEP (2018/2019: OR = 4.41, 3.93–4.94; 2020/2021: OR = 5.12, 4.54–5.77) and ii) by non-German native language (2018/2019: OR = 2.22, 1.86–2.66; 2020/2021: OR = 2.54, 2.19–2.95). During the pandemic, both migration background and kindergarten attendance determined LD prevalence in the high and middle SEP strata. However, the measured factors did not contribute to LD prevalence in children from families with low SEP.

Conclusion
Social inequalities in LD increased due to opposing trends in prevalence comparing low and high SEP families. To promote health equity across the life course, early childhood should be of interest for tailored public health actions (e.g. through targeted interventions for kindergarten groups). Further analytical studies should investigate determinants (e.g., parental investment).
Repurposed drugs in combinations exert additive anti-chikungunya virus activity: an in-vitro study
Authors: Davuluri Kusuma Sai , Ghanghav Rajnandini , Ahire Gunwant , Kakade Mahadeo , Cherian Sarah , Alagarasu Kalichamy , Parashar Deepti 
Published: January 2024

AbstractChikungunya virus (CHIKV) infection causes chikungunya, a viral disease that currently has no specific antiviral treatment. Several repurposed drug candidates have been investigated for the treatment of the disease. In order to improve the efficacy of the known drugs, combining drugs for treatment is a promising approach. The current study was undertaken to explore the antiviral activity of a combination of repurposed drugs that were reported to have anti-CHIKV activity. We explored the effect of different combinations of six effective drugs (2-fluoroadenine, emetine, lomibuvir, enalaprilat, metyrapone and resveratrol) at their non-toxic concentrations against CHIKV under post infection treatment conditions in Vero cells. Focus-forming unit assay, real time RT-PCR, immunofluorescence assay, and western blot were used to determine the virus titre. The results revealed that the combination of 2-fluoroadenine with either metyrapone or emetine or enalaprilat exerted inhibitory activity against CHIKV under post-infection treatment conditions. The effect of these drug combinations was additive in nature compared to the effect of the individual drugs. The results suggest an additive anti-viral effect of these drug combinations against CHIKV. The findings could serve as an outline for the development of an innovative therapeutic approach in the future to treat CHIKV-infected patients.
Prevalence of KIG-grades 3–5 in an orthodontic practice in North Rhine Westphalia compared with results of the DMS•6 and with KZBV data
Authors: Kinzinger Gero Stefan Michael , Hourfar Jan , Lisson Jörg Alexander 
Published: January 2024

Abstract
Background and aim
The prevalence of tooth and jaw malocclusions in 8- to 9-year-olds was surveyed in a nationwide setting as part of the orthodontic module of the Sixth German Study on Oral Health (DMS•6), using the orthodontic indication groups (KIG) as index. Aim of this study was the detection of the prevalence of malocclusions requiring treatment according to the KIG index in statutorily insured patients of an orthodontic practice in North Rhine Westphalia, Germany, and to compare results with corresponding DMS•6 and KZBV data.

Patients and methods
Between 2017–2021, n = 953 statutorily insured patients called for an initial consultation and subsequent determination of the KIG-classification and -grades. The malocclusions were classified and graded in the highest possible KIG-grade according to valid SHI guidelines. Multiple classifications were not recorded. KIG-grade > 3 according to the valid guidelines was detected in n = 815 patients. Since the DMS•6 does not contain information on KIG classifications "U" and "S", their inclusion was waived despite evaluation, leaving data from n = 683 patients for analysis and comparison.

Results
During the study period, n = 235 patients (34.4%) had KIG-classification "D". More than 10% were classified as "K" (120 patients, 17.6%), "P" (98 patients, 14.2%), "M" (89 patients, 13.0%), and "E" (81 patients, 11.9%). Of 16 possible classifications with KIG-grade > 3, "D4" was the most common with 26.6% (182 patients). The results confirm the findings from the multicentric DMS•6 from2021 and corresponding KZBV data from 2020.

Conclusions
Sagittal deviations described by classifications "D" and "M" represent with 47.4% almost half of the malocclusions with treatment need. KIG-grade D4 is the most frequent classification. There were no regional deviations of the prevalence of KIG-grades 3–5 in the district of Viersen / North Rhine compared with the national average, not even when scrutinizing a five-year-period.
The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
Authors: Siqueira Stella Meireles , Campos-do-Carmo Gabriella , da Silva Paulo Ricardo Garcia , Small Isabele Ávila , De Melo Andreia Cristina 
Published: January 2024

Abstract
Background
Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles.

Methods
Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant.

Results
A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%.

Conclusions
This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.
Genomic surveillance of Anopheles mosquitoes on the Bijagós Archipelago using custom targeted amplicon sequencing identifies mutations associated with insecticide resistance
Authors: Moss Sophie , Pretorius Elizabeth , Ceesay Sainey , Hutchins Harry , da Silva Eunice Teixeira , Ndiath Mamadou Ousmane , Jones Robert T. , Vasileva Hristina , Phelan Jody , Acford-Palmer Holly , Collins Emma , Rodrigues Amabelia , Krishna Sanjeev , Clark Taane G. , Last Anna , Campino Susana 
Published: January 2024

Abstract
Background
Insecticide resistance is reducing the efficacy of vector control interventions, consequently threatening efforts to control vector-borne diseases, including malaria. Investigating the prevalence of molecular markers of resistance is a useful tool for monitoring the spread of insecticide resistance in disease vectors. The Bijagós Archipelago (Bijagós) in Guinea-Bissau is a region of stable malaria transmission where insecticide-treated nets are the mainstay for malaria control. However, the prevalence of molecular markers of insecticide resistance in malaria vectors is not well understood.

Methods
A total of 214 Anopheles mosquitoes were analysed from 13 islands across the Bijagós. These mosquitoes were collected using CDC light traps in November 2019, during the peak malaria transmission season. High-throughput multiplex amplicon sequencing was used to investigate the prevalence of 17 different molecular markers associated with insecticide resistance in four genes: vgsc, rdl, ace1 and gste2.

Results
Of the 17 screened mutations, four were identified in mosquitoes from the Bijagós: vgsc L995F (12.2%), N1570Y (6.2%) and A1746S (0.7%) and rdl A269G (1.1%). This study is the first to report the L995F knock-down resistance (kdr)-west allele in Anopheles melas on the Archipelago. An additional eight non-synonymous single-nucleotide polymorphisms were identified across the four genes which have not been described previously. The prevalences of the vgsc L995F and N1570Y mutations were higher on Bubaque Island than on the other islands in this study; Bubaque is the most populous island in the archipelago, with the greatest population mobility and connection to continental Guinea-Bissau.

Conclusions
This study provides the first surveillance data for genetic markers present in malaria vectors from islands across the Bijagós Archipelago. Overall prevalence of insecticide resistance mutations was found to be low. However, the identification of the vgsc L995F and N1570Y mutations associated with pyrethroid resistance warrants further monitoring. This is particularly important as the mainstay of malaria control on the islands is the use of pyrethroid insecticide-treated nets.

Graphical Abstract