bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airway inflammation in asthma: current and future targets and therapies
Authors: Hanania N. 
Published: October 2024

Educational aimsTo provide an overview of airway inflammation in asthma.To review current management guidelines' recommendations for the use of anti-inflammatory therapies in asthma.To discuss current treatment options for airway inflammation in asthma.To outline unmet needs for treating airway inflammation in asthma.To describe novel targets for treating airway inflammation in asthma based on current knowledge.SummaryAsthma is a chronic inflammatory disease of the airways that requires long-term anti-inflammatory therapy. Inhaled corticosteroids (ICS) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, such as a long-acting β2-agonist (LABA) or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to accumulate, and additional anti-inflammatory options become available, it may be possible to target anti-inflammatory therapy to various aspects of the disease and consequently to improve treatment of patients who respond inadequately to standard ICS-based therapy. Several novel anti-inflammatory therapies are at different stages of clinical development. This article will provide an overview of current and future approaches targeting airway inflammation in asthma.
Home noninvasive ventilation in COPD
Authors: Cheung A.P.S. , Chan V.L. , Chu C-M. 
Published: October 2024

Educational aimsTo explain the rationales for home noninvasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients.To review available evidence on the use of home NIV in COPD patients.To review the current consensus on the indications for home NIV in COPD patients.To describe recent evidence in support of home NIV in a selected group of severe COPD patients.To outline future research directions in this area.SummaryNIV is now considered the standard care for COPD patients with hypercapnic exacerbations of their disease. There are theoretical benefits of long-term NIV in COPD patients, but evidence from randomised controlled trials (RCTs) is conflicting and inconclusive. This article will address the following issues:• What are the physiological and clinical rationales for the use of home NIV in COPD patients?• What is the available evidence on the use of home NIV in COPD patients?• What are the limitations of previous studies performed in this area?• Recent advances in home NIV.• Future directions.
Prognostic value of the CRM-status in pancreatic ductal adenocarcinoma - data from a regional cancer registry
Authors: Schuhbaur Jasmin , Surovtsova Irina , Seufferlein Thomas , Kokh Daria , Szotyori-Artz Gertrud , Winzler Claudia , Schütz Juliane , Uhl Waldemar , Tannapfel Andrea , Morakis Philipp 
Published: October 2024

Abstract
Background
Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been established and has been incorporated into the German national S3 guideline on exocrine pancreatic cancer. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline corresponds with overall and progression free survival in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany.

Methods
Data from the cancer registry of the State of Baden-Württemberg, Germany, were used to assess the relationship between CRM-status and progression free survival (PFS) as well as 3-year overall survival (OS) using documented patients diagnosed with resectable ductal adenocarcinoma of the pancreas between 2015 and 2020. Patients were residents of the State of Baden-Württemberg and underwent surgery for PDAC. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is > 1 mm from the tumour, R0 narrow/CRM + when CRM is ≤ 1 mm from the tumour and R1 when tumour cells are found at the resection margin.

Results
In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM + resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM + and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading and tumour location.

Conclusions
CRM is prognostic for patients with resectable PDAC making the pathological assessment of the R-status according to the CRM concept worthwhile.
Factors influencing the choice of specialization - a cross-sectional study with civilian medical students and prospective medical officers in Germany
Authors: Goetz Katja , Grienitz Katharina , Steinhäuser Jost 
Published: October 2024

Abstract
Background
The recruitment of physicians is an increasing challenge. The aim of the study was to explore factors that might influence future civilian and military doctors’ choice of specialization.

Methods
A 28 item author developed questionnaire was used to survey civilian medical students and prospective medical officers. The questionnaire consisted of 20 items addressing choice of specialization, and eight socio-demographic factors. Response options were available in the form of open and closed questions as well as in the form of a Likert scale (1 ‘not at all’ to 6 ‘very much’). The questionnaire was completed online by prospective medical officer from June to September 2021 and by civilian students from November 2020 to March 2021.

Results
In total, 2,030 students (56.1% female, mean age = 24, mean semester 6.5) participated in the survey, 1,553 civilian students and 477 prospective medical officers. Regular feedback and clear structures (mean = 5.35) followed by good teamwork (mean = 5.33) during postgraduate training was rated particularly important. Moreover, a secure job after graduation (mean = 5.23) and a compatibility of family and job (mean = 5.14) were important parameters for career choice. The specializations most frequently chosen were surgery (32.0%), internal medicine (27.1%) and anesthesiology (22.1%). The regression models showed that the choice depends on own attitude concerning the specialty would be a patient-orientation job, or a job with more manual work or more career option within in the job preferred.

Conclusions
Considering the value students place on receiving feedback and the structure of their specialist training, this seems to be a promising strategy for future recruitment. Good team dynamics and job security are key concerns for prospective physicians.
Review of MrsFreqPhase methods: methods designed to estimate statistically malaria parasite multiplicity of infection, relatedness, frequency and phase
Authors: Taylor Aimee R. , Neubauer Vickers Eric , Greenhouse Bryan 
Published: October 2024

AbstractMalaria parasites are haploid within humans, but infections often contain genetically distinct groups of clonal parasites. When the per-infection number of genetically distinct clones (i.e., the multiplicity of infection, MOI) exceeds one, and per-infection genetic data are generated in bulk, important information are obfuscated. For example, the MOI, the phases of the haploid genotypes of genetically distinct clones (i.e., how the alleles concatenate into sequences), and their frequencies. This complicates many downstream analyses, including relatedness estimation. MOIs, parasite sequences, their frequencies, and degrees of relatedness are used ubiquitously in malaria studies: for example, to monitor anti-malarial drug resistance and to track changes in transmission. In this article, MrsFreqPhase methods designed to estimate statistically malaria parasite MOI, relatedness, frequency and phase are reviewed. An overview, a historical account of the literature, and a statistical description of contemporary software is provided for each method class. The article ends with a look towards future method development, needed to make best use of new data types generated by cutting-edge malaria studies reliant on MrsFreqPhase methods.
Human mesenchymal stroma/stem-like cell-derived taxol-loaded EVs/exosomes transfer anti-tumor microRNA signatures and express enhanced SDF-1-mediated tumor tropism
Authors: Hass Ralf , von der Ohe Juliane , Luo Tianjiao 
Published: October 2024

Abstract
Background
The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds.

Methods
EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA.

Results
EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%.

Conclusions
These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products.
Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study
Authors: Fehér Tamás , Széll Noémi , Nagy István , Maróti Zoltán , Kalmár Tibor , Sohajda Zoltán , Barboni Mirella T. S. 
Published: October 2024

Abstract
Background
Myopia-26, a Mendelian form of early-onset high-myopia (eoHM) caused by mutations in the X-chromosomal ARR3 gene and predominantly affecting females, curiously, may provide an alternative route of investigation to unveil retinal mechanisms underlying pathological eye growth. We conducted a case-control cross-sectional prospective electrophysiological study in genetically characterized Myopia-26 patients (ARR3 heterozygous symptomatic females) compared with high myopes harboring intact ARR3 alleles and one carrier hemizygous male.

Results
Participants were 26 volunteers: 10 healthy control females (E-CTRL, mean age = 31.5 ± 8.8 years), one healthy control male, one carrier male of the mutant ARR3 allele and 14 female eoHM patients (mean age = 27.0 ± 13.1 years) divided in two groups: seven without (M-CTRL) and seven with (MYP-26) genetic alteration in the ARR3 gene. The clinical evaluation included complete eye screening and full-field electroretinograms (ERGs) recorded from both eyes under mydriasis. Spherical equivalent was comparable (mean=-9.55 ± 2.46 and − 10.25 ± 3.22 for M-CTRL and MYP-26, respectively) and best corrected visual acuity (BCVA) was significantly different between M-CTRL and MYP-26 (1.0 vs. 0.406 ± 0.253, respectively). E-CTRL and M-CTRL showed similar light-adapted flash and flicker ERG amplitudes; however, the prior values were reduced by ~ 35% (a- and b-waves alike), the latter by ~ 55% in the MYP-26 group (F(2, 45) > 21.821, p < 0.00001). Dark-adapted a-wave amplitudes were slightly reduced (by ~ 20%) in all myopic patients compared to E-CTRL, irrespective of the ARR3 genotype (E-CTRL vs. eoHM, p = 0.038).

Conclusions
The cone dysfunction observed in Myopia-26 patients is specifically linked to the mutation of ARR3, and is not the consequence of eoHM, i.e. elongation of the eye. It may play a role in myopic refractive error development through a yet unconfirmed pathomechanism.
Targeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest
Authors: Mancarella Serena , Gigante Isabella , Pizzuto Elena , Serino Grazia , Terzi Alberta , Dituri Francesco , Maiorano Eugenio , Vincenti Leonardo , De Bellis Mario , Ardito Francesco , Calvisi Diego F. , Giannelli Gianluigi 
Published: October 2024

Abstract
Background
Cancer-associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely have a role in tumor aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor, namely Crenigacestat, may affect cancer progression.

Methods
We used different in vitro models in 2D and established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. The results were confirmed in a xenograft model, and explanted tumoral tissues underwent transcriptomic and bioinformatic analysis.

Results
hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, while Crenigacestat significantly inhibits only the cross-talk stimulated migration. Hetero-spheroids grew larger than homo-spheroids, formed by only iCCA cells. Crenigacestat significantly reduced the invasion and growth of hetero- but not of homo-spheroids. In xenograft models, hCAFs/KKU-M213 tumors grew significantly larger than KKU-M213 tumors, but were significantly reduced in volume by Crenigacestat treatment, which also significantly decreased the fibrotic reaction. Ingenuity pathway analysis revealed that genes of hCAFs/KKU-M213 but not of KKU-M213 tumors increased tumor lesions, and that Crenigacestat treatment inhibited the modulated canonical pathways. Cell cycle checkpoints were the most notably modulated pathway and Crenigacestat reduced CCNE2 gene expression, consequently inducing cell cycle arrest. In hetero-spheroids, the number of cells increased in the G2/M cell cycle phase, while Crenigacestat significantly decreased cell numbers in the G2/M phase in hetero but not in homo-spheroids.

Conclusions
The hCAFs/iCCA cross-talk is a new target for reducing cancer progression with drugs such as Crenigacestat.

Graphical abstract
Recruitment of pregnant and breastfeeding women in pharmacokinetic studies: strategies, opportunities, barriers, and recommendations
Authors: Nakijoba Ritah , Kawuma Aida N. , Asiimwe Simon Peter , Turyahabwe Christine , Tabwenda Jovia Christine , Kyeyune Jacqueline , Magoola Johnson , Ojara Francis Williams , Waitt Catriona 
Published: October 2024

AbstractPregnant and breastfeeding women are often under-represented in clinical research, including pharmacokinetic studies, due to ethical and logistical challenges. This paper examines strategies to improve the recruitment and retention of this demographic in pharmacokinetic research, drawing on experiences from five studies conducted at the Infectious Diseases Institute, Makerere University, Uganda. Key strategies implemented include Community Advisory Board meetings, the involvement of Peer Mothers as Co-Investigators, established recruitment sites, the use of safety protocols, and the utilization of diverse communication platforms, including social media and stakeholder meetings. Despite these efforts, substantial barriers, such as scheduling conflicts and frequent staff turnover at recruitment sites, continue to threaten progress. The paper recommends flexible scheduling, strengthening public engagement, and transparent demonstration of adherence to ethical principles; justice, non-maleficence, respect, and beneficence to ensure the safety and inclusivity of pregnant and breastfeeding women. The inclusion of this population in pharmacokinetic studies is essential for providing evidence-based care that meets their unique health needs.
Performance evaluation of compansion-based clipped OFDM systems
Authors: Pfletschinger Stephan , Dietl Guido 
Published: October 2024

AbstractThe peak-to-average power ratio (PAPR), commonly used to describe the amplitude variations of an OFDM (orthogonal frequency-division multiplex) signal, does not accurately reflect its impact on the system performance. This paper applies the mutual information as a metric to assess the effects of nonlinear PAPR reduction schemes on the performance of OFDM systems. Evaluation of the achieved mutual information shows that a significant capacity loss from clipping occurs only at high SNR (signal-to-noise ratio) and a simple compression/expansion technique is proposed to achieve close to optimal performance in this regime. The effectiveness of this method is validated through WER (word error rate) simulations with several modulation and coding schemes.
Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing
Authors: Chen Sunfang , Yao Jun , Huo Shicheng , Xu Chennan , Yang Ruting , Tao Danhua , Fang Bin , Ma Gaoxiang , Zhu Zaihua , Zhang Ye , Guo JingJing 
Published: October 2024

AbstractHydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.
Graphical Abstract
Impulsivity and epilepsy: a bidirectional mendelian randomization study
Authors: Chen Tao , Liao Yuqi , Hong Peiwei 
Published: October 2024

Abstract
Background
Previous studies have found that patients with epilepsy are more likely to suffer impulsivity. However, the causal relationship between impulsivity and epilepsy is unknown. In this study, we conduct a bidirectional Mendelian randomization (MR) study to explore the causal relationship between impulsivity and epilepsy with recurrent seizure.

Methods
Data of the genome-wide association studies (GWAS) on 14 impulsivity traits and epilepsy were obtained from the GWAS catalog and UK Biobank. Inverse-variance weighted (IVW) and weighted median (WM) methods were utilized for MR estimates. IVW, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used to assess heterogeneity and pleiotropy.

Results
Single-nucleotide polymorphisms (SNPs) related to the lack of perseverance were associated with a decreased risk of epilepsy with recurrent seizures according to the results of IVW (odd ratio [OR] = 0.93, 95% confident interval [CI] = 0.90–0.97, P = 0.001) and WM (OR = 0.93, 95%CI = 0.87–0.98, P = 0.007). Meanwhile, heterogeneity was not observed with a Cochran Q-derived P value of 0.819 for MR egger and a P value of 0.808 for IVW. Pleiotropy was not found according to the MR-PRESSO (P = 0.273). The other 13 impulsivity traits had no causal effect on epilepsy with recurrent seizures. Meanwhile, SNPs related with epilepsy with recurrent seizures had no causal effect on the 14 impulsivity traits.

Conclusions
This MR study suggests that lack of perseverance may be a protective factor against epilepsy with recurrent seizures. However, epilepsy with recurrent seizures does not affect impulsivity.