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Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

This study aimed to investigate the skeletal and dental effects of the maxillary skeletal expander (MSE) using cone beam computed tomography (CBCT) images analyzed in the coronal zygomatic and axial palatal sections (APS). Pre- and post-expansion CBCT images of 18 subjects (10 females and 8 males) aged 12-16 years with maxillary transverse deficiency who were treated with MSE 2 were included in this retrospective study. In the coronal zygomatic section (CZS), upper interzygomatic distance and lower interzygomatic distances (LID), orbital distance (OD), alveolar distances (AD), and dental distances (DD), as well as nasal cavity width (NCW) and molar basal bone angle, were assessed. In the APS, the separation between the anterior nasal spine (ANS) and posterior nasal spine (PNS) was assessed. All measurements were performed using OnDemand3D software. Pre- and post-expansion treatment changes were compared using paired t-tests, with statistical significance set at p<0.05. In the CZS, a pyramidal skeletal expansion pattern was observed, with the greatest increase in DD (R: 2.83 mm, L: 3.18 mm), followed by AD (R: 1.63 mm, L: 1.97 mm), NCW (R: 1.66 mm, L: 2.28 mm), LID (R: 1.48 mm, L: 1.92 mm), and OD (R: 0.42 mm, L: 0.56 mm). Along with greater skeletal expansion, slightly reduced dental tipping and minimal alveolar bone bending were observed. In the APS, a nearly equal separation was observed at both the ANS (R: 1.79 mm, L: 2.46 mm) and PNS (R: 1.85 mm, L: 2.49 mm), indicating a parallel split of the midpalatal suture. Furthermore, among the 36 pterygopalatine sutures examined, only three showed separation between the medial and lateral pterygoid processes. MSE 2 application provides more favorable skeletal outcomes reduces dentoalveolar side effects, and results in a more parallel midpalatal suture split.

Background To investigate Doppler parameters, including Amniotic Fluid/Umbilical Cerebral Ratio (AUCR), in patients with gestational diabetes mellitus (GDM) and to determine which indices best predict composite adverse perinatal outcomes (CAPO) in GDM. Methods This prospective case-control study included 70 insulin-treated GDM patients and 70 healthy controls from a tertiary referral center between December 2023 to April 2024. Ultrasonographic evaluations comprised single deepest vertical pocket (SDVP) and Doppler indices of the middle cerebral artery (MCA) and umbilical artery (UA). Derived ratios, including the cerebro-placental ratio (CPR), umbilico-cerebral ratio (UCR), and the AUCR, were compared between the study and control groups, as well as within the GDM group based on the presence of CAPO. Results AUCR and SDVP were significantly higher in GDM patients compared to controls ( p  = 0.009 and p  = 0.042, respectively). In the GDM group with CAPO, SDVP and AUCR values were also higher than in the non-CAPO group ( p  = 0.022 and p  = 0.005). In contrast, there were no statistically significant differences in UA PI, MCA PI, CPR, or UCR values either between the GDM and control groups or between GDM patients with and without CAPO (all p  > 0.05). ROC analysis showed AUCR predicted CAPO at a cut-off of 10.050 (AUC = 0.703). Conclusion AUCR is a promising ultrasonographic parameter for predicting adverse perinatal outcomes in GDM patients. Given that conventional Doppler parameters did not show significant differences in this study, AUCR may offer an additional tool for identifying GDM cases at risk for adverse outcomes, particularly in the absence of overt Doppler abnormalities.

Distal hereditary motor neuronopathies (dHMN) are a genetically heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and progressive distal muscle weakness. A heterozygous missense variant in FBXO38 has been previously described in two families affected by autosomal-dominant dHMN. In this paper, we describe a homozygous missense variant in FBXO38 (c.1577G>A; p.(Arg526Gln)) in a young Turkish female, offspring of consanguineous parents, with a congenital mild neuronopathy with idiopathic toe walking, normal sensory examination, and hearing loss. This work is the first to describe a novel homozygous variant and a suggested loss of function mechanism in FBXO38, expanding the dHMN type IID phenotype.

Introduction: Stenotrophomonas maltophilia (S. Maltophilia) is a multidrug-resistant pathogen causing severe infections in intensive care units (ICUs). This study aimed to identify the risk factors influencing 30-day mortality and evaluate antimicrobial susceptibility patterns in ICU patients with S. maltophilia infections. Methodology: A prospective, multicenter, international observational study was conducted between 15 October 2023 and 15 April 2024, in 36 ICUs across 12 countries. Adult patients (≥ 18 years) with S. maltophilia isolated from blood, urine, or respiratory cultures were included if isolates were considered clinically consistent with infection. Colonized or coinfected patients were excluded. Clinical, laboratory data were collected prospectively. Thirty-day outcome was defined as survival or death after the first positive culture. Results: A total of 207 patients were included; 109 (52.7%) died within 30 days. The primary infection sites were pneumonia (28.5%) and bloodstream infections (38.0%). Resistance rates were 7.2% for trimethoprim-sulfamethoxazole (TMP-SMX), 10.4% for levofloxacin, and 27% for ceftazidime. None of the patients received effective empiric therapy. Older age (p = 0.030), acute renal failure (p = 0.016), chronic obstructive pulmonary disease (COPD; p = 0.008), malignancy (p = 0.001), and sequential organ failure assessment (qSOFA) ≥ 2 (p = 0.001) were independently associated with higher mortality. Repeat culturing and antimicrobial modification according to susceptibility testing reduced mortality (p = 0.017). Conclusions: S. maltophilia remains a lethal ICU pathogen. Early risk assessment, cultures, susceptibility testing, and therapy changes are vital. TMP-SMX and levofloxacin stay effective; but surveillance, infection control, and prudent antibiotic use remain essential.

Introduction and Objective. Disadvantages associated with direct high b-value measurements may be avoided with use of computed diffusion-weighted imaging (cDWI). The purpose of this study is to assess the diagnostic performance of cDWI image sets calculated for high b-values of 1500, 2000, and 3000 s/mm2. Materials and Methods. Twenty-eight patients who underwent multiparametric MRI of the prostate and radical prostatectomy consecutively were enrolled in this retrospective study. Using a software developed at our institute, cDWI1500, cDWI2000, and cDWI3000 image sets were generated by fitting a monoexponential model. Index lesions on cDWI image sets were scored by two radiologists in consensus considering lesion conspicuity, suppression of background prostate tissue, distortion, image set preferability, and contrast ratio measurements were performed. Results. Lesion detection rates are the same for computed b-values of 2000 and 3000 s/mm2 and are better than b-values of 1500 s/mm2. Best lesion conspicuity and best background prostate tissue suppression are provided by cDWI3000 image set. cDWI2000 image set provides the best zonal anatomical delineation and less distortion and was chosen as the most preferred image set. Average contrast ratio measured on these image sets shows almost a linear relation with the b-values. Conclusion. cDWI2000 image set with similar conspicuity and the same lesion detection rate, but better zonal anatomical delineation, and less distortion, was chosen as the preferable image set.

Introduction: Cytomegalovirus (CMV) infection during pregnancy poses a significant risk of congenital infection, particularly in seronegative women. This study aimed to assess CMV seroprevalence among pregnant women and evaluate the incidence of primary CMV infections during pregnancy. Materials and Methods: This retrospective multicenter study included pregnant women aged ≥18 year who were hospitalized between January 2018 and December 2022. Demographic data - including maternal age, gravidity, and educational and occupational status - along with CMV serological results, gestational age at CMV diagnosis, and fetal ultrasonographic (USG) findings were collected and analyzed. In cases with positive CMV immunoglobulin M (IgM) and IgG, CMV-IgG avidity values, amniotic fluid CMV-DNA polymerase chain reaction results, and fetal USG findings were recorded to assess the likelihood of primary infection. Results: Among 16,761 pregnant women, 261 (1.6%) tested positive for CMV-IgM. Of these, 126 (48.3%) underwent CMV-IgG avidity testing, and three cases demonstrated low avidity, indicating recent primary infection. Ultrasonographic abnormalities in these three fetuses included hydrops fetalis, polyhydramnios, skin edema, and hyperechogenic bowel. Despite high CMV-IgG avidity, five cases showed abnormal findings on detailed fetal ultrasonography namely intrauterine growth restriction, oligohydramnios, and cranial anomalies. Conclusion: Primary CMV infection during pregnancy is associated with adverse outcomes such as fetal anomalies, spontaneous abortion, and preterm birth. Preventive strategies, including educating CMV-seronegative women about transmission routes and routine assessment of CMV-IgG avidity and fetal USG findings, are essential for early diagnosis and improved perinatal outcomes.

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, , ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets and , and provides insight into the impact of long term fingolimod use on ILC populations.

Polymeric coatings of styrene derivatives due to its ease of production and application have been employed in fascinating range of applications. Distinct from other polymerization techniques, electrodeposition offers as a convenient strategy to achieve strong adherence between the polymer films and electrode surfaces which is highly desirable for functional coatings. In this study, it was aimed to electrosynthesize and characterize the functional polymer, poly (4-amino-3-nitrostyrene), for the first time. Electrosynthesis from 4-amino-3-nitrostyrene monomer onto gold electrodes was investigated in 0.1 M tetrabutyl ammonium perchlorate/dichloromethane solution. Cathodic electropolymerization was performed by cyclic voltammetry (CV) with a potential range of 0.4 V to − 2.0 V vs. SCE. The properties of the obtained polymeric coatings were investigated via electrochemical, microscopic and spectrochemical methods. The redox and charge transfer resistance behaviour of the resulting polymer was examined via CV and electrochemical impedance spectroscopy (EIS) measurements. Spectroscopic (UV–Vis, ATR-FTIR) techniques were employed to distinguish between the monomer and the obtained polymer film. The polymeric film thickness was measured by an optical profilometer and the optical energy gap of the obtained film was 2.41 eV. Scanning electron microscopy characterization of the polymer on the substrate revealed a compact film structure. Contact angle measurements displayed the low wettability of the polymer. Due to the good adhesion of the coatings, its usability for future corrosion protection studies was examined via EIS measurements. Electropolymerized poly (4-amino-3-nitrostyrene) showed a good potential to be used as a corrosion protection coating material since it preserved a long-term corrosion resistance. Graphical abstract

With the increased recognition of the capabilities of prostate multiparametric (mp) magnetic resonance imaging (MRI), attempts are being made to incorporate MRI into routine prostate biopsies. In this study, we aimed to analyze the diagnostic yield via cognitive fusion, transrectal ultrasound (TRUS)-guided, and in-bore MRI-guided biopsies in biopsy-naive patients with positive findings for prostate cancer screening. Charts of 140 patients, who underwent transrectal prostate biopsy after the adaptation of mp-MRI into our routine clinical practice, were reviewed retrospectively. Patients with previous negative biopsies (n=24) and digital rectal examination findings suspicious for ≥cT3 prostate cancer (n=16) were excluded. T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging were included in mp-MRI. Cognitive fusion biopsies were performed after a review of mp-MRI data, whereas TRUS-guided biopsies were performed blinded to MRI information. In-bore biopsies were conducted by means of real-time targeting under MRI guidance. Between January 2012 and February 2014, a total of 100 patients fulfilling the inclusion criteria underwent TRUS-guided (n=37), cognitive fusion (n=49), and in-bore (n=14) biopsies. Mean age, serum prostate specific antigen level, and prostate size did not differ significantly among the study groups. In TRUS-guided biopsy group, 51.3% were diagnosed with prostate cancer, while the same ratio was 55.1% and 71.4% in cognitive fusion and in-bore biopsy groups, respectively (P = 0.429). Clinically significant prostate cancer detection rate was 69.1%, 70.3%, and 90% in TRUS-guided, cognitive fusion, and in-bore biopsy groups, respectively (P = 0.31). According to histopathologic variables in the prostatectomy specimen, significant prostate cancer was detected in 85.7%, 93.3%, and 100% of patients in TRUS-guided, cognitive fusion, and in-bore biopsy groups, respectively. In the first set of transrectal prostate biopsies, mp-MRI guidance did not increase the diagnostic yield significantly.