bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sense of smell in chronic rhinosinusitis: A multicentric study on 811 patients
Authors: Macchi Alberto , Giorli Alessia , Cantone Elena , Carlotta Pipolo Giorgia , Arnone Flavio , Barbone Umberto , Bertazzoni Giacomo , Bianchini Chiara , Ciofalo Andrea , Cipolla Federica , De Massimi Alessio , De Vita Carla , Di Lieto Cristina , Ghidini Angelo , Govoni Marco , Gramellini Giulia , Maselli Del Giudice Alessandro , Ottaviano Giancarlo , Seccia Veronica , Sireci Federico , Sollini Giacomo , Staffieri Claudia , Gallo Stefania , Heffler Enrico , Mantia Ignazio La , De Corso Eugenio , Canevari Frank Rikki , Lombardo Nicola , Malvezzi Luca , Orietti Gabriele , Pasquini Ernesto , Presutti Livio , Monti Giulia 
Published: April 2023

IntroductionThe impairment of the sense of smell is often related to chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP, CRSsNP). CRSwNP is a frequent condition that drastically worsens the quality of life of those affected; it has a higher prevalence than CRSsNP. CRSwNP patients experience severe loss of smell with earlier presentation and are more likely to experience recurrence of their symptoms, often requiring revision surgery.MethodsThe present study performed a multicentric data collection, enrolling 811 patients with CRS divided according to the inflammatory endotype (Type 2 and non-Type 2). All patients were referred for nasal endoscopy for the assessment of nasal polyposis using nasal polyp score (NPS); Sniffin’ Sticks olfactory test were performed to measure olfactory function, and SNOT-22 (22-item sinonasal outcome test) questionnaire was used to assess patients’ quality of life; allergic status was evaluated with skin prick test and nasal cytology completed the evaluation when available.ResultsData showed that Type 2 inflammation is more common than non-type 2 (656 patients versus 155) and patients suffer from worse quality of life and nasal polyp score. Moreover, 86.1% of patients with Type 2 CRSwNP were affected by a dysfunction of the sense of smell while it involved a lesser percentage of non-Type 2 patients. Indeed, these data give us new information about type-2 inflammation patients’ characteristics.DiscussionThe present study confirms that olfactory function weights on patients’ QoL and it represents an important therapeutic goal that can also improve patients’ compliance when achieved. In a future – and present – perspective of rhinological precision medicine, an impairment of the sense of smell could help the clinician to characterize patients better and to choose the best treatment available.
Antibiotic susceptibility pattern of Portuguese environmental Legionella isolates
Authors: Cruz Carolina , Rodrigues Lúcia , Fernandes Filipa , Santos Ricardo , Paixão Paulo , Chasqueira Maria Jesus 
Published: April 2023

IntroductionLegionnaires’ Disease is a pneumonia caused by Legionella spp., currently treated empirically with fluoroquinolones and macrolides. In this study, we aim to describe the antibiotic susceptibility pattern of environmental Legionella recovered in the south of Portugal.MethodsMinimal inhibitory concentration (MIC) determination of 57 Legionella isolates (10 Lp sg 1, 32, Lp sg 2-14 15 L. spp) was achieved by broth microdilution, as described by EUCAST, for azithromycin, clarithromycin, ciprofloxacin, levofloxacin, and doxycycline. ResultsFluoroquinolones were the most active antibiotic, displaying the lowest MIC values in contrast to doxycycline which had the highest. MIC90 and epidemiological cut-off (ECOFF) values were, respectively, 0.5/1 mg/L for azithromycin, 0.125/0.25 mg/L for clarithromycin, 0.064/0.125 mg/L for ciprofloxacin, 0.125/0.125 mg/L for levofloxacin and 16/32 mg/L for doxycycline.DiscussionMIC distributions were higher than reported by EUCAST for all antibiotics. Interestingly, two phenotypically resistant isolates with high-level quinolone resistance were identified. This is the first time that MIC distributions, lpeAB and tet56 genes have been investigated in Portuguese environmental isolates of Legionella.
Amlodipine rescues advanced iron overload cardiomyopathy in hemojuvelin knockout murine model: Clinical implications
Authors: Zhabyeyev Pavel , Sadasivan Chandu , Shah Saumya , Wang Faqi , Oudit Gavin Y. 
Published: April 2023

BackgroundIron overload cardiomyopathy (IOC) is a major co-morbidity of genetic hemochromatosis and secondary iron overload with limited therapeutic options. We aim to investigate mechanisms of rescue action of amlodipine in the murine model of iron overload, characterize changes in human cardiac tissue due to IOC, and compare them to the changes in the animal model of IOC.Methods and resultsAs an animal model, we used male hemojuvelin knockout (HJVKO) mice, which lacked hemojuvelin (a co-receptor protein for hepcidin expression). The mice were fed a high-iron diet from 4 weeks to 1 year of age. As a rescue, iron-fed mice received the Ca2+ channel blocker, amlodipine, from 9 to 12 months. Iron overload resulted in systolic and diastolic dysfunctions and changes in the cardiac tissue similar to the changes in the explanted human heart with IOC. An IOC patient (β-thalassemia) with left-ventricular ejection fraction (LVEF) 25% underwent heart transplantation. The murine model and the explanted heart showed intra-myocyte iron deposition, fibrosis, hypertrophy, oxidative stress, remodeling of Ca2+ cycling proteins, and metabolic kinases typical of heart failure. Single-myocyte contractility and Ca2+ release were diminished in the murine model. The amlodipine-treated group exhibited normalization of cellular function and reversed fibrosis, hypertrophy, oxidative stress, and metabolic remodeling. We also report a clinical case of primary hemochromatosis successfully treated with amlodipine.ConclusionsThe aged HJVKO murine model on the iron-rich diet reproduced many features of the human case of IOC. The use of amlodipine in the murine model and clinical case reversed IOC remodeling, demonstrating that amlodipine is effective adjuvant therapy for IOC.
Abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability
Authors: Yan Kun-wu , Tian Xiao-fei , Wu Yan-ni , Cai Meng , Guo Ming-tao 
Published: April 2023

BackgroundThere is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability.Methods83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression.ResultsThe results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m2, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P&gt;0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability.ConclusionThe purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.
GH treatment in pediatric Down syndrome: a systematic review and mini meta-analysis
Authors: Shaki David , Hershkovitz Eli , Tamam Shai , Bollotin Arkadi , David Odeya , Yalovitsky Guy , Loewenthal Neta , Carmon Lior , Walker Dganit , Nowak Raphael , Haim Alon 
Published: April 2023

ObjectiveTo analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved.DesignSystematic review and mini meta-analysis of the literature.MethodsA search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility.ResultsIn total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option.ConclusionsAs GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.
Are inflammatory bowel diseases associated with an increased risk of COVID-19 susceptibility and severity? A two-sample Mendelian randomization study
Authors: Ai Qixiong , Yang Bo 
Published: April 2023

Background: Due to inconsistent findings in observational studies regarding the relationship between inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), and COVID-19, our objective is to explore a potential causative correlation between IBD and COVID-19 susceptibility and its severity using a two-sample Mendelian randomization (MR) analysis.Methods: Using summary data from genome-wide association studies, IBD, including UC and CD, were used as exposure instruments, while COVID-19 susceptibility, hospitalization, and very severe illness were employed as the outcome. The five analysis methods were adopted to evaluate the causal relationship between two diseases, with the inverse variance weighted (IVW) method being the most important. Also, sensitivity analyses were done to make sure that the main results of the MR analyses were reliable.Results: In the analysis using five methods, all p-values were higher than 0.05. There was no association between IBD and COVID-19 susceptibility, hospitalization, and severity in our MR study. The random-effect model was applied due to the existence of heterogeneity. MR-Egger regression revealed no indication of directional pleiotropy, and sensitivity analysis revealed similar relationships.Conclusion: This MR study found no evidence to support that IBD (which includes UC and CD) increases the risk of COVID-19 susceptibility or severity. Our result needs further confirmation through larger epidemiological studies.
mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals
Authors: Lozano-Rodríguez Roberto , Avendaño-Ortíz José , Terrón Verónica , Montalbán-Hernández Karla , Casalvilla-Dueñas José , Bergón-Gutiérrez Marta , Mata-Martínez Pablo , Martín-Quirós Alejandro , García-Garrido Miguel Ángel , del Balzo-Castillo Álvaro , Peinado María , Gómez Laura , Llorente-Fernández Irene , Martín-Miguel Gema , Herrero-Benito Carmen , López-Morejón Lissette , Vela-Olmo Carmen , Cubillos-Zapata Carolina , López-Collazo Eduardo , del Fresno Carlos 
Published: April 2023

IntroductionCOVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose.MethodsWe have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant.ResultsAll these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination.ConclusionThis work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.
Prognostic significances of PD-L1- and CTLA-4-positive T cells and positive correlations of immunosuppressive marker expression between cancer tissue and peripheral blood in patients with gastric cancer
Authors: Lee Kun Hee , Kim So Jung , Woo Jin Seok , Lee Seung Yoon , Jhun Jooyeon , Moon Jeonghyeon , Jung Yoon Ju , Cho Mi-La , Song Kyo Young 
Published: April 2023

IntroductionAlthough tumor, node, metastasis (TNM) staging has been used for prognostic assessment of gastric cancer (GC), the prognosis may vary among patients with the same TNM stage. Recently, the TNM-Immune (TNM-I) classification staging system has been used for prognostic assessment of colorectal cancer based on intra-tumor T-cell status, which is a superior prognostic factor compared with the American Joint Committee on Cancer staging manual. However, an immunoscoring system with prognostic significance for GC has not been established.MethodHere, we evaluated immune phenotypes in cancer and normal tissues, then examined correlations between tissues and peripheral blood. GC patients who underwent gastrectomy at Seoul St. Mary’s Hospital between February 2000 and May 2021 were included. We collected 43 peripheral blood samples preoperatively and a pair of gastric mucosal samples postoperatively, including normal and cancer mucosa, which did not influence tumor diagnosis and staging. Tissue microarray samples of GC were collected from 136 patients during surgery. We investigated correlations of immune phenotypes between tissues and peripheral blood using immunofluorescence imaging and flow cytometry, respectively. GC mucosa exhibited an increased number of CD4+ T cells, as well as increased expression levels of immunosuppressive markers (e.g., programmed death-ligand-1 [PD-L1], cytotoxic T lymphocyte antigen-4 [CTLA-4], and interleukin-10), in CD4+ T cells and non-T cells. ResultThe expression levels of immunosuppressive markers were significantly increased in cancer tissues and peripheral blood mononuclear cells. In gastric mucosal tissues and peripheral blood of GC patients, similar immunosuppression phenotypes were observed, including increased numbers of PD-L1- and CTLA-4-positive T cells. DiscussionTherefore, peripheral blood analysis may be an important tool for prognostic assessment of GC patients.
Efficacy and safety of serplulimab plus nab-paclitaxel in previously treated patients with PD-L1–positive advanced cervical cancer: a phase II, single-arm study
Authors: An Jusheng , Li Xiumin , Wang Jing , Zhu Lijing , An Ruifang , Jiang Kui , Huang Yi , Wang Ke , Li Guiling , Wang Chunyan , Yuan Jianlin , Hou Xiaoli , Yang Guiyu , Li Jing , Wang Qingyu , Zhu Jun , Wu Lingying 
Published: April 2023

ObjectiveWe report the efficacy and safety of serplulimab, a novel humanized anti–programmed death-1 antibody, plus nanoparticle albumin-bound (nab)-paclitaxel in previously treated patients with programmed death ligand-1 (PD-L1)–positive advanced cervical cancer.MethodsPatients diagnosed with PD-L1–positive (combined positive score ≥1) cervical cancer were enrolled in this single-arm, open-label, phase II study. They were given serplulimab 4.5 mg/kg for up to 2 years (35 dosing cycles) plus nab-paclitaxel 260 mg/m2 for up to six cycles once every 3 weeks. Primary endpoints were safety and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST version 1.1. Secondary endpoints included ORR assessed by the investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsBetween December 2019 and June 2020, 52 patients were screened and 21 were enrolled. IRRC-assessed ORR was 57.1% (95% confidence interval [CI] 34.0–78.2%); 3 (14.3%) patients achieved complete response and 9 (42.9%) partial response. The median DOR was not reached (NR) (95% CI 4.1–NR). IRRC-assessed median PFS was 5.7 months (95% CI 3.0–NR), and median OS was 15.5 months (95% CI 10.5–NR). Investigator-assessed ORR was 47.6% (95% CI 25.7–70.2%). Seventeen (81.0%) patients experienced grade ≥3 treatment-emergent adverse events. Grade ≥3 adverse drug reactions were reported in 7 (33.3%) patients. Immune-related adverse events occurred in 12 (57.1%) patients.ConclusionsIn previously treated patients with PD-L1–positive advanced cervical cancer, serplulimab plus nab-paclitaxel provided durable clinical activity and a manageable safety profile.Clinical trial registrationClinicalTrials.gov, identifier NCT04150575.
Early maladaptive schemas in episodic and chronic migraine in adolescents
Authors: Güler Aksu Gülen , Kayar Ozan , Tufan Ali Evren , Kütük Meryem Özlem , Özdağ Acarli Ayşe Nur , Sucu Damla Hazal , Taşdelen Bahar , Toros Fevziye , Özge Aynur 
Published: April 2023

IntroductionPsychotherapies, such as schema therapy, are receiving increasing attention in the management of pediatric headaches. The purpose of this study was to investigate early maladaptive schemas (EMSs) in adolescents with episodic migraine (EM) and chronic migraine (CM).MethodsThis clinic-based, cross-sectional study consisted of 167 adolescents, aged 12–18, who were diagnosed with EM (n = 140) and CM (n = 27). The clinical characteristics of migraine, its accompanying symptoms, EMSs, the interrelationship of EMSs, depression, and anxiety were evaluated. We specifically analyzed psychopathology and abuse history as covariates in this study.ResultsDefectiveness/shame, mistrust/abuse, abandonment/instability, enmeshment/undeveloped self, self-sacrifice, and subjugation schemas were more prevalent in the CM group. In terms of schema domains, the CM group scored significantly higher in disconnection/rejection and other orientations. Psychopathology did not affect the EMS scores, but a history of sexual abuse did. In patients with EM, a relationship was found between the variables of anxiety, depression, and five of the EMS domains. On the other hand, the CM group showed a significant relationship with anxiety, hypervigilance/inhibition, disconnection/rejection, and other orientation domains.DiscussionThis study highlights the value of EMSs, anxiety, and depression in young people with EM and CM. Schema therapy and schema-based therapeutic interventions should be researched, especially in pediatric migraine, as they may potentially prevent the progression to treatment-resistant migraine.
Does Internet use connect smallholder farmers to a healthy diet? Evidence from rural China
Authors: Yang Mingwei , Zhang Zhiyong , Wang Zheng 
Published: April 2023

IntroductionUndernutrition and micronutrient malnutrition remain problems of significant magnitude among small-scale subsistence farmers, posing a serious threat to their health and well-being. Developing a healthy diet can effectively reduce this threat. Fortunately, the Internet can speed up the process.MethodsBased on survey data from 5,114 farm households in nine provinces in China, this study quantitatively assesses the impact of Internet use on the dietary quality of smallholder farmers using OLS regression models and PSM models.Results/Discussion(1) Internet use can significantly contribute to dietary diversity and dietary rationality among smallholder farmers, thus optimizing their dietary structure. (2) Internet use significantly increased the average consumption amounts of milk and its products (2.9 g), fruits (21.5 g), eggs (7.5 g), and vegetables (27.1 g), while also decreasing the intake of salts (1.5 g) and oil (3.8 g). (3) The pull of internet use to improve diet quality is more significant for smallholder households with lower levels of education, older heads of households, and higher household incomes. (4) A possible mechanism is that Internet use increases household income and information access skills of rural residents, thus improving their dietary quality. In summary, governments should further promote Internet penetration in rural areas for health purposes.