bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy
Authors: Hampe Lovis , Küffer Stefan , Niemeier Tim , Scheele Niklas Christian , Hampe Laetitia Zoe , Riedl Anna Luisa , Fischer Laura Anna , Ziegler David Alexander , Leu Martin , Dröge Leif Hendrik , König Alexander , Ghadimi Michael , Braulke Friederike , Rieken Stefan , Bohnenberger Hanibal , El Shafie Rami A. 
Published: December 2024

BackgroundEsophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the impact of neoadjuvant CRT on PD-L1 surface expression in esophageal cancer both in vitro and in vivo considering its implications for immunotherapy.MethodsPD-L1 expression dynamics were assessed in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) cell lines (OE-33, FLO-1, KYSE-180) treated with Carboplatin, Paclitaxel, radiotherapy (RT), and CRT. PD-L1 expression was measured by flow cytometry at 48- and 72 hours post-treatment. Temporal changes of surface PD-L1 were further investigated in KYSE-180 cells following RT, up to 168h after treatment. Additionally, PD-L1 expression was analyzed via immunohistochemistry in histological samples from 19 patients (9 EAC, 10 ESCC) treated with neoadjuvant CRT according to the CROSS-scheme.ResultsPD-L1 expression was upregulated the most by Carboplatin, a combination of chemotherapy, or CRT in all cell lines. Higher irradiation doses were more effective in inducing PD-L1 expression, while Paclitaxel alone did not consistently increase PD-L1. The ESCC cell line KYSE-180 showed the highest relative PD-L1 increase. Measurement of PD-L1 kinetics revealed a transient upregulation of surface PD-L1, which peaked at 72 hours post-treatment and subsequently returned to baseline levels by 168 hours. In vivo, data demonstrated no significant PD-L1 expression changes when comparing pre- and post-treatment levels.ConclusionsChemotherapy, RT, and CRT can induce PD-L1 expression in various esophageal cancer cell lines. However, neoadjuvant CRT according to the CROSS protocol does not significantly induce PD-L1 in vivo. Considering the difference in time between pre- and post-therapeutic measurements, these findings suggest that PD-L1 upregulation due to neoadjuvant therapy may be transient in vivo as well. This highlights the potential benefit of administering immunotherapy in a neoadjuvant setting.
Epithelial immunotherapy for food allergy in children: a systematic review and meta-analysis
Authors: Chen Bin , Gao Hu , Li Xihong , Zou Zhuan , Wu Shanshan , Tang Fajuan 
Published: December 2024

ObjectivesTraditional methods of treating allergies primarily revolve around avoiding allergens and promptly using rescue medications when allergic symptoms occur. However, this approach is known for its inefficiency and limited success in achieving long-term relief. Our aim was to conduct a comprehensive analysis of previously published randomized controlled trials (RCTs) that explore the effectiveness and safety of epicutaneous immunotherapy (EPIT) as a means to manage food allergies in children.MethodsWe conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, and Cochrane Library, to identify RCTs comparing EPIT versus placebo for the management of allergen-triggered allergic reactions in children. Only RCTs published in English that evaluated the efficacy and safety of EPIT in pediatric patients with allergic diseases were considered eligible for inclusion. The quality assessment of the included studies was performed using the Cochrane risk-of-bias tool. The analysis comprised of seven RCTs involving a total of 1141 participants. The meta-analysis demonstrated that EPIT significantly facilitated desensitization in patients with food allergy (RR: 2.12, 95% CI: 1.74-2.59, P = 0.296, I² = 17.5%), particularly in individuals with peanut allergy (RR: 2.29, 95% CI: 1.83-2.86, P = 0.463, I² = 0%). However, it is important to note that EPIT was associated with an increased occurrence of treatment-related adverse events (TRAEs; RR: 1.24, 95% CI: 1.14-1.34, P &lt; 0.01, I² = 99.2%). Notably, there were no notable disparities in the frequency of serious adverse events or utilization of rescue medications between the EPIT and placebo groups. EPIT may potentially induce desensitization of peanut allergy in children, but also carries an elevated risk of TRAEs.
Inflammatory discoveries two years after acute severe COVID-19: a longitudinal biomarker profile assessment in long COVID individuals in the Brazilian Amazon
Authors: Maciel Alex Bezerra Silva , Pinto Arlene Santos , Maia Silva Bernardo , Goulart Cassia Luz , Silva Luis Felipe Alho , Chaves Amanda Silva , Mouta Gabriel Santos , Sato Camila Miriam Suemi , Valente Jefferson , Mwangi Victor Irungu , de Melo Gisely Cardoso , Monteiro Wuelton , Lacerda Marcus , Arêas Guilherme Peixoto Tinoco , Sampaio Vanderson Souza , Costa Allyson Guimaraes , Almeida-Val Fernando 
Published: December 2024

BackgroundIn SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19.ObjectivesI) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms.MethodsThis study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization.ResultsFour months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual’s recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; p=0.054). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years.ConclusionAlthough the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID.
Effects of microplastics pollution in sediments on physicochemical properties and microbial community distribution in coastal Spartina alterniflora-invaded wetlands
Authors: Li Guo , Ran Jiao , Dong Jing , Yang Kai , Hu Jingru , Shi Jing , Zhang Yumiao , Chen Jiabin , Zhao Yu , Zhu Ensheng , Huang Suzhen , Zheng Zheng 
Published: December 2024

IntroductionCoastal wetlands play an important role in the global ecosystem, yet they are increasingly facing ecological degradation due to pollution and the spread of invasive Spartina alterniflora (S. alterniflora). Among the environmental challenges, microplastics (MPs) contamination in S. alterniflora-invaded coastal wetlands is of growing concern. However, the effects of MPs pollution in S. alterniflora-invaded coastal wetlands are not clear.MethodsThis study investigated the effects of S. altemiflora invasion on the distribution of MPs and the effects of MPs pollution on the physicochemical properties of sediments and the structure of microbial communities in the Tiaozini wetland of Jiangsu Province, China.Results and discussionThe total MPs abundance of the S. altemiflora single-plant area was the highest (16.338 x103 items/kg d.w.). Polyurethane and Chlorinated polyisoprene are typical MPs types in the study area. Polyurethane exhibits high abundance at all sampling sites, while Chlorinated polyisoprene is one of the dominant MPs types in the single-plant and sub-mature area of S. alterniflora. The results showed that the invasion of S. alterniflora promoted the accumulation of MPs in the sediments of the coastal wetland. This accumulation increased the total organic carbon (TOC), available phosphorus (AP) and total nitrogen (TN) contents. Moreover, MPs pollution increased the ALP and SUC enzyme activities of sediment. In addition, MPs contamination increased the abundance of Proteobacteria and Bacteroidota in the sediments. This study highlights the complex interactions between MPs pollution and S. alterniflora invasion, providing the foundation for understanding the synergistic impacts of these stressors on coastal wetland ecosystems.
Fungal keratitis caused by Neurospora: a case report
Authors: Lu Yao , Mo Yijun , Weng Yuesong , Li Xiaohui 
Published: December 2024

BackgroundWe report a rare case of fungal keratitis caused by Neurospora, a filamentous fungus that is widely distributed in soil and graminaceous plants.Case presentationA 40-year-old Mongoloid male patient came to our outpatient clinic with painful swelling of the left eye and redness, after being cut by a tree branch 1 week prior. After examination, the patient was diagnosed with a corneal ulcer of the left eye, and was given levofloxacin eye drops and levofloxacin ophthalmic gel. However, the patient did not respond to the treatment. After admission to the hospital, fungal mycelium was found in the corneal smear. To further identify the pathogen, a corneal scraping culture was used to extract fungal DNA and PCR amplification was performed using ITS universal primers, which was later sequenced and identified as Neurospora. We used fluconazole injections (0.2 g/100 mL) as eye drops to treat the patient once every hour, and itraconazole (200 mg) was administered orally once a day. After a few days, the patient’s condition improved.ConclusionTo the best of our knowledge, this is the first reported case of fungal keratitis caused by Neurospora in China. In this case, conventional topical and systemic treatment resulted in a favorable outcome. In patients with suspected fungal keratitis, medical treatment should be started urgently, and the treatment plan should be adjusted according to the subsequent experimental results and the patient’s condition.
Evolution of community-associated MRSA: a 20-year genomic and epidemiological study in Region Örebro County, Sweden
Authors: Kekki Jan , Thegel Annethe , Stenmark Bianca , Söderquist Bo 
Published: December 2024

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has been an issue in healthcare since the 1960s. It was initially found only in healthcare facilities, but in the late 1990s it began to be seen with no healthcare connexion. The mechanisms of intercontinental and national spread are not fully understood, as sometimes novel outbreaks occur without any identifiable source or connexion to locally dominant clonal clusters.MethodsThis study investigated the epidemiology and genomics of community-associated MRSA in Region Örebro County, Sweden, through 330 isolates collected between 2000 and 2019.ResultsA shift in the dominant sequence type (ST) from ST80 to ST22 occurred in 2011–2019, along with an increase in the prevalence of STs belonging to clonal complexes CC5 and CC22. Both ST8 and ST80 isolates seemed to give way to emerging ST22 isolates, also indicated by the declining presence of the USA300 clone. The staphylococcal chromosomal cassette mec (SCCmec) type IV Remained dominant.ConclusionsThe SCCmec type IV characteristic appears to be relatively geographically stable, possibly due to its low fitness cost and transductal capabilities. This warrants further studies of SCCmec type IV variant's survival mechanics as well as the effects of migratory flow on local epidemiology, in preparation for future possible outbreaks.
Can there be calm during a cytokine storm? Immune checkpoint pathways affecting the severity of COVID-19 disease
Authors: Meggyes Matyas , Nagy David U. , Toth Ildiko , Feik Timoteus , Peterfalvi Agnes , Polgar Beata , Sipos David , Kemeny Agnes , Szereday Laszlo 
Published: December 2024

IntroductionThe COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients.MethodsWe performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex.ResultsSevere patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection.ConclusionThese findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease.
The value of radiomics-based hyperdense middle cerebral artery sign in predicting hemorrhagic transformation in acute ischemic stroke patients undergoing endovascular treatment
Authors: Gong Chundan , Liu Yun , Ma Wei , Jing Yang , Liu Li , Huang Yan , Yang Jinlin , Feng Chen , Fang Yuan , Fang Weidong 
Published: December 2024

ObjectiveTo establish and validate a model based on hyperdense middle cerebral artery sign (HMCAS) radiomics features for predicting hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after endovascular treatment (EVT).MethodsPatients with AIS who presented with HMCAS on non-contrast computed tomography (NCCT) at admission and underwent EVT at three comprehensive hospitals between June 2020 and January 2024 were recruited for this retrospective study. A radiomics model was constructed using the HMCAS radiomics features most strongly associated with HT. In addition, clinical and radiological independent factors associated with HT were identified. Subsequently, a combined model incorporating radiomics features and independent risk factors was developed via multivariate logistic regression and presented as a nomogram. The models were evaluated via receiver operating characteristic curve, calibration curve, and decision curve analysis.ResultsOf the 118 patients, 71 (60.17%) developed HT. The area under the curve (AUC) of the radiomics model was 0.873 (95% CI 0.797–0.935) in the training cohort and 0.851 (95%CI 0.721–0.942) in the test cohort. The Alberta Stroke Program Early CT score (ASPECTS) was the only independent predictor among 24 clinical and 4 radiological variables. The combined model further improved the predictive performance, with an AUC of 0.911 (95%CI 0.850–0.960) in the training cohort and 0.877 (95%CI 0.753–0.960) in the test cohort. Decision curve analysis demonstrated that the combined model had greater clinical utility for predicting HT.ConclusionHMCAS-based radiomics is expected to be a reliable tool for predicting HT risk stratification in AIS patients after EVT.
Postoperative dizziness after cochlear implant surgery: can it be caused by air?
Authors: Ketterer Manuel Christoph , Everad Friederike , Lützen Niklas , Rauch Ann-Kathrin , Aschendorff Antje , Arndt Susan , Jakob Till F. 
Published: December 2024

ObjectivesMultiple studies have described the onset and variable incidence of postoperative acute vertigo following cochlear implant (CI) surgery. However, postoperative imaging has not yet been specifically evaluated with special focus on vertigo. The aim of this study is to assess the incidence and causes of new-onset, acute postoperative vertigo following CI surgery using cone beam computed tomography (CBCT).Materials and methodsThis is a retrospective study involving ten patients who experienced postoperative dizziness and ten matched controls without dizziness. All patients received a cochlear implant (CI) between 2020 and 2024. The matching analysis was performed based on the implant, electrode array, and access to the cochlear. We analyzed the postoperative CBCT scans for changes suspicious of air trapping, a so-called pneumolabyrinth in the vestibule using minimal Hounsfield Units (HU).ResultsWe compared postoperative CBCT images for electrode array position monitoring in ten patients with vertigo versus ten patients without vertigo after CI surgery. Among the ten patients with postoperative dizziness, six showed suspicious changes in the vestibule consistent with the presence of air. These air-related changes were observed in the vestibule and, in one patient, additionally in the horizontal semicircular canal. Minimal HU were significantly different and confirmed the suspicion of intravestibular air.ConclusionThis is the first study to describe the suspicion of intravestibular air in CI patients with postoperative vertigo. Therefore, suctioning after the fenestration of the round window membrane or the endosteum after cochleostomy, as well as actions such as bending, pressing, and nose-blowing by the patient, should be strictly avoided. Furthermore, this finding highlights the importance of carefully sealing the electrode array at the cochleostomy site with connective tissue. Risk factors for the development of a pneumolabyrinth with air in the vestibule include intralabyrinthine or intracranial pressure changes, large cochleostomies or a second cochleostomy and electrode placement in the scala tympani.
The impact of typological similarities and differences between German and Italian on the acquisition of language-specific phonetic cues in bilingual children: insights from the T-complex
Authors: Bloder Theresa , Shinohara Yasuaki , Rinker Tanja , Shafer Valerie L. 
Published: December 2024

IntroductionLateral temporal neural measures (Na and T-complex Ta and Tb) of the auditory evoked potential (AEP) index auditory/speech processing and have been observed in children and adults. While Na is already present in children under 4 years of age, Ta emerges from 4 years of age, and Tb appears even later. The T-complex has been found to be sensitive to language experience in Spanish-English and Turkish-German children and adults. In particular, Ta elicited to a vowel has been found to be sensitive to language experience in bilingual preschool children. This paper examines neural responses in 4-to-6-year-old Italian-German bilingual and German monolingual children using language-specific phonetic cues for voicing.MethodsWe tested children's processing of voicing features in bilabial stop consonants in relation to (1) their language status (i.e., being monolingual vs. bilingual) as well as to (2) their relative amount of current exposure to the heritage (Italian) and the societal language (German). Italian-German bilingual and German monolingual children were hypothesized to encode the temporal properties of a set of Voice Onset Time (VOT) stimuli differently as indexed by Ta and Tb.ResultsThe results revealed no main effects of language group, but interactions of group with hemisphere and stimulus. In particular, bilingual children showed less hemispheric differentiation and an attenuated (less positive) response at the right site (T8) for the 0 ms VOT stimulus during the Ta-Tb time window. Children with more German (and consequently, less Italian) input showed a more positive T8 response for the Na, Ta and Tb time intervals.DiscussionThese findings partially replicated previous studies, but also revealed that stimulus factors modulate the response. They suggest that a delay in commitment is found only in bilinguals with less input in the target language, and those who are strongly dominant in one of the two languages will resemble monolinguals in the development of T-complex responses. However, the finding of greater Na positivity for German-dominant bilinguals suggests that their specific experience also influences processing, but perhaps via a different mechanism than found for the more balanced bilinguals.
Optimization of Rosa roxburghii Tratt pomace fermentation process and the effects of mono- and mixed culture fermentation on its chemical composition
Authors: Yi Xinxin , Zhang Shuo , Meng Duo , Zhang Jian , Lai Chencen , Zhang Min , Sun Xiaodong , Yu Haoxiang , Wang Pengjiao , Gao Xiuli 
Published: December 2024

BackgroundRosa roxburghii Tratt pomace (RRTP) contains valuable components like polyphenols and polysaccharides, which have high utilization value. Fermentation is an effective technique for creating beneficial nutrients that can improve the taste, appearance, and nutritional benefits of foods. Nevertheless, there is a lack of research on the alterations in chemical composition of RRTP during fermentation.Objective and MethodsThis study aimed to ferment RRTP using Bacillus subtilis and Saccharomyces cerevisiae to improve its chemical composition. The optimal fermentation conditions for RRTP were determined through single-factor experiments and Box–Behnken design (BBD). Total phenols, total flavonoids, total triterpenes, ellagic acid, and vitamin C levels were higher in the fermented group with different strains and in the optimized group with mixed bacteria post-fermentation compared to the uninoculated group. Fermentation with different strains led to an increase in the ABTS radical scavenging capacity, DPPH radical scavenging capacity, and total antioxidant capacity (T-AOC) of RRTP.ConclusionThe HPLC-ESI-Q-Exactive Plus Orbitrap-MS method identified 20 compounds before fermentation and 34 compounds after optimized fermentation with mixed bacteria. The levels of polyphenols, flavonoids, and triterpenoids increased after the optimization with mixed bacteria. This research offers a potential approach to enhance the nutritional profile of RRTP and utilize it for the production of high-value food or feed materials.