bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraneoplastic isolated adrenocorticotropic hormone deficiency revealed after immune checkpoint inhibitors therapy: new insights into anti-corticotroph antibody
Authors: Urai Shin , Watanabe Miki , Bando Hironori , Motomura Yuma , Yamamoto Masaaki , Tachihara Motoko , Kanzawa Maki , Fukuoka Hidenori , Iguchi Genzo , Ogawa Wataru 
Published: November 2023

IntroductionA recently discovered facet of paraneoplastic adrenocorticotropic hormone (ACTH) deficiency exists in two forms: a paraneoplastic spontaneous isolated ACTH deficiency (IAD) and an immune checkpoint inhibitor (ICI)-related hypophysitis. Autoantibodies against corticotrophs, such as circulating anti-proopiomelanocortin (POMC) antibodies are considered disease markers. However, the number of identified cases was limited, implying that the characteristics of these autoantibodies are not fully understood.MethodsWe investigate circulating autoimmune autoantibodies in detail through a novel case of IAD that developed as a paraneoplastic autoimmune ACTH deficiency.ResultsThe patient developed IAD after 25 weeks of ICI therapy for metastasis of large-cell neuroendocrine carcinoma at 69 years of age. Ectopic ACTH expression and infiltration of CD3+, CD4+, CD8+, and CD20+ lymphocytes were observed in the tumor tissues and circulating anti-POMC antibodies were detected specifically in the patient’s serum. Moreover, detailed analyses of immunofluorescence staining using patient serum revealed that the recognition site of the autoantibody was ACTH25-39, which had not been identified in previous cases of paraneoplastic autoimmune ACTH deficiency.ConclusionThis case involved a combination of paraneoplastic spontaneously acquired IAD and ICI-related hypophysitis occupying the middle ground. Moreover, our study reveals new aspects of anti-POMC antibodies in patients with paraneoplastic ACTH deficiency. This report expands our understanding of the immunological landscape and provides new insights for the identification of antibodies associated with paraneoplastic autoimmune ACTH deficiency.
What did we learn about tocilizumab use against COVID-19? A single-center observational study from an intensive care unit in Serbia
Authors: Adzic-Vukicevic Tatjana , Markovic Dejan , Reljic Aleksandar , Brkovic Voin 
Published: November 2023

BackgroundSelection of effective and safe therapy for management of patients with coronavirus disease is challenging. Tocilizumab (TZB) has emerged as a potential treatment option for COVID-19. Several aspects regarding Tocilizumab treatment remain uncertain, such as the optimal timing for its administration and the safety profile, including the potential risk of infections. The aim of the study is to present the clinical characteristics of patients with COVID-19 following the application of Tocilizumab.MethodsThis is a retrospective analysis of 121 patients with severe forms of COVID-19 previously treated with Tocilizumab was conducted. All patients were admitted to intensive care units (ICUs).ResultsOf 121 patients, the majority were men 72 (59.5%) with a median age at presentation of 65 ± 13 years. Only 9 (7.43%) patients were without comorbidities, while the other 112 (92.55%) had two or more comorbidities. Almost all of the 120 patients (99.2%) needed oxygen therapy, such as nasal cannulas in 110 (90.9%) patients, high flow nasal catheter (HFNC) in 4 (3.3%) patients, and continuous positive airway pressure (CPAP) in 5 (4.1%) patients while 1 patient was intubated at the time of hospital admission. The average time from Tocilizumab application to admission to the ICU was 3 days. During clinical deterioration, almost half 57 (47.1%) of the patients were intubated, and 52 (82.5%) of these intubated patients (p &lt; 0.001) had lethal outcomes. The most significant predictors for a lethal outcome according to multivariate analysis were diabetes mellitus (p &lt; 0.001) followed by a subsequent elevation in C-reactive protein levels (CRP; p &lt; 0.002) and ferritin (p &lt; 0.013) after Tocilizumab application. Bloodstream infections were found in 20 (16.5%) patients, most frequently with Gram-negative pathogens like Acinetobacter spp. as in 12 (18.6%) patients, Klebsiella spp. in 6 (8%) patients, and Pseudomonas spp. in 2 (3.2%) patients. Urine culture isolates were found in 9 (7.43%) patients, with Candida spp. being most frequently isolated in 7 (5.8%) patients, followed by Klebsiella spp. and Pseudomonas spp. in 1 patient each (0.8%). Significantly lower survival was seen in patients with proven infection.ConclusionThe benefit of tocilizumab was not found in our study. The high mortality rate among intubated patients after Tocilizumab use suggests appropriate patient selection and monitoring and emphasizes the risk of superinfections. Diabetes mellitus, increased levels of CRP, and ferritin were identified as the most significant predictors of poor outcomes in contrast to increased levels of IL-6.
Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium
Authors: Song Ann , Phandthong Rattapol , Talbot Prue 
Published: November 2023

IntroductionBoth spill over and spill back of SARS-CoV-2 virus have been reported on mink farms in Europe and the United States. Zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback.MethodsThe purpose of our study was to determine the SARS-CoV-2 entry mechanism using the mink lung epithelial cell line (Mv1Lu) and to block entry with drug inhibitors.ResultsMv1Lu cells were susceptible to SARS-CoV-2 viral pseudoparticle infection, validating them as a suitable disease model for COVID-19. Inhibitors of TMPRSS2 and of endocytosis, two pathways of viral entry, were tested to identify those that blocked infection. TMPRSS2 inhibitors had minimal impact, which can be explained by the apparent lack of activity of this enzyme in the mink and its localization within the cell, not on the cell surface.DiscussionDyngo4a, a small molecule endocytosis inhibitor, significantly reduced infection, supporting the conclusion that the entry of the SARS-CoV-2 virus into Mv1Lu cells occurs primarily through endocytosis. The small molecule inhibitors that were effective in this study could potentially be used therapeutically to prevent SARS-CoV-2 infection in mink populations. This study will facilitate the development of therapeutics to prevent zoonotic transmission of SARS-CoV-2 variants to other animals, including humans.
Cortical gyrification pattern of depression in Parkinson’s disease: a neuroimaging marker for disease severity?
Authors: Shen Qin , Liao Haiyan , Cai Sainan , Liu Qinru , Wang Min , Song Chendie , Zhou Fan , Liu Yujing , Yuan Jiaying , Tang Yuqing , Li Xu , Liu Jun , Tan Changlian 
Published: November 2023

BackgroundAlthough the study of the neuroanatomical correlates of depression in Parkinson’s Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression.MethodsLGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group.ResultsCompared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group.ConclusionThe present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.
Research progress of ferroptosis in Parkinson’s disease: a bibliometric and visual analysis
Authors: Lu Yangguang , Chen Yiqun , Jiang Zihan , Ge Yaoying , Yao Ruotong , Geng Shangze , Zhang Jinxiu , Chen Feng , Wang Yukai , Chen Guangyong , Yang Dehao 
Published: November 2023

BackgroundIn recent years, the role of ferroptosis in Parkinson’s disease (PD) has become a research hotspot based on evidence of abnormal iron deposition and lipid peroxidation damage in the brains of PD patients. This study aims to examine the relevant research on ferroptosis and PD from a bibliometric perspective.MethodsOriginal research and review articles related to ferroptosis and PD were retrieved from the Web of Science Core Collection (WOSCC) database. Statistical analysis and visualization of information including countries, institutions, authors, journals, and keywords of the included studies were conducted using the R software package “bibliometrix.”ResultsA total of 414 articles met the inclusion criteria, averaging 37.86 citations per article. From 2012 to 2022, the average annual growth rate of research in this area was 63.44%. The corresponding authors of published articles were mainly affiliated with institutions in China, the United States, and Australia. Shanghai Jiao Tong University in China and the University of Melbourne in Australia emerged as the most active and influential institutions. The journal with the highest H-index and publication output was Free Radical Biology and Medicine. “Ferroptosis,” “immunotherapy,” “prognosis” and “microenvironment” were identified as high-frequency keywords, indicating current and future research directions in this field.ConclusionThis bibliometric study provides insights into current research hotspots and emerging trends in the growing field of ferroptosis research related to PD. The high-frequency keywords identified highlight active areas of investigation involving methods, mechanisms, and populations of interest.
A predictive model for the recurrence of intracranial aneurysms following coil embolization
Authors: He Tao , Chen Kun , Chen Ru-Dong 
Published: November 2023

ObjectiveThis study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation.MethodsA total of 302 patients with 312 IAs undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs.ResultsDiameter maximum (D max) (p &lt; 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (p = 0.004, HR = 2.852), and ruptured status (p &lt; 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2 * RROC (II or III; yes = 1, no = 0) + 6 * ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test, p &lt; 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively.ConclusionThe D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.
Relapsing polychondritis-associated meningoencephalitis initially presenting as seizure: a case report and literature review
Authors: Zhang Dan , Shi Jiamin , Zhang Xinhua , Wang Jin , Shao Yuquan 
Published: November 2023

Background and purposeRelapsing polychondritis (RP) is a rare rheumatologic disorder that may affect the neurological system with various presentations. In this study, we present a case and summarize the clinical characteristics of RP-associated meningoencephalitis.Case presentationA 48-year-old man presented with first-ever seizures that were well controlled by valproate. Physical examination results were unremarkable, except for binaural deformation. The initial brain magnetic resonance imaging (MRI) without contrast and electroencephalogram (EEG) findings were normal. However, the patient subsequently developed recurrent fever, scleritis, headache, lethargy, and left arm paresis. Repeated brain MRI with contrast demonstrated increased enhancement of the pia mater and abnormal diffusion-weighted imaging (DWI) signals in the bilateral auricles. The cerebrospinal fluid (CSF) analysis showed 2 leukocytes/μL, 736.5 mg/L of protein, and no evidence of infectious disease or autoimmune encephalitis. Meningoencephalitis secondary to RP was considered. The patient's condition improved significantly and quickly with the administration of dexamethasone (10 mg per day). Oral methylprednisolone was continued, and the patient remained well without relapse during the 9-month follow-up period.ConclusionRP-associated meningoencephalitis is rare but fatal. Although symptoms vary, red or deformed ears remain the most common and suggestive features. Non-specific parenchymal changes and/or meningeal enhancement can be observed on brain MRI scans. CSF lymphocytic pleocytosis with mild protein elevation was observed in most patients.
Altered neural encoding of vowels in noise does not affect behavioral vowel discrimination in gerbils with age-related hearing loss
Authors: Heeringa Amarins N. , Jüchter Carolin , Beutelmann Rainer , Klump Georg M. , Köppl Christine 
Published: November 2023

IntroductionUnderstanding speech in a noisy environment, as opposed to speech in quiet, becomes increasingly more difficult with increasing age. Using the quiet-aged gerbil, we studied the effects of aging on speech-in-noise processing. Specifically, behavioral vowel discrimination and the encoding of these vowels by single auditory-nerve fibers were compared, to elucidate some of the underlying mechanisms of age-related speech-in-noise perception deficits.MethodsYoung-adult and quiet-aged Mongolian gerbils, of either sex, were trained to discriminate a deviant naturally-spoken vowel in a sequence of vowel standards against a speech-like background noise. In addition, we recorded responses from single auditory-nerve fibers of young-adult and quiet-aged gerbils while presenting the same speech stimuli.ResultsBehavioral vowel discrimination was not significantly affected by aging. For both young-adult and quiet-aged gerbils, the behavioral discrimination between /eː/ and /iː/ was more difficult to make than /eː/ vs. /aː/ or /iː/ vs. /aː/, as evidenced by longer response times and lower d’ values. In young-adults, spike timing-based vowel discrimination agreed with the behavioral vowel discrimination, while in quiet-aged gerbils it did not. Paradoxically, discrimination between vowels based on temporal responses was enhanced in aged gerbils for all vowel comparisons. Representation schemes, based on the spectrum of the inter-spike interval histogram, revealed stronger encoding of both the fundamental and the lower formant frequencies in fibers of quiet-aged gerbils, but no qualitative changes in vowel encoding. Elevated thresholds in combination with a fixed stimulus level, i.e., lower sensation levels of the stimuli for old individuals, can explain the enhanced temporal coding of the vowels in noise.DiscussionThese results suggest that the altered auditory-nerve discrimination metrics in old gerbils may mask age-related deterioration in the central (auditory) system to the extent that behavioral vowel discrimination matches that of the young adults.
Structural modeling of hERG channel–drug interactions using Rosetta
Authors: Emigh Cortez Aiyana M. , DeMarco Kevin R. , Furutani Kazuharu , Bekker Slava , Sack Jon T. , Wulff Heike , Clancy Colleen E. , Vorobyov Igor , Yarov-Yarovoy Vladimir 
Published: November 2023

The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity. We used Rosetta electron density refinement and homology modeling to build structural models of open-state hERG channel wild-type and mutant variants (Y652A, F656A, and Y652A/F656 A) and a closed-state wild-type channel based on cryo-electron microscopy structures of hERG and EAG1 channels. These models were used as protein targets for molecular docking of charged and neutral forms of amiodarone, nifekalant, dofetilide, d/l-sotalol, flecainide, and moxifloxacin. We selected these drugs based on their different arrhythmogenic potentials and abilities to facilitate hERG current. Our docking studies and clustering provided atomistic structural insights into state-dependent drug–channel interactions that play a key role in differentiating safe and harmful hERG blockers and can explain hERG channel facilitation through drug interactions with its open-state hydrophobic pockets.
Parasitic infections related to anti-type 2 immunity monoclonal antibodies: a disproportionality analysis in the food and drug administration’s adverse event reporting system (FAERS)
Authors: Pera Victor , Brusselle Guy G. , Riemann Sebastian , Kors Jan A. , Van Mulligen Erik M. , Parry Rowan , de Wilde Marcel , Rijnbeek Peter R. , Verhamme Katia M. C. 
Published: November 2023

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab.Methods: Spontaneous reports were used from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR).Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24–63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4–29.3).Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.
Effects of a dry-land strengthening exercise program with elastic bands following the Kabat D2 diagonal flexion pattern for the prevention of shoulder injuries in swimmers
Authors: Della Tommasina Ivan , Trinidad-Morales Alfonso , Martínez-Lozano Pedro , González-de-la-Flor Ángel , Del-Blanco-Muñiz José Ángel 
Published: November 2023

Background: During the repetitive execution of the swimming strokes, the muscles responsible for the internal rotations of the shoulders tend to become stronger compared to the muscles that oppose these movements. The aim of this study was to analyse the effect of a strengthening program for the shoulder rotator muscles using elastic band exercises in a diagonal Kabat pattern (D2 for flexion) in swimmers, to develop an effective, quick and easy-to-implement protocol for preventive training routines.Methods: A randomized controlled trial design was carried out. Internal and external rotation range of movement, isometric strength of the muscles responsible for internal and external rotation of the shoulder, scapular movements, was measured at the beginning of the study and after 8 weeks post-intervention. A total of 22 male swimmers participated in the study and were randomly assigned to either an experimental group (n = 11) or a control group (n = 11). The experimental group underwent a 8-week shoulder-strength program using elastic bands, while the control group focused on aquatic training.Results: The strength-training program resulted in an improvement in the isometric strength of the muscles responsible for external rotation and a better balance between the shoulder rotator muscles in the experimental group. However, these improvements have not been significant (p &gt; 0.05).Conclusion: The strengthening exercise program showed minimal improvement in shoulder rotation strength and range of motion. These findings suggest that the prescribed shoulder-strengthening exercise could be a quick-beneficial dry-land training option to improve external rotation shoulder strength or range of motion, but more studies with larger sample sizes and more weeks of treatment are needed to determine the efficacy of this protocol.