bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced FEV1 as Prognostic Factors in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors
Authors: Shen Yi-Luen , Shen Chia-I , Chiang Chi-Lu , Huang Hsu-Ching , Chou Kun-Ta , Chiu Chao-Hua , Chen Yuh-Min , Luo Yung-Hung 
Published: March 2022

BackgroundThe aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI).Patients and MethodsData were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV1 since ICI therapy started; the secondary outcomes were objective response rate.ResultsAmong 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV1 had inferior PFS (FEV1 &lt; 80% vs. FEV1 ≥ 80%, adjusted HR = 1.80, P = 0.006) and OS (FEV1 &lt; 80% vs. FEV1 ≥ 80%, adjusted HR = 2.50, P &lt; 0.001). Median PFS and OS in the preserved FEV1 group (≥80% predicted FEV1) compared to the reduced FEV1 group (&lt;80% predicted FEV1) were 5.4 vs. 2.9 months (HR = 1.76, P = 0.003) and 34.9 vs. 11.1 months (HR = 2.44, P &lt; 0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR = 0.57, P = 0.037), initial liver metastasis (adjusted HR = 2.00, P = 0.049), ICI monotherapy (adjusted HR = 1.73, P = 0.042) and ICI related pneumonitis (adjusted HR = 3 .44, P = 0.025).ConclusionsReduced FEV1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.
Blockage of ERCC6 Alleviates Spinal Cord Injury Through Weakening Apoptosis, Inflammation, Senescence, and Oxidative Stress
Authors: Zou Peng , Zhang Xiaoping , Zhang Rui , Chai Xin , Zhao Yuanting , Li Erliang , Zhang Qian , Yan Rongbao , Yang Junsong , Liao Bo 
Published: March 2022

Objective: Spinal cord injury (SCI) is a devastating disease resulting in lifelong disability, but the molecular mechanism remains unclear. Our study was designed to observe the role of excision repair cross-complementing group 6 (ERCC6) following SCI and to determine the underlying mechanism.Methods: SCI mouse models and LPS-induced microglia cell models were established. ERCC6 expression was blocked by ERCC6-siRNA-carrying lentivirus. Nissl staining was utilized for detecting neuronal damage, and apoptosis was analyzed with TUNEL and Western blotting (apoptotic markers). Immunofluorescence was used for measuring macrophage markers (CD68 and F4/80) and astrocyte and microglia markers (GFAP and Iba-1). Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured via ELISA. Senescent cells were estimated via SA-β-Gal staining as well as Western blot (senescent markers p21 and p27). Oxidative stress was investigated by detecting the expression of 4-HNE, Nrf2, and Keap1, and intracellular ROS levels.Results: ERCC6 expression was remarkably upregulated both in the spinal cord of SCI mice and LPS-induced microglia cells. ERCC6 deficiency alleviated neuronal damage and apoptosis. Macrophage infiltration and inflammatory response were suppressed by si-ERCC6 treatment. Moreover, ERCC6 blockage ameliorated astrocyte and microglia activation and cell senescence in the damaged spinal cord. Excessive oxidative stress was significantly decreased by ERCC6 knockdown in SCI.Conclusion: Collectively, ERCC6 exerts crucial functions in mediating physiological processes (apoptosis, inflammation, senescence, and oxidative stress), implying that ERCC6 might act as a prospective therapeutic target against SCI.
Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation for Post-stroke Vascular Cognitive Impairment: A Prospective Pilot Study
Authors: Cha Byoungwoo , Kim Jongwook , Kim Jong Moon , Choi Joo-Wan , Choi Jeein , Kim Kakyeong , Cha Jiook , Kim MinYoung 
Published: March 2022

ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsolateral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i.e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (p &lt; 0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r = 0.928) and CFT (r = 0.886) were found immediately after the rTMS treatment (p &lt; 0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.
Reliability and Validity of the Composite Activity-Related Fall Risk Scale
Authors: Jiang Yan N. , Wang Jing X. , Chen Lin Y. , Yao Jia J. , Ni Ling , Sheng Jie M. , Shen Xia 
Published: March 2022

IntroductionThe newly developed Composite Activity-related Risk of Falls Scale (CARFS) is designed to measure composite activity-related risk of falls (CARF) in relation to the activity-specific fear of falling and physical behavior. This study tested the reliability and validity of the CARFS in older people with various health statuses and persons with stroke or spinal cord injury.MethodsParticipants included 70 older adults, 38 persons with stroke, and 18 with spinal cord injury. They were first surveyed using a combined questionnaire including the CARFS and activity-specific balance confidence (ABC) scale in addition to items asking for personal and disease-related information, fall history, walking independence levels for examining internal consistency, ceiling and floor effects, and convergent validity in each participant group. One week after the initial survey, 33 older participants were reexamined using the CARFS to analyze test-retest reliability, where a minimal detectable change was found. Significance was set at α = 0.05 for all analyses.ResultsThe CARFS showed excellent test-retest reliability in the dimensions of fear of falling, physical behavior, and CARF [ICC (3,1) = 0.972, 0.994, and 0.994, respectively for their overall score], with a minimal detectable change of 3.944 in the older population. The internal consistency of CARFS items was excellent in the older participants, good in participants with stroke or spinal cord injury (Cronbach's alpha = 0.945, 0.843, 0.831 in each participant group, respectively). No ceiling and floor effects were demonstrated in the wide range of people. For the convergent validity, overall CARF score was significantly correlated with the average ABC score in each participant group (rho = −0.824, −0.761, and −0.601, respectively; p &lt; 0.01), and was significantly correlated with walking independence levels in each participant group (rho = −0.636, −0.423, and −0.522, respectively; p &lt; 0.01). It showed weak correlation with the number of previous falls only in participants with stroke (rho = 0.291, p = 0.076).ConclusionThe CARFS is a reliable and valid tool for measuring fall risk in older people and persons with stroke or spinal cord injury.
The Effect of Inter-pulse Interval on TMS Motor Evoked Potentials in Active Muscles
Authors: Matilainen Noora , Soldati Marco , Laakso Ilkka 
Published: March 2022

ObjectiveThe time interval between transcranial magnetic stimulation (TMS) pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals (IPIs). However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials (MEPs).MethodsIn our study, we delivered sets of 30 TMS pulses with three different IPIs (2, 5, and 10 s) to the left primary motor cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants (N = 9 and N = 10). MEP amplitudes were recorded through electromyography.ResultsWe found that the IPI had no significant effect on the MEP amplitudes in the active muscle (p = 0.36), whereas in the resting muscle, the IPI significantly affected the MEP amplitudes (p &lt; 0.001), decreasing the MEP amplitude of the 2 s IPI.ConclusionsThese results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies.
Low Prevalence of Anti-DFS70 Antibodies in Children With ANA-Associated Autoimmune Disease
Authors: Freudenhammer Mirjam , Salzer Ulrich , Heselich Aileen , Hufnagel Markus , Janda Ales 
Published: March 2022

IntroductionAnti-DFS70 antibodies occur in healthy individuals with various medical conditions. Unlike other anti-nuclear autoantibodies (ANA), they are not associated with systemic autoimmune disease in adult patients. To date, only a few studies have addressed the prevalence and/or clinical relevance of anti-DFS70 autoantibodies in children with and without autoimmune disease.MethodsIncluded in this retrospective cross-sectional mono-centric study were 308 pediatric patients with suspected or known autoimmune conditions who had a positive ANA in indirect immune fluorescence (IIF) screening and who were screened for anti-DFS70 antibodies by extractable nuclear antigen antibodies (ENA) immunoblot. Patients were assigned to four different diagnostic categories according to their diagnosis in the corresponding medical record: (a) absence of autoimmune or rheumatic disease (noARD, n = 116); (b) suspected autoimmunity without definitive diagnosis (sAI, n = 48); (c) other rheumatic disease (ORD) (n = 115); and (d) ANA-associated autoimmune disease (AARD, n = 29).ResultsThe prevalence of anti-DFS70 antibodies in the overall cohort was 33.8%. Among children without ARD (46.6%, 54/116), prevalence was significantly higher than among children with ORD (23.7%, 27/115, p = 0.0003) or AARD (17.2%, 5/29, p = 0.0054). Among all of the anti-DFS70 positive patients with AARD, other autoantibodies were found in the ENA immunoblot. In contrast, among anti-DFS70 positive patients with ORD (11.5%, 4/27), sAI (33.3%, 6/18) and noARD (16.7%, 9/54), other autoantibodies infrequently were detected (p = 0.0005). Patients with uveitis rarely were positive for anti-DFS70 antibodies (7.7%, 1/13). No association was found between anti-DFS70 antibodies and a history of allergic conditions (p = 0.51). The concordance between a typical DFS pattern in IIF and the detection of anti-DFS70 antibodies by immunoblot was 59.3%.ConclusionAs with adults, the higher prevalence of anti-DFS70 among children without autoimmune disease confirms the mutual exclusion for this autoantibody in the pathogenesis of ARD. Among ANA-positive children, monospecific anti-DFS70 antibodies may help to discriminate between AARD and not-AARD-related conditions.
Unravelling the Novel Effects of Three Volatile Compounds in Preventing Fibril Formation of Disease Related Tau and α-Synuclein Proteins- Towards Identifying Candidate Aromatic Substances for Treating Neurodegenerative Diseases
Authors: Moeini Zahra , Seraj Zahra , Zohoorian Abootorabi Toktam , Ashrafi-Kooshk Mohammadreza , Riazi Gholamhossein , Saboury Ali Akbar , Seyedarabi Arefeh 
Published: March 2022

Background:The aggregation of tau and α-synuclein into fibrillary assemblies in nerve cells is the molecular hallmark of Alzheimer’s and Parkinson’s diseases, respectively. In our previous studies, we investigated the anti-amyloidogenic effects of three different aroma-producing (volatile) compounds including cinnamaldehyde, phenyl ethyl alcohol, and TEMED on the fibrillation process of HEWL, as a model protein. Our previous results showed that while TEMED was able to completely stop the process of fibril formation, cinnamaldehyde and phenyl ethyl alcohol gave rise to oligomeric/protofibrillar forms and were involved in the entrapment of intermediate species of HEWL. In this study, we investigated the anti-amyloidogenic effect of the same three volatile compounds on recombinantly produced tau and α-synuclein proteins.Methods:The thioflavin T fluorescence assay, circular dichroism, SDS-PAGE/native-PAGE, dynamic light scattering, and atomic force microscopy were used, where necessary, to further our understanding of the inhibitory effects of the three volatile compounds on the fibril formation of tau and α-synuclein proteins and allow for a comparison with previous data obtained for HEWL.Results:Our results revealed that contrary to the results obtained for HEWL (a globular protein), the volatile compound TEMED was no longer able to prevent fibril formation in either of the natively unstructured tau or α-synuclein proteins, and instead, cinnamaldehye and phenyl ethyl alcohol, in particular, had the role of preventing fibril formation of tau or α-synuclein.Conclusion:The results of this study further emphasized the exclusion of HEWL as a model protein for fibrillation studies and highlighted the importance of studying brain-related proteins such as tau or α-synuclein and the need to assess the effects of volatile compounds such as cinnamaldehye and phenyl ethyl alcohol as potential substances in the treatment of neurodegenerative diseases.
RETRACTED: Melatonin Mediates Osteoblast Proliferation Through the STIM1/ORAI1 Pathway
Authors: Cao Lili , Yang Keda , Yuan Wei , Zhou Siming , Zhao Rui , Qiu Shui 
Published: March 2022

Based on the positive correlation between bone mineral density and melatonin levels in blood, this study confirmed that melatonin supplementation prevents postmenopausal osteoporosis. We further confirmed that melatonin promotes an increase in intracellular calcium concentrations through the STIM1/ORAI1 pathway, thereby inducing the proliferation of osteoblasts.Introduction: Osteoporosis (OP) is a progressive, systemic bone disease that is one of the main causes of disability and death in elderly female patients. As an amine hormone produced by the human pineal gland, melatonin plays an important role in regulating bone metabolism. This study intends to investigate the relationship between melatonin levels in human blood and bone density and to suggest the efficacy of melatonin in treating osteoporosis by performing in vivo and in vitro experiments.Methods: We used liquid chromatography-tandem mass spectrometry to determine the serum melatonin levels in postmenopausal women with osteoporosis and young women with a normal bone mass. The bone density, BV/TV, Tb.Th, Tb.Sp and other indicators of postmenopausal osteoporosis and mice with a normal bone mass were detected by measuring bone density and micro-CT. The intracellular calcium ion concentration was detected using fluorescence microscopy and a full-wavelength multifunctional microplate reader, and the expression of SOCE-related genes and STIM1/ORAI1 proteins was detected using PCR and WB.Results: This study confirmed that bone density positively correlates with the melatonin level in human blood. In the animal model, melatonin supplementation reverses postmenopausal osteoporosis. We explored the internal mechanism of melatonin treatment of osteoporosis. Melatonin promotes an increase in intracellular calcium ion concentrations through the STIM1/ORAI1 pathway to induce osteoblast proliferation.Conclusions: This study provides an important theoretical basis for the clinical application of melatonin in patients with osteoporosis and helps to optimize the diagnosis and treatment of postmenopausal osteoporosis.
N-Acetyl-L-Cysteine Protects Organ Function After Hemorrhagic Shock Combined With Seawater Immersion in Rats by Correcting Coagulopathy and Acidosis
Authors: Liu Yiyan , Zhu Yu , Zhang Zisen , Bao Daiqin , Deng Haoyue , Liu Liangming , Li Tao 
Published: March 2022

BackgroundThe mortality of trauma combined with seawater immersion is higher than that of land injury, however, research on how to treat this critical case and which treatments to adopt is lacking.MethodsThe effect of the thiol compound, N-acetyl-L-Cysteine (NAC), on survival, acidosis, coagulopathy, vital signs, oxidative stress, and mitochondrial and multi-organ function was assessed in a rat model of hemorrhagic shock combined with seawater immersion (Sea-Shock).ResultsHemorrhagic shock combined with seawater immersion caused a severe lethal triad: multi-organ impairment, oxidative stress, and mitochondrial dysfunction. NAC (30 mg/kg) with lactated Ringer’s (LR) solution (2 × blood volume lost) significantly improved outcomes compared to LR or hetastarch (HES 130/0.4) alone. NAC significantly prolonged survival time to 52.48 ± 30.09 h and increased 72 h survival rate to 11/16 (68%). NAC relieved metabolic acidosis and recovered the pH back to 7.33. NAC also restored coagulation, with APTT, PT, and PT-INR decreased by 109.31, 78.09, and 73.74%, respectively, while fibrinogen level increased 246.23% compared with untreated Sea-Shock. Administration of NAC markedly improved cardiac and liver function, with some improvement of kidney function.ConclusionThe addition of NAC to crystalloid resuscitation fluid alleviated oxidative stress, restored redox homeostasis, and provided multi-organ protection in the rats after Sea-Shock. NAC may be an effective therapeutic measure for hemorrhagic shock combined with seawater immersion.
The Link Between Cannabis Use and Violent Behavior in the Early Phase of Psychosis: The Potential Role of Impulsivity
Authors: Moulin Valerie , Framorando David , Gasser Jacques , Dan-Glauser Elise 
Published: March 2022

IntroductionRecently, the literature has shown that Cannabis Use (CU) was a risk factor for Violent Behavior (VB) in patients with psychosis, and those in the early phase of psychosis (EPP). These findings are relevant because of the high prevalence of CU in this EPP, and the potential for prevention during this phase of illness. However, there is still a lack of clear explanations, supported by empirical evidence, about what underlies the link between CU and VB against other.MethodThis viewpoint reviews the scientific literature on the link between CU and VB, and the involvement of impulsivity in this relationship. This last point will be addressed at clinical and neurobiological levels.ResultsRecent studies confirmed that CU is particularly high in the EPP, and is a risk factor for VB in the EPP and schizophrenia. Studies have also shown that impulsivity is a risk factor for VB in psychosis, is associated with CU, and may mediate the link between CU and VB. Research suggests a neurobiological mechanism, as CU affects the structures and function of frontal areas, known to play a role in impulsive behavior.ConclusionScientific evidence support the hypothesis of an involvement of impulsivity as a variable that could mediate the link between CU and aggression, particularly, when CU has an early onset. However, this hypothesis should be confirmed with longitudinal studies and by taking into account confounding factors. The studies highlight the relevance of early prevention in the EPP, in addition to interventions focusing on psychotic disorders.
Violent Radicalization and Post-traumatic Dissociation: Clinical Case of a Young Adolescent Girl Radicalized
Authors: Rolling Julie , Corduan Guillaume , Roth Martin , Schroder Carmen M. , Mengin Amaury C. 
Published: March 2022

IntroductionSince 2014, the profiles of radicalized individuals have changed with the appearance of radical groups composed of a large proportion of adolescents. Various individual, relational, and social vulnerabilities have been identified as being involved in the radicalization process of adolescents. Among these factors, it appears that early and repeated history of personal and/or family psychotraumatism may constitute factors of vulnerability to violent radicalization.Material and MethodsThe clinical situation of a 17-year-old woman convicted of “links with a terrorist group (DAECH)” was recruited from the 130 radicalized young people followed by the teams of the Maison des Adolescents and the Child and Adolescent Psychiatry Service of the University Hospitals of Strasbourg since May 2015. Based on the analysis of this clinical case, we present the hypothesis that post-traumatic antecedents can constitute vulnerability factors to violent radicalization, and that post-traumatic symptoms can be “used” by recruiters of radical movements at different moments of the radicalization process by reactivating post-traumatic psychic mechanisms, but also, for a smaller number of subjects, by the induction of the trauma (viewing of propaganda videos).ResultsWe show a possible link between violent radicalization and complex psycho-traumatism with an impact of the reactivation of post-traumatic mechanisms such as (i) the activation of the autonomic nervous system and emotional dysregulation on violent acts, (ii) the activation of dissociation mechanisms (psychic sideration and post-traumatic amnesia) on indoctrination and violent acts, (iii) the activation of control mechanisms on the search for a strict framework of life and a radical ideology and (iv) relational avoidance on the processes of relational rupture and radical socialization. Thus, we highlight that the radicalization process can respond to the needs and psychic functioning of psycho-traumatized individuals (channeling tensions, being recognized and active in one's life).DiscussionWe discuss the central role of propaganda videos in the activation of the ANS and dissociation, and the self-perpetuating process between these two posttraumatic mechanisms. We also discuss clinical and therapeutic perspectives (therapies targeting complex psychotrauma).ConclusionPsychotrauma can promote radicalization due to vulnerability mechanisms. Treatments targeting psychotrauma may be one of the ways to get these young people out of violent radicalization.