bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience
Authors: Shamriz Oded , Rubin Limor , Simon Amos J. , Lev Atar , Barel Ortal , Somech Raz , Korem Maya , Matza Porges Sigal , Freund Tal , Hagin David , Garty Ben Zion , Nahum Amit , Molho Pessach Vered , Tal Yuval 
Published: December 2022

BackgroundAutosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (STAT3) is characterized by recurrent Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.ObjectivesTo describe our experience with the diagnosis and treatment of adult patients with AD-HIES induced by DN-STAT3 variants.MethodsThe medical records of adult patients (&gt;18 years) treated at the Allergy and Clinical Immunology Clinic of Hadassah Medical Center, Jerusalem, Israel, were retrospectively analyzed. Immune and genetic workups were used to confirm diagnosis.ResultsThree adult patients (2 males; age 29-41 years) were diagnosed with DN-STAT3 variants. All patients had non-immunological features, including coarse faces and osteopenia. Serious bacterial infections were noted in all patients, including recurrent abscesses, recurrent pneumonia, and bronchiectasis. CMC and diffuse dermatophytosis were noted in two patients. Two patients had severe atopic dermatitis refractory to topical steroids and phototherapy. Immune workup revealed elevated IgE in three patients and eosinophilia in two patients. Whole exome sequencing revealed DN-STAT3 variants (c.1166C&gt;T; p.Thr389Ile in two patients and c.1268G&gt;A; p. Arg423Gln in one patient). Variants were located in DNA-binding domain (DBD) and did not hamper STAT3 phosphorylation Treatment included antimicrobial prophylaxis with trimethoprim/sulfamethoxazole (n=2) and amoxycillin-clavulanic acid (n=1), and anti-fungal treatment with fluconazole (n=2) and voriconazole (n=1). Two patients who had severe atopic dermatitis, were treated with dupilumab with complete resolution of their rash. No adverse responses were noted in the dupilumab-treated patients.DiscussionDupilumab can be used safely as a biotherapy for atopic dermatitis in these patients as it can effectively alleviate eczema-related symptoms. Immunologists and dermatologists treating AD-HIES adult patients should be aware of demodicosis as a possible manifestation. DN-STAT3 variants in DBD do not hamper STAT3 phosphorylation.
The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study
Authors: Li Meng , Huang Zhenyu , Tao Zhi , Meng Yiting , Wen Jia , Zhang Qiongqiong , Liu Ying , Shang Mengyuan , Wang Ying , Wang Yufeng , Chen Rui , Wang Xiaoqian , Cao Yang , Zhang Lei , Liao Qinping 
Published: December 2022

ObjectiveThis study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients.MethodsWe prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture.ResultsA total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant.ConclusionThe N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.
Pre-analytical processing of plasma and serum samples for combined proteome and metabolome analysis
Authors: Gegner Hagen M. , Naake Thomas , Dugourd Aurélien , Müller Torsten , Czernilofsky Felix , Kliewer Georg , Jäger Evelyn , Helm Barbara , Kunze-Rohrbach Nina , Klingmüller Ursula , Hopf Carsten , Müller-Tidow Carsten , Dietrich Sascha , Saez-Rodriguez Julio , Huber Wolfgang , Hell Rüdiger , Poschet Gernot , Krijgsveld Jeroen 
Published: December 2022

Metabolomic and proteomic analyses of human plasma and serum samples harbor the power to advance our understanding of disease biology. Pre-analytical factors may contribute to variability and bias in the detection of analytes, especially when multiple labs are involved, caused by sample handling, processing time, and differing operating procedures. To better understand the impact of pre-analytical factors that are relevant to implementing a unified proteomic and metabolomic approach in a clinical setting, we assessed the influence of temperature, sitting times, and centrifugation speed on the plasma and serum metabolomes and proteomes from six healthy volunteers. We used targeted metabolic profiling (497 metabolites) and data-independent acquisition (DIA) proteomics (572 proteins) on the same samples generated with well-defined pre-analytical conditions to evaluate criteria for pre-analytical SOPs for plasma and serum samples. Time and temperature showed the strongest influence on the integrity of plasma and serum proteome and metabolome. While rapid handling and low temperatures (4°C) are imperative for metabolic profiling, the analyzed proteomics data set showed variability when exposed to temperatures of 4°C for more than 2 h, highlighting the need for compromises in a combined analysis. We formalized a quality control scoring system to objectively rate sample stability and tested this score using external data sets from other pre-analytical studies. Stringent and harmonized standard operating procedures (SOPs) are required for pre-analytical sample handling when combining proteomics and metabolomics of clinical samples to yield robust and interpretable data on a longitudinal scale and across different clinics. To ensure an adequate level of practicability in a clinical routine for metabolomics and proteomics studies, we suggest keeping blood samples up to 2 h on ice (4°C) prior to snap-freezing as a compromise between stability and operability. Finally, we provide the methodology as an open-source R package allowing the systematic scoring of proteomics and metabolomics data sets to assess the stability of plasma and serum samples.
Dual-task related frontal cerebral blood flow changes in older adults with mild cognitive impairment: A functional diffuse correlation spectroscopy study
Authors: Udina Cristina , Avtzi Stella , Mota-Foix Miriam , Rosso Andrea L. , Ars Joan , Kobayashi Frisk Lisa , Gregori-Pla Clara , Durduran Turgut , Inzitari Marco 
Published: December 2022

IntroductionIn a worldwide aging population with a high prevalence of motor and cognitive impairment, it is paramount to improve knowledge about underlying mechanisms of motor and cognitive function and their interplay in the aging processes.MethodsWe measured prefrontal cerebral blood flow (CBF) using functional diffuse correlation spectroscopy during motor and dual-task. We aimed to compare CBF changes among 49 older adults with and without mild cognitive impairment (MCI) during a dual-task paradigm (normal walk, 2- forward count walk, 3-backward count walk, obstacle negotiation, and heel tapping). Participants with MCI walked slower during the normal walk and obstacle negotiation compared to participants with normal cognition (NC), while gait speed during counting conditions was not different between the groups, therefore the dual-task cost was higher for participants with NC. We built a linear mixed effects model with CBF measures from the right and left prefrontal cortex.ResultsMCI (n = 34) showed a higher increase in CBF from the normal walk to the 2-forward count walk (estimate = 0.34, 95% CI [0.02, 0.66], p = 0.03) compared to participants with NC, related to a right- sided activation. Both groups showed a higher CBF during the 3-backward count walk compared to the normal walk, while only among MCI, CFB was higher during the 2-forward count walk.DiscussionOur findings suggest a differential prefrontal hemodynamic pattern in older adults with MCI compared to their NC counterparts during the dual-task performance, possibly as a response to increasing attentional demand.
Comparison of the efficacy of acupuncture-related Therapies for post-stroke motor aphasia: A Bayesian network meta-analysis
Authors: Feng Sisi , Tang Mingzhi , Huang Gan , Wang Jumei , Lv Yulan , He Sijin , Liu Duo , Gu Lihua 
Published: December 2022

BackgroundMotor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA).MethodsEight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data.ResultsA total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA.ConclusionThe NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.
Immediate effects of short-term meditation on sensorimotor rhythm-based brain–computer interface performance
Authors: Kim Jeehyun , Jiang Xiyuan , Forenzo Dylan , Liu Yixuan , Anderson Nancy , Greco Carol M. , He Bin 
Published: December 2022

IntroductionMeditation has been shown to enhance a user’s ability to control a sensorimotor rhythm (SMR)-based brain-computer interface (BCI). For example, prior work have demonstrated that long-term meditation practices and an 8-week mindfulness-based stress reduction (MBSR) training have positive behavioral and neurophysiological effects on SMR-based BCI. However, the effects of short-term meditation practice on SMR-based BCI control are still unknown.MethodsIn this study, we investigated the immediate effects of a short, 20-minute meditation on SMR-based BCI control. Thirty-seven subjects performed several runs of one-dimensional cursor control tasks before and after two types of 20-minute interventions: a guided mindfulness meditation exercise and a recording of a narrator reading a journal article.ResultsWe found that there is no significant change in BCI performance and Electroencephalography (EEG) BCI control signal following either 20-minute intervention. Moreover, the change in BCI performance between the meditation group and the control group was found to be not significant.DiscussionThe present results suggest that a longer period of meditation is needed to improve SMR-based BCI control.
Blood-nerve barrier disruption and coagulation system activation induced by mechanical compression injury participate in the peripheral sensitization of trigeminal neuralgia
Authors: Zhou Lu-Xi , Lin Shao-Wei , Qiu Rong-Hui , Lin Ling , Guo Yue-Feng , Luo Dao-Shu , Li Yun-Qing , Wang Feng 
Published: December 2022

IntroductionThe aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ).MethodsVon Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia.ResultsA compression injury of a rat’s TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia.ConclusionA compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.
DNA damage stress-induced translocation of mutant FUS proteins into cytosolic granules and screening for translocation inhibitors
Authors: Nogami Masahiro , Sano Osamu , Adachi-Tominari Keiko , Hayakawa-Yano Yoshika , Furukawa Takako , Iwata Hidehisa , Ogi Kazuhiro , Okano Hideyuki , Yano Masato 
Published: December 2022

Fused in sarcoma/translated in liposarcoma (FUS) is an RNA-binding protein, and its mutations are associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), through the DNA damage stress response, aberrant stress granule (SG) formation, etc. We previously reported that translocation of endogenous FUS into SGs was achieved by cotreatment with a DNA double-strand break inducer and an inhibitor of DNA-PK activity. In the present study, we investigated cytoplasmic SG formation using various fluorescent protein-tagged mutant FUS proteins in a human astrocytoma cell (U251) model. While the synergistic enhancement of the migration of fluorescent protein-tagged wild-type FUS to cytoplasmic SGs upon DNA damage induction was observed when DNA-PK activity was suppressed, the fluorescent protein-tagged FUSP525L mutant showed cytoplasmic localization. It migrated to cytoplasmic SGs upon DNA damage induction alone, and DNA-PK inhibition also showed a synergistic effect. Furthermore, analysis of 12 sites of DNA-PK–regulated phosphorylation in the N-terminal LC region of FUS revealed that hyperphosphorylation of FUS mitigated the mislocalization of FUS into cytoplasmic SGs. By using this cell model, we performed screening of a compound library to identify compounds that inhibit the migration of FUS to cytoplasmic SGs but do not affect the localization of the SG marker molecule G3BP1 to cytoplasmic SGs. Finally, we successfully identified 23 compounds that inhibit FUS-containing SG formation without changing normal SG formation.HighlightsCharacterization of DNA-PK-dependent FUS stress granule localization.A compound library was screened to identify compounds that inhibit the formation of FUS-containing stress granules.
Association of caffeine intake with all-cause and cardiovascular mortality in elderly patients with hypertension
Authors: Chen Shuaijie , Li Jing , Gao Menghan , Li Duanbin , Shen Ruming , Lyu Lingchun , Shen Jiayi , Shen Xiaohua , Fu Guosheng , Wei Tiemin , Zhang Wenbin 
Published: December 2022

BackgroundCaffeine is widely consumed not only in coffee but also in soft drinks and tea. However, the long-term health effects of caffeine are still controversial, especially in people with high cardiovascular risk such as elderly patients with hypertension.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey 2003–2018. Caffeine intake was calculated by two 24-h dietary recall interviews. Complex sampling-weighted multivariable Cox proportional hazards models were used to compare the hazard ratios (HRs) of all-cause and cardiovascular mortality in elderly hypertensive patients with different caffeine intake (&lt;10, 10 to &lt;100, 100 to &lt;200, 200 to &lt;300, and ≥300 mg/day).ResultsThis study included 6,076 elderly hypertensive patients. The mean ± standard error follow-up duration was 6.86 ± 0.12 years. During this period, a total of 2,200 all-cause deaths occurred, of which 765 were cardiovascular deaths. Taking patients with caffeine intake &lt; 10 mg/day as a reference, patients with moderate caffeine intake (200 to &lt;300 mg/day) had a lower risk of all-cause (HR, 0.70 [95% CI, 0.56–0.87]) and cardiovascular (HR, 0.55 [95% CI, 0.39–0.77]) mortality. The benefit of reducing all-cause mortality risk was significant in female patients (HR, 0.65 [95% CI, 0.50–0.85]) or patients with well-controlled blood pressure (HR, 0.63 [95% CI, 0.46–0.87]), but not in male patients or patients with poorly controlled blood pressure. In addition, non-linear relationship analysis also showed that moderate caffeine intake had the lowest HRs of all-cause (Non-linear p = 0.022) and cardiovascular mortality (Non-linear p = 0.032) in the present study.ConclusionModerate caffeine intake is associated with reduced risk of all-cause and cardiovascular mortality in elderly hypertensive patients.
Efficacy, safety, and controversy of ultrasound-guided radiofrequency ablation in the treatment of T1N0M0 papillary thyroid carcinoma
Authors: Yi Zhang , Siyu Li , Lijun Fu , Danhua Zhang , Jianhua Li , Xinguang Qiu 
Published: December 2022

ObjectiveTo evaluate the safety effect, and controversy on the treatment outcomes of radiofrequency ablation (RFA) for T1N0M0 papillary thyroid carcinoma (PTC).Materials and methodsThis study is assessed the medical records of 142 patients with primary T1N0M0 PTC tumors after RFA between 2014 and 2022. 4 patients underwent delayed surgery (DS) after RFA and 411 T1N0M0 patients underwent DS were recorded. Outcomes were compared between RFA and DS groups after propensity score matching (PSM).ResultsThe maximal diameter (MD) and volume (V) increased in months 1 (P &lt; 0.01) and reduced after the 6-month follow-up (all P &lt; 0.01). The disappearance and disease progression rates were 53.5% and 2.1%, respectively. The complication and disease progression rates had no significant difference between RFA and DS (P&gt;0.05). In some cases, the tumors were not fully inactivated after RFA, and the central compartment lymph node (CCLN) were metastasis. The CCLN metastasis rate was 13.4%. MD, V and clustered calcifications were independent risk factors for CCLN metastasis by univariate analysis.ConclusionsRFA is an effective and safe treatment option in selected patients with solitary T1N0M0 PTC. There are the risks of tumor incompletely ablated and CCLN metastasis.
Combination of the parent analogue of remdesivir (GS-441524) and molnupiravir results in a markedly potent antiviral effect in SARS-CoV-2 infected Syrian hamsters
Authors: Abdelnabi Rana , Maes Piet , de Jonghe Steven , Weynand Birgit , Neyts Johan 
Published: December 2022

Remdesivir was the first antiviral drug to be approved for the treatment of severe COVID-19; followed by molnupiravir (another prodrug of a nucleoside analogue) and the protease inhibitor nirmatrelvir. Combination of antiviral drugs may result in improved potency and help to avoid or delay the development of resistant variants. We set out to explore the combined antiviral potency of GS-441524 (the parent nucleoside of remdesivir) and molnupiravir against SARS-CoV-2. In SARS-CoV-2 (BA.5) infected A549-Dual™ hACE2-TMPRSS2 cells, the combination resulted in an overall additive antiviral effect with a synergism at certain concentrations. Next, the combined effect was explored in Syrian hamsters infected with SARS-CoV-2 (Beta, B.1.351); treatment was started at the time of infection and continued twice daily for four consecutive days. At day 4 post-infection, GS-441524 (50 mg/kg, oral BID) and molnupiravir (150 mg/kg, oral BID) as monotherapy reduced infectious viral loads by 0.5 and 1.6 log10, respectively, compared to the vehicle control. When GS-441524 (50 mg/kg, BID) and molnupiravir (150 mg/kg, BID) were combined, infectious virus was no longer detectable in the lungs of 7 out of 10 of the treated hamsters (4.0 log10 reduction) and titers in the other animals were reduced by ∼2 log10. The combined antiviral activity of molnupiravir which acts by inducing lethal mutagenesis and GS-441524, which acts as a chain termination appears to be highly effective in reducing SARS-CoV-2 replication/infectivity. The unexpected potent antiviral effect of the combination warrants further exploration as a potential treatment for COVID-19.