bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Gene Expression Profiles in Viable Hepatocellular Carcinoma Treated With Liver-Directed Therapy
Authors: Núñez Kelley G. , Sandow Tyler , Lakey Meredith A. , Fort Daniel , Cohen Ari J. , Thevenot Paul T. 
Published: June 2022

BackgroundHepatocellular carcinoma is a heterogeneous tumor that accumulates a mutational burden and dysregulated signaling pathways that differ from early to advanced stages. Liver transplant candidates with early-stage hepatocellular carcinoma (HCC) undergo liver-directed therapy (LDT) to delay disease progression and serve as a bridge to liver transplantation (LT). Unfortunately, &gt;80% of LDT-treated patients have viable HCC in the explant liver, dramatically increasing recurrence risk. Understanding the effect of LDT on early-stage HCC could help identify therapeutic targets to promote complete pathologic necrosis and improve recurrence-free survival. In this study, transcriptomic data from viable HCC in LDT-treated bridged to transplant patients were investigated to understand how treatment may affect tumor signaling pathways.MethodsMultiplex transcriptomic gene analysis was performed with mRNA extracted from viable tumors of HCC patients bridged to transplant using LDT. The NanoString nCounter® Tumor Signaling 360 panel was used that contained 780 genes from 48 pathways involved in tumor biology within the microenvironment as well as antitumoral immune responses.ResultsHierarchical clustering separated tumors into three subtypes (HCC-1, HCC-2, and HCC-3) each with distinct differences in anti-tumoral signaling and immune infiltration within the tumor microenvironment. Immune infiltration (neutrophils, T cells, and macrophages) were all lowest in subtype HCC-3. The tumor inflammatory signature consisting of 18 genes associated with PD-1/PD-L1 inhibition, antigen presentation, chemokine secretion, and adaptive immune responses was highest in subtype HCC-1 and lowest in HCC-3. History of decompensation and etiology were associated with HCC subtype favoring downregulations in inflammation and immune infiltration with upregulation of lipid metabolism. Gene expression among intrahepatic lesions was remarkably similar with &gt;85% of genes expressed in both lesions. Genes differentially expressed (&lt;8 genes per patient) in multifocal disease were all upregulated in LDT-treated tumors from pathways involving epithelial mesenchymal transition, extracellular matrix remodeling, and/or inflammation potentially implicating intrahepatic metastases.ConclusionIncomplete response to LDT may drive expression patterns that inhibit an effective anti-tumoral response through immune exclusion and induce intrahepatic spread.
Sclerostin Suppression Facilitates Uveal Melanoma Progression Through Activating Wnt/β-Catenin Signaling Via Binding to Membrane Receptors LRP5/LRP6
Authors: Wang Hanqing , Zhao Sidi , Liu Yang , Sun Fengyuan , Huang Xiaoming , Wu Tong 
Published: June 2022

ObjectiveUveal melanoma (UM) is the most frequent primary eye cancer in adults with a 50% mortality rate. Characterizing the fundamental signaling pathways that drive UM is of importance for the development of targeted therapy. This study aims to probe the impact of sclerostin (SOST) on malignant progression of UM and regulation of Wnt/β-catenin signaling.MethodsEpithelial-type (n=20) and spindle-type (n=16) UM tissues were collected for immunohistochemical staining of SOST, Wnt-1, and β-catenin expressions. SOST was silenced in three UM cell lines (primary spindle-type OCM-1 cells, metastatic epithelial Mum-2B cells, and metastatic spindle-type Mum-2C cells) through transfecting specific siRNA. RT-qPCR and Western blot were presented for examining the levels of SOST, and markers in Wnt/β-catenin signaling. Flow cytometry, MTT, EdU, transwell, and tube formation assays were conducted, respectively. By implanting BALB/c nude murine models in situ, the function of SOST on tumor growth was investigated, followed by immunofluorescence double staining of SOST and LRP5/6.ResultsLow SOST expression as well as high Wnt-1 and β-catenin expressions were found in epithelial-type (high malignancy) than spindle-type (low malignancy) UM tissues. Silencing SOST activated the markers in Wnt/β-catenin signaling as well as accelerated cell cycle progression, migration, invasion, angiogenesis, and reduced apoptosis in UM cells. In situ tumor formation in murine eyes showed that SOST knockdown promoted tumor growth. Moreover, SOST interacted with LRP5/LRP6.ConclusionSOST silencing may facilitate the malignant progression of UM cells through activating Wnt/β-catenin signaling. Mechanistically, SOST may exert this function by interacting with LRP5/LRP6 membrane receptors.
Factors Associated With Choriocarcinoma Syndrome Development in Poor-Risk Patients With Germ Cell Tumors
Authors: Rejlekova Katarina , Kalavska Katarina , Makovnik Marek , Hapakova Nikola , Chovanec Michal , De Angelis Valentina , Obertova Jana , Palacka Patrik , Sycova-Mila Zuzana , Mardiak Jozef , Mego Michal 
Published: June 2022

BackgroundGerm cell tumors (GCTs) represent a highly curable cancer. However, a small proportion of poor-risk patients can develop choriocarcinoma syndrome (CS) connected with acute respiratory distress syndrome (ARDS) with a high mortality rate. Our retrospective study aimed to determine the risk factors of poor-risk GCTs susceptible to CS development.Patients and MethodsUsing a computerized database and a systematic chart review, we identified the records of 532 patients with GCTs treated at the National Cancer Institute from 2000 to 2018. Ninety eligible patients with poor-risk GCTs based on IGCCCG classification were identified. All patients were treated with platinum-based induction chemotherapy. Clinicopathological variables were collected and analyzed in correlation with CS development.ResultsNine (10%) of 90 patients developed CS in a median of 1 day (1–9 days) after chemotherapy administration. All patients died shortly after the chemotherapy start with a median of 4 days (3–35 days) due to ARDS development. In univariate analysis, metastatic lung involvement ≥50% of lung parenchyma, choriocarcinoma elements in histology specimen, dyspnea, cough, hemoptysis, ECOG PS ≥2, weight loss, hemoglobin ≤100 g/l, and NLR ≥3.3 at the time of presentation were associated with CS development. In multivariate analysis, ECOG PS ≥2 and metastatic lung involvement ≥50% were independently associated with CS. All patients with these two characteristics developed CS, compared to 0% with zero or one of these factors (p &lt; 0.000001).ConclusionsIn our study, we identified factors associated with CS development. These factors might improve the risk stratification of the patients susceptible to CS and improve their outcome.
Systematic Pelvic and Para-Aortic Lymphadenectomy During Fertility-Sparing Surgery in Patients With Early-Stage Epithelial Ovarian Cancer: A Retrospective Study
Authors: Li Tingting , Liu Ya , Xie Sixia , Wang Hongjing 
Published: June 2022

ObjectiveThe implication of pelvic and para-aortic lymphadenectomy in surgical staging of early-stage epithelial ovarian cancer (eEOC) is still debated. Limited data are available about systematic lymphadenectomy during fertility-sparing surgery (FSS) in patients with eEOC.MethodsThe medical records of 38 patients with FIGO stage I EOC and below 40 years who underwent FSS at our hospital between January 2003 and December 2018 were retrospectively reviewed.ResultsAmong them, 18 patients (47.4%) underwent comprehensive lymphadenectomy, 11 patients (28.9%) underwent lymph node sampling, and 9 patients (23.7%) did not undergo lymphadenectomy. There was no statically significant difference in age, histology, grade, surgical approach, chemotherapy, and gestation among the three groups. With a median follow-up of 52.5 months (range: 24–153), three patients (7.9%) with FIGO stage IC EOC developed tumor recurrence. In these patients, progress-free survival (PFS) was 92.1%, and overall survival (OS) was 94.7%. No significant difference in the OS. Three patients had among all the patients, 15 patients (39.5%) had gestation after treatment, and 23 patients (60.5%) did not have gestation after treatment.ConclusionThe number of lymph nodes removed did not significantly affect survival eEOC with FSS. Systematic pelvic and para-aortic lymphadenectomy could not be performed for mucious eEOC patients with FSS if intraoperative freezing in confirmed and no suspicious lymph nodes are found. A better understanding of sentinel lymph node biopsy may help to identify whether the patient requires FSS.
Exercise-induced Laryngeal Obstruction: Protocol for a Randomized Controlled Treatment Trial
Authors: Clemm Hege , Røksund Ola D. , Andersen Tiina , Heimdal John-Helge , Karlsen Tom , Hilland Magnus , Fretheim-Kelly Zoe , Hufthammer Karl Ove , Sandnes Astrid , Hjelle Sigrun , Vollsæter Maria , Halvorsen Thomas ,   Bergen ILO-group
Published: June 2022

BackgroundExercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high-intensity exercise. Empirical data suggest that EILO consists of different subtypes, possibly requiring different therapeutic approaches. Currently applied treatments do not rest on randomized controlled trials, and international guidelines based on good evidence can therefore not be established. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO.Methods and AnalysisConsenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four non-invasive treatment arms, based on promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the non-invasive approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimally invasive laser supraglottoplasty or (G) no surgery. Power calculations are based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions.Ethics and DisseminationThe study will assess approaches to EILO treatments that despite widespread use, are insufficiently tested in structured, verifiable, randomized, controlled studies, and is therefore considered ethically sound. The study will provide knowledge listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5–7% of young people. Dissemination will occur in peer-reviewed journals, at relevant media platforms and conferences, and by engaging with patient organizations and the healthcare bureaucracy.
TLRs-JNK/ NF-κB Pathway Underlies the Protective Effect of the Sulfide Salt Against Liver Toxicity
Authors: Abdel-latif Rania , Heeba Gehan Hussein , Hassanin Soha Osama , Waz Shaimaa , Amin Amr 
Published: June 2022

Hydrogen sulfide (H2S) is an endogenously gas transmitter signaling molecule with known antioxidant, anti-inflammatory, and cytoprotective properties. Although accumulating evidence shows the therapeutic potential of H2S in various hepatic diseases, its role in cyclophosphamide (CP)-induced hepatotoxicity remains elusive. The present study was undertaken to investigate the impact of endogenous and exogenous H2S on toll-like receptors (TLRs)-mediated inflammatory response and apoptosis in CP-induced hepatotoxicity. Either an H2S donor (NaHS (100 μM/kg) or an H2S blocker [dl-propargylglycine (PAG) (30 mg/kg, i. p.)], was administered for 10 days before a single ip injection of CP (200 mg/kg). NaHS attenuated conferred hepatoprotection against CP-induced toxicity, significantly decreasing serum hepatic function tests and improving hepatic histopathology. Additionally, NaHS-treated rats exhibited antioxidant activity in liver tissues compared with the CP group. The upregulated hepatic levels of TLR2/4 and their downstream signaling molecules including c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) were also suppressed by NaHS protective treatment. NaHS showed anti-inflammatory and antiapoptotic effects; reducing hepatic level tumor necrosis factor-alpha (TNF-α) and caspase-3 expression. Interestingly, the cytotoxic events induced in CP-treated rats were not significantly altered upon the blocking of endogenous H2S. Taken together, the present study suggested that exogenously applied H2S rather than the endogenously generated H2S, displayed a hepatoprotective effect against CP-induced hepatotoxicity that might be mediated by TLRs-JNK/NF-κB pathways.
Food for Thought: Leptin and Hippocampal Synaptic Function
Authors: Harvey Jenni 
Published: June 2022

It is well documented that the endocrine hormone, leptin controls energy homeostasis by providing key signals to specific hypothalamic nuclei. However, our knowledge of leptin’s central actions has advanced considerably over the last 20 years, with the hippocampus now established as an important brain target for this hormone. Leptin receptors are highly localised to hippocampal synapses, and increasing evidence reveals that activation of synaptically located leptin receptors markedly impacts cognitive processes, and specifically hippocampal-dependent learning and memory. Here, we review the recent actions of leptin at hippocampal synapses and explore the consequences for brain health and disease.
Design and Analysis of Novel Folded Optical Multi-Pass Cell
Authors: Cheng Gang , Cao Ya-Nan , Tian Xing , Chen Jia-Jin , Wang Jing-Jing 
Published: June 2022

A novel folded multi-pass cell consisting of three non-coaxial mirrors (spherical mirror or plane mirror) is proposed for laser spectroscopy. Three mirrors of the folded multi-pass cell can arrange in V-shape to form a stable non-coaxial multi-pass cell. Furthermore, in order to research the stability of the multi-pass cell under off-axis mirror’s astigmatism circumstance, an equivalent coaxial multi-pass cell and modified ABCD matrix model for the spot pattern of the folded multi-pass cell is proposed, by which a series of the detailed numerical calculations were implemented to analyze the optical path length of the multi-pass cell. Many spot patterns obtained with a high fill factor improve the utilization efficiency of the surface of the mirror and produce a longer total optical path length. The several typical types of folded multi-pass cells consisting of the different mirrors and base lengths were selected to demonstrate the cell’s self-consistent condition and power for a longer-optical path length. Three effective optical path lengths of 49.6, 97.6 and 173.6 m were obtained, respectively.
Multi-Beam Large Fundamental Mode Neodymium Glass Regenerative Amplifier With Uniform Performance
Authors: Gao Song , Xie Xudong , Tang Jun , Fan Chen , Fu Xuejun , Chen Zhifei , Yao Ke 
Published: June 2022

In this study, the designing method of multi-beam regenerative amplifiers with the repetitive rate was proposed and demonstrated. To obtain multi-beam regenerative amplifiers with uniform performance, the disparities in output energy, energy stability, and mode size were analyzed, and the detailed optimizing method was presented. With the designs, eight-beam regenerative amplifiers were developed. The output performances of eight-beam regenerative amplifiers were uniform. The output energies were in the range of 25.4–28.8 mJ, and the energy stabilities over two hours were in the range of 2.4%–5.1% (PV) and 0.3%–0.9% (RMS).
Cepstral Analysis for Scoring the Quality of Electrocardiograms for Heart Rate Variability
Authors: Castiglioni Paolo , Parati Gianfranco , Faini Andrea 
Published: June 2022

Mobile-health solutions based on heart rate variability often require electrocardiogram (ECG) recordings by inexperienced operators or real-time automatic analyses of long-term recordings by wearable devices in free-moving individuals. In this context, it is useful to associate a quality index with the ECG, scoring the adequacy of the recording for heart rate variability to identify noise or arrhythmias. Therefore, this work aims to propose and validate a computational method for assessing the adequacy of single-lead ECGs for heart rate variability analysis that may run in real time on wearable systems with low computational power. The method quantifies the ECG pseudo-periodic structure employing cepstral analysis. The cepstrum (spectrum of log-spectrum) is estimated on a running ECG window of 10 s before and after “liftering” (filtering in the cepstral domain) to remove slower noise components. The ECG periodicity generates a dominant peak in the liftered cepstrum at the “quefrency” of the mean cardiac interval. The Cepstral Quality Index (CQI) is the ratio between the cepstral-peak power and the total power of the unliftered cepstrum. Noises and arrhythmias reduce the relative power of the cepstral peak decreasing CQI. We analyzed a public dataset of 6072 single-lead ECGs manually classified in normal rhythm or inadequate for heart rate variability analysis because of noise or atrial fibrillation, and the CQI = 47% cut-off identified the inadequate recordings with 79% sensitivity and 85% specificity. We showed that the performance is independent of the lead considering a public dataset of 1,000 12-lead recordings with quality classified as “acceptable” or “unacceptable” by visual inspection. Thus, the cepstrum describes the ECG periodic structure effectively and concisely and CQI appears to be a robust score of the adequacy of ECG recording for heart rate variability analysis, evaluable in real-time on wearable devices.
Abnormal Ventral Somatomotor Network Homogeneity in Patients With Temporal Lobe Epilepsy
Authors: Li Dongbin , Liu Ruoshi , Meng Lili , Xiong Pingan , Ren Hongwei , Zhang Liming , Gao Yujun 
Published: June 2022

BackgroundAbnormalities of functional connectivity in the somatomotor network have been thought to play an essential role in the pathophysiology of epilepsy. However, there has been no network homogeneity (NH) study about the ventral somatomotor network (VSN) in patients with temporal lobe epilepsy (TLE). Therefore, we explored the NH of the VSN in TLE patients in this study.MethodsThe sample included 52 patients with left temporal lobe epilepsy, 83 patients with right temporal lobe epilepsy, and 68 healthy controls. The NH method was utilized to analyze the resting-state functional magnetic resonance imaging data.ResultsCompared to the controls, rTLE patients had significantly higher NH in the bilateral postcentral gyrus, and significantly lower NH in the bilateral Rolandic operculum and the right superior temporal gyrus (STG). The NH values of the left postcentral gyrus were significantly higher in lTLE patients than in the healthy controls, and lTLE patients had lower NH in the right Rolandic operculum. The altered NH in the postcentral gyrus was negatively correlated with the illness duration, and the decreased NH in the left Rolandic operculum was negatively correlated with the executive control reaction time (ECRT).ConclusionOur findings suggest that altered NH of the postcentral gyrus, Rolandic operculum and STG might be associated with the pathophysiology of TLE, and thus, highlight the contribution of the VSN to the pathophysiology of TLE.
A Resting State Functional Magnetic Resonance Imaging Study of Unmedicated Adolescents With Non-suicidal Self-Injury Behaviors: Evidence From the Amplitude of Low-Frequency Fluctuation and Regional Homogeneity Indicator
Authors: Zhou Yi , Yu Renqiang , Ai Ming , Cao Jun , Li Xiao , Hong Su , Huang Qian , Dai Linqi , Wang LiXia , Zhao Lin , Zhang Qi , Shi Lei , Kuang Li 
Published: June 2022

BackgroundNon-suicidal self-injury (NSSI) behaviors are common in adolescents with major depressive disorder (MDD). Brain studies specifically targeting adolescents with MDD and NSSI may provide new insights into suicide warnings in adolescents with MDD.MethodsThis study examined the whole-brain neural activity in adolescents aged between 12–17 years, 50 unmedicated MDD patients with (nsMDDs) or without NSSI (nnsMDDs), and 25 healthy controls (HCs) participated in this study, and analyzed the correlation between the values of amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in significantly different brain regions and the scores of the relevant clinical psychological scale.ResultsCompared with nnsMDDs, nsMDDs had enhanced ALFF values in left middle occipital gyrus and left median cingulate and paracingulate gyri; the fALFF values of the right caudate nucleus was weakened in the nsMDDs; the ReHo values of right middle occipital gyrus and right middle temporal gyrus weakened and the ReHo values of right medial cingulate gyrus enhanced in nsMDDs. And all of differences were statistically significant. In nsMDDs, the value of ALFF in the left calcarine fissure and surrounding cortex was negatively correlated with the score of Children's depression Inventory (CDI); the value of fALFF in the right caudate nucleus was positively correlated with the score of Beck Scale for Suicidal Ideations (BSSI); the value of ReHo in the right middle temporal gyrus was positively correlated with the score of Multidimensional Anxiety Scale for Children (MASC); and the value of ReHo in the right median cingulate and paracingulate gyri was negatively correlated with the score of BSSI.ConclusionsWe found that in ALFF, fALFF and ReHo, the significant differences between nsMDDs and nnsMDDs are mainly located in default mode network (DMN) and visual network (VN), and there may be brain regions related to NSSI in DMN and VN. The significant differences brain regions in ALFF, fALFF and ReHo between nsMDDs and nnsMDDs were related to the total score of the relevant clinical psychological scale, and may be related to NSSI.