bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway
Authors: Tao Zhang , Chun-Yan Hu , Hua Peng , Bin-Bin Yang , Xiaoping Tang 
Published: August 2020

Background: Epilepsy is a chronic, complex, unprovoked, and recurrent disorder of the nervous system that affected several people worldwide. Phyllanthus amarus (PA) has been documented to have neuroprotective potential. Aim: To evaluate the potential of standardized extract of PA and its possible mechanism of action against the Pentylenetetrazol (PTZ)-induced convulsion and kindling associated post-ictal depression in experimental mice. Materials and Methods: Phyllathin was isolated from methanolic extract of PA and well-characterized using HPTLC, ESI-MS/MS, and LC/MS. Phyllathin containing a standardized extract of PA (50, 100, and 200 mg/kg) was administered in convulsed and kindled mice, followed by an assessment of various parameters. Results: The spectral analysis confirmed the molecular formula and weight of phyllanthin as C24H34O6 and 418.2342 Da. PA (100 and 200 mg/kg) significantly ameliorated PTZ-induced ( p < 0.05) duration, onset of tonic-clonic convulsion, and mortality in mice. It also significantly attenuated ( p < 0.05) PTZ-induced kindling in mice. Alteration in brain GABA, dopamine, and glutamate, Na+K+ATPase, Ca+2-ATPase activities, and oxido-nitrosative stress in kindled mice was significantly restored ( p < 0.05) by PA treatment. It also significantly ( p < 0.05) down-regulated brain mRNA expressions of NF-κB, TNF-α, IL-1β, COX-2, and TLR-4. Histological aberrations induced by PTZ in the brain of a kindled rat was significantly ( p < 0.05) ameliorated by PA. Conclusion: Phyllanthin containing a standardized extract of PA exerts its antiepileptic potential via balancing excitatory (glutamate) and inhibitory (GABA) brain monoamines, voltage-gated ion channels (Na+K+/Ca+2-ATPase) and inhibition of NF-κB/TLR-4 pathway to ameliorate neuroinflammation (TNF-α, IL-1β, and COX-2) in experimental mice.
Differential functional connectivity in thalamic and dopaminergic pathways in restless legs syndrome: a meta-analysis
Authors: Kocar Thomas Derya , Müller Hans-Peter , Kassubek Jan 
Published: August 2020

Objective: Restless legs syndrome (RLS) is a sensorimotor disorder with alterations in somatosensory processing in association with a dysfunctional cerebral network, involving the basal ganglia, limbic network, and sensorimotor pathways. Resting state functional magnetic resonance imaging (MRI) is a powerful tool to provide in vivo insight into functional processing and as such is of special interest in RLS considering the widespread pattern of networks involved in this disorder. In this meta-analysis of resting state functional MRI studies, we analyzed the preponderance of functional connectivity changes associated with RLS and discussed possible links to sensorimotor dysfunction and somatosensory processing. Methods: A systematic research using the online library PubMed was conducted and a total of seven studies passed the inclusion criteria of the meta-analysis. The results of these studies were merged and a statistical probability map was generated that indicated the likelihood of functional connectivity changes within the combined cohort, both for increased and decreased connectivity. Results: The meta-analysis demonstrated decreased functional connectivity within the dopaminergic network in participants with RLS compared with healthy controls, including the nigrostriatal, mesolimbic, and mesocortical pathways. Increased functional connectivity was observed bilaterally in the thalamus, including its ventral lateral, ventral anterior, and ventral posterior lateral nuclei, and the pulvinar. Discussion: Sensorimotor dysfunction in RLS seems to be reflected by decreased functional connectivity within the dopaminergic pathways. Network extension in the thalamus can be regarded as an adaptation to somatosensory dysfunction in RLS. This differential functional connectivity pattern extends prior findings on cerebral somatosensory processing in RLS and offers an explanation for the efficacy of dopaminergic treatment.
Calcaneoplasty coupled with an insertional Achilles tendon reattachment procedure for the prevention of secondary calcaneal impingement: a retrospective study
Authors: Pi Yanbin , Hu Yuelin , Guo Qinwei , Jiang Dong , Xie Xin , Zhao Feng , Chen Linxin , Ao Yingfang , Jiao Chen 
Published: August 2020

Background: Posterior heel pain may occur after an Achilles insertional rupture reattachment procedure and could be attributed to an impingement between the calcaneal tuberosity and Achilles tendon, which could be observed using postoperative magnetic resonance imaging (MRI). Moreover, such impingement, which may be associated with postoperative pain symptoms, could be relieved by calcaneoplasty. Methods: Postoperative Visual Analog Pain Scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) score, Foot Function Index (FFI), Ankle Activity Score (AAS), and Tegner score were obtained and compared between 10 patients who underwent calcaneoplasty (calcaneoplasty group) and 11 patients who did not receive calcaneoplasty (non-calcaneoplasty group). Several signs of calcaneal tuberosity impingement identified in MRI were also compared between the two groups, which included retrocalcaneal bursitis, postoperative tendinopathy, tendon calcification, bone marrow edema, increased Achilles tendon diameter, and bony spurs. Results: The VAS score was 2.00 ± 1.41 and 2.18 ± 1.83 ( p = 0.803), the AOFAS score was 90.60 ± 4.22 and 81.82 ± 7.77 ( p = 0.005), the FFI was 5.00 ± 2.86 and 17.18 ± 15.92 ( p = 0.028), the AAS was 5.50 ± 2.55 and 5.82 ± 2.04 ( p = 0.750), and the Tegner score was 4.30 ± 1.49 and 4.45 ± 1.21 ( p = 0.797) in the calcaneoplasty and non-calcaneoplasty groups, respectively. The AOFAS score and FFI were significantly different between the groups. MRI findings revealed that the non-calcaneoplasty group had significant signs of calcaneal impingement compared with the calcaneoplasty group. Conclusions: Secondary calcaneal impingement due to insertional tendon enlargement may occur, and prophylactic calcaneoplasty coupled with an insertional reattachment procedure could achieve promising postoperative outcomes for patients with insertional Achilles tendon rupture.
The Effect of Irreducible Dislocation on Functional Outcomes in Knees With Multiligament Injuries: A Matched-Cohort Analysis
Authors: Zhang Zhong , Zhang Kai-Bo , Mao Bei-Ni , Lai Si-Ke , Li Jian , Fu Wei-Li 
Published: August 2020

Background: Most cases of bicruciate knee dislocation (KD) with associated posteromedial disruption (KD-IIIM) are reducible, but some cannot be reduced by closed reduction because of soft tissue incarceration. Purpose: To compare the clinical characteristics and functional outcomes of KD-IIIM injuries in patients with or without incarceration of soft tissue requiring open or arthroscopic reduction. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective cohort study of patients with KD was conducted between January 2013 and December 2017 at a single large institution. We applied a 1:2 matching ratio between patients with irreducible KD-IIIM injuries (irreducible group; n = 14) and those with reducible KD-IIIM injuries (control group; n = 28). There were 13 patients in the irreducible group and 25 in the control group who completed follow-up (≥2 years) and were included in our analysis. The efficacy of treatment in patients with KD was evaluated based on range of motion, the Tegner score, the Lysholm score, and the International Knee Documentation Committee (IKDC) score. Results: At the end of follow-up, the mean Tegner score was 4.5 (range, 4-6), the mean Lysholm score was 79.2 (range, 60-95), and the mean IKDC score was 78.6 (range, 60.9-95.4) in the irreducible group. The respective results in the control group were 4.6 (range, 3-8), 83.1 (range, 39-100), and 80.6 (range, 42.5-96.6). These scores did not differ significantly between the 2 groups. Similarly, mean range of motion was similar between groups (irreducible, 118.1°; control, 124.8°). In the irreducible group, the acute subgroup showed significantly higher Lysholm and IKDC scores than the chronic subgroup, while the acute and chronic subgroups in the control group showed no significant differences in these respective outcome scores. Conclusion: In the present study, the treatment of irreducible KD led to similar functional outcomes compared with reducible KD. However, the treatment of chronic irreducible KD led to worse outcomes compared with acute irreducible KD, and therefore, urgent reduction is recommended in these patients.
Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia
Authors: Franco Cosimo , Facciolongo Nicola , Tonelli Roberto , Dongilli Roberto , Vianello Andrea , Pisani Lara , Scala Raffaele , Malerba Mario , Carlucci Annalisa , Negri Emanuele Alberto , Spoladore Greta , Arcaro Giovanna , Tillio Paolo Amedeo , Lastoria Cinzia , Schifino Gioachino , Tabbì Luca , Guidelli Luca , Guaraldi Giovanni , Ranieri V. Marco , Clini Enrico , Nava Stefano 
Published: August 2020

IntroductionThe severe acute respiratory syndrome-coronavirus 2 outbreak spread rapidly in Italy and the lack of intensive care unit (ICU) beds soon became evident, forcing the application of noninvasive respiratory support (NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff and the feasibility and outcomes of NRS applied to patients outside the ICU.MethodsIn this observational study, data from 670 consecutive patients with confirmed coronavirus disease 2019 referred to pulmonology units in nine hospitals between March 1 and May 10, 2020 were analysed. Data collected included medication, mode and usage of NRS (i.e.high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation (NIV)), length of stay in hospital, endotracheal intubation (ETI) and deaths.Results42 (11.1%) healthcare workers tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean±sdage was 68±13 years. The arterial oxygen tension/inspiratory oxygen fraction ratio at baseline was 152±79, and the majority (49.3%) of patients were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9%, with 16%, 30% and 30% for HFNC, CPAP and NIV, respectively, while the total ETI rate was 27%, with 29%, 25% and 28%, respectively; the relative probability of death was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression.ConclusionsThe application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.
Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis
Authors: Ramalho Anabela S. , Fürstová Eva , Vonk Annelotte M. , Ferrante Marc , Verfaillie Catherine , Dupont Lieven , Boon Mieke , Proesmans Marijke , Beekman Jeffrey M. , Sarouk Ifat , Vazquez Cordero Carlos , Vermeulen Francois , De Boeck Kris 
Published: August 2020

RationaleGiven the vast number of cystic fibrosis transmembrane conductance regulator (CFTR) mutations, biomarkers predicting benefit from CFTR modulator therapies are needed for subjects with cystic fibrosis (CF).ObjectivesTo study CFTR function in organoids of subjects with common and rareCFTRmutations and evaluate correlations between CFTR function and clinical data.MethodsIntestinal organoids were grown from rectal biopsies in a cohort of 97 subjects with CF. Residual CFTR function was measured by quantifying organoid swelling induced by forskolin and response to modulators by quantifying organoid swelling induced by CFTR correctors, potentiator and their combination. Organoid data were correlated with clinical data from the literature.ResultsAcross 28 genotypes, residual CFTR function correlated (r2=0.87) with sweat chloride values. When studying the same genotypes, CFTR function rescue by CFTR modulators in organoids correlated tightly with mean improvement in lung function (r2=0.90) and sweat chloride (r2=0.95) reported in clinical trials. We identified candidate genotypes for modulator therapy, such as E92K, Q237E, R334W and L159S. Based on organoid results, two subjects started modulator treatment: one homozygous for complex allele Q359K_T360K, and the second with mutation E60K. Both subjects had major clinical benefit.ConclusionsMeasurements of residual CFTR function and rescue of function by CFTR modulators in intestinal organoids correlate closely with clinical data. Our results for reference genotypes concur with previous results. CFTR function measured in organoids can be used to guide precision medicine in patients with CF, positioning organoids as a potentialin vitromodel to bring treatment to patients carrying rareCFTRmutations.
Elevated TG/HDL-C and non-HDL-C/HDL-C ratios predict mortality in peritoneal dialysis patients
Authors: Xia Wenkai , Yao Xiajuan , Chen Yan , Lin Jie , Vielhauer Volker , Hu Hong 
Published: August 2020

Abstract
Background and aims
Dyslipidemia is common in patients with chronic kidney disease and particular prevalent in patients receiving peritoneal dialysis. However, whether markers of atherogenic dyslipidemia correlate with outcomes in dialysis patients as in the general population is uncertain. The aim of this study was to explore the prognostic value of the serum triglyceride/HDL cholesterol (TG/HDL-C) ratio and non-HDL-C/HDL-C ratio to predict mortality in peritoneal dialysis patients.

Methods
Two hundred fourteen peritoneal dialysis patients were retrospectively analyzed from January 2011 to December 2015, with a median follow-up of 59 months. We used receiver operating curves (ROC) to determine the optimal threshold for TG/HDL-C and non-HDL/HDL-C ratios at baseline to predict overall survival during follow-up. Prognostic values were accessed by univariate and multivariate COX regression analysis and Kaplan-Meier curve. A predictive nomogram was developed to predict prognosis for overall survival, and the predictive accuracy was evaluated by concordance index (c-index).

Results
The optimal cut-off values for TG/HDL-C ratio and non-HDL-C/HDL-C ratio to predict mortality were 1.94 and 2.86, respectively. A high TG/HDL-C ratio and a high non-HDL-C/HDL-C ratio strongly correlated with worse overall survival in peritoneal dialysis patients. Multivariate analysis demonstrated that elevated TG/HDL-C ratio (HR 3.57, 95% CI 1.99, 6.39, P < 0.000) as well as non-HDL/HDL-C ratio (HR 2.58, 95%CI 1.39–4.81, P = 0.003) were independent markers to predict reduced OS. A nomogram was constructed to predict overall survival, with a c-index for predictive accuracy of 0.795.

Conclusion
TG/HDL-C ratio and non-HDL-C/HDL-C may serve as potential prognostic biomarkers in PD patients.
Risk adapted approach: How to treat splenic marginal zone lymphoma in resource-poor settings? - The real-life experience of a Brazilian cancer treatment center
Authors: de Pádua Covas Lage Luís Alberto , dos Santos Felipe Faganelli Caboclo , Levy Débora , Moreira Frederico Rafael , Couto Samuel Campanelli Freitas , Culler Hebert Fabrício , de Oliveira Costa Renata , Rocha Vanderson , Pereira Juliana 
Published: August 2020

Abstract
Background
Splenic marginal zone lymphoma (SMZL) is a rare lymphoid B-cell malignant neoplasm with primary involvement of the spleen. It is a chronic disease, of indolent behavior and prolonged survival. However, 25% of cases have higher biological aggressiveness, propensity for histological transformation to high grade B-cell non-Hodgkin lymphoma and shortened survival. Recognition of these cases of reserved outcome is important for selecting a risk-adapted therapeutic approach in a resource-poor settings.

Methods
We described clinical and epidemiological characteristics, survival analysis and prognostic factors in a retrospective cohort of 39 SMZL patients, treated in Latin America.

Results
We observed a predominance of female (71.8%), median age of 63 years and higher incidence of B symptoms (56.4%) and extra-splenic involvement (87.1%) than in European and North-American series. With a median follow-up of 8.7 years (0.6-20.2 years), estimated 5-year overall survival (OS) and progression-free survival (PFS) were 76.9% and 63.7%, respectively. Factors with adverse prognostic impact on OS and PFS were Hb < 100 g/L, platelet count < 100 x 109/L, albumin < 3.5 g/dL, LDH > 480 U/L and high-risk Arcaini and SMZL/WG scores. Despite a relative low number of patients, no superiority was observed among the therapeutic regimens used including rituximab monotherapy, splenectomy and cytotoxic chemotherapy.

Conclusion
Therefore, in resource-poor settings, where access to immunotherapy is not universal for all SMZL patients, we suggest that first-line should consist on rituximab therapy for elderly patients or with high surgical risk or with at least 1 risk factor identified in our study. Remainders can be safely managed with splenectomy.
Identification of a protein signature for predicting overall survival of hepatocellular carcinoma: a study based on data mining
Authors: Wu Zeng-hong , Yang Dong-liang 
Published: August 2020

Abstract
Background
Hepatocellular carcinoma (HCC), is the fifth most common cancer in the world and the second most common cause of cancer-related deaths. Over 500,000 new HCC cases are diagnosed each year. Combining advanced genomic analysis with proteomic characterization not only has great potential in the discovery of useful biomarkers but also drives the development of new diagnostic methods.

Methods
This study obtained proteomic data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and validated in The Cancer Proteome Atlas (TCPA) and TCGA dataset to identify HCC biomarkers and the dysfunctional of proteogenomics.

Results
The CPTAC database contained data for 159 patients diagnosed with Hepatitis-B related HCC and 422 differentially expressed proteins (112 upregulated and 310 downregulated proteins). Restricting our analysis to the intersection in survival-related proteins between CPTAC and TCPA database revealed four coverage survival-related proteins including PCNA, MSH6, CDK1, and ASNS.

Conclusion
This study established a novel protein signature for HCC prognosis prediction using data retrieved from online databases. However, the signatures need to be verified using independent cohorts and functional experiments.
The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland
Authors: Mickiewicz Marcin , Czopowicz Michał , Kawecka-Grochocka Ewelina , Moroz Agata , Szaluś-Jordanow Olga , Várady Marián , Königová Alżbeta , Spinu Marina , Górski Paweł , Bagnicka Emilia , Kaba Jarosław 
Published: August 2020

AbstractBackgroundProphylactic anthelmintic treatment with one of three basic classes of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) is still the mainstay of control of gastrointestinal nematode infections in small ruminants worldwide. As a consequence, anthelmintic resistance is a serious threat to small ruminant health and production. While the resistance to one class of anthelmintics has already been reported in most of countries, the newly-emerging problem is the resistance to two or even all of classes referred to as multidrug resistance. This study aimed to evidence the presence of multidrug resistance of gastrointestinal nematodes in goats in Poland.ResultsThe combination of one in vivo method (fecal egg count reduction test) and two in vitro methods (egg hatch test and larval development test) performed in two goat herds in the southern Poland showed the presence of gastrointestinal nematodes resistant to fenbendazole and ivermectin in both herds. Moreover, in one herd it revealed the development of resistance to the last effective anthelmintic, levamisole, in response to one-year intensive use.Haemonchus contortuswas the most prevalent gastrointestinal nematode in samples in which resistance to benzimidazoles and ivermectin was found, whereasTrichostrongylus colubriformispredominated when resistance to levamisole was observed.ConclusionThis study shows for the first time that multidrug resistance of gastrointestinal nematodes to three basic classes of anthelmintics is already present in goat population in Poland. Moreover, it may indicate that different species or genera of gastrointestinal nematodes are responsible for the resistance to specific anthelmintics.
Pregnancy-associated plasma protein A – a new indicator of pulmonary vascular remodeling in chronic thromboembolic pulmonary hypertension?
Authors: Kriechbaum Steffen D. , Rudolph Felix , Wiedenroth Christoph B. , Mielzarek Lisa , Haas Moritz , Guth Stefan , Hamm Christian W. , Mayer Eckhard , Liebetrau Christoph , Keller Till 
Published: August 2020

Abstract
Background
In chronic thromboembolic pulmonary hypertension (CTEPH) impaired pulmonary hemodynamics lead to right heart failure. Natriuretic peptides reflect hemodynamic disease severity. Pregnancy-associated plasma protein-A (PAPP-A) might address another aspect of CTEPH - chronic tissue injury and inflammation. This study assessed dynamics of PAPP-A in CTEPH patients who undergo therapy with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA).

Methods
The study included a total of 125 CTEPH patients scheduled for treatment (55 PEA/ 70 BPA) and a control group of 58 patients with pulmonary hypertension other than CTEPH. Biomarker measurement was performed at baseline and follow-up in the CTEPH cohort, prior to each BPA in the BPA cohort and once in the control group.

Results
The median PAPP-A level was slightly higher (p = 0.05) in CTEPH patients [13.8 (11.0–18.6) mU/L], than in the control group [12.6 (8.6–16.5) mU/L], without a difference between the BPA and PEA group (p = 0.437) and without a correlation to mean pulmonary artery pressure (p = 0.188), pulmonary vascular resistance (p = 0.893), cardiac index (p = 0.821) and right atrial pressure (p = 0.596). PEA and BPA therapy decreased the mean pulmonary artery pressure (p < 0.001) and pulmonary vascular resistance (p < 0.001) and improved the WHO-functional-class (baseline: I:0/II:25/III:80/IV:20 vs. follow-up: I:55/II:58/III:10/IV:2). PAPP-A levels decreased after PEA [13.5 (9.5–17.5) vs. 11.3 (9.8–13.6) mU/L; p = 0.003) and BPA treatment [14.3 (11.2–18.9) vs. 11.1 (9.7–13.3) mU/L; p < 0.001). The decrease of PAPP-A levels is delayed in comparison to N-terminal pro-B-type natriuretic peptide.

Conclusion
PAPP-A is overexpressed in CTEPH and decrease significantly after surgical or interventional therapy, however without association to hemodynamics. Further investigation is needed to define the underlying mechanism of PAPP-A expression and changes after therapy in CTEPH.