bluuebunny/crossref_metadata_2025_split huggingface dataset:
RIP3/MLKL pathway‐regulated necroptosis: A new mechanism of paclitaxel‐induced peripheral neuropathy
Authors: Ma Dongyang , Zhao Shuang , Liu Xin , Li Zhao , Li Huizhou , Liu Jiaxin , Cao Jing , Wang Xiuli 
Published: June 2021

AbstractPaclitaxel (PTX) chemotherapy treatment often leads to neuropathic pain, which is resistant to available analgesic treatments. Death of cells and neuroinflammatory response are associated with PTX‐induced peripheral neuropathy (PIPN). Necroptosis is a form of regulated necrotic cell death that accompanies strong inflammatory response. It is mediated by receptor‐interacting protein kinase 3 (RIP3) and mixed‐lineage kinase domain‐like protein (MLKL), which contribute to the pathogenesis of several neurodegenerative diseases. Nevertheless, the role of necroptosis in PIPN remains unexplored. The aim of this study was to investigate the role of necroptosis in PIPN using its antagonists (necrostatin‐1 and Nec‐1). The quartic PTX administration (accumulated dose: 8 mg/kg, ip) in rats induced robust hyperalgesia and allodynia with significant cell necrosis and an increase in proinflammatory cytokines in the dorsal root ganglion (DRG). PTX application also increased RIP3 and MLKL protein levels in DRG, which were primarily in neurons. Moreover, it also promoted satellite glial cells (SGCs) activation, as assayed by glial fibrillary acidic protein (GFAP) upregulation. All these PTX‐induced changes were prevented by the Nec‐1 treatment. When taken together, the present study indicated that RIP3/MLKL pathway‐regulated neuronal necroptosis, which promoted an inflammatory cascade reaction in DRG, might be a new mechanism of PIPN.
More constructions for Sperner partition systems
Authors: Gowty Adam , Horsley Daniel 
Published: June 2021

AbstractAn ‐Sperner partition system is a set of partitions of some ‐set such that each partition has nonempty parts and no part in any partition is a subset of a part in a different partition. The maximum number of partitions in an ‐Sperner partition system is denoted . In this paper we introduce a new construction for Sperner partition systems based on a division of the ground set into many equal‐sized parts. We use this to asymptotically determine in many cases where is bounded as becomes large. Further, we show that this construction produces a Sperner partition system of maximum size for numerous small parameter sets . By extending a separate existing construction, we also establish the asymptotics of when for almost all odd values of .
The role of psychosocial factors in Black women's self‐efficacy in receiving genetic counseling and testing
Authors: Ding Huanghe , Sutton Arnethea L. , Hurtado‐de‐Mendoza Alejandra , Sheppard Vanessa B. 
Published: June 2021

AbstractHigher self‐efficacy in receiving genetic counseling and testing (GCT) has been associated with greater participation in GCT for women at risk of hereditary breast and ovarian cancer (HBOC), but little is known about correlates of self‐efficacy in Black women eligible for GCT. The goal of this secondary analysis was to identify sociodemographic and psychosocial factors regarding GCT. Multivariable regression analysis was conducted to assess the relationship between self‐efficacy and correlates of interest. Of the 100 Black women surveyed, most women had a college degree (64%), were employed (84%), and had health insurance (93%). In the multivariable model, greater self‐efficacy was associated with more positive attitudes toward GCT (Β = 0.126; CI = 0.01 to 0.25; p = 0.039), greater confidence in the Genetic Information Nondiscrimination Act (GINA) (Β = 0.250; CI = 0.04 to 0.46; p = 0.019), and lower ratings of perceived difficulty obtaining GCT (Β = −0.219; CI = −0.46 to −0.10; p = 0.003). Community‐level interventions to promote self‐efficacy are needed that address perceived barriers to GCT, with the goals of increasing GINA Law awareness in the general public, increasing accessibility to genetic counseling (e.g., telemedicine), and promoting more positive attitudes about GCT.
Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica
Authors: Rosales Carlos 
Published: June 2021

AbstractEntamoeba histolytica is a protozoan parasite with high prevalence in developing countries, and causes amoebiasis. This disease affects the intestine and the liver, and is the third leading cause of human deaths among parasite infections. E. histolytica infection of the intestine or liver is associated with a strong inflammation characterized by a large number of infiltrating neutrophils. Consequently, several reports suggest that neutrophils play a protective role in amoebiasis. However, other reports indicate that amoebas making direct contact with neutrophils provoke lysis of these leukocytes, resulting in the release of their lytic enzymes, which in turn provoke tissue damage. Therefore, the role of neutrophils in this parasitic infection remains controversial. Neutrophils migrate from the circulation to sites of infection, where they display several antimicrobial functions, including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NET). Recently, it was found that E. histolytica trophozoites are capable of inducing NET formation. Neutrophils in touch with amoebas launched NET in an explosive manner around the amoebas and completely covered them in nebulous DNA and cell aggregates where parasites got immobilized and killed. In addition, the phenotype of neutrophils can be modified by the microbiome resulting in protection against amoebas. This review describes the mechanisms of E. histolytica infection and discusses the novel view of how neutrophils are involved in innate immunity defense against amoebiasis. Also, the mechanisms on how the microbiome modulates neutrophil function are described.
Cyclovirus detection in Chilean adults with and without community‐acquired pneumonia
Authors: Prades Yara , Pizarro Rolando , Ruiz Mauricio , Moreno Cristian , Avendaño Luis F. , Luchsinger Vivian 
Published: June 2021

AbstractCycloviruses (CyV) (genus Cyclovirus, family Circoviridae) are nonenveloped DNA viruses. The first report in humans was in 2010 and research has focused only on disease‐associated human sample detection. The only HuACyV (CyCV‐ChileNPA1, HuACyV10) reported in the Chilean population was in children (3.3%) with an acute respiratory infection. Its detection in respiratory samples from adults, with/without respiratory disease remains unknown. The aim of this study was to detect HuACyV10 in adults with and without respiratory disease. HuACyV10 was studied in nasopharyngeal swabs from 105 hospitalized adults with community‐acquired pneumonia (CAP) and 104 adults without respiratory symptoms. Total nucleic acids were extracted, and viral rep and cp gene fragments were amplified by real‐time polymerase chain reaction. HuACyV10 was detected in 19.05% adults with CAP and in 0.96% asymptomatic adults, being significantly higher in adult CAP than asymptomatic (n = 1) ones (p = 0.0001). C
t values were between 26.7 and 39.6, and the median was 34.1 for rep and 33.8 for the CAP in adults CAP (p = 0.68), and 35.7 and 36.0, respectively, in the asymptomatic case. HuACyV10 detection in CAP adults concentrated in the Autumn–Winter season of the Southern hemisphere. The only asymptomatic adult with HuACyV10 was detected in the Spring–Summer period. In this first report of HuACyV10 in respiratory samples from adults, detection was significantly higher in CAP than in asymptomatic adults. As the sensitivity of both rep and cp genes was similar, both can be applied for detecting HuACyV10. It would be advisable to investigate the pathogenic role of HuACyV10 in adult respiratory infections.​
Efficient extra‐mitochondrial aerobic ATP synthesis in neuronal membrane systems
Authors: Ravera Silvia , Bartolucci Martina , Calzia Daniela , Morelli Alessandro M. , Panfoli Isabella 
Published: June 2021

AbstractThe nervous system displays high energy consumption, apparently not fulfilled by mitochondria, which are underrepresented therein. The oxidative phosphorylation (OxPhos) activity, a mitochondrial process that aerobically provides ATP, has also been reported also in the myelin sheath and the rod outer segment (OS) disks. Thus, commonalities and differences between the extra‐mitochondrial and mitochondrial aerobic metabolism were evaluated in bovine isolated myelin (IM), rod OS, and mitochondria‐enriched fractions (MIT). The subcellular fraction quality and the absence of contamination fractions have been estimated by western blot analysis. Oxygen consumption and ATP synthesis were stimulated by conventional (pyruvate + malate or succinate) and unconventional (NADH) substrates, observing that oxygen consumption and ATP synthesis by IM and rod OS are more efficient than by MIT, in the presence of both kinds of respiratory substrates. Mitochondria did not utilize NADH as a respiring substrate. When ATP synthesis by either sample was assayed in the presence of 10–100 µM ATP in the assay medium, only in IM and OS it was not inhibited, suggesting that the ATP exportation by the mitochondria is limited by extravesicular ATP concentration. Interestingly, IM and OS but not mitochondria appear able to synthesize ATP at a later time with respect to exposure to respiratory substrates, supporting the hypothesis that the proton gradient produced by the electron transport chain is buffered by membrane phospholipids. The putative transfer mode of the OxPhos molecular machinery from mitochondria to the extra‐mitochondrial structures is also discussed, opening new perspectives in the field of neurophysiology.
Resonance Raman spectroscopic analysis of the iron–sulfur cluster redox chain of the Ralstonia eutropha membrane‐bound [NiFe]‐hydrogenase
Authors: Siebert Elisabeth , Schmidt Andrea , Frielingsdorf Stefan , Kalms Jacqueline , Kuhlmann Uwe , Lenz Oliver , Scheerer Patrick , Zebger Ingo , Hildebrandt Peter 
Published: June 2021

AbstractIron–sulfur (Fe–S) centers are versatile building blocks in biological electron transfer chains because their redox potentials may cover a wide potential range depending on the type of the cluster and the specific protein environment. Resonance Raman (RR) spectroscopy is widely used to analyze structural properties of such cofactors, but it remains still a challenge to disentangle the overlapping signals of metalloproteins carrying several Fe–S centers. In this work, we combined RR spectroscopy with protein engineering and X‐ray crystallography to address this issue on the basis of the oxygen‐tolerant membrane‐bound hydrogenase from Ralstonia eutropha that catalyzes the reversible conversion of hydrogen into protons and electrons. Besides the NiFe‐active site, this enzyme harbors three different Fe–S clusters constituting an electron relay with a distal [4Fe–4S], a medial [3Fe–4S], and an unusual proximal [4Fe–3S] cluster that may carry a hydroxyl ligand in the superoxidized state. RR spectra were measured from protein crystals by varying the crystal orientation with respect to the electric field vector of the incident laser to achieve a preferential RR enhancement for individual Fe–S clusters. In addition to spectral discrimination by selective reduction of the proximal cluster, protein engineering allowed for transforming the proximal and medial cluster into standard cubane‐type [4Fe–4S] centers in the C19G/C120G and P242C variants, respectively. The latter variant was structurally characterized for the first time in this work. Altogether, the entirety of the RR data provided the basis for identifying the vibrational modes characteristic of the various cluster states in this “model” enzyme as a prerequisite for future studies of complex (FeS)‐based electron transfer chains.
Three‐dimensional printing‐based personalized limb salvage and reconstruction treatment of pelvic tumors
Authors: Wu Junxiang , Xie Kai , Luo Dinghao , Wang Lei , Wu Wen , Yan Mengning , Ai Songtao , Dai Kerong , Hao Yongqiang 
Published: June 2021

AbstractBackground and ObjectivesThe treatment of pelvic tumors is widely recognized to be challenging. The purpose of this study was to evaluate the efficacy of personalized three‐dimensional (3D) printing‐based limb salvage and reconstruction treatment for pelvic tumors.MethodsTwenty‐eight pelvic tumor patients were enrolled. 3D printing lesion models and osteotomy templates were prepared for surgery planning, prosthesis design, and osteotomy assistance during surgery. 3D printing‐based personalized pelvic prostheses were manufactured and used in all 28 patients. Follow‐up of postoperative survival, prosthesis survival, imaging examinations, and Musculoskeletal Tumor Society (MSTS) lower limb functional scores were carried out.ResultsThe mean follow‐up period was 32.2 months, during which 16 patients had disease‐free survival, 3 survived with the disease, and 9 died. The prostheses were stable, and the mean offset of the center of rotation was 5.48 mm. The prosthesis‐bone interface showed good integration. For the 19 surviving patients, the mean MSTS lower limb functional score was 23.2. Postoperative complications included superficial infection in six patients and hip dislocation in three patients.ConclusionsPersonalized 3D printing‐based limb salvage and reconstruction was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery.
Major modifications to minimize thoracic esophago‐gastric leak and eradicate esophageal stricture after Ivor Lewis esophagectomy
Authors: Housman Brian , Lee Dong‐Seok , Wolf Andrea , Nicastri Daniel , Kaufman Andrew , Rizk Nabil , Housman Arno , Song Kimberly , Hakami Ardeshir , Flores Raja M. 
Published: June 2021

AbstractBackgroundThe Ivor Lewis esophagectomy (ILE) remains the procedure of choice for localized middle or lower esophageal carcinoma. Nevertheless, anastomotic leak remains a common complication with rates from 3% to 25% and a stricture rate as high as 40%. The frequency of these complications suggests that the procedure itself may have inherent limitations including the use of potentially ischemic tissue for the esophagogastric anastomosis. We introduce a modified technique that reduces operative steps, preserves blood supply, and uses a modified esophagogastric anastomosis.MethodsAll consecutive patients undergoing ILE with the described modified technique were identified. An esophagram was performed on postoperative day six or seven. To ensure that all cases were identified, anastomotic leaks were defined as any radiographic evidence of contrast extravasation.ResultsA total of 110 patients underwent the modified esophagectomy with 2 anastomotic leaks (1.82%) and zero strictures. There was 1 late death but no early deaths (<30 or 90 days) or early re‐admissions (<30 days). The average number of risk factors was 2.12, and 98 patients (90%) had at least 1 risk factor in their medical history.ConclusionsThe modifications proposed simplify procedural steps, limit unnecessary dissection and introduce a technique that ends the practice of connecting ischemic tissue. We believe this technique contributes to surgical durability and reduces the rate of postoperative leak and eliminates stricture.
Obesity is not associated with disease‐free interval, melanoma‐specific survival, or overall survival in patients with clinical stage IB‐II melanoma after SLNB
Authors: Deckers Eric A. , Kruijff Schelto , Bastiaannet Esther , van Ginkel Robert J. , Hoekstra‐Weebers Josette E. H. M. , Hoekstra Harald J. 
Published: June 2021

AbstractBackground and ObjectivesClinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma.MethodsProspectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS).ResultsOf the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated.ConclusionObesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB.
The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis
Authors: Wang Hong‐Wei , Wang Li‐Jun , Jin Ke‐Min , Bao Quan , Li Juan , Wang Kun , Xing Bao‐Cai 
Published: June 2021

AbstractBackgroundSurgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score.MethodsR1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0–3) and high‐risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence‐free survival rate (RFS) were examined.ResultsIn total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection.ConclusionThe prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.
Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models‐An initiative of the ORSspine section
Authors: Gullbrand Sarah E. , Ashinsky Beth G. , Lai Alon , Gansau Jennifer , Crowley James , Cunha Carla , Engiles Julie B. , Fusellier Marion , Muehleman Carol , Pelletier Matthew , Presciutti Steven , Schol Jordy , Takeoka Yoshiki , Yurube Takashi , Zhang Yejia , Masuda Koichi , Iatridis James C. 
Published: June 2021

AbstractBackgroundThe rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models.AimsThe purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.Materials and MethodsThe scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors.ResultsThe final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus.DiscussionOverall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field.ConclusionThis study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.
Determination of eight endocrine disruptor pesticides in bovine milk at trace levels by dispersive liquid‐liquid microextraction followed by GC‐MS determination
Authors: Sharma Nisha , Thakur Pragati , Chaskar Manohar G. 
Published: June 2021

AbstractEndocrine disrupting chemicals are chemicals that interfere with any aspect of the endocrine system. Several natural and synthetic chemicals, including pesticides, have been identified as endocrine disruptors, which potentially inhibit the reproductive activity of the hormonal system. The pervasive occurrence with trace level concentrations and extensive variety are the reported characteristics of these chemicals.In this study, a dispersive liquid‐liquid microextraction method coupled with gas chromatography and mass spectrometry for the determination of eight potential endocrine disruptor pesticides (Lindane, Diazinon, Fenitrothion, Malathion, Aldrin, α‐Endosulfan, β‐Endosulfan, Methoxychlor) in bovine milk samples was developed. Several parameters that can influence the extraction efficiency were studied. Under optimized conditions, the calibration curves of all eight analytes presented coefficient of determination higher than 0.998 (range level of 2.0‐1000 ng/mL). The limits of detection and quantification ranged from 0.90 to 5.00 ng/mL and 2.50 to 15.0 ng/mL, respectively.