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LFA-1 antagonist (BIRT377) similarly reverses peripheral neuropathic pain in male and female mice with underlying sex divergent peripheral immune proinflammatory phenotypes

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Neuroimmunology and Neuroinflammation 2019年第7期6卷 12-43页

作者： Shahani Noor Melody S.Sun Arden G.Vanderwall Mara A.Havard jacob e.sanchez Nathan W.Harris Monique V.Nysus Jeffrey P.Norenberg Harrison T.West Carsten R.Wagner Lauren L.Jantzie Nikolaos Mellios erin D.Milligan Department of Neurosciences School of MedicineUniversity of New MexicoAlbuquerqueNM 87131USA Department of Anesthesiology and Critical Care University of New MexicoAlbuquerqueNM 87131USA Department of Pediatrics and Neurology Johns Hopkins University School of MedicineBaltimoreMD 21205-2196USA Department of Radiopharmaceutical Sciences College of PharmacyNew Mexico Center for Isotopes in MedicineUniversity of New MexicoAlbuquerqueNM 87131USA Department of Medicinal Chemistry University of MinnesotaCollege of PharmacyMinneapolisMN 55455USA

Aim:The majority of preclinical studies investigating aberrant glial-neuroimmune actions underlying neuropathic pain have focused on male rodent ***,studies have shown peripheral immune cells play a more prominent role than glial cells in mediating pathological pain in ***,we compared the onset and duration of allodynia in males and females,and the anti-allodynic action of a potentially novel therapeutic drug(BIRT377)that not only antagonizes the action of lymphocyte function-associated antigen-1(LFA-1)to reduce cell migration in the periphery,but may also directly alter the cellular inflammatory ***:Male and female mice were subjected to peripheral nerve injury chronic constriction injury(CCI)applying two methods,using either 4-0 or 5-0 chromic gut suture material,to examine potential sex differences in the onset,magnitude and duration of *** sensitivity before and after CCI and application of intravenous BIRT377 was *** and spinal tissues were analyzed for protein(multiplex electrochemiluminescence technology)and mRNA expression(quantitative real-time PCR).The phenotype of peripheral T cells was determined using flow ***:Sex differences in proinflammatory CCL2 and IL-1βand the anti-inflammatory IL-10 were observed from a set of cytokines analyzed.A profound proinflammatory T cell(Th17)response in the periphery and spinal cord was also observed in neuropathic ***377 reversed pain,reduced IL-1βand TNF,and increased IL-10 and transforming growth factor(TGF)-β1,also an anti-inflammatory cytokine,in both ***,female-derived T cell cytokines are transcriptionally regulated by BIRT377,as demonstrated by reducing proinflammatory IL-17A production with concurrent increases in IL-10,TGF-β1 and the anti-inflammatory regulatory T cell-related factor,***:This study supports that divergent peripheral immune and neuroimmune responses during neuropathy exists between males and

关键词： Neuropathic pain glia neuroimmune peripheral immune T cells

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Targeting sepsis through inflammation and oxidative metabolism

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World Journal of Critical Care Medicine 2025年第1期14卷 69-81页

作者： Salena jacob Sanjana Ann jacob Joby Thoppil Halmos College of Arts and Sciences Nova Southeastern UniversityFort LauderdaleFL 33328United States Dell School of Medicine University of Texas at Austin Medical SchoolAustinTX 78712United States emergency Medicine UT Southwestern Medical CenterDallasTX 75390United States

Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic *** is characterized by a dysregulated immune response to *** shock is the most severe form of sepsis which leads to distributive shock and high mortality *** have been significant advances in sepsis management mainly focusing on early identification and ***,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick *** limitations have underscored the modest progress in reducing sepsis-related *** review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.

关键词： Sepsis Inflammation Oxidative Metabolism Infection Reactive oxygen species

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The effects of local variations in conditions on carbon storage and release in the continental mantle

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National Science Review 2024年第6期11卷 22-36页

作者： Stephen F.Foley Chunfei Chen Dorrit e.jacob School of Natural Sciences Macquarie University Research School of earth Sciences Australian National University State Key Laboratory of Geological Processes and Mineral Resources School of Earth Sciences China University of Geosciences

Recent advances indicate that the amount of carbon released by gradual degassing from the mantle needs to be revised upwards, whereas the carbon supplied by plumes may have been overestimated in the *** in rock types and oxidation state may be very local and exert strong influences on carbon storage and release mechanisms. Deep subduction may be prevented by diapirism in thick sedimentary packages,whereas carbonates in thinner sequences may be subducted. Carbonates stored in the mantle transition zone will melt when they heat up, recognized by coupled stable isotope systems(e.g. Mg, Zn, Ca). There is no single ‘mantle oxygen fugacity’, particularly in the thermal boundary layer(TBL) and lowermost lithosphere, where very local mixtures of rock types coexist. Carbonate-rich melts from either subduction or melting of the uppermost asthenosphere trap carbon by redox freezing or as carbonate-rich dykes in this zone. Deeply derived, reduced melts may form further diamond reservoirs, recognized as polycrystalline diamonds associated with websteritic silicate minerals. Carbon is released by either edge-driven convection,which tears sections of the TBL and lower lithosphere down so that they melt by a mixture of heating and oxidation, or by lateral advection of solids beneath rifts. Both mechanisms operate at steps in lithosphere thickness and result in carbonate-rich melts, explaining the spatial association of craton edges and carbonate-rich magmatism. High-pressure experiments on individual rock types, and increasingly on reactions between rocks and melts, are fine-tuning our understanding of processes and turning up unexpected results that are not seen in studies of single rocks. Future research should concentrate on elucidating local variations and integrating these with the interpretation of geophysical signals. Global concepts such as average sediment compositions and a uniform mantle oxidation state are not appropriate for small-scale processes; an increa

关键词： lithospheric mantle carbonate melts deep carbon cycle craton destruction continental rifts

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Spectroscopic studies of gel-grown lanthanum malonate crystals

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Journal of Rare earths 2012年第3期30卷 245-249页

作者： Varghese Mathew Sabu jacob Lizymol Xavier K.e.Abraham Department of Physics St.Aloysius'CollegeEdathua-689573India Department of Physics S.B.CollegeChanganacherry-686101India

Lanthanum malonate crystals were grown by single tube ionic diffusion through silica gel. The crystallinity of the grown crystals was analyzed by powder X-ray diffraction studies. Fourier transform infrared spectroscopy （FTIR） and fourier transform （FT） Raman studies confirmed the presence of functional groups in the title compound. The optical band gap energy of the material was extracted from diffuse reflectance spectrum.

关键词： lanthanum malonate crystal growth X-ray diffraction analysis DRS studies FTIR and FT Raman studies rare earths

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Hepatitis C infection and lymphoproliferative disease:Accidental comorbidities?

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World Journal of Gastroenterology 2014年第43期20卷 16197-16202页

作者： Tawfik Khoury Shmuel Chen Tomer Adar e Ollech jacob Meir Mizrahi Department of Internal Medicine Hebrew University-Hadassah Medical CenterJerusalemIL 91120Israel Institute for Gastroenterology and Liver Disease Hebrew University-Hadassah Medical CenterJerusalemIL 91120Israel

Chronic hepatitis C virus(HCV)infection has been associated with liver cancer and cirrhosis,autoimmune disorders such as thyroiditis and mixed cryoglobulinema,and alterations in immune function and chronic inflammation,both implicated in B cell lymphoproliferative diseases that may progress to non-Hodgkin lymphoma(NHL).HCV bound to B cell surface receptors can induce lymphoproliferation,leading to DNA mutations and/or lower antigen response *** findings and epidemiological reports suggest an association between HCV infection and *** performed a systematic review of the literature to clarify this potential *** searched the english-language literature utilizing Medline,embase,Paper First,Web ofScience,Google Scholar,and the Cochrane Database of Systematic Reviews,with search terms broadly defined to capture discussions of HCV and its relationship with NHL and/or lymphoproliferative *** were screened to further identify relevant studies and literature in the basic sciences.A total of 62 reports discussing the relationship between HCV,NHL,and lymphoproliferative diseases were *** studies suggest that at least a portion of NHL may be etiologically attributable to HCV,particularly in areas with high HCV *** that showed a lack of association between HCV infection and lymphoma may have been influenced by small sample size,short follow-up periods,and database *** association appears strongest with the B-cell lymphomas relative to other lymphoproliferative *** by which chronic HCV infection promotes lymphoproliferative disease remains *** is a multifactorial process involving genetic,environmental,and infectious *** most probably have a role in the lymphomagenesis but further study to clarify the association and underlying mechanisms is warranted.

关键词： Blood Hepatitis C infection Non-Hodgkin’ s lymphoma Pathogenesis Treatment

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Azathioprine-induced fever in autoimmune hepatitis

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World Journal of Gastroenterology 2013年第25期19卷 4083-4086页

作者： Tawfik Khoury jacob e Ollech Shmuel Chen Meir Mizrahi Meir Shalit Departments of Internal Medicine Hadassah-Hebrew University Medical Center Departments of Gastroenterology and Hepatology Gastroenterology and Liver Disease Institute Hadassah-Hebrew University Medical Center Jerusalem

Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient's fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause druginduced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the bestof our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis.

关键词： Autoimmune hepatitis Adverse drug reactions Azathioprine Drug fever

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Systematic review of dynamization vs exchange nailing for delayed/non-union femoral fractures

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World Journal of Orthopedics 2018年第7期9卷 92-99页

作者： jacob e Vaughn Ronit V Shah Tarek Samman jacob Stirton Jiayong Liu Nabil A ebraheim College of Medicine and Life Sciences University of Toledo Department of Orthopedic Surgery University of Toledo Medical Center

AIM To analyze the literature on efficacy of dynamamization vs exchange nailing in treatment of delayed and nonunion femur *** Ultimately, 31 peer-reviewed articles with 644 exchanged nailing patients and 131 dynamization patients were identified and analyzed. The following key words were inputted in different combinations in order to search the field of publications in its entirety: "nonunion", "delayed union", "ununited", "femur fracture", "femoral fracture", "exchange nailing", "dynaiz(s)ation", "secondary nailing", "dynamic", "static", and "nail revision". The initial search yielded over 150 results, and was refined based on the inclusion criteria: Only studies reporting on humans, non-unions and delayed unions, and the usage of exchange nailing and/or dynamization as a secondary treatment after failed IM nailing. The resulting 66 articles were obtained through online journal access. The results were filtered further based on the exclusion criteria: No articles that failed to report overall union rates, differentiate between success rates of their reported techniques, or articles that analyzed less than 5 patients. ReSULTS exchange nailing lead to fracture union in 84.785% of patients compared to the 66.412% of dynamization with statistically comparable durations until union(5.193 ± 2.310 mo and 4.769 ± 1.986 mo respectively). Dynamically locking exchange nails resulted in an average union time of 5.208 ± 2.475 mo compared to 5.149 ± 2.366 mo(P = 0.8682) in statically locked exchange nails. The overall union rate of the two procedures, statically and dynamically locked exchange nailing yielded union rates of 84.259% and 82.381% respectively. Therefore, there was no significant difference between the different locking methods of exchange nailing for union rate or time to union at a significance value of P e analysis showed exchange nailing to be the more successful choice in the treatment of femoral non-unions in respect to its higher succ

关键词： Non-union Delayed union Dynamization Femoral fracture exchange nailing

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Leisure-time physical activity,anthropometrics,and body composition as predictors of quality of life domains after spinal cord injury:an exploratory cross-sectional study

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Neural Regeneration Research 2022年第6期17卷 1369-1375页

作者： Melody N.Mickens Paul Perrin jacob A.Goldsmith Refka e.Khalil William e.Carter III Ashraf S.Gorgey Division of Physical Medicine and Rehabilitation University of Utah School of MedicineSalt Lake CityUTUSA Department of Psychology Virginia Commonwealth UniversityRichmondVAUSA Spinal Cord Injury&Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Physical Medicine and Rehabilitation Virginia Commonwealth University School of MedicineRichmondVAUSA

The objective of the current work was to examine the relationships between quality of life(QOL)domains in persons with spinal cord injury(SCI)and their levels of weekly leisure-time physical activity(LTPA),anthropometric variables,and body composition *** exploratory cross-sectional study consisted of baseline data collected as part of a randomized clinical trial at a VA Medical Center and SCI center.A convenience sample of 36 community-dwelling persons with SCI participated in the current *** measures included the World Health Organization Quality of Life Short Form(WHOQOL-BReF),Leisure-Time Physical Activity Questionnaire for People with Spinal Cord Injury(LTPAQ-SCI),anthropomorphic measures(waist,hip,and abdominal circumference),and dual-energy x-ray absorptiometry(DXA)to quantify regional and total body *** regression models suggested that engagement in LTPA accounted for 35.7%of the variance in physical health QOL,33.5%in psychological QOL,14.2%in social relationships QOL,and 38.2%in environmental *** measures accounted for 11.3%,3.1%,12.0%,and 6.7%of the variance in these QOL indices,respectively,and DXA indices accounted for 18.7%,17.5%,27.4%,and 21.9%.Within these models,the number of minutes of heavy LTPA per day uniquely predicted physical health QOL,the number of mild LTPA days per week uniquely predicted psychological QOL,and the amount of mild LTPA per day uniquely predicted environmental *** analyses also suggested that android and trunk fat,as well as supine waist and abdominal circumferences,were positively associated with social relationships *** individuals with SCI to engage in LTPA may robustly enhance multiple aspects of QOL while reducing the risk for cardiovascular and metabolic morbidities associated with ***,this may lead to a further understanding of how QOL may impact longitudinal intervention *** study protocol and procedures were reviewed and appro

关键词： anthropometrics body composition dual-energy-x-ray absorptiometry exercise physical activity quality of life spinal cord injury

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evaluation of the 20 L dust explosibility testing chamber and comparison to a modified 38 L vessel for underground coal

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International Journal of Mining Science and Technology 2018年第6期28卷 885-890页

作者： Robert eades Kyle Perry Catherine Johnson jacob Miller Department of Mining and Nuclear engineering Missouri University of Science and Technology

The phenomenon of combustible dust explosions is present within many industries. Tests for explosibility of dust clouds per ASTM e1226 use a 20 L explosive chamber that places the combustible dust directly below the dispersion nozzle which generates a thorough mixture for testing purposes. However, in the underground coal mining industry, there are a number of geologic, mining, and regulatory factors that change the deposition scheme of combustible coal dust. This causes the atmosphere of a coal mine to have a variable rock dust-coal dust mixture at the time of ignition. To investigate the impact of this variable atmosphere, a series of lean explosibility tests were conducted on a sample of Pittsburgh Pulverized coal dust. These explosibility tests were conducted in a 38 L chamber with a 5 kJ Sobbe igniter. The 38 L chamber generates a variable air-dust mixture prior to ignition. The test results indicate that the 38 L chamber experiences reduced explosive pressures, and lower explosibility index values when compared to the 20 L chamber.

关键词： Dust explosion Coal mining Coal dust explosibility testing

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endemics and endangered species in the biodiversity hotspot of the Shada Mountains, Saudi Arabia

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Journal of Arid Land 2017年第1期9卷 109-121页

作者： jacob THOMAS Mohamed A eL-SHeIKH Abdulrehman A ALATAR Department of Botany & Microbiology College of Science King Saud University Riyadh 11451 Saudi Arabia Botany Department Faculty of Science Damanhour University Damanhour 22516 Egypt

Shada Mountains in Saudi Arabia, separated by Maleel Wadi into twin mountains（i.e., Shada Alalah and Shada Asfal）, are rich in biodiversity. We investigated the diversity of endemics and endangered species of the mountains based on the data collected from 38 stands falling in 8 elevational zones ranging from 500 to 2215 m a.s.l. Results indicated that 495 plant species falling in 314 genera and 76 families occurred in the Shada Mountains, including 19 endemic species and 43 endangered species, and accounting for 22% of the total flora in Saudi Arabia. Canonical correlation analysis indicated that physiographic features, particularly altitude play an important role in the frequency and abundance of species. endemics were not evenly distributed in the Shada Mountains and mostly restricted in the elevation zone of 1000–1500 or ＆gt;1500 m a.s.l. When the altitude reached up to 2000 m a.s.l., the endemics decreased substantially due to the significantly low temperature. The endangered species existed three different distribution patterns：（i） most endangered species distributed in the altitudes of 1000–1800 m a.s.l.;（ii） endangered trees, lianas, and shrubs occupied the altitudes 1000–1300 m a.s.l.; and（iii） endangered subshrubs and herbs inhabited the altitudes 1500–2100 m a.s.l. The results demonstrated that the biodiversity of endangered species in the Shada Mountains is high and undisturbed by invasive species, and protective measures should be taken against human disturbances to the small-scale hotspot.

关键词： elevational gradient invasion Shada Alalah Shada Asfal Wadi Jof

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