bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential synthesis and release of IL-18 and its antagonist, IL-18 binding protein, from human platelets (CCR4P.209)
Authors: Ahmad Ali , Allam Ossama , Aldbah Zainab , Samarani Suzanne , Sagala Patrick 
Published: December 2022

Abstract
IL-18 is a multifunctional pro-inflammatory cytokine belonging to the IL-1 family. The cytokine is known to be produced from macrophages, dendritic cells, keratinocytes, adrenal cortex etc in the human body. We found that the cytokine as well as its antagonist, IL-18 Binding Protein (IL-18BP), are produced in human platelets. Interestingly, the two of them are synthesized and released differentially from these anuclear cellular elements. Human platelets contain transcripts for the cytokine and synthesize it de novo upon activation as an inactive precursor protein, which is cleaved into mature form by activated caspase 1, whose activation occurs in activated platelets. The platelets continue to release IL-18 over several hours after activation. Freshly isolated resting platelets as well as paraformaldehyde-fixed ones contain very little IL-18. In a sharp contrast to IL-18, its antagonist (IL-18BP) is present pre-made in platelets and is released upon their activation. Platelets contain no transcripts for it and do not synthesize de novo upon activation. Freshly isolated resting platelets as well as paraformaldehyde-fixed platelets contain IL-18BP. Furthermore we found that the two soluble mediators are secreted from platelets via different mechanisms: glyburide inhibits synthesis of active IL-18 but not of IL-18BP from activated human platelets. Our findings bear important implications for a variety human diseases which are accompanied by chronic inflammation.
Identification and characterization of a novel inflammatory DC precursor (HEM5P.235)
Authors: Rogers Peter , Schwartz Elizabeth 
Published: December 2022

Abstract
DC differentiated through culture with GM-CSF are used in many clinically promising applications including vaccines. However, the developmental timeline during which specific stimulatory or immunosuppressive functions are acquired by these cells is poorly understood. Here, we developed a method of isolating progenitor populations at specific stages of development to monitor their phenotype and function. Bone marrow cells were cultured in GM-CSF for three days, then sorted based on Ly6c and CSF-1R (CD115) expression, two hallmarks of myeloid cell development. We then monitored the developmental progression and differentiation of each population based on the expression of these proteins as well as several other hallmarks of the dendritic cell phenotype. We measured their gene expression profiles by qRT-PCR and their response to inflammatory stimuli at each stage of development. Through this analysis, we have identified five distinct cell types representative of Common Myeloid Progenitors (CMP), Granulocyte Macrophage Progenitors (GMP), Monocytes, inflammatory DC (iDC), and a novel dendritic cell precursor which is phenotypically and functionally distinct from previously described myeloid cells. Our findings suggest this novel cell type, Inflammatory DC precursor (IDP), arises from monocytes and serves as an immediate precursor to immature inflammatory DCs. These studies will aid in the refinement of protocols to acquire cells for specific clinical applications.
Pharmacological targeting of luteinizing hormone-releasing hormone receptor promotes survival after lethal irradiation (HEM5P.222)
Authors: Velardi Enrico , Tsai Jennifer , Young Lauren , Lieberman Sophie , Gupta Jyotsna , Dudakov Jarrod , Van Den Brink Marcel 
Published: December 2022

Abstract
Sex steroid inhibition (SSI) is a well-described strategy to promote lymphopoiesis in the bone marrow and thymus of aged and immunodepleted mice. Although the precise mechanisms underlying this regenerative effect are unclear, there is increasing evidence that sex hormones can have a profound impact on hematopoietic stem cell (HSC) function. Here we show that SSI induced by a novel class of Luteinizing Hormone-Releasing Hormone Receptor antagonist (LHRH-Ant) protected both male and female mice from BM failure, increased the recovery of myeloid and lymphoid compartments, and ultimately promoted overall mouse survival when administered 24 hours after lethal total body irradiation (LTBI). Underlying this, we could demonstrate both phenotypically and functionally that LHRH-Ant spared HSCs from radiation-induced depletion and induced HSCs into cell cycle, thereby promoting hematopoiesis. Intriguingly, use of an LHRH agonist, which causes an initial surge in sex steroids, also mediated enhanced survival from LTBI but surgical castration did not, suggesting that the benefit of SSI is not mediated by the sex steroids themselves but rather by upstream regulators such as LH. Consistent with this, irradiated mice receiving LHRH-Ant and treated daily with LH were no longer protected from radiation injury. Taken together these data not only reveal a novel mechanism that regulates HSC function, but also offer a therapeutic approach to regenerate hematopoiesis after radiation exposure.
An essential role for Birc5 in innate lymphocyte development (HEM5P.223)
Authors: Beaulieu Aimee , Sun Joseph 
Published: December 2022

Abstract
NK cells and innate lymphoid cells (ILCs) are two important classes of innate lymphocytes, and both have essential roles in early immune responses. NK cells provide systemic protection against viruses and cancer, while ILCs defend against a broad range of pathogens, including viruses, helminths, and bacteria, particularly at barrier organs such as the lung, gut, and skin. The molecular pathways that regulate innate lymphocyte development and function are an area of active investigation. Here we show that the inhibitor of apoptosis (IAP) protein, Birc5, is essential for the development of NK cells and ILC subsets. We observed high expression of Birc5 in NK cell and ILC precursor populations in the bone marrow, and consistent with a non-redundant role for Birc5 in innate lymphocyte development, steady-state populations of NK cells and ILCs were severely reduced in mice with cell-specific deletions of the Birc5 gene. BrdU-labeling experiments indicated an important role for Birc5 in cell cycle progression in developing innate lymphocytes in the bone marrow. Moreover, Birc5-deficient NK cells in the peripheral organs of these mice exhibited a maturation defect. Together, these findings highlight a new and crucial role for Birc5 in the proliferation and maturation of developing innate lymphocytes.
Regulation of NK cell maturation by the intramembrane protease SPPL3 (HEM5P.224)
Authors: Hamblet Corinne , Makowski Stefanie , Tritapoe Julia , Pomerantz Joel 
Published: December 2022

Abstract
Natural killer (NK) cells play an essential role in tumor surveillance through direct tumor cell lysis. Signal peptide peptidase-like 3 (SPPL3) is a highly conserved intramembrane aspartyl protease, but very little is known about its functions in vivo. We developed an SPPL3 conditional knockout mouse and found that deletion of SPPL3 within the hematopoietic system using Vav1-iCre resulted in a peripheral defect in NK cell number. The reduced NK cell population was hypofunctional in tumor clearance in vivo and direct tumor lysis in vitro. Analysis of SPPL3-deficient NK cells revealed a substantial block in terminal maturation, at the CD27+CD11b- stage. Deletion of SPPL3 in NK cells by NKp46-iCre confirmed a cell-autonomous requirement for SPPL3 in NK development and function. CRISPR/Cas9 genome editing was used to create a knockin mouse expressing a protease-dead SPPL3 knockin allele, D271A. NK cells expressing SPPL3 D271A exhibited the same block in terminal differentiation as SPPL3-deficient NK cells. Our results reveal that the proteolytic function of the SPPL3 intramembrane protease is critical for normal NK cell maturation at a checkpoint that regulates the transition from CD11b- to CD11b+ cells.
Influenzal Antibodies in Lymphocytes of Rabbits Following the Local Injection of Virus
Authors: Harris Susanna , Harris T. N. 
Published: December 2022

Summary
Following the injection of inactivated influenzal virus into the foot-pad of the rabbit antibodies to the viral protein can be found in the popliteal lymphnode, which drains the site of injection, and in lymph obtained from the efferent lymphatic vessel of that node. These antibodies are found earlier in the local lymphatic system that in the serum and in higher titer until the 4th day after the injection. Thereafter the serum-titer rises above that in the lymphatic tissues.
At the same time there is a burst of activity in the local lymphatic tissue. There is marked enlargement of the lymphnode, almost entirely of cortical tissue. This consists of diffuse lymphocytic hyperplasia which very soon becomes organized into the conventional follicular structure of lymphnodes. The absolute and relative count of lymphocytes in the lymph emerging from the popliteal lymphnode rises sharply.
Injection of serologically distinct strains of influenzal virus into the two legs of individual rabbits give results which corroborate the specificity of the antibodies produced.
On separation of lymph emerging from the popliteal lymphnode into cells and plasma and testing each for antibody-content, it is found that the titer of antibody in the lymph-cells exceeds that in the lymph-plasma, by ratios as high as 16:1. This ratio is found to be highest at the time when the rate of increase of antibody-content of the local lymphatic system is greatest.
These findings are interpreted to mean that the lymphocyte can be a primary source, or site of final synthesis, of antibodies to viral protein. This conclusion is in keeping with those of earlier studies in which a similar role was demonstrated for the lymphocyte in the formation of antibodies to bacterial and cellular antigens.
Immunologic Studies of Japanese Encephalitis Virus in Japan
Authors: Scherer William F. , Kitaoka Masami , Grossberg Sidney E. , Okuno Takeshi , Ogata Takayuki , Chanock Robert M. 
Published: December 2022

Summary
Following inapparent infection by Japanese encephalitis virus in August and September 1956, 14 children without preexisting JE virus neutralizing antibody, developed a primary hemagglutination-inhibition antibody response by November; 13 of the 14 children formed neutralizing antibody and 11 of 14 children developed complement fixing antibody. Neutralizing antibody usually appeared concurrently with HI antibody, though in some children it appeared before or after HI antibody.
Inapparent “reinfections” by JE virus occurred during August and September 1956 in seven children with preexisting neutralizing antibody in plasma. The HI and neutralizing antibody responses were similar in time of occurrence and frequency to those seen in the 14 children without preexisting neutralizing antibody; however, complement fixing antibody more promptly and uniformly rose to detectable levels in the “reinfected” children than in the group with primary infection. Although the exact mechanism of antibody stimulation following “reinfection” of humans by JE virus is uncertain, this phenomenon may play a role in Japan in maintenance of JE virus antibody levels and immunity in humans and possibly in animals.
Maximal HI antibody titers that develop within two months of inapparent infection were lower than those usually found after overt Japanese encephalitis. Contrariwise CF antibody did not display a difference in maximal titers. Neutralizing, CF and HI antibodies persisted at detectable levels in plasma and serum for different periods of time after inapparent infection (neutralizing for many years, CF for at least 5–6 weeks but less than 9 months, and HI for years in many persons.)
Immunologic Studies of Japanese Encephalitis Virus in Japan
Authors: Buescher Edward L. , Scherer William F. , Rosenberg Murray Z. , Kutner Leon J. , McClure H. Elliott 
Published: December 2022

Summary
Maternal antibodies reacting with JE virus were found in newly hatched domestic chicks and wild birds near Tokyo, Japan. The neutralization test detected these antibodies more frequently than the hemagglutination-inhibition test; in wild birds of the family Ardeidae, an average of only 25% of birds with maternal neutralizing antibody during the first 15 days of life were positive at 1:10 plasma dilution by HI test. Neutralizing antibody disappeared below detectable levels (log neutralization index less than 1.0) in half the ardeids by 5–15 days after hatching and in all birds by 21–30 days. Maternal neutralizing antibody in chicks prevented viremia upon challenge with JE virus, but did not affect viremia from WEE virus. In ardeids, maternal antibody apparently prevented infection by JE virus in one bird but not in another, suggesting that some ardeid hens have specific antibody to JE virus and others have nonspecific “antibody”. This observation is compatible with summer infection of some ardeids with JE virus in Japan and winter infection of others with immunologically-related Group B arthropod-borne viruses in southeast Asia. Nevertheless after maternal antibody becomes undetectable, ardeids and chicks are fully susceptible to JE virus.
Specific and Cross Reactions by Complement Fixation with Boston Exanthem Disease Virus (ECHO-16)
Authors: Neva Franklin A. , Malone Mary F. 
Published: December 2022

Summary
Satisfactory complement fixing antigens were prepared from strains of Boston exanthem viruses by the concentration of fluids from infected tissue cultures. CF antibody responses were readily demonstrated in patients infected with these agents. No definite antigenic differences were found between the viruses isolated from several exanthem disease patients, when the agents were studied by the complement fixation reaction. However, cross reactions to these exanthem virus antigens were observed on study of sera from patients with certain Coxsackie and certain heterologous ECHO virus infections.
Immunological Studies of Anthrax
Authors: DeArmon Ira A. , Klein Frederick , Lincoln Ralph E. , Mahlandt Bill G. , Fernelius Albert L. 
Published: December 2022

Summary
Immunized and nonimmunized guinea pigs, rats and mice given graded challenge doses of Bacillus anthracis spores were compared. The reciprocal of time-to-death was found to be linearly related to log10 challenge dose over a reasonable range of doses, and, therefore, a difference in position of the parallel regression lines represented a difference in response of control and immunized animals. This difference in position of regression lines is the log increase in dose required to cause the immunized group to give the same response as the control. This log increase is called the mean Immunity Index. The mean index of an immunized population of guinea pigs was 3.2. The distribution of individuals in the control and immunized groups overlapped and thus it was concluded the variability of response of immunized guinea pigs was greater than the control animals, and that only 46% of the immunized population had a significant protection against B. anthracis challenge.
Preparation and Properties of Antibodies to Sheep Erythrocytes
Authors: Amiraian Kenneth , Leikhim Edward J. 
Published: December 2022

Summary
The use of anion-exchange chromatography for purification of rabbit antisheep hemolysin (γ1) is confirmed. The technique is extended to the purification of γ2 hemolytic and agglutinating antibodies. The latter types of antibodies have been digested with papain and some immunologic properties of the fragments so derived are reported.
Purification of Complement-Fixing Antigen of Rickettsia Orientalis
Authors: Kobayashi Yuzuru , Tachibana Nobuyoshi 
Published: December 2022

Summary
A stable complement-fixing antigen of Rickettsia orientalis, free of anti-complementary substance, was obtained by sodium deoxycholate (DCA) sucrose extraction of yolk sac suspensions previously treated with Amberlite XE-64.
The optimum concentration of DCA, 1.0% in 0.25 M sucrose solution, yielded an antigen containing approximately one tenth of the nitrogen of the material extracted by sucrose alone without any change in the complement fixation titer of antigen.
The DCA-extracted antigen was stable on storage at -70°C for periods of 5 months or more.
The Heterogeneity of Combining Sites of Antibodies as Determined by Specific Immunoadsorbents
Authors: Kitagawa Masayasu , Yagi Yasuo , Pressman David 
Published: December 2022

Summary
Anti-Xp antibodies were fractionated by adsorption on immunoadsorbents and elution with haptens.
Different types of immunoadsorbent and various programs of elution with either different concentrations of a particular hapten or different haptens were used. In several cases, the eluted antibody was evaluated further with respect to heterogeneity by re-fractionation.
Some anti-Xp antibodies adsorbed on Xp-RSA-PAS could be eluted by o-substituted benzoate (0.3 M). Others not eluted by the first procedure were eluted by m-substituted benzoate and still others were eluted only by p-substituted benzoate. The observed order of effectiveness of substituents on elution was p-NO2 &gt; p-Cl, m-NO2 &gt; m-Cl &gt; o-NO2 = o-Cl. There were some antibodies that were eluted by m-nitrobenzoate but not by p-chlorobenzoate and other that were eluted by p-chlorobenzoate but not by m-nitrobenzoate.
Very clear evidence was obtained that some of the antibodies could well accommodate an o-substituent on the hapten whereas other antibodies could not.
Each program of elution produced fractions with different properties. This indicated the heterogeneity of the original group of antibodies. However, each one of these fractions, when subjected to refractionation with a second program of elution, reflected the heterogeneity of the original population of antibody molecules going through this same second program.
The elution patterns were also characteristic of the immunoadsorbent. Almost all of the antibodies could be adsorbed on Xp-RSA-PAS, o-ClXp-RSA-PAS and m-NO2Xp-RSA-PAS but were eluted more easily by p-nitrobenzoate from the immunoadsorbents in the order, o-ClXp-, m-NO2Xp and Xp-RSA-PAS. X′-RSA-PAS and Xp-R-PAS failed to adsorb all antibodies and a part of the antibodies which were adsorbed was eluted more easily from these immunoadsorbents than from Xp-RSA-PAS.
The results provide evidence that some antibodies are directed not only to the haptenic group but also to the protein portion surrounding the haptenic group.
The amount of antibody was determined by labeling it with I131 or I125 and measuring the radioactivity. Effort and time could be saved and very close comparisons could be made by using the paired label technique in which one antibody fraction was labeled with I131 and the other labeled with I125 and the two passed simultaneously through the same column.
Financial Impact of Embedded Injury-Prevention Experts in US Army Initial Entry Training
Authors: Clifton Daniel R. , Nelson D. Alan , Sammy Choi Y. , Edgeworth Daniel , Shell Donald , Deuster Patricia A. 
Published: December 2022

Context
The US Army embedded injury-prevention experts (IPEs), specifically athletic trainers and strength and conditioning coaches, into initial entry training (IET) to limit musculoskeletal (MSK) conditions and their negative consequences. However, little is known about the financial impact of IPEs.

Objective
To assess whether IPEs were associated with fewer sunk training costs due to MSK-related early discharges from service.

Design
Retrospective cohort study.

Setting
Database of US Army soldiers’ administrative, medical, and readiness records.

Patients or Other Participants
A total of 198 166 soldiers (age = 20.7 ± 3.2 years, body mass index = 24.4 ± 3.5 kg/m2) who began IET during 2014 to 2017.

Main Outcome Measure(s)
Early discharge from service was defined as occurring within 6 months of beginning IET. All IET sites employed IPEs from 2011 to 2017, except for 2 sites during April to November 2015. Soldiers who began IET at these 2 sites during these times were categorized as not having IPE exposure. All others were categorized as having IPE exposure. The unadjusted association between IPE access and MSK-related early discharge from service was assessed using logistic regression. Financial impact was assessed by quantifying differences in yearly sunk costs between groups with and those without IPE exposure and subtracting IPE hiring costs.

Results
Among 14 094 soldiers without IPE exposure, 2.77% were discharged early for MSK-related reasons. Among 184 072 soldiers with IPE exposure, 1.01% were discharged. Exposure to IPEs was associated with reduced odds of MSK-related early discharge (odds ratio = 0.36, 95% CI = 0.32, 0.40, P &lt; .001) and a decrease in yearly sunk training costs of $11.19 to $20.00 million.

Conclusions
Employing IPEs was associated with reduced sunk costs because of fewer soldiers being discharged from service early for MSK-related reasons. Evidence-based recommendations should be developed for guiding policy on the roles and responsibilities of IPEs in the military to reduce negative outcomes from MSK conditions and generate a positive return on investment.
Diagnostic dilemma in a patient with chronic non–healing ulcer on leg
Authors: Vibhu Mendiratta , Amit Meena , Smita Singh 
Published: December 2022

Rationale:
Though cutaneous tuberculosis accounts for a small proportion of all tuberculosis cases, it becomes an important health issue considering its high prevalence in tropical countries. Due to its myriad clinical manifestations, it becomes difficult to diagnose and may pose a great diagnostic dilemma.

Patient concerns:
A 17-year-old male complaint of ulcerproliferative lesion on the left lower leg for 5 years. There was no history suggestive of tuberculosis. On cutaneous examination, single well-defined erosiocrustive plaque of size 14 cm × 13 cm with yellowish adherent crust presented over the left lower leg. The underlying surface shows ulceration after removing the crust.

Diagnosis:
Ulcerative Lupus vulgaris.

Interventions:
Anti-tubercular drug therapy (isoniazid, rifampicin, pyrazinamide and ethambutol).

Outcomes:
Lesion showed dramatic improvement after one month of anti-tubercular therapy.

Lessons:
Dermatologists should be aware of variable clinical presentations of cutaneous tuberculosis so as to diagnose it timely and correctly.