33:
441:, including metropolitan Toronto, and, most notably, has areas of high endemicity throughout northern Ontario. Remarkably high incidence is noted for some parts of the Kenora area and climatologically similar areas of northwestern Ontario. To the west, the range of endemic blastomycosis extends across southern Manitoba and into adjacent Saskatchewan. A few cases have been reported from north central Alberta, e.g., the Edmonton area, though in these cases an atypical genetic group of the fungus may be involved.
374:(sexual spores) are produced in small round reproductive sacs (asci). The ascospores, at 1.5โ2.0 ฮผm, are among the smallest reproductive particles produced by fungi, and are within the respirable size range. The budding yeast cells seen in infected tissues and bodily fluids are generally relatively large (c. 8โ15 ฮผm) and characteristically bud through a broad base or neck, making them highly recognizable to the pathologist. A small ("nanic") form is rarely seen with cells under 6 ฮผm.
54:
466:
by sacrifice of the animals when they appear ill or at the end of six weeks. The internal organs of the mice are then checked microscopically for evidence of blastomycosis. Needless to say, the cost and complexity of performing such studies is imposing, especially as the ethical clearance procedures for work involving animals become ever more involved. More direct and economical mycological techniques for environmental isolation, such as
366:(asexual spores). These conidia are probably the main infectious particles produced by the fungus. They form on individual short stalks and readily become airborne when the colony is disturbed; their size places them well within the respirable size range for particles, meaning that they can deposit deeply in the lungs when inhaled. Sexual reproduction by the fungus requires the meeting of colonies of + and โ
263:, a potentially very serious disease that typically begins with a characteristically subtle pneumonia-like infection that may progress, after 1โ6 months, to a disseminated phase that causes lesions to form in capillary beds throughout the body, most notably the skin, internal organs, central nervous system and bone marrow. The sexual form of this fungus was formerly known as
370:, probably a relatively rare event, and results in the production of small ascomata (sexual fruiting bodies) 200โ350 ฮผm, looking, to the naked eye, similar to a woollen fuzz ball, and in microscopic view consisting of a layer of spiralling, springy guard hairs surrounding a fertile core in which groups of 8
191:, an invasive and often serious fungal infection found occasionally in humans and other animals. It lives in soil and wet, decaying wood, often in an area close to a waterway such as a lake, river or stream. Indoor growth may also occur, for example, in accumulated debris in damp sheds or shacks. The fungus is
449:
antigens, while southern
African isolates lack the A antigen. Isolates from the middle east possess both antigens. The sub-Saharan African isolates differ in the laboratory from other isolates by being exceedingly difficult to convert to the yeast phase, and they also show some enzymatic distinctions.
517:
may associate in nature with one or more indigenous North
American mammalian host species. To date, however, all the animal species that have been subjected to focused investigation have been exonerated of this specific connection. Unsubstantiated suspicion has particularly focused on the beaver, but
382:
One of the unexplained regularities of nature is that there are several fungi of different phylogenetic ancestry that show a similar pattern of existence: dimorphism (conversion from a filamentous form in the environment to a yeast form in warm-blooded host tissues), virulent pathogenesis (ability to
342:
itself is a sexual organism, occurring in nature as both a + mating type and a โ mating type. This is epidemiologically important for two reasons: firstly, it implies that the organism will be genetically variable, potentially leading to variations in disease severity, treatment response and habitat
239:
and the Indian subcontinent. Though it has never been directly observed growing in nature, it is thought to grow there as a cottony white mold, similar to the growth seen in artificial culture at 25 ยฐC (77 ยฐF). In an infected human or animal, however, it converts in growth form and becomes
465:
has only been isolated from the environment 21 times. Most of these isolations have been based on the arduous isolation techniques involving the suspension of soil or other environmental materials in aqueous medium with antibacterial antibiotics, and injection of mice with these materials, followed
460:
is one of the most ecologically mysterious organisms causing human and animal disease. Prediction of disease risk and prevention of disease are both made extraordinarily difficult by our very poor understanding of where and how this organism normally grows in nature. Despite decades of attempts at
501:
tends to be associated with soils and wood debris in areas "characterized by an acidic pH, high organic content (due to rotting or decayed wood or vegetation and animal or bird droppings), abundant moisture, and proximity to waterways". Recent PCR detections, for example, concerned a
Kentucky dog
448:
occurs at low levels in various parts of Africa, from
Algeria to South Africa, as well as in and near the Arabian Peninsula. The African isolates are divided into two biologically different antigen groups: isolates from north of the Sahara are similar to North American isolates in having A and K
424:
is largely focused around the waterways of the St. Lawrence and
Mississippi River systems of North America. There is a widely distributed and much republished, partially erroneous map that shows the U.S. portion of this range accurately, inclusive of occurrence in Minnesota, Wisconsin, Ohio,
548:
Avoidance of exposure in endemic areas is the principal means of disease prevention. Because the agent is known to distribute in dusts, the minimization of dust-generating activities, such as digging, sweeping, etc., is key. Although a method of soil decontamination has been described and
343:
preference; secondly, it implies that a suitable, stable habitat must exist for the complex process of sexual reproduction to take place. This habitat is as yet unknown. In its asexual form, the fungus grows as a typical colonial microfungus, comparable to
478:
will grow readily from clinical samples on common laboratory media, the lack of success in isolating it from environmental materials is generally ascribed to the inhibitory effects of co-occurring common molds and antibiotic-resistant bacteria.
383:
cause a significant infection in an animal host that is otherwise in good health), pulmonary infectivity (infection mainly via the lungs) and sharply delimited endemism (occurrence in only a limited geographic range.).
1188:
Klein, Bruce S.; Vergeront, James M.; Weeks, Robert J.; Kumar, U. Nanda; Mathai, George; Varkey, Basil; Kaufman, Leo; Bradsher, Robert W.; Stoebig, James F.; Davis, Jeffrey P. (1986). "Isolation of
1098:
Ajello, L., and R. J. Weeks. 1983. Soil decontamination and other control measures. Pp. 229-238. In A. F. DiSalvo (ed.), Occupational
Mycoses. Lea and Febiger, Philadelphia, Pennsylvania.
851:
Dwight, P.J.; Naus, M; Sarsfield, P; Limerick, B (2000). "An outbreak of human blastomycosis: the epidemiology of blastomycosis in the Kenora catchment region of
Ontario, Canada".
425:
Kentucky, Arkansas, Tennessee, North and South
Carolina, the Virginias, Mississippi, Louisiana, and a few regions of states adjacent to those named. The Canadian range of
1549:
502:
kennel where 35 of 100 dogs had contracted blastomycosis. Previous isolations have been from comparable sites such as soil and wood debris from an abandoned
Wisconsin
1409:
Chaturvedi, VP; Randhawa, HS; Kini, S; Khan, ZU (1986). "Survival of
Blastomyces dermatitidis in the gastrointestinal tract of an orally infected insectivorous bat,
407:
279:
1150:
Baumgardner, DJ; Buggy, BP; Mattson, BJ; Burdick, JS; Ludwig, D (1992). "Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin".
433:
and the low endemicity in southeastern corner of Manitoba. Though the Quebec distribution is reasonably accurate, the rest of Canada is strongly misrepresented.
301:
289:
602:
Brown, Elizabeth M.; McTaggart, Lisa R.; Zhang, Sean X.; Low, Donald E.; Stevens, David A.; Richardson, Susan E.; Litvintseva, Anastasia P. (22 March 2013).
429:
shows an abundance of blastomycosis in broad areas north and south of the St. Lawrence River in Quebec, as well as high endemicity along the north shore of
522:
have also been focal points of interest, with no conclusive interspecies association being demonstrated to date. The closely related pathogenic fungus
338:": fungi that switch from a mold-like (filamentous) growth form in the natural habitat to a yeast-like growth form in the warm-blooded animal host.
755:
717:
Size-selective health hazard sampling. Pp. . In BS Cohen, CS McCammon (eds.), Air Sampling Instruments, 9th edition. ACGIH Press, Cincinnati, Ohio
1657:
1683:
362:
that penetrates the substratum on which it grows, and then after 3โ5 days of growth begins to reproduce asexually with small (2โ10 ฮผm)
1618:
549:
demonstrated to be effective, it uses hazardous chemicals and its use is best reserved for situations that cannot be managed otherwise.
1644:
1364:
Baumgardner, DJ; Summerbell, R; Krajden, S; Alexopoulou, I; Agrawal, B; Bergeson, M; Fuksa, M; Bemis, C; Baumgardner, MA (2005).
1561:
1734:
719:. Cincinnati, Ohio: in BS Cohen, CS McCammon (eds.), Air Sampling Instruments, 9th edition. ACGIH Press. pp. 93โ134.
739:
526:
in South America has a well substantiated, though not well understood, ecological link with the nine-banded armadillo,
486:
culture was gained via use of a novel enrichment broth technique. Recently, in an important breakthrough, a specific
1729:
1688:
585:
Bennett, John E. (2014). "Introduction to Mycoses". In John E. Bennett; Raphael Dolin; Martin J. Blaser (eds.).
1341:
1316:
395:
316:
919:
Sekhon, AS; Jackson, FL; Jacobs, HJ (1982). "Blastomycosis: report of the first case from Alberta Canada".
248:
once it is correctly diagnosed; however, delayed diagnosis is very common except in highly endemic areas.
494:
in three environmental samples from a dog kennel that had been experiencing problems with blastomycosis.
53:
1636:
1450:"Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado"
487:
1542:
665:
Untereiner, Wendy A.; Scott, James A.; Naveau, F.; Sigler, Lynne; Bachewich, J.; Angus, A. (2004).
1739:
164:
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310:
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is absent or nearly so from the Lake Erie area, but occurs sporadically on the north shore of
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8:
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334:. The three principal pathogens in this family are all grouped physiologically as "
331:
184:
115:
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335:
245:
1363:
1293:
1205:
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Lester, RS; DeKoven, JG; Kane, J; Simor, AE; Krajden, S; Summerbell, RC (2000).
1631:
1609:
95:
1506:
1426:
1386:
1365:
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1052:
588:
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
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188:
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1082:
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651:
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What has been learned from direct isolation and recent PCR studies is that
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1213:
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1032:
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in soil associated with a large outbreak of blastomycosis in Wisconsin".
962:
Frean, JA; Carman, WF; Crewe-Brown, HH; Culligan, GA; Young, CN (1989). "
519:
367:
345:
265:
125:
1447:
968:
South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde
667:"The Ajellomycetaceae, a new family of vertebrate-associated Onygenales"
1649:
932:
690:
608:, sp. nov. within the Human Pathogenic Fungus Blastomyces dermatitidis"
503:
371:
228:
105:
85:
231:. In addition, it occurs rarely in Africa both north and south of the
1675:
1408:
510:
was also accomplished from an earthen floor indoors on one occasion.
430:
220:
65:
1580:
1280:
Bradsher, RW (1987). "Water and blastomycosis: don't blame beaver".
850:
682:
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1449:
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359:
351:
200:
192:
995:"Enzymatic activity profiling as a potential biotyping method for
809:
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Baumgardner, DJ; Paretsky, DP (1999). "The in vitro isolation of
768:
363:
196:
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to parts of eastern North America, particularly boreal northern
204:
75:
1314:
513:
There has been a long history of justifiable speculation that
506:, and woody materials from a Wisconsin woodpile. Isolation of
244:. Blastomycosis is generally readily treatable with systemic
215:
and interconnected eastern mountain chains, the west bank of
227:
including the valleys of some major tributaries such as the
1448:
De Groote, MA; Bjerke, R; Smith, H; Rhodes III, LV (2000).
1226:
992:
918:
771:"Novel cases of blastomycosis acquired in Toronto, Ontario"
664:
730:
Kwon-Chung, K.J., Bennett, J.E.; Bennett, John E. (1992).
729:
570:
DiSalvo, A.F. (1992). Al-Doory, Y.; DiSalvo, A.F. (eds.).
1342:
10.1580/1080-6032(1996)007[0192:ltte]2.3.co;2
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877:
1489:
Vergara, ML; Martinez, R (1999). "Role of the armadillo
283:, which subsumes certain strains previously assigned to
1110:
377:
308:
Along with two other important human-pathogenic fungi,
1233:
from an earthen floor in southwestern Ontario, Canada"
358:
In nature, the fungus forms a network of thread-like
273:
In 2013, a second species was described in the genus
1053:"PCR-based detection of DNA from the human pathogen
810:
Kane, J; Righter, J; Krajden, S; Lester, RS (1983).
1576:
http://pathmicro.med.sc.edu/mycology/mycology-6.htm
1488:
1115:from a woodpile in north central Wisconsin, USA".
1106:
1104:
536:has no close relatives in the geographic range of
604:"Phylogenetic Analysis Reveals a Cryptic Species
1716:
1493:in the epidemiology of paracoccidioidomycosis".
490:technique was developed that was able to detect
1357:
1315:Gaus, DP; Baumgardner, DJ; Paretsky, D (1996).
1220:
1143:
1101:
461:isolating organisms from epidemiological foci,
1402:
1370:from native shrews in northern Wisconsin, USA"
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1044:
1042:
986:
812:"Blastomycosis: a new endemic focus in Canada"
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710:
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563:
561:
1558:Mycology Online ยง Dimorphic Fungal Pathogens
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1183:
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993:Summerbell, RC; Kane, J; Pincus, DH (1990).
754:: CS1 maint: multiple names: authors list (
723:
1482:
1227:Bakerspigel, A; Kane, J; Schaus, D (1986).
1039:
871:
251:
1415:Journal of Medical and Veterinary Mycology
1282:The American Review of Respiratory Disease
1089:
1051:Burgess, JW; Schwan, WR; Volk, TJ (2006).
912:
705:
558:
482:In just one experiment, a single positive
470:, have never yielded positive results for
355:mold forms commonly seen on mouldy bread.
287:. Three more species have been described:
31:
1541:at the U.S. National Library of Medicine
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1385:
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878:Vallabh, V; Martin, T; Conly, JM (1988).
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591:. Elsevier Health Sciences. p. 2874.
1560:. University of Adelaide. Archived from
1308:
1279:
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1329:Wilderness & Environmental Medicine
803:
714:
584:
569:
1717:
543:
387:is one of these fungi; the others are
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1584:
532:. This member of the mammalian order
816:Canadian Medical Association Journal
775:Canadian Medical Association Journal
378:Geographic distribution and variants
734:. Philadelphia: Lea & Febiger.
572:Ecology of Blastomyces dermatitidis
13:
853:Canada Communicable Disease Report
14:
1751:
1532:
1321:from rectal cultures of beaver (
1237:Journal of Clinical Microbiology
1129:10.1111/j.1365-280x.1999.00214.x
1003:Journal of Clinical Microbiology
52:
1411:Rhinopoma hardwickei hardwickei
1325:) from north central Wisconsin"
1194:New England Journal of Medicine
1015:10.1128/jcm.28.5.1054-1056.1990
884:The Western Journal of Medicine
880:"Blastomycosis in Saskatchewan"
578:
1:
1249:10.1128/jcm.24.5.890-891.1986
552:
396:Paracoccidioides brasiliensis
317:Paracoccidioides brasiliensis
1454:Clinical Infectious Diseases
1152:Clinical Infectious Diseases
633:10.1371/journal.pone.0059237
7:
1206:10.1056/NEJM198602273140901
518:the shrew, the bat and the
10:
1756:
1735:Fungal pathogens of humans
1057:from natural soil samples"
452:
444:In the rest of the world,
1593:
1427:10.1080/02681218680000521
1387:10.1080/13693780400008191
1294:10.1164/ajrccm/136.6.1324
1074:10.1080/13693780600954749
574:. Plenum. pp. 43โ73.
154:
147:
49:Scientific classification
47:
39:
30:
23:
1595:Blastomyces dermatitidis
1552:Blastomyces dermatitidis
1543:Medical Subject Headings
1368:Blastomyces dermatitidis
1366:"Attempted isolation of
1319:Blastomyces dermatitidis
1317:"Attempted isolation of
1231:Blastomyces dermatitidis
1190:Blastomyces dermatitidis
1113:Blastomyces dermatitidis
1055:Blastomyces dermatitidis
997:Ajellomyces dermatitidis
966:infections in the RSA".
964:Blastomyces dermatitidis
458:Blastomyces dermatitidis
435:Blastomyces dermatitidis
420:The geographic range of
385:Blastomyces dermatitidis
340:Blastomyces dermatitidis
257:Blastomyces dermatitidis
252:Morphology and phylogeny
180:Blastomyces dermatitidis
158:Blastomyces dermatitidis
41:Blastomyces dermatitidis
25:Blastomyces dermatitidis
1730:Fungi described in 1898
1507:10.1023/A:1007034215003
606:Blastomyces gilchristii
259:is the causal agent of
1164:10.1093/clind/15.4.629
390:Histoplasma capsulatum
311:Histoplasma capsulatum
414:Talaromyces marneffei
330:belong to the family
302:Blastomyces percursus
213:Appalachian mountains
1491:Dasypus novemcinctus
529:Dasypus novemcinctus
402:Coccidioides immitis
323:Polytolypa hystricis
290:Blastomyces emzantsi
235:, as well as in the
211:, parts of the U.S.
140:B. dermatitidis
715:Lippman, M (2001).
624:2013PLoSO...859237B
544:Preventive measures
933:10.1007/bf00468081
296:Blastomyces parvus
225:Mississippi Valley
209:St. Lawrence River
1712:
1711:
1697:Open Tree of Life
1587:Taxon identifiers
1323:Castor canadensis
237:Arabian Peninsula
223:, and the entire
176:
175:
16:Species of fungus
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468:dilution plating
332:Ajellomycetaceae
246:antifungal drugs
185:dimorphic fungus
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116:Ajellomycetaceae
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781:(10): 1309โ12.
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683:10.2307/3762114
663:
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538:B. dermatitidis
524:P. brasiliensis
515:B. dermatitidis
508:B. dermatitidis
499:B. dermatitidis
492:B. dermatitidis
484:B. dermatitidis
476:B. dermatitidis
463:B. dermatitidis
455:
446:B. dermatitidis
427:B. dermatitidis
422:B. dermatitidis
380:
336:dimorphic fungi
285:B. dermatitidis
254:
240:a large-celled
219:, the state of
199:, southeastern
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1533:External links
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1495:Mycopathologia
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1467:10.1086/313717
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1401:
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1272:
1229:"Isolation of
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1200:(9): 529โ534.
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921:Mycopathologia
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741:978-0812114638
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474:growth. Since
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1601:
1600:
1598:
1596:
1592:
1588:
1583:
1577:
1574:
1564:on 2007-08-17
1563:
1559:
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1477:
1473:
1468:
1463:
1459:
1455:
1451:
1444:
1436:
1432:
1428:
1424:
1421:(4): 349โ52.
1420:
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1412:
1405:
1397:
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1388:
1383:
1379:
1375:
1371:
1369:
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1330:
1326:
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1320:
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1299:
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1291:
1288:(6): 1324โ6.
1287:
1283:
1276:
1268:
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1250:
1246:
1242:
1238:
1234:
1232:
1223:
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1211:
1207:
1203:
1199:
1195:
1191:
1184:
1182:
1173:
1169:
1165:
1161:
1158:(4): 629โ35.
1157:
1153:
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1118:
1114:
1107:
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1058:
1056:
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1030:
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1020:
1016:
1012:
1009:(5): 1054โ6.
1008:
1004:
1000:
998:
989:
981:
977:
973:
969:
965:
958:
950:
946:
942:
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926:
922:
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903:
898:
893:
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881:
874:
866:
862:
859:(10): 82โ91.
858:
854:
847:
839:
835:
830:
825:
822:(7): 728โ31.
821:
817:
813:
806:
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780:
776:
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765:
757:
751:
743:
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733:
726:
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688:
684:
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677:(4): 812โ21.
676:
672:
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634:
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329:
326:, species of
325:
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304:
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298:
297:
292:
291:
286:
282:
281:
276:
271:
269:
267:
262:
261:blastomycosis
258:
249:
247:
243:
242:budding yeast
238:
234:
233:Sahara Desert
230:
226:
222:
218:
217:Lake Michigan
214:
210:
207:south of the
206:
202:
198:
194:
190:
189:blastomycosis
186:
182:
181:
170:
166:
161:
159:
153:
150:
149:Binomial name
146:
142:
141:
136:
133:
132:
129:
128:
124:
121:
120:
117:
114:
111:
110:
107:
104:
101:
100:
97:
94:
91:
90:
87:
84:
81:
80:
77:
74:
71:
70:
67:
64:
61:
60:
55:
50:
46:
43:, yeast form
42:
38:
34:
29:
26:
22:
19:
1594:
1566:. Retrieved
1562:the original
1557:
1551:
1501:(3): 131โ3.
1498:
1494:
1490:
1484:
1460:(3): 582โ4.
1457:
1453:
1443:
1418:
1414:
1410:
1404:
1380:(5): 413โ6.
1377:
1373:
1367:
1359:
1332:
1328:
1322:
1318:
1310:
1285:
1281:
1275:
1243:(5): 890โ1.
1240:
1236:
1230:
1222:
1197:
1193:
1189:
1155:
1151:
1145:
1123:(3): 163โ8.
1120:
1116:
1112:
1067:(8): 741โ8.
1064:
1060:
1054:
1006:
1002:
996:
988:
971:
967:
963:
957:
924:
920:
914:
890:(4): 460โ2.
887:
883:
873:
856:
852:
846:
819:
815:
805:
778:
774:
764:
731:
725:
716:
674:
670:
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615:
611:
605:
597:
587:
580:
571:
547:
537:
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523:
514:
512:
507:
498:
496:
491:
483:
481:
475:
471:
462:
457:
456:
445:
443:
439:Lake Ontario
434:
426:
421:
419:
412:
408:C. posadasii
406:
400:
394:
388:
384:
381:
357:
350:
344:
339:
327:
321:
315:
309:
307:
300:
294:
288:
284:
278:
274:
272:
268:dermatitidis
264:
256:
255:
187:that causes
179:
178:
177:
157:
155:
139:
138:
126:
40:
24:
18:
1539:Blastomyces
974:(1): 13โ6.
927:(2): 65โ9.
520:prairie dog
472:Blastomyces
368:mating type
346:Penicillium
328:Blastomyces
275:Blastomyces
266:Ajellomyces
127:Blastomyces
1725:Onygenales
1719:Categories
1568:2007-08-04
1335:(2): 192.
553:References
504:beaver dam
372:ascospores
229:Ohio River
169:W.R.Stokes
106:Onygenales
86:Ascomycota
82:Division:
750:cite book
671:Mycologia
431:Lake Erie
221:Wisconsin
165:Gilchrist
134:Species:
72:Kingdom:
66:Eukaryota
1671:MycoBank
1663:11345518
1632:Fungorum
1624:60018908
1619:AusFungi
1610:Q3012311
1604:Wikidata
1523:35693829
1515:10531678
1476:10722448
1396:16178369
1351:11990111
1137:10421847
1083:17127631
949:27296444
865:10893821
797:11107469
699:21148901
652:23533607
612:PLOS ONE
534:Edentata
360:mycelium
352:Rhizopus
201:Manitoba
112:Family:
62:Domain:
1650:5257877
1435:3746588
1413:Gray".
1302:3688633
1267:3771778
1214:3945290
1172:1420675
1033:2351722
980:2662433
941:6813742
906:3388850
897:1026149
838:6616383
829:1875443
691:3762114
643:3606480
620:Bibcode
453:Ecology
364:conidia
197:Ontario
193:endemic
122:Genus:
102:Order:
92:Class:
1702:124557
1676:361754
1637:361754
1545:(MeSH)
1521:
1513:
1474:
1433:
1394:
1349:
1300:
1265:
1258:269057
1255:
1212:
1170:
1135:
1081:
1031:
1024:267864
1021:
978:
947:
939:
904:
894:
863:
836:
826:
795:
785:
738:
697:
689:
650:
640:
205:Quebec
171:(1898)
167:&
1658:IRMNG
1519:S2CID
945:S2CID
788:80342
687:JSTOR
183:is a
76:Fungi
1689:5039
1684:NCBI
1645:GBIF
1511:PMID
1472:PMID
1431:PMID
1392:PMID
1347:PMID
1298:PMID
1263:PMID
1210:PMID
1168:PMID
1133:PMID
1079:PMID
1029:PMID
976:PMID
937:PMID
902:PMID
861:PMID
834:PMID
793:PMID
756:link
736:ISBN
695:PMID
648:PMID
411:and
320:and
299:and
1503:doi
1499:144
1462:doi
1423:doi
1382:doi
1337:doi
1290:doi
1286:136
1253:PMC
1245:doi
1202:doi
1198:314
1160:doi
1125:doi
1069:doi
1019:PMC
1011:doi
929:doi
892:PMC
888:148
824:PMC
820:129
783:PMC
779:163
679:doi
638:PMC
628:doi
488:PCR
349:or
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1103:^
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1007:28
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1001:.
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970:.
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900:.
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882:.
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616:8
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