bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing heartworm diagnosis in dogs using multiple test combinations
Authors: Lane Jennifer N. , Litster Annette , Little Susan E. , Rodriguez Jessica Y. , Mwacalimba Kennedy K. , Sundstrom Kellee D. , Amirian E. Susan , Guerios Simone D. , Serrano Maria A. , Hays Kellie M. , Levy Julie K. 
Published: April 2021

Abstract
Background
Various heartworm (HW) diagnostic testing modalities detect products of, or reactions to, different life cycle stages of Dirofilaria immitis. Microfilariae (Mf) can be directly visualized in blood, antigen (Ag) from immature and adult heartworms may be detected on commercial assays, and antibody (Ab) tests detect the host immune response to larval stages. Ag and Mf tests are commonly used in dogs, which frequently carry adult HW infections, but Ab tests have only been validated for use in cats. In some HW-infected dogs, Ag is blocked by immune complexing leading to false-negative results. Heat-treatment (HT) to disrupt these complexes can increase the sensitivity of HW Ag tests. The aim of this study was to compare different methods for diagnosing HW infection in dogs at high risk using individual and paired diagnostic tests, including an exploration of using Ab tests designed for cats to test canine samples.

Methods
One hundred stray adult (≥ 2-year-old) dogs in Florida shelters were tested using Mf, HW Ag, and HW Ab tests (feline HW Ab tests currently not commercially validated/approved for use in dogs); two versions of each test platform were used.

Results
Fourteen dogs tested positive using point-of-care (POC) Ag tests; an additional 2 dogs tested positive with microtiter well assay, and an additional 12 dogs tested positive using HT Ag testing. For individual tests, Ag test sensitivity/specificity compared to HT Ag was 50–57%/100%, and Ab tests were 46–64%/82–94%. Sensitivity estimates for individual tests were higher when comparing to non-HT Ag. Pairing POC Ag tests with Mf tests improved sensitivity without loss of specificity, while pairing POC Ag and Ab tests modestly increased sensitivity at the expense of specificity.

Conclusions
Screening dogs for HW infection using both POC Ag and Mf detection, which is recommended by the American Heartworm Society, improved diagnostic performance in this study compared to single Ag test use, but may have missed more than one in four infected dogs. The need to improve access to highly accurate, rapid, and inexpensive large-scale HW testing for dogs in animal shelters remains largely unmet by current testing availability. The development of practical and validated protocols that incorporate heat or chemical treatment to disrupt Ag-Ab complexes in POC testing or decreasing the cost and time required for such testing in reference laboratories might provide solutions to this unmet need. Similar studies performed in countries where the prevalence of parasites such as D. repens or A. vasorum is different to the USA could potentially yield very different positive predictive values for both HT and non-HT Ag tests.

Graphical abstract
Drug-related problems and associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Adem Fuad , Abdela Jemal , Edessa Dumessa , Hagos Bisrat , Nigussie Abraham , Mohammed Mohammed A. 
Published: April 2021

AbstractBackgroundDrug-related problems (DRPs) can occur at any stages of medication use processes, and a single drug could be associated with multiple DRPs. Once happened, it adversely affects health outcomes. In Ethiopia, evaluation of the magnitude and factors associated with DRPs had not been attempted at the national level.MethodThe literature search was conducted in the following databases; PubMed, Embase, Medline, and Google Scholar. The quality of the included studies was checked using Joanna Brigg’s Institute (JBI’s) checklist, and data were analyzed using Stata software (version 14.0). The pooled estimate of DRPs was computed by a Random effect model (DerSimonian–Laird method). Cochran’s Q test (I2) statistic)), and Begg’s correlation and Egger’s regression test were assessed for heterogeneity and publication bias, respectively.ResultOverall, 32 studies with a total sample size of 7,129 were included in the review. The estimated pooled prevalence of DRPs was 70% [0.70 (95% CI 0.64—0.76;I2 = 97.6%p = 0.000)]. Polypharmacy (taking ≥ 5 drugs) [RR = 1.3], medical comorbidity [RR = 1.3], poor medication adherence [RR = 1.7], uncontrolled blood pressure [RR = 1.4], substance use [RR = 1.2], type 2 diabetes [RR = 1.8], significant drug interaction [RR = 1.33], and a negative medication belief [RR = 3.72] significantly influenced the occurrence of DRPs.ConclusionThe estimated national prevalence of DRPs in Ethiopia was high.Presence of medical comorbidity, using multiple drugs, significant drug interaction, poor medication adherence, uncontrolled blood pressure, type 2 diabetes, substance use and a negative belief about medication significantly influenced the occurrence of DRPs. Initiating and/or strengthening pharmaceutical care services at the health care facilities could lower the occurrence of DRPs. PROSPERO registration number CRD42020162329.
Genetic variability among three Egyptian isolates of Heterorhabditis indica using a new marker technique (SCoT)
Authors: Abd El Azim Amany M. , Khashaba Etr H. K. 
Published: April 2021

Abstract
Background
Entomopathogenic nematodes (EPNs) are a group of nematode families, have the ability to search for their hosts, and are considered as promising biological control candidates for insect pests, providing protection to non-target organisms and the environment.

Results
This study was conducted to isolate indigenous EPN isolates from Egyptian agricultural soils for further use in biological control programs and study their genetic polymorphism among the previously isolated isolates under accession no. MH553167 and MK300683 and the new isolate (MH496627), using the start codon targeted (SCoT) marker. One out of 15 soil samples obtained from a banana cultivated field was positive for the presence of EPNs, using the Galleria baiting method. Morphological analysis and sequencing of the internal transcribed spacer (ITS) region suggested that the isolate obtained belongs to Heterorhabditis indica. The sequence of the ITS was submitted to the National Center for Biotechnology Information (NCBI) and registered under accession no. MH496627. Ten SCoT primers were used in the study; the polymorphic bands were 68 out of 76 with 89% as polymorphism percentage. The highest numbers of bands were 10 bands generated by SCoT 1 and SCoT 18 while SCoT 48 and SCoT 60 recorded the lowest band number (5 bands).

Conclusions
The present study is considered as a preliminary study to demonstrate the effectiveness of the SCoT marker for the first time in assessing genetic relationships in EPNs.
Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance
Authors: Huang-Doran Isabel , Kinzer Alexandra B , Jimenez-Linan Mercedes , Thackray Kerrie , Harris Julie , Adams Claire L , de Kerdanet Marc , Stears Anna , O’Rahilly Stephen , Savage David B , Gorden Phillip , Brown Rebecca J , Semple Robert K 
Published: April 2021

Abstract

Context
Insulin resistance (IR) is associated with polycystic ovaries and hyperandrogenism, but underpinning mechanisms are poorly understood and therapeutic options are limited.

Objective
To characterize hyperandrogenemia and ovarian pathology in primary severe IR (SIR), using IR of defined molecular etiology to interrogate disease mechanism. To extend evaluation of gonadotropin-releasing hormone (GnRH) analogue therapy in SIR.

Methods
Retrospective case note review in 2 SIR national referral centers. Female patients with SIR with documented serum total testosterone (TT) concentration.

Results
Among 185 patients with lipodystrophy, 65 with primary insulin signaling disorders, and 29 with idiopathic SIR, serum TT ranged from undetectable to 1562 ng/dL (54.2 nmol/L; median 40.3 ng/dL [1.40 nmol/L]; n = 279) and free testosterone (FT) from undetectable to 18.0 ng/dL (0.625 nmol/L; median 0.705 ng/dL [0.0244 nmol/L]; n = 233). Higher TT but not FT in the insulin signaling subgroup was attributable to higher serum sex hormone–binding globulin (SHBG) concentration. Insulin correlated positively with SHBG in the insulin signaling subgroup, but negatively in lipodystrophy. In 8/9 patients with available ovarian tissue, histology was consistent with polycystic ovary syndrome (PCOS). In 6/6 patients treated with GnRH analogue therapy, gonadotropin suppression improved hyperandrogenic symptoms and reduced serum TT irrespective of SIR etiology.

Conclusion
SIR causes severe hyperandrogenemia and PCOS-like ovarian changes whether due to proximal insulin signaling or adipose development defects. A distinct relationship between IR and FT between the groups is mediated by SHBG. GnRH analogues are beneficial in a range of SIR subphenotypes.
Genetically Determined Higher TSH Is Associated With a Lower Risk of Diabetes Mellitus in Individuals With Low BMI
Authors: Bos Maxime M , van Vliet Nicolien A , Mooijaart Simon P , Noordam Raymond , van Heemst Diana 
Published: April 2021

Abstract

Context
Thyroid status is hypothesized to be causally related with the risk of diabetes mellitus (DM), but previous results were conflicting possibly because of a complex interaction between thyrotropin (TSH), body mass index (BMI) and DM.

Objective
This work aims to investigate the causal association between thyroid status with DM and glucose homeostasis and to what extent this association is dependent on BMI.

Methods
A mendelian randomization study was conducted of European-ancestry participants from the UK Biobank population. The present study involved 408 895 individuals (mean age 57.4 years [SD 8.0], 45.9% men), of whom 19 773 had DM. Genetic variants for circulatory TSH, free thyroxine (fT4) concentrations and BMI to calculate weighted genetic risk scores. The main outcome measures included self-reported DM-stratified analyses by BMI. Analyses were repeated for nonfasting glucose and glycated hemoglobin A1c (HbA1c) among individuals without DM.

Results
Genetically determined TSH and fT4 levels were not associated with risk of DM in the total UK Biobank population. However, in analyses stratified on genetically determined BMI, genetically determined higher TSH, and not fT4, was associated with a lower risk for DM only in the low BMI group (odds ratio 0.91; 95% CI, 0.85-0.98 in low BMI; P value for interaction = .06). Similar results were observed for glucose and HbA1c among individuals without DM.

Conclusion
TSH, but not fT4, is a potential causal risk factor for DM in individuals with genetically determined low BMI highlighting potential protective effects of TSH only in low-risk populations.
The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens
Authors: Mills Edouard G , Yang Lisa , Nielsen Morten F , Kassem Moustapha , Dhillo Waljit S , Comninos Alexander N 
Published: April 2021

AbstractReproductive hormones play a crucial role in the growth and maintenance of the mammalian skeleton. Indeed, the biological significance for this hormonal regulation of skeletal homeostasis is best illustrated by common clinical reproductive disorders, such as primary ovarian insufficiency, hypothalamic amenorrhea, congenital hypogonadotropic hypogonadism, and early menopause, which contribute to the clinical burden of low bone mineral density and increased risk for fragility fracture. Emerging evidence relating to traditional reproductive hormones and the recent discovery of newer reproductive neuropeptides and hormones has deepened our understanding of the interaction between bone and the reproductive system. In this review, we provide a contemporary summary of the literature examining the relationship between bone biology and reproductive signals that extend beyond estrogens and androgens, and include kisspeptin, gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, inhibin, activin, and relaxin. A comprehensive and up-to-date review of the recent basic and clinical research advances is essential given the prevalence of clinical reproductive disorders, the emerging roles of upstream reproductive hormones in bone physiology, as well as the urgent need to develop novel safe and effective therapies for bone fragility in a rapidly aging population.
Reflex and Behaviour Patterns Elicited from Implanted Supernumerary Limbs in the Chick
Authors: Székely George , Szentágothai John 
Published: April 2021

ABSTRACTLimb primordia, both leg and wing, have been transplanted heterotopically in chick embryos on the 3rd day of incubation. Of 11 chicks hatched, 1 had a limb graft situated in the neck, 9 in the thoracic, and 1 in the lumbar region. These supernumerary limbs were supplied with nerves from the respective segments. Muscle tissues underwent degeneration and the joints were ankylotic. The covering skin and feathers were normal and sensitive to mechanical stimuli. Responses of the hosts to stimulation of the supernumerary limbs have been studied. The most common reflex response to light mechanical stimulation of the graft was a flexion reflex of the host’s ipsilateral leg. If the graft was situated in close vicinity of the wing, elevation of the host’s own wing could be elicited. These Timb-specific’ reflexes could be exclusively evoked from the grafts, but never from their neighbourhood. Four cases yielded more complex behaviour reactions always referred to one of the host’s own limbs, i.e. lame walking after stronger stimulation of the graft and cleaning of the host’s foot with the beak when a permanent, painful, stimulus was applied to the supernumerary limb. There was no correlation whatever between the type of the graft and the evoked ‘limb-specific’ responses which appeared only some days after hatching. Pain sensitivity and specific reflexogenic capacity were not strictly associated, since Timb-specific’ responses could be elicited from painless parts of the grafts and the reverse. According to anatomical investigation most of the grafts were supplied exclusively by intercostal nerves which never under normal circumstances convey limb signals and stimulation of which normally never evokes Timb-specific’ responses. Grafts producing only simple reflexes were generally supplied by a single segmental nerve, whereas complex behaviour reactions could be exclusively evoked from grafts with multisegmental inervation and some plexus formation among the supplying nerves. It is difficult to explain the observations made on supernumerary limbs of chicks on the basis of the Weiss-Sperry concept of ‘specific modulation’. As alternative hypothesis the capacity of ‘analysis’ and ‘recognition’ of specific afferent impulse patterns by the c.n.s. is suggested.
Les effets du chloramphénicol sur le développement de l’œuf d’Oursin
Authors: Lallier par R. 
Published: April 2021

ABSTRACTLe développement normal de l’œuf d’oursin dépend de l’équilibre entre deux tendances opposées qui favorisent respectivement la différenciation de l’ectoderme et de l’entomésoderme (Runnstrôm, 1928a). Cet équilibre peut être rompu expérimentalement par des méthodes opératoires ou sous l’influence d’agents chimiques déterminés. On provoque ainsi l’extension des structures ectodermiques (animalisation) ou entomésodermiques (végétalisation). Un troisième type de modification du développement, la radialisation, est caractérisé par la formation de larves à symétrie radiale. La radialisation s’obtient en traitant les œufs par des agents animalisants en faibles concentrations.
The Development of the Notochord in Chick Embryos
Authors: Jurand A. 
Published: April 2021

ABSTRACTThe literature on the notochord, a structure characteristic of all vertebrates, is very extensive, due to the phylogenetic importance of this organ, its role in early embryonic development, and its central position in the developing vertebral column. As early as 1834 the notochord tissue was described by Müller as being similar in appearance to the parenchyma of plants. Surprisingly, however, in the chick embryo, which is so widely used by embryologists, its development has not very often been the subject of descriptive or experimental investigations. From the early days most work on this fundamental organ was done on fish and amphibians, probably because the notochord in lower vertebrates is more suitable for investigations, as it persists longer, carrying out its function as an embryonic and larval skeleton.
The morphogenesis of the chick primary corneal stroma: I. New observations on collagen organization in vivo help explain stromal deposition and growth
Authors: Bard Jonathan B. L. , Bansal Mohinder K. 
Published: April 2021

Abstract
The primary stroma of the avian cornea contains collagen fibrils in orthogonal array. While investigating the processes underlying its morphogenesis, we have found that stromal organization is not as expected in three important respects. First, the fibrils are not uniform: those near the epithelium (newly laid down) have a maximum diameter of about 20 nm (mean: 17·7 nm), while those near the endothelium (laid down for approx. 40 h) have diameters up to 40 nm (mean: 22·8 nm). Fibrils thus grow rapidly to 20 nm and then continue to enlarge slowly, presumably by diffusion of collagen molecules from the epithelium. Second, the collagen, although orthogonally organized, does not contain layers of parallel fibrils. Instead, SEM observation shows that only a few fibrils lie in a parallel array before this shortrange order is broken by orthogonal fibrils in the same plane. Furthermore, fibrils in corneas that had been freeze dried but not critical-point dried for SEM were widely spaced and the intervening gaps were filled by an extensive matrix that was probably composed of the proteoglycans known to be in the stroma. Third, we have shown experimentally that the stromal undulations seen in sections are not present in vivo but are shrinkage artifacts: the less corneas were shrunk for SEM preparation, the less pronounced were the stromal undulations. We also noted that, even after the distortions required for the stroma to undulate, the constituent fibrils remained orthogonally organized.
These results give insight into the mechanisms underlying stromal morphogenesis and growth. The observations on the growth of collagen fibrils and on collagen organization show that stromal deposition is a more stochastic process than previously thought and, hence, provides support for the view that a complex self-assembly mechanism underlies both fibrillogenesis and the generation of orthogonal organization. The experiments on, and the analysis of, stromal folding show that fibrils slide over one another as undulations form, with the extensive matrix of hydrated proteoglycans being the likely lubricant. This fluidity of the stromal components probably explains how growth can occur without the structure being distorted.
Spontaneous generation of bilateral symmetry in the paired claws and closer muscles of adult snapping shrimps
Authors: Pearce Joanne , Govind C. K. 
Published: April 2021

Abstract
Adult snapping shrimps Alpheus heterochelis (Say) have paired asymmetric claws consisting of a major or snapper claw and a minor or pincer claw. An unusual condition of bilateral symmetry consisting of paired snapper claws arose spontaneously in several snapping shrimps by transformation of the pincer to a snapper in the presence of an existing contralateral snapper claw. Transformation in the external morphology and fibre composition of the closer muscle was completed within two intermoult periods in the majority of cases where true symmetry was achieved and once established became permanent. Thus snapping shrimps, which are by nature solitary, when continually exposed to each other in the laboratory may transform their pincer to a snapper without any trauma to the existing snapper claw.
Identity of cells containing apolipoprotein B messenger RNA, in 6- to 12-week postfertilization human embryos
Authors: Hopkins B. , Brice A. L. , Schofield P. N. , Baralle F. E. , Graham C. F. 
Published: April 2021

Abstract
Apolipoprotein B (Apo B) mRNA has been localized by in situ hybridization to various cell types in the liver, gut and yolk sack of the 6- to 12-week postfertilization human conceptus.
In the fetal liver it is probable that the immature hepatocytes contain Apo B mRNA. In the yolk sack, the Apo B cDNA probe hybridizes mainly to the large endodermal cells and in the fetal gut the epithelium seems responsible for the majority of Apo B mRNA production. The fetal brain did not show any detectable hybridization to the Apo B probe.
Unlike the situation seen in the adult, immunoprecipitation experiments demonstrated that only the B100 form of the protein was synthesized and secreted by the liver, gut and yolk sack at this early stage of human development.
Structure and development of the egg of the glossiphoniid leech Theromyzon rude: characterization of developmental stages and structure of the early uncleaved egg
Authors: Fernández Juan , Olea Nancy , Matte Cecilia 
Published: April 2021

ABSTRACT
Some aspects of the reproductive biology of the glossiphoniid leech, Theromyzon rude, under laboratory conditions, and the staging and structure of its uncleaved egg were studied. Sexually mature animals form breeding communities and fertilization occurs in the ovisacs, presumably around the time of egg laying. Opposition may be postponed for hours or days, but the eggs in the ovisacs remain blocked at first meiotic metaphase. Development of the uncleaved egg, from the time of oviposition to completion of the first cleavage division, has been sub-divided into six stages. At 20°C, the six developmental stages take 5–6 h. Characterization of the stages is based on observations of both live and fixed/cleared eggs. Discharge of the first pole cell, by the end of stage la, is associated with the movement of a ring of contraction between the equator and the animal pole. Discharge of the second pole cell, by the end of stage 1b, is accompanied by contraction of the animal hemisphere which becomes a cone-shaped structure. Polar rings and meridional bands of contraction make their appearance by stages 1c and 1d, respectively. Constriction of the polar rings and shortening of the meridional bands, during stage le, lead to accumulation of ooplasm at both egg poles. In this manner, the teloplasm or pole plasm forms. Completion of the first cleavage furrow, by the end of stage If, is preceded by dorsoventral flattening of the egg and rearrangement of its teloplasm and perinuclear plasm. Structure of the early uncleaved egg has been studied with transmission and scanning electron mi-croscopy of intact or permeabilized preparations. The plasmalemma forms numerous long and some short microvilli evenly distributed across the egg surface. The ectoplasm includes many vesicles, mitochondria, granules and an elaborate network of filament bundles. Staining of this network with rhodamine-labelled phalloidin indicates that it contains F-actin. A less complex network of similar filaments is also present throughout the yolky endoplasm. The meiotic spindle lies close to the egg surface and not far from the presumptive animal pole ectoplasm. It comprises highly developed poles whose structure and relationships are described.