bluuebunny/crossref_metadata_2025 huggingface dataset:
Why PRP works only on certain patients with tennis elbow? Is PDGFB gene a key for PRP therapy effectiveness? A prospective cohort study
Authors: Niemiec Paweł , Szyluk Karol , Balcerzyk Anna , Kalita Marcin , Jarosz Alicja , Iwanicka Joanna , Iwanicki Tomasz , Nowak Tomasz , Negru Marius , Francuz Tomasz , Garczorz Wojciech , Grzeszczak Władysław , Górczyńska-Kosiorz Sylwia , Kania Wojciech , Żak Iwona
Published: August 2021

Background

There is variability in individual response to platelet-rich plasma (PRP) therapy in tennis elbow treatment. Genetic variation, especially within genes encoding growth factors may influence the observed inter-individual differences. The purpose of this study was to identify polymorphic variants of the platelet-derived growth factor beta polypeptide gene (PDGFB) that determine an improved individual response to PRP therapy in tennis elbow patients.

Methods

This prospective cohort study was designed in accordance with STROBE and MIBO guidelines. A cohort of 107 patients (132 elbows, 25 bilateral) was studied, including 65 females (77 elbows) and 42 males (55 elbows), aged 24–64 years (median 46.00 ± 5.50), with lateral elbow tendinopathy treated with autologous PRP injection. The effectiveness of PRP therapy was recorded in all subjects at 2, 4, 8, 12, 24 and 52 weeks after PRP injection using the Visual Analog Scale (VAS), quick version of Disabilities of the Arm, Shoulder and Hand score (QDASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE). In order to determine the PDGFB variants with the best response to PRP therapy, patient reported outcome measures were compared between individual genotypes within studied polymorphic variants (rs2285099, rs2285097, rs2247128, rs5757572, rs1800817 and rs7289325). The influence of single nucleotide polymorphisms on blood and PRP parameters, including the concentration of PDGF-AB and PDGF-BB proteins was also analyzed.

Results

Our analysis identified genetic variants of the PDGFB gene that lead to a better response to PRP therapy. The TT (rs2285099) and CC (rs2285097) homozygotes had higher concentration of platelets in whole blood than carriers of other genotypes (p = 0.018) and showed significantly (p < 0.05) lower values of VAS (weeks 2–12), QDASH and PRTEE (weeks 2–24). The rs2285099 and rs2285097 variants formed strong haplotype block (r2 = 98, D’=100). The AA homozygotes (rs2247128) had significantly lower values of VAS (weeks 4–52), QDASH and PRTEE (weeks 8, 12).

Conclusions

PDGFB gene’s polymorphisms increase the effectiveness of PRP therapy in tennis elbow treatment. Genotyping two polymorphisms of the PDGFB gene, namely rs2285099 (or rs2285097) and rs2247128 may be a helpful diagnostic tool while assessing patients for PRP therapy and modifying the therapy to improve its effectiveness.
Applying real-time Delphi methods: development of a pain management survey in emergency nursing
Authors: Varndell Wayne , Fry Margaret , Elliott Doug
Published: August 2021

The modified Delphi technique is widely used to develop consensus on group opinion within health services research. However, digital platforms are offering researchers the capacity to undertake a real-time Delphi, which provides novel opportunities to enhance the process. The aim of this case study is to discuss and reflect on the use of a real-time Delphi method for researchers in emergency nursing and cognate areas of practice. A real-time Delphi method was used to develop a national survey examining knowledge, perceptions and factors influencing pain assessment and management practices among Australian emergency nurses. While designing and completing this real-time Delphi study, a number of areas, emerged that demanded careful consideration and provide guidance to future researchers.
Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study
Authors: Haverfield Eden V. , Esplin Edward D. , Aguilar Sienna J. , Hatchell Kathryn E. , Ormond Kelly E. , Hanson-Kahn Andrea , Atwal Paldeep S. , Macklin-Mantia Sarah , Hines Stephanie , Sak Caron W.-M. , Tucker Steven , Bleyl Steven B. , Hulick Peter J. , Gordon Ora K. , Velsher Lea , Gu Jessica Y. J. , Weissman Scott M. , Kruisselbrink Teresa , Abel Christopher , Kettles Michele , Slavotinek Anne , Mendelsohn Bryce A. , Green Robert C. , Aradhya Swaroop , Nussbaum Robert L.
Published: August 2021

Background

The use of proactive genetic screening for disease prevention and early detection is not yet widespread. Professional practice guidelines from the American College of Medical Genetics and Genomics (ACMG) have encouraged reporting pathogenic variants that confer personal risk for actionable monogenic hereditary disorders, but only as secondary findings from exome or genome sequencing. The Centers for Disease Control and Prevention (CDC) recognizes the potential public health impact of three Tier 1 actionable disorders. Here, we report results of a large multi-center cohort study to determine the yield and potential value of screening healthy individuals for variants associated with a broad range of actionable monogenic disorders, outside the context of secondary findings.

Methods

Eligible adults were offered a proactive genetic screening test by health care providers in a variety of clinical settings. The screening panel based on next-generation sequencing contained up to 147 genes associated with monogenic disorders within cancer, cardiovascular, and other important clinical areas. Sequence and intragenic copy number variants classified as pathogenic, likely pathogenic, pathogenic (low penetrance), or increased risk allele were considered clinically significant and reported. Results were analyzed by clinical area and severity/burden of disease using chi-square tests without Yates’ correction.

Results

Among 10,478 unrelated adults screened, 1619 (15.5%) had results indicating personal risk for an actionable monogenic disorder. In contrast, only 3.1 to 5.2% had clinically reportable variants in genes suggested by the ACMG version 2 secondary findings list to be examined during exome or genome sequencing, and 2% had reportable variants related to CDC Tier 1 conditions. Among patients, 649 (6.2%) were positive for a genotype associated with a disease of high severity/burden, including hereditary cancer syndromes, cardiovascular disorders, or malignant hyperthermia susceptibility.

Conclusions

This is one of the first real-world examples of specialists and primary care providers using genetic screening with a multi-gene panel to identify health risks in their patients. Nearly one in six individuals screened for variants associated with actionable monogenic disorders had clinically significant results. These findings provide a foundation for further studies to assess the role of genetic screening as part of regular medical care.
Enhancing the value of meat inspection records for broiler health and welfare surveillance: longitudinal detection of relational patterns
Authors: Buzdugan S. N. , Alarcon P. , Huntington B. , Rushton J. , Blake D. P. , Guitian J.
Published: August 2021

Background

Abattoir data are under-used for surveillance. Nationwide surveillance could benefit from using data on meat inspection findings, but several limitations need to be overcome. At the producer level, interpretation of meat inspection findings is a notable opportunity for surveillance with relevance to animal health and welfare. In this study, we propose that discovery and monitoring of relational patterns between condemnation conditions co-present in broiler batches at meat inspection can provide valuable information for surveillance of farmed animal health and welfare.

Results

Great Britain (GB)-based integrator meat inspection records for 14,045 broiler batches slaughtered in nine, four monthly intervals were assessed for the presence of surveillance indicators relevant to broiler health and welfare.K-means and correlation-based hierarchical clustering, and association rules analyses were performed to identify relational patterns in the data. Incidence of condemnation showed seasonal and temporal variation, which was detected by association rules analysis. Syndrome-related and non-specific relational patterns were detected in some months of meat inspection records. A potentially syndromic cluster was identified in May 2016 consisting of infection-related conditions: pericarditis, perihepatitis, peritonitis, and abnormal colour. Non-specific trends were identified in some months as an unusual combination of condemnation reasons in broiler batches.

Conclusions

We conclude that the detection of relational patterns in meat inspection records could provide producer-level surveillance indicators with relevance to broiler chicken health and welfare.
Brainstem intraparenchymal schwannoma with genetic analysis: a case report and literature review
Authors: Ishigami Daiichiro , Miyawaki Satoru , Nakatomi Hirofumi , Takayanagi Shunsaku , Teranishi Yu , Ohara Kenta , Hongo Hiroki , Dofuku Shogo , Kin Taichi , Abe Hiroyuki , Mitsui Jun , Komura Daisuke , Katoh Hiroto , Ishikawa Shumpei , Saito Nobuhito
Published: August 2021

Background

Schwannomas are neoplasms that typically arise from the myelin sheath of peripheral nerves and rarely originate within the brain parenchyma. Some case reports present schwannomas arising from the brainstem, but regrowth of the tumor and the efficacy of postoperative irradiation have not been examined. In addition, the genetic background of schwannomas arising from the brainstem has not been investigated.

Case presentation

A 21-year-old male presented with diplopia, dysphagia, and left-sided hemiparesis, dysesthesia, and ataxia. Intracranial imaging showed a heterogeneous mass with a cystic lesion in the pontomedullary junction. Since the tumor caused obstructive hydrocephalus, the patient underwent subtotal tumor resection. A histopathologic evaluation aided a diagnosis of brainstem intraparenchymal schwannoma. Gradual postoperative mass regrowth was recognized. Three-dimensional conformal radiotherapy was performed on the residual mass and surgical cavity. No tumor regrowth was observed 4 years after surgery. To investigate the genetic background of the tumor, target sequences for 36 genes, includingNF2,SMARCB1, andLZTR1, and microsatellite analysis for loss of 22q did not show any somatic variants or 22q loss.

Conclusions

We suggest that brainstem schwannomas might differ from conventional schwannomas in their genetic background.
Remote-controllable bone-targeted delivery of estradiol for the treatment of ovariectomy-induced osteoporosis in rats
Authors: Guo Yuanyuan , Liu Yongwei , Shi Chen , Wu Tingting , Cui Yongzhi , Wang Siyuan , Liu Ping , Feng Xiaobo , He Yu , Fu Dehao
Published: August 2021

Background

Osteoporosis (OP) is a systemic skeletal disease marked by bone mass reduction and bone tissue destruction. Hormone replacement therapy is an effective treatment for post-menopausal OP, but estrogen has poor tissue selectivity and severe side effects.

Results

In this study, we constructed a poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)-based drug delivery system to co-load 17β estradiol (E2) and iron oxide (Fe3O4) together, modified with alendronate (AL) to achieve bone targeting and realize a magnetically remote-controllable drug release. The NPs were fabricated through the emulsion solvent diffusion method. The particle size was approximately 200 nm while the encapsulation efficiency of E2 was 58.34 ± 9.21%. The NPs were found to be spherical with a homogenous distribution of particle size. The NPs showed good stability, good biocompatibility, high encapsulation ability of E2 and excellent magnetic properties. The NPs could be effectively taken up by Raw 264.7 cells and were effective in enriching drugs in bone tissue. The co-loaded NPs exposed to an external magnetic field ameliorated OVX-induced bone loss through increased BV/TV, decreased Tb.N and Tb.Sp, improved bone strength, increased PINP and OC, and downregulated CTX and TRAP-5b. The haematological index and histopathological analyses displayed the NPs had less side effects on non-skeletal tissues.

Conclusions

This study presented a remote-controlled release system based on bone-targeted multifunctional NPs and a new potential approach to bone-targeted therapy of OP.

Graphic abstract
Move to health-a holistic approach to the management of chronic low back pain: an intervention and implementation protocol developed for a pragmatic clinical trial
Authors: Rhon Daniel I. , Fritz Julie M. , Greenlee Tina A. , Dry Katie E. , Mayhew Rachel J. , Laugesen Mary C. , Dragusin Edita , Teyhen Deydre S.
Published: August 2021

Background

The prevalence of chronic pain conditions is growing. Low back pain was the primary cause of disability worldwide out of 156 conditions assessed between 1990 and 2016, according to the Global Burden of Disease Study. Conventional medical approaches have failed to identify effective and long-lasting approaches for the management of chronic pain, and often fail to consider the multiple domains that influence overall health and can contribute to the pain experience. Leading international organizations that focus on pain research have stated the importance of considering these other domains within holistic and multidisciplinary frameworks for treating pain. While the research behind the theoretical link between these domains and chronic pain outcomes has expanded greatly over the last decade, there have been few practical and feasible methods to implement this type of care in normal clinical practice.

Methods

The purpose of this manuscript is to describe an implementation protocol that is being used to deliver a complex holistic health intervention at multiple sites within a large government health system, as part of a larger multisite trial for patients with chronic low back pain. The Move to Health program developed by the US Army Medical Command was tailored for specific application to patients with low back pain and begins by providing an empirical link between eight different health domains (that include physical, emotional, social, and psychological constructs) and chronic low back pain. Through a six-step process, a health coach leverages motivational interviewing and information from a personal health inventory to guide the patient through a series of conversations about behavioral lifestyle choices. The patient chooses which domains they want to prioritize, and the health coach helps implement the plan with the use of SMART (Specific, Measurable, Attainable, Realistic, Time-bound) goals and a series of resources for every domain, triaged from self-management to specialist referral.

Discussion

Complex interventions described in clinical trials are often challenging to implement because they lack sufficient details. Implementation protocols can improve the ability to properly deliver trial interventions into regular clinical practice with increased fidelity.

Trial registration

Implementation of this intervention protocol was developed for a clinical trial that was registered a priori (clinicaltrials.gov #NCT04172038).
Estimation of nitrate nitrogen content in cotton petioles under drip irrigation based on wavelet neural network approach using spectral indices
Authors: Dong Zhiqiang , Liu Yang , Ci Baoxia , Wen Ming , Li Minghua , Lu Xi , Feng Xiaokang , Wen Shuai , Ma Fuyu
Published: August 2021

Background

Estimation of nitrate nitrogen (NO3−–N) content in petioles is one of the key approaches for monitoring nitrogen (N) nutrition in crops. Rapid, non-destructive, and accurate evaluation of NO3−–N contents in cotton petioles under drip irrigation is of great significance.

Methods

In this study, we discussed the use of hyperspectral data to estimate NO3−–N contents in cotton petioles under drip irrigation at different N treatments and growth stages. The correlations among trilateral parameters and six vegetation indices and petiole NO3−–N contents were first investigated, after which a traditional regression model for petioles NO3−–N content was established. A wavelet neural network (WNN) model for estimating petiole NO3−–N content was also established. In addition, the performance of WNN was compared to those of random forest (RF), radial basis function neural network (RBF) and back propagation neural network (BP).

Results

Between the blue edge amplitude (Db) and blue edge area (SDb) of the blue edge parameters was the optimal index for the estimation model of petiole NO3−–N content. We found that the prediction results of the blue edge parameters and WNN were 7.3% higher than the coefficient of determination (R2) of the first derivative vegetation index and WNN. Root mean square error (RMSE) and mean absolute error (MAE) were 25.2% and 30.9% lower than first derivative vegetation, respectively, and the performance was better than that of RF, RBF and BP.

Conclusions

An inexpensive approach consisting of the WNN algorithm and blue edge parameters can be used to enhance the accuracy of NO3−–N content estimation in cotton petioles under drip irrigation.
Zimmer Natural Nail and ELOS nails in pertrochanteric fractures
Authors: Gargano Giuseppe , Poeta Nicola , Oliva Francesco , Migliorini Filippo , Maffulli Nicola
Published: August 2021

Background

Pertrochanteric fractures of the femur in the elderly are very common. As the average age of the population increases, the incidence of such fractures also raises, resulting in high healthcare costs. The type of surgical devices employed for their surgical management influences these costs.

Methods

A comparative clinical study was conducted on patients operated by one single surgeon between December 2018 and November 2020 in a high-volume regional referral centre. All patients who received a Zimmer Natural Nail (ZNN) or ELOS devices were included.

Results

In 119 (66.48%) of the 179 fractures, a ZNN nail was used. Post-operatively, the TAD (tip-to-apex distance) was measured at an average value of 17.05 (4.42–41.85) mm and the CalTAD (calcar-referenced TAD) at an average of 20.76 (10.82–43.63) mm. The mean hospitalization time was 10.19 (4–22) days. In the other 60 trochanteric fractures, an ELOS nail was used. Post-operative imaging indicated a TAD of 19.65 (5.08–31.4) mm and a CalTAD of 22.86 mm (12.66–33.77). The average time of the operation was 45.82 (20–110) min. The average period of hospitalization was 10.45 (5–24) days.

Conclusion

Both devices give similar results in terms of short-term post-operative outcome and hospitalization. The price difference between the devices does not translate in different short-term results on the operated patients.
Downregulation of miR-1-3p expression inhibits the hypertrophy and mineralization of chondrocytes in DDH
Authors: Ding Rui , Liu Xijuan , Zhang Jian , Yuan Jinghong , Zheng Sikuan , Cheng Xigao , Jia Jingyu
Published: August 2021

Background

Developmental dysplasia of the hip (DDH) is a highly prevalent hip disease among children. However, its pathogenesis remains unclear. MicroRNAs (miRNA) are important regulators of cartilage development. In a previous study, high-throughput miRNA sequencing of tissue samples from an animal model of DDH showed a low level of miR-1-3p in the cartilage of the acetabular roof (ARC), but its role in DDH pathogenesis was not addressed. Therefore, our aim here was to investigate the effects of miR-1-3p in the ARC.

Methods

The diagnosis of acetabular dysplasia was confirmed with X-ray examination, while imaging and HE staining were conducted to further evaluate the ARC thickness in each animal model. FISH was employed to verify miR-1-3p expression in the ARC and chondrocytes. The miR-1-3p target genes were predicted by a bioinformatics database. A dual-luciferase reporter assay was used to confirm the targeting relationship between miR-1-3p and SOX9. The gene expression of miR-1-3p, SOX9, RUNX2 and collagen type X was evaluated by qPCR analysis. The protein expression of SOX9, RUNX2 and collagen type X was detected by western blot analysis. The levels of SOX9, RUNX2, and collagen type X in the ARC were further assessed via immunohistochemistry analysis. Finally, Alizarin Red S staining was used to observe the mineralized nodules produced by the chondrocytes.

Results

We observed low expression of miR-1-3p in the ARC of animals with DDH. SOX9 is a miR-1-3p target gene. Using miR-1-3p silencing technology in vitro, we demonstrated significantly reduced chondrocyte-generated mineralized nodules compared to those of the control. We also confirmed that with miR-1-3p silencing, SOX9 expression was upregulated, whereas the expression of genes associated with endochondral osteogenesis such as RUNX2 and collagen type X was downregulated. To confirm the involvement of miR-1-3p silencing in abnormal ossification through SOX9, we also performed a rescue experiment in which SOX9 silencing restored the low expression of RUNX2 and collagen type X produced by downregulated miR-1-3p expression. Finally, the elevated SOX9 levels and reduced RUNX2 and collagen type X levels in the ARC of rabbits with DDH were also verified using immunohistochemistry, RT-PCR, and western blots.

Conclusion

The relatively low expression of miR-1-3p in the ARC may be the cause of abnormal endochondral ossification in the acetabular roof of animals with DDH.
Efficacy and safety of the Chinese herbal formula Hewei Jiangni recipe for NERD with cold-heat complex syndrome: study protocol for a double-blinded randomized controlled trial
Authors: Zhang Xiaosi , Cheng Yuan , Li Xiaohong , Tan Xiang , Shi Lei , Shi Xiaojun , Zhang Xiancui , Xie Chun’e , Li Junxiang
Published: August 2021

Background

Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites.

Methods

This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively.

Discussion

The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR.

ChiCTR2000041225. Registered on 22 December 2020
Effect of wing length on the prevalence of trypanosomes in Glossina morsitans morsitans in eastern Zambia
Authors: Mweempwa Cornelius , Chilongo Kalinga , Hayashida Kyoko , Namangala Boniface
Published: August 2021

Background

Tsetse flies (Diptera:Glossinidae) transmit trypanosomiasis (sleeping sickness in humans and nagana in livestock). Several studies have indicated that age, sex, site of capture, starvation and microbiome symbionts, among others, are important factors that influence trypanosome infection in tsetse flies. However, reasons for a higher infection rate in females than in males still largely remain unknown. Considering that tsetse species and sexes of larger body size are the most mobile and the most available to stationary baits, it was hypothesized in this study that the higher trypanosome prevalence in female than in male tsetse flies was a consequence of females being larger than males.

Methods

Black screen fly rounds and Epsilon traps were used to collect tsetse flies in eastern Zambia. Measurement of wing vein length and examination for presence of trypanosomes in the flies were carried out by microscopy. Principal component method was carried out to assess the potential of wing vein length as a predictor variable. The multilevel binary logistic regression method was applied on whole data, one-method data and one-sex data sets to evaluate the hypothesis.

Results

Data derived from a total of 2195Glossina morsitans morsitanswere evaluated (1491 males and 704 females). The wing length variable contributed the highest variance percentage (39.2%) to the first principal component. The variable showed significant influence on prevalence of trypanosomes when the analysis was applied on the whole data set, with the log odds for the prevalence of trypanosomes significantly increasing by 0.1 (P =  0.032), per unit increase in wing length. Females had higher trypanosome prevalence rates than males, though not always significant. Furthermore, moving from females to males, wing length significantly reduced by 0.2 (P <  0.0001).

Conclusions

We conclude that wing length is an important predictor variable for trypanosome prevalence inGlossina morsitans morsitansand could partially explain the higher prevalence of trypanosomes in females than in males. However, reasonably representative population data are required for analysis—a serious challenge with the current tsetse sampling methods. Thus, analysis combining data from mobile and stationary methods that include both sexes' data could be useful to verify this hypothesis.

Graphical abstract
Diagnostic accuracy of a novel enzyme-linked immunoassay for the detection of IgG and IgG4 against Strongyloides stercoralis based on the recombinant antigens NIE/SsIR
Authors: Tamarozzi Francesca , Longoni Silvia Stefania , Mazzi Cristina , Pettene Sofia , Montresor Antonio , Mahanty Siddhartha , Bisoffi Zeno , Buonfrate Dora
Published: August 2021

Background

The diagnosis of strongyloidiasis is challenging. Serological tests are acknowledged to have high sensitivity, but issues due to cross-reactions with other parasites, native parasite antigen supply and intrinsic test variability do occur. Assays based on recombinant antigens could represent an improvement. The aim of this study was to assess the sensitivity and specificity of two novel immunoglobulin (Ig)G and IgG4 enzyme-linked immunosorbent assays (ELISAs) based on the recombinant antigens NIE/SsIR for the diagnosis of strongyloidiasis.

Methods

This was a retrospective diagnostic accuracy study. We included serum samples collected from immigrants from strongyloidiasis endemic areas for whom there was a matched result for Strongyloides stercoralis on agar plate culture and/or PCR assay, or a positive microscopy for S. stercoralis larvae. For the included samples, results were also available from an in-house indirect fluorescent antibody test (IFAT) and a commercial (Bordier ELISA; Bordier Affinity Products SA) ELISA. We excluded: (i) samples with insufficient serum volume; (ii) samples from patients treated with ivermectin in the previous 6 months; and (iii) sera from patients for whom only routine coproparasitology was performed after formol–ether concentration, if negative for S. stercoralis larvae. The performance of the novel assays was assessed against: (i) a primary reference standard, with samples classified as negative/positive on the basis of the results of fecal tests; (ii) a composite reference standard (CRS), which also considered patients to be positive who had concordant positive results for the IFAT and Bordier ELISA or with a single “high titer” positive result for the IFAT or Bordier ELISA. Samples with a single positive test, either for the IFAT or Bordier ELISA, at low titer, were considered to be “indeterminate,” and analyses were carried out with and without their inclusion.

Results

When assessed against the primary reference standard, the sensitivities of the IgG and IgG4 ELISAs were 92% (95% confidence interval [CI]: 88–97%) and 81% (95% CI: 74–87%), respectively, and the specificities were 91% (95% CI: 88–95%) and 94% (95% CI: 91–97%), respectively. When tested against the CRS, the IgG ELISA performed best, with 78% sensitivity (95% CI: 72–83%) and 98% specificity (95% CI: 96–100%), when a cut-off of 0.675 was applied and the indeterminate samples were excluded from the analysis.

Conclusion

The NIE-SsIR IgG ELISA demonstrated better accuracy than the IgG4 assay and was deemed promising particularly for serosurveys in endemic areas.

Graphical abstract
Molecular identification of Sarcocystis halieti in the muscles of two species of birds of prey from Spain
Authors: Prakas Petras , Bea Antonio , Juozaitytė-Ngugu Evelina , Olano Iñaki , Villanúa Diego , Švažas Saulius , Butkauskas Dalius
Published: August 2021

Background

Members of the genus Sarcocystis are protozoan parasites characterized by a prey–predator two-host life-cycle. Sarcocysts are formed in the muscles or central nervous system of the intermediate host (IH), while sporocysts develop in the small intestine of the definitive host (DH). Various birds of prey have been confirmed to be DH for Sarcocystis spp. Three Sarcocystis species, S. wobeseri, S. halieti and S. falcatula, have been identified in the muscles of birds of prey, of which the latter are known to be pathogenic and can cause encephalitis in various birds. The aim of this study was to identify Sarcocystis spp. in the muscles of birds of prey from Spain.

Methods

Between 2019 and 2020, muscle tissue samples taken from 59 birds of prey admitted to the Wildlife Recovery Centre in Ilundain (Navarra, Spain) were examined for the presence of Sarcocystis spp. Sarcocysts in fresh squashed samples were morphologically characterized under the light microscope (LM). Sarcocystis spp. were identified by means of 28S ribosomal RNA and internal transcribed spacer 1 sequence analysis.

Results

Microscopic examination of squashed tissue samples stained with methylene blue revealed the presence of sarcocysts in three of the 59 (5.1%) birds examined. Only one sarcocyst type was observed under the LM. Sarcocysts were thread-like (1050–2160 × 130–158 μm) and had a thin (0.7–1.4 μm) and smooth cyst wall. Septa divided the cysts into compartments filled with banana-shaped (5.9 × 1.7 μm) bradyzoites. On the basis of DNA sequence results, S. halieti was identified in the western marsh harrier (Circus aeruginosus) and the black kite (Milvus migrans) for the first time. Sarcocysts of S. halieti were shorter and wider compared to those observed in the great cormorant (Phalacrocorax carbo) and the herring gull (Larus argentatus). According to current knowledge, S. halieti may infect birds belonging to four different orders: Suliformes, Charadriiformes, Strigiformes and Accipitriformes.

Conclusions

This is the first report of S. halieti in the western marsh harrier and the black kite as IH. So far, little research has been conducted on birds of prey as IH for Sarcocystis spp. These results indicate that further studies combining morphological, histopathological, and molecular methods are required.

Graphical abstract
Clinical manifestations, risk factors, and prognostic factors of cytomegalovirus enteritis
Authors: Yeh Pai-Jui , Chiu Cheng-Tang , Lai Ming-Wei , Wu Ren-Chin , Chen Chien-Ming , Kuo Chia-Jung , Hsu Jun-Te , Su Ming-Yao , Lin Wei-Pin , Chen Tsung-Hsing , Le Puo-Hsien
Published: August 2021

Background

To comprehensively analyze the risk factors, clinical characteristics, outcomes, and prognostic factors of Cytomegalovirus (CMV) enteritis.

Methods

This retrospective cohort study enrolled patients who had undergone pathological examinations for CMV enteritis. They were divided into CMV and non-CMV groups according to immunohistochemistry staining results. The risk factors, clinical presentations, endoscopic features, treatments, outcomes, and prognostic factors of CMV enteritis were then analyzed.

Results

Forty-two patients (18 CMV, 24 non-CMV group) were included in the study. Major clinical presentations in the CMV group included gastrointestinal bleeding (72.2%), abdominal pain (55.6%), and fever (33.3%); ulcers (72.2%) were the most common endoscopic findings. In-hospital and overall mortality rates were 27.8% and 38.9%, respectively; and longer hospital stays and higher overall mortality rates were observed. Radiotherapy and C-reactive protein levels were prognostic factors for in-hospital mortality. The risk factors for CMV enteritis included immunocompromised status (p = 0.013), steroid use (p = 0.014), shock (p = 0.031), concurrent pneumonia (p = 0.01), antibiotic exposure (p < 0.001), radiotherapy (p = 0.027), chronic kidney disease (p = 0.041), and CMV colitis (p = 0.031).

Conclusions

Physicians should pay attention to the characteristics of CMV enteritis in high-risk patients to make an early diagnosis and potentially improve the clinical outcome.
Use of electronic medical records to describe the prevalence of allergic diseases in Canada
Authors: Singer Alexander G. , Kosowan Leanne , Nankissoor Nerissa , Phung Ryan , Protudjer Jennifer L. P. , Abrams Elissa M.
Published: August 2021

Background

Leveraging the data management resources of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is a viable approach for describing the prevalence of allergic disease documented in primary care settings.

Methods

The dataset used for this study was inclusive of data from EMR initiation up to Dec 31st 2018. The sample included 1235 primary care providers representing 1,556,472 patients across Canada.

Results

In total, there were 536,005 patients with a documented allergy that fit into one of the 10 suggested categories. The allergy table includes 718,032 distinct entries representing 564,242 unique patients, which is 36.3% of the patients within the CPCSSN repository. The most common allergies recorded were drug allergy (39.0%), beta-lactam allergy (14.4%), environmental allergy (11.0%), and food allergy (8.0%). Anticipated upcoming studies include physician-documented drug allergy with a focus on beta-lactam allergy, as well as stinging insect allergy, among others. To our knowledge, these will also be the first such prevalence studies of primary care physician-documented allergic disease done in Canada.

Interpretation

The CPCSSN dataset represents electronic medical records from 1.5 million patients across Canada including documentation of allergic diseases. This dataset provides a national representative population to describe and characterize Canadian patients with common allergic conditions. This robust dataset provides the opportunity for health surveillance, and in particular data to explore the impact of allergic disease on primary care practice.

Trial registration

Not applicable.
Magnetic resonance imaging in the management of Crohn’s disease: a systematic review and meta-analysis
Authors: Ahmad Rani , Ajlan Amr M. , Eskander Ayman A. , Alhazmi Turki A. , Khashoggi Khalid , Wazzan Mohammad A. , Abduljabbar Ahmed H.
Published: August 2021

Objectives

Crohn’s disease (CD) is a condition that can occur in any part of the gastrointestinal tract, although usually forms in the colon and terminal ileum. Magnetic resonance imaging (MRI) has become a beneficial modality in the evaluation of small bowel activity. This study reports on a systematic review and meta-analysis of magnetic resonance enterography for the prediction of CD activity and evaluation of outcomes and possible complications.

Methods

Following the PRISMA guidelines, a total of 25 low-risk studies on established CD were selected, based on a QUADAS-II score of ≥ 9.

Results

A sensitivity of 90% was revealed in a pooled analysis of the 19 studies, with heterogeneity of χ2 = 81.83 and I2 of 80.3%. Also, a specificity of 89% was calculated, with heterogeneity of χ2 = 65.12 and I2 of 70.0%.

Conclusion

It was concluded that MRI provides an effective alternative to CT enterography in the detection of small bowel activity in CD patients under supervision of radiologist for assessment of disease activity and its complications. Its advantages include the avoidance of radiation exposure and good diagnostic accuracy.
Primary diffuse large B-cell lymphoma of the cranial vault with Trousseau syndrome: a case report
Authors: Uchida Tatsuya , Amagasaki Kenichi , Hosono Atsushi , Nakaguchi Hiroshi
Published: August 2021

Background

It is extremely rare for primary non-Hodgkin’s lymphomas to occur singly in the cranial vault. One case diagnosed as primary diffuse large B-cell lymphoma is reported, initially misdiagnosed as metastatic skull tumor, complicated with Trousseau syndrome.

Case description

The patient was a 60-year-old Japanese woman with no particular previous medical history. In a head computed tomography examination for vertigo, bone destructive skull tumor covering the right frontal, parietal, and temporal bones was incidentally discovered. As positron emission tomography indicated an abnormal accumulation in the large intestine and multiple cerebral infarctions suspicious of Trousseau syndrome were observed on magnetic resonance images, a metastatic skull tumor due to colorectal cancer was first considered. However, various tumor markers were negative, and colonoscopic biopsy indicated no colorectal abnormality. After pathological examination of the resected tumor, it was diagnosed as diffuse large B-cell lymphoma. The tumor affected muscles and skin but did not develop in the brain or the dura mater. As further general examination revealed no other abnormalities, we considered that it was primary diffuse large B-cell lymphoma in the cranial vault associated with Trousseau syndrome. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and high-dose methotrexate reduced the residual lesion; coagulation abnormalities, which are frequently associated with Trousseau syndrome, also improved.

Conclusions

Skull tumors can result from a variety of malignancies, and their diagnosis may be complicated with Trousseau syndrome. However, even in cases of a single lesion in the cranial vault without invasion of the central nervous system, diffuse large B-cell lymphoma should be considered as a differential diagnosis.
Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques
Authors: Tian Chuan , He Jie , An Yuanyuan , Yang Zailing , Yan Donghai , Pan Hang , Lv Guanke , Li Ye , Wang Yanying , Yang Yukun , Zhu Gaohong , He Zhixu , Zhu Xiangqing , Pan Xinghua
Published: August 2021

Background

Female sex hormone secretion and reproductive ability decrease with ageing. Bone marrow mesenchymal stem cells (BMMSCs) have been postulated to play a key role in treating ovarian ageing.

Methods

We used macaque ovarian ageing models to observe the structural and functional changes after juvenile BMMSC treatment. Moreover, RNA-seq was used to analyse the ovarian transcriptional expression profile and key pathways through which BMMSCs reverse ovarian ageing.

Results

In the elderly macaque models, the ovaries were atrophied, the regulation ability of sex hormones was reduced, the ovarian structure was destroyed, and only local atretic follicles were observed, in contrast with young rhesus monkeys. Intravenous infusion of BMMSCs in elderly macaques increased ovarian volume, strengthened the regulation ability of sex hormones, reduced the degree of pulmonary fibrosis, inhibited apoptosis, increased density of blood vessels, and promoted follicular regeneration. In addition, the ovarian expression characteristics of ageing-related genes of the elderly treatment group reverted to that of the young control group, 1258 genes that were differentially expressed, among which 415 genes upregulated with age were downregulated, 843 genes downregulated with age were upregulated after BMMSC treatment, and the top 20 differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network were significantly enriched in oocyte meiosis and progesterone-mediated oocyte maturation pathways.

Conclusion

The BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.
Exosomes from primed MSCs can educate monocytes as a cellular therapy for hematopoietic acute radiation syndrome
Authors: Forsberg Matthew H. , Kink John A. , Thickens Anna S. , Lewis Bryson M. , Childs Charlie J. , Hematti Peiman , Capitini Christian M.
Published: August 2021

Background

Acute radiation syndrome (ARS) is caused by acute exposure to ionizing radiation that damages multiple organ systems but especially the bone marrow (BM). We have previously shown that human macrophages educated with exosomes from human BM-derived mesenchymal stromal cells (MSCs) primed with lipopolysaccharide (LPS) prolonged survival in a xenogeneic lethal ARS model. The purpose of this study was to determine if exosomes from LPS-primed MSCs could directly educate human monocytes (LPS-EEMos) for the treatment of ARS.

Methods

Human monocytes were educated by exosomes from LPS-primed MSCs and compared to monocytes educated by unprimed MSCs (EEMos) and uneducated monocytes to assess survival and clinical improvement in a xenogeneic mouse model of ARS. Changes in surface molecule expression of exosomes and monocytes after education were determined by flow cytometry, while gene expression was determined by qPCR. Irradiated human CD34+ hematopoietic stem cells (HSCs) were co-cultured with LPS-EEMos, EEMos, or uneducated monocytes to assess effects on HSC survival and proliferation.

Results

LPS priming of MSCs led to the production of exosomes with increased expression of CD9, CD29, CD44, CD146, and MCSP. LPS-EEMos showed increases in gene expression of IL-6, IL-10, IL-15, IDO, and FGF-2 as compared to EEMos generated from unprimed MSCs. Generation of LPS-EEMos induced a lower percentage of CD14+ monocyte subsets that were CD16+, CD73+, CD86+, or CD206+ but a higher percentage of PD-L1+ cells. LPS-EEMos infused 4 h after lethal irradiation significantly prolonged survival, reducing clinical scores and weight loss as compared to controls. Complete blood counts from LPS-EEMo-treated mice showed enhanced hematopoietic recovery post-nadir. IL-6 receptor blockade completely abrogated the radioprotective survival benefit of LPS-EEMos in vivo in female NSG mice, but only loss of hematopoietic recovery was noted in male NSG mice. PD-1 blockade had no effect on survival. Furthermore, LPS-EEMos also showed benefits in vivo when administered 24 h, but not 48 h, after lethal irradiation. Co-culture of unprimed EEMos or LPS-EEMos with irradiated human CD34+ HSCs led to increased CD34+ proliferation and survival, suggesting hematopoietic recovery may be seen clinically.

Conclusion

LPS-EEMos are a potential counter-measure for hematopoietic ARS, with a reduced biomanufacturing time that facilitates hematopoiesis.
Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies
Authors: Li Deng-Yuan , Li Ru-Fang , Sun Dan-Xiong , Pu Dan-Dan , Zhang Yun-Hui
Published: August 2021

Background

Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF.

Methods

We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software.

Results

A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI −2.58 to −1.51, P < 0.001, I2 = 90%).

Conclusions

MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.
Stem cell therapy for Crohn’s disease: systematic review and meta-analysis of preclinical and clinical studies
Authors: Wang Ruo , Yao Qigu , Chen Wenyi , Gao Feiqiong , Li Pan , Wu Jian , Yu Jiong , Cao Hongcui
Published: August 2021

Background

We explored whether stem cell therapy was effective for animal models and patients with Crohn’s disease (CD).

Methods

We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality.

Results

We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD − 4.58, p = 0.000; rats: SMD − 1.41, P = 0.000) and lower myeloperoxidase levels (SMD − 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD − 2.10, P = 0.000), the CD endoscopic index of severity (SMD − 3.40, P = 0.000) and simplified endoscopy score for CD (SMD − 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3–24 months after transplantation.

Conclusions

Stem cell transplantation is a valuable supplementary therapy for CD.