bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic Reconstitution of Human Umbilical Cord Mesenchymal Stem Cells after Leukemia Chemotherapy: Effectiveness and Safety
Authors: Tan Yuxin , Ding Lu , Can Can , Zhou Fuling
Published: November 2021

Objective: As the incidence of tumors increases, more patients need chemotherapy. Patients receiving chemotherapy also inevitably suffer side effects from treatment. Damage to the immune and hematopoietic system causes the failure of therapies. Mesenchymal stem cells have excellent capabilities in immune regulation and hematopoietic support. This study preliminarily explored the safety and effectiveness and of human umbilical cord mesenchymal stem cells (UCMSC) in myelosuppressive patient-derived tumor xenograft (PDX) models of acute myeloid leukemia (AML).

Methods: B-NDG mice were used to establish the PDX models. The mice were randomly divided into three groups: AML group, AML+Ara-C group and AML+Ara-C+MSC group. Mice in the AML+Ara-C group and AML+Ara-C+MSC group were injected intraperitoneally with cytarabine (Ara-C) 60mg/kg on day1-day3 to induce myelosuppression. Mice in the AML+Ara-C+MSC group were injected 3×10 6 UCMSC through the tail vein on day4. We observed the changes in peripheral blood, bone marrow signaling pathways, and AML progression in mice.

Results: The experiment found that UCMSC rescued the body weight and peripheral blood. We also found that UCMSC could increase the number of bone marrow CD117 + hematopoietic stem/progenitor cells and CD41 + megakaryocytes through flow cytometry. We verified at protein level that the hematopoiesis-related signaling pathway JAK2/STAT3 was up-regulated in AML+Ara-C+MSC group compared with AML+Ara-C group through flow cytometry and immunohistochemistry. At the same time, the infusion of UCMSC after Ara-C had no influence on disease progression. On day15, the proportion of human CD45 + cells in the bone marrow of between AML+Ara-C+MSC group and AML+Ara-C group was similar, and there was no statistical difference (21.96±3.10 vs. 23.04±1.51; P=0.6792).

Conclusion: Infusion of exogenous UCMSC after chemotherapy in PDX models could promote the recovery of hematopoiesis without affecting the efficacy of Ara-C. A reasonable UCMSC infusion scheme is potential to be used in the treatment of AML patients and it requires a lot of preclinical exploration in the future.

Disclosures

No relevant conflicts of interest to declare.

OffLabel Disclosure:

Cytarabine (Ara-C) was administrated to mice models to induce myelosuppression.
Human Genetic Diversity Alters Therapeutic Gene Editing Off-Target Outcomes
Authors: Lin Linda Yingqi , Cancellieri Samuele , Zeng Jing , Masillo Francesco , Nguyen My Anh , Bombieri Nicola , Maitland Stacy A. , Ciuculescu Marioara-Felicia , Katta Varun , Tsai Shengdar Q. , Armant Myriam , Wolfe Scot A. , Giugno Rosalba , Pinello Luca , Bauer Daniel E.
Published: November 2021

CRISPR gene editing holds great promise to modify somatic genomes to ameliorate disease. In silico prediction of homologous sites coupled with biochemical evaluation of possible genomic off-targets may predict genotoxicity risk of individual gene editing reagents. However, standard computational and biochemical methods focus on reference genomes and do not consider the impact of genetic diversity on off-target potential. Here we developed a web application called CRISPRme that explicitly and efficiently integrates human genetic variant datasets with orthogonal genomic annotations to predict and prioritize off-target sites at scale. The method considers both single-nucleotide variants (SNVs) and indels, accounts for bona fide haplotypes, accepts spacer:protospacer mismatches and bulges, and is suitable for personal genome analyses. We tested the tool with a guide RNA (gRNA) targeting the BCL11A erythroid enhancer that has shown therapeutic promise in clinical trials for sickle cell disease (SCD) and β-thalassemia (Frangoul et al. NEJM 2021). We find that the top predicted off-target site is produced by a non-reference allele common in African-ancestry populations (rs114518452, minor allele frequency (MAF) = 4.5%) that introduces a protospacer adjacent motif (PAM) for SpCas9. We validate that SpCas9 generates indels (~9.6% frequency) and chr2 pericentric inversions in a strictly allele-specific manner in edited CD34+ hematopoietic stem/progenitor cells (HSPCs), although a high-fidelity Cas9 variant mitigates this off-target. This report illustrates how population and private genetic variants should be considered as modifiers of genome editing outcomes. We expect that variant-aware off-target assessment will be required for therapeutic genome editing efforts going forward, including both ongoing and future clinical trials, and we provide a powerful approach for comprehensive off-target prediction. CRISPRme is available at crisprme.di.univr.it.

Disclosures

No relevant conflicts of interest to declare.
Prognosis and Therapeutic Response Transfer Learning Model for Multiple Myeloma
Authors: Voegeli Jerome , Moreno Dana , Kryukov Maxim , Mathez Gregory , Petremand Remy , Pere Arthur , Ekstrom Leeland , Jaun Andre
Published: November 2021

The combination of clinical knowledge (applicable for a majority of patients, published in the form of review articles), real world evidence (describing more nuanced outcomes for small cohorts) and innovative artificial intelligence algorithms opens potent avenues to re-examine clinical findings and uncover new biomarkers for the prognosis / prediction of therapeutic responses--in a manner that can directly be incorporated in clinical decision support tools.

In this work, neural networks are first developed to reproduce clinical guidelines with >95% accuracy. After mastering the complex knowledge that is generally expected from human doctors, a transfer learning technique was used to sift through de-identified longitudinal data of 9267 patients with multiple myeloma-related conditions at the Vanderbilt University Medical Center using progression free survival (PFS) to quantify therapeutic outcomes. The "precision medicine neural networks" obtained as a result can be compared with conventional and less portable survival model algorithms, using Shapley values to explain prediction differences.

Testing a first hypothesis that "lytic bone lesions are a prognostic factor for poor PFS", a study involving 1530 patients confirmed that the median PFS of 54 ± 6 months (684 censored patients showing progression) in the presence of bone lesions is significantly lower than the 107 ± 40 months (90 censored patients) in the absence of lesions.

Keeping only 179 patients for which a full range of cytogenetic factors are available and using a Cox regression & Random Survival Forests that provide the best fit of the data, we confirmed previous findings for high-risk trisomies 1 and 7, monosomy 13, deletion 12p and translocation t(11;14)(q13;q32). We furthermore uncovered new additional adverse factors del6q, 2+, 21-, 16- to formulate a model that achieves a statistically significant concordance of 0.72 ± 0.07.

Comparing therapeutic effects for patients in a real-world hospital setting with clinical trials, we found that lenalidomide + bortezomib + dexamethasone used in a first-line therapy resulted in lower median PFS of 17-47 months than the 39-52 months published in the SWOG S0777 trial, most likely because comorbidities contributed to shortening the PFS in real-world settings.

We conclude with an analysis of concrete examples where therapeutic recommendations differ from guidelines, explaining the reason with statistically significant cohorts observed in the data.

Disclosures

No relevant conflicts of interest to declare.
Factor VIII Epitope Analysis Using a Random Peptide Phage-Display Library Approach in the Sippet Cohort
Authors: Hassan Shermarke , Baselli Guido , Palm Kaia , Rosendaal Frits Richard , Palla Roberta , Peyvandi Flora
Published: November 2021

Background Inhibitor development is the most severe complication of hemophilia A care, and is associated with increased morbidity and mortality.

Aims The aim of this study was to use a novel epitope mapping method to explore the factor VIII (FVIII)-specific epitope profile in the SIPPET cohort population.

Methods The population consisted of 122 previously untreated patients with severe hemophilia A that were followed-up for 50 days of exposure to FVIII. Sampling was performed before FVIII treatment and at the end of the follow-up. The outcome was inhibitor development. The FVIII-specific IgG epitope repertoire was assessed by means of a novel high-throughput epitope mapping technique using a random peptide phage-display library. Using this assay, a set of affinity-selected 12-mer peptide sequences (also called mimotopes) that were strongly bound by FVIII-specific antibodies were identified. These mimotopes were clustered on the basis of sequence similarity and a consensus motif was generated for each mimotope cluster. Discriminative performance of these mimotope clusters was assessed by ROC analysis. Mimotope clusters were mapped onto the 3D structure of a B-domain deleted FVIII model using a B-cell epitope prediction algorithm (Mapitope).

Results The FVIII-specific antibody response is polyclonal with several mimotope clusters. The most predominant mimotope clusters in inhibitor patients were mapped to the heavy chain of the FVIII molecule. Using plasma samples taken before exposure to FVIII, three mimotopes (with the consensus motifs "QM", "PSLxWK" and "SWPHxxxxK") were identified that predicted inhibitor development (with an AUC of 0.76, 0.80 and 0.76 respectively).

Conclusion Information on immunodominant epitope clusters can be used to generate novel, less immunogenic FVIII proteins and set up diagnostic tests that predict the risk of inhibitor development before starting treatment with FVIII.

Figure 1 Figure 1.

Disclosures

Palm: Protobios LLC: Current Employment, Patents & Royalties: Inventor of the patent application (PCT Application No. US/14079626) filed by Protobios that covers the use of phage display method to manipulate and monitor humoral immunity.. Palla: Pfizer: Other: Travel support; Kedrion: Other: Travel support; Novonordisk: Speakers Bureau. Peyvandi: Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.
The Role of Endothelial Superoxide Dismutase 2 in Modulating Sickle Pathology
Authors: Dosunmu-Ogunbi Atinuke , Yuan Shuai , Straub Adam C
Published: November 2021

Sickle cell disease (SCD) patients suffer from hemolysis in microcirculation. On the one hand, hemoglobin and heme released from sickled red blood cells catalyze reactive oxygen species (ROS) generation by Fenton chemistry. On the other hand, sickled red blood cells occlude capillaries, creating a hypoxic condition that exacerbates ROS production. As an essential antioxidant mechanism, superoxide dismutase 2 (SOD2) detoxifies superoxide by converting it to hydrogen peroxide (H 2O 2) in the mitochondria. In SCD patients, despite the elevated ROS production, we found that SOD2 expression is suppressed in the pulmonary endothelium (Figure 1A,B). Therefore, we hypothesize the depletion of endothelial SOD2 compromises endothelial function and exacerbates the progression of SCD.

To examine the role of endothelial SOD2, we silenced SOD2 gene expression (SOD2 KD) with siRNA in primary human pulmonary microvascular endothelial cells (hPMVECs). Knocking down SOD2 in hPMVECs accelerated mitochondrial superoxide production and compromised mitochondrial potential. However, mitochondrial respiration, the activity of respiratory complexes, and the cellular ATP content were not affected by SOD2 KD. An important function of endothelial cells is to form a barrier and sequester cellular and molecular contents in the blood. SOD2 KD hPMVECs exhibited increased albumin leakage and decreased transendothelial resistance, indicating a disrupted endothelial barrier(Figure 1C). The defect in the endothelial barrier was rescued by adding 4 mM H 2O 2(Figure 1D), suggesting SOD2-derived H 2O 2 may serve as a critical signaling molecule. Moreover, cell migration or proliferation was inhibited in SOD2 KD hPMVECs, which was examined by a scratch assay.

Since both cell migration and barrier maintenance require focal adhesion assembly, we next investigated the role of SOD2 in focal adhesion dynamics. In an attachment assay, SOD2 KD reduced cell attachment rate on uncoated plates, which was blunted by fibronectin precoating, indicating a fibronectin-dependent defect in cell adhesion(Figure 1E,F). Notably, although fibronectin protein expression in hPMVECs was not altered, SOD2 KD decreased the dimer/monomer ratio. Furthermore, confocal images showed that fibronectin was retained in SOD2 KD cells(Figure 1G), highlighting the importance of SOD2 in fibronectin assembly.

In conclusion, we demonstrated for the first time that SOD2 expression is diminished in the pulmonary endothelium of SCD patients and that endothelial SOD2 is crucial for endothelial function by facilitating fibronectin assembly. The importance of SOD2 in endothelial function may prove therapeutic value in SCD patients, which requires further investigation.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
The Small Gtpase Rap1 in Platelets Is Critical for Arterial but Not Venous Thrombosis in Mice
Authors: Mwiza Jean , Lee Robert H , Paul David , Holle Lori A , Cooley Brian C , Wolberg Alisa S. , Bergmeier Wolfgang
Published: November 2021

Background: Platelets and their main adhesion receptors, integrins, are critical in hemostasis and arterial thrombosis, i.e., in situations involving severe insult to the vasculature and elevated shear stress, respectively. We recently demonstrated that integrin activation under both of these conditions depends on the small GTPase Rap1 directly activating the integrin adapter protein, Talin1. Our studies further suggested that the Rap1-talin1 axis is less important for platelet function at sites of inflammation, i.e., in situations of mild endothelial insult and low shear stress.

Aim: To investigate the contribution of the platelet Rap1-Talin1-integrin signaling axis in the pathogenesis of venous thrombosis (VT).

Methods: The following mice with documented deficiencies in platelets were subjected to the inferior vena cava (IVC) stenosis VT model: Rap1amKO (Rap1a fl/fl pf4-Cre+), Rap1bmKO (Rap1b fl/fl pf4-Cre+), or both isoforms (Rap1a fl/flRap1b fl/fl pf4-Cre+ [Rap1dKO]), and Talin1mKO (Tln1 fl/flpf4-Cre+). Thrombus weight was determined 48 hours after flow restriction. Clot contraction and tissue plasminogen activator (tPA)-mediated lysis of whole blood clots were studied ex vivo to characterize effects on clot consolidation and stability .

Results: Compared to control mice, thrombus weight was markedly reduced in Talin1mKO mice (13.1±2 and 2.2±1.2 mg, p<0.05), but not Rap1dKO or single knockout mice. Ex vivo clot contraction was significantly impaired in whole blood from Talin1mKO (clot weight: control 13.35±3.4 mg vs. 34.63±4.2 mg), Rap1amKO (control 18.0±3.9 mg vs. 25.6±6.0 mg), Rap1bmKO (control 18.0±3.9 vs 23.0±6.6 mg) and in Rap1dKO (control 18.03±3.9 mg vs. 30.02±4.6 mg). Clot weights were not significantly different between Rap1dKO and Talin1mKO mice. However, ex vivo clot lysis assays revealed that compared to controls, clots formed in whole blood from Talin1mKO mice lysed faster, whereas clots from Rap1dKO did not.

Conclusions: Platelet Talin1 is critical for VT in mice, and this role is partially independent of its best-known upstream regulator, Rap1. Future studies will identify the alternative mechanism allowing for Rap1-independent Talin1 signaling and platelet function in VT and how these signaling affect various phases of VT.

Disclosures

Wolberg: Takeda: Research Funding; Bristol Myers Squibb: Research Funding; CSL Behring: Consultancy.
Histogram analysis based on multi-parameter MR imaging as a biomarker to predict lymph node metastasis in T3 stage rectal cancer
Authors: Zhou Yang , Yang Rui , Wang Yuan , Zhou Meng , Zhou Xueyan , Xing JiQing , Wang Xinxin , Zhang Chunhui
Published: November 2021

Background

Preoperative identification of rectal cancer lymph node status is crucial for patient prognosis and treatment decisions. Rectal magnetic resonance imaging (MRI) plays an essential role in the preoperative staging of rectal cancer, but its ability to predict lymph node metastasis (LNM) is insufficient. This study explored the value of histogram features of primary lesions on multi-parametric MRI for predicting LNM of stage T3 rectal carcinoma.

Methods

We retrospectively analyzed 175 patients with stage T3 rectal cancer who underwent preoperative MRI, including diffusion-weighted imaging (DWI) before surgery. 62 patients were included in the LNM group, and 113 patients were included in the non-LNM group. Texture features were calculated from histograms derived from T2 weighted imaging (T2WI), DWI, ADC, and T2 maps. Stepwise logistic regression analysis was used to screen independent predictors of LNM from clinical features, imaging features, and histogram features. Predictive performance was evaluated by receiver operating characteristic (ROC) curve analysis. Finally, a nomogram was established for predicting the risk of LNM.

Results

The clinical, imaging and histogram features were analyzed by stepwise logistic regression. Preoperative carbohydrate antigen 199 level (p = 0.009), MRN stage (p < 0.001), T2WIKurtosis (p = 0.010), DWIMode (p = 0.038), DWICV (p = 0.038), and T2-mapP5 (p = 0.007) were independent predictors of LNM. These factors were combined to form the best predictive model. The model reached an area under the ROC curve (AUC) of 0.860, with a sensitivity of 72.8% and a specificity of 85.5%.

Conclusion

The histogram features on multi-parametric MRI of the primary tumor in rectal cancer were related to LN status, which is helpful for improving the ability to predict LNM of stage T3 rectal cancer.
Association between polymorphisms rs2228001 and rs2228000 in XPC and genetic susceptibility to preeclampsia: a case control study
Authors: Wang Jingli , Guan Chengcheng , Sui Jing , Zang Yucui , Wu Yuwen , Zhang Ru , Qi Xiaoying , Piao Shunfu
Published: November 2021

Background

Xeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein that plays an important role in nucleotide excision repair and can reduce oxidative stress, which may be involved in the development of preeclampsia (PE). Therefore, the aim of this study was to explore whether XPC polymorphisms were relevant to the genetic susceptibility to PE in Chinese Han women.

Method

A total of 1276 healthy pregnant women were included as the control group and 958 pregnant women with PE as the case group. DNA was extracted from peripheral blood samples to perform genotyping of loci rs2228001 and rs2228000 in XPC through real-time quantitative polymerase chain reaction (PCR). The relationship between XPC and susceptibility to PE was evaluated by comparing the genotypic and allelic frequencies between the two groups of pregnant women.

Results

Polymorphism of rs2228000 may be associated with PE risk and allele T may play a protective role (genotype, χ2 = 38.961, P < 0.001 and allele χ2 = 21.746 P < 0.001, odds ratio (OR) = 0.885, 95% confidence interval (CI) = 0.840-0.932). No significant difference was found between the two groups in rs2228001,(genotype χ2 = 3.148, P = 0.207 and allele χ2 = 0.59, P = 0.442, OR = 1.017, 95% CI = 0.974–1.062). When the frequencies of genotypes and alleles for early- and late-onset PE, mild PE and severe PE were compared with those of controls, the results were consistent with the large clinical sample.

Conclusion

Our data suggest that the genetic variant rs2228000 in XPC may be associated with PE risk in Chinese Han women, and that pregnant women with the TT genotype have a reduced risk of PE. Further investigations are needed to confirm these findings in other regions or larger prospective populations.
Os acromiale may be a contraindication of the clavicle hook plate: case reports and literature review
Authors: Sun Qi , Cai Ming , Wu Xiaoming
Published: November 2021

Background

Os acromiale can be potentially missed or misdiagnosed as acromion fracture, and this can affect treatment determination if it is complicated with an ipsilateral shoulder injury. The clavicle hook plate is a widely used technique for distal clavicle injuries, leading to transacromial erosion, particularly when in the presence of os acromiale.

Case presentation

A 70-year-old man and a 78-year-old man who had limited mobility and severe pain in their right shoulders following falls attended the emergency center. Both patients were diagnosed with os acromiale with CT or MRI and acute distal clavicle fracture or acromioclavicular joint dislocation. Following a comprehensive evaluation, os acromiale may limit the application of a clavicle hook plate due to potential transacromial erosion. The distal clavicle fracture with ipsilateral os acromiale received treatment with a volar radius locking T plate, and the acromioclavicular joint dislocation with ipsilateral os acromiale was reconstructed using suture anchors. Both yielded satisfactory outcomes and voided transacromial erosion.

Conclusions

Ipsilateral os acromiale may be a relative contraindication to the clavicle hook plate. An axillary lateral radiograph is recommended to detect potential os acromiale in patients using a hook plate.
A diagnostic tool for people with lumbar instability: a criterion-related validity study
Authors: Chatprem Thiwaphon , Puntumetakul Rungthip , Kanpittaya Jaturat , Selfe James , Yeowell Gillian
Published: November 2021

Background

Several clinical tests used to identify patients with lumbar instability have reported diagnostic accuracy in separate studies with conflicting results. To augment the diagnostic process, tests that are better able to identify lumbar instability suitable for use in the clinical setting are required. The aim of this study was to identify the probability to diagnose patients with lumbar instability, using x-ray imaging as the reference standard.

Methods

This study was a cross-sectional, diagnostic validity study. One hundred forty participants with chronic low back pain underwent an x-ray assessment and 14 clinical examinations. Data were analysed using multivariate regression methods to determine which clinical tests were most diagnostic for lumbar instability when they were applied together.

Results

Eighteen (12.85%) participants had radiological lumbar instability. Three clinical tests i) interspinous gap change during flexion-extension, ii) passive accessory intervertebral movement tests, iii) posterior shear test demonstrated an ability to diagnose lumbar instability of 67% when they were all positive. At this probability threshold, sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) were 5.56, 99.18%, 6.78, and 0.95.

Conclusions

These 3 clinical tests could be useful in identifying patients with lumbar instability in the general community. These three tests are simple to perform by physical therapists, reliable to use in a clinical setting, and safe for patients. We recommend physical therapists use these three tests to assess patients who are suspected of having lumbar instability, in the absence of an x-ray assessment, to receive appropriate targeted intervention or referral for further investigation.

Trial registration

Thai Clinial Trial Registry (TCTR 20180820001; 19th August 2018).
An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Wirth Klaus J. , Scheibenbogen Carmen , Paul Friedemann
Published: November 2021

There is accumulating evidence of endothelial dysfunction, muscle and cerebral hypoperfusion in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In this paper we deduce the pathomechanisms resulting in central nervous pathology and the myriad of neurocognitive symptoms. We outline tentative mechanisms of impaired cerebral blood flow, increase in intracranial pressure and central adrenergic hyperactivity and how they can well explain the key symptoms of cognitive impairment, brain fog, headache, hypersensitivity, sleep disturbances and dysautonomia.
Nanoparticles of conformation-stabilized canine distemper virus hemagglutinin are highly immunogenic and induce robust immunity
Authors: Dong Jingjian , Chen Yan , Shi Lili , Shen Bing , Sun Xianliang , Ruan Kaiyi , Xia Xianzhu , Feng Hao , Feng Na
Published: November 2021

Background

Canine distemper virus (CDV) infection of ferrets, dogs, and giant pandas causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system. In this study, we tested a new candidate CDV vaccine-CDV nanoparticles-based on hemagglutinin protein.

Methods

The nanoparticles were generated from conformation-stabilized CDV hemagglutinin tetramers. Immune responses against CDV were evaluated in mice. Immunization was initiated 6 weeks after birth and boosted two times with 4-week intervals. The blood and mucosal samples were collected 2 weeks after each immunization.

Results

Vaccination with CDV nanoparticles elicited high levels of IgG antibody titers in mice (approximately sevenfold to eightfold higher than that obtained with soluble CDV H protein) and mucosal immune responses and developed increased CDV-specific neutralizing antibody. The mice that received nanoparticles showed significantly higher IFN-γ- and IL-4-secreting cell population in the spleen and lymph node compared with mice immunized with soluble H protein. The co-stimulatory molecular expression of CD80 and CD86 on the surface of DCs was also upregulated.

Conclusion

The results demonstrate that self-assembly into nanoparticles can increase the immunogenicity of vaccine antigens, and nanoparticles assembled from conformation-stabilized CDV H protein can serve as a new CDV vaccine.
Efficacy of intra-articular ketorolac for pain control in arthroscopic surgeries: a systematic review and meta-analysis
Authors: Yang Jingjing , Ni Bin , Fu Xiaoyan
Published: November 2021

Background

The current systematic review and meta-analysis aimed to synthesize evidence on the efficacy of intra-articular ketorolac for patients undergoing arthroscopic surgeries.

Methods

PubMed, Embase, ScienceDirect, and Google Scholar databases were searched for randomized controlled trials assessing the analgesic effect of intra-articular ketorolac for arthroscopic surgery of hip/knee or shoulder joint.

Results

Six studies were included. Two studies were on shoulder arthroscopy, while others were on knee joint. Meta-analysis revealed that patients receiving intra-articular ketorolac had significantly lower pain scores at 2–4 h (MD: − 0.58 95% CI: − 0.88, − 0.19 I2 = 49% p = 0.002), 6–8 h (MD: − 0.77 95% CI: − 1.11, − 0.44 I2 = 31% p < 0.00001), 12 h (MD: − 0.94 95% CI: − 1.21, − 0.67 I2 = 0% p < 0.00001), and 24 h (MD: − 1.28 95% CI: − 1.85, − 0.71 I2 = 84% p < 0.00001) as compared to the control group (Certainty of evidence: low-moderate). Analysis of three studies revealed a tendency of reduced analgesic consumption in patients receiving intra-articular ketorolac, but the difference did not reach statistical significance (MD: − 0.53 95% CI: − 1.07, 0.02 I2 = 55% p = 0.06).

Conclusions

Preliminary evidence from a limited number of studies indicates that additional intra-articular ketorolac to multimodal analgesia results in reduced pain scores up to 24 h after arthroscopic surgery. The clinical relevance of small changes in pain scores is debatable. Also, scarce data suggest that consumption of analgesics may not be reduced with intra-articular ketorolac. Since pain scores can be influenced by the primary diagnosis and dose of ketorolac, the results should be interpreted with caution. The certainty of the evidence is low-moderate. There is a need for future RCTs to further strengthen current evidence.
Optic pathway glioma and the sex association in neurofibromatosis type 1: a single-center study
Authors: Henning Anne Munk , Handrup Mette Møller , Kjeldsen Sia Mariann , Larsen Dorte Ancher , Ejerskov Cecilie
Published: November 2021

Background

Low-grade optic pathway glioma (OPG) develops in 15–20% of children with neurofibromatosis type 1 (NF1). OPGs are symptomatic in 30–50% and one-third of these require treatment. A few studies have suggested female sex as a risk factor for visual impairment associated with NF1-OPG. This descriptive study investigated the correlation between NF1-OPG growth, sex and visual impairment.

Method

We based our cross-sectional study on a systematic, retrospective data collection in a NF1 cohort of children and adolescents below 21 years of age followed at Center for Rare Diseases, Aarhus University Hospital, Denmark. For each patient with OPG a medical chart review was performed including demographics, ophthalmological examinations and magnetic resonance imaging (MRI) of OPG.

Results

Of 176 patients with NF1 (85 females, 91 males), we identified 21 patients with OPG (11.9%) with a preponderance of females, p = 0.184. Eight females (62%) and one male (13%) had visual impairment at the last ophthalmological evaluation. Five out of 21 children with OPG (24%) underwent diagnostic MRI because of clinical findings at the ophthalmological screening. Nine children (43%) had symptoms suggestive of OPG and seven (33%) experienced no OPG-related symptoms before the diagnostic MRI. Of eight children diagnosed with OPG ≤ two years of age, one had visual impairment. Of 13 children diagnosed > two years of age, eight had visual impairment; in each group, four of the children were treated with chemotherapy. The study suggested no correlation between NF1-OPG growth and sex.

Conclusion

Our data suggest sex as a risk factor for visual impairment, while an OPG diagnose ≤ two years of age was a protective factor for visual impairment. Females with NF1-OPG had a higher prevalence of visual impairment outcome compared to males. Interestingly, our data also suggest a better response to treatment in children with OPG diagnosed ≤ two years of age compared to older children. The findings in our study suggest sex as a potential prognostic factor for visual impairment.
Phased repatriation of Lebanese expatriates stranded abroad during coronavirus disease 2019 (COVID-19) pandemic
Authors: Youssef Dalal , Berry Atika , Ghosn Nada , Zalzali Mahmoud , Fadlallah Riad , Abou-Abbas Linda , Hassan Hamad
Published: November 2021

Background

The coronavirus disease (COVID-19) pandemic represents a serious worldwide threat. Stranded Lebanese citizens abroad appealed to the Lebanese government to embark on citizen repatriation missions. We aim to document the Lebanese experience in the repatriation of citizens during COVID-19 which allow us to disclose encountered challenges and lessons learned.

Methods

This is a retrospective description of processes involved in the phased repatriation of Lebanese citizens. The Mission consisted of 4 phases starting, April 5th until June 19th 2020. The prioritization of returnees was based on both medical and social risk assessment. The repatriation team was divided into four groups: the aircraft team, the airport team, the hotel team and the follow up team. On arrival, all returning citizens were tested using Polymerase chain Reaction (PCR) based technique, and were obliged to adhere to a mandatory facility quarantine for 24 to 48 h. Returning travelers who were tested positive for COVID-19 were transferred to the hospital. Those who were tested negative were urged to strictly comply with home-quarantine for a duration of 14 days. They were followed up on a daily basis by the repatriation team.

Results

Overall, 25,783 Lebanese citizens have returned home during the phased repatriation. The third phase ranked the uppermost in regard of the number of citizens repatriated. The total number of performed PCR tests at the airport upon arrival was 14,893 with an average percentage of around 1% positivity for COVID-19. On the other hand, more than 10,687 repatriates underwent external PCR requisite in the third and fourth phases. Two hundred seventy-two repatriates were tested positive for COVID-19 upon their arrival.

Conclusion

Considering the limited human and financial resources besides the economic and political crisis, the overall repatriation mission could be considered as a successful experience. Such processes would not have been achieved without the professionalism of all involved stakeholders.
Postoperative mediastinitis after cardiac surgery caused by Mycoplasma hominis: a case report
Authors: Kitagawa Hiroki , Shimizu Haruna , Katayama Keijiro , Tadera Kayoko , Nomura Toshihito , Omori Kietaro , Shigemoto Norifumi , Takasaki Taiichi , Ohge Hiroki , Takahashi Shinya
Published: November 2021

Background

Mycoplasma hominis is a human commensal bacterium of the urogenital tract, and extragenital infection caused by M. hominis has rarely been reported. The identification of M. hominis is challenging, and surgeons are generally not aware that this bacteria can cause postoperative infection. Here, we report a rare case of postoperative mediastinitis caused by M. hominis after cardiac surgery in an immunocompetent patient.

Case presentation

A 54-year-old man presented with pain and purulent discharge from the wound after aortic valve replacement and patent foramen ovale closure. However, Gram staining and culture of bacteria from the purulent discharge was negative, and empiric sulbactam/ampicillin therapy was not effective. This patient developed mediastinitis and rupture of a pseudoaneurysm of the ascending aorta caused by mediastinitis, and re-operation was performed. Then, postoperative mediastinitis caused by M. hominis or Ureaplasma species was suspected and bacterial cultures targeting these pathogens were performed. M. hominis was identified from abscess and tissue obtained from the surgical site and urine. A final diagnosis of postoperative mediastinitis caused by M. hominis was determined. The patient was initially treated with levofloxacin and then with minocycline for 3 weeks. The patient’s clinical condition improved; the patient was transferred to another hospital.

Conclusion

The role of M. hominis as a cause of postoperative infection might be underestimated in cardiac surgery. M. hominis should be considered when culture-negative purulent discharge is observed or there is no response to standard empiric treatment of postoperative infections.
A comparative analysis of changes in anti-immigrant and anti-Muslim attitudes in Europe: 1990–2017
Authors: Bell David Andreas , Valenta Marko , Strabac Zan
Published: November 2021

Muslims and immigrants have both been subjected to negative attitudes over the past several decades in Europe. Using data from the European Values Study, this study analyses the changes in these attitudes in the period 1990–2017. We find that negative attitudes have been increasing on average in Europe as a whole, with anti-Muslim attitudes being more prevalent than anti-immigrant attitudes. However, when split into a Western European set and an Eastern European set, from 2008, there is a divergence between the two halves. Our findings reveal that negative attitudes towards Muslims and immigrants have decreased in Western Europe, whereas they have increased significantly in Eastern Europe. Further analyses find that there are large discrepancies between anti-Muslim and anti-immigrant attitudes in different countries. These discrepancies are discussed in detail and related to several relevant factors, such as the differences in size of the Muslim and immigrant populations, variations in the refugee influx and other possible factors and developments.
Changes in nocturnal insect communities in forest-dominated landscape relevant to artificial light intensity
Authors: Hakbong Lee , Yong-Chan Cho , Sang-Woo Jung , Yoon-Ho Kim , Seung-Gyu Lee
Published: November 2021

Background

Artificial light at night has recently been identified as a major factor adversely affecting global insect diversity. Here, we compared the insect diversity in Gwangneung Forest Biosphere Reserve, specifically in the Korea National Arboretum (with no artificial light at night), with that of three nearby urban sites with a gradient of artificial light at night (five locations at each site). We analyzed the effects of the artificial night lighting index, mean annual temperature, and field light intensity (lux) at night on the insect community structure.

Results

The urban sites generally exhibited higher species richness and abundance as well as clear indicator species compared with the control site. The size distribution of the collected insects markedly differed between the control and the three urban sites. The abundance of herbivorous and omnivorous insects increased and decreased, respectively, with the increase in light intensity. Species richness of herbivorous and omnivorous insects was likely correlated with the field light intensity at night and artificial night lighting index, respectively.

Conclusions

This study demonstrates the association between nighttime environment and marked changes in insect community structure and revealed consequent transition of ecosystem services by changes in trophic group composition.
A case of tuberculosis of the rare azygos lobe of the right lung
Authors: Awal Sandeep Singh , Biswas Som Subhro , Goyal Hitesh , Awal Sampreet Kaur
Published: November 2021

Background

The azygos lobe is a rare anatomical variant seen in the upper lobe of right lung. It occurs during embryological development due to the failure of posterior cardinal vein to migrate supero-medially. It is often an incidental finding on imaging and is asymptomatic in majority of cases. Tuberculosis involving the azygos lobe is extremely rare. Only a few cases of tuberculosis involving the azygos lobe have been reported in literature.

Case presentation

We present a rare case report of tuberculosis infection involving the azygos lobe in a 57-year-old male with history of chronic cough, fever, hemoptysis, and weight loss.

Conclusions

The azygos lobe is usually asymptomatic, but it may be misdiagnosed as bulla, lung cyst, or abscess. In rare cases it may be associated with certain pathology such as tuberculosis, other infections, and lung cancer. Hence, it is pertinent for a radiologist to be aware of this variant when reporting chest imaging cases.
Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?
Authors: Srinivasan Kavya , Pandey Ashutosh Kumar , Livingston Ashlena , Venkatesh Sundararajan
Published: November 2021

The recent emergence of severe acute respiratory syndrome-Corona Virus 2 (SARS-CoV-2) in late 2019 and its spread worldwide caused an acute pandemic of Coronavirus disease 19 (COVID-19). Since then, COVID-19 has been under intense scrutiny as its outbreak led to significant changes in healthcare, social activities, and economic settings worldwide. Although angiotensin-converting enzyme-2 (ACE-2) receptor is shown to be the primary port of SARS-CoV-2 entry in cells, the mechanisms behind the establishment and pathologies of COVID-19 are poorly understood. As recent studies have shown that host mitochondria play an essential role in virus-mediated innate immune response, pathologies, and infection, in this review, we will discuss in detail the entry and progression of SARS-CoV-2 and how mitochondria could play roles in COVID-19 disease. We will also review the potential interactions between SARS-CoV-2 and mitochondria and discuss possible treatments, including whether mitochondria as a potential therapeutic target in COVID-19. Understanding SARS-CoV-2 and mitochondrial interactions mediated virus establishment, inflammation, and other consequences may provide a unique mechanism and conceptual advancement in finding a novel treatment for COVID-19.
Two Cases of Extensive Venous Thrombosis Incidentally Discovered With Bedside Ultrasound for Intravenous Access
Authors: Harms Casey , Cushman Tera
Published: November 2021

Perioperative deep vein thrombosis (DVT) is a serious and increasingly common complication. While point-of-care ultrasound is commonly used in regional nerve blocks, central vascular access, and difficult peripheral vascular, access there are very few reports of DVT incidentally discovered by anesthesiologists. We report 2 cases of diagnosis of DVT that resulted from ultrasound for difficult peripheral venous access. In the course of ultrasound-guided procedures, anesthesiologists are in a position to incidentally discover DVT and potentially change management to reduce the likelihood of DVT leading to pulmonary embolism.
Brain metastases: the role of clinical imaging
Authors: Derks Sophie H. A. E. , van der Veldt Astrid A. M. , Smits Marion
Published: November 2021

Imaging of brain metastases (BMs) has advanced greatly over the past decade. In this review, we discuss the main challenges that BMs pose in clinical practice and describe the role of imaging.

Firstly, we describe the increased incidence of BMs of different primary tumours and the rationale for screening. A challenge lies in selecting the right patients for screening: not all cancer patients develop BMs in their disease course.

Secondly, we discuss the imaging techniques to detect BMs. A three-dimensional (3D) T1W MRI sequence is the golden standard for BM detection, but additional anatomical (susceptibility weighted imaging, diffusion weighted imaging), functional (perfusion MRI) and metabolic (MR spectroscopy, positron emission tomography) information can help to differentiate BMs from other intracranial aetiologies.

Thirdly, we describe the role of imaging before, during and after treatment of BMs. For surgical resection, imaging is used to select surgical patients, but also to assist intraoperatively (neuronavigation, fluorescence-guided surgery, ultrasound). For treatment planning of stereotactic radiosurgery, MRI is combined with CT. For surveillance after both local and systemic therapies, conventional MRI is used. However, advanced imaging is increasingly performed to distinguish true tumour progression from pseudoprogression.

FInally, future perspectives are discussed, including radiomics, new biomarkers, new endogenous contrast agents and theranostics.
Epistaxis etiology and treatment
Authors: Kożuchowski Marcin , Prylińska Monika
Published: November 2021

Epistaxis occurs in approximately 60% of the general population. Every tenthperson requires treatment in a hospital setting. Epistaxis occurs in all age groups,reaching its peak in children around 10 years of age and in adults around 80years of age. The frequency and intensity of epistaxis are anatomically based onnumerous vascular connections. The cause of epistaxis in most cases can bedetermined on the basis of a detailed history and physical examination. Thereare a number of treatments available for nose bleeds. From widely availablemethods such as nasal tamponade to more advanced endovascular procedures.
Samorząd szlachecki województw poznańskiego i kaliskiego wobec cudzoziemskich żołnierzy i oficerów w wojsku powiatowym podczas panowania Jana Kazimierza (1648-1668).
Authors: Staręgowski Bartosz
Published: November 2021

Wojsko powiatowe, jako siła zbrojna samorządu, było w całości organizowane przez sejmiki. To one decydowały jakiego rodzaju formacje i oficerowie wchodzili w jego skład. Sejmik obu województw poznańskiego i kaliskiego, często stawał przed problemem powoływania wojska autoramentu cudzoziemskiego i narodowego. Wielkopolska graniczyła przecież z Brandenburgią i Śląskiem, będąc pod silnym wpływem trendów zachodnioeuropejskich. Z drugiej jednak strony tamtejsza szlachta odnosiła się nieprzychylnie do służby cudzoziemców w armii koronnej, co zresztą było wówczas typowe dla przedstawicieli całego stanu Rzeczypospolitej. Problem ten nasilił się w okresie powstania Chmielnickiego. Po śmierci Władysława IV, w uniwersałach interreksa, pojawiło się zalecenie zaciągania formacji cudzoziemskich, szczególnie tych dysponujących dużą siłą ognia. Powszechnie miano nadzieję, że wobec porażek armii koronnej, Wielkopolska sięgnie po weteranów wojny trzydziestoletniej zaciągając chorągwie powiatowe, które miały zostać posłane na Ukrainę. Celem tematu podjętego w artykule jest ukazanie postawy Wielkopolan wobec żołnierzy i oficerów zaciągu cudzoziemskiego, problemów, jakie występowały w wojskach tego typu, ustosunkowania się do presji wywieranej przez władze centralne oraz alternatywnych propozycji szlachty wielkopolskiej dotyczących służby „obcych” w wojskach samorządowych.
Formal Hierarchy As a Source of Upward Status Disagreement? A Theoretical Perspective
Authors: Yap Andy J. , Madan Nikhil , Puranam Phanish
Published: November 2021

Formal hierarchies may be presumed to reduce uncertainty about the status ordering of employees as they imply a consistent global ranking. However, formal hierarchies in organizations are not merely linear, but are characterized by branching and nesting (i.e., they comprise subunits within the organization and subunits within other subunits), which creates a local ranking of individuals within each subunit. This can create tension between global and local formal ranks as status cues. Moreover, individuals may also draw on informal status cues that are inconsistent with formal ranks. Consequently, organizational members may experience upward status disagreement (USD), whereby each assumes they have higher status than the other. We offer a theoretical model that identifies important conditions under which cues arising from the structure of the formal hierarchy—either on their own or in conjunction with informal status cues—can be a source of USD. We also explore when USD can result in status conflict and identify moderators of this relationship. Our research has implications for how the frequency of USD can be mitigated as organizational structures become more complex and the workforce becomes increasingly diverse.
Mitigasi Bencana bagi Masyarakat Penyandang Disabilitas
Authors: Hayati Arina , Bararatin Kirami , Rizqiyah Fardilla , Defiana Ima , Erwindi Collinthia
Published: November 2021

Saat ini, tingkat kerentanan terhadap bencana di Indonesia meningkat seiring dengan isu pemanasan global dan permasalahan lingkungan. Isu ini juga menjadi sorotan tujuan SDG terutama pasal 3 tentang kesehatan yang baik dan kesejahteraan (good health and well-being) dan pasal 13 tentang penangan perubahan iklim (climate action). Meskipun pemerintah telah mengeluarkan beberapa peraturan baik tentang mitigasi dan tanggap bencana, namun masyarakat kurang mendapatkan informasi yang cukup dan berkelanjutan, sehingga, tingkat kerentanan masyarakat tinggi khususnya penyadang disabilitas, lansia dan anak-anak.
Kegiatan pengabdian ini berupa workshop yang diikuti oleh 5 peserta disabilitas dan 28 mahasiswa Arsitektur ITS serta 7 anggota pengabdi. Workshop ini tidak hanya sebagai wadah untuk meningkatkan tingkat pengetahuan dan kewaspadaan terhadap bencana (alam/non-alam), tetapi juga menjadi wadah aktivitas dan diskusi bersama dan memberikan kesempatan mahasiswa Arsitektur ITS untuk berkegiatan KKN. 
Pengabdian ini merupakan kerjasama antara pengabdi dari Departemen Arsitektur FT-SPK, PIK (Pusat Informasi & Konsultasi Perempuan Penyandang Disabilitas) Sidoarjo dan Paguyupan Sehati Sukoharjo yang dilakukan dengan menggunakan strategi partisipasi dan kolaborasi. Hasil pengabdian berupa kegiatan workshop yang dilaksanakan dalam waktu 1(satu) hari dan hasil diskusi workshop dijadikan beberapa artikel ilmiah oleh mahasiswa dan tim pengabdian.