bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors associated with comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: a cross-sectional study
Authors: Li Fangyuan , Wang Xuechen , Shen Shen , Huang Kai , Wang Ming , Liu Xiaofang , Wang Chengshuo , Jin Jianmin , Zhang Luo
Published: September 2022

Background

Although 20–60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients.

Methods

This report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named “modelling” group and “validation” group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group.

Results

Totally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; P < 0.001), allergic rhinitis (OR = 2.9; P = 0.021), serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L (OR = 12.0; P < 0.001), and blood eosinophil count  ≥ 0.35 × 109/L (OR = 4.0; P = 0.001) were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA (Kappa = 0.513, P < 0.001), with sensitivity 76.9% and specificity 74.4%.

Conclusions

Female gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients.
Modified Borggreve–Van Nes-Winkelmann rotationplasty for surgery in developing countries
Authors: Sommerauer Laura , Phyo Aung , Pion Eric , Zucal Isabel , Klingelhoefer Eric , Thu Si , Win Than , Khin Sopyay , Kyaw Thura , Zaw Hein Htet , Htwe Maung Mg , Fabbri Nicola , Haerteis Silke , Aung Thiha
Published: September 2022

Background

Amputation is still the most common therapy for patients suffering from osteosarcoma in Myanmar, despite the fact that limb salvage surgery e.g. Borggreve–Van Nes-Winkelmann rotationplasty for malignant tumors located within the distal femur or proximal tibia is the current state-of-the-art reconstructive procedure. A safe and reliable operation technique is crucial in order to perform a complex surgical procedure like the rotationplasty in lower-middle income economies with limited infrastructure and resources. The authors present seven cases of patients with osteosarcomas that received a Borggreve–Van Nes-Winkelmann rotationplasty with an evaluation of the procedures focusing on safety and sustainability.

Methods

From 2019 until 2020, seven young patients with osteosarcomas of the distal femur or proximal tibia were treated with Borggreve–Van Nes-Winkelmann rotationplasties in the Orthopaedic Hospital in Mandalay, Myanmar. As modification of the standard procedure the dissection and subsequent clamping of the femoral artery in order to minimize blood loss as well as the formation of an adipocutaneous flap that minimizes swelling and decreases the pressure on the vessels were successfully performed. This modified procedure resembles a safe and simplified surgical technique that is feasible under the circumstances of lower-middle income economies with good outcomes.

Results

All patients showed good functional and aesthetic results. One of the seven patients needed secondary wound closure due to wound dehiscence.

Conclusions

A simplified and safe operation technique for the performance of the Van Nes-Borggreve rotationplasty was adapted to the given constraints in lower-middle income economies and proved to be successful.

Trial registration All patients approved to participate in the study and have given consent to publication.
Vitamin D insufficiency is associated with inflammation and deregulation of adipokines in patients with metabolic syndrome
Authors: Khademi Zeinab , Hamedi-Shahraki Soudabeh , Amirkhizi Farshad
Published: September 2022

Background

Previous studies have been reported that vitamin D deficiency increased the risk of metabolic syndrome (MetS). Nonetheless, the exact mechanisms underlying this association is unclear. Besides, inflammation and deregulation of adipokines secretion have been recognized as pivotal factors that contribute to the pathogenesis of these conditions. Therefore, we assessed whether serum vitamin D status is associated with serum levels of adipokines and inflammatory markers in these patients.

Methods

This case-control study was carried out among 65 patients with MetS who had vitamin D insufficiency (cases) and 130 MetS patients who had vitamin D sufficiency (controls). Cases and controls were recruited from among those referred to health centers in Zabol County, Iran. Vitamin D insufficiency was regarded as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 30 ng/ml. Serum concentrations of leptin, adiponectin, visfatin, and resistin and also adiponectin/leptin ratio along with serum levels of interleukin 6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α), were evaluated.

Results

Serum levels of leptin, resistin, and TNF-α were significantly higher, whereas, serum adiponectin and adiponectin/leptin ratio were significantly lower in cases than the controls. There was no significant difference in serum visfatin, IL-6, and IL-10 between the groups. Serum levels of 25(OH)D were inversely correlated with leptin, resistin, and TNF-α in both unadjusted models and after adjustment for potential confounders.

Conclusion

Our findings indicated that vitamin D insufficiency in MetS patients is associated with increased inflammation and serum adipokine abnormalities which may be associated with developing metabolic complications in these patients.
Next-generation sequencing-assisted diagnosis of a case of leprosy misdiagnosed as erythema multiforme
Authors: Zhang Yanfang , Lei Xuezhong , Lu Jiajie
Published: September 2022

Background

Leprosy is a chronic infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that is mainly transmitted through droplets from the nose and mouth of untreated patients. Owing to the lack of specific serological markers and clinical manifestations, leprosy can be easily confused with other skin lesion-related diseases and is difficult to distinguish.

Case presentation

This study introduces and summarises the diagnosis and treatment process of a case of leprosy misdiagnosed as erythema multiforme for a long time. A 43-year-old female was admitted to our hospital because of “repeated fever with superficial lymphadenopathy and systemic rash in May”. The diagnosis of the patient was based on the two main clinical characteristics of superficial lymphadenopathy and systemic pleomorphic erythema by using a combination of multiple samples of lymph nodes and skin, routine pathological examination, immunohistochemistry, acid-fast, silver hexamine, periodic acid-Schiff (PAS) staining, and second-generation gene sequencing of fresh biopsy tissue. The patient was treated with dapsone, rifampicin, and clofazimine at the Institute of Dermatology and Venereal Diseases. After treatment for 1 year, her temperature returned to normal, the area of facial erythema decreased, and the volume of axillary lymph nodes had gradually reduced.

Conclusions

In conclusion, special pathological staining and second-generation gene sequencing show promising advantages in distinguishing leprosy from other skin lesion-related diseases.
Abnormal molecular signatures of inflammation, energy metabolism, and vesicle biology in human Huntington disease peripheral tissues
Authors: Neueder Andreas , Kojer Kerstin , Hering Tanja , Lavery Daniel J. , Chen Jian , Birth Nathalie , Hallitsch Jaqueline , Trautmann Sonja , Parker Jennifer , Flower Michael , Sethi Huma , Haider Salman , Lee Jong-Min , Tabrizi Sarah J. , Orth Michael
Published: September 2022

Background

A major challenge in neurodegenerative diseases concerns identifying biological disease signatures that track with disease progression or respond to an intervention. Several clinical trials in Huntington disease (HD), an inherited, progressive neurodegenerative disease, are currently ongoing. Therefore, we examine whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in HD patients.

Results

We generate large, high-quality human datasets from skeletal muscle, skin and adipose tissue to probe molecular changes in human premanifest and early manifest HD patients—those most likely involved in clinical trials. The analysis of the transcriptomics and proteomics data shows robust, stage-dependent dysregulation. Gene ontology analysis confirms the involvement of inflammation and energy metabolism in peripheral HD pathogenesis. Furthermore, we observe changes in the homeostasis of extracellular vesicles, where we find consistent changes of genes and proteins involved in this process. In-depth single nucleotide polymorphism data across the HTT gene are derived from the generated primary cell lines.

Conclusions

Our ‘omics data document the involvement of inflammation, energy metabolism, and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials. The generated data, complemented by the primary cell lines established from peripheral tissues, and a large panel of iPSC lines that can serve as human models of HD are a valuable and unique resource to advance the current understanding of molecular mechanisms driving HD pathogenesis.
Genomic insights into the evolutionary history and diversification of bulb traits in garlic
Authors: Li Ningyang , Zhang Xueyu , Sun Xiudong , Zhu Siyuan , Cheng Yi , Liu Meng , Gao Song , Zhang Jiangjiang , Wang Yanzhou , Yang Xiai , Chen Jianrong , Li Fu , He Qiaoyun , Zeng Zheng , Yuan Xiaoge , Zhou Zhiman , Ma Longchuan , Wang Taotao , Li Xiang , Liu Hanqiang , Pan Yupeng , Zhou Mengyan , Gao Chunsheng , Zhou Gang , Han Zhenlin , Liu Shiqi , Su Jianguang , Cheng Zhihui , Tian Shilin , Liu Touming
Published: September 2022

Background

Garlic is an entirely sterile crop with important value as a vegetable, condiment, and medicine. However, the evolutionary history of garlic remains largely unknown.

Results

Here we report a comprehensive map of garlic genomic variation, consisting of amazingly 129.4 million variations. Evolutionary analysis indicates that the garlic population diverged at least 100,000 years ago, and the two groups cultivated in China were domesticated from two independent routes. Consequently, 15.0 and 17.5% of genes underwent an expression change in two cultivated groups, causing a reshaping of their transcriptomic architecture. Furthermore, we find independent domestication leads to few overlaps of deleterious substitutions in these two groups due to separate accumulation and selection-based removal. By analysis of selective sweeps, genome-wide trait associations and associated transcriptomic analysis, we uncover differential selections for the bulb traits in these two garlic groups during their domestication.

Conclusions

This study provides valuable resources for garlic genomics-based breeding, and comprehensive insights into the evolutionary history of this clonal-propagated crop.
AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles
Authors: Simone Laura , Pisani Francesco , Binda Elena , Frigeri Antonio , Vescovi Angelo L. , Svelto Maria , Nicchia Grazia P.
Published: September 2022

Background

Extracellular vesicles (EVs) are membrane-enclosed particles released systemically by all cells, including tumours. Tumour EVs have been shown to manipulate their local environments as well as distal targets to sustain the tumour in a variety of tumours, including glioblastoma (GBM).

We have previously demonstrated the dual role of the glial water channel aquaporin-4 (AQP4) protein in glioma progression or suppression depending on its aggregation state. However, its possible role in communication mechanisms in the microenvironment of malignant gliomas remains to be unveiled.

Results

Here we show that in GBM cells AQP4 is released via EVs that are able to affect the GBM microenvironment. To explore this role, EVs derived from invasive GBM cells expressing AQP4-tetramers or apoptotic GBM cells expressing orthogonal arrays of particles (AQP4-OAPs) were isolated, using a differential ultracentrifugation method, and were added to pre-seeded GBM cells. Confocal microscopy analysis was used to visualize the interaction and uptake of AQP4-containing EVs by recipient cells. Chemoinvasion and Caspase3/7 activation assay, performed on recipient cells after EVs uptake, revealed that EVs produced by AQP4-tetramers expressing cells were able to drive surrounding tumour cells toward the migratory phenotype, whereas EVs produced by AQP4-OAPs expressing cells drive them toward the apoptosis pathway.

Conclusion

This study demonstrates that the different GBM cell phenotypes can be transferred by AQP4-containing EVs able to influence tumour cell fate toward invasiveness or apoptosis.

This study opens a new perspective on the role of AQP4 in the brain tumour microenvironment associated with the EV-dependent communication mechanism.

Graphical Abstract
Increasing the intensity of regeneration treatments decreased beta diversity of temperate hardwood forest understory 20 years after disturbance
Authors: Jaeger Romain , Delagrange Sylvain , Aubin Isabelle , Joanisse Gilles , Raymond Patricia , Rivest David
Published: September 2022

Context

In temperate hardwood forests, increased intensity of soil and canopy disturbances tends to increase species richness due to the establishment of numerous early-successional plant species. However, while competitive pioneer species from early stages of succession can become recalcitrant and alter patterns of natural regeneration, very few studies have examined longer-term effects of these treatments on plant biodiversity.

Aims

In this study, we investigated mid-term (ca. 20 years) effects of different regeneration treatments with varying soil and canopy disturbance intensities. We compared understory plant communities in temperate hardwood forests from all the South of Quebec (Canada).

Methods

Using circular experimental plots of 1962.5 m2 (radius = 25 m), we measured taxonomic and functional diversity indices and soil properties using four levels of disturbance intensity in six temperate hardwood forests of Quebec distributed along a longitudinal gradient. Reference forests, i.e. control forests with no silvicultural treatment known for ≥ 80 years, were compared to 20-year-old single-tree selection cuts, group-selection cuts and group-selection cuts with soil scarification.

Results

Species richness in both group-selection treatments was higher than that in reference forests. Plant equitability and beta diversity among sites in both group-selection treatments were lower than in single-tree selection cuts and control forests. More intense treatments contributed to the mid-term persistence of recalcitrant competitor species (e.g. Rubus idaeus L., Prunus pensylvanica L.f.) whereas soil scarification appears to have negative sustained effects on species known to be sensitive to regeneration treatments (e.g. Monotropa uniflora L., Dryopteris spinulosa Kuhn).

Conclusions

In temperate hardwood forests of Southern Quebec, silvicultural treatments of higher intensities resulted in detrimental effects on soil properties, especially in the surface horizon, 20 years after disturbance. This legacy, in turn, affected the composition and diversity of understory plant communities. The more intense silvicultural treatments contributed to the persistence of pioneer species better adapted to a wider range of environmental conditions and resulted in a decrease in understory plant community heterogeneity among sites. Conversely, single-tree selection cutting appeared to be the most appropriate silvicultural treatment for maintaining soil functions and heterogeneity of understory plant communities after 20 years; composition and structure being similar to long-undisturbed forests.
The putative mechanistic insights on how SARS-CoV-2 might influence the outcomes in cancer patients
Authors: Deng Jingwen , Cai Xiaopeng , Chen Zhi
Published: September 2022

Early evidence indicated that cancer patients are at increased risk of adverse outcomes and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To determine the putative mechanism by which SARS-CoV-2 affects patients with cancers, we conducted a preliminary exploration at the molecular level. We collected differentially expressed proteins (DEPs) in the lung, liver, kidney, and thyroid of postmortem coronavirus disease 2019 (COVID-19) and non-COVID-19 patients from iProX database. Furthermore, we collected differentially expressed genes (DEGs) related to overall survival (OS) in lung cancer, liver cancer, kidney cancer and thyroid cancer based on the Cancer Genome Atlas (TCGA) database. We obtained the intersection of DEPs and DEGs and identified the roles of shared and remaining DEPs in corresponding cancers based on published research. Finally, we found 192, 179, 154 and 147 DEPs in lung, liver, kidney and thyroid tissues and 486, 1140, 2245 and 31 DEGs related to OS in lung cancer, liver cancer, kidney cancer and thyroid cancer, respectively. 4, 8, 6 and 0 shared genes/proteins and 48, 42, 14 and 10 remaining proteins were verified to play a role in lung cancer, liver cancer, kidney cancer and thyroid cancer, respectively. Changes in 85% (44/52), 78% (39/50), 80% (16/20) and 90% (9/10) of the verified genes/proteins, including shared and remaining genes, showed poor effects on patients with the 4 cancer types with COVID-19. In conclusion, the changes in genes/proteins caused by SARS-CoV-2 might dictate the different degrees of adverse outcomes in patients with different tumors.
Tsunami deposits associated with the 1983 Nihonkai-Chubu earthquake tsunami in coastal forests near Happo Town, Akita Prefecture, Japan
Authors: Chiba Takashi , Nishimura Yuichi
Published: September 2022

On 26 May 1983 the Nihonkai-Chubu earthquake occurred off the western coast of Noshiro City, Akita Prefecture, Japan. The tsunami associated with this earthquake caused widespread damage to the northeastern coastal region of the Sea of Japan, including Akita Prefecture, and left behind sand and mud deposits. These deposits were first described in the 1990s, but have not been studied further. During December 2019 and January 2020, we conducted geological surveys to investigate post-1948 soil thinning in the pine-based coastal protective forests planted near Happo Town. A sand layer that thinned inland was observed in the soil at depths greater than 10 cm. Because the sand layer contained well-preserved fossil brackish–marine diatoms and exhibited a high bulk density, it is likely that the sand was transported inland from the coast. The sand layer was distributed from the coast to 150–270 m inland, but only within the coastal protective forest. By reference to historical records, we concluded that this sand layer was deposited by the 1983 tsunami, because this region could not have been reached by any event other than the tsunami produced by the Nihonkai-Chubu earthquake. We also observed another sand layer above the tsunami deposits, which may have been formed by Typhoon 9119 on 28 September 1991.

Graphical Abstract
Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide–Based Vaccine in Patients With Refractory Advanced Non–Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study
Authors: Adotévi Olivier , Vernerey Dewi , Jacoulet Pascale , Meurisse Aurélia , Laheurte Caroline , Almotlak Hamadi , Jacquin Marion , Kaulek Vincent , Boullerot Laura , Malfroy Marine , Orillard Emeline , Eberst Guillaume , Lagrange Aurélie , Favier Laure , Gainet-Brun Marie , Doucet Ludovic , Teixeira Luis , Ghrieb Zineb , Clairet Anne-Laure , Guillaume Yves , Kroemer Marie , Hocquet Didier , Moltenis Mélanie , Limat Samuel , Quoix Elisabeth , Mascaux Céline , Debieuvre Didier , Fagnoni-Legat Christine , Borg Christophe , Westeel Virginie
Published: September 2022

PURPOSE

Universal cancer peptide–based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year.

RESULTS

A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders ( P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( P = .005), respectively.

CONCLUSION

UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.
Η κοινότητα της Σύμης κατά την οθωμανική περίοδο
Authors: Πούλιος Στέφανος
Published: September 2022

Η διατριβή έχει ως αντικείμενο μελέτης την κοινωνία και την οικονομία της Σύμης κατά την οθωμανική περίοδο (1522-1912), τον βαθμό ένταξης του νησιού στους μηχανισμούς ελέγχου της οθωμανικής αυτοκρατορίας και τη βασική δραστηριότητα που διαμόρφωνε τον χαρακτήρα του νησιού, τη σπογγαλιεία. Η εργασία επιχειρεί να συμπληρώσει την εικόνα των νησιωτικών ελληνορθόδοξων κοινοτήτων, να μεταβάλει τις κυρίαρχες παραδοχές για το αφορολόγητο και τον προνομιακό χαρακτήρα του διοικητικού καθεστώτος αυτών των κοινοτήτων παίρνοντας ως ανάλυση περίπτωσης τη Σύμη, η οποία στη δωδεκανησιακή βιβλιογραφία παρουσιάζεται ως το νησί που είχε αποσπάσει προνόμια επικυρωμένα με φιρμάνια πρώτα από τον Σουλεϊμάν τον Μεγαλοπρεπή κατά την κατάκτηση των Δωδεκανήσων από τους Οθωμανούς και έπειτα από τους μεταγενέστερους σουλτάνους. Στη διατριβή αναθεωρούνται οι παραδοχές περί απουσίας της οθωμανικής διοίκησης στο νησί και περιγράφονται με αναλυτικό τρόπο οι σχέσεις οθωμανικών θεσμών και κοινότητας. Παράλληλα, αναδεικνύεται μία κοινωνία που βασίζεται σε μία ιδιαίτερη καθολική και συνεχή χρονικά δραστηριότητα, τη σπογγαλιεία, συνδέοντας τον ιδιαίτερο χαρακτήρα του νησιού με τη διαμόρφωση της σχέσης του με την οθωμανική εξουσία ήδη από τον 16ο αιώνα. Περιγράφεται ο μετασχηματισμός των σχέσεων εργασίας και οι αλλαγές που συμβαίνουν με την εκμηχάνιση και τη διεθνοποίηση της σπογγαλιείας και τη συσσώρευση κεφαλαίων με την αύξηση των επενδύσεων και του κύκλου εργασιών. Εξετάζεται το κίνημα κατά των μηχανών και οι αντιδράσεις των εφοπλιστών αλλά και της οθωμανικής διοίκησης στις κινητοποιήσεις των παραδοσιακών δυτών απέναντι στην εκμηχάνιση της εργασίας τους. Τέλος, εξηγείται με ποιον τρόπο ήταν εφικτή σε συνθήκες δανεισμού και ανταγωνιστικής εκμετάλλευσης της σπογγαλιείας η διατήρηση μιας κοινοτικής κοινωνικής διαχείρισης που εξασφάλιζε εκπαίδευση και πρωτοβάθμια υγεία σε όλα τα μέλη της. Συζητούνται οι παραδοσιακές θεωρήσεις για την οθωμανική Σύμη και μελετώνται οι εσωτερικές ισορροπίες της κοινότητας, η εξέλιξη της σχέσης με την οθωμανική εξουσία και ο μετασχηματισμός της οικονομίας του νησιού. Η διατριβή βασίζεται σε αδημοσίευτες οθωμανικές και ελληνικές πηγές που απόκεινται σε αρχεία στην Ελλάδα και την Τουρκία, υλικό από τις γαλλικές προξενικές πηγές, από τα νοταριακά έγγραφα και από άλλες σωζόμενες ελληνικές πηγές, όπως και από τις περιηγητικές αναφορές και άλλες αγγλικές ή γαλλικές πηγές που πλαισιώθηκαν από εκτεταμένη βιβλιογραφική υποστήριξη.
Quantitative proteomic analysis of SARS-CoV-2 infection of primary human airway ciliated cells and lung epithelial cells demonstrates the effectiveness of SARS-CoV-2 innate immune evasion
Authors: Crozier Thomas W.M. , Greenwood Edward J.D. , Williamson James C. , Guo Wenrui , Porter Linsey M. , Gabaev Ildar , Teixeira-Silva Ana , Grice Guinevere L. , Wickenhagen Arthur , Stanton Richard J. , Wang Eddie C. Y. , Wilson Sam J. , Matheson Nicholas J. , Nathan James A. , McCaughan Frank , Lehner Paul J.
Published: September 2022

Background: Quantitative proteomics is able to provide a comprehensive, unbiased description of changes to cells caused by viral infection, but interpretation may be complicated by differential changes in infected and uninfected ‘bystander’ cells, or the use of non-physiological cellular models.

Methods: In this paper, we use fluorescence-activated cell sorting (FACS) and quantitative proteomics to analyse cell-autonomous changes caused by authentic SARS-CoV-2 infection of respiratory epithelial cells, the main target of viral infection in vivo. First, we determine the relative abundance of proteins in primary human airway epithelial cells differentiated at the air-liquid interface (basal, secretory and ciliated cells). Next, we specifically characterise changes caused by SARS-CoV-2 infection of ciliated cells. Finally, we compare temporal proteomic changes in infected and uninfected ‘bystander’ Calu-3 lung epithelial cells and compare infection with B.29 and B.1.1.7 (Alpha) variants.

Results: Amongst 5,709 quantified proteins in primary human airway ciliated cells, the abundance of 226 changed significantly in the presence of SARS-CoV-2 infection (q <0.05 and >1.5-fold). Notably, viral replication proceeded without inducing a type-I interferon response. Amongst 6,996 quantified proteins in Calu-3 cells, the abundance of 645 proteins changed significantly in the presence of SARS-CoV-2 infection (q < 0.05 and > 1.5-fold). In contrast to the primary cell model, a clear type I interferon (IFN) response was observed. Nonetheless, induction of IFN-inducible proteins was markedly attenuated in infected cells, compared with uninfected ‘bystander’ cells. Infection with B.29 and B.1.1.7 (Alpha) variants gave similar results.

Conclusions: Taken together, our data provide a detailed proteomic map of changes in SARS-CoV-2-infected respiratory epithelial cells in two widely used, physiologically relevant models of infection. As well as identifying dysregulated cellular proteins and processes, the effectiveness of strategies employed by SARS-CoV-2 to avoid the type I IFN response is illustrated in both models.
CERVICAL-ISTHMIAN PREGNANCY: A CLINICAL CASE OF GESTATION AND BIRTH OF A CHILD
Authors: Cheremiskin V. , Filyanina A.
Published: September 2022

Cervical-isthmian pregnancy is a very rare form of ectopic pregnancy, characterized by the localization of the fetus in the isthmus and cervix. This pathology is associated with disorders of ovum fixation in the uterine body in patients with a burdened obstetric and gynecological history and is characterized by a high risk of maternal mortality due to the possible development of life-threatening complications (DIC syndrome, bleeding). But, unlike other forms of ectopic pregnancy, it is with her that you can carry and give birth to a child. The article presents such a case.
Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis, A Review of Pathogenesis, Clinical Features, Diagnosis and Treatment
Authors: Rozenbajgier Martyna , Wójcik-Grudzień Justyna , Pawłowska Paulina , Ozga-Stachurska Alicja
Published: September 2022

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, acute conditions, potentially life-threatening, immune-mediated and often unpredictable.

Characteristic for SJS and TEN is acute necrosis of the epidermis and mucous membranes, caused by the extensive death of keratinocytes. These syndromes are considered hypersensitivity reactions. They are most often caused by drugs. There have also been reports of SJS / TEN being caused by infection,

SJS/TEN disease is very rare and due to its rarity there is no specific pharmaceutical algorythm. Supportive care and treatment of symptoms are very important. The most crucial part of non-pharmacologic treatment of SJS/TEN is the detection and cessation of the pharmaceutical that caused the disease.

The aim of this literature review was to summarize current knowledge about the pathogenesis, clinical features, diagnosis and treatment of Stevens- Johnson Syndrom and Toxic Epidermal Necrolysis.

Standard criteria were used to review the literature data. The search of articles in the PubMed and Google Scholar database was carried out using the following keywords: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, cutaneous adverse drug reactions
Erken Çocukluk Döneminde Kalıtsal Metabolik Hastalığı Olan Çocukların COVİD-19 Pandemisinde Gelişimsel Risk Etmenleri
Authors: ÖZALP AKIN Ezgi , EMİNOĞLU Fatma Tuba
Published: September 2022

Amaç: Koronavirus hastalığı 2019 (COVİD-19) pandemisi, yeni gelişimsel risk faktörlerinin ortaya çıkmasına neden olmuştur. Ancak kalıtsal metabolik hastalıkları olan küçük çocuklar için gelişimsel risk faktörleri, kapsamlı bir çerçeveye dayalı olarak çalışılmamıştır. Bu araştırmanın amacı COVİD-19 pandemisinde kalıtsal metabolik hastalığı olan küçük çocukların biyoekolojik kuram çerçevesinde gelişimsel risk etmenlerini belirlemektir.
Gereç ve Yöntemler: Kesitsel desendeki araştırmada, Ankara Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı (AUÇH) Çocuk Metabolizma Bilim Dalında kalıtsal metabolik hastalık tanısı ile randevusu olan 0-42 aylık  çocuklar, 1 Ekim 2020-1 Ocak 2021 tarihleri arasında çalışmaya alındı ve AUÇH Gelişimsel Pediatri Bilim Dalında Genişletilmiş Gelişimi İzlenme ve Destekleme Rehberi’nin sorularına dayalı olarak yarı yapılandırılmış bir görüşme ile gelişimsel risk etmenleri değerlendirildi.
Bulgular: Örneklem, kalıtsal metabolik bozukluğu olan 95 çocuktan oluşmaktadır (ortanca yaş: 25, ÇAA: 17-35 ay, %57.9 erkek). Çocukların çoğunda (54 çocuk, %56.8) aminoasit metabolizma bozukluğu tanısı bulunmaktaydı. Çocukla ilgili gelişimsel risk etmenleri alanında örneklemin çoğunda (53 çocuk, %55.8) yeni ortaya çıkan davranış sorunları ve 26 çocukta (%27.3) artmış ekran süresi saptandı. Aile ile ilgili gelişimsel risk etmenleri olarak, 40 çocuğun (%42.1) evinde majör depresyon tanısı almış bir birey bulunmaktaydı. Çevre ile ilgili gelişimsel risk etmenleri alanında 41 aile (%43.2) pandemide hane gelirinde azalma, 21 aile (%22.1) iş kaybı, 17 aile (%17.9) sağlık izlemlerinde gecikme, girişim ve rehabilitasyon hizmetleri alan 28 ailenin 8’i (%28.6) kesinti bildirdi, 42 (%44.2) çocuğun yaşama katılımı ciddi şekilde sınırlıydı.
Sonuç: Türkiye’de ve büyük olasılıkla diğer düşük ve orta gelirli ülkelerde kalıtsal metabolik hastalığı olan çocuklar yaşamı tehdit eden tıbbi sorunların yanı sıra birden fazla çevresel gelişimsel risk etmeni ile karşı karşıyadır. Bu çocukların pandemi ve diğer olası kriz dönemlerinde gelişimlerini desteklemek için önlenebilir risk etmenleri önlenmeli ve mümkün olduğunca risk etmenleri azaltılmalıdır.
Specially Designed Instruction of Early Numeracy in the Inclusive Elementary Classroom for Students With Extensive Support Needs
Authors: Jimenez Bree A. , Barron Tammy
Published: September 2022

Inclusive opportunities for students with extensive support needs are a predictor of both in school and post-school outcomes; however, successful inclusion must consider how student learning needs and evidence-based practices are incorporated. Potential exists to align evidence-based instruction for students with extensive support needs utilizing the Multi-tiered System of Support (MTSS) framework for all students within the inclusive math classroom across tier 2 and tier 3. Findings of this single-case, multiple probe, across student research study suggest that embedded instruction is an effective and feasible instructional practice to support specially designed instruction in early numeracy within a tiered support model for students with extensive support needs in the inclusive math classroom. Based upon our findings, we sought to develop a model of practice for specially designed instruction (SDI) within tiered systems of support for students with extensive support needs that educational teams, school administrators, and policymakers can use to design math instruction within inclusive settings.
Distance insensitive reflectance setup for the spectrally resolved determination of the optical properties of highly turbid media
Authors: Hank Philipp , Pink Karsten , Junior Luismar Barbosa da Cruz , Foschum Florian , Kienle Alwin
Published: September 2022

A measurement system for a distance insensitive acquisition of the reflectance from turbid media is presented. The geometric relationships of the detection unit are discussed theoretically and subsequently verified using Monte Carlo simulations. In addition, an experimental setup is presented to prove the theoretical considerations and simulations. The use of the presented measurement system allows measurements of the reflectance in a distance range of approximately

2.5

c
m

with a deviation of less than

±

0.5
%

for highly scattering media. This contrasts with the use of a fiber in a classical detection unit placed at a defined angle and position relative to the sample surface, which results in deviations of

±

30
%

in the measured reflectance over the same distance range.
Haze optical-model-based nighttime image dehazing by modifying attenuation and atmospheric light
Authors: Lin Sen , Sun Penghui , Gao Hongwei , Ju Zhaojie
Published: September 2022

Scene imaging is often affected by artificial light sources within a hazy environment at night, causing degraded images with low brightness, color distortion, and glow. These problems render the traditional atmospheric scattering optical model obsolete and incompatible. To address this issue, we established an optical imaging model suitable for nighttime dehazing, and an illumination component is incorporated into the attenuation term. We also introduced the near-light source coefficient to redefine the glow. Based on this model, we propose a new nighttime dehazing method. First, the rough atmospheric light is estimated using its low-frequency characteristics. Then, the glow is calculated by the near-light source coefficient. Finally, we remove the haze and illumination to get a clear image. Extensive experiments prove that our method exhibits a better color recovery effect, which effectively improves the visibility and detail. Furthermore, we believe our method outperforms other methods, both qualitatively and quantitatively.
Imp interacts with Lin28 to regulate adult stem cell proliferation in the Drosophila intestine
Authors: Sreejith Perinthottathil , Malik Sumira , Kim Changsoo , Biteau Benoît
Published: September 2022

Stem cells are essential for the development and long-term maintenance of tissues and organisms. Preserving tissue homeostasis requires exquisite control of all aspects of stem cell function: cell potency, proliferation, fate decision and differentiation. RNA binding proteins (RBPs) are essential components of the regulatory network that control gene expression in stem cells to maintain self-renewal and long-term homeostasis in adult tissues. While the function of many RBPs may have been characterized in various stem cell populations, how these interact and are organized in genetic networks remains largely elusive. In this report, we show that the conserved RNA binding protein IGF2 mRNA binding protein (Imp) is expressed in intestinal stem cells (ISCs) and progenitors in the adultDrosophilamidgut. We demonstrate that Imp is required cell autonomously to maintain stem cell proliferative activity under normal epithelial turnover and in response to tissue damage. Mechanistically, we show that Imp cooperates and directly interacts with Lin28, another highly conserved RBP, to regulate ISC proliferation. We found that both proteins bind to and control the InR mRNA, a critical regulator of ISC self-renewal. Altogether, our data suggests that Imp and Lin28 are part of a larger gene regulatory network controlling gene expression in ISCs and required to maintain epithelial homeostasis.
Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins
Authors: Gavor Edem , Choong Yeu Khai , Liu Yonghao , Pompon Julien , Ooi Eng Eong , Mok Yu Keung , Liu Haiyan , Kini R Manjunatha , Sivaraman J.
Published: September 2022

Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11Ae.aegyptisalivary gland proteins (SGPs) (e.g., apyrase,Ae.aegyptivenom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), anAe.aegyptisaliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections.
Mobile application development for improving medication safety in tuberculosis patients: A quasi-experimental study protocol
Authors: Wijayanti Erlina , Bachtiar Adang , Achadi Anhari , Rachmawati Ummi Azizah , Sjaaf Amal Chalik , Eryando Tris , Besral  , Trihono  , Siregar Kemal N. , Vidiawati Dhanasari
Published: September 2022

The COVID-19 pandemic, the growth of smartphones, and the internet have driven the use of technology for monitoring TB patients. Innovation in management of TB patients is needed to improve treatment outcomes. The study was conducted to obtain a predictive model of medication safety and solution model for at-risk patients, and to improve medication safety through mobile applications. The research was conducted in 4 stages, namely qualitative, quantitative (cross-sectional), qualitative, and quantitative (quasi-experimental, post-test group control design). Data were taken at the Public Health Center in Jakarta, Indonesia. Samples were taken by cluster random sampling. For quantitative research, 2nd phase (n = 114) and 4th phase (n = 96) were analyzed using logistic regression. This study analyzed predictors of medication safety to assist in monitoring patients undergoing treatment. At-risk patients were educated using an algorithm programmed in the application.
Morbidities, health problems, health care seeking and utilization behaviour among elderly residing on urban areas of eastern Nepal: A cross-sectional study
Authors: Poudel Mukesh , Ojha Asmita , Thapa Jeevan , Yadav Deepak Kumar , Sah Ram Bilakshan , Chakravartty Avaniendra , Ghimire Anup , Sundar Budhathoki Shyam
Published: September 2022

Background

Morbidity increases with age and enhances the burden of health problems that result in new challenges to meet additional demands. In the ageing population, health problems, and health care utilization should be assessed carefully and addressed. This study aimed to identify chronic morbidities, health problems, health care seeking behaviour and health care utilization among the elderly.

Methods

We conducted a community based, cross-sectional study in urban areas of the Sunsari district using face-to-face interviews. A total of 530 elderly participants were interviewed and selected by a simple proportionate random sampling technique.

Results

About half, 48.3%, elderly were suffering from pre-existing chronic morbidities, of which, 30.9% had single morbidity, and 17.4% had multi-morbidities. This study unfurled more than 50.0% prevalence of health ailments like circulatory, digestive, eye, musculoskeletal and psychological problems each representing the burden of 68.7%, 68.3%, 66.2%, 65.8% and 55.7% respectively. Our study also found that 58.7% preferred hospitals as their first contact facility. Despite the preferences, 46.0% reported visiting traditional healers for treatment of their ailments. About 68.1% reported having difficulty seeking health care and 51.1% reported visits to a health care facility within the last 6 months period. The participants with pre-existing morbidity, health insurance, and an economic status above the poverty line were more likely to visit health care facilities.

Conclusion

Elderly people had a higher prevalence of health ailments, but unsatisfactory health care seeking and health care utilization behaviour. These need further investigation and attention by the public health system in order to provide appropriate curative and preventive health care to the elderly. There is an urgent need to promote geriatric health services and make them available at the primary health care level, the first level of contact with a national health system.
Long-term health-related quality of life, healthcare utilisation and back-to-work activities in intensive care unit survivors: Prospective confirmatory study from the Frisian aftercare cohort
Authors: Beumeler Lise F. E. , van Wieren Anja , Buter Hanneke , van Zutphen Tim , Navis Gerjan J. , Boerma E. Christiaan
Published: September 2022

Purpose

More substantial information on recovery after Intensive Care Unit (ICU) admission is urgently needed. In a previous retrospective study, the proportion of non-recovery patients was 44%. The aim of this prospective follow-up study was to evaluate changes in Health-Related Quality of Life (HRQoL) in the first year after ICU-admission.

Methods

Long-stay adult ICU-patients (≥ 48 hours) were included. HRQoL was evaluated with the Dutch translation of the RAND-36 item Health Survey (RAND-36) at baseline via proxy measurement, and at three, six, and twelve months after ICU admission. Subsequently, the relation between physical functioning, healthcare utilisation, and work activities was explored.

Results

A total of 81 patients were included in this study. Fifty-five percent of patients did not meet criteria for full recovery and were allocated to the Non Recovery (NR)-group (Physical Functioning domain-score: 35 [15–55]). Baseline physical HRQoL differed significantly between the Recovery (R) and NR-group. Patients in the NR-group received home care more often and had higher healthcare utilisation (44 versus 17% in the first three months post-ICU, p = 0.013). Only fourteen percent of NR-patients were able to participate in work activities. Moreover, NR-patients persistently showed impaired overall HRQoL throughout the year after critical illness.

Conclusions

Limited recovery in ICU survivors is reflected in overall impaired HRQoL, as well as in far-reaching consequences for patients’ healthcare needs and their ability to reintegrate into society. In our study, baseline HRQoL appeared to be an important predictor of long-term outcomes, but not Clinical Frailty Scale (CFS) score. And, (proxy-derived) HRQoL may help to identify patients at risk of long-term non-recovery.
Early rapid weight gain, parental body mass index and the association with an increased waist-to-height ratio at 5 years of age
Authors: Lindholm Annelie , Almquist-Tangen Gerd , Alm Bernt , Bremander Ann , Dahlgren Jovanna , Roswall Josefine , Staland-Nyman Carin , Bergman Stefan
Published: September 2022

Background/Objectives

Obesity-related adverse health consequences are closely associated with abdominal obesity. Risk factors for overweight and obesity have been studied but there is a lack of information regarding risk factors for abdominal obesity, especially in the preschool population. The aim of the present study was to examine early life risk factors for an increased waist-to-height ratio (WHtR) in children at five years of age and, in addition, to investigate if these risk factors also were associated with overweight or obesity.

Subjects/Methods

The study population comprised 1,540 children from a population-based longitudinal birth cohort study that included 2,666 Swedish children. The children were included if they had complete growth data for the analyses used in this study. Children were classified as having WHtR standard deviation scores (SDS) ≥ 1 or < 1 at five years of age, according to Swedish reference values, and as having body mass index standard deviation scores (BMISDS) for overweight/obesity, or normal weight/underweight according to the International Obesity Task Force criteria. Associations between child-related, socioeconomic status-related, parental health-related and nutrition- and feeding practice-related factors during the first two years and a WHtRSDS ≥1 or a BMISDSfor overweight/obesity at five years were investigated with logistic regression analyses.

Results

At five years of age, 15% of the children had WHtRSDS ≥1 and 11% had overweight or obesity. In multivariable analyses, rapid weight gain (RWG) during 0–6 months (OR: 1.90, 95% CI: 1.23–2.95, p = 0.004), maternal pre-pregnancy BMI (1.06, 1.01–1.11, p = 0.019) and paternal BMI (1.11, 1.01–1.21, p = 0.028) were associated with WHtRSDS ≥1. RWG during 0–6 months (2.53, 1.53–4.20, p<0.001), 6–12 months (2.82, 1.37–5.79, p = 0.005), and maternal pre-pregnancy BMI (1.11, 1.06–1.17, p<0.001) were associated with overweight or obesity.

Conclusions

Early risk factors, including rapid weight gain, are associated with increased WHtRSDSand overweight or obesity at 5 years of age. Preventive interventions should target early RWG and parental overweight and obesity.