bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma
Authors: Herviou Laurie , Ovejero Sara , Izard Fanny , Karmous-Gadacha Ouissem , Gourzones Claire , Bellanger Celine , De Smedt Eva , Ma Anqi , Vincent Laure , Cartron Guillaume , Jin Jian , De Bruyne Elke , Grimaud Charlotte , Julien Eric , Moreaux Jérôme
Published: September 2021

Background

Multiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. In addition to a wide panel of genetic mutations, epigenetic alterations also appear as important players in the development of this cancer, thereby offering the possibility to reveal novel approaches and targets for effective therapeutic intervention.

Results

Here, we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for the mono-methylation of histone H4 at lysine 20, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Primary malignant plasma cells are particularly addicted to the activity of this epigenetic enzyme. Indeed, the inhibition of SETD8 by the chemical compound UNC-0379 and the subsequent decrease in histone H4 methylation at lysine 20 are highly toxic in MM cells compared to normal cells from the bone marrow microenvironment. At the molecular level, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and, as observed in other cancers, triggers an activation of the tumor suppressor p53, which together cause an impairment of myeloma cell proliferation and survival. However, a deadly level of replicative stress was also observed in p53-deficient myeloma cells treated with UNC-0379, indicating that the cytotoxicity associated with SETD8 inhibition is not necessarily dependent on p53 activation. Consistent with this, UNC-0379 triggers a p53-independent nucleolar stress characterized by nucleolin delocalization and reduction of nucleolar RNA synthesis. Finally, we showed that SETD8 inhibition is strongly synergistic with melphalan and may overcome resistance to this alkylating agent widely used in MM treatment.

Conclusions

Altogether, our data indicate that the up-regulation of the epigenetic enzyme SETD8 is associated with a poor outcome and the deregulation of major signaling pathways in MM. Moreover, we provide evidences that myeloma cells are dependent on SETD8 activity and its pharmacological inhibition synergizes with melphalan, which could be beneficial to improve MM treatment in high-risk patients whatever their status for p53.
Comparison of weight per volume and protein nitrogen units in non-standardized allergen extracts: implications for prescribing subcutaneous immunotherapy
Authors: Dua Benny , Park Jane , Kim Harold
Published: September 2021

Background

Allergen extracts used in subcutaneous immunotherapy can be standardized or non-standardized. Standardized extracts are available in specific biological potencies, presumably making their biological activity more consistent. The majority of allergen extracts are non-standardized and may have less consistent potencies. Non-standardized extracts are labeled as weight per volume or protein nitrogen units (PNUs). Neither method provides direct information regarding the extract’s biologic potency. The purpose of this study was to compare weight per volume versus PNU concentrations for 4 non-standardized allergen extracts prepared by two allergen manufacturers. The potencies were compared to current North American practice recommendations.

Methods

The weight per volume and PNU values were provided for 4 non-standardized extracts—birch, short ragweed, dog hair and Alternaria—from HollisterStier and Stallergenes Greer. Weight per volume and PNU concentrations were compared for each of these extracts from both manufacturers. From the raw data, we calculated the corresponding PNU values for a weight per volume of 1:100 and 1:200 for each extract. Similarly, we calculated the corresponding weight per volume including a range of PNU values, for 1000, 2000, 3000, 4000 and 5000 PNU/ml.

Results

Birch extract has low PNU concentration, below 5000, for a weight per volume of 1:200 for both HollisterStier and Stallergenes Greer. In contrast, for both HollisterStier and Stallergenes Greer ragweed extract, a weight per volume of 1:200 corresponds to a PNU concentration greater than 5000. Dog extract for a weight per volume of 1:200, and even for 1:100, corresponds to very low PNUs for both companies. For Alternaria, corresponding PNU concentrations for HollisterStier is low at only 500 while over 5000 for Stallergenes Greer.

Conclusions

Our results show variability when comparing weight per volume and PNU concentrations for both Hollister-Stier and Stallergenes Greer products. We suggest selecting a PNU dose that corresponds to a weight per volume of 1:200 as this may improve patient safety. Our recommendations for starting PNU dose for the four non-standardized extracts are 1500 for birch, 5000 for ragweed, 25 for dog, and 500 for Alternaria when using HollisterStier products; 2300 for birch, 5000 for ragweed, 1200 for dog, and 5000 for Alternaria when using Stallergenes Greer products. If the starting PNU concentration is considerably below 5000 for a weight per volume of 1:200 slow up-titration is advised. Conversely, for PNU concentrations above 5000 for weight per volume of 1:200 we suggest a maintenance dose of 5000 PNU.
Gonococcus infection probably acquired from bathing in a natural thermal pool: a case report
Authors: Goodyear-Smith Felicity , Schabetsberger Robert
Published: September 2021

Background

Authorities need to recognize that, while rare, gonorrhea can be transmitted nonsexually, and should not be presumed definitive evidence of abuse. We report the unusual case of a girl diagnosed withNeisseria gonorrhoeaeafter bathing in a heavily frequented hot pool at the edge of the crater lake Specchio di Venere (“Mirror of Venus”) on Pantelleria Island, Italy.

Case presentation

Two days after bathing in the pool, this 11-year-old Austrian girl developed vulvovaginitis that partially settled with antifungal cream. Subsequent swabs cultured positive forNeisseria gonorrhoeae.Family members tested negative. The child adamantly denied any sexual contact, and no opportunities for sexual exposure could be identified. It was therefore concluded that she must have acquired the infection from pool water contaminated by gonococcus after a 2-day incubation period. The infection was successfully treated with ceftriaxone and azithromycin with no adverse effects.

Conclusions

The pools are shallow, close to body temperature, isotonic, slightly acidic from CO2bubbles, and contain organic particles, all potentially supporting survival of gonococcus. There are historical case reports in the literature of gonococcal epidemics in children’s hospitals being traced to common baths. It is imperative that all cases of gonococcal infection in children are fully investigated, including examining all other relevant family members, to determine whether sexual assault has occurred. This is not a diagnosis to be missed. However, both sexual and nonsexual transmission are possible. A presumption that a gonococcal infection is diagnostic of sexual abuse can be dire, with children wrongfully removed from their parents’ care, and their caregivers facing false charges of sexual crimes. Our case serves to illustrate that the very uncommon diagnosis of gonorrhea in a child may be the result of nonsexual transmission of the infection, and that contaminated hot pools are a very rare source of infection that should be considered.
Canard solutions in neural mass models: consequences on critical regimes
Authors: Köksal Ersöz Elif , Wendling Fabrice
Published: September 2021

Mathematical models at multiple temporal and spatial scales can unveil the fundamental mechanisms of critical transitions in brain activities. Neural mass models (NMMs) consider the average temporal dynamics of interconnected neuronal subpopulations without explicitly representing the underlying cellular activity. The mesoscopic level offered by the neural mass formulation has been used to model electroencephalographic (EEG) recordings and to investigate various cerebral mechanisms, such as the generation of physiological and pathological brain activities. In this work, we consider a NMM widely accepted in the context of epilepsy, which includes four interacting neuronal subpopulations with different synaptic kinetics. Due to the resulting three-time-scale structure, the model yields complex oscillations of relaxation and bursting types. By applying the principles of geometric singular perturbation theory, we unveil the existence of the canard solutions and detail how they organize the complex oscillations and excitability properties of the model. In particular, we show that boundaries between pathological epileptic discharges and physiological background activity are determined by the canard solutions. Finally we report the existence of canard-mediated small-amplitude frequency-specific oscillations in simulated local field potentials for decreased inhibition conditions. Interestingly, such oscillations are actually observed in intracerebral EEG signals recorded in epileptic patients during pre-ictal periods, close to seizure onsets.
Ultra- and micro-structural changes of respiratory tracts in SARS-CoV-2 infected Syrian hamsters
Authors: Yang Myeon-Sik , Oh Byung Kwan , Yang Daram , Oh Eun Young , Kim Yeonhwa , Kang Kyung Won , Lim Chae Woong , Koh Gou Young , Lee Sang-Myeong , Kim Bumseok
Published: September 2021

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is causing a global crisis. It is still unresolved. Although many therapies and vaccines are being studied, they are still in their infancy. As this pandemic continues, rapid and accurate research for the development of therapies and vaccines is needed. Therefore, it is necessary to understand characteristics of diseases caused by SARS-CoV-2 through animal models. Syrian hamsters are known to be susceptible to SARS-CoV-2. They were intranasally inoculated with SARS-CoV-2. At 2, 4, 8, 12, and 16 days post-infection (dpi), these hamsters were euthanized, and tissues were collected for ultrastructural and microstructural examinations. Microscopic lesions were prominent in the upper and lower respiratory tracts from 2 and 4 dpi groups, respectively. The respiratory epithelium in the trachea, bronchiole, and alveolar showed pathological changes. Inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils were infiltrated in/around tracheal lamina propria, pulmonary vessels, alveoli, and bronchiole. In pulmonary lesions, alveolar wall was thickened with infiltrated inflammatory cells, mainly neutrophils and macrophages. In the trachea, epithelial damages started from 2 dpi and recovered from 8 dpi, consistent with microscopic results, High levels of SARS-CoV-2 nucleoprotein were detected at 2 dpi and 4 dpi. In the lung, lesions were most severe at 8 dpi. Meanwhile, high levels of SARS-CoV-2 were detected at 4 dpi. Electron microscopic examinations revealed cellular changes in the trachea epithelium and alveolar epithelium such as vacuolation, sparse micro-organelle, and poor cellular margin. In the trachea epithelium, the number of cytoplasmic organelles was diminished, and small vesicles were prominent from 2 dpi. Some of these electron-lucent vesicles were filled with virion particles. From 8 dpi, the trachea epithelium started to recover. Because of shrunken nucleus and swollen cytoplasm, the N/C ratio of type 2 pneumocyte decreased at 8 and 12 dpi. From 8 dpi, lamellar bodies on type 2 pneumocyte cytoplasm were increasingly observed. Their number then decreased from 16 dpi. However, there was no significant change in type 1 pneumocyte. Viral vesicles were only observed in the cytoplasm of type 2 pneumocyte. In conclusion, ultra- and micro-structural changes presented in this study may provide useful information for SARS-CoV-2 studies in various fields.
Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice
Authors: Aoki Ryo , Onuki Masayoshi , Hattori Koya , Ito Masato , Yamada Takahiro , Kamikado Kohei , Kim Yun-Gi , Nakamoto Nobuhiro , Kimura Ikuo , Clarke Julie M. , Kanai Takanori , Hase Koji
Published: September 2021

Background

Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and it can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear.

Results

We found that the consumption of the prebiotic inulin markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice. Inulin consumption resulted in global changes in the gut microbiome, including concomitant enrichment of the genera Bacteroides and Blautia, and increased concentrations of short-chain fatty acids, particularly acetate, in the gut lumen and portal blood. The consumption of acetate-releasing resistant starch protected against NAFLD development. Colonisation by Bacteroides acidifaciens and Blautia producta in germ-free mice resulted in synergetic effects on acetate production from inulin. Furthermore, the absence of free fatty acid receptor 2 (FFAR2), an acetate receptor, abolished the protective effect of inulin, as indicated by the more severe liver hypertrophy, hypercholesterolaemia and inflammation. These effects can be attributed to an exacerbation of insulin resistance in the liver, but not in muscle or adipose tissue.

Conclusion

These findings demonstrated that the commensal microbiome–acetate–FFAR2 molecular circuit improves insulin sensitivity in the liver and prevents the development of NAFLD/NASH.
VEDAS: an efficient GPU alternative for store and query of large RDF data sets
Authors: Makpaisit Pisit , Chantrapornchai Chantana
Published: September 2021

Resource Description Framework (RDF) is commonly used as a standard for data interchange on the web. The collection of RDF data sets can form a large graph which consumes time to query. It is known that modern Graphic Processing Units (GPUs) can be employed to execute parallel programs in order to speedup the running time. In this paper, we propose a novel RDF data representation along with the query processing algorithm that is suitable for GPU processing. Since the main challenges of GPU architecture are the limited memory sizes, the memory transfer latency, and the vast number of GPU cores. Our system is designed to strengthen the use of GPU cores and reduce the effect of memory transfer. We propose a representation consists of indices and column-based RDF ID data that can reduce the GPU memory requirement. The indexing and pre-upload filtering techniques are then applied to reduce the data transfer between the host and GPU memory. We add the index swapping process to facilitate the sorting and joining data process based on the given variable and add the pre-upload step to reduce the size of results’ storage, and the data transfer time. The experimental results show that our representation is about 35% smaller than the traditional NT format and 40% less compared to that of gStore. The query processing time can be speedup ranging from 1.95 to 397.03 when compared with RDF3X and gStore processing time with WatDiv test suite. It achieves speedup 578.57 and 62.97 for LUBM benchmark when compared to RDF-3X and gStore. The analysis shows the query cases which can gain benefits from our approach.
Novel method of transpulmonary pressure measurement with an air-filled esophageal catheter
Authors: Massion Paul Bernard , Berg Julien , Samalea Suarez Nicolas , Parzibut Gilles , Lambermont Bernard , Ledoux Didier , Massion Pierre Pascal
Published: September 2021

Background

There is a strong rationale for proposing transpulmonary pressure-guided protective ventilation in acute respiratory distress syndrome. The reference esophageal balloon catheter method requires complex in vivo calibration, expertise and specific material order. A simple, inexpensive, accurate and reproducible method of measuring esophageal pressure would greatly facilitate the measure of transpulmonary pressure to individualize protective ventilation in the intensive care unit.

Results

We propose an air-filled esophageal catheter method without balloon, using a disposable catheter that allows reproducible esophageal pressure measurements. We use a 49-cm-long 10 Fr thin suction catheter, positioned in the lower-third of the esophagus and connected to an air-filled disposable blood pressure transducer bound to the monitor and pressurized by an air-filled infusion bag. Only simple calibration by zeroing the transducer to atmospheric pressure and unit conversion from mmHg to cmH2O are required. We compared our method with the reference balloon catheter both ex vivo, using pressure chambers, and in vivo, in 15 consecutive mechanically ventilated patients. Esophageal-to-airway pressure change ratios during the dynamic occlusion test were close to one (1.03 ± 0.19 and 1.00 ± 0.16 in the controlled and assisted modes, respectively), validating the proper esophageal positioning. The Bland–Altman analysis revealed no bias of our method compared with the reference and good precision for inspiratory, expiratory and delta esophageal pressure measurements in both the controlled (largest bias −0.5 cmH2O [95% confidence interval: −0.9; −0.1] cmH2O; largest limits of agreement −3.5 to 2.5 cmH2O) and assisted modes (largest bias −0.3 [−2.6; 2.0] cmH2O). We observed a good repeatability (intra-observer, intraclass correlation coefficient, ICC: 0.89 [0.79; 0.96]) and reproducibility (inter-observer ICC: 0.89 [0.76; 0.96]) of esophageal measurements. The direct comparison with pleural pressure in two patients and spectral analysis by Fourier transform confirmed the reliability of the air-filled catheter-derived esophageal pressure as an accurate surrogate of pleural pressure. A calculator for transpulmonary pressures is available online.

Conclusions

We propose a simple, minimally invasive, inexpensive and reproducible method for esophageal pressure monitoring with an air-filled esophageal catheter without balloon. It holds the promise of widespread bedside use of transpulmonary pressure-guided protective ventilation in ICU patients.
Technology upgrading and labor degrading? A sociological study of three robotized factories
Authors: Xu Yi , Ye Xin
Published: September 2021

In recent years, the technology-driven industrial upgrading in China has resulted in human labor being replaced with robots. This article explores the impact of "intelligent manufacturing" on workers from the following two perspectives: labor relations and the labor process. The authors argue that workers on the shopfloor are experiencing some forms of labor degradation due to robotization, i.e., more flexible labor relations, deskilling, and strengthened technical control. Such a corporation-led and machine-centered industrial upgrading is driven by state policy, capital, and the labor market.
The Effectiveness of Neuromuscular Warmups for Lower Extremity Injury Prevention in Basketball: A Systematic Review
Authors: Davis Anna C. , Emptage Nicholas P. , Pounds Dana , Woo Donna , Sallis Robert , Romero Manuel G. , Sharp Adam L.
Published: September 2021

Background

Neuromuscular warmups have gained increasing attention as a means of preventing sports-related injuries, but data on effectiveness in basketball are sparse. The objective of this systematic review was to evaluate evidence of the effectiveness of neuromuscular warmup-based strategies for preventing lower extremity injuries among basketball athletes.

Methods

PubMed and Cochrane Library databases were searched in February 2019. Studies were included if they were English-language randomized controlled, non-randomized comparative, or prospective cohort trials, tested neuromuscular and/or balance-focused warmup interventions among basketball players, and assessed at least one type of lower extremity injury as a primary outcome. Criteria developed by the USPSTF were used to appraise study quality, and GRADE was used to appraise the body of evidence for each outcome. Due to heterogeneity in the included studies, meta-analyses could not be performed.

Results

In total, 825 titles and abstracts were identified. Of the 13 studies which met inclusion criteria for this review, five were balance interventions (3 randomized controlled trials) and eight were multicomponent interventions involving multiple categories of dynamic neuromuscular warmup (5 randomized controlled trials). Authors of four of the studies were contacted to obtain outcome data specific to basketball athletes. Basketball specific results from the studies suggest significant protective effects for the following lower extremity injuries: ankle injuries (significant in 4 out of the 9 studies that assessed this outcome); ACL injuries (2 of 4 studies); knee injuries generally (1 of 5 studies); and overall lower extremity injuries (5 of 7 studies). All but one of the non-significant results were directionally favorable. Evidence was moderate for the effect of multicomponent interventions on lower extremity injuries generally. For all other outcomes, and for balance-based interventions, the quality of evidence was rated as low.

Conclusion

Overall, the evidence is supportive of neuromuscular warmups for lower extremity injury prevention among basketball players. However, most studies are underpowered, some used lower-quality research study designs, and outcome and exposure definitions varied. Due to the nature of the study designs, effects could not be attributed to specific intervention components. More research is needed to identify the most effective bundle of warmup activities.
Association between physical activity and activity space in different farming seasons among rural Lao PDR residents
Authors: Jiang Hongwei , Lin Lin , Yonto Daniel Anthony , Pongvongsa Tiengkham , Kounnavong Sengchanh , Moji Kazuhiko
Published: September 2021

Background

Southeast Asia is experiencing a health transition, where non-communicable diseases (NCD) are exceeding communicable diseases. Despite NCDs accounting for roughly 60–85% of deaths in the region, many developing Southeast Asian countries are beginning to address the impacts of a physically inactive lifestyle for the first time. Our study aims to bridge this gap by objectively measuring physical activity in rural Lao PDR to reveal the association among physical activity, activity space, and seasonal variation.

Methods

Multiple waves of survey data were collected in Songkhon District, Lao PDR between March 2010 and March 2011. Adults aged between 18 and 65 were recruited (n = 48). A portable GPS recorded participants’ activity and farmland locations and an accelerometer recorded participants’ physical activity level and daily steps for seven consecutive days. Using a directional distribution tool in ArcGIS 10.5, the activity space area of each participant in each wave was calculated. Concurrently, participants recorded time spent on each daytime activity. Linear mixed models with the fixed effects as the observations from different waves and the random effects as individual participants were developed to identify factors associated with areas of activity space and counts of daily steps, respectively.

Results

A total of 48 respondents aged between 19 and 57 took part in the study. Half of the participants were females. Walking was found to be the most frequent travel mode. Females were physically less active, with a smaller activity space, and were more overweight than the males in the study. Participants were physically less active during the off-farming seasons.

Conclusions

Findings contribute to the surveillance of risk factors needed to create healthy living environments. Our research is also one of the first to use empirical evidence demonstrating seasonal variations of rural residents’ activities in mainland Southeast Asia.
Transition of clinical and basic studies on liver cirrhosis treatment using cells to seek the best treatment
Authors: Terai Shuji , Tsuchiya Atsunori , Watanabe Yusuke , Takeuchi Suguru
Published: September 2021

The liver is a highly regenerative organ; however, its regeneration potential is reduced by chronic inflammation with fibrosis accumulation, leading to cirrhosis. With an aim to tackle liver cirrhosis, a life-threatening disease, trials of autologous bone marrow cell infusion (ABMi) therapy started in 2003. Clinical studies revealed that ABMi attenuated liver fibrosis and improved liver function in some patients; however, this therapy has some limitations such as the need of general anesthesia. Following ABMi therapy, studies have focused on specific cells such as mesenchymal stromal cells (MSCs) from a variety of tissues such as bone marrow, adipose tissue, and umbilical cord tissues. Particularly, studies have focused on gaining mechanistic insights into MSC distribution and effects on immune cells, especially macrophages. Several basic studies have reported the use of MSCs for liver cirrhosis models, while a number of clinical studies have used autologous and allogeneic MSCs; however, there are only a few reports on the obvious substantial effect of MSCs in clinical studies. Since then, studies have analyzed and identified the important signals or components in MSCs that regulate immune cells, such as macrophages, under cirrhotic conditions and have revealed that MSC-derived exosomes are key regulators. Researchers are still seeking the best approach and filling the gap between basic and clinical studies to treat liver cirrhosis. This paper highlights the timeline of basic and clinical studies analyzing ABMi and MSC therapies for cirrhosis and the scope for future studies and therapy.
Sex estimation using the human vertebra: a systematic review
Authors: Rohmani Afiana , Shafie Mohamed Swarhib , Nor Faridah Mohd
Published: September 2021

Background

The vertebral column has been used in forensic studies for its weight-bearing function and relative density. Sex estimation is one of the essential elements in an anthropological examination, as it may narrow down the possibility of a match by half. Hence, it is crucial to derive the population-specific reference data in each vertebra for sex estimation. This systematic review explored the most sexually dimorphic vertebra by using the conventional anthropometric analysis.

Main body

An electronic comprehensive search was conducted using databases such as Scopus, Web of Science (WOS) and EBSCO Medline for relevant studies between 2008 and 2020. The main inclusion criteria were studies in English, and studies on sex estimation by morphometric analysis of vertebra by CT scan or dry bone. Only studies related to human adult age and vertebra were analysed. Literature search identified 84 potentially relevant articles, in which 19 articles had fulfilled the inclusion criteria. This review included studies on the cervical, thoracic and lumbar vertebrae in different populations.

Conclusion

The vertebral spine has demonstrated significant sexual dimorphism with variable prediction accuracies, whereby the body of a vertebra was found to be sexually dimorphic. It was shown that high accuracy of sex classification was provided by the second cervical, twelfth thoracic and first lumbar vertebrae, especially when they were used in combination.
Functioning in the fibromyalgia syndrome: validity and reliability of the WHODAS 2.0
Authors: Barreto Marina Carvalho Arruda , Moraleida Fabianna Resende Jesus , Graminha Cristiane Vitaliano , Leite Camila Ferreira , Castro Shamyr Sulyvan , Nunes Ana Carla Lima
Published: September 2021

Background

Fibromyalgia syndrome (FMS) is both a challenging and disabling condition. The International Association for the Study of Pain (IASP) classifies FMS as chronic primary pain, and it can negatively impact individuals’ functioning including social, psychological, physical and work-related factors. Notably, while guidelines recommend a biopsychosocial approach for managing chronic pain conditions, FMS assessment remains clinical. The WHODAS 2.0 is a unified scale to measure disability in the light of the International Classification of Functioning, Disability and Health. Thus, this study aimed to evaluate the reliability and validity of the Brazilian version of WHODAS 2.0 for use in individuals with FMS.

Methods

Methodological study of the validity and reliability of the Brazilian version of the 36-item WHODAS 2.0 with 110 individuals with FMS. The instrument gives a score from 0 to 100, the higher the value, the worse the level of functioning. We assessed participants with Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (0–100), Fibromyalgia Impact Questionnaire (FIQ) (0–10) and Beck Depression Inventory instrument (BDI) (0–63). The construct validity, internal consistency, and test–retest stability. We used SF-36, FIQ and BDI to study construct validity analysis. For statistical analysis, we performed the intraclass correlation (ICC), Spearman correlation, and Cronbach's alpha, with a statistical level of 5%.

Results

Most participants were female (92.27%), aged 45 (± 15) years. The test–retest reliability analysis (n = 50) showed stability of the instrument (ICC = 0.54; ρ = 0.84, p < 0.05). The test–retest correlation between the domains was moderate to strong (ρ > 0.58 and < 0.90). Internal consistency was satisfactory for total WHODAS 2.0 (0.91) and also for domains, ranging from 0.44 to 0.81. The construct validity showed satisfactory values with all moderately correlated with WHODAS 2.0 instruments (> 0.46 and < 0.64; p < 0.05). WHODAS 2.0 evaluates the functioning encompassing components of health-related quality of life, functional impact, and depressive symptoms in those with FMS.

Conclusions

WHODAS 2.0 is a reliable and valid instrument to evaluate functioning of Brazilians with FMS. It provides reliable information on individuals' health through of a multidimensional perspective, that allows for individual-centered care.
Zebrafish toxicological screening could aid Leishmaniosis drug discovery
Authors: Fukushima Hirla Costa Silva , Bailone Ricardo Lacava , Corrêa Tatiana , Janke Helena , De Aguiar Luís Kluwe , Setti Princia Grejo , Borra Ricardo Carneiro
Published: September 2021

Background

Recently a screen from a library of 1.8 million compounds identified in vitro a potent activity of the 2-aminobenzimidazoles series against Leishmania infantum, the etiological agent responsible by over 20.000 deaths each year. Several analogs were synthesized and in vitro tested through an optimization program, leading to a promising 2-aminobenzimidazoles derived compound (2amnbzl-d) that was progressed to in vivo mice studies. However, the not expected toxic effects prevented its progression to more advanced preclinical and clinical phases of drug development. Due to limitations of cell models in detecting whole organism complex interactions, 90% of the compounds submitted to pre-clinical tests are reproved. The use of Zebrafish embryo models could improve this rate, saving mammals, time and costs in the development of new drugs. To test this hypothesis, we compared 2amnbzl-d with two compounds with already established safety profile: carbamazepine and benznidazole, using an embryo Zebrafish platform based on acute toxicity, hepatotoxicity, neurotoxicity and cardiotoxicity assays (Pltf-AcHpNrCd).

Results

Tests were performed blindly, and the results demonstrated the presence of lethal and teratogenic effects (CL50%: 14.8 µM; EC50%: 8.6 µM), hepatotoxic in concentrations above 7.5 µM and neurotoxic in embryos exposed to 15 µM of 2amnbzl-d. Nevertheless, benznidazole exposition showed no toxicity and only the 100 µM of carbamazepine induced a bradycardia.

Conclusions

Results using Pltf-AcHpNrCd with zebrafish reproduced that found in the toxicological tests with mammals to a portion of the costs and time of experimentation.
Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study
Authors: Moon Sang Won , Park Sinhyung , Oh Minkyung , Wang Joon Ho
Published: September 2021

Background

The study investigated whether allogeneic human umbilical cord blood-derived MSCs (hUCB-MSCs) could be safely used without treatment-related adverse events, reducing tunnel enlargement, and improve clinical results in human anterior cruciate ligament (ACL) reconstruction.

Methods

Thirty patients were enrolled consecutively. They were divided into three groups by randomization. In the negative control group, ACL reconstruction surgery without additional treatment was performed. In the experimental group, a hUCB-MSC and hyaluronic acid mixture was applied to the tendon-bone interface of the femoral tunnels during ACL reconstruction surgery. In the positive control group, only hyaluronic acid was applied. Finally, 27 patients were analyzed after the exclusion of three patients. The incidence of treatment-related adverse events, clinical outcomes, including second-look arthroscopic findings, and the amount of tunnel enlargement, were evaluated.

Results

There were no treatment-related adverse events in the treatment groups. Tunnel enlargement in the experimental group (579.74 ± 389.85 mm3) was not significantly different from those in the negative (641.97 ± 455.84 mm3) and positive control (421.96 ± 274.83 mm3) groups (p = 0.6468). There were no significant differences between the groups in clinical outcomes such as KT-2000 measurement (p = 0.793), pivot shift test (p = 0.9245), International Knee Documentation Committee subjective score (p = 0.9195), Tegner activity level (p = 0.9927), and second-look arthroscopic findings (synovial coverage of the graft, p = 0.7984; condition of the graft, p = 0.8402).

Conclusions

Allogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes.

Trial registration

CRIS, Registration Number: KCT0000917. Registered on 12 November 2013; https://cris.nih.go.kr/cris/index.jsp
Giant descending aortic pseudo-aneurysm in an adult man with uncorrected aortic coarctation
Authors: Jabbary Zahra , Toufan Mehrnoush
Published: September 2021

Background

Aortic coarctation (CoAo) accounts for 6 to 8% of all congenital heart diseases and occurs two to five times more often in males. The uncorrected aortic coarctation is complicated by hypertension, ascending and descending aortic aneurysms, endarteritis, and heart failure. The aortic pseudo-aneurysm (APD) usually occurs in patients with endarteritis. We report an adult man with bicuspid aortic valve, perimembranous ventricular septal defect, and uncorrected aortic coarctation complicated by descending aortic pseudo-aneurysm without aortic endarteritis.

Case presentation

A 40-year-old man was referred to our division for hemoptysis and severe aortic coarctation. Echocardiography confirmed the aortic coarctation diagnosis and showed a large aortic pseudo-aneurysm at the coarctation site with intra-cavity mural thrombus. Subsequently, the patient underwent contrast-enhanced computed tomography angiography, and diagnosis of coarctation and APD was confirmed. Due to various malformations and considering that the patient had become unstable due to hemoptysis, it was discussed in the heart team, and it was decided that the patient would undergo staged surgery.

Conclusions

The aortic pseudo-aneurysm is a rare complication in patients with untreated coarctation that requires prompt surgery, and this complication should be considered in patients with untreated aortic coarctation who present with hemoptysis.
Association of COVID-19 infection with large thrombi in left and right atrial appendages
Authors: Ghodsi Saeed , Taghi Sara , Alizadeh-Sani Zahra , Jenab Yaser , Hosseini Zahra , Vaskelyte Laura
Published: September 2021

Background

Multiple intra-atrial thrombi are found rarely except in the presence of prosthetic valves, intra-cardiac devices, structural connections like foramen ovale and thrombophilia.

Case presentation

We reported acute thrombosis formation in right and left atrial appendages of a 66-year old man admitted due to progressive dyspnea since 7 days earlier. He had a history of prior laryngeal Squamous Cell Carcinoma, apical hypertrophic cardiomyopathy (HCM), and atrial fibrillation (AF). Infection with COVID-19 was confirmed thereafter. Cardiac Magnetic Resonance Imaging (CMR) suggested the diagnosis of atrial clot superior to neoplasm. After surgical removal of the thrombi, symptoms as well as imaging features of pneumonia were resolved.

Conclusions

We should focus on different presentations and complications of systemic inflammation especially in the setting of COVID-19 infection. Although risk factors of thrombosis are present in some of these patients, rapid progression as well as unusual types of involvement may indicate to a new trigger.
Inhaled prostacyclin analogues in COVID-19 associated acute respiratory distress syndrome: scientific rationale
Authors: Mulia Eka Prasetya Budi , Luke Kevin
Published: September 2021

Background

COVID-19 associated acute respiratory distress syndrome (CARDS) is a severe form of SARS CoV-2 infection and affects about 15–30% of hospitalized patients with a high mortality rate. Growing research and data suggest several available drugs with appropriate pharmacological effects to treat COVID-19.

Main body

Prostacyclin analogues are regiments for pulmonary artery hypertension. Prostacyclin analogues are expected to be beneficial in treating CARDS based on at least four rationales: (1) inhaled prostacyclin analogues improve oxygenation, V/Q mismatch, and act as an ARDS therapy alternative; (2) it alleviates direct SARS-CoV-2-related coagulopathy; (3) increases nitric oxide production; and (4) possible anti-inflammatory effect. Prostacyclin analogues are available in oral, intravenous, and inhaled forms. The inhaled form has the advantage over other forms, such as parenteral administration risks. Previously, a meta-analysis demonstrated the beneficial effects of inhaled prostaglandins for ARDS treatment, such as improved PaO2/FiO2 and PaO2 along with reduced pulmonary artery pressure. Currently, two ongoing randomized controlled trials are evaluating inhaled epoprostenol (VPCOVID [NCT04452669]) and iloprost (ILOCOVID [NCT04445246]) for severe COVID-19 patients.

Conclusions

Inhaled prostacyclin could be considered in patients with refractory, life-threatening hypoxia despite standard management.
Implementation of a central-line bundle: a qualitative study of three clinical units
Authors: Goldman Joanne , Rotteau Leahora , Shojania Kaveh G. , Baker G. Ross , Rowland Paula , Christianson Marlys K. , Vogus Timothy J. , Cameron Connie , Coffey Maitreya
Published: September 2021

Background

Evidence for the central line-associated bloodstream infection (CLABSI) bundle effectiveness remains mixed, possibly reflecting implementation challenges and persistent ambiguities in how CLABSIs are counted and bundle adherence measured. In the context of a tertiary pediatric hospital that had reduced CLABSI by 30% as part of an international safety program, we aimed to examine unit-based socio-cultural factors influencing bundle practices and measurement, and how they come to be recognized and attended to by safety leaders over time in an organization-wide bundle implementation effort.

Methods

We used an interpretivist qualitative research approach, based on 74 interviews, approximately 50 h of observations, and documents. Data collection focused on hospital executives and safety leadership, and three clinical units: a medical specialty unit, an intensive care unit, and a surgical unit. We used thematic analysis and constant comparison methods for data analysis.

Results

Participants had variable beliefs about the central-line bundle as a quality improvement priority based on their professional roles and experiences and unit setting, which influenced their responses. Nursing leaders were particularly concerned about CLABSI being one of an overwhelming number of QI targets for which they were responsible. Bundle implementation strategies were initially reliant on unit-based nurse education. Over time there was recognition of the need for centralized education and reinforcement tactics. However, these interventions achieved limited impact given the influence of competing unit workflow demands and professional roles, interactions, and routines, which were variably targeted in the safety program. The auditing process, initially a responsibility of units, was performed in different ways based on individuals’ approaches to the process. Given concerns about auditing reliability, a centralized approach was implemented, which continued to have its own variability.

Conclusions

Our findings report on a contextualized, dynamic implementation approach that required movement between centralized and unit-based approaches and from a focus on standardization to some recognition of a role for customization. However, some factors related to bundle compliance and measurement remain unaddressed, including harder to change socio-cultural factors likely important to sustainability of the CLABSI reductions and fostering further improvements across a broader safety agenda.
Analytical method development and validation for simultaneous estimation of Fimasartan Potassium Trihydrate and Cilnidipine in synthetic mixture by HPLC for the treatment of hypertension stage-II
Authors: Sojitra Radhika G. , Chotaliya Urvi J.
Published: September 2021

Background

A specific, accurate, precise, robust, and cost-effective HPLC method was developed and validated for quantitative analysis of Fimasartan Potassium Trihydrate and Cilnidipine in fixed-dose combination. The isocratic elution was accomplished by Symmetry C18 column (150 mm × 4.6 mm, 5 µm) at 25 °C. Mobile phase composition is Methanol: Acetonitrile: Potassium Dihydrogen Phosphate buffer (pH 3) (60:05:35%v/v/v) at a flow rate of 1.0 mL/min, injection volume 20 µL with DAD detection at 240 nm.

Result

Fimasartan Potassium Trihydrate and Cilnidipine were eluted with retention time 2.65 min and 5.51 min respectively. This method was validated as per ICH guideline (Q2 R1). The calibration plots were over the concentration range of 15–90 μg/mL and 2.5–15 μg/mL for Fimasartan Potassium Trihydrate and Cilnidipine with correlation coefficient 0.9992 and 0.9989 respectively. Accuracy was obtained between 99.51–101.65% and 100.06–101.20% for Fimasartan Potassium Trihydrate and Cilnidipine respectively. LOD were found to be 0.97 μg/mL and 0.57 μg/mL and LOQ were found to be 2.95 μg/mL and 1.75 μg/mL for Fimasartan Potassium Trihydrate and Cilnidipine respectively.

Conclusion

The results showed that the developed method is reliable for the routine analysis for simultaneous determination of Fimasartan Potassium Trihydrate and Cilnidipine.
Identifying Barriers and Facilitators to Scalp Cooling Therapy Through a National Survey of the Awareness, Practice Patterns, and Attitudes of Oncologists
Authors: Novice Madison , Novice Taylor , Henry N. Lynn , Johnson Kyle , Jeruss Jacqueline S. , Kidwell Kelley M. , Burness Monika L.
Published: September 2021

PURPOSE:

Scalp cooling therapy (SCT) is the most effective method to reduce chemotherapy-induced alopecia (CIA), a highly distressing side effect of cancer treatment. Despite data supporting SCT efficacy and safety, SCT use in the United States is not widespread. Oncologists' interactions with scalp cooling were examined to identify facilitators and barriers to SCT implementation.

METHODS:

A 33-question survey was distributed through the ASCO Research Survey Pool to a nationally representative, random sample of 600 oncology providers. Outcome measures included knowledge of SCT, frequency of initiating conversations about SCT with patients, degree of support, and barriers for SCT. Significance was defined as P < .001.

RESULTS:

Of 155 (25.8%) responding providers, 62% of providers were in favor of SCT always or most of the time, but only 26% reported initiating discussions about SCT always or most of the time. Providers who treat breast cancer ( P ≤ .0001), those who report being very familiar with SCT ( P ≤ .0001), those who report having read SCT literature in the past 2 years ( P ≤ .0001), and those who work at a facility with machine SCT ( P ≤ .0001) were significantly more likely to initiate conversations with patients about SCT. Financial concerns (58%) were the primary reason for not recommending SCT use; efficacy (31%), staff or facility (24%), and safety (15%) concerns were also noted. Although safety concerns have decreased markedly over time, 14% of providers report patients who continue to express these concerns and 17% of providers see safety issues as barriers to supporting SCT.

CONCLUSION:

Our findings suggest that oncology provider familiarity and experience with SCT lead to increased support for scalp cooling, which may ultimately result in greater availability and utilization of SCT when indicated.
Echo Rounds: Partial Anomalous Systemic and Pulmonary Venous Return
Authors: Maddali Madan Mohan , Thomas Eapen , Al-Farqani Abdulla , Al-Kindi Hamood Nasar
Published: September 2021

Anomalous drainage of a right-sided superior vena cava to the left atrium is a rare variant of systemic venous return anomalies. During the course of investigation for a heart murmur, an asymptomatic child was found to have a superior sinus venosus atrial septal defect with partial anomalous systemic and pulmonary venous drainage. Despite the right superior vena cava overriding the upper end of the atrial septum and draining into the left atrium, the child did not exhibit hypoxemia. Saline contrast transesophageal echocardiography suggested an explanation for the absence of hypoxemia.
Advances in live imaging early mouse development: exploring the researcher's interdisciplinary toolkit
Authors: Stower Matthew J. , Srinivas Shankar
Published: September 2021

Live imaging is an important part of the developmental biologist's armoury of methods. In the case of the mouse embryo, recent advances in several disciplines including embryo culture, microscopy hardware and computational analysis have all contributed to our ability to probe dynamic events during early development. Together, these advances have provided us with a versatile and powerful ‘toolkit’, enabling us not only to image events during mouse embryogenesis, but also to intervene with them. In this short Spotlight article, we summarise advances and challenges in using live imaging specifically for understanding early mouse embryogenesis.
Development of follicular dendritic cells in lymph nodes depends on retinoic acid-mediated signaling
Authors: Koning Jasper J. , Rajaraman Anusha , Reijmers Rogier M. , Konijn Tanja , Pan Junliang , Ware Carl F. , Butcher Eugene C. , Mebius Reina E.
Published: September 2021

Specialized stromal cells occupy and help define B- and T-cell domains, which are crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF receptors is crucial for the development of different stromal subsets, which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known. Using in vitro cultures of embryonic mouse stromal cells, we show that retinoic acid-mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, and also blocks lymphotoxin-mediated Ccl19pos fibroblastic reticular cell lineage differentiation. Accordingly, at the day of birth we observe the presence of Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, and complete blockade of retinoic acid signaling prevents the formation of FDC networks in lymph nodes.