bluuebunny/crossref_metadata_2025 huggingface dataset:
A universal multi-platform 3D printed bioreactor chamber for tendon tissue engineering
Authors: Janvier Adam J , Canty-Laird Elizabeth , Henstock James R
Published: September 2020

A range of bioreactors use linear actuators to apply tensile forces in vitro, but differences in their culture environments can limit a direct comparison between studies. The widespread availability of 3D printing now provides an opportunity to develop a ‘universal’ bioreactor chamber that, with minimal exterior editing can be coupled to a wide range of commonly used linear actuator platforms, for example, the EBERS-TC3 and CellScale MCT6, resulting in a greater comparability between results and consistent testing of potential therapeutics. We designed a bioreactor chamber with six independent wells that was 3D printed in polylactic acid using an Ultimaker 2+ and waterproofed using a commercially available coating (XTC-3D), an oxirane resin. The cell culture wells were further coated with Sylgard-184 polydimethylsiloxane (PDMS) to produce a low-adhesion well surface. With appropriate coating and washing steps, all materials were shown to be non-cytotoxic by lactate dehydrogenase assay, and the bioreactor was waterproof, sterilisable and reusable. Tissue-engineered tendons were generated from human mesenchymal stem cells in a fibrin hydrogel and responded to 5% cyclic strain (0.5 Hz, 5 h/day, 21 days) in the bioreactor by increased production of collagen-Iα1 and decreased production of collagen-IIIα1. Calcification of the extracellular matrix was observed in unstretched tendon controls indicating abnormal differentiation, while tendons cultured under cyclic strain did not calcify and exhibited a tenogenic phenotype. The ease of manufacturing this bioreactor chamber enables researchers to quickly and cheaply reproduce this culture environment for use with many existing bioreactor actuator platforms by downloading the editable CAD files from a public database and following the manufacturing steps we describe.
The erosion of nongambling spheres by smartphone gambling: A qualitative study on workplace and domestic disordered gambling
Authors: Lopez-Gonzalez Hibai , Jiménez-Murcia Susana , Griffiths Mark D.
Published: September 2020

The potential dangers of internet-based gambling as compared with more traditional land-based gambling have been increasingly investigated over the past decade. The general consensus appears to be that although internet gambling might not be a more dangerous medium for gambling per se, the 24/7 availability it generates for problem gamblers, however, is. Because smartphones have become the most used way of gambling online, internet gambling must, therefore, be further subcategorized according to the device by which it is accessed. This study examines the issue by exploring the views of smartphone gamblers undergoing treatment for gambling disorder in focus group settings ( N=35). Utilizing thematic analysis, the paper shows that smartphone gambling has colonized spaces previously regarded as nongambling spheres. The workplace, especially in male-dominated contexts, emerged as an accommodator and stimulator of gambling behavior, raising issues of productivity rather than criminality. Domestic gambling was mostly characterized by an invasion of bathroom and bedtime spheres of intimacy. The study examines the implications of prevention and treatment, focusing on the minimization of exposure to gambling stimuli, the erosion of intimacy that recovering gamblers must endure, and the necessity of embracing a broader definition of gambling-related harm.
Emerging models of data governance in the age of datafication
Authors: Micheli Marina , Ponti Marisa , Craglia Max , Berti Suman Anna
Published: September 2020

The article examines four models of data governance emerging in the current platform society. While major attention is currently given to the dominant model of corporate platforms collecting and economically exploiting massive amounts of personal data, other actors, such as small businesses, public bodies and civic society, take also part in data governance. The article sheds light on four models emerging from the practices of these actors: data sharing pools, data cooperatives, public data trusts and personal data sovereignty. We propose a social science-informed conceptualisation of data governance. Drawing from the notion of data infrastructure we identify the models as a function of the stakeholders’ roles, their interrelationships, articulations of value, and governance principles. Addressing the politics of data, we considered the actors’ competitive struggles for governing data. This conceptualisation brings to the forefront the power relations and multifaceted economic and social interactions within data governance models emerging in an environment mainly dominated by corporate actors. These models highlight that civic society and public bodies are key actors for democratising data governance and redistributing value produced through data. Through the discussion of the models, their underpinning principles and limitations, the article wishes to inform future investigations of socio-technical imaginaries for the governance of data, particularly now that the policy debate around data governance is very active in Europe.
The queer Global South: Transnational video activism between China and Africa
Authors: Bao Hongwei
Published: September 2020

In this article, I examine grassroots cinematic connections between China and Africa by using Queer University, short for the Queer University Video Capacity Building Training Program, a 3-year (2017–2019) participatory video production program between Chinese and African queer filmmakers and activists, as a case study. Through interviews with Queer University organizers and participants, I discuss the transnational politics and decolonial potentials underpinning these grassroots initiatives. Drawing on Françoise Lionnet and Shu-mei Shih’s critical term “minor transnationalism,” I study transnational queer grassroots collaborations in the Global South, and, in doing so, unravel the hopes, promises, and precariousness of emerging people-to-people exchanges taking place in the Global South.
TEAM to Defeat COVID-19: A Management Strategy Plan to Address Return to Play in Sports Medicine
Authors: Santos-Ferreira Diana , Tomás Rita , Dores Hélder
Published: September 2020

A new viral disease named COVID-19 spread rapidly into a pandemic in early 2020. Most countries have active community transmission and imposed measures such as social distancing and travel restrictions to mitigate its effect. Many sporting events all over the globe were canceled or postponed. In this article, we briefly discuss some important topics regarding the COVID-19 pandemic and propose a strategy to manage return to play in professional athletes. We searched the PubMed and Google Scholar databases to identify articles published through May 12, 2020, using the following keywords: “coronavirus,” “COVID-19,” “SARS-CoV-2,” “athlete,” and “return to play.” Although athletes have a lower risk of severe disease, preventive measures are still very important for minimizing time away from training, avoiding potential complications, slowing the pandemic spread, and ultimately protecting the health of those with a higher risk of complications and death. Athletes may present with mild disease, but complications such as pulmonary fibrosis and myocardial injuries have to be considered. Although still controversial, athletes should be evaluated before return to play and monitored accordingly afterward via proper clinical assessments and testing.
Burden of Nasal Polyps in the United States
Authors: Ference Elisabeth H. , Reddy Sheila R. , Tieu Ryan , Gokhale Sohum , Park Siyeon , LeCocq Jason
Published: September 2020

Objective

To investigate the clinical and health care burden of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in the United States.

Study Design

Retrospective, cross‐sectional design with analyses of patient visits from 2 databases.

Setting

National Ambulatory Medical Care Survey (NAMCS, 2012‐2016) and State Ambulatory Surgery and Services Databases (SASD, 2012‐2015) in available states.

Methods

In each analysis, we identified patients (≥18 years old) with a diagnosis of CRSwNP (ICD‐9‐CM: 471.x; ICD‐10‐CM: J33.x) in the visit record during the study period. CRS patients without polyps (CRSsNP: ICD‐9‐CM: 473.x, ICD‐10‐CM: J32.x; without CRSwNP codes) were identified for comparison. In the SASD, we focused on visits involving relevant sinus procedures. Outcomes included comorbidities, diagnostic testing, and prescribed medication (NAMCS) and surgery visit characteristics (SASD).

Results

We identified 2272 NAMCS records from physician offices (183 CRSwNP, 2089 CRSsNP). Most visits were for patients aged <65 years (78.8%, 80.6%) and privately insured (67.7%, 61.5%); CRSwNP visits had a male majority (56.3%, 35.4%). CRSwNP vs CRSsNP visits more often reported asthma (40.2%, 10.3%), allergic rhinitis (14.0%, 8.7%), and congestion (22.0%, 21.1%), with the use of glucocorticoids (21.0%, 17.7%) and nasal allergy medication (26.2%, 10.2%). In the SASD, 427,306 surgery visits were identified (71,195 CRSwNP, 356,111 CRSsNP); demographics were similar to NAMCS. CRSwNP surgeries involved more sinus types (59.3%, 41.4%). Surgeries were mostly elective (>99%) and completed quickly (<2 hours), without perioperative complications (>99%), followed by routine discharge (>91%); follow‐up visits were common (14.9%, 13.9%).

Conclusion

CRSwNP compared to CRSsNP patients have a distinct clinical experience, with moderately higher medication need and more extensive surgery.
PYK-1105: Preclinical Evaluation of a Novel Biodegradable Vitreous Substitute for Retinal Tamponade
Authors: Stryjewski Tomasz P. , Stefater James A. , Roth Larry , Li Jun , Awh Carl C. , Moshfeghi Darius M. , Kim Leo A. , Eliott Dean
Published: September 2020

Purpose:

Current retinal tamponade strategies are limited by anatomic considerations (retinal break location), durability (short-term vs need for removal), and patient adherence (positioning, travel/altitude restrictions). Here we describe the preclinical safety and toxicology of a novel biodegradable hydrogel tamponade agent (PYK-1105) with the potential to improve both patient experience and outcomes after retina surgery.

Methods:

We studied in vitro performance to assess hydrogel gelation time, modulus, viscosity, degradation time, refractive index, and transmittance. In addition to studying in vitro and in vivo (mice and rabbits) biocompatibility, testing was performed to assess cytotoxicity, intraocular irritation, acute systemic toxicity, genotoxicity, and pyrogenicity. Furthermore, clinical safety was assessed using in vivo (rabbits and minipigs) response to vitrectomy with PYK-1105 insertion with the following measures: clinical examination, multimodal imaging, full-field electroretinography, and histopathology.

Results:

PYK-1105 met the predefined performance testing criteria for optimal tamponade and demonstrated excellent biocompatibility. Animal studies showed the PYK-1105 formulation to be well tolerated and nontoxic in mice, rabbits, and pigs.

Conclusions:

PYK-1105 holds promise as a new biodegradable tamponade agent that has the potential to improve both the patient experience and outcomes after retina surgery. Human pilot studies are warranted to further assess for safety and efficacy.
Placental thromboinflammation impairs embryonic survival by reducing placental thrombomodulin expression
Authors: Kohli Shrey , Singh Kunal Kumar , Gupta Anubhuti , Markmeyer Paulina , Lochmann Franziska , Gupta Dheerendra , Rana Rajiv , Elwakiel Ahmed , Huebner Hanna , Ruebner Matthias , Isermann Berend
Published: September 2020

Excess platelet activation by extracellular vesicles (EVs) results in trophoblast inflammasome activation, interleukin 1β (IL-1β) activation, preeclampsia (PE), and partial embryonic lethality. Embryonic thrombomodulin (TM) deficiency, which causes embryonic lethality hallmarked by impaired trophoblast proliferation, has been linked with maternal platelet activation. We hypothesized that placental TM loss, platelet activation, and embryonic lethality are mechanistically linked to trophoblast inflammasome activation. Here, we uncover unidirectional interaction of placental inflammasome activation and reduced placental TM expression: although inflammasome inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine IL-1β reduced trophoblast TM expression and impaired pregnancy outcome. EVs, known to induce placental inflammasome activation, reduced trophoblast TM expression and proliferation. Trophoblast TM expression correlated negatively with IL-1β expression and positively with platelet numbers and trophoblast proliferation in human PE placentae, implying translational relevance. Soluble TM treatment or placental TM restoration ameliorated the EV-induced PE-like phenotype in mice, preventing placental thromboinflammation and embryonic death. The lethality of TM-null embryos is not a consequence of placental NLRP3 inflammasome activation. Conversely, EV-induced placental inflammasome activation reduces placental TM expression, promoting placental and embryonic demise. These data identify a new function of placental TM in PE and suggest that soluble TM limits thromboinflammatory pregnancy complications.
A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia
Authors: Fenwarth Laurène , Thomas Xavier , de Botton Stéphane , Duployez Nicolas , Bourhis Jean-Henri , Lesieur Auriane , Fortin Gael , Meslin Paul-Arthur , Yakoub-Agha Ibrahim , Sujobert Pierre , Dumas Pierre-Yves , Récher Christian , Lebon Delphine , Berthon Céline , Michallet Mauricette , Pigneux Arnaud , Nguyen Stéphanie , Chantepie Sylvain , Vey Norbert , Raffoux Emmanuel , Celli-Lebras Karine , Gardin Claude , Lambert Juliette , Malfuson Jean-Valère , Caillot Denis , Maury Sébastien , Ducourneau Benoît , Turlure Pascal , Lemasle Emilie , Pautas Cécile , Chevret Sylvie , Terré Christine , Boissel Nicolas , Socié Gérard , Dombret Hervé , Preudhomme Claude , Itzykson Raphael
Published: September 2020

A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P = .01 and P = .02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar time-dependent analysis, a significant interaction between KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01). We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.
Long-term results of PET-guided radiation in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP
Authors: Freeman Ciara L. , Savage Kerry J. , Villa Diego R. , Scott David W. , Srour Line , Gerrie Alina S. , Brown Maura J. , Slack Graham W. , Farinha Pedro , Skinnider Brian , Morris James , Bénard François , Aquino-Parsons Christina , Lo Andrea , Pickles Tom , Wilson Don C. , Tonseth Petter , Connors Joseph M. , Sehn Laurie H.
Published: September 2020

Consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) remains controversial, with routine practice continuing to include RT in patients with initial bulky disease or residual masses. Positron emission tomography (PET)-computed tomography is a sensitive modality for detecting the presence of residual disease at the end of treatment (EOT). A PET-guided approach to selectively administering RT has been the policy in British Columbia since 2005. Patients with advanced-stage DLBCL diagnosed from 1 January 2005 to 1 March 2017 and treated with at least 6 cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab), who underwent EOT PET, were included in this analysis. Those with complete metabolic response (PET-negative [PET-NEG]) were observed; those with PET-positive (PET-POS) scans were offered consolidative RT, when feasible. Of the patient records reviewed, 723 were identified, with median follow-up of 4.3 years: 517 (72%) were PET-NEG; 206 (28%) were PET-POS. Time to progression (TTP) and overall survival (OS) at 3 years were 83% vs 56% and 87% vs 64%, in patients with PET-NEG and PET-POS scans, respectively. PET-POS patients with nonprogressing disease treated with consolidative RT (109 and 206; 53%) had outcomes approaching those of PET-NEG patients, with 3-year estimates of 76% and 80% for TTP and OS. PET-NEG patients who had bulky disease (≥10 cm) at diagnosis had outcomes indistinguishable from those without bulk, despite the omission of RT. These data suggest that patients with advanced-stage DLBCL who are PET-NEG at EOT and receive no RT have excellent outcomes. 18F-fluorodeoxyglucose-PET can reliably guide selective administration of consolidative RT, even in patients with initially bulky disease.
Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma
Authors: Griffin Gabriel K. , Weirather Jason L. , Roemer Margaretha G. M. , Lipschitz Mikel , Kelley Alyssa , Chen Pei-Hsuan , Gusenleitner Daniel , Jeter Erin , Pak Christine , Gjini Evisa , Chapuy Bjoern , Rosenthal Michael H. , Xu Jie , Chen Benjamin J. , Sohani Aliyah R. , Lovitch Scott B. , Abramson Jeremy S. , Ishizuka Jeffrey J. , Kim Austin I. , Jacobson Caron A. , LaCasce Ann S. , Fletcher Christopher D. , Neuberg Donna , Freeman Gordon J. , Hodi F. Stephen , Wright Kyle , Ligon Azra H. , Jacobsen Eric D. , Armand Philippe , Shipp Margaret A. , Rodig Scott J.
Published: September 2020

T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune “neighborhoods” in which malignant B cells are surrounded by exceptionally high numbers of PD-L1–expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types.
Development of an In Vitro 3D Model for Investigating Ligamentum Flavum Hypertrophy
Authors: Lin Cheng-Li , Kuo Yi-Ting , Tsao Che-Hao , Shyong Yan-Jye , Shih Shu-Hsien , Tu Ting-Yuan
Published: September 2020

Background

Ligamentum flavum hypertrophy (LFH) is among the most crucial factors in degenerative lumbar spinal stenosis, which can cause back pain, lower extremity pain, cauda equina syndrome and neurogenic claudication. The exact pathogenesis of LFH remains elusive despite extensive research. Most in vitro studies investigating LFH have been carried out using conventional two-dimensional (2D) cell cultures, which do not resemble in vivo conditions, as they lack crucial pathophysiological factors found in three-dimensional (3D) LFH tissue, such as enhanced cell proliferation and cell cluster formation. In this study, we generated ligamentum flavum (LF) clusters using spheroid cultures derived from primary LFH tissue.

Results

The cultured LF spheroids exhibited good viability and growth on an ultra-low attachment 96-well plate (ULA 96-plate) platform according to live/dead staining. Our results showed that the 100-cell culture continued to grow in size, while the 1000-cell culture maintained its size, and the 5000-cell culture exhibited a decreasing trend in size as the culture time increased; long-term culture was validated for at least 28 days. The LF spheroids also maintained the extracellular matrix (ECM) phenotype, i.e., fibronectin, elastin, and collagen I and III. The 2D culture and 3D culture were further compared by cell cycle and Western blot analyses. Finally, we utilized hematoxylin and eosin (H&E) staining to demonstrate that the 3D spheroids resembled part of the cell arrangement in LF hypertrophic tissue.

Conclusions

The developed LF spheroid model has great potential, as it provides a stable culture platform in a 3D model that can further improve our understanding of the pathogenesis of LFH and has applications in future studies.
Effect of recent and ancient inbreeding on production and fertility traits in Canadian Holsteins
Authors: Makanjuola Bayode O. , Maltecca Christian , Miglior Filippo , Schenkel Flavio S. , Baes Christine F.
Published: September 2020

Background

Phenotypic performances of livestock animals decline with increasing levels of inbreeding, however, the noticeable decline known as inbreeding depression, may not be due only to the total level of inbreeding, but rather could be distinctly associated with more recent or more ancient inbreeding. Therefore, splitting inbreeding into different age classes could help in assessing detrimental effects of different ages of inbreeding. Hence, this study sought to investigate the effect of recent and ancient inbreeding on production and fertility traits in Canadian Holstein cattle with both pedigree and genomic records. Furthermore, inbreeding coefficients were estimated using traditional pedigree measure (FPED) and genomic measures using segment based (FROH) and marker-by-marker (FGRM) based approaches.

Results

Inbreeding depression was found for all production and most fertility traits, for example, every 1% increase in FPED, FROH and FGRM was observed to cause a − 44.71, − 40.48 and − 48.72 kg reduction in 305-day milk yield (MY), respectively. Similarly, an extension in first service to conception (FSTC) of 0.29, 0.24 and 0.31 day in heifers was found for every 1% increase in FPED, FROH and FGRM, respectively. Fertility traits that did not show significant depression were observed to move in an unfavorable direction over time. Splitting both pedigree and genomic inbreeding into age classes resulted in recent age classes showing more detrimental inbreeding effects, while more distant age classes caused more favorable effects. For example, a − 1.56 kg loss in 305-day protein yield (PY) was observed for every 1% increase in the most recent pedigree age class, whereas a 1.33 kg gain was found per 1% increase in the most distant pedigree age class.

Conclusions

Inbreeding depression was observed for production and fertility traits. In general, recent inbreeding had unfavorable effects, while ancestral inbreeding had favorable effects. Given that more negative effects were estimated from recent inbreeding when compared to ancient inbreeding suggests that recent inbreeding should be the primary focus of selection programs. Also, further work to identify specific recent homozygous regions negatively associated with phenotypic traits could be investigated.
Elevated expansion of follicular helper T cells in peripheral blood from children with acute measles infection
Authors: Shen Weiyun , Ye Hongzhou , Zhang Xilin , Huo Lixia , Shen Jingli , Zhu Li , Wang Xiang , Cui Dawei
Published: September 2020

Background

Measles outbreaks have threatened the global elimination and eradication of measles in recent years. Measles virus (MeV)-specific antibodies are successful in clearing MeV infection. Follicular helper T (Tfh) cells play a crucial role in promoting antibody production. This study investigated the potential role of Tfh cells in peripheral blood mononuclear cells (PBMCs) from children with acute MeV infection.

Results

The frequencies of CXCR5+CD4+ Tfh, ICOShigh Tfh, and PD-1high Tfh cells in PBMCs and levels of IL-6 and IL-21 in plasma were significantly elevated in patients with acute MeV infection. Moreover, a positive correlation was discovered among the frequency of ICOShigh Tfh cells, plasma levels of IL-21 and optical density (OD) values of MeV-specific IgM antibodies in the patients with acute MeV infection. However, elevated plasma MeV-specific NAb titres were not associated with the frequency of Tfh, ICOShigh Tfh, or PD-1high Tfh cells in the patients with acute MeV infection.

Conclusion

These results suggest that an elevated Tfh cell frequency and associated molecules possibly play a key role in children with acute MeV infection, which contributes to the prevention and treatment of MeV infection in children.
Feasibility and efficacy of lung ultrasound to investigate pulmonary complications in patients who developed postoperative Hypoxaemia-a prospective study
Authors: Xie Chen , Sun Kai , You Yueyang , Ming Yue , Yu Xiaoling , Yu Lina , Huang Jiapeng , Yan Min
Published: September 2020

Background

Postoperative pulmonary complications (PPCs) and hypoxaemia are associated with morbidity and mortality. We aimed to evaluate the feasibility and efficacy of lung ultrasound (LUS) to diagnose PPCs in patients suffering from hypoxaemia after general anaesthesia and compare the results to those of thoracic computed tomography (CT).

Methods

Adult patients who received general anaesthesia and suffered from hypoxaemia in the postanaesthesia care unit (PACU) were analysed. Hypoxaemia was defined as an oxygen saturation measured by pulse oximetry (SPO2) less than 92% for more than 30 s under ambient air conditions. LUS was performed by two trained anaesthesiologists once hypoxaemia occurred. After LUS examination, each patient was transported to the radiology department for thoracic CT scan within 1 h before returning to the ward.

Results

From January 2019 to May 2019, 113 patients (61 men) undergoing abdominal surgery (45 patients, 39.8%), video-assisted thoracic surgery (31 patients, 27.4%), major orthopaedic surgery (17 patients, 15.0%), neurosurgery (10 patients, 8.8%) or other surgery (10 patients, 8.8%) were included. CT diagnosed 327 of 1356 lung zones as atelectasis, while LUS revealed atelectasis in 311 of the CT-confirmed zones. Pneumothorax was detected by CT scan in 75 quadrants, 72 of which were detected by LUS. Pleural effusion was diagnosed in 144 zones on CT scan, and LUS detected 131 of these zones. LUS was reliable in diagnosing atelectasis (sensitivity 98.0%, specificity 96.7% and diagnostic accuracy 97.2%), pneumothorax (sensitivity 90.0%, specificity 98.9% and diagnostic accuracy 96.7%) and pleural effusion (sensitivity 92.9%, specificity 96.0% and diagnostic accuracy 95.1%).

Conclusions

Lung ultrasound is feasible, efficient and accurate in diagnosing different aetiologies of postoperative hypoxia in healthy-weight patients in the PACU.

Trial registration

Current Controlled TrialsNCT03802175, 2018/12/05,www.ClinicalTrials.gov
Clinical and imaging findings of discharged patients with SARS-CoV-2 positive anal swab samples: a descriptive study
Authors: Zhou Hui , Zhu Liping , Leng Yueshuang , Wang Dongcui , Bai Harrison X. , Xiong Zeng , Shi Linbo , Liao Weihua
Published: September 2020

Background

To explore the clinical features and CT findings of clinically cured coronavirus disease 2019 (COVID-19) patients with viral RNA positive anal swab results after discharge.

Methods

Forty-two patients with COVID-19 who were admitted to Yongzhou Central Hospital, Hunan, China, between January 20, 2020, and March 2, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using anal swab viral RT-PCR. In this report, we present the clinical characteristics and chest CT features of six patients with positive anal swab results and compare the clinical, laboratory, and CT findings between the positive and negative groups.

Results

The anal swab positivity rate for SARS-CoV-2 RNA in discharged patients was 14.3% (6/42). All six patients were male. In the positive group, 40% of the patients (2/5) had a positive stool occult blood test (OBT), but none had diarrhea. The median duration of fever and major symptoms (except fever) in the positive patients was shorter than that of the negative patients (1 day vs. 6 days, 4.5 days vs. 10.5 days, respectively). The incidence of asymptomatic cases in the positive group (33.3%) was also higher than that of the negative group (5.6%). There were no significant differences in the CT manifestation or evolution of the pulmonary lesions between the two groups.

Conclusion

In our case series, patients with viral RNA positive anal swabs did not exhibit gastrointestinal symptoms, and their main symptoms disappeared early. They had similar CT features to the negative patients, which may be easier to be ignored. A positive OBT may indicate gastrointestinal damage caused by SARS-CoV-2 infection.
Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU
Authors: Sharifipour Ehsan , Shams Saeed , Esmkhani Mohammad , Khodadadi Javad , Fotouhi-Ardakani Reza , Koohpaei Alireza , Doosti Zahra , EJ Golzari Samad
Published: September 2020

Background

COVID-19 is known as a new viral infection. Viral-bacterial co-infections are one of the biggest medical concerns, resulting in increased mortality rates. To date, few studies have investigated bacterial superinfections in COVID-19 patients. Hence, we designed the current study on COVID-19 patients admitted to ICUs.

Methods

Nineteen patients admitted to our ICUs were enrolled in this study. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed. Endotracheal aspirate samples were also collected and cultured on different media to support the growth of the bacteria. After incubation, formed colonies on the media were identified using Gram staining and other biochemical tests. Antimicrobial susceptibility testing was carried out based on the CLSI recommendations.

Results

Of nineteen COVID-19 patients, 11 (58%) patients were male and 8 (42%) were female, with a mean age of ~ 67 years old. The average ICU length of stay was ~ 15 days and at the end of the study, 18 cases (95%) expired and only was 1 case (5%) discharged. In total, all patients were found positive for bacterial infections, including seventeenAcinetobacter baumannii(90%) and twoStaphylococcus aureus(10%) strains. There was no difference in the bacteria species detected in any of the sampling points. Seventeen of 17 strains ofAcinetobacter baumanniiwere resistant to the evaluated antibiotics. No metallo-beta-lactamases -producingAcinetobacter baumanniistrain was found. One of theStaphylococcus aureusisolates was detected as methicillin-resistantStaphylococcus aureusand isolated from the patient who died, while anotherStaphylococcus aureusstrain was susceptible to tested drugs and identified as methicillin-sensitiveStaphylococcus aureus.

Conclusions

Our findings emphasize the concern of superinfection in COVID-19 patients due toAcinetobacter baumanniiandStaphylococcus aureus. Consequently, it is important to pay attention to bacterial co-infections in critical patients positive for COVID-19.
A very early diagnosis of Alstrӧm syndrome by next generation sequencing
Authors: Gatticchi Leonardo , Miertus Jan , Maltese Paolo Enrico , Bressan Simone , De Antoni Luca , Podracká Ludmila , Piteková Lucia , Rísová Vanda , Mällo Mari , Jaakson Kaie , Joost Kairit , Colombo Leonardo , Bertelli Matteo
Published: September 2020

Background

Alström syndrome is a rare recessively inherited disorder caused by variants in the ALMS1 gene. It is characterized by multiple organ dysfunction, including cone-rod retinal dystrophy, dilated cardiomyopathy, hearing loss, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus and systemic fibrosis. Heterogeneity and age-dependent development of clinical manifestations make it difficult to obtain a clear diagnosis, especially in pediatric patients.

Case presentation

Here we report the case of a girl with Alström syndrome. Genetic examination was proposed at age 22 months when suspected macular degeneration was the only major finding. Next generation sequencing of a panel of genes linked to eye-related pathologies revealed two compound heterozygous variants in the ALMS1 gene. Frameshift variants c.1196_1202del, p.(Thr399Lysfs*11), rs761292021 and c.11310_11313del, (p.Glu3771Trpfs*18), rs747272625 were detected in exons 5 and 16, respectively. Both variants cause frameshifts and generation of a premature stop-codon that probably leads to mRNA nonsense-mediated decay. Validation and segregation of ALMS1 variants were confirmed by Sanger sequencing.

Conclusions

Genetic testing makes it possible, even in childhood, to increase the number of correct diagnoses of patients who have ambiguous phenotypes caused by rare genetic variants. The development of high-throughput sequencing technologies offers an exceptionally valuable screening tool for clear genetic diagnoses and ensures early multidisciplinary management and treatment of the emerging symptoms.
A case report of severe tuberous sclerosis complex detected in utero and linked to a novel duplication in the TSC2 gene
Authors: Mongrain Valérie , van Doesburg Nicolaas H. , Rypens Françoise , Fallet-Bianco Catherine , Maassen Justine , Dufort-Gervais Julien , Côté Lucie , Major Philippe
Published: September 2020

Background

Disease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes remains a challenge, in part due to the large number of mutations linked to TSC. In this report, we describe a case of severe TSC diagnosed in utero and associated with a specific mutation in the gene tuberous sclerosis complex 2 (TSC2).

Case presentation

A mother was referred for a thorough investigation following the observation by ultrasound of cardiac abnormalities in her fetus. The mother was healthy and reported frequent, intense and long-lasting hiccups/spasms in the fetus. The fetus of gestational age 33 weeks and 4 days was found to have multiple cardiac tumors with cardiac ultrasound. Brain magnetic resonance imaging (MRI) performed in utero revealed the presence of sub-ependymal nodules and of abnormal signals disseminated in the white matter, in the cerebral cortex and in the cerebellum. Following diagnosis of definite TSC, pregnancy interruption was chosen by the parents. Genetic testing of the fetus exposed a duplication in exon 41 of TSC2 (c.5169dupA), which was absent in the parents. The autopsy ascertained the high severity of brain damage characterized by an extensive disorganisation of white and grey matter in most cerebral lobes.

Conclusions

This case presentation is the first to depict the association between a de novo TSC2 c.5169dupA and multi-organ manifestation together with indications of a particularly high disease severity. This report can help physicians to perform early clinical diagnosis of TSC and to evaluate the prognosis.
A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report
Authors: Santoro Claudia , Giugliano Teresa , Bernardo Pia , Palladino Federica , Torella Annalaura , del Vecchio Blanco Francesca , Onore Maria Elena , Carotenuto Marco , Nigro Vincenzo , Piluso Giulio
Published: September 2020

Background

Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson’s disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype.

Case presentation

Here we report a 7-year-old boy with multiple café-au-lait macules (CALMs) and freckling, severe macrocephaly, peculiar facial gestalt, severe ID with absent speech, epilepsy, autistic traits, self-harming, and aggressiveness. Proband is an only child born to a father aged 47. Parents did not present signs of NF1, while a maternal uncle showed severe ID, epilepsy, and tremors.By RNA analysis of NF1, we identified a de novo splicing variant (NM_000267.3:c.6579+2T>C) in proband, which explained NF1 clinical features but not the severe ID, behavioral problems, and aggressiveness. Family history suggested an X-linked condition and massively parallel sequencing of X-exome identified a novel RAB39B mutation (NM_171998.2:c.436_447del) in proband, his mother, and affected maternal uncle, subsequently validated by Sanger sequencing in these and other family members.

Conclusions

The case presented here highlights how concurrent genetic defects should be considered in NF1 patients when NF1 mutations cannot reasonably explain all the observed clinical features.
Racial differences in 5-year relative survival rates of cervical cancer by stage at diagnosis, between African American (black) and white women, living in the state of Alabama, USA
Authors: Abdalla Ehsan , Troy Roberta , Fall Souleymane , Elhussin Isra , Egiebor-Aiwan Oyoyo , Nganwa David
Published: September 2020

Background

Our objective was to assess racial differences in the 5-year relative survival rates (RSRs) of Cervical Cancer (CerCancer) by stage at diagnosis, between Black and White women, living in Alabama, USA.

Methods

Data for 3484 Blacks and 21,059 Whites diagnosed with CerCancer were extracted from the 2004 to 2013 Surveillance, Epidemiology, and End Results (SEER) database. We incorporated age groups, CerCancer stages, county, and year of diagnosis to compare the RSR between Blacks and Whites, using SEER*Stat software.

Results

In urban, Black Belt (BB) and other rural counties, Whites diagnosed with localized stage of CerCancer always had better chances of survival because their RSRs were always more than 77%, compared to Blacks. Only exception was in Blacks living in other rural counties, who had a significantly higher RSR of 83.8% (95% Cl, 74.2–90.1). Which was the same as in Whites (83.8% (95% CI 74.5–89.9) living in BBC. Although, in other rural counties, Whites had a slightly lower RSR of 83.7% (95% CI 79.9–86.8%), their RSR was better compared to Blacks and Whites living in BB and other rural counties who had slightly higher RSRs of 83.8%. This was due to statistical precision, which depended on their larger sample size and a lower variability therefore, more reliability resulting in a tighter confidence interval with a smaller margin of error. In all the three county groups, Whites 15–44 years old diagnosed with localized stage of CerCancer had a higher RSR of 93.6% (95% CI 91.4–95.2%) for those living in urban and BB counties, and 94.6% (95% CI 93.6–95.4) for those living in other rural counties. The only exception was in Blacks 65–74 years old living in other rural counties who had the highest RSR of 96.9% (95% Cl, 82.9–99.5). However, Whites were considered to have a better RSR. This was also due to the statistical precision as mentioned above.

Conclusion

There were significant racial differences in the RSRs of CerCancer. Overall, Black women experienced the worst RSRs compared to their White counterparts.
Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study
Authors: Hsieh Ching-Yun , Lein Ming-Yuh , Yang Shih-Neng , Wang Yao-Ching , Lin Yin-Jun , Lin Chen-Yuan , Hua Chun-Hung , Tsai Ming-Hsul , Lin Ching-Chan
Published: September 2020

Background

Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN.

Methods

In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT.

Results

Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS.

Conclusions

Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival.

Trial registration

ClinicalTrials.gov Identifier: NCT04397341, May 21, 2020, retrospectively registered.
Calculating the overall survival probability in patients with cervical cancer: a nomogram and decision curve analysis-based study
Authors: Xie Guilan , Wang Ruiqi , Shang Li , Qi Cuifang , Yang Liren , Huang Liyan , Yang Wenfang , Chung Mei Chun
Published: September 2020

Background

Cervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer.

Methods

Data of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010–2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell’s C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models.

Result

Eleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model.

Conclusion

A clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.
Toxicity of Povidone-iodine to the ocular surface of rabbits
Authors: Kim Sunyoung , Ahn Yongsun , Lee Yeojin , Kim Hyunseung
Published: September 2020

Background

We evaluated the toxicity of 5% (w/v) povidone-iodine (PI) applied to the ocular surface of rabbits.

Methods

Twenty-three white rabbits were divided into four groups; these were a control group and three study groups in which the ocular surface was exposed to PI for different times. In control group, one drop of phosphate-buffered saline (PBS) was applied once for 10 min. In study groups, one drop of 5% (w/v) PI was topically applied once for 1 min, 3 min, and 10 min, and then the animals were observed for 7 days. The Schirmer test, Rose Bengal staining, corneal fluorescein staining and conjunctival impression cytology were performed on day 0, 3, and 7. After 7 days, the rabbits were sacrificed and conjunctiva and cornea were collected and evaluated by light and electron microscope. Immunofluorescence staining was also performed to detect mucin 5 subtype AC (MUC5AC).

Results

The decrease in goblet cell density, reductions in MUC5AC level and histopathological and ultrastructural changes of conjunctiva and cornea were more prominent in the 5% (w/v) PI groups than the control group (p < 0.05). Moreover, these changes were more prominent when PI was applied for 3 and 10 min rather than 1 min (both p values < 0.05).

Conclusions

5% (w/v) povidone-iodine caused damages to the ocular surface in a time-dependent manner. Therefore, we should be aware of that excessive PI exposure during ophthalmic procedures could be a pathogenic factor of dry eye syndrome after surgery.