bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractConsolidative 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundPostoperative 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).MethodsAdult 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.ResultsFrom 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%).ConclusionsLung ultrasound is feasible, efficient and accurate in diagnosing different aetiologies of postoperative hypoxia in healthy-weight patients in the PACU.Trial registrationCurrent 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

Abstract
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

AbstractBackgroundCOVID-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.MethodsNineteen 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.ResultsOf 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.ConclusionsOur 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.