bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled safety results across phase 3 randomized trials of intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis
Authors: Husni M. Elaine , Deodhar Atul , Schwartzman Sergio , Chakravarty Soumya D. , Hsia Elizabeth C. , Leu Jocelyn H. , Zhou Yiying , Lo Kim H. , Kavanaugh Arthur 
Published: March 2022

Abstract
Background
Intravenous (IV) golimumab, a TNFi, is approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We analyzed pooled safety results from three phase 3 IV golimumab trials in these rheumatologic diseases and hypothesized that the safety profile of IV golimumab would be similar to that established for other TNFi, including subcutaneous golimumab.

Methods
Data from three double-blind, randomized trials of IV golimumab in patients with RA, PsA, and AS, each with a placebo-controlled period and an extension of active treatment, were included. Golimumab 2 mg/kg was administered at weeks 0 and 4, then every 8 weeks through week 100 (RA) or week 52 (PsA, AS). Concomitant low-dose, oral corticosteroids were permitted. Concomitant methotrexate was required in the RA trial and permitted in the PsA and AS trials; placebo patients crossed over to golimumab at weeks 24 (RA, PsA) and 16 (AS), respectively. Adverse events (AEs), including infections, serious infections, malignancies, and major adverse cardiovascular events (MACE), were assessed through week 112 (RA) or week 60 (PsA, AS).

Results
In total, 539 patients were randomized to placebo, and 740 patients were randomized to golimumab; 1248 patients received ≥ 1 golimumab administration. Among the placebo and golimumab patients, respectively, during the placebo-controlled periods, 40.6% and 50.3% had an AE, 2.4% and 3.8% had a serious AE, and 0.4% and 0.8% had a serious infection. Among all golimumab-treated patients, the numbers of events/100 patient-years (95% CI) were as follows: AEs, 175.2 (169.0, 181.6); serious AEs, 12.7 (11.0, 14.5); serious infections, 3.4 (2.5, 4.4); active tuberculosis, 0.4 (0.1, 0.8); opportunistic infection, 0.2 (0.1, 0.6); malignancies, 0.4 (0.2, 0.9), and MACE, 0.5 (0.2, 1.0). There were no cases of lymphoma. Three (0.6%) placebo-treated patients and 6 (0.5%) golimumab-treated patients died during the studies. Concomitant methotrexate was associated with increased occurrence of elevated alanine transaminase levels and lower incidence of antibodies to golimumab. During the placebo-controlled periods, serious infections in the placebo and golimumab groups were more common in patients receiving concomitant low-dose oral corticosteroids vs. those not receiving corticosteroids.

Conclusions
IV golimumab demonstrated a safety profile that was broadly consistent across these rheumatologic indications and with other TNFi, including subcutaneous golimumab. Concomitant methotrexate or corticosteroids were associated with an increase in specific AEs.

Trial registrations
ClinicalTrials.gov, NCT00973479. Registered on September 9, 2009. ClinicalTrials.gov, NCT02181673. Registered on July 4, 2014. ClinicalTrials.gov, NCT02186873. Registered on July 10, 2014.
Single-centre survival analysis over 10 years after MR-guided radiofrequency ablation of liver metastases from different tumour entities
Authors: Olthof Susann-Cathrin , Wessling Daniel , Winkelmann Moritz T. , Rempp Hansjörg , Nikolaou Konstantin , Hoffmann Rüdiger , Clasen Stephan 
Published: March 2022

Abstract
Background
Radiofrequency ablation (RFA) is a minimal-invasive, local therapy in patients with circumscribed metastatic disease. Although widely used, long time survival analysis of treated liver metastases is still pending while also analysing the patients’ experience of MR-based radiofrequency.

Methods
Monocentric, retrospective analysis of long-time overall and progression free survival (OS; PFS) of 109 patients, treated with MRI-guided hepatic RFA between 1997 and 2010, focusing on colorectal cancer patients (CRC). Complimentary therapies were evaluated and Kaplan Meier-curves were calculated. Patients’ experience of RFA was retrospectively assessed in 28 patients.

Results
1-, 3-, 5-, 10-year OS rates of 109 patients with different tumour entities were 83.4%, 53.4%, 31.0% and 22.9%, median 39.2 months, with decreasing survival rates for larger metastases size. For 72 CRC patients 1-, 3-, 5-, 10-year OS rates of 90.2%, 57.1%, 36.1% and 26.5% were documented (median 39.5 months). Thereof, beneficial outcome was detected for patients with prior surgery of the CRC including chemotherapy (median 53.0 months), and for liver metastases up to 19 mm (28.5% after 145 months). Hepatic PFS was significantly higher in patients with liver lesions up to 29 mm compared to larger ones (p = 0.035). 15/28 patients remembered RFA less incriminatory than other applied therapies.

Conclusions
This is the first single-centre, long-time OS and PFS analysis of MRI-guided hepatic RFA of liver metastases from different tumour entities, serving as basis for further comparison studies. Patients’ experience of MR based RFA should be analysed simultaneously to the performed RFA in the future.
Anti-PD-L1 monoclonal antibody for the management of chronic disseminated intravascular coagulation secondary to a urothelial carcinoma: a case report
Authors: Maiorano Silvia , Gulden-Sala Wiebke , Gerber Bernhard , Ghilardi Guido 
Published: March 2022

Abstract
Background
Thrombocytopenia is often considered a risk factor for bleeding, but conversely may be associated with an increased thrombotic risk in several clinical situations. Here we present a patient with arterial thrombosis and chronic disseminated intravascular coagulation caused by metastatic urothelial carcinoma. As the treatment for a disseminated intravascular coagulation caused by a neoplasia is the treatment of the underlying disease itself, our case highlights a new therapeutic approach—immunotherapy—in a patient prone to hematological complications due to conventional chemotherapy.

Clinical case
A 74-year-old Caucasian male patient with a history of urothelial carcinoma of the bladder and moderate thrombocytopenia had multiple arterial thrombotic events despite antiplatelet therapy and anticoagulation. A diagnosis of chronic disseminated intravascular coagulation in the setting of a metastatic bladder urothelial carcinoma was made. The patient was treated with an anti-PD-L1 monoclonal antibody, and achieved a rapid response with subsequent reversal of the disseminated intravascular coagulation.

Conclusion
Unexplained arterial or venous thrombosis despite adequate thromboprophylaxis should be investigated, especially in the setting of thrombocytopenia. Chronic disseminated intravascular coagulation is a possible, life-threatening reason for this clinical picture, and should prompt rapid identification of the underlying disease. To the best of our knowledge, this is the second case of chronic disseminated intravascular coagulation due to neoplastic disease treated with immunotherapy.
Dendritic epidermal T cells secreting exosomes promote the proliferation of epidermal stem cells to enhance wound re-epithelialization
Authors: Liu Mian , Liu Zhihui , Chen Yunxia , Peng Shiya , Yang Jiacai , Chen Cheng , Wang Jue , Shang Ruoyu , Tang Yuanyang , Huang Yong , Zhang Xiaorong , Hu Xiaohong , Liou Yih-Cherng , Luo Gaoxing , He Weifeng 
Published: March 2022

Abstract
Background
Efficient re-epithelialization is important for successful skin wound healing. The proportion of epidermal stem cells (EpSCs) and dendritic epidermal T cells (DETCs) determines the extent of wound re-epithelialization, especially in large areas of skin tissue loss. However, it remains unknown whether and how DETCs regulate the status of EpSCs to impact wound re-epithelialization.

Methods
To investigate how DETCs regulate EpSCs in skin re-epithelialization, we utilized normal or full-thickness skin deficient wide type (WT) mice and Tcrσ knockout (Tcrσ−/−) mice with DETCs or DETCs-derived exosomes (Exos) treatment. Flow cytometry analysis (FCAS), BrdU labelled experiments, immunofluorescence and immunohistochemical assays were performed to detect the proportion of EpSCs in the epidermis. Wound closure rate and re-epithelialization were assayed by a macroscopical view and hematoxylin–eosin (H&E) staining. EpSCs in vitro were co-cultured with DETCs in a transwell-dependent or -independent manner, or supplement with GW4869 or Exos (5 µg/mL, 15 µg/mL and 45 µg/mL), and the proliferation of EpSCs was detected by means of FCAS and CFSE.

Results
Our data showed that the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the normal epidermis of Tcrδ−/− mice had no significant difference compared to WT mice. For wounded Tcrδ−/− mice, DETCs treatment increase the proportion of CD49fbriCD71dim cells, K15+ cells and BrdU+ cells in the epidermis around the wound in comparison to PBS treatment. DETCs significantly increased the number of CD49fbriCD7dim cells and K15+ cells through transwell-dependent or -independent manners relative to control group. Furthermore, Exos stimuli remarkedly promote the proliferation of EpSCs compared to control group, while the increasement was suppressed when DETCs were interfered with GW4869. Gross observation and H&E staining showed that Exos significantly accelerated wound closure and increased re-epithelialization length in Tcrδ−/− mice when compared to control mice. Additionally, we found in vivo that Exos observably facilitated the proliferation of CD49fbriCD7dim cells and K15+ cells.

Conclusions
We revealed that DETCs enhanced the proliferation of EpSCs in the epidermis around the wounds to accelerate re-epithelialization in which Exos played important roles in the remote regulation of EpSCs proliferation. Together, these findings suggest a mechanistic link among DETC-derived exosomes, the proliferation of EpSCs, and wound re-epithelialization in the skin.
Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis
Authors: Cui Jiehan , Jin Lu , Ding Meng , He Jingjing , Yang Lin , Cui Shaoxin , Wang Xiaoping , Ma Jun , Liu Aijing 
Published: March 2022

Abstract
Background
Systemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc.

Methods
PubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher.

Results
A total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P < 0.00001). 2. MSCs decreased the number of digital ulcer, mouth handicap scale, and visual analog scale of hand pain in SSc patients (P = 0.0007 and P = 0.03, respectively). 3. No statistical differences were detected in Raynaud's condition score and Cochin hand function scale score at 6 months of MSCs therapy (P = 0.5 and P = 0.62). 4. After 12 months of follow-up, MSCs improve carbon monoxide diffusing capacity and forced vital capacity of SSc patients (P < 0.05). 5. Overall, MSCs application was safe; a few cases exhibited swelling at the injection site, diarrhea and arthralgia, which had self-recovery, and no severe adverse events occurred in the included trials.

Conclusions
MSC therapy improves the degree of skin thickening, lung function, and mouth opening and relieves finger ulcers and pain in patients with SSc without severe adverse events. Thus, MSCs or MSCs combined with plasma and traditional medicine might be an effective and promising treatment of SSc patients.
PROSPERO registration number: CRD42020200350
Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention
Authors: Li Yan-Ruide , Dunn Zachary Spencer , Garcia Gustavo , Carmona Camille , Zhou Yang , Lee Derek , Yu Jiaji , Huang Jie , Kim Jocelyn T. , Arumugaswami Vaithilingaraja , Wang Pin , Yang Lili 
Published: March 2022

Abstract
Background
New COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation.

Methods
We produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application.

Results
We reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD.

Conclusions
Here, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses.
Assessment of automated assays for serum amyloid A, haptoglobin (PIT54) and basic biochemistry in broiler breeders experimentally infected with Escherichia coli
Authors: Kromann Sofie , Olsen Rikke Heidemann , Bojesen Anders Miki , Jensen Henrik Elvang , Thøfner Ida 
Published: March 2022

AbstractBiomarkers of inflammation are valuable tools for health status evaluation in numerous species. However, in poultry, methods for measuring acute phase proteins (APP) are sparse and rely on manual laboratory labour reserving these parameters mainly for research studies with APP as a focus point. To extend the use of APP beyond tightly focused research studies, blood from experimentally infected and control hens was analysed using equipment available in many veterinary clinics in order to identify easily accessible biomarkers of infection. Blood samples from broiler breeders (n = 30) inoculated intratracheally with either Escherichia coli or sterile vehicle were randomly selected at 2, 4 and 7 days post-infection (dpi) and subjected to biochemical analysis. Samples for bacteriological testing were collected, and all animals were subjected to a full necropsy for disease confirmation. Significantly higher levels of serum amyloid A were evident in the infected birds at 2 and 4 dpi (p < 0.01) compared to the controls. Likewise, haptoglobin (PIT54) levels were significantly elevated at 4 dpi (p < 0.01) in the infected animal, whilst at 2 dpi magnesium and calcium were significantly lower in the infected group (p < 0.05). Gross pathology and bacteriology confirmed the presence of infection in the E. coli inoculated birds. In conclusion, equipment routinely used in other species for rapid analysis of blood samples, successfully differentiated between sick and healthy birds, hereby, showing great potential as an easily added parameter of evaluation in research studies, and as a valuable decision-making tool for poultry veterinarians.
Acute rhabdomyolysis in hepatitis-associated aplastic anemia patient undergoing allogeneic hematopoietic stem-cell transplantation: case report and literature review
Authors: Li Yuzhu , Hong Yilei , Shen Yingying , Liu Qi , Chen Ying , Shao Keding , Shen Yiping , Ye Baodong , Wu Dijiong 
Published: March 2022

Abstract
Background
Hepatitis-associated aplastic anemia (HAAA) is a specific type of aplastic anemia, and hematopoietic stem-cell transplantation (HSCT) is recommended as the first-line. Acute rhabdomyolysis (AR) during hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication, with only 10 cases reported in the world so far.

Case presentation
Herein, we present a case of AR developing during HLA-haploidentical HSCT in a 55-year-old man who suffered from HAAA. On day 7 after stem cell transfusion, the patient reported a muscle pull in thigh and complained of muscle swelling, pain and change in urine color. Despite the timely diagnosis (based on the levels of myoglobin and creatine kinase, and muscle MRI findings, etc.) and rapid hydration and alkalization, the situation progressed dramatically, and the patient died of multi-organ failure during the preparation for continuous renal replacement therapy (CRRT). Five days after his death, the whole-exome sequencing result confirmed that the patient had a germline missense mutation in SCN4A I 1545 V and ACTN3 R577X.

Conclusion
AR is a rare but threatening complication during HSCT, especially in cases with kidney dysfunction. The creatine kinase level may not truly and completely reflect the severity and prognosis for cases with localized lesion. We suggest that genetic analysis should be performed for better understanding the pathological changes of AR during HSCT, especially for patients with bone marrow failure.
Anaerobic RSH-dependent tellurite reduction contributes to Escherichia coli tolerance against tellurite
Authors: Muñoz-Diaz P. , Jiménez K. , Luraschi R. , Cornejo F. , Figueroa M. , Vera C. , Rivas-Pardo A. , Sandoval J. M. , Vásquez C. , Arenas F. 
Published: March 2022

Abstract
Background
Tellurium is a rare metalloid that exerts high toxicity on cells, especially on bacteria, partly due to reactive oxygen species (ROS) generation. Moreover, it has also been observed that tellurite can target free cell thiols groups (RSH) (i.e. reduced glutathione (GSH)), enhancing the cellular redox imbalance. Additionally, in vitro experiments have suggested that several enzymes can reduce tellurite (IV) to its elemental form (0); where RSH present on their active sites may be responsible for the process. Nevertheless, the mechanisms implemented by bacteria for tellurite reduction and its role in resistance have not been evaluated in vivo.

Results
This work shows that tellurite reduction to elemental tellurium is increased under anaerobic conditions in E. coli cells. The in vivo tellurite reduction is related to the intracellular concentration of total RSH, in the presence and absence of oxygen. This metabolization of tellurite directly contributes to the resistance of the bacteria to the oxyanion.

Conclusions
We demonstrated that in vivo tellurite reduction is related to the intracellular thiol concentration, i.e. large availability of cellular RSH groups, results in a more significant reduction of tellurite. Furthermore, we observed that, when the bacterium exhibits less resistance to the oxyanion, a decreased tellurite reduction was seen, affecting the growth fitness. Together, these results let us propose that tellurite reduction and the intracellular RSH content are related to the oxyanion bacterial resistance, this tripartite mechanism in an oxygen-independent anaerobic process.
Communication with face masks during the COVID-19 pandemic for adults with hearing loss
Authors: Poon Brenda T. , Jenstad Lorienne M. 
Published: March 2022

AbstractFace masks have become common protective measures in community and workplace environments to help reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Face masks can make it difficult to hear and understand speech, particularly for people with hearing loss. An aim of our cross-sectional survey was to investigate the extent that face masks as a health and safety protective measure against SARS-CoV-2 have affected understanding speech in the day-to-day lives of adults with deafness or hearing loss, and identify possible strategies to improve communication accessibility. We analyzed closed- and open-ended survey responses of 656 adults who self-identified as D/deaf or hard of hearing. Over 80% of respondents reported difficulty with understanding others who wore face masks. The proportion of those experiencing difficulty increased with increasing hearing loss severity. Recommended practical supports to facilitate communication and social interaction included more widespread use of clear face masks to aid lip-reading; improved clarity in policy guidance on face masks; and greater public awareness and understanding about ways to more clearly communicate with adults with hearing loss while wearing face masks.
Platform placemaking and the digital urban culture of Airbnbification
Authors: Törnberg Petter 
Published: March 2022

AbstractThis paper develops the notion of “platform placemaking”, describing how platforms mobilize user data to remake urban spatial imaginaries in their interests. Using Airbnb as a case, the paper studies the digital urban culture of “Airbnbification” – examining how Airbnb’s reviews and descriptions become part of reshaping urban place, while contributing to the place alienation of long-term residents. Airbnb feeds a surge in urban tourists on the hunt for “real urban experiences”: off-the-beaten-track, everyday and mundane urban life, seen as representing something “real” and “authentic”. This paper situates Airbnb in the literature on postmodern consumption, and examines the way hosts and guests on Airbnb stage, perform and construct cosmopolitanism and “authentic” urban place to cater to the values of new urban tourism. The paper introduces an approach to studying digital urban culture through platform data, using computational discourse analysis to examine Airbnb in New York City. By linking narratives in reviews and neighborhood descriptions to census data, we examine how authenticity and cosmopolitanism is staged and marketed. The paper argues that Airbnb serves to promote a value system that devalues the cultural and spatial capital of long-term residents, implying that the new tourists’ cosmopolitan longing to belong may thus come at the cost of the locals’ own sense of belonging. The platform placemaking of Airbnb thus emphasizes urban place as a consumption experience, while depressing other ways of experiencing the city.