bluuebunny/crossref_metadata_2025_split huggingface dataset:
suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19
Authors: Altintas Izzet , Eugen-Olsen Jesper , Seppälä Santeri , Tingleff Jens , Stauning Marius Ahm , El Caidi Nora Olsen , Elmajdoubi Sanaá , Gamst-Jensen Hejdi , Lindstrøm Mette B , Rasmussen Line Jee Hartmann , Kristiansen Klaus Tjelle , Rasmussen Christian , Nehlin Jan O , Kallemose Thomas , Hyppölä Harri , Andersen Ove 
Published: August 2021

Objectives: Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations between plasma suPAR levels (testing the cut-offs ⩽4, 4-6, and ⩾6 ng/mL) with risk of 14-day mortality, and with the risk of mechanical ventilation in patients that tested positive for SARS-CoV-2. Methods: Observational cohort study of patients presenting with symptoms of COVID-19 at Department of Emergency Medicine, Amager and Hvidovre Hospital, Denmark from March 19th, 2020 to April 3rd, 2020. Plasma suPAR was measured using suPARnostic technologies. Patients were followed for development of mechanical ventilation and mortality for 14 days. Validation of our findings were carried out in a similar sized COVID-19 patient cohort from Mikkeli Central Hospital, Finland. Results: Among 386 patients with symptoms of COVID-19, the median (interquartile range) age was 64 years (46-77), 57% were women, median suPAR was 4.0 ng/mL (2.7-5.9). In total, 35 patients (9.1%) died during the 14 days follow-up. Patients with suPAR ⩽4 ng/mL (N = 196; 50.8%) had a low risk of mortality (N = 2; 1.0%; negative predictive value of 99.0%, specificity 55.3%, sensitivity 95.2%, positive predictive value 17.4%). Among patients with suPAR ⩾6 ng/mL (N = 92; 23.8%), 16 died (17.4%). About 99 patients (25.6%) tested positive for SARS CoV-2 and of those 12 (12.1%) developed need for mechanical ventilation. None of the SARS-CoV-2 positive patients with suPAR ⩽4 ng/mL (N = 28; 38.8%) needed mechanical ventilation or died. The Mikkeli Central Hospital validation cohort confirmed our findings concerning suPAR cut-offs for risk of development of mechanical ventilation and mortality. Conclusions: Patients with symptoms of COVID-19 and suPAR ⩽4 or ⩾6 ng/mL had low or high risk, respectively, concerning the need for mechanical ventilation or mortality. We suggest cut-offs for identification of risk groups in patients presenting to the ED with symptoms of or confirmed COVID-19.
Who are the young users of tobacco products? Prevalence and characteristics of Danish adolescents who have either smoked cigarettes, used alternative tobacco products, or used both
Authors: Kjeld Simone Gad , Andersen Susan , Andersen Anette , Glenstrup Stine , Lund Lisbeth , Danielsen Dina , Bast Lotus Sofie 
Published: August 2021

Aims: We examined characteristics (smoking in social relations, binge drinking, and well-being measures) of Danish 13-year-olds in relation to their tobacco use patterns. Ever use of cigarettes exclusively, ever use of alternative tobacco products (ATPs; e-cigarettes, snus, or waterpipe) exclusively, and use of both cigarettes and ATPs were studied. Methods: We used self-reported data from students at 46 Danish schools in 2017 comprising 2,307 students (response rate = 86%). Multi-level logistic regression analyses were used to examine the associations between student characteristics and the odds for having ever used any tobacco products, smoked cigarettes exclusively, used ATPs exclusively, or used both cigarettes and ATPs compared with never use of any tobacco products. Unadjusted estimates and estimates adjusted for gender were reported. Results: A significant minority of youth (13.2%) had used one or more tobacco products. Of these, 2.0% had exclusively smoked cigarettes, 7.2% had exclusively used ATPs, and 4.0% had used both. Findings showed that all included characteristics (families’ and friends’ smoking, binge drinking, and well-being characteristics) were associated with using any tobacco product; however, students with friends who smoked, had been binge drinking, and had low well-being at home had notably higher odds for having both smoked cigarettes and used ATPs compared to the other tobacco use patterns. Conclusion: ATPs were popular among Danish adolescents compared with conventional cigarettes. Thus, prevention efforts among adolescents should not merely focus on the health risks of conventional cigarette smoking but also on ATPs. Students with diverse tobacco use patterns were similar on various characteristics. However, findings indicate that adolescents who had used both conventional cigarettes and ATPs constitute a more risk-averse group in special need of prevention efforts. Gender did not markedly influence the results. These findings may help future strategies aiming at the youngest adolescents at risk of using tobacco products.
How I treat bleeding disorder of unknown cause
Authors: Baker Ross I. , O’Donnell James S. 
Published: August 2021

AbstractRecent studies have demonstrated that only 30% of patients referred for assessment of a possible bleeding tendency will eventually be diagnosed with a mild bleeding disorder (MBD) such as von Willebrand disease (VWD) or platelet function defect (PFD). Rather, most of these patients will be diagnosed with bleeding disorder of unknown cause (BDUC). There remains an important unmet need to define consensus regarding the clinical and laboratory criteria necessary for a formal BDUC diagnosis. Accumulating recent data suggest that BDUC is being diagnosed with increasing frequency. Objective assessment of bleeding phenotype using a standardized bleeding assessment tool (BAT) therefore represents a fundamental first step in the diagnosis of BDUC. Because BDUC is a diagnosis by exclusion, accurate quantification of bleeding phenotype is critical because this will be the primary determinant on which a diagnosis of BDUC is reached. Importantly, BAT scores suggest that patients with BDUC display bleeding phenotypes comparable to those seen in patients with VWD or PFD. Despite the prevalence of BDUC, diagnosis and management of these patients commonly pose significant clinical dilemmas. We consider these challenges in the context of a number of typical case studies, discuss the available evidence, and outline our approach to the management of these patients.
Sexual activities during the COVID-19 pandemic in Indonesia
Authors: Kusuma A. H. Wisda , Brodjonegoro Sakti R. , Soerohardjo Indrawarman , Hendri Ahmad Z. , Yuri Prahara 
Published: August 2021

Abstract
Background
Corona Virus Disease 2019 (COVID-19) has spread globally starting from late 2019. The WHO declared it a global pandemic in March 2020, causing nations around the world to introduce various control measures to halt the rapid spread of the disease, such as quarantines, lockdowns, and work from home (WFH) policies. These policies often force people to spend more time at home with their cohabitants, or possibly sexual partners. Various negative feelings experienced during those policies are considered to affect the general mood and sexual life of the population. This study aimed to investigate the difference in mood and sexual activity before and during the COVID-19 pandemic.

Methods
This research was a cross-sectional pilot study. Authors collected data from 131 randomly selected, sexually active volunteer subjects using a self-administered online questionnaire. Subjects’ mood status, behavior, and frequency of sexual intercourse before and during COVID-19 pandemic in Indonesia were analyzed.

Results
Subjects consisted of 67 (51.1%) men and 64 (48.9%) women. Our analysis shows that there was a decline in overall mood scale, and also sexual activity frequency, before and during the pandemic (4.63 vs. 4.03; 80.2% vs. 67.9%, respectively). The COVID-19 pandemic control measures may enable subjects to have more time with their sexual partners at home, but it does not increase the frequency of their sexual activities.

Conclusion
There was a slight decrease in overall mood scale and sexual activity frequency during the COVID-19 pandemic recorded among subjects. The authors suspect that depression symptoms, fear, anxiety, irritability, boredom, confusion, and feeling of being isolated experienced during strict pandemic control measures, caused by stressors such as job loss, decreased monthly income, and the current state of the pandemic are influencing these phenomena.
Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study
Authors: Zeng Qing-Lei , Yu Zu-Jiang , Ji Fanpu , Li Guang-Ming , Zhang Guo-Fan , Xu Jiang-Hai , Lin Wan-Bao , Zhang Guo-Qiang , Li Guo-Tao , Cui Guang-Lin , Wang Fu-Sheng 
Published: August 2021

Abstract
Background
Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods
In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline.

Results
In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding.

Conclusions
SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.
A novel treatment strategy for lapatinib resistance in a subset of HER2-amplified gastric cancer
Authors: Ning Gang , Zhu Qihui , Kang Wonyoung , Lee Hamin , Maher Leigh , Suh Yun-Suhk , Michaud Michael , Silva Mayerlin , Kwon Jee Young , Zhang Chengsheng , Lee Charles 
Published: August 2021

Abstract
Background
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Human epidermal growth factor receptor 2 (HER2) amplification occurs in approximately 13–23% of all GC cases and patients with HER2 overexpression exhibit a poor prognosis. Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, is an effective agent to treat HER2-amplified breast cancer but it failed in gastric cancer (GC) clinical trials. However, the molecular mechanism of lapatinib resistance in HER2-amplified GC is not well studied.

Methods
We employed an unbiased, genome-scale screening with pooled CRISPR library on HER2-amplified GC cell lines to identify genes that are associated with resistance to lapatinib. To validate the candidate genes, we applied in vitro and in vivo pharmacological tests to confirm the function of the target genes.

Results
We found that loss of function of CSK or PTEN conferred lapatinib resistance in HER2-amplified GC cell lines NCI-N87 and OE19, respectively. Moreover, PI3K and MAPK signaling was significantly increased in CSK or PTEN null cells. Furthermore, in vitro and in vivo pharmacological study has shown that lapatinib resistance by the loss of function of CSK or PTEN, could be overcome by lapatinib combined with the PI3K inhibitor copanlisib and MEK inhibitor trametinib.

Conclusions
Our study suggests that loss-of-function mutations of CSK and PTEN cause lapatinib resistance by re-activating MAPK and PI3K pathways, and further proved these two pathways are druggable targets. Inhibiting the two pathways synergistically are effective to overcome lapatinib resistance in HER2-amplified GC. This study provides insights for understanding the resistant mechanism of HER2 targeted therapy and novel strategies that may ultimately overcome resistance or limited efficacy of lapatinib treatment for subset of HER2 amplified GC.
Multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapist-led care for femoroacetabular impingement (FAI) syndrome on hip cartilage metabolism: the Australian FASHIoN trial
Authors: Hunter David J. , Eyles Jillian , Murphy Nicholas J. , Spiers Libby , Burns Alexander , Davidson Emily , Dickenson Edward , Fary Camdon , Foster Nadine E. , Fripp Jurgen , Griffin Damian R. , Hall Michelle , Kim Young Jo , Linklater James M. , Molnar Robert , Neubert Ales , O’Connell Rachel L. , O’Donnell John , O’Sullivan Michael , Randhawa Sunny , Reichenbach Stephan , Schmaranzer Florian , Singh Parminder , Tran Phong , Wilson David , Zhang Honglin , Bennell Kim L. 
Published: August 2021

AbstractBackgroundArthroscopic surgery for femoroacetabular impingement syndrome (FAI) is known to lead to self-reported symptom improvement. In the context of surgical interventions with known contextual effects and no true sham comparator trials, it is important to ascertain outcomes that are less susceptible to placebo effects. The primary aim of this trial was to determine if study participants with FAI who have hip arthroscopy demonstrate greater improvements in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to participants who undergo physiotherapist-led management.MethodsMulti-centre, pragmatic, two-arm superiority randomised controlled trial comparing physiotherapist-led management to hip arthroscopy for FAI. FAI participants were recruited from participating orthopaedic surgeons clinics, and randomly allocated to receive either physiotherapist-led conservative care or surgery. The surgical intervention was arthroscopic FAI surgery. The physiotherapist-led conservative management was an individualised physiotherapy program, named Personalised Hip Therapy (PHT). The primary outcome measure was change in dGEMRIC score between baseline and 12 months. Secondary outcomes included a range of patient-reported outcomes and structural measures relevant to FAI pathoanatomy and hip osteoarthritis development. Interventions were compared by intention-to-treat analysis.ResultsNinety-nine participants were recruited, of mean age 33 years and 58% male. Primary outcome data were available for 53 participants (27 in surgical group, 26 in PHT). The adjusted group difference in change at 12 months in dGEMRIC was -59 ms (95%CI − 137.9 to - 19.6) (p = 0.14) favouring PHT. Hip-related quality of life (iHOT-33) showed improvements in both groups with the adjusted between-group difference at 12 months showing a statistically and clinically important improvement in arthroscopy of 14 units (95% CI 5.6 to 23.9) (p = 0.003).ConclusionThe primary outcome of dGEMRIC showed no statistically significant difference between PHT and arthroscopic hip surgery at 12 months of follow-up. Patients treated with surgery reported greater benefits in symptoms at 12 months compared to PHT, but these benefits are not explained by better hip cartilage metabolism.Trial registration detailsAustralia New Zealand Clinical Trials Registry reference:ACTRN12615001177549. Trial registered 2/11/2015.
CpG immunostimulatory oligodeoxynucleotide 1826 as a novel nasal ODN adjuvant enhanced the protective efficacy of the periodontitis gene vaccine in a periodontitis model in SD rats
Authors: Bai Guohui , Yu Hang , Guan Xiaoyan , Zeng Fengjiao , Liu Xia , Chen Bin , Liu Jianguo , Tian Yuan 
Published: August 2021

Abstract
Background
We previously demonstrated that nasal administration of periodontitis gene vaccine (pVAX1-HA2-fimA) or pVAX1-HA2-fimA plus IL-15 as adjuvant provoked protective immunity in the periodontal tissue of SD rats. This study evaluated the immune effect of pVAX1-HA2-fimA plus CpG-ODN 1826 as an adjuvant in the SD rat periodontitis models to improve the efficacy of the previously used vaccine.

Methods
Periodontitis was induced in maxillary second molars in SD rats receiving a ligature and infected with Porphyromonas gingivalis. Forty-two SD rats were randomly assigned to six groups: A, control without P. gingivalis; B, P. gingivalis with saline; C, P. gingivalis with pVAX1; D, P. gingivalis with pVAX1-HA2-fimA; E, P. gingivalis with pVAX1-HA2-fimA/IL-15; F, P. gingivalis with pVAX1-HA2-fimA+CpG ODN 1826 (30 µg). The levels of FimA-specific and HA2-specific secretory IgA antibodies in the saliva of rats were measured by ELISA. The levels of COX-2 and RANKL were detected by immunohistochemical assay. Morphometric analysis was used to evaluate alveolar bone loss. Major organs were observed by HE staining.

Results
30 μg could be the optimal immunization dose for CpG-ODN 1826 and the levels of SIgA antibody were consistently higher in the pVAX1-HA2-fimA+CpG-ODN 1826 (30 µg) group than in the other groups during weeks 1–8 (P < 0.05, except week 1 or 2). Morphometric analysis demonstrated that pVAX1-HA2-fimA+CpG-ODN 1826 (30 µg) significantly reduced alveolar bone loss in ligated maxillary molars in group F compared with groups B–E (P < 0.05). Immunohistochemical assays revealed that the levels of COX-2 and RANKL were significantly lower in group F compared with groups B–E (P < 0.05). HE staining results of the major organs indicated that pVAX1-HA2-fimA with or without CpG-ODN 1826 was not toxic for in vivo use.

Conclusions
These results indicated that CpG-ODN 1826 (30 µg) could be used as an effective and safe mucosal adjuvant for pVAX1-HA2-fimA in SD rats since it could elicit mucosal SIgA responses and modulate COX-2 and RANKL production during weeks 1–8, thereby inhibiting inflammation and decreasing bone loss.
Providing dignity therapy to patients with advanced cancer: a feasibility study within the setting of a hospital palliative care unit
Authors: Nunziante Francesca , Tanzi Silvia , Alquati Sara , Autelitano Cristina , Bedeschi Enrica , Bertocchi Elisabetta , Dragani Matilde , Simonazzi Davide , Turola Elena , Braglia Luca , Masini Luciano , Di Leo Silvia 
Published: August 2021

AbstractBackgroundDignity is a basic principle of palliative care and is intrinsic in the daily practice of professionals assisting individuals with incurable diseases. Dignity Therapy (DT) is a short-term intervention aimed at improving the sense of purpose, meaning and self-worth and at reducing the existential distress of patients facing advanced illness. Few studies have examined how DT works in countries of non-Anglo Saxon culture and in different real-life settings. Moreover, most studies do not provide detailed information on how DT is conducted, limiting a reliable assessment of DT protocol application and of its evaluation procedure.The aim of this study was to assess the feasibility and acceptability of a nurse-led DT intervention in advanced cancer patients receiving palliative care.MethodThis is a mixed-method study using before and after evaluation and semistructured interviews. Cancer patients referred to a hospital palliative care unit were recruited and provided with DT. The duration of sessions, and timeframes concerning each step of the study, were recorded, and descriptive statistical analyses were performed.The patients' dignity-related distress and feedback toward the intervention were assessed through the Patient Dignity Inventory and the Dignity Therapy Patient Feedback Questionnaire, respectively. Three nurses were interviewed on their experience in delivering the intervention, and the data were analyzed qualitatively.ResultsA total of 37/50 patients were enrolled (74.0%), of whom 28 (75.7%) completed the assessment. In 76.7% of cases, patients completed the intervention in the time limit scheduled in the study. No statistically significant reduction in the Patient Dignity Inventory scores was observed at the end of the intervention; most patients found DT to be helpful and satisfactory. Building opportunities for personal growth and providing holistic care emerged among the facilitators to DT implementation. Nurses also highlighted too great of a time commitment and a difficult collaboration with ward colleagues among the barriers.ConclusionsOur findings strongly support the acceptability, but only partially support the feasibility, of nurse-led DT in advanced cancer patients in a hospital setting. Further research is needed on how to transfer the potential benefits of DT into clinical practice.Trial registrationRetrospectively registered on ClinicalTrial.govNCT04738305.
Intrauterine devices migrated into the bladder: two case reports and literature review
Authors: Liu Guangtao , Li Feifei , Ao Min , Huang Guimin 
Published: August 2021

Abstract
Background
Intrauterine devices (IUD) are widely used all over the world. One of the most serious complications is uterine perforation, and it is very rare for the IUD to penetrate the bladder after perforation. Here we report two cases of IUD migration into the bladder, and review the literature to analyze the possible causes and solutions of such complications.

Case presentation
Case NO. 1 is a 37-year-old female who presented lower urinary tract symptoms for a year. Cystoscopy showed that a strip of metal penetrated into the bladder, and the surface was covered with stones. The patient underwent cystotomy and foreign body removal under general anesthesia. Case NO. 2 is a 46-year-old woman who previously inserted an IUD in 1998, but she had an unexpected pregnancy in 1999. Her doctor believed that "the IUD had spontaneously expulsed" and a new IUD was inserted after her pregnancy was terminated. Her CT scan showed an IUD on the left side of the bladder and another IUD in the uterus. Her foreign body was removed by cystotomy.

Conclusion
Patients with IUD should be suggested to check the device regularly, and those who with a missed IUD have to rule out the possibility of IUD migration. For patients with IUD combined with lower urinary tract symptoms, it is necessary to be aware of whether IUD perforation affects the bladder.