bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Enhancer RNA CDK6-AS1 as a Potential Novel Prognostic Biomarker in Gastric Cancer
Authors: Yang Shifeng , Zou Xiaoming , Yang Hao , Li Jiacheng , Zhang Ange , Zhang Lisha , Li Changjian , Zhu Lei , Ma Zhen 
Published: April 2022

Background: This study aimed to confirm the role of enhancer RNAs (eRNAs) in gastric cancer and their clinical utility.Methods: We used Cox survival and relevance analysis to identify the candidate eRNAs in gastric cancer and performed Gene Ontology and Reactome pathway enrichment to determine the potential functions of eRNAs. Correlation between eRNA, tumor-infiltrating immune cells, and drug sensitivity was then analyzed.Results:CDK6-AS1, a long non-coding RNA cyclin-dependent kinase 6, may serve as a poor potential prognostic biomarker candidate in gastric cancer with a positive correlation with its target gene CDK6. The low CDK6-AS1 expression group showed more frequent mutated driver genes than the high expression group. Moreover, CDK6-AS1 is involved in a key oncogenic pathway of the cell cycle and RNA transcription. CDK6-AS1 also shows dysregulations and associations with prognosis at the pan-cancer level. This eRNA may also be associated with immune cell infiltration and drug sensitivity.Conclusion:CDK6-AS1 may be a potential prognostic biomarker and chemotherapeutic drug sensitivity predictor in gastric cancer.
A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days
Authors: Liang Xian-Ming , Xu Qiu-Yan , Jia Zhi-Juan , Wu Meng-Juan , Liu Yan-Yun , Lin Li-Rong , Liu Li-Li , Yang Tian-Ci 
Published: April 2022

BackgroundDue to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection.ObjectivesTo evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens.MethodsA prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days.ResultsThe neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)).ConclusionsCompared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.
Functionalized Silicone Elastomer via Alkaline Solution to Coat Phosphorylcholine-Based Copolymer Containing Organosilane to Improve Hemocompatibility for Medical Devices
Authors: Chou Fang-Yu , Hara Shintaro , Uchida Kazuto , Matsuo Youichi , Masuda Tsukuru , Yokoi Ryo , Ono Toshiya , Anraku Masaki , Isoyama Takashi , Takai Madoka 
Published: April 2022

Surface modification of hemocompatible copolymers on silicone elastomers (SEs) is crucial for the long-term use of medical devices. Both physical adsorption and chemical conjugation are important for modification of SE. Oxygen plasma treatment is widely used to produce silanol groups on SE for silane coupling. However, the plasma reaction is difficult to apply to the surface modification of three-dimensional complex devices. This study demonstrated an appropriate and efficient method with alkaline solution for producing silanol groups on SE for modifying phosphorylcholine-based copolymer with organosilane (cross-MPC copolymer). A 2.5 wt% aqueous solution of potassium hydroxide (KOH) was effective in producing silanol groups and for coating the cross-MPC copolymer. Additionally, we successfully modified the cross-MPC copolymer on the inner surface of SE tubes after pretreatment with the 2.5 wt% KOH aqueous solution, and the copolymer film was coated homogeneously. The cross-MPC copolymer film on SE was stable for one month under fluidic condition with a shear stress of 3.2 Pa. The hollow fiber membrane with the polymer coating inhibited blood coagulation after one week implantation with extracorporeal circulation device using a goat. Therefore, pretreatment of SE using an alkaline solution is an appropriate method for producing silanol groups for coating the cross-MPC copolymer by silane-coupling reaction.
Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities
Authors: Mallhi Tauqeer Hussain , Alanazi Abdullah Salah , Khan Yusra Habib , Alotaibi Nasser Hadal , Salman Muhammad , Alzarea Abdulaziz Ibrahim , Khan Salah-Ud-Din , Alruwaili Nabil K. , Alenazi Alaa Salah , Alatawi Ahmed D. , Iqbal Zafar , Butt Muhammad Hammad , Iqbal Muhammad Shahid 
Published: April 2022

BackgroundDespite a series of “boxed warnings” (BWs) issued by the US Food and Drug Administration (FDA), fluoroquinolones (FQs) are among the most prescribed antibiotics across the world. Moreover, few studies demonstrated that BW of FQs had less or no impact on prescribing patterns among healthcare professionals (HCPs), which might be attributed to the lack of knowledge toward such warnings. Since FQs contribute to a major proportion of antimicrobial prescriptions in the Kingdom of Saudi Arabia (KSA), this study aimed to ascertain the extent of knowledge toward safety profile, use, and BW of FQs among HCPs working in the KSA.MethodsThis cross-sectional study (May–August 2021) was conducted among HCPs working in KSA through a validated questionnaire. The HCPs were requested to identify the indications, adverse effects (AEs), and BW of FQs. The knowledge score (out of 40) was estimated among participants, and its association with demographics was ascertained through the chi-square test, Student's t-test, or Mann-Whitney U-test and one-way ANOVA, or Kruskal-Wallis test, where appropriate.ResultsOf the 573 participants (age: 36.1 ± 10.6 years, men: 59.7%), 262 (45.8%) were prescribers reporting frequent use of ciprofloxacin, levofloxacin, and ofloxacin. One-fourth (25.6%) of the prescribers did not recognize nalidixic acid as an agent from FQs class. About 60% of participants correctly identified the mechanism of action of FQs. The average knowledge score was 14.8 ± 6.4, where only 21.5% of respondents scored ≥50%. The average knowledge score for indications, AEs, and BW domains was 5.29 ± 3.05, 6.17 ± 4.05, and 2.3 ± 1.5, respectively. Only 75 (13.1%) participants recognized half of the BW, and 38.6% of participants identified at least one warning. The HCPs aged &gt;40 years (p = 0.043), having non-Saudi's nationality (p &lt; 0.001), working in Riyadh and Eastern regions (p &lt; 0.001), having pharmacy and medicine disciplines (p &lt; 0.001), practicing in public sectors (p = 0.004), and having more than 10 years of experience (p &lt; 0.001) were significantly associated with high knowledge score.ConclusionThis study demonstrates the unsatisfactory knowledge toward safety profile, use, and BW of FQs among HCPs which may put patients at increased risks of AEs. The knowledge score differed among various socio-demographic groups. There is a dire need to initiate the antimicrobial-focused educational campaigns among HCPs regardless of their specialties and methods to improve education and disseminate FDA warnings in practice.
A Qualitative Study Exploring Perceptions to the Human T Cell Leukaemia Virus Type 1 in Central Australia: Barriers to Preventing Transmission in a Remote Aboriginal Population
Authors: Fowler Fiona , Einsiedel Lloyd 
Published: April 2022

BackgroundCentral Australia has the highest recorded prevalence of infection with the human T cell leukaemia virus type 1 (HTLV-1) worldwide. Each of the clinical diseases associated with HTLV-1 have been reported in this region, including deaths due to adult T cell leukaemia, which is causally linked to HTLV-1. Nevertheless, no public health response has been implemented to reduce HTLV-1 transmission among the affected Aboriginal population. In the first study to explore the perceptions of healthcare professionals along with those of Aboriginal people whose communities are actually impacted by HTLV-1, we sought to understand the barriers to preventing HTLV-1 transmission in this remote area.Methodology/Principal FindingsSemi and un-structured interviews were conducted with 30 Australian Aboriginal people, 26 non-Aboriginal healthcare professionals and 3 non-Aboriginal community workers. The purpose of the interviews was to explore perceptions towards HTLV-1 in a health context with a focus on sexual and reproductive rights. Deductive and inductive analyses were applied to the data and a decolonizing lens brought peripheral stories to the fore. A major finding was the contrast between views expressed by Aboriginal participants and healthcare professionals regarding the provision of knowledge to those affected. Aboriginal participants consistently articulated that they and their communities should be informed of, and can hold, knowledges pertaining to HTLV-1. This finding controverted the perceptions of healthcare professionals that the complexities of the virus would not be well-understood by their Aboriginal patients and that sharing HTLV-1 knowledges might overwhelm Aboriginal people. Further analyses revealed a spectrum of understanding and clinical practice, while also delineating signs of an imagined public health response.Conclusions/SignificanceHTLV-1 remains a neglected infection in Australia. Knowledge of HTLV-1 is held by a privileged medical elite and does not flow to marginalised Aboriginal people living in affected communities. We demonstrate that differences in the perspectives of stakeholders presents a significant barrier to the development of cohesive, culturally safe prevention programs that foster a shared knowledge of HTLV-1. The interview data suggests that a successful public health program is likely to require a dual approach that includes clinical care and community-driven health promotion. Aspects of this approach, which would raise awareness and potentially reduce transmission and lower HTLV-1 prevalence in Central Australia, may be applicable to other endemic settings with similar conditions of social disadvantage, geographic remoteness, resource limitations and cross-cultural challenges.
Dry-Lensectomy Assisted Lensectomy in the Management for End-Stage Familial Exudative Vitreoretinopathy Complicated With Anterior Segment Abnormalities
Authors: Peng Jie , Zhao Ziwei , Zou Yihua , Zhang Xuerui , Yang Yuan , Huang Qiujing , Xu Mingpeng , Xu Yu , Zhao Peiquan 
Published: April 2022

PurposeTo report a modified technique of dry-lensectomy assisted lensectomy in the management of end-stage familial exudative vitreoretinopathy (FEVR) complicated with capsule-endothelial, iris-endothelial adhesion and secondary glaucoma.Methods24 eyes of 16 patients with severe complications of advanced pediatric total retinal detachment caused by FEVR who received limbus-based dry-lensectomy were studied retrospectively. Preoperative and postoperative clinical information was collected and reviewed.ResultsAmong the 24 eyes, three eyes (12.50%) underwent lensectomy combined with vitrectomy and membrane peeling simultaneously. 21 (87.50%) eyes underwent lensectomy without membrane peeling due to severe corneal opacity or retinal vascular activity, of which eight underwent another vitrectomy combined with membrane peeling. At the last visit (mean:13.86 ± 5.24 months of follow-up), all eyes had a reconstructed anterior chamber with normal depth. Among 21 eyes having preoperative corneal opacity, 15 (71.43%) had a clearer cornea with reduced opacity, 5 (23.81%) showed similar corneal opacification without deterioration. Among 11 eyes undergone retrolental fibroplasia peeling, seven (63.64%) eyes showed partial retinal reattachment in open-funnel type.ConclusionDry-lensectomy offered a simple way to lower the intraocular pressure and simplified the surgery, which helped to solve the severe anterior segment complications and offer a chance for following retrolental fibroplasia peeling and potential visual gain for selected end-stage FEVR patients.
Predictors of Maternal Near Miss in Public Hospitals of West Shoa Zone, Central Ethiopia: A Case-Control Study
Authors: Danusa Kababa Temesgen , Debelo Bikila Tefera , Wakgari Negash , Seifu Benyam , Kenasa Ketema , Daba Gurmesa , Wondimu Fikadu , Berhanu Keneni 
Published: April 2022

BackgroundMaternal mortality reduction remains a priority to ensure healthy lives and promote wellbeing for mothers and newborns in the new sustainable development goals agenda. There is no evidence-based study done regarding maternal complications and near-miss in the study area.ObjectivesThis study assessed the predictors of maternal near-miss in public hospitals of West Shoa Zone, Central Ethiopia, 2020.MethodsAn unmatched case-control study was conducted among 664 (166 cases and 498 controls) women who gave birth in public institutions in the West Shewa zone. Structured questionnaires and checklists were used to collect the data. Bivariate, multivariable logistic regression, and adjusted odds ratios were used to describe the strength and directions of association.ResultsThe odds of maternal near-miss were higher among mothers with increased maternal age [Adjusted odds ratio (AOR) = 1.065, 95%CI: (1.015–1.117)], who could not read and write (AOR = 3.06, 95%CI: 1.314–7.135), had primary (AOR = 3.49, 95%CI: 1.518–8.044), and secondary (AOR = 3.213, 95%CI: 1.418–7.282), had no antenatal care (ANC) follow-up (AOR = 2.25, 95%CI: 1.100–4.607), mothers who had a first delay of more than 6 h [AOR = 2.38, 95%CI: (1.517–3.735)] and the distance from health facility of &gt; 60 min [AOR = 4.021, 95%CI: (1.817–8.896)].ConclusionIn this study, delay in decision making and reaching the health facility, lower educational status, not having ANC follow-up, and increased maternal age were significantly associated with maternal near misses. Therefore, the Ethiopian federal ministry of health and other stakeholders should work on increasing ANC coverage, awareness creation, and strong means of transportation to tackle the complications of a maternal near miss.
The Prognostic Significance of C-Reactive Protein to Albumin Ratio in Patients With Severe Fever With Thrombocytopenia Syndrome
Authors: Yang Xiaozhou , Yin Huimin , Xiao Congshu , Li Rongkuan , Liu Yu 
Published: April 2022

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with the high case-fatality rate, lacking effective therapies and vaccines. Inflammation-based indexes have been widely used to predict the prognosis of patients with cancers and some inflammatory diseases. In our study, we aim to explore the predictive value of the inflammation-based indexes in SFTS patients.MethodsWe retrospectively analyzed 82 patients diagnosed with SFTS. The inflammation-based indexes, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and C-reactive protein to albumin ratio (CAR), were compared between the survival and death patients. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of MLR, AISI, and CAR. The survival analysis was based on the Kaplan–Meier (KM) method. Multivariate logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with SFTS.ResultsThe CAR is higher in the death group while MLR and AISI were higher in the survival group. The ROC curve analysis indicated CAR exhibited more predictive value than the other indexes and the optimal cut-off value of CAR was equal to or greater than 0.14. KM survival curve showed that higher CAR was significantly correlated to the lower overall survival in SFTS patients. Multivariate logistic regression analysis indicated that CAR was an independent risk factor for poor prognosis in patients with SFTS.ConclusionThe CAR is an independent risk factor for death in patients with SFTS and could predict the poor prognosis of SFTS patients. It could be used as a biomarker to help physicians to monitor and treat patients more aggressively to improve clinical prognosis.
Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study
Authors: Huang Li-Kai , Chao Shu-Ping , Hu Chaur-Jong , Chien Li-Nien , Chiou Hung-Yi , Lo Yu-Chun , Hsieh Yi-Chen 
Published: April 2022

IntroductionPost-stroke cognitive impairment (PSCI) cannot be neglected because it drastically influences the daily life of patients and their families. However, there are no studies exploring the association between preclinical blood biomarkers of neurodegeneration including plasma amyloid-β (Aβ), tau, and brain-derived neurotrophic factor (BDNF) together with the risk of PSCI. This longitudinal study was to investigate whether these blood biomarkers with imaging markers of cerebral small vessel disease can improve the prediction for PSCI. In addition, we also explored the association between blood biomarkers with the trajectories of PSCI.MethodsAdult patients with first-ever acute ischemic stroke were recruited, and the cognitive and functional abilities of these patients were evaluated. Furthermore, blood biomarkers of neurodegeneration including plasma Aβ-40, Aβ-42, total tau, phosphorylated tau 181 (p-tau181), and BDNF levels and image markers of cerebral small vessel disease were measured. Each patient was followed up at 3 and 12 months at the outpatient department.ResultsOf 136 patients, 40 and 50 patients developed PSCI at 3 and 12 months after stroke, respectively. In functional trajectories, 27 patients did not have PSCI at 3 months but did at 12 months. By contrast, the PSCI status of 17 patients at 3 months was reversed at 12 months. Patients with high-acute plasma p-tau181 had a significantly lower PSCI risk at 3 months (odds ratio [OR] = 0.62, 95% CI = 0.40–0.94, p = 0.0243) and 12 months (OR = 0.69, 95% CI = 0.47–0.99, p = 0.0443) after adjustment for covariates and image biomarkers. Discrimination and reclassification statistics indicated that the p-tau181 level can improve discrimination ability for PSCI at 3 and 12 months, respectively. In addition, the plasma p-tau181 level was the highest in subjects without PSCI followed by those with delayed-onset PSCI and early-onset PSCI with reversal, whereas the lowest plasma p-tau181 level was found among those with persistent PSCI, showing a significant trend test (p = 0.0081).ConclusionPlasma p-tau181 is a potential biomarker for predicting early- and delayed-onset PSCI. Future studies should incorporate plasma p-tau181 as an indicator for timely cognitive intervention in the follow-up of patients with stroke.
Antiepileptic Effect and Safety Profile of Rapamycin in Pediatric Patients With Tuberous Sclerosis Complex
Authors: Sadowski Krzysztof , Sijko Kamil , Domańska-Pakieła Dorota , Borkowska Julita , Chmielewski Dariusz , Ulatowska Agata , Józwiak Sergiusz , Kotulska Katarzyna 
Published: April 2022

BackgroundEpilepsy develops in 70–90% of children with Tuberous Sclerosis Complex (TSC) and is often resistant to medication. Treatment with mTOR pathway inhibitors is an important therapeutic option in drug-resistant epilepsy associated with TSC. Our study evaluated the antiepileptic effect of rapamycin in the pediatric population of patients diagnosed with TSC.MethodsThis single center, open-label study evaluated safety and anti-epileptic efficacy of 12 months of rapamycin treatment in 32 patients aged from 11 months to 14 years with drug-resistant TSC- associated epilepsy.ResultsAfter the first 6 months of treatment, the improvement in seizure frequency, defined as at least a 50% reduction in the number of seizures per week compared to baseline, was seen in 18 individuals (56.25%). We observed no change in 12 individuals (37.5%) and worsening, defined as increase in the number of seizures—in 2 patients (6.25%). The overall improvement defined as at least a 50% reduction in seizure frequency was found in 65.6% of all patients after 12 months with 28% of patients obtaining complete remission. Another five patients experienced at least an 80% reduction in the frequency of seizures. Concomitant treatment with vigabatrin, and to a much lesser extent topiramate and levetiracetam, was an additional favorable prognostic factor for the success of the therapy. A linear relationship between the cumulative dose of rapamycin and its therapeutic effect was observed. The safety profile of the drug was satisfactory. In none of the observed cases did the adverse events reach the level that required withdrawal of the rapamycin treatment. The reason for dropouts was insufficient drug efficacy in 3 cases.ConclusionsLong-term use of rapamycin, especially in combination with vigabatrin, might be a beneficial therapeutic option in the treatment of drug-resistant epilepsy in children with TSC.