bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-rich plasma inhibits inflammation, apoptosis, and the NLRP3/Caspase-1 pathway and induces matrix metalloproteinases and proliferation of IL-1β-induced articular chondrocytes by downregulating T-box transcription factor 3
Authors: Zhuo Feng , Li Jun , Wang Yong-Hong , Li Ming , Song Fang-Fei , Liu Yu-Liang , Tao Zong-Yu 
Published: May 2022

Objectives Osteoarthritis (OA) is a chronic joint disease characterized by osteoproliferation and the degeneration and destruction of articular cartilage. Platelet-rich plasma (PRP) is rich in various growth factors that have been reported to promote bone defect repair. This study examined the specific role and mechanism of PRP in OA. Methods OA model cells were created by treating articular chondrocytes with IL-1β. After treatment of the model cells with PRP or/and a T-box transcription factor 3 (TBX3)-overexpression plasmid, TBX3 expression was monitored via RT-qPCR, western blotting, and immunofluorescence assays. IL-1β, IL-33, and Caspase-3 levels were detected with ELISA kits. Levels of NLRP3, Caspase-1, MMP9, MMP13, and COL2A1 expression were evaluated by western blotting, and cell proliferation was assessed by the CCK-8 assay. Results Our results showed that TBX3 expression was upregulated in IL-1β-induced articular chondrocytes. IL-1β stimulation induced inflammation and the production of matrix metalloproteinases, activated Caspase-3 and the NLRP3/Caspase-1 pathway, inhibited the proliferation of articular chondrocytes; however, all those affects mediated by IL-1β could be markedly reversed by PRP. We also found that PRP alleviated IL-1β-induced inflammation, apoptosis, and extracellular matrix degradation in articular chondrocytes by inhibiting TBX3. Our findings suggest that PRP alleviates OA progression in vitro by downregulating TBX3. Conclusion PRP suppressed OA progression in vitro by inhibiting TBX3, which may be its mechanism of action in treating OA.
Albumin versus balanced crystalloid for resuscitation in the treatment of sepsis: A protocol for a randomised controlled feasibility study, “ABC-Sepsis”
Authors: Cafferkey John , Ferguson Andrew , Grahamslaw Julia , Oatey Katherine , Norrie John , Lone Nazir , Walsh Timothy , Horner Daniel , Appelboam Andy , Hall Peter , Skipworth Richard , Bell Derek , Rooney Kevin , Shankar-Hari Manu , Corfield Alasdair , Gray Alasdair 
Published: May 2022

Background Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. Methods ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. Objectives Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. Discussion This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected.
An online survey and interview of GPs in the UK for assessing their satisfaction regarding the medical training curriculum and NICE guidelines for the management of menopause
Authors: Dintakurti Nitya , Kalyanasundaram Shreya , Jha Prashant , Talaulikar Vikram 
Published: May 2022

Background: The UK is home to 13 million menopausal women. The aim of this study was to determine the views of GPs on their levels of confidence and comfort when advising or treating menopausal women and assess the need for further training. Method: An anonymous online questionnaire was sent out to GPs working within the NHS across the UK between January 2021 and March 2021. The questionnaire was circulated via GP e-mail lists, Facebook, and LinkedIn, and included an option for respondents to volunteer for a semi-structured interview. Results: The questionnaire had 173 responses. 52% of GPs indicated that they were not offered enough support to be able to advise and treat women with menopausal symptoms appropriately. 77.5% of GPs expressed that there is a need to improve training provided on menopause in medical school and GP training. 60.7% of GPs felt comfortable managing menopausal women and offering them management options. 22.5% of the respondents felt that the NICE guidelines are easy and clear guidance for clinical practice. Five GPs were further interviewed, and the analysis of the responses showed the perceived need by the GPs for improvements in medical training regarding menopause. Conclusion: There is a need for better support and medical training for GPs to help them advice and treat women with menopausal symptoms. This is key for ensuring that every woman in the UK feels supported in their journey during the menopausal transition and is offered evidence-based advice to help them make informed decisions.
Tracheostomy Outcomes in Patients With COVID‐19 at a New York City Hospital
Authors: Sharma Rahul K. , Grewal Maeher R. , Long Sallie M. , DiDonna Brendon , Sturm Joshua , Hills Susannah E. , Troob Scott H. 
Published: May 2022

ObjectiveTracheostomies have been performed in patients with prolonged intubation due to COVID‐19. Understanding outcomes in different populations is crucial to tackle future epidemics.Study DesignProspective cohort study.SettingTertiary academic medical center in New York City.MethodsA prospectively collected database of patients with COVID‐19 undergoing open tracheostomy between March 2020 and April 2020 was reviewed. Primary endpoints were weaning from the ventilator and from sedation and time to decannulation.ResultsSixty‐six patients underwent tracheostomy. There were 42 males (64%) with an average age of 62 years (range, 23‐91). Patients were intubated for a median time of 26 days prior to tracheostomy (interquartile range [IQR], 23‐30). The median time to weaning from ventilatory support after tracheostomy was 18 days (IQR, 10‐29). Of those sedated at the time of tracheostomy, the median time to discontinuation of sedation was 5 days (IQR, 3‐9). Of patients who survived, 39 (69%) were decannulated. Of those decannulated before discharge (n = 39), the median time to decannulation was 36 days (IQR, 27‐49) following tracheostomy. The median time from ventilator liberation to decannulation was 14 days (IQR, 8‐22). Thirteen patients (20.0%) had minor bleeding requiring packing. Two patients (3%) had bleeding requiring neck exploration. The all‐cause mortality rate was 10.6%. No patients died of procedural causes, and no surgeons acquired COVID‐19.ConclusionOpen tracheostomies were successfully and safely performed at our institution in the peak of the COVID‐19 pandemic. The majority of patients were successfully weaned from the ventilator and sedation. Approximately 60% of patients were decannulated prior to hospital discharge.
COVID-19 therapies: do we see substantial progress?
Authors: Matusewicz Lucyna , Golec Marlena , Czogalla Aleksander , Kuliczkowski Kazimierz , Konka Adam , Zembala-John Joanna , Sikorski Aleksander F. 
Published: May 2022

AbstractThe appearance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its spread all over the world is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has recently resulted in almost 400 million confirmed cases and 6 million deaths, not to mention unknown long-term or persistent side effects in convalescent individuals. In this short review, we discuss approaches to treat COVID-19 that are based on current knowledge of the mechanisms of viral cell receptor recognition, virus–host membrane fusion, and inhibition of viral RNA and viral assembly. Despite enormous progress in antiviral therapy and prevention, new effective therapies are still in great demand.
Receiving screened donor human milk for their infant supports parental wellbeing: a mixed-methods study
Authors: Brown A. , Shenker N. 
Published: May 2022

Abstract
Background
Access to donor human milk (DHM) has primarily been based on the health and development outcomes of premature infants but there has been little examination of the broader impact of an infant receiving it upon parental mental health. Breastfeeding and mental health are closely tied with women who experience breastfeeding difficulties or are unable to meet their own breastfeeding goals often experiencing feelings of guilt, sadness and anger, alongside an increased risk of postnatal depression. The aim of the current study was to explore how experience of receiving DHM for their baby affected the wellbeing of parents.

Methods
UK parents of infants aged 0 – 12 months who had received screened DHM from a milk bank (typically on the neonatal unit or in some cases in the community) completed an online questionnaire exploring their experiences. The questionnaire included Likert scale items examining perceived impact upon infant health, own wellbeing and family functioning alongside open-ended questions exploring perceptions of how receiving DHM affected wellbeing.

Results
Almost all of the 107 participants (women = 102) agreed that receiving DHM had a positive impact upon infant health and development, their own mental and physical health, and their family’s wellbeing. Parents felt relieved that their infant was receiving DHM for health reasons but also due to the experience of being listened to, supported and having their infant feeding decisions facilitated. Receiving DHM helped mothers to process some of their emotions at not being able to breastfeed, in part because knowing their baby was being fed gave them the space to focus on recovery and bonding with their baby. Some parents did experience challenges, feeling guilty at receiving DHM, insecure that another woman was able to feed their baby when they could not, or negative reactions from family. Although the impact of receiving DHM upon breastfeeding was not measured, some women who were working to build their own milk supply noted that it helped motivate them to continue.

Conclusions
DHM may play an important role not only in protecting infant health and development but in supporting the mental health and wellbeing of mothers for whom their infant receiving human milk is important.
Nitric-Oxide Synthase trafficking inducer (NOSTRIN) is an emerging negative regulator of colon cancer progression
Authors: Paul Madhurima , Gope Tamal Kanti , Das Priyanka , Ain Rupasri 
Published: May 2022

Abstract
Background
NOSTRIN, abundantly expressed in colon, was reported to be anti-angiogenic, anti-invasive and anti-inflammatory. NOSTRIN expression was inversely related to survival of pancreatic ductal adeno-carcinoma patients. Yet its function and regulatory mechanism in CRC remains elusive.

Methods
NOSTRIN’s influence on EMT of CRC cells were analysed using realtime PCR array containing the functional EMT-transcriptome followed by western blotting. Regulation of oncogenic potential of CRC cells by NOSTRIN was elucidated using soft agar colony formation, trans-well invasion, wound healing and colonosphere formation assays. Biochemical assays were used to reveal mechanism of NOSTRIN function. Human CRC tissue array was used to test NOSTRIN mark in control and CRC disease stages.

Results
We showed here that CRC cell lines with less NOSTRIN expression has more invasive and migratory potential. NOSTRIN affected EMT-associated transcriptome of CRC cells by down regulating 33 genes that were functionally annotated to transcription factors, genes important for cell growth, proliferation, migration, cell adhesion and cytoskeleton regulators in CRC cells. NOSTRIN over-expression significantly reduced soft agar colony formation, wound healing and cell invasion. In line with this, RNA interference of Nostrin enhanced metastatic potential of CRC cells. Furthermore, stable overexpression of NOSTRIN in CRC cell line not only curtailed its ability to form colonosphere but also decreased expression of stemness markers CD133, CD44 and EpCAM. NOSTRIN’s role in inhibiting self-renewal was further confirmed using BrdU incorporation assay. Interestingly, NOSTRIN formed immune-complex with Cdk1 in CRC cells and aided in increase of inhibitory Y15 and T14 phosphorylation of Cdk1 that halts cytokinesis. These ex vivo findings were substantiated using human colon cancer tissue array containing cDNAs from patients’ samples with various stages of disease progression. Significant decrease in NOSTRIN expression was found with initiation and progression of advanced colon cancer disease stages.

Conclusion
We illustrate function of a novel molecule, NOSTRIN in curtailing EMT and maintenance of CRC cell stemness. Our data validates importance of NOSTRIN mark during onset and disease progression of CRC indicating its diagnostic potential.
Depth of field and visual performance after implantation of a new hydrophobic trifocal intraocular lens
Authors: Palomino-Bautista Carlos , Cerviño Alejandro , Cuiña-Sardiña Ricardo , Carmona-Gonzalez David , Castillo-Gomez Alfredo , Sanchez-Jean Ruben 
Published: May 2022

Abstract
Purpose
To assess the depth of field (DOF) by means of defocus curve analysis applying different visual acuity criteria in patients following cataract surgery and bilateral implantation of a new trifocal diffractive intraocular lens (IOL).

Methods
Fifty eyes of 25 consecutive patients who underwent implantation of the Asqelio™ trifocal IOL (AST Products Inc., USA) were enrolled in this observational prospective study. Monocular subjective DOF was obtained from defocus curves with absolute and relative criteria of tolerance for different visual acuities values. Patient’s visual satisfaction, postoperative refraction and visual acuity at far, intermediate (67 cm) and near (40 cm) distances were also measured at 1 and 3-months post-surgery. Analysis of variance was used to assess differences in refractive error after the surgical procedure, and paired t-tests were used to assess differences in VA. Patient satisfaction results were reported as percentages.

Results
Spherical equivalent was 0.05 ± 0.23 D and residual cylinder 0.01 ± 0.23 D 3-months after the surgery. Absolute DOF obtained was 3.29 ± 0.91 D considering 0.1 LogMAR as cut-off value, and 4.82 ± 0.69 D when 0.3 logMAR as cutoff value. Relative DOF considering a drop of 0.1 logMAR from maximum visual acuity was 2.57 ± 0.82 D, and 1.27 ± 0.70 D when a drop of 0.04 logMAR was considered. Visual acuities obtained 3-months after the surgery were 0.03 ± 0.13, − 0.05 ± 0.06, 0.03 ± 0.08 and 0.04 ± 0.08 logMAR for uncorrected and best-corrected for distance, and best distance-corrected for intermediate and near distances, respectively. Average response to visual satisfaction queries was 8.24/10 at distance, 8.04/10 at intermediate, and 7.88/10 at near.

Conclusions
Patients implanted with this trifocal IOL showed a significant improvement in visual acuity at different distances providing wide absolute and relative DOF values. The outcomes demonstrate that this lens is predictable yielding good patient satisfaction rates.
The effect of A2E on lysosome membrane permeability during blue light-induced human RPEs apoptosis
Authors: Xu Yan , Li Dan , Su Gang , Cai Shanjun 
Published: May 2022

Abstract
Background
To investigate the effect of N-retinyl-N-retinylidene ethanolamine (A2E) on lysosome membrane permeability (LMP) during blue light-induced human retinal pigment epithelium cells (RPEs) apoptosis.

Methods
By building an A2E and blue light irradiation inducing RPEs damage model, the CCK-8 assay was used to detect RPEs viability loaded with different concentrations of A2E after different culturing time to determine the optimum A2E loading concentration. And the RPEs fluorescence intensity changes were observed by fluorescence microscopy loaded with different concentration of A2E. The RPEs were divided into four groups randomly: control group, A2E-loaded group, blue light irradiation group, and A2E-loaded + blue light irradiation group. Annexin V-FITC/PI and TUNEL/DAPI methods were used to detect RPEs apoptotic rate. Laser scanning confocal microscopy (LSCM) was used to observe RPEs LMP changes stained by acridine orange (AO) method.

Results
The CCK-8 result showed a downward trend in cells viability of RPEs loaded with increasing concentration of A2E and extending culturing time. The optimum A2E loading concentration was determined at 25 μmol/L. With increasing A2E loading concentrations, the intensity of fluorescence in RPEs decreased gradually. The RPEs apoptotic rate in blue light irradiation + A2E-loaded group was significantly higher than those in other three groups detected by Annexin V-FITC/PI method, which was similar to TUNEL/DAPI’s result. After AO staining, cytoplasmic and nucleolar RNAs emits green fluorescence; lysosomes emit red fluorescence. Through the interference of A2E and blue light on RPEs, red fluorescent leakage from the lysosomes (means LMP increasing) can be observed. The mean red fluorescence intensity was chosen as the statistics indicator to estimate LMP change in RPEs cultured in vitro. Compared with the control group, the red fluorescence intensity decreased in A2E-loaded group, blue light irradiation group, and blue light irradiation + A2E-loaded group. Meanwhile, the mean red fluorescence intensity in blue light irradiation + A2E-loaded group was the lowest.

Conclusions
Both A2E-loaded and blue light irradiation could induce human RPEs apoptosis, and the two factors had a synergistic effect. In addition, both A2E and blue light can lead to LMP increasing, which indicated LMP change might be the upstream part in inducing mitochondrion-dependent apoptotic pathway. These data provided evidence that A2E as the most important auto-fluorescence substance in lipofuscin is an initiator of blue light-mediated damage of RPEs and participate in pathogenesis of retinal degenerative diseases in humans.
Qualitative comparative analysis of the implementation fidelity of a workplace sedentary reduction intervention
Authors: Leonard Krista S. , Mullane Sarah L. , Golden Caitlin A. , Rydell Sarah A. , Mitchell Nathan R. , Koskan Alexis , Estabrooks Paul A. , Pereira Mark A. , Buman Matthew P. 
Published: May 2022

Abstract
Background
Stand and Move at Work was a 12-month, multicomponent, peer-led (intervention delivery personnel) worksite intervention to reduce sedentary time. Although successful, the magnitude of reduced sedentary time varied by intervention worksite. The purpose of this study was to use a qualitative comparative analysis approach to examine potential explanatory factors that could distinguish higher from lower performing worksites based on reduced sedentary time.

Methods
We assessed 12-month changes in employee sedentary time objectively using accelerometers at 12 worksites. We ranked worksites based on the magnitude of change in sedentary time and categorized sites as higher vs. lower performing. Guided by the integrated-Promoting Action on Research Implementation in Health Services framework, we created an indicator of intervention fidelity related to adherence to the protocol and competence of intervention delivery personnel (i.e., implementer). We then gathered information from employee interviews and surveys as well as delivery personnel surveys. These data were aggregated, entered into a truth table (i.e., a table containing implementation construct presence or absence), and used to examine differences between higher and lower performing worksites.

Results
There were substantive differences in the magnitude of change in sedentary time between higher (-75.2 min/8 h workday, CI95: -93.7, -56.7) and lower (-30.3 min/8 h workday, CI95: -38.3, -22.7) performing worksites. Conditions that were present in all higher performing sites included implementation of indoor/outdoor walking route accessibility, completion of delivery personnel surveys, and worksite culture supporting breaks (i.e., adherence to protocol). A similar pattern was found for implementer willingness to continue role and employees using face-to-face interaction/stair strategies (i.e., delivery personnel competence). However, each of these factors were also present in some of the lower performing sites suggesting we were unable to identify sufficient conditions to predict program success.

Conclusions
Higher intervention adherence and implementer competence is necessary for greater program success. These findings illustrate the need for future research to identify what factors may influence intervention fidelity, and in turn, effectiveness.

Trial registration
ClinicalTrials.gov Identifier: NCT02566317. Registered 2 October 2015, first participant enrolled 11 January 2016.
Type 1 diabetes management and hospitalisation in the over 25’s at an Australian outer urban diabetes clinic
Authors: Patel Shivani , Farkash Celine , Simmons David 
Published: May 2022

Abstract
Aims
To describe clinic management and referral pathways among adults with type 1 diabetes (T1D) aged > 25 years attending a public outpatient diabetes service.

Methods
Retrospective cohort study of people with T1D aged > 25 years seen by endocrinologists in one Australian urban public outpatient in 2017. Electronic and paper medical records were reviewed using a dataset adapted from the UK National Institute for Health and Care Excellence 2015 guidelines.

Results
Among the 111 people with T1D (mean age 41 ± 13 years, 55% men, mean body mass index 27.1 ± 5.6 kg/m2), mean HbA1c was 8.1 ± 1.9% (66 ± 19 mmol/mol) (lower than the Australian National Diabetes Audit: 8.5%/69 mmol/mol) with 25.5% meeting the guideline target of < 53 mmol/mol (7.0%). Most people had seen a diabetes educator (80.2%) or dietitian (73.0%) and had complication screening. Complication rates were high (nephropathy 20.4%, retinopathy 27.4%, peripheral neuropathy 30.1%, ischaemic heart disease/acute infarction 10.5%). Overall, 27% of referrals occurred following an acute inpatient admission or emergency department presentation and 13% for management of diabetes in pregnancy.

Conclusions
A high proportion of people with T1D accessed public specialist care either during pregnancy or after a largely avoidable acute glycaemia-related hospital presentation. Subsequent care was in line with national specialist standards. This area has a “wait for acute event” rather than “complication prevention” model of care, associated with under-referral to the local multidisciplinary specialist service. Understanding how widespread this model of care is, and ways to reduce its prevalence, are urgently required.