bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic-di-GMP stimulates keratinocyte innate immune responses and attenuates methicillin-resistant Staphylococcus aureus colonization in a murine skin wound infection model
Authors: Gao Shuai , Khan Abidullah , Chen Xuhong , Xiao Guohui , van der Veen Stijn , Chen Yin , Lin Xu’ai 
Published: July 2022

AbstractBackgroundStaphylococcus aureusis a leading cause for morbidity and mortality associated with skin and burn wound infections. Therapeutic options for methicillin-resistantS. aureus(MRSA) have dwindled and therefore alternative treatments are urgently needed. In this study, the immuno-stimulating and anti-MRSA effects of cyclic di-guanosine monophosphate (c-di-GMP), a uniquely bacterial second messenger and immuno-modulator, were investigated in HaCaT human epidermal keratinocytes and a murine skin wound infection model.ResultsStimulation of HaCaT cells with 125 μM c-di-GMP for 12 h prior to MRSA challenge resulted in a 20-fold reduction in bacterial colonization compared with untreated control cells, which was not the result of a direct c-di-GMP toxic effect, since bacterial viability was not affected by this dose in the absence of HaCaT cells. C-di-GMP-stimulated or MRSA-challenged HaCaT cells displayed enhanced secretion of the antimicrobial peptides human β-defensin 1 (hBD-1), hBD-2, hBD-3 and LL-37, but for hBD1 and LL-37 the responses were additive in a c-di-GMP-dose-dependent manner. Secretion of the chemokines CXCL1 and CXCL8 was also elevated after stimulation of HaCaT cells with lower c-di-GMP doses and peaked at a dose of 5 μM. Finally, pre-treatment of mice with a 200 nmol dose of c-di-GMP 24 h before a challenge with MRSA in skin wound infection model resulted in a major reduction (up to 1,100-fold by day 2) in bacterial CFU counts recovered from challenged skin tissue sections compared PBS-treated control animals. Tissue sections displayed inflammatory cell infiltration and enhanced neutrophil influx in the c-di-GMP pre-treated animals, which might account for the reduced ability of MRSA to colonize c-di-GMP pre-treated mice.ConclusionsThese results demonstrate that c-di-GMP is a potent immuno-modulator that can stimulate anti-MRSA immune responses in vivo and might therefore be a suitable alternative prophylactic or therapeutic agent for MRSA skin or burn wound infections.
Assessing the ability of an instrumental variable causal forest algorithm to personalize treatment evidence using observational data: the case of early surgery for shoulder fracture
Authors: Brooks John M. , Chapman Cole G. , Floyd Sarah B. , Chen Brian K. , Thigpen Charles A. , Kissenberth Michael 
Published: July 2022

Abstract
Background
Comparative effectiveness research (CER) using observational databases has been suggested to obtain personalized evidence of treatment effectiveness. Inferential difficulties remain using traditional CER approaches especially related to designating patients to reference classes a priori. A novel Instrumental Variable Causal Forest Algorithm (IV-CFA) has the potential to provide personalized evidence using observational data without designating reference classes a priori, but the consistency of the evidence when varying key algorithm parameters remains unclear. We investigated the consistency of IV-CFA estimates through application to a database of Medicare beneficiaries with proximal humerus fractures (PHFs) that previously revealed heterogeneity in the effects of early surgery using instrumental variable estimators.

Methods
IV-CFA was used to estimate patient-specific early surgery effects on both beneficial and detrimental outcomes using different combinations of algorithm parameters and estimate variation was assessed for a population of 72,751 fee-for-service Medicare beneficiaries with PHFs in 2011. Classification and regression trees (CART) were applied to these estimates to create ex-post reference classes and the consistency of these classes were assessed. Two-stage least squares (2SLS) estimators were applied to representative ex-post reference classes to scrutinize the estimates relative to known 2SLS properties.

Results
IV-CFA uncovered substantial early surgery effect heterogeneity across PHF patients, but estimates for individual patients varied with algorithm parameters. CART applied to these estimates revealed ex-post reference classes consistent across algorithm parameters. 2SLS estimates showed that ex-post reference classes containing older, frailer patients with more comorbidities, and lower utilizers of healthcare were less likely to benefit and more likely to have detriments from higher rates of early surgery.

Conclusions
IV-CFA provides an illuminating method to uncover ex-post reference classes of patients based on treatment effects using observational data with a strong instrumental variable. Interpretation of treatment effect estimates within each ex-post reference class using traditional CER methods remains conditional on the extent of measured information in the data.
Methodology for the development of National Multidisciplinary Management Recommendations using a multi-stage meta-consensus initiative
Authors: Hardman John C. , Harrington Kevin , Roques Tom , Sood Sanjai , Jose Jemy , Lester Shane , Pracy Paul , Simo Ricard , Repanos Costa , Stafford Frank , Jennings Chris , Winter Stuart C. , Wheatly Hugh , Homer Jarrod , Kumar B. Nirmal , Paleri Vinidh 
Published: July 2022

Abstract
Background
Methods for developing national recommendations vary widely. The successful adoption of new guidance into routine practice is dependent on buy-in from the clinicians delivering day-to-day patient care and must be considerate of existing resource constraints, as well as being aspirational in its scope. This initiative aimed to produce guidelines for the management of head and neck squamous cell carcinoma of unknown primary (HNSCCUP) using a novel methodology to maximise the likelihood of national adoption.

Methods
A voluntary steering committee oversaw 3 phases of development: 1) clarification of topic areas, data collection and assimilation, including systematic reviews and a National Audit of Practice; 2) a National Consensus Day, presenting data from the above to generate candidate consensus statements for indicative voting by attendees; and 3) a National Delphi Exercise seeking agreement on the candidate consensus statements, including representatives from all 58 UK Head and Neck Multidisciplinary Teams (MDT). Methodology was published online in advance of the Consensus Day and Delphi exercise.

Results
Four topic areas were identified to frame guideline development. The National Consensus Day was attended by 227 participants (54 in-person and 173 virtual). Results from 7 new systematic reviews were presented, alongside 7 expert stakeholder presentations and interim data from the National Audit and from relevant ongoing Clinical Trials. This resulted in the generation of 35 statements for indicative voting by attendees which, following steering committee ratification, led to 30 statements entering the National Delphi exercise.
After 3 rounds (with a further statement added after round 1), 27 statements had reached ‘strong agreement’ (n = 25, 2, 0 for each round, respectively), a single statement achieved ‘agreement’ only (round 3), and ‘no agreement’ could be reached for 3 statements (response rate 98% for each round). Subsequently, 28 statements were adopted into the National MDT Guidelines for HNSCCUP.

Conclusions
The described methodology demonstrated an effective multi-phase strategy for the development of national practice recommendations. It may serve as a cost-effective model for future guideline development for controversial or rare conditions where there is a paucity of available evidence or where there is significant variability in management practices across a healthcare service.
Validation of remote height and weight assessment in a rural randomized clinical trial
Authors: Forseth Bethany , Davis Ann M. , Bakula Dana M. , Murray Megan , Dean Kelsey , Swinburne Romine Rebecca E. , Fleming Kandace 
Published: July 2022

AbstractBackgroundThe purpose of this study is to describe and assess a remote height and weight protocol that was developed for an ongoing trial conducted during the SARS COV-2 pandemic.MethodsThirty-eight rural families (children 8.3 ± 0.7 years; 68% female; and caregivers 38.2 ± 6.1 years) were provided detailed instructions on how to measure height and weight. Families obtained measures via remote data collection (caregiver weight, child height and weight) and also by trained staff. Differences between data collection methods were examined.ResultsPer absolute mean difference analyses, slightly larger differences were found for child weight (0.21 ± 0.21 kg), child height (1.53 ± 1.29 cm), and caregiver weight (0.48 ± 0.42 kg) between school and home measurements. Both analyses indicate differences had only minor impact on child BMI percentile (− 0.12, 0.68) and parent BMI (0.05, 0.13). Intraclass coefficients ranged from 0.98 to 1.00 indicating that almost all of the variance was due to between person differences and not measurement differences within a person.ConclusionResults suggest that remote height and weight collection is feasible for caregivers and children and that there are minimal differences in the various measurement methods studied here when assessing group differences. These differences did not have clinically meaningful impacts on BMI. This is promising for the use of remote height and weight measurement in clinical trials, especially for hard-to reach-populations.Trial registrationClinical. Registered inclinicaltrials.gov(NCT03304249) on 06/10/2017.
Morphological changes of Intervertebral Disc detectable by T2-weighted MRI and its correlation with curve severity in Adolescent Idiopathic Scoliosis
Authors: Yeung Kwong Hang , Man Gene Chi Wai , Deng Min , Lam Tsz Ping , Cheng Jack Chun Yiu , Chan Ka Chi , Chu Winnie Chiu Wing 
Published: July 2022

Abstract
Background
Our previous studies found disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves in adolescent idiopathic scoliosis (AIS) patients. Subsequent studies showed wedging of vertebral bodies (VB) had less contribution than intervertebral discs (IVD) to the anterior–posterior vertebral column length discrepancy in severe-AIS. However, the exact morphological changes of IVD were not clearly defined. This study aimed to evaluate the morphological and pathological changes of IVD and VB in AIS girls and healthy female controls.

Methods
This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were also evaluated on volumetric images. One-way ANOVA with Bonferroni correction and Pearson correlation tests were used.

Results
There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. In addition, Cobb angle was significantly correlated with wedge angle and height ratio, and inversely correlated with the volume of NP.

Conclusions
In addition to wedging of VB and IVD, there was significantly reduced volume of IVD and NP in AIS patients with severe curve, insinuating the mechanical effect of scoliosis leads to a compression on both IVD and NP before significant disc desiccation occurs. We postulate that the compression of IVD and NP can contribute to curve progression in severe-AIS, these patients are more prone to disc degeneration in adulthood if no operative treatment is offered. Further longitudinal study on these parameters is still warranted.
Hydroalcoholic extract of Haematoxylum brasiletto protects Caenorhabditis elegans from cadmium-induced toxicity
Authors: Duran-Izquierdo Margareth , Taboada-Alquerque María , Sierra-Marquez Lucellys , Alvarez-Ortega Neda , Stashenko Elena , Olivero-Verbel Jesus 
Published: July 2022

Abstract
Background
H. brasiletto is used in popular culture due to its therapeutic properties, including antioxidant, anti-inflammatory and antiproliferative properties, although little is known about its role as a protector against metal toxicity. This study aimed to investigate the chemical composition and efficacy of the hydroalcoholic extract from H. brasiletto (HAE-Hbrasiletto) collected in northern Colombia to defend against cadmium (Cd)-induced toxicity.

Methods
Phytochemical characterization was performed using HPLC-ESI-QTOF. Caenorhabditis elegans was employed to assess the shielding effect of HAE-Hbrasiletto against Cd toxicity in vivo, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was utilized to measure radical scavenging activity.

Results
The main secondary metabolites identified by HPLC-ESI-QTOF in the extracts were hematoxylins (brazilein and hematein) and protosappanins (protosappanin A, B and C, 10-O-methylprotosappanin B, and protosappanin A dimethyl acetal). The HAE-Hbrasiletto elicited low lethality in N2 worms and significantly reduced the Cd-induced death of the nematodes. It also improved Cd-induced motility inhibition, as well as body length and reproduction reduction provoked by the heavy metal. The extract displayed a good capacity to halt Cd-induced DAF-16 translocation. As this last process was associated with lethality (r = 0.962, p < 0.01), the antioxidant properties of the extract may contribute to ameliorating tissue damage induced by oxidative stress from Cd exposure.

Conclusion
HAE-Hbrasiletto has remarkable properties to protect against Cd-induced toxicity.
Design, development, and evaluation of a surveillance system for suicidal behaviors in Iran
Authors: Shafiee Mohsen , Mahboubi Mohammad , Shanbehzadeh Mostafa , Kazemi-Arpanahi Hadi 
Published: July 2022

AbstractBackgroundSuicide is a serious cause of morbidity and mortality in Iran and worldwide. Although several organizations gather information on suicide and suicide attempts, there is substantial misperception regarding the description of the phenomenon. This study proposes the minimum data set (MDS) for suicidal behaviors surveillance.MethodsA literature review was first conducted to achieve a thorough overview of suicide-related items and map the existing evidence supporting the development of the MDS. The data items included in the literature review were then analyzed using a two-round Delphi technique with content validation by an expert panel. The suicidal behaviors surveillance system was then established based on the confirmed MDS, and ultimately, its performance was assessed by involving the end-users.ResultsThe panel of experts consisted of 50 experts who participated in the Delphi phase and validity content review. Of these, 46% were men, and their mean age and average work experience were (36.4, SD ± 6.4) and (12.32, SD ± 5.2) years, respectively. The final MDS platform of our study contained 108 items classified into eight main categories. A web-based system with a modular and layered architecture was developed based on the derived MDS.ConclusionThe developed system provides a framework for recording suicidal behaviors' data. The integration of multiple suicide-related information systems at the regional and national levels makes it possible to assess the long-term outcomes and evolutions of suicide prevention interventions.
How responding in Spanish affects CAHPS results
Authors: Fowler Floyd J. , Brenner Philip S. , Cosenza Carol , Cleary Paul D. 
Published: July 2022

AbstractBackgroundThe most widely used surveys for assessing patient health care experiences in the U.S. are the Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. Studies examining the associations of language and ethnicity with responses to CAHPS surveys have yielded inconsistent findings. More research is needed to assess the effect of responding to CAHPS surveys in Spanish.MethodsSubjects were patients who had received care at a study community health center in Connecticut within 6 or 12 months of being sent a CAHPS survey that asks about care experiences. The survey included four multi-item measures of care plus an overall rating of the provider. Sampled patients were mailed dual language (English and Spanish) cover letters and questionnaires. Those who did not respond after follow-up mailings were contacted by bilingual interviewers to complete the survey by telephone.We tested three hypotheses for any observed differences by ethnicity and language:1. Spanish speakers are more likely than others to choose extreme response options.2. The semantic meaning of the Spanish translation is not the same as the English version of the questions, resulting in Spanish speakers giving different answers because of meaning differences.3. Spanish speakers have different expectations regarding their health care than those who answer in English.Analyses compared the answers on the survey measures for three groups: non-Hispanics answering in English, Hispanics answering in English, and Hispanics answering in Spanish.ResultsThe overall response rate was 45%. After adjusting for differences in demographic characteristics and self-rated health, those answering in Spanish gave significantly more positive reports than the other two groups on three of the five measures, and higher than the non-Hispanic respondents on a fourth.ConclusionsThose answering in Spanish gave more positive reports of their medical experiences than Hispanics and non-Hispanics answering in English. Whether these results reflect different response tendencies, different standards for care, or better care experiences is a key issue in whether CAHPS responses in Spanish need adjustment to make them comparable to responses in English.
“It wasn’t here, and now it is. It’s everywhere": fentanyl’s rising presence in Oregon’s drug supply
Authors: Shin Sarah S. , LaForge Kate , Stack Erin , Pope Justine , Leichtling Gillian , Larsen Jessica E. , Leahy Judith M. , Seaman Andrew , Hoover Daniel , Chisholm Laura , Blazes Christopher , Baker Robin , Byers Mikaela , Branson Katie , Korthuis P. Todd 
Published: July 2022

Abstract
Background
Illicit fentanyl has contributed to a drastic increase in overdose drug deaths. While fentanyl has subsumed the drug supply in the Northeastern and Midwestern USA, it has more recently reached the Western USA. For this study, we explored perspectives of people who use drugs (PWUD) on the changing drug supply in Oregon, experiences of and response to fentanyl-involved overdose, and recommendations from PWUD to reduce overdose risk within the context of illicit fentanyl’s dramatic increase in the recreational drug supply over the past decade.

Methods
We conducted in-depth interviews by phone with 34 PWUD in Oregon from May to June of 2021. We used thematic analysis to analyze transcripts and construct themes.

Results
PWUD knew about fentanyl, expressed concern about fentanyl pills, and were aware of other illicit drugs containing fentanyl. Participants were aware of the increased risk of an overdose but remained reluctant to engage with professional first responders due to fear of arrest. Participants had recommendations for reducing fentanyl overdose risk, including increasing access to information, harm reduction supplies (e.g., naloxone, fentanyl test strips), and medications for opioid use disorder; establishing drug checking services and overdose prevention sites; legalizing and regulating the drug supply; and reducing stigma enacted by healthcare providers.

Conclusion
PWUD in Oregon are aware of the rise of fentanyl and fentanyl pills and desire access to tools to reduce harm from fentanyl. As states in the Western USA face an inflection point of fentanyl in the drug supply, public health staff, behavioral health providers, and first responders can take action identified by the needs of PWUD.
Cross-sectional associations between mental health indicators and social vulnerability, with physical activity, sedentary behaviour and sleep in urban African young women
Authors: Draper Catherine E. , Cook Caylee J. , Redinger Stephanie , Rochat Tamsen , Prioreschi Alessandra , Rae Dale E. , Ware Lisa J. , Lye Stephen J. , Norris Shane A. 
Published: July 2022

Abstract
Background
Relationships between mental health and multiple health behaviours have not been explored in young South African women experiencing social constraints. The aim of this study was to identify associations between mental health indicators and risk factors with physical activity, sedentary behaviour, and sleep, amongst young women living in Soweto, a predominantly low-income, urban South African setting.

Methods
For this cross-sectional study, baseline measurements for participants (n = 1719, 18.0–25.9 years old) recruited for the Healthy Life Trajectories Initiative were used including: physical activity, sedentary behaviour (sitting, screen and television time), sleep (duration and quality), depression and anxiety indicators, emotional health, adverse childhood experiences, alcohol-use risk; social vulnerability, self-efficacy, and social support.

Results
Multiple regression analyses showed that depression (β = 0.161, p < 0.001), anxiety (β = 0.126, p = 0.001), adverse childhood experiences (β = 0.076, p = 0.014), and alcohol-use risk (β = 0.089, p = 0.002) were associated with poor quality sleep. Alcohol-use risk was associated with more screen time (β = 0.105, p < 0.001) and television time (β = 0.075, p < 0.016). Social vulnerability was associated with lower sitting time (β = − 0.187, p < 0001) and screen time (β = − 0.014, p < 0.001). Higher self-efficacy was associated with more moderate- to vigorous-intensity physical activity (β = 0.07, p = 0.036), better-quality sleep (β = − 0.069, p = 0.020) and less television time (β = − 0.079, p = 0.012). Having no family support was associated with more sitting time (β = 0.075, p = 0.022). Binomial logistic regression analyses supported these findings regarding sleep quality, with anxiety and depression risk doubling the risk of poor-quality sleep (OR = 2.425, p < 0.001, OR = 2.036, p = 0.003 respectively).

Conclusions
These findings contribute to our understanding of how mental health indicators and risk factors can be barriers to health behaviours of young women in Soweto, and that self-efficacy and social support can be protective for certain of these behaviours for these women. Our results highlight the uniqueness of this setting regarding associations between mental health and behaviours associated with non-communicable diseases risk.