bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis
Authors: Gramegna Andrea , Majo Fabio , Alicandro Gianfranco , Leonardi Gloria , Cristiani Luca , Amati Francesco , Contarini Martina , Aliberti Stefano , Fiocchi Alessandro Giovanni , Blasi Francesco 
Published: June 2023

Abstract
Background
The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy.

Methods
We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment’s effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term.

Results
The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively.

Conclusions
Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.
Alveolar macrophages from EVALI patients and e-cigarette users: a story of shifting phenotype
Authors: Warren Kristi J. , Beck Emily M. , Callahan Sean J. , Helms My N. , Middleton Elizabeth , Maddock Sean , Carr Jason R. , Harris Dixie , Blagev Denitza P. , Lanspa Michael J. , Brown Samuel M. , Paine Robert 
Published: June 2023

AbstractExposure to e-cigarette vapors alters important biologic processes including phagocytosis, lipid metabolism, and cytokine activity in the airways and alveolar spaces. Little is known about the biologic mechanisms underpinning the conversion to e-cigarette, or vaping, product use-associated lung injury (EVALI) from normal e-cigarette use in otherwise healthy individuals. We compared cell populations and inflammatory immune populations from bronchoalveolar lavage fluid in individuals with EVALI to e-cigarette users without respiratory disease and healthy controls and found that e-cigarette users with EVALI demonstrate a neutrophilic inflammation with alveolar macrophages skewed towards inflammatory (M1) phenotype and cytokine profile. Comparatively, e-cigarette users without EVALI demonstrate lower inflammatory cytokine production and express features associated with a reparative (M2) phenotype. These data indicate macrophage-specific changes are occurring in e-cigarette users who develop EVALI.
Effect of pre-operative hypoxemia on the occurrence and outcomes of post-operative ARDS in Stanford type a aortic dissection patients
Authors: Teng Cai  , Fei Zhonghua , Liu Hongsheng , Liu Xinmei , Hu Zhansheng 
Published: June 2023

Abstract
Background
Pre-operative and post-operative hypoxemia are frequent complications of Stanford type A aortic dissection (AAD). This study explored the effect of pre-operative hypoxemia on the occurrence and outcome of post-operative acute respiratory distress syndrome (ARDS) in AAD.

Method
A total of 238 patients who underwent surgical treatment for AAD between 2016 and 2021 were enrolled. Logistic regression analysis was conducted to investigate the effect of pre-operative hypoxemia on post-operative simple hypoxemia and ARDS. Post-operative ARDS patients were divided into pre-operative normal oxygenation group and pre-operative hypoxemia group that were compared for clinical outcomes. Post-operative ARDS patients with pre-operative normal oxygenation were classified as the real ARDS group. Post-operative ARDS patients with pre-operative hypoxemia, post-operative simple hypoxemia, and post-operative normal oxygenation were classified as the non-ARDS group. Outcomes of real ARDS and non-ARDS groups were compared.

Result
Logistic regression analysis showed that pre-operative hypoxemia was positively associated with the risk of post-operative simple hypoxemia (odds ratios (OR) = 4.81, 95% confidence interval (CI): 1.67–13.81) and post-operative ARDS (OR = 8.514, 95% CI: 2.64–27.47) after adjusting for the confounders. The post-operative ARDS with pre-operative normal oxygenation group had significantly higher lactate, APACHEII score and longer mechanical ventilation time than the post-operative ARDS with pre-operative hypoxemia group (P < 0.05). Pre-operative the risk of death within 30 days after discharge was slightly higher in ARDS patients with pre-operative normal oxygenation than in ARDS patients with pre-operative hypoxemia, but there was no statistical difference(log-rank test, P = 0.051). The incidence of AKI and cerebral infarction, lactate, APACHEII score, mechanical ventilation time, intensive care unit and post-operative hospital stay, and mortality with 30 days after discharge were significantly higher in the real ARDS group than in the non-ARDS group (P < 0.05). After adjusting for confounding factors in the Cox survival analysis, the risk of death within 30 days after discharge was significantly higher in the real ARDS group than in the non-ARDS group (hazard ratio(HR): 4.633, 95% CI: 1.012–21.202, P < 0.05).

Conclusion
Preoperative hypoxemia is an independent risk factor for post-operative simple hypoxemia and ARDS. Post-operative ARDS with pre-operative normal oxygenation was the real ARDS, which was more severe and associated with a higher risk of death after surgery.
A framework for stakeholder engagement in the adoption of new anti-malarial treatments in Africa: a case study of Nigeria
Authors: Mokuolu Olugbenga Ayodeji , Bolarinwa Oladimeji Akeem , Opadiran Oluwatumobi Racheal , Ameen Hafsat Abolore , Dhorda Mehul , Cheah Phaik Yeong , Amaratunga Chanaki , de Haan Freek , Tindana Paulina , Dondorp Arjen M. 
Published: June 2023

Abstract
Background
Recent reports of artemisinin partial resistance from Rwanda and Uganda are worrisome and suggest a future policy change to adopt new anti-malarials. This is a case study on the evolution, adoption, and implementation of new anti-malarial treatment policies in Nigeria. The main objective is to provide perspectives to enhance the future uptake of new anti-malarials, with an emphasis on stakeholder engagement strategies.

Methods
This case study is based on an analysis of policy documents and stakeholders’ perspectives drawn from an empirical study conducted in Nigeria, 2019–2020. A mixed methods approach was adopted, including historical accounts, review of programme and policy documents, and 33 qualitative in-depth interviews and 6 focus group discussions.

Results
Based on policy documents reviewed, the adoption of artemisinin-based combination therapy (ACT) in Nigeria was swift due to political will, funding and support from global developmental partners. However, the implementation of ACT was met with resistance from suppliers, distributors, prescribers, and end-users, attributed to market dynamics, costs and inadequate stakeholder engagement. Deployment of ACT in Nigeria witnessed increased developmental partner support, robust data generation, ACT case-management strengthening and evidence on anti-malarial use in severe malaria and antenatal care management. A framework for effective stakeholder engagement for the future adoption of new anti-malarial treatment strategies was proposed. The framework covers the pathway from generating evidence on drug efficacy, safety and uptake; to making treatment accessible and affordable to end-users. It addresses which stakeholders to engage with and the content of engagement strategies with key stakeholders at different levels of the transition process.

Conclusion
Early and staged engagement of stakeholders from global bodies to community level end-users is critical to the successful adoption and uptake of new anti-malarial treatment policies. A framework for these engagements was proposed as a contribution to enhancing the uptake of future anti-malarial strategies.
Improvement studies for equitable and evidence-based innovation: an overview of the ‘IM-SEEN’ model
Authors: Allen Luke N. , Nkomazana Oathokwa , Mishra Sailesh Kumar , Gichangi Michael , Macleod David , Ramke Jacqueline , Bolster Nigel , Marques Ana Patricia , Rono Hilary , Burton Matthew , Kim Min , Ratshaa Bakgaki , Karanja Sarah , Ho-Foster Ari , Bastawrous Andrew 
Published: June 2023

Abstract
Background
Health inequalities are ubiquitous, and as countries seek to expand service coverage, they are at risk of exacerbating existing inequalities unless they adopt equity-focused approaches to service delivery.

Main text
Our team has developed an equity-focused continuous improvement model that reconciles prioritisation of disadvantaged groups with the expansion of service coverage. Our new approach is based on the foundations of routinely collecting sociodemographic data; identifying left-behind groups; engaging with these service users to elicit barriers and potential solutions; and then rigorously testing these solutions with pragmatic, embedded trials. This paper presents the rationale for the model, a holistic overview of how the different elements fit together, and potential applications. Future work will present findings as the model is operationalised in eye-health programmes in Botswana, India, Kenya, and Nepal.

Conclusion
There is a real paucity of approaches for operationalising equity. By bringing a series of steps together that force programme managers to focus on groups that are being left behind, we present a model that can be used in any service delivery setting to build equity into routine practice.
Integrative analysis of the gut microbiota and faecal and serum short-chain fatty acids and tryptophan metabolites in patients with cirrhosis and hepatic encephalopathy
Authors: Wang Qiang , Chen Chengxin , Zuo Shi , Cao Kun , Li Haiyang 
Published: June 2023

Abstract
Objective
The purpose of this study was to describe the changes in the gut microbiome of patients with cirrhosis and hepatic encephalopathy (HE), as well as quantify the variations in short-chain fatty acid (SCFA) and tryptophan metabolite levels in serum and faeces.

Methods
Fresh faeces and serum were collected from 20 healthy volunteers (NC group), 30 cirrhosis patients (Cir group), and 30 HE patients (HE group). Then, 16S rRNA sequencing and metabolite measurements were performed using the faeces. Gas chromatography‒mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry were used to measure SCFA and tryptophan levels, respectively. The results were analysed by SIMCA16.0.2 software. Differences in species were identified using MetaStat and t tests. The correlations among the levels of gut microbes and metabolites and clinical parameters were determined using Spearman correlation analysis.

Results
Patients with cirrhosis and HE had lower microbial species richness and diversity in faeces than healthy volunteers; these patients also had altered β-diversity. Serum valeric acid levels were significantly higher in the HE group than in the Cir group. Serum SCFA levels did not differ between the Cir and NC groups. Serum melatonin and 5-HTOL levels were significantly higher in the HE group than in the Cir group. The Cir and NC groups had significant differences in the levels of eight serum tryptophan metabolites. Furthermore, the levels of faecal SCFAs did not differ between the HE and Cir groups. Faecal IAA-Ala levels were significantly lower in the HE group than in the Cir group. There were significant differences in the levels of 6 faecal SCFAs and 7 faecal tryptophan metabolites between the Cir and NC groups. Certain gut microbes were associated with serum and faecal metabolites, and some metabolites were associated with certain clinical parameters.

Conclusion
Reduced microbial species richness and diversity were observed in patients with HE and cirrhosis. In both serum and faeces, the levels of different SCFAs and tryptophan metabolites showed varying patterns of change. In HE patients, the levels of some serum tryptophan metabolites, and not SCFAs, were correlated with liver function and systemic inflammation. Systemic inflammation in patients with cirrhosis was correlated with faecal acetic acid levels. In summary, this study identified metabolites important for HE and cirrhosis.
Characteristics of corticomuscular coupling during wheelchair Tai Chi in patients with spinal cord injury
Authors: Zu Yangmin , Luo Lina , Chen Xinpeng , Xie Haixia , Yang Chich-Haung Richard , Qi Yan , Niu Wenxin 
Published: June 2023

Abstract
Background
Wheelchair Tai Chi (WCTC) has been proved to have benefits for the brain and motor system of spinal cord injury (SCI) patients. However, the characteristics of corticomuscular coupling during WCTC are scarcely known. We aimed to investigate changes following SCI on corticomuscular coupling, and further compare the coupling characteristics of WCTC with aerobic exercise in SCI patients.

Methods
A total of 15 SCI patients and 25 healthy controls were recruited. The patients had to perform aerobic exercise and WCTC, while healthy controls needed to complete a set of WCTC. The participants accomplished the test following the tutorial video in a sitting position. The upper limb muscle activation was measured from upper trapezius, medial deltoid, biceps brachii and triceps brachii with surface electromyography. Cortical activity in the prefrontal cortex, premotor cortex, supplementary motor area and primary motor cortex was simultaneously collected by functional near-infrared spectroscopy. The functional connectivity, phase synchronization index and coherence values were then calculated and statistically analyzed.

Results
Compared to healthy controls, changes in functional connectivity and higher muscle activation were observed in the SCI group. There was no significant difference in phase synchronization between groups. Among patients, significantly higher coherence values between the left biceps brachii as well as the right triceps brachii and contralateral regions of interest were found during WCTC than during aerobic exercise.

Conclusion
The patients may compensate for the lack of corticomuscular coupling by enhancing muscle activation. This study demonstrated the potential and advantages of WCTC in eliciting corticomuscular coupling, which may optimize rehabilitation following SCI.
Structure of cellulose in birch phloem fibres in tension wood: an X-ray nanodiffraction study
Authors: Viljanen Mira , Muranen Sampo , Kinnunen Outi , Kalbfleisch Sebastian , Svedström Kirsi 
Published: June 2023

Abstract
Background
To gain a better understanding of bark layer structure and function, especially of the phloem fibres and their contribution to the posture control of trees, it is important to map the structural properties of these cells. The role of bark can also be linked to the reaction wood formation and properties which are essential when it comes to studying the questions related to tree growth. To offer new insights into the role of bark in the postural control of trees, we studied the micro- and nanoscale structures of the phloem and its nearest layers. This study is the first time, in which phloem fibres in trees have been extensively examined using X-ray diffraction (XRD).
We determined the orientation of cellulose microfibrils in phloem fibres of Silver birch saplings by using scanning synchrotron nanodiffraction. The samples consisted of phloem fibres extracted from tension, opposite and normal wood (TW, OW, NW).

Results
Using scanning XRD, we were able to obtain new information about the mean microfibril angle (MFA) in cellulose microfibrils in phloem fibres connected to reaction wood. A slight but consistent difference was detected in the average MFA values of phloem fibres between the TW and OW sides of the stem. Using scanning XRD, different contrast agents (intensity of the main cellulose reflection or calcium oxalate reflection, mean MFA value) were used to produce 2D images with 200 nm spatial resolution.

Conclusions
Based on our results, the tension wood formation in the stem might be related to the structure and properties of phloem fibres. Thus, our results suggest that the nanostructure of phloem fibres is involved in the postural control of trees containing tension and opposite wood.
Biological roles of A-to-I editing: implications in innate immunity, cell death, and cancer immunotherapy
Authors: Yuan Jing , Xu Li , Bao Hai-Juan , Wang Jie-lin , Zhao Yang , Chen Shuo 
Published: June 2023

AbstractAdenosine-to-inosine (A-to-I) editing, a key RNA modification widely found in eukaryotes, is catalyzed by adenosine deaminases acting on RNA (ADARs). Such RNA editing destabilizes endogenous dsRNAs, which are subsequently recognized by the sensors of innate immune and other proteins as autologous dsRNAs. This prevents the activation of innate immunity and type I interferon-mediated responses, thereby reducing the downstream cell death induced by the activation of the innate immune sensing system. ADARs-mediated editing can also occur in mRNAs and non-coding RNAs (ncRNAs) in different species. In mRNAs, A-to-I editing may lead to missense mutations and the selective splicing of coding regions. Meanwhile, in ncRNAs, A-to-I editing may affect targeting and disrupt ncRNAs maturation, leading to anomalous cell proliferation, invasion, and responses to immunotherapy. This review highlights the biological functions of A-to-I editing, its role in regulating innate immunity and cell death, and its potential molecular significance in tumorigenesis and cancer targeted therapy and immunotherapy.
Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial
Authors: Nay Mai-Anh , Hindre Raphaël , Perrin Christophe , Clément Jérémy , Plantier Laurent , Sève Aymeric , Druelle Sylvie , Morrier Marine , Lainé Jean-Baptiste , Colombain Léa , Corvaisier Grégory , Bizien Nicolas , Pouget-Abadie Xavier , Bigot Adrien , Jamard Simon , Nyamankolly Elsa , Planquette Benjamin , Fossat Guillaume , Boulain Thierry 
Published: June 2023

Abstract
Background
Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone.

Methods
In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days.

Results
Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30–133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14–1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01–0.89 and aOR 0.09; 95% CI 0.01–0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01–0.90, and aOR 0.09; 95% CI 0.03–0.27, respectively).

Conclusions
Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death.
Trial registration ClinicalTrials.gov Identifier: NCT04363463. Registered 27 April 2020.
Synthesis, antimicrobial and antioxidant activity of triazole, pyrazole containing thiazole derivatives and molecular docking studies on COVID-19
Authors: Matta Raghavender , Pochampally Jalapathi , Dhoddi Bala Narsimha , Bhookya Shankar , Bitla Sampath , Akkiraju Anjini Gayatri 
Published: June 2023

AbstractNew series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e,12f and 12 kpossess the highest growth inhibitory activity at MIC values of4.8, 5.1and4.0 μg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positiveS. aureustopoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds12a-lwere ranging from − 10.0 to − 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from − 8.2 to − 9.3 kcal/mol. These docking studies reveal that the compounds12a-lcould be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.