bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process evaluation of a pragmatic implementation trial to support self-management for the prevention and management of type 2 diabetes in Uganda, South Africa and Sweden in the SMART2D project
Authors: van Olmen Josefien , Absetz Pilvikki , Mayega Roy William , Timm Linda , Delobelle Peter , Alvesson Helle Mölsted , Naggayi Glorai , Kasujja Francis , Hassen Mariam , de Man Jeroen , Sidney Annerstedt Kristi , Puoane Thandi , Östenson Claes-Göran , Tomson Goran , Guwatudde David , Daivadanam Meena 
Published: September 2022

IntroductionType 2 diabetes (T2D) and its complications are increasing rapidly. Support for healthy lifestyle and self-management is paramount, but not adequately implemented in health systems. Process evaluations facilitate understanding why and how interventions work through analyzing the interaction between intervention theory, implementation and context. The Self-Management and Reciprocal Learning for Type 2 Diabetes project implemented and evaluated community-based interventions (peer support program; care companion; and link between facility care and community support) for persons at high risk of or having T2D in a rural community in Uganda, an urban township in South Africa, and socioeconomically disadvantaged urban communities in Sweden.Research design and methodsThis paper reports implementation process outcomes across the three sites, guided by the Medical Research Council framework for complex intervention process evaluations. Data were collected through observations of peer support group meetings using a structured guide, and semistructured interviews with project managers, implementers, and participants.ResultsThe countries aligned implementation in accordance with the feasibility and relevance in the local context. In Uganda and Sweden, the implementation focused on peer support; in South Africa, it focused on the care companion part. The community–facility link received the least attention. Continuous capacity building received a lot of attention, but intervention reach, dose delivered, and fidelity varied substantially. Intervention-related and context-related barriers affected participation.ConclusionsIdentification of the key uncertainties and conditions facilitates focus and efficient use of resources in process evaluations, and context relevant findings. The use of an overarching framework allows to collect cross-contextual evidence and flexibility in evaluation design to adapt to the complex nature of the intervention. When designing interventions, it is crucial to consider aspects of the implementing organization or structure, its absorptive capacity, and to thoroughly assess and discuss implementation feasibility, capacity and organizational context with the implementation team and recipients. These recommendations are important for implementation and scale-up of complex interventions.Trial registration numberISRCTN11913581.
3* Evaluation of an Artificial Intelligence (AI) system to augment clinical risk prediction of Trauma Induced Coagulopathy in the pre-hospital setting: a prospective observational study
Authors: Marsden Max , Perkins Zane , Marsh William , Christian Michael , Lyon Richard , Davenport Ross , Tai Nigel 
Published: September 2022

BackgroundThe potential of AI systems to support pre-hospital clinical decision-making in both military and civilian settings is significant. However, whilst such algorithms are increasingly available, far less attention has been paid to understanding the impact of such systems on clinical performance. This study had two aims; first, to compare the performance of expert clinicians against an AI system in a real-world clinical setting and second, to assess the impact of augmenting expert clinical prediction with an AI system.MethodsTwo civilian UK Air Ambulances were selected as surrogate settings relevant to military practice. We performed a prospective study over a six-month period where expert pre-hospital clinicians’ judgement of the risk of Trauma Induced Coagulopathy (TIC) in injured patients was assessed and compared to the performance of an AI system. Two TIC risk predictions were generated for every patient: an AI prediction and a human prediction. Measures of predictive performance included discrimination, calibration, and overall accuracy.ResultsOverall, 51 expert clinicians were enrolled in the study providing 184 patient interactions for analysis. The studied patients had a median age of 31 (range 16, 89), median injury severity score of 17 (IQR 9, 34), 75% were male, and 19% developed TIC.Aim 1: The AI system performed better than clinicians; higher discrimination [AUROC 0.87 (0.79, 0.95) versus 0.83 (0.74, 0.92)] better calibration [0.37 (-0.14, 0.89) versus -1.19 (-1.73, -0.65)] and more accurate [Brier Skill Score 0.34 (0.19, 0.48) versus 0.00 (-0.41, 0.30)].Aim 2: Risk prediction was better in all performance metrics when clinicians were assisted with the AI system [AUROC 0.88 (0.80, 0.95) versus 0.83 (0.74, 0.92)]ConclusionsAI systems can improve human risk prediction in the pre-hospital setting. In the military environment, where austerity and lack of senior clinical expertise may affect outcomes, the benefit of implementing predictive AI should be substantial.(*awarded First Place)
6 Cortical hypoperfusion on intensive care unit admission identifies the development of acute kidney injury. The microshock renal study
Authors: Watchorn Jim , Huang Dean , Bramham Kate , Hutchings Sam 
Published: September 2022

BackgroundUK Defence has a vested interest in shock resuscitation and has limited access to renal replacement therapy. The aetiology of acute kidney injury (AKI) as a component of multiorgan failure is unclear and experimental data is conflicting. Clinical evidence is equally limited and novel methods of assessing the kidney in critical illness are needed. We assessed renal perfusion in septic shock using a novel method of contrast enhanced ultrasound (CEUS).MethodsLongitudinal observational study of 50 patients at four timepoints commenced within 24 hours of admission, two of the groups were defined retrospectively by the occurrence or absence of severe AKI. Contrast ultrasound was administered by infusion with subsequent replenishment kinetics. Renal artery Doppler ultrasonography, transthoracic echocardiography, sublingual video microscopy and biomarkers were measured to determine macro-haemodynamics, the severity of tubular damage and AKI subphenotype. Identical observations were performed in healthy controls, the third group. The primary outcome was the cortical perfusion differences between groups. Secondary outcomes were perfusion differences between subphenotypes, correlation of renal and sublingual microcirculatory perfusion and the differences in renal and global macro-haemodynamics.ResultsPatients with septic shock have reduced cortical perfusion in comparison to healthy controls (average cortical mean transit time (mTT) 13.6s vs 2.2s p<0.0001) and patients who develop severe AKI have reduced perfusion from admission to ICU in comparison to patients without severe AKI (cortical mTT 16.1s vs 7.2s p=0.006). These differences are independent of both cardiac output (6.1l vs 5.7l, p=0.6) and renal artery blood flow (1.56l/min vs 1.81l/min, p=0.4). Biomarker data to identify perfusion abnormalities in AKI subphenotypes are awaited.ConclusionCortical hypoperfusion is detectable on admission to ICU using CEUS and identifies patients who will develop severe AKI. This paves the way for interventional study, individualizing renal resuscitation with vasoactive therapies.
Risk factors for suicide in adults: systematic review and meta-analysis of psychological autopsy studies
Authors: Favril Louis , Yu Rongqin , Uyar Abdo , Sharpe Michael , Fazel Seena 
Published: September 2022

QuestionEffective prevention of suicide requires a comprehensive understanding of risk factors.Study selection and analysisFive databases were systematically searched to identify psychological autopsy studies (published up to February 2022) that reported on risk factors for suicide mortality among adults in the general population. Effect sizes were pooled as odds ratios (ORs) using random-effects models for each risk factor examined in at least three independent samples.FindingsA total of 37 case–control studies from 23 countries were included, providing data on 40 risk factors in 5633 cases and 7101 controls. The magnitude of effect sizes varied substantially both between and within risk factor domains. Clinical factors had the strongest associations with suicide, including any mental disorder (OR=13.1, 95% CI 9.9 to 17.4) and a history of self-harm (OR=10.1, 95% CI 6.6 to 15.6). By comparison, effect sizes were smaller for other domains relating to sociodemographic status, family history, and adverse life events (OR range 2–5).ConclusionsA wide range of predisposing and precipitating factors are associated with suicide among adults in the general population, but with clear differences in their relative strength.PROSPERO registration numberCRD42021232878.
Novel photocatalyst system to deep desulfurization of petroleum model and gas condensate by Box–Behnken design
Authors: Raeisi Ilnaz , Derakhshi Pirouz , Azar Parviz Aberoomand , Tehrani Mohammad Saber 
Published: September 2022

In this research, cobalt (Co)/molybdenum (Mo) and nickel (Ni) doped with titanium dioxide (TiO2) were loaded onto multi-walled carbon nanotubes (MWCNTs). Then, the magnetization catalyst, iron oxide (Fe3O4), was loaded on them, which was used for the deep desulfurization of dibenzothiophene (DBT). These catalysts were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, differential reflectance spectroscopy, and Brunauer–Emmett–Teller, Barrett–Joyner–Halenda, and vibrating sample magnetometer techniques. The photocatalytic activity of these catalysts was experienced under visible light using DBT. The response surface methodology based on the Box–Behnken design was used to evaluate parameters, including catalyst dosage (g), time (min), and concentration of DBT (mg L−1). The highest degradation efficiency under optimal conditions for CoMoNi/TiO2/MWCNTs/Fe3O4catalysts with a catalyst dosage of 0.3 g, a time of 180 min, and a concentration of 50 mg L−1was 99.99%. Optimum conditions were studied for desulfurization of the gas condensate. The highest desulfurization efficiency (90.33%) was obtained by the CoMoNi/TiO2/MWCNTs/Fe3O4catalyst.
Transient Systemic Autophagy Inhibition Is Selectively and Irreversibly Deleterious to Lung Cancer
Authors: Khayati Khoosheh , Bhatt Vrushank , Lan Taijin , Alogaili Fawzi , Wang Wenping , Lopez Enrique , Hu Zhixian Sherrie , Gokhale Samantha , Cassidy Liam , Narita Masashi , Xie Ping , White Eileen , Guo Jessie Yanxiang 
Published: September 2022

Abstract

Autophagy is a conserved catabolic process that maintains cellular homeostasis. Autophagy supports lung tumorigenesis and is a potential therapeutic target in lung cancer. A better understanding of the importance of tumor cell-autonomous versus systemic autophagy in lung cancer could facilitate clinical translation of autophagy inhibition. Here, we exploited inducible expression of Atg5 shRNA to temporally control Atg5 levels and to generate reversible tumor-specific and systemic autophagy loss mouse models of KrasG12D/+;p53−/− (KP) non–small cell lung cancer (NSCLC). Transient suppression of systemic but not tumor Atg5 expression significantly reduced established KP lung tumor growth without damaging normal tissues. In vivo13C isotope tracing and metabolic flux analyses demonstrated that systemic Atg5 knockdown specifically led to reduced glucose and lactate uptake. As a result, carbon flux from glucose and lactate to major metabolic pathways, including the tricarboxylic acid cycle, glycolysis, and serine biosynthesis, was significantly reduced in KP NSCLC following systemic autophagy loss. Furthermore, systemic Atg5 knockdown increased tumor T-cell infiltration, leading to T-cell-mediated tumor killing. Importantly, intermittent transient systemic Atg5 knockdown, which resembles what would occur during autophagy inhibition for cancer therapy, significantly prolonged lifespan of KP lung tumor-bearing mice, resulting in recovery of normal tissues but not tumors. Thus, systemic autophagy supports the growth of established lung tumors by promoting immune evasion and sustaining cancer cell metabolism for energy production and biosynthesis, and the inability of tumors to recover from loss of autophagy provides further proof of concept that inhibition of autophagy is a valid approach to cancer therapy.

Significance:
Transient loss of systemic autophagy causes irreversible damage to tumors by suppressing cancer cell metabolism and promoting antitumor immunity, supporting autophagy inhibition as a rational strategy for treating lung cancer.
See related commentary by Gan, p. 4322
Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers
Authors: Gazinska Patrycja , Milton Charlotte , Iacovacci Jacopo , Ward Joseph , Buus Richard , Alaguthurai Thanussuyah , Graham Rosalind , Akarca Ayse , Lips Esther , Naidoo Kalnisha , Wesseling Jelle , Marafioti Teresa , Cheang Maggie , Gillett Cheryl , Wu Yin , Khan Aadil , Melcher Alan , Salgado Roberto , Dowsett Mitch , Tutt Andrew , Roxanis Ioannis , Haider Syed , Irshad Sheeba 
Published: September 2022

Abstract

Purpose:
To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)–resistant triple-negative breast cancer (TNBC) and ER+HER2– breast cancer disease.

Experimental Design:
Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2–n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2– cases. Bright-field hematoxylin and eosin assessment allowed for tumor-infiltrating lymphocyte (TIL) evaluation in all cases. Multiplexed immunofluorescence was used to identify the abundance and distribution of immune cell subsets. Levels of checkpoints including PD-1/PD-L1 expression were also quantified. Findings were then validated using expression profiling of cancer and immune-related genes. Cytometry by time-of-flight characterized the dynamic changes in circulating immune cells with NAC.

Results:
RCB II/III TNBC and ER+HER2– breast cancer were immunologically “cold” at baseline and end of NAC. Although the distribution of immune cell subsets across subtypes was similar, the mRNA expression profiles were both subtype- and chemotherapy-specific. TNBC RCB II/III disease was enriched with genes related to neutrophil degranulation, and displayed strong interplay across immune and cancer pathways. We observed similarities in the dynamic changes in B-cell biology following NAC irrespective of subtype. However, NAC induced changes in the local and circulating tumor immune microenvironment (TIME) that varied by subtype and response. Specifically, in TNBC residual disease, we observed downregulation of stimulatory (CD40/OX40L) and inhibitory (PD-L1/PD-1) receptor expression and an increase in NK cell populations (especially non-cytolytic, exhausted CD56dimCD16–) within both the local TIME and peripheral white cell populations.

Conclusions:
This study identifies several potential immunologic pathways in residual disease, which may be targeted to benefit high-risk patients.
Treatment Strategies and Mechanisms Associated with the Prevention of NASH-Associated HCC by a Toll-like Receptor 4 Inhibitor
Authors: Kwan Suet-Ying , Slayden Alyssa N. , Coronado Aubrey R. , Marquez Rosamaria C. , Chen Huiqin , Wei Peng , Savage Michelle I. , Vornik Lana A. , Fox Jennifer T. , Sei Shizuko , Liang Dong , Stevenson Heather L. , Wilkerson Gregory K. , Gagea Mihai , Brown Powel H. , Beretta Laura 
Published: September 2022

Abstract

We evaluated the cancer preventive efficacy of TAK-242, an inhibitor of Toll-like receptor 4 (TLR4), in a mouse model of hepatocellular carcinoma (HCC) occurring in the context of nonalcoholic steatohepatitis (NASH). We also assessed the cellular events associated with the preventive treatment efficacy. We tested oral administration of TAK-242, at clinically relevant but toxicity-reducing doses and scheduling, in mice with hepatocyte-specific deletion of Pten (HepPten−). The optimal dose and oral gavage formulation of TAK-242 were determined to be 30 mg/kg in 5% DMSO in 30% 2-hydroxypropyl-β-cyclodextrin. Daily oral administration of 30 mg/kg TAK-242 over 18 weeks was well tolerated and resulted in reduced development of tumors (lesions &gt; 7.5 mm3) in HepPten− mice. This effect was accompanied by reduced macrovesicular steatosis and serum levels of alanine aminotransferase. In addition, 30 mg/kg TAK-242 daily treatment of small preexisting adenomas (lesions &lt; 7.5 mm3) over 18 weeks, significantly reduced their progression to HCC. RNA sequencing identified 220 hepatic genes significantly altered upon TAK-242 treatment, that significantly correlated with tumor burden. Finally, cell deconvolution analysis revealed that TAK-242 treatment resulted in reduced hepatic populations of endothelial cells and myeloid-derived immune cells (Kupffer cells, Siglec-H high dendritic cells, and neutrophilic granule protein high neutrophils), while the proportion of mt-Nd4 high hepatocytes significantly increased, suggesting a decrease in hepatic inflammation and concomitant increase in mitochondrial function and oxidative phosphorylation upon TLR4 inhibition. In conclusion, this study identified treatment strategies and novel molecular and cellular mechanisms associated with the prevention of HCC in the context of NASH that merit further investigations.

Prevention Relevance:
Means to prevent development of HCC or progression of small adenomas to HCC in patients with NASH are urgently needed to reduce the growing mortality due to HCC. We characterized the chemopreventive effect of oral administration of the TLR4 inhibitor TAK-242 in a model of NASH-associated HCC.
Risk of Macrovascular and Microvascular Disease in Diabetes Diagnosed Using Oral Glucose Tolerance Test With and Without Confirmation by Hemoglobin A1c: The Whitehall II Cohort Study
Authors: Tabák Adam G. , Brunner Eric J. , Lindbohm Joni V. , Singh-Manoux Archana , Shipley Martin J. , Sattar Naveed , Kivimäki Mika 
Published: September 2022

Background:
It is unclear whether replacing oral glucose tolerance test (OGTT) with hemoglobin A1c (HbA1c) measurement for diagnosing diabetes is justified. We aimed to assess the proportion of OGTT-diagnosed diabetes cases that can be confirmed by HbA1c and to examine whether individuals with OGTT diagnosis but nondiagnostic HbA1c are at higher risk of macrovascular and microvascular disease.

Methods:

Participants were 5773 men and women from the population-based Whitehall II prospective cohort study in the United Kingdom. New OGTT diabetes cases diagnosed in clinical examinations in 2002 to 2004 and 2007 to 2009 were assessed for HbA1c confirmation (≥6.5%) in these and subsequent clinical examinations in 2012 to 2013 and 2015 to 2016. All participants were followed up for major cardiovascular events through linkage to electronic health records until 2017 and for incident chronic kidney disease (estimated glomerular filtration rate <60 mL·min
−1
·1.73 m
−2
) until the last clinical examination. In analysis of vascular disease risk, new OGTT-diagnosed diabetes cases with and without diagnostic HbA1c and preexisting diabetes cases were compared with diabetes-free participants.

Results:
Of the 378 (59.3%) participants with OGTT-diagnosed diabetes, 224 were confirmed by HbA1c during 4.1 years (SD, 4.1 years) of follow-up. We recorded 942 cardiovascular events over 12.1 years. After adjustment for nonmodifiable risk factors and compared with the 4997 diabetes-free participants, 371 participants with new HbA1c-confirmed diabetes and 405 participants with preexisting diabetes had increased risk of cardiovascular disease (hazard ratio, 1.53 [95% CI, 1.12–2.10] and 1.85 [95% CI, 1.50–2.28], respectively). The corresponding hazard ratios in the analysis of incident chronic kidney disease (487 cases; follow-up, 6.6 years) were 1.69 (95% CI, 1.09–2.62) for 282 participants with new HbA1c-confirmed diabetes and 1.67 (95% CI, 1.22–2.28) for 276 participants with preexisting diabetes. In both analyses, OGTT cases with nondiagnostic HbA1c (n=149 and 107) had a risk (hazard ratio, 0.99–1.07) similar to that of the diabetes-free population.

Conclusions:
More than 40% of OGTT-diagnosed diabetes cases were not confirmed by HbA1c during an extended follow-up. However, because these individuals have a risk of cardiovascular disease and chronic kidney disease similar to that of the diabetes-free population, replacement of OGTT with HbA1c-based diagnosis appears justified.
Stent‐Assisted Coiling Versus Balloon‐Assisted Coiling for the Treatment of Ruptured Wide‐Necked Aneurysms: A 2‐Center Experience
Authors: Vivanco‐Suarez Juan , Wallace Adam N. , Dandapat Sudeepta , Lopez Gloria V. , Mendez‐Ruiz Aldo , Kayan Yasha , Copelan Alexander Z. , Dajles Andres , Zevallos Cynthia B. , Quispe‐Orozco Darko , Mendez‐Ruiz Alan , Galecio‐Castillo Milagros , Samaniego Edgar A. , Farooqui Mudassir , Delgado Josser E. , Ortega‐Gutierrez Santiago 
Published: September 2022

Background
Balloon‐assisted coiling (BAC) and stent‐assisted coiling (SAC) have been established as feasible approaches to manage ruptured wide‐necked intracranial aneurysms. Antiplatelet medications used with SAC theoretically increase risk of thrombotic and hemorrhagic complications. This study aims to evaluate safety and efficacy of SAC versus BAC for acutely ruptured wide‐necked intracranial aneurysms.

Methods
We performed a 2‐center retrospective observational study of consecutive patients treated with SAC or BAC for ruptured wide‐necked intracranial aneurysms from 2015 to 2020. Baseline demographics, comorbidities, and aneurysm characteristics were collected. Primary and secondary efficacy outcomes were radiographic aneurysm occlusion at follow‐up and functional status at 3 months. Safety outcomes included periprocedural hemorrhagic/ischemic complications and symptomatic ventriculostomy tract and cerebrospinal shunt hemorrhage rates. Univariable and multivariable analyses with multiple imputations to account for follow‐up loss were performed.

Results

A total of 112 and 109 patients underwent SAC and BAC, respectively. Median cohort age was 56 years, and 72% were female. Baseline characteristics were similar. Hydrocephalus rate was higher in the SAC group (78% versus 64%;
P
=0.02). Median aneurysm size was 5.1 mm. Anterior circulation aneurysms were most common (81%). Aneurysm and neck size were different, more aneurysms measuring <7 mm (80% versus 67%;
P
=0.02) and larger neck size aneurysms (3.7 versus 3.2 mm;
P
=0.02) were treated with SAC. At first follow‐up, SAC showed higher rates of complete occlusion (61% versus 45%;
P
=0.02) before and after adjusting for confounders. Functional outcome was not different in the multivariable models after adjustment. Coil herniation was higher in the BAC group (8% versus 2%;
P
=0.03). Thromboembolic, hemorrhagic, and ventriculostomy complications were not different. The use of acute antithrombotic therapy was not associated with symptomatic ventriculostomy tract hemorrhage.

Conclusion
Our findings suggest that SAC may be as safe as BAC for the acute management of ruptured wide‐necked intracranial aneurysms without significant risk of ischemic and hemorrhagic complications.