Search

Purpose: To assess the utility of [18F]fluoroethyl-L-tyrosine PET co-registered with magnetic resonance imaging ([18F]FET-PET/MRICR) in patients with difficult-to-localize prolactinoma to inform clinical decision-making and (surgical) treatment planning. Methods: Retrospective cohort study of 17 consecutive patients with prolactinoma undergoing [18F]FET-PET/MRICR between October 2020 and September 2022 for either (1) additional information in case of difficult-to-visualize remnants after prior transsphenoidal surgery (TSS), or pharmacological treatment, or (2) radiological diagnosis in absence of a (clear) adenoma on diagnostic/post-treatment conventional MRI. Results: [18F]FET-PET/MRICR identified a lesion in 14/17 patients, yet failed to identify active lesions in 2 patients with negative conventional MRI despite prolactin > 7.5 times upper limit of normal. [18F]FET-PET/MRICR results were inconclusive in 1 patient due to diffuse tracer uptake 10 weeks post-surgery. [18F]FET-PET/MRICR was completely concordant with a suspected lesion on conventional MRI in 10/17 patients, and partially concordant in 3/17 patients. New foci were identified in 4/17 patients. The [18F]FET-PET/MRICR conclusions influenced clinical shared decision-making in 15/17 patients, of whom 7 patients underwent TSS and 8 refrained from TSS. One patient underwent TSS despite negative [18F]FET-PET/MRICR, and one patient underwent additional imaging. Intraoperative findings corresponded with [18F]FET-PET/MRICR in 5/8 patients, and immunohistochemistry was positive in 5/8 patients. The treatment goal was achieved in 7/8 patients, and remission was achieved in 5/7 patients in whom total resection was considered feasible. Conclusion: [18F]FET-PET/MRICR can be of added value in the preoperative decision-making process for selected patients with difficult-to-localize prolactinoma (remnants), or patients lacking a substrate on conventional MRI. [ABSTRACT FROM AUTHOR]

Recently, the German Federal Institute for Medicines and Medical Products restricted the use of fosfomycin in transrectal biopsy of the prostate (TRBP). Accordingly, the need for other antibiotic agents for prophylaxis in TRBP is urgent since antibiotic prophylaxis is mandatory in accordance with these guidelines. After the restriction of the use of ciprofloxacin, and before the use of fosfomycin in Germany was falsely allowed, amoxicillin/clavulanic acid was evaluated as an alternative for antibiotic prophylaxis in TRBP. Regarding hospitalization for post-interventional infections, 359 patients at the Department of Urology of the University of Regensburg, at Caritas-St. Josef Medical Center as a single center, underwent TRBP between 2 July 2019 and 30 June 2020. Regarding antibiotic prophylaxis, the post-interventional hospitalization rate due to bacterial complications was relevant. Of the 359 patients, 10 (2.8%) had an infection requiring hospitalization post-TRBP. A total of 349 (97.2%) patients had no infection-related hospitalization. This corresponds to an incidence rate of only 2.8%. Referring to the previous infection rates under the now obsolete ciprofloxacin, amoxicillin/clavulanic acid can show a similar, if not tendentially even lower, risk of infection, and so this substance can be an alternative for antibiotic prophylaxis in TRBP. Another advantage is that, according to the WHO's AWaRe classification, amoxicillin/clavulanic acid is one of the so-called Access antibiotics. This study is limited as rectal swabs and urine cultures were not performed on every patient before TRBP. [ABSTRACT FROM AUTHOR]

Purpose: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. Materials and Methods: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. Results: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. Conclusion: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation. [ABSTRACT FROM AUTHOR]

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. Also, the context-dependent interaction partners and binding loci of p53 remain largely elusive. To be able to examine these questions, we here developed knock-in mice expressing triple-FLAG-tagged p53 to facilitate p53 pull-down and two p53 response reporter mice, knocking tdTomato and GFP into the Puma/Bbc3 and p21 gene loci, respectively. By crossing these reporter mice into a p53-deficient background, we show that the new reporters reliably inform on p53-dependent and p53-independent initiation of both apoptotic or cell cycle arrest/senescence programs, respectively, in vitro and in vivo. Synopsis: The respective contribution of tumour suppressor p53-activated cellular response pathways to prevention of tumour development remains debated. This resource introduces three novel mouse strains for studying p53's interaction biochemistry and for assessing its contribution to cell cycle arrest and apoptosis in vitro and in vivo. Knock-in mice expressing N-terminally triple-FLAG tagged p53 facilitate identification of p53-interacting proteins and of genomic p53 binding sites. Knock-in mice expressing a p21-IRES-GFP reporter allow in situ imaging of p21-initiated cell cycle arrest and cell senescence in response to p53-dependent and p53-independent stimuli. Knock-in mice expressing a Puma-tdTomato allow in situ imaging of PUMA-initiated apoptotic programs activated in response to p53-dependent and p53-independent stimuli. Novel p53 knock-in and p53 target gene mouse strains enable interaction proteomics, DNA binding studies, as well as the imaging of p53 contributions to cell cycle arrest and apoptosis in situ. [ABSTRACT FROM AUTHOR]

Background Endoscopic transmural drainage (ETD) using double-pigtail stents (DPSs) is a well-established treatment for walled-off pancreatic necrosis (WON). This study aimed to compare outcomes in patients undergoing ETD with DPSs left indwelling versus those where stents were removed or migrated. Methods This retrospective multicenter cohort study included patients with WON who underwent ETD using DPSs between July 2001 and December 2019. The primary outcome was recurrence of a pancreatic fluid collection (PFC). Secondary outcomes were long-term complications and recurrence-associated factors. Competing risk regression analysis considered DPS removal or migration as time-varying covariates. Results Among 320 patients (median age 58; 36% women), DPSs were removed in 153 (47.8%), migrated spontaneously in 27 (8.4%), and remained indwelling in 140 (43.8%). PFC recurrence was observed in 57 patients (17.8%): after removal (n = 39; 25.5%); after migration (n = 4; 14.8%); in patients with indwelling DPSs (n = 14; 10.0%). In 25 patients (7.8%), drainage of recurrent PFC was indicated. Risk factors for recurrence were DPS removal or migration (hazard ratio [HR] 3.45, 95%CI 1.37–8.70) and presence of a disconnected pancreatic duct (HR 5.08, 95%CI 1.84–14.0). Conclusions Among patients who undergo ETD of WON, leaving DPSs in situ seems to lower the risk of recurrent fluid collections, without any long-term DPS-related complications. These results suggest that DPSs should not be routinely removed and can be safely left indwelling indefinitely. [ABSTRACT FROM AUTHOR]

Recurrent cystitis in women represents an everyday challenge; however, little to no data regarding this population are available. This study aimed to evaluate this collective with respect to a rational calculated antibiotic therapy. Urine cultures and antibiograms from a urological office were retrospectively evaluated from patient data collected between January 2017 and June 2019. The evaluation was conducted using SPSS ©. In total, 84 female patients, who were aged between 18 and 87 years old (median 60 years), suffered from recurrent cystitis. Escherichia coli was found in 53.9% of cases, Staphylococcus aureus and enterococci were each found in 6.7%, and Proteus spp. and Streptococcus agalactiae were each found in 5.6%. The resistance levels to ciprofloxacin (CIP), trimethoprim–sulfamethoxazole (TRS), nitrofurantoin (NIT), and nitroxoline (NOX) were 18.2%, 30.7%, 16.1%, and 12.5% in the tested cases, respectively. Regarding E. coli, resistance to CIP, TRS, and NIT was found in 17.8%, 25%, and 4.2% of the tested cases, and no resistance to NOX was found. The resistance level to CIP was in a tolerable range of <20% in the overall cohort and the E. coli subgroup. More than a quarter of the bacteria were resistant to TRS. The low resistance rates for NIT and NOX are remarkable, promoting the use of these substances if they are not yet used. [ABSTRACT FROM AUTHOR]

Climate change increases the need to understand the effect of predicted future temperature and nutrient scenarios on marine phytoplankton. However, experimental studies addressing the effects of both drivers use a variety of design approaches regarding their temperature change rate and nutrient supply regimes. This study combines a systematic literature map to identify the existing bias in the experimental design of studies evaluating the phytoplankton response to temperature change, with a laboratory experiment. The experiment was designed to quantify how different temperature levels (6°C, 12°C, and 18°C), temperature regimes (abrupt vs. gradual increase), timings of nutrient addition (before or after the temperature change) and nutrient regimes (limiting vs. balanced) alter the growth and stoichiometry of a natural marine phytoplankton community. The systematic map revealed three key biases in marine global change experiments: (1) 66% of the studies do not explicitly describe the experimental temperature change or nutrient regime, (2) 84% applied an abrupt temperature exposure, and (3) only 15% experimentally manipulated the nutrient regime. Our experiment demonstrated that the identified biases in experimental design toward abrupt temperature exposure induced a short‐term growth overshoot compared to gradually increasing temperatures. Additionally, the timing of nutrient availability strongly modulated the direction of the temperature effect and strength of growth enhancement along balanced N : P supply ratios. Our study stresses that the rate of temperature change, the timing of nutrient addition and the N : P supply ratio should be considered in experimental planning to produce ecologically relevant results as different setups lead to contrasting directions of outcome. [ABSTRACT FROM AUTHOR]

Objective: To report our experience with 18F‐fluoro‐ethyl‐tyrosine (FET) positron emission tomography‐computed tomography (PET‐CT) co‐registered with magnetic resonance imaging (MRI) (FET‐PET/MRICR) in the care trajectory for persistent acromegaly. Design: Prospective case series. Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. Measurements: FET‐PET/MRICR was used to support decision‐making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. Results: FET‐PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET‐PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET‐PET/MRICR identified suggestive new foci in four other patients. Surgical re‐exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET‐PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF‐1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET‐PET/MRICR is a new tracer to provide additional information to aid decision‐making by the multidisciplinary pituitary team. [ABSTRACT FROM AUTHOR]

Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals. [ABSTRACT FROM AUTHOR]

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though Candida albicans is the main causative agent, other Candida species, such as Candida tropicalis, are relevant etiological agents of candidiasis and candidemia. Compared with C. albicans, there is currently limited information about C. tropicalis' biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains O-linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where O-linked mannans and other wall components are affected. Here, we generated a C. tropicalis pmt2∆ null mutant, which was affected in the first step of the O-linked mannosylation pathway. The null mutant was viable, contrasting with C. albicans where this gene is essential. The phenotypical characterization showed that O-linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in Galleria mellonella larvae. Thus, O-linked mannans are minor components of the cell wall that are involved in different aspects of C. tropicalis' biology. [ABSTRACT FROM AUTHOR]

Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post‐ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty‐two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher. [ABSTRACT FROM AUTHOR]

The dystrophin protein has well‐characterized roles in force transmission and maintaining membrane integrity during muscle contraction. Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine‐rich region of dystrophin enhances binding between dystrophin and β‐dystroglycan, and mimicking phosphorylation at this site by site‐directed mutagenesis attenuates myotube atrophy in vitro. To determine whether dystrophin phosphorylation can attenuate muscle wasting in vivo, CRISPR‐Cas9 was used to generate mice with whole body mutations of S3059 to either alanine (DmdS3059A) or glutamate (DmdS3059E), to mimic a loss of, or constitutive phosphorylation of S3059, on all endogenous dystrophin isoforms, respectively. Sciatic nerve transection was performed on these mice to determine whether phosphorylation of dystrophin S3059 could attenuate denervation atrophy. At 14 days post denervation, atrophy of tibialis anterior (TA) but not gastrocnemius or soleus muscles, was partially attenuated in DmdS3059E mice relative to WT mice. Attenuation of atrophy was associated with increased expression of β‐dystroglycan in TA muscles of DmdS3059E mice. Dystrophin S3059 phosphorylation can partially attenuate denervation‐induced atrophy, but may have more significant impact in less severe modes of muscle wasting. [ABSTRACT FROM AUTHOR]

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71–0.96), a sensitivity of 0.98 (95% CI 0.75–1.00) and a specificity of 0.73 (95% CI 0.58–0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65–0.94), ECG branch: 0.54 (95% CI 0.26–0.82), Clinical branch: 0.64 (95% CI 0.39–0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation. [ABSTRACT FROM AUTHOR]

Attaining Sustainable Development Goal 3 (SDG 3: Health and Well‐Being) faces a dual challenge of diminishing returns of established intervention designs, and a threat to future gains from complex inter‐connected global health challenges like antimicrobial resistance and global biodiversity loss. The growing movement of context‐sensitive approaches could help realise yet untapped potential for intervention designs, but contemporary global health policy and research still remain dominated by a model of individual market style choices. This paper therefore aims to support the development of global health planning processes that are more grounded and integrative across the SDGs. Reiterating calls for disruptive policy change is unlikely to impact the modus operandi of global health policy and research. This paper therefore builds on a logic that already finds widespread and intuitive application in their underlying planning processes: 'the market'. However, it challenges the dominant supply‐and‐demand approach to healthcare markets and redefines them from a strategic marketing perspective. Translated to the interface of populations and health systems, the strategic market is a site for solving problems that are defined by people with multidimensional health needs. This framework offers four guiding questions to define the strategic market and six premises as a simple intellectual starting point and checklist for more grounded and inter‐sectorial action across the SDGs. The analysis of data from one of the largest behavioural survey data sets, covering 6683 villagers across China, India, Lao PDR and Thailand, demonstrates the relevance of the premises empirically. [ABSTRACT FROM AUTHOR]

The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this class of emerging contaminants. In this context, our work focuses on synthesizing a composite material, FexOy/MAF-32, through a streamlined one-pot reaction process, as an adsorbent for diclofenac, an emerging environmental contaminant frequently found in freshwater environments and linked to potential toxicity towards several organisms such as fish and mussels. A thorough characterization was performed to elucidate the structural composition of the composite. The material presents magnetic properties attributed to its superparamagnetic behavior, which facilitates the recovery efficiency of the composite post-diclofenac adsorption. Our study further involves a comparative analysis between the FexOy/MAF-32 and a non-magnetic counterpart, comprised solely of 2-ethylimidazolate zinc polymer. This comparison aims to discern the relative advantages and disadvantages of incorporating magnetic iron oxide nanoparticles in the contaminant removal process facilitated by a coordination polymer. Our findings reveal that even a minimal incorporation of iron oxide nanoparticles substantially enhanced the composite's overall performance in pollutant adsorption. [ABSTRACT FROM AUTHOR]

Joubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability, and a peculiar cerebellar and brainstem malformation, the "molar tooth sign." Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper, we developed an in vitro neuronal differentiation model using patient-derived induced pluripotent stem cells (iPSCs), to evaluate possible neurodevelopmental defects in JS. To this end, iPSCs from four JS patients harboring mutations in distinct JS genes (AHI1, CPLANE1, TMEM67, and CC2D2A) were differentiated alongside healthy control cells to obtain mid-hindbrain precursors and cerebellar granule cells. Differentiation was monitored over 31 days through the detection of lineage-specific marker expression by qRT-PCR, immunofluorescence, and transcriptomics analysis. All JS patient-derived iPSCs, regardless of the mutant gene, showed a similar impairment to differentiate into mid-hindbrain and cerebellar granule cells when compared to healthy controls. In addition, analysis of primary cilium count and morphology showed notable ciliary defects in all differentiating JS patient-derived iPSCs compared to controls. These results confirm that patient-derived iPSCs are an accessible and relevant in vitro model to analyze cellular phenotypes connected to the presence of JS gene mutations in a neuronal context. [ABSTRACT FROM AUTHOR]

Studying past ecosystems from ancient environmental DNA preserved in lake sediments (sedaDNA) is a rapidly expanding field. This research has mainly involved Holocene sediments from lakes in cool climates, with little known about the suitability of sedaDNA to reconstruct substantially older ecosystems in the warm tropics. Here, we report the successful recovery of chloroplast trnL (UAA) sequences (trnL‐P6 loop) from the sedimentary record of Lake Towuti (Sulawesi, Indonesia) to elucidate changes in regional tropical vegetation assemblages during the lake's Late Quaternary paleodepositional history. After the stringent removal of contaminants and sequence artifacts, taxonomic assignment of the remaining genuine trnL‐P6 reads showed that native nitrogen‐fixing legumes, C3 grasses, and shallow wetland vegetation (Alocasia) were most strongly associated with >1‐million‐year‐old (>1 Ma) peats and silts (114–98.8 m composite depth; mcd), which were deposited in a landscape of active river channels, shallow lakes, and peat‐swamps. A statistically significant shift toward partly submerged shoreline vegetation that was likely rooted in anoxic muddy soils (i.e., peatland forest trees and wetland C3 grasses (Oryzaceae) and nutrient‐demanding aquatic herbs (presumably Oenanthe javanica)) occurred at 76 mcd (~0.8 Ma), ~0.2 Ma after the transition into a permanent lake. This wetland vegetation was most strongly associated with diatom ooze (46–37 mcd), thought to be deposited during maximum nutrient availability and primary productivity. Herbs (Brassicaceae), trees/shrubs (Fabaceae and Theaceae), and C3 grasses correlated with inorganic parameters, indicating increased drainage of ultramafic sediments and laterite soils from the lakes' catchment, particularly at times of inferred drying. Downcore variability in trnL‐P6 from tropical forest trees (Toona), shady ground cover herbs (Zingiberaceae), and tree orchids (Luisia) most strongly correlated with sediments of a predominantly felsic signature considered to be originating from the catchment of the Loeha River draining into Lake Towuti during wetter climate conditions. However, the co‐correlation with dry climate‐adapted trees (i.e., Castanopsis or Lithocarpus) plus C4 grasses suggests that increased precipitation seasonality also contributed to the increased drainage of felsic Loeha River sediments. This multiproxy approach shows that despite elevated in situ temperatures, tropical lake sediments potentially comprise long‐term archives of ancient environmental DNA for reconstructing ecosystems, which warrants further exploration. [ABSTRACT FROM AUTHOR]

Background Current duodenoscope reprocessing protocols are insufficient to prevent contamination and require adaptations to prevent endoscopy-associated infections (EAIs). This study aimed to investigate the effect of a new endoscope cleaning brush on the contamination rate of ready-to-use duodenoscopes. Methods This retrospective before-and-after intervention study collected duodenoscope surveillance culture results from March 2018 to June 2022. Contamination was defined as ≥1 colony-forming unit of a microorganism of gut or oral origin (MGO). In December 2020, an endoscope cleaning brush with a sweeper design was introduced as an intervention in the manual cleaning of duodenoscopes. A logistic mixed-effects model was used to study the effects of this intervention. Results Data were collected from 176 culture sets before the new brush's introduction and 81 culture sets afterwards. Pre-introduction, culture sets positive with an MGO comprised 45.5% (95%CI 38.3%–52.8%; 80/176), decreasing to 17.3% (95%CI 10.6%–26.9%; 14/81) after implementation of the new brush. Compared with the former brush, duodenoscopes cleaned with the new brush had lower odds of contamination with MGOs (adjusted odds ratio 0.25, 95%CI 0.11–0.58; P =0.001) Conclusions Use of the new brush in manual cleaning reduced contamination with MGOs and is expected to prevent EAIs. These findings should be confirmed in future prospective randomized studies. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis of the hand can lead to pain, stiffness, and deformation, and thus to functional disability. The purpose of this study was to compare short-term clinical outcomes of 2 silicone proximal interphalangeal (PIP) joint implants, NeuFlex and Integra, in patients with primary osteoarthritis. Methods: We included 72 PIP joints, of which 40 were replaced by a NeuFlex implant and 32 by an Integra implant. The average follow-up was 12 months for the Integra group and 16 months for the NeuFlex group. Results: There was no change in active flexion preoperatively and postoperatively. Extension lag and Disabilities of the Arm, Shoulder, and Hand score decreased substantially in both groups, whereas grip strength and Patient-Specific Functional Scale (PSFS) score increased. All patients were satisfied. Between groups, there was a significant difference in the PSFS score, in favor of the Integra group. Conclusions: Both implants have excellent results, but more research is needed with more patients to prevent bias and to determine the long-term outcome of these implants. [ABSTRACT FROM AUTHOR]

Among the technologies for the recovery of energy from waste, in particular residual municipal solid waste (rMSW), combustion is the most widely used thermo-chemical treatment process associated with thermal and electric power production by a steam cycle, named, shortly, Waste to Energy (WtE). Today, more than 500 WtE plants in the EU, about 400 in China and 76 in the USA are in operation, based on efficient technologies and advanced air pollution control systems. Energy recovery can be accomplished also by means of gasification; however, the presence of impurities together with the atmospheric pressure, at which syngas is normally produced, impose the feeding of syngas to a conventional steam cycle, leading to generally lower performances than WtE. The energy recovered by WtE offsets traditional energy sources such as fossil fuels and related emissions, providing savings in term of climate change. However, the savings obtainable by replacing electricity and/or heat will diminish as the energy systems will hopefully become increasingly renewable. Over this medium–long-term horizon, one possibility is to capture the CO2 from WtE flue gases and to store/use it. From the life cycle assessment perspective, it has been calculated that the introduction of CO2 capture and storage in WtE, despite energy penalties, is able to reduce the impact on climate change. The alternative approach, proposed to contain the emissions of greenhouse gases in the thermal treatment of waste, is using the carbon contained in it to produce commonly used chemical compounds (waste to chemicals). The benefits, in terms of reductions of greenhouse gases, are expected from the possibility of obtaining chemicals that can replace their analogue normally produced from fossil sources. To date, only one WtC demonstration plant is operating by being fed by rMSW-derived waste, and some similar initiatives are planned, but still adequate assurances in terms of robust knowledge of the involved complex processes, above all, if applied to highly inhomogeneous feed streams such as those obtained from rMSW, are not available. Once the several initiatives come to completion, it will enable waste management professionals to assess performance and to begin to consider such a facility in their planning. [ABSTRACT FROM AUTHOR]

In 2016, IODP‐ICDP Expedition 364 recovered an 829‐meter‐long core within the peak ring of the Chicxulub impact crater (Yucatán, Mexico), allowing us to investigate the post‐impact recovery of the heat‐sterilized deep continental microbial biosphere at the impact site. We recently reported increased cell biomass in the impact suevite, which was deposited within the first few hours of the Cenozoic, and that the overall microbial communities differed significantly between the suevite and the other main core lithologies (i.e., the granitic basement and the overlying Early Eocene marine sediments; Cockell et al., 2021). However, only seven rock intervals were previously analyzed from the geologically heterogenic and impact‐deformed 587‐m‐long granitic core section below the suevite interval. Here, we used 16S rRNA gene profiling to study the microbial community composition in 45 intervals including (a) 31 impact‐shocked granites, (b) 7 non‐granitic rocks (i.e., consisting of suevite and impact melt rocks intercalated into the granites during crater formation and strongly serpentinized pre‐impact sub‐volcanic, ultramafic basanite/dolerite), and (c) 7 cross‐cut mineral veins of anhydride and silica. Most recovered microbial taxa resemble those found in hydrothermal systems. Spearman correlation analysis confirmed that the borehole temperature, which gradually increased from 47 to 69°C with core depth, significantly shaped a subset of the vertically stratified modern microbial community composition in the granitic basement rocks. However, bacterial communities differed significantly between the impoverished shattered granites and nutrient‐enriched non‐granite rocks, even though both lithologies were at similar depths and temperatures. Furthermore, Spearman analysis revealed a strong correlation between the microbial communities and bioavailable chemical compounds and suggests the presence of chemolithoautotrophs, which most likely still play an active role in metal and sulfur cycling. These results indicate that post‐impact microbial niche separation has also occurred in the granitic basement lithologies, as previously shown for the newly formed lithologies. Moreover, our data suggest that the impact‐induced geochemical boundaries continue to shape the modern‐day deep biosphere in the granitic basement underlying the Chicxulub crater. [ABSTRACT FROM AUTHOR]

Background: The dynamics of Staphylococcus aureus in patients and the hospital environment are relatively unknown. We studied these dynamics in a tertiary care hospital in the Netherlands. Methods: Nasal samples were taken from adult patients at admission and discharge. Isolates cultured from clinical samples taken before and during hospitalization from these patients were included. Environmental samples of patient rooms were taken over a three-year period. Finally, isolates from clinical samples from patients with an epidemiological link to S. aureus positive rooms were included. Staphylococcal protein A (spa) typing was performed. Results: Nasal samples were taken from 673 patients. One hundred eighteen (17.5%) were positive at admission and discharge, 15 (2.2%) patients acquired S. aureus during hospitalization. Nineteen patients had a positive clinical sample during hospitalization, 15.9% of the S. aureus were considered as from an exogenous source. One hundred and forty (2.8%) environmental samples were S. aureus positive. No persistent contamination of surfaces was observed. Isolates were highly diverse: spa typing was performed for 893 isolates, identifying 278 different spa types, 161 of these spa types were observed only once. Conclusion: Limited transmission could be identified between patients and the hospital environment, and from patient-to-patient. Exogenous acquisition was assumed to occur in 15% of clinical samples. Environmental contamination was infrequent, temporarily, and coincided with the strain from the patient admitted to the room at that time. MRSA was rare and not found in the environment. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to assess prevalence and prognostic implications of pre-existing peripheral artery disease (PAD) in patients infected by the SARS-CoV-2 by means of a systematic review and meta-analysis. Material and methods: We searched MEDLINE and Scopus to locate all the articles published up to 10 December 2021, reporting data on pre-existing PAD among COVID-19 survivors (S) and non survivors (NS). The pooled prevalence of pre-existing PAD in COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel–Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. Results: Eight investigations, enrolling 13,776 COVID-19 patients (mean age: 67.1 years, 3.863 males), met the inclusion criteria and were included in the final analysis. The pooled prevalence of pre-existing PAD was 5.7% of cases (95% CI: 3.8–8.4%, p < 0.0001), with high heterogeneity (I2 = 84.5%), which was directly correlated with age (p < 0.0001), previous hypertension (p = 0.003), and dyslipidaemia (p = 0.02) as demonstrated by the meta-regression. Moreover, pre-existing PAD was significantly associated with higher risk of short-term death in patients with SARS-CoV-2 infection (OR: 2.78, 95% CI: 2.37–3.27, p < 0.0001 I2 = 0%); the sensitivity analysis confirmed yielded results. Conclusions: Pre-existing PAD represents a comorbidity in about 1 out of 6 COVID-19 patients, but it is associated with a twofold higher risk of short-term mortality. [ABSTRACT FROM AUTHOR]

Squamous dysplasia is the histological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. We aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country. This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide pathology databank (Palga). Squamous dysplasia was divided in mild-to-moderate dysplasia (mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, carcinoma in situ). ESCC were identified in Palga and the Netherlands Cancer Registry. The primary endpoint was diagnosis of prevalent (≤6 months) and incident (>6 months after squamous dysplasia) ESCC. In total, 873 patients (55% male, aged 68 years SD ± 13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n  = 456), higher-grade dysplasia (n  = 393), and dysplasia not otherwise specified (n  = 24). ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent , 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent , 34 incident ESCC). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7–5.7%) in patients with mild-to-moderate dysplasia and 8.5% (95% CI: 5.9–11.7%) in patients with higher-grade dysplasia. All patients with squamous dysplasia, including those with mild-to-moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa or endoscopic resection of dysplasia should be considered for patients with mild-to-moderate dysplasia in Western countries. KEY MESSAGES What is already known on this topic? Squamous dysplasia is the histological precursor of ESCC and is divided in distinct grades, based on the proportion of the squamous epithelium with histopathological abnormalities. In Western countries, the optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. What this study adds The ESCC risk of patients with squamous dysplasia was increased for all patients with squamous dysplasia in a Western country; 2.1% for patients with mild dysplasia, 5.1% for low-grade dysplasia, and 5.2% for moderate dysplasia. Increasing grades of squamous dysplasia were associated with an increased ESCC risk. How this study might affect research, practice, or policy We recommend that endoscopic follow-up or treatment should be considered in all patients with esophageal squamous dysplasia in Western countries: 1) for patients with mild, low-grade, and moderate dysplasia, endoscopic surveillance with careful inspection with narrow band imaging or dye-based chromoendoscopy of the esophageal mucosa is indicated; and 2) for patients with high-grade dysplasia, severe dysplasia and carcinoma in situ adequate endoscopic staging and in case of suspected neoplasia endoscopic treatment should be performed. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the use of single-use duodenoscopes in endoscopic retrograde cholangiopancreatography (ERCP) procedures. The study found that single-use duodenoscopes have comparable safety profiles and technical performance to reusable duodenoscopes, suggesting they may be a viable alternative to reduce the risk of infections. The study also examined the characteristics of ERCP procedures, including completion time, referral sources, and medications used. Additionally, the article discusses the outcomes of ERCP procedures using single-use duodenoscopes, finding no significant differences in outcomes between expert and less expert endoscopists. The study identified several serious adverse events related to the device or procedure, but rates were similar across different levels of complexity and expertise. The article concludes that while single-use duodenoscopes are a viable option, efforts should be made to minimize adverse events and address the costs and environmental impact of single-use devices. [Extracted from the article]

Background: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). Methods: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. Results: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. Conclusion: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study. [ABSTRACT FROM AUTHOR]

The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis. PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion. This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice. Netherlands Trial Registry (NL8852). Prospectively registered. [ABSTRACT FROM AUTHOR]

A letter to the editor of the journal European Radiology discusses the use of quantitative perfusion cardiovascular magnetic resonance (CMR) to detect obstructive coronary artery disease (CAD). The letter highlights a recent study that evaluated the diagnostic performance of fully automated pixel-wise quantitative CMR to identify hemodynamically significant CAD. The study found that the automated CMR method accurately detected CAD, but the integration of coronary magnetic resonance angiography did not provide significant additive value. The letter raises questions about the study's results and suggests that further clarification is needed. [Extracted from the article]

Severe infections with potentially fatal outcomes are caused by parasites from the genera Trypanosoma and Leishmania (class Kinetoplastea). The diseases affect people of remote areas in the tropics and subtropics with limited access to adequate health care. Besides insufficient diagnostics, treatment options are limited, with tenuous developments in recent years. Therefore, new antitrypanosomal antiinfectives are required to fight these maladies. In the presented approach, new compounds were developed and tested on the target trypanothione synthetase (TryS). This enzyme is crucial to the kinetoplastids' unique trypanothione-based thiol redox metabolism and thus for pathogen survival. Preceding studies have shown that N5-substituted paullones display antitrypanosomal activity as well as TryS inhibition. Herein, this compound class was further examined regarding the structure-activity relationships (SAR). Diverse benzazepinone derivatives were designed and tested in cell-based assays on bloodstream Trypanosoma brucei brucei (T. b. brucei) and intracellular amastigotes of Leishmania infantum (L. infantum) as well as in enzyme-based assays on L. infantum TryS (LiTryS) and T. b. brucei TryS (TbTryS). While an exchange of just the substituent in the 9-position of paullones led to potent inhibitors on LiTryS and T. b. brucei parasites, new compounds lacking the indole moiety showed a total loss of activity in both assays. Conclusively, the indole as part of the paullone structure is pivotal for keeping the TryS inhibitory and antitrypanosomal activity of this substance class. [ABSTRACT FROM AUTHOR]

One of the defining features of acute myeloid leukemia (AML) is an arrest of myeloid differentiation whose molecular determinants are still poorly defined. Pharmacological removal of the differentiation block contributes to the cure of acute promyelocytic leukemia (APL) in the absence of cytotoxic chemotherapy, but this approach has not yet been translated to non‐APL AMLs. Here, by investigating the function of hypoxia‐inducible transcription factors HIF1α and HIF2α, we found that both genes exert oncogenic functions in AML and that HIF2α is a novel regulator of the AML differentiation block. Mechanistically, we found that HIF2α promotes the expression of transcriptional repressors that have been implicated in suppressing AML myeloid differentiation programs. Importantly, we positioned HIF2α under direct transcriptional control by the prodifferentiation agent all‐trans retinoic acid (ATRA) and demonstrated that HIF2α blockade cooperates with ATRA to trigger AML cell differentiation. In conclusion, we propose that HIF2α inhibition may open new therapeutic avenues for AML treatment by licensing blasts maturation and leukemia debulking. Synopsis: Hypoxia‐inducible transcription factor HIF2α contributes to acute myeloid leukemia (AML) pathogenesis by taking part to the molecular network that suppresses differentiation of leukemic blasts along the myeloid lineage. Hypoxia‐inducible factors HIF1α and HIF2α promote leukemia progression in cell and patient‐derived models of established AML.In AML cells, HIF2α regulates a novel gene signature that contains Runx2 and BCL11A and transcriptional repressors implicated in suppressing AML myeloid differentiation programs.HIF2α targeting via gene silencing or pharmacological inhibition triggers a myeloid differentiation program and promotes leukemia debulking.All‐trans retinoid acid induces HIF2α expression via direct activity of RAR proteins.Targeting HIF2α cooperates with ATRA to promote myeloid differentiation. [ABSTRACT FROM AUTHOR]

Programmed cell death pathways play an important role in innate immune responses to infection. Activation of intrinsic apoptosis promotes infected cell clearance; however, comparatively little is known about how this mode of cell death is regulated during infections and whether it can induce inflammation. Here, we identify that the pro‐survival BCL‐2 family member, A1, controls activation of the essential intrinsic apoptotic effectors BAX/BAK in macrophages and monocytes following bacterial lipopolysaccharide (LPS) sensing. We show that, due to its tight transcriptional and post‐translational regulation, A1 acts as a molecular rheostat to regulate BAX/BAK‐dependent apoptosis and the subsequent NLRP3 inflammasome‐dependent and inflammasome‐independent maturation of the inflammatory cytokine IL‐1β. Furthermore, induction of A1 expression in inflammatory monocytes limits cell death modalities and IL‐1β activation triggered by Neisseria gonorrhoeae‐derived outer membrane vesicles (NOMVs). Consequently, A1‐deficient mice exhibit heightened IL‐1β production in response to NOMV injection. These findings reveal that bacteria can induce A1 expression to delay myeloid cell death and inflammatory responses, which has implications for the development of host‐directed antimicrobial therapeutics. Synopsis: Cell death and inflammatory signalling crosstalk is critical for innate immune responses to pathogens. This study identifies the BCL‐2 family member A1 as a temporal regulator of these processes in myeloid cells upon bacterial recognition. LPS‐induced A1 expression in macrophages and monocytes delays apoptosis and NLRP3 inflammasome activation.Monocyte survival upon pathogen sensing is regulated by the short‐lived pro‐survival proteins MCL‐1 and A1.A1‐deficient myeloid cells can engage necroptotic signalling when apoptotic caspase activity is compromised.A1‐deficiency enhances IL‐1β responses to Neisseria gonorrhoeae‐derived outer membrane vesicles (NOMVs). [ABSTRACT FROM AUTHOR]

Gully erosion has been identified as a severe land degradation process with environmental and socio‐economic consequences. Identifying areas susceptible to gully erosion will aid in developing strategies to inhibit future degradation. Various approaches have been implemented to predict and map gully erosion susceptibility but are mostly restricted to small geographical extents because of process limitations. Here, we introduce a novel method that predicts gully erosion susceptibility on a regional/national scale (1.22 million km2) by synthesising literature directives with a statistical approach. Findings from a literature review were used to extract physiographic properties associated with gully erosion that was conditioned to characterise susceptibility by using the Frequency Ratio model. The conditioned physiographic properties were aggregated by a weighted overlay procedure using an aggregation of controlling factors derived from the literature review as a weighting system. The gully susceptibility index (GSI) model was validated against a published gully inventory map (n = 163 019) and randomly generated 1‐km2 tessellation zones from which primary validation data were derived. Although uncertainties within the modelling procedure exist (e.g., gully site distribution, the spatial resolution of input data and determination of gully points), the validation shows that the GSI model is generally robust, identifying areas of contrasting susceptibilities. Furthermore, findings converge with other susceptibility metrics, which have been derived by different methodologies. Because empirical gully erosion research has been conducted worldwide, this model could be applied to regional‐scale gully susceptibility modelling assessments (as a solitary method or combined with primary data) in other parts of the world. Additionally, the GSI model can be adopted to model environmental change scenarios. [ABSTRACT FROM AUTHOR]

Graph Introduction In Western countries, approximately 11 % of patients with head and neck squamous cell carcinoma (HNSCC) develop a second primary tumor (SPT) [1]. Metachronous screening performed 1 year after synchronous screening resulted in the detection of one SPT (1/48; 2.1 %), while metachronous screening alone led to the detection of four SPTs in three patients (3/117; 2.6 %). 1 s b ), 10 patients with HNSCC had already been diagnosed with an esophageal SPT before these patients could be approached for endoscopic screening ( B Table 2 s b , patients 11-20). SPTs detected with endoscopic screening A total of 11 esophageal SPTs were detected in 10 /202 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during 250 screening endoscopies (Table 2, patients 1-10). [Extracted from the article]

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1−/− mice, which when infected with CHIKV or o'nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1−/− and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease. FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o'nyong-nyong infections but not Ross River or mayaro virus infection. [ABSTRACT FROM AUTHOR]

The Belt and Road Initiative (BRI) is among the largest transnational development initiatives globally. In this article, we review the research on the BRI in Myanmar, a developing country that is of considerable geopolitical importance. To date, the BRI literature has made three central contributions: it has captured much of the complexity of BRI projects, filled a notable research gap in BRI studies, and raised awareness of local voices. In addition, two analytically meaningful topics are worth exploring, namely the contested relations (1) between China's Ministry of Foreign Affairs and prospective Chinese BRI investors and (2) between the Myanmar government and local anti-BRI groups. Responding to the current focus of the literature and to advance future research, we recommend that scholars consider the analytical framework of state transformation to disaggregate statehood, account for diverse actors, and explain their contested relations. Because it challenges state-centric frameworks (e.g., realism and Westphalian national sovereignty), the state-transformation model can yield theoretically and empirically stimulating findings. [ABSTRACT FROM AUTHOR]