bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic alerts in acute kidney injury: why does evidence of benefit remain elusive?
Authors: Horne Kerry , Noble Rebecca , Karelia Shivaali , Selby Nicholas M. 
Published: August 2023

Purpose of review
Acute kidney injury (AKI) is a common syndrome characterized by a sudden reduction in kidney function. It is strongly associated with high mortality and longer, more expensive hospital stays. As AKI often presents silently, a lack of recognition can prevent recommended standards of care. Over the last decade or more, electronic alerts (eAlerts) for AKI have been studied and implemented to address this. This review will summarize the major randomized trials in this area.

Recent findings
A number of randomized trials now exist that study the effectiveness of AKI eAlerts in isolation or as part of more complex interventions. Varying results arise from differences in study design, healthcare system in which the eAlert is introduced, nature of alert, supporting interventions, implementation plan, stated aim (prevention or treatment of established AKI) and choice of outcome measures.

Summary
Current randomized trial evidence does not show any benefit of eAlerts on mortality. However, variously reported reductions in AKI incidence, AKI progression and AKI duration support a conclusion that strategies incorporating eAlerts can meaningfully benefit delivery of AKI care. Future work should consider how best eAlerts can be utilised, targeted and implemented.
Monte Carlo simulation of SPECT characterization for 223Ra post-injection scintigraphy
Authors: Saikouk Hind , El Khayati Naïma , Matrane Aboubakr 
Published: August 2023

Objectives

223Ra is a promising α-emitting radionuclide for prostate cancer metastasis palliative treatment. Post-injection scintigraphy is of major importance to verify the concentration of the radiopharmaceutical in the targeted sites. Given the low activity administered to patients, the choice of acquisition parameters, including the collimator type, the energy window’s width and the photopeak energy to be used, is primordial for the image quality. The purpose of our work was to select the SPECT configuration suitable for 223Ra post-injection scintigraphy.

Methods
We conducted simulation studies with a Symbia T6 Siemens SPECT-CT, available in our department. 223Ra photons energy spectra were assessed for low energy high resolution (LEHR), medium energy (ME) and high energy (HE) collimators. Then, depending on the energy window, we calculated the scatter fraction, the sensitivity and the spatial resolution.

Results
Scatter fraction was low for all collimators; however, the contribution of photons that scattered more than twice under the low energy photopeaks was important in the case of LEHR. Sensitivity’s best values were obtained in the case of the LEHR collimator; nevertheless, the spatial resolution was very low for this collimator. The latter was best for ME and HE collimators.

Conclusion
A combination between a good sensitivity, a high spatial resolution and a low scatter fraction has been determined in the case of the ME collimator, followed by HE collimator as an alternative. To increase the image acquisition statistics with ME collimator, we recommend to use simultaneous energy windows: 20% centered at 82 keV, 20% centered at 154 keV and 20% centered at 270 keV.
A Co-Designed Online Education Resource on Gastrostomy Feeding for Parents and Caregivers to Support Clinical Care
Authors: Murphy Nada , Ravikumara Madhur , Butterworth Mary , Glasson Emma , Rennison Catherine , Prevett Bree , Fitzpatrick Jayne , Phillips Wayne , Burton Christel , Downs Jenny ,   the Co-Design Reference Group
Published: August 2023

Objective:
Children with complex needs and severe disability may undergo gastrostomy insertion to support feeding difficulties. Parent education programs are critical components of clinical care pathways but there is little information on parent-reported educational needs. This study describes the collaborative process that yielded a resource to assist parents considering gastrostomy tube placement for their children, and the evaluation of the resource.

Methods:
A qualitative descriptive study was conducted to identify parent needs for gastrostomy education. Based on these data and codesigning with parents with a child with gastrostomy tube, an online resource comprising video and written materials was developed. Twenty parents then evaluated its suitability for parent learning.

Results:
Data describing parent needs were coded into categories which represented the gastrostomy “journey”—Decision Making, Hospital Stay and Living with Gastrostomy. Called Nourish, the gastrostomy training resource comprised 19 videos and 18 accompanying worksheets. Twenty parent caregivers rated it highly for its support for learning, confidence building, and planning.

Conclusion:
The process that created Nourish generated a useful resource for parents considering or managing gastrostomy tube feedings for their child. Positive feedback suggests that this approach could be a valuable adjunct to clinical care.
Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study
Authors: Rogerson Colin M. , Hogan Alexander H. , Waldo Briana , White Benjamin R. , Carroll Christopher L , Shein Steven L. 
Published: August 2023

OBJECTIVES:Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use.DESIGN:Multicenter retrospective cohort study.SETTING:Administrative data from the Pediatric Health Information Systems (PHIS) database.PATIENTS:All inpatients 2–18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5,p< 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS (p= 0.81) nor the percentage of encounters with PICU admission (p= 0.47).CONCLUSIONS:Use of adjunctive therapies for status asthmaticus varies widely among large children’s hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.
Experiences of persons with lower limb amputation after prosthetic rehabilitation in Ghana: A qualitative inquiry
Authors: Dordunu Rebecca , Adjei Charles Ampong , Kyei Josephine Mpomaa , Ani-Amponsah Mary 
Published: August 2023

Background:
Lower limb amputations (LLAs) have long been associated with physical, social, and psychological consequences. Individuals with LLAs have challenges with mobility and often become isolated from their social networks. Disability rehabilitation technologies such as prosthetic devices are used to improve the mobility capabilities of lower limb amputees. To improve clinical outcomes, feedback from the prosthetic users is a key element to consider.

Objectives:
The study sort to explore the experiences of lower-limb prosthetic users after prosthetic rehabilitation in a prosthetic and orthotic rehabilitation center in the Eastern Region of Ghana.

Study design:
This study adopted an exploratory descriptive qualitative study design.

Methods:
A purposive sampling technique and semistructured interview guide was used to interview 17 participants by the first author. The social model of disability underpinned the study. Lower-limb prosthetic users (≥18 years) with unilateral LLA attending outpatient follow-up at a prosthetic and orthotic rehabilitation center were recruited. The interviews were audio recoded, transcribed verbatim, and analyzed using the procedure for thematic content analysis by Braun and Clarke (2013).

Results:
Participants reported injuries and tingling in their residual limb. Internal stigma resulting from negative comments and labeling from the public were reported. Prosthetic users experienced empathy and being treated as weaklings by their family/peers. Participants avoided relationships because of recurrent rejection, embarrassment, fear of sexual abuse, and exploitation. As a coping method, some participants chose to isolate themselves to avoid humiliation and public disgrace. Other coping mechanisms included watching television, listening to music, conversing with others, ignoring criticism, and having faith in God.

Conclusion:
Participants’ narrative in this study gave insight into the varied lived experiences on the individual level, family/peer level, and the coping mechanisms used. Challenges relating to discomfort from the prosthesis, internal stigma, relationship avoidance, and altered sexual life should be given much attention and used in implementing initiatives to improve clinical outcomes.
Diagnostic Yield of Investigations in Symmetric Optic Neuropathy
Authors: Handzic Armin , Xie Jim S. , Margolin Edward A. 
Published: August 2023

Background:
Symmetric optic neuropathy (SON) is commonly seen in neuro-ophthalmic practice and is often discovered incidentally. Although multiple investigations might be performed to discover the underlying cause, they are not always indicated. The aim of this study was to report a clinically reasonable and cost-effective approach to investigating patients with SON.

Methods:
SON was defined as bilateral optic neuropathy with normal and/or symmetrically decreased central visual acuity, absence of relative afferent pupillary defect, presence of symmetric optic disc pallor, symmetric thinning of peripapillary retinal nerve fiber layer on optical coherence tomography, and absence of other identifiable causes of optic neuropathy. Records of all patients diagnosed with SON seen at a tertiary university-affiliated neuro-ophthalmology practice from 2016 to 2022 were reviewed to identify the yield of various investigations. Clinical data from the initial and last follow-up visit were obtained. Subgroup analysis was performed to ascertain whether diagnostic yield is higher in patients with severe visual loss (central acuity worse than 20/40) compared with those with mild visual loss (acuity 20/40 or better).

Results:
One hundred thirty-six patients met inclusion criteria. Testing for OPA1 and OPA2 mutations had the highest diagnostic yield (16.0%), followed by mitochondrial genome sequencing (13.6%), serum vitamin B12 (6.1%), and serum folate (1.6%). MRI brain was performed in 54.4% of patients and had a diagnostic yield of only 5%. Both patients who had abnormal MRI had symptoms of demyelination at presentation. Patients were followed for a mean of 15.0 (SD 21.3) months. The most frequently identified etiologies of SON were Leber hereditary optic neuropathy (8.1%), alcohol/tobacco amblyopia (7.4%), vitamin B12 deficiency (5.9%), and dominant optic atrophy (2.9%). Patients with severe visual impairment were more likely to have a final diagnosis compared with those with milder visual impairment (63.9% vs 12.0%, P < 0.001).

Conclusions:
The diagnostic yield of investigating SON in patients with preserved visual function, normal diet, and absence of other neurological symptoms is very low. It is reasonable to observe patients with SON with mild visual impairment, reserving costly investigations for those with the visual acuity worse than 20/40 or progressive course.
Association between self-reported STI symptoms and stillbirth in sub-Saharan Africa using nationally representative household surveys
Authors: Pulver Skylar , Pinto Casey N. , Ba Djibril M. , Risher Kathryn A. 
Published: August 2023

AbstractStillbirths are a known outcome of untreated sexually transmitted infections (STIs). Sub-Saharan Africa (SSA) shares a disproportionate burden of both stillbirths (2015: 29/1000 births vs 3/1000 births in high income countries globally) and STIs. Nationally representative survey data can inform stillbirth prevention measures in multiple countries in the SSA region, with greater generalizability than clinic-based studies. We assessed the association between any self-reported STI symptoms (STI diagnosis, abnormal genital discharge, genital sore or ulcer) in the last 12 months and stillbirth in the prior five years, among women aged 15-49 years participating in nationally representative Demographic and Health Surveys (DHS) in 19 countries in SSA between 2015-2021 and reporting a pregnancy in the five years prior to interview. We used multivariable logistic regression models adjusting for maternal age, wealth index, education level of mother, cigarette smoking behaviors, health care utilization and country of residence. Among 160,995 SSA women who reported being pregnant at least once between 2011-2021, 18.0% (25,596) reported any STI symptom in the prior year and 1.9% (3,205) reported a stillbirth in the past five years. Women who self-reported STI symptoms in the past year had 1.30 (95% CI 1.16-1.47) times the odds of stillbirth in the prior five years compared to women who did not report STI symptoms. Women 35-49 years old had 1.17 (95% CI 1.04-1.33) times the odds of stillbirth compared to those 15-24 years old. The association found between self-reported STI symptoms and stillbirth highlights the need for increased screening for STI symptoms and subsequent treatment among pregnant women in SSA.
Network state changes in sensory thalamus represent learned outcomes
Authors: Hasegawa Masashi , Huang Ziyan , Gründemann Jan 
Published: August 2023

AbstractThalamic brain areas play an important role in adaptive behaviors. Nevertheless, the population dynamics of thalamic relays during learning across sensory modalities remain mostly unknown. Using a cross-modal sensory reversal learning paradigm combined with deep brain two-photon calcium imaging of large populations of auditory thalamus (MGB) neurons, we identified that MGB neurons are biased towards reward predictors independent of modality. Additionally, functional classes of MGB neurons aligned with distinct task periods and behavioral outcomes, both dependent and independent of sensory modality. During non-sensory delay periods, MGB ensembles developed coherent neuronal representation as well as distinct co-activity network states reflecting predicted task outcome. These results demonstrate flexible cross-modal ensemble coding in auditory thalamus during adaptive learning and highlight its importance in brain-wide cross-modal computations during complex behavior.SummaryDeep brain imaging reveals flexible network states of sensory thalamus predicting task outcome in mice.
D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance
Authors: Kula Bartosz , Antal Botond , Weistuch Corey , Gackière Florian , Barre Alexander , Velado Victor , Hubbard Jeffrey M , Kukley Maria , Mujica-Parodi Lilianne R , Smith Nathan A 
Published: August 2023

1.AbstractThe brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-ꞵ-hydroxybutyrate (D-ꞵHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ꞵHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential (AP) properties, while D-ꞵHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.2.Significance statementThis study investigates the impact of acute insulin resistance on the functionality of the hippocampal circuit and the potential protective effects of ketone body supplementation. By inhibiting GLUT4 receptors to induce acute insulin resistance, we reveal several detrimental changes caused by impaired neuronal glucose uptake. These changes include impairments in synaptic activity, axonal conduction, and neuronal firing properties. The study further examines the distinctive effects of acute insulin resistance and the rescue agent D-βHb on synaptic activity, long-term potentiation, axonal conduction, synchronization, and neuronal firing. By shedding light on neuronal responses during insulin resistance, this investigation advances our understanding of neurological disorders associated with hypometabolism and highlights the potential therapeutic value of D-βHb.
The basement membrane regulates the cellular localization and the cytoplasmic interactome of Yes-Associated Protein (YAP) in mammary epithelial cells
Authors: Manucci Antonio Carlos , Fiore Ana Paula Zen Petisco , Genesi Giovani Luiz , Bruni-Cardoso Alexandre 
Published: August 2023

AbstractThe Hippo pathway, a signaling cascade involved in the regulation of organ size and several other processes, acts as a conduit between ECM cues and cellular responses. We asked whether the basement membrane (BM), a specialized ECM component known to induce quiescence and differentiation in mammary epithelial cells, would regulate the localization, activity and interactome of YAP, a Hippo pathway effector. To address this question, we used a broad range of experimental approaches, including 2D and 3D cultures of both mouse and human mammary epithelial cells, as well as the developing mouse mammary gland. In contrast to malignant cells, non-tumoral cells cultured with a reconstituted BM (rBM) displayed higher concentrations of YAP in the cytoplasm. Incidentally, when in the nucleus of rBM-treated cells, YAP resided preferentially at the nuclear periphery. In agreement with our cell culture experiments, YAP exhibited cytoplasmic predominance in ductal cells of developing mammary epithelia, where a denser BM is found. Conversely, terminal end bud (TEB) cells with a thinner BM displayed higher nucleus-to-cytoplasm ratios of YAP. Bioinformatic analysis revealed that genes regulated by YAP were overrepresented in the transcriptomes of microdissected TEBs. Consistently, mouse epithelial cells exposed to the rBM expressed lower levels of YAP-regulated genes, although the protein level of YAP and Hippo components were slightly altered by the treatment. Mass spectrometry analysis identified a differential set of proteins interacting with YAP in cytoplasmic fractions of mouse epithelial cells in the absence or presence of rBM. In untreated cells, YAP interactants were enriched in processes related to ubiquitin-mediated proteolysis, whereas in cells exposed to rBM YAP interactants were mainly key proteins related to amino acid, amino sugar and carbohydrate metabolism. Collectively, our multifaceted approach unraveled that the BM induces YAP translocation or retention in the cytoplasm of non-tumoral epithelial cells and that in the cytoplasm YAP seems to undertake novel functions in metabolic pathways.
Redefining development inStreptomycesbacteria: integrating exploration into the classical sporulating life cycle
Authors: Shepherdson Evan M.F. , Elliot Marie A. 
Published: August 2023

ABSTRACTTwo growth modes have been described for the filamentousStreptomycesbacteria. Their classic developmental life cycle culminates in the formation of dormant spores, where movement to new environments is mediated through spore dispersal. In contrast, exploratory growth proceeds as a rapidly expanding vegetative mycelium that leads to extensive surface colonization and is associated with the release of volatile compounds that promote alkalinization (and reduced iron bioavailability) of its surrounding environment. Here we report that exploratory growth can proceed in tandem with classic sporulating development in response to specific nutritional cues. Sporulating exploration is not accompanied by a rise in environmental pH but has the same iron acquisition requirements as conventional exploration. We found that mutants that were defective in their ability to sporulate were unaffected in exploration, but mutants undergoing precocious sporulation were compromised in their exploratory growth and this appeared to be mediated through premature activation of the developmental regulator WhiI. Cell envelope integrity was also found to be critical for exploration, as mutations in the cell envelope stress-responsive extracytoplasmic function sigma factor SigE led to a failure to explore robustly under all exploration-promoting conditions. Finally, in expanding the known exploration-promoting conditions, we discovered that the model speciesStreptomyces lividansexhibited exploration capabilities, supporting the proposal that exploration is broadly conserved throughout the streptomycetes.SIGNIFICANCEStreptomycesbacteria have evolved diverse developmental and metabolic strategies to thrive in dynamic environmental niches. Here, we report the amalgamation of previously disparate developmental pathways, showing that colony expansion via exploration can proceed in tandem with colony sporulation. This developmental integration extends beyond phenotype to include shared genetic elements, with sporulation-specific repressors being required for successful exploration. Comparing this new exploration mode with previously identified strategies has revealed key differences (e.g. no need for environmental alkalinization), and simultaneously allowed us to define unifying requirements forStreptomycesexploration. The ‘reproductive exploration’ phenomenon reported here represents a unique bet-hedging strategy, with theStreptomycescolony engaging in an aggressive colonization strategy while transporting a protected genetic repository.