bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pierre Robin Sequence: An Updated Evidence-Based Treatment Proposal
Authors: Gomez Oswaldo J. , Lopez Andrea , Gutierrez Esteban 
Published: May 2024

Background:
The Pierre Robin sequence (PRS) is characterized by the presence of micrognathia, glossoptosis, and respiratory obstruction during the neonatal period, its prompt recognition allows to mitigate the associated morbidity and mortality. A diagnosis and treatment algorithm was previously proposed based on data from the literature to guide therapeutic efforts; therefore, it was proposed to carry out a new search for relevant evidence to update or complement it.

Methods:
A literature review of the subject was conducted in PubMed, Embase, and Cochrane databases, corresponding to the period between November 2016 and September 2021. Using the GRADE methodology, 38 articles from different clinical studies that discussed diagnostic tests or therapeutic approaches, directly or indirectly compared, were selected and evaluated.

Results:
After evaluating and analyzing the selected articles, the new information was incorporated into an updated algorithm according to the most recent evidence found for the diagnosis and comprehensive management of patients with PRS.

Conclusion:
To date, there is no consensus in the literature on the treatment of patients with PRS nor are there multicenter studies comparing different management modalities. The indications to proceed with surgical strategies do not present changes with respect to the previous article. Nutritional monitoring is the main objective, and the study of oral feeding is essential in all scenarios.
A Retrospective Review on the Effects of Nasoalveolar Molding on Infant Weight Gain and Time to Primary Lip Repair in Unilateral and Bilateral Cleft Lip and Palate
Authors: Ndem Idorenyin E. , Kugar Meredith , Caruso Deanna , Duchesneau Emilie , Agala Chris B. , Mehta Nina , Van Aalst John , Wood Jeyhan S. 
Published: May 2024

Background:
In patients with severe cleft deformities, nasoalveolar molding (NAM) can improve long-term lip and nasal symmetry by reducing the size of the cleft, better aligning the alveolus, lip, and nose, and making the primary lip repair more predictable. Despite the increasing number of published studies on modified NAM techniques, the effects of NAM on weight gain and time to primary lip repair remain less studied.

Purpose:
This study aims to evaluate the effect of NAM on feeding, weight gain, growth velocity, and time to primary lip repair in patients with complete unilateral and bilateral cleft lip and palate (BCLP).

Methods:
A retrospective, single-institution review was conducted to identify patients with complete unilateral and BCLP treated between January 2005 and June 2020. The following outcomes were measured: age at the time of lip and palate repairs; weight, height, and BMI on the date of lip repair; and growth velocity. Crude and standardized morbidity ratio-weighted differences in outcome means and 95% confidence intervals were estimated using t tests.

Results:
Seventy-one patients were included in the study, 30 of whom underwent NAM. On average, patients treated with preoperative NAM underwent lip repair later than patients who were not treated with NAM. They also had a greater growth velocity and BMI when compared to their non-NAM counterparts. These differences, however, were not statistically significant.

Conclusion:
This study explores the relationships between the use of NAM and preoperative weight gain, as well as time to lip repair in patients with complete unilateral and BCLP. Additional studies may be needed to better elucidate the effect of NAM on weight gain and the time required for surgical repair of the cleft lip and palate.
Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis
Authors: Mathis Simon , Putzer Gabriel , Gasteiger Lukas , Eschertzhuber Stephan , Schneeberger Stefan , Cardini Benno , Hell Tobias , Martini Judith 
Published: May 2024

Background.
Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements.

Methods.
Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared.

Results.
After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0–1.5] g versus SCS group 2 [0–4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups.

Conclusions.
This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.
Expanding Access to High KDPI Kidney Transplant for Recipients Aged 60 y and Older: Cost Utility and Survival
Authors: Bamforth Ryan J. , Trachtenberg Aaron , Ho Julie , Wiebe Chris , Ferguson Thomas W. , Rigatto Claudio , Forget Evelyn , Dodd Nancy , Tangri Navdeep 
Published: May 2024

Background.
Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease.

Methods.
We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario).

Results.
The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive.

Conclusions.
Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care.
Sex-dependent adipose glucose partitioning by the mitochondrial pyruvate carrier
Authors: Shannon Christopher E , Bakewell Terry , Fourcaudot Marcel J , Ayala Iriscilla , Romero Giovanna , Asmis Mara , Freitas Lima Leandro C , Wallace Martina , Norton Luke 
Published: May 2024

ABSTRACTObjectiveThe mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice.MethodsThe impact of pharmacological and genetic disruption of the MPC on mitochondrial pathways of triglyceride assembly (lipogenesis and glyceroneogenesis) was assessed in 3T3L1 adipocytes and murine adipose explants, combined with analyses of adipose MPC expression in metabolically compromised humans. Whole-body and adipose-specific glucose metabolism were subsequently investigated in male and female mice lacking adipocyte MPC1 (Mpc1AD-/-) and fed either standard chow, high-fat western style, or high-sucrose lipid restricted diets for 24 weeks, using a combination of radiolabeled tracers and GC/MS metabolomics.ResultsTreatment with UK5099 or siMPC1 impaired the synthesis of lipids and glycerol-3-phosphate from pyruvate and blunted triglyceride accumulation in 3T3L1 adipocytes, whilst MPC expression in human adipose tissue was negatively correlated with indices of whole-body and adipose tissue metabolic dysfunction. Mature adipose explants fromMpc1AD-/-mice were intrinsically incapable of incorporating pyruvate into triglycerides.In vivo, MPC deletion restricted the incorporation of circulating glucose into adipose triglycerides, but only in female mice fed a zero fat diet, and this associated with sex-specific reductions in tricarboxylic acid cycle pool sizes and compensatory transcriptional changes in lipogenic and glycerol metabolism pathways. However, whole-body adiposity and metabolic health were preserved inMpc1AD-/-mice regardless of sex, even under conditions of zero dietary fat.ConclusionThese findings highlight the greater capacity for mitochondrially driven triglyceride assembly in adipose from female versus male mice and expose a reliance upon MPC-gated metabolism for glucose partitioning in female adipose under conditions of dietary lipid restriction.
Maximizing photon utilization in spectroscopic single-molecule localization microscopy using symmetrically dispersed dual-wedge prisms
Authors: Yeo Wei-Hong , Brenner Benjamin , Lee Youngseop , Kweon Junghun , Sun Cheng , Zhang Hao F. 
Published: May 2024

AbstractSingle-molecule localization microscopy (SMLM) enables super-resolution imaging on conventional fluorescent microscopes. Spectroscopic SMLM (sSMLM) further allows highly multiplexed super-resolution imaging. We report an easy-to-implement symmetrically dispersed dual-wedge prism (SDDWP)-sSMLM design that maximizes photon utilization. We first symmetrically dispersed photons to the −1stand +1storders in an optical assembly using two identical dual-wedge prisms (DWPs). Then we computationally extracted the fluorophores’ spatial position and spectral characteristics using photons in both the −1stand +1storders. Theoretical analysis and experimental validation showed lateral and spectral precisions of 10.1 nm and 0.3 nm, respectively, representing improvements of 28% and 48% over our previous DWP-based system, where emitted photons are divided separately for spatial and spectral analyses.
Cortical evoked activity is modulated by the sleep state in a ferret model of tinnitus. A case study
Authors: Milinski Linus , Nodal Fernando R. , Emmerson Matthew K.J. , King Andrew J. , Vyazovskiy Vladyslav V. , Bajo Victoria M. 
Published: May 2024

AbstractSubjective tinnitus is a phantom auditory perception in the absence of an actual acoustic stimulus. It affects 15% of the global population and can be associated with disturbed sleep, poor mental health and quality of life. To date, there is no effective treatment for tinnitus. We used adult ferrets exposed to mild noise trauma as an animal model of tinnitus. We assessed the phantom percept using two operant paradigms sensitive to tinnitus, silent gap detection and silence detection, before and up to six months after the mild acoustic trauma. The integrity of the auditory brainstem was assessed over the same period using auditory brainstem response recordings.Following noise overexposure, ferrets developed lasting, frequency–specific impairments in operant behaviour and evoked brainstem activity. To explore the interaction between sleep and tinnitus, in addition to tracking the behavioural markers of noise–induced tinnitus and hearing impairment after noise overexposure, we evaluated sleep–wake architecture and spontaneous and auditory–evoked EEG activity across vigilance states. Behavioural performance and auditory–evoked activity measurements after noise overexposure suggested distinct degrees of tinnitus and hearing impairment between individuals. Animals that developed signs of tinnitus consistently developed sleep impairments, suggesting a link between the emergence of noise–induced tinnitus and sleep disruption. However, neural markers of tinnitus were reduced during sleep, suggesting that sleep may transiently mitigate tinnitus.These results reveal the importance of sleep–wake states in tinnitus and suggest that understanding the neurophysiological link between sleep and tinnitus may provide a new angle for research into the causes of phantom percepts and inform future treatments.
BODY SURFACE GASTRIC MAPPING DELINEATES SPECIFIC PATIENT PHENOTYPES IN ADOLESCENTS WITH FUNCTIONAL DYSPEPSIA AND GASTROPARESIS
Authors: Humphrey Gayl , Keane Celia , Schamberg Gabriel , Benitez Alain , Calder Stefan , Xu Binghong , Sadaka Christian , Andrews Christopher N. , O’Grady Greg , Gharibans Armen , Mousa Hayat 
Published: May 2024

ABSTRACTImportancePersistent upper gastroduodenal symptoms, such as nausea, vomiting, bloating, and abdominal pain, are widespread among pediatric patients. Multiple overlapping symptoms complicate the diagnostic process, necessitating the development of novel gastric function tests with actionable biomarkers. Body Surface Gastric Mapping (BSGM) has emerged as a promising diagnostic tool for gastroduodenal disorders, and this is the first detailed evaluation in adolescents.ObjectiveThis study aimed to assess the utility of BSGM in delineating specific patient phenotypes among adolescents with functional dyspepsia (FD) and gastroparesis in order to guide clinical decision-making.DesignA prospective cross-sectional study recruited adolescents aged 12 to 21 between 2022 and 2024.SettingControls were recruited from New Zealand (controls) and Patients from the Children’s Hospital of Philadelphia, USA.ParticipantsProspectively recruited participants included controls without gastroduodenal symptoms or motility-related medication usage and patients diagnosed with either gastroparesis (delayed gastric emptying test (GET)) or FD according to ROME IV criteria and a normal GET.ProceduresBSGM was performed using a standardized protocol, including simultaneous symptom reporting and the completion of validated symptom, psychometric and physical health questionnaires.Main OutcomeThe primary outcome was to evaluate if BSGM could delineate specific patient phenotypes and provide clinically meaningful distinctions between gastroparesis and FD diagnoses, utilizing BSGM spectral outcome data.ResultsFifty-six subjects were recruited (31 controls, 25 patients); median age 16; 96% of patients were female. Control data showed that adult reference intervals provided an acceptable interpretation framework. Patients with FD (n=10) and gastroparesis (n=15) had common symptoms, mental health, quality of life and functional disability (all p>0.05). Three distinct BSGM phenotypes were identified:BSGM Normal(n=10),BSGM Delay(n=8), andLow Stability/Low Amplitude(n=7), having spectral differences in BMI-Adjusted Amplitude 34.6 vs 39.1 vs 19.9 (p=.01) and Gastric Alimetry Rhythm Index: 0.45 vs 0.45 vs 0.19 (p=.003).BSGM phenotypes demonstrated differences in symptoms (nauseap=0.04), physical health (p=.04) and psychometrics (anxietyp=.03).Conclusion and RelevanceAdolescent patients with FD and gastroparesis have overlapping clinical profiles, making individualized treatment challenging. Conversely, employing BSGM to categorize patients into distinct phenotypes revealed clinically relevant differences, offering potential avenues for individualized therapeutic pathways.
Empowering PET Imaging Reporting with Retrieval-Augmented Large Language Models and Reading Reports Database: A Pilot Single Center Study
Authors: Choi Hongyoon , Lee Dongjoo , Kang Yeon-koo 
Published: May 2024

AbstractIntroductionThe potential of Large Language Models (LLMs) in enhancing a variety of natural language tasks in clinical fields includes medical imaging reporting. This pilot study examines the efficacy of a retrieval-augmented LLM system considering zero-shot learning capability of LLMs, integrated with a comprehensive PET reading reports database, in improving referring previous reports and decision-making.MethodsWe developed a custom LLM framework enhanced with retrieval capabilities, leveraging a database encompassing nine years of PET imaging reports from a single center. The system employs vector space embedding of the reports database to facilitate retrieval based on similarity metrics. Queries prompt the system to retrieve embedded vectors, generating context-based answers and identifying similar cases or differential diagnoses from the historical reports database.ResultsThe system efficiently organized embedded vectors from PET reading reports, showing that imaging reports were accurately clustered within the embedded vector space according to the diagnosis or PET study type. Based on this system, a proof-of-concept chatbot was developed and showed the framework’s potential in referencing reports of previous similar cases and identifying exemplary cases for various purposes. Additionally, it demonstrated the capability to offer differential diagnoses, leveraging the vast database to enhance the completeness and precision of generated reports.ConclusionsThe integration of a retrieval-augmented LLM with a large database of PET imaging reports represents an advancement in medical reporting within nuclear medicine. By providing tailored, data-driven insights, the system not only improves the relevance of PET report generation but also supports enhanced decision-making and educational opportunities. This study underscores the potential of advanced AI tools in transforming medical imaging reporting practices.
Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina
Authors: Kuo Sidney P. , Yu Wan-Qing , Srivastava Prerna , Okawa Haruhisa , Santina Luca Della , Berson David M. , Awatramani Gautam B. , Wong Rachel O.L. , Rieke Fred 
Published: May 2024

AbstractParallel processing is a fundamental organizing principle in the nervous system, and understanding how parallel neural circuits generate distinct outputs from common inputs is a key goal of neuroscience. In the mammalian retina, divergence of cone signals into multiple feed-forward bipolar cell pathways forms the initial basis for parallel retinal circuits dedicated to specific visual functions. Here, we used patch-clamp electrophysiology, electron microscopy and two photon imaging of a fluorescent glutamate sensor to examine how kinetically distinct responses arise in transient versus sustained ON alpha RGCs (ON-T and ON-S RGCs) of the mouse retina. We directly compared the visual response properties of these RGCs with their presynaptic bipolar cell partners, which we identified using 3D electron microscopy reconstruction. Different ON bipolar cell subtypes (type 5i, type 6 and type 7) had indistinguishable light-driven responses whereas extracellular glutamate signals around RGC dendrites and postsynaptic excitatory currents measured in ON-T and ON-S RGCs in response to the identical stimuli used to probe bipolar cells were kinetically distinct. Anatomical examination of the bipolar cell axon terminals presynaptic to ON-T and ON-S RGCs suggests bipolar subtype-specific differences in the size of synaptic ribbon-associated vesicle pools may contribute to transient versus sustained kinetics. Our findings indicate bipolar cell synapses are a primary point of divergence in kinetically distinct visual pathways.
Hemin-induced platelet activation is regulated via ACKR3 chemokine surface receptor - implications for passivation of vulnerable atherosclerotic plaque
Authors: Laspa Zoi , Dicenta-Baunach Valerie , Schaale David , Sigle Manuel , Hochuli Ravi , Castor Tatsiana , Bayrak Alp , Harm Tobias , Mueller Karin Anne Lydia , Pillaiyar Thanigaimalai , Laufer Stefan , Rohlfing Anne-Katrin , Gawaz Meinrad Paul 
Published: May 2024

AbstractIn vulnerable atherosclerotic plaques intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release of hemoglobin and free hemin. Hemin activates platelets and leads to thrombosis. Agonism of the inhibitory platelet receptor ACKR3 inhibits hemin-dependent platelet activation and thrombus formation.To characterize the effect of hemin and ACKR3 agonism on isolated human platelets, multi-color flow cytometry and classical experimental setup such as light transmission aggregometry and a flow chamber assay have been used.Hemin induces platelet aggregation andex vivoplatelet-dependent thrombus formation on immobilized collagen under low shear rate 500 s-1indicating that free hemin is a strong activator for platelet-dependent thrombosis. Recently, we described that ACKR3 is a prominent inhibitory receptor of platelet activation. Specific ACKR3 agonists but not conventional antiplatelet compounds such as COX-1 inhibitor (indomethacin), ADP-receptor blocker (cangrelor), or PAR1 inhibitor (ML161) inhibit both hemin-dependent aggregation and thrombus formation. To further characterize the effect of hemin on platelet subpopulations we established a multi-color flow cytometry assay. We found that hemin induces procoagulant (CD42bpos/ PAC-1neg/ AnnexinVpos), aggregatory (CD42bpos/ PAC-1pos/ AnnexinVneg) and inflammatory (CD42bpos/ CXCR4pos/ACKR3pos/ AnnexinVpos) platelet subpopulations. Treatment with ACKR3 agonists significantly decrease the formation of procoagulant and ACKR3posplatelets in response to hemin.We conclude that hemin is a strong activator for the formation of procoagulant platelets and thrombus formation which is dependent on the function of ACKR3. Activation of ACKR3 through specific agonists may offer a therapeutic strategy to control vulnerability of atherosclerotic plaques in areas of IPH.Graphical abstractIntraplaque hemorrhages (IPH) results in hemolysis and liberation of iron containing heme and its oxidized metabolite hemin. Hemin activates platelets and has strong pro-thrombotic activity. Agonism of the atypical chemokine receptor 3 (ACKR3) inhibits hemin-induced platelet activation.