bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Incidental Detection of Breast Cancer Osteolytic Bone Metastasis Using a 99mTc-TRODAT-1 SPECT Scan
Authors: Kuo Chun-Liang , Chang Yu-Hong , Yang Rong-Hsin 
Published: August 2024

Abstract
This report presents a case of suspected Parkinson disease in a 76-year-old woman with a history of slurred speech, general weakness, unstable gait, and bradykinesia for months. A 99mTc-TRODAT-1 SPECT scan revealed a symmetrically decreased bilateral nigrostriatal system, including bilateral putamen and caudate nuclei. The scintigraphic findings may reflect normal aging or atypical parkinsonism. The bilateral frontal bones and left temporal bone exhibited increased uptake of 99mTc-TRODAT-1, and previous 99mTc-MDP bone scan and CT images were reviewed. Osteolytic lesions at the corresponding site indicated bone metastasis from breast cancer.
Evaluation of Factors Influencing Postoperative Cognitive Dysfunction in Patients After Cranial Tumor Surgery
Authors: Cheng Fang , Lin Hua-Fu , Liang Xiao-Jie , Wu Shu-Yun , Wu Xu-Fang , Tu Wei-Feng 
Published: August 2024

Background:
The authors retrospectively analyzed the perioperative data of 81 patients who underwent cranial tumor surgery to explore the factors influencing POCD in patients after the surgery.

Methods:
The authors evaluated preoperative cognitive dysfunction using the Mini-Mental State Examination (MMSE) score measured. For patients whose cognitive function was normal, the authors retrieved the MMSE score on the seventh day after surgery and compared it to determine whether the patients had POCD. The authors used a univariate logistic regression analysis to analyze the perioperative factors in patients, namely, age, gender, history of underlying diseases, tumor size, peritumoral edema, duration of surgery, blood loss, intraoperative fluid infusion, and type of anesthetic drugs. The authors then performed a multivariate logistic regression analysis for the statistically significant factors.

Results:
The authors found that 23 of 81 patients (28.4%) developed POCD. Univariate logistic analysis showed that a history of diabetes mellitus, peritumoral edema, intraoperative blood loss, and anesthetic drugs were the risk factors for patients developing POCD after cranial tumor surgery. Multivariate logistic regression analysis showed that a history of diabetes mellitus, peritumoral edema, and use of ciprofol as the anesthetic drug were independent risk factors for POCD after cranial tumor surgery.

Conclusions:
A history of diabetes mellitus, the degree of brain tumor edema, and the choice of anesthetic drugs significantly influence the occurrence of POCD in patients after cranial tumor surgery.
MECHANICAL LEFT VENTRICULAR UNLOADING IN CARDIOGENIC SHOCK TREATED WITH VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kotani Yuki , Yamamoto Taihei , Koroki Takatoshi , Yaguchi Takahiko , Nakamura Yuta , Tonai Mayuko , Karumai Toshiyuki , Nardelli Pasquale , Landoni Giovanni , Hayashi Yoshiro 
Published: August 2024

ABSTRACT

Objective: To evaluate if mechanical left ventricular unloading could reduce mortality in patients with cardiogenic shock undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials and propensity score–matched studies published until December 20, 2023. The primary outcome was mortality at the longest follow-up. We used a Mantel-Haenszel random effects meta-analysis and reported the pooled results with a risk ratio (RR) and 95% confidence interval (CI). The review protocol was registered on PROSPERO International prospective register of systematic review (CRD42024498665). Results: We identified two randomized controlled trials and 11 propensity score–matched studies, totaling 9,858 patients. Mechanical left ventricular unloading was significantly associated with reduced mortality at the longest follow-up (RR, 0.89; 95% CI, 0.84–0.94; P = 0.0001; moderate certainty of evidence), which was confirmed in studies using intra-aortic balloon pump. Benefits of mechanical unloading were also observed in terms of successful VA-ECMO weaning (RR, 1.15; 95% CI, 1.02–1.29; P = 0.02; low certainty of evidence) and favorable neurological outcome (two studies; RR, 2.45; 95% CI, 1.62–3.69; P < 0.0001; low certainty of evidence), although we observed an increased incidence of major bleeding (RR, 1.27; 95% CI, 1.02–1.59; P = 0.03; low certainty of evidence) and hemolysis (RR, 1.49; 95% CI, 1.10–2.02; P = 0.01; moderate certainty of evidence). Conclusions: Among adult patients with cardiogenic shock treated with VA-ECMO, mechanical left ventricular unloading was associated with reduced mortality, which was confirmed in studies using intra-aortic balloon pump as an unloading device.
FACS-based detection of extracellular ASC specks from NLRP3 inflammasomes in inflammatory diseases
Authors: Topping Joanne , Lara-Reyna Samuel , Ibbotson Alice , Jarosz-Griffiths Heledd , Chang Leon , Poulter James , Peckham Daniel , McDermott Michael F. , Savic Sinisa 
Published: August 2024

ABSTRACTThe apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is crucial for inflammasome assembly and activation of several inflammasomes, including NLRP3. ASC aggregates are detected in human sera post pyroptotic cell death, but their inflammasome origin remains unclear. This study aimed to develop a method to detect ASC aggregates originating from NLRP3 inflammasomes. Initially, human monocytes, macrophages, and THP-1 ASC reporter cells were employed to validate the detection of ASC/NLRP3-positive events through flow cytometry. The presence of ASC/NLRP3 specks was confirmed in cell supernatants from monocytes and macrophages treated with LPS and nigericin or ATP. Flow cytometry analysis identified double-positive specks in patient sera from inflammatory conditions when compared to healthy controls. Elevated ASC/NLRP3 specks were observed in conditions such as CAPS and Schnitzler’s syndrome. We validated FACS as a reliable method for detecting ASC/NLRP3 specks in human sera, with potential diagnostic and monitoring applications in certain systemic autoinflammatory diseases.
Inequalities in Mental Health: Age-related Trends Across Pandemic Phases in Singapore
Authors: Goh Nicole Shu En , Morgenstern Christian , Wei Yap Alex Jie , Yin Wong Stanford Chun , Subramaniam Mythily , Bin Abdin Edimansyah , Boon Lye David Chien , Tan Kelvin Bryan , Xuan Tan Sharon Hui 
Published: August 2024

AbstractBackgroundIn the sphere of mental health, little population wide-scale research has been done in Asia on the pandemic’s differential impacts on different sociodemographic groups over time.MethodsThis study evaluates symptoms of anxiety and depression within different age groups in Singapore across different pandemic phases. Symptoms of depression and anxiety were measured using the Patient Health Questionnaire-4 (PHQ-4), in which higher scores indicate more symptoms and lower scores indicate less. Cross-sectional data from 34,429 individuals aged 18 years and above in Singapore between 27 April 2020 and 27 September 2021 were analyzed. Multivariable logistic and linear regression were performed on PHQ-4 scores over pandemic phases and by age.FindingsOverall symptoms of depression and anxiety did not vary significantly across pandemic phases in Singapore. However, compared to Circuit Breaker, younger age groups reported higher PHQ-4 scores as restrictions lifted (ages 18-29:beta (β)=0·59, 95% CI [0·22, 0·97]; ages 30-39: β=0·44, 95% CI [0·08, 0·80]), while older adults reported lower scores (ages 50-59: β=-0·45, 95% CI [-0·80, -0·10];ages 60 and above: β=-0·38, 95% CI [-0·73, -0·02]). This was associated with more symptoms of anxiety among younger adults, and less symptoms of depression and anxiety among older adults.InterpretationIn Singapore, psychological responses to pandemic restrictions may be heterogenous across different age groups and across time. The study can inform policymakers’ decisions in distributing mental health resources during a crisis.FundingThe funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Adaptive Deep Brain Stimulation in Parkinson’s Disease: A Delphi Consensus Study
Authors: Guidetti M. , Bocci T. , De Pedro Del Álamo M. , Deuschl G. , Fasano A. , Fernandez R. Martinez , Gasca-Salas C. , Hamani C. , Krauss J.K. , Kühn A. A. , Limousin P. , Little S. , Lozano A.M. , Maiorana N.V. , Marceglia S. , Okun M.S. , Oliveri S. , Ostrem J. L. , Scelzo E. , Schnitzler A. , Starr P.A. , Temel Y. , Timmermann L. , Tinkhauser G. , Visser-Vandewalle V. , Volkmann J. , Priori A. 
Published: August 2024

ABSTRACTImportanceIf history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS.ObservationsWe identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson’s disease patients and for those with motor fluctuations and dyskinesias.Conclusions and RelevanceDespite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.
Conditional Knockout of Striatal Gnal Produces Dystonia-like Motor Phenotypes
Authors: Chambers Nicole E. , Hall Dominic , Barsoum Stephanie , Miller Evan , Curry Tiffany , Kaplan Morgan , Garan Sarah , Gallardo Ignacio , Staab Rick , Nabert Douglas , Hutchinson Kevin , Millett Michael , Moehle Mark S. 
Published: August 2024

AbstractLoss-of-function mutations inGNALhave been linked to an adult-onset, isolated dystonia that is largely indistinguishable from idiopathic dystonia.GNALencodes Gαolf, a heterotrimeric G-protein α subunit with a defined molecular function to increase the production of the second messenger cAMP. Gαolfis abundant in the striatum, and is the only stimulatory G-protein in many cell types of the striatum. Due to the defined molecular signaling pathway and expression pattern of Gαolf, the clear genetic link to dystonia makesGNALan exciting target to understand the pathological mechanisms of not only this genetic dystonia, but also the larger idiopathic disease. To better understandGNAL-linked dystonia, we generated a novel genetic mouse model that allows us to conditionally knock outGnalin a site and time-specific manner. In the current study we used genetic or AAV based approaches to express Cre to knockout striatalGnalin our novelGnal fl/flmodel. We then performed motor behavioral testing andex vivowhole-cell patch clamp electrophysiology of striatal spiny projection neurons to interrogate how loss ofGnalleads to dystonia. Mice with conditional striatal knockout ofGnalshow hindlimb clasping, other dystonia-like postures, less motor coordination, slowness, and torticollis as compared to age-matched controls. Furthermore, striatal spiny projection neurons show increased excitability inGnalknockout animals. These exciting data are the first to report uninduced, overt dystonia in a mouse model ofGNAL-linked dystonia, and directly correlate these with changes in spiny projection neuron electrophysiological properties. Our results show that adult loss ofGnalin the striatum leads to the development of dystonia, through homeostatic, paradoxical increases in spiny projection neuron excitability, and suggest that therapeutic strategies aimed at decreasing this hyperexcitable phenotype may provide symptomatic relief for patients with disease.One Sentence Summary:WhenGnalis knocked out in the striatum of mice we observe overt behavioral symptoms and hyperexcitability in striatal spiny projection neurons.
Deep Learning-powered CT-less Multi-tracer Organ Segmentation from PET Images: A solution for unreliable CT segmentation in PET/CT Imaging
Authors: Salimi Yazdan , Mansouri Zahra , Shiri Isaac , Mainta Ismini , Zaidi Habib 
Published: August 2024

AbstractIntroductionThe common approach for organ segmentation in hybrid imaging relies on co-registered CT (CTAC) images. This method, however, presents several limitations in real clinical workflows where mismatch between PET and CT images are very common. Moreover, low-dose CTAC images have poor quality, thus challenging the segmentation task. Recent advances in CT-less PET imaging further highlight the necessity for an effective PET organ segmentation pipeline that does not rely on CT images. Therefore, the goal of this study was to develop a CT-less multi-tracer PET segmentation framework.MethodsWe collected 2062 PET/CT images from multiple scanners. The patients were injected with either18F-FDG (1487) or68Ga-PSMA (575). PET/CT images with any kind of mismatch between PET and CT images were detected through visual assessment and excluded from our study. Multiple organs were delineated on CT components using previously trained in-house developed nnU-Net models. The segmentation masks were resampled to co-registered PET images and used to train four different deep-learning models using different images as input, including non-corrected PET (PET-NC) and attenuation and scatter-corrected PET (PET-ASC) for18F-FDG (tasks #1 and #2, respectively using 22 organs) and PET-NC and PET-ASC for68Ga tracers (tasks #3 and #4, respectively, using 15 organs). The models’ performance was evaluated in terms of Dice coefficient, Jaccard index, and segment volume difference.ResultsThe average Dice coefficient over all organs was 0.81±0.15, 0.82±0.14, 0.77±0.17, and 0.79±0.16 for tasks #1, #2, #3, and #4, respectively. PET-ASC models outperformed PET-NC models (P-value < 0.05). The highest Dice values were achieved for the brain (0.93 to 0.96 in all four tasks), whereas the lowest values were achieved for small organs, such as the adrenal glands. The trained models showed robust performance on dynamic noisy images as well.ConclusionDeep learning models allow high performance multi-organ segmentation for two popular PET tracers without the use of CT information. These models may tackle the limitations of using CT segmentation in PET/CT image quantification, kinetic modeling, radiomics analysis, dosimetry, or any other tasks that require organ segmentation masks.
Biological Insights from Schizophrenia-associated Loci in Ancestral Populations
Authors: Bigdeli Tim B. , Chatzinakos Chris , Bendl Jaroslav , Barr Peter B. , Venkatesh Sanan , Gorman Bryan R. , Clarence Tereza , Genovese Giulio , Iyegbe Conrad O. , Peterson Roseann E. , Kolokotronis Sergios-Orestis , Burstein David , Meyers Jacquelyn L. , Li Yuli , Rajeevan Nallakkandi , Sayward Frederick , Cheung Kei-Hoi ,   Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS),   Consortium on the Genomics of Schizophrenia (COGS),   Genomic Psychiatry Cohort (GPC) Investigators, DeLisi Lynn E. , Kosten Thomas R. , Zhao Hongyu , Achtyes Eric , Buckley Peter , Malaspina Dolores , Lehrer Douglas , Rapaport Mark H. , Braff David L. , Pato Michele T. , Fanous Ayman H. , Pato Carlos N. , Consortium PsychAD ,   Cooperative Studies Program (CSP) #572,   Million Veteran Program (MVP), Huang Grant D. , Muralidhar Sumitra , Gaziano J. Michael , Pyarajan Saiju , Girdhar Kiran , Lee Donghoon , Hoffman Gabriel E. , Aslan Mihaela , Fullard John F. , Voloudakis Georgios , Harvey Philip D. , Roussos Panos 
Published: August 2024

ABSTRACTLarge-scale genome-wide association studies of schizophrenia have uncovered hundreds of associated loci but with extremely limited representation of African diaspora populations. We surveyed electronic health records of 200,000 individuals of African ancestry in the Million Veteran and All of Us Research Programs, and, coupled with genotype-level data from four case-control studies, realized a combined sample size of 13,012 affected and 54,266 unaffected persons. Three genome-wide significant signals — nearPLXNA4,PMAIP1, andTRPA1— are the first to be independently identified in populations of predominantly African ancestry. Joint analyses of African, European, and East Asian ancestries across 86,981 cases and 303,771 controls, yielded 376 distinct autosomal loci, which were refined to 708 putatively causal variants via multi-ancestry fine-mapping. Utilizing single-cell functional genomic data from human brain tissue and two complementary approaches, transcriptome-wide association studies and enhancer-promoter contact mapping, we identified a consensus set of 94 genes across ancestries and pinpointed the specific cell types in which they act. We identified reproducible associations of schizophrenia polygenic risk scores with schizophrenia diagnoses and a range of other mental and physical health problems. Our study addresses a longstanding gap in the generalizability of research findings for schizophrenia across ancestral populations, underlining shared biological underpinnings of schizophrenia across global populations in the presence of broadly divergent risk allele frequencies.
Naloxone Administration and Survival in Overdoses Involving Opioids and Stimulants: An Analysis of Law Enforcement Data from 63 Pennsylvania Counties
Authors: Cano Manuel , Jones Abenaa , Silverstein Sydney M. , Daniulaityte Raminta , LoVecchio Frank 
Published: August 2024

AbstractBackgroundIn consideration of rising opioid-stimulant deaths in the United States, this study explored rates of naloxone administration and survival in suspected opioid overdoses with, versus without, stimulants co-involved.MethodsThe study analyzed 26,635 suspected opioid-involved overdoses recorded by law enforcement/first-responders in the Pennsylvania Overdose Information Network in 63 Pennsylvania counties, January 2018-July 2024. All measures, including suspected drug involvement, were based on first-responder assessment/report. Relative frequencies and chi-square tests were first used to compare suspected opioid overdoses with, versus without, stimulants (cocaine or methamphetamine) co-involved. Next, mediation analyses tested naloxone administration as a mediator in the association between stimulant co-involvement (in opioid overdoses) and survival.ResultsNaloxone was reportedly administered in 72.2% of the suspected opioid-no-cocaine overdoses, compared to 55.1% of the opioid-cocaine-involved overdoses, and 72.1% of the opioid-no-methamphetamine overdoses vs. 52.4% of the opioid-methamphetamine-involved overdoses. With respect to survival rates, 18.0% of the suspected opioid-no-cocaine overdoses ended in death, compared to 41.3% of the opioid-cocaine overdoses; 18.1% of the opioid-no-methamphetamine overdoses ended in death, versus 42.9% of the opioid-methamphetamine overdoses. In mediation analyses (adjusted for demographics, county, year, and other drug co-involvement), naloxone administration mediated 38.7% (95% Confidence Interval [CI], 31.3%-46.0%) of the association between suspected cocaine co-involvement and survival and 39.2% (95% CI, 31.3%-47.1%) of the association between suspected methamphetamine co-involvement and survival.ConclusionsAmong suspected opioid overdoses recorded in the Pennsylvania Overdose Information Network, stimulant co-involvement was associated with lower naloxone administration and higher fatality, with naloxone partially mediating the association between stimulant co-involvement and death.
Impact of Multiple Episodes of Cytomegalovirus Infection on Patient Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Using a Pre-emptive Monitoring Strategy
Authors: Messina Julia A. , Saullo Jennifer L. , Wolf Steven , Li Yanhong , Tang Helen , Hill Lauren B. , Foster Gena G. , Grant Michael , Thomas Samantha M. , Miller Rachel A. , Alexander Barbara D. , Horwitz Mitchell , Sung Anthony D. 
Published: August 2024

AbstractThe impact of multiple episodes of clinically significant cytomegalovirus infection (csCMVi) on clinical outcomes during pre-emptive CMV monitoring in allogeneic hematopoietic stem cell transplant recipients (HCT) is not well understood.We performed a retrospective cohort study of all consecutive patients undergoing their first allogeneic HCT at Duke between January 1, 2009 and December 31, 2013, during an era of pre-emptive CMV monitoring, prior to widespread use of letermovir prophylaxis. Consensus definitions were utilized for refractory and resistant CMV infection, bacteremia, invasive fungal disease, and renal dysfunction. The Kaplan-Meier method was used to estimate survival.Three hundred eighty-eight adult patients underwent allogeneic HCT during the study time period with 91 patients (23%) having one episode of csCMVi and 79 patients (20%) having ≥ one episode of csCMVi. Risk factors for multiple episodes of csCMVi included having a transplant from a matched unrelated donor, cord blood as HCT source, and graft-versus-host disease prophylaxis with highly T-cell suppressive agents such as alemtuzumab. Patients with multiple episodes tended to develop csCMVi earlier post-transplant and were more likely to have CMV disease and to develop resistant CMV infection. There was no difference in rates of refractory CMV infection, bacteremia, invasive fungal disease, or survival. However, patients with multiple episodes of csCMV had reduced one-year relapse-related mortality compared to patients with one csCMVi episode.
The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development
Authors: Leone M , Kinz N , Eichin F , Obwegs D , Sladky VC , Braun VZ , Rizzotto D , Englmaier L , Manzl C , Moos K , Mergner Julia , Giansanti P , Garcia MN , Marques MM , Jacotot ED , Savko C , Boerries M , Sussman MA , Villunger A 
Published: August 2024

AbstractThe adult mammalian heart is characterized by post-mitotic polyploid cardiomyocytes (CMs). Understanding how CMs regulate cell cycle exit and ploidy can help developing new heart regenerative therapies. Here, we uncover that the PIDDosome, a multi-protein complex activating the endopeptidase Caspase-2, helps to implement a CM-specific differentiation program that limits ploidy during postnatal heart development. DNA content analyses show that PIDDosome-loss causes a cell-autonomous increase in nuclear and cellular CM ploidy. Remarkably, increased ploidy does not affect cardiac structure nor function. PIDDosome-imposed ploidy restriction commences at postnatal day 7 (P7), reaching a plateau on P14. PIDDosome activation requires ANKRD26, targeting PIDD1 to mother centrioles. Opposite to prior observations in liver development, the PIDDosome limits CM polyploidization in a p53-independent manner but reliant onp21/Cdkn1a, a notion supported by nuclear RNA sequencing and genetic deletion experiments. Our results provide new insights how proliferation of polyploid CMs is restricted during postnatal heart development.