bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of hyperoxygenation and targeted temperature management improves functional outcomes of post cardiac arrest syndrome irrespective of causes of arrest in rats
Authors: Li Jingru , Shen Yiming , Wang Jianjie , Chen Bihua , Li Yongqin 
Published: April 2024

Abstract

Background
The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA.

Methods and Results
One hundred and sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: 1) Normoxia-normothermia (NO-NT): ventilated with 21% oxygen under normothermia; 2) Hyperoxia-normothermia (HO-NT): ventilated with 100% oxygen for 3 h under normothermia; 3) Normoxia-hypothermia (NO-HT): ventilated with 21% oxygen for 3 h under hypothermia; 4) Hyperoxia-hypothermia (HO-HT): ventilated with 100% oxygen for 3 h under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed.
For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7 ± 14.9% and 40.3 ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0 ± 5.7% and 28.0 ± 13.3%) were significantly reduced.

Conclusions
The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.
The difficult cholecystectomy: What you need to know
Authors: Seshadri Anupamaa , Peitzman Andrew B. 
Published: April 2024

ABSTRACT
This review discusses the grading of cholecystitis, the optimal timing of cholecystectomy, adopting a culture of safe cholecystectomy, understanding the common error traps that can lead to intraoperative complications, and how to avoid them.
1–28
The Tokyo Guidelines, American Association for the Surgery of Trauma, Nassar, and Parkland scoring systems are discussed. The patient factors, physiologic status, and operative findings that predict a difficult cholecystectomy or conversion from laparoscopic to open cholecystectomy are reviewed. With laparoscopic expertise and patient conditions that are not prohibitive, early laparoscopic cholecystectomy is recommended. This is ideally within 72 hours of admission but supported up to the seventh hospital day. The majority of bile duct injuries are due to misidentification of normal anatomy. Strasberg's four error traps and the zones of danger to avoid during a cholecystectomy are described. The review emphasizes the importance of a true critical view of safety for identification of the anatomy. In up to 15% of operations for acute cholecystitis, a critical view of safety cannot be achieved safely. Recognizing these conditions and changing your operative strategy are mandatory to avoid harm. The principles to follow for a safe cholecystectomy are discussed in detail. The cardinal message of this review is, “under challenging conditions, bile duct injuries can be minimized via either a subtotal cholecystectomy or top-down cholecystectomy if dissection in the hepatocystic triangle is avoided”.
21
The most severe biliary/vascular injuries usually occur after conversion from laparoscopic cholecystectomy. Indications and techniques for bailout procedures including the fenestrating and reconstituting subtotal cholecystectomy are presented. Seven percent to 10% of cholecystectomies for acute cholecystitis currently result in subtotal cholecystectomy. Level of evidence: III
Elevation of Donor-derived Cell-free DNA Before Biopsy-proven Rejection in Kidney Transplant
Authors: Bromberg Jonathan S. , Bunnapradist Suphamai , Samaniego-Picota Milagros , Anand Sanjiv , Stites Erik , Gauthier Philippe , Demko Zachary , Prewett Adam , Armer-Cabral Madeleine , Marshall Kyle , Kaur Navchetan , Bloom Michelle S. , Tabriziani Hossein , Bhorade Sangeeta , Cooper Matthew ,   on behalf of the ProActive Investigators
Published: April 2024

Background.
Standard-of-care biomarkers for renal allograft rejection are lagging indicators, signaling existing organ injury. This precludes early intervention, when immunological cascades leading to rejection are most susceptible. Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment. This analysis was designed to assess this promise using real-world dd-cfDNA testing evidence.

Methods.
This retrospective analysis of the prospective, observational ProActive registry study (NCT04091984) assessed dd-cfDNA and serum creatinine levels before biopsy in 424 patients with ≥1 dd-cfDNA test (n = 1013) in the 6 mo before biopsy.

Results.
Of 4667 enrolled patients, 1631 patients had ≥18 mo of follow-up data, of which 424 had a biopsy and were included in this analysis. Twenty-six biopsies showed antibody-mediated rejection (ABMR), 62 showed T cell–mediated rejection, and 336 showed nonrejection; each from a unique patient. dd-cfDNA fractions were significantly elevated 5 mo before ABMR biopsies, and 2 mo before T cell–mediated rejection biopsies, compared with nonrejection biopsies. In contrast, serum creatinine did not discriminate between rejection and nonrejection in advance, or concurrent with biopsy. Among patients with nonrejection biopsies, estimated glomerular filtration rate was significantly lower in cases with ≥2 increased dd-cfDNA results (≥1%), compared with those with 0 or 1 increased dd-cfDNA result.

Conclusions.
These data indicate that dd-cfDNA is an early indicator of biopsy-proven rejection, especially ABMR, suggesting a greater role for dd-cfDNA in surveillance to identify patients at high risk of ongoing or future rejection, thus requiring closer monitoring, biopsy, or other management changes.
Long-Term Mortality Prediction with Pooled Cohort Equations: Implications for Lipid-Lowering Therapy
Authors: Ma Zhiyuan , Moran Lynn N. , Shirani Jamshid 
Published: April 2024

AbstractBackgroundCurrent guidelines recommend primary prevention statin therapy based on 10-year risk of atherosclerotic cardiovascular disease (ASCVD) assessed by the pooled cohort equations (PCE), while assessing effectiveness through low-density lipoprotein cholesterol levels. It remains uncertain whether 10-year ASCVD risk can accurately predict the mortality impact of lipid-lowering therapy.MethodsA retrospective analysis of National Health and Nutrition Examination Survey (NHANES) (III and 1999-2008) linked to the National Death Index was conducted with propensity score matching. The study included 6647 adults without lipid-lowering therapy and 2484 with lipid-lowering therapy. Cox regression models and C statistic were used to assess the association between 10-year ASCVD risk and mortality.ResultsIn the matched cohort with 4802 individuals with similar ASCVD risks, 10-year risk of ASCVD by PCE was comparable for predicating all-cause mortality at 10 years in the lipid-lowering therapy group (area under curve [AUC], 0.75; 95% CI 0.73-0.77) and without lipid-lowering therapy (0.74; 95% CI 0.71-0.77;P= 0.50). Similarly, PCE was comparable for predicting cardiovascular mortality at 10 years in both groups (AUC, 0.75; 95% CI 0.70-0.79 versus 0.77; 95% CI 0.73-0.80;P= 0.47). Lipid-lowering therapy was significantly associated with reduced all-cause mortality (adjusted hazard ratio [HR], 0.70; 95% CI 0.61-0.82;P< 0.01) and cardiovascular mortality (adjusted HR, 0.65; 95% CI, 0.51-0.83;P< 0.01), particularly in those with a 10-year ASCVD risk of 7.5% or higher.ConclusionsPCE provides comparable predictions of mortality in individuals with and without lipid-lowering therapy. Moreover, individuals on lipid-lowering therapy exhibited lower all-cause and cardiovascular mortality compared to those without lipid-lowering therapy but with a similar 10-year risk of ASCVD. These findings suggest that mortality risk reduction can be assessed by 10-year ASCVD risk estimated by PCE for primary prevention both prior and after treatment.
Tonotopic organization of auditory cortex in awake marmosets revealed by multi-modal wide-field optical imaging
Authors: Song Xindong , Guo Yueqi , Chen Chenggang , Lee Jong Hoon , Wang Xiaoqin 
Published: April 2024

ABSTRACTTonotopic organization of the auditory cortex has been extensively studied in many mammalian species using various methodologies and physiological preparations. Tonotopy mapping in primates, however, is more limited due to constraints such as cortical folding, use of anesthetized subjects, and mapping methodology. Here we applied a combination of through-skull and through-window intrinsic optical signal imaging, wide-field calcium imaging, and neural probe recording techniques in awake marmosets (Callithrix jacchus), a New World monkey with most of its auditory cortex located on a flat brain surface. Coarse tonotopic gradients, including a recently described rostral-temporal (RT) to parabelt gradient, were revealed by the through-skull imaging of intrinsic optical signals and were subsequently validated by single-unit recording. Furthermore, these tonotopic gradients were observed with more details through chronically implanted cranial windows with additional verifications on the experimental design. Moreover, the tonotopy mapped by the intrinsic-signal imaging methods was verified by wide-field calcium imaging in an AAV-GCaMP labeled subject. After these validations and with the further effort to expand the field of view more anteroventrally in both windowed and through-skull subjects, an additional putative tonotopic gradient was observed more rostrally to the area RT, which has not been previously described by the standard model of tonotopic organization of the primate auditory cortex. Together, these results provide the most comprehensive data of tonotopy mapping in awake primate species with unprecedented coverage and details in the rostral proportion and supports a caudorostrally arranged mesoscale organization of at least three repeats of functional gradients in the primate auditory cortex, similar to the ventral stream of primate visual cortex.
Task-specific topology of brain networks supporting working memory and inhibition
Authors: Adamovich Timofey , Ismatullina Victoria , Chipeeva Nadezhda , Zakharov Ilya , Feklicheva Inna , Malykh Sergey 
Published: April 2024

AbstractNetwork neuroscience investigates the brain’s connectome, revealing that cognitive functions are underpinned by dynamic neural networks. This study investigates how distinct cognitive abilities—working memory and inhibition—are supported by unique brain network configurations, which are constructed by estimating whole-brain networks through mutual information. The study involved 195 participants who completed the Sternberg Item Recognition and Flanker tasks while undergoing EEG recording. A mixed-effects linear model analyzed the influence of network metrics on cognitive performance, considering individual differences and task-specific dynamics. Results indicate that working memory and inhibition are associated with different network attributes, with working memory relying on distributed networks and inhibition on more segregated ones. Our analysis suggests that both strong and weak connections contribute to cognitive processes, as weak connections could potentially lead to a more stable and support networks of memory and inhibition. The findings indirectly support the Network Neuroscience Theory of Intelligence, suggesting different functional topology of networks inherent to various cognitive functions. Nevertheless, we propose that understanding individual variations in cognitive abilities requires recognizing both shared and unique processes within the brain’s network dynamics.Author summaryThis study analyzes how working memory and inhibition correspond to distinct neural network patterns by constructing whole-brain networks via mutual information from EEG data of 195 subjects performing cognitive tasks. Findings reveal working memory is supported by distributed connections while inhibition depends on segregated ones. The research underscores the importance of both strong and weak neural connections in cognitive function and supports the notion that cognitive functions emerge from the brain network of distinct topology. Moreover, it highlights the need to account for individual and task-specific variations to fully grasp the diverse network dynamics influencing cognitive abilities.
Resource: A Curated Database of Brain-Related Functional Gene Sets (Brain.GMT)
Authors: Hagenauer Megan H. , Sannah Yusra , Hebda-Bauer Elaine K. , Rhoads Cosette , O’Connor Angela M. , Watson Stanley J. , Akil Huda 
Published: April 2024

AbstractTranscriptional profiling has become a common tool for investigating the nervous system. During analysis, differential expression results are often compared to functional ontology databases, which contain curated gene sets representing well-studied pathways. This dependence can cause neuroscience studies to be interpreted in terms of functional pathways documented in better studied tissues (e.g., liver) and topics (e.g., cancer), and systematically emphasizes well-studied genes, leaving other findings in the obscurity of the brain “ignorome”.To address this issue, we compiled a curated database of918gene sets related to nervous system function, tissue, and cell types (“Brain.GMT”) that can be used within common analysis pipelines (GSEA, limma, edgeR) to interpret results from three species (rat, mouse, human). Brain.GMT includes brain-related gene sets curated from the Molecular Signatures Database (MSigDB) and extracted from public databases (GeneWeaver, Gemma, DropViz, BrainInABlender, HippoSeq) and published studies containing differential expression results.Although Brain.GMT is still undergoing development and currently only represents a fraction of available brain gene sets, “brain ignorome” genes are already better represented than in traditional Gene Ontology databases. Moreover, Brain.GMT substantially improves the quantity and quality of gene sets identified as enriched with differential expression in neuroscience studies, enhancing interpretation.Graphical abstractSpecifications table
Parameter estimation for the oral minimal model and parameter distinctions between obese and non-obese type 2 diabetes
Authors: Aravindakshan Manoja Rajalakshmi , Ghosh Devleena , Mandal Chittaranjan , Venkatesh K V , Sarkar Jit , Chakrabarti Partha , Maity Sujay K 
Published: April 2024

AbstractOral Glucose Tolerance Test (OGTT) is the primary test used to diagnose type 2 diabetes mellitus (T2DM) in a clinical setting. Analysis of OGTT data using the Oral Minimal Model (OMM) along with the rate of appearance of ingested glucose (Ra) is performed to study differences in model parameters for control and T2DM groups. The differentiation of parameters of the model gives insight into the behaviour and physiology of T2DM. The model is also studied to find parameter differences among obese and non-obese T2DM subjects and the sensitive parameters were co-related to the known physiological findings. Sensitivity analysis is performed to understand changes in parameter values with model output and to support the findings, appropriate statistical tests are done. This seems to be the first preliminary application of the OMM with obesity as a distinguishing factor in understanding T2DM from estimated parameters of insulin-glucose model and relating the statistical differences in parameters to diabetes pathophysiology.HighlightsAn established oral minimal model is used for estimation of parameters obese and non-obese type 2 diabetes.This is a novel attempt to use oral minimal model to co-relate the parameters for different diabetic groups using oral glucose tolerance test (OGTT) data.The data of different diabetes groups were utilised for model parameter determination and through statistical tests, distinctions in parameter distribution were identified.It was observed that obese diabetic group are more insulin resistant compared to non-obese diabetic group.
Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner
Authors: Troop Leia D. , Puetzer Jennifer L. 
Published: April 2024

AbstractHierarchical collagen fibers are the primary source of strength in tendons and ligaments, however these fibers do not regenerate after injury or with repair, resulting in limited treatment options. We previously developed a culture system that guides ACL fibroblasts to produce native-sized fibers and fascicles by 6 weeks. These constructs are promising ligament replacements, but further maturation is needed. Mechanical cues are critical for developmentin vivoand in engineered tissues; however, the effect on larger fiber and fascicle formation is largely unknown. Our objective was to investigate whether intermittent cyclic stretch, mimicking rapid muscle activity, drives further maturation in our system to create stronger engineered replacements and to explore whether cyclic loading has differential effects on cells at different degrees of collagen organization to better inform engineered tissue maturation protocols. Constructs were loaded with an established intermittent cyclic loading regime at 5 or 10% strain for up to 6 weeks and compared to static controls. Cyclic loading drove cells to increase hierarchical collagen organization, collagen crimp, and tissue mechanics, ultimately producing constructs that matched or exceeded immature ACL properties. Further, the effect of loading on cells varied depending on degree of organization. Specifically, 10% load drove early improvements in mechanics and composition, while 5% load was more beneficial later in culture, suggesting a cellular threshold response and a shift in mechanotransduction. This study provides new insight into how cyclic loading affects cell-driven hierarchical fiber formation and maturation, which will help to develop better rehabilitation protocols and engineer stronger replacements.
Insulin-like Growth Factor 2 mRNA-binding protein 2 (IGF2BP2) Promotes Castration-Resistant Prostate Cancer Progression by Regulating AR-V7 mRNA Stability
Authors: Saini Taruna , Srivastava Devesh , Raut Rajnikant , Mishra Parul , Misra Ashish 
Published: April 2024

AbstractThe emergence of constitutively active androgen receptor (AR) splice variant AR-V7 poses a formidable challenge in treating prostate cancer, as it lacks the ligand binding region targeted by androgen deprivation therapies such as enzalutamide and abiraterone. AR-V7 is critical for castration-resistant prostate cancer (CRPC) development and progression, however the molecular mechanisms regulating its expression and biological function remain poorly understood. Here, we investigate the role of IGF2BP2 in regulating AR-V7 expression and CRPC progression. We demonstrate that IGF2BP2 silencing leads to downregulation of AR-V7 and its downstream target genes without affecting AR levels. Additionally, IGF2BP2 knockdown also enhances the sensitivity of CRPC cells to enzalutamide while overexpression increases AR-V7 expression and confers increased resistance to enzalutamide. Mechanistically, our experiments demonstrate that IGF2BP2 binds to the intronic splicing enhancer (ISE) region of AR-V7, thereby enhancing its mRNA stability Furthermore, our domain-deletion analysis pinpoints the role of KH3 and KH4 domains of IGF2BP2 in regulating AR-V7 stability and enzalutamide resistance. Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR-V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.
Creative tempo: Spatiotemporal dynamics of the default mode network in improvisational musicians
Authors: Watters Harrison , Fazili Abia , Daley Lauren , Belden Alex , LaGrow TJ , Bolt Taylor , Loui Psyche , Keilholz Shella 
Published: April 2024

AbstractThe intrinsic dynamics of human brain activity display a recurring pattern of anti-correlated activity between the default mode network (DMN), associated with internal processing and mentation, and task positive regions, associated with externally directed attention. In human functional magnetic resonance imaging (fMRI) data, this anti-correlated pattern is detectable on the infraslow timescale (<0.1 Hz) as a quasi-periodic pattern (QPP). While the DMN is implicated in creativity and musicality in traditional time-averaged functional connectivity studies, no one has yet explored how creative training may alter dynamic spatiotemporal patterns involving the DMN such as QPPs. In the present study, we compare the outputs of two QPP detection approaches, sliding window algorithm and complex principal components analysis (cPCA). We apply both methods to an existing dataset of musicians captured with resting state fMRI, grouped as either classical, improvisational, or minimally trained non-musicians. The original time-averaged functional connectivity (FC) analysis of this dataset used improvisation as a proxy for creative thinking and found that the DMN and visual networks (VIS) display higher connectivity in improvisational musicians. We expand upon this dataset’s original study and find that QPP analysis detects convergent results at the group level with both methods. In improvisational musicians, dynamic functional correlation in the group-averaged QPP was found to be increased between the DMN-VIS and DMN-FPN for both the QPP algorithm and complex principal components analysis (cPCA) methods. Additionally, we found an unexpected increase in FC in the group-averaged QPP between the dorsal attention network and amygdala in improvisational musicians; this result was not reported in the original seed-based study of this dataset. The current study represents a novel application of two dynamic FC detection methods with results that replicate and expand upon previous seed-based FC findings. The results show the robustness of both the QPP phenomenon and its detection methods. This study also demonstrates the value of dynamic FC methods in reproducing seed-based findings and their promise in detecting group-wise or individual differences that may be missed by traditional seed-based resting state fMRI studies.