bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selecting Flap Transfer Methods to Repair Helix Soft Tissue Defect Based on the Direction of Long Axis
Authors: Zhu Jingjing , Zhang Yuxin , Wang Wei , Zhou Yiqun , Guo Yu , Chen Liang , Wang Heng , Dong Dong , Liu Tianyi 
Published: June 2024

Background:
The posterior auricular flap has long been favored for repairing skin defects on the ear’s surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair.

Objective:
To propose a modified flap transfer approach based on the orientation of the auricular defect’s long axis and assess the postoperative esthetic outcomes.

Methods:
The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale.

Results:
All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes.

Conclusion:
The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect’s long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.
Bone Density of the Midpalatal Suture After Surgically Assisted Rapid Maxillary Expansion: A Retrospective Cohort Study
Authors: da Silva Alexandre Augusto Ferreira , Lima Carlos Alysson Aragão , Montano-Pedroso Juan Carlos , Pereira Max Domingues 
Published: June 2024

Objectives:
To evaluate the bone density in the midpalatal suture after 10 months of surgically assisted rapid maxillary expansion (SARME) with the separation of the maxilla into 2 segments.

Methods:
Sixty multislice computed tomography (MCT) from 20 patients undergoing SARME were analyzed in 3 periods of time (1 MCT per patient on each occasion): (1) 1 week before surgery, (2) postsurgery immediately after completing the expander activation, and (3) 10 months after the expander activation. On all occasions, the bone density was measured in Hounsfield units on MCT scans in axial and coronal sections, in the anterior (A1), middle (A2), and posterior (A3) regions of the midpalatal suture.

Results:
The mean percentage values of bone density in Hounsfield units, from the 10-month postactivation period to preoperative in the A1, A2, and A3 regions were 68.38%, 38.21%, and 55.90%, respectively, in the axial norm, and 64.06%, 36.81%, and 55.50% in coronal norm (A1 = A3>A2), with no significant difference in the tomographic cuts (P >0.05). There was no correlation between patient age or amount of expansion in the expander and bone density.

Conclusions:
The bone density in the midpalatal suture 10 months after SARME is lower than preexpansion. A denser new bone formation along the suture concentrates closer to the extremities rather than in the central region. Although the maturation of the new bone formation in the midpalatal suture is lower 10 months after SARME, it appears to be sufficient for satisfactory clinical results, regardless of patient age or the amount of expansion in the expander.
Sleep and quiet wakefulness signify an idling brain hub for creative insights
Authors: Fayed Mostafa R. , Ghandour Khaled , Inokuchi Kaoru 
Published: June 2024

Long-term potentiation of synaptic strength is a fundamental aspect of learning and memory. Memories are believed to be stored within specific populations of neurons known as engram cells, which are subsequently reactivated during sleep, facilitating the consolidation of stored information. However, sleep and offline reactivations are associated not only with past experiences but also with anticipation of future events. During periods of offline reactivation, which occur during sleep and quiet wakefulness, the brain exhibits a capability to form novel connections. This process links various past experiences, often leading to the emergence of qualitatively new information that was not initially available. Brain activity during sleep and quiet wakefulness is referred to as the ‘idling brain’. Idling brain activity is believed to play a pivotal role in abstracting essential information, comprehending underlying rules, generating creative ideas and fostering insightful thoughts. In this review, we will explore the current state of research and future directions in understanding how sleep and idling brain activity are interconnected with various cognitive functions, especially creative insights. These insights have profound implications for our daily lives, impacting our ability to process information, make decisions and navigate complex situations effectively.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer’s dementia
Authors: Naveed K. , Rashidi-Ranjbar N. , Kumar S. , Zomorrodi R. , Blumberger D. M. , Fischer C. E. , Sanches M. , Mulsant B. H. , Pollock B. G. , Voineskos A. N. , Rajji T. K. 
Published: June 2024

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer’s dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)—a tract important to induce PAS-LTP—were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
To update or to create? The influence of novelty and prior knowledge on memory networks
Authors: Sekeres Melanie J. , Schomaker Judith , Nadel Lynn , Tse Dorothy 
Published: June 2024

Schemas are foundational mental structures shaped by experience. They influence behaviour, guide the encoding of new memories and are shaped by associated information. The adaptability of memory schemas facilitates the integration of new information that aligns with existing knowledge structures. First, we discuss how novel information consistent with an existing schema can be swiftly assimilated when presented. This cognitive updating is facilitated by the interaction between the hippocampus and the prefrontal cortex. Second, when novel information is inconsistent with the schema, it likely engages the hippocampus to encode the information as part of an episodic memory trace. Third, novelty may enhance hippocampal dopamine through either the locus coeruleus or ventral tegmental area pathways, with the pathway involved potentially depending on the type of novelty encountered. We propose a gradient theory of schema and novelty to elucidate the neural processes by which schema updating or novel memory traces are formed. It is likely that experiences vary along a familiarity–novelty continuum, and the degree to which new experiences are increasingly novel will guide whether memory for a new experience either integrates into an existing schema or prompts the creation of a new cognitive framework.
This article is part of the theme issue ‘Long-term potentiation: 50 years on’.
Alpha-secretase inhibition impairs Group I metabotropic glutamate receptor-mediated protein synthesis, long-term potentiation and long-term depression
Authors: Mockett Bruce G. , Davies James W. T. , Mills Zoë B. , Kweon Do Y. , Abraham Wickliffe C. 
Published: June 2024

Group I metabotropic glutamate receptors (Gp1-mGluRs) exert a host of effects on cellular functions, including enhancement of protein synthesis and the associated facilitation of long-term potentiation (LTP) and induction of long-term depression (LTD). However, the complete cascades of events mediating these events are not fully understood. Gp1-mGluRs trigger α-secretase cleavage of amyloid precursor protein, producing soluble amyloid precursor protein-α (sAPPα), a known regulator of LTP. However, the α-cleavage of APP has not previously been linked to Gp1-mGluR’s actions. Using rat hippocampal slices, we found that the α-secretase inhibitor tumour necrosis factor-alpha protease inhibitor-1, which inhibits both disintegrin and metalloprotease 10 (ADAM10) and 17 (ADAM17) activity, blocked or reduced the ability of the Gp1-mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) to stimulate protein synthesis, metaplastically prime future LTP and elicit sub-maximal LTD. In contrast, the specific ADAM10 antagonist GI254023X did not affect the regulation of plasticity, suggesting that ADAM17 but not ADAM10 is involved in mediating these effects of DHPG. However, neither drug affected LTD that was strongly induced by either high-concentration DHPG or paired-pulse synaptic stimulation. Our data suggest that moderate Gp1-mGluR activation triggers α-secretase sheddase activity targeting APP or other membrane-bound proteins as part of a more complex signalling cascade than previously envisioned.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Temporal genomic analysis ofPlasmodium falciparumreveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia
Authors: Fola Abebe A. , Kobayashi Tamaki , Shields Timothy , Hamapumbu Harry , Musonda Michael , Katowa Ben , Matoba Japhet , Stevenson Jennifer C. , Norris Douglas E. , Thuma Philip E. , Wesolowski Amy , Moss William J. , Juliano Jonathan J. , Bailey Jeffrey A. 
Published: June 2024

AbstractThe emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) ofPlasmodium falciparumsamples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160Nmutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.
High serum Cholesterol and Triglyceride levels in older adults: associations with sleep and nighttime behavior disorders at baseline and a prediction analysis of incidental cases at 12 months follow-up
Authors: Hallab Asma ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2024

AbstractIntroductionThis study explored the association between dyslipidemia and sleep and nighttime behavior disorders (SNBD) in the elderly.MethodsADNI population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between dyslipidemia and SNBD at baseline and 12 months. Relevant confounders were adjusted for.ResultsAmong the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 (IQR: 68, 78). At baseline, 357 (16%) had SNBD, and 327 (18%) at 12 months; 187 were incident cases.There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%,p-value=0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%,p-value=0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL,p-value<0.001).Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR=1.43, 95%CI: 1.13,1.80,p-value=0.003), even after adjustment for confounding factors (adj.OR=1.36, 95%CI: 1.06,1.74,p-value=0.016) and (BMI-adj.OR=1.29, 95%CI: 1.00,1.66,p-value=0.048). None of the dyslipidemia forms did predict incident cases at 12 months.ConclusionsHypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. None of the dyslipidemia forms predicted incidental SNBD over 12 months.
Two Decades of Rheumatology Research (2000-2023): A Dynamic Topic Modeling Perspective
Authors: Madrid-García Alfredo , Freites-Núñez Dalifer , Rodríguez-Rodríguez Luis 
Published: June 2024

AbstractBackgroundRheumatology has experience notably changes in last decades. New drugs, including biologic agents and janus kinase inhibitors, have bloosom. Concepts such aswindow of opportunity,arthralgia suspicious for progression, ordifficult-to-treat rheumatoid arthritishave appeared; and new management approaches and strategies such astreat-to-targethave become popular. Statistical learning methods, gene therapy, telemedicine or precision medicine are other advancements that have gained relevance in the field. To better characterise the research landscape and advances in rheumatology, automatic and efficient approaches based on natural language processing should be used. The objective of this study is to use topic modeling techniques to uncover key topics and trends in the rheumatology research conducted in the last 23 years.MethodsThis study analysed 96,004 abstracts published between 2000 and December 31, 2023, drawn from 34 specialised rheumatology journals obtained from PubMed. BERTopic, a novel topic modeling approach that considers semantic relationships among words and their context, was used to uncover topics. Up to 30 different models were trained. Based on the number of topics, outliers and topic coherence score, two of them were finally selected, and the topics manually labeled by two rheumatologists. Word clouds and hierarchical clustering visualizations were computed. Finally, hot and cold trends were identified using linear regression models.ResultsAbstracts were classified into 45 and 47 topics. The most frequent topics were rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis. Expected topics such as COVID-19 or JAK inhibitors were identified after conducting the dynamic topic modeling. Topics such as spinal surgery or bone fractures have gained relevance in last years, however, antiphospholipid syndrome, or septic arthritis have lost momentum.ConclusionsOur study utilized advanced natural language processing techniques to analyse the rheumatology research landscape, and identify key themes and emerging trends. The results highlight the dynamic and varied nature of rheumatology research, illustrating how interest in certain topics have shifted over time.
Mutation and cell state compatibility is required and targetable in Ph+acute lymphoblastic leukemia minimal residual disease
Authors: Winter Peter S. , Ramseier Michelle L. , Navia Andrew W. , Saksena Sachit , Strouf Haley , Senhaji Nezha , DenAdel Alan , Mirza Mahnoor , An Hyun Hwan , Bilal Laura , Dennis Peter , Leahy Catharine S. , Shigemori Kay , Galves-Reyes Jennyfer , Zhang Ye , Powers Foster , Mulugeta Nolawit , Gupta Alejandro J. , Calistri Nicholas , Van Scoyk Alex , Jones Kristen , Liu Huiyun , Stevenson Kristen E. , Ren Siyang , Luskin Marlise R. , Couturier Charles P. , Amini Ava P. , Raghavan Srivatsan , Kimmerling Robert J. , Stevens Mark M. , Crawford Lorin , Weinstock David M. , Manalis Scott R. , Shalek Alex K. , Murakami Mark A. 
Published: June 2024

SUMMARYEfforts to cure BCR::ABL1 B cell acute lymphoblastic leukemia (Ph+ ALL) solely through inhibition of ABL1 kinase activity have thus far been insufficient despite the availability of tyrosine kinase inhibitors (TKIs) with broad activity against resistance mutants. The mechanisms that drive persistence within minimal residual disease (MRD) remain poorly understood and therefore untargeted. Utilizing 13 patient-derived xenograft (PDX) models and clinical trial specimens of Ph+ ALL, we examined how genetic and transcriptional features co-evolve to drive progression during prolonged TKI response. Our work reveals a landscape of cooperative mutational and transcriptional escape mechanisms that differ from those causing resistance to first generation TKIs. By analyzing MRD during remission, we show that the same resistance mutation can either increase or decrease cellular fitness depending on transcriptional state. We further demonstrate that directly targeting transcriptional state-associated vulnerabilities at MRD can overcome BCR::ABL1 independence, suggesting a new paradigm for rationally eradicating MRD prior to relapse. Finally, we illustrate how cell mass measurements of leukemia cells can be used to rapidly monitor dominant transcriptional features of Ph+ ALL to help rationally guide therapeutic selection from low-input samples.HIGHLIGHTSRelapse after remission on TKI can harbor mutations in ABL1, RAS, or neitherMutations and development-like cell state dictate fitness in residual diseaseCo-targeting cell state and ABL1 markedly reduces MRDBiophysical measurements provide an integrative, rapid measurement of cell state
Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer
Authors: Gómez-Banoy Nicolás , Ortiz Eduardo , Jiang Caroline S. , Dagher Christian , Sevilla Carlo , Girshman Jeffrey , Pagano Andrew , Plodkowski Andrew , Zammarrelli William A. , Mueller Jennifer J. , Aghajanian Carol , Weigelt Britta , Makker Vicky , Cohen Paul , Osorio Juan C. 
Published: June 2024

AbstractBackgroundObesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.MethodsWe analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAE) after ICI was also assessed based on BMI status.Results524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared to normal BMI patients after treatment with ICI. Multivariable Cox regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared to normal BMI individuals.ConclusionObesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype.FundingNIH/NCI Cancer Center Support Grant P30CA008748 (MSK). K08CA266740 and MSK Gerstner Physician Scholars Program (J.C.O). RUCCTS Grant #UL1 TR001866 (N.G-B and C.S.J). Cycle for survival and Breast Cancer Research Foundation grants (B.W).
BMAL1-HIF2α heterodimers contribute to ccRCC
Authors: Mello Rebecca M. , Gomez Ceballos Diego , Sandate Colby R. , Agudelo Daniel , Jouffe Celine , Uhlenhaut Nina Henriette , Thomä Nicolas H. , Simon M. Celeste , Lamia Katja A. 
Published: June 2024

AbstractCircadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock geneBMAL1is higher in ccRCC than in healthy kidneys, unlike in other tumor types. BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion ofBMAL1reprograms HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higherBMAL1in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). We show that BMAL1-HIF2α is more sensitive than ARNT-HIF2α to suppression by PT2399, and increasingBMAL1sensitizes 786O cells to growth inhibition by PT2399. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 contributes to HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.