bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large cell neuroendocrine carcinoma transformation: A novel acquired drug resistance mechanism in colorectal adenocarcinoma
Authors: Du Feng , Han Ying , Hu Xiao , Xiao Yanjie , Shi Youwu , Sun Jing , Sun Zhiwei , Yang Ying , Yu Jing , Zhang Xiaodong , Jia Jun 
Published: March 2023

AbstractAcquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer (mCRC). Histological transformation is an important mechanism underlying the acquired resistance of non‐small cell lung cancer and prostate cancer to targeted therapy. However, no report has examined the role of histological transformation in mCRC. Here, we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti‐PD‐1 combination therapy. The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor. Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process. The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival. This case calls for more attention to histological transformation in mCRC. Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.
Comprehensive transcriptomic analysis to identify biological and clinical differences in cholangiocarcinoma
Authors: Silvestri Marco , Nghia Vu Trung , Nichetti Federico , Niger Monica , Di Cosimo Serena , De Braud Filippo , Pruneri Giancarlo , Pawitan Yudi , Calza Stefano , Cappelletti Vera 
Published: March 2023

AbstractBackgroundCholangiocarcinoma (CC) is a rare and aggressive disease with limited therapeutic options and a poor prognosis. All available public records of cohorts reporting transcriptomic data on intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) were collected with the aim to provide a comprehensive gene expression‐based classification with clinical relevance.MethodsA total of 543 patients with primary tumor tissues profiled by RNAseq and microarray platforms from seven public datasets were used as a discovery set to identify distinct biological subgroups. Group predictors developed on the discovery sets were applied to a single cohort of 131 patients profiled with RNAseq for validation and assessment of clinical relevance leveraging machine learning techniques.ResultsBy unsupervised clustering analysis of gene expression data we identified both in the ICC and ECC discovery datasets four subgroups characterized by a distinct type of immune infiltrate and signaling pathways. We next developed class predictors using short gene list signatures and identified in an independent dataset subgroups of ICC tumors at different prognosis.ConclusionsThe developed class‐predictor allows identification of CC subgroups with specific biological features and clinical behavior at single‐sample level. Such results represent the starting point for a complete molecular characterization of CC, including integration of genomics data to develop in clinical practice.
Radiological lymph‐node size improves the prognostic value of systemic inflammation index in rectal cancer with pathologically negative nodes
Authors: Peng Shaoyong , Liu Xiaoxia , Li Yingjie , Yu Huichuan , Xie Yumo , Wang Xiaolin , Zhou Jiaming , Zhu Mingxuan , Luo Yanxin , Huang Meijin 
Published: March 2023

AbstractBackgroundThe relationship between the radiological lymph node (rLN) size and survival outcome in node‐negative rectal cancer is still uncertain. In this study, we aimed to explore the role of enlarged rLN in predicting the survival of node‐negative rectal cancers.MethodsWe retrospectively reviewed the records of 722 node‐negative rectal cancer who underwent curative resection. Factors associated with DFS (disease‐free survival) and CSS (cancer‐specific survival) were assessed with univariate and multivariate analysis. Survival analysis was performed according to presence with or without enlarged rLN. Combining rLN with NLR as a new index‐inflammation immune score (IIS) for predicting survival. Comparing different models to assess the predictive powers.ResultsA total of 119 patients had tumor recurrence and 73 patients died due to cancer. Patients with enlarged rLN (≥5 mm) was significantly associated with better DFS (HR:0.517, 95%CI:0.339–0.787, p = 0.002) and CSS (HR:0.43, 95%CI:0.242–0.763, p = 0.004). The risk factors of recurrence were rLN, neutrophil‐lymphocyte ratio (NLR), CEA level, and distance from the anal verge. The risk of recurrence increased by 1.88‐ and 2.83‐fold for the high score in IIS compared with the low and intermediate score group (All p < 0.001). Similarly, the high score in IIS also increased the risk of cancer‐specific death. In the model comparison, the AIC and LR were improved by including the rLN into the NLR model for DFS and CSS prediction (All p < 0.05).ConclusionsNode‐negative rectal cancer patients with enlarged rLN had a better survival outcome. IIS might be a more comprehensive and complete inflammation immune index for survival prediction.
Progress in the Total Synthesis of Antitumor Tetrahydroisoquinoline Alkaloids
Authors: Gao Yi , Tu Ni , Liu Xiaoting , Lu Kangkang , Chen Siyu , Guo Ju 
Published: March 2023

AbstractAmong the tetrahydroisoquinoline(THIQ) of natural products, a family of THIQ alkaloids has the characteristics of similar biosynthetic pathway. Such THIQ alkaloids family mainly include Renieramycins, Ecteinasicdins, Tetrazaomine, Lemonomycin, etc. Most of these natural compounds have strong antitumor activities, and its family member Ecteinasicdins743 (ET‐743, Trabectedin) has been marketed in the European Union and the United States for the treatment of advanced soft tissue tumors and ovarian cancer. Because of the excellent biological activity and complex chemical structure of this kind of THIQ products, it has aroused great interest of biologists and chemists, and many synthetic chemists have paid considerable efforts to their total synthesis over the past decade. Based on this, the recent advances in the total synthesis of such THIQ alkaloids are reviewed.
Stereodivergent Biocatalytic Formal Reduction of α‐Angelica Lactone to (R)‐ and (S)‐γ‐Valerolactone in a One‐Pot Cascade
Authors: Tonoli Alessia , Wagner Karla , Bacchin Arianna , Reiter Tamara , Bergantino Elisabetta , Robescu Marina S. , Hall Mélanie 
Published: March 2023

AbstractThe formal asymmetric and stereodivergent enzymatic reduction of α‐angelica lactone to both enantiomers of γ‐valerolactone was achieved in a one‐pot cascade by uniting the promiscuous stereoselective isomerization activity of Old Yellow Enzymes with their native reductase activity. In addition to running the cascade with one enzyme for each catalytic step, a bifunctional isomerase‐reductase biocatalyst was designed by fusing two Old Yellow Enzymes, thereby generating an unprecedented case of an artificial enzyme catalyzing the reduction of nonactivated C=C bonds to access (R)‐valerolactone in overall 41 % conversion and up to 91 % ee. The enzyme BfOYE4 could be used as single biocatalyst for both steps and delivered (S)‐valerolactone in up to 84 % ee and 41 % overall conversion. The reducing equivalents were provided by a nicotinamide recycling system based on formate and formate dehydrogenase, added in a second step. This enzymatic system provides an asymmetric route to valuable chiral building blocks from an abundant bio‐based chemical.
SHORES: A suicide protective factors mnemonic with applications in career counseling
Authors: Cureton Jenny L. , Tovey Bridget E. 
Published: March 2023

AbstractAn established suicide protective factors mnemonic is beneficial to career counselors as career‐related suicide concerns increase. SHORES stands for skills and strategies for coping (S), hope (H), objections (O), reasons to live and restricted means (R), engaged care (E), and support (S). This literature‐backed suicide resiliency tool applies across client populations and to career assessment, intervention, and ongoing counseling. We establish the clear overlap between work and suicide, describe SHORES applied in career counseling, and provide an illustrative case example. Particular implications include SHORES in screening and comprehensive client conceptualization as well as needed research on SHORES in career practice.
Enhancing reversibility of LiNi0.5Mn1.5O4 by regulating surface oxygen deficiency
Authors: Wang Dandan , Gao Cong , Zhou Xuefeng , Peng Shang , Tang Mingxue , Wang Yonggang , Huang Lujun , Yang Wenge , Gao Xiang 
Published: March 2023

AbstractOxygen deficiency has crucial effects on the crystal structure and electrochemical performance of spinel oxide lithium electrode materials such as LiNi0.5Mn1.5O4 (LNMO) cathode. In particular, the oxygen stoichiometry on the crystal surface differs from that on the crystal interior in LNMO. The detection of local oxygen loss in LNMO and its correlation with the crystal structure and the cycling stability of LNMO remain challenging. In this study, the effect of oxygen deficiency in LNMO controlled by sintering temperature on the surface crystal structure and electrochemical performance of LNMO is comprehensively investigated. The high concentration of oxygen vacancies segregates at the surface regions of LNMO forming a thin rock‐salt and/or deficient spinel surface layer. The atomic‐level surface structure reconstruction was demonstrated by annular dark‐field and annular bright‐field techniques. For the synthesis of LNMO, the higher sintering temperature results in higher crystallinity but the higher oxygen deficiency in LNMO. The high crystallinity of LNMO would increase the thermal stability of LNMO cathodes while the high content of oxygen deficiency would decrease the surface structural stability of LNMO. Therefore, the LNMO sintered at a medium temperature of 850°C achieved the best capacity retention. The results suggest a competitive function mechanism between oxygen stoichiometry and the crystallinity of LNMO on the cycling performance of LNMO.
Identifying Protein‐Protein Interactions by Proximity Biotinylation with AirID and splitAirID
Authors: Schaack Grace A. , Sullivan Owen M. , Mehle Andrew 
Published: March 2023

AbstractProteins frequently function in high‐order complexes. Defining protein‐protein interactions is essential to acquiring a full understanding of their activity and regulation. Proximity biotinylation has emerged as a highly specific approach to capture transient and stable interactions in living cells or organisms. Proximity biotinylation exploits promiscuous biotinylating enzymes fused to a bait protein, resulting in the biotinylation of adjacent endogenous proteins. Biotinylated interactors are purified under very strict conditions and identified by mass spectrometry to obtain a high‐confidence list of candidate binding partners. AirID is a recently described biotin ligase specifically engineered for proximity labeling. This protocol details proximity biotinylation by AirID, using protein complexes that form during a type I interferon response as an example. It covers the construction and validation of AirID fusion proteins and the enrichment and identification of biotinylated interactors. We describe a variation on the protocol using splitAirID. In this case, AirID is split into two inactive fragments and ligase activity is only restored upon dimerization of the bait proteins. This permits selective detection of proteins that interact with homo‐ or heterodimeric forms of the bait. The protocol considers design strategies, optimization, and the properties of different biotin ligases to identify optimal conditions for each experimental question. We also discuss common pitfalls and how to troubleshoot them. These approaches allow proximity biotinylation to be a powerful tool for defining protein interactomes. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Construction and functional validation of AirID fusion proteinsAlternate Protocol: Construction and functional validation of splitAirID fusion proteinsSupport Protocol: Western blot for biotinylated proteinsBasic Protocol 2: Biotinylation, enrichment, and identification of protein interactors
Computerized cognitive practice effects in relation to amyloid and tau in preclinical Alzheimer's disease: Results from a multi‐site cohort
Authors: Young Christina B. , Mormino Elizabeth C. , Poston Kathleen L. , Johnson Keith A. , Rentz Dorene M. , Sperling Reisa A. , Papp Kathryn V. 
Published: March 2023

AbstractScalable cognitive paradigms that provide metrics such as the Computerized Cognitive Composite (C3) may be sensitive enough to relate to Alzheimer's disease biomarkers in the preclinical clinically unimpaired (CU) stage. We examined CU older adults (n = 3287) who completed alternate versions of the C3 approximately 51 days apart. A subset of CU with abnormal amyloid also completed tau positron emission tomography (PET) imaging. C3 initial performance and practice effects were examined in relation to amyloid status and continuous regional tau burden. Initial C3 performance was associated with amyloid status across all participants, and with tau burden in the medial temporal lobe and early cortical regions in CU with abnormal amyloid. Short‐term practice effects were associated with reduced tau in these regions in CU with abnormal amyloid, but were not associated with amyloid status. Thus, computerized cognitive testing repeated over a short follow‐up period provides additional insights into early Alzheimer's disease processes.
Brief group cognitive‐behavioral therapy for bulimia nervosa and binge‐eating disorder: A pilot study of feasibility and acceptability
Authors: Moore Elana , Waller Glenn 
Published: March 2023

AbstractObjectiveBrief cognitive‐behavioral therapy for non‐underweight eating disorders (CBT‐T) has been shown to be clinically useful in non‐underweight samples, when delivered one‐to‐one. This pilot study assessed the acceptance, compliance and feasibility levels of a group version of CBT‐T, which has the potential to enhance patient access.MethodA group CBT‐T protocol was developed and piloted in two therapy groups (N = 8). Eating disorder attitudes and behaviors, depression and anxiety were assessed at the beginning and end of treatment.ResultsA third of all patients approached accepted the offer of group CBT‐T, and entered treatment. Among that group of treatment starters, none were lost to treatment. The therapy was feasible in practical terms, including online delivery. Finally, mean scores on measures suggested improvement in clinical profiles.DiscussionThis pilot study demonstrated that a group CBT‐T is a feasible intervention for non‐underweight eating disorders in adults, with low acceptance but high compliance. Group CBT‐T has the potential to reduce demand on services and in turn increase availability of treatment to those with eating disorders.Public SignificanceThe present research contributes to the treatment of non‐underweight adults with eating disorders. Group CBT‐T was shown to be feasible in this pilot study. It was associated with low acceptance but strong compliance. If supported by further research, group CBT‐T has the potential to reduce waitlists, ensure throughput in services, and ultimately improve the lives of many who are affected by eating disorders.
Optimizing differential equations to fit data and predict outcomes
Authors: Frank Steven A. 
Published: March 2023

AbstractMany scientific problems focus on observed patterns of change or on how to design a system to achieve particular dynamics. Those problems often require fitting differential equation models to target trajectories. Fitting such models can be difficult because each evaluation of the fit must calculate the distance between the model and target patterns at numerous points along a trajectory. The gradient of the fit with respect to the model parameters can be challenging to compute. Recent technical advances in automatic differentiation through numerical differential equation solvers potentially change the fitting process into a relatively easy problem, opening up new possibilities to study dynamics. However, application of the new tools to real data may fail to achieve a good fit. This article illustrates how to overcome a variety of common challenges, using the classic ecological data for oscillations in hare and lynx populations. Models include simple ordinary differential equations (ODEs) and neural ordinary differential equations (NODEs), which use artificial neural networks to estimate the derivatives of differential equation systems. Comparing the fits obtained with ODEs versus NODEs, representing small and large parameter spaces, and changing the number of variable dimensions provide insight into the geometry of the observed and model trajectories. To analyze the quality of the models for predicting future observations, a Bayesian‐inspired preconditioned stochastic gradient Langevin dynamics (pSGLD) calculation of the posterior distribution of predicted model trajectories clarifies the tendency for various models to underfit or overfit the data. Coupling fitted differential equation systems with pSGLD sampling provides a powerful way to study the properties of optimization surfaces, raising an analogy with mutation‐selection dynamics on fitness landscapes.
Wildfire disturbance reveals evidence of ecosystem resilience and precariousness in a forest–grassland mosaic
Authors: Hamilton Nicholas P. , Burton Philip J. 
Published: March 2023

AbstractForest and grassland ecosystems are sometimes located adjacently within the same climate. In Interior British Columbia, Canada, there are complex forest–grassland mosaics within the Interior Douglas‐fir biogeoclimatic zone. Historically, both grassland and forest ecosystems experienced high‐frequency, low‐severity fire regimes. Since European settlement and introduction of livestock grazing and fire exclusion, trees have encroached on grasslands, and tree densities in forests have increased. In this study, we characterize plant communities and near‐surface soil moisture in forest and grassland sites, and in historical grassland sites affected by tree encroachment. We hypothesized that spatial and temporal patterns of near‐surface soil moisture are reflected in aboveground plant community composition and structure. After initial sampling of soil moisture and plant communities, the study area was burned in a wildfire. Applying a multifactorial approach to comparing adjacent grassland and forest sites, we treated the wildfire event as a natural experiment, sampling post‐wildfire plant species composition and soil moisture, and measuring the severity and spatial heterogeneity of surface burn conditions. Evidence supports the concept of mutually exclusive fire‐reinforced bistable grassland and forest states, with greater spatial heterogeneity of soil moisture and burn severity in forests, and highly uniform patterns of soil moisture, vegetation, and burn severity in grasslands. Areas of forest encroachment on grasslands had understory plant communities dominated by exotic species, while restored grasslands had native bunchgrass cover like typical grasslands of the region. Additionally, there was post‐wildfire divergence of forest‐ and grassland‐associated plant communities. Viewed through a resilience theory conceptual framework, we suggest that ecosystem legacies are reinforcing post‐wildfire ecosystem identity and associated native plant communities. External factors—particularly past heavy livestock grazing and fire suppression—have caused ecosystem precariousness that can be addressed with management actions.
Aquatic vegetation types identified during early and late phases of vegetation recovery in the Upper Mississippi River
Authors: Larson Danelle M. , Carhart Alicia M. , Lund Eric M. 
Published: March 2023

AbstractAssemblage patterns and processes of aquatic vegetation in most large floodplain rivers are not well understood, particularly after plant recovery. Identifying vegetation types, which are recurring plant groupings based on species composition, diversity, and abundances, can describe plant assembly patterns and environmental drivers that aid conservation planning and management. We used a 22‐year dataset (n = 18,000 sampling plots) to identify aquatic vegetation types during an “early phase” and “late phase” of plant recovery at multiple spatial scales nested within a 500‐km river reach of the Upper Mississippi River, USA. We hypothesized that vegetation types varied according to scale because of the stark environmental differences among riverine habitats and differing regional species pools along the river's latitudinal gradient, and that the late phase of recovery had developed several new vegetation types. We first used cluster analyses at multiple spatiotemporal scales to identify the number of vegetation types and their characteristics, such as indicator species, species compositions and abundances, and diversity index. Then we applied a multivariate regression to pinpoint environmental factors (such as hydrodynamics, system productivity, local habitat, and water quality) that structured those vegetation types. Clustering revealed that ~90% of plots irrespective of recovery phase were not classified into vegetation types, which indicated that most aquatic sampling plots are unique in species composition and unpredictable. However, impounded areas upriver from dams had matured five vegetation types: lotus (Nelumbo lutea Willd.), submersed (a mix of 11 common submersed species), watercelery (Vallisneria americana Michx.), arrowheads (Sagittaria rigida Pursh and Sagittaria latifolia Willd.), and a diverse community (with high diversity indices and multiple life forms). The vegetation types were associated with three environmental gradients related to inundation depth and duration, system productivity, and water clarity. These five vegetation types are known to be of high ecological value to fish and wildlife and thus targets for restoration, for example, the watercelery community is principal forage for migrating canvasback ducks (Aythya valisineria) along the Mississippi River flyway. Our results provide insights on vegetation assembly during recovery and aid habitat conservation by providing quantitative, environmental targets for restoration.
Catalytic N‐Alkylation of Amines with Aldehydes by a Molecular Mo Oxide Catalyst
Authors: Su Wei , Xie Ya , Chen Ming , Xu Zhenmin , Shi Da , Yu Weiguo , Jiang Feng , Yu Han 
Published: March 2023

AbstractSecondary and tertiary amine derivatives are very important in chemical and pharmaceutical industries. The N‐alkylation of amines with aldehydes is a proper way to form secondary and tertiary amines. However, the traditional catalyst systems for this transformation bring a series of problems such as narrow substrate scope, challenges of difficult catalyst preparation and metal residues and toxicity. Herein an efficient way to perform N‐alkylation of amines with aldehydes was described which used a molecular Mo oxide catalyst. In this pathway, various aldehyde and amine derivatives were successfully converted to the corresponding secondary and tertiary amines with high selectivity and efficiency. In addition, the catalyst was easy to prepare, and could be recycled six times without appreciable loss of conversion. Finally, the reaction mechanism was presented based on the observation of the possible intermediates and control experiments.