bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti–platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin
Authors: Warkentin Theodore E. , Cook Richard J. , Marder Victor J. , Sheppard Jo-Ann I. , Moore Jane C. , Eriksson Bengt I. , Greinacher Andreas , Kelton John G.
Published: August 2005

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti–PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti–PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti–PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.
Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance
Authors: Verhaak Roel G. W. , Goudswaard Chantal S. , van Putten Wim , Bijl Maarten A. , Sanders Mathijs A. , Hugens Wendy , Uitterlinden André G. , Erpelinck Claudia A. J. , Delwel Ruud , Löwenberg Bob , Valk Peter J. M.
Published: August 2005

Mutations in nucleophosmin NPM1 are the most frequent acquired molecular abnormalities in acute myeloid leukemia (AML). We determined the NPM1 mutation status in a clinically and molecularly well-characterized patient cohort of 275 patients with newly diagnosed AML by denaturing high-performance liquid chromatography (dHPLC). We show that NPM1 mutations are significantly underrepresented in patients younger than 35 years. NPM1 mutations positively correlate with AML with high white blood cell counts, normal karyotypes, and fms-like tyrosine kinase-3 gene (FLT3) internal tandem duplication (ITD) mutations. NPM1 mutations associate inversely with the occurrence of CCAAT/enhancer-binding protein-α (CEBPA) and NRAS mutations. With respect to gene expression profiling, we show that AML cases with an NPM1 mutation cluster in specific subtypes of AML with previously established gene expression signatures, are highly associated with a homeobox gene–specific expression signature, and can be predicted with high accuracy. We demonstrate that patients with intermediate cytogenetic risk AML without FLT3 ITD mutations but with NPM1 mutations have a significantly better overall survival (OS) and event-free survival (EFS) than those without NPM1 mutations. Finally, in multivariable analysis NPM1 mutations express independent favorable prognostic value with regard to OS, EFS, and disease-free survival (DFS).
Glacier and lake-level variations in west-central Europe over the last 3500 years
Authors: Holzhauser Hanspeter , Magny Michel , Zumbuühl Heinz J.
Published: August 2005

On the basis of glacier and lake-level records, this paper attempts, for the first time, a comparison between high-resolution palaeohydrological and palaeoglaciological data in west-central Europe over the past 3500 years. A data set of tree-ring width, radiocarbon and archaeological data, in addition to historical sources, were used to reconstruct fluctuations of the Great Aletsch, the Gorner and the Lower Grindelwald glaciers in the Swiss Alps. The three ice-streams experienced nearly synchronous advances at c. 1000-600 BC and AD 500-600, 800-900, 1100-1200 and 1300-1860. These glacier fluctuations show strong correspondence with lake-level variations reconstructed in eastern France (Jura mountains and Pre-Alps) and on the Swiss Plateau. This supports the hypothesis of climatically driven fluctuations. Historical data available for the period since AD 1550 reveal, in detail, various meteorological conditions behind the successive glacier advances. However, in agreement with the general trend shown by the historical data, the synchroneity between glacier advances and periods of higher lake level suggests the impact of general winter cooling and an increase in summer moisture as responsible for reinforced feeding of both glaciers and lakes in west-central Europe over the past 3500 years. Finally, a comparison between the Great Aletsch glacier and the residual 14C records supports the hypothesis that variations in solar activity were a major forcing factor of climatic oscillations in west-central Europe during the late Holocene.
Variable isostatic uplift patterns during the Holocene in southeast Sweden, based on high-resolution AMS radiocarbon datings of lake isolations
Authors: Risberg Jan , Alm Goran , Goslar Tomasz
Published: August 2005

The construction of a new highway between Uppsala and Mehedeby in northern Uppland, southeastern Sweden, has motivated extensive archaeological excavations. To describe changes in shoreline configuration over time, the isolation of nine lake basins has been interpreted from diatom analysis. Their isolation ages were determined from 45 AMS radiocarbon dates (five per site) of terrestrial macrofossils, mainly Betula and Alnus seeds. The isolation ages and the corresponding altitudes indicate a complicated pattern of isostatic uplift during the late Holocene. Neither the present-day isobases nor those for the ‘Neolithic Sea’ seem to explain their isolation ages and corresponding altitudes in relation to their geographic distribution. Since at least some of the lakes are situated in a relatively pronounced topographic landscape we are inclined to explain the observations as the result of small-scale irregular uplift. Earthquakes are rare in the area at present suggesting short-term tectonic activities along existing fault lines.
Holocene climatic and environmental changes inferred from midge records (Diptera: Chironomidae, Chaoboridae, Ceratopogonidae) at Lake Berkut, southern Kola Peninsula, Russia
Authors: Ilyashuk Elena A. , Ilyashuk Boris P. , Hammarlund Dan , Larocque Isabelle
Published: August 2005

A radiocarbon-dated sediment sequence from Lake Berkut in the southern part of the Kola Peninsula, northwest Russia, was investigated by means of midge analysis in order to reconstruct the Holocene climatic and environmental history of the region. Past mean July air temperatures at the study site and hypolimnetic oxygen contents of the lake water were inferred from chironomid-based transfer functions. The early Holocene ( c. 10 100-8400 cal. yr BP) is characterized by summer temperatures and hypolimnetic oxygen concentrations broadly similar to present-day conditions. The midge records give evidence of a lake-level fall at c. 7000 cal. yr BP, resulting in weakened thermal stratification of the lake water, and improvement of the hypolimnetic oxygen conditions. After c. 4000 cal. yr BP midge assemblages suggest a lake-level rise related to increased effective moisture. A secondary mid-Holocene climatic optimum with inferred mean July air temperatures of c. 12.1° C was recorded between 6000 and 4400 cal. yr BP, followed by minimum values (c. 11.3°C) between 3500 and 1500 cal. yr BP, accompanied by the onset of natural acidification of the lake. The late-Holocene midge assemblages suggest weakly acidic conditions, low hypolimnetic oxygen contents and a general warming trend during the last c. 1500 years, although paludification and natural acidification may have influenced the temperature reconstruction at this stage. However, the modern chironomid-inferred mean July air temperature (12.5°C) is consistent with meteorological data from a nearby station. In general, the midge records reflect relatively warm and moist conditions at Lake Berkut before c. 7000 cal. yr BP, a relatively warm and dry climate at c. 7000-4000 cal. yr BP, and a shift to cooler and wetter climatic conditions in the region after c. 4000 cal. yr BP.
The Breast Cancer Susceptibility Gene BRCA1 Regulates Progesterone Receptor Signaling in Mammary Epithelial Cells
Authors: Ma Yongxian , Katiyar Pragati , Jones Laundette P. , Fan Saijun , Zhang Yiyu , Furth Priscilla A. , Rosen Eliot M.
Published: August 2005

The progesterone receptor (PR) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory and inhibitory actions. Previously, the breast cancer susceptibility gene product BRCA1 was found to interact with and inhibit the transcriptional activity of estrogen receptor-α. In this study, we found that exogenous wild-type BRCA1 inhibited the activity of the PR in transient transfection assays utilizing a mouse mammary tumor virus-Luc reporter. Wild-type BRCA1 inhibited the activity of endogenous PR in human breast cancer cells (T47D and MCF-7) and inhibited the activity of exogenous PR-A, PR-B, and [PR-A plus PR-B] isoforms. On the other hand, knockdown of endogenous BRCA1 using small interfering RNA enhanced the progesterone-stimulated activity of the PR by about 4-fold. We documented an in vivo association of the endogenous BRCA1 with PR isoforms A and B and a direct in vitro interaction between BRCA1 and PR, which was partially mapped. Whereas down-regulation of the coactivator p300 contributes to the BRCA1-mediated repression of estrogen receptor-α, this mechanism does not contribute to inhibition of PR activity, because exogenous p300 did not rescue the BRCA1 repression of PR activity. The BRCA1-PR interaction has functional consequences. Thus, we showed that BRCA1 inhibits the expression of various endogenous progesterone-responsive genes and inhibits progesterone-stimulated proliferation of T47D cells. Finally, exogenous progesterone caused an exaggerated proliferative response in the mammary glands of mice harboring a mammary-targeted conditional deletion of the full-length isoform of Brca1. These findings suggest that BRCA1 regulates the activity of progesterone, a major hormone of pregnancy that may also participate in mammary carcinogenesis.
Qualitative Aspects of an Inductively Coupled Plasma in the Spectral Region between 120 and 185 nm
Authors: Heine D. R. , Babis J. S. , Denton M. B.
Published: August 2005

Investigations of the atomic emission lines produced by a variety of non-metals in the vacuum ultraviolet spectral region are reported. A number of promising analytical lines for oxygen, nitrogen, carbon, bromine, sulfur, and chlorine was observed between 120 and 185 nm using both photographic and electronic detection. A unique experimental configuration employing a side-arm torch which directly couples to the vacuum spectrometer/spectrograph is described.
Applications of the Optical Multichannel Analyzer for Low Light Level Signal Averaging and Two-Dimensional Mode Detection of Picosecond Laser-Generated Raman Spectra
Authors: Chao J. L.
Published: August 2005

Techniques developed for the use of a programmable optical multichannel analyzer are discussed. Two different signal-limited areas which are of general spectroscopic interest are the focus of the paper. The first area involves using extended delay target integration techniques for low level light signal averaging. The second application area describes techniques developed for capturing spectral information from pulsed laser experiments. Multiple tracks are shown in order to demonstrate the two-dimensional applications in spectroscopy. The paper also contains information about the design and operating principles of vidicon detectors and other imaging technologies are considered as well.
Development of strategies for the use of anti-growth factor treatments
Authors: Jones H E , Gee J M W , Taylor K M , Barrow D , Williams H D , Rubini M , Nicholson R I
Published: August 2005

Aberrant signalling through the epidermal growth factor receptor (EGFR) is associated with increased cancer cell proliferation, reduced apoptosis, invasion and angiogenesis. Over-expression of the EGFR is seen in a variety of tumours and is a rational target for antitumour strategies. Among the classes of agent targeting the EGFR are small-molecule inhibitors, which include gefitinib (IRESSA™), which acts by preventing EGFR phosphorylation and downstream signal transduction. De novo and acquired resistance, however, have been reported to gefitinib and here we describe evidence which indicates that the type II receptor tyrosine kinases (RTKs) insulin-like growth factor-I receptor (IGF-IR) and/or insulin receptor (InsR) play important roles in the mediation of responses to gefitinib in the de novo- and acquired-resistance phenotypes in several cancer types. Moreover, combination strategies that additionally target the IGF-IR/InsR can enhance the antitumour effects of gefitinib.
From learning optimization to learner flourishing: Reimagining AI in Education at the Institute for Student‐AI Teaming (iSAT)
Authors: D'Mello Sidney K. , Biddy Quentin , Breideband Thomas , Bush Jeffrey , Chang Michael , Cortez Arturo , Flanigan Jeffrey , Foltz Peter W. , Gorman Jamie C. , Hirshfield Leanne , Monica Ko Mon‐Lin , Krishnaswamy Nikhil , Lieber Rachel , Martin James , Palmer Martha , Penuel William R. , Philip Thomas , Puntambekar Sadhana , Pustejovsky James , Reitman Jason G. , Sumner Tamara , Tissenbaum Michael , Walker Lyn , Whitehill Jacob
Published: February 2024

The Institute for Student‐AI Teaming (iSAT) addresses the foundational question: how to promote deep conceptual learning via rich socio‐collaborative learning experiences for all students?—a question that is ripe for AI‐based facilitation and has the potential to transform classrooms. We advance research in speech, computer vision, human‐agent teaming, computer‐supported collaborative learning, expansive co‐design, and the science of broadening participation to design and study next generation AI technologies (called AI Partners) embedded in student collaborative learning teams in coordination with teachers. Our institute ascribes to theoretical perspectives that aim to create a normative environment of widespread engagement through responsible design of technology, curriculum, and pedagogy in partnership with K–12 educators, racially diverse students, parents, and other community members.
Unveiling the Intricacies of a Ductile‐Phase Toughened Intermetallic: An In‐Depth Exploration of a Eutectic Mo–Si–Ti Alloy and its Mechanical Behavior
Authors: Vikram Raja Jothi , Aramanda Shanmukha Kiran , Schliephake Daniel , Kauffmann Alexander , Choudhury Abhik , Heilmaier Martin , Suwas Satyam
Published: February 2024

Herein, the development of directional solidification for a novel high‐temperature Mo–20Si–52.8Ti (at%) ternary alloy using a modified Bridgeman type apparatus is presented. The resulting alloy exhibits a microstructure consisting of a body‐centered cubic solid solution (BCCss) and a hexagonal silicide (Ti,Mo)5Si3 with approximate volume fractions of 50% for each phase. The phases exhibit a crystallographic orientation relationship with and . Different solidification velocities are imposed, which reveal an inverse relationship to the lamellar spacing according to a Jackson–Hunt type scaling. Mechanical characterization using Vickers indentation demonstrates that the BCCss accommodates plasticity through dislocation motion, while the silicide phase exhibits high hardness and brittleness, serving as a crack initiation site. Crack propagation is arrested and deflected at the interface to the BCCss. Fracture toughness measurements via indentation yield a fracture toughness of 3.7 MPa√m for the silicide, somewhat higher than previously reported values for Nb‐, Mo‐, and Cr‐based silicides at room temperature. The directionally solidified specimens show an enhanced fracture toughness attributed to a greater BCCss length scale; thus, combining the ductile and hard phases results in a ductile‐phase toughened intermetallic composite. The findings open up new possibilities for the design of advanced intermetallic composites with improved toughness performance.
A Low‐Cost and Do‐It‐Yourself Pressure Sensor Enable Human Motion Detection and Human–Machine Interface Applications
Authors: Heikkinen Mari , Basarir Fevzihan , Miikki Kim , Al Haj Yazan , Mohan Mithila , Vapaavuori Jaana
Published: February 2024

In this work, cost‐effective and do‐it‐yourself capacitive pressure sensors are fabricated using readily available commercial components. The sensors are created in a single‐step process ‐by simply applying electrically conductive paint onto both sides of a porous melamine sponge. These sensors exhibit a wide‐range pressure sensing capability, spanning from 10 Pa to 100 kPa. The sensors showcase an impressively low limit of detection, detecting pressures as low as 10 Pa, and exhibit a moderate response time of 123 ms. Moreover, the sensors display remarkable repeatability and stability over 10 000 loading and unloading cycles without experiencing fatigue. Notably, these exceptional qualities come at an exceptionally low material cost, with the sensor measuring 20 × 20 × 2 mm. To showcase their potential applications, the fabricated sensors are successfully employed in real‐time human motion detection, proximity detection, and wearable keyboard applications.
Tumor‐Associated Monocytes Reprogram CD8+ T Cells into Central Memory‐Like Cells with Potent Antitumor Effects
Authors: Yang Zeliang , Liu Liang , Zhu Zhenyu , Hu Zixi , Liu Bowen , Gong Jingjing , Jin Yuan , Luo Juan , Deng Yichen , Jin Yan , Wang Guangxi , Yin Yuxin
Published: February 2024

CD8+ T cells are critical for host antitumor responses, whereas persistent antigenic stimulation and excessive inflammatory signals lead to T cell dysfunction or exhaustion. Increasing early memory T cells can improve T cell persistence and empower T cell‐mediated tumor eradication, especially for adoptive cancer immunotherapy. Here, it is reported that tumor‐associated monocytes (TAMos) are highly correlated with the accumulation of CD8+ memory T cells in human cancers. Further analysis identifies that TAMos selectively reprogram CD8+ T cells into T central memory‐like (TCM‐like) cells with enhanced recall responses. L‐NMMA, a pan nitric oxide synthase inhibitor, can mitigate TAMo‐mediated inhibition of T cell proliferation without affecting TCM‐like cell generation. Moreover, the modified T cells by TAMo exposure and L‐NMMA treatment exhibit long‐term persistence and elicit superior antitumor effects in vivo. Mechanistically, the transmembrane protein CD300LG is involved in TAMo‐mediated TCM‐like cell polarization in a cell‐cell contact‐dependent manner. Thus, the terminally differentiated TAMo subset (CD300LGhighACElow) mainly contributes to TCM‐like cell development. Taken together, these findings establish the significance of TAMos in boosting T‐cell antitumor immunity.
Growth charts for weight and height of Indian children with Down syndrome
Authors: Bhalla Anil Kumar , Kaur Harvinder , Kaur Rupinder , Panigrahi Inusha
Published: February 2024

Age and gender specific growth charts for Indian children with Down syndrome (DS) based on longitudinal data have not been published. To establish percentile growth charts for DS children inhabiting northwestern parts of India, body weight and length/height of 1125 (Male: 752, Female: 373) children with DS aged <1 month to 10 years, enrolled from the “Genetics Clinic” were measured at half yearly age intervals in the “Growth Clinic” of the Institute from August 1994 to November 2018. A total of 2089 observations were made on these children using standardized anthropometric techniques and instruments following a prospective mixed‐longitudinal growth research design. Using the LMS method, age and sex‐specific percentile growth charts (<1 month to 10 years) for weight, and length/ height were generated. Unpaired t‐test was used to compare mean growth attainments of study children with those of DS patients representing other population groups as well as their normal Multicentre Growth Reference Study (MGRS and Indian Academy of Pediatrics (IAP) counterparts. The 50th percentile growth curves for both weight and length/height of Indian children with DS demonstrated a regular increase. As compared to their normal MGRS and Indian (IAP) counterparts, the children with DS had lower weight and height attainments. The boys and girls with Down syndrome showed short stature (height < 3rd centile) from the age of 1 year till 10 years and also became underweight beyond 5 years. As compared to their normal counterparts, children with Down syndrome exhibited compromised auxological attainments. The use of growth charts presented herein may be used to compare and monitor growth and nutritional status of Indian children with Down syndrome.
Bifunctional Potential Structure Design Breaks Electrolyte Limitations of Zinc Ion Battery
Authors: Gong Shengen , Chao Yunfeng , Yang Fang , Wu Shuangyu , Wang Yifan , Chao Danming , Jia Xiaoteng
Published: February 2024

Aqueous zinc‐ion batteries (ZIBs) are safe and economical for grid applications. However, current ZIBs have limitations in terms of inferior capacity and low output voltage, which are hampered by the electrolyte applicability of the Zn2+ hosts. In this study, we propose a novel organic cathode design strategy with a bifunctional potential region. This polymeric Zn2+ host combines the conjugated polyaniline backbone to tune the molecular surface pH and [Fe(CN)6]3−/4− redox couple for high output voltage and capacity. The polyaniline doped with ferricyanide (PAF) electrode exhibits two forms of charge storage in ZIBs: proton‐assisted Zn2+ doping below 1.2 V (mechanism I), and [Fe(CN)6]3−/4− redox pair above 1.8 V (mechanism II). Density functional theory calculations and in situ pH experiments demonstrated that the H+ doping process of mechanism I forms a localized pH regulation on the molecular chain surface, providing a favorable reaction environment for mechanism II. The Zn‐polymer battery delivered an outstanding discharge capacity (405.2 mAh g−1) and high output voltage (1.8 V) in the Zn(CF3SO3)2 electrolyte. This study provides a new route for enhancing the structural stability of electrodes and overcoming the electrolyte limitations of ferricyanide in weakly acidic electrolytes.
A High‐Yielding Active Template Click Reaction (AT−CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops
Authors: May James H. , Fehr Julia M. , Lorenz Jacob C. , Zakharov Lev N. , Jasti Ramesh
Published: February 2024

Mechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments—[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles—may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal‐ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu‐catalyzed azide‐alkyne cycloaddition (AT−CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2′‐bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT−CuAAC reaction to provide [2]rotaxanes in near‐quantitative yield, which can then be converted into the fully π‐conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3‐triazole moiety replacing one phenylene ring in the [n]CPP backbone).
Orienting Group Directed Cascade Borylation for Efficient One‐Shot Synthesis of 1,4‐BN‐Doped Polycyclic Aromatic Hydrocarbons as Narrowband Organic Emitters
Authors: Wu Lin , Huang Zhongyan , Miao Jingsheng , Wang Shuni , Li Xinyao , Li Nengquan , Cao Xiaosong , Yang Chuluo
Published: February 2024

1,4‐BN‐doped polycyclic aromatic hydrocarbons (PAHs) have emerged as very promising emitters in organic light‐emitting diodes (OLEDs) due to their narrowband emission spectra that may find application in high‐definition displays. While considerable research has focused on investigating the properties of these materials, less attention has been placed on their synthetic methodology. Here we developed an efficient synthetic method for 1,4‐BN‐doped PAHs, which enables sustainable production of narrowband organic emitting materials. By strategically introducing substituents, such as methyl, tert‐butyl, phenyl, and chloride, at the C5 position of the 1,3‐benzenediamine substrates, we achieved remarkable regioselective borylation in the para‐position of the substituted moiety. This approach facilitated the synthesis of a diverse range of 1,4‐BN‐doped PAHs emitters with good yields and exceptional regioselectivity. The synthetic method demonstrated excellent scalability for large‐scale production and enabled late‐stage transformation of the borylated products. Mechanistic investigations provided valuable insights into the pivotal roles of electron effect and steric hindrance effect in achieving highly efficient regioselective borylation. Moreover, the outstanding device performance of the synthesized compounds 10 b and 6 z, underscores the practicality and significance of the developed method.
Catalytic and Base‐free Suzuki‐type α‐Arylation of Cyclic 1,3‐Dicarbonyls via a Cyclic Iodonium Ylide Strategy
Authors: Liang Mingxuan , He Mengling , Zhong Zhiqing , Wan Bei , Du Qingfeng , Mai Shaoyu
Published: February 2024

To date, it remains challenging to achieve a general and catalytic α‐arylation of cyclic 1,3‐dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3‐dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium‐catalyzed α‐arylation with arylboronic reagents via carbene coupling. This approach is mild, operationally simple, base‐free, biocompatible, and exhibits broad substrate scope (>100 examples), especially with respect to various heteroaromatic 1,3‐dicarbonyls and ortho‐substituted or base‐sensitive arylboronic acids. Importantly, owing to the excellent compatibility with various arylboronic acids or boronate esters (ArBpin, ArBneop, or ArBF3K), this method allows the late‐stage installation of heterocyclic 1,3‐dicarbonyl motifs in highly complex settings. The utility of this transformation is further demonstrated through significantly simplifying the synthesis of several bioactive molecules and natural products.
Synthesis ofC21‐C41fragment of the reported structure ofNeaumycin B
Authors: Choi Eun Gyeong , Kim Eun Bi , Lee Duck Hyung
Published: February 2024

Stereoselective synthesis of the C21‐C41fragment4of the reported structure of Neaumycin B(1), a 28‐membered macrolide compound with 19‐chiral centers and 6,6‐spiroketal structure, has been described. C21‐C27fragment5was synthesized from the commercially available(S)‐Roche ester7using stereoselective allylation and Brownanti‐crotylation as key steps. C28‐C41fragment6was constructed from chiral oxazolidinone auxiliary13using Evanssyn‐aldol reaction, diastereoselective epoxidation, and(S)‐CBS reduction as key steps. Finally, boron‐mediated acetate aldol reaction of5and6led to the synthesis of C21‐C41fragment4for the reported structure of Neaumycin B (1).
Correlation of GABA+ levels in the medial prefrontal cortex and circulating follicular helper T cells in neuromyelitis optica spectrum disorder patients with cognitive impairment
Authors: Duan Yinghui , Rui Qianyun , Yang Yang , Tian Jingluan , Cao Shugang , Zhu Feng , Duan Xiaoyu , Gao Hanqing , Ji Xiaopei , Xiao Xinyi , Li Yonggang , Xue Qun
Published: February 2024

Background

Neuromyelitis optica spectrum disorder (NMOSD) associated with cognitive impairment (CI) is acknowledged. However, the underlying pathogenesis and involvement of the immune system remain unclear.

Objectives

This study aimed to investigate the alterations in immune cells, cytokines, and GABA+ levels in NMOSD patients with cognitive deficits.

Methods

Thirty‐eight NMOSD patients and 38 healthy controls (HCs) were included. NMOSD patients were stratified as NMOSD‐CI and NMOSD‐CP groups. The difference in cognitive functions, Tfh and cytokines, and GABA+ levels were assessed, and their correlations were calculated.

Results

NMOSD‐CI patients showed worse performance on all cognitive tests, and the percentage of circulating follicular helper T cells (cTfh) was significantly elevated. The frequency of cTfh was positively and negatively correlated with Stroop‐A and AVLT long‐delayed scores, respectively. IL‐21 was remarkably higher in NMOSD‐CI and NMOSD‐CP. The level of GABA+ in medial prefrontal cortex (mPFC) was significantly decreased in NMOSD‐CI and was proved positively and negatively correlated with Symbol Digit Modalities Test and the frequency of circulating Tfh cells, respectively.

Conclusion

In NMOSD‐CI patients, all cognitive domains were impacted, , while GABA+ levels in mPFC were decreased. GABA+ levels in NMOSD‐CI were negatively correlated with the frequency of cTfh, suggesting the underlying coupling mechanism between immune responses and neurotransmitter metabolism in CI in NMOSD patients.
Urolithin a Partially Protects against Oxidative Damage Induced for Microcistyn‐lr in C6 Cells
Authors: Von Sulzback Brasil Allana , Castro Caurio Aline , Ramos Boldori Jean , Rosa Rodrigues Nathane , Schmidt Luana , Casagrande Denardin Cristiane , Rossini Augusti Paula
Published: February 2024

Microcystin‐LR (MIC–LR) is a toxin which the mechanism of intoxication involves oxidative stress. Urolithin A (URO‐A) is a metabolic product from the colonic fermentation of ellagic acid with antioxidant potential. This study aimed to evaluate the putative protective effect of URO‐A against MIC–LR toxicity in C6 cells. C6 cells were incubated with MIC–LR (1 and 10 μM) and/or URO‐A (3, 30, 60 and 100 μM) for 24 h. MIC–LR induced reactive species (RS) generation, depletion of total thiol (SH) groups, and survival loss when compared with the control group. Also, at 10 μM, MIC–LR induced CAT activity inhibition. URO‐A caused CAT activity inhibition and showed a trend to increase RS generation (60 and 100 μM) per se. URO‐A at 3 μM completely attenuated the RS generation and the impairment in SH groups caused by MIC–LR. Our results demonstrated that URO‐A might offer a protective effect against toxicity caused by MIC–LR in glial cells by restoring the levels of RS and thiol groups.
Drug‐coated balloon therapy for in‐stent restenosis in patients with iliofemoral deep vein thrombosis: A single‐arm observational study
Authors: Lei Jiahao , Pu Hongji , Zhang Linjie , Zeng Chenlin , Peng Zhaoxi , Wu Zhaoyu , Jiang Yihong , Wang Ruihua , Lu Xinwu
Published: February 2024

Background

Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in‐stent restenosis (ISR) has become an emerging non‐negligible problem.

Methods

To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug‐coated balloon (DCB) on venous ISR lesions, we conducted a single‐center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel‐coated balloon dilatation.

Results

We found a collagen‐rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow‐up (p < 0.0001). During follow‐up, the VEINES‐QOL scores (p < 0.0001), VEINES‐Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed.

Conclusions

The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.
Classic pyoderma gangrenosum
Authors: Prete Marcella , Racanelli Vito , Leone Patrizia , Favoino Elvira , Perosa Federico
Published: February 2024

Key Clinical Message

Pyoderma gangrenosum is a rare inflammatory ulcerative skin disease of unknown etiology. We report an image of a patient with pyoderma gangrenosum who presented right leg ulcers with violaceous margins, histologically characterized by mono‐ and polynuclear cell infiltrates. The patient was successfully treated with cyclosporin A.
The explore/exploit trade‐off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders
Authors: Hagan Kelsey E. , Aimufua Ivieosa , Haynos Ann F. , Walsh B. Timothy
Published: February 2024

The explore/exploit trade‐off is a decision‐making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non‐human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision‐making and psychopathology through the explore/exploit trade‐off. In this article, we propose that explore/exploit trade‐off holds promise for advancing our mechanistic understanding of decision‐making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision‐making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade‐off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision‐making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision‐making in psychopathology. Additionally, understanding explore/exploit decision‐making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy.

Public Significance Statement

The explore/exploit trade‐off is a cross‐species decision‐making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision‐making can promote disordered eating and present preliminary data. We propose that explore/exploit trade‐off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.
An Aspergillus flavus strain from bee bread of the Western honey bee (Apis mellifera) displays adaptations to distinctive features of the hive environment
Authors: Bush Daniel S. , Calla Bernarda , Berenbaum May R.
Published: February 2024

Aspergillus fungi are ubiquitous inhabitants of colonies of the western honey bee (Apis mellifera), where they interact with bees in associations ranging from parasitism to possible mutualism. Aspergillus Flavi fungi are frequently found in bee bread (pollen processed for longterm storage) and are thought to contribute to food preparation, processing, preservation, and digestion. Conditions in the hive are challenging for fungi due, in part, to xeric and acidic properties of bee bread and the omnipresence of propolis, an antimicrobial product manufactured by bees from plant resins. We used quantitative and qualitative assays to determine whether A. flavus isolated from bee bread demonstrates tolerance for hive environmental conditions in terms of temperature, pH, osmotic pressure, and propolis exposure. Comparisons made use of three strains of A. flavus: a fungal biocontrol product not known from beehives (AF36), a strain isolated from bee bread (AFBB) in hives from central Illinois, and a pathogenic strain from a honey bee colony displaying symptoms of stonebrood (AFPA). Strain AFBB displayed higher tolerance of acidic conditions, low matric potential (simulating xeric substrate), and propolis exposure than did other strains. A genomic comparison between this new strain and the reference NRRL‐3357 showed that AFBB, like AF36, might be blocked from carrying out aflatoxin biosynthesis. Sequence comparisons also revealed several missense variants in genes that encode proteins regulating osmotolerance and osmotic pressure in Aspergillus spp., including SakA, SskB, GfdA, and TcsB/Sln1. Collectively, results of our laboratory assays and genetic analyses are consistent with the suggestion that the strain isolated from bee bread is adapted to the bee bread environment and may have persisted due to a coevolutionary relationship between Aspergillus and A. mellifera. This finding bolsters recent concerns about the effects of fungicide use near bee colonies and broadens the ecological importance of highly adaptable fungal strains.
Exploring the impact of cold plasma treatment on the antioxidant capacity, ascorbic acid, phenolic profile, and bioaccessibility of fruits and fruit juices
Authors: Zargarchi Sina , Hornbacher Johann , Afifi Sherif M. , Saremnezhad Solmaz , Günal‐Köroğlu Deniz , Capanoglu Esra , Esatbeyoglu Tuba
Published: February 2024

In recent years, cold plasma (CP) has emerged as a promising preservation technology for fruit products. Several CP sources include dielectric barrier discharge, plasma jets, corona discharges, micro‐discharges, glow discharges, and gliding arc discharges. However, the effects of these different types of CP on the chemical compounds of fruits and juices are not fully understood. In this review, we summarize (I) the current knowledge on the use of CP for the preservation and processing of fruits and juices; (II) the diverse types of CP sources and explore their applications within a scientific context; (III) the physicochemical transformations that take place in fruits and juices following CP treatment; and (IV) the changes observed in antioxidant activity, vitamin C content, phenolic compounds, and their bioaccessibility. Numerous studies have explored CP's influence on microbial contamination, shelf life, enzymes, and various physicochemical changes. This review uniquely centers its attention on the impact of CP on bioactive phenolic compounds, their bioaccessibility, vitamin C content, and antioxidant activity in different types of fruits and fruit juices. Additionally, this review delves into the assessment of selected sensory properties, notably color, which is an important parameter for consumer acceptance. By focusing on these particular aspects, we aim to provide a targeted and comprehensive analysis of CP's effects on essential nutritional and quality attributes of fruits and fruit juices, distinct from the broader spectrum covered in the existing literature.
Correlation of Hydrogen and Methane Production to Rice Carbohydrate Malabsorption In Burmese (Myanmar) Children
Authors: Bolin T. D. , Myo‐Khin  , Soe‐Aung  , Genge J. R. , Duncombe V. M.
Published: February 2024

Rice carbohydrate malabsorption is common in Burmese village children and adults and may contribute to diminished growth. Its diagnosis depends on a rice breath hydrogen test, which has limitations. Almost 20% of Burmese children under age 5 produce methane, compared with less than 7% of children in Africa and Hong Kong. If an increased carbohydrate load in the colon due to rice malabsorption provides increased substrate for methanogenic bacteria in the left colon, higher fasting breath methane concentrations might be a simpler method of diagnosing rice malabsorption. We tested breath hydrogen and methane over a 4‐h period and did anthropometric measurements in 142 subjects, 79 children, and 63 adults. Seventy percent of children were rice‐malabsorbers. Methane production occurred in 20% of children under 5 years of age and increased to 60% of adults. There is an association of rice malabsorption with reduced length. There was not correlation between rice malabsorption and breath methane, and the concentration of breath methane does not, therefore, indicate rice absorption status and cannot replace rice breath hydrogen tests.
Thiamine, Riboflavin, Folate, and Vitamin B12 Status of Infants with Low Birth Weights Receiving Enteral Nutrition
Authors: Friel James K. , Andrews Wayne L. , Long David R. , Herzberg Gene , Levy Ryna
Published: February 2024

The purpose of the present study was to monitor the vitamin status of 14 low‐birth‐weight (LBW) infants (<1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 μg/100 kcal thiamine, 617 μg/100 kcal riboflavin, 37 μg/100 kcal folate, and 0.55 μg/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 ± 259 g, and mean gestational age was 29 ± 2 weeks. Weekly blood, 24‐h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 μg/100 kcal thiamine and 370 μg/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 ± 11 ng/ml at 2 weeks and 18 ± 5 ng/ml at 3 weeks. RBC folate levels were 455 ± 280 ng/ml at 2 weeks and 391 ± 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 ± 394 pg/ml at 2 weeks and 768 ± 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive.
Increase in Density of Jejunal IgA2 Cells during Infancy without Change in IgA1 Cells
Authors: Hacsek Gabor , Savilahti Erkki
Published: February 2024

To determine any association between densities of cells containing IgA, IgA1, IgA2, IgG, and IgM in the lamina propria of the jejunum and the age of the individual, we restudied 65 specimens from 65 patients in the age range 66 days to 4 years. Indications for jejunal biopsy were minor symptoms; none of the patients had any gastrointestinal disease, and the specimens showed normal morphology. We used murine anti‐human monoclonal antibodies to IgA, IgA1, IgA2, IgG, and IgM and an indirect immunoperoxidase method and found a significant increase with advancing age in the densities of cells containing IgA, IgA2, and IgG, whereas the densities of IgA1‐ and IgM‐positive cells did not change with age. Densities of IgA2 and IgG cells in children over 1 year were significantly greater than in infants under 9 months (upper vs. lower quartile of the study group, p < 0.05 in both comparisons). In the jejunum, an increase in IgA2 cells was responsible for the increase in total IgA production for the age range studied.
Nutritional Status in Untreated Children with Acute Leukemia as Compared with Children without Malignancy
Authors: Uderzo Cornelio , Rovelli Attilio , Bonomi Massimo , Barzaghi Anna , Strada Simona , Balduzzi Adriana , Pirovano Letizia , Masera Giuseppe
Published: February 2024

We evaluated the nutritional status of 173 consecutive children with newly diagnosed leukemia compared with that of 307 children with benign acute diseases. Nutritional status was assessed by anthropometric measurements including weight, height, weight for height, midarm circumference (MAC) and triceps skinfold (TSF), and by biochemical indices, in particular prealbumin (TBPA) and retinol‐binding protein (RBP). On admission, no significant differences were found between groups in weight, height, weight for height, MAC, and TSF values. TBPA and RBP, lower than normal in most cases, were not significantly different in the two groups. Furthermore, no differences were observed when children with high‐risk leukemia were compared with those at standard risk. In conclusion, children with newly diagnosed leukemia do not seem to present significant nutritional depletion, and their nutritional status is similar to that of children admitted for other nonmalignant acute diseases. However, nutritional indices should be monitored in children with high‐risk leukemia because treatment intensity is likely to result in a malnutritional status later, which might be prevented by early adequate nutritional support.
Growth Hormone Insensitivity in Children with Biliary Atresia
Authors: Bucuvalas John C. , Horn Jo Ann , Slusher Joyce , Alfaro Mary Pat , Chernausek Steven D.
Published: February 2024

Malnutrition is a critical predictor of mortality and morbidity in children with biliary atresia who undergo orthotopic liver transplantation. Growth hormone (GH) enhances nitrogen retention in patients with chronic obstructive lung disease, sepsis, and in fasted adult volunteers. The goal of this study was to assess the acute response to recombinant human GH (rhGH) treatment in children with biliary atresia to determine whether GH therapy was likely to improve pretransplant nutritional status. Five children, aged 10‐32 months, with biliary atresia and persistent cholestasis despite surgical attempts to reestablish bile flow, were studied. All five children had portal hypertension, conjugated hyperbilirubinemia, and decreased serum albumin concentrations. Length, weight, and growth velocity were decreased in all five children. Despite adequate energy and protein intake, fat stores were depleted in all five subjects, and somatic protein stores were diminished in all except one child. Baseline serum concentrations of insulin‐like growth factor‐1 (IGF‐1) and IGF‐binding protein‐3 (IGFBP‐3) were low (8.4 ± 2 ng/ml and 0.2 ± 0.1 mg/l respectively). In the four children who completed the study, serum IGF‐I and IGFBP‐3 levels did not change after treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings indicate that children with biliary atresia awaiting liver transplantation are insensitive to GH and that treatment with GH is unlikely to promote anabolism. A rationale exists for examining the effect of treatment with IGF‐I, which mediates the anabolic effects of GH.