bluuebunny/crossref_metadata_2025_split huggingface dataset:
UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology
Authors: Mondal Milon , Conole Daniel , Nautiyal Jaya , Tate Edward W. 
Published: September 2021

AbstractBreast cancer has the highest incidence and death rate among cancers in women worldwide. In particular, metastatic estrogen receptor negative (ER–) breast cancer and triple-negative breast cancer (TNBC) subtypes have very limited treatment options, with low survival rates. Ubiquitin carboxyl terminal hydrolase L1 (UCHL1), a ubiquitin C-terminal hydrolase belonging to the deubiquitinase (DUB) family of enzymes, is highly expressed in these cancer types, and several key reports have revealed emerging and important roles for UCHL1 in breast cancer. However, selective and potent small-molecule UCHL1 inhibitors have been disclosed only very recently, alongside chemical biology approaches to detect regulated UHCL1 activity in cancer cells. These tools will enable novel insights into oncogenic mechanisms driven by UCHL1, and identification of substrate proteins deubiquitinated by UCHL1, with the ultimate goal of realising the potential of UCHL1 as a drug target in breast cancer.
PRMT7 targets of Foxm1 controls alveolar myofibroblast proliferation and differentiation during alveologenesis
Authors: He Huacheng , Chen Jilin , Zhao Jian , Zhang Peizhun , Qiao Yulong , Wan Huajing , Wang Jincheng , Mei Mei , Bao Shilai , Li Qiuling 
Published: September 2021

AbstractAlthough aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. In PRMT7-deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin of Foxm1 to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression of Foxm1 in isolated myofibroblasts (MYFs) significantly rescued PRMT7-deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activates Foxm1 transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases.
Smoking shifts human small airway epithelium club cells toward a lesser differentiated population
Authors: Rostami Mahboubeh R. , LeBlanc Michelle G. , Strulovici-Barel Yael , Zuo Wulin , Mezey Jason G. , O’Beirne Sarah L. , Kaner Robert J. , Leopold Philip L. , Crystal Ronald G. 
Published: September 2021

AbstractThe club cell, a small airway epithelial (SAE) cell, plays a central role in human lung host defense. We hypothesized that subpopulations of club cells with distinct functions may exist. The SAE of healthy nonsmokers and healthy cigarette smokers were evaluated by single-cell RNA sequencing, and unsupervised clustering revealed subpopulations of SCGCB1A1+KRT5loMUC5AC− club cells. Club cell heterogeneity was supported by evaluations of SAE tissue sections, brushed SAE cells, and in vitro air–liquid interface cultures. Three subpopulations included: (1) progenitor; (2) proliferating; and (3) effector club cells. The progenitor club cell population expressed high levels of mitochondrial, ribosomal proteins, and KRT5 relative to other club cell populations and included a differentiation branch point leading to mucous cell production. The small proliferating population expressed high levels of cyclins and proliferation markers. The effector club cell cluster expressed genes related to host defense, xenobiotic metabolism, and barrier functions associated with club cell function. Comparison of smokers vs. nonsmokers demonstrated that smoking limited the extent of differentiation of all three subclusters and altered SAM pointed domain-containing Ets transcription factor (SPDEF)-regulated transcription in the effector cell population leading to a change in the location of the branch point for mucous cell production, a potential explanation for the concomitant reduction in effector club cells and increase in mucous cells in smokers. These observations provide insights into both the makeup of human SAE club cell subpopulations and the smoking-induced changes in club cell biology.
Use of a small molecule integrin activator as a systemically administered vaccine adjuvant in controlling Chagas disease
Authors: Lokugamage Nandadeva , Chowdhury Imran H. , Biediger Ronald J. , Market Robert V. , Khounlo Sayadeth , Warier Navin D. , Hwang Shen-An , Actor Jeffrey K. , Woodside Darren G. , Marathi Upendra , Vanderslice Peter , Garg Nisha Jain 
Published: September 2021

AbstractThe development of suitable safe adjuvants to enhance appropriate antigen-driven immune responses remains a challenge. Here we describe the adjuvant properties of a small molecule activator of the integrins αLβ2 and α4β1, named 7HP349, which can be safely delivered systemically independent of antigen. 7HP349 directly activates integrin cell adhesion receptors crucial for the generation of an immune response. When delivered systemically in a model of Chagas disease following immunization with a DNA subunit vaccine encoding candidateT. cruziantigens, TcG2 and TcG4, 7HP349 enhanced the vaccine efficacy in both prophylactic and therapeutic settings. In a prophylactic setting, mice immunized with 7HP349 adjuvanted vaccine exhibited significantly improved control of acute parasite burden in cardiac and skeletal muscle as compared to vaccination alone. When administered with vaccine therapeutically, parasite burden was again decreased, with the greatest adjuvant effect of 7HP349 being noted in skeletal muscle. In both settings, adjuvantation with 7HP349 was effective in decreasing pathological inflammatory infiltrate, improving the integrity of tissue, and controlling tissue fibrosis in the heart and skeletal muscle of acutely and chronically infected Chagas mice. The positive effects correlated with increased splenic frequencies of CD8+T effector cells and an increase in the production of IFN-γ and cytolytic molecules (perforin and granzyme) by the CD4+and CD8+effector and central memory subsets in response to challenge infection. This demonstrates that 7HP349 can serve as a systemically administered adjuvant to enhance T cell-mediated immune responses to vaccines. This approach could be applied to numerous vaccines with no reformulation of existing stockpiles.
Cells of the human intestinal tract mapped across space and time
Authors: Elmentaite Rasa , Kumasaka Natsuhiko , Roberts Kenny , Fleming Aaron , Dann Emma , King Hamish W. , Kleshchevnikov Vitalii , Dabrowska Monika , Pritchard Sophie , Bolt Liam , Vieira Sara F. , Mamanova Lira , Huang Ni , Perrone Francesca , Goh Kai’En Issac , Lisgo Steven N. , Katan Matilda , Leonard Steven , Oliver Thomas R. W. , Hook C. Elizabeth , Nayak Komal , Campos Lia S. , Domínguez Conde Cecilia , Stephenson Emily , Engelbert Justin , Botting Rachel A. , Polanski Krzysztof , van Dongen Stijn , Patel Minal , Morgan Michael D. , Marioni John C. , Bayraktar Omer Ali , Meyer Kerstin B. , He Xiaoling , Barker Roger A. , Uhlig Holm H. , Mahbubani Krishnaa T. , Saeb-Parsy Kourosh , Zilbauer Matthias , Clatworthy Menna R. , Haniffa Muzlifah , James Kylie R. , Teichmann Sarah A. 
Published: September 2021

AbstractThe cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
Authors: Shaikh Ambreen , Sriraman Kalpana , Vaswani Smriti , Oswal Vikas , Rao Sudha , Mistry Nerges 
Published: September 2021

AbstractEffective treatment reduces a tuberculosis patient's ability to infect others even before they test negative in sputum or culture. Currently, the basis of reduced infectiousness of the Mycobacterium tuberculosis (Mtb) with effective treatment is unclear. We evaluated changes in aerosolized bacteria expelled by patients through a transcriptomic approach before and after treatment initiation (up to 14 days) by RNA sequencing. A distinct change in the overall transcriptional profile was seen post-treatment initiation compared to pretreatment, only when patients received effective treatment. This also led to the downregulation of genes associated with cellular activities, cell wall assembly, virulence factors indicating loss of pathogenicity, and a diminished ability to infect and survive in new host cells. Based on this, we identified genes whose expression levels changed with effective treatment. The observations of the study open up avenues for further evaluating the changes in bacterial gene expression during the early phase of treatment as biomarkers for monitoring response to tuberculosis treatment regimens and provide means of identifying better correlates of Mtb transmission.
Diagnostic accuracy of ultrasound-guided core needle biopsy versus incisional biopsy in soft tissue sarcoma: an institutional experience
Authors: Cernakova Miroslava , Hobusch Gerhard M. , Amann Gabriele , Funovics Philipp T. , Windhager Reinhard , Panotopoulos Joannis 
Published: September 2021

AbstractCore needle biopsy (CNB) is gaining in importance due to its advantages in the matter of patient morbidity, time and cost. Nevertheless, controversies still exist regarding the biopsy technique of choice for the accurate diagnosis of soft tissue sarcoma (STS). This retrospective cohort study compared the diagnostic performance between ultrasound-guided CNB and incisional biopsy (IB), both performed by orthopedic surgeons. The aims of the study were to answer the following questions: (1) Is ultrasound-guided CNB a highly reliable modality for diagnosing STSs? (2) Is CNB equally useful to IB for identifying histologic subtype? (3) Had patients who underwent CNB a reduced risk of complications? One-hundred and fifty-three patients who underwent resection of soft tissue sarcoma were classified into two groups according to biopsy technique prior to surgery; CNB group (n = 95) and IB group (n = 58). The final surgical specimens were in 40 patients liposarcoma (myxoid, pleomorphic and dedifferentiated), 39 undifferentiated pleomorphic sarcoma (UPS), 33 myxofibrosarcoma, 10 synovial sarcoma, 10 leiomyosarcoma and in the remaining 21 patients different soft tissue sarcoma entities. Sarcoma location of 71 patients was in the thigh, 19 in the lower leg, 22 in the upper arm and shoulder area; 10 in the knee and gluteal region, 9 in the thoracic region, the residual 12 in other body areas. Malignancy was correctly diagnosed in 87% (83 of 95) for the CNB group and 93% (54/58) for the IB group. Correct identification rate of histologic subtype was 80% (76 of 95) in the CNB group and 83% (48 of 58) in the IB group. There were no significant differences in the correct diagnosis rates of malignancy and subtype between the two techniques. No complications were seen in the CNB group, whereas 2 patients in whom IB was performed developed pulmonary embolism and 1 patient surgical site infection. Ultrasound-guided CNB is highly accurate and not inferior to IB in diagnosing the dignity of lesions and histologic subtype in patients with suspected STSs.
Mechanism of charge accumulation of poly(heptazine imide) gel
Authors: Seo Goichiro , Saito Yuki , Nakamichi Miyu , Nakano Kyohei , Tajima Keisuke , Kanai Kaname 
Published: September 2021

AbstractPhoto-stimuli response in materials is a fascinating feature with many potential applications. A photoresponsive gel of poly(heptazine imide), PHI, termed PHIG, exhibits photochromism, photoconductivity, and photo-induced charge accumulation, and is generated using ionic liquids and PHI. Although there are several examples of ionic liquid gels that exhibit photochromism and photoconductivity, this is the first report of an ionic liquid gel that exhibits both these properties as well as charge accumulation. We conducted experimental and theoretical investigations to understand the mechanism of the photostimulus response of PHIG, especially charge accumulation. The proposed model explains both the mechanism of charge accumulation and dark photocatalysis by PHI and provides new concepts in the field of photofunctional materials.
Analysis of the forced convection of two-phase Ferro-nanofluid flow in a completely porous microchannel containing rotating cylinders
Authors: Aghamiri Hamidreza , Niknejadi Mohammadreza , Toghraie Davood 
Published: September 2021

AbstractIn the present work, the forced convection of nanofluid flow in a microchannel containing rotating cylinders is investigated in different geometries. The heat flux applied to the microchannel wall is 10,000 W m−2. The effects of Reynolds number, the volume fraction of nanoparticles, and the porosity percentage of the porous medium are investigated on the flow fields, temperature, and heat transfer rate. Reynolds number values vary from Re = 250–1000, non-dimensional rotational velocities 1 and 2, respectively, and volume fraction of nanoparticles 0–2%. The results show that increasing the velocity of rotating cylinders increases the heat transfer; also, increasing the Reynolds number and volume fraction of nanoparticles increases the heat transfer, pressure drop, and Cf,ave. By comparing the porosity percentages with each other, it is concluded that due to the greater contact of the nanofluid with the porous medium and the creation of higher velocity gradients, the porosity percentage is 45% and the values of are 90% higher than the porosity percentage. Comparing porosity percentages with each other, at porosity percentage 90% is greater than at porosity percentage 45%. On the other hand, increasing the Reynolds number reduces the entropy generation due to heat transfer and increases the entropy generation due to friction. Increasing the volume fraction of nanoparticles increases the entropy generations due to heat transfer and friction.
Organochlorine pesticide residues in plants and their possible ecotoxicological and agri food impacts
Authors: Chandra Rachna , Sharpanabharathi N. , Prusty B. Anjan Kumar , Azeez P. A. , Kurakalva Rama Mohan 
Published: September 2021

AbstractScientific investigations on levels of Organochlorine Pesticide (OCP) residues in plants largely consider the edible parts (crops, vegetables, and fruit plants). Though the non-edible parts of plants are not eaten by human beings directly, these parts are consumed by livestock and other animals, thereby facilitating the flow of chemical residues through the food chain. The objective of the present investigation was to evaluate the concentration of OCP residues in non-edible plant parts to provide insights on their potential ecotoxicological impacts. Eighteen OCP residues were extracted in nine different plant species (banana Musa acuminate, brinjal Solanum melongena, Casuarina equisetifolia, Eucalyptus globulus, lotus Nelumbo nucifera, paddy Oryza sativa, sugarcane Saccharum officinarum, tapioca Manihot esculenta, tomato Lycopersicon esculentum) following QuEChERS method. The concentrations of OCP residues in plant extracts were determined using Gas Chromatography coupled with Mass Spectrometry (GC–MS). The OCP residues, namely: γ-HCH (lindane), heptachlor epoxide isomer, dieldrin, endrin, endrin aldehyde and endrin ketone were found predominantly in seven plant species. Residues of γ-HCH (lindane) were reported in different parts of plant species such as stem (581.14 ng/g in paddy and 585.82 ng/g in tapioca) and leaf (583.3 ng/g in tomato). Seven samples contained residues of heptachlor epoxide isomer (512.53 to 1173.8 ng/g). Dieldrin was found in paddy stem (489.97 ng/g), tapioca stem (490.21 ng/g) and tapioca leaf (490.32 ng/g). The detected OCPs in the present study were 10–50 times higher than the Maximum Residue Limits (MRL, 0.01–0.1 mg/Kg) as prescribed in the Codex Alimentarius of the FAO/WHO. Their elevated concentrations in the plant parts therefore pose risk of contamination to the consumers in the food chain, including human beings those are dependent on the animals as source of protein. The findings of this study are the first report on residue levels of OCPs in non-edible plant parts in the agricultural landscape of Puducherry region, India. Since, this study assumes significance for the strategic location of Oussudu Lake, an interstate lake spread over Puducherry and Tamil Nadu states, regular monitoring of OCP residues in different environmental segments in strategic locations in both the states is suggested, which will help the authorities in devising a comprehensive environmental management plan aiming at the ecosystem at large.
Impact of extreme (flat and steep) keratometry on the safety and efficacy of small incision lenticule extraction (SMILE)
Authors: Luft Nikolaus , Siedlecki Jakob , Reinking Franziska , Mayer Wolfgang J. , Schworm Benedikt , Kassumeh Stefan , Priglinger Siegfried G. , Dirisamer Martin 
Published: September 2021

AbstractLittle is known about the connection between preoperative keratometry and postoperative results of myopic small-incision lenticule extraction (SMILE). To determine the influence of extreme (flat and steep) corneal keratometry on the safety and efficacy of SMILE, the databases of the Department of Ophthalmology, Ludwig-Maximilians-University Munich, Germany, and SMILE Eyes Linz, Austria, were screened for patients with steep and flat keratometry who had undergone SMILE. In this cross-sectional matched comparative cohort study, eyes with markedly flat (< 42.0 diopters; D) or steep (≥ 47.0D) preoperative corneal keratometry were matched to a cohort of eyes with regular keratometry (42.0–46.9D) by preoperative manifest refractive spherical equivalent and cylinder, age, corrected distance visual acuity and surgical SMILE parameters. The standardized graphs and terms for refractive surgery results were applied to compare the three groups. Changes in higher order aberrations (HOAs) were evaluated on Scheimpflug imaging. In total, 63 eyes (21 each) of 54 patients with a mean refractive spherical equivalent of  − 5.21 ± 1.59 D were followed up for a mean of 9.2 ± 6.1 (minimum ≥ 3) months. Mean baseline keratometry was 41.3 ± 0.7D (flat), 45.5 ± 1.0D (regular) and 47.7 ± 0.6D (steep) (p < 0.0001). Compared to the regular group, the flat and the steep cornea group resulted in a non-inferior percentage of eyes within ± 0.50 D of target refraction (p = 0.20), uncorrected distance visual acuity (p = 0.95) and corrected distance visual acuity (p = 0.20). Flat corneas however experienced a stronger induction of spherical aberration (SA) compared to the steep group (p = 0.0005). In conclusion, non-inferior outcomes of SMILE can also be expected in eyes with steep (≥ 47D) or flat (< 42D) preoperative keratometry, while SMILE however induces more SA in eyes with a flat keratometry.
Polarization insensitivity characterization of dual-band perfect metamaterial absorber for K band sensing applications
Authors: Hakim Mohammad Lutful , Alam Touhidul , Almutairi Ali F. , Mansor Mohd Fais , Islam Mohammad Tariqul 
Published: September 2021

AbstractPolarization insensitive metamaterial absorbers (MA) are currently very attractive due to their unique absorption properties at different polarization angles. As a result, this type of absorber is widely used in sensing, imaging, energy harvesting, etc. This paper presents the design and characterization of a dual-band polarization-insensitive metamaterial absorber (MA) for K-band applications. The metamaterial absorber consists of two modified split ring resonators with an inner cross conductor to achieve a 90% absorption bandwidth of 400 MHz (21.4–21.8 GHz) and 760 MHz (23.84–24.24 GHz) at transverse electromagnetic (TEM), transverse electric (TE), and transverse magnetic (TM) mode. Polarization insensitivity of different incident angles for TE and TM mode is also investigated, which reveals a similar absorption behavior up to 90°. The metamaterial structure generates single negative (SNG) property at a lower frequency of 21.6 GHz and double negative property (DNG) at an upper frequency of 24.04 GHz. The permittivity and pressure sensor application are investigated for the proposed absorber, which shows its useability in these applications. Finally, a comparison with recent works is also performed to demonstrate the feasibility of the proposed structure for K band application, like sensor, filter, invasive clock, etc.
A multi‐agent system for itinerary suggestion in smart environments
Authors: De Paola Alessandra , Gaglio Salvatore , Giammanco Andrea , Lo Re Giuseppe , Morana Marco 
Published: September 2021

AbstractModern smart environments pose several challenges, among which the design of intelligent algorithms aimed to assist the users. When a variety of points of interest are available, for instance, trajectory recommendations are needed to suggest users the most suitable itineraries based on their interests and contextual constraints. Unfortunately, in many cases, these interests must be explicitly requested and their lack causes the so‐called cold‐start problem. Moreover, lengthy travelling distances and excessive crowdedness of specific points of interest make itinerary planning more difficult. To address these aspects, a multi‐agent itinerary suggestion system that aims at assisting the users in an online and collaborative way is proposed. A profiling agent is responsible for the detection of groups of users whose movements are characterised by similar semantic, spatial and temporal features; then, a recommendation agent leverages contextual information and dynamically associates the current user with the trajectory clusters according to a Multi‐Armed Bandit policy. Framing the trajectory recommendation as a reinforcement learning problem permits to provide high‐quality suggestions while avoiding both cold‐start and preference elicitation issues. The effectiveness of the approach is demonstrated by some deployments in real‐life scenarios, such as smart campuses and theme parks.