bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular structure and transformation of the glucose dehydrogenase gene in Drosophila melanogaster.
Authors: Whetten R , Organ E , Krasney P , Cox-Foster D , Cavener D 
Published: January 2021

Abstract
We have precisely mapped and sequenced the three 5' exons of the Drosophila melanogaster Gld gene and have identified the start sites for transcription and translation. The first exon is composed of 335 nucleotides and does not contain any putative translation start codons. The second exon is separated from the first exon by 8 kb and contains the Gld translation start codon. The inferred amino acid sequence of the amino terminus contains two unusual features: three tandem repeats of serine-alanine, and a relatively high density of cysteine residues. P element-mediated transformation experiments demonstrated that a 17.5-kb genomic fragment contains the functional and regulatory components of the Gld gene.
Capturing the complexity of topologically associating domains through multi-feature optimization
Authors: Sauerwald Natalie , Kingsford Carl 
Published: January 2021

AbstractThe three-dimensional structure of human chromosomes is tied to gene regulation and replication timing, but there is still a lack of consensus on the computational and biological definitions for chromosomal substructures such as topologically associating domains (TADs). TADs are described and identified by various computational properties leading to different TAD sets with varying compatibility with biological properties such as boundary occupancy of structural proteins. We unify many of these computational and biological targets into one algorithmic framework that jointly maximizes several computational TAD definitions and optimizes TAD selection for a quantifiable biological property. Using this framework, we explore the variability of TAD sets optimized for six different desirable properties of TAD sets: high occupancy of CTCF, RAD21, and H3K36me3 at boundaries, reproducibility between replicates, high intra- vs inter-TAD difference in contact frequencies, and many CTCF binding sites at boundaries. The compatibility of these biological targets varies by cell type, and our results suggest that these properties are better reflected as subpopulations or families of TADs rather than a singular TAD set fitting all TAD definitions and properties. We explore the properties that produce similar TAD sets (reproducibility and inter- vs intra-TAD difference, for example) and those that lead to very different TADs (such as CTCF binding sites and inter- vs intra-TAD contact frequency difference).
Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria
Authors: El Rayes Jessica , Szewczyk Joanna , Deghelt Michael , Matagne André , Iorga Bogdan I. , Cho Seung-Hyun , Collet Jean-François 
Published: January 2021

AbstractGram-negative bacteria express structurally diverse lipoproteins in their envelope. Here we found that approximately half of lipoproteins destined to theEscherichia coliouter membrane display an intrinsically disordered linker at their N-terminus. Intrinsically disordered regions are common in proteins, but establishing their importancein vivohas remained challenging. Here, as we sought to unravel how lipoproteins mature, we discovered that unstructured linkers are required for optimal trafficking by the Lol lipoprotein sorting system: linker deletion re-routes three unrelated lipoproteins to the inner membrane. Focusing on the stress sensor RcsF, we found that replacing the linker with an artificial peptide restored normal outer membrane targeting only when the peptide was of similar length and disordered. Overall, this study reveals the role played by intrinsic disorder in lipoprotein sorting, providing mechanistic insight into the biogenesis of these proteins and suggesting that evolution can select for intrinsic disorder that supports protein function.
Neuromyelitis optica spectrum disorder in Asia: Epidemiology and risk factors
Authors: Hor Jyh Yung , Wong Chee Keong , Ew Ju Vern , Idris Syafiq , Tan Hui Jieh , Wong Daniel Yi Jie 
Published: January 2021

AbstractIn Asia, prior to the discovery of aquaporin 4 (AQP4) antibody, many cases of neuromyelitis optica spectrum disorder (NMOSD) were misdiagnosed as multiple sclerosis (MS) or the so‐called opticospinal multiple sclerosis (OSMS). The AQP4 antibody discovery was an important milestone in the field of NMOSD, leading to correct diagnosis and reclassification of NMOSD cases, and the subsequent appropriate therapy. This is especially pertinent in Asia where the prevalence of MS is generally much lower than the Caucasian populations. East Asians have a higher NMOSD prevalence rate (~4/100 000) than Caucasians (~1‐1.5/100 000) and other Asian racial groups (Austronesians: 1.2‐1.5/100 000; South Asians: ~1/100 000; Arabs: ~1‐1.5/100 000). Myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) comprises cases of AQP4‐antibody‐negative NMOSD, optic neuritis, myelitis, and certain unique phenotypes such as cases with acute disseminated encephalomyelitis (ADEM)‐like presentation, and cerebral cortical encephalitis. MOGAD appears not too uncommon among Japanese, Chinese, Sri Lankans and Indians, but data in different Asian populations and geographical locations are needed. There exist some differences in clinical features of NMOSD and MOGAD between Asians and other populations. As for risk factors, genetic studies have identified certain HLA associations with NMOSD among Asians that were different from other populations. North‐South latitudinal gradient as seen in MS was not observed in NMOSD in Japan and China. Seasonal variation and preceding infection are among some risk factors worth further investigations. Population‐based MOGAD study in Asia, and further genetic and environmental studies are useful to further inform the epidemiology and potential pathogenetic mechanism of this unique neuroinflammatory disease.
The development of past and future life stories in adolescence: Overall emotional tone, coherence and life script events
Authors: Ramsgaard Stine B. , Bohn Annette 
Published: January 2021

Research has shown that identity in adolescence takes the shape of a coherent life story that integrates the past with the present self and provides meaning and purpose in the person’s life. One stable feature of narrative identity identified in adults is emotional tone. Here, the development of emotional tone in life stories was investigated across childhood and adolescence. A total of 142 adolescents aged 10 to 14 years wrote about their past weekend, their past and future life stories and generated a cultural life script. Across age groups, adolescents told past life stories that were overall mixed (both positive and negative) or moderately positive in emotional tone, and future life stories that were positive or highly positive. In relation to life story development, we replicated findings on age‐related development of life story coherence in both past and future life stories in 10–14‐year‐olds. Lastly, the study highlights the link between life story coherence and cultural life script abilities. Cultural life script typicality was linked to life story coherence for both past and future life stories and across all age groups, and a majority of events mentioned in future life stories overlapped with cultural life script events.
Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy
Authors: Prokopi Anastasia , Tripp Christoph H , Tummers Bart , Hornsteiner Florian , Spoeck Sarah , Crawford Jeremy Chase , Clements Derek R , Efremova Mirjana , Hutter Katharina , Bellmann Lydia , Cappellano Giuseppe , Cadilha Bruno L , Kobold Sebastian , Boon Louis , Ortner Daniela , Trajanoski Zlatko , Chen Suzie , de Gruijl Tanja D , Idoyaga Juliana , Green Douglas R , Stoitzner Patrizia 
Published: January 2021

BackgroundImmunotherapy with checkpoint inhibitors has shown impressive results in patients with melanoma, but still many do not benefit from this line of treatment. A lack of tumor-infiltrating T cells is a common reason for therapy failure but also a loss of intratumoral dendritic cells (DCs) has been described.MethodsWe used the transgenic tg(Grm1)EPv melanoma mouse strain that develops spontaneous, slow-growing tumors to perform immunological analysis during tumor progression. With flow cytometry, the frequencies of DCs and T cells at different tumor stages and the expression of the inhibitory molecules programmed cell death protein-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells were analyzed. This was complemented with RNA-sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR) analysis to investigate the immune status of the tumors. To boost DC numbers and function, we administered Fms-related tyrosine 3 ligand (Flt3L) plus an adjuvant mix of polyI:C and anti-CD40. To enhance T cell function, we tested several checkpoint blockade antibodies. Immunological alterations were characterized in tumor and tumor-draining lymph nodes (LNs) by flow cytometry, CyTOF, microarray and RT-qPCR to understand how immune cells can control tumor growth. The specific role of migratory skin DCs was investigated by coculture of sorted DC subsets with melanoma-specific CD8+ T cells.ResultsOur study revealed that tumor progression is characterized by upregulation of checkpoint molecules and a gradual loss of the dermal conventional DC (cDC) 2 subset. Monotherapy with checkpoint blockade could not restore antitumor immunity, whereas boosting DC numbers and activation increased tumor immunogenicity. This was reflected by higher numbers of activated cDC1 and cDC2 as well as CD4+ and CD8+ T cells in treated tumors. At the same time, the DC boost approach reinforced migratory dermal DC subsets to prime gp100-specific CD8+ T cells in tumor-draining LNs that expressed PD-1/TIM-3 and produced interferon γ (IFNγ)/tumor necrosis factor α (TNFα). As a consequence, the combination of the DC boost with antibodies against PD-1 and TIM-3 released the brake from T cells, leading to improved function within the tumors and delayed tumor growth.ConclusionsOur results set forth the importance of skin DC in cancer immunotherapy, and demonstrates that restoring DC function is key to enhancing tumor immunogenicity and subsequently responsiveness to checkpoint blockade therapy.
Current status of use of high throughput nucleotide sequencing in rheumatology
Authors: Boegel Sebastian , Castle John C , Schwarting Andreas 
Published: January 2021

ObjectiveHere, we assess the usage of high throughput sequencing (HTS) in rheumatic research and the availability of public HTS data of rheumatic samples.MethodsWe performed a semiautomated literature review on PubMed, consisting of an R-script and manual curation as well as a manual search on the Sequence Read Archive for public available HTS data.ResultsOf the 699 identified articles, rheumatoid arthritis (n=182 publications, 26%), systemic lupus erythematous (n=161, 23%) and osteoarthritis (n=152, 22%) are among the rheumatic diseases with the most reported use of HTS assays. The most represented assay is RNA-Seq (n=457, 65%) for the identification of biomarkers in blood or synovial tissue. We also find, that the quality of accompanying clinical characterisation of the sequenced patients differs dramatically and we propose a minimal set of clinical data necessary to accompany rheumatological-relevant HTS data.ConclusionHTS allows the analysis of a broad spectrum of molecular features in many samples at the same time. It offers enormous potential in novel personalised diagnosis and treatment strategies for patients with rheumatic diseases. Being established in cancer research and in the field of Mendelian diseases, rheumatic diseases are about to become the third disease domain for HTS, especially the RNA-Seq assay. However, we need to start a discussion about reporting of clinical characterisation accompany rheumatological-relevant HTS data to make clinical meaningful use of this data.
Development of arabic sign language dictionary using 3D avatar technologies
Authors: H. Aliwy Ahmed , A. Alethary Ahmed 
Published: January 2021

<span>The arabic sign language (ArSL) is the natural language of the deaf community in Arabic countries. ArSL suffers from a lack of resources such as unified dictionaries and corpora. In this work, a dictionary of Arabic language to ArSL has been constructed as a part of a translation system. The Arabic words are converted into hamburg notation system (HamNoSys) using eSign editor Software. HamNoSys was used to create manual parameters (handshape, hand orientation, hand location, and hand movement), while non-manual parameters (facial expressions, shoulder raising, mouthing gesture, head tilting, and body movement) added by using (mouth, face, and limbs) in the eSign editor software. The sign then converted to the sign gesture markup language (SiGML) file, and later 3D avatar interprets the SiGML file scripts to the animated sign. The constructed dictionary has three thousand signs; therefore, it can be adopted for the translation system in which written text can be transformed into sign language and can be utilized for the education of deaf people. The dictionary will be available as a free resource for researchers. It is hard and time-consuming work, but it is an essential step in machine translation of whole Arabic text to ArSL with 3D animations. </span>
Comparative study of logistic regression and artificial neural networks on predicting breast cancer cytology
Authors: Mohammed Yosra Abdulaziz , Saleh Eman Gadban 
Published: January 2021

<p>Currently, breast cancer is one of the most common cancers and a main reason of women death worldwide particularly in<strong> </strong>developing countries such as Iraq. our work aims to predict the type of tumor whether benign or malignant through models that were built using logistic regression and neural networks and we hope it will help doctors in detecting the type of breast tumor. Four models were set using binary logistic regression and two different types of artificial neural networks namely multilayer perceptron MLP and radial basis function RBF. Evaluation of validated and trained models was done using several performance metrics like accuracy, sensitivity, specificity, and AUC (area under receiver operating characteristic ROC). Dataset was downloaded from UCI ml repository; it is composed of 9 attributes and 699 samples. The findings are clearly showing that the RBF NN classifier is the best in prediction of the type of breast tumors since it had recorded the highest performance in terms of correct classification rate (accuracy), sensitivity, specificity, and AUC (area under Receiver Operating Characteristic ROC) among all other models.</p>
Body, Mind, and Spirit in Early Chinese Medicine
Authors: Raphals Lisa 
Published: January 2021

Abstract
Medical texts especially of the Huangdi neijing 黃帝內經 tradition provide an important counterpoint to philosophical debates about the relation of body and mind in early China and in particular to the understanding of the “mind” (xin 心), since medical texts must address the role of the xin-heart as one of the visceral systems. This paper surveys accounts of both “mind” and “spirit” (shen 神) in the Huangdi neijing and proposes a view of a person in which cognitive and affective faculties are decentralized and corporeal, rather than being centered in the mind.
Hippocrate empiriste? Un idolum entre philosophie et praxis médicale (Du régime, I, 4)
Authors: Maselli Mila 
Published: January 2021

Abstract
This paper offers a reconstruction of the fortuna of a Hippocratic formula that has been conspicuously misunderstood since the sixteenth century by physicians and philosophers. For several centuries, and despite the increasing care with which translators and editors have examined classical texts and their circulation, the quote in question by Hippocrates has been expounded as a sentence advocating the primacy of sensory experience as a means of knowledge. This article aims to highlight the philological, cultural, and epistemic circumstances that produced and reinforced this misunderstanding, which persisted until the nineteenth century.
Closing the Gaps in US Rocket Propellant Production, 1940–1945
Authors: Bergman Yoel 
Published: January 2021

Abstract
The article supplements and revises past historiographical explanations on why the US entered World War ii without propellant based engines, for tactical rockets and how that gap was overcome. Short range rockets were used extensively by all sides in the War for various purposes, but in the interwar period (1919–1939), rocket advances were made mostly in Europe with the US lagging behind. The rockets engines were based on solid propellant tubes, but in 1940 there was hardly any US tubes design knowledge and no production facilities. Technological and production gaps had to be closed, and from 1940 were made with a significant help from Britain and under the leadership of the civilian National Defense Research Council (ndrc) agency, merged in 1941 into the Office of Scientific Research and Development (osrd). Due to the pressing needs to equip American forces with rockets, a joint group of ndrc and Army developers modified in early 1942 an existing gun propellant production technology for rocket tubes. Used initially for the Bazooka this adoption was found later to be extremely problematic in production and performance of tubes in the widely-used, Army’s 4.5-inch barrage and fighter plane rockets. Working in parallel, a joint group of ndrc and navy developers was able to construct the more modern tube production process already used abroad, avoiding the main army difficulties and taking the lead. The growing needs for these superior Navy rockets, some of which were used extensively by the Army, led to gaps between supplies and demands by 1943. Two fortunate events, one of them connected with the Soviet Union, helped to relieve the shortage.
“The Enthusiasm Expressed by Our Industry Friends”
Authors: Givens Adam 
Published: January 2021

Abstract
This article analyzes the groundbreaking 1952 plan by US Army leadership to develop a sizeable cargo helicopter program in the face of interservice opposition. It examines the influence that decision had in the next decade on the Army, the helicopter industry, and vtol technology. The Army’s procurement of large helicopters that could transport soldiers and materiel was neither a fait accompli nor based on short-term needs. Rather, archival records reveal that the decision was based on long-range concerns about the postwar health of the helicopter industry, developing the state of the art, and fostering new doctrinal concepts. The procurement had long-term consequences. Helicopters became central to Army war planning, and the ground service’s needs dictated the next generation of helicopter designs. That technology made possible the revolutionary airmobility concept that the Army took into Vietnam and also led to a flourishing commercial helicopter field.
Effect of dental intervention on improvements in metabolic syndrome patients: a randomized controlled clinical trial
Authors: Doke Midori , Komagamine Yuriko , Kanazawa Manabu , Iwaki Maiko , Suzuki Hiroyuki , Miyazaki Yasunari , Mizuno Tetsuya , Okayasu Kaori , Minakuchi Shunsuke 
Published: January 2021

Abstract
Background
Metabolic syndrome (MetS), caused by the accumulation of visceral fat, is considered a major cause of cardiovascular disease. This randomized controlled trial aimed to clarify the effect of dental intervention, including prosthodontics and/or periodontal treatment, combined with dietary and exercise guidance on MetS.

Methods
In total, 112 patients who met the Japanese waist circumference criteria of MetS were recruited. The intervention group (ITG) received dental intervention along with dietary and exercise guidance, while the control group (CTG) received dietary and exercise guidance alone. Three outcome measurements were obtained before intervention (BL), 1 month after intervention (1M), and 3 months after intervention (3M).

Results
Body water rate (p = 0.043) was significantly higher in ITG than in CTG at 1M. Simultaneously, fasting blood sugar level (p = 0.098) tended to be lower in ITG than in CTG. Lean mass (p = 0.037) and muscle mass (p = 0.035) were significantly higher and body weight (p = 0.044) significantly lower in ITG than in CTG at 3M. Body mass index (p = 0.052) tended to be lower in ITG than in CTG.

Conclusions
Dental intervention combined with lifestyle guidance may improve anthropometric status and reduce the risk of MetS.

Trial registration

University Hospital Medical Information Network Center Unique UMIN000022753. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000026176.
Resistin-like molecule β acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK signaling pathways
Authors: Tian Heshen , Liu Lei , Wu Ying , Wang Ruiwen , Jiang Yongliang , Hu Ruicheng , Zhu Liming , Li Linwei , Fang Yanyan , Yang Chulan , Ji Lianzhi , Liu Guoyu , Dai Aiguo 
Published: January 2021

AbstractBackgroundPulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule β (RELM-β) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-β has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-β in HPH remain unclear.MethodsWe assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-β in a rat HPH model and in hPASMCs.ResultsOverexpression of RELM-β caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-β partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-β gene overexpression or silencing, respectively. Recombinant RELM-β protein increased the intracellular Ca2+concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-β on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+inhibitor.ConclusionsOur findings suggest that RELM-β acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-β are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.