bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal-scale de novo genome assemblies of Cynomolgus Macaque and Common Marmoset
Authors: Jayakumar Vasanthan , Nishimura Osamu , Kadota Mitsutaka , Hirose Naoki , Sano Hiromi , Murakawa Yasuhiro , Yamamoto Yumiko , Nakaya Masataka , Tsukiyama Tomoyuki , Seita Yasunari , Nakamura Shinichiro , Kawai Jun , Sasaki Erika , Ema Masatsugu , Kuraku Shigehiro , Kawaji Hideya , Sakakibara Yasubumi 
Published: June 2021

AbstractCynomolgus macaque (Macaca fascicularis) and common marmoset (Callithrix jacchus) have been widely used in human biomedical research. Long-standing primate genome assemblies used the human genome as a reference for ordering and orienting the assembled fragments into chromosomes. Here we performed de novo genome assembly of these two species without any human genome-based bias observed in the genome assemblies released earlier. We assembled PacBio long reads, and the resultant contigs were scaffolded with Hi-C data, which were further refined based on Hi-C contact maps and alternate de novo assemblies. The assemblies achieved scaffold N50 lengths of 149 Mb and 137 Mb for cynomolgus macaque and common marmoset, respectively. The high fidelity of our assembly is also ascertained by BAC-end concordance in common marmoset. Our assembly of cynomolgus macaque outperformed all the available assemblies of this species in terms of contiguity. The chromosome-scale genome assemblies produced in this study are valuable resources for non-human primate models and provide an important baseline in human biomedical research.
Automated segmentation of macular edema for the diagnosis of ocular disease using deep learning method
Authors: Wang Zhenhua , Zhong Yuanfu , Yao Mudi , Ma Yan , Zhang Wenping , Li Chaopeng , Tao Zhifu , Jiang Qin , Yan Biao 
Published: June 2021

AbstractMacular edema is considered as a major cause of visual loss and blindness in patients with ocular fundus diseases. Optical coherence tomography (OCT) is a non-invasive imaging technique, which has been widely applied for diagnosing macular edema due to its non-invasive and high resolution properties. However, the practical applications remain challenges due to the distorted retinal morphology and blurred boundaries near macular edema. Herein, we developed a novel deep learning model for the segmentation of macular edema in OCT images based on DeepLab framework (OCT-DeepLab). In this model, we used atrous spatial pyramid pooling (ASPP) to detect macular edema at multiple features and used the fully connected conditional random field (CRF) to refine the boundary of macular edema. OCT-DeepLab model was compared against the traditional hand-crafted methods (C-V and SBG) and the end-to-end methods (FCN, PSPnet, and U-net) to estimate the segmentation performance. OCT-DeepLab showed great advantage over the hand-crafted methods (C-V and SBG) and end-to-end methods (FCN, PSPnet, and U-net) as shown by higher precision, sensitivity, specificity, and F1-score. The segmentation performance of OCT-DeepLab was comparable to that of manual label, with an average area under the curve (AUC) of 0.963, which was superior to other end-to-end methods (FCN, PSPnet, and U-net). Collectively, OCT-DeepLab model is suitable for the segmentation of macular edema and assist ophthalmologists in the management of ocular disease.
Detection of pathological mechano-acoustic signatures using precision accelerometer contact microphones in patients with pulmonary disorders
Authors: Gupta Pranav , Wen Haoran , Di Francesco Lorenzo , Ayazi Farrokh 
Published: June 2021

AbstractMonitoring pathological mechano-acoustic signals emanating from the lungs is critical for timely and cost-effective healthcare delivery. Adventitious lung sounds including crackles, wheezes, rhonchi, bronchial breath sounds, stridor or pleural rub and abnormal breathing patterns function as essential clinical biomarkers for the early identification, accurate diagnosis and monitoring of pulmonary disorders. Here, we present a wearable sensor module comprising of a hermetically encapsulated, high precision accelerometer contact microphone (ACM) which enables both episodic and longitudinal assessment of lung sounds, breathing patterns and respiratory rates using a single integrated sensor. This enhanced ACM sensor leverages a nano-gap transduction mechanism to achieve high sensitivity to weak high frequency vibrations occurring on the surface of the skin due to underlying lung pathologies. The performance of the ACM sensor was compared to recordings from a state-of-art digital stethoscope, and the efficacy of the developed system is demonstrated by conducting an exploratory research study aimed at recording pathological mechano-acoustic signals from hospitalized patients with a chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, and acute decompensated heart failure. This unobtrusive wearable system can enable both episodic and longitudinal evaluation of lung sounds that allow for the early detection and/or ongoing monitoring of pulmonary disease.
Plasmodium falciparum phenotypic and genotypic resistance profile during the emergence of Piperaquine resistance in Northeastern Thailand
Authors: Boonyalai Nonlawat , Thamnurak Chatchadaporn , Sai-ngam Piyaporn , Ta-aksorn Winita , Arsanok Montri , Uthaimongkol Nichapat , Sundrakes Siratchana , Chattrakarn Sorayut , Chaisatit Chaiyaporn , Praditpol Chantida , Fagnark Watcharintorn , Kirativanich Kirakarn , Chaorattanakawee Suwanna , Vanachayangkul Pattaraporn , Lertsethtakarn Paphavee , Gosi Panita , Utainnam Darunee , Rodkvamtook Wuttikon , Kuntawunginn Worachet , Vesely Brian A. , Spring Michele D. , Fukuda Mark M. , Lanteri Charlotte , Walsh Douglas , Saunders David L. , Smith Philip L. , Wojnarski Mariusz , Sirisopana Narongrid , Waters Norman C. , Jongsakul Krisada , Gaywee Jariyanart 
Published: June 2021

AbstractMalaria remains a public health problem in Thailand, especially along its borders where highly mobile populations can contribute to persistent transmission. This study aimed to determine resistant genotypes and phenotypes of 112 Plasmodium falciparum isolates from patients along the Thai-Cambodia border during 2013–2015. The majority of parasites harbored a pfmdr1-Y184F mutation. A single pfmdr1 copy number had CVIET haplotype of amino acids 72–76 of pfcrt and no pfcytb mutations. All isolates had a single pfk13 point mutation (R539T, R539I, or C580Y), and increased % survival in the ring-stage survival assay (except for R539I). Multiple copies of pfpm2 and pfcrt-F145I were detected in 2014 (12.8%) and increased to 30.4% in 2015. Parasites containing either multiple pfpm2 copies with and without pfcrt-F145I or a single pfpm2 copy with pfcrt-F145I exhibited elevated IC90 values of piperaquine. Collectively, the emergence of these resistance patterns in Thailand near Cambodia border mirrored the reports of dihydroartemisinin-piperaquine treatment failures in the adjacent province of Cambodia, Oddar Meanchey, suggesting a migration of parasites across the border. As malaria elimination efforts ramp up in Southeast Asia, host nations militaries and other groups in border regions need to coordinate the proposed interventions.
Impact of preoperative renal replacement therapy on the clinical outcome of heart transplant patients
Authors: Kim Darae , Choi Jin-Oh , Cho Yang Hyun , Sung Kiick , Oh Jaewon , Cho Hyun Jai , Jung Sung-Ho , Lee Hae-Young , Park Jin Joo , Choi Dong-Ju , Kang Seok-Min , Kim Jae-Joong , Jeon Eun-Seok 
Published: June 2021

AbstractRenal dysfunction is considered as a relative contraindication for heart transplantation (HTx). However, in the real world setting, many patients with advanced heart failure (HF) experience worsening of renal function and some even require renal replacement therapy (RRT) by the time they undergo HTx. We aimed to investigate the prognosis and clinical outcomes of HTx patients who required RRT during the perioperative period. The Korean Organ Transplant Registry (KOTRY) is a nationwide organ transplant registry in Korea. A total of 501 HTx patients had been prospectively enrolled in the KOTRY registry during 2014–2018. Among the 501 patients, 13 underwent combined heart and kidney transplantation (HKTx). The 488 patients who underwent isolated HTx were grouped according to their pre- and postoperative RRT status. The primary outcome was progression to dialysis-dependent end-stage renal disease (ESRD) after HTx. The secondary outcome was all-cause mortality after HTx. The median follow-up was 22 months (9–39 months). Patients who needed preoperative RRT but were free from postoperative RRT showed comparable overall survival and renal outcome to patients who were free from both pre- and postoperative RRT. In multivariable analysis, preoperative RRT was not associated with progression to ESRD or all-cause mortality after HTx; however, postoperative RRT was a significant predictor for both progression to ESRD and all-cause mortality after HTx. Preoperative creatinine or estimated glomerular filtration rate (eGFR) were not predictive of progression to ESRD after HTx. The present analysis suggests that preoperative RRT requirement does not indicate irreversible renal dysfunction in patients waiting for HTx. However, postoperative RRT was associated with progression to ESRD and mortality after HTx.
Risk of early-onset dementia among persons with tinnitus: a retrospective case–control study
Authors: Cheng Yen-Fu , Xirasagar Sudha , Yang Tzong-Han , Wu Chuan-Song , Kao Yi-Wei , Lin Herng-Ching 
Published: June 2021

AbstractHigher rates of poor cognitive performance are known to prevail among persons with tinnitus in all age groups. However, no study has explored the association between tinnitus and early-onset dementia. We hypothesize that tinnitus may precede or occur concurrently with subclinical or early onset dementia in adults younger than 65 years of age. This case–control study used data from the Taiwan National Health Insurance Research Database, identifying 1308 patients with early-onset dementia (dementia diagnosed before 65 years of age) and 1308 matched controls. We used multivariable logistic regressions to estimate odds ratios (ORs) for prior tinnitus among patients with dementia versus controls. Among total 2616 sample participants, the prevalence of prior tinnitus was 18%, 21.5% among cases and 14.5% among controls (p < 0.001). Multivariable logistic regression showed and adjusted OR for prior tinnitus of 1.6 for cases versus controls (95% CI: 1.3 ~ 2.0). After adjusting for sociodemographic characteristics and medical co-morbidities, patients with early-onset dementia had a 67% higher likelihood of having prior tinnitus (OR = 1.628; 95% CI = 1.321–2.006). Our findings showed that pre-existing tinnitus was associated with a 68% increased risk of developing early-onset dementia among young and middle-aged adults. The results call for greater awareness of tinnitus as a potential harbinger of future dementia in this population.
Repeated use of SSRIs potentially associated with an increase on serum CK and CK-MB in patients with major depressive disorder: a retrospective study
Authors: Wu Shengwei , Zhou Yufang , Xuan Zhengzheng , Xiong Linghui , Ge Xinyu , Ye Junrong , Liu Yun , Yuan Lexin , Xu Yan , Ding Guoan , Xiao Aixiang , Guo Jianxiong , Yu Lin 
Published: June 2021

AbstractThere is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605–35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287–3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935–50.886; MD = 4.613, P = 0.000, 95% CI 2.846–6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.
Generation of vascular chimerism within donor organs
Authors: Cohen Shahar , Partouche Shirly , Gurevich Michael , Tennak Vladimir , Mezhybovsky Vadym , Azarov Dmitry , Soffer-Hirschberg Sarit , Hovav Benny , Niv-Drori Hagit , Weiss Chana , Borovich Adi , Cohen Guy , Wertheimer Avital , Shukrun Golan , Israeli Moshe , Yahalom Vered , Leshem-Lev Dorit , Perl Leor , Kornowski Ran , Wiznitzer Arnon , Tobar Ana , Feinmesser Meora , Mor Eytan , Atar Eli , Nesher Eviatar 
Published: June 2021

AbstractWhole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.
Rspo2 inhibits TCF3 phosphorylation to antagonize Wnt signaling during vertebrate anteroposterior axis specification
Authors: Reis Alice H. , Sokol Sergei Y. 
Published: June 2021

AbstractThe Wnt pathway activates target genes by controlling the β-catenin-T-cell factor (TCF) transcriptional complex during embryonic development and cancer. This pathway can be potentiated by R-spondins, a family of proteins that bind RNF43/ZNRF3 E3 ubiquitin ligases and LGR4/5 receptors to prevent Frizzled degradation. Here we demonstrate that, during Xenopus anteroposterior axis specification, Rspo2 functions as a Wnt antagonist, both morphologically and at the level of gene targets and pathway mediators. Unexpectedly, the binding to RNF43/ZNRF3 and LGR4/5 was not required for the Wnt inhibitory activity. Moreover, Rspo2 did not influence Dishevelled phosphorylation in response to Wnt ligands, suggesting that Frizzled activity is not affected. Further analysis indicated that the Wnt antagonism is due to the inhibitory effect of Rspo2 on TCF3/TCF7L1 phosphorylation that normally leads to target gene activation. Consistent with this mechanism, Rspo2 anteriorizing activity has been rescued in TCF3-depleted embryos. These observations suggest that Rspo2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling.
Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
Authors: Cai Chengyuan , Zeng Danning , Gao Qing , Ma Lei , Zeng Bohang , Zhou Yi , Wang He 
Published: June 2021

AbstractIron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin(FPN1). However, the functions ofFPN1in hepatocyte secretion and macrophage polarization remain unknown.CD68immunohistochemical staining and double immunofluorescence staining forF4/80andKi67in transgenic mouse livers showed that the number of macrophages inFPN1−/+andFPN1−/−mouse livers was significantly increased compared to that in WT (FPN+/+) mice.FPN1downregulation in hepatic cells increased the levels of the M2 markersCD206,TGF- β,VEGF,MMP-9,Laminin,Collagen,IL-4andIL-10. Furthermore, the expression ofCD16/32andiNOS, as M1 markers, exhibited the opposite trend. Meanwhile,α-SMAimmunohistochemistry and Sirius red staining showed that the trend of liver fibrosis inFPN1−/−mice was more significant than that in control mice. Similarly, in vitroFPN1knockdown in L02-Sh/L02-SCR liver cell lines yielded similar results. Taken together, we demonstrated that downregulatedFPN1expression in hepatocytes can promote the proliferation and polarization of macrophages, leading to hepatic fibrosis. Above all, theFPN1axis might provide a potential target for hepatic fibrosis.
Blue light directly modulates the quorum network in the human pathogen Acinetobacter baumannii
Authors: Tuttobene Marisel Romina , Müller Gabriela Leticia , Blasco Lucía , Arana Natalia , Hourcade Mónica , Diacovich Lautaro , Cribb Pamela , Tomás María , Nieto-Peñalver Carlos Gabriel , Mussi María Alejandra 
Published: June 2021

AbstractQuorum sensing modulates bacterial collective behaviors including biofilm formation, motility and virulence in the important human pathogen Acinetobacter baumannii. Disruption of quorum sensing has emerged as a promising strategy with important therapeutic potential. In this work, we show that light modulates the production of acyl-homoserine lactones (AHLs), which were produced in higher levels in the dark than under blue light at environmental temperatures, a response that depends on the AHL synthase, AbaI, and on the photoreceptor BlsA. BlsA interacts with the transcriptional regulator AbaR in the dark at environmental temperatures, inducing abaI expression. Under blue light, BlsA does not interact with AbaR, but induces expression of the lactonase aidA and quorum quenching, consistently with lack of motility at this condition. At temperatures found in warm-blooded hosts, the production of AHLs, quorum quenching as well as abaI and aidA expression were also modulated by light, though in this case higher levels of AHLs were detected under blue light than in the dark, in a BlsA-independent manner. Finally, AbaI reduces A. baumannii's ability to kill C. albicans only in the dark both at environmental as well as at temperatures found in warm-blooded hosts. The overall data indicate that light directly modulates quorum network in A. baumannii.
The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19
Authors: Tojo Kentaro , Sugawara Yoh , Oi Yasufumi , Ogawa Fumihiro , Higurashi Takuma , Yoshimura Yukihiro , Miyata Nobuyuki , Hayami Hajime , Yamaguchi Yoshikazu , Ishikawa Yoko , Takeuchi Ichiro , Tachikawa Natsuo , Goto Takahisa 
Published: June 2021

AbstractCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.
Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study
Authors: Cammarota Gianmaria , Vaschetto Rosanna , Azzolina Danila , De Vita Nello , Olivieri Carlo , Ronco Chiara , Longhini Federico , Bruni Andrea , Colombo Davide , Pissaia Claudio , Prato Federico , Maestrone Carlo , Maestrone Matteo , Vetrugno Luigi , Bove Tiziana , Lemut Francesco , Taretto Elisa , Locatelli Alessandro , Barzaghi Nicoletta , Cerrano Martina , Ravera Enrico , Zanza Christian , Selva Andrea Della , Blangetti Ilaria , Salvo Francesco , Racca Fabrizio , Longhitano Yaroslava , Boscolo Annalisa , Sguazzotti Ilaria , Bonato Valeria , Grossi Francesca , Crimaldi Federico , Perucca Raffaella , Boniolo Ester , Verdina Federico , Vignazia Gian Luca , Santangelo Erminio , Tarquini Riccardo , Zanoni Marta , Messina Antonio , Marin Matteo , Bacigalupo Paola , Sileci Graziana , Sella Nicolò , De Robertis Edardo , Corte Francesco Della , Navalesi Paolo 
Published: June 2021

AbstractIn patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6–11] days in early extubated patients versus 11 [6–15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.