bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsupervised explainable artificial intelligence for molecular evolutionary studies of over forty thousand SARS-CoV-2 genomes
Authors: Ikemura Toshimichi , Wada Kennosuke , Wada Yoshiko , Iwasaki Yuki , Abe Takashi
Published: November 2020

Unsupervised AI (artificial intelligence) can obtain novel knowledge from big data without particular models or prior knowledge and is highly desirable for unveiling hidden features in big data. SARS-CoV-2 poses a serious threat to public health and one important issue in characterizing this fast-evolving virus is to elucidate various aspects of their genome sequence changes. We previously established unsupervised AI, a BLSOM (batch-learning SOM), which can analyze five million genomic sequences simultaneously. The present study applied the BLSOM to the oligonucleotide compositions of forty thousand SARS-CoV-2 genomes. While only the oligonucleotide composition was given, the obtained clusters of genomes corresponded primarily to known main clades and internal divisions in the main clades. Since the BLSOM is explainable AI, it reveals which features of the oligonucleotide composition are responsible for clade clustering. The BLSOM has powerful image display capabilities and enables efficient knowledge discovery about viral evolutionary processes.
The meaning of postpartum sexual health for women living in Spain: A phenomenological inquiry.
Authors: Pardell-Dominguez Lidia , Palmieri Patrick Albert , Dominguez-Cancino Karen A. , Camacho-Rodriguez Doriam E. , Edwards Joan E. , Watson Jean , Leyva-Moral Juan M.
Published: November 2020

Background: Sexual health is a multidimensional phenomenon constructed by personal, social, and cultural factors but continues to be studied with a biomedical approach. During the postpartum period, a woman transitions to mother, as well as partner-to-parent and couple-to-family. There are new realities in life in the postpartum period, including household changes and new responsibilities that can impact the quality of sexual health. This phenomenon is understudied especially in the context of Spain. The purpose of this study was to describe the lived experience of postpartum sexual health among primiparous women giving birth in Catalonia (Spain).Methods: This was a phenomenological study with a purposive sample of primiparous women. Data was collected through semi-structured interviews until saturation. Analysis followed Colaizzi's seven-step process with an eighth translation step added to limit cross-cultural threats to validity. Also, the four dimensions of trustworthiness were established through strategies and techniques during data collection and analysis.Results: Ten women were interviewed from which five themes emerged, including: Not feeling ready, inhibiting factors, new reality at home, socio-cultural factors, and the clinician within the health system. Returning to sexual health led women to engage in experiential learning through trial and error. Most participants reported reduced libido, experienced altered body image, and recounted resumption of sexual activity before feeling ready. A common finding was fatigue and feeling overloaded by the demands of the newborn. Partner support was described as essential to returning to a meaningful relationship. Discussions about postpartum sexual health with clinicians were described as taboo, and largely absent from the care model.Conclusion: Evidence-based practices should incorporate the best evidence from research, consider the postpartum sexual health experiences and preferences of the woman, and use clinician expertise in discussions that include the topic of postpartum sexual health to make decisions. As such, human caring practices should be incorporated into clinical guidelines to recognize the preferences of women. Clinicians need to be authentically present, engage in active communication, and individualize their care. More qualitative studies are needed to understand postpartum sexual health in different contexts, cultures, and countries and to identify similarities and differences through meta-synthesis.
Nationwide population-based cohort study of adverse obstetric outcomes in pregnancies with myoma or following myomectomy: Retrospective cohort study
Authors: Lee Se Jin , Ko Hyun Sun , Na Sunghun , Bae Jin Young , Seong Won Joon , Kim Jong Woon , Shin Jaeeun , Cho Hae Joong , Choi Gyu Yeon , Kim Jinsil , Cho Geum Joon , Park In Yang
Published: November 2020

Background: Our objective was to evaluate risks of adverse obstetric outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy.Methods: We analyzed the national health insurance database, which covers almost the entire Korean population, between 2004 and 2015. The risks of adverse pregnancy outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy, compared to those in women without a diagnosed myoma, were analyzed in multivariate logistic regression analysis.Results: During the study period, 38,402 women with diagnosed myoma(s), 9,890 women with a history of myomectomy, and 740,675 women without a diagnosed myoma gave birth. Women with a history of diagnosed myoma(s) and women with a history of myomectomy had significantly higher risks of cesarean section (aOR 1.13, 95% CI 1.1-1.16 and aOR 7.46, 95% CI 6.97-7.98, respectively) and placenta previa (aOR 1.41, 95% CI 1.29-1.54 and aOR 1.58, 95% CI 1.35-1.83, respectively), compared to women without a diagnosed myoma. And the risk of uterine rupture was significantly higher in women with previous myomectomy (aOR 12.78, 95% CI 6.5-25.13), compared to women without a diagnosed myoma, which was much increased (aOR 41.35, 95% CI 16.18-105.69) in nulliparous women. The incidence of uterine rupture was the highest at delivery within one year after myomectomy and decreased over time after myomectomy. Conclusions: Women with a history of myomectomy had significantly higher risks of cesarean section and placenta previa compared to women without a diagnosed myoma.
Experiences of oral health: before, during and after becoming a regular user of GC Tooth Mousse Plus ®
Authors: Sbaraini Alexandra , Adams Geoffrey G , Reynolds Eric C
Published: November 2020

Background: Clinical trials and laboratory studies from around the world have shown that GC Tooth Mousse Plus® (TMP) is effective in protecting teeth from tooth decay and erosion, buffering dental plaque pH, remineralising white spot lesions and reducing dentine hypersensitivity. However, no other study has assessed the experiences of oral health, before, during and after individuals becoming regular users of TMP. Aim: To identify how participants’ oral health status changed after introducing TMP into their oral hygiene routine.Methods: A qualitative study using Charmaz’s grounded theory methodology was conducted. Fifteen purposively sampled regular users of TMP were interviewed. Transcripts were analysed after each interview. Data analysis consisted of transcript coding, detailed memo writing, and data interpretation.Results: Participants described their experiences of oral health and disease, before, during and after introducing TMP into their daily oral hygiene routine, together with the historical, biological, financial, psychosocial, and habitual dimensions of their experiences. Before becoming a regular user of TMP, participants described themselves as having a damaged mouth with vulnerable teeth, dry mouth, and sensitivity. Various aspects of participants’ histories were relevant, such as, family history and history of oral disease. Having a damaged mouth with vulnerable teeth, dry mouth and sensitivity was explained by those elements. Despite some initial barriers, once being prescribed TMP by a dental professional, a three-fold process of change was initiated: starting a new oral hygiene routine, persevering daily, and experiencing reinforcing outcomes. This process led to a fundamental lifestyle change. Participants transitioned from having a damaged mouth with vulnerable teeth to having a comfortable mouth with strong teeth; at the same time participants felt empowered by this newly found status of being able to keep their teeth for life. Barriers and facilitators for incorporating TMP on daily oral hygiene routine were also identified.Conclusions: Participants valued having a comfortable mouth with strong teeth, which did not require repeated restorations. Seeing concrete results in their mouths and experiencing a more comfortable mouth boosted adherence to daily applications of TMP, which was maintained over time.
Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice
Authors: Wang Qiu-bo , Du Yun-ting , Liu Fei , Sun Xiao-dan , Sun Xun , Chen Guang , Pang Wei , Cao Yaming
Published: November 2020

Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between children and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4 + T-bet + IFN-γ + Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4 + GATA3 + IL-4 + Th2 cells and CD4 + CXCR5 + Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4 + or activated CD4 + T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4 + T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.
Effect of hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes: a prospective, randomized, open-label, blinded endpoint, cross-over study
Authors: Noh Radzi M , Graveling AJ , Lang Ninian N , White Audrey C , Lee Kuan Ken , Mills Nicholas L , Newby David E , Lang Chim C , Frier Brian M
Published: November 2020

Aims: Hypoglycemia provokes a profound autonomic response in humans including cardiovascular effects. This study examined the effect of experimentally-induced hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.Methods and Results: In a prospective, randomized, open-label, blinded, endpoint cross-over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non-diabetic volunteers, underwent hyperinsulinemic euglycemic (blood glucose 4.5-5.5 mmol/L) and hypoglycemic (2.2-2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high-sensitivity cardiac troponin I (hs-cTnI) concentration.During euglycemia, a non-significant trend for lower CFR was observed in participants with type 1 diabetes than in those without type 1 diabetes (3.66±0.47 versus 3.92±0.85), and a non-significant lower trend also occurred during hypoglycemia (type 1 diabetes: 3.54±0.58 versus non-diabetes: 3.80±0.84). A generalized linear mixed-model analysis was performed, with diabetes status and euglycemia or hypoglycemia as factors affecting CFR. No significant statistical difference in CFR was observed for diabetes status (p=0.23) or between euglycemia and hypoglycemia (p=0.31). No changes in hs-cTnI occurred during hypoglycemia or in the recovery period (p=0.86).Conclusions: While the observed reduction in coronary flow reserve did not achieve significance during exposure to insulin-induced hypoglycemia in healthy young men with type 1 diabetes, with no evidence of myocardial injury, adverse cardiovascular effects of hypoglycemia cannot be excluded in older people who have coronary disease. Further studies are required to investigate this putative problem.
Effects of Er:YAG laser pre-treatment on dentin structure and bonding strength of primary teeth: An in vitro study
Authors: WANG Jun hui , YANG Kuan , ZHANG Bai ze , ZHOU Zhi fei , WANG Zi rui , GE Xin , WANG Lu lu , CHEN Yu jiang , WANG Xiao jing
Published: November 2020

Background: To investigate the effects of Er:YAG laser pre-treatment on the dentin structure and shear bond strength of primary teeth.Methods: Dentin specimens were prepared using freshly extracted intact primary molars and divided randomly into four groups based on the surface treatment applied. The control and etchant groups received no treatment and conventional acid etching treatment, respectively, while the energy and frequency groups received laser surface treatment with variable energy (50-300 mJ) and frequency (5-30 Hz) parameters. The morphology was observed using scanning electron microscopy. The surface-treated dentin slices were bonded to resin tablets, followed by thermocycle treatment. The shear strength was determined using a universal testing machine and de-bonded surfaces were observed using a stereomicroscope.Results: SEM observation showed that the surface morphology of the dentin slices changed after etching as well as after Er:YAG laser pre-treatment with different energy and frequency values. The dentin tubules opened within a specific energy (50-200 mJ) and frequency (5-20 Hz) range. Beyond this range, the intertubular dentin showed cracks and structural disintegration. Shear strength tests showed no significant changes after acid etching. The shear strength increased significantly (P<0.05) after Er:YAG laser pre-treatment compared with that of the control group. The shear strength increased within the same energy (50-200 mJ) and frequency (5-20 Hz) range as the tubule opening, but not significantly (P>0.05). The most common mode of interface failure was adhesive (interface) failure, followed by mixed and resin cohesive failure.Conclusions: Pre-treatment using Er:YAG laser opens the dentinal tubules without the formation of a smear layer and improves the bonding strength between the primary teeth dentin and the resin composites.
The onset of nausea and vomiting of pregnancy: a prospective cohort study
Authors: Gadsby Roger , Ivanova Diana , Trevelyan Emma , Hutton Jane Luise , Johnson Sarah
Published: November 2020

Background
Nausea and vomiting are experienced by most women during pregnancy. The onset is usually related to Last Menstrual Period (LMP) the date of which is often unreliable. This study describes the time to onset of nausea and vomiting symptoms from date of ovulation and compares this to date of last menstrual period
Methods
Prospective cohort of women seeking to become pregnant, recruited from 12 May 2014 to 25 November 2016, in the United Kingdom. Daily diaries of nausea and vomiting were kept by 256 women who were trying to conceive. The main outcome measure is the number of days from last men­strual period (LMP) or luteinising hormone surge until onset of nausea or vomiting.

Results
Almost all women (88%) had Human Chorionic Gonadotrophin rise within 8 to 10 days of ovulation; the equivalent interval from LMP was 20 to 30 days. Many (67%) women experience symp­toms within 11 to 20 days of ovulation.

Conclusions
Onset of nausea and vomiting occurs earlier than previously reported and there is a narrow window for onset of symptoms. This indicates that its etiology is associated with a specific developmental stage at the foetal-maternal interface.

Trial registration NCT01577147
Tissue-Specific Transcriptome Analysis Reveals Lignocellulose Synthesis Regulation in Elephant Grass (Pennisetum purpureum Schum.)
Authors: Zhang Wenqing , Zhang Shengkui , Lu Xianqin , Li Can , Liu Xingwang , Dong Geyu , Xia Tao
Published: November 2020

Background: The characteristics of elephant grass, especially its stem lignocellulose, are of great significance for its quality as feed or other industrial raw materials. However, the research on lignocellulose biosynthesis pathway and key genes is limited because the genome of elephant grass has not been deciphered.Results: In this study, RNA sequencing (RNA-seq) combined with lignocellulose content analysis and cell wall morphology observation using elephant grass stems from different development stages as materials were applied to reveal the genes that regulate the synthesis of cellulose and lignin. A total of 3852 differentially expressed genes (DEGs) were identified in three periods of T1, T2, and T3 through RNA-seq analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of all DEGs showed that the two most abundant metabolic pathways were phenylpropane metabolism, starch and sucrose metabolism, which were closely related to cell wall development, hemicellulose, lignin and cellulose synthesis. Through weighted gene co-expression network analysis (WGCNA) of DEGs, a ‘blue’ module highly associated with cellulose synthesis and a ‘turquoise’ module highly correlated with lignin synthesis were exhibited. A total of 43 candidate genes were screened, of which 17 had function annotations in other species. Besides, by analyzing the content of lignocellulose in the stem tissues of elephant grass at different developmental stages and the expression levels of genes such as CesA, PAL, CAD, C4H, COMT, CCoAMT, F5H and CCR, it was found that the content of lignocellulose was related to the expression level of these structural genes.Conclusions: This study provides a basis for further understanding the molecular mechanisms of cellulose and lignin synthesis pathways of elephant grass, and offers a unique and extensive list of candidate genes for future specialized functional studies which may promote the development of high-quality elephant grass varieties with high cellulose and low lignin content.
Does prophylactic antibiotic administration for tooth extraction affect PT-INR in patients taking warfarin?
Authors: Iwata Eiji , Tachibana Akira , Kusumoto Junya , Takata Naoki , Hasegawa Takumi , Akashi Masaya
Published: November 2020

Background: Various antibiotics and analgesics have been reported to interact with　warfarin. Reports that investigate the effects of medication taken for just a few days during tooth extraction on the prothrombin time-international normalized ratio (PT-INR) are rare.Methods: A total of 110 patients receiving long-term stable warfarin therapy underwent tooth extraction without interruption of warfarin treatment. INR values were measured one month before the tooth extraction, the day of the extraction, and one week after the extraction. We investigated the changes in INR values between the day of extraction and one week after extraction, as well as the various risk factors for increases in INR values.Results: Before and after tooth extraction, the number of patients taking cefcapene pivoxil, amoxicillin, and azithromycin was 57, 36, and 8, respectively. Nine patients were administered ampicillin before tooth extraction and received amoxicillin after their tooth extraction. One week after tooth extraction, the INR values increased beyond the therapeutic range in 3 out of 110 patients (2.7%). The INR values before tooth extraction in these three patients were close to 3.0. The INR value increased by more than twice as much in 1 out of 110 patients (0.9%).Conclusion: Our results suggest that prophylactic antibiotic administration has little effect on INR values when patients on stable warfarin therapy undergo tooth extraction. Surgeons have to take attention if the patients whose INR values are close to 3.0 before their extraction.
Genome-wide occupancy reveals the localization of H1T2 (H1fnt) to repeat regions and a subset of transcriptionally active chromatin domains in rat spermatids
Authors: Vasantha Shalini , Bhaduri Utsa , Ravikkumar Anjhana C , Rengarajan Anusha , Rao Satyanarayana
Published: November 2020

Background H1T2/H1FNT is a germ cell specific linker histone variant expressed during spermiogenesis specifically in round and elongating spermatids. Infertile phenotype of homozygous H1T2 mutant male mice revealed the essential function of H1T2 for the DNA condensation and histone to protamine replacement in spermiogenesis. However, the mechanism by which H1T2 imparts the inherent polarity within spermatid nucleus including the additional protein partners and the genomic domains occupied by this linker histone are unknown.Results Sequence analysis revealed the presence of Walker motif, SR domains and putative coiled-coil domains in the C-terminal domain of rat H1T2 protein. Genome wide occupancy analysis using highly specific antibody against the CTD of H1T2 demonstrated the binding of H1T2 to the LINE L1 repeat elements and to a significant percentage of the genic regions (promoter-TSS, exons and introns) of the rat spermatid genome. Immunoprecipitation followed by mass spectrometry analysis revealed the open chromatin architecture of H1T2 occupied chromatin encompassing the H4 acetylation and other histone PTMs characteristic of transcriptionally active chromatin. In addition, the present study has identified the interacting protein partners of H1T2 associated chromatin mainly as nucleo-skeleton components, RNA binding proteins and chaperones.Conclusions Linker histone H1T2 possesses unique domain architecture which can account for the specific functions associated with chromatin remodeling events facilitating the initiation of histone to transition proteins/protamine transition in the polar apical spermatid genome. Our results directly establish the unique function of H1T2 in nuclear shaping associated with spermiogenesis by mediating the interaction between chromatin and nucleo-skeleton, positioning the epigenetically specialized chromatin domains involved in transcription coupled histone replacement initiation towards the apical pole of round/elongating spermatids.
Ease and equity of access to free DR-TB services in Nigeria- a qualitative analysis of policies, structures and processes
Authors: Oga-Omenka Charity , Bada Florence , Agbaje Aderonke , Dakum Patrick , Menzies Dick , Zarowsky Christina
Published: November 2020

Introduction: Persistent low rates of case notification and treatment coverage reflect that accessing free diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in Nigeria remains a challenge. Equity in health access requires availability of comparable, appropriate services to all, based on needs, and irrespective of socio-demographic characteristics. Our study analyzed elements that facilitate or hinder equitable access for different groups of patients within the current health system to support DR-TB management in Nigeria. Methods: We conducted documentary review of guidelines and workers manuals, as well as 29 qualitative interviews, including 5 focus group discussions, with a total of 62 participants, in Nigeria. Between August and November 2017, we conducted qualitative interviews of patients who were on treatment, their treatment supporter, and providers in Ogun and Plateau States, as well as program managers in Benue and Abuja. We adapted and used Levesque’s patient-centered access to care framework to analyze DR-TB policy documents and interview data. Results: Thematic analysis revealed inequitable access to DR-TB care for some patient socio-demographic groups. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Health system factors including positive provider attitudes and financial support provided to the patients facilitated equity and ease of access. However, limited coverage and the absence of patients’ access rights protection and considerations in the treatment guidelines and workers manuals likely hampered access. Conclusion: In the context of Nigeria’s low case-finding and treatment coverage, applying an equity of access framework was necessary to highlight gaps in care. Differing social contexts of patients adversely affected their access to DR-TB care. We identified several strengths in DR-TB care delivery, including the current financial support that should be sustained. Our findings highlight the need for government’s commitment and continued interventions.
Clinical profiles of subclinical disease among pulmonary tuberculosis patients: a prospective cohort study in South Korea
Authors: Min Jinsoo , Chung Chaeuk , Jung Sung Soo , Park Hye Kyeong , Lee Sung-Soon , Lee Ki Man
Published: November 2020

Background: Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. We aimed to describe the clinical and laboratory findings of subclinical disease among pulmonary TB patients and compared treatment outcomes for subclinical and active diseases. Methods: In this prospective cohort study, we enrolled adult patients aged ≥19 years with pulmonary TB between 2016 and 2018. Subclinical TB was defined as radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented a two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active diseases using multivariable binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort. Results: Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariable analysis showed that age <65 years was the only variable significantly associated with subclinical disease. Subclinical disease had a significantly lower proportion of acid-fast bacilli smear and culture positivity and multiple lobe involvement compared to active disease. The white blood cell counts, platelet counts, and C-reactive protein levels were significantly higher among patients with active disease than among those with subclinical disease. Among 319 patients with treatment success in the drug-susceptible cohort, six (1.9%) recurrent cases were identified, and all were active disease. Patients with subclinical disease had a higher proportion of favourable outcomes; however, its odds ratio was insignificant. Conclusions: Nearly one-fifth of tuberculosis cases were subclinical in South Korea. Despite its milder clinical presentation and lower level of inflammatory markers, the treatment outcomes of subclinical TB were not significantly different from that of active disease.
Bivalves are NO different: nitric oxide as negative regulator of metamorphosis in the Pacific oyster, Crassostrea gigas.
Authors: Vogeler Susanne , Carboni Stefano , Li Xiaoxu , Nevejan Nancy , Monaghan Sean J , Ireland Jacqueline H , Joyce Alyssa
Published: November 2020

Background: Nitric oxide (NO) is presumed to be a regulator of metamorphosis in many invertebrate species, and although NO pathways have been comparatively well-investigated in gastropods, annelids and crustaceans, there has been very limited research on the effects of NO on metamorphosis in bivalve shellfish.Results: In this paper, we investigate the effects of NO pathway inhibitors and NO donors on metamorphosis induction in larvae of the Pacific oyster, Crassostrea gigas. The nitric oxides synthase (NOS) inhibitors s-methylisothiourea hemisulfate salt (SMIS), aminoguanidine hemisulfate salt (AGH) and 7-nitroindazole (7-NI) induced metamorphosis ranging from 75%, 76% to 83% respectively, and operating in a concentration-dependent manner. Additional induction of up to 54% resulted from exposures to 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, with which NO interacts to catalyse the synthesis of cyclic guanosine monophosphate (cGMP). Conversely, high concentrations of the NO donor sodium nitroprusside dihydrate in combination with metamorphosis inducers epinephrine, MK-801 or SMIS, significantly decreased metamorphosis, although a potential harmful effect of excessive NO unrelated to metamorphosis pathway cannot be excluded. Expression of CgNOS also decreased in larvae after metamorphosis regardless of the inducers used, but intensified again post-metamorphosis in spat. Fluorescent detection of NO in competent larvae with DAF-FM diacetate and localisation of the oyster nitric oxide synthase CgNOS expression by in-situ hybridisation showed that NO occurs primarily in two key larval structures, the velum and foot. cGMP was also detected in the foot using immunofluorescent assays, and is potentially involved in the foot’s smooth muscle relaxation.Conclusion: Together, these results suggest that the NO pathway acts as negative regulator of metamorphosis in Pacific oyster larvae, and that NO reduction induces metamorphosis by inhibiting swimming or crawling behaviour, in conjunction with a cascade of additional neuroendocrine downstream responses.
Integrated Transcriptomic and Metabolomic Analysis Reveals a Transcriptional Regulation Network for the Biosynthesis of Carotenoids and Flavonoids in ‘Cara cara’ Navel Orange
Authors: Zhang Haipeng , Chen Jiajing , Peng Zhaoxin , Shi Meiyan , Liu Xiao , Wen Huan , Jiang Youwu , Cheng Yunjiang , Xu Juan , Zhang Hongyan
Published: November 2020

Background: Carotenoids and flavonoids are important secondary metabolites in plants, which exert multiple bioactivities and benefits to human health. Although the genes that encode carotenogenesis and flavonoid biosynthetic enzymes are well characterized, the transcriptional regulatory mechanisms that are related to the pathway genes remain to be investigated. In this study, ‘Cara cara’ navel orange (CNO) fruit at four development stages were used to identify the key genes and TFs for carotenoids and flavonoids accumulation.Results: In this study, CNO was used to investigate the profiles of carotenoids and flavonoids by a combination of metabolomic and transcriptomic analyses. The important stage for the accumulation of the major carotenoid, lycopene was found to be at 120 days after florescence (DAF). The transcripts of five carotenogenesis genes were highly correlated with lycopene contents, and 16, 40, 48, 24 and 18 transcription factors (TFs) were predicted to potentially bind 1-deoxy-D-xylulose-5-phosphate synthase (DXS1), deoxyxylulose 5-phosphate reductoisomerase (DXR), geranylgeranyl diphosphate synthase (GGPPS2), phytoene synthase (PSY1) and lycopene β-cyclase (LCYB) promoters, respectively. Narirutin was the most abundant flavonoid in the flesh at the early stages, 60 DAF was the most important stage for the accumulation of flavonoids, and 17, 22, 14, 25, 24 and 16 TFs could potentially bind phenylalanine ammonia-lyase (PAL-1 and PAL-4), 4-Coumarate-CoA ligase (4CL-2 and 4CL-5), chalcone synthase (CHS-1) and chalcone isomerase (CHI) promoters, respectively. Furthermore, Both sets of fifteen candidate TFs might regulate at least three key genes and contribute to carotenoids/flavonoids accumulation in CNO fruit. Finally, a hierarchical model for the regulatory network among the pathway genes and TFs was proposed.Conclusions: Collectively, our results suggest that DXS1, DXR, GGPPS2, PSY1 and LCYB genes were the most important genes for carotenoids accumulation, while PAL-1, PAL-4, 4CL-2, 4CL-5, CHS-1 and CHI for flavonoids biosynthesis. A total of 24 TFs were postulated as co-regulators in both pathways directly, which might play important roles in carotenoids and flavonoids accumulation in CNO fruit.
The effect of preoperative chemotherapy on liver regeneration after portal vein embolization/ligation or liver resection in patients with colorectal liver metastasis: a systematic review protocol
Authors: Pavel Mihai-Calin , Casanova Raquel , Estalella Laia , Memba Robert , Llàcer-Millán Erik , Achalandabaso Mar , Julià Elisabet , Geoghegan Justin , Jorba Rosa
Published: November 2020

Introduction: Liver resection (LR) in patients with liver metastasis from colo-rectal cancer remains the only curative treatment. Perioperative chemotherapy improves prognosis of these patients. However, there are concerns regarding the effect of preoperative chemotherapy on liver regeneration, which is a key event in avoiding liver failure after LR. The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after (LR) or portal vein embolization (PVE) in patients with liver metastasis from colo-rectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and postoperative liver failure.Methods: The design of this systematic review will follow the current recommendations of PRISMA. Pubmed, Scopus, Web of Science, Embase and Cochrane databases will be searched We will include studies reporting liver regeneration rates in patients submitted to LR or PVE. Only studies comparing neoadjuvant vs no chemotherapy, or comparing chemotherapy characteristics (bevacizumab administration, number of cycles and time from finishing chemotherapy until intervention) will be included. We will select studies from 1990 to present. Two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. Bias of the studies will be evaluated with the ROBINS-I tool and quality of evidence for all outcomes will be determined with the GRADE system. The data will be registered in a predesigned database. If selected studies are sufficiently homogeneous, we will perform a meta-analysis of reported results. In the event of a substantial heterogeneity, a qualitive systematic review will be performed.Discussion: The results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures.Systematic Review Registration: PROSPERO registration number: CRD42020178481 (July 5th 2020).
Strength and Size of Phosphorus-Rich Patches Determine the Foraging Strategy of Neyraudia reynaudiana
Authors: Cai Liping , Wang Yuzhen , Tigabu Mulualem , Hou Xiaolong , Wu Pengfei , Zhou Chuifan , Ma Xiangqing , Cai Liping
Published: November 2020

Background: Under natural conditions, soil nutrients are heterogeneously distributed, and plants have developed adaptation strategies to efficiently forage patchily distributed nutrient. Most previous studies examined either patch strength or patch size separately and focused mainly on root morphological plasticity (increased root proliferation in nutrient-rich patch), thus the effects of both patch strength and size on morphological and physiological plasticity are not well understood. In this study, we examined the foraging strategy of Neyraudia reynaudiana (Kunth) Keng ex Hithc, a pioneer grass colonizing degraded sites, with respect to patch strength and size in heterogeneously distributed phosphorus (P), and how foraging patchily distributed P affects total plant biomass production. Plants were grown in sand-culture pots divided into ½, ¼, 1/6 compartments and full size and supplied with 0 + 0/30, 0 + 7.5/30 and 7.5 + 0/30 mg P/kg dry soil as KH2PO4 or 0 + 15/15, 0 + 18.5/ 18.5, 7.5 + 15/15 mg kg−1 in the homogenous treatment. The first amount was the P concentration in the central region, and that the second amount was the P concentration in the outer parts of the pot. Results: After 3 months of growth under experimental conditions, significantly (p < 0.05) high root elongation, root surface area, root volume and average root diameter was observed in large patches with high patch strength. Roots absorbed significantly more P in P-replete than P-deficient patches. Whole plant biomass production was significantly higher in larger patches with high patch strength than small patches and homogeneous P distribution. Conclusion: The result demonstrates that root morphological and physiological plasticity are important adaptive strategies for foraging patchily distributed P and the former is largely determined by patch strength and size. The results also establish that foraging patchily distributed P resulted in increased total plant biomass production compared to homogeneous P distribution.
Responses to drought stress modulate the susceptibility to Plasmopara viticola in grapevine
Authors: Heyman Lisa , Chrysargyris Antonios , Demeestere Kristof , Tzortzakis Nikolaos , Höfte Monica
Published: November 2020

BackgroundClimate change will increase the occurrence of plants simultaneously suffering drought and pathogen stress. Although it is well-known that drought can alter the way plants respond to pathogens, knowledge about the effect of concurrent drought and biotic stress in grapevine is scarce. This is especially true for Plasmopara viticola, the causal agent of grapevine downy mildew. This research addresses how vines with different drought tolerance respond to the challenge with P. viticola, drought stress or their combination, and how one stress affects the other. ResultsArtificial inoculation was performed on two cultivars, exposed to full or deficit irrigation, in the Mediterranean climate of Cyprus. In parallel, leaf disks from these plants were inoculated in controlled conditions. Leaves were sampled at an early infection stage to determine the influence of the single and combined stresses on oxidative parameters, chlorophyll, and phytohormones. Under irrigation, the local Cypriot cultivar Xynisteri was more susceptible to P. viticola than the drought-sensitive Chardonnay. The successful infection by P. viticola at 1.5 days post inoculation was associated with high levels of indole-3-acetic acid (IAA), salicylic acid (SA), jasmonic acid (JA), and proline and strong decreases in antioxidant enzyme activity. Drought, on the other hand, triggered the accumulation of IAA and abscisic acid (ABA), which antagonized JA and SA. Exposure to drought stress increased the susceptibility to P. viticola of the leaves inoculated in controlled conditions. Conversely, both cultivars showed resistance against P. viticola when inoculated in planta under continued deficit irrigation. Despite their resistance, the pathogen-associated responses in IAA, antioxidant enzyme activity, and proline still occurred in these drought-stressed plants. Surprisingly, abscisic acid, rather than the generally implicated jasmonic and salicylic acid, seemed to play a prominent role in this resistance. ConclusionsDrought exposure increased the susceptibility of in vitro inoculated leaves. Conversely, deficit irrigation induced resistance to P. viticola in both Chardonnay and Xynisteri when inoculated in planta. ABA, rather than JA and SA, was implicated in this resistance. The irrigation-dependent susceptibility highlights that the changing climate and the practices used to mitigate its effects, may have a profound impact on plant pathogens.
Outcomes of infants born to pregnant women with syphilis: A nationwide study in Korea
Authors: Lim Joohee , Yoon So Jin , Shin Jeong Eun , Han Jungho , Lee Soon Min , Eun Ho Seon , Park Min soo , Park Kook In
Published: November 2020

Background. Despite expansion of antenatal syphilis screening programs, congenital syphilis (CS) remains a concern. Purpose. This study aimed to analyze the manifestation and progress of CS including treatment and follow-up based on a nationwide study. Methods. From the Korean National Health Insurance Service database, a total of 548 infants were examined for CS during their first year of life from 2013 to 2018. Neurosyphilis and complications were investigated using International Classification of Diseases-10 codes.Results. The birth rate of infants from mothers with syphilis was 2.8 per 10,000 live births for 5 years, which is not indicative of a decreasing trend. Overall, 148 infants were proven or highly probable or possible of having CS with treatment over 10 days; 66 infants were possible or less likely of having CS with only 1-day treatment. Jaundice (56%) was common, followed by hearing impairment (14%), renal disease (8%), and mental retardation (8%). Fourteen cases of neurosyphilis occurred. Infants with complications, including mental retardation, eye involvement, hearing impairment, or renal disease, were significantly associated with neurosyphilis (OR 8.49, P<0.0001). Of 250 patients who received treatment, 92.8% were treated with one medication: benzathine penicillin was used in 73% of patients. Only 4 patients were re-treated due to treatment failure. In addition to the treponemal test, fluorescent treponemal antibody-absorption was the most utilized tool for diagnosis and follow up. Conclusion. Establishing standardized guidelines for the evaluation of and for treatment regimens and follow up plans for CS at a national level would help improve maternal and neonatal care and facilitate the eradication of CS in Korea.
Computational Barthel Index: An Automated Tool for Assessing and Predicting Activities of Daily Living Among Nursing Home Patients
Authors: Wojtusiak Janusz , Asadzadehzanjani Negin , Levy Cari , Alemi Farrokh , Williams Allison E.
Published: November 2020

Background: Assessment of functional ability, including Activities of Daily Living (ADLs), is a manual process completed by skilled health professionals. In the presented research, an automated decision support tool, the Computational Barthel Index Tool (CBIT), was constructed that can automatically assess and predict probabilities of current and future ADLs based on patients’ medical history. Methods: The data used to construct the tool include the demographic information, inpatient and outpatient diagnosis codes, and reported disabilities of 181,213 residents of the Department of Veterans Affairs’ (VA) Community Living Centers. Supervised machine learning methods were applied to construct the CBIT. Temporal information about times from the first and the most recent occurrence of diagnoses was encoded. Ten-fold cross-validation was used to tune hyperparameters, and independent test sets were used to evaluate models using AUC, accuracy, recall and precision. Random forest achieved the best model quality. Models were calibrated using isotonic regression. Results: The unabridged version of CBIT uses 578 patient characteristics and achieved average AUC of 0.94 (0.93-0.95), accuracy of 0.90 (0.89-0.91), precision of 0.91 (0.89-0.92), and recall of 0.90 (0.84-0.95) when re-evaluating patients. CBIT is also capable of predicting ADLs up to one year ahead, with accuracy decreasing over time, giving average AUC of 0.77 (0.73-0.79), accuracy of 0.73 (0.69-0.80), precision of 0.74 (0.66-0.81), and recall of 0.69 (0.34-0.96). A simplified version of CBIT with 50 top patient characteristics reached performance that does not significantly differ from full CBIT.Conclusion: Discharge planners, disability application reviewers and clinicians evaluating comparative effectiveness of treatments can use CBIT to assess and predict information on functional status of patients.
Analysis of cesarean section rates using Robson Ten Group Classification System in a tertiary teaching hospital, Addis Ababa, Ethiopia: a cross-sectional study
Authors: Abubeker Ferid A. , Gashawbeza Biruck , Gebre Thomas Mekuria , Wondafrash Mekitie , Teklu Alula M. , Degu Demis , Bekele Delayehu
Published: November 2020

Background Cesarean section (CS) is an important indicator of access to, and quality of maternal health services. The World Health Organization recommends the Robson ten group classification system as a global standard for assessing, monitoring and comparing CS rates at all levels. This study aimed to assess the rate of CS and perform an analysis based on Robson classification system. Methods A facility-based cross-sectional study was conducted at a tertiary hospital in Addis Ababa, Ethiopia. Data were collected from medical charts of all women who delivered from January-June 2018. The overall CS rate was calculated then women were categorized into one of the ten Robson groups. Relative size of each group, contribution of each group to the overall CS rate, and CS rate within each group were calculated. Results A total of 4,200 deliveries were analyzed. Of these 1,459 (34.7%) were CS. The largest contributors to the overall CS rate were Group 10 (19.1%), Group 2 (18.3%), Group 5 (17.1%), and Group 4 (15.8%). There was also a high rate of pre-labor CS in Group 2, Group 4, and Group 10. Conclusion Through implementation of the Robson ten group classification system, we identified the contribution of each group to the overall CS rate as well as the CS rate within each group. Group 10 was the leading contributor to the overall CS rate. This study also revealed a high rate of CS among low-risk groups. These target groups require more in-depth analysis to identify possible modifiable factors and to apply specific interventions to reduce the CS rate. Evaluation of existing management protocols and further studies into indications of CS and outcomes are needed to design tailored strategies and improve outcomes.
Cell Banking of HEK293T cell line for clinical-grade lentiviral particles manufacturing
Authors: Perpiña Unai , Herranz Cristina , Martin-Ibañez Raquel , Boronat Anna , Chiappe Felipe , Monforte Verónica , Orpella-Arecet Gemma , González Ester , Olive Myriam , Castella Maria , Suñe Guillermo , Urbano Alvaro , Delgado Julio , Juan Manel , Canals Josep M.
Published: November 2020

Background: Cell banks are widely used to preserve cell properties as well as to record and control the use of cell lines in biomedical research. The generation of cell banks for the manufacturing of Advanced Therapy Medicinal Products, such as cell and gene therapy products, must comply with current Good Manufacturing Practice regulations. The quality of the cell lines used as starting materials in viral-vector manufacturing processes must be also assessed.Methods: Three batches of a Master Cell Bank and a Working Cell Bank of the HEK293T cell line were manufactured under current Good Manufacturing Practices regulations. Quality control tests were performed according to product specifications. Process validation includes the training of manufacturing personnel by performing simulation tests, and the continuous measurement of environmental parameters such as air particles and microorganisms. Cell number and viability of cryopreserved cells were periodically measured in order to define the stability of these cellular products.Results: All batches of HEK293T Master and Working Cell Banks met the acceptance criteria of their specifications showing the robustness and homogeneity of the processes. In addition, both Master and Working Cell Banks maintained the defined cell viability and concentration over a 37 month-period after cryopreservation. Conclusions: Manufacturing cell banks under Good Manufacturing Practice regulations for their use as raw materials or final cellular products is feasible. HEK293T cell banks were used to manufacture clinical-grade lentiviral particles for Chimeric Antigen Receptor T-cell based clinical trials.