bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Routine Laboratory Parameters in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: A Long-Term Follow-Up
Authors: Tamalunas Alexander , Buchner Alexander , Kretschmer Alexander , Jokisch Friedrich , Schulz Gerald , Eismann Lennert , Stief Christian G. , Grimm Tobias
Published: February 2020

Objectives: Patients’ oncological outcome after radical cystectomy (RC) due to urothelial carcinoma of the urinary bladder (UCB) is always up for debate. There is accumulating evidence on the influence of routine blood parameters. We aimed to identify reasonable and easy-to-detect biomarkers, such as preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels, as predictors of overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RC for UCB. Materials and Methods: This is a large single-center study in which both preoperative CRP and Hb levels were available in 1,043 patients undergoing RC for UCB from 2004 to 2018 with a median follow-up time of 22 months (mean 38, max. 170). We used the Kaplan-Meier method, log-rank test, and Cox regression models for assessment of OS and CSS. Using our data, we validated an existing outcome prediction score (TNR-C). Results: Median CRP level was 0.5 mg/dL (IQR 0.2–1.4), and median Hb level was 13.4 g/dL (IQR 11.9–14.7). We found that patients with CRP values above the median reached a significantly lower median survival than those with CRP values below the median (23 vs. 83 months, p < 0.001). The TNR-C score was successfully validated, and we discriminated between 3 risk groups (5-year CSS: 76, 40, and 16% for low, intermediate, and high risk, respectively). We observed a similar outcome for patients with a Hb level below the median: CSS was significantly poorer than with Hb levels above the median (median CSS 27 vs. 91 months, p < 0.001). Multivariant analysis showed CRP and Hb levels to be independent prognostic parameters for CSS and OS. Conclusions: We found elevated preoperative CRP levels and decreased Hb levels to be independent prognostic factors indicating an unfavorable outcome in patients undergoing RC for UCB and were able to validate the TNR-C score in a large patient cohort. We propose using these routine biomarkers for individual risk stratification and optimization of therapeutic strategies in patients undergoing RC for UCB.
Questões de romance: notas sobre Antonio Candido e a crítica brasileira
Authors: Otsuka Edu Teruki
Published: February 2020

Este artigo focaliza alguns artigos de Antonio Candido sobre o romance, publicados nos anos 1940 e 1950, e examina algumas discussões sobre o desenvolvimento do romance no Brasil no período de redação de Formação da literatura brasileira, buscando situar as ideias de Candido em seu contexto crítico particular.
Expediente
Authors: Carvalho Lauro
Published: February 2020

Expediente
An fMRI Study of Affective Congruence across Visual and Auditory Modalities
Authors: Gao Chuanji , Weber Christine E. , Wedell Douglas H. , Shinkareva Svetlana V.
Published: February 2020

Evaluating multisensory emotional content is a part of normal day-to-day interactions. We used fMRI to examine brain areas sensitive to congruence of audiovisual valence and their overlap with areas sensitive to valence. Twenty-one participants watched audiovisual clips with either congruent or incongruent valence across visual and auditory modalities. We showed that affective congruence versus incongruence across visual and auditory modalities is identifiable on a trial-by-trial basis across participants. Representations of affective congruence were widely distributed with some overlap with the areas sensitive to valence. Regions of overlap included bilateral superior temporal cortex and right pregenual anterior cingulate. The overlap between the regions identified here and in the emotion congruence literature lends support to the idea that valence may be a key determinant of affective congruence processing across a variety of discrete emotions.
The “Internal” Dimension of the Safe Country Concept: the Interpretation of the Safe Third Country Concept in the Dublin System by International and Internal Courts
Authors: Morgades-Gil Sílvia
Published: February 2020

The non-refoulement principle has been interpreted extensively as regards what kind of threats prevent removal to another country through the interpretation of the international instruments for the protection of human rights. Nevertheless, authors and institutions acknowledge that this principle does not prohibit the removal to a safe country and thus that a number of States participate in a system of shared responsibility, in which refugees and asylum seekers are transferred from one country to another in order to try to obtain (the Dublin EU system) or to benefit from international protection (resettlement). The academic literature has extensively addressed the meaning of the concept of the safe third country. This contribution is aimed at analyzing the application of this concept within a system where all States are supposed to be safe for all asylum seekers, and the principle of mutual trust and equivalence of protection applies. The paper reviews the safe country concept in the context of the Dublin system and examines when and why International, European and internal courts and other institutions have considered that one of the States participating in the system was not safe ad intra. Some final thoughts consider the impact that the analysis may have on the principle of mutual trust that is at the heart of the area of Freedom, Security and Justice.
Physalin B induces apoptosis in hepatocellular carcinoma through reactive oxygen species activation via TGF-β, NF-κB and PI3K/AKT signaling pathways
Authors: Zhao Zhendong , Zhou Guohong , Yang Yanjun , Xia Li , Xu Dandan , Huang Huiqing , Lin Jin , Li Ziqian
Published: February 2020

It is acknowledged that hepatocellular carcinoma (HCC) cause the most cancer-associated mortality all around the world and the traditional Chinese medicine has been widely used in HCC treatment. Physalin B (PB) is the most important chemical compounds of a Chinese traditional herb,
Physalis alkekengi var. franchetii. In this research, it is the first time in the world that we illustrated PB exhibits obvious apoptotic activity in SMMC-7721 and HepG2 human HCC cell lines in the does-dependent way. Moreover, decrease in mitochondrial membrane potential (MMP) was
found and the cellular reactive oxygen species (ROS) was obviously upregulated in PB-treated cell lines. Furthermore, the expression of apoptosis-associated proteins and ROS were increased after the treatment of PB, which were reversed by the inhibitor of TGF-β, NF-κB
or PI3K/AKT signaling pathways. Therefore, PB illustrates potent anticancer activity, which might be studied as a potentiation therapeutic medicine for HCC.
The Interdecadal Shift of ENSO Properties in 1999/2000: A Review
Authors: Hu Zeng-Zhen , Kumar Arun , Huang Bohua , Zhu Jieshun , L’Heureux Michelle , McPhaden Michael J. , Yu Jin-Yi
Published: February 2020

Following the interdecadal shift of El Niño–Southern Oscillation (ENSO) properties that occurred in 1976/77, another regime shift happened in 1999/2000 that featured a decrease of variability and an increase in ENSO frequency. Specifically, the frequency spectrum of Niño-3.4 sea surface temperature shifted from dominant variations at quasi-quadrennial (~4 yr) periods during 1979–99 to weaker fluctuations at quasi-biennial (~2 yr) periods during 2000–18. Also, the spectrum of warm water volume (WWV) index had almost no peak in 2000–18, implying a nearly white noise process. The regime shift was associated with an enhanced zonal gradient of the mean state, a westward shift in the atmosphere–ocean coupling in the tropical Pacific, and an increase in the static stability of the troposphere. This shift had several important implications. The whitening of the subsurface ocean temperature led to a breakdown of the relationship between WWV and ENSO, reducing the efficacy of WWV as a key predictor for ENSO and thus leading to a decrease in ENSO prediction skill. Another consequence of the higher ENSO frequency after 1999/2000 was that the forecasted peak of sea surface temperature anomaly often lagged that observed by several months, and the lag increased with the lead time. The ENSO regime shift may have altered ENSO influences on extratropical climate. Thus, the regime shift of ENSO in 1999/2000 as well as the model default may account for the higher false alarm and lower skill in predicting ENSO since 1999/2000.
9/11 Truth and the Silence of the IR Discipline
Authors: Hughes David A.
Published: February 2020

International Relations (IR) scholars uncritically accept the official narrative regarding the events of 9/11 and refuse to examine the massive body of evidence generated by the 9/11 truth movement. Nevertheless, as calls for a new inquiry into the events of 9/11 continue to mount, with the International 9/11 Consensus Panel and World Trade Centre Building 7 Evaluation inquiries having recently published their findings, and with a U.S. Federal Grand Jury on 9/11 having been announced, now would be an opportune moment for IR scholars to start taking the claims of 9/11 truth seriously. A survey of the 9/11 truth literature reveals that the official 9/11 narrative cannot be supported at multiple levels. Two planes did not bring down three towers in New York. There is no hard evidence that Muslims were responsible for 9/11 other than in a patsy capacity. Various U.S. government agencies appear to have had foreknowledge of the events and to have covered up evidence. Important questions regarding the hijacked planes need answering, as do questions about the complicity of the mainstream media in 9/11. IR scholars avoid looking at evidence regarding the events of 9/11 for several reasons. They may be taken in by the weaponized term, “conspiracy theory.” A taboo on questioning the ruling structures of society means that individuals do not wish to fall outside the spectrum of acceptable opinion. Entertaining the possibility that 9/11 was a false flag requires Westerners to reject fundamental assumptions that they have been socialized to accept since birth. The “War on Terror” has created a neo-McCarthyite environment in which freedom to speak out has been stifled. Yet, if IR scholars are serious about truth, the first place they need to start is 9/11 truth.
Retrospective Study of Fire Setting Among Boys in a Child Welfare Sample
Authors: Brereton Alexandra L. , Lamade Raina V. , Lee Austin F. , Schuler Ann , Prentky Robert A.
Published: February 2020

This study aimed to assess fire-setting behaviors within a child welfare sample. The youth were divided into four groups based on their fire-setting behavior (e.g., no incidents, one incident, multiple minor incidents, and multiple severe incidents). Groups were compared based on five factors: overt antisocial behavior, covert antisocial behavior, global adjustment, psychiatric history, and learning deficits. Fire setters displayed more delinquent behavior and had more extensive psychiatric histories than non-fire-setting youth. Further, the youth with multiple serious incidents of fire-setting behavior displayed more delinquent behavior and had more extensive psychiatric histories than any of the fire-setting groups. These findings clearly suggest that fire setters, as a group, are not homogeneous with respect to antisocial behavior or psychiatric impairment and that gravity of fire setting increased as a function of greater psychopathology and greater delinquency when compared to their peers.
Use and Removal of Inferior Vena Cava Filters in Patients With Acute Brain Injury
Authors: Melmed Kara , Chen Monica L. , Al-Kawaz Mais , Kirsch Hannah L. , Bauerschmidt Andrew , Kamel Hooman
Published: February 2020

Background:

Few data exist regarding the rate of inferior vena cava (IVC) filter retrieval among brain-injured patients.

Methods:

We conducted a retrospective cohort study using inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients aged ≥65 years who were hospitalized with acute brain injury. The primary outcome was the retrieval of IVC filter at 12 months and the secondary outcomes were the association with 30-day mortality and 12-month freedom from pulmonary embolism (PE). We used Current Procedural Terminology codes to ascertain filter placement and retrieval and International Classification of Diseases, Ninth Revision, Clinical Modification codes to ascertain venous thromboembolism (VTE) diagnoses. We used standard descriptive statistics to calculate the crude rate of filter placement. We used Cox proportional hazards analysis to examine the association between IVC filter placement and mortality and the occurrence of PE after adjustment for demographics, comorbidities, and mechanical ventilation. We used Kaplan-Meier survival statistics to calculate cumulative rates of retrieval 12 months after filter placement.

Results:

Among 44 641 Medicare beneficiaries, 1068 (2.4%; 95% confidence interval [CI], 2.3%-2.5) received an IVC filter, of whom 452 (42.3%; 95% CI, 39.3%-45.3) had a diagnosis of VTE. After adjusting for demographics, comorbidities, and mechanical ventilation, filter placement was not associated with a reduced risk of mortality (hazard ratio [HR], 1.0; 95% CI, 0.8-1.3) regardless of documented VTE. The occurrence of pulmonary embolism at 12 months was associated with IVC filter placement (HR, 3.19; 95% CI, 1.3-3.3) in the most adjusted model. The cumulative rate of filter retrieval at 12 months was 4.4% (95% CI, 3.1%-6.1%); there was no significant difference in retrieval rates between those with and without VTE.

Conclusions:

In a large cohort of Medicare beneficiaries hospitalized with acute brain injury, IVC filter placement was uncommon, but once placed, very few filters were removed. IVC filter placement was not associated with a reduced risk of mortality and did not prevent future PE.
Impact of National Culture on Governance and Management of Family Businesses: Australia Versus India
Authors: Kalé Sudhir H. , Harland David , Moores Ken
Published: February 2020

A family is the primary social unit in which individuals are born and get acclimatised to societal culture. Most researches on family businesses are derived from frameworks developed in the United States or other Western societies. The premise of this article is that the way family businesses across the world are managed will vary drastically based on the culture of the society where these businesses operate. Using Australia and India as country examples, we apply Hofstede’s six dimensions of culture to formulate illustrative propositions highlighting the impact of culture on family business governance and management. These propositions are of particular significance to human resource management across areas of both governance and management, and concern, in particular, intergenerational matters associated with succession, management style, employment and developing next-generation leaders.
A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers
Authors: Leung Jacqueline M. , Nagayasu Eiji , Hwang Yu-Chen , Liu Jun , Pierce Phillip G. , Phan Isabelle Q. , Prentice Robin A. , Murray John M. , Hu Ke
Published: February 2020

Background

TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25α and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella.

Results

We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a “C”-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or “C”-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite.

Conclusions

These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion.
Effects of sample age on data quality from targeted sequencing of museum specimens: what are we capturing in time?
Authors: McGaughran Angela
Published: February 2020

Background

Next generation sequencing (NGS) can recover DNA data from valuable extant and extinct museum specimens. However, archived or preserved DNA is difficult to sequence because of its fragmented, damaged nature, such that the most successful NGS methods for preserved specimens remain sub-optimal. Improving wet-lab protocols and comprehensively determining the effects of sample age on NGS library quality are therefore of vital importance. Here, I examine the relationship between sample age and several indicators of library quality following targeted NGS sequencing of ~ 1300 loci using 271 samples of pinned moth specimens (Helicoverpa armigera) ranging in age from 5 to 117 years.

Results

I find that older samples have lower DNA concentrations following extraction and thus require a higher number of indexing PCR cycles during library preparation. When sequenced reads are aligned to a reference genome or to only the targeted region, older samples have a lower number of sequenced and mapped reads, lower mean coverage, and lower estimated library sizes, while the percentage of adapters in sequenced reads increases significantly as samples become older. Older samples also show the poorest capture success, with lower enrichment and a higher improved coverage anticipated from further sequencing.

Conclusions

Sample age has significant, measurable impacts on the quality of NGS data following targeted enrichment. However, incorporating a uracil-removing enzyme into the blunt end-repair step during library preparation could help to repair DNA damage, and using a method that prevents adapter-dimer formation may result in improved data yields.
Neuromyelitis optica: a pilot study of clinical presentation and status of serological biomarker AQP4 among patients admitted to a tertiary centre in NCNS, Sudan
Authors: Ibrahim Etedal Ahmed AbuElbasher , Gammer Fatima , Gassoum Alsadig
Published: February 2020

Background

Neuromyelitis optica (NMO) is a demyelinating disease primarily affecting the optic nerves and spinal cord. It is distinguished from other demyelinating conditions by the presence of AQP4-IgG and serum aquaporin 4 (AQP4), found mainly in the blood–brain barrier. This descriptive study was conducted from January 2015 to June 2018 at the National Center for Neurological Sciences (NCNS) in Khartoum, Sudan. All participants were Sudanese patients diagnosed with NMO. In our study the selection of cases was based on Dean Wingerchuk diagnostic criteria (2006), which states that the diagnosis of NMO should meet two absolute criteria and two supportive criteria. The absolute criteria are myelitis and optic neuritis, whereas supportive criteria include radiological findings obtained from brain and spinal cord MRI. Furthermore, AQP4-IgG levels were measured from cerebrospinal fluid (CSF) and serum using immunofluorescence. Data were collected by a pre-designed questionnaire and analyzed using SPSS version 17. A p value < 0.05 was considered statistically significant.

Results

A total of 31 patients were enrolled in this study [6 male (19.4%) and 25 female (80.6%)]. The mean age was 38 ± 12.8 years. Motor and visual difficulties were the initial symptoms and occurred in 21 (67.7%) and 10 (32.3%) patients, respectively. Fundoscopy confirmed optic atrophy in 22 (71.0%) patients. The course of the disease revealed one relapse in 21 patients (67.7%). Seropositive AQP4-IgG were seen in 23 patients (79.31%). There was a significant correlation between AQP4 and response to treatment (p ≤ 0.038). The correlation between serum AQP4-IgG, showed that, complete improvement was detected in 2 patients (6.9%) one of them was positive and the other was negative, 20 (69.0%) patients presented with some disability, among them 18 (62.1%) were positive and 2 (6.9%) were negative, while 7 patients showed no improvement (24.1%) 4 out of them were positive (13.8%) and 3 were negative (10.3%).

Conclusion

At the initial presentation of NMO, longitudinal myelitis was observed more frequently than optic neuritis. More than two third of the patients showed strong seropositivity for serum AQP4. Most seropositive patients showed a good response to treatment but with residual disabilities.
Nerylneryl diphosphate is the precursor of serrulatane, viscidane and cembrane-type diterpenoids in Eremophila species
Authors: Gericke Oliver , Hansen Nikolaj Lervad , Pedersen Gustav Blichfeldt , Kjaerulff Louise , Luo Dan , Staerk Dan , Møller Birger Lindberg , Pateraki Irini , Heskes Allison Maree
Published: February 2020

Background

Eremophila R.Br. (Scrophulariaceae) is a diverse genus of plants with species distributed across semi-arid and arid Australia. It is an ecologically important genus that also holds cultural significance for many Indigenous Australians who traditionally use several species as sources of medicines. Structurally unusual diterpenoids, particularly serrulatane and viscidane-types, feature prominently in the chemical profile of many species and recent studies indicate that these compounds are responsible for much of the reported bioactivity. We have investigated the biosynthesis of diterpenoids in three species: Eremophila lucida, Eremophila drummondii and Eremophila denticulata subsp. trisulcata.

Results

In all studied species diterpenoids were localised to the leaf surface and associated with the occurrence of glandular trichomes. Trichome-enriched transcriptome databases were generated and mined for candidate terpene synthases (TPS). Four TPSs with diterpene biosynthesis activity were identified: ElTPS31 and ElTPS3 from E. lucida were found to produce (3Z,7Z,11Z)-cembratrien-15-ol and 5-hydroxyviscidane, respectively, and EdTPS22 and EdtTPS4, from E. drummondii and E. denticulata subsp. trisulcata, respectively, were found to produce 8,9-dihydroserrulat-14-ene which readily aromatized to serrulat-14-ene. In all cases, the identified TPSs used the cisoid substrate, nerylneryl diphosphate (NNPP), to form the observed products. Subsequently, cis-prenyl transferases (CPTs) capable of making NNPP were identified in each species.

Conclusions

We have elucidated two biosynthetic steps towards three of the major diterpene backbones found in this genus. Serrulatane and viscidane-type diterpenoids are promising candidates for new drug leads. The identification of an enzymatic route to their synthesis opens up the possibility of biotechnological production, making accessible a ready source of scaffolds for further modification and bioactivity testing.
Peripheral arterial disease and its correlates in patients with type 2 diabetes mellitus in a teaching hospital in northern Nigeria: a cross-sectional study
Authors: Agboghoroma Orighomisan Freda , Akemokwe Fatai Momodu , Puepet Fabian H.
Published: February 2020

Background

Peripheral arterial disease (PAD) is a risk factor for diabetic foot ulcer, limb amputation as well as coronary heart disease. It is more common in patients with diabetes mellitus (DM) and co-exists with peripheral neuropathy. Prevalence of PAD in type 2 DM patients in northern Nigeria is largely unknown. We investigated the occurrence and factors associated with PAD among patients with type 2 DM in a tertiary hospital in northern Nigeria.

Methods

This was a cross- sectional analytic study. We recruited 200 patients with type 2 DM consecutively from the diabetes clinic of the Jos University Teaching Hospital. Ankle brachial index was assessed for each participant. Clinical information, anthropometric indices and blood samples were collected for assay. Data was analysed using CDC Epi-Info and logistic regression analysis was used to determine independent correlates of PAD.

RESULTS:PAD was present in 38.5%(n = 77) of subjects and it was associated with the female sex, age ≥ 50 years, Body mass index (BMI) ≥ 25 kg/m2 and low HDL cholesterol levels. However, on multiple logistic regression, a BMI ≥ 25 kg/m2 and a low HDL cholesterol level were independent correlates of PAD(adjusted OR = 2.13,95% CI = 1.04–4.36 and adjusted OR = 2.31, 95% CI = 1.04–5.15, respectively).

Conclusion

PAD is present in more than a third of patients with type 2 DM in a tertiary hospital in northern Nigeria. A BMI of ≥25 kg/m2 and low HDL cholesterol levels were independent correlates of PAD.
SLC5A2 mutations, including two novel mutations, responsible for renal glucosuria in Chinese families
Authors: Yu Lei , Wu Meng , Hou Ping , Zhang Hong
Published: February 2020

Background

Familial renal glucosuria (FRG) is characterized by persistent glucosuria without other impairments of tubular function in the presence of normal serum glucose. SGLT2, which is almost exclusively expressed in the kidney, accounts for most of the glucose reabsorption. Recently, some studies have confirmed that SLC5A2 mutations are responsible for the pathogenesis of familial renal glucosuria, but FRG cases are still rare. Furthermore, there are a few reports about splice-site mutations in previous studies, but the effect of these variants at the mRNA level has hardly been verified.

Methods

Ten patients were recruited in our renal division because of persistent glucosuria, and clinical data of the patients and their family members were recorded as much as possible. The entire coding region and adjacent intronic segments of SLC5A2 were sequenced in FRG patients and their relatives. Permanent growing lymphoblastoid cell lines from FRG patients were established to better preserve genetic information.

Results

A total of nine different mutations were identified: IVS1-16C > A, c.305C > T/p.(A102V), c.395G > A/p.(R132H), c.736C > T/p.(P246S), c.886(−10_-31)delGCAAGCGGGCAGCTGAACGCCC, c.1152_1163delGGTCATGCTGGC/p.(Val385_Ala388del), c.1222G > T/p.(D408Y), c.1496G > A/p.(R499H) and c.1540C > T/p.(P514S); two novel mutations in SLC5A2, c.1222G > T/p.(D408Y) and c.1496G > A/p.(R499H), were identified in the Chinese FRG pedigrees. Ten individuals with heterozygous or compound heterozygous variants had glucosuria in the range of 3.1 to 37.6 g/d.

Conclusion

We screened ten additional Chinese FRG pedigrees for mutations in the SLC5A2 gene and found nine mutations, including two novel mutations. Most variants were private, but IVS1-16C > A and c.886(−10_-31) del may be high frequency splice-site mutations that could be preferentially screened when variants cannot be found in the SLC5A2 exon. Furthermore, we successfully established a permanent growing lymphoblastoid cell line from patients with FRG, which could facilitate further studies of the SLC5A2 gene. The current study provides a valuable clue for further research on the molecular mechanism of SGLT2.
Comparison of frequency-domain and continuous-wave near-infrared spectroscopy devices during the immediate transition
Authors: van Essen Tanja , Goos Tom G. , van Ballegooijen Liza , Pichler Gerhard , Urlesberger Berndt , Reiss Irwin K. M. , de Jonge Rogier C. J.
Published: February 2020

Background

Non-invasive monitoring of cerebral tissue oxygen saturation (rcSO2) during transition is of growing interest. Different near-infrared spectroscopy (NIRS) techniques have been developed to measure rcSO2. We compared rcSO2 values during the immediate transition in preterm neonates measured with frequency-domain NIRS (FD-NIRS) with those measured with continuous-wave NIRS (CW-NIRS) devices in prospective observational studies.

Methods

We compared rcSO2 values measured with an FD-NIRS device during the first 15 min after birth in neonates with a gestational age ≥ 30 weeks but < 37 weeks born at the Erasmus MC- Sophia Children’s Hospital, Rotterdam, the Netherlands, with similar values measured with a CW-NIRS device in neonates born at the Medical University of Graz, Austria. Mixed models were used to adjust for repeated rcSO2 measurements, with fixed effects for time (non-linear), device, respiratory support and the interaction of device and respiratory support with time. Additionally, parameters such as total haemoglobin concentration and oxygenated and deoxygenated haemoglobin concentrations measured by FD-NIRS were analysed.

Results

Thirty-eight FD-NIRS measurements were compared with 58 CW-NIRS measurements. The FD-NIRS rcSO2 values were consistently higher than the CW-NIRS rcSO2 values in the first 12 min, irrespective of respiratory support. After adjustment for respiratory support, the time-dependent trend in rcSO2 differed significantly between techniques (p < 0.01).

Conclusion

As cerebral saturation measured with the FD-NIRS device differed significantly from that measured with the CW-NIRS device, differences in absolute values need to be interpreted with care. Although FD-NIRS devices have technical advantages over CW-NIRS devices, FD-NIRS devices may overestimate true cerebral oxygenation and their benefits might not outweigh the usability of the more clinically viable CW-NIRS devices.
Acute respiratory infection and its associated factors among children under-five years attending pediatrics ward at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: institution-based cross-sectional study
Authors: Dagne Henok , Andualem Zewudu , Dagnew Baye , Taddese Asefa Adimasu
Published: February 2020

Background

Acute respiratory infection is manifested by cough accompanied by short rapid breathing which may be associated with death especially when there are other co-morbidities. From an estimated 5.4 million children under –five years that died in 2017—roughly half of those deaths occurred in sub-Saharan Africa and acute respiratory infection contributed to the highest number of deaths. The current study aimed at evaluating the prevalence of, and risk factors associated with, acute respiratory infection hospitalization in under-five years children hospitalized at the University of Gondar Comprehensive Specialized Hospital.

Method

An institution-based cross-sectional study was carried out from May 01/2019 to July 10/2019. After the selection of participants using simple random sampling, face to face interview was performed using a semi-structured pre-tested questionnaire. Data were also extracted from medical registration charts. We used EPI Info 7 for data entry and exported into SPSS 21 for analysis. Results were presented by simple frequency, percentage and mean for descriptive variables. Binary logistic regression analysis was used to test the association of covariates and outcome variable. Variables with ap < 0.2 during the bivariable binary logistic regression analysis were included in the multivariable logistic regression analysis. Variables withp < 0.05 were considered as significantly associated with acute respiratory infection. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology guideline.

Results

Four hundred and twenty-two under-five years’ children attending the Pediatrics ward were included in this study. The prevalence of acute respiratory infection among under-five years’ children in this study was 27.3%. Children aged below 12 months (AOR:3.39, 95% CI: 1.19, 9.65), maternal age of 16 to 27 years (AOR: 1.95, 95% CI: 1.03, 3.70), maternal age of 28 to 33 years (AOR: 2.73, 95% CI: 1.40, 5.34), lack of maternal awareness of handwashing (AOR: 2.79, 95% CI: 1.15, 6.76), rural residence (AOR:2.27, 95% CI: 1.18, 4.39), and lack of meningitis (AOR: 0.22, 95% CI: 0.08, 0.55), were significantly associated with acute respiratory infection.

Conclusion

Acute respiratory infection was common among children under-five years. Child and maternal age, residence and maternal hand hygiene information were significant factors identified to be associated with an acute respiratory infection.
Validation of the global lung initiative 2012 multi-ethnic spirometric reference equations in healthy urban Zimbabwean 7–13 year-old school children: a cross-sectional observational study
Authors: Madanhire Tafadzwa , Ferrand Rashida A. , Attia Engi F. , Sibanda Elopy N. , Rusakaniko Simba , Rehman Andrea M.
Published: February 2020

Background

The 2012 Global Lung Function Initiative (GLI2012) provide multi-ethnic spirometric reference equations (SRE) for the 3–95 year-old age range, but Sub-Saharan African populations are not represented. This study aimed to evaluate the fit of the African-American GLI2012 SRE to a population of healthy urban and peri-urban Zimbabwean school-going children (7–13 years).

Methods

Spirometry and anthropometry were performed on black-Zimbabwean children recruited from three primary schools in urban and peri-urban Harare, with informed consent and assent. Individuals with a history or current symptoms of respiratory disease or with a body mass index-z score (BMI) < − 2 were excluded. Spirometry z-scores were generated from African-American GLI2012 SRE, which adjust for age, sex, ethnicity and height, after considering all GLI2012 modules. Anthropometry z-scores were generated using the British (1990) reference equations which adjust for age and sex. The African-American GLI2012 z-score distribution for the four spirometry measurements (FVC, FEV1, FEV1/FVC and MMEF) were evaluated across age, height, BMI and school (as a proxy for socioeconomic status) to assess for bias. Comparisons between the African-American GLI2012 SRE and Polgar equations (currently adopted in Zimbabwe) on the percent-predicted derived values were also performed.

Results

The validation dataset contained acceptable spirometry data from 712 children (344 girls, mean age: 10.5 years (SD 1.81)). The spirometry z-scores were reasonably normally distributed, with all means lower than zero but within the range of ±0.5, indicating a good fit to the African-American GLI2012 SRE. The African-American GLI2012 SRE produced z-scores closest to a normal distribution. Z-scores of girls deviated more than boys. Weak correlations (Pearson’s correlation coefficient < 0.2) were observed between spirometry and anthropometry z-scores, and scatterplots demonstrated no systematic bias associated with age, height, BMI or socioeconomic status. The African-American GLI2012 SRE provided a better fit for Zimbabwean paediatric spirometry data than Polgar equations.

Conclusion

The use of African-American GLI2012 SRE in this population could help in the interpretation of pulmonary function tests.
Incidence and location of heterotopic ossification following hip arthroscopy
Authors: Zheng Long , Hwang Jung-Mo , Hwang Deuk-Soo , Kang Chan , Lee Jeong-Kil , Park Young-Cheol
Published: February 2020

Background

We investigated the incidence and location of heterotopic ossification (HO) following hip arthroscopy.

Methods

This retrospective study enrolled 327 patients who underwent hip arthroscopy from January 2010 to December 2015. From this cohort, we extracted an HO group with simple radiographs or three-dimensional computed tomography (3D CT). Findings consistent with HO were classified according to the Brooker classification aided with 3D CT for the location of HO. The indication for revision arthroscopic excision of HO was painful, functional impairment of the hip. Patient clinical outcomes were assessed pre- and postoperatively, with modified Harris Hip Scores (mHHS), a visual analogue scale (VAS) for pain, and the Hip Outcome Score-Activity of Daily Living (HOS-ADL) and Sport Specific Subscales (HOS-SSS).

Results

In all, 14 (4.28%) of the 327 patients had confirmed HO radiographically. The mean follow-up was 39 months. In 13 patients, HO formed in the central area of the arthroscopic portals or capsulotomy. Ten patients had Brooker Grade 1 and four had Grade 2. At the last follow-up, 12 asymptomatic patients had significant (P < 0.001) improvements in all clinical outcome scores (mHHS, pain VAS, HOS-ADL, and HOS-SSS). Two patients developed symptoms sufficient to require revision hip arthroscopy for HO excision. After revision hip arthroscopy, both symptomatic patients had improved significantly in all clinical outcomes at the final follow-up.

Conclusions

HO is a minor complication of hip arthroscopy, but sometimes induces severe pain and functional impairment. Usually, HO forms in the arthroscopic portal or capsulotomy area.
Electrolyte outpatient clinic at a local hospital – experience from diagnostics, treatment and follow-up
Authors: Tazmini Kiarash , Ranhoff Anette Hylen
Published: February 2020

Background

Electrolyte imbalances (EI) are common among patients. Many patients have repeated hospitalizations with the same EI without being investigated and treated. We established an electrolyte outpatient clinic (EOC) to diagnose and treat patients with EI to improve symptoms and increase their quality of life (QoL). In addition, we also wanted to reduce the number of admissions with the same EI.

Methods

Uncontrolled before-after study reporting experiences from this outpatient clinic as a quality assurance project. From October 2010 to October 2015, doctors at our local hospital and general practitioners could refer adult patients with EI to the EOC. Ninety patients with EI were referred, of whom 60 were included. Medical history, clinical examination and laboratory tests were performed, and results registered. Admissions with the same EI were recorded 1 year before and 1 year after consultation at the EOC. Patients responded to a questionnaire, composed by the authors, about symptoms before the first consultation, as well as symptom and QoL improvement after the last consultation.

Results

Hyponatremia was the reason for referral in 45/60 patients. The total number of admissions with the same EI 1 year before the first consultation was 71, compared with 20 admissions 1 year after the last consultation. Improvement of symptoms was reported by 60% of patients, and 62% reported improvement in QoL.

Conclusions

An EOC may be an appropriate way to organize the assessment and treatment of patients with EI.
Remission of autoimmune diabetes by anti-TCR combination therapies with anti-IL-17A or/and anti-IL-6 in the IDDM rat model of type 1 diabetes
Authors: Jörns Anne , Ishikawa Daichi , Teraoku Hiroki , Yoshimoto Toshiaki , Wedekind Dirk , Lenzen Sigurd
Published: February 2020

Background

The cytokine IL-17 is a key player in autoimmune processes, while the cytokine IL-6 is responsible for the chronification of inflammation. However, their roles in type 1 diabetes development are still unknown.

Methods

Therefore, therapies for 5 days with anti-IL-17A or anti-IL-6 in combination with a T cell-specific antibody, anti-TCR, or in a triple combination were initiated immediately after disease manifestation to reverse the diabetic metabolic state in the LEW.1AR1-iddm (IDDM) rat, a model of human type 1 diabetes.

Results

Monotherapies with anti-IL-6 or anti-IL-17 showed no sustained anti-diabetic effects. Only the combination therapy of anti-TCR with anti-IL-6 or anti-IL-17 at starting blood glucose concentrations up to 12 mmol/l restored normoglycaemia. The triple antibody combination therapy was effective even up to very high initial blood glucose concentrations (17 mmol/l). The β cell mass was raised to values of around 6 mg corresponding to those of normoglycaemic controls. In parallel, the apoptosis rate of β cells was reduced and the proliferation rate increased as well as the islet immune cell infiltrate was strongly reduced in double and abolished in triple combination therapies.

Conclusions

The anti-TCR combination therapy with anti-IL-17 preferentially raised the β cell mass as a result of β cell proliferation while anti-IL-6 strongly reduced β cell apoptosis and the islet immune cell infiltrate with a modest increase of the β cell mass only. The triple combination therapy achieved both goals in a complimentary anti-autoimmune and anti-inflammatory action resulting in sustained normoglycaemia with normalized serum C-peptide concentrations.
HDAC8 inhibitor attenuates airway responses to antigen stimulus through synchronously suppressing galectin-3 expression and reducing macrophage-2 polarization
Authors: Li Meng-lu , Su Xin-ming , Ren Yuan , Zhao Xuan , Kong Ling-fei , Kang Jian
Published: February 2020

Background

This study was to investigate of the mechanism by which histone deacetylase (HDAC) 8 inhibitor ameliorated airway hyperresponsiveness (AHR) and allergic airway inflammation.

Methods

Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). The raw264.7 cells were treated with interleukin (IL)-4 and PCI or shRNA alone. Repetitive measurements of enhanced pause (Penh) were executed by increasing concentrations of acetyl-β-methacholine chloride (0 - 50 mg/ml). Cells in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs were examined, respectively. The expression levels of HDAC8, Galecitn (Gal)-3, CD68, CD86, CD163, Arg1 and NOS2 in lungs were measured. Co-regulation of HDAC8 and Gal-3 proteins was observed by immunofluorescence staining and co-immunoprecipitation assay (Co-IP).

Results

Significant increases in Penh and IL-4 level were detected with a large inflammatory infiltrate, comprised predominantly of macrophages and eosinophils, into the BALF in OVA-exposed lungs. HDAC8, Gal-3, CD68, CD86, CD163, Arg1 and NOS2 proteins were over-expressed with the significant changes in the Arg1 and NOS2 mRNA levels in the lungs and the IL-4-treated cells. PCI intervention obviously reduced the counts of CD163+cells. Furthermore, Gal-3 knockdown suppressed Arg1 expression in the cells. Immunofluorescence staining displayed simultaneous changes in HDAC8 and Gal-3 expression in the investigated samples. Treatment with PCI resulted in synchronous reduction of HDAC8 and Gal-3 expression in the Co-IP complexes.

Conclusions

The HDAC8 inhibitor ameliorates AHR and airway inflammation in animal model of allergic asthma through reducing HDAC8-Gal-3 interaction and M2 macrophage polarization.
METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST
Authors: Yang Xiao , Zhang Sen , He Changyu , Xue Pei , Zhang Luyang , He Zirui , Zang Lu , Feng Bo , Sun Jing , Zheng Minhua
Published: February 2020

Background

N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A in colorectal cancer (CRC) is very limited. We designed this study to investigate the role of m6A in CRC.

Methods

Expression level of METTL14 was extracted from public database and tissue array to investigate the clinical relevance of METTL14 in CRC. Next, gain/loss of function experiment was used to define the role of METTL14 in the progression of CRC. Moreover, transcriptomic sequencing (RNA-seq) was applied to screen the potential targets of METTL14. The specific binding between METTL14 and presumed target was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Furthermore, rescue experiment and methylated RNA immunoprecipitation (Me-RIP) were performed to uncover the mechanism.

Results

Clinically, loss of METTL14 correlated with unfavorable prognosis of CRC patients. Functionally, knockdown of METTL14 drastically enhanced proliferative and invasive ability of CRC cells in vitro and promoted tumorigenicity and metastasis in vivo. Mechanically, RNA-seq and Me-RIP identified lncRNA XIST as the downstream target of METTL14. Knockdown of METTL14 substantially abolished m6A level of XIST and augmented XIST expression. Moreover, we found that m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. Consistently, XIST expression negatively correlated with METTL14 and YTHDF2 in CRC tissues.

Conclusion

Our findings highlight the function and prognostic value of METTL14 in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.
Personality traits and the risk of becoming lonely in old age: A 5-year follow-up study
Authors: Ormstad Heidi , Eilertsen Grethe , Heir Trond , Sandvik Leiv
Published: February 2020

Background

Although many people experience loneliness in old age, there is little knowledge of predisposing personality factors. The aim of the present study was to explore to what extent personality traits are associated with the risk of becoming lonely, in women and men aged 60–79 years at baseline.

Methods

The panel data are from The Norwegian study on Life course, Ageing and Generations (NorLAG). Our sample consisted of 516 men and 419 women aged 60–79 years, who were surveyed in both 2002–2003 (baseline) and 2007–2008 (follow-up), and who reported not being lonely at baseline. Personality traits were measured by the Big Five scale. Multivariable logistic regression analyses were used to investigate the association between a personality trait and the risk of becoming lonely, with adjustment for age, mental health and living with a partner.

Results

At follow-up 59 women and 54 men reported loneliness (14.1% vs. 10.5%, p = 0.092). Among women, high agreeableness at baseline was significantly associated with a higher risk of becoming lonely. Among men, low agreeableness, low conscientiousness and high neuroticism at baseline were significantly associated with a higher risk of becoming lonely.

Conclusions

Personality traits related differently to loneliness depending on gender. These findings may be useful when developing strategies for preventing loneliness in old age.