bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarker A+T−: is this Alzheimer’s disease or not? A combined CSF and pathology study
Authors: Vromen Eleonora M , de Boer Sterre C M , Teunissen Charlotte E , Rozemuller Annemieke , Sieben Anne , Bjerke Maria ,   for the Alzheimer’s Disease Neuroimaging Initiative, Visser Pieter Jelle , Bouwman Femke H , Engelborghs Sebastiaan , Tijms Betty M
Published: April 2022

The biological definition of Alzheimer’s disease using CSF biomarkers requires abnormal levels of both amyloid (A) and tau (T). However, biomarkers and corresponding cutoffs may not always reflect the presence or absence of pathology. Previous studies suggest that up to 32% of individuals with autopsy-confirmed Alzheimer’s disease show normal CSF p-tau levels in vivo, but these studies are sparse and had small sample sizes. Therefore, in three independent autopsy cohorts, we studied whether or not CSF A+T− excluded Alzheimer’s disease based on autopsy.

We included 215 individuals, for whom ante-mortem CSF collection and autopsy had been performed, from three cohorts: (i) the Amsterdam Dementia Cohort (ADC) [n = 80, 37 (46%) Alzheimer’s disease at autopsy, time between CSF collection and death 4.5 ± 2.9 years]; (ii) the Antwerp Dementia Cohort (DEM) [n = 92, 84 (91%) Alzheimer’s disease at autopsy, time CSF collection to death 1.7 ± 2.3 years]; and (iii) the Alzheimer’s Disease Neuroimaging Initiative (ADNI) [n = 43, 31 (72%) Alzheimer’s disease at autopsy, time CSF collection to death 5.1 ± 2.5 years]. Biomarker profiles were based on dichotomized CSF Aβ1-42 and p-tau levels. The accuracy of CSF AT profiles to detect autopsy-confirmed Alzheimer’s disease was assessed. Lastly, we investigated whether the concordance of AT profiles with autopsy diagnosis improved when CSF was collected closer to death in 9 (10%) DEM and 30 (70%) ADNI individuals with repeated CSF measurements available.

In total, 50–73% of A+T− individuals and 100% of A+T+ individuals had Alzheimer’s disease at autopsy. Amyloid status showed the highest accuracy to detect autopsy-confirmed Alzheimer’s disease (accuracy, sensitivity and specificity in the ADC: 88%, 92% and 84%; in the DEM: 87%, 94% and 12%; and in the ADNI cohort: 86%, 90% and 75%, respectively). The addition of CSF p-tau did not further improve these estimates. We observed no differences in demographics or degree of Alzheimer’s disease neuropathology between A+T− and A+T+ individuals with autopsy-confirmed Alzheimer’s disease. All individuals with repeated CSF measurements remained stable in Aβ1-42 status during follow-up. None of the Alzheimer’s disease individuals with a normal p-tau status changed to abnormal; however, four (44%) DEM individuals and two (7%) ADNI individuals changed from abnormal to normal p-tau status over time, and all had Alzheimer’s disease at autopsy.

In summary, we found that up to 73% of A+T− individuals had Alzheimer’s disease at autopsy. This should be taken into account in both research and clinical settings.
Human Immunodeficiency Virus Is Associated With Elevated FibroScan–Aspartate Aminotransferase (FAST) Score
Authors: Price Jennifer C , Ma Yifei , Kuniholm Mark H , Adimora Adaora A , Fischl Margaret , French Audrey L , Golub Elizabeth T , Konkle-Parker Deborah , Minkoff Howard , Ofotokun Ighovwerha , Plankey Michael , Sharma Anjali , Tien Phyllis C
Published: April 2022

Background

Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan–aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort.

Methods

Vibration-controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women with HIV (WWH) and 381 women without HIV (WWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score.

Results

Median age of WWH and WWOH was 51 years and 48 years, respectively. Most (90%) WWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WWH compared to WWOH (6.3% vs 1.8%, respectively; P = .001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P = .002), and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (P < .001). In analysis limited to WWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score.

Conclusions

Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons with HIV are warranted.
Emergence of Dalbavancin, Vancomycin, and Daptomycin Nonsusceptible Staphylococcus aureus in a Patient Treated With Dalbavancin: Case Report and Isolate Characterization
Authors: Zhang Rutan , Polenakovik Hari , Barreras Beltran Ismael A , Waalkes Adam , Salipante Stephen J , Xu Libin , Werth Brian J
Published: April 2022

A patient with end-stage renal disease received 2 doses of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) arteriovenous fistula infection and presented 5 weeks later with infective endocarditis secondary to vancomycin, daptomycin, and dalbavancin nonsusceptible MRSA. Resistance was associated with walK and scrA mutations, reduced long-chain lipid content, and reduced membrane fluidity.
Survival of conventionally bonded mandibular retainers with or without enamel sandblasting in orthodontic patients over a 12-month period. A single-centre, split-mouth randomized clinical trial
Authors: Laspos Christodoulos , Seehra Jadbinder , Katsaros Christos , Pandis Nikolaos
Published: April 2022

Background

The aim of this trial was to assess the effect of enamel sandblasting in addition to the acid-etch technique in reducing first-time failures of fixed mandibular retainers placed over a 12-month period.

Materials and methods

Ethical approval was obtained. Participants were recruited in a single private practice. The primary outcome of this study was any first-time failure of the mandibular fixed retainer assessed at three timepoints over a 12-month period. Three consecutive teeth either on the left or right side (from lower canine-lower central incisor) were randomly allocated to the intervention (sandblasting) and the control (non-sandblasted). Randomization was performed using a centralized randomization service. The patients were randomized in blocks of four and eight with allocation concealment secured by contacting the sequence generator for group assignment. Blinding of either the patient or clinicians was not possible at time of placement of the mandibular retainer.

Results

One hundred and ninety-seven participants were randomized to receive enamel sandblasting (intervention) and non-sandblasting (control) in the region of the six anterior mandibular teeth in a split-mouth fashion. Participants were recruited between December 2018 to October 2020. The data for all participants were analysed resulting in 394 observations. Overall, the risk of first-time failure was 11.4%. No difference in first-time failures was observed between the intervention (sandblasting) and control (non-sandblasting) groups [hazard ratio (HR), 1.05; 95% confidence interval (CI), 0.59, 1.88, P = 0.88]. Males had a higher instant probability of first-time failures (HR, 3.18; 95% CI, 1.65–6.14; P < 0.01). Participants with a fair level of co-operation had a lower instant probability of first-time failures (HR, 0.37; 95% CI, 0.16-0.86; P = 0.02). There were no harms reported to either the participant or their dentition.

Conclusions

No difference in the first-time failures of mandibular bonded retainers placed with conventional etch-bond technique with or without enamel sandblasting was observed. The overall risk of first-time failure was 11.4%.

Registration

This trial was not registered prior to trial commencement.
The Role of Parents’ Native and Migrant Contacts on the Labour Market in the School-to-Work Transition of Adolescents in Germany
Authors: Roth Tobias , Weißmann Markus
Published: April 2022

This study investigates how parents’ native and migrant contacts in the German labour market affect the likelihood of children obtaining a company-based apprenticeship [dual vocational education and training (VET)] after lower secondary education. Furthermore, it assesses the extent to which characteristics of parents’ social networks explain ethnic inequalities in this school-to-work transition. Using longitudinal data from Starting Cohort 4 (ninth-graders) of the National Educational Panel Study, we show that the number of migrant contacts in parents’ networks does not affect the outcome of adolescents’ apprenticeship search. This applies to both migrant and native adolescents. However, if parents have many native contacts, the chances of adolescents obtaining a company-based apprenticeship increases in both groups. In addition, controlling for the composition of parents’ networks substantially reduces the gap between natives and migrants in the transition to dual VET. Further analyses show that this is mainly due to differences in the number of native labour market contacts between native and migrant parents. Our findings indicate that differences in parents’ endowment with labour market relevant social capital constitute yet another hurdle for immigrant children in the transition from school to working life.
Dark survival in biofilm-forming microalgae: potential for colonizing benthic ecosystems
Authors: Patil Jagadish S , D'souza Samantha
Published: April 2022

The biofilm-forming microalgae are known to experience periods of continuous darkness (upto several days), in addition to the natural day–night cycle, especially in the intertidal sediment regions (when transported to deeper sediments) and the ships’ ballast water tanks (during voyages). However, the information on community and physiological responses to different periods of darkness is limited. Here, the survival capability of biofilm-forming microalgae to varying periods of darkness (7–35 days) and the growth patterns upon resumption of normal 12 h light:dark photocycle has been addressed through simulation experiments. Diatoms dominated the seawater biofilms, but the dark survival period varied and was species-specific. Of the 25 diatoms, only Amphora, potential toxin producer, followed by Navicula remained viable and photosynthetically healthy under darkness without undergoing asexual reproduction. Both diatoms are essential contributors to fouling and microphytobenthic community. Upon re-exposure of dark-adapted biofilms to 12 h light:dark photocycle, the improvement in photosynthetic efficiency and resumption of growth via asexual-reproduction was observed. However, the lag-phase duration increased with a long dark history. Nevertheless, eurytolerant nature and high dark survival capability (with its quick response to light) of Amphora and Navicula indicated that they have the potential to colonize benthic-ecosystems thus impacting the benthic and fouling community.
Coseismic deformation and slip distribution of the 2017 Mw 6.3 Jinghe, Xinjiang, western China earthquake based on InSAR observations: a buried reverse event on previously unknown fault
Authors: Yanfang Dong , Guojie Meng , Shunying Hong
Published: April 2022

The 2017 Mw 6.3 Jinghe earthquake occurred in the orogenic zone of the North Tianshan mountain range, Xinjiang, western China. No evident surface rupture was identified by field investigation conducted immediately after the earthquake. We investigate the coseismic and post-seismic deformation fields due to the Jinghe event using the C-band Sentinel-1 SAR imagery, and further analyse its causative fault. The Generic Atmospheric Correction Online Service for InSAR (GACOS) model is employed to remove the atmospheric phase delay of multiple InSAR deformation maps. Coseismic deformation fields are resolved by averaging the high quality deformation maps. A nonlinear inversion scheme is used to find the optimized fault geometry in a layered elastic crust. The results imply that the Jinghe earthquake is characterized by thrust faulting, with striking and dipping angles of ∼62° and ∼28°, respectively. Subsequently coseismic slip distribution is estimated using the steepest descent method program, constrained by the derived coseismic deformation fields. The inversion results show that the average slip is ∼0.08 m and the average rake angle is ∼98°. The maximum slip is ∼0.24 m, located at the depth of 12.9 km. The moment magnitude is estimated to be Mw 6.38. The fault geometry is generally consistent with the relocated aftershocks distribution. Both the InSAR-derived deformation field and the aftershock distribution indicate that the Jinghe earthquake is attributed to a previously unknown buried fault beneath the Yongji fold with a strike of 62°. No significant post-seismic deformation is identified in the zone of coseismic deformation. This study shows that the Jinghe earthquake is a typical inland thrust event in the North Tianshan area, which is affected by south to north compression due to the Indian-Eurasian collision.
The Integrated Defense System: Optimizing Defense against Predators, Pathogens, and Poisons
Authors: Adamo Shelley
Published: April 2022

Insects, like other animals, have evolved defense responses to protect against predators, pathogens, and poisons (i.e., toxins). This paper provides evidence that these three defense responses (i.e., fight-or-flight, immune, and detoxification responses) function together as part of an Integrated Defense System (IDS) in insects. The defense responses against predators, pathogens, and poisons are deeply intertwined. They share organs, resources, and signaling molecules. By connecting defense responses into an IDS, animals gain flexibility, and resilience. Resources can be redirected across fight-or-flight, immune, and detoxification defenses to optimize an individual's response to the current challenges facing it. At the same time, the IDS reconfigures defense responses that are losing access to resources, allowing them to maintain as much function as possible despite decreased resource availability. An IDS perspective provides an adaptive explanation for paradoxical phenomena such as stress-induced immunosuppression, and the observation that exposure to a single challenge typically leads to an increase in the expression of genes for all three defense responses. Further exploration of the IDS will require more studies examining how defense responses to a range of stressors are interconnected in a variety of species. Such studies should target pollinators and agricultural pests. These studies will be critical for predicting how insects will respond to multiple stressors, such as simultaneous anthropogenic threats, for example, climate change and pesticides.
Sublobar resection versus lobectomy for patients with stage T1-2N0M0 pulmonary typical carcinoid tumours: a population-based propensity score matching analysis
Authors: Yang Hao , Mei Tonghua
Published: April 2022

OBJECTIVES

It is widely accepted that surgical resection of localized pulmonary typical carcinoid (TC) tumours remains the primary curative modality. However, the optimal extent of resection remains controversial. This study aimed to investigate the survival rates of patients with stage T1-2N0M0 TC tumours who underwent sublobar resection or lobectomy.

METHODS

We queried the Surveillance, Epidemiology, and End Results database for patients who underwent surgery after being diagnosed with stage T1-2N0M0 TCs from 2004 to 2016. Propensity score matching (PSM) analysis was used to equalize the baseline characteristics between the sublobar resection group and the lobectomy group. Kaplan–Meier analysis and the Cox proportional hazard model were performed for survival analysis.

RESULTS

Of the 2469 patients included, 658 (26.65%) underwent sublobar resection and 1811 (73.35%) underwent lobectomy. All 2469 patients were analysed with PSM and, following PSM, 812 patients were included in the final analysis and divided into 2 groups of 406 patients. In the matched cohort, Kaplan–Meier analysis demonstrated no significant difference in survival curves between the sublobar resection and lobectomy groups in patients with stage T1-2N0M0 TC tumours [5-year overall survival (OS) = 90.78% vs 93.30%; hazard ratio 1.18, 95% confidence interval: 0.77–1.80; P = 0.505]. Subgroup analysis by tumour size showed that the sublobar resection group was identical to the lobectomy group in OS for tumours ≤3.0 cm. In addition, no difference in OS between surgical groups was observed in any subgroups. In the multivariable Cox analysis, age ≤65 years, female sex, married status and adequate lymph node assessment (≥5) were associated with improved OS, whereas the extent of resection was not.

CONCLUSIONS

Sublobar resection seems to be associated with similar survival to lobectomy for stage T1-2N0M0 TC tumours if lymph node assessment is performed adequately. This analysis suggests that sublobar resection should be considered an appropriate alternative for stage T1-2N0M0 TC tumours. However, further validations are needed in large, multicentre prospective studies.
Clinical and Viral Factors Associated With Disease Severity and Subsequent Wheezing in Infants With Respiratory Syncytial Virus Infection
Authors: McGinley Joseph P , Lin Gu Lung , Öner Deniz , Golubchik Tanya , O’Connor Daniel , Snape Matthew D , Gruselle Olivier , Langedijk Annefleur C , Wildenbeest Joanne , Openshaw Peter , Nair Harish , Aerssens Jeroen , Bont Louis , Martinón-Torres Federico , Drysdale Simon B , Pollard Andrew J ,   the RESCEU Investigators, Nair Harish , Campbell Harry , Cunningham Steve , Bogaert Debby , Beutels Philippe , Bont Louis , Wildenbeest Joanne , Langedijk Annefleur C , Pollard Andrew , Butler Christopher , Snape Matthew , Drysdale Simon , Lin Gu-Lung , O’Connor Daniel , Clutterbuck Elizabeth , McGinley Joseph , Openshaw Peter , Thwaites Ryan , Wiseman Dexter , Martinón-Torres Federico , Gómez-Carballa Alberto , Rodríguez-Tenreiro Carmen , Rivero-Calle Irene , Dacosta-Urbieta Ana , Heikkinen Terho , Meijer Adam , Fischer Thea K , van den Berge Maarten , Giaquinto Carlo , Abram Michael , Myint Tin Tin , Gruselle Olivier , Rizkalla Bishoy , Vernhes Charlotte , Gallichan Scott , Aerssens Jeroen , Öner Deniz , Kumar Veena , Molero Eva
Published: April 2022

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants and young children worldwide. Here we evaluated host demographic and viral factors associated with RSV disease severity in 325 RSV-infected infants under 1 year of age from 3 European countries during 2017–2020. Younger infants had a higher clinical severity (ReSViNET) score and were more likely to require hospitalization, intensive care, respiratory support, and/or mechanical ventilation than older infants (<3 months vs 3 to <6 months and 3 to <6 months vs ≥6 months). Older age (≥6 months vs <3 months), higher viral load, and RSV-A were associated with a greater probability of fever. RSV-A and RSV-B caused similar disease severity and had similar viral dynamics. Infants with a more severe RSV infection, demonstrated by having a higher ReSViNET score, fever, and requiring hospitalization and intensive care, were more likely to have developed subsequent wheezing at 1 year of age.

Clinical Trials Registration

NCT03756766.
Metternich’s collection of Talbot’s photographs
Authors: Trnkova Petra
Published: April 2022

The earliest era of photograph collecting in Central Europe is largely unexplored. One of the few pioneering collectors we know about was Klemens Wenzel Nepomuk Lothar, Prince von Metternich-Winneburg (1773–1859). As this article demonstrates, in the early 1840s he acquired dozens of ‘photogenic drawings’ and calotypes from the inventor W.H.F. Talbot (1800–1877) and incorporated them into his extensive collections at Kynžvart Castle. Most of the series is lost, but drawing on recently recognized evidence and documents – starting with Talbot’s correspondence and period catalogues of the Kynžvart collection and ending with later reproductions and the research interests of the historians and collectors Egon Corti and Erich Stenger – we can form a detailed idea of the origin, form, content and development of the series. We can also better understand Metternich’s interest in photograph collecting and his role in the early development of paper photography in this part of Europe.
Duration of Antibiotic Therapy and Timing of Shunt Reimplantation in Pediatric CSF Shunt Infections: A Retrospective Multicenter Case Series
Authors: Robinson Joan L , McAlpine Alastair , Barton Michelle , Balamohan Archana , Davies H Dele , Skar Gwenn , Lefebvre Marie-Astrid , Almadani Ahmed , Freire Dolores , Le Saux Nicole , Bowes Jennifer , Srigley Jocelyn A , Passarelli Patrick , Bradley John , Khan Sarah , Purewal Rupeena , Viel-Thériault Isabelle , Hawkes Michael T
Published: April 2022

In this retrospective multicenter series of 154 children with cerebrospinal fluid shunt infections, the median (interquartile range) duration of antibiotic therapy was 18 (14-26) days. The time to shunt replacement was 14 (10-19) days. Management appeared to potentially differ according to the targeted pathogen and site.
SXP 15.6 – an accreting pulsar close to spin equilibrium?
Authors: Coe M J , Monageng I M , Kennea J A , Buckley D A H , Evans P A , Udalski A , Groot Paul , Bloemen Steven , Vreeswijk Paul , McBride Vanessa , Klein-Wolt Marc , Woudt Patrick , Körding Elmar , Le Poole Rudolf , Pieterse Danielle
Published: April 2022

SXP 15.6  is a recently established Be star X-ray binary system in the Small Magellanic Cloud (SMC). Like many such systems, the variable X-ray emission is driven by the underlying behaviour of the mass donor Be star. It is shown here that the neutron star in this system is exceptionally close to spin equilibrium averaged over several years, with the angular momentum gain from mass transfer being almost exactly balanced by radiative losses. This makes SXP 15.6 exceptional compared to all other known members of its class in the SMC, all of whom exhibit much higher spin period changes. In this paper, we report on X-ray observations of the brightest known outburst from this system. These observations are supported by contemporaneous optical and radio observations, as well as several years of historical data.
Search for hybrid morphology radio galaxies from the FIRST survey at 1400 MHz
Authors: Kumari Shobha , Pal Sabyasachi
Published: April 2022

Hybrid Morphology Radio Sources (HyMoRS) are a very rare subclass of radio galaxies with apparent mixed FR morphology, i.e. these galaxies seem to have an FR-I structure on one side of the core and an FR-II structure on the other side of the core. We systematically searched for HyMoRS using Very Large Array (VLA) Faint Images of the Radio Sky at Twenty-cm (FIRST) survey with 1400 MHz frequency and identified 33 candidate HyMoRS. Our finding significantly increased the known sample size of HyMoRS. HyMoRS may play an essential role in understanding the interaction of jets with the interstellar medium and the much-debated topic of the FR dichotomy. We identified optical counterparts for 29 sources in our catalogue. In our sample of sources, one source (J1106+1355) had quasar-like behaviour. Four sources were BRCLG (Brightest Cluster Galaxies) and six were LRG (Luminous Red Galaxies). We have estimated the spectral index and radio luminosity of HyMoRS in our catalogue, when possible. We found that J1136–0328 was the most luminous source in our sample (log L = 27.01 W Hz−1sr−1). It was also the farthest HyMoRS (with a redshift z = 0.82) in our sample. With the help of a large sample size of discovered sources, various statistical properties of detected galaxies were studied.
Cosmological simulations predict that AGN preferentially live in gas-rich, star-forming galaxies despite effective feedback
Authors: Ward S R , Harrison C M , Costa T , Mainieri V
Published: April 2022

Negative feedback from active galactic nuclei (AGN) is the leading mechanism for the quenching of massive galaxies in the vast majority of modern galaxy evolution models. However, direct observational evidence that AGN feedback causes quenching on a population scale is lacking. Studies have shown that luminous AGN are preferentially located in gas-rich and star-forming galaxies, an observation that has sometimes been suggested to be in tension with a negative AGN feedback picture. We investigate three of the current cosmological simulations (illustrisTNG, EAGLE, and SIMBA) along with post-processed models for molecular hydrogen gas masses and perform similar tests to those used by observers. We find that the simulations predict: (i) no strong negative trends between Lbol and $f_{\mathrm{ H}_2}$ or specific star formation rate (sSFR); (ii) both high-luminosity ($L_{\rm {bol}} \ge 10^{44}\rm {\, erg\, s^{-1}}$) and high Eddington ratio (λEdd $\ge 1{{\ \rm per\ cent}}$) AGN are preferentially located in galaxies with high molecular gas fractions and sSFR; and (iii) that the gas-depleted and quenched fractions of AGN host galaxies are lower than a control sample of non-active galaxies. These three findings are in qualitative agreement with observational samples at z = 0 and z = 2 and show that such results are not in tension with the presence of strong AGN feedback, which all simulations we employ require to produce realistic massive galaxies. However, we also find quantifiable differences between predictions from the simulations, which could allow us to observationally test the different subgrid feedback models.
Decreased levels of histidine-rich glycoprotein and increased levels of high-mobility group box 1 are risk factors for refractory Kawasaki disease
Authors: Namba Takahiro , Yashiro Masato , Fujii Yosuke , Tsuge Mitsuru , Liu Keyue , Nishibori Masahiro , Tsukahara Hirokazu
Published: April 2022

Objectives

Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD.

Methods

This study was prospectively performed. Patients were divided into two groups and analysed depending on whether KD symptoms improved by Day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards for assessing trends.

Results

In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment.

Conclusions

HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.
Secondary Metabolite Transcriptomic Pipeline (SeMa-Trap), an expression-based exploration tool for increased secondary metabolite production in bacteria
Authors: Mungan Mehmet Direnç , Harbig Theresa Anisja , Perez Naybel Hernandez , Edenhart Simone , Stegmann Evi , Nieselt Kay , Ziemert Nadine
Published: April 2022

For decades, natural products have been used as a primary resource in drug discovery pipelines to find new antibiotics, which are mainly produced as secondary metabolites by bacteria. The biosynthesis of these compounds is encoded in co-localized genes termed biosynthetic gene clusters (BGCs). However, BGCs are often not expressed under laboratory conditions. Several genetic manipulation strategies have been developed in order to activate or overexpress silent BGCs. Significant increases in production levels of secondary metabolites were indeed achieved by modifying the expression of genes encoding regulators and transporters, as well as genes involved in resistance or precursor biosynthesis. However, the abundance of genes encoding such functions within bacterial genomes requires prioritization of the most promising ones for genetic manipulation strategies. Here, we introduce the ‘Secondary Metabolite Transcriptomic Pipeline’ (SeMa-Trap), a user-friendly web-server, available at https://sema-trap.ziemertlab.com. SeMa-Trap facilitates RNA-Seq based transcriptome analyses, finds co-expression patterns between certain genes and BGCs of interest, and helps optimize the design of comparative transcriptomic analyses. Finally, SeMa-Trap provides interactive result pages for each BGC, allowing the easy exploration and comparison of expression patterns. In summary, SeMa-Trap allows a straightforward prioritization of genes that could be targeted via genetic engineering approaches to (over)express BGCs of interest.
IBS 2.0: an upgraded illustrator for the visualization of biological sequences
Authors: Xie Yubin , Li Huiqin , Luo Xiaotong , Li Hongyu , Gao Qiuyuan , Zhang Luowanyue , Teng Yuyan , Zhao Qi , Zuo Zhixiang , Ren Jian
Published: April 2022

The visualization of biological sequences with various functional elements is fundamental for the publication of scientific achievements in the field of molecular and cellular biology. However, due to the limitations of the currently used applications, there are still considerable challenges in the preparation of biological schematic diagrams. Here, we present a professional tool called IBS 2.0 for illustrating the organization of both protein and nucleotide sequences. With the abundant graphical elements provided in IBS 2.0, biological sequences can be easily represented in a concise and clear way. Moreover, we implemented a database visualization module in IBS 2.0, enabling batch visualization of biological sequences from the UniProt and the NCBI RefSeq databases. Furthermore, to increase the design efficiency, a resource platform that allows uploading, retrieval, and browsing of existing biological sequence diagrams has been integrated into IBS 2.0. In addition, a lightweight JS library was developed in IBS 2.0 to assist the visualization of biological sequences in customized web services. To obtain the latest version of IBS 2.0, please visit https://ibs.renlab.org.
SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples
Authors: Ianevski Aleksandr , Giri Anil K , Aittokallio Tero
Published: April 2022

SynergyFinder (https://synergyfinder.fimm.fi) is a free web-application for interactive analysis and visualization of multi-drug combination response data. Since its first release in 2017, SynergyFinder has become a popular tool for multi-dose combination data analytics, partly because the development of its functionality and graphical interface has been driven by a diverse user community, including both chemical biologists and computational scientists. Here, we describe the latest upgrade of this community-effort, SynergyFinder release 3.0, introducing a number of novel features that support interactive multi-sample analysis of combination synergy, a novel consensus synergy score that combines multiple synergy scoring models, and an improved outlier detection functionality that eliminates false positive results, along with many other post-analysis options such as weighting of synergy by drug concentrations and distinguishing between different modes of synergy (potency and efficacy). Based on user requests, several additional improvements were also implemented, including new data visualizations and export options for multi-drug combinations. With these improvements, SynergyFinder 3.0 supports robust identification of consistent combinatorial synergies for multi-drug combinatorial discovery and clinical translation.
Assessment of Internalizing Disorders
Authors: Naragon-Gainey Kristin , McMahon Tierney P. , Park Juhyun
Published: April 2022

Internalizing disorders, which include depression and anxiety as well as several other syndromes, are common and impairing conditions that form one of the spectra in structural models of psychopathology (i.e., the Hierarchical Taxonomy of Psychopathology). This chapter reviews the hierarchical structure and contents of the Internalizing spectrum, as well as their key features and challenges that commonly arise when assessing these symptoms. Four types of assessment tools are presented—self-report measures, clinical interviews, ambulatory assessment, and performance-based clinician-rated measures (i.e., behavioral avoidance tasks)—along with their strengths and limitations, applications, and example measures as they relate to the Internalizing spectrum. The chapter also discusses considerations for assessment of internalizing symptoms in diverse populations and future directions in this area.
Construct Validation of Personality Measures
Authors: Smith Gregory T. , Atkinson Emily A.
Published: April 2022

Current construct validity theory emphasizes the following points. The process of validating measures of unobservable constructs is also the process of validating theories of psychological functioning. That process is ongoing for each measure and theory: Construct validity is never fully established but, rather, evidence for the validity of measures and theories accrues over time. To facilitate the process, researchers should conduct validation tests that are as informative as possible—that is, that directly address core components of one’s theory. Measure and theory validation should be conducted on measures of homogeneous constructs: The use of single scores to represent multidimensional entities cannot be defended. An important issue concerning validating the claims of personality theory involves understanding the relationship between self-reports of general tendencies and daily moment-to-moment reports of reactions and behavior. Noting the significant amount of variance shared between various forms of psychopathology and facets of personality, researchers have utilized bifactor modeling to extract general factors of psychopathology and personality. These new models present unique challenges for construct validation. Extraordinary progress has been made in the study of personality, and the further implementation of sound construct validation principles will lead to continued, improved, and successful measure and theory validation in the future.
Rice CIRCADIAN CLOCK ASSOCIATED 1 transcriptionally regulates ABA signaling to confer multiple abiotic stress tolerance
Authors: Wei Hua , Xu Hang , Su Chen , Wang Xiling , Wang Lei
Published: April 2022

The circadian clock facilitates the survival and reproduction of crop plants under harsh environmental conditions such as drought and osmotic and salinity stresses, mainly by reprogramming the endogenous transcriptional landscape. Nevertheless, the genome-wide roles of core clock components in rice (Oryza sativa L.) abiotic stress tolerance are largely uncharacterized. Here, we report that CIRCADIAN CLOCK ASSOCIATED1 (OsCCA1), a vital clock component in rice, is required for tolerance to salinity, osmotic, and drought stresses. DNA affinity purification sequencing coupled with transcriptome analysis identified 692 direct transcriptional target genes of OsCCA1. Among them, the genes involved in abscisic acid (ABA) signaling, including group A protein phosphatase 2C genes and basic region and leucine zipper 46 (OsbZIP46), were substantially enriched. Moreover, OsCCA1 could directly bind the promoters of OsPP108 and OsbZIP46 to activate their expression. Consistently, oscca1 null mutants generated via genome editing displayed enhanced sensitivities to ABA signaling. Together, our findings illustrate that OsCCA1 confers multiple abiotic stress tolerance likely by orchestrating ABA signaling, which links the circadian clock with ABA signaling in rice.
Circadian entrainment in Arabidopsis
Authors: Wang Shouming , Steed Gareth , Webb Alex A R
Published: April 2022

Circadian clocks coordinate physiology and development as an adaption to the oscillating day/night cycle caused by the rotation of Earth on its axis and the changing length of day and night away from the equator caused by orbiting the sun. Circadian clocks confer advantages by entraining to rhythmic environmental cycles to ensure that internal events within the plant occur at the correct time with respect to the cyclic external environment. Advances in determining the structure of circadian oscillators and the pathways that allow them to respond to light, temperature, and metabolic signals have begun to provide a mechanistic insight to the process of entrainment in Arabidopsis (Arabidopsis thaliana). We describe the concepts of entrainment and how it occurs. It is likely that a thorough mechanistic understanding of the genetic and physiological basis of circadian entrainment will provide opportunities for crop improvement.
Geochemical ice-core constraints on the timing and climatic impact of Aniakchak II (1628 BCE) and Thera (Minoan) volcanic eruptions
Authors: Pearson Charlotte , Sigl Michael , Burke Andrea , Davies Siwan , Kurbatov Andrei , Severi Mirko , Cole-Dai Jihong , Innes Helen , Albert Paul G , Helmick Meredith
Published: April 2022

Decades of research have focused on establishing the exact year and climatic impact of the Minoan eruption of Thera, Greece (c.1680 to 1500 BCE). Ice cores offer key evidence to resolve this controversy, but attempts have been hampered by a lack of multivolcanic event synchronization between records. In this study, Antarctic and Greenland ice-core records are synchronized using a double bipolar sulfate marker, and calendar dates are assigned to each eruption revealed within the ‘Thera period’. From this global-scale sequence of volcanic sulfate loading, we derive indications toward each eruption’s latitude and potential to disrupt the climate system. Ultrafine sampling for sulfur isotopes and tephra conclusively demonstrate a colossal eruption of Alaska’s Aniakchak II as the source of stratospheric sulfate in the now precisely dated 1628 BCE ice layer. These findings end decades of speculation that Thera was responsible for the 1628 BCE event, and place Aniakchak II (52 ± 17 Tg S) and an unknown volcano at 1654 BCE (50 ± 13 Tg S) as two of the largest Northern Hemisphere sulfur injections in the last 4,000 years. This opens possibilities to explore widespread climatic impacts for contemporary societies and, in pinpointing Aniakchak II, confirms that stratospheric sulfate can be globally distributed from eruptions outside the tropics. Dating options for Thera are reduced to a series of precisely dated, constrained stratospheric sulfur injection events at 1611 BCE, 1561/1558/1555BCE, and c.1538 BCE, which are all below 14 ± 5 Tg S, indicating a climatic forcing potential for Thera well below that of Tambora (1815 CE).
Graphene oxide and mineralized collagen-functionalized dental implant abutment with effective soft tissue seal and romotely repeatable photodisinfection
Authors: Gao Yichun , Kang Ke , Luo Bin , Sun Xiaoqing , Lan Fang , He Jing , Wu Yao
Published: April 2022

Grasping the boundary of antibacterial function may be better for the sealing of soft tissue around dental implant abutment. Inspired by ‘overdone is worse than undone’, we prepared a sandwich-structured dental implant coating on the percutaneous part using graphene oxide (GO) wrapped under mineralized collagen. Our unique coating structure ensured the high photothermal conversion capability and good photothermal stability of GO. The prepared coating not only achieved suitable inhibition on colonizing bacteria growth of Streptococcus sanguinis, Fusobacterium nucleatum and Porphyromonas gingivalis but also disrupted the wall/membrane permeability of free bacteria. Further enhancements on the antibacterial property were generally observed through the additional incorporation of dimethylaminododecyl methacrylate. Additionally, the coating with sandwich structure significantly enhanced the adhesion, cytoskeleton organization and proliferation of human gingival fibroblasts, which was effective to improve soft tissue sealing. Furthermore, cell viability was preserved when cells and bacteria were cultivated in the same environment by a coculture assay. This was attributed to the sandwich structure and mineralized collagen as the outmost layer, which would protect tissue cells from photothermal therapy and GO, as well as accelerate the recovery of cell activity. Overall, the coating design would provide a useful alternative method for dental implant abutment surface modification and functionalization.
Critically ill COVID-19 patients in northeast Brazil: mortality predictors during the first and second waves including SAPS 3
Authors: Lázaro Ana Paula Pires , Albuquerque Polianna Lemos Moura Moreira , Meneses Gdayllon Cavalcante , Zaranza Marza de Sousa , Batista Ana Beatriz , Aragão Natalia Linhares Ponte , Beliero Andrea Mazza , Guimarães Álvaro Rolim , Aragão Nilcyeli Linhares , Leitão Alessandra Marjorye Maia , de Carvalho Marcelo Costa Freire , Cavalcante Maria Isabel de Alencar , Mota Fabio Augusto Xerez , Daher Elizabeth De Francesco , Martins Alice Maria Costa , da Silva Junior Geraldo Bezerra
Published: April 2022

Background

The Simplified Acute Physiology Score (SAPS) 3 is a reliable score to predict mortality. This study aims to investigate the predictive values of SAPS 3 and other clinical parameters for death in critically ill coronavirus disease 2019 (COVID-19) patients.

Methods

This is a prospective study in a tertiary hospital for patients who required intensive care due to COVID-19 infection in northeast Brazil. Two distinct groups were constructed according to the epidemiological data: first wave and second wave. The severity of patients admitted was estimated using the SAPS 3 score.

Results

A total of 767 patients were included: 290 were enrolled in the first wave and 477 in the second wave. Patients in the first wave had more comorbidities, were put on mechanical ventilation and required dialysis and vasopressors more frequently (p<0.05). During the second wave, non-invasive ventilation was more often required (p<0.05). In both periods, older patients and higher SAPS 3 scores on admission were associated with death (p<0.05). Non-invasive ventilation use showed a negative association with death only in the second wave period. In the first wave, the SAPS 3 score was more useful (area under the curve [AUC] 0.897) in predicting death in critically ill COVID-19 patients than in the second wave (AUC 0.810).

Conclusion

The SAPS 3 showed very reliable predictive values for death during the waves of the COVID-19 pandemic, mostly together with kidney and pulmonary dysfunction.
Applying Lean Six Sigma to evidence-based practice projects
Authors: McCoy Cole , Douglas Claudia
Published: April 2022

Process improvement methodology minimizes barriers to implementing new knowledge
Increased Fatigability in Women With Persistent Cancer-Related Fatigue After Breast Cancer Treatment: A Pilot Study
Authors: Wood Magee Lisa J. , Kneiss Janet , Wechsler Stephen , Singh Ayesha Bani , Fox Annie B. , Peppercorn Jeffrey , Pirl William F.
Published: April 2022

Purpose:

To examine whether survivors of breast cancer (SBC) with persistent cancer-related fatigue (CRF) have greater fatigability than their nonfatigued counterparts.

Methods:

Measures of fatigability, including endurance, perceived exertion, lower extremity muscle force and power, and sit-to-stand time (STST), were assessed in 43 women (21 with persistent CRF) after a sit-to-stand fatigue (STSF) task. Group differences in fatigability outcomes were examined using analysis of variance.

Results:

SBC with persistent CRF had lower endurance (P = .003, ηp
2 = 0.205) and reported greater perceived exertion (P < .001, ηp
2 = 0.284) during the STSF task, and demonstrated lower postexertional force (P = .035, ηp
2 = 0.109), power (P = .001, ηp
2 = 0.242), and slower STST (P = .001, ηp
2 = 0.258) compared with SBC without CRF.

Conclusions:

SBC with persistent CRF have increased fatigability compared with those without CRF. Our findings suggest that exercise recommendations for women with persistent CRF after breast cancer treatment should include activities that increase lower limb muscle force and power, such as heavy resistance or explosive-type strength training.
Advances in Neuroimaging and Monitoring to Defend Cerebral Perfusion in Noncardiac Surgery
Authors: Fanning Jonathon P. , Huth Samuel F. , Robba Chiara , Grieve Stuart M. , Highton David
Published: April 2022

Noncardiac surgery conveys a substantial risk of secondary organ dysfunction and injury. Neurocognitive dysfunction and covert stroke are emerging as major forms of perioperative organ dysfunction, but a better understanding of perioperative neurobiology is required to identify effective treatment strategies. The likelihood and severity of perioperative brain injury may be increased by intraoperative hemodynamic dysfunction, tissue hypoperfusion, and a failure to recognize complications early in their development. Advances in neuroimaging and monitoring techniques, including optical, sonographic, and magnetic resonance, have progressed beyond structural imaging and now enable noninvasive assessment of cerebral perfusion, vascular reserve, metabolism, and neurologic function at the bedside. Translation of these imaging methods into the perioperative setting has highlighted several potential avenues to optimize tissue perfusion and deliver neuroprotection. This review introduces the methods, metrics, and evidence underlying emerging optical and magnetic resonance neuroimaging methods and discusses their potential experimental and clinical utility in the setting of noncardiac surgery.
How Audiology Alienates Transgender Audiologists
Authors: Kirjava Shade Avery
Published: April 2022

There are more transgender and gender-diverse clinical audiologists working today than might at first be apparent. The field of audiology, however, has unique interpersonal and structural factors that cause transgender audiologists to experience significant prejudice and discrimination from their patients and colleagues. Transgender audiologists who experience discrimination are at higher risk of stress, burnout, and leaving the field of audiology altogether. Improved education for healthcare professionals on LGBTQIA+ topics in graduate and continuing education may resolve many of the unequitable experiences that transgender audiologists experience and lead to improved patient care for our gender diverse patients.