bluuebunny/crossref_metadata_2025 huggingface dataset:
The variability in potential biomarkers for cochlear synaptopathy after recreational noise exposure
Authors: Maele Tine Vande , Keshishzadeh Sarineh , Poortere Nele De , Dhooge Ingeborg , Keppler Hannah , Verhulst Sarah
Published: January 2021

Purpose

Speech-in-noise tests and suprathreshold auditory evoked potentials are promising biomarkers to diagnose cochlear synaptopathy (CS) in humans. This study investigated whether these biomarkers changed after recreational noise exposure.

Method

The baseline auditory status of 19 normal hearing young adults was analyzed using questionnaires, pure-tone audiometry, speech audiometry and auditory evoked potentials. Nineteen subjects attended a music festival and completed the same tests again at day one, day three and day five after the music festival.

Results

No significant relations were found between lifetime noise-exposure history and the hearing tests. Changes in biomarkers from the first session to the follow-up sessions were non-significant, except for speech audiometry, that showed a significant learning effect (performance improvement).

Conclusions

Despite the individual variability in pre-festival biomarkers, we did not observe changes related to the noise-exposure dose caused by the attended event. This can indicate the absence of noise-exposure-driven cochlear synaptopathy in the study cohort, or reflect that biomarkers were not sensitive enough to detect mild CS. Future research should include a more diverse study cohort, dosimetry and results from test-retest reliability studies to provide more insight into the relationship between recreational noise-exposure and cochlear synaptopathy.
Context and Phase Dependent Effects of Delta transcranial Alternating Current Stimulation on Dynamic Attending
Authors: Shelp Adam , Mioni Giovanna , Wiener Martin
Published: January 2021

Attention requires the allocation of limited resources to properly interpret our environment, making it ultimately unsustainable. Dynamic Attending Theory suggests that, in order to realistically maintain vigilance to our surroundings, attention likely fluctuates between high and low energetic states, such that information can be processed more quickly and accurately during attentional peaks and vice versa. Additionally, prior studies have suggested that the phase of delta oscillations (1-4 Hz) are critically involved in the entrainment of attention. We investigated the physiological and behavioral entrainment of attention and the role that delta phase plays to moderate the benefits of this attending. Participants (N=28) passively listened to a background auditory rhythm and were required to complete a visual discrimination task while undergoing 2 Hz transcranial alternating current stimulation (tACS). The task involved identifying an image, either upright or inverted, presented either on or before the final beat, while receiving delta stimulation that was either aligned or unaligned with image presentation. As expected, reaction times (RTs) were faster for on-beat than off-beat stimuli, and for upright images than inverted. Crucially, tACS phase-aligned with the beat led to faster RTs over out-of-phase stimulation, but only for upright images; remarkably, this pattern was reversed for inverted images presented on-beat, with slower RTs for inverted stimuli during in-phase tACS. These results suggest that the effects of delta tACS are both phase and context dependent, and mediate a potential form of speed-accuracy tradeoff in the allocation of attentional resources during rhythmic entrainment.
Introducing Novel Molecular-based Method for Quantification of Homologous Recombination Efficiency
Authors: Dibbasey Mustapha , Gaymes Terry
Published: January 2021

Background

Homologous recombination (HR) pathway is a DNA double-stranded breaks repair pathway well-known for its high level of accuracy. Low HR pathway efficiency clinically known as homologous recombination deficiency (HRD) was identified in some cancers such as breast and ovarian cancers and studies have reported the sensitivity of HRD cancer cells to DNA repair inhibitors such as Olaparib. However, current techniques including immunofluorescence-based technique are qualitative-based, hence lack sensitivity to determine the functionality of HR pathway. Additionally, some of the techniques including gene expression arrays require expression study of wide range genes involve in HR pathway, which is not cost-effective. The aim of the study is to optimise a PCR-based assay (Norgen’s Homologous Recombination kit) that can be employed to quantitate HR efficiency in cells, which accurately reflects the functional status of HR pathway.

Methods and Findings

The kit has two test plasmids (dl-1 and dl-2) with partial deletions in the LacZ gene and the plasmids are generated from modification of pUC19. HR-proficient (HeLa and AsPC-1) and HR-deficient (CAPAN-1 cells) cancer cell lines were transfected with the two plasmids to generate functional LacZ gene (i.e. recombinant product). The recombinant product was quantified by real-time PCR. Although recombinant product was generated in all the cell lines, our real-time PCR demonstrated a high quantity of recombinant product in HeLa cell line whilst low quantity in CAPAN-1 and AsPC-1 cell lines. The quantity of recombinant product generated and quantified reflects HR pathway efficiency.

Conclusion

Overall, the results have provided some evidence that the PCR-based kit can be suitably employed for quantification of HR efficiency provided appropriate transfection method and reagent are used. However, further study is required to confirm HR efficiency status of AsPC-1 cells to ascertain the low HR efficiency detected by the kit in these cells.
2-kupl: mapping-free variant detection from DNA-seq data of matched samples
Authors: Wang Yunfeng , Xue Haoliang , Pourcel Christine , Du Yang , Gautheret Daniel
Published: January 2021

The detection of genome variants, including point mutations, indels and structural variants, is a fundamental and challenging computational problem. We address here the problem of variant detection between two deep-sequencing (DNA-seq) samples, such as two human samples from an individual patient, or two samples from distinct bacterial strains. The preferred strategy in such a case is to align each sample to a common reference genome, collect all variants and compare these variants between samples. Such mapping-based protocols have several limitations. DNA sequences with large indels, aggregated mutations and structural variants are hard to map to the reference. Furthermore, DNA sequences cannot be mapped reliably to genomic low complexity regions and repeats. Herein, we introduce 2-kupl, a k-mer based, mapping-free protocol to detect variants between two DNA-seq samples. On simulated and actual data, 2-kupl achieves a higher precision than other mapping-free protocols. Applying 2-kupl to prostate cancer whole exome data, we identify a number of candidate variants in hard-to-map regions and propose potential novel recurrent variants in this disease.
Covid-19 respiratory protection: the filtration efficiency assessment of decontaminated FFP2 masks responding to associated shortages
Authors: Benboubker M. , Oumokhtar B. , Hmami F. , Mabrouk K. El , Alami L.EL , Arhoune B. , Belahsen M F. , Aboutajeddine A.
Published: January 2021

During the Covid-19 pandemic, healthcare workers were extremely vulnerable to infection with the virus and needed continuous protection. One of the most effective and widely used means of protection was the FFP2 respirator. Unfortunately, this crisis created a shortage of these masks, prompting hospitals to explore opportunities to reuse them after decontamination.

An approach for assessing the filtration efficiency of decontaminated FFP2 masks has been proposed and applied to evaluate the possibilities of their safe reuse. The decontamination processes adopted are those based on moist heat or hydrogen peroxide. The approach introduces efficiency measures that define the filtration and protection capacity of the masks, which characterize both chemical and structural changes, and encompasses many techniques including scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The test protocol was applied to mask samples that had endured different decontamination cycles and the results of their efficiency measures were compared to brand-new masks’ performances.

The main result was that chemical and structural characterization of the decontaminated masks have shown no substantial change or deformation of their filter media structures. Indeed, the respiratory resistance test has shown that the results of both the FFP2 masks that have undergone a hydrogen peroxide disinfection cycle or a steam autoclave cycle remained constant with a small variation of 10 Pa from the EN149 standard. The chemical characterization, on the other hand, has shown that the filter media of the decontaminated masks remains unchanged, with no detectable chemical derivatives in its constituents.
The Association between Early Country-level Testing Capacity and Later COVID-19 Mortality Outcomes
Authors: Kannoth Sneha , Kandula Sasikiran , Shaman Jeffrey
Published: January 2021

Background

The COVID-19 pandemic has overrun hospital systems while exacerbating economic hardship and food insecurity on a global scale. In an effort to understand how early action to find and control the virus is associated with cumulative outcomes, we explored how country-level testing capacity affects later COVID-19 mortality.

Methods

We used the Our World in Data database to explore testing and mortality records in 27 countries from December 31, 2019 to September 30, 2020; we applied ordinary-least squares regression with clustering on country to determine the association between early COVID-19 testing capacity (cumulative tests per case) and later COVID-19 mortality (time to specified mortality thresholds), adjusting for country-level confounders, including median age, GDP, hospital bed capacity, population density, and non-pharmaceutical interventions.

Results

Higher early testing implementation, as indicated by more cumulative tests per case when mortality was still low, was associated with longer accrual time for higher per capita deaths. For instance, a higher cumulative number of tests administered per case at the time of 6 deaths per million persons was positively predictive of a longer time to reach 15 deaths per million, after adjustment for all confounders (β=0.659;P=0.001).

Conclusions

Countries that developed stronger COVID-19 testing capacity at early timepoints, as measured by tests administered per case identified, experienced a slower increase of deaths per capita. Thus, this study operationalizes the value of testing and provides empirical evidence that stronger testing capacity at early timepoints is associated with reduced mortality and better pandemic control.
Cumulative effects of particulate matter pollution and meteorological variables on the risk of influenza-like illness in Bialystok, Poland
Authors: Toczylowski Kacper , Wietlicka-Piszcz Magdalena , Grabowska Magdalena , Sulik Artur
Published: January 2021

The cold season is usually accompanied by an increased incidence of respiratory infections and increased air pollution from combustion sources. As we are facing the growing numbers of COVID-19 cases caused by the novel SARS-CoV-2 coronavirus, an understanding of the impact of air pollutants and meteorological variables on the incidence of respiratory infections is crucial. The influenza-like illness (ILI) incidence might be used as a close proxy for the circulation of influenza viruses. Recently, SARS-CoV-2 has also been detected in patients with ILI. Using distributed lag nonlinear models, we analyzed the association between ILI, meteorological variables and particulate matter concentration in Bialystok, Poland, from 2013-2019. We found an exponential relation between cumulative PM2.5 pollution and the incidence of ILI that remained significant after adjusting for air temperatures and a long-term trend. Pollution had the greatest effect during the same week, but the risk of ILI was increased for the four following weeks. The risk of ILI was also increased by low air temperatures, low absolute humidity, and high wind speed. Altogether, our results show that all measures implemented to decrease PM2.5 concentrations would be beneficial to reduce the transmission of SARS-CoV-2 and other respiratory infections.

Capsule summary

Low/medium high concentrations of particulate matter pollution increase the risk of influenza-like illness. The effect is independent from air temperatures and lasts for the four following weeks.
Endothelial cell-activating antibodies in COVID-19
Authors: Shi Hui , Zuo Yu , Navaz Sherwin , Harbaugh Alyssa , Hoy Claire K. , Gandhi Alex A. , Sule Gautam , Yalavarthi Srilakshmi , Gockman Kelsey , Madison Jacqueline A. , Wang Jintao , Zuo Melanie , Shi Yue , Maile Michael D. , Knight Jason S. , Kanthi Yogendra
Published: January 2021

Objective

While endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.

Methods

Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA.

Results

Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation.

Conclusion

These data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.
Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis
Authors: Wolf Vinzent , Kühnel Anne , Teckentrup Vanessa , Koenig Julian , Kroemer Nils B.
Published: January 2021

Non-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g= 0.011,CIshortest= [−0.103, 0.125],BF01= 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.
Kinetic analysis of ASIC1a delineates conformational signaling from proton-sensing domains to the channel gate
Authors: Vullo Sabrina , Ambrosio Nicolas , Kucera Jan P. , Bignucolo Olivier , Kellenberger Stephan
Published: January 2021

Acid-sensing ion channels (ASICs) are neuronal Na+channels that are activated by a drop in pH. Their established physiological and pathological roles, involving fear behaviors, learning, pain sensation and neurodegeneration after stroke, make them promising targets for future drugs. Currently, the ASIC activation mechanism is not understood. Here we used voltage-clamp fluorometry (VCF) combined with fluorophore-quencher pairing to determine the kinetics and direction of movements. Molecular dynamics simulations were used to further evaluate VCF-predicted movements. We show that conformational changes with the speed of channel activation occur close to the gate and in more distant extracellular sites, where they may be driven by local protonation events. Further, we provide evidence for fast conformational changes in a pathway linking protonation sites to the channel pore, in which an extracellular interdomain loop interacts via aromatic residue interactions with the upper end of a transmembrane helix and would thereby open the gate.
Brain networks are decoupled from external stimuli during internal cognition
Authors: Cohen Dror , Nakai Tomoya , Nishimoto Shinji
Published: January 2021

Our cognition can be directed to external stimuli or to internal information. While there are many different forms of internal cognition (mind-wandering, recall, imagery etc.), their essential feature is independence from the immediate sensory input. This is thought to be reflected in the decoupling of brain networks from the external stimuli, but a quantitative investigation of this remains outstanding. Here we present a conceptual and analysis framework that links stimulus responses to connectivity between brain networks. This allows us to quantify the coupling of brain networks to the external stimuli. We tested this framework by presenting subjects with an audiovisual stimulus and instructing them to either attend to the stimulus (external task) or engage in mental imagery, recall or arithmetic (internal tasks) while measuring the evoked brain activity using functional MRI. We found that stimulus responses were generally attenuated for the internal tasks, though they increased in a subset of tasks and brain networks. However, using our new measure of coupling, we showed that brain networks became increasingly decoupled from the stimulus, even in the subset of tasks and brain networks in which stimulus responses increased. These results quantitatively demonstrate that during internal cognition brain networks are decoupled from external stimuli, opening the door for a fundamental and quantitative understanding of internal cognition.
Resolving when (and where) the Thylacine went extinct
Authors: Brook Barry W. , Sleightholme Stephen R. , Campbell Cameron R. , Jarić Ivan , Buettel Jessie C.
Published: January 2021

Like the Dodo and Passenger Pigeon before it, the predatory marsupial Thylacine (Thylacinus cynocephalus), or ‘Tasmanian tiger’, has become an iconic symbol of human-caused extinction. The last captive animal died in 1936, but even today reports of the Thylacine’s possible ongoing survival in remote regions of Tasmania are newsworthy and capture the public’s imagination. Extirpated from mainland Australia in the mid-Holocene, the large island of Tasmania became the species’ final stronghold. Following European settlement in the 1800s, the Thylacine was heavily persecuted and pushed to the margins of its range, although many sightings were reported thereafter—even well beyond the 1930s. To gain a new depth of insight into the extinction of the Thylacine, we assembled an exhaustive database of 1,237 observational records from Tasmania (from 1910 onwards), quantified their uncertainty, and charted the patterns these revealed. We also developed a new method to visualize the species’ 20th-century spatio-temporal dynamics, to map potential post-bounty refugia and pinpoint the most-likely location of the final persisting subpopulation. A direct reading of the high-quality records (confirmed kills and captures, in combination with sightings by past Thylacine hunters and trappers, wildlife professionals and experienced bushmen) implies a most-likely extinction date within four decades following the last capture (i.e., 1940s to 1970s). However, uncertainty modelling of the entire sighting record, where each observation is assigned a probability and the whole dataset is then subject to a sensitivity analysis, suggests that extinction might have been as recent as the late 1980s to early 2000s, with a small chance of persistence in the remote south-western wilderness areas. Beyond the intrinsically fascinating problem of reconstructing the final fate of the Thylacine, the new spatio-temporal mapping of extirpation developed herein would also be useful for conservation prioritization and search efforts for other rare taxa of uncertain status.
Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry
Authors: Chang Chia-Wei , Lee Ming-Cheng , Lin Bor-Ru , Lu Yen-Pei , Hsu Yih-Jen , Chuang Chun-Yu , Huang Tsung-Tao , Chen Yin-Kai
Published: January 2021

Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.
An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike S1 protein
Authors: Lin Yen-Hung , Han Yang , Sharma Abhinav , AlGhamdi Wejdan S. , Liu Chien-Hao , Chang Tzu-Hsuan , Xiao Xi-Wen , Seitkhan Akmaral , Mottram Alexander D. , Pattanasattayavong Pichaya , Faber Hendrik , Heeney Martin , Anthopoulos Thomas D.
Published: January 2021

Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining cost-effective manufacturing with high sensitivity, specificity and fast sensing response, remains challenging. Here we develop low-temperature solution-processed In2O3/ZnO heterojunction transistors featuring a geometrically engineered tri-channel architecture for rapid real-time detection of different biomolecules. The sensor combines a high electron mobility channel, attributed to the quasi-two-dimensional electron gas (q2DEG) at the buried In2O3/ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried q2DEG and the minute electronic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (aM) concentrations. By functionalizing the tri-channel surface with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibody receptors, we demonstrate real-time detection of the SARS-CoV-2 spike S1 protein down to attomolar concentrations in under two minutes.
Polycomb suppresses a female gene regulatory network to ensure testicular differentiation
Authors: Maezawa So , Yukawa Masashi , Hasegawa Kazuteru , Sugiyama Ryo , Hu Mengwen , Vidal Miguel , Koseki Haruhiko , Barski Artem , DeFalco Tony , Namekawa Satoshi H.
Published: January 2021

Gonadal sex determination is controlled by the support cells of testes and ovaries. In testes, the epigenetic mechanism that maintains cellular memory to suppress female sexual differentiation remains unknown. Here, we show that Polycomb suppresses a female gene regulatory network in Sertoli cells, the specific support cells for postnatal testes. Through genetic ablation, we removed Polycomb repressive complex 1 (PRC1) from embryonic Sertoli cells after sex determination. PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed the specific, critical genes required for granulosa cells, the support cells of ovaries, thereby inactivating the female gene regulatory network. The underlying chromatin of female genes was coated with Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, we identify a critical mechanism centered on Polycomb that maintains the male fate in adult testes.
Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts
Authors: Valesano Andrew L. , Rumfelt Kalee E. , Dimcheff Derek E. , Blair Christopher N. , Fitzsimmons William J. , Petrie Joshua G. , Martin Emily T. , Lauring Adam S.
Published: January 2021

Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified a viral load threshold that minimizes false positives. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.
Young domestic chicks spontaneously represent the absence of objects
Authors: Szabó Eszter , Chiandetti Cinzia , Téglás Ernő , Versace Elisabetta , Csibra Gergely , Kovács Ágnes Melinda , Vallortigara Giorgio
Published: January 2021

Absence is a notion that is usually captured by language-related concepts like zero or negation. Whether non-linguistic creatures encode similar thoughts is an open question, as everyday behavior marked by absence (of food, of social partners) can be explained solely by expecting presence somewhere else. We investigated 8-day-old chicks’ looking behavior in response to events violating expectations about the presence or absence of an object. We found different behavioral responses to violations of presence and absence, suggesting distinct underlying mechanisms. Importantly, chicks displayed an avian signature of novelty detection to violations of absence, namely a sex-dependent left-eye-bias. Follow-up experiments excluded accounts that would explain this bias by perceptual mismatch or by representing the object at different locations. These results suggest that the ability to spontaneously form thoughts about the absence of objects likely belongs to the initial cognitive repertoire of vertebrate species.
Consensus for management of portal vein thrombosis in liver cirrhosis (2020, Shanghai)
Authors:   Hepatobiliary Disease Study Group, Chinese Society of Gastroenterology, Chinese Medical Association
Published: January 2021

Portal vein thrombosis (PVT) is a common and severe complication of liver cirrhosis. So far, there have been few consensuses or practice guidelines on the management of PVT in liver cirrhosis. In this expert consensus, we systematically review the epidemiology, risk factors, imaging examinations, diagnosis, assessment of disease severity, and treatment strategy of PVT in liver cirrhosis, based on the most recent evidence and expert opinions, to further standardize the diagnosis and treatment of the disease in clinical practice.
Reproduction response of Colletotrichum fungi under the fungicide stress reveals new aspects of chemical control of fungal diseases
Authors: Han Yong‐chao , Zeng Xiang‐guo , Guo Cong , Zhang Qing‐hua , Chen Feng‐ying , Ren Li , Chen Wei‐dong , Qin Li
Published: January 2021

Systemic fungicides and antifungals are used as frontline treatments for fungal diseases in plants and humans. It is generally accepted that fungicides will bring significant negative side‐effects to the environment and result in fungicide resistance in the pathogenic fungi. Although previous research has focused on fungicide application rates and fungal resistance for a long time, little attention has been paid to fungicide residues after treatment, especially their potential role in fungal growth and sporulation. Here we investigated the effect of fungicides at sublethal concentrations on fungal sporulation. The results showed that two kinds of 14α‐demethylase inhibitors (DMIs) fungicides increased the number of isolates of Colletotrichum spp. to sporulate on PDA. Both on PDA medium and plant tissue, low concentration of DMI fungicides could promote spore production of Colletotrichum spp., whereas pyraclostrobin, a quinone outside inhibitor (QoIs), had no significant effects on sporulation of Colletotrichum spp. Transcriptomic analysis suggested that the DMIs fungicide stress signal may be transmitted to the central regulatory pathway through the FluG‐mediated signalling pathway, and further confirmed the morphological effect of DMI fungicide on promoting sporulation of Colletotrichum. To our knowledge, this is the first study to provide insights into the reproductive response of fungi in response to fungicide stress. Our findings indicate that fungicides have two‐way effects on the growth and reproduction of pathogenic fungi and provide a new basis for the scientific and rational use of fungicides.
HN1L promotes invasion and metastasis of the esophagogastric junction adenocarcinoma
Authors: Wang Zhao Yang , Xiao Wen , Jiang Yuan Zhu , Dong Wei , Zhang Xiang Wei , Zhang Lin
Published: January 2021

Background

Adenocarcinoma of the esophagogastric junction (AEG) refers to cancer that crosses the line of the gastroesophageal junction and includes distal esophageal cancer and proximal gastric cancer. It is characterized by early metastasis and a poor prognosis and has few treatment options. Here, we report a novel potential therapeutic target, hematological and neurological expressed 1‐like (HN1L), in AEG.

Methods

A total of 38 patients who underwent surgical resection of AEG at the Department of Thoracic Surgery of Shandong Provincial Hospital from September 2018 to June 2019 were enrolled into the study. We detected the expression of HN1L in AEG and adjacent nontumor tissues by IHC staining. The clinicopathological characteristics of HN1L were statistically analyzed. Then, the expression of HN1L in different cell lines was detected by RT‐q PCR. Finally, AGS and HGC‐27 cell lines were performed to inhibit HN1L by shRNA in order to explore its role in the development of AEG.

Results

Immunohistochemical staining showed that the expression of HN1L in cancer tissues was higher than that in nontumor tissue (p < 0.001). High expression of HN1L was significantly correlated with TNM stage (p = 0.013) and lymph node metastasis (p = 0.03). The expression of HN1L was upregulated in tumor cell lines compared with normal cell line. Additionally, Cell function studies demonstrated that lentivirus‐mediated shRNA silencing of HN1L expression could effectively reduce the proliferation, invasion, and metastasis of tumor cell lines and promote their apoptosis (p < 0.05).

Conclusions

HN1L expression might contribute to the invasion and metastasis of AEG and is a promising therapeutic target.
Evaluation of N95 respirators, modified snorkel masks and low‐cost powered air‐purifying respirators: a prospective observational cohort study in healthcare workers
Authors: Clinkard D. , Mashari A. , Karkouti K. , Fedorko L.
Published: January 2021

Disposable N95 respirator masks are the current standard for healthcare worker respiratory protection in the COVID‐19 pandemic. In addition to shortages, qualitative fit testing can have low sensitivity for detecting poor fit, leading to inconsistent protection. Multiple groups have developed alternative solutions such as modified snorkel masks to overcome these limitations, but validation of these solutions has been lacking. We sought to determine if N95s and snorkel masks with attached high‐efficiency filters provide consistent protection levels in healthcare workers and if the addition of positive pressure via an inexpensive powered‐air purifying respirator to the snorkel mask would provide enhanced protection. Fifty‐one healthcare workers who were qualitatively fitted with N95 masks underwent quantitative mask fit testing according to a simulated workplace exercise protocol. N95, snorkel masks with high‐efficiency filters and snorkel masks with powered‐air purifying respirators were tested. Respiratory filtration ratios were collected for each step and averaged to obtain an overall workplace protocol fit factor. Failure was defined as either an individual filtration ratio or an overall fit factor below 100. N95s and snorkel masks with high‐efficiency filters failed one or more testing steps in 59% and 20% of participants, respectively, and 24% and 12% failed overall fit factors, respectively. The snorkel masks with powered‐air purifying respirators had zero individual or overall failures. N95 and snorkel masks with high‐efficiency filter respirators were found to provide inconsistent respiratory protection in healthcare workers.
Structural recirculation and refractory hypoxemia under femoro‐jugular veno‐venous extracorporeal membrane oxygenation
Authors: Charbit Jonathan , Deras Pauline , Courvalin Elie , Laumon Thomas , Dagod Geoffrey , Martinez Orianne , Capdevila Xavier
Published: January 2021

The performance of each veno‐venous extracorporeal membrane oxygenation (vv‐ECMO) configuration is determined by the anatomic context and cannula position. A mathematical model was built considering bicaval specificities to simulate femoro‐jugular configuration. The main parameters to define were cardiac output (QC), blood flow in the superior vena cava (QSVC), extracorporeal pump flow (QEC), and pulmonary shunt (kS‐PULM). The obtained variables were extracorporeal flow ratio in the superior vena cava (EFRSVC = QEC/[QEC + QSVC]), recirculation coefficient (R), effective extracorporeal pump flow (Qeff‐EC = [1 – R] × QEC), Qeff‐EC/QC ratio, and arterial blood oxygen saturation (SaO2). EFRSVC increased logarithmically when QEC increased. High QC or high QSVC/QC decreased EFRSVC (range, 68%‐85% for QEC of 5 L/min). R also increased following a logarithmic shape when QEC increased. The R rise was earlier and higher for low QC and high QSVC/QC (range, 12%‐49% for QEC of 5 L/min). The Qeff‐EC/QC ratio (between 0 and 1) was equal to EFRSVC for moderate and high QEC. The Qeff‐EC/QC ratio presented the same logarithmic profile when QEC increased, reaching a plateau (range, 0.67‐0.91 for QEC/QC = 1; range, 0.75‐0.94 for QEC/QC = 1.5). The Qeff‐EC/QC ratio was linearly associated with SaO2 for a given pulmonary shunt. SaO2 < 90% was observed when the pulmonary shunt was high (Qeff‐EC/QC ≤ 0.7 with kS‐PULM = 0.7 or Qeff‐EC/QC ≤ 0.8 with kS‐PULM = 0.8). Femoro‐jugular vv‐ECMO generates a systematic structural recirculation that gradually increases with QEC. EFRSVC determines the Qeff‐EC/QC ratio, and thereby oxygen delivery and the superior cava shunt. EFRSVC cannot exceed a limit value, explaining refractory hypoxemia in extreme situations.
Intraoperative prothrombin complex concentrate administration and outcomes in patients undergoing left ventricular assist device implantation
Authors: Boswell Michael R. , Stulak John M. , Tchantchaleishvili Vakhtang , Weber Matthew P. , Warner Matthew A. , Smith Bradford B. , Smith Mark M.
Published: January 2021

Prothrombin complex concentrate (PCC) administration has increased among cardiac surgery patients in recent years; however, use in LVAD implantation/exchange is not widespread due to the fear of thrombotic complications. The purpose of this study was to compare the clinical outcomes of patients undergoing LVAD implantation/exchange with intraoperative PCC administration versus traditional transfusion practices alone. Adult LVAD implants/exchanges at our institution between 2015 and 2018 were included. Patients were categorized as receiving intraoperative PCC or no‐PCC (traditional). The primary outcome was the need for allogenic transfusion and transfusion volume at 48 hours after initial intensive care unit (ICU) admission. Secondary outcomes included metrics of morbidity and mortality. A total of 160 patients (39 PCC, 121 traditional) were analyzed. In unadjusted analysis, patients in the PCC group received lower intraoperative transfusion volumes compared to the traditional group although not statistically significant (1464 mL [IQR 796, 4876] vs. 2568 mL [IQR 1292, 3606]; P value .37). In the fully adjusted analysis, patients in the PCC group had increased odds of transfusion within 48 hours of ICU admission (OR 4.06, 95% CI: 1.35‐12.20; P < .01); however, there was no significant difference in transfusion volumes (P = .09). Patients receiving PCCs had higher incidence of deep vein thrombosis (10.3% vs. 0%; P  < .01) and 30‐day mortality (17.9% vs. 4.1%; P < .01). LVAD pump thrombosis occurred in 2.6% versus 0.8% in the PCC and traditional groups, respectively; P = .98. Patients undergoing LVAD implantation and exchange represent a complex surgical cohort. The results of this study suggest that the intraoperative PCC use during LVAD implant/exchange was associated with reduced intraoperative transfusions. Intraoperative PCC use was, however, associated with higher odds of postoperative transfusion, although transfusion volumes were not significantly different. While the deep vein thrombosis and 30‐day mortality rates were higher in the PCC group, these results are likely related to the degree of surgical and patient complexity rather than PCC use itself. Further studies are needed to assess PCC use in this surgical cohort.
Sickle cell disease: progress towards combination drug therapy
Authors: Pace Betty S. , Starlard‐Davenport Athena , Kutlar Abdullah
Published: January 2021

Dr. John Herrick described the first clinical case of sickle cell anaemia (SCA) in the United States in 1910. Subsequently, four decades later, Ingram and colleagues characterized the A to T substitution in DNA producing the GAG to GTG codon and replacement of glutamic acid with valine in the sixth position of the βS‐globin chain. The establishment of Comprehensive Sickle Cell Centers in the United States in the 1970s was an important milestone in the development of treatment strategies and describing the natural history of sickle cell disease (SCD) comprised of genotypes including homozygous haemoglobin SS (HbSS), HbSβ0thalassaemia, HbSC and HbSβ+thalassaemia, among others. Early drug studies demonstrating effective treatments of HbSS and HbSβ0thalassaemia, stimulated clinical trials to develop disease‐specific therapies to induce fetal haemoglobin due to its ability to block HbS polymerization. Subsequently, hydroxycarbamide proved efficacious in adults with SCA and was Food and Drug Administration (FDA)‐approved in 1998. After two decades of hydroxycarbamide use for SCD, there continues to be limited clinical acceptance of this chemotherapy drug, providing the impetus for investigators and pharmaceutical companies to develop non‐chemotherapy agents. Investigative efforts to determine the role of events downstream of deoxy‐HbS polymerization, such as endothelial cell activation, cellular adhesion, chronic inflammation, intravascular haemolysis and nitric oxide scavenging, have expanded drug targets which reverse the pathophysiology of SCD. After two decades of slow progress in the field, since 2018 three new drugs were FDA‐approved for SCA, but research efforts to develop treatments continue. Currently over 30 treatment intervention trials are in progress to investigate a wide range of agents acting by complementary mechanisms, providing the rationale for ushering in the age of effective and safe combination drug therapy for SCD. Parallel efforts to develop curative therapies using haematopoietic stem cell transplant and gene therapy provide individuals with SCD multiple treatment options. We will discuss progress made towards drug development and potential combination drug therapy for SCD with the standard of care hydroxycarbamide.
Contrasting off‐line segmentation decisions with on‐line word segmentation during reading
Authors: He Liyuan , Song Ziming , Chang Min , Zang Chuanli , Yan Guoli , Liversedge Simon P.
Published: January 2021

In two experiments, we investigated the correspondences between off‐line word segmentation and on‐line segmentation processing during Chinese reading. In Experiment 1, participants were asked to read sentences which contained critical four‐character strings, and then, they were required to segment the same sentences into words in a later off‐line word segmentation task. For each item, participants were split into 1‐word segmenters (who segmented four‐character strings as a single word) and 2‐word segmenters (who segmented four‐character strings as 2 two‐character words). Thus, we split participants into two groups (1‐word segmenters and 2‐word segmenters) according to their off‐line segmentation bias. The data analysis showed no reliable group effect on all the measures. In order to avoid the heterogeneity of participants and stimuli in Experiment 1, two groups of participants (1‐word segmenters and 2‐word segmenters) and three types of critical four‐character string (1‐word strings, ambiguous strings, and 2‐word strings) were identified in a norming study in Experiment 2. Participants were required to read sentences containing these critical strings. There was no reliable group effect in Experiment 2, as was the case in Experiment 1. However, in Experiment 2, participants spent less time and made fewer fixations on 1‐word strings compared to ambiguous and 2‐word strings. These results indicate that the off‐line word segmentation preferences do not necessarily reflect on‐line word segmentation processing during Chinese reading and that Chinese readers exhibit flexibility such that word, or multiple constituent, segmentation commitments are made on‐line.
Wood species identity alters dominant factors driving fine wood decomposition along a tree diversity gradient in subtropical plantation forests
Authors: Wu Donghao , Pietsch Katherina A. , Staab Michael , Yu Mingjian
Published: January 2021

Microclimate and biotic factors drive wood decomposition. Yet, relatively few studies have been conducted in warmer tropical and subtropical forests compared with colder temperate and boreal forests, where climate might have stronger limitations on decomposition. Besides, conclusions on decomposition are generally based on single wood species or standardized materials. Thus, a general assessment if wood species identity alters dominant factors of decomposition in subtropical forest could improve the predictability of current C cycle models. We measured fine wood mass‐loss rates of seven widespread tree species in southeast China at two time steps (after 1 and 2 years) in subtropical plantation forests with tree species diversity manipulated. We found that termites exceeded fungi in consuming fine woody debris, and termite foraging intensity decreased with lignin content. Tree species diversity increased fungal hyphal coverage on fine wood samples and had different effects on wood mass‐loss rates depending on wood species. Higher minimum temperature and amplitude of relative humidity suppressed termite foraging intensity, with humidity having inconsistent effects on mass‐loss rates among wood species. Interestingly, microclimate outweighed biotic factors for Castanopsis eyrei but not for the other species. Three traits, that is, wood density, phenolics, and lignin content, were higher than the average for C. eyrei, making it the least attractive species for decomposers. Our findings suggest that species identity influences the effects and relative importance of biotic factors and microclimate for wood decomposition in subtropical forests. Furthermore, species identity effects are possibly mediated by multiple wood traits.

Abstract in Chinese is available with online material.
Caring for a child with a disability in a Zambian community: A study using photo‐elicitation
Authors: Hepperlen Renee A. , Rabaey Paula , Ament‐Lemke Amanda , Manley Hayley
Published: January 2021

Background

Over the past 25 years, caregivers of children with disabilities (CWD) in low‐ and middle‐income countries (LMIC) have received limited attention from researchers. Previous research identified the physical, emotional, and social challenges of caregiving in resource‐limited areas. Researchers also identified protective factors, such as problem‐focused coping and emotion‐focused coping. This study seeks to explore experiences of caregivers of CWD through participant‐driven photo‐elicitation, in a low‐income subdistrict of Lusaka, Zambia.

Methods

Researchers considered the experiences of caregivers providing support to their children with disabilities (CWD). Ten parent participants completed this qualitative study using photo‐elicitation. Parent participants completed an individual interview to describe their experiences reflected in the pictures they took. The research team used qualitative content analysis to identify the themes.

Results

Five general themes emerged from the data. The last two themes, “Also, a human being,” and “The community should learn,” are unique in research of CWD caregivers in LMIC settings. It indicates ways that these parents sought to encourage more inclusion and acceptance of their CWD in the community and to speak to other parents who might be struggling with providing care for their CWD.

Conclusions

This study expanded disability research to include perspectives from a low‐income area in Lusaka, Zambia. In doing so, we acquire a new viewpoint and enhanced understanding of their community experiences. Practice considerations include encouraging disability advocates to continue their work of educating the community about the inherent dignity and worth of people with disabilities and supporting CWD's rights.