bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental filtering affects fungal communities more than dispersal limitation in a high-elevation hyperarid basin on Qinghai–Tibet Plateau
Authors: Xing Rui , Gao Qing-bo , Zhang Fa-qi , Wang Jiu-li , Chen Shi-long
Published: March 2021

The Qaidam Basin is the most extensive (120 000 km2) basin on the Qinghai–Tibet Plataea (QTP). Recent studies have shown that environmental selection and dispersal limitation influence the soil fungal community significantly in a large-scale distance. However, less is known about large-scale soil fungal community assemblages and its response to the elevation gradient in the high-elevation basin ecosystems. We studied fungal assemblages using Illumina sequencing of the ITS1 region from 35 sites of the Qaidam Basin. As the increase of elevation, fungal species richness and Chao1 index also increased. The Ascomycota was the most abundant phylum (more than 70% of total sequences), and six of the 10 most abundance fungal family was detected in all 35 soil samples. The key factors influencing the soil fungal community composition in the Qaidam Basin were environmental filtering (soil properties and climate factors). The Mantel test showed no significant relationship between geographic distance and community similarity (r = 0.05; p = 0.81). The absence of the distance effect might be caused by lacking dispersal limitation for the soil fungal community.
Divide and Rule: Discursive Authority, Identity Dissonance, Ethnic Lobbies, and US Foreign Policy, or How President Obama Defeated AIPAC over the 2015 Iran Deal
Authors: Rynhold Jonathan
Published: March 2021

This article addresses the influence of diaspora lobbies on US foreign policy by analyzing the failure of the paradigmatic lobby—AIPAC—to block the 2015 Iran deal. The literature on the efficacy of diaspora lobbies focuses on structural material factors. In contrast, this study introduces an agency-orientated constructivist approach focused on ideational factors. While the material institutional setting contributed to AIPAC's defeat by establishing a high bar to overcome, this was not insurmountable. Consequently, such material factors must be combined with ideational factors to fully explain AIPAC's defeat. In this vein, the prevalence of negative affective partisanship generated a “cultural opportunity structure” for the President to wield party loyalty to obtain the support of Congressional Democrats. Yet, this too was not insurmountable for AIPAC, had opposition to the deal not become tainted by partisanship. However, the “Republican first” strategy pursued by the public face of the campaign, Israeli Prime Minister Benjamin Netanyahu, undermined AIPAC's “discursive authority.” This generated “identity dissonance” within the American Jewish community and for other Democratic supporters of Israel, by casting their identification with Israel against their identification with the Democratic Party. In contrast, President Obama successfully framed the issue to minimize identity dissonance.
Factors that influence bidirectional long-tract homozygosis due to double-strand break repair in Candida albicans
Authors: Marton Timea , Chauvel Murielle , Feri Adeline , Maufrais Corinne , D’enfert Christophe , Legrand Mélanie
Published: March 2021

Genomic rearrangements have been associated with the acquisition of adaptive phenotypes, allowing organisms to efficiently generate new favorable genetic combinations. The diploid genome of Candida albicans is highly plastic, displaying numerous genomic rearrangements that are often the by-product of the repair of DNA breaks. For example, DNA double-strand breaks (DSB) repair using homologous-recombination pathways are a major source of loss-of-heterozygosity (LOH), observed ubiquitously in both clinical and laboratory strains of C. albicans. Mechanisms such as break-induced replication (BIR) or mitotic crossover (MCO) can result in long tracts of LOH, spanning hundreds of kilobases until the telomere. Analysis of I-SceI-induced BIR/MCO tracts in C. albicans revealed that the homozygosis tracts can ascend several kilobases toward the centromere, displaying homozygosis from the break site toward the centromere. We sought to investigate the molecular mechanisms that could contribute to this phenotype by characterizing a series of C. albicans DNA repair mutants, including pol32-/-, msh2-/-, mph1-/-, and mus81-/-. The impact of deleting these genes on genome stability revealed functional differences between Saccharomyces cerevisiae (a model DNA repair organism) and C. albicans. In addition, we demonstrated that ascending LOH tracts toward the centromere are associated with intrinsic features of BIR and potentially involve the mismatch repair pathway which acts upon natural heterozygous positions. Overall, this mechanistic approach to study LOH deepens our limited characterization of DNA repair pathways in C. albicans and brings forth the notion that centromere proximal alleles from DNA break sites are not guarded from undergoing LOH.
Bayesian inversion of the Martian structure using geodynamic constraints
Authors: Drilleau Mélanie , Samuel Henri , Rivoldini Attilio , Panning Mark , Lognonné Philippe
Published: March 2021

The ongoing InSight mission has recently deployed very broad band seismometers to record the Martian seismic activity. These recordings constitute the first seismic data set collected at the surface of Mars. This unique but sparse record compels for the development of new techniques tailored to make the best use of the specific context of single station-multiple events with several possible ranges of uncertainties on the event location. To this end, we conducted sets of Markov chain Monte Carlo inversions for the 1-D seismic structure of Mars. We compared two inversion techniques that differ from the nature of the parametrization on which they rely. A first classical approach based on a parametrization of the 1-D seismic profile using Bézier curves. A second, less conventional approach that relies on a parametrization in terms of quantities that influence the thermochemical evolution of the planet (mantle rheology, initial thermal state and composition), which accounts for 4.5 Gyr of planetary evolution. We considered several combinations of true model parameters to retrieve, and explored the influence of the type of seismic data (body waves with or without surface waves), the number of events and their associated epicentral distances and uncertainties, and the presence of potential constraints on Moho depth inferred from independent measurements/considerations (receiver functions and gravity data). We show that due to its inherent tighter constraints the coupled approach allows a considerably better retrieval of Moho depth and the seismic structure underneath it than the classical inversion, under the condition that the physical assumptions made in the coupled approach are valid for Mars. In addition, our tests indicate that in order to constrain the seismic structure of Mars with InSight data, the following independent conditions must be met: (1) The presence of surface waves triggered by an internal source to constrain the epicentral distance. (2) The presence of just a few well-localized impact sources, with at least one located at close epicentral distance (<5°) to illuminate independently the crust and the mantle. In addition to providing tighter constraints of Mars seismic structure, geodynamically constrained inversions allow one to reconstruct the thermochemical and rheological history of Mars until present. Therefore, even with a relatively small amount of large events and in absence of surface waves, constraining the present-day structure and long-term evolution of the red planet remains possible through the use of tailored hybrid inversion schemes.
Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry
Authors: Anderson Alyce , Cherfane Cynthia , Click Benjamin , Ramos-Rivers Claudia , Koutroubakis Ioannis E , Hashash Jana G , Babichenko Dmitriy , Tang Gong , Dunn Michael , Barrie Arthur , Proksell Siobhan , Dueker Jeffrey , Johnston Elyse , Schwartz Marc , Binion David G
Published: March 2021

Background

Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization.

Methods

We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type.

Results

A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05).

Conclusions

Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.
The Pathogenesis and Clinical Management of Stricturing Crohn Disease
Authors: Schmoyer Christopher J , Saidman Jakob , Bohl Jaime L , Bierly Claire L , Kuemmerle John F , Bickston Stephen J
Published: March 2021

Stricturing of the gastrointestinal tract is a common complication in Crohn disease and is a significant cause of morbidity and mortality among this population. The inflammatory process initiates fibrosis, leading to aberrant wound healing and excess deposition of extracellular matrix proteins. Our understanding of this process has grown and encompasses cellular mechanisms, epigenetic modifications, and inherent genetic predisposition toward fibrosis. Although medications can improve inflammation, there is still no drug to attenuate scar formation. As such, management of stricturing disease requires a multidisciplinary and individualized approach including medical management, therapeutic endoscopy, and surgery. This review details the current understanding regarding the pathogenesis, detection, and management of stricturing Crohn disease.
Vedolizumab Tissue Concentration Correlates to Mucosal Inflammation and Objective Treatment Response in Inflammatory Bowel Disease
Authors: Pauwels Renske W M , Proietti Elisa , van der Woude Christien J , Oudijk Lindsey , Crombag Marie-Rose B S , Peppelenbosch Maikel P , Grohmann Ursula , Fuhler Gwenny M , de Vries Annemarie C
Published: March 2021

Background

The association between vedolizumab (VDZ) exposure and treatment response is unclear and seems insufficiently explained by serum levels. The aim of this study was to assess the correlation between VDZ concentrations in serum and intestinal tissue and their association with mucosal inflammation and response to VDZ.

Methods

This prospective study included 37 adult patients with inflammatory bowel disease with endoscopic inflammation at baseline who started VDZ. At week 16, serum and biopsies were collected for VDZ measurement by enzyme-linked immunosorbent assay. Nonlinear mixed-effects modeling was used to calculate serum trough concentrations and to assess intestinal tissue concentrations. Validated clinical and endoscopic scores were used to define clinical and endoscopic response and remission, and fecal calprotectin levels were used to assess biochemical response. Histologic remission was determined by the Nancy score.

Results

A positive correlation was observed between VDZ concentrations in serum and tissue (r2 = 0.83; P < 0.0001). High mucosal rather than serum VDZ levels correlated with a reduced endoscopic (P = 0.06) grade of mucosal inflammation. Furthermore, patients with a positive biochemical and endoscopic outcome had higher tissue levels of VDZ than patients without biochemical and endoscopic response (P < 0.01 and P = 0.04, respectively).

Conclusions

Tissue levels of VDZ may provide a better marker than serum levels for mucosal inflammation and objective treatment outcome at week 16. The potential of VDZ tissue levels for therapeutic drug monitoring in inflammatory bowel disease warrants further exploration.
Quasi-Newton variable preconditioning for nonlinear nonuniformly monotone elliptic problems posed in Banach spaces
Authors: Borsos B , Karátson J
Published: March 2021

Quasi-Newton-type iterative solvers are developed for a wide class of nonlinear elliptic problems. The presented generalization of earlier efficient methods covers various nonuniformly elliptic problems arising, e.g., in non-Newtonian flows or for certain glaciology models. The robust estimates are reinforced by several examples.
Unconditional uniqueness for the periodic modified Benjamin–Ono equation by normal form approach
Authors: Kishimoto Nobu
Published: March 2021

We show that the solution (in the sense of distribution) to the Cauchy problem with the periodic boundary condition associated with the modified Benjamin–Ono equation is unique in $L^\infty _t(H^s(\mathbb{T} ))$ for $s>1/2$. The proof is based on the analysis of a normal form equation obtained by infinitely many reduction steps using integration by parts in time after a suitable gauge transform.
ISO standard 20776-1 or serial 2-fold dilution for antifungal susceptibility plate preparation: that is the question!
Authors: Arendrup Maiken Cavling , Jørgensen Karin Meinike , Hanemaaijer Nicolien , Verweij Paul E
Published: March 2021

Background

Since the ISO standard 20776-1 and serial dilution procedures were compared in 2010 for fluconazole and itraconazole, several new antifungals that are hydrophobic and highly potent have been introduced.

Objectives

To investigate the impact of the number of tip changes during serial dilution, and ISO and serial dilution for nine antifungals.

Methods

EUCAST E.Def 7.3.2 with serial (0–10 tip changes) and ISO dilution. Candida parapsilosis ATCC 22019, Candida albicans ATCC 64548, C. albicans CNM CL-F8555, Candida krusei ATCC 6258, Aspergillus flavus ATCC 204304 and clinical isolates (n = 5) of C. albicans, Candida dubliniensis, Candida glabrata, C. krusei, A. flavus and Aspergillus terreus were included. GM MICs were compared for ISO and serial dilution and with QC values where available.

Results

Increasing the number of tip changes (0/1/2/10 times) during serial dilution for plate preparation increased the MICs 1 to >2 dilutions for amphotericin B, anidulafungin, micafungin, fluconazole, voriconazole and isavuconazole against C. albicans ATCC 64548 but only isavuconazole MICs against C. parapsilosis ATCC 22019 (3 dilutions). ISO and serial dilution (two tip changes) were compared for eight compounds and four Candida QC strains (352 MICs). Six/41 GM MIC pairs deviated with 1–1.8 dilution (14.6%). Comparing the GM MIC with the QC values, the ISO method GM MIC was closest to the target in 30.8%, the serial dilution in 34.6% and the methods identical in 34.6% of the cases. Finally, ISO and serial dilution MICs were compared for clinical isolates (920 MICs). Five/23 GM MIC pairs (21.7%) deviated 1.0–1.1 dilutions.

Conclusions

The ISO and serial dilution (two tip changes) method were in acceptable agreement and thus equally applicable for EUCAST testing.
Associations of physician burnout with organizational electronic health record support and after-hours charting
Authors: Eschenroeder H. C , Manzione Lauren C , Adler-Milstein Julia , Bice Connor , Cash Robert , Duda Cole , Joseph Craig , Lee John S , Maneker Amy , Poterack Karl A , Rahman Sarah B , Jeppson Jacob , Longhurst Christopher
Published: March 2021

In 2017, 43.9% of US physicians reported symptoms of burnout. Poor electronic health record (EHR) usability and time-consuming data entry contribute to burnout. However, less is known about how modifiable dimensions of EHR use relate to burnout and how these associations vary by medical specialty. Using the KLAS Arch Collaborative’s large-scale nationwide physician (MD/DO) data, we used ordinal logistic regression to analyze associations between self-reported burnout and after-hours charting and organizational EHR support. We examined how these relationships differ by medical specialty, adjusting for confounders. Physicians reporting ≤ 5 hours weekly of after-hours charting were twice as likely to report lower burnout scores compared to those charting ≥6 hours (aOR: 2.43, 95% CI: 2.30, 2.57). Physicians who agree that their organization has done a great job with EHR implementation, training, and support (aOR: 2.14, 95% CI: 2.01, 2.28) were also twice as likely to report lower scores on the burnout survey question compared to those who disagree. Efforts to reduce after-hours charting and improve organizational EHR support could help address physician burnout.
Public vs physician views of liability for artificial intelligence in health care
Authors: Khullar Dhruv , Casalino Lawrence P , Qian Yuting , Lu Yuan , Chang Enoch , Aneja Sanjay
Published: March 2021

The growing use of artificial intelligence (AI) in health care has raised questions about who should be held liable for medical errors that result from care delivered jointly by physicians and algorithms. In this survey study comparing views of physicians and the U.S. public, we find that the public is significantly more likely to believe that physicians should be held responsible when an error occurs during care delivered with medical AI, though the majority of both physicians and the public hold this view (66.0% vs 57.3%; P = .020). Physicians are more likely than the public to believe that vendors (43.8% vs 32.9%; P = .004) and healthcare organizations should be liable for AI-related medical errors (29.2% vs 22.6%; P = .05). Views of medical liability did not differ by clinical specialty. Among the general public, younger people are more likely to hold nearly all parties liable.
Evaluation of vitamin A status on myogenic gene expression and muscle fiber characteristics
Authors: Wellmann Kimberly B , Kim Jongkyoo , Urso Phil M , Smith Zachary K , Johnson Bradley J
Published: March 2021

A randomized complete block design experiment with 30 yearling crossbred steers (average BW = 436.3 ± 39.8 kg) fed a steam-flaked corn-based diet was used to evaluate the effects dietary vitamin A (Rovimix A 1000; DSM Nutritional Products Ltd., Sisseln, SUI) supplementation on myogenic gene expression and skeletal muscle fiber characteristics during the finishing phase. Steers were blocked by BW (n = 5 blocks; 6 steers/block), randomly assigned to pens (n = 2 steers/pen), and one of the following treatments: no added vitamin A (0 IU; 0.0 IU/kg of dietary dry matter intake of additional vitamin A), vitamin A supplemented at the estimated requirement (2,200 IU; 2,200 IU/kg of dietary dry matter (DM) of additional vitamin A), and vitamin A supplemented at 5× the estimated requirement (11,000 IU; 11,000 IU/kg of dietary DM of additional vitamin A). After all treatments underwent a 91-d vitamin A depletion period, additional vitamin A was top-dressed at feeding via a ground corn carrier. Blood, longissimus muscle, and liver biopsy samples were obtained on days 0, 28, 56, 84, and 112. Biopsy samples were used for immunohistochemical and mRNA analysis. Sera and liver samples were used to monitor circulating vitamin A and true vitamin A status of the cattle. Expression for myosin heavy chain (MHC)-I diminished and rebounded (P = 0.04) over time. The intermediate fiber type, MHC-IIA, had a similar pattern of expression (P = 0.01) to that of MHC-I. On day 84, C/EBPβ expression was also the greatest (P = 0.03). The pattern of PPARγ (P < 0.01) and PPARδ (P < 0.01) expression seemed to mimic that of MHC-I expression, increasing from days 84 to 112. Distribution of MHC-IIA demonstrated a change over time (P = 0.02). Muscle fiber cross-sectional area increased by day (P < 0.01) for each MHC with the notable increase between days 0 and 56. Total nuclei density decreased (P = 0.02) over time. Cells positive for only Myf5 increased (P < 0.01) in density early in the feeding period, then declined, indicating that satellite cells were fusing into fibers. The dual-positive (PAX7+Myf5) nuclei also peaked (P < 0.01) around day 56 then declined. These data indicated that gene expression associated with oxidative proteins may be independent of vitamin A status in yearling cattle.
The effects of road transportation with or without homeopathic remedy supplementation on growth performance, apparent nutrient digestibility, fecal microbiota, and serum cortisol and superoxide dismutase levels in growing pigs
Authors: Dang De Xin , Kim In Ho
Published: March 2021

The specialization of swine production and the market demand for pigs at different growth stages makes road transportation inevitable. However, road transportation usually causes a stress response in pigs. It is reported that homeopathic remedies supplementation could alleviate the stress response in pigs. This study investigated the effects of road transportation with or without homeopathic remedy (Convermax) supplementation on growth performance, nutrient digestibility, fecal microbiota, and serum cortisol and superoxide dismutase (SOD) concentrations in growing pigs. A total of 180 crossbred 49-d-old growing pigs [(Yorkshire × Landrace) × Duroc] with an initial body weight of 13.17 ± 0.02 kg were randomly allotted to 2 groups based on the initial body weight, containing 18 replicates with 5 pigs (mixed sex) in each. The pigs were fed dietary supplementation of a homeopathic remedy (Convermax) (0 or 200 mg/kg of feed, as-fed) for 35 d. On day 21, 45 pigs (70-d old; 25.25 ± 0.37 kg) were randomly selected from each group and assigned to either 2 hr of road transportation or no road transportation, resulting in a 2 × 2 factorial design. We found that road transportation led to an increase in the fecal coliform bacteria counts (P = 0.023) and serum cortisol concentration (P = 0.039) and a decrease in the serum SOD concentration (P < 0.001). However, supplementing homeopathic remedy (Convermax) to the diet of growing pigs increased gain to feed ratio (P = 0.042), apparent nitrogen digestibility (P = 0.019), and serum SOD concentration (P = 0.007), whereas decreased serum cortisol concentration (P = 0.022). In brief, road transportation induced stress response for growing pigs and increased harmful bacteria counts in their intestines. Dietary supplementation of homeopathic remedy (Convermax) alleviated stress response, improved apparent nitrogen digestibility, and increased gain to feed ratio. However, no significant interactive effects between road transportation with or without dietary homeopathic remedy (Convermax) levels were observed on the detected parameters in growing pigs.
Structural analysis and reaction mechanism of malate dehydrogenase from Geobacillus stearothermophilus
Authors: Shimozawa Yuya , Himiyama Tomoki , Nakamura Tsutomu , Nishiya Yoshiaki
Published: March 2021

Malate dehydrogenase (MDH) catalyzes the reversible reduction of oxaloacetate (OAA) to L-malate using nicotinamide adenine dinucleotide hydrogen. MDH has two characteristic loops, the mobile loop and the catalytic loop, in the active site. On binding to the substrate, the enzyme undergoes a structural change from the open-form, with an open conformation of the mobile loop, to the closed-form, with the loop in a closed conformation. In this study, three crystals of MDH from a moderate thermophile, Geobacillus stearothermophilus (gs-MDH) were used to determine four different enzyme structures (resolutions, 1.95–2.20 Å), each of which was correspondingly assigned to its four catalytic states. Two OAA-unbound structures exhibited the open-form, while the other two OAA-bound structures exhibited both the open- and closed-form. The structural analysis suggested that the binding of OAA to the open-form gs-MDH promotes conformational change in the mobile loop and simultaneously activates the catalytic loop. The mutations on the key amino acid residues involving the proposed catalytic mechanism significantly affected the gs-MDH activity, supporting our hypothesis. These findings contribute to the elucidation of the detailed molecular mechanism underlying the substrate recognition and structural switching during the MDH catalytic cycle.
Muḥammad Bahjat al-Bīṭār and the Decline of Modernist Salafism in Twentieth-Century Syria
Authors: Weismann Itzchak , Adawi Rokaya
Published: March 2021

The Salafī version of the Islamic Modernist trend emerged in the late nineteenth century among middle-ranked ulema-cum-intellectuals in the major Arab urban centres of the Ottoman Empire. Modernist Salafīs strove to strike a balance between modernization along Western lines and an authenticity based on the model of the pious ancestors (al-salaf al-ṣāliḥ). They differed from other early modernists such as the Young Ottomans and the celebrated Jamāl al-Dīn al-Afghānī and Muḥammad ʿAbduh by drawing their inspiration from the teachings of the medieval theologian Aḥmad Ibn Taymiyya and his early modern successors, the Wahhābīs and the Indian Ahl-i Ḥadīth. The major components of the quasi-liberal and open religious reform they professed were adherence to the Qurʾān and Sunna, denunciation of saint worship, reasoned ijtihād, selective adoption of Western innovations, revival of the Arab-Islamic civilization, and opposition to autocratic rule.
When More is Less: Mosquito Population Suppression Using Sterile, Incompatible and Genetically Modified Male Mosquitoes
Authors: Dobson Stephen L
Published: March 2021

The current review of the Sterile Insect Technique (SIT) is motivated by new technologies and the recent renaissance of male release field trials, which is driving an evolution in mosquito control and regulation. Practitioners that are releasing male mosquitoes would do well to learn from past successes and failures, including political and public engagement complications. With examples that include nuanced integrations of the different technologies, e.g., combinations of Wolbachia and irradiation, it is critical that scientists understand and communicate accurately about the technologies, including their evolving management by different regulatory agencies in the USA. Some male release approaches are considered ‘pesticides’ and regulated by federal and state agencies, while other male release approaches are unregulated. It is important to consider how the new technologies fit with the more ‘traditional’ chemical applications of adulticides and larvicides. The economics of male release programs are substantially different from traditional control costs, which can be a challenge to their adoption by abatement districts. However, there is substantial need to overcome these complications and challenges, because the problem with invasive mosquitoes grows ever worse with factors that include insecticide resistance, globalization and climate change.
Effect of Parental Photoperiod on Body Size and Developmental Time ofAedes aegypti(Diptera: Culicidae) in Buenos Aires City
Authors: Loetti Verónica , De Majo María Sol , Campos Raúl E , Di Battista Cristian M , Fischer Sylvia
Published: March 2021

Many insects use photoperiod as a signal to anticipate upcoming unfavorable conditions. Photoperiod sensitivity may be a relevant factor in Aedes (Stegomyia) aegypti (L.) populations at the cool margins of the species’ range, where winter conditions have a strong effect on population dynamics. In this study, we evaluated the effect of parental photoperiod on preimaginal survival and developmental time, and on wing length for the first generation of Ae. aegypti from a temperate region (Buenos Aires City, Argentina). Our experiment started with eggs from parents exposed to short-day (SD; 10:14 [L:D]) or long-day (LD; 14:10 [L:D]) photoperiods during their entire life span. Eggs were stored under the same photoperiod (SD or LD) as their parents for 91 d, until immersion. After hatching, larvae were reared until adult emergence in thermal baths at one of two constant temperatures (17 or 23°C), at a photoperiod of 12:12 (L:D) h and fed ad libitum. Survival from larva I to adult emergence was not affected either by parental photoperiod or rearing temperature. At a rearing temperature of 23°C, female offspring from the SD parental photoperiod developed faster and had shorter wings compared with those from the LD parental photoperiod. No effect of parental photoperiod was observed on female offspring reared at 17°C. In male offspring, parental photoperiod had no effect on developmental time and wing length, independently of the rearing temperature. Results indicate that the parental photoperiod may affect some offspring traits. This effect may be a characteristic of Ae. aegypti populations in temperate regions to deal with the winter conditions.
Diversity of Culturable Bacteria Isolated From the Feces of Wild Anopheles darlingi (Diptera: Culicidae) Mosquitoes From the Brazilian Amazon
Authors: Arruda Andrelisse , Ferreira Gabriel E M , Santos Júnior Antônio , Matos Najla B , Carvalho Tatiane S , Ozaki Luiz S , Stabeli Rodrigo G , Silva Alexandre A E
Published: March 2021

Microorganisms living in the midgut of Anopheles mosquitoes have been studied to fight vector-borne diseases, such as malaria. Studies on the microbiota of the Neotropical Anopheles darlingi, the most important Brazilian vector for malaria, have been reported for the same purpose. Our aims were to isolate and identify culturable bacteria from An. darlingi mosquito guts through their feces and to estimate the species richness and the frequency distribution of the sampled bacteria. Sixty wild females of An. darlingi mosquitoes were captured at two rural locations, near Porto Velho, Rondônia, Brazil. Bacteria were isolated from mosquito feces, which were collected using cages which permit the collection of feces on LB nutrient agar plates. Sixty bacterial colonies were isolated and stored in glycerol at −80°C. Bacteria were identified by sequencing their 16S rRNA gene obtained using PCR and Sanger sequencing. To aid in species identification, MALDI-TOF, VITEK2, and BBL Crystal were used as complementary protocols. The sequences obtained from the 60 bacterial isolates were compared to sequences deposited in GenBank (NCBI) using BLAST. Homology greater than 97% between the query and the subject was used as the criteria for assigning the identity of each isolate. Fourteen species from eight different genera were identified among the 60 isolates. The most frequent species were Serratia liquefaciens (20%) and Serratia marcescens (15%). Due to their established apathogenicity and according to previous studies, we suggest Serratia and Pantoea species as suitable for paratransgenesis development to fight malaria in Brazilian Amazon.
Current Effector and Gene-Drive Developments to Engineer Arbovirus-Resistant Aedes aegypti (Diptera: Culicidae) for a Sustainable Population Replacement Strategy in the Field
Authors: Reid William R , Olson Ken E , Franz Alexander W E
Published: March 2021

Arthropod-borne viruses (arboviruses) such as dengue, Zika, and chikungunya viruses cause morbidity and mortality among human populations living in the tropical regions of the world. Conventional mosquito control efforts based on insecticide treatments and/or the use of bednets and window curtains are currently insufficient to reduce arbovirus prevalence in affected regions. Novel, genetic strategies that are being developed involve the genetic manipulation of mosquitoes for population reduction and population replacement purposes. Population replacement aims at replacing arbovirus-susceptible wild-type mosquitoes in a target region with those that carry a laboratory-engineered antiviral effector to interrupt arboviral transmission in the field. The strategy has been primarily developed for Aedes aegypti (L.), the most important urban arbovirus vector. Antiviral effectors based on long dsRNAs, miRNAs, or ribozymes destroy viral RNA genomes and need to be linked to a robust gene drive to ensure their fixation in the target population. Synthetic gene-drive concepts are based on toxin/antidote, genetic incompatibility, and selfish genetic element principles. The CRISPR/Cas9 gene editing system can be configurated as a homing endonuclease gene (HEG) and HEG-based drives became the preferred choice for mosquitoes. HEGs are highly allele and nucleotide sequence-specific and therefore sensitive to single-nucleotide polymorphisms/resistant allele formation. Current research efforts test new HEG-based gene-drive designs that promise to be less sensitive to resistant allele formation. Safety aspects in conjunction with gene drives are being addressed by developing procedures that would allow a recall or overwriting of gene-drive transgenes once they have been released.
Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes
Authors: Varghese Anna M , Singh Isha , Singh Rituraj , Kunte Siddharth , Chou Joanne F , Capanu Marinela , Wong Winston , Lowery Maeve A , Stadler Zsofia K , Salo-Mullen Erin , Saadat Lily V , Wei Alice C , Reyngold Marsha , Basturk Olca , Benayed Ryma , Mandelker Diana , Iacobuzio-Donahue Christine A , Kelsen David P , Park Wungki , Yu Kenneth H , O’Reilly Eileen M
Published: March 2021

Background

Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC).

Methods

Institutional databases were queried for demographics, treatment history, genomic results, and outcomes. Overall survival from date of diagnosis was estimated using Kaplan-Meier method.

Results

Between 2008 and 2018, 450 patients with EOPC were identified at Memorial Sloan Kettering. Median overall survival was 16.3  (95% confidence interval [CI] = 14.6 to 17.7) months in the entire cohort and 11.3  (95% CI = 10.2 to 12.2) months for patients with stage IV disease at diagnosis. Of the patients, 132 (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1, and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. A total of 138 patients (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV), and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a PGV. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared with patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95% CI = 0.26 to 0.69).

Conclusions

PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.
Lymphangitis-Associated Rickettsiosis by Rickettsia sibirica mongolitimonae
Authors: Echevarría-Zubero Regina , Porras-López Elena , Campelo-Gutiérrez Carolina , Rivas-Crespo Juan Carlos , Lucas Arantxa Muñiz-De , Cobo-Vázquez Elvira
Published: March 2021

Rickettsia sibirica mongolitimonae is considered a rare pathogen that can cause different clinical presentations. Approximately, one-third of the patients with this infection experience lymphangitis from the inoculation eschar to the draining lymph nodes, and, in that case, the infection is named “lymphangitis-associated rickettsiosis” (LAR). There are several reports of infections by this Rickettsia but none of LAR in children. We report a case of LAR in a Spanish child, which confirms the distribution of this agent in our country, and his implication in pediatric population.
Performance Evaluation of the Siemens SARS-CoV-2 Total Antibody and IgG Antibody Test
Authors: Florin Lisa , Maelegheer Karel , Vandewal Wouter , Bernard Dirk , Robbrecht Johan
Published: March 2021

Objective

In this study, the performance of 2 commercially available SARS-CoV-2 antibody assays is evaluated.

Methods

The Siemens SARS-CoV-2 Total (COV2T) and IgG (COV2G) antibody tests were evaluated on a Siemens Atellica IM1300 analyzer. Imprecision was assessed with the CLSI EP15 protocol using positive controls. Ninety control group specimens were analyzed for specificity, and 175 specimens from 58 patients with polymerase chain reaction–confirmed SARS-CoV-2 were measured for the sensitivity and kinetics of the antibody response.

Results

Within-run and total imprecision were acceptable for both assays. Both tests showed a specificity of 100%. Sensitivity earlier in the disease state was greater for the COV2T assay than for the COV2G assay, but sensitivity >14 days after onset of symptoms approached 100% for both. For all patients, antibody titers remained above the seroconversion cutoff for all follow-up specimens.

Conclusion

This study shows acceptable performance for both the Siemens COV2T and COV2G test, although seroconversion occurs earlier with the COV2T test.
Transient-optimized real-bogus classification with Bayesian convolutional neural networks – sifting the GOTO candidate stream
Authors: Killestein T L , Lyman J , Steeghs D , Ackley K , Dyer M J , Ulaczyk K , Cutter R , Mong Y-L , Galloway D K , Dhillon V , O’Brien P , Ramsay G , Poshyachinda S , Kotak R , Breton R P , Nuttall L K , Pallé E , Pollacco D , Thrane E , Aukkaravittayapun S , Awiphan S , Burhanudin U , Chote P , Chrimes A , Daw E , Duffy C , Eyles-Ferris R , Gompertz B , Heikkilä T , Irawati P , Kennedy M R , Levan A , Littlefair S , Makrygianni L , Mata Sánchez D , Mattila S , Maund J , McCormac J , Mkrtichian D , Mullaney J , Rol E , Sawangwit U , Stanway E , Starling R , Strøm P A , Tooke S , Wiersema K , Williams S C
Published: March 2021

Large-scale sky surveys have played a transformative role in our understanding of astrophysical transients, only made possible by increasingly powerful machine learning-based filtering to accurately sift through the vast quantities of incoming data generated. In this paper, we present a new real-bogus classifier based on a Bayesian convolutional neural network that provides nuanced, uncertainty-aware classification of transient candidates in difference imaging, and demonstrate its application to the datastream from the GOTO wide-field optical survey. Not only are candidates assigned a well-calibrated probability of being real, but also an associated confidence that can be used to prioritize human vetting efforts and inform future model optimization via active learning. To fully realize the potential of this architecture, we present a fully automated training set generation method which requires no human labelling, incorporating a novel data-driven augmentation method to significantly improve the recovery of faint and nuclear transient sources. We achieve competitive classification accuracy (FPR and FNR both below 1 per cent) compared against classifiers trained with fully human-labelled data sets, while being significantly quicker and less labour-intensive to build. This data-driven approach is uniquely scalable to the upcoming challenges and data needs of next-generation transient surveys. We make our data generation and model training codes available to the community.
Directed Evolution of an Enhanced POU Reprogramming Factor for Cell Fate Engineering
Authors: Tan Daisylyn Senna , Chen Yanpu , Gao Ya , Bednarz Anastasia , Wei Yuanjie , Malik Vikas , Ho Derek Hoi-Hang , Weng Mingxi , Ho Sik Yin , Srivastava Yogesh , Velychko Sergiy , Yang Xiaoxiao , Fan Ligang , Kim Johnny , Graumann Johannes , Stormo Gary D. , Braun Thomas , Yan Jian , Schöler Hans R. , Jauch Ralf
Published: March 2021

Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, and maturity for widespread adoption and clinical translation. Here, we used Oct4, Sox2, Klf4, and c-Myc driven pluripotency reprogramming to evaluate methods for enhancing and tailoring cell fate transitions, through directed evolution with iterative screening of pooled mutant libraries and phenotypic selection. We identified an artificially evolved and enhanced POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency. In contrast to Oct4, not only can ePOU induce pluripotency with Sox2 alone, but it can also do so in the absence of Sox2 in a three-factor ePOU/Klf4/c-Myc cocktail. Biochemical assays combined with genome-wide analyses showed that ePOU possesses a new preference to dimerize on palindromic DNA elements. Yet, the moderate capacity of Oct4 to function as a pioneer factor, its preference to bind octamer DNA and its capability to dimerize with Sox2 and Sox17 proteins remain unchanged in ePOU. Compared with Oct4, ePOU is thermodynamically stabilized and persists longer in reprogramming cells. In consequence, ePOU: 1) differentially activates several genes hitherto not implicated in reprogramming, 2) reveals an unappreciated role of thyrotropin-releasing hormone signaling, and 3) binds a distinct class of retrotransposons. Collectively, these features enable ePOU to accelerate the establishment of the pluripotency network. This demonstrates that the phenotypic selection of novel factor variants from mammalian cells with desired properties is key to advancing cell fate conversions with artificially evolved biomolecules.
Persistence of antibody response to SARS-CoV-2 in a cohort of haemodialysis patients with COVID-19
Authors: Forbes Suzanne , Davari Maria , Gnanasampanthan Sahana , Roth Noam , Young Gregor , Rajakariar Ravindra , Cove-Smith Andrea , Yaqoob Muhammed Magdi , Cutino-Moguel Teresa , Mahalingasivam Viyaasan , McCafferty Kieran
Published: March 2021

Background

Haemodialysis (HD) patients are extremely vulnerable to coronavirus disease 2019 (COVID-19). Their immune response after infection is unclear. We have found high seroconversion rates in this population, with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody (Ab) testing.

Methods

We identified HD patients who had confirmedsevere acute respiratory syndrome coronavirus 2 between March and May 2020 and measured monthly antibodies (immunoglobulin G/immunoglobulin M) in those who survived. We used a semiquantitative cut-off index to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity and comorbidities.

Results

A total of 122 patients were analysed. All remained Ab positive during follow-up for a minimum of 148 days. Seventy-one percent had a positive gradient indicating increasing Ab positivity over time. We found that age (P = 0.01), duration of polymerase chain reaction positivity (P = 0.06) and the presence of symptoms (P = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD, and more patients had a subsequent decrease in Ab levels (P = 0.02). Diabetic patients were more likely to have a positive slope (odds ratio 2.26).

Conclusions

These results indicate that HD patients have a robust and sustained Ab response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although it is unclear what protection these antibodies confer, this is encouraging that HD patients should respond to vaccination.
Effect of dietary advanced glycation end-products restriction on type 2 diabetes mellitus control: a systematic review
Authors: Oliveira Julia S , de Almeida Carolina , de Souza Ângela M N , da Cruz Luciana D , Alfenas Rita C G
Published: March 2021

Context

Reducing dietary advanced glycation end-products (AGEs) may favor diabetes control.

Objective

Critically analyze studies about the effect of dietary AGEs restriction on inflammation, oxidative stress, and glycemic control in patients with type 2 diabetes mellitus (DM2).

Data Source

This systematic review was conducted according to PRISMA methodology. The PubMed, Web of Science, LILACS, and Cochrane Library databases were searched, using the terms “type 2 diabetes,” “advanced glycation end products” and “diet.”

Data Extraction

Seven original studies were included in this review. The duration of the studies ranged from 1 day to 16 weeks. All extracted data were compiled, compared, and critically analyzed.

Data Analysis

Glycemic variables were considered the primary outcomes. The secondary outcomes were glycation, inflammatory, and oxidative stress markers.

Conclusion

Although serum insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin values were lower after the consumption of AGEs restricted diets in most studies, there was a lack of unanimity regarding dietary AGEs’ positive effect on inflammation, oxidative stress, and blood glucose.

Systematic Review Registration

PROSPERO registration no. CRD42020152640.
Integration of Cell Growth and Asymmetric Division during Lateral Root Initiation in Arabidopsis thaliana
Authors: Schütz Lilli Marie , Louveaux Marion , Vilches Barro Amaya , Bouziri Sami , Cerrone Lorenzo , Wolny Adrian , Kreshuk Anna , Hamprecht Fred A , Maizel Alexis
Published: March 2021

Lateral root formation determines to a large extent the ability of plants to forage their environment and thus their growth. In Arabidopsis thaliana and other angiosperms, lateral root initiation requires radial cell expansion and several rounds of anticlinal cell divisions that give rise to a central core of small cells, which express different markers than the larger surrounding cells. These small central cells then switch their plane of divisions to periclinal and give rise to seemingly morphologically similar daughter cells that have different identities and establish the different cell types of the new root. Although the execution of these anticlinal and periclinal divisions is tightly regulated and essential for the correct development of the lateral root, we know little about their geometrical features. Here, we generate a four-dimensional reconstruction of the first stages of lateral root formation and analyze the geometric features of the anticlinal and periclinal divisions. We identify that the periclinal divisions of the small central cells are morphologically dissimilar and asymmetric. We show that mother cell volume is different when looking at anticlinal vs. periclinal divisions and the repeated anticlinal divisions do not lead to reduction in cell volume, although cells are shorter. Finally, we show that cells undergoing a periclinal division are characterized by a strong cell expansion. Our results indicate that cells integrate growth and division to precisely partition their volume upon division during the first two stages of lateral root formation.