bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Paul Bindu D. , Lemle Marian D. , Komaroff Anthony L. , Snyder Solomon H.
Published: August 2021

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.
1.36 million years of Mediterranean forest refugium dynamics in response to glacial–interglacial cycle strength
Authors: Donders Timme , Panagiotopoulos Konstantinos , Koutsodendris Andreas , Bertini Adele , Mercuri Anna Maria , Masi Alessia , Combourieu-Nebout Nathalie , Joannin Sébastien , Kouli Katerina , Kousis Ilias , Peyron Odile , Torri Paola , Florenzano Assunta , Francke Alexander , Wagner Bernd , Sadori Laura
Published: August 2021

Significance

Forest conservation and restoration are important means to counter threats caused by habitat fragmentation and global change. Diverse and resilient forests can only be maintained if we understand their sensitivity to past climate change. The sedimentary record of the oldest extant lake in Europe, Lake Ohrid (North Macedonia, Albania), shows the survival and extinction of tree species during glacial and interglacial stages (G–IG) of the Quaternary. Pollen analysis reveals that the area was an effective refuge for tree populations through G–IG periods. The lake body locally buffered the climate, allowing repeated recovery of tree populations that were close to disappearance. However, extended periods of aridity during G–IG intensification after 0.94 Ma caused many tree taxa to disappear.
Adaptive staffing can mitigate essential worker disease and absenteeism in an emerging epidemic
Authors: Aguilar Elliot , Roberts Nicholas J. , Uluturk Ismail , Kaminski Patrick , Barlow John W. , Zori Andreas G. , Hébert-Dufresne Laurent , Zusman Benjamin D.
Published: August 2021

Essential worker absenteeism has been a pressing problem in the COVID-19 pandemic. Nearly 20% of US hospitals experienced staff shortages, exhausting replacement pools and at times requiring COVID-positive healthcare workers to remain at work. To our knowledge there are no data-informed models examining how different staffing strategies affect epidemic dynamics on a network in the context of rising worker absenteeism. Here we develop a susceptible–infected–quarantined-recovered adaptive network model using pair approximations to gauge the effects of worker replacement versus redistribution of work among remaining healthy workers in the early epidemic phase. Parameterized with hospital data, the model exhibits a time-varying trade-off: Worker replacement minimizes peak prevalence in the early phase, while redistribution minimizes final outbreak size. Any “ideal” strategy requires balancing the need to maintain a baseline number of workers against the desire to decrease total number infected. We show that one adaptive strategy—switching from replacement to redistribution at epidemic peak—decreases disease burden by 9.7% and nearly doubles the final fraction of healthy workers compared to pure replacement.
Spatiotemporal evolution of the Jehol Biota: Responses to the North China craton destruction in the Early Cretaceous
Authors: Zhou Zhonghe , Meng Qingren , Zhu Rixiang , Wang Min
Published: August 2021

Significance

The Early Cretaceous Jehol Biota is a terrestrial lagerstätte that produces exquisitely preserved fossils that have furnished enormous evidence on the origins and early evolution of diverse vertebrate groups. On the basis of the latest paleontological and geochronologic evidence, we discuss the three stages of the biota, and suggest that the spatiotemporal evolution of the Jehol Biota coincides with the initial and peak stages of the North China craton destruction in the Early Cretaceous. Such linkage presents an example of how regional tectonics influence the terrestrial biota that points to a new path for future studies involving multidisciplinary methods to explore the biosphere in deep time.
Bindin is essential for fertilization in the sea urchin
Authors: Wessel Gary M. , Wada Yuuko , Yajima Mamiko , Kiyomoto Masato
Published: August 2021

Species-specific sperm−egg interactions are essential for sexual reproduction. Broadcast spawning of marine organisms is under particularly stringent conditions, since eggs released into the water column can be exposed to multiple different sperm. Bindin isolated from the sperm acrosome results in insoluble particles that cause homospecific eggs to aggregate, whereas no aggregation occurs with heterospecific eggs. Therefore, Bindin is concluded to play a critical role in fertilization, yet its function has never been tested. Here we report that Cas9-mediated inactivation of the
bindin
gene in a sea urchin results in perfectly normal-looking embryos, larvae, adults, and gametes in both males and females. What differed between the genotypes was that the
bindin
−/−
sperm never fertilized an egg, functionally validating Bindin as an essential gamete interaction protein at the level of sperm–egg cell surface binding.
Apology responses and gender differences in spoken British English
Authors: An Yi , Su Hang , Xiang Mingyou
Published: August 2021

This study presents a corpus-based sociopragmatic investigation into apology responses (ARs) and gender differences in ARs in spoken British English. Using data taken from the recently released Spoken BNC2014, the investigation leads to an adjusted taxonomy of ARs which comprises five categories and several sub-categories. The investigation shows that ‘Lack of response’ is the most typical response, followed by ‘Acceptance’, ‘Rejection’, ‘Evasion’, and ‘Acknowledgement’. The results are discussed in relation to the process of attenuation that apologies have undergone (e.g.Jucker 2019), i.e. apologies are becoming more routinised and less meaningful. The proposed taxonomy is subsequently used to examine the extent to which male and female recipients respond to apologies differently. While the investigation suggests no significant differences in ARs across genders, it has been observed that there is some correlation between ARs and the gender of the apologiser. Finally, the implications and applications of the study are briefly discussed.
Invoking divine blessing
Authors: Badarneh Muhammad A. , Migdadi Fathi , Al-Jahmani Maram
Published: August 2021

This study explores the speech act of congratulation in university graduation notebooks, a new communicative context in Jordan. Using the concept of thepragmemeas a situated speech act, a total of 1064 congratulatory messages, found in 35 notebooks, were analyzed. The analysis demonstrated that the cultural concept ofbaraka‘blessing’ plays a central role in the Arabic congratulation speech act. Embedded in its production are other speech acts such as compliments and advice, sociocultural beliefs and concepts such as fatalism and collectivism, and sociocultural practices such asnaqout‘money given as a gift’. Invoking these values and beliefs when performing congratulations was accomplished through ritualistic religious invocations, formulaic expressions, reference to collective identity, and acts of material support, showing how this Arabic speech act is situated in sociocultural beliefs and values.
A SHHecret target of relapsed medulloblastoma: Astrocytes
Authors: Qadeer Zulekha A. , Weiss William A.
Published: August 2021

In this issue of JEM, Guo et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202350) examine the importance of tumor-derived astrocytes in SHH-medulloblastoma recurrence. They show that tumor cells transdifferentiate to tumor-derived astrocytes via bone morphogenetic proteins and Sox9, which excitingly can be targeted by BMP inhibitors.
Correction of periodic displacement non-linearities by two-wavelength interferometry
Authors: Bridges Angus , Yacoot Andrew , Kissinger Thomas , Humphreys David A , Tatam Ralph P
Published: August 2021

Non-linearities in interferometric displacement measurements commonly affect both homodyne and heterodyne optical interferometers. Unwanted back reflections (ghost reflections) or polarisation leakage introduce non-linearity terms at harmonics of the illuminating wavelength that cannot be fully corrected for with standard non-linearity correction techniques. A two-wavelength interferometric approach, operating at 632.8 and 785 nm, is presented here that is capable of correcting such non-linearities. Non-linearities are separated from the difference between two displacement measurements made at differing wavelengths with a Fourier approach. Compared to a standard Heydemann ellipse fitting correction, the proposed approach reduces estimated residual non-linearities from 84 to 11 pm in the case of a linear displacement profile. In particular this approach is applicable to the correction of higher order non-linearities that are caused by multiple reflections, and that are therefore very sensitive to alignment conditions.
A laser cooling scheme for precision measurements using fermionic barium monofluoride (137Ba19F) molecules
Authors: Kogel Felix , Rockenhäuser Marian , Albrecht Ralf , Langen Tim
Published: August 2021

We theoretically investigate the laser cooling of fermionic barium monofluoride (137BaF) molecules, which are promising candidates for precision studies of weak parity violation and nuclear anapole moments. This molecular species features two nuclear spins, resulting in a hyperfine structure that is considerably more complicated than the one found in the usual laser-cooled diatomics. We use optical Bloch equations and rate equations to show that optical cycling, sub-Doppler cooling and bichromatic forces can all be realized under realistically achievable experimental conditions.
Greenhouse gas footprints of utility-scale photovoltaic facilities at the global scale
Authors: Bosmans Joyce H C , Dammeier Louise C , Huijbregts Mark A J
Published: August 2021

Technological characteristics and meteorological conditions are major determinants of the greenhouse gas (GHG) footprints of photovoltaic facilities. By accounting for technological and meteorological differences, we quantified the GHG footprints of 9992 utility-scale photovoltaic facilities worldwide. We obtained a median greenhouse gas footprint of 58.7 g CO2-eq kWh−1, with a 3-fold spread (28.2–94.6 g CO2-eq kWh−1, 2.5th and 97.5th percentiles). Differences in panel type appeared to be the most important determinant of variability in the GHG footprint, followed by irradiation and a facility’s age. We also provided a meta-model based on these three predictors for users to determine the facility-specific greenhouse gas footprint. The total cumulative electricity produced by the utility-scale photovoltaic fleet worldwide is 457 TWh yr−1, 99.6% of which is produced at footprints below 100 g CO2-eq kWh−1. Compared to earlier studies, the footprints we computed of global utility-scale facilities show a relatively large spread. In order to further improve the accuracy of facility-specific footprints, more information on panel type as well as production country is required.
Effect of interface orientation on the adhesion strength and fracture toughness of Ni/CrN interfaces by first-principles study
Authors: Wang Miao , Liu Gang , Luo Xian , Levchenko Vladimir A
Published: August 2021

The brittleness and relatively poor adhesion properties of CrN materials have been extensively addressed by developing Ni/CrN composites with a separate Ni phase. However, conditions at the Ni/CrN interfaces, which are the key features leading to the enhanced toughness, remain poorly understood. The present work addresses this issue by investigating the effect of interface orientation on adhesion strength and fracture toughness of Ni/CrN interfaces using first-principles calculations. To this end, we build seven Ni/CrN interface models, including Ni(100)/CrN(100), Ni(110)/CrN(110), Ni(110)/CrN(111), and Ni(111)/CrN(111), with different interface orientation and stacking orders. The results demonstrate that the interface orientation plays a predominant role in determining the mechanical properties of the Ni/CrN interfaces, while the effect of stacking order can be neglected. The Ni(111)/CrN(111) interface is demonstrated to provide the greatest adhesion strength, interfacial stability, and fracture toughness among the Ni/CrN interfaces considered, and is therefore the preferred orientation for Ni/CrN composite applications.
Application of green synthesized silver nanoparticles in cancer treatment—a critical review
Authors: Jabeen Shazina , Qureshi Rahmatullah , Munazir Mehmooda , Maqsood Muhammad , Munir Mubashrah , Shah Syed Sabir Hussain , Rahim Bakht Zareen
Published: August 2021

With the breakthrough in advance technologies, researchers are looking to devise novel approaches to control different types of deadly cancers. Progress in medicinal plants research and nanotechnology has drawn scientist’s attention toward green synthesis of metallic nanoparticles by exploiting plants secondary metabolites owing to its advantage over routinely used physical and chemical synthesis (simple, one step approach to reduce and stabilize bulk silver into silver nanoparticles (AgNPs), cost effectiveness, energy efficient, biocompatibility and therapeutic significance). Owing to control size, shape and functional surface corona, AgNPs hold considerable potentiality for therapeutic applications by opting different mechanistic pathways such as mitochondrial disruption, DNA fragmentation, cell membrane disruption, interruption of cellular signaling pathways, altered enzyme activity and reactive oxygen species (ROS) production leading to apoptosis etc In this review, we discussed the green synthesized AgNPs in the possible cancer treatment by harnessing phytochemicals present in plant extract. In addition, this review also provides recent advances and achievements in utilization of green synthesized AgNPs in cancer treatment and proposes mechanistic action for their anticancer and cytotoxic potential. By understanding the mechanistic action of AgNPs responsible for their therapeutic efficacy will help to devise customized therapies and treatment against cancer as a potential cancer therapeutic tool.
‘Flat-pack pasta’ morphs into 3D shapes when cooked
Authors: Johnston Hamish
Published: August 2021

Flat sheets of fresh and dried pasta that morph into tubes or spirals when cooked have been created by researchers in the US and China.
Boost for Majorana-based quantum computing
Authors: Marks Jacob
Published: August 2021

Researchers at the University of Maryland, US, have identified an experimentally feasible way to generate Majorana fermions, potentially paving the way for Majorana-based quantum computation.
Publishers announce name-change policies
Authors: Bawagan Juanita
Published: August 2021

The introduction of trans-inclusive journal policies has been broadly welcomed, but some say that more needs to be done, as Juanita Bawagan reports
NASA Ingenuity rotorcraft completes first flight on another planet
Authors: Kruesi Liz
Published: August 2021

NASA’s Ingenuity rotorcraft has successfully completed five test flights on Mars, the last of which involved travelling as far as 130 m.
China launches first space-station module
Authors: Banks Michael
Published: August 2021

The core module of the Chinese Space Station (CSS) has arrived in orbit after being launched in late April by a Long March 5B rocket from the Wenchang Space Launch Centre on the southern island of Hainan.
Science has moved online during the pandemic
Authors: Allen Michael
Published: August 2021

Science is being done differently since the start of the pandemic last year – but the pace of effort has not slowed. That’s the conclusion of a survey conducted by the professional network ResearchGate
It’s topology, naturally
Authors: Cartwright Jon
Published: August 2021

One of the hottest topics in solid-state physics is having a fluid makeover. As Jon Cartwright reports, the consequences of topological behaviours in fluid dynamics could be far-reaching for our understanding of the natural world and other complex systems, such as fusion tokamaks
What does physics look like, and does it matter?
Authors: Starkey Anna
Published: August 2021

The conceptual worlds of physics have long inspired artists and thinkers across disciplines. Anna Starkey explores how different approaches to visualizing physics can open up the way that society thinks and feels about physics as an imaginative human endeavour
Solving the proton puzzle
Authors: Cartlidge Edwin
Published: August 2021

Why were so many physicists so wrong about the size of the proton for so long? As Edwin Cartlidge explains, the solution to this “proton radius puzzle” has as much to do with bureaucracy and politics as it does with physics
Reaching out to the stars
Authors: Lea Rob
Published: August 2021

Luz Ángela García, a cosmology postdoc in Bogotá, Colombia, talks to Rob Lea about her journey into physics and astronomy as a woman from South America
Finite-key analysis for quantum conference key agreement with asymmetric channels
Authors: Li Zhao , Cao Xiao-Yu , Li Chen-Long , Weng Chen-Xun , Gu Jie , Yin Hua-Lei , Chen Zeng-Bing
Published: August 2021

As an essential ingredient of quantum networks, quantum conference key agreement (QCKA) provides unconditional secret keys among multiple parties, which enables only legitimate users to decrypt the encrypted message. Recently, some QCKA protocols employing twin-field was proposed to promote transmission distance. These protocols, however, suffer from relatively low conference key rate and short transmission distance over asymmetric channels, which demands a prompt solution in practice. Here, we consider a tripartite QCKA protocol utilizing the idea of sending-or-not-sending twin-field scheme and propose a high-efficiency QCKA over asymmetric channels by removing the symmetry parameters condition. Besides, we provide a composable finite-key analysis with rigorous security proof against general attacks by exploiting the entropic uncertainty relation for multiparty system. Our protocol greatly improves the feasibility to establish conference keys over asymmetric channels.
Voluntary Adolescent-Onset Alcohol Drinking Fails to Influence Alcohol Consumption or Anxiety-Like Behaviour in Adulthood in Female Alcohol-Preferring Rats
Authors: Mugantseva Ekaterina , Hyytiä Petri , Latvala Antti
Published: August 2021

Aims

Alcohol exposure during adolescence is associated with both increased risk for alcohol use disorders and anxiety in adulthood. Our present experiments examined this association using alcohol-preferring AA (Alko Alcohol) rats selected for high voluntary alcohol drinking.

Methods

Two groups of female AA rats acquired alcohol drinking at different ages. We gave the adolescent-onset group free choice to 10% alcohol and water for seven weeks, starting on post-natal day 42 (PND 42), whereas the adult-onset group started drinking alcohol on PND 112. After the 7-week drinking, we withdrew the adolescent group from alcohol for two weeks, followed by another voluntary 7-week drinking period, started at the same age as the adult-onset group. We assessed anxiety-like behaviour repeatedly during alcohol drinking with open field and elevated plus maze tests. At the end of alcohol drinking, we also tested the rats using the light/dark box, stress-induced body temperature test and social dominance test.

Results

During the first 7-week alcohol drinking, adolescent rats exhibited significantly slower acquisition of alcohol drinking and lower alcohol preference than the adult-onset group. However, when tested at the same age as the adult-onset rats, they displayed identical alcohol intake and preference. We found no alcohol-induced effects on anxiety- or stress-related behaviour in the experimental groups at any time points.

Conclusions

These data show that the genetically determined phenotype of high alcohol drinking of the female alcohol-preferring AA rats is not associated with a predisposition to develop anxiety-like behaviour following voluntary alcohol exposure, even when initiated during adolescence.
Distinctive Connectivities of Near-Stream and Watershed-Wide Land Uses Differentially Degrade Rural Aquatic Ecosystems
Authors: Jackson C Rhett , Cecala Kristen K , Wenger Seth J , Kirsch Joseph E , Webster Jackson R , Leigh David S , Sanders Jennifer M , Love Jason P , Knoepp Jennifer D , Fraterrigo Jennifer M , Rosemond Amy D
Published: August 2021

The water-quality effects of low-density rural land-use activities are understudied but important because of large rural land coverage. We review and synthesize spatially extensive studies of oligotrophic mountain streams in the rural Southern Appalachian Mountains, concluding that rural land-use activities significantly degrade water quality through altered and mostly enhanced landscape–stream connections, despite high forest retention. Some connections (insolation, organic inputs, root–channel interactions, stream–field connectivity, individual landowner discharges) are controlled by near-stream land-use activities, whereas others (reduced nitrogen uptake and cycling, enhanced biological nitrogen fixation, nutrient subsidy, runoff from compacted soils, road runoff delivery) are controlled by basin-wide land use. These connections merge to alter basal resources and shift fish, salamander, and invertebrate assemblages toward species tolerant of higher turbidity and summer temperatures and those more competitive in mesotrophic systems. Rural water quality problems could be mitigated substantially with well-known best management practices, raising socioecological governance questions about best management practice adoption.
Functional Differentiation of Dorsal and Ventral Posterior Parietal Cortex of the Rat: Implications for Controlled and Stimulus-Driven Attention
Authors: Yang Fang-Chi , Dokovna Lisa B , Burwell Rebecca D
Published: August 2021

The posterior parietal cortex (PPC) is important for visuospatial attention. The primate PPC shows functional differentiation such that dorsal areas are implicated in top–down, controlled attention, and ventral areas are implicated in bottom–up, stimulus-driven attention. Whether the rat PPC also shows such functional differentiation is unknown. Here, we address this open question using functional neuroanatomy and in vivo electrophysiology. Using conventional tract-tracing methods, we examined connectivity with other structures implicated in visuospatial attention including the lateral posterior nucleus of the thalamus (LPn) and the postrhinal cortex (POR). We showed that the LPn projects to the entire PPC, preferentially targeting more ventral areas. All parts of the PPC and POR are reciprocally connected with the strongest connections evident between ventral PPC and caudal POR. Next, we simultaneously recorded neuronal activity in dorsal and ventral PPC as rats performed a visuospatial attention (VSA ) task that engages in both bottom–up and top–down attention. Previously, we provided evidence that the dorsal PPC is engaged in multiple cognitive process including controlled attention (Yang et al. 2017). Here, we further showed that ventral PPC cells respond to stimulus onset more rapidly than dorsal PPC cells, providing evidence for a role in stimulus-driven, bottom–up attention.
Impaired Filtering and Hyperfocusing: Neural Evidence for Distinct Selective Attention Abnormalities in People with Schizophrenia
Authors: Hahn Britta , Robinson Benjamin M , Kiat John E , Geng Joy , Bansal Sonia , Luck Steven J , Gold James M
Published: August 2021

Although schizophrenia is classically thought to involve impaired attentional filtering, people with schizophrenia (PSZ) exhibit a more intense and more exclusive attentional focus than healthy control subjects (HCS) in many tasks. To resolve this contradiction, this functional magnetic resonance imaging study tested the impact of attentional control demands on the modulation of stimulus-induced activation in the fusiform face area and parahippocampal place area when participants (43 PSZ and 43 HCS) were looking for a target face versus house. Stimuli were presented individually, or as face-house overlays that challenged attentional control. Responses were slower for house than face stimuli and when prioritizing houses over faces in overlays, suggesting a difference in salience. Blood-oxygen-level-dependent activity reflected poorer attentional selectivity in PSZ than HCS when attentional control was challenged most, that is, when stimuli were overlaid and the task required detecting the lower-salience house target. By contrast, attentional selectivity was exaggerated in PSZ when control was challenged least, that is, when stimuli were presented sequentially and the task required detecting the higher-salience face target. These findings are consistent with 2 distinct attentional abnormalities in schizophrenia leading to impaired and exaggerated selection under different conditions: attentional control deficits, and hyperfocusing once attention has been directed toward a stimulus.
Early Start of Infliximab in Crohn’s Disease Increases Rates of Endoscopic Remission and Decreases Stenosis Formation: Experiences From a Single Center Cohort
Authors: Schnitzler Fabian , Seitz Theresia , Tillack-Schreiber Cornelia , Lange Silke , Waggershauser Constanze , Ochsenkühn Thomas
Published: August 2021

Background

Over 10 years ago, the step-up/top-down trial demonstrated favorable outcomes of Crohn’s disease (CD) after early initiation of infliximab (IFX) in patients with CD. However, data on long-term effects of this treatment strategy in daily clinical practice are scarce.

Methods

This retrospective study investigated effects of early (<24 months after diagnosis) versus late intervention (>24 months) of IFX in CD on endoscopic remission (ER) rates, surgery rates, and course of CD, long term.

Results

Overall, 242 CD patients (94 early, 148 late intervention) were started on IFX and followed for 24 months. Sixty-one patients with early and 86 with late intervention underwent endoscopy after start of IFX. After IFX induction, 90.3% of patients with early versus 87.8% with late intervention were in clinical remission (P = .676), compared to 89.1% versus 85.8% after 24 months (P = .554). Almost half of patients with early IFX (45.9%, n = 28/61) achieved ER within 24 months compared to only one forth with late IFX intervention (25.6%, n = 22/86, P = .013). In addition, significantly less patients with early IFX intervention (9.8%, n = 6/61) developed intestinal stenosis during 24 months follow-up compared to late IFX start (29.1%, n = 25/86, P = .007). Logistic regression revealed early IFX intervention as only relevant factor achieving ER with an odds ratio of 2.386 (95% confidence interval [1.1180; 4.825], P = .016).

Conclusions

Our data on early IFX therapy in CD support early IFX intervention with more patients achieving ER, and less patients developing stricturing disease behavior. Early IFX intervention could therefore change the course of CD.
Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn’s Disease: Results From the VISIBLE 2 Randomised Trial
Authors: Vermeire Séverine , D’Haens Geert , Baert Filip , Danese Silvio , Kobayashi Taku , Loftus Edward V , Bhatia Siddharth , Agboton Christian , Rosario Maria , Chen Chunlin , Zhang Wenwen , Kisfalvi Krisztina , Sandborn William J
Published: August 2021

Background and Aims

To report results from VISIBLE 2, a randomised, double-blind, placebo-controlled, phase 3 trial evaluating a new subcutaneous [SC] vedolizumab formulation as maintenance treatment in adults with moderately to severely active Crohn’s disease [CD].

Methods

Following open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2, Week 6 clinical responders (≥70-point decrease in CD Activity Index [CDAI] score from baseline) were randomised 2:1 to receive double-blind maintenance vedolizumab 108 mg SC or placebo every 2 weeks until Week 50. Assessments at Week 52 included clinical remission [primary endpoint; CDAI ≤150], enhanced clinical response [≥100-point decrease in CDAI from baseline], corticosteroid-free clinical remission among patients using a corticosteroid at baseline, clinical remission in anti-tumour necrosis factor [anti-TNF]-naïve patients, and safety.

Results

Following vedolizumab intravenous induction, 275 patients were randomised to vedolizumab SC and 135 to placebo maintenance. At Week 52, 48.0% of patients receiving vedolizumab SC versus 34.3% receiving placebo were in clinical remission [p = 0.008]. Enhanced clinical response at Week 52 was achieved by 52.0% versus 44.8% of patients receiving vedolizumab SC versus placebo, respectively [p = 0.167]. At Week 52, 45.3% and 18.2% of patients receiving vedolizumab SC and placebo, respectively, were in corticosteroid-free clinical remission, and 48.6% of anti-TNF-naïve patients receiving vedolizumab SC and 42.9% receiving placebo were in clinical remission. Injection site reaction was the only new safety finding observed for vedolizumab SC [2.9%].

Conclusions

Vedolizumab SC is an effective and safe maintenance therapy in patients with CD who responded to two infusions of vedolizumab intravenous induction therapy.
Microbially mediated nitrogen removal and retention in the York River Estuary
Authors: G. Fortin Samantha , Song Bongkeun , C. Anderson Iris
Published: August 2021

Denitrification, anaerobic ammonium oxidation and dissimilatory nitrate reduction to ammonium (DNRA) are important microbial processes determining the fate of nitrogen (N) in estuaries. This study examined these processes in sediments of the York River Estuary, a tributary of Chesapeake Bay, and investigated environmental and microbial drivers of the rates of denitrification and DNRA. Nitrate reduction followed a consistent pattern throughout the year and across the estuary with nitrogen removal, primarily through denitrification, decreasing from the head of the estuary to the mouth and nitrogen retention, through DNRA, following the opposite pattern. At the mouth of the estuary, nitrogen retention was consistently higher than nitrogen removal. Denitrification rates showed strong linear relationships with concentrations of organic matter, nitrate and chlorophyll a, and the abundance of the nirS gene. DNRA rates were best correlated with the relative abundance of three bacterial families, Anaerolineaceae,Ectothiorhodospiraceae and Prolixibacteraceae, which carry the nrfA gene. The controls responsible for retention or removal of N from an estuary are complex, involving both geochemical and microbial factors. The N retained within estuaries may support primary production and seasonal algae blooms and result in estuarine eutrophication.
Efficacy of Clonal Propagation in Andaman Padauk (Pterocarpus dalbergioides): Augmenting Conservation of an Endemic Ornamental Timber Species of Andaman & Nicobar Islands, India
Authors: Jaisankar Iyyappan , Varadan R Jayakumara , Vijayakumar S , Jambhulkar Nitiprasad Namdeorao , Jerard Bosco Augustine , Ganguly Nabanita , Rajkumar Muthu , Moses Ezekiel Manasseh , Simhachalam Putcha
Published: August 2021

The population of Andaman padauk (Pterocarpus dalbergioides Roxb.), an endemic ornamental timber species, is fast depleting in the Andaman Islands. Afforestation through seedlings is hindered by low germination and high mortality rates. This study attempts to assess the efficacy of clonal propagation methods to hasten mass multiplication by trying out different combinations of growth hormones, concentration, and dipping duration in semi-hardwood stem cuttings and different combinations of growth hormone concentration and substrate in air layering. Dipping the cuttings in indole-3-butyric acid (IBA) 1,500 ppm for 24 hours and spraying the modified stem-cut layers with IBA 2,000 ppm and binding with top soil and decomposed coir dust turned out to be the best treatment combination for cutting and air layering, respectively. Among the considered factors, the concentration of growth hormone is crucial for cutting, as the performance is enhanced with concentration under a given growth hormone and dipping duration. Similarly, the substrate is crucial for air layering, as modified stem-cut air layers bound with top soil and decomposed coir dust not only achieve the best performance, but also catalyze IBA for further improvement when other substrates remain unresponsive. Successful outcome of both clonal propagation techniques gives hope for disseminating the species across the tropics at global level.
Volatility Decay and Diversification Role of Timberland as the Investment Horizon Lengthens
Authors: Zhang Weiyi , Mei Bin
Published: August 2021

Under the mean-variance efficiency framework, we investigate the role of timberland asset in a mixed-asset portfolio in the United States. Starting from a single period (quarterly) view, we first reveal the crucial role of serial correlation in defining an asset’s financial performance. Accordingly, we modify return, volatility, and correlation for multiyear horizons to account for the nature of long-term investments. Our results show that, although timberland is persistent in all portfolios, private-equity timberland can be substituted by other liquid assets, including public-equity timberland, as the lengthening holding period substantially reduces their volatilities. We conclude that private-equity timberland is a risk diversifier regardless of the length of the investment horizon, whereas public-equity timberland becomes a suitable diversifier only for long-term investors with high risk tolerance.
Speeding up eQTL scans in the BXD population using GPUs
Authors: Trotter Chelsea , Kim Hyeonju , Farage Gregory , Prins Pjotr , Williams Robert W , Broman Karl W , Sen Śaunak
Published: August 2021

The BXD family of mouse strains are an important reference population for systems biology and genetics that have been fully sequenced and deeply phenotyped. To facilitate interactive use of genotype–phenotype relations using many massive omics data sets for this and other segregating populations, we have developed new algorithms and code that enable near-real-time whole-genome quantitative trait locus (QTL) scans for up to one million traits. By using easily parallelizable operations including matrix multiplication, vectorized operations, and element-wise operations, our method is more than 700 times faster than a R/qtl linear model genome scan using 16 threads. We used parallelization of different CPU threads as well as GPUs. We found that the speed advantage of GPUs is dependent on problem size and shape (the number of cases, number of genotypes, and number of traits). Our approach is ideal for interactive web services, such as GeneNetwork.org that need to display results in real-time. Our implementation is available as the Julia language package LiteQTL at https://github.com/senresearch/LiteQTL.jl.
BPIFB4 Circulating Levels and Its Prognostic Relevance in COVID-19
Authors: Ciaglia Elena , Lopardo Valentina , Montella Francesco , Sellitto Carmine , Manzo Valentina , De Bellis Emanuela , Iannaccone Teresa , Franci Gianluigi , Zannella Carla , Pagliano Pasquale , Di Pietro Paola , Carrizzo Albino , Vecchione Carmine , Conti Valeria , Filippelli Amelia , Puca Annibale Alessandro
Published: August 2021

Aging and comorbidities make individuals at greatest risk of COVID-19 serious illness and mortality due to senescence-related events and deleterious inflammation. Long-living individuals (LLIs) are less susceptible to inflammation and develop more resiliency to COVID-19. As demonstrated, LLIs are characterized by high circulating levels of BPIFB4, a protein involved in homeostatic response to inflammatory stimuli. Also, LLIs show enrichment of homozygous genotype for the minor alleles of a 4 missense single-nucleotide polymorphism haplotype (longevity-associated variant [LAV]) in BPIFB4, able to counteract progression of diseases in animal models. Thus, the present study was designed to assess the presence and significance of BPIFB4 level in COVID-19 patients and the potential therapeutic use of LAV-BPIFB4 in fighting COVID-19. BPIFB4 plasma concentration was found significantly higher in LLIs compared to old healthy controls while it significantly decreased in 64 COVID-19 patients. Further, the drop in BPIFB4 values correlated with disease severity. Accordingly to the LAV-BPIFB4 immunomodulatory role, while lysates of SARS-CoV-2-infected cells induced an inflammatory response in healthy peripheral blood mononuclear cells in vitro, the co-treatment with recombinant protein (rh) LAV-BPIFB4 resulted in a protective and self-limiting reaction, culminating in the downregulation of CD69 activating-marker for T cells (both TCD4+ and TCD8+) and in MCP-1 reduction. On the contrary, rhLAV-BPIFB4 induced a rapid increase in IL-18 and IL-1b levels, shown largely protective during the early stages of the virus infection. This evidence, along with the ability of rhLAV-BPIFB4 to counteract the cytotoxicity induced by SARS-CoV-2 lysate in selected target cell lines, corroborates BPIFB4 prognostic value and open new therapeutic possibilities in more vulnerable people.
Application of explicit precautionary principles in data-limited fisheries management
Authors: Fischer Simon H , De Oliveira José A A , Mumford John D , Kell Laurence T
Published: August 2021

Many management bodies require applying the precautionary approach when managing marine fisheries resources to achieve sustainability and avoid exceeding limits. For data-limited stocks, however, defining and achieving management objectives can be difficult. Management procedures can be optimized towards specific management objectives with genetic algorithms. We explored the feasibility of including an objective that limited the risk of a stock falling below various limit reference points in the optimization routine for an empirical data-limited control rule that uses a biomass index, mean catch length, and includes constraints (the “rfb-rule”). This was tested through management strategy evaluation on several fish stocks representing various life-history traits. We show that risk objectives could be met, but more restrictive risk limits can lead to a potential loss of yield. Outcomes were sensitive to simulation conditions such as observation uncertainty, which can be highly uncertain in data-limited situations. The rfb-rule outperforms the method currently applied by ICES, particularly when risk limitation objectives are considered. We conclude that the application of explicit precautionary levels is useful to avoid overfishing. However, we caution against the indiscriminate use of arbitrary risk limits without scientific evaluation to analyse their impact on stock yields and sustainability.
The Illegal Economy and Crime as a Service
Authors: Fairman David
Published: August 2021

With the significant advances of technology over many years, not only have law-abiding citizens, organisations and governments leveraged this to their advantage to grow and prosper, so too have criminals, writes David Fairman, CSO APAC at Netskope.
How Chaos Theory is Changing Management Tech
Authors: Taylor Paul
Published: August 2021

As technology infrastructures are becoming more dynamical and business critical, so they are susceptible to chaos theory, writes Freelance Consultant Paul Taylor MBCS.
Advantages and Challenges of Using Breast Biopsy Markers
Authors: Alshafeiy Taghreed I , Matich Alison , Rochman Carrie M , Harvey Jennifer A
Published: August 2021

Percutaneous image-guided biopsy procedures are the standard of care for histologic assessment of suspicious breast lesions. Post-biopsy tissue markers (clips) optimize patient management by allowing for assessment on follow-up imaging and precise lesion localization. Markers are used to ensure accurate correlation between imaging modalities, guide preoperative localization for malignant and high-risk lesions, and facilitate accurate identification of benign lesions at follow-up. Local practices differ widely, and there are no data detailing the exact frequency of use of clips for different breast biopsies. There are many indications for biopsy marker deployment, and some difficulties may be encountered after placement. The placement of biopsy markers has many advantages and few disadvantages, such that deployment should be routinely used after percutaneous biopsy procedures with rare exception.
A new species ofSalentinellaRuffo, 1947 from a thermo-mineral cave in southern Spain, with comments on the systematic position of the family Salentinellidae (Amphipoda)
Authors: Jaume Damià , Vonk Ronald
Published: August 2021

A new species of the stygobiont amphipod genus SalentinellaRuffo, 1947 is described from a thermo-mineral cave of Granada, southern Spain. Detailed observation of the appendages of the new species and of fresh specimens of S. angelieriDelamare-Deboutteville & Ruffo, 1952, and their comparison with the descriptions of other members of the family, have revealed that a simple callynophore is present on the antennule in both sexes of salentinellids. Furthermore, salentinellids have resulted to show a non-senticaudatan (i.e., lack of apical spines on rami) condition of uropods I and II. Both features question the current placement of the family within the senticaudatan parvorder Bogidiellidira. An identification key to all known members of the family Salentinellidae is provided.
The Uses of Stages of Change and Language Within a Forestry Context
Authors: Sarmiento Irene G , Van Swol Lyn M , Shaw Bret R , Chung Jennifer H , Koshollek Alanna
Published: August 2021

Advising landowners can be difficult for foresters. Landowners’ motivations towards behavior change should be considered prior to giving advice. The Stages of Change Model, also known as the Transtheoretical Model, assesses whether individuals are ready to perform new behaviors. This model was used to understand how landowner’s motivations towards behavior change affect future reforestation efforts, which could help foresters better advise landowners. Landowners from Wisconsin were recruited, reported current behaviors, and separated into either predecisional or postdecisional stages, based on self-reported stage of behavior. They received advice, reported future reforestation intentions, and provided comments. Using Ordinary Least Squares (OLS) regression and language analyses, predecisional stage perceived more barriers towards reforestation efforts and used more negative emotion words, whereas postdecisional stage reported more past habits of reforestation efforts and used more positive emotion words. Foresters should provide advice that reduces barriers for the predecisional stage and build on positive aspects of reforestation for the postdecisional stage.
Is the eclipsing binary RR Dra dancing with a hidden tertiary black hole candidate?
Authors: Wang Zhi-Hua , Zhu Li-Ying
Published: August 2021

Analysis of timing variation of the eclipsing binary RR Dra implies the existence of an additional object with mass of no less than 3.5(±0.2) M⊙. This third object is orbiting around the central eclipsing pair once every 98(±1) yr, making the whole a hierarchical triple system. However, reliable photometric solutions based on light curves from Transiting Exoplanet Survey Satellite and WASP show that contribution of the third-light takes only about 2 per cent of the total luminosity. It could photometrically be attributed to other unrelated star located within the aperture. The tertiary component is thus a massive object but invisible in optical wavelengths. Besides, evidence of misalignment between the barycenter and the centre of light of the system is also found. This strengthen the existence of a hidden black hole candidate in the form of the third body. The potential black hole may play an essential role in extracting angular momentum from the central binary pair, forming the current state. As a good laboratory, RR Dra is an interesting system that can help to study stellar-mass black hole under the circumbinary case.
Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus Infection
Authors: El Kamari Vanessa , Rodriguez Katherine , Moser Carlee , Currier Judith S , Kelesidis Theodoros , Stein James H , Brown Todd T , Howell Scott K , Beisswenger Paul J , McComsey Grace A
Published: August 2021

Background

Despite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains unclear.

Methods

ACTG A5260s is a prospective open-label randomized trial in which ART-naive people living with HIV were randomized to tenofovir disoproxil fumarate /emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir over 96 weeks. Changes in circulating AGEs with ART initiation were assessed, and linear regression was used to examine the associations between serum AGEs with carotid intima-media thickness (cIMT), visceral and subcutaneous adipose tissue, total fat, lean mass, body mass index, insulin resistance, leptin, and adiponectin.

Results

Overall, 214 participants were included. Ninety percent were male, 48% were White, the median age was 36 years, median HIV-1 RNA was 4.58 log10 copies/mL, and median CD4 count was 338 cells/µL. Most AGEs remained relatively unchanged following 96 weeks of ART initiation, except for methylglyoxal-derived hydroimidazolone 1 (MG-H1), which increased following 96 weeks of ART (mean fold change, 1.15 [95% confidence interval, 1.02–1.30]). No differences were detected across ART regimens. Increases in AGE levels over time were associated with worsening body fat composition measures, insulin resistance, and cIMT, even after adjusting for clinically relevant factors.

Conclusions

AGE levels did not decrease following ART initiation. Most AGE levels remained stable, except for MG-H1, which increased. In people with HIV on ART, the accumulation of circulating AGEs over time appears to be independently associated with worsening cardiometabolic biomarkers.

Summary: Antiretroviral therapy (ART) does not appear to be effective in reducing advanced glycation end product (AGE) levels. On the contrary, AGE levels seem to increase following ART initiation. Accumulation of AGEs was found to be independently associated with cardiometabolic complications in treated people living with HIV.