bluuebunny/crossref_metadata_2025 huggingface dataset:
PWL1, a G‐type lectin receptor‐like kinase, positively regulates leaf senescence and heat tolerance but negatively regulates resistance to Xanthomonas oryzae in rice
Authors: Xu Jiangmin , Wang Chunlian , Wang Fujun , Liu Yapei , Li Man , Wang Hongjie , Zheng Yuhan , Zhao Kaijun , Ji Zhiyuan
Published: August 2023

Plant leaf senescence, caused by multiple internal and environmental factors, has an important impact on agricultural production. The lectin receptor‐like kinase (LecRLK) family members participate in plant development and responses to biotic and abiotic stresses, but their roles in regulating leaf senescence remain elusive. Here, we identify and characterize a rice premature withered leaf 1 (pwl1) mutant, which exhibits premature leaf senescence throughout the plant life cycle. The pwl1 mutant displayed withered and whitish leaf tips, decreased chlorophyll content, and accelerated chloroplast degradation. Map‐based cloning revealed an amino acid substitution (Gly412Arg) in LOC_Os03g62180 (PWL1) was responsible for the phenotypes of pwl1. The expression of PWL1 was detected in all tissues, but predominantly in tillering and mature leaves. PWL1 encodes a G‐type LecRLK with active kinase and autophosphorylation activities. PWL1 is localized to the plasma membrane and can self‐associate, mainly mediated by the plasminogen‐apple‐nematode (PAN) domain. Substitution of the PAN domain significantly diminished the self‐interaction of PWL1. Moreover, the pwl1 mutant showed enhanced reactive oxygen species (ROS) accumulation, cell death, and severe DNA fragmentation. RNA sequencing analysis revealed that PWL1 was involved in the regulation of multiple biological processes, like carbon metabolism, ribosome, and peroxisome pathways. Meanwhile, interfering of biological processes induced by the PWL1 mutation also enhanced heat sensitivity and resistance to bacterial blight and bacterial leaf streak with excessive accumulation of ROS and impaired chloroplast development in rice. Natural variation analysis indicated more variations in indica varieties, and the vast majority of japonica varieties harbour the PWL1Hap1 allele. Together, our results suggest that PWL1, a member of LecRLKs, exerts multiple roles in regulating plant growth and development, heat‐tolerance, and resistance to bacterial pathogens.
Nitrate improves aluminium resistance through SLAH‐mediated citrate exudation from roots
Authors: Wang Peng , Cao Hongrui , Quan Shuxuan , Wang Yong , Li Mu , Wei Ping , Zhang Meng , Wang Hui , Ma Hongyu , Li Xiaofeng , Yang Zhong‐Bao
Published: August 2023

Aluminium (Al) toxicity is one of the major constraint for crop production in acidic soil, and the inappropriate utilization of nitrogen fertilizer can accelerate soil acidification. Despite previous studies investigating the regulation of nitrogen forms in Al toxicity of plants, the underlying mechanism, particularly at the molecular level, remains unclear. This study aims to uncover the potentially regulatory mechanism of nitrate (NO3−) in the Al resistance of maize and Arabidopsis. NO3− conservatively improves Al resistance in maize and Arabidopsis, with nitrate‐elevated citrate synthesis and exudation potentially playing critical roles in excluding Al from the root symplast. ZmSLAH2 in maize and AtSLAH1 in Arabidopsis are essential for the regulation of citrate exudation and NO3−‐promoted Al resistance, with ZmMYB81 directly targeting the ZmSLAH2 promoter to activate its activity. Additionally, NO3− transport is necessary for NO3−‐promoted Al resistance, with ZmNRT1.1A and AtNRT1.1 potentially playing vital roles. The suppression of NO3− transport in roots by ammonium (NH4+) may inhibit NO3−‐promoted Al resistance. This study provides novel insights into the understanding of the crucial role of NO3−‐mediated signalling in the Al resistance of plants and offers guidance for nitrogen fertilization on acid soils.
Event‐related EEG synchronization and desynchronization in patients with obsessive–compulsive disorder
Authors: Pronina Marina V. , Ponomarev Valery A. , Poliakov Yury I. , Martins‐Mourao Antonio , Plotnikova Irina V. , Müller Andreas , Kropotov Yury D.
Published: August 2023

Symptoms in patients with obsessive–compulsive disorder (OCD) are associated with impairment in cognitive control, attention, and action inhibition. We investigated OCD group differences relative to healthy subjects in terms of event‐related alpha and beta range synchronization (ERS) and desynchronization (ERD) during a visually cued Go/NoGo task. Subjects were 62 OCD patients and 296 healthy controls (HC). The OCD group in comparison with HC, showed a changed value of alpha/beta oscillatory power over the central cortex, in particular, an increase in the alpha/beta ERD over the central‐parietal cortex during the interstimulus interval (Cue condition) as well as changes in the postmovement beta synchronization topography and frequency. Over the frontal cortex, the OCD group showed an increase in magnitude of the beta ERS in NoGo condition. Within the parietal‐occipital ERS/ERD modulations, the OCD group showed an increase in the alpha/beta ERD over the parietal cortex after the presentation of the visual stimuli as well as a decrease in the beta ERD over the occipital cortex after the presentation of the Cue and Go stimuli. The specific properties in the ERS/ERD patterns observed in the OCD group may reflect high involvement of the frontal and central cortex in action preparation and action inhibition processes and, possibly, in maintaining the motor program, which might be a result of the dysfunction of the cortico‐striato‐thalamo‐cortical circuits involving prefrontal cortex. The data about enhanced involvement of the parietal cortex in the evaluation of the visual stimuli are in line with the assumption about overfocused attention in OCD.
The vernacularization of Paduan medicine and philosophy in the seventeenth century: Troilo Lancetta's Raccolta medica, et astrologica
Authors: Martin Craig
Published: August 2023

In 1645 Troilo Lancetta saw to the publication of a compilation of texts, Raccolta medica, et astrologica, under the anagrammatic and implausible pseudonym Lootri Nacattel. Most of these texts were translations into the Italian vernacular. They include writings by Girolamo Cardano; Hippocrates; Aristotle, and his commentators; Girolamo Fracastoro; Lancetta’s teacher, the philosopher Cesare Cremonini; and a handful of ancient Greek and Latin historians, in addition to excerpts from Lancetta’s medical writings. The presentation of the selected texts advances a set of polemics against the practice of bloodletting as a cure for fevers and against astrology, especially its use in medicine. The collection employs a range of authorities both classical and recent to bring anti‐Galenic and anti‐astrological teachings, already present in the University of Padua, to a broader readership. This transfer reinforced Lancetta’s identity as an erudite expert in philosophy and in medicine, an identity that he cultivated in other publishing endeavors, which included Latin editions of Cremonini’s psychological and dialectical writings. Lancetta’s Raccolta reflects a sophisticated employment of medical humanism, which used Aristotelian and Hippocratic texts to undermine interpretations of Galen and promoted Cremonini’s teachings about Meteorology as part of arguments about the subalternation of medicine to philosophy, the vanity of astrology, and the denial of the predictive power of prodigious meteorological phenomena.
(En‐)‘lightening’ children: Assessing the impacts of access to electricity on learning achievement levels
Authors: Chatterjee Somdeep , Hastawala Shiv , Kamal Jai
Published: August 2023

The welfare impacts of electrification are well documented in the literature, including the effects of electricity on school enrolment. However, the spillover effects of electrification on children's achievement levels are scarce. We use three complementary but distinct econometric models to establish a causal relationship between electrification and test scores using nationally representative household panel data from India. We find positive results irrespective of the choice of econometric model, and these results seem to be mediated by changing time‐use patterns of children with access to electricity. We first exploit the plausibly exogenous variation in access to electricity due to a universal electrification program in the state of West Bengal in India and we find positive effects of electrification on children's test scores. By age group, we find that younger cohorts benefit more in terms of their reading scores than older cohorts. Then, to ascertain external validity of these results, we replicate them over a nationally representative sample using fixed effects and instrumental variables estimation and find similar results. At the intensive margin, we find that access to more hours of electricity positively affects test scores. We identify an increase in time spent by children on study‐related activities as the potential channel for these results.
Do natural resources and foreign direct investment tend to erode or support the development of national institutions?
Authors: Chiyaba Grivas , Singleton Carl
Published: August 2023

This paper explores the relationships between natural resources, foreign direct investment (FDI) and the quality of national institutions, also known as “the rules of the game”. Using a data set of 69 developing countries over the period 1970–2015 to estimate a dynamic panel data model, we find negative and significant effects of natural resources use or extraction on the development of national institutions. We focus on legal and property rights, but these findings also apply to the quality of some other national institutions. Our results align with a theory that abundant natural resources lead to weakened institutions because of the potential for firms to secure monopoly rents. Furthermore, we find that the effects of FDI inflows on institutional development are not robust to controlling for natural resources rents. This suggests that the latter tend to erode institutions regardless of whether those resources are exploited alongside increased foreign investment into the local economy.
Retrospective evaluation of hypersensitivity reactions and anaphylaxis in dogs (2003–2014): 86 cases
Authors: Fosset Fabrice T. J. , Lucas Benjamin E. G. , Wolsic Cassandra L. , Billhymer Audrey C. , Lavergne Sidonie N.
Published: August 2023

Objective

To characterize anaphylactic reactions in dogs, including clinical signs, severity, treatments, prognosis, and estimated incidence. To determine whether glucocorticoids influence clinical recovery and survival.

Design

Retrospective study between January 1, 2003 and April 28, 2014.

Setting

University teaching hospital.

Animals

Eighty‐six dogs treated for a type I hypersensitivity reaction. Nineteen dogs fulfilled the criteria for anaphylaxis, and 67 dogs had mild cutaneous reactions.

Interventions

None.

Measurements and Main Results

The estimated incidence was 0.04% for anaphylaxis and 0.15% for mild hypersensitivity reactions. The female:male ratio (2.3:1) was significantly higher (P = 0.032) compared to our source population (ratio of 1:1.158). Vaccines were the most frequent trigger for anaphylaxis (57.9%) and mild hypersensitivity reactions (28.4%). Seventy‐four (86%) dogs had cutaneous signs, and 11 (57.9%) dogs with anaphylaxis had no cutaneous signs reported. Forty‐two (48.8%) dogs received both an H1 antagonist and a glucocorticoid, 34 (39.5%) dogs received an H1 antagonist only, and 6 (6.9%) dogs received a glucocorticoid only. The majority of the dogs survived, and 1 was euthanized due to complications. Clinical signs associated with nonsurvival included respiratory signs (P = 0.006), particularly respiratory distress (P < 0.00001) and cyanosis (P < 0.00001), and circulatory shock (P = 0.005). The analysis of the interaction between etiology, clinical signs, treatment, and outcome did not show any association between pairs of variables.

Conclusions

In the current study, anaphylaxis had a relatively good prognosis, and cutaneous signs were not always present. Based on the present data, the use of glucocorticoids to treat mild type I hypersensitivity reactions and anaphylaxis in dogs was not associated with clinical improvement or survival.
Minimizing properties of networks via global and local calibrations
Authors: Pluda Alessandra , Pozzetta Marco
Published: August 2023

In this note, we prove that minimal networks enjoy minimizing properties for the length functional. A minimal network is, roughly speaking, a subset of composed of straight segments joining at triple junctions forming angles equal to ; in particular such objects are just critical points of the length functional a priori. We show that a minimal network : (i) minimizes mass among currents with coefficients in an explicit group (independent of ) having the same boundary of , (ii) identifies the interfaces of a partition of a neighborhood of solving the minimal partition problem among partitions with same boundary traces. Consequences and sharpness of such results are discussed. The proofs reduce to rather simple and direct arguments based on the exhibition of (global or local) calibrations associated to the minimal network.
A dichotomy phenomenon for bad minus normed Dirichlet
Authors: Kleinbock Dmitry , Rao Anurag
Published: August 2023

Given a norm ν on , the set of ν‐Dirichlet improvable numbers was defined and studied in the papers (Andersen and Duke, Acta Arith. 198 (2021) 37–75 and Kleinbock and Rao, Internat. Math. Res. Notices 2022 (2022) 5617–5657). When ν is the supremum norm, , where is the set of badly approximable numbers. Each of the sets , like , is of measure zero and satisfies the winning property of Schmidt. Hence for every norm ν, is winning and thus has full Hausdorff dimension. In this article, we prove the following dichotomy phenomenon: either or else has full Hausdorff dimension. We give several examples for each of the two cases. The dichotomy is based on whether the critical locus of ν intersects a precompact ‐orbit, where is the one‐parameter diagonal subgroup of acting on the space X of unimodular lattices in . Thus, the aforementioned dichotomy follows from the following dynamical statement: for a lattice , either is unbounded (and then any precompact ‐orbit must eventually avoid a neighborhood of Λ), or not, in which case the set of lattices in X whose ‐trajectories are precompact and contain Λ in their closure has full Hausdorff dimension.
Restoring connexin‐36 function in diabetogenic environments precludes mouse and human islet dysfunction
Authors: St. Clair Joshua R. , Westacott Matthew J. , Miranda Jose , Farnsworth Nikki L. , Kravets Vira , Schleicher Wolfgang E. , Dwulet JaeAnn M. , Levitt Claire H. , Heintz Audrey , Ludin Nurin W.F. , Benninger Richard K.P.
Published: August 2023

The secretion of insulin from β‐cells in the islet of Langerhans is governed by a series of metabolic and electrical events, which can fail during the progression of type 2 diabetes (T2D). β‐cells are electrically coupled via connexin‐36 (Cx36) gap junction channels, which coordinates the pulsatile dynamics of [Ca2+] and insulin release across the islet. Factors such as pro‐inflammatory cytokines and free fatty acids disrupt gap junction coupling under in vitro conditions. Here we test whether gap junction coupling and coordinated [Ca2+] dynamics are disrupted in T2D, and whether recovery of gap junction coupling can recover islet function. We examine islets from donors with T2D, from db/db mice, and islets treated with pro‐inflammatory cytokines (TNF‐α, IL‐1β, IFN‐ɣ) or free fatty acids (palmitate). We modulate gap junction coupling using Cx36 over‐expression or pharmacological activation via modafinil. We also develop a peptide mimetic (S293) of the c‐terminal regulatory site of Cx36 designed to compete against its phosphorylation. Cx36 gap junction permeability and [Ca2+] dynamics were disrupted in islets from both human donors with T2D and db/db mice, and in islets treated with pro‐inflammatory cytokines or palmitate. Cx36 over‐expression, modafinil treatment and S293 peptide all enhanced Cx36 gap junction coupling and protected against declines in coordinated [Ca2+] dynamics. Cx36 over‐expression and S293 peptide also reduced apoptosis induced by pro‐inflammatory cytokines. Critically, S293 peptide rescued gap junction coupling and [Ca2+] dynamics in islets from both db/db mice and a sub‐set of T2D donors. Thus, recovering or enhancing Cx36 gap junction coupling can improve islet function in diabetes.

image

Key points

Connexin‐36 (Cx36) gap junction permeability and associated coordination of [Ca2+] dynamics is diminished in human type 2 diabetes (T2D) and mouse models of T2D.

Enhancing Cx36 gap junction permeability protects against disruptions to the coordination of [Ca2+] dynamics.

A novel peptide mimetic of the Cx36 c‐terminal regulatory region protects against declines in Cx36 gap junction permeability.

Pharmacological elevation in Cx36 or Cx36 peptide mimetic recovers [Ca2+] dynamics and glucose‐stimulated insulin secretion in human T2D and mouse models of T2D.
Numerical Investigation of Reversed Flow Solar Air Heater Roughened With Circular- and Triangular-Shaped Tubes
Authors: Lal Sharma Sohan , Debbarma Ajoy
Published: August 2023

The roughness geometry has been introduced to improve the rate of heat transfer in a solar air heater duct. In the current work, circular and triangular shape geometries are used as roughness elements in the rectangular channel to enhance the thermal performance of reversed flow solar air heater (RFSAH). The important parameters selected for the research are Reynolds number (Re = 5000–18,000 (5 values)), pitch ratio (P/e = 4–12 (5 values)), and height ratio (e/D = 0.0392–0.1571 (4 values)). A 2D-computational fluid dynamics (CFD) model was developed using ansys (fluent 2022r1), and simulation was performed using the k−ε (RNG) turbulence model and validated with one set of experimental results for smooth duct and previous research. The findings revealed that the highest value of heat transfer was augmented about 2.18 times and 2.35 times for circular and triangular roughness geometry, respectively, as compared to the smooth channel at a Reynolds number of 12,000. The thermohydraulic performance factor (TPF) is 1.58 and 1.7 at pitch ratios of 6 and 5 for circular and triangular roughness geometry respectively, at Re of 12,000.
The Growth Engine Concept and Its Potential for an Electrified Aviation Future
Authors: Kavvalos Mavroudis D. , Kyprianidis Konstantinos G. , Padulo Mattia
Published: August 2023

The emerging need for cost- and energy-efficient propulsion systems have shifted the research interest to radical concepts, with several challenges to overcome in order to enter into service. However, revitalizing old yet provably successful engine designs—a practice followed by engine manufacturers over the years—can provide low-risk alternative solutions to move immediate market demands. The paper reviews this approach, known as concept of growth engines or core commonality, and investigates how a geometrically fixed or geometrically similar engine core can be utilized across a family of engines. The development programs of the highly successful CFM56 and PT6 engine families are analyzed, proving the success of this concept over the years. The idea is based on the engineering paradigm of product families and is briefly presented from a theoretical perspective. Implementation methods and simulation tools to initiate, conceptualize, design, and evaluate an engine family program are reviewed. The potential application of engine core commonality into electrified propulsion systems is investigated. Design challenges and opportunities that electrification imposes to the growth engine concept are discussed. Finally, the concept of growth electrified propulsion systems is introduced, conveying future research directions to achieve a successful family of engines for electrified applications.
Use of reverse noise to measure ongoing delay
Authors: Joris Philip X.
Published: August 2023

Counts of spike coincidences provide a powerful means to compare responses to different stimuli or of different neurons, particularly regarding temporal factors. A drawback is that these methods do not provide an absolute measure of latency, i.e., the temporal interval between stimulus features and response. It is desirable to have such a measure within the analysis framework of coincidence counting. Single neuron responses were obtained, from 130 fibers in several tracts (auditory nerve, trapezoid body, lateral lemniscus), to a broadband noise and its polarity-inverted version. The spike trains in response to these stimuli are the “forward noise” responses. The same stimuli were also played time-reversed. The resulting spike trains were then again time-reversed: These are the “reverse-noise” responses. The forward and reverse responses were then analyzed with the coincidence count methods we have introduced earlier. Correlograms between forward- and reverse-noise responses show maxima at values consistent with latencies measured with other methods; the pattern of latencies with characteristic frequency, sound pressure level, and recording location was also consistent. At low characteristic frequencies, correlograms were well-predicted by reverse-correlation functions. We conclude that reverse noise provides an easy and reliable means to estimate latency of auditory nerve and brainstem neurons.
A low-background, fluorescent assay to evaluate inhibitors of diverse viral proteases
Authors: Leonard Rebecca A. , Rao Vishwas N. , Bartlett Alexandria , Froggatt Heather M. , Luftig Micah A. , Heaton Brook E. , Heaton Nicholas S.
Published: August 2023

Multiple coronaviruses (CoVs) can cause respiratory diseases in humans. While prophylactic vaccines designed to prevent infection are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), incomplete vaccine efficacy, vaccine hesitancy, and the threat of other pathogenic CoVs for which vaccines do not exist have highlighted the need for effective antiviral therapies. While antiviral compounds targeting the viral polymerase and protease are already in clinical use, their sensitivity to potential resistance mutations as well as their breadth against the full range of human and preemergent CoVs remain incompletely defined. To begin to fill that gap in knowledge, we report here the development of an improved, noninfectious, cell-based fluorescent assay with high sensitivity and low background that reports on the activity of viral proteases, which are key drug targets. We demonstrate that the assay is compatible with not only the SARS-CoV-2 M
pro
protein but also orthologues from a range of human and nonhuman CoVs as well as clinically reported SARS-CoV-2 drug-resistant M
pro
variants. We then use this assay to define the breadth of activity of two clinically used protease inhibitors, nirmatrelvir and ensitrelvir. Continued use of this assay will help define the strengths and limitations of current therapies and may also facilitate the development of next-generation protease inhibitors that are broadly active against both currently circulating and preemergent CoVs.

IMPORTANCE

Coronaviruses (CoVs) are important human pathogens with the ability to cause global pandemics. Working in concert with vaccines, antivirals specifically limit viral disease in people who are actively infected. Antiviral compounds that target CoV proteases are already in clinical use; their efficacy against variant proteases and preemergent zoonotic CoVs, however, remains incompletely defined. Here, we report an improved, noninfectious, and highly sensitive fluorescent method of defining the sensitivity of CoV proteases to small molecule inhibitors. We use this approach to assay the activity of current antiviral therapies against clinically reported SARS-CoV-2 protease mutants and a panel of highly diverse CoV proteases. Additionally, we show this system is adaptable to other structurally nonrelated viral proteases. In the future, this assay can be used to not only better define the strengths and limitations of current therapies but also help develop new, broadly acting inhibitors that more broadly target viral families.
A single dominant locus restricts retrovirus replication in YBR/Ei mice
Authors: Beilinson Helen A. , Sevilleja Amanda , Spring Jessica , Benavides Fernando , Beilinson Vera , Neokosmidis Nickolas , Golovkina Tatyana
Published: August 2023

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the anti-virus response in susceptible mice. Virus control is unrelated to virus-neutralizing antibodies, cytotoxic CD8
+
T cells, NK cells, and NK T cells, which are the best characterized mechanisms of resistance to retroviruses. We identified a single, dominant locus that controls the resistance mechanism, which we provisionally named attenuation of virus titers (
Avt
) and mapped to the distal region of chromosome 18.

IMPORTANCE

Elucidation of the mechanism that mediates resistance to retroviruses is of fundamental importance to human health, as it will ultimately lead to knowledge of the genetic differences among individuals in susceptibility to microbial infections.
Draft genome sequence of a docosahexaenoic-acid-producing marine protist, thraustochytrid strain 12B
Authors: Sahara Takehiko , Adachi Takumi , Nagamine Tadashi , Fukano Toru , Morita Naoki
Published: August 2023

We sequenced the draft genome of thraustochytrid strain 12B. This strain shows a high production of polyunsaturated fatty acids, such as docosahexaenoic acid. The draft genome sequence of approximately 65 Mbp will provide insights into metabolic engineering to improve the production of polyunsaturated fatty acids in the microorganism.
Absorption of Microwaves During Plasma Heating at the Second Harmonic of Electron Cyclotron Resonance in Tokamaks and Stellarators: Linear Theory and Experiment
Authors: Dnestrovskij Yu. N. , Melnikov A. V. , Andreev V. F. , Lysenko S. E. , Nurgaliev M. R. , Shalashov A. G.
Published: August 2023

We study the microwave absorption during electron cyclotron resonance heating (ECRH) by the extraordinary wave at second harmonic (X2 mode) in the T-10 tokamak and TJ-II stellarator in a wide range of plasma densities, and compare experiments with the classical formulas for the absorption of the injected ECR power. Empirical relations for the absorption efficiency and for the critical plasma density $${{n}_{{{\text{cr}}}}}$$, which separates the regions with full and partial absorption of the injected ECR power, are obtained using the numerical simulation of the heat transport with the transport model of canonical profiles. It is shown that in both devices, the range of densities exists, where the absorption predicted by the classical formulas is almost full, while according with the empirical formula, only a small fraction of the power is absorbed. The obtained relations allow ones to optimize the conditions of ECRH in toroidal systems for magnetic plasma confinement.
Effects of Single Noninvasive Spinal Cord Stimulation in Patients with Post-Stroke Motor Disorders
Authors: Skvortsov D. V. , Bogacheva I. N. , Shcherbakova N. A. , Grishin A. A. , Kaurkin S. N. , Moshonkina T. R. , Gerasimenko Yu. P.
Published: August 2023

Post-stroke gait disorders are often characterized by abnormal kinematic and kinetic patterns, deviations in spatiotemporal features, altered muscle activation, and increased power requirements while walking. The investigation is aimed at determining the possibility of using transcutaneous spinal cord stimulation (TSCS) to influence the kinematics of walking in stroke patients with hemiparesis in the early and late recovery periods (1–12 months) after stroke. Continuous and phasic stimulation was used during motor training on a treadmill. For stimulation of spinal neuroprosthesis including a multichannel stimulator for TSCS (Cosyma, Russia) with sensors for determining the phases of walking was used. The biomechanical study of the walking function was carried out with the Steadys system (Neurosoft, Russia). The study involved 15 patients (ages from 33 to 79 years). We analyzed the parameters of stepping movements when walking on the floor without stimulation before and after training on a treadmill using TSCS. A comparative analysis of the kinematics of walking before and after training showed an increase in walking speed, the length of the step cycle, and an increase in the range of movements in the hip, knee, and ankle joints, in 40% patients the height of the paretic foot lift increased by 1–2 cm. The results show that the training with the use of TSCS can be considered as a rehabilitation method for correcting walking after a stroke.
Continuous interstitial glucose monitoring for term newborns: analysis of the first day of life
Authors: Azevedo Nathália , Liberatore Junior Raphael Del Roio , Camelo Junior José Simon , Aragon Davi Casale , Martinelli Junior Carlos Eduardo
Published: August 2023

Objective

Glycaemia in newborns changes significantly after birth; however, little is known about these changes. The objective was to describe continuous interstitial glucose values in term newborns who were exclusively breast fed on the first day of life.

Design

We studied 159 newborns with appropriate weights for gestational age, who were exclusively breast fed on the first day of life, using a continuous glucose monitoring device that calculates interstitial glucose every 5 min. The device was removed after 24 hours, and the results were analysed using the R program, which provides the minimum, maximum, median and a standard curve with centiles.

Results

At the second hour of life, the moment in which the sensor started to identify the newborn’s glycaemia, interstitial glucose levels were 2.59–4.43 mmol/L (46.7–79.9 mg/dL). The median interstitial glucose level of the newborns during the first day of life was 3.33±0.48 mmol/L (60±8.6 mg/dL). Interstitial glucose levels dropped until the sixth hour of life, reaching 2.19–3.95 mmol/L (39.5–71.1 mg/dL), and then increased again. The maximum values were found at the 20th and 21st hours of life, which were 2.81–4.64 mmol/L (50.6–83.6 mg/dL).

Conclusion

The interstitial glucose during the first 24 hours of life declined until the sixth hour of life, then increased around the 20th hour and remained stable until the end of the first day of life.
Rare but life-threatening cause of massive haemoptysis in an adolscent with tuberculosis: Rasmussen's aneurysm
Authors: Yu Michelle Wai Ling , Li Albert M , Lai Ming Hei , Chan Kate Ching Ching
Published: August 2023

Rasmussen’s aneurysm is a rare yet fatal cause of massive haemoptysis in pulmonary tuberculosis. Early identification and timely intervention are of utmost importance to reduce the associated mortality. A girl in early adolescence presented with persistent fever and massive haemoptysis who required intubation and was subsequently confirmed to have tuberculosis. CT pulmonary angiogram showed the presence of pseudoaneurysms in the left upper and lower lobes. The haemoptysis resolved following the embolisation of the culprit’s vessel. Residual lung destruction was evident on CT after a 12-month course of antituberculosis therapy. Rasmussen’s aneurysm is a significant vascular complication of cavitary tuberculosis and needs to be considered in patients presenting with massive haemoptysis.
Evaluating primary care networks in low-income and lower middle-income countries: a scoping review
Authors: Agyemang-Benneh Adwoa , Francetic Igor , Hammond Jonathan , Checkland Katherine
Published: August 2023

Introduction

Primary care networks (PCNs) are claimed to be an effective model to organise and deliver primary healthcare through collaborative relationships and effective coordination of primary care activities. Though increasingly implemented in different contexts, there is limited evidence on the effectiveness of PCNs in low-income and lower middle-income countries (LLMICs).

Objective

Our scoping review aims to understand how PCNs in LLMICs have been conceptualised, implemented and analysed in the literature and further explores the evidence of the effectiveness of these networks.

Methods

We structured our review using Arksey and O’Malley’s framework for scoping reviews and recommendations by Levacet al. We also used the population, concept and context (PCC) guide of the Joanna Briggs Institute (JBI) methodology for scoping reviews to define the search strategy. The identified documents were then mapped, using Cunningham’s evaluation framework for health networks, to understand how PCNs are conceived in LLMIC settings.

Results

We identified 20 documents describing PCNs in five LLMICs. The selected documents showed differing forms and complexities of networks, with a majority resourced by government, non-governmental and donor entities. Most networks were mandated, and established with defined goals, although these were not always understood by stakeholders. Unlike PCNs in developed settings, the scoping review did not identify integration of care as a major goal for the establishment of PCNs in LLMICs. Network evaluation relationships, outputs and outcomes also varied across the five networks in the identified documents, and perceptions of effectiveness differed across stakeholder groups.

Conclusion

PCNs in LLMICs benefit from clearly stated goals and measurable outcomes, which facilitates evaluation. In order to maximise the benefits, careful attention to the aspects of network design and operation is required. Future research work could shed light on some of the missing pieces of evidence on their effectiveness by, for example, considering differential consequences of modes of network establishment and operation, including unintended consequences in the systems within which they reside, and evaluating long-term implications.
Multivariate analysis of refractive state in eyes with keratoconus
Authors: Chetty Elizabeth
Published: August 2023

Objective

To demonstrate a multivariate method of analysis of the short-term variation of refractive state in keratoconus (KC) patients.

Methods and analysis

In this observational study, 19 eyes with KC and 19 healthy control eyes were measured. The study included both male and female participants and the mean age was 23.6 years (range 18–34 years) and 23.2 years (range 22–26 years) for KC and control participants, respectively. Forty consecutive autorefractor measurements were taken for each participant and the short-term variation thereof was analysed using multivariate methods of analysis.

Results and conclusion

Short-term variation of refractive state is greater in eyes with KC than in healthy control eyes and variation increases with severity of disease. A novel finding was that there was much more ortho-astigmatic and oblique-astigmatic variation seen in KC eyes than in control eyes which had predominately stigmatic variation. Refractive state is described by three components, namely, sphere, cylinder and axis. Although it is multivariate in nature, it is often analysed using univariate statistical methods. In diseases such as KC, where early diagnosis is crucial for a good prognosis, it is necessary that researchers endeavour to investigate the disease from different perspectives to fully understand the nature of the disease. This paper comprehensively demonstrates the multivariate statistical methods of analysis of refractive data. The implementation of this analysis provides insight into the short-term variation of refractive data in healthy and keratoconic eyes, and these findings have not been demonstrated before using univariate statistics.
Effect of a targeted quality improvement education on opioid prescribing
Authors: Kaley Amanda , Brenner Jay M , Prince Anna M , Wojcik Susan M
Published: August 2023

Background

The opioid epidemic is a serious social, economic and public health problem. This study was designed to evaluate the effectiveness of individual institutional opioid prescriber training on prescriber adherence to the Centers for Disease Control and Prevention (CDC’s) guidelines for responsible opioid prescribing practices to treat acute pain.

Methods

Opioid prescribing data were collected from an academic medical centre and its associated outpatient clinics. A baseline for opioid prescribing practices was collected for 2 years and 2 months prior to the planned intervention. Departments responsible for 5% or more of the total institutional opioid prescriptions were chosen to study in detail. A number of opioid prescriptions per department per day and their compliance with the maximum daily dose (MDD) recommendations put out by the CDC were determined.

Intervention

The hospital administration implemented a mandatory opioid prescriber training as part of their standard annual provider education for all medical staff, who were all required to attest having read it and pass a quiz by 30 September 2019, which was chosen as the end date for the pre-intervention data. Data were analysed preintervention and postintervention to assess the effect of this intervention on opioid prescribing.

Results

Overall opioid prescribing rates decreased by 18.3% and there were significant decreases in opioid prescribing rate in five out of the seven departments/divisions. Overall, there was a statistically significant decrease in the compliance with MDD before (71.3%) and after (67.3%) the intervention (4%, 95% CI 3.13% to 4.87% difference, p<0.001). Additionally, there were statistically significant increases in compliance with CDC guidelines in three departments/divisions. However, there was a statistically significant decrease in compliance with CDC guidelines after intervention in two departments.

Conclusions

The results of this study were largely encouraging for the effectiveness of this institutional mandatory prescriber training.
T-cell tolerant fraction as a predictor of immune-related adverse events
Authors: Ostmeyer Jared , Park Jason Y , von Itzstein Mitchell S , Hsiehchen David , Fattah Farjana , Gwin Mary , Catalan Rodrigo , Khan Shaheen , Raj Prithvi , Wakeland Edward K , Xie Yang , Gerber David E
Published: August 2023

Background

Immune checkpoint inhibitor (ICI) therapies may cause unpredictable and potentially severe autoimmune toxicities termed immune-related adverse events (irAEs). Because T cells mediate ICI effects, T cell profiling may provide insight into the risk of irAEs. Here we evaluate a novel metric—the T-cell tolerant fraction—as a predictor of future irAEs.

Methods

We examined T-cell receptor beta (TRB) locus sequencing from baseline pretreatment samples from an institutional registry and previously published studies. For each patient, we used TRB sequences to calculate the T-cell tolerant fraction, which was then assessed as a predictor of future irAEs (classified as Common Terminology Criteria for Adverse Event grade 0–1 vs grade ≥2). We then compared the tolerant fraction to TRB clonality and diversity. Finally, the tolerant fraction was assessed on (1) T cells enriched against napsin A, a potential autoantigen of irAEs; (2) thymic versus peripheral blood T cells; and (3) TRBs specific for various infections and autoimmune diseases.

Results

A total of 77 patients with cancer (22 from an institutional registry and 55 from published studies) receiving ICI therapy (43 CTLA4, 19 PD1/PDL1, 15 combination CTLA4+PD1/PDL1) were included in the study. The tolerant fraction was significantly lower in cases with clinically significant irAEs (p<0.001) and had an area under the receiver operating curve (AUC) of 0.79. The tolerant fraction was lower for each ICI treatment category, reaching statistical significance for CTLA4 (p<0.001) and demonstrating non-significant trends for PD1/PDL1 (p=0.21) and combination ICI (p=0.18). The tolerant fraction for T cells enriched against napsin A was lower than other samples. The tolerant fraction was also lower in thymic versus peripheral blood samples, and lower in some (multiple sclerosis) but not other (type 1 diabetes) autoimmune diseases. In our study cohort, TRB clonality had an AUC of 0.62, and TRB diversity had an AUC of 0.60 for predicting irAEs.

Conclusions

Among patients receiving ICI, the baseline T-cell tolerant fraction may serve as a predictor of clinically significant irAEs.
Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients withZNF148mutations
Authors: Szakszon Katalin , Lourenco Charles Marques , Callewaert Bert Louis , Geneviève David , Rouxel Flavien , Morin Denis , Denommé-Pichon Anne-Sophie , Vitobello Antonio , Patterson Wesley G , Louie Raymond , Pinto e Vairo Filippo , Klee Eric , Kaiwar Charu , Gavrilova Ralitza H , Agre Katherine E , Jacquemont Sebastien , Khadijé Jizi , Giltay Jacques , van Gassen Koen , Merő Gabriella , Gerkes Erica , Van Bon Bregje W , Rinne Tuula , Pfundt Rolph , Brunner Han G , Caluseriu Oana , Grasshoff Ute , Kehrer Martin , Haack Tobias B , Khelifa Melik Malek , Bergmann Anke Katharina , Cueto-González Anna Maria , Martorell Ariadna Campos , Ramachandrappa Shwetha , Sawyer Lindsey B , Fasel Pascale , Braun Dominique , Isis Atallah , Superti-Furga Andrea , McNiven Vanda , Chitayat David , Ahmed Syed Anas , Brennenstuhl Heiko , Schwaibolf Eva MC , Battisti Gladys , Parmentier Benoit , Stevens Servi J C
Published: August 2023

Background

Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in theZNF148gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far.

Methods

As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals.

Results

The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of theZNF148gene. Heterozygous deletion including the entireZNF148gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families.

Conclusion

The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term ‘GDACCF syndrome’ with ‘ZNF148-related neurodevelopmental disorder’.
Swelling damage evolution of argillaceous slate in a water-rich environment
Authors: Zuo Qingjun , Li Pan , Li Xinyi , Chen Fubang
Published: August 2023

The swelling of rock is a key issue in engineering. With large infrastructure construction trending towards complex geological conditions, an increasing number of projects could suffer from soft-rock swelling. To solve this problem, an understanding of the evolution of damage occurring during the swelling process is essential. Argillaceous slate is a typical metamorphic rock and shows strong swelling characteristics in a water-rich environment due to its abundance of hydrophilic minerals. In this paper, argillaceous slate was selected as the research object. The evolution of damage in argillaceous slate during swelling was explored via laboratory tests that included swelling characteristic tests, soft-rock needle penetration tests and scanning electron microscope tests, and damage theory. The research findings reveal that the slate swelling process in a water-rich environment can be divided into three stages, with the swelling rate being highest in the early stage of the tests, then slowing over time and finally stabilizing. However, the strength of the argillaceous slate decreased rapidly in the early stage, and the degradation rate was generally slow in the later stage. After water absorption, the clay mineral particles begin to expand and the microscopic structure of the argillaceous slate becomes complicated, with the pore area increasing and the pore diameter decreasing. A low degree of microscopic damage was found to induce a high degree of macroscopic mechanical degradation. In addition, the damage mechanism that occurs during argillaceous slate swelling is discussed in this paper from both a microscopic and a macroscopic perspective. Indeed, a relationship between macroscopic mechanical degradation and microscopic damage to argillaceous slate was established that can provide theoretical support for further research on soft-rock swelling characteristics: the microscopic damage drives the macroscopic mechanical degradation.
Collocated Clothing Synthesis with GANs Aided by Textual Information: A Multi-Modal Framework
Authors: Liu Linlin , Zhang Haijun , Li Qun , Ma Jianghong , Zhang Zhao
Published: August 2023

Synthesizing realistic images of fashion items which are compatible with given clothing images, as well as conditioning on multiple modalities, brings novel and exciting applications together with enormous economic potential. In this work, we propose a multi-modal collocation framework based on generative adversarial network (GAN) for synthesizing compatible clothing images. Given an input clothing item that consists of an image and a text description, our model works on synthesizing a clothing image which is compatible with the input clothing, as well as being guided by a given text description from the target domain. Specifically, a generator aims to synthesize realistic and collocated clothing images relying on image- and text-based latent representations learned from the source domain. An auxiliary text representation from the target domain is added for supervising the generation results. In addition, a multi-discriminator framework is carried out to determine compatibility between the generated clothing images and the input clothing images, as well as visual-semantic matching between the generated clothing images and the targeted textual information. Extensive quantitative and qualitative results demonstrate that our model substantially outperforms state-of-the-art methods in terms of authenticity, diversity, and visual-semantic similarity between image and text.