bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and clinical descriptions of patients with GABAA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype–phenotype correlation
Authors: Maillard Pierre‐Yves , Baer Sarah , Schaefer Élise , Desnous Béatrice , Villeneuve Nathalie , Lépine Anne , Fabre Alexandre , Lacoste Caroline , El Chehadeh Salima , Piton Amélie , Porter Louise Frances , Perriard Caroline , Wardé Marie‐Thérèse Abi , Spitz Marie‐Aude , Laugel Vincent , Lesca Gaëtan , Putoux Audrey , Ville Dorothée , Mignot Cyril , Héron Delphine , Nabbout Rima , Barcia Giulia , Rio Marlène , Roubertie Agathe , Meyer Pierre , Paquis‐Flucklinger Véronique , Patat Olivier , Lefranc Jérémie , Gerard Marion ,   Epigen Consortium, de Bellescize Julietta , Villard Laurent , De Saint Martin Anne , Milh Mathieu
Published: June 2022

Objective

γ‐Aminobutyric acid (GABA)A‐receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABAA‐receptor–related disorders as a whole and seek possible genotype–phenotype correlations.

Methods

We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAA‐receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using the EPIGENE network and compared these data to the one already described in the literature.

Results

We gathered the reported patients in three epileptic phenotypes: 15 patients with fever‐related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA‐receptor subunit gene, whereas N‐terminal variants seemed to be related to milder phenotypes.

Significance

GABAA‐receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.
Trading rule of law for recovery? The new EU strategy in the post‐Covid era
Authors: Fromont Louise , Van Waeyenberge Arnaud
Published: June 2022

The ambition of this article is twofold. First, it argues that, in order to enhance respect for the rule of law by its Member States, the EU has launched a new strategy albeit essentially based on mechanisms which were not specifically designed to protect the rule of law. Second, the article aims to clarify the notion of rule of law resulting from this strategy and to subsequently analyse its consequences. In doing so, this article will thereby demonstrate that the instruments used by the new strategy promote a notion of the EU rule of law which implies a constant arbitrage between the rule of law and the economic objectives pursued by the EU. The risk may be, however, that it would subjugate fundamental values (as defined in Article 2 TEU) to the logic of European economic integration, thus inverting the hierarchy between protection for the rule of law and economic values.
Macro‐meso fatigue damage and instability of a fault bimrock exposed to multistage cyclic triaxial loads with different confining pressure
Authors: Wang Yu , Mao Tianqiao , Zhang Bo , Xia Yingjie , Yi Xuefeng
Published: June 2022

A series of cyclic triaxial tests combined with post‐test CT scanning were performed on a fault bimrock (block‐in‐matrix‐rock). The influence of confining pressure on the macro‐meso fatigue damage and instability characteristics were investigated in terms of strength, stiffness, volumetric deformation, damage evolution, and mesoscopic failure pattern. It is revealed that bimrock strength, deformation, and stiffness increase with increasing of confining pressure. A larger confining pressure leads to a lower rate of axial and volumetric strain. An early instability precursor corresponding to the strong volumetric dilatancy was issued using the strain rate than the volumetric strain. An inverted “L” and “S” shaped damage evolution pattern were revealed and modelled, and the proposed model fits well to the testing data. Post‐test 3D computed tomography scanning visualizes the multiple interface cracking behaviors and volumetric change. It is suggested that the skeleton role of blocks was strengthened and the block‐matrix interactions were influenced by the applied confining pressure.
Microbiome assembly in thawing permafrost and its feedbacks to climate
Authors: Ernakovich Jessica G. , Barbato Robyn A. , Rich Virginia I. , Schädel Christina , Hewitt Rebecca E. , Doherty Stacey J. , Whalen Emily D. , Abbott Benjamin W. , Barta Jiri , Biasi Christina , Chabot Chris L. , Hultman Jenni , Knoblauch Christian , Vetter Maggie C. Y. Lau , Leewis Mary‐Cathrine , Liebner Susanne , Mackelprang Rachel , Onstott Tullis C. , Richter Andreas , Schütte Ursel M. E. , Siljanen Henri M. P. , Taş Neslihan , Timling Ina , Vishnivetskaya Tatiana A. , Waldrop Mark P. , Winkel Matthias
Published: June 2022

The physical and chemical changes that accompany permafrost thaw directly influence the microbial communities that mediate the decomposition of formerly frozen organic matter, leading to uncertainty in permafrost–climate feedbacks. Although changes to microbial metabolism and community structure are documented following thaw, the generality of post‐thaw assembly patterns across permafrost soils of the world remains uncertain, limiting our ability to predict biogeochemistry and microbial community responses to climate change. Based on our review of the Arctic microbiome, permafrost microbiology, and community ecology, we propose that Assembly Theory provides a framework to better understand thaw‐mediated microbiome changes and the implications for community function and climate feedbacks. This framework posits that the prevalence of deterministic or stochastic processes indicates whether the community is well‐suited to thrive in changing environmental conditions. We predict that on a short timescale and following high‐disturbance thaw (e.g., thermokarst), stochasticity dominates post‐thaw microbiome assembly, suggesting that functional predictions will be aided by detailed information about the microbiome. At a longer timescale and lower‐intensity disturbance (e.g., active layer deepening), deterministic processes likely dominate, making environmental parameters sufficient for predicting function. We propose that the contribution of stochastic and deterministic processes to post‐thaw microbiome assembly depends on the characteristics of the thaw disturbance, as well as characteristics of the microbial community, such as the ecological and phylogenetic breadth of functional guilds, their functional redundancy, and biotic interactions. These propagate across space and time, potentially providing a means for predicting the microbial forcing of greenhouse gas feedbacks to global climate change.
Focus groups revealed how community health workers in North Carolina find, verify, and process health information for migrant and seasonal farmworkers
Authors: LePrevost Catherine E. , Cofie Leslie E. , Bloss Jamie E. , Lee Joseph G. L.
Published: June 2022

Background

Community health workers (CHWs) bridge the gap in health and social services delivery for marginalized communities, providing critical health information to those with limited access to health resources.

Objectives

The purpose of our study was to understand CHWs' approaches to identifying salient and credible health information for migrant and seasonal farmworkers in rural North Carolina (NC).

Methods

Two focus group discussions were held with CHWs in eastern NC and one in western NC in February 2020.

Results

CHWs seek health information on chronic health conditions disproportionately experienced by farmworkers such as diabetes and high blood pressure. They search for information from existing resources in their possession, via the internet, and through consultation with health professionals. CHWs also verify the information and transform the content into resources that are accessible to farmworkers.

Discussion

Our findings suggest that CHWs possess a strong set of information literacy skills that could be enhanced through additional training in crediting sources, creating new materials, and organization and storage.

Conclusion

This study adds to the very limited body of knowledge about how CHWs seek and transmit information to their communities and sheds light on their information need and literacy abilities.
Physicochemical parameters, volatile compounds and organoleptic properties of bread prepared with substituted sucrose with rare sugar D‐allulose
Authors: Sawettanun Saranta , Ogawa Masahiro
Published: June 2022

D‐Allulose (Alu), a very low‐calorie monosaccharide with several disease‐preventing effects, is expected to be used as a substitute for sucrose (Suc) in bakery products. This study assessed the physical, chemical and sensory characteristics of bread in which 25%, 50%, 75% and 100% of Suc was replaced by Alu. The replacement of up to 75% of Suc by Alu did not affect bread appearance: loaf height, volume and colour texture properties. Bread in which up to 75% of Suc was replaced by Alu had similar hardness values to 100% Suc bread. GC–MS analyses of the head space of the bread identified 25 volatile compounds (7 alcohols, 8 ketones, 8 aldehydes and 2 other compounds) in the Alu‐substituted bread. Bread with the higher ratio of Alu substitution had stronger roasted and caramel‐like odours and lighter fermented and alcoholic odours. Hedonic sensory results suggested that 100% Alu‐substituted bread had a lower score in a preference test, while up to 75% Alu‐substituted bread was equivalent to bread using traditional sugar, Suc.
Exit regime for international students: The case of Georgia
Authors: Krannich Sascha , Hunger Uwe
Published: June 2022

In this paper, we focus on an exit regime for an important and fast rising, but still under‐researched form of migration: student migration. More and more countries in the Global South—which suffered large emigration numbers of students to the Global North in the past—have started to establish their own exit regimes to regulate student emigration in their own interests. How do these exit regimes for students studying abroad operate? And are they actually successful in regulating student migration in the interest of the emigration state? Here, we take a closer look at the exit regime of the Caucasian state of Georgia. Drawing on Krasner's regime theory and on a larger empirical study, we identified a sophisticated exit regime of the Georgian state that operates on the basis of various scholarship programmes for Georgian students who study abroad and who have to return to Georgia after graduation.
Voluntary assisted dying: peak bodies must provide practical guidance
Authors: Close Eliana , Willmott Lindy , White Ben P.
Published: June 2022

Despite widespread reform in Australia, the Australian Medical Association (AMA) remains ethically opposed to voluntary assisted dying (VAD). This article argues that the AMA should abandon its opposition to VAD to fulfil better its mandate of providing the best outcomes for doctors, patients and the community. A neutral stance enables peak bodies to engage more fully in implementation and support diverse perspectives.
Unusual presentations of central nervous system myeloid sarcoma
Authors: Chatterton Sophie , Helou Jacob , Drummond James , Gill Anthony J. , Ward Christopher , Coyle Luke , Kerridge Ian , Ng Karl
Published: June 2022

Myeloid sarcoma (MS), also termed ‘chloroma’ or ‘granulocytic sarcoma’, is a tumour mass consisting of myeloid blasts occurring at an anatomical site other than the bone marrow. MS occurs in up to 8% of patients with acute myeloid leukaemia. While MS typically involves the skin or lymph nodes, almost any tissue can be affected, and symptoms largely depend on the organ involved and subsequent mass effect. We present a case series of patients that presented to a tertiary hospital with MS affecting the central nervous system over a 4‐month period. These three cases demonstrate the vast spectrum of clinical presentations of MS and, furthermore, show rare examples of intramedullary spinal cord involvement and disseminated intraparenchymal brain disease.
Update on the current knowledge of lymphatic drainage system and its emerging roles in glioma management
Authors: Lan Yu‐Long , Wang Hongjin , Chen Aiqin , Zhang Jianmin
Published: June 2022

The draining of brain interstitial fluid (ISF) to cerebrospinal fluid (CSF) and the subsequent draining of CSF to meningeal lymphatics is well‐known. Nonetheless, its role in the development of glioma is a remarkable finding that has to be extensively understood. The glymphatic system (GS) collects CSF from the subarachnoid space and brain ISF through aquaporin‐4 (AQP4) water channels. The glial limiting membrane and the perivascular astrocyte‐end‐feet membrane both have elevated levels of AQP4. CSF is thought to drain through the nerve sheaths of the olfactory and other cranial nerves as well as spinal meningeal lymphatics via dorsal or basal lymphatic vessels. Meningeal lymphatic vessels (MLVs) exist below the skull in the dorsal and basal regions. In this view, MLVs offer a pathway to drain macromolecules and traffic immunological cells from the CNS into cervical lymph nodes (CLNs), and thus can be used as a candidate curing strategy against glioma and other associated complications, such as neuro‐inflammation. Taken together, the lymphatic drainage system could provide a route or approach for drug targeting of glioma and other neurological conditions. Nevertheless, its pathophysiological role in glioma remains elusive, which needs extensive research. The current review aims to explore the lymphatic drainage system, its role in glioma progression, and possible therapeutic techniques that target MLVs in the CNS.
Syringic acid mitigates isoproterenol‐induced cardiac hypertrophy and fibrosis by downregulating Ereg
Authors: Han Xiongyi , Bai Liyan , Kee Hae Jin , Jeong Myung Ho
Published: June 2022

Gallic acid has been reported to mitigate cardiac hypertrophy, fibrosis and arterial hypertension. The effects of syringic acid, a derivative of gallic acid, on cardiac hypertrophy and fibrosis have not been previously investigated. This study aimed to examine the effects of syringic acid on isoproterenol‐treated mice and cells. Syringic acid mitigated the isoproterenol‐induced upregulation of heart weight to bodyweight ratio, pathological cardiac remodelling and fibrosis in mice. Picrosirius red staining, quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting analyses revealed that syringic acid markedly downregulated collagen accumulation and fibrosis‐related factors, including Fn1. The results of RNA sequencing analysis of Ereg expression were verified using qRT‐PCR. Syringic acid or transfection with si‐Ereg mitigated the isoproterenol‐induced upregulation of Ereg, Myc and Ngfr. Ereg knockdown mitigated the isoproterenol‐induced upregulation of Nppb and Fn1 and enhancement of cell size. Mechanistically, syringic acid alleviated cardiac hypertrophy and fibrosis by downregulating Ereg. These results suggest that syringic acid is a potential therapeutic agent for cardiac hypertrophy and fibrosis.
Analysis of the problems of drug sampling and testing programme under tripartite system reform in China
Authors: Li Shiqi , Sun Lihua
Published: June 2022

Rationale

To ensure that quality medicines are available to the populace.

Aim and Objective

To provide a new perspective for drug sampling and testing using a risk‐based approach globally, and provide a reference for improving the efficiency of the drug sampling and testing programme in China.

Method

This study used a combination of theoretical analysis and problem analysis. First, we analysed the high‐risk drugs that should be given attention to theoretically in the drug sampling testing programme based on the healthcare reform in China. Second, this study leveraged on data on the sampling and testing of drugs extracted from self‐constructed data by the China Food and Drug Administration (CFDA). The integrated and structured data sets were used to conduct an innovative analysis that identifies the actual content of the drug sampling and testing programme and contrasts them with the theoretical content to understand the problems. This study used quantitative and qualitative approaches for data analysis.

Results

Following analysis, we discovered that there is still a big gap between the reality of drug sampling and testing in China and the ideal state of the objective requirements of healthcare reforms. The major sources of risk are the retail pharmacies or hospital pharmacies in the distribution chain of drugs; however, the CFDA sampled mostly drugs from drug manufacturers. Additionally, the CFDA did not sample adequate essential medicines, bid‐winning drugs (especially those with large price drops in centralized procurement), biological products and other high‐risk drug varieties. The high‐risk drugs produced by companies or enterprises with a history of noncompliance, especially bid‐winning enterprises in centralized procurement, were not sampled.

Conclusion

We suggest that the major content of drug sampling and testing in China should focus on the link of drug utilization, varieties of drugs with large price drops in centralized procurement and bid‐winning enterprises with a history of noncompliance.
Integrated thermal and routing analysis applied for cold supply chain
Authors: Bezerra Luíza Moreira , Silva Vanina Macowski Durski , da Silva Diogo Lôndero
Published: June 2022

A challenge in the distribution of cold chain products is ensuring product quality while minimizing the process costs. This study proposes an integrated method to analyze the route generation and its impact on the temperature variation of refrigerated loads during their physical distribution. Hence, two heuristic methods for route generation are compared (Clarke and Wright and the Nearest Neighbor). Therefore, a simulation tool is proposed for planning routes for the physical distribution of refrigerated products, making the entire logistics process more efficient, reducing the unwanted gain of internal temperature of the vehicle and the product, considering the time windows available, number of vehicles and its available capacity. Five scenarios in total were compared and, as a result, the Clarke and Wright method with temperature restriction proved to be more effective for routing within the imposed temperature limits and aiming at savings of 20% in the number of vehicles and 7% in the distance traveled.

Practical applications

The proposed model can be used as a tool for the route planners of cold chain products who can choose a shorter route or a route that guarantees the maintenance of the desired temperature, without harming transported products. It can contribute to the quality of the products of cold chain.
Use of physical restraints and its associated risk factors in the aged care facilities: A multicentre cross‐sectional study
Authors: Pu Haixu , Zhang Xiaoqin , Luo Liangchu , Yu Qian , Feng Xiaolin , Yan Lichun , Zhang Yinhua
Published: June 2022

Aims and Objectives

To investigate the use of physical restraints in aged care facilities(ACFs)and analyse its associated risk factors.

Background

Physical restraints have been widely used in ACFs worldwide, but they can cause physical and mental harm to older people. It is important to regulate the use of physical restraint.

Design

A cross‐sectional observational and correlational multicentre study.

Methods

By convenience sampling method, we selected eight ACFs in four representative regions of Hunan province, China, for this study. The ACF‐related information was obtained by interviewing the managers and reviewing records. We conducted investigation and observation on the elderly in the ACFs to understand the use of physical restraints at three different times: 9:30–11:30, 16:00–18:00 and 19:30–21:30 on a working day. The STROBE checklist was followed for this cross‐sectional study.

Results

This study found that the utilisation rate of physical restraints was 23.2%. The critical risk factors affecting the use of physical restrains include the following: (1) the ratio of nursing staff to the elderly residents; (2)whether there is a dementia care unit at the facility; (3) the number of elderly residents in each room; (4) the elderly residents' age, degree of education, marital status, care dependence and cognitive impairment; (5) whether the elderly has suffered from a stroke or senile dementia; (6) whether the elderly carries medical catheters.

Conclusion

There is a lack of standardisation in the use of physical restraints in ACFs of central China. Chinese ACFs should develop guidelines and reduction measures to standardise the use of physical restraints, basing on the key factors affecting the use of physical restraints.

Relevance to clinical practice

The use of physical restraints in ACFs is threatening the safety of the elderly residents. Understanding the implementation of physical restraint in ACFs can provide reference for reducing the use of physical restraint.
Impact of oral motor task training on corticomotor pathways and diadochokinetic rates in young healthy participants
Authors: Boscato Noéli , Hayakawa Hidetoshi , Iida Takashi , Costa Yuri M. , Kothari Simple Futarmal , Kothari Mohit , Svensson Peter
Published: June 2022

Background

Studies addressing the training‐induced neuroplasticity and interrelationships of the lip, masseter, and tongue motor representations in the human motor cortex using single syllable repetition are lacking.

Objective

This study investigated the impact of a repeated training in a novel PaTaKa diadochokinetic (DDK) orofacial motor task (OMT) on corticomotor control of the lips, masseter, and tongue muscles in young healthy participants.

Methods

A total of 22 young healthy volunteers performed 3 consecutive days of training in an OMT. Transcranial magnetic stimulation was applied to elicit motor evoked potentials (MEPs) from the lip, masseter, tongue, and first dorsal interosseous (FDI, internal control) muscles. MEPs were assessed by stimulus–response curves and corticomotor mapping at baseline and after OMT. The DDK rate from PaTaKa single syllable repetition and numeric rating scale (NRS) scores were also obtained at baseline and immediately after each OMT. Repeated‐measures analysis of variance was used to detect differences at a significance level of 5%.

Results

There was a significant effect of OMT and stimulus intensity on the lips, masseter, and tongue MEPs compared to baseline (p < .001), but not FDI MEPs (p > .05). OMT increased corticomotor topographic maps area (p < .001), and DDK rates (p < .01).

Conclusion

Our findings suggest that 3 consecutive days of a repeated PaTaKa training in an OMT can induce neuroplastic changes in the corticomotor pathways of orofacial muscles, and it may be related to mechanisms underlying the improvement of orofacial fine motor skills due to short‐term training. The clinical utility should now be investigated.
Effect of non‐starch polysaccharide enzyme supplementation with gradually reduced energy diet on growth performance, nutrient digestibility, lean meat percentage and backfat thickness of growing pigs
Authors: Hoque Md Raihanul , Kim In Ho
Published: June 2022

This study was conducted with the objective of evaluating a way to reduce feed costs with better meat characteristics for growing pigs by supplementing non‐starch polysaccharide enzyme (NSPE) in energy reduced diets. A total of 200 growing pigs [(Landrace × Yorkshire) × Duroc] weighing 22.94 ± 0.22 kg were divided into five dietary treatments, each with eight replication pens (three barrows and two gilts). The pigs were allotted in a completely randomised block design according to body weight and sex. The dietary treatments were: CON (control), basal diet (NE 2500 kcal); NSPE1, basal diet + 0.04% NSPE; NSPE2, (basal diet—20 kcal) + 0.04% NSPE; NSPE3, (basal diet—30 kcal) + 0.04% NSPE; NSPE4, (basal diet—50 kcal) + 0.04% NSPE. We have assessed growth performance, lean meat percentage (LMP) and backfat thickness at initial, Week 4 and 8. Apparent nutrient digestibility was assessed in Weeks 4 and 8. There was no significant difference (p > 0.05) among the groups on growth performance. In Week 8, gradual reduction of energy caused a linear reduction (p = 0.028) of backfat thickness and a linear increase (p < 0.05) of LMP. In addition, at Week 8, supplementation of NSPE enzyme showed improved digestibility of nitrogen (p < 0.05) and energy (p < 0.05) in the NSPE1 group than in the CON group. In short, gradual reduction of dietary energy supplemented with NSPE showed consistent growth performance through higher nutrient digestibility with positive changes in backfat thickness and LMP of growing pigs.
Extrahepatic carcinogenicity of oral nucleos(t)ide analogues in chronic hepatitis B carriers: A 35,000‐Korean outcome study
Authors: Lim Jihye , Lee Jung‐Bok , An Jihyun , Song Gi‐Won , Kim Kang Mo , Lee Han Chu , Shim Ju Hyun
Published: June 2022

Evidence on the carcinogenicity of oral nucleos(t)ide analogues (NAs) is inconclusive and lacks data on the effects by chemical structure of the NAs in patients with chronic hepatitis B (CHB). We aimed to provide definitive results on this issue using a large set of CHB patients and data on all major NA drugs. The study population consisted of 10,331 patients with CHB receiving primary NA treatment for more than 6 months, and 24,836 untreated controls followed for at least as long as the treated patients. Using the inverse‐probability‐of‐treatment‐weighted (IPTW) method, the cumulative incidence of extrahepatic cancers was compared in the treated and untreated patients and across the cyclopentane, L‐nucleoside and acyclic phosphonate categories of NAs. Analyses of individual cancers as sub‐endpoints were also performed. The cumulative incidence of overall extrahepatic malignancies did not differ between the two groups in the IPTW cohort (hazard ratio [HR] 1.002; 95% confidence interval [CI] [0.859–1.169]). Similar statistical trends were observed in analyses across the three NA chemical subsets and controls. Per‐cancer analyses indicated that NA treatment was significantly associated with increased risks of colorectal/anal cancers (HRs [95% CI], 1.538 [1.175–2.013]) and lymphoma (1.784 [1.196–2.662]). Conversely, breast cancer (HRs [95% CI], 0.669 [0.462–0.967]) and prostate cancer (0.521 [0.329–0.825]) were less prevalent in the NA‐treated group. In conclusion, prolonged NA treatment presents carcinogenic risks for colorectal/anal and lymphoid tissues in CHB patients, although it does not affect most extrahepatic organs. The protective effect of NAs on breast and prostate cancers should be confirmed.
Real‐world study on HBsAg loss of combination therapy in HBeAg‐negative chronic hepatitis B patients
Authors: Chu Jun‐Hao , Huang Yan , Xie Dong‐Ying , Deng Hong , Wei Jia , Guan Yu‐Juan , Li Guo‐Jun , Zeng Yi‐Lan , Yang Jia‐Hong , Chen Xin‐Yue , Shang Jia , Li Jia‐Bin , Gao Na , Gao Zhi‐Liang
Published: June 2022

Combination therapy with pegylated interferon (PEG‐IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add‐on PEG‐IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real‐world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)‐negative NAs‐treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add‐on PEG‐IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south‐central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.
Testing the niche variation hypothesis in pinnipeds
Authors: Franco‐Trecu Valentina , Botta Silvina , de Lima Renan C. , Negrete Javier , Naya Daniel E.
Published: June 2022

Individual trophic specialisation (ITS) has many important consequences for ecological and evolutionary processes. An old hypothesis highlighting the relevance of ITS is the niche variation hypothesis (NVH), which proposes that populations composed of trophically specialised individuals have a wider population niche than populations composed of more generalist individuals. Pinnipeds are a good model to test the NVH because they are mostly generalist species, living in dense colonies, and exhibiting variation in trophic niche width among populations.

We tested the NVH in pinnipeds using longitudinal isotopic data: published δ13C and δ15N data obtained from sequential sections of whiskers (vibrissae) from individuals belonging to 14 populations. To the best of our knowledge, this is the first study evaluating the NVH by using longitudinal isotopic data.

We compiled studies that published raw data on δ13C and δ15N for pinniped whisker segments to estimate the within‐individual and the between‐individuals components of variance, the total niche width (TNW), and ITS. One‐dimensional (i.e. δ13C or δ15N) and multi‐dimensional (i.e. δ13C and δ15N) analyses were used. Also, we tested whether an evolutionary component would affect the degree of ITS among pinniped species with different levels of shared ancestry.

Our results indicate that, in line with the NVH, pinniped populations composed of more specialised individuals tend to show wider trophic niches. When analysing each sex separately, the hypothesis is supported for females but not for males.

We believe that physiological and behavioural differences between sexes may explain this result. In females, high TNW is mainly related to greater differentiation among individuals, while in males, it is mainly related to high diversity of resources consumed by all individuals.
Polyketide reductases in defense‐related parasorboside biosynthesis in Gerbera hybrida share processing strategies with microbial polyketide synthase systems
Authors: Zhu Lingping , Pietiäinen Milla , Kontturi Juha , Turkkelin Anna , Elomaa Paula , Teeri Teemu H.
Published: June 2022

Plant polyketides are well‐known for their crucial functions in plants and their importance in the context of human health. They are synthesized by type III polyketide synthases (PKSs) and their final functional diversity is determined by post‐PKS tailoring enzymes. Gerbera hybrida is rich in two defense‐related polyketides: gerberin and parasorboside. Their synthesis is known to be initiated by GERBERA 2‐PYRONE SYNTHASE 1 (G2PS1), but the polyketide reductases (PKRs) that determine their final structure have not yet been identified.

We identified two PKR candidates in the pathway, GERBERA REDUCTASE 1 (GRED1) and GRED2. Gene expression and metabolite analysis of different gerbera tissues, cultivars, and transgenic gerbera plants, and in vitro enzyme assays, were performed for functional characterization of the enzymes.

GRED1 and GRED2 catalyze the second reduction step in parasorboside biosynthesis. They reduce the proximal keto domain of the linear CoA bound intermediate before lactonization.

We identified a crucial tailoring step in an important gerbera PKS pathway and show that plant polyketide biosynthesis shares processing strategies with fungi and bacteria. The two tailoring enzymes are recruited from the ancient sporopollenin biosynthetic pathway to a defense‐related PKS pathway in gerbera. Our data provide an example of how plants recruit conserved genes to new functions in secondary metabolism that are important for environmental adaptation.
Centromeres: From chromosome biology to biotechnology applications and synthetic genomes in plants
Authors: Zhou Jingwei , Liu Yang , Guo Xianrui , Birchler James A. , Han Fangpu , Su Handong
Published: June 2022

Centromeres are the genomic regions that organize and regulate chromosome behaviours during cell cycle, and their variations are associated with genome instability, karyotype evolution and speciation in eukaryotes. The highly repetitive and epigenetic nature of centromeres were documented during the past half century. With the aid of rapid expansion in genomic biotechnology tools, the complete sequence and structural organization of several plant and human centromeres were revealed recently. Here, we systematically summarize the current knowledge of centromere biology with regard to the DNA compositions and the histone H3 variant (CENH3)‐dependent centromere establishment and identity. We discuss the roles of centromere to ensure cell division and to maintain the three‐dimensional (3D) genomic architecture in different species. We further highlight the potential applications of manipulating centromeres to generate haploids or to induce polyploids offspring in plant for breeding programs, and of targeting centromeres with CRISPR/Cas for chromosome engineering and speciation. Finally, we also assess the challenges and strategies for de novo design and synthesis of centromeres in plant artificial chromosomes. The biotechnology applications of plant centromeres will be of great potential for the genetic improvement of crops and precise synthetic breeding in the future.
High frequency of delayed milk delivery to neonates in tropical beef herds
Authors: Muller Jarud , Prada e Silva Luis , Fordyce Geoffry
Published: June 2022

Beef‐calf mortality rates across tropical and subtropical Australia are high, with sub‐optimal nutrition in pregnant cows being the primary risk. The nutritional deficiencies associated with calf mortality are the same as those associated with reduced milk yields. Although the highest mortality risk occurs during neonatal life, the role of inadequate milk delivery to beef neonates is not well established. This study investigated the frequency of low milk delivery in tropically adapted neonatal calves and the time for their dams to initiate full lactation in five management groups of Brahman and Droughtmaster calving cows in the dry tropics of northern Queensland, Australia. Change in calf weight in the days following birth was the primary measure of milk uptake. Plasma globulin concentration was used to indicate colostrum uptake. Across management groups, data were available on 250 calves for regression analysis of average daily gain vs. globulin and on 78 for plotting calf growth profiles. Calves had one of two growth profiles, either with immediate high growth from birth (day one) or with high growth delayed until day three. The frequency of delayed growth calves (with inadequate milk intake to gain at least 0.5 kg by day three after birth) was on average 30% across management groups, with management groups ranging 25%–50%. The frequency of calves growing ≤0.2 kg/day to day three was 15%–37%, depending on management group. The frequency of calves growing ≤0.2 kg/day to day five was 7%–20%, depending on management group. Calf globulin explained only 25% of the variation in calf average daily gain. Our study shows that a third of tropically adapted calves may experience a three‐day delay to initiation of full lactation by their dams. Although study conditions were relatively benign, any additional risks with milk delivery, such as those that occur widely in tropical and subtropical northern Australia, would place such calves at risk of dehydration and mortality. Calf plasma globulin should not be used as a standalone measure of adequacy of neonatal milk delivery, especially when comparing across herds. This study demonstrates a fundamental problem of high frequency in northern Australia. The underlying risks for delayed milk delivery should be considered in the quest for practical solutions to reduce tropically adapted beef‐calf mortalities.
High concentration of growth differentiation factor‐9 (GDF‐9) to the ram semen had a negative effect on the sperm positive rheotaxis
Authors: Abdel‐Ghani Mohammed A. , Alhaider Abdulrahman
Published: June 2022

Herein, the microfluidic device technique was used to investigate the effects of GDF‐9 concentrations and exposure time on the ram sperm positive rheotaxis (PR). Semen was collected from six rams and utilized for PR, motility and sperm kinetic parameter analysis using a computer‐assisted sperm analysis program with controlled flow velocity following 0, 10, 20 or 30 min of incubation at 37°C with GDF‐9 (200 , 400 or 600 ng/ml; semen sample without GDF‐9 was used as a control). Results revealed that there was not an interaction between effects of GDF‐9 concentrations and incubation duration on PR% (p = .457) and TM% (p = .099). A simple main effects analysis showed that GDF‐9 concentrations had an effect on PR% (p = .003). However, the incubation duration did not have an effect on PR% (p = .101). GDF‐9 concentrations had not an effect on TM% (p = .817). By contrast, the incubation duration affected on TM% (p = .026). A higher PR% was found (p < .05) at 200 ng GDF‐9 after 10 min (46.7 ± 10.3) and 20 min (45.5 ± 11.5) of incubation. After 30 min of incubation, the PR% was found lowest (p < .05) at 400 ng of GDF‐9 (30.6 ± 14.1) and 600 ng of GDF‐9 (32.2 ± 9.6). There was no difference (p > .05) in the sperm kinetic parameters between the four treatment groups. In conclusion, the ram sperms had the best rheotaxis properties after 10 and 20 min of incubation with 200 ng of GDF‐9 and were sensitive to high concretions.
Flood risk map from hydrological and mobility data: A case study in São Paulo (Brazil)
Authors: Tomás Lívia Rodrigues , Soares Giovanni Guarnieri , Jorge Aurelienne A. S. , Mendes Jeferson Feitosa , Freitas Vander L. S. , Santos Leonardo B. L.
Published: June 2022

Cities increasingly face flood risk primarily due to extensive changes of the natural land cover to built‐up areas with impervious surfaces. In urban areas, flood impacts come mainly from road interruption. This article proposes an urban flood risk map from hydrological and mobility data, considering the megacity of São Paulo, Brazil, as a case study. We estimate the flood susceptibility through the Height Above the Nearest Drainage algorithm; and the potential impact through the exposure and vulnerability components. We aggregate all variables into a regular grid and then classify the cells of each component into three classes: Moderate, High, and Very High. All components, except the flood susceptibility, have few cells in the Very High class. The flood susceptibility component reflects the presence of watercourses, and it has a strong influence on the location of those cells classified as Very High.
Emulating the Effective Ankle Stiffness of Commercial Prosthetic Feet Using a Robotic Prosthetic Foot Emulator
Authors: Halsne Elizabeth G. , Curran Carl S. , Caputo Joshua M. , Hansen Andrew H. , Hafner Brian J. , Morgenroth David C.
Published: June 2022

Prosthetic foot selection for individuals with lower limb amputation relies primarily on clinician judgment. The prosthesis user rarely has an opportunity to provide experiential input into the decision by trying different feet. A prosthetic foot emulator (PFE) is a robotic prosthetic foot that could facilitate prosthesis users' ability to trial feet with different mechanical characteristics. Here, we introduce a procedure by which a robotic PFE is configured to emulate the sagittal plane effective ankle stiffness of a range of commercial prosthetic forefeet. Mechanical testing was used to collect data on five types of commercial prosthetic feet across a range of foot sizes and intended user body weights. Emulated forefoot profiles were parameterized using Bezier curve fitting on ankle torque-angle data. Mechanical testing was repeated with the PFE, across a subset of emulated foot conditions, to assess the accuracy of the emulation. Linear mixed-effects regression and Bland–Altman Limits of Agreement analyses were used to compare emulated and commercial ankle torque-angle data. Effective ankle stiffness of the emulated feet was significantly associated with the corresponding commercial prosthetic feet (p <0.001). On average, the emulated forefeet reproduced the effective ankle stiffness of corresponding commercial feet within 1%. Furthermore, differences were independent of prosthetic foot type, foot size, or user body weight. These findings suggest that commercial prosthetic foot properties can be effectively mimicked by a PFE, which is the important first step toward enabling prosthesis users to quickly trial different feet using a PFE as part of prosthetic foot prescription.
Motion-Based Ground Reaction Forces and Moments Prediction Method for Interaction With a Moving and/or Non-Horizontal Structure
Authors: Demestre Louise , Morin Pauline , May François , Bideau Nicolas , Nicolas Guillaume , Pontonnier Charles , Dumont Georges
Published: June 2022

Inverse dynamics methods are commonly used for the biomechanical analysis of human motion. External forces applied on the subject are required as an input data to solve the dynamic equilibrium of the subject. Force platforms measure ground reaction forces and moments (GRF&Ms) but they limit the ecological aspect of experimental conditions. Motion-based GRF&Ms prediction may circumvent this limitation. The current study aims at evaluating the accuracy of an optimization-based GRF&Ms prediction method modified to be applied to the interaction with a moving and/or nonhorizontal structure (MNHS). The main improvement of the method deals with contact detection in such a MNHS. To evaluate the accuracy of the method, 20 subjects performed squats and steps on an instrumented moving structure, measuring both motion and GRF&Ms. The comparison of the root-mean-square error between the predicted and measured GFR&Ms divided by the subjects mass showed a similar order of magnitude than those from the method without the studied modification (0.14 N/kg for antero-posterior forces, 0.29 N/kg for medio lateral forces, 0.61 N/kg for longitudinal forces, 0.06 Nm/kg for frontal moments, 0.13 Nm/kg for sagittal moments, and 0.03 Nm/kg for transverse moments). The results showed the suitability of the method to study human motions for tasks performed on a MNHS.
Position-Access Workspace of Slender Soft Manipulators
Authors: Amehri Walid , Zheng Gang , Kruszewski Alexandre
Published: June 2022

In this article, we investigate the position-access workspace estimation of slender soft manipulators controlled via arranged bounded actuators. For this, we implement a so-called forward-backward approach on the mathematical model of the investigated soft robot deduced via the adopted Discrete Cosserat method. The proposed methodology is validated on several planar and spatial slender soft manipulators’ configurations, where we show its advantage of reducing computation complexity for estimating the workspace, compared to traditional forward approach.
Natural Convection With Surface Radiation From the Infrared Suppression Device and Estimation of Cooling Time: A Computational Analysis
Authors: Chandrakar Vikrant , Senapati Jnana Ranjan , Mohanty Aurovinda
Published: June 2022

The thermofluid characteristics of the infrared suppression (IRS) device used in the marine gas turbine as an exhaust system are numerically investigated here. The prime objective is to observe the impact of convection united with surface radiation on the cooling of the IRS. Furthermore, the time taken to cool down the device is also estimated. A comparison exercise is also carried out to elucidate the impact of radiation considering the surface radiation and without it (taking only convection). The numerical solution of the Navier–Stokes equation, energy equation, and radiation equation, along with the turbulence equations, are performed using ANSYS FLUENT 15.0. Various relevant parameters are taken for the analysis, namely, Rayleigh number (Ra) (1 × 1010 ≤ Ra ≤ 1 × 1012), diameter ratio (DR) (1.01 ≤ DR ≤ 1.3), funnel overlapping (OL) (−20% ≤ OL ≤ 20%), and emissivity of the surface (ε) (0 ≤ ε ≤ 1). It is noticed that surface radiation has an enormous contribution to the total heat transfer and, thus, could not be neglected. The total heat transfer rate and mass flowrate increase with Ra and DR. Also, the contribution of convective heat transfer drops with the rise in emissivity. In addition, the convection united with surface radiation case reduces the cooling time (almost half) than the natural convection alone case.
Iterative Image Correction Scheme for Optoacoustic Tomography
Authors: Rudnitskii A. G.
Published: June 2022

Abstract—

An iterative algorithm to enhance the quality of optoacoustic images is proposed based on the Banach fixed point theorem. Numerical simulation of the propagation of ultrasound waves and image reconstruction for media with characteristics close to soft biological tissues has been performed. The problem of eliminating distortions and artifacts in optoacoustic images has been modeled for four iterative schemes. The efficiency of the approach has been demonstrated even for a few iterations.
Effect of four combined procedures to achieve inframalleolar correction for advanced varus ankle arthritis
Authors: Choi Jun Young , Suh Jin Soo
Published: June 2022

A man in his early 60s with Takakura stage IIIB varus ankle arthritis underwent four combined procedures (Dwyer’s osteotomy with lateral displacement, superficial/deep deltoid ligament release, anterior talofibular ligament/calcaneofibular ligament reconstruction with suture tape augmentation and posterior tibial tendon lengthening). Decreased talar tilt and talar centre lateral shifting and improved hindfoot varus were observed 2 years postoperatively. Also, excellent clinical outcome could be achieved.
Complexities in diagnosing and treating endophthalmitis in the post stem cell transplant setting
Authors: Conlon Peter , Creedon Margaret , Houlihan Elaine , O'Rourke Sadhbh
Published: June 2022

Endophthalmitis is a rare but sight-threatening manifestation of systemic infection. Immunosuppression is a well-recognised risk factor for development of endophthalmitis. Determining the aetiology can be complex, particularly in the context of immunosuppression, we present the diagnostic and treatment dilemmas associated with a patient who complains of blurred vision 2 weeks following an allogeneic stem cell transplant for refractory Hodgkin’s disease. We demonstrate that in the context of immunosuppression post stem cell transplantation, a broad differential should be maintained until a microbiological diagnosis can be confirmed. In particular, we evaluate how clinical suspicion can diverge from typical fundoscopic findings in the diagnosis of endophthalmitis.