bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam
Authors: Kletzl Heidemarie , Ajmi Hassan , Antys Izabela , Heinig Katja , Jaber Birgit , Marbury Thomas C. , Young Annie , Günther Andreas
Published: March 2022

Aim

This phase I, multicentre, open‐label, nonrandomised, parallel‐group, two‐part study aimed to evaluate the effect of mild to moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of risdiplam.

Methods

Adult subjects (aged 18‐70 years) with mild (Child‐Pugh Class A; Part 1) or moderate (Child‐Pugh Class B; Part 2) hepatic impairment were matched with subjects with normal hepatic function on sex, age, body mass index and smoking status. Each subject received a single oral dose of 5 mg of risdiplam. Plasma concentrations of risdiplam and its metabolite M1 were measured and PK parameters were compared. Adverse events, laboratory abnormalities, vital signs and electrocardiogram measurements were assessed.

Results

After a single dose (5 mg) of risdiplam, the risdiplam PK parameters area under the plasma concentration‐time curve from time zero to infinity and maximum observed plasma concentration were approximately 20% and 5% lower, respectively, in subjects with mild hepatic impairment and approximately 8% and 20% higher, respectively, in subjects with moderate hepatic impairment compared with subjects with normal hepatic function. These differences were not statistically significant; all 90% confidence intervals for geometric least squares‐means ratios spanned unity. No new risdiplam‐related safety findings were observed in subjects with mild or moderate hepatic impairment.

Conclusion

Mild or moderate hepatic impairment did not have a clinically relevant impact on the PK of risdiplam. Therefore, no dose adjustment is required in patients with mild or moderate hepatic impairment when receiving risdiplam.
Checkpoint CD47 expression in classical Hodgkin lymphoma
Authors: Gholiha Alex Reza , Hollander Peter , Löf Liza , Glimelius Ingrid , Hedstrom Gustaf , Molin Daniel , Hjalgrim Henrik , Smedby Karin E. , Hashemi Jamileh , Amini Rose‐Marie , Enblad Gunilla
Published: March 2022

The glycoprotein CD47 regulates antiphagocytic activity via signal regulatory protein alpha (SIRPa). This study investigated CD47 expression on Hodgkin and Reed–Sternberg (HRS) cells in the classical Hodgkin lymphoma (cHL) tumour microenvironment and its correlation with prognosis, programmed‐death (PD) immune markers, and SIRPa+ leukocytes. We conducted immunohistochemistry with CD47 and SIRPa antibodies on diagnostic biopsies (tissue microarrays) from cHL patients from two cohorts (n = 178). In cohort I (n = 136) patients with high expression of CD47 on HRS cells (n = 48) had a significantly inferior event‐free survival [hazard ratio (HR) = 5.57; 95% confidence interval (CI), 2.78–11.20; p < 0.001] and overall survival (OS) (HR = 8.54; 95% CI, 3.19–22.90; p < 0.001) compared with patients with low expression (n = 88). The survival results remained statistically significant in multivariable Cox regression adjusted for known prognostic factors. In cohort II (n = 42) high HRS cell CD47 expression also carried shorter event‐free survival (EFS) (HR = 5.96; 95% CI, 1.20–29.59; p = 0.029) and OS (HR = 5.61; 95% CI, 0.58–54.15; p = 0.136), although it did not retain statistical significance in the multivariable analysis. Further, high CD47 expression did not correlate with SIRPa+ leukocytes or PD‐1, PD‐L1 and PD‐L2 expression. This study provides a deeper understanding of the role of CD47 in cHL during an era of emerging CD47 therapies.
Oxygen sensing in the ductus arteriosus—A unifying vision for two concepts
Authors: Coceani Flavio
Published: March 2022

Closure of the ductus arteriosus at birth is known to be related to the physiological rise in blood oxygen tension. Two main schemes have been proposed to explain the peculiar contraction of the ductus to oxygen, and their function is based on distinct sensor‐effector complexes. Specifically, these schemes comprise a cytochrome P450 monooxygenase‐endothelin complex or, alternatively, a mitochondrial redox mechanism‐voltage gated potassium channel complex. However, it is not clear how these systems may relate to the closure process. Here, it is proposed that they operate jointly within a single functional entity, with their combined activation being required for a full‐fledged contraction of the vessel to oxygen. This arrangement is thought to ensure a smooth transition from the powerful relaxant mechanism that is evident through the early postnatal period. Validation of this concept would not only settle a central question in the operation of the ductus but may also afford a broader perspective in any future translational research.
Reappraisal of a second examination after standard colonoscopy withdrawal in the proximal colon: Retroflex or forward view?
Authors: Imai Kenichiro
Published: March 2022

This Editorial refers to the article by X.‐H. Lv et al., p 33‐42 of the issue DEN 34:1.
Convolutional neural network‐aided tuber segmentation in tuberous sclerosis complex patients correlates with electroencephalogram
Authors: Park David K. , Kim Woojoong , Thornburg Olivia S. , McBrian Danielle K. , McKhann Guy M. , Feldstein Neil A. , Maddocks Alexis B. , Gonzalez Elena , Shen Min Y. , Akman Cigdem , Provenzano Frank A.
Published: March 2022

Objective

One of the clinical hallmarks of tuberous sclerosis complex (TSC) is radiologically identified cortical tubers, which are present in most patients. Intractable epilepsy may require surgery, often involving invasive diagnostic procedures such as intracranial electroencephalography (EEG). Identifying the location of the dominant tuber responsible for generating epileptic activities is a critical issue. However, the link between cortical tubers and epileptogenesis is poorly understood. Given this, we hypothesized that tuber voxel intensity may be an indicator of the dominant epileptogenic tuber. Also, via tuber segmentation based on deep learning, we explored whether an automatic quantification of the tuber burden is feasible.

Methods

We annotated tubers from structural magnetic resonance images across 29 TSC subjects, summarized tuber statistics in eight brain lobes, and determined suspected epileptogenic lobes from the same group using EEG monitoring data. Then, logistic regression analyses were performed to demonstrate the linkage between the statistics of cortical tuber and the epileptogenic zones. Furthermore, we tested the ability of a neural network to identify and quantify tuber burden.

Results

Logistic regression analyses showed that the volume and count of tubers per lobe, not the mean or variance of tuber voxel intensity, were positively correlated with electrophysiological data. In 47.6% of subjects, the lobe with the largest tuber volume concurred with the epileptic brain activity. A neural network model on the test dataset showed a sensitivity of .83 for localizing individual tubers. The predicted masks from the model correlated highly with the neurologist labels, and thus may be a useful tool for determining tuber burden and searching for the epileptogenic zone.

Significance

We have proven the feasibility of an automatic segmentation of tubers and a derivation of tuber burden across brain lobes. Our method may provide crucial insights regarding the treatment and outcome of TSC patients.
Post‐partum paralysis following dystocia in a miniature horse
Authors: Hilliard Rachel , Haines Greg , Lillich James
Published: March 2022

An approximately 5‐year‐old American Miniature Horse mare presented for dystocia of several hours’ duration. Upon arrival she was in sternal recumbency and unable to stand, with both pelvic limbs splayed perpendicular to her body. The mare was induced under general anaesthesia and a controlled vaginal delivery with partial fetotomy was performed. After resolution of the dystocia, the mare could not stand without support but was able to bear weight and ambulate with her hind legs hobbled. The mare was diagnosed with bilateral obturator neuropathy following radiographs to rule out orthopaedic injury. She was hobbled, confined for 24 h, and treated with corticosteroids, anti‐inflammatories and antibiotics. After 24 h, the mare could comfortably bear weight, and after 96 h she could walk without hobbles. She was discharged 6 days after admission with only mild lateral hindlimb instability.
Clinical implications of differential functional capacity between tissue‐specific human mesenchymal stromal/stem cells
Authors: Yen B. Linju , Liu Ko‐Jiunn , Sytwu Huey‐Kang , Yen Men‐Luh
Published: March 2022

Over the past two decades, there has been an explosion in the numbers of clinical trials using mesenchymal stem cells (MSCs). While the safety profile of MSC therapy has been excellent, therapeutic success has not been as robust as expected. In addition to variabilities inherent in all live‐cell products because of donor‐specific differences and manufacturing practices, MSCs may have an additional layer of complexity due to the availability of many tissues/organ sources for isolation. Since first isolation from the bone marrow (BM) over 50 years ago, human MSCs have been robustly found in multiple tissues/organs. The increased variety of MSC sources is reflected in clinical trials: while BMMSCs was used in nearly all trials prior to 2008, they are used in less than 50% of clinical trials in recent years. While the majority of single‐source MSC preclinical data accumulated over the past several decades do reveal biological differences between tissue‐specific sources of MSCs, studies directly comparing different MSC sources are relatively rare. In this Review, we summarise these past findings and also specifically focus on studies comparing MSCs isolated from the most commonly utilised sources of BM, adipose tissue and post‐partum discarded extraembryonic tissue. The MSC functions discussed here include paraxial mesodermal trilineage differentiation capacity, and also other well‐studied and translationally relevant MSC functions of haematopoietic support, immunomodulation and paracrine capacities. Finally, we will discuss the implications of tissue‐specific MSC functional differences on future research avenues, manufacturing practices, as well as clinical implementation.
Microbial translocation is associated with advanced liver fibrosis among people with HIV
Authors: He Jiayu , Shi Ruizi , Duan Song , Ye Runhua , Yang Yuecheng , Wang Jibao , Zu Zhipeng , Tang Renhai , Gao Jie , Liu Xing , He Na
Published: March 2022

Background

The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China.

Method

A total of 665 people living with HIV were enrolled at baseline and had at least one follow‐up visit during the 3‐year study period. We calculated the Liver Fibrosis Index (FIB‐4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide‐binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF.

Results

Of the participants, 61 (9.17%) had advanced LF (FIB‐4 >3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB‐4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow‐up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR] = 1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR = 1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/μl (aOR = 3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR = 2.52; 95% CI 1.41~4.51) and age >50 years (aOR = 32.66; 95% CI 15.89~66.36). LF progression (increasing FIB‐4) was significantly associated with increasing sCD14 level (β = 1.11; 95% CI 0.97~1.26; p < 0.001) with covariate adjustment.

Conclusion

The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China.
Development of photocatalysts based on TiO2 films with embedded Ag nanoparticles
Authors: Roldán María Virginia , Porta Estanislao , Durán Alicia , Castro Yolanda , Pellegri Nora
Published: March 2022

In this work, the synthesis, characterization, and study of the photocatalytic activity of polycrystalline TiO2 coatings with embedded Ag nanoparticles (Ag‐TiO2) were presented. In particular, the TiO2 and Ag‐TiO2 coatings were developed using a simple and improved sol‐gel technique. Very stable TiO2 sols containing Ag nanoparticles were prepared and deposited by dip‐coating process onto glass substrates obtaining homogeneous and transparent thin films. The well‐distribution of silver nanoparticles into the TiO2 sol allows TiO2 coatings with Ag nanoparticles distributed throughout the volume of the material to be obtained. A significant improvement of the photocatalytic activity was observed for the Ag‐TiO2 coatings. The photocatalytic mechanism implicated in the dye degradation (methyl orange) by hydroxyl (•OH) and superoxide (•O2–) radicals was studied using several scavengers. Thus, it is concluded that the addition of Ag nanoparticles does not modify the mechanisms involved in the dye degradation, evidencing the good stability of the photocatalyst.
Secretive fish diversity: A new species of Listrura (Siluriformes, Trichomycteridae) from a supposedly well‐known river in south‐eastern Brazil
Authors: Villa‐Verde Leandro , de Pinna Mario C. C. , Reis Vinícius J. C. , Oyakawa Osvaldo T.
Published: March 2022

The trichomycterid catfish Listrura menezesi, new species, is described from a flooded area adjacent to Rio das Panelas, Rio São João basin, Cachoeiras de Macacu municipality, Rio de Janeiro State, Brazil. It represents a most valuable remnant of Atlantic Forest biome that still resists the devastation of Brazilian coastlands. Listrura menezesi can be distinguished from its congeners, except L. boticario and L. depinnai, by the absence of a dorsal fin. It mainly differs from L. boticario and L. depinnai by a continuous midlateral dark stripe along the entire body (vs. discontinuous) and a longitudinal row of irregular dots along the dorsal limit of the abdomen extending for nearly the entire body (vs. only on the posterior half of the body in L. boticario and not forming a distinct row in L. depinnai). Although the new species shares with L. boticario and L. depinnai the absence of dorsal fin, recent phylogenetic analyses show a close relationship between L. menezesi and L. macaensis, the latter having a dorsal fin. A putative apomorphic condition for this clade is presented: the abrupt widening on the mesethmoid axis starting posteriorly on the horizontal through the middle region of the autopalatine (vs. anteriorly, on the horizontal through the anterior region of the autopalatine). Listrura menezesi comes as an addition to the ichthyofauna of the Rio São João drainage, a region extensively sampled for the past 20 years and supposedly well known. This paper also highlights the vulnerability of this species and the possibility of its disappearance in the near future.
Effects of oral contraceptives plus orlistat in patients with polycystic ovary syndrome and overweight/obesity: A meta‐analysis
Authors: Chen Zhangming , Cai Zhaowei
Published: March 2022

Aim

This meta‐analysis was conducted to compare the effect and safety of oral contraceptive pills (OCP) plus orlistat with OCP alone in clinical, hormonal, and lipid metabolism outcomes in patients with polycystic ovary syndrome (PCOS) and overweight/obesity.

Methods

Pubmed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and SinoMed were systematically reviewed. A random‐effects or fixed‐effects model was used to pool the estimate.

Results

Eight studies were included in this meta‐analysis. Significant reductions in BMI, WHR, and waist circumference were observed in combination group as compared with OCP alone group. Regarding the hormonal outcome, T, SHBG, FAI, LH, DHEAS, FSH, and E2 levels were significantly improved in combination group compared with OCP alone group. However, the TT and FT did not change significantly between the two groups. Regarding the lipid metabolism outcomes, TC, LDL‐C, and TG levels were reduced and HDL‐C level was increased in the combination group. Regarding the insulin metabolism outcomes, FINS and HOMA‐IR levels were reduced in combination group than in OCP group. The ovulation rate, pregnancy rate, and overall effective rate were significantly higher in combination group than in OCP alone group. Fewer complications were observed in the combination group than in OCP group, and the difference between them was significant.

Conclusion

This combination treatment of OCP and orlistat was more effective than OCP alone in reducing the weight, hormonal, lipid, and insulin metabolism profiles, as well as improving the ovulation rate, pregnancy rate, and overall effective rate, as compared with OCP alone.
FRACTURED LANDSCAPES AND THE POLITICS OF SPACE: Remembrance and Memory in Nwadjahane (Southern Mozambique)
Authors: Cruz M. Dores
Published: March 2022

abstract

Nwadjahane, a small village in southern Mozambique, is set apart from other settlements as the birthplace of Eduardo Mondlane, one of the nation's founding fathers. Declared a national heritage site and made into an open‐air museum, Nwadjahane has become a landscape where national and local memories are negotiated. Mondlane is at once a national hero celebrated with statues, exhibitions, and commemorations, as well as locally linked to ancestors and memorialized through ritual sites and sacred trees. I examine how diverse audiences engage, appropriate, and contest the different spaces of Nwadjahane: the village, the museum, the space of ancestors. Highlighting the fractured nature and the politics of this landscape, the tensions, contradictions, claims, and counterclaims made upon a single locale, I use Foucault's concept of heterotopia as an analytical tool to interrogate the juxtaposition of distinct spaces and temporalities, focusing particularly on local interpretations and the historical conditions that made Nwadjahane a national heritage site.
Overestimating Reported Prejudice Causes Democrats to Believe Disadvantaged Groups Are Less Electable
Authors: Mercier Brett , Celniker Jared B. , Shariff Azim F.
Published: March 2022

Four studies show that Democrats overestimate the explicit prejudice reported by the American electorate, leading them to perceive presidential candidates from disadvantaged groups as less electable. Study 1 (MTurk; n = 728) found that Democrats overestimated the percentage of Americans who say they would not vote for presidential candidates from disadvantaged groups. Study 2 (MTurk; n = 597) replicated this finding and demonstrated that Democrats who perceive high levels of explicit prejudice toward a group also believe presidential candidates from that group are less electable. Moreover, Democrats who more frequently interacted with Republicans were more accurate in estimating the amount of explicit prejudice reported by Republicans, Democrats, and Americans in general. Studies 3A (Prolific; n = 930) and 3B (YouGov; n = 747) found that presenting information about true levels of reported prejudice made Democrats believe generic presidential candidates from disadvantaged groups would be more electable. We did not find evidence that information about true levels of reported prejudice affected Democrats' beliefs about the electability of specific candidates in the 2020 Democratic Primary or their support for these candidates.
Tertiary succession: a new concept to help vegetation restoration
Authors: Rapson Gillian L.
Published: March 2022

Restoration is the human activity of manipulating vegetation with the aim of accelerating attainment of stable vegetation. But current procedures seem to arrest succession instead. A comparison of primary and secondary successions with restoration activities suggests there is little overlap in these concepts. Thinking of the process of restoration as a tertiary succession helps highlight managerial options which may improve success, especially by addressing environmental and biological legacies.
Severe combined immunodeficiencies: Expanding the mutation spectrum in Turkey and identification of 12 novel variants
Authors: Aykut Ayca , Durmaz Asude , Karaca Neslihan , Gulez Nesrin , Genel Ferah , Celmeli Fatih , Ozturk Gulyuz , Atay Didem , Aydogmus Cigdem , Kiykim Ayca , Aksu Guzide , Kutukculer Necil
Published: March 2022

Human Inborn Errors of Immunity (IEIs) are clinically and genetically heterogeneous group of diseases, with relatively mild clinical course or severe types that can be life‐threatening. Severe combined immunodeficiency (SCID) is the most severe form of IEIs, which is caused by monogenic defects that impair the proliferation and function of T, B, and NK cells. According to the most recent report by the International Union of Immunological Societies (IUIS), SCID is caused by mutations in IL2RG, JAK3, FOXN1, CORO1A, PTPRC, CD3D, CD3E, CD247, ADA, AK2, NHEJ1, LIG4, PRKDC, DCLRE1C, RAG1 and RAG2 genes. The targeted next‐generation sequencing (TNGS) workflow based on Ion AmpliSeq™ Primary Immune Deficiency Research Panel was designed for sequencing 264 IEI‐related genes on Ion S5™ Sequencer. Herein, we present 21 disease‐causing variants (12 novel) which were identified in 22 patients in eight different SCID genes. Next‐generation sequencing allowed a rapid and an accurate diagnosis SCID patients.
Oily wastewater treatment by blend polyether imide‐sulfonated poly (ether ether keton) hollow fibre membrane through a side‐stream MBR process
Authors: Safdari Mohsen , Mansourizadeh Amir , Ghaedi Abdol Mohammad , Jelvegar Filband Ali
Published: March 2022

The blend polyether imide‐sulfonated poly (ether ether keton) (PEI‐sPEEK) hollow fibre membrane was prepared for oily wastewater treatment of the natural gas liquid plant (NGL‐900, Gachsaran, Iran) through a side‐stream membrane bioreactor (MBR) process. Using PEI/sPEEK ratio of 90/10, a good compatibility of PEI and sPEEK polymers was achieved by DSC analysis. The modified membrane showed an open structure with large finger‐likes, overall porosity of about 80% and mean surface pore size of 10 nm. In addition, the membrane hydrophilicity significantly improved as water contact angle reduced from about 82° to 58°. In the MBR process, the improved membrane presented oil rejection, COD, TSS and turbidity reduction of about 99.9%, 99.7%, 98.9%, and 99.7%, respectively. The membrane showed a good antifouling property with flux recovery ratio (FRR) of 80.2% where the cake filtration was the dominant fouling mechanism. The modified membrane can be a promising alternative for treatment of industrial oily wastewater due to the enhanced properties.
Usage of treated greywater as an alternative irrigation source for tomatoes cultivation
Authors: Hajlaoui Hichem , Akrimi Rawaa , Sayehi Safa , Hachicha Salma
Published: March 2022

Optimizing water reuse is an important issue in the context of water scarcity and low water quality. Greywater would provide more sustainable water supply, once using appropriate treatment. This study aimed to appraise the efficacy of treated greywater (TGW) use on soil and tomato cultivation, in comparison with ground water (GW) use. Greywater (from laundry and tableware) was treated using a wetland mini‐reactor with a horizontal underground flow. Growth, photosynthetic activity, plant water status, osmotic potential and yield of tomato cultivars (Dart and Firenze) were evaluated. Sodium, potassium (analysed by flame photometer) and heavy metals (examined by atomic absorption photometer) were quantified in leaves, stems and roots. Results showed that TGW does not affect soil salinity. The TGW improved plant height and yield, of both cultivars. Although net photosynthesis increased only in Dart whereas Firenze had elevated water potential, less relative water content and photosynthetic water use efficiency suggesting a pronounced water restriction. Also, Firenze had higher Zn2+ and Fe2+ content than Dart indicating less selectivity. Our results imply that greywater treatment had an encouraging potential for soil preservation and tomatoes irrigation. Plant resistance is possibly acquired by ionic balance and photosynthetic capacity. Further studies are desirable to inspect long‐term effects on soil and health.
Comparing the emergence of Echinochloa crus‐galli populations in different locations. Part II: similarities and threshold parameters
Authors: Royo‐Esnal Aritz , Onofri Andrea , Taab Alireza , Loddo Donato , Necajeva Jevgenija , Uludag Ahmet , Synowiec Agnieszka , Calha Isabel M. , Lars Andersson , Jensen Peter K. , Uremis Ilhan , Economou Garifalia , Murdoch Alistair J. , Tørresen Kirsten S.
Published: March 2022

The variability in the emergence process of different populations was confirmed for two Echinochloa crus‐galli populations, one from Italy (IT) and the second from Norway (NO). Seeds were sown in 12 localities over Europe and the Middle East, and the emergence patterns of IT and NO were compared with those of several local populations at each location. Seeds of each population were sown in pots buried to the ground level. The base temperature (Tb) for emergence was estimated by (1) analysing logistic models applied to the field emergence of IT and NO, and (2) a germination assay set in winter 2020 at constant temperatures (8, 11, 14, 17, 20, 26, 29°C) with newly collected seeds in 2019 from the same fields where IT and NO had previously been harvested in 2015. The logistic models developed for IT and NO in each location showed that the emergence pattern of IT was similar to that of the local populations in Poland, Italy, Spain, Turkey South and Iran, while NO fitted better to those in Sweden and Latvia. No germination was obtained for IT in a germination chamber, but the estimated Tb with the logistic model was 11.2°C. For NO, the estimated Tb was 8.8°C in the germination chamber and 8.1°C in the field. Results suggest that adaptation to local environmental conditions has led to inter‐population differences in Tb and parameter estimates of thermal‐time models to predict the emergence of E. crus‐galli should only be used for populations with similar climatic and habitat conditions.
A national study through a ‘Farm‐to‐fork’ Approach to determine Salmonella dissemination along with the Lebanese poultry production chain
Authors: El Hage Rima , El Rayess Youssef , Bonifait Laetitia , El Hafi Bassam , Baugé Louise , Viscogliosi Eric , Hamze Mounzer , Mathieu Florence , Matar Ghassan M. , Chemaly Marianne
Published: March 2022

This cross‐sectional study was conducted to determine the prevalence of Salmonella at different stages of the broiler production chain and layer flocks in addition to their antibiotic resistance profile and molecular patterns. Over a period of 3 years, different sample matrices were collected from Lebanese farms, slaughterhouses and retail markets. Out of 672 Salmonella serotyped, 514 were analysed for antimicrobial resistance and 214 for clonality using Pulsed‐field gel electrophoresis (PFGE). The results highlighted an important prevalence of Salmonella, 30% in farms, 35.8% in slaughterhouses and 22.4% at retail level. A large diversity of serotypes was identified with predominance among Salmonella Infantis (32.9%), Salmonella Enteritidis (28.4%) and Salmonella Kentucky (21.4%). High resistance to nalidixic acid was revealed in all the isolates. The most prominent resistance was exhibited in S. Kentucky and S. Infantis. The latter was resistant to tetracycline (99%), streptomycin (88.2%) and remarkable multi‐drug resistance (MDR) (89.7%). All S. Kentucky isolates were resistant to ciprofloxacin, MDR (62.4%) and 6% were resistant to extended‐spectrum cephalosporin (ESCs). One persistent clone of S. Enteritidis was found common between poultry and humans. Similar genomic profiles were detected between farms, slaughterhouses and retail suggesting the dissemination of identical clones throughout the food chain possibly due to weak barriers preventing such transmission.
Antitruste under pressure: crises econômicas e impactos nas estratégias de intervenção.
Authors: De Carvalho Vinicius Marques
Published: March 2022

Em um cenário de crise conjuntural, torna-se necessário uma visão sistêmica para reinvenção do sistema econômico. Neste contexto, há espaço para utilizar o conhecimento acumulado para entender como a Política de Defesa da Concorrência (PDC) pode amortecer os impactos dessas crises conjunturais. Para tanto, (i) inicia-se com uma caracterização do impacto da crise sobre em mercados; (ii) examinam-se as rotas de fuga e safe-harbours disponíveis (notadamente, as teorias da firma falimentar, de mercados em declínio e a cooperação de agentes econômicos); e (iii) delineiam-se os riscos da PDC se tornar uma política de baixa intensidade. Conclui-se pela necessidade de maleabilidade e pelo reforço do caráter instrumental da PDC. Por fim, aponta-se para o risco de perda implícita da capacidade de intervenção da PDC, que pode ser reduzido através do diálogo com as empresas e a sociedade.
The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology
Authors: Schroder Elizabeth A. , Ono Makoto , Johnson Sidney R. , Rozmus Ezekiel R. , Burgess Don E. , Esser Karyn A. , Delisle Brian P.
Published: March 2022

Daily variations in cardiac electrophysiology and the incidence for different types of arrhythmias reflect ≈24 h changes in the environment, behaviour and internal circadian rhythms. This article focuses on studies that use animal models to separate the impact that circadian rhythms, as well as changes in the environment and behaviour, have on 24 h rhythms in heart rate and ventricular repolarization. Circadian rhythms are initiated at the cellular level by circadian clocks, transcription–translation feedback loops that cycle with a periodicity of 24 h. Several studies now show that the circadian clock in cardiomyocytes regulates the expression of cardiac ion channels by multiple mechanisms; underlies time‐of‐day changes in sinoatrial node excitability/intrinsic heart rate; and limits the duration of the ventricular action potential waveform. However, the 24 h rhythms in heart rate and ventricular repolarization are primarily driven by autonomic signalling. A functional role for the cardiomyocyte circadian clock appears to buffer the heart against perturbations. For example, the cardiomyocyte circadian clock limits QT‐interval prolongation (especially at slower heart rates), and it may facilitate the realignment of the 24 h rhythm in heart rate to abrupt changes in the light cycle. Additional studies show that modifying rhythmic behaviours (including feeding behaviour) can dramatically impact the 24 h rhythms in heart rate and ventricular repolarization. If these mechanisms are conserved, these studies suggest that targeting endogenous circadian mechanisms in the heart, as well as modifying the timing of certain rhythmic behaviours, could emerge as therapeutic strategies to support heart function against perturbations and regulate 24 h rhythms in cardiac electrophysiology.

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AMP‐activated protein kinase activation in skeletal muscle modulates exercise‐induced uncoupled protein 1 expression in brown adipocyte in mouse model
Authors: Kim Hye Jin , Kim Youn Ju , Seong Je Kyung
Published: March 2022

Aerobic exercise is an effective intervention in preventing obesity and is also an important factor associated with thermogenesis. There is an increasing interest in the factors and mechanisms induced by aerobic exercise that can influence the metabolism and thermogenic activity in an individual. Recent studies suggest that exercise induced circulating factors (known as ‘exerkines’), which are able to modulate activation of brown adipose tissue (BAT) and browning of white adipose tissue. However, the underlying molecular mechanisms associated with the effect of exercise‐induced peripheral factors on BAT activation remain poorly understood. Furthermore, the role of exercise training in BAT activation is still debatable. Hence, the purpose of our study is to assess whether exercise training affects the expression of uncoupled protein 1 (UCP1) in brown adipocytes via release of different blood factors. Four weeks of exercise training significantly decreased the body weight gain and fat mass gain. Furthermore, trained mice exhibit higher levels of energy expenditure and UCP1 expression than untrained mice. Surprisingly, treatment with serum from exercise‐trained mice increased the expression of UCP1 in differentiated brown adipocytes. To gain a better understanding of these mechanisms, we analysed the conditioned media obtained after treating the C2C12 myotubes with an AMP‐activated protein kinase (AMPK) activator (AICAR; 5‐aminoimidazole‐4‐carboxamide ribonucleotide), which leads to an increased expression of UCP1 when added to brown adipocytes. Our observations suggest the possibility of aerobic exercise‐induced BAT activation via activation of AMPK in skeletal muscles.

Key points

Exercise promotes thermogenesis by activating uncoupling protein 1 (UCP1), which leads to a decrease in the body weight gain and body fat content. However, little is known about the role of exerkines in modulating UCP1 expression and subsequent brown adipose tissue (BAT) activation.

Four weeks of voluntary wheel‐running exercise reduces body weight and fat content.

Exercise induces the increase in AMP‐activated protein kinase (AMPK) and slow‐type muscle fibre marker genes in skeletal muscles and promotes UCP1 expression in white and brown adipose tissues.

Incubation of brown adipocytes with serum isolated from exercise‐trained mice significantly increased their UCP1 gene and protein levels; moreover, conditioned media of AMPK‐activator‐treated C2C12 myotubes induces increased UCP1 expression in brown adipocytes.

These results show that aerobic exercise‐induced skeletal muscle AMPK has a significant effect on UCP1 expression in BAT.
A Novel Method to Classify Rolling Element Bearing Faults Using K-Nearest Neighbor Machine Learning Algorithm
Authors: Vishwendra More A. , Salunkhe Pratiksha S. , Patil Shivanjali V. , Shinde Sumit A. , Shinde P. V. , Desavale R. G. , Jadhav P. M. , Dharwadkar Nagaraj V.
Published: March 2022

A novel method is proposed in this work for the classification of fault in the ball bearings. Applications of K-nearest neighbor (KNN) techniques are increasing, which redefines the state-of-the-art technology for defect diagnosis and classification. Vibration characteristics of deep groove ball bearing with different defects are studied in this paper. Experimentation is conducted at different loads and speeds with artificially created defects, and vibration data are processed using kurtosis to find frequency band of interest and amplitude demodulation (Envelope spectrum analysis). Bearing fault amplitudes are extracted from the filtered signal spectrum at bearing characteristic frequency. The decision of fault classification is made using a KNN machine learning classifier by training feature data. The training features are created using characteristics amplitude at different fault and bearing conditions. The results showed that the KNN's accuracies are 100% and 97.3% when applied to two different experimental databases. The quantitative results of the KNN classifier are applied as the guidance for investigating the type of defects of bearing. The KNN Classifier method proved to be an effective method to quantify defects and significantly improve classification efficiency.
Experimental and Simulation Analysis on Spray Characteristics of Hydrous Ethanol–Gasoline Blends
Authors: Shi Xiuyong , Qian Weiwei , Liao Yansu , Ma Xiao , Wang Qiwei , Ni Jimin
Published: March 2022

Hydrous ethanol application in engines can not only improve combustion and reduce emissions but also save energy consumption in the production process, which is a potential alternative fuel for engines. However, little research has been conducted on the influences of hydrous ethanol, gasoline, and hydrous ethanol–gasoline blends on spray characteristics, especially the phenomenon of flash boiling. In this investigation, the spray characteristics of hydrous ethanol and gasoline have been conducted using a constant volume chamber system, and the spray characteristics of hydrous ethanol–gasoline blends have been simulated using validated models. The results show that hydrous ethanol fuel is more likely to enter a flash-boiling state in comparison with gasoline. In addition, the spray penetration of hydrous ethanol is higher than that of gasoline, which increases by 10% approximately under the same temperature. Moreover, the spray cone angle of test fuels is between 32 deg and 43 deg and decreases with the increase of back pressure in trend. Besides, the spray projection area of hydrous ethanol and gasoline decreases significantly with the increase of back pressure. In terms of simulation, the spray penetration of E10w, E20w, E50w, and E85w fuels decreases with the increase of back pressure.
Computational Investigations of Spray Atomization and Evaporation Under Cold-Start Conditions of a Diesel Engine
Authors: Sonawane Utkarsha , Agarwal Avinash Kumar
Published: March 2022

Unburnt hydrocarbon emissions and combustion instability are severe issues in diesel engines during cold starting. This simulation study aims to provide insights for improving the cold-start issues of diesel engines. Computational analysis of the diesel spray and evolution of plumes from a 7-hole injector was done in a constant volume quiescent spray chamber for analyzing the effect of fuel temperature. This study was based on a comprehensive numerical analysis using CONVERGE computational fluid dynamics (CFD) software, where an Eulerian–Lagrangian approach was adopted in a large eddy simulation (LES) framework. Diesel engine-like cold-start conditions were replicated by reducing the fuel temperatures to 250 K to simulate freezing conditions outside. This computational study compares fuel sprays at 250 K with 312 K into a relatively colder ambient temperature of 626 K vis-a-vis high-temperature diesel engine-like ambient conditions with ambient temperature to 961 K to investigate the degree of spray characteristics improvements due to increased fuel temperature. The predicted liquid spray penetration obtained by simulations agreed well with the experimental data for fuel temperatures injected into the ambient at cold (626 K) and hot (961 K) engine-like ambient conditions. The available empirical relations justify the simulation results of this study. Results showed that fuel and ambient temperatures significantly affected the spray atomization and evaporation characteristics. A higher reduction in liquid penetration length was found with increasing fuel temperature at hot ambient conditions. Increasing ambient temperature also improved the evaporation characteristics of the spray droplets. Vapor formation for the same increase in fuel temperature was higher at hot ambient temperature than the cold. Fuel temperature had a major role in the spray atomization process, whereas the ambient temperature affected the spray evaporation process. However, fuel and ambient temperatures had only a minor effect on the distribution of total kinetic energy (TKE). Among all test conditions, a fuel temperature of 312 K sprayed in hot ambient conditions showed superior fuel spray atomization and evaporation. Hence, to tackle the cold-start of diesel engines, measures taken to increase the fuel and ambient temperatures simultaneously proved to be useful.
A Model of Perfectionism, Moral Disengagement, Altruism, and Antisocial and Prosocial Behaviors in Wheelchair Athletes
Authors: Atkinson Frazer , Martin Jeffrey J. , Moore E. Whitney G.
Published: March 2022

Two forms of perfectionism were examined in the present study to see whether they predicted prosocial and antisocial behaviors in sport through moral disengagement and altruism in a sample of 327 wheelchair basketball and rugby athletes (M = 33.57 years, SD = 10.51; 83% male). Using structural equation modeling, the following significant direct and indirect effects were found. First, perfectionistic strivings positively predicted perceived prosocial behaviors and altruism. Second, perfectionistic concerns negatively predicted altruism and prosocial behaviors and positively predicted moral disengagement. Third, antisocial behaviors were positively predicted by moral disengagement and altruism. Furthermore, perfectionistic concerns indirectly predicted antisocial behaviors positively through moral disengagement and negatively through altruism. Finally, perfectionistic strivings positively predicted antisocial behaviors through altruism. Results provided partial support for the role of perfectionism in predicting prosocial and antisocial behaviors through moral disengagement among athletes with a disability.
Supplemental Material: Five million years of high atmospheric CO2 in the aftermath of the Permian-Triassic mass extinction
Authors: Joachimski Michael M , al. et
Published: March 2022

Detailed description of locations, samples, and methods, Figures S1–S3, and Tables S1–S4.
Supplemental Material: Looking upstream with clumped and triple oxygen isotopes of estuarine oyster shells in the early Eocene of California, USA
Authors: Kelson Julia R. , al. et
Published: March 2022

Additional details on the sample preparation, analytical methods, screening for diagenesis and vital effects, carbonate-water triple oxygen isotope fractionation, and the mixing model and code that is used to calculate δ 18Ofw
Supplemental Material: Fluid inclusion evidence for extreme overpressure induced by gas generation in sedimentary basins
Authors: Wang Xiaolin , al. et
Published: March 2022

Geological background, methods, discussion, Figures S1–S6, and Tables S1–S5
Specificity of Growth and Synthesis of Secondary Metabolites in Cultures in vitro Digitalis lanata Ehrh.
Authors: Tomilova S. V. , Kochkin D. V. , Tyurina T. M. , Glagoleva E. S. , Labunskaya E. A. , Galishev B. A. , Nosov A. M.
Published: March 2022

Rhizogenic, callus, and suspension cultures in vitro were obtained for Digitalis lanata and their growth, cytophysiological and biochemical characteristics were investigated. The obtained cultures were characterized by good growth characteristics (growth indexes I in the range of 5–13). Suspension cell culture had a specific growth rate μ within 0.2–0.3 days–1 and it was characterized by a two-phase growth curve (growth retardation during the exponential phase). In the obtained cultures, a study of the qualitative and quantitative composition of secondary metabolites by UPLC-ESI-MS and HPLC-ESI-MS showed the absence of cardiac glycosides. At the same time, phenylethanoids and steroidal glycosides of the furostanol type were found in all studied cultures. The total content of phenylethanoids in callus and suspension cultures was approximately 0.5% of the dry biomass. Based on the results of mass spectrometry, ten phenylethanoid structures, including digiciliside A, digiciliside B, maxoside, purpureaside E, and their methyl derivatives and isomers, and also seven furostanol glycosides with aglycones tigogenin and gitogenin were identified. It has been shown that the composition of secondary metabolites depends on the degree of cell differentiation: furostanol glycosides were prevalent in a rhizogenic culture consisting mainly of differentiated cells, while the diversity of phenylethanoids significantly increases in callus and suspension cell cultures consisting of dedifferentiated cells. The results of the study confirm the hypothesis put forward in our previous works about the specificity of secondary metabolism and its high intensity in plant cell cultures.
Microcystic stromal tumour of testis
Authors: Hoogland Marije , Bleumer Ivar , Suurmeijer Albert
Published: March 2022

Within the group of gonadal sex cord-stromal tumours, microcystic stromal tumour (MCST) is a rare entity. In the literature, most case series and reviews discussed MCST arising in the ovary, only one case-report concerned a testicular MCST. We present a Caucasian man in his late 30s, who presented with an MCST in his right testis. The tumour was encapsulated and composed of vaguely lobulated cellular nodules and cystic spaces with bland spindle cells and hyalinised fibrous stroma. By immunohistochemistry, the tumour cells expressed cluster designation 10, androgen receptor, steroidogenic factor-1 and nuclear beta-catenine, and there was focal nuclear expression of cyclin D1. Molecular diagnostics confirmed the presence of an exon 3 mutation (c.98C>T) in theCTNNB1gene. These features are similar to MSCT described in the ovary. Clinical follow-up (more than 1 year) was uneventful.

Although the clinical and radiological presentation was that of a possible malignant testicular lesion, this entity is benign.
Household food insecurity, maternal nutrition, environmental risks and infants’ health outcomes: protocol of the IMPALA birth cohort study in Uganda
Authors: Terfa Zelalem G , Nantanda Rebecca , Lesosky Maia , Devereux Graham , Obasi Angela , Mortimer Kevin , Khan Jahangir , Rylance Jamie , Niessen Louis Wihelmus
Published: March 2022

Introduction

In low- and middle-income countries (LMICs), food insecurity and undernutrition disproportionately affect women of reproductive age, infants and young children. The disease burden from undernutrition in these vulnerable sections of societies remains a major concern in LMICs. Biomass fuel use for cooking is also common in LMICs. Empirical evidence from high-income countries indicates that early life nutritional and environmental exposures and their effect on infant lung function are important; however, data from sub-Saharan Africa are scarce.

Aim

To estimate the association between infant lung function and household food insecurity, energy poverty and maternal dietary diversity.

Methods and analysis

Pregnant women will be recruited in an existing Health and Demographic Surveillance Site in South-West Uganda. Household food insecurity, sources and uses of energy, economic measures and maternal dietary diversity will be collected during pregnancy and after birth. Primary health outcomes will be infant lung function determined by tidal breath flow and volume analysis at 6–10 weeks of age. Infant weight and length will also be collected.

A household Food Consumption Score and Minimum Dietary Diversity for Women (MDD-W) indicator will be constructed. The involved cost of dietary diversity will be estimated based on MDD-W. The association between household level and mothers’ food access indicators and infant lung function will be evaluated using regression models. The Multidimensional Energy Poverty Index (MEPI) will be estimated and used as an indicator of households’ environmental exposures. The association between household MEPI and infant lung function will be assessed using econometric models.

Ethics and dissemination

Ethical approvals have been obtained from Liverpool School of Tropical Medicine (18-059), the Uganda Virus Research Institute Ethics Committee (097/2018) and Uganda National Council for Science and Technology (SS 4846). Study results will be shared with participants, policy-makers, other stakeholders and published in peer-reviewed journals.