bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evaluation of the potential drug–drug interactions of savolitinib: Interaction with rifampicin, itraconazole, famotidine or midazolam
Authors: Ren Song , Vishwanathan Karthick , Cantarini Mireille , Frewer Paul , Hara Indira , Scarfe Graeme , Burke Wendy , Schalkwijk Stein , Li Yan , Han David , Goldwater Ronald
Published: July 2021

Aims

We investigated savolitinib pharmacokinetics (PK) when administered alone or in combination with rifampicin, itraconazole or famotidine, and investigated midazolam PK when administered with or without savolitinib in healthy males.

Methods

Savolitinib PK was evaluated before/after: rifampicin (600 mg once daily [QD] for 5 days); itraconazole (200 mg QD for 5 days); a single dose of famotidine (40 mg QD) 2 hours before savolitinib. Midazolam PK was evaluated before/after midazolam (1 mg QD) with or without savolitinib (600 mg QD). Each study enrolled 20, 16, 16 and 14 volunteers, respectively. Plasma samples were collected to determine the effect on PK.

Results

The geometric mean ratios (GMR, %) (90% confidence intervals [CIs]) for savolitinib alone and in combination for Cmax, AUC respectively, were 45.4 (41.4–49.9), 38.5 (34.2–43.3) in the rifampicin study (n = 18); 105.2 (87.7–126.3), 108.4 (96.3–122.1) in the itraconazole study (n = 16); and 78.8 (67.7–91.7), 87.4 (81.2–94.2) in the famotidine study (n = 16). The GMRs (90% CIs) for midazolam alone and in combination with savolitinib for Cmax, AUC respectively, were 84.1 (70.0–101.0), 96.7 (92.4–101.1) (n = 14). Savolitinib alone or in combination was well tolerated.

Conclusions

Co‐dosing of rifampicin significantly reduced exposure to savolitinib vs savolitinib alone; co‐dosing of itraconazole or midazolam with savolitinib had no clinically significant effect on savolitinib or midazolam PK, respectively. Co‐dosing of famotidine with savolitinib reduced exposure to savolitinib, although this was not considered clinically meaningful. No new savolitinib‐related safety findings were observed.
Haemophilia: factoring in new therapies
Authors: Fassel Hannah , McGuinn Catherine
Published: July 2021

Haemophilia is an inherited bleeding disorder in which the haemostatic defect results from deficiency of coagulation factor VIII (FVIII) in haemophilia A or factor IX (FIX) in haemophilia B. Traditional treatments for haemophilia have largely worked by directly replacing the missing coagulation factor, but face challenges due to the short half‐life of FVIII and FIX, the need for frequent intravenous access and development of neutralising antibodies to coagulation factors (inhibitors). Recent advances in haemophilia therapy have worked to eliminate these challenges. Half‐life extension of factor concentrates has lengthened the time needed between infusions, enhancing quality of life. Subcutaneous administration of therapeutics utilising alternative mechanisms to overcome inhibitors have expanded the options to prevent bleeding. Finally, initial successes with gene therapy offer a cautious hope for durable cure. In the present review, we will discuss currently available treatments, as well as highlight therapeutics in various stages of clinical development for the treatment of haemophilia A and B. In this review, we present therapies that are currently clinically available and highlight therapeutics that are in various stages of clinical development for the treatment of haemophilia A and B.
Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas
Authors: Nakao Tomoe , Matsuse Michiko , Saenko Vladimir , Rogounovitch Tatiana , Tanaka Aya , Suzuki Keiji , Higuchi Miyoko , Sasai Hisanori , Sano Tsutomu , Hirokawa Mitsuyoshi , Miyauchi Akira , Kawakami Atsushi , Mitsutake Norisato
Published: July 2021

Objective

Telomerase reverse transcriptase promoter (TERT‐p) mutations are strongly associated with tumour aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs). Since the TERT‐p mutations have been reported to be subclonal, it is unclear how accurately they can be detected by preoperative fine‐needle aspiration (FNA). The objective of this study was to analyse the concordance rate of the TERT‐p mutations between preoperative FNA and corresponding postoperative surgical specimens.

Design and Patients

Ninety‐six cases of PTC aged 55 years or older were studied. The mutational status of TERT‐p was detected by droplet digital polymerase chain reaction assay.

Results

The mutational status of the TERT‐p in FNA samples was highly concordant with that in postoperative formalin‐fixed and paraffin‐embedded (FFPE) specimens. The TERT‐p mutation was significantly associated with age, tumour size, extrathyroidal extension and the Ki‐67 labelling index in multivariate analysis in both FNA and FFPE samples.

Conclusions

The detection of the TERT‐p mutations using FNA samples has a good ability to predict disease aggressiveness and, therefore, could be clinically useful in the determination of PTC management.
Expression of microRNA‐21 and TIMP‐3 in paradoxical psoriasiform reactions during treatment with antitumor necrosis factor agents
Authors: Navarro Raquel , Delgado‐Jiménez Yolanda , Guinea‐Viniegra Juan , Llamas‐Velasco Mar , Daudén Esteban
Published: July 2021

Background

Expression of microRNA‐21 (miR‐21) is increased in psoriasis, leading to reduced levels of epidermal tissue inhibitor of matrix metalloproteinase 3 (TIMP‐3), a highly potent inhibitor of the tumor necrosis factor alpha (TNFα) sheddase TACE (TNFα‐converting enzyme)/ADAM17. We described the profile of miR‐21 and TIMP‐3 in paradoxical psoriasiform reactions induced by anti‐TNFα drugs and in a control group to elucidate the pathogenesis of this reactions.

Methods

We performed an analytic, cross‐sectional, prospective, experimental case‐control study. We compared our findings with those of non‐induced psoriasis.

Results

We included 15 patients with a change of morphology (plaque to guttate psoriasis) and 10 patients with induced psoriasis (six palmoplantar pustulosis and four plaque psoriasis). Consecutive patients with different subtypes of non‐induced, non‐systemically treated psoriasis were included as a control group. We found that most cases with guttate psoriasis and with induced plaque psoriasis cases showed high expression of TIMP‐3 expression and decreased or poorly increased levels of miR‐21. The expression pattern was not homogeneous in the cases of induced palmoplantar pustulosis. These profiles differ from those of non‐induced psoriasis.

Conclusion

We conclude that various pro‐inflammatory cytokine profiles are involved in the pathogenesis of paradoxical psoriasiform reactions and non‐induced psoriasis.
Efficacy of double‐balloon enteroscopy‐assisted endoscopic balloon dilatation combined with stent deployment for hepaticojejunostomy anastomotic stricture
Authors: Tomoda Takeshi , Kato Hironari , Ueki Toru , Ogawa Tsuneyoshi , Hirao Ken , Akimoto Yutaka , Matsumoto Kazuyuki , Horiguchi Shigeru , Tsutsumi Koichiro , Okada Hiroyuki
Published: July 2021

Background

Hepaticojejunostomy anastomotic stricture (HJAS) is a significant complication of biliary reconstruction surgery. Endoscopic management of HJAS using double‐balloon enteroscopy has expanded; however, retrospective reports in this setting are limited. This study aimed to evaluate the efficacy of endoscopic balloon dilatation combined with stent deployment for HJAS.

Methods

This was a single‐arm prospective clinical trial involving 40 patients with treatment‐naïve HJAS enrolled between March 2016 and August 2019 at four endoscopy units in Japan. For HJAS, plastic stents combined with balloon dilatation were placed for 6 months after initial stenting. The primary outcome was HJ anastomosis patency 12 months after stent removal.

Results

The technical success rate was 97.5% (39/40). The failed case required percutaneous transhepatic biliary drainage using the rendezvous technique. All cases achieved successful endoscopic treatment. During the treatment period, four of 40 patients (10%) ended the study protocol due to unrelated causes and were excluded from the primary analysis. Among the 36 patients, clinical success was achieved in 34 (94.4%) patients. The remaining two patients achieved HJAS resolution after an additional 3 months. All 36 patients achieved HJAS resolution. Adverse events were observed in two patients (5.0%) who developed moderate cholangitis. During a median follow‐up of 21.3 months, HJAS recurrence was observed in 8.3% (3/36) with a median time to recurrence of 4.3 months and HJ anastomosis patency at 12 months was 94.4%.

Conclusions

Endoscopic balloon dilatation combined with plastic stent deployment for 6 months was a safe and effective strategy for HJAS. (Clinical Trial Registry no. UMIN000020613).
Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells
Authors: Hayashi Yoshiki , Shibata Arisa , Kamimura Keisuke , Kobayashi Satoru
Published: July 2021

The Drosophila female germline stem cell (GSC) niche provides an excellent model for understanding the stem cell niche in vivo. The GSC niche is composed of stromal cells that provide growth factors for the maintenance of GSCs and the associated extracellular matrix (ECM). Although the function of stromal cells/growth factors has been well studied, the function of the ECM in the GSC niche is largely unknown. In this study, we investigated the function of syndecan and perlecan, molecules of the heparan sulfate proteoglycan (HSPG) family, as the main constituents of the ECM. We found that both of these genes were expressed in niche stromal cells, and knockdown of them in stromal cells decreased GSC number, indicating that these genes are important niche components. Interestingly, our genetic analysis revealed that the effects of syndecan and perlecan on the maintenance of GSC were distinct. While the knockdown of perlecan in the GSC niche increased the number of cystoblasts, a phenotype suggestive of delayed differentiation of GSCs, the same was not true in the context of syndecan. Notably, the overexpression of syndecan and perlecan did not cause an expansion of the GSC niche, opposing the results reported in the context of glypican, another HSPG gene. Altogether, our data suggest that HSPG genes contribute to the maintenance of GSCs through multiple mechanisms, such as the control of signal transduction, and ligand distribution/stabilization. Therefore, our study paves the way for a deeper understanding of the ECM functions in the stem cell niche.
A systematic review of outcome reporting for interventions to treat people with diabetic foot ulceration
Authors: Dovell George , Staniszewska Aleksandra , Ramirez Jozel , Murray Ines , Ambler Graeme K. , Twine Christopher P. , Hinchliffe Robert J.
Published: July 2021

Background

Diabetic foot ulceration (DFU) is a challenging clinical problem that affects up to a quarter of patients with diabetes in their lifetime. An agreed set of outcomes for assessing treatments or interventions for DFU has not previously been considered. The aim of this study was to identify outcomes that are reported in clinical studies assessing a treatment or intervention for DFU, to inform the development of a core outcome set (COS).

Methods

Systematic literature searches were performed between January 2016 and March 2019. The search strategy was pre‐registered with PROSPERO (CRD42019128250). Two authors independently screened abstracts for full text review. Outcomes were extracted from selected papers verbatim and categorized into domains according to established taxonomy. Consistency of outcome reporting was assessed. Overlapping outcomes were merged independently to condense the extracted list of outcomes for use in forthcoming consensus processes.

Results

Of 4645 abstracts identified, 114 studies met the inclusion criteria. There were 69 randomized studies, 40 prospective studies and 5 protocols. Some 948 outcomes were extracted verbatim. Outcome reporting was consistent for 474 (53%) outcomes. De‐duplication left 714 unique verbatim outcomes across 33 domains. Merging of overlapping unique verbatim outcomes established 95 merged outcomes.

Conclusion

This study describes contemporary outcomes reported in studies assessing interventions for DFU. Outcome reporting is considered to be poor as it was consistent in just over half of outcomes extracted. Merging of outcomes has identified 95 outcomes that can be taken forward in the development of a COS.
Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin‐treated adults with type 2 diabetes and risk factors for hypoglycaemia
Authors: Goldenberg Ronald M. , Aroda Vanita R. , Billings Liana K. , Christiansen A. Sia Louise , Meller Donatsky Anders , Parvaresh Rizi Ehsan , Podgorski Gracjan , Raslova Katarina , Klonoff David C. , Bergenstal Richard M.
Published: July 2021

Aims

To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes.

Materials and Methods

We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin‐treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16‐week titration and 2‐week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once‐weekly titration (target: 3.9–5.0 mmol/L) was based on pre‐breakfast self‐measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9–7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels.

Results

At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD −0.88% [95% CI: −1.34, −0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed.

Conclusions

Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin‐treated people with type 2 diabetes.
Temporal prediction elicits rhythmic preactivation of relevant sensory cortices
Authors: Barne Louise Catheryne , Cravo André Mascioli , de Lange Floris P. , Spaak Eelke
Published: July 2021

Being able to anticipate events before they happen facilitates stimulus processing. The anticipation of the contents of events is thought to be implemented by the elicitation of prestimulus templates in sensory cortex. In contrast, the anticipation of the timing of events is typically associated with entrainment of neural oscillations. It is so far unknown whether and in which conditions temporal expectations interact with feature‐based expectations, and, consequently, whether entrainment modulates the generation of content‐specific sensory templates. In this study, we investigated the role of temporal expectations in a sensory discrimination task. We presented participants with rhythmically interleaved visual and auditory streams of relevant and irrelevant stimuli while measuring neural activity using magnetoencephalography. We found no evidence that rhythmic stimulation induced prestimulus feature templates. However, we did observe clear anticipatory rhythmic preactivation of the relevant sensory cortices. This oscillatory activity peaked at behaviourally relevant, in‐phase, intervals. Our results suggest that temporal expectations about stimulus features do not behave similarly to explicitly cued, nonrhythmic, expectations, yet elicit a distinct form of modality‐specific preactivation.
Long‐term effect of biochar on physical properties of agricultural soils with different textures at pre‐industrial charcoal kiln sites in Wallonia (Belgium)
Authors: Zanutel Martin , Garré Sarah , Bielders Charles L.
Published: July 2021

Besides its carbon (C) sequestration potential, biochar is being promoted as an amendment to improve soil quality. Burying biochar in soils is known to affect soil physical quality in the short‐term (<5 years), although the intensity of these effects depends on soil texture and biochar concentration especially. However, the long‐term effects of biochar remain largely unknown, yet are important to quantify given biochar's persistency in soils. The objective of this study was therefore to assess the long‐term effect of biochar on physical properties as a function of biochar concentration for soils with differing textures. For this purpose, soil physical properties were measured in the topsoil of three fields (silt loam, loam and sandy loam textures) in Wallonia (southern Belgium) presenting former kiln sites containing charcoal more than 150 years old. Particle density and bulk density slightly decreased as a function of charcoal‐C content but the presence of charcoal in kiln sites did not affect total porosity. The water retention curve measurements revealed that water content was mostly affected in the mesopore range by the century‐old charcoal‐C content. This effect was strongest for the sandy loam. On the other hand, the presence of century‐old charcoal increased the hydraulic conductivity for pF values between 1.5 and 2 for the silt loam, whereas no effect of charcoal was observed for the loamy and sandy loam soils. Results are discussed with respect to biochar characteristics and the various ways in which biochar particles could be distributed within soils. Overall, the present study highlights a limited effect of century‐old charcoal on the pore size distribution (at constant porosity) and on the resulting soil physical properties.

Highlights

The effect of century‐old biochar on physical properties was investigated for 3 different soil textures.

Water retention was affected mostly in the mesopore range by biochar.

Small effect of biochar on hydraulic conductivity was observed for silt loam soil only.

Overall, there was a limited effect of century‐old biochar on soil physical properties.
COVID‐19 diagnosis system by deep learning approaches
Authors: Bhuyan Hemanta Kumar , Chakraborty Chinmay , Shelke Yogesh , Pani Subhendu Kumar
Published: July 2021

The novel coronavirus disease 2019 (COVID‐19) has been a severe health issue affecting the respiratory system and spreads very fast from one human to other overall countries. For controlling such disease, limited diagnostics techniques are utilized to identify COVID‐19 patients, which are not effective. The above complex circumstances need to detect suspected COVID‐19 patients based on routine techniques like chest X‐Rays or CT scan analysis immediately through computerized diagnosis systems such as mass detection, segmentation, and classification. In this paper, regional deep learning approaches are used to detect infected areas by the lungs' coronavirus. For mass segmentation of the infected region, a deep Convolutional Neural Network (CNN) is used to identify the specific infected area and classify it into COVID‐19 or Non‐COVID‐19 patients with a full‐resolution convolutional network (FrCN). The proposed model is experimented with based on detection, segmentation, and classification using a trained and tested COVID‐19 patient dataset. The evaluation results are generated using a fourfold cross‐validation test with several technical terms such as Sensitivity, Specificity, Jaccard (Jac.), Dice (F1‐score), Matthews correlation coefficient (MCC), Overall accuracy, etc. The comparative performance of classification accuracy is evaluated on both with and without mass segmentation validated test dataset.
Corporate social responsibility and shareholder wealth: New insights from information spillovers
Authors: Ge Qi , Li Ting
Published: July 2021

Utilizing comprehensive business news data, we examine the link between corporate social responsibility (CSR) and shareholder wealth through the information spillovers of news announcements. Specifically, we leverage competitor's news as an exogenous shock to peer firms' stock returns and explore how the resulting abnormal returns may be explained by their respective CSR performance. Our findings not only confirm an inverse relationship between CSR engagement and the size of stock market reactions but also suggest that such dampening effect may extend beyond the traditional product differentiation strategy and can be magnified with respect to the types and salience of news.
Treatment of medication overuse headache: Effect and predictors after 1 year—A randomized controlled trial
Authors: Carlsen Louise N. , Rouw Carolien , Westergaard Maria L. , Nielsen Mia , Munksgaard Signe B. , Bendtsen Lars , Jensen Rigmor H.
Published: July 2021

Background

Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow‐up period are lacking.

Objective

(1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year.

Methods

Patients with MOH and migraine and/or tension‐type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year.

Results

Of 120 patients, 96 completed 1‐year follow‐up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4–25.8) to 15.0 (13.0–17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7–13.9) in the W+P group, 10.8 days (95% CI: 7.6–14) in the P+pW group, and 7.9 days (95% CI: 5.1–10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09–1.31), more days with acute medication (aOR 1.11; 1.03–1.19), higher pain intensity (aOR 1.04; 1.01–1.08), and depression (aOR 4.7; 1.38–18.95), whereas higher self‐rated health (aOR 0.61; 0.36–0.97) and high caffeine consumption (aOR 0.40; 0.16–0.96) were predictors of a lower risk of chronic headache. No adverse events were reported.

Conclusions

All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.
Efficacy and safety of fremanezumab for episodic migraine prevention: Multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group trial in Japanese and Korean patients
Authors: Sakai Fumihiko , Suzuki Norihiro , Kim Byung‐Kun , Tatsuoka Yoshihisa , Imai Noboru , Ning Xiaoping , Ishida Miki , Nagano Kaori , Iba Katsuhiro , Kondo Hiroyuki , Koga Nobuyuki
Published: July 2021

Objective

To evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine.

Background

Episodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene‐related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine.

Methods

This Phase 3 randomized, placebo‐controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12‐week treatment period after the first dose.

Results

Of 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least‐squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (−4.0 ± 0.4, n = 121) and fremanezumab quarterly (−4.0 ± 0.4, n = 117) than with placebo (−1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12‐week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection‐site reactions were more common in fremanezumab‐treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%).

Conclusion

Fremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.
Finding a lost species in the ‘Lost World’: predicted habitat occupancy by an endemic butterfly in a Neotropical sky‐island archipelago
Authors: Rabelo Rafael M. , Oliveira Isabela Freitas , Magnusson William E.
Published: July 2021

Pantepui is a Neotropical archipelago of remote sky islands (tepuis) that harbours a unique and poorly known biota, such as the endemic butterfly Antirrhea ulei. The Vicariance‐Migration hypothesis argues that Pantepui biota originated from a complex succession of climatic shifts, causing up‐and‐down migrations of cool‐adapted species from the last glacial maximum (LGM) to the present.

We evaluated how environmental gradients affect A. ulei habitat occupancy and predict its distribution across the Eastern Pantepui. We also test whether the species had a broader distribution during the LGM, following the Vicariance‐Migration hypothesis.

We surveyed for butterflies across 14 plots at Uei tepui, following an elevational gradient. We used Bayesian occupancy modelling to evaluate how environmental gradients affect A. ulei occurrence and to predict the current and past species distribution.

Species habitat occupancy was strongly associated with environmental gradients. Our model correctly predicted the species occurrence at all localities previously reported to be occupied by the species, and also predicted the potential species occurrence on other tepuis. Our historical prediction of species distribution showed that the species likely had a broader distribution during the LGM, in comparison with its current restricted distribution.

Our historical predictions suggest that the species may have spread across the Eastern Pantepui during LGM and migrated up the tepuis during the Holocene warming, in accordance with the Vicariance‐Migration hypothesis. Our study shows how data from local standardised surveys can be useful to estimate the distribution pattern of other little‐studied species of the Pantepui biota.
Familiarity, attitudes and behaviours as key factors to explore plantain and amaranth flours as potential ingredients for sandwich bread
Authors: Bringas‐Gonzalez Valeria , Contreras‐Oliva Adriana , López‐Espíndola Mirna , Bello‐Pérez Luis Arturo , Herrera‐Corredor José Andrés
Published: July 2021

The objective was to identify the familiarity, attitudes and behaviours of consumers regarding amaranth and plantain‐based foods focusing on sandwich bread (SB). A total of 221 responses from Mexican consumers were collected using a questionnaire implemented in Google® Forms. Results showed that consumers were more familiar with foods based on amaranth (95%) than plantain (36%). A significant relationship (P < 0.05) of gender and familiarity with health implications of SB consumption was found. Women were aware of health implications, whereas men were not. Age had an important relationship with the emotions elicited from the consumption of SB. Younger participants indicated that they feel calm and older participants guilty. Age and gender are potential factors to guide the development of the SB formulation as a viable proposal to diversify products based on plantain and amaranth flours.
Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment
Authors: Yang Xiuxiu , Guo Yaxin , Chen Chen , Shao Bo , Zhao Luyang , Zhou Quanbo , Liu Jinbo , Wang Guixian , Yuan Weitang , Sun Zhenqiang
Published: July 2021

In recent years, an increasing number of studies have reported that intestinal microbiota have an important effect on tumour immunity by affecting the tumour microenvironment (TME). The intestinal microbiota are closely associated with various immune cells, such as T lymphocytes, natural killer cells (NK cells) and macrophages. Some bacteria, such asAkkermansia muciniphila (A.muciniphila)andLactobacillus reuteri (L.reuteri), have been shown to improve the effect of tumour immunity. Furthermore, microbial imbalance, such as the increased abundance ofFusobacterium nucleatum (F.nucleatum)andHelicobacter hepaticus (H.hepaticus), generally causes tumour formation and progression. In addition, some microbiota also play important roles in tumour immunotherapy, especially PD‐L1‐related therapies. Therefore, what is the relationship between these processes and how do they affect each other? In this review, we summarize the interactions and corresponding mechanisms among the intestinal microbiota, immune system and TME to facilitate the research and development of new targeted drugs and provide new approaches to tumour therapy.
Highly pathogenic avian influenza virus H5N2 (clade 2.3.4.4) challenge of mallards age appropriate to the 2015 midwestern poultry outbreak
Authors: Hall Jeffrey S. , Grear Daniel A. , Krauss Scott , Seiler J. Patrick , Dusek Robert J. , Nashold Sean W. , Webster Robert G.
Published: July 2021

Background

The 2015 highly pathogenic avian influenza virus (HPAIV) H5N2 clade 2.3.4.4 outbreak in upper midwestern U.S. poultry operations was not detected in wild birds to any great degree during the outbreak, despite wild waterfowl being implicated in the introduction, reassortment, and movement of the virus into North America from Asia. This outbreak led to the demise of over 50 million domestic birds and occurred mainly during the northward spring migration of adult avian populations.

Objectives

There have been no experimental examinations of the pathogenesis, transmission, and population impacts of this virus in adult wild waterfowl with varying exposure histories—the most relevant age class.

Methods

We captured, housed, and challenged adult wild mallards (Anas platyrhynchos) with HPAIV H5N2 clade 2.3.4.4 and measured viral infection, viral excretion, and transmission to other mallards.

Results

All inoculated birds became infected and excreted moderate amounts of virus, primarily orally, for up to 14 days. Cohoused, uninoculated birds also all became infected. Serological status had no effect on susceptibility. There were no obvious clinical signs of disease, and all birds survived to the end of the study (14 days).

Conclusions

Based on these results, adult mallards are viable hosts of HPAIV H5N2 regardless of prior exposure history and are capable of transporting the virus over short and long distances. These findings have implications for surveillance efforts. The capture and sampling of wild waterfowl in the spring, when most surveillance programs are not operating, are important to consider in the design of future HPAIV surveillance programs.
Incidence rates of influenza illness during pregnancy in Suzhou, China, 2015–2018
Authors: Chen Liling , Zhou Suizan , Bao Lin , Millman Alexander J. , Zhang Zhongwei , Wang Yan , Tan Yayun , Song Ying , Cui Pengwei , Pang Yuanyuan , Liu Cheng , Qin Jiangchun , Zhang Ping , Thompson Mark G. , Iuliano A. Danielle , Zhang Ran , Greene Carolyn M. , Zhang Jun
Published: July 2021

Background

Data on influenza incidence during pregnancy in China are limited.

Methods

From October 2015 to September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow‐up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza.

Results

In total, we enrolled 18 724 pregnant women median aged 28 years old, 37% in first trimester, 48% in second trimester, and 15% in third trimester, with seven self‐reported influenza vaccination during pregnancy. In the 18‐week epidemic period during October 2015 to September 2016, influenza incidence was 0.7/100 person‐months (95% CI: 0.5–0.9). In the cumulative 29‐week‐long epidemic during October 2016 to September 2017, influenza incidence was 1.0/100 person‐months (95% CI: 0.8–1.2). In the 11‐week epidemic period during October 2017 to September 2018, influenza incidence was 2.1/100 person‐months (95% CI: 1.9–2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza‐associated ARIs were mild, and <5.1% required hospitalization.

Conclusions

Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.
Responses to outgroup help: The role of type of help and sense of control
Authors: Halabi Samer , Dovidio John F. , Nadler Arie
Published: July 2021

Helping may be motivated by a variety of reasons, including the desire of helpers to enhance the power of the ingroup and diminish the power of the outgroup. Accordingly, receiving unsolicited assistance from an outgroup member is often responded to negatively by ingroup members because it can undermine feelings of the efficacy of one's group and ultimately threaten the position of one's group relative to the helper's group. The present research explored how a sense of control, induced incidentally, can ameliorate such negative consequences of being helped. Two studies employed a minimal group paradigm and examined the response to an offer of help from a member of another group (Experiments 1 and 2) compared to an offer from a member of the same group (Experiment 2). The results of these two experiments converged to reveal that having the opportunity to exert control, even incidentally, can ameliorate negative responses to an outgroup helper and to the outgroup as a whole. These findings have both theoretical and practical implications. Identifying factors, such as control, that can promote the acceptance of assistance from members of other groups can complement previous work focusing on influences that exacerbate negative reactions to help, providing a more comprehensive understanding of intergroup helping relations and informing interventions to improve relations between groups.

Theoretical and applied implications are discussed.
Adiponectin up‐regulates the decrease of myocardial autophagic flux induced by β1‐adrenergic receptor autoantibody partly dependent on AMPK
Authors: Sun Cong , Lu Jiebei , Long Yaolin , Guo Shuai , Jia Weiwei , Ning Na , Hao Haihu , Wang Xiaohui , Bian Yunfei , Liu Huirong , Wang Li
Published: July 2021

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β1‐adrenergic receptor autoantibody (β1‐AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β1‐AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up‐regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β1‐AA by up‐regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β1‐AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β1‐AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β1‐AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β1‐AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β1‐AA in cardiomyocytes. This study is the first time to confirm that β1‐AA could inhibit myocardial autophagic flux by down‐regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β1‐AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β1‐AA‐positive cardiac dysfunction.
Effects of codeine on esophageal peristalsis in humans using high resolution manometry
Authors: Chen Chien‐Lin , Wong Ming‐Wun , Hung Jui‐Sheng , Liang Shu‐Wei , Liu Tso‐Tsai , Yi Chih‐Hsun , Lin Lin , Orr William C. , Lei Wei‐Yi
Published: July 2021

Background and Aim

Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension‐induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults.

Methods

Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20–43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid‐esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed.

Results

Codeine significantly increased 4‐s integrated relaxation pressure (IRP‐4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP‐4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305).

Conclusions

In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.
A new palatable oral rehydration solution: A randomised controlled cross‐over study in patients with a high output stoma
Authors: Culkin Alison , Gabe Simon M. , Nightingale Jeremy M. D.
Published: July 2021

Background

Patients with a jejunostomy or high output stoma may need a glucose–sodium oral rehydration solution drink to maintain hydration. These solutions are unpalatable and a new flavoured pre‐packaged solution was developed.

Methods

After 8 h of fasting, 27 patients took 500 mL of the modified World Health Organization (WHO) cholera solution or Glucodrate® (Vitaflo) on two occasions in a cross‐over random order and urine and stomal output was collected for 6 h.

Results

There was a small but significant difference in net sodium absorption in favour of the modified WHO cholera solution (10 ± 28 mmol modified WHO cholera solution vs. −1 ± 26 mmol Glucodrate®, p = 0.01). However the Glucodrate® was more palatable, with 24 patients (89%) preferring it to the modified WHO cholera solution (p < 0.005).

Conclusions

Glucodrate® is a more palatable solution than the modified WHO cholera solution and is almost as effective and so can be used when patients find the modified WHO cholera solution unpalatable.
Language work and affect in adult language education
Authors: Barakos Elisabeth
Published: July 2021

This article considers the connection of language work and affect in the exemplary site of a private language education company as part of a larger discourse‐ethnography in Vienna, Austria. Using the lens of affect, I analyse the experience, management, and performance of affect as part of language trainers’ language work. I theorise on the connection of affect, ideology, and emotional labour to make sense of the tensions that language workers face over their neoliberal selfhood and their precarious and elite forms of employment. These findings show the pervasive role of affect in organizing language work, its costs and effects, and the ways in which affect is tied to ‘feeling rules’ through which language workers (have to) perform emotional labour by managing their own and others’ feelings and performances. The article expands current sociolinguistic engagements with affect as mediated modes of meaning‐making in the production networks of the new economy.
Sensory impairment: Natural result of aging
Authors: Tam Melissa , Koppel Kadri
Published: July 2021

Over the next 10 years, a generational group known as the Baby Boomers will become America's senior citizens and account for 22% of the country's population. Aging challenges such as sensory impairment may cause older adults to develop eating habits that may not align with developing medical conditions. This review addresses prevalence and severity of impairment for the five senses and the role of texture as human's age, such as the decline of olfactory acuity and the increase in basic taste thresholds. Despite the heterogenous impact of sensory impairment on older adults, it is not associated with reduced food liking. The food industry can implement strategies to help older adults overcome age‐related sensory decline to make food choices that promote healthy aging. Food products should be evaluated holistically, from packaging to last bite, to better guide and encourage food purchase, consumption, and liking toward healthy aging among older adults.

Practical Applications

Understanding the implications of age on the accuracy of senses helps the industry develop better strategies to encourage healthy food purchases and consumption toward healthy aging. Product development strategies should address both intrinsic and extrinsic attributes to overcome sensory impairment and to promote healthy nutrition and aging.
Vitamin D metabolism and disorders in dogs and cats
Authors: Clarke K. E. , Hurst E. A. , Mellanby R. J.
Published: July 2021

Vitamin D plays an important role in regulating calcium metabolism and in the development and maintenance of skeletal health of companion animals. There is also a growing interest in understanding the role vitamin D plays in non‐skeletal health in both human and veterinary patients. This review provides an update of our current understanding of vitamin D biology in dogs and cats and gives an overview of how vitamin D metabolism can be assessed in companion animals. Congenital and acquired vitamin D disorders are then summarised before the review concludes with a summary of recent studies which have explored the role of vitamin D in the development and outcomes of non‐skeletal diseases of dogs and cats.
Generalized binary vector autoregressive processes
Authors: Jentsch Carsten , Reichmann Lena
Published: July 2021

Vector‐valued‐60 extensions of univariate generalized binary auto‐regressive (gbAR) processes are proposed that enable the joint modeling of serial and cross‐sectional‐50 dependence of multi‐variate binary data. The resulting class of generalized binary vector auto‐regressive (gbVAR) models is parsimonious, nicely interpretable and allows also to model negative dependence. We provide stationarity conditions and derive moving‐average‐type representations that allow to prove geometric mixing properties. Furthermore, we derive general stochastic properties of gbVAR processes, including formulae for transition probabilities. In particular, classical Yule–Walker equations hold that facilitate parameter estimation in gbVAR models. In simulations, we investigate the estimation performance, and for illustration, we apply gbVAR models to particulate matter (PM10, ‘fine dust’) alarm data observed at six monitoring stations in Stuttgart, Germany.
Of bars and stripes: A Malawi cichlid hybrid cross provides insights into genetic modularity and evolution of modifier loci underlying colour pattern diversification
Authors: Gerwin Jan , Urban Sabine , Meyer Axel , Kratochwil Claudius F.
Published: July 2021

Understanding the origins of phenotypic diversity among closely related species remains an important largely unsolved question in evolutionary biology. With over 800 species, Lake Malawi haplochromine cichlid fishes are a prominent example of extremely fast evolution of diversity including variation in colouration. Previously, a single major effect gene, agrp2 (asip2b), has been linked to evolutionary losses and gains of horizontal stripe patterns in cichlids, but it remains unknown what causes more fine‐scale variation in the number and continuity of the stripes. Also, the genetic basis of the most common colour pattern in African cichlids, vertical bars, and potential interactions between the two colour patterns remain unknown. Based on a hybrid cross of the horizontally striped Lake Malawi cichlid Pseudotropheus cyaneorhabdos and the vertically barred species Chindongo demasoni we investigated the genetic basis of both colour patterns. The distribution of phenotypes in the F2 generation of the cross indicates that horizontal stripes and vertical bars are independently inherited patterns that are caused by two sets of genetic modules. While horizontal stripes are largely controlled by few major effect loci, vertical bars are a highly polygenic trait. Horizontal stripes show substantial variation in the F2 generation that, interestingly, resemble naturally occurring phenotypes found in other Lake Malawi cichlid species. Quantitative trait loci (QTL) mapping of this cross reveals known (agrp2) and unknown loci underlying horizontal stripe patterns. These findings provide novel insights into the incremental fine‐tuning of an adaptive trait that diversified through the evolution of additional modifier loci.