bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical trial: seven‐day vonoprazan‐ versus 14‐day proton pump inhibitor‐based triple therapy for first‐line Helicobacter pylori eradication
Authors: Ang Daphne , Koo Seok Hwee , Chan Yiong Huak , Tan Thean Yen , Soon Gaik Hong , Tan Chin Kimg , Lin Kenneth Weicong , Krishnasamy‐Balasubramanian Jaydeesh‐Khanna , Wong Yu Jun , Kumar Rahul , R Rajesh , Tan Yiyuan , Ong Peng‐Lan Jeannie , Tan Yi‐Lyn Jessica , Li James Weiquan , Kwek Andrew Boon‐Eu , Ang Tiing Leong
Published: June 2022

Background

One‐week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)‐based triple therapy for first‐line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2‐week PPI‐based triple therapy.

Aim

To verify the non‐inferiority of 1‐week vonoprazan‐based triple therapy versus 2‐week PPI‐based triple therapy as first‐line H. pylori eradication in a multiracial Asian cohort.

Methods

Randomised controlled trial of treatment‐naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups.

Results

Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan‐ (n = 119) or PPI‐based (n = 125) triple therapy. Eradication rates by intention‐to‐treat analysis were 87.4% (vonoprazan‐based triple therapy) versus 88.0% (PPI‐based triple therapy. By per protocol analysis: 96.3% (vonoprazan‐based triple therapy) versus 94.0% (PPI‐based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4–96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups.

Conclusion

One‐week vonoprazan‐based triple therapy achieved comparable efficacy to 2‐week PPI‐based triple therapy and was well tolerated.
Functional variants in the promoter region of sulfotransferase 1C1 gene associated with estrogen degradation in gilts
Authors: Gao Qinxue , Chu Qingpo , Liu Mingzheng , Gao Siyuan , Xu Qinglei , Zhou Bo
Published: June 2022

Chinese indigenous Mi gilts have clearer estrus expression than European Large White gilts, and sulfotransferase 1C1 (SULT1C1) gene was differentially expressed between them. To investigate the differential expression mechanism of porcine SULT1C1 gene, we cloned its promoter region and predicted its activity. Six deletion expression vectors (P1, P2, P3, P4, P5, and P6) for the promoter of SULT1C1 gene were constructed. Vector P3 (−1084/+261) had the highest expression activity, whereas vector P4 (−642/+261) showed a reduced in promoter activity, which suggests that the core promoter region of SULT1C1 gene is located between −1084 bp and −642 bp. Two single nucleotide polymorphisms (SNPs), c. – 994 G > A (rs345070974) and c. – 946 G > A (rs337902009) were found in Mi and Large White gilts between −1100 and −661 bp, and the expression vectors with four haplotypes (GG, AA, GA, and AG) of two SNPs were constructed. The relative luciferase activity of vector with haplotype GG was the greatest among four vectors. These indicate that c. – 994 G > A and c. – 946 G > A are key mutations for promoter activity of SULT1C1 gene. Porcine SULT1C1 promoter with −994 G allele and −946 G allele significantly improved the gene expression level. It could be involved in different estrus expression between Large White and Mi gilts.
Risk factors for vancomycin‐associated acute kidney injury: A systematic review and meta‐analysis
Authors: Kim Jee Yun , Yee Jeong , Yoon Ha Young , Han Ji Min , Gwak Hye Sun
Published: June 2022

Aims

This systematic literature review and meta‐analysis aimed to evaluate the risk factors for vancomycin‐associated acute kidney injury (AKI) incidence.

Methods

This study assessed risk factors for vancomycin‐associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Fifty‐three studies were included in our meta‐analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16–1.87), Caucasian (OR 0.72, 95% CI: 0.58–0.90) and obesity (OR 1.46, 95% CI: 1.12–1.90) were associated with an increase in vancomycin‐associated AKIs. In terms of vancomycin‐related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06–2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43–3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48–5.44) increased the risks of vancomycin‐associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51–3.17) showed the highest odds of vancomycin‐associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44–7.87) showed the highest odds of vancomycin‐associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39–7.46), vasopressors, loop diuretics, piperacillin–tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17–2.58) increased the odds of vancomycin‐associated AKI.

Conclusion

Our results may help predict the risk of vancomycin‐associated AKI in the clinical setting.
Association between NMDAR antagonists, drug abuse and dependence: A disproportionality analysis from the WHO pharmacovigilance database
Authors: Revol Bruno , Lapeyre‐Mestre Maryse , Fouilhé Sam‐Laï Nathalie , Jouanjus Emilie
Published: June 2022

Ketamine and dextromethorphan are widely abused psychoactive substances. Inhibition of N‐methyl‐d‐aspartate receptors (NMDARs) results in neurobehavioural effects including hallucinations, “out of body” sensations and dissociative effects. However, little is known about a possible extended addictive class effect linked to pharmacologically‐related amino‐adamantane derivatives (e.g., amantadine and memantine). Using a quasi‐Bayesian analytic method, we investigated the potential association between the use of approved NMDAR antagonists (i.e., dextromethorphan, ketamine, amantadine and memantine) and the reporting of drug abuse and dependence in the WHO pharmacovigilance database (VigiBase®), which includes >21 million individual case safety reports collected from >130 countries. This disproportionality analysis identified a significant association for all investigated drugs: dextromethorphan (IC = 3.03 [2.97–3.09]), ketamine (IC = 1.70 [1.57–1.83]), amantadine (IC = 0.21 [0.06–0.35]) and memantine (IC = 0.27 [0.13–0.40]), suggesting a class effect for drug abuse and dependence. This first signal requires further investigations, but health professionals need to be alert to the potential of abuse of NMDAR antagonists, especially in the current “opioid epidemic” context, due to their growing interest as non‐opioid antinociceptive drugs.
Impact of combining vancomycin with proton pump inhibitors on the incidence of acute kidney injury
Authors: Aljohani Hanouf A. , Alharbi Hadeel A. , Basurrah Sarah A. , Alamoudi Sarah A. , Thabit Abrar K.
Published: June 2022

Vancomycin is a potent antibiotic against Gram‐positive bacteria; however, its use can be limited by nephrotoxicity. Several reports showed that proton pump inhibitors (PPIs) are associated with renal impairment. Many hospitalized patients are prescribed both drugs. As the literature lacks data on the potential augmentation of acute kidney injury (AKI) risk with this combination, we aimed to assess such risk. This was a retrospective cohort study of hospitalized patients receiving either VAN‐PPI or VAN alone for ≥72 h. Patients with a baseline serum creatinine (SCr) of ≥1.5 mg/dL were excluded. AKI incidence was assessed 3–5 days post VAN‐PPI or VAN initiation. Of 300 patients, 186 were in the VAN‐PPI group and 114 in the VAN group. The percentage of patients meeting AKI definition was not different between the two groups (11.8% vs. 7.9%; P = 0.277); however, the percentage change in SCr on Days 3–5 was only numerically higher in the VAN‐PPI group (1% vs. −2.4%; P = 0.242). The distribution of patients meeting different RIFLE class criteria was not different (P = 0.320). Using VAN with PPI was not associated with augmented AKI risk. However, monitoring kidney function would still be recommended as a standard good clinical practice when either drug is used.
Boy's math performance, compared to girls', jumps at age 6 (in the ELFE's data at least)
Authors: Fischer Jean‐Paul , Thierry Xavier
Published: June 2022

The mathematics achievement discrepancy between girls and boys, with its subsequent occupational consequences, is an issue that has received considerable attention in the literature. It is often referred to as the ‘math‐gap’ and favours boys. A major component of the explanation of this gap resides in determining its age of onset. We analyse here data from more than 10,000 (cross‐sectional study) and 2000 (longitudinal study) French students aged 4–7 years, tested in the framework of the Etude Longitudinale Française depuis l'Enfance (ELFE). The results allow to precisely determine the age of onset, since the gender difference, non‐existent (or even slightly in favour of girls) in kindergarten (4–5 years), is clearly in favour of boys in first grade (6–7 years). They could therefore provide an important element in the controversial debate on the origin of gender‐differentiated performance in mathematics.
Menstrual problems in chronic immune thrombocytopenia: A monthly challenge ‐ a cohort study and review
Authors: van Dijk Wobke E. M. , Punt Marieke C. , van Galen Karin P. M. , van Leeuwen Jeanette , Lely A. Titia , Schutgens Roger E. G.
Published: June 2022

Immune thrombocytopenia (ITP) may cause menstrual problems. This cross‐sectional study assessed menstrual problems in premenopausal chronic ITP women by several questionnaires, including the pictorial bleeding assessment calendar (PBAC; score ≥100 indicates heavy menstrual bleeding [HMB]), and the menorrhagia multiattribute scale (MMAS). Spearman was used for assessing correlations. A literature review was performed in Pubmed. The cohort comprised 37 women (mean age 31 ± 9). A total of 29/37 (78%) had experienced clinical menstrual problems in the present or past. Of the 33 patients who returned the PBAC, 13 (39%) had a score of ≥100. The median MMAS score was 79 (IQR 60–95). The PBAC scores correlated with the MMAS. Both questionnaires were unrelated to the platelet count. Patients with a levonorgestrel intrauterine device (LNG‐IUD) had lower PBAC scores than patients with other or no hormonal therapy. MMAS scores were correlated with fatigue. The review identified 14 papers. HMB occurred in 6%–55% at ITP diagnosis and 17%–79% during disease. Menstrual symptoms influenced the quality of life, particularly in patients with a low platelet count. This explorative study suggested that HMB is frequent in women with chronic ITP despite management and platelet counts >50 *109/l. An LNG‐IUD seemed to reduce blood loss significantly.
Repayment performance of joint‐liability microcredits: Metropolitan evidence on social capital and group names
Authors: Sahan Selay , Phimister Euan
Published: June 2022

This study empirically tests the predictions of four primary theories applicable to joint‐liability microcredit programs’ repayment performance using an administrative data in a metropolitan setting. We introduce a new variable, group names, as a proxy for social capital to capture cooperation, solidarity, and drive for success, which shows a significant positive impact of 9.9% on repayment performance. Precise calculations of residential distance between group members show a deterioration of repayment performance by 1.1% with a 15‐min increase in minimum walking distance. The results also show that joint liability, sectoral diversification, type of sector that the borrowers facilitate, the ratio of new members in a group, characteristics of loan officers, loan amount, interest rate, income‐loan amount coverage ratio, the existence of senior members, average education, and diversity in income streams significantly affect repayment performance.
Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 2: feasibility data from a multicentre prospective observational cohort study to inform a future randomized controlled trial
Authors: Gilberts Rachael , McGinnis Elizabeth , Ransom Myka , Pynn Emma V. , Walker Benjamin , Brown Sarah , Trehan Pooja , Jayasekera Prativa , Veitch David , Hussain Walayat , Collins Jemma , Abbott Rachel Angharad , Chen Kun Sen , Nixon Jane
Published: June 2022

Background

Compression therapy is considered beneficial for postsurgical lower leg wound healing by secondary intention; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed.

Aim

To determine the feasibility of recruitment and estimate recruitment rate; to understand the standard postoperative wound management pathway; to determine uptake of optional additional clinic visits for healing confirmation; and to explore patient acceptability of compression bandaging and plan a future RCT.

Methods

Participant recruitment was performed from secondary care dermatology clinics, during a period of 22 months. Inclusion criteria were age ≥ 18 years, planned excision of keratinocyte cancer on the lower leg with healing by secondary intention and an ankle–brachial pressure index of ≥ 0.8. Exclusion criteria were planned primary closure/graft or flap; inability to receive, comply with or tolerate high compression; planned compression; or suspected melanoma. Patients were followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information was collected on healthcare resource use, unplanned compression, wound healing and an optional clinic visit to confirm healing.

Results

This study recruited 58 patients from 9 secondary care dermatology clinics over 22 months. Mean recruitment/centre/month was 0.8 (range 0.1–2.3). Four centres had dedicated Research Nurse support. The analysis population (n = 53) had weekly follow-up assessments. Standard care clinical contacts were: general practitioner (7 visits; 1.2%), community nurse (169; 28.5%), practice nurse visits (189; 31.8%) and dermatology clinic visits (138; 23.2%). Participants whose wounds healed (34 of 45; 75.6%) attended an optional clinic visit.

Conclusion

Data were obtained to inform a future RCT. Recruitment rates were found to be higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.
Current activities between the DevTox Berlin workshops and the Japanese Teratology Society Terminology Committee in harmonizing the terminology for classifying anomalies in laboratory animals in developmental toxicity studies: Report from the Satellite Workshop of the 60th Annual Meeting of the Japanese Teratology Society
Authors: Kuwagata Makiko , Sato Akira , Izumi Yuko , Chihara Kazuhiro , Yamasaki Hanako , Katsumata Yoshihiro , Ooshima Yojiro , Buschmann Jochen , Fujiwara Michio
Published: June 2022

In recent years, the Japanese Teratology Society has worked with the DevTox Berlin Workshops project to provide internationally consistent terminology for teratogenic effects. This paper summarizes a satellite workshop of the 60th Annual Meeting of the Japanese Teratology Society, which was entitled “Current activities between DevTox Berlin Workshops to develop a harmonized terminology for classifying anomalies in laboratory animals in developmental toxicity studies.” The Japanese Teratology Society ‐ Laboratory Animal Terminology Project (JTS‐LATP) reviewed “gray zone” anomalies and focused on developing criteria for reclassifying a large number of gray zone anomalies to clarify them and to make it easier to judge fetal categories. This effort will lead to international agreement, based on shared conceptions. The present article aimed to provide the reader with a summary of the issues discussed at the 2020 satellite meeting, which included discussions on open issues from the DevTox Berlin Workshops, ongoing work by the JTS‐LATP on gray zone (GZ) anomalies, current industrial concerns, and future challenges.
Further characterization of Borjeson‐Forssman‐Lehmann syndrome in females due to de novo variants in PHF6
Authors: Gerber Céline B. , Fliedner Anna , Bartsch Oliver , Berland Siren , Dewenter Malin , Haug Marte , Hayes Ian , Marin‐Reina Purificacion , Mark Paul R. , Martinez‐Castellano Francisco , Maystadt Isabelle , Karadurmus Deniz , Steindl Katharina , Wiesener Antje , Zweier Markus , Sticht Heinrich , Zweier Christiane
Published: June 2022

While inherited hemizygous variants in PHF6 cause X‐linked recessive Borjeson‐Forssman‐Lehmann syndrome (BFLS) in males, de novo heterozygous variants in females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, and linear skin pigmentation. By personal communication with colleagues, we assembled 11 additional females with BFLS due to variants in PHF6. We confirm the distinct phenotype to include variable intellectual disability, recognizable facial dysmorphism and other anomalies. We observed skewed X‐inactivation in blood and streaky skin pigmentation compatible with functional mosaicism. Variants occurred de novo in 10 individuals, of whom one was only mildly affected and transmitted it to her more severely affected daughter. The mutational spectrum comprises a two‐exon deletion, five truncating, one splice‐site and three missense variants, the latter all located in the PHD2 domain and predicted to severely destabilize the domain structure. This observation supports the hypothesis of more severe variants in females contributing to gender‐specific phenotypes in addition to or in combination with effects of X‐inactivation and functional mosaicism. Therefore, our findings further delineate the clinical and mutational spectrum of female BFLS and provide further insights into possible genotype–phenotype correlations between females and males.
Modeling the Remote Associates Test as Retrievals from Semantic Memory
Authors: Schatz Jule , Jones Steven J. , Laird John E.
Published: June 2022

The Remote Associates Test (RAT) is a word association retrieval task that consists of a series of problems, each with three seemingly unrelated prompt words. The subject is asked to produce a single word that is related to all three prompt words. In this paper, we provide support for a theory in which the RAT assesses a person's ability to retrieve relevant word associations from long‐term memory. We present a computational model of humans solving the RAT and investigate how prior knowledge and memory retrieval mechanisms influence the model's ability to match human behavior. We expand prior modeling attempts by investigating multiple large knowledge bases and by creating a cognitive process model that uses long‐term memory spreading activation retrieval processes inspired by ACT‐R and implemented in Soar. We evaluate multiple model variants for their ability to model human problem difficulty, including the incorporation of noise and base‐level activation into memory retrieval. We conclude that the main factors affecting human difficulty are the existence of associations between prompt words and solutions, the relative strengths and directions of those associations compared to associations to other words, and the ability to perform multiple retrievals.
The Emergence of Gender Associations in Child Language Development
Authors: Prystawski Ben , Grant Erin , Nematzadeh Aida , Lee Spike W. S. , Stevenson Suzanne , Xu Yang
Published: June 2022

Gender associations have been a long‐standing research topic in psychological and social sciences. Although it is known that children learn aspects of gender associations at a young age, it is not well understood how they might emerge through the course of development. We investigate whether gender associations, such as the association of dresses with women and bulldozers with men, are reflected in the linguistic communication of young children from ages 1–5. Drawing on recent methods from machine learning, we use word embeddings derived from large text corpora including news articles and web pages as a proxy for gender associations in society, and we compare those with the gender associations of words uttered by caretakers and children in children's linguistic environment. We quantify gender associations in childhood language throughgender probability, which measures the extent to which word usage frequencies in speech to and by girls and boys are gender‐skewed. By analyzing 4,875 natural conversations between children and their caretakers in North America, we find that frequency patterns in word usage of both caretakers and children correlate strongly with the gender associations captured in word embeddings through the course of development. We discover that these correlations diminish from the 1970s to the 1990s. Our work suggests that early linguistic communication and social changes may jointly contribute to the formation of gender associations in childhood.
A Cross‐Modal and Cross‐lingual Study of Iconicity in Language: Insights From Deep Learning
Authors: de Varda Andrea Gregor , Strapparava Carlo
Published: June 2022

The present paper addresses the study of non‐arbitrariness in language within a deep learning framework. We present a set of experiments aimed at assessing the pervasiveness of different forms of non‐arbitrary phonological patterns across a set of typologically distant languages. Different sequence‐processing neural networks are trained in a set of languages to associate the phonetic vectorization of a set of words to their sensory (Experiment 1), semantic (Experiment 2), and word‐class representations (Experiment 3). The models are then tested, without further training, in a set of novel instances in a language belonging to a different language family, and their performance is compared with a randomized baseline. We show that the three cross‐domain mappings can be successfully transferred across languages and language families, suggesting that the phonological structure of the lexicon is pervaded with language‐invariant cues about the words' meaning and their syntactic classes.
Finish What you Started: 2‐Year‐Olds Motivated by a Preference for Completing Others’ Unfinished Actions in Instrumental Helping Contexts
Authors: Michael John , Green Alexander , Siposova Barbora , Jensen Keith , Kita Sotaro
Published: June 2022

A considerable body of research has documented the emergence of what appears to be instrumental helping behavior in early childhood. The current study tested the hypothesis that one basic psychological mechanism motivating this behavior is a preference for completing unfinished actions. To test this, a paradigm was implemented in which 2‐year‐olds (n = 34, 16 females/18 males, mostly White middle‐class children) could continue an adult's action when the adult no longer wanted to complete the action. The results showed that children continued the adult's actions more often when the goal had been abandoned than when it had been reached (OR = 2.37). This supports the hypothesis that apparent helping behavior in 2‐year‐olds is motivated by a preference for completing unfinished actions.
Abnormal expression and clinical value analysis of long noncoding RNA cancer susceptibility candidate 2 in children with severe pneumonia complicated with respiratory failure
Authors: Ni Jie , Lu Junfei , Lu Ding
Published: June 2022

Objective

Severe pneumonia occurs commonly in children and is the main cause of clinical infant mortality. This study tested the expression pattern of long noncoding RNA cancer susceptibility candidate 2 (CASC2) in the serum of children with severe pneumonia and explored its clinical values.

Methods

Serum levels of CASC2 were detected in 145 children with severe pneumonia. All cases were divided into two groups based on their respiratory failure (RF) condition. Receiver operating characteristic (ROC) and Kaplan–Meier (K‐M) curves were plotted for the diagnostic and prognostic ability evaluation. Multivariate cox regression analysis was done for the examination of independent influence factors.

Results

The serum levels of CASC2 significantly decreased in children with severe pneumonia in contrast with healthy individuals and reached the lowest value in those with RF. Serum CASC2 can distinguish severe pneumonia and predicted the development of RF. Based on the 28‐day survival data, cases with low CASC2 levels had a poor survival rate. CASC2 (hazard ratio [HR] = 0.068, 95% confidence interval [CI] = 0.016–0.292, P < 0.001) and age (HR = 2.806, 95% CI = 1.240–6.394, P < 0.001) were independent influence factor for the poor prognosis of children with severe pneumonia.

Conclusion

Downregulation of serum CASC2 was related to the occurrence of RF in children with severe pneumonia and may be a predictor of the poor prognosis. This study will provide a potential biomarker for severe pneumonia treatment in clinic.
Prevalence of hookah smoking among Iranian pupils and university students: An updated systematic review and meta‐analysis
Authors: Zaheri Hamid , Raziani Yosra , Khademi Nesa , Moradi Yousef , Shahriari Hossein , Ghanei‐Gheshlagh Reza
Published: June 2022

Objective

Today, smoking is considered a pressing global health issue. The present study aimed to estimate the total prevalence of hookah smoking among pupils and university students in Iran.

Materials and Methods

This systematic review and meta‐analysis were conducted via searching in databases such as Scientific Information Database (SID), MagIran, Scopus, PubMed and Web of Sciences from inception to October 2021. We targeted observational studies evaluating the prevalence or frequency of hookah smoking among Iranian pupils and university students. Data analysis was performed using a random‐effects model, and the heterogeneity of the articles was assessed using Cochran'sQtest and theI2statistic.

Results

In total, 124 studies conducted on 155 115 subjects were reviewed. The lifetime prevalence of hookah smoking among high school students and university students was estimated at 34.4% and 32.3%, respectively. In addition, the frequency of hookah smoking within the past month/week (point prevalence) was estimated at 21.5% and 16.6% in university students and pupils, respectively. The frequency of hookah smoking within the past year (period prevalence) was also reported to be 22.5% and 20.8% in these groups, respectively. No significant correlation was observed between the prevalence of hookah smoking, sample size, year of publication and the mean age of the participants. Region 5 had the highest lifetime prevalence (41.7%) and period prevalence (27.1%). However, Region 1 had the highest point prevalence of hookah smoking (27.2%).

Conclusions

According to the results, hookah smoking is highly prevalent among Iranian pupils and university students. Therefore, proper educational interventions are required in the form of workshops and curricula to raise awareness regarding the hazardous effects of this unhealthy habit on the young generation.
Molecular analysis of NUT‐positive poromas and porocarcinomas identifies novel break points of YAP1::NUTM1 fusions
Authors: Snow Justin T. , Georgantzoglou Natalia , Green Donald C. , Parra Ourania , LeBlanc Robert E. , Yan Shaofeng , Sriharan Aravindhan , Momtahen Shabnam , Winnick Kimberley N. , Dimonitsas Emmanouil , Stavrianos Spiros , Lakiotaki Eleftheria , Korkolopoulou Penelope , Revelos Kyriakos , Guo Ruifeng , Linos Konstantinos
Published: June 2022

Background

Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1‐MAML2, YAP1‐NUTM1, and infrequently WWTR1‐NUTM1; YAP1‐NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1‐translocated tumors. This study sought to investigate potential novel NUTM1‐fusion partners among NUT IHC‐positive poromas and porocarcinomas.

Methods

Thirteen NUT IHC‐positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi‐institutional international cohort. Next‐generation sequencing (NGS) assessed for NUTM1 fusion partners.

Results

NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1‐NUTM1 (11/12 cases) and WWTR1‐NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read‐spanning YAP1‐NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case.

Conclusion

While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1‐NUTM1 fusion was detected in 11 cases (92%) and WWTR1‐NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.
Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes
Authors: Klein Klara R. , Boeder Schafer C. , Freeman Jennifer L. R. , Dunn Imogene , Dvergsten Chris , Madduri Supradeep , Giovannetti Erin R. , Valcarce Carmen , Buse John B. , Pettus Jeremy H.
Published: June 2022

Aims

To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D).

Materials and methods

Twenty‐three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta‐hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater.

Results

During the 7‐ to 10‐day treatment period, mean fasting plasma glucose was significantly reduced ( −27.6 vs. −4.4 mg/dL [−1.5 vs. −0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399‐treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399‐treated participants. As a result of higher bicarbonate values, none of the TTP399‐treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo‐treated participants.

Conclusions

When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.
RBP‐J deficiency promoted the proliferation and differentiation of CD133‐positive cells in both in vitro and in vivo studies
Authors: Ye Xin , Li Mengyi , Bian Wei , Wu Anting , Zhang Ting , Li Junwei , Zhou Peng , Cui Huairui , Ding Yu‐Qiang , Liao Min , Sun Chenyou
Published: June 2022

Although Notch signalling pathway could control the proliferation and differentiation of neural stem cells (NSCs), it is largely unknown about the effect of Notch signalling pathway on the neurogenesis of CD133‐positive cells. By using the primary cultured ependymal cells and the transgenic mouse, we found that CD133 immunoreactivity was exclusively localized in the ependymal layer of ventricles; moreover, most CD133‐positive cells were co‐labelled with Nestin. In addition, recombination signal binding protein J (RBP‐J), a key nuclear effector of Notch signalling pathway, was highly active in CD133‐positive cells. CD133‐positive cells can differentiate into the immature and mature neurons; in particular, the number of CD133‐positive cells differentiating into the immature and mature neurons was significantly increased following the deficiency or interference of RBP‐J in vivo or in vitro. By using real‐time qPCR and Western blot, we found that RBP‐J and Hes1 were downregulated, whereas Notch1 was upregulated in the expression levels of mRNAs and proteins following the deficiency or interference of RBP‐J. These results demonstrated RBP‐J deficiency promoted the proliferation and differentiation of CD133‐positive cells. Therefore, we speculated that RBP‐J could maintain CD133‐positive cells in the characteristics of NSCs possibly by regulating Notch1/RBP‐J/Hes1 pathway. It will provide a novel molecular insight into the function of RBP‐J as well as facilitate a future investigation of CD133‐positive cells with respect to their potential application in neurodegenerative disorder.
Evidence for origin of lavender foal syndrome among Egyptian Arabian horses in Egypt
Authors: AbouEl Ela Nahla Hussien , El Araby Iman E. , Saleh Ayman A. , Abd El‐fattah Amir H. , Hagag Naglaa M. , Brooks Samantha A. , Radwan Mohamed A. , Kalbfleisch Ted
Published: June 2022

Background

Lavender foal syndrome (LFS) is a fatal hereditary condition that is inherited in an autosomal recessive pattern. This detrimental mutation is more common in Arabian foals of Egyptian origin than foals from other bloodlines. Heterozygous horses are carriers of the LFS trait and appear normal, while recessive homozygous foals died shortly after birth due to serious complications. In Egypt, in 2014, an Egyptian foal died after manifestations of neurological signs and abnormal coat colour as LFS signs. Therefore, it is important to identify LFS carriers in the population of Arabian horses in Egypt and to encourage improvement of the Arabian horse industry in Egypt by constructing a breeding system based on genetic background in order to avoid mating between carriers and reduce financial losses from deaths of affected foals.

Objectives

To establish a PCR‐based test for detecting the MYO5A gene mutation causing LFS in the registered Arabian horse population in Egypt prior to breeding.

Study design

Cross sectional survey (n = 170) plus targeted sampling (n = 30).

Methods

A total of 200 samples were collected from an Arabian farm in Egypt and some of them were traced for LFS based on the farm records. The LFS genotypes were identified using the PCR‐RFLP technique, fragment analysis followed by sequence analysis.

Results

The overall mutated allele and genotype frequencies (N/L) were 0.08 and 16%, respectively.

Conclusion

The observed frequency of heterozygotes suggests foals affected with LFS will be produced among Arabian horses in Egypt. Therefore, screening of the entire population for this mutation should be undertaken in the breeding program.
Comparison of Malassezia spp. colonization between human skin exposed to high‐ and low‐ambient air pollution
Authors: Chueachavalit Chutinan , Meephansan Jitlada , Payungporn Sunchai , Sawaswong Vorthon , Chanchaem Prangwalai , Wongpiyabovorn Jongkonnee , Thio Hok Bing
Published: June 2022

The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air. Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analysed using high‐throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA. A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area. This study demonstrates that high‐ambient air pollution may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders.
Microalgal food sources greatly improve macroinvertebrate growth in detritus‐based headwater streams: Evidence from an instream experiment
Authors: Labed‐Veydert Tiphaine , Danger Michael , Felten Vincent , Bec Alexandre , Laviale Martin , Cellamare Maria , Desvilettes Christian
Published: June 2022

In forested headwater streams, inconspicuous food resources such as epilithic microalgae can play a major role owing to their content of long chain polyunsaturated fatty acids (PUFAs) that are essential for macroinvertebrate development. Yet, the use of these resources and their consequences for consumers and life‐history traits remain scarcely studied, especially for non‐herbivorous taxa.

Using instream mesocosms, we aimed to understand how two macroinvertebrate species, a shredder detritivore (Gammarus pulex) and a scraper (Rhithrogena semicolorata), use available organic resources under light versus shaded conditions (high and low amounts of phototrophic biofilm, respectively). We specifically focused on the origin of carbon (C) and essential lipids (PUFAs, sterols) assimilated by the two species and the effects of these compounds on their survival and growth.

When autotrophic biofilms were available (mesocosms exposed to light), both species experienced significantly higher growth than in mesocosms placed in the dark. In Rhithrogena nymphs, the survival and imago emergence rates were positively affected by access to autotrophic biofilms.

Using stable isotope analysis (δ13C and δ15N), we demonstrated that under dark conditions both macroinvertebrates assimilated C of detrital origin. Under light conditions, most of the C assimilated by R. semicolorata was derived from autotrophic biofilms and around 11% from fine detrital particles (FPOM). Gammarus pulex derived part of its C from detrital sources (mainly FPOM) and from autotrophic biofilms.

The results of isotopic analyses (δ13C) on fatty acids (FAs) and sterols showed that the scraper Rhithrogena was entirely dependent on autotrophic biofilms to meet its dietary FAs and sterol requirements. In contrast, detrital sources were quantitatively important for G. pulex both in terms of C and sterol supply, irrespective of the conditions tested. For these consumers, microalgae seemed to be a complementary food source, but yet essential to cover a large part of their requirements in long‐chain PUFAs.

This study clearly confirmed the ecological importance of autotrophic biofilms for two functional feeding groups of macroinvertebrates in headwater streams providing new insights on the trophic origin of sterols and long‐chain PUFAs in their diet.
Non‐native plant invasion can accelerate global climate change by increasing wetland methane and terrestrial nitrous oxide emissions
Authors: Bezabih Beyene Bahilu , Li Junjie , Yuan Junji , Dong Yanhong , Liu Deyan , Chen Zengming , Kim Jinhyun , Kang Hojeong , Freeman Chris , Ding Weixin
Published: June 2022

Approximately 17% of the land worldwide is considered highly vulnerable to non‐native plant invasion, which can dramatically alter nutrient cycles and influence greenhouse gas (GHG) emissions in terrestrial and wetland ecosystems. However, a systematic investigation of the impact of non‐native plant invasion on GHG dynamics at a global scale has not yet been conducted, making it impossible to predict the exact biological feedback of non‐native plant invasion to global climate change. Here, we compiled 273 paired observational cases from 94 peer‐reviewed articles to evaluate the effects of plant invasion on GHG emissions and to identify the associated key drivers. Non‐native plant invasion significantly increased methane (CH4) emissions from 129 kg CH4 ha−1 year−1 in natural wetlands to 217 kg CH4 ha−1 year−1 in invaded wetlands. Plant invasion showed a significant tendency to increase CH4 uptakes from 2.95 to 3.64 kg CH4 ha−1 year−1 in terrestrial ecosystems. Invasive plant species also significantly increased nitrous oxide (N2O) emissions in grasslands from an average of 0.76 kg N2O ha−1 year−1 in native sites to 1.35 kg N2O ha−1 year−1 but did not affect N2O emissions in forests or wetlands. Soil organic carbon, mean annual air temperature (MAT), and nitrogenous deposition (N_DEP) were the key factors responsible for the changes in wetland CH4 emissions due to plant invasion. The responses of terrestrial CH4 uptake rates to plant invasion were mainly driven by MAT, soil NH4+, and soil moisture. Soil NO3−, mean annual precipitation, and N_DEP affected terrestrial N2O emissions in response to plant invasion. Our meta‐analysis not only sheds light on the stimulatory effects of plant invasion on GHG emissions from wetland and terrestrial ecosystems but also improves our current understanding of the mechanisms underlying the responses of GHG emissions to plant invasion.
More than a feeling? What does compassion in healthcare ‘look like’ to patients?
Authors: Baguley Sofie I. , Pavlova Alina , Consedine Nathan S.
Published: June 2022

Objective

Compassion is important to patients and their families, predicts positive patient and practitioner outcomes, and is a professional requirement of physicians around the globe. Yet, despite the value placed on compassion, the empirical study of compassion remains in its infancy and little is known regarding what compassion ‘looks like’ to patients. The current study addresses limitations in prior work by asking patients what physicians do that helps them feel cared for.

Methods

Topic modelling analysis was employed to identify empirical commonalities in the text responses of 767 patients describing physician behaviours that led to their feeling cared for.

Results

Descriptively, seven meaningful groupings of physician actions experienced as compassion emerged: listening and paying attention (71% of responses), following‐up and running tests (11%), continuity and holistic care (8%), respecting preferences (4%), genuine understanding (2%), body language and empathy (2%) and counselling and advocacy (1%).

Conclusion

These findings supplement prior work by identifying concrete actions that are experienced as caring by patients. These early data may provide clinicians with useful information to enhance their ability to customize care, strengthen patient–physician relationships and, ultimately, practice medicine in a way that is experienced as compassionate by patients.

Public Contribution

This study involves the analysis of data provided by a diverse sample of patients from the general community population of New Zealand.
Analysis of protein denaturation, and chemical visualisation, of frozen grass carp surimi containing soluble soybean polysaccharides
Authors: Gao Wenhong , Wu Xinru , Ye Ruisen , Zeng Xin‐an , Brennan Margaret A. , Brennan Charles S. , Ma Ji
Published: June 2022

The mechanism of protein denaturation of frozen surimi enriched with soluble soybean polysaccharides (SSPS) was investigated. Near‐infrared (NIR) and hyperspectral imaging (HSI) technology were used to predict protein denaturation. The fresh grass carp surimi was divided into four groups with SSPS additions of 0%, 1%, 3% and 5%, respectively, which were frozen and stored at −18 °C. Samples were examined after 0, 1, 2, 4 and 8 weeks, for salt‐soluble protein content, total SH, NIR hyperspectral image and Raman spectrum features. The results showed that addition of SSPS decelerated protein degradation. After 8 weeks of storage, the 5% SSPS addition maintained the highest salt‐soluble protein content, while for total SH, 3% and 5% SSPS addition had similar effect. Raman spectra illustrated that SSPS had the ability of maintaining an α‐helix content, as well as decreasing the exposure of polar groups, and reducing the oxidation of SH group into disulphide bonds. NIR spectra showed that the overall reflectance of frozen surimi increased with the increase in SSPS. Two partial least squares regression (PLSR) models were established after pretreatment of HSI spectral statistics and selection of characteristic wavelengths. The distribution maps were finally generated based on the simplified PLSR models.
Glycaemic response of pseudocereal‐based gluten‐free food products: a review
Authors: Punia Bangar Sneh , Sharma Nitya , Singh Arashdeep , Phimolsiripol Yuthana , Brennan Charles S.
Published: June 2022

Rapid digestion and absorption of carbohydrates have become a health issue (high glycaemic index, GI), which can be a matter of greater concern when consumed in large quantities. Depending upon the influence of carbohydrates on the blood sugar levels, GI classifies carbohydrates (on a scale of 100) as low (<55), medium (55–70) and high (>70) GI foods. Among the pseudocereals, chia seed possesses relatively lower GI (28.53), as compared to buckwheat (52.35), amaranth (47.65) and quinoa (61.50). Consumers now prefer foods with a high GI over the ones with low GI to prevent various metabolic alterations. Celiac disease is a lifelong disorder prevalent worldwide and can only be controlled by following a strict lifelong gluten‐free diet. Therefore, pseudocereals could be a potential alternate for low GI food and developing gluten‐free food products, including bread, cookies, noodles and pasta. This review synthesises the recently published literatures on pseudocereals as a lowering GI and healthy food option. This review also gives insights into developing pseudocereals as a potential and novel ingredient for gluten‐free food applications and the latest research conducted worldwide.