bluuebunny/crossref_metadata_2025 huggingface dataset:
Probiotic vs. placebo and metformin: probiotic dietary intervention in polycystic ovary syndrome – A randomized controlled trial
Authors: Borzan Valentin , Riedl Regina , Obermayer-Pietsch Barbara
Published: April 2023

Background

Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as metformin, however both treatments are limited to specific symptoms and have common side effects.

Methods

This phase IV study is a monocentric, double blinded randomized clinical trial comparing the effects of six months of probiotic intervention to a placebo, with an additional open-label metformin arm as a positive control in a total of 180 participants with PCOS. The first of three visits is the screening visit, where inclusion/exclusion criteria are assessed. At the first visit, they are randomised into one of the three treatment arms equally and receive their study medication. After six months, all assessments from the first two visits are repeated. The primary endpoint is the change in free testosterone levels after the intervention, while secondary endpoints include changes in hormonal and metabolic parameters associated with PCOS as well as the gut microbial composition and diversity after intervention.

Discussion

Based on new insights into the role of the gut microbiome in PCOS development, this study is exploring the potential of using probiotics to treat women with PCOS symptoms. If successful, this new therapy approach could open a new realm of possibilities for treating PCOS. To our knowledge, this is the first study comparing probiotic intervention with not only placebo treatment, but also metformin. This study has been approved by the ethics committee of the Medical University of Graz (EC number 32–230 ex 19/20).

Registration

EudraCT number: 2020-000228-20. Clinicaltrials.gov identifier: NCT04593459.

Protocol version

Version 1.5 dated 29th November 2021.
Polycystic ovarian syndrome awareness among females in the UAE: a cross-sectional study
Authors: Zaitoun Balkis , Al Kubaisi Abdullah , AlQattan Noora , Alassouli Yahya , Mohammad Alshaima , Alameeri Huriya , Mohammed Ghada
Published: April 2023

Background

Polycystic Ovarian Syndrome (PCOS) is a common hormonal disorder affecting females of reproductive age. Clinical guidelines recommend following the diagnostic criteria of PCOS based on an appropriate assessment of the patient’s clinical presentation. Sufficient awareness among the population will prompt females to seek medical attention when necessary. This study aimed to assess knowledge and awareness about PCOS among females above the age of 18 years in the United Arab Emirates (UAE) and to correlate the level of awareness with women's backgrounds, demographics, and education levels.

Methods

This was a cross-sectional study conducted in early 2020. 430 females over the age of 18 years were conveniently selected and interviewed in the UAE using a 21-item questionnaire that assessed participants' awareness of PCOS as a term, its causes, symptoms, complications, treatment, and prevention. 414 entries were eligible for data analysis. IBM® SPSS® Statistics version 25 was used for data entry and analysis.

Results

349 participants (84.3%) were familiar with the term PCOS. However, only 21.7% of them had sufficient awareness of the syndrome (95% CI = 17.77–25.71%). Being knowledgeable of PCOS was significantly associated with having a previous diagnosis (p = 0.002) and with studying or working in a medical field (p < 0.001). In addition, females who knew someone diagnosed with PCOS were 5 times more likely to be more aware compared to those who didn’t (95% CI = 2.5–10.8; p < 0.001). Age, education level, and nationality showed no correlation with the level of awareness.

Conclusions

Overall, the level of PCOS awareness was insufficient in the study sample. Participants whose source of information was medical practitioners demonstrated more accurate knowledge. Accordingly, awareness of PCOS needs to be raised among females in the UAE, aiding early diagnosis and improving patient-oriented outcomes.
Perceived effects of the COVID-19 pandemic on clinical psychology internships in Sweden
Authors: Bergvall Hillevi , Larsson Cornelia , Strålin Elinor Eskilsson , Bohman Benjamin , Alfonsson Sven
Published: April 2023

Background

The COVID-19 pandemic has had an unprecedented impact on societies and health care services worldwide, including the clinical training of psychology interns. Some of the pandemic-related restrictions were in breach of the internship requirements, increasing the risk of failed internships and a shortage of new health care professionals. This situation needed to be assessed.

Methods

Web-based surveys were administered to clinical psychology interns in Sweden 2020 (n = 267) and 2021 (n = 340), as well as to supervisors in 2020 (n = 240). The supervisors also provided information about their interns (n = 297).

Results

Risk factors for a prolonged internship, such as pandemic-related absence from work (12.4% in 2020 and 7.9% in 2021), unqualified work (0% in 2020, 3% in 2021), and change in internship content were low. However, remote interactions using digital services increased. Face-to-face patient contacts decreased significantly from 2020 to 2021 (Χ2 = 5.17, p = .023), while remote work and remote supervision increased significantly (Χ2 = 53.86, p < .001 and Χ2 = 8.88, p = .003, respectively). Still, the content in patient contacts and supervision was maintained. Most interns reported no difficulties with remote supervision or supervision in personal protective equipment. However, of the interns who reported difficulties, role-play and skills training in remote supervision were perceived as significantly harder (Χ2 = 28.67, p < .001) than in supervision using personal protective equipment.

Conclusions

The present study indicates that clinical training of psychology interns in Sweden could proceed despite a societal crisis. Results suggest that the psychology internship was flexible in the sense that it could be realized in combined face-to-face and remote formats without losing much of its value. However, the results also suggest that some skills may be harder to train in remote supervision.
Comparison lecture and concept map methods on the level of learning and satisfaction in puerperal sepsis education of midwifery students: a quasi-experimental study
Authors: Yarmohammadi Azita , Mostafazadeh Farideh , Shahbazzadegan Samira
Published: April 2023

Background

Education and training about emergency cases are necessary for different medical groups such as midwives. Teaching puerperal sepsis is important for midwives. The teaching method is one of the challenges of the educational system in universities. This study was conducted to compare lecture and concept map methods on the level of learning and satisfaction in puerperal sepsis education of midwifery students.

Method

This semi-experimental study was conducted in 2022 at Ardabil Nursing and Midwifery School on 50 midwifery students. Students randomly were placed in lecture and concept map teaching groups. To collect data, a 23-question satisfaction questionnaire and a 15-question test taken from the WHO books on the management of puerperal sepsis were used to check students' knowledge and learning. The data were analyzed by using descriptive statistics and independent and paired t-test SPSS software.

Findings

The average learning score of the students after teaching in the concept map group was 10.28 ± 1.90 and the lecture group 9.20 ± 1.70, the difference was statistically significant (p = 0.04). The average satisfaction score in the concept map group was 107.92 ± 4.46 and in the lecture group 105.68 ± 6.84, this difference was statistically significant (p = 0.03).

Conclusion

The teaching of puerperal sepsis with the concept map method had a greater effect on the learning and satisfaction of midwifery students. Therefore, it is recommended to use this educational method.
The gut symbiont Sphingomonas mediates imidacloprid resistance in the important agricultural insect pest Aphis gossypii Glover
Authors: Lv Nannan , Li Ren , Cheng Shenhang , Zhang Lei , Liang Pei , Gao Xiwu
Published: April 2023

Background

Neonicotinoid insecticides are applied worldwide for the control of agricultural insect pests. The evolution of neonicotinoid resistance has led to the failure of pest control in the field. The enhanced detoxifying enzyme activity and target mutations play important roles in the resistance of insects to neonicotinoid resistance. Emerging evidence indicates a central role of the gut symbiont in insect pest resistance to pesticides. Existing reports suggest that symbiotic microorganisms could mediate pesticide resistance by degrading pesticides in insect pests.

Results

The 16S rDNA sequencing results showed that the richness and diversity of the gut community between the imidacloprid-resistant (IMI-R) and imidacloprid-susceptible (IMI-S) strains of the cotton aphid Aphis gossypii showed no significant difference, while the abundance of the gut symbiont Sphingomonas was significantly higher in the IMI-R strain. Antibiotic treatment deprived Sphingomonas of the gut, followed by an increase in susceptibility to imidacloprid in the IMI-R strain. The susceptibility of the IMI-S strain to imidacloprid was significantly decreased as expected after supplementation with Sphingomonas. In addition, the imidacloprid susceptibility in nine field populations, which were all infected with Sphingomonas, increased to different degrees after treatment with antibiotics. Then, we demonstrated that Sphingomonas isolated from the gut of the IMI-R strain could subsist only with imidacloprid as a carbon source. The metabolic efficiency of imidacloprid by Sphingomonas reached 56% by HPLC detection. This further proved that Sphingomonas could mediate A. gossypii resistance to imidacloprid by hydroxylation and nitroreduction.

Conclusions

Our findings suggest that the gut symbiont Sphingomonas, with detoxification properties, could offer an opportunity for insect pests to metabolize imidacloprid. These findings enriched our knowledge of mechanisms of insecticide resistance and provided new symbiont-based strategies for control of insecticide-resistant insect pests with high Sphingomonas abundance.
Rapid identification of carbapenem-resistant Klebsiella pneumoniae based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry and an artificial neural network model
Authors: Zhang Yu-Ming , Tsao Mei-Fen , Chang Ching-Yu , Lin Kuan-Ting , Keller Joseph Jordan , Lin Hsiu-Chen
Published: April 2023

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens.

Methods

A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously.

Results

Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision–recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da.

Conclusions

Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients’ outcomes and lower the prevalence of antimicrobial resistance.
The interaction effect of transfusion history and previous stroke history on the risk of venous thromboembolism in stroke patients: a prospective cohort study
Authors: Sun Changqing , Wang Rongrong , Wang Lianke , Wang Panpan , Qin Ying , Zhou Qianyu , Guo Yuanli , Zhao Mingyang , He Wenqian , Hu Bo , Yao Zihui , Zhang Peijia , Wu Tiantian , Wang Yu , Zhang Qiang
Published: April 2023

Background

Blood transfusion and previous stroke history are two independent risk factors of venous thromboembolism (VTE) in stroke patients. Whether the potential interaction of transfusion history and previous stroke history is associated with a greater risk of VTE remains unclear. This study aims to explore whether the combination of transfusion history and previous stroke history increases the risk of VTE among Chinese stroke patients.

Methods

A total of 1525 participants from the prospective Stroke Cohort of Henan Province were enrolled in our study. Multivariate logistic regression models were used to explore the associations among transfusion history, previous stroke history and VTE. The interaction was evaluated on both multiplicative and additive scales. The odds ratio (95% CI), relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (S) of interaction terms were used to examine multiplicative and additive interactions. Finally, we divided our population into two subgroups by National Institutes of Health Stroke Scale (NIHSS) score and re-evaluated the interaction effect in both scales.

Results

A total of 281 (18.4%) participants of 1525 complicated with VTE. Transfusion and previous stroke history were associated with an increased risk of VTE in our cohort. In the multiplicative scale, the combination of transfusion and previous stroke history was statistically significant on VTE in both unadjusted and adjusted models (P<0.05). For the additive scale, the RERI shrank to 7.016 (95% CI: 1.489 ~ 18.165), with the AP of 0.650 (95% CI: 0.204 ~ 0.797) and the S of 3.529 (95% CI: 1.415 ~ 8.579) after adjusting for covariates, indicating a supra-additive effect. In subgroups, the interaction effect between transfusion history and previous stroke history was pronouncedly associated with the increased risk of VTE in patients with NIHSS score > 5 points (P<0.05).

Conclusions

Our results suggest that there may be a potential synergistic interaction between transfusion history and previous stroke history on the risk of VTE. Besides, the percentage of VTE incidence explained by interaction increased with the severity of stroke. Our findings will provide valuable evidence for thromboprophylaxis in Chinese stroke patients.
Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells
Authors: Barman Madhumanti , Dandasena Debabrata , Suresh Akash , Bhandari Vasundhra , Kamble Sonam , Singh Sakshi , Subudhi Madhusmita , Sharma Paresh
Published: April 2023

Background

Bovine theileriosis caused by the eukaryotic parasite Theileria annulata is an economically important tick-borne disease. If it is not treated promptly, this lymphoproliferative disease has a significant fatality rate. Buparvaquone (BPQ) is the only chemotherapy-based treatment available right now. However, with the emergence of BPQ resistance on the rise and no backup therapy available, it is critical to identify imperative drugs and new targets against Theileria parasites.

Methods

Artemisinin and its derivatives artesunate (ARS), artemether (ARM), or dihydroartemisinin (DHART) are the primary defence line against malaria parasites. This study has analysed artemisinin and its derivatives for their anti-Theilerial activity and mechanism of action.

Results

ARS and DHART showed potent activity against the Theileria-infected cells. BPQ in combination with ARS or DHART showed a synergistic effect. The compounds act specifically on the parasitised cells and have minimal cytotoxicity against the uninfected host cells. Treatment with ARS or DHART induces ROS-mediated oxidative DNA damage leading to cell death. Further blocking intracellular ROS by its scavengers antagonised the anti-parasitic activity of the compounds. Increased ROS production induces oxidative stress and DNA damage causing p53 activation followed by caspase-dependent apoptosis in the Theileria-infected cells.

Conclusions

Our findings give unique insights into the previously unknown molecular pathways underpinning the anti-Theilerial action of artemisinin derivatives, which may aid in formulating new therapies against this deadly parasite.
The impact of 12 modifiable lifestyle behaviours on depressive and anxiety symptoms in middle adolescence: prospective analyses of the Canadian longitudinal COMPASS study
Authors: Dabravolskaj Julia , Veugelers Paul J. , Amores Angelica , Leatherdale Scott T. , Patte Karen A. , Maximova Katerina
Published: April 2023

Background

Unhealthy lifestyle behaviours are becoming increasingly common and might contribute to the growing burden of mental disorders in adolescence. We examined the associations between a comprehensive set of lifestyle behaviours and depression and anxiety in middle adolescents.

Methods

School-based survey responses were collected from 24,274 Canadian high school students at baseline and 1-year follow-up (average age 14.8 and 15.8 years, respectively). Using linear mixed-effects models, we examined prospective associations of adherence to recommendations for vegetables and fruit, grains, milk and alternatives, meat and alternatives, sugar-sweetened beverages [SSB], physical activity, screen time, sleep, and no use of tobacco, e-cigarettes, cannabis, and binge drinking at baseline with the depressive and anxiety symptoms (measured by CESD-R-10 and GAD-7 scales, respectively) at follow-up.

Results

Adherence to recommendations was low overall, particularly for vegetables and fruit (3.9%), grains (4.5%), and screen time (4.9%). Students adhering to individual recommendations, particularly for meat and alternatives, SSB, screen time, sleep, and no cannabis use, at baseline had lower CESD-R-10 and GAD-7 scores at follow-up. Adhering to every additional recommendation was associated with lower CESD-R-10 (β=-0.15, 95% CI -0.18, -0.11) and GAD-7 scores (β=-0.10, 95% CI -0.14, -0.07) at follow-up. Assuming cumulative impact, this might translate into 7.2- and 4.8-point lower CESD-R-10 and GAD-7 scores, respectively, among students adhering to 12 vs. 0 recommendations over four years of high school.

Conclusions

The results highlight the preventive potential of population-based approaches promoting healthy lifestyle behaviours, particularly those with the lowest prevalence, as a strategy to improve mental health in adolescence.
Congenitally corrected transposition of the great arteries and implantation of a leadless pacemaker: a case report
Authors: Li Qiao-yuan , Dai Wen-long , Lin can-can , Liu Xu , Guo Cheng-jun , Jian-zeng Dong
Published: April 2023

Background

Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac anomaly and can lead to abnormal electrical activity of the heart. The implant of a pacemaker in such patients is more complicated than conventional operations. This case report of an adult with ccTGA who had a leadless pacemaker implant will provide a reference for diagnosing and treating such patients.

Case presentation

A 50-year-old male patient was admitted to hospital having experienced intermittent vision loss for a month. An electrocardiogram and Holter monitoring showed intermittent third-degree atrioventricular block, and echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging confirmed a diagnosis of ccTGA. A leadless pacemaker was successfully implanted into the patient’s anatomical left ventricle, and the postoperative parameters were stable.

Conclusion

Implanting a leadless pacemaker into a patient with a rare anatomical and electrophysiological abnormality, such as ccTGA, is feasible and efficacious, but preoperative imaging evaluation is of considerable importance.
Malignant transformation of a solitary tracheal papilloma in the absence of human papillomavirus infection in a patient with 48, XYYY syndrome: case report
Authors: Nasralla Awrad , Lau Esther , Sur Ranjan , Shargall Yaron
Published: April 2023

The diagnosis and management of tracheobronchial papilloma is challenging due to its rarity, and non-specific presenting symptoms. Small percentage undergoes malignant transformation. Herein, we report an unusual case of tracheal papilloma initially misdiagnosed as chronic obstructive pulmonary disease (COPD) in 36-year-old male with triple Y syndrome. It was successfully treated with local debridement and brachytherapy. To the best of our knowledge, this is the first description of brachytherapy for such a condition.
JBrowse 2: a modular genome browser with views of synteny and structural variation
Authors: Diesh Colin , Stevens Garrett J , Xie Peter , De Jesus Martinez Teresa , Hershberg Elliot A. , Leung Angel , Guo Emma , Dider Shihab , Zhang Junjun , Bridge Caroline , Hogue Gregory , Duncan Andrew , Morgan Matthew , Flores Tia , Bimber Benjamin N. , Haw Robin , Cain Scott , Buels Robert M. , Stein Lincoln D. , Holmes Ian H.
Published: April 2023

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. It retains core features of JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. It allows users to share sessions, open multiple genomes, and navigate between views. It can be embedded in a web page, used as a standalone application, or run from Jupyter notebooks or R sessions. These improvements are enabled by a ground-up redesign using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers.
Metabolic independence drives gut microbial colonization and resilience in health and disease
Authors: Watson Andrea R. , Füssel Jessika , Veseli Iva , DeLongchamp Johanna Zaal , Silva Marisela , Trigodet Florian , Lolans Karen , Shaiber Alon , Fogarty Emily , Runde Joseph M. , Quince Christopher , Yu Michael K. , Söylev Arda , Morrison Hilary G. , Lee Sonny T. M. , Kao Dina , Rubin David T. , Jabri Bana , Louie Thomas , Eren A. Murat
Published: April 2023

Background

Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.

Results

Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.

Conclusions

These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of “dysbiosis” that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
Antitumoral effects of Bortezomib in malignant mesothelioma: evidence of mild endoplasmic reticulum stress in vitro and activation of T cell response in vivo
Authors: Benvenuto Monica , Angiolini Valentina , Focaccetti Chiara , Nardozi Daniela , Palumbo Camilla , Carrano Raffaele , Rufini Alessandra , Bei Riccardo , Miele Martino Tony , Mancini Patrizia , Barillari Giovanni , Cirone Mara , Ferretti Elisabetta , Tundo Grazia Raffaella , Mutti Luciano , Masuelli Laura , Bei Roberto
Published: April 2023

Background

Malignant mesothelioma (MM) is a rare tumor with a dismal prognosis. The low efficacy of current treatment options highlights the urge to identify more effective therapies aimed at improving MM patients’ survival. Bortezomib (Bor) is a specific and reversible inhibitor of the chymotrypsin-like activity of the 20S core of the proteasome, currently approved for the treatment of multiple myeloma and mantle cell lymphoma. On the other hand, Bor appears to have limited clinical effects on solid tumors, because of its low penetration and accumulation into tumor tissues following intravenous administration. These limitations could be overcome in MM through intracavitary delivery, with the advantage of increasing local drug concentration and decreasing systemic toxicity.

Methods

In this study, we investigated the effects of Bor on cell survival, cell cycle distribution and modulation of apoptotic and pro-survival pathways in human MM cell lines of different histotypes cultured in vitro. Further, using a mouse MM cell line that reproducibly forms ascites when intraperitoneally injected in syngeneic C57BL/6 mice, we investigated the effects of intraperitoneal Bor administration in vivo on both tumor growth and the modulation of the tumor immune microenvironment.

Results

We demonstrate that Bor inhibited MM cell growth and induced apoptosis. Further, Bor activated the Unfolded Protein Response, which however appeared to participate in lowering cells’ sensitivity to the drug’s cytotoxic effects. Bor also affected the expression of EGFR and ErbB2 and the activation of downstream pro-survival signaling effectors, including ERK1/2 and AKT. In vivo, Bor was able to suppress MM growth and extend mice survival. The Bor-mediated delay of tumor progression was sustained by increased activation of T lymphocytes recruited to the tumor microenvironment.

Conclusions

The results presented herein support the use of Bor in MM and advocate future studies aimed at defining the therapeutic potential of Bor and Bor-based combination regimens for this treatment-resistant, aggressive tumor.
d-xylose accelerated death of pentose metabolizing Saccharomyces cerevisiae
Authors: Nijland Jeroen G. , Zhang Xiaohuan , Driessen Arnold J. M.
Published: April 2023

Rapid and effective consumption of d-xylose by Saccharomyces cerevisiae is essential for cost-efficient cellulosic bioethanol production. Hence, heterologous d-xylose metabolic pathways have been introduced into S. cerevisiae. An effective solution is based on a xylose isomerase in combination with the overexpression of the xylulose kinase (Xks1) and all genes of the non-oxidative branch of the pentose phosphate pathway. Although this strain is capable of consuming d-xylose, growth inhibition occurs at higher d-xylose concentrations, even abolishing growth completely at 8% d-xylose. The decreased growth rates are accompanied by significantly decreased ATP levels. A key ATP-utilizing step in d-xylose metabolism is the phosphorylation of d-xylulose by Xks1. Replacement of the constitutive promoter of XKS1 by the galactose tunable promoter Pgal10 allowed the controlled expression of this gene over a broad range. By decreasing the expression levels of XKS1, growth at high d-xylose concentrations could be restored concomitantly with increased ATP levels and high rates of xylose metabolism. These data show that in fermentations with high d-xylose concentrations, too high levels of Xks1 cause a major drain on the cellular ATP levels thereby reducing the growth rate, ultimately causing substrate accelerated death. Hence, expression levels of XKS1 in S. cerevisiae needs to be tailored for the specific growth conditions and robust d-xylose metabolism.
Notch1 signaling is limited in healthy mature kidneys in vivo
Authors: Sugiura Ryosuke , Nakayama Takahiro , Nishino Teppei , Sambe Naoto , Radtke Freddy , Yoshihara Masaharu , Takahashi Satoru
Published: April 2023

Objective

A Delta-Notch signaling component, Notch1, is involved in the normal development and multiple disorders of the kidney. Although the increase in Notch1 signaling is crucial to these pathogeneses, the basal signaling level in ‘healthy’ mature kidneys is still unclear. To address this question, we used an artificial Notch1 receptor fused with Gal4/UAS components in addition to the Cre/loxP system and fluorescent proteins in mice. This transgenic reporter mouse system enabled labeling of past and ongoing Notch1 signaling with tdsRed or Cre recombinase, respectively.

Results

We confirmed that our transgenic reporter mouse system mimicked the previously reported Notch1 signaling pattern. Using this successful system, we infrequently observed cells with ongoing Notch1 signaling only in Bowman’s capsule and tubules. We consider that Notch1 activation in several lines of disease model mice was pathologically significant itself.
Dissolved storage glycans shaped the community composition of abundant bacterioplankton clades during a North Sea spring phytoplankton bloom
Authors: Sidhu Chandni , Kirstein Inga V. , Meunier Cédric L. , Rick Johannes , Fofonova Vera , Wiltshire Karen H. , Steinke Nicola , Vidal-Melgosa Silvia , Hehemann Jan-Hendrik , Huettel Bruno , Schweder Thomas , Fuchs Bernhard M. , Amann Rudolf I. , Teeling Hanno
Published: April 2023

Background

Blooms of marine microalgae play a pivotal role in global carbon cycling. Such blooms entail successive blooms of specialized clades of planktonic bacteria that collectively remineralize gigatons of algal biomass on a global scale. This biomass is largely composed of distinct polysaccharides, and the microbial decomposition of these polysaccharides is therefore a process of prime importance.

Results

In 2020, we sampled a complete biphasic spring bloom in the German Bight over a 90-day period. Bacterioplankton metagenomes from 30 time points allowed reconstruction of 251 metagenome-assembled genomes (MAGs). Corresponding metatranscriptomes highlighted 50 particularly active MAGs of the most abundant clades, including many polysaccharide degraders. Saccharide measurements together with bacterial polysaccharide utilization loci (PUL) expression data identifiedβ-glucans (diatom laminarin) andα-glucans as the most prominent and actively metabolized dissolved polysaccharide substrates. Both substrates were consumed throughout the bloom, withα-glucan PUL expression peaking at the beginning of the second bloom phase shortly after a peak in flagellate and the nadir in bacterial total cell counts.

Conclusions

We show that the amounts and composition of dissolved polysaccharides, in particular abundant storage polysaccharides, have a pronounced influence on the composition of abundant bacterioplankton members during phytoplankton blooms, some of which compete for similar polysaccharide niches. We hypothesize that besides the release of algal glycans, also recycling of bacterial glycans as a result of increased bacterial cell mortality can have a significant influence on bacterioplankton composition during phytoplankton blooms.
Experiential COVID-19 factors predicting resilience among Spanish adults
Authors: Álvarez Mar Alcolea , Pinto Natalia Solano
Published: April 2023

Background

The pandemic caused by COVID-19 has meant for spanish citizens a constant adaptation to health measures in order to try to stop transmission of the virus. During this adaptation process, different psychosocial aspects have caused consequences for people?s mental health to a greater or lesser extent. Makes sense of an emotional torrent who has gone through fear, anxiety, loneliness and anger. The interaction between perception and reality has given rise to situations where loneliness and social isolation have been imposed and lived with a load of emotional discomfort. In others, social isolation and measures to stop the pandemic have been accepted as a protection system and has been experienced since serenity and the feeling of self-protection fostering individual resilience. Studying the predictors of resilience is going to be key since it is the ideal antidote to stop the appearance of mental disorders associated with the pandemic (such as depression, anxiety, post-traumatic stress, social phobia, cleaning obsessions, and generalized anxiety disorder). The objective of this research is to analyze the relationship between resilience and experiential COVID-19 factors.

Methods

Sample was comprised of Spanish adults (n = 1000; age 18-79 [mean =40.43],793 female, 201 male, and 2 non binary sex). These people participating in an online study focused on the impact of COVID-19 experiences. The research has been cross-sectional, descriptive and correlational design. The instrument created for this research was a specific online questionnaire, including the “Scale of resilience” (RS, Wagnild & Young, 1993, Spanish version, Sánchez-Teruel, et al., 2015). That questionnaire has been administered during the months of April 2022 to July 2022.

Results

The results obtained show how people who have been able to face the pandemic in a responsive and adaptive way have high resilience. Specifically, those participants that accepting the use of masks, vaccinations and confinement obtained high resilience.

Conclusions

Using public funding and allocating research to the development of programs to promote resilience, adaptative beliefs and prosocial behaviors becomes basic to live in a world in constant change.
Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches
Authors: Huang Ruichen , Zhao Bi , Hu Shi , Zhang Qian , Su Xiaoping , Zhang Wei
Published: April 2023

Neoantigens generated by non-synonymous mutations of tumor genes can induce activation of neoantigen-reactive T (NRT) cells which have the ability to resist the growth of tumors expressing specific neoantigens. Immunotherapy based on NRT cells has made preeminent achievements in melanoma and other solid tumors. The process of manufacturing NRT cells includes identification of neoantigens, preparation of neoantigen expression vectors or peptides, induction and activation of NRT cells, and analysis of functions and phenotypes. Numerous improvement strategies have been proposed to enhance the potency of NRT cells by engineering TCR, promoting infiltration of T cells and overcoming immunosuppressive factors in the tumor microenvironment. In this review, we outline the improvement of the preparation and the function assessment of NRT cells, and discuss the current status of clinical trials related to NRT cell immunotherapy.
Crabs ride the tide: incoming tides promote foraging of Giant Mud Crab (Scylla serrata)
Authors: Hewitt Daniel E. , Johnson Daniel D. , Suthers Iain M. , Taylor Matthew D.
Published: April 2023

Background

Effective fisheries management of mobile species relies on robust knowledge of animal behaviour and habitat-use. Indices of behaviour can be useful for interpreting catch-per-unit-effort data which acts as a proxy for relative abundance. Information about habitat-use can inform stocking release strategies or the design of marine protected areas. The Giant Mud Crab (Scylla serrata; Family: Portunidae) is a swimming estuarine crab that supports significant fisheries harvest throughout the Indo-West Pacific, but little is known about the fine-scale movement and behaviour of this species.

Methods

We tagged 18 adult Giant Mud Crab with accelerometer-equipped acoustic tags to track their fine-scale movement using a hyperbolic positioning system, alongside high temporal resolution environmental data (e.g., water temperature), in a temperate south-east Australian estuary. A hidden Markov model was used to classify movement (i.e., step length, turning angle) and acceleration data into discrete behaviours, while also considering the possibility of individual variation in behavioural dynamics. We then investigated the influence of environmental covariates on these behaviours based on previously published observations.

Results

We fitted a model with two well-distinguished behavioural states describing periods of inactivity and foraging, and found no evidence of individual variation in behavioural dynamics. Inactive periods were most common (79% of time), and foraging was most likely during low, incoming tides; while inactivity was more likely as the high tide receded. Model selection removed time (hour) of day and water temperature (°C) as covariates, suggesting that they do not influence Giant Mud Crab behavioural dynamics at the temporal scale investigated.

Conclusions

Our study is the first to quantitatively link fine-scale movement and behaviour of Giant Mud Crab to environmental variation. Our results suggest Giant Mud Crab are a predominantly sessile species, and support their status as an opportunistic scavenger. We demonstrate a relationship between the tidal cycle and foraging that is likely to minimize predation risk while maximizing energetic efficiency. These results may explain why tidal covariates influence catch rates in swimming crabs, and provide a foundation for standardisation and interpretation of catch-per-unit-effort data—a commonly used metric in fisheries science.
The locus coeruleus input to the rostral ventromedial medulla mediates stress-induced colorectal visceral pain
Authors: Kong Dexu , Zhang Yunchun , Gao Po , Pan Chao , Deng Haoyue , Xu Saihong , Tang Dan , Xiao Jie , Jiao Yingfu , Yu Weifeng , Wen Daxiang
Published: April 2023

Unlike physiological stress, which carries survival value, pathological stress is widespread in modern society and acts as a main risk factor for visceral pain. As the main stress-responsive nucleus in the brain, the locus coeruleus (LC) has been previously shown to drive pain alleviation through direct descending projections to the spinal cord, but whether and how the LC mediates pathological stress-induced visceral pain remains unclear. Here, we identified a direct circuit projection from LC noradrenergic neurons to the rostral ventromedial medulla (RVM), an integral relay of the central descending pain modulation system. Furthermore, the chemogenetic activation of the LC-RVM circuit was found to significantly induce colorectal visceral hyperalgesia and anxiety-related psychiatric disorders in naïve mice. In a dextran sulfate sodium (DSS)-induced visceral pain model, the mice also presented colorectal visceral hypersensitivity and anxiety-related psychiatric disorders, which were associated with increased activity of the LC-RVM circuit; LC-RVM circuit inhibition markedly alleviated these symptoms. Furthermore, the chronic restraint stress (CRS) model precipitates anxiety-related psychiatric disorders and induces colorectal visceral hyperalgesia, which is referred to as pathological stress-induced hyperalgesia, and inhibiting the LC-RVM circuit attenuates the severity of colorectal visceral pain. Overall, the present study clearly demonstrated that the LC-RVM circuit could be critical for the comorbidity of colorectal visceral pain and stress-related psychiatric disorders. Both visceral inflammation and psychological stress can activate LC noradrenergic neurons, which promote the severity of colorectal visceral hyperalgesia through this LC-RVM circuit.
Acid scarification as a potent treatment for an in vitro germination of mature endozoochorous Vanilla planifolia seeds
Authors: Šoch Jan , Šonka Josef , Ponert Jan
Published: April 2023

Background

Vanilla planifolia is the most widely cultivated species of vanilla with high economic importance. However, seed germination under artificial conditions is difficult and yields low germination percentages. The seeds are adapted to endozoochorous dispersal, and we therefore tried to simulate the conditions in the digestive tract by acid scarification of seeds.

Results

Immature seeds lacking dormancy, used as a control, showed the highest germination percentage. Among the treatments tested for mature seeds, the hydrochloric acid treatments were significantly the best in breaking dormancy and inducing germination, irrespective of the acid concentration and the presence of pepsin. Conventional treatment with a hypochlorite solution induced much lower germination percentage. Sulphuric acid at concentration 50% was too strong and caused damage to the seeds. Important factor is also high cultivation temperature 30 °C as there was nearly no germination at 25 °C.

Conclusions

Our protocol significantly improves the efficiency of generative propagation of vanilla and allows for significantly higher germination percentages than previously described. The strongly positive effect of hydrochloric acid may be related to the adaptation of seeds to endozoochorous dispersal.
Mendel’s terminology and notation reveal his understanding of genetics
Authors: Ellis T. H. Noel , van Dijk Peter J.
Published: April 2023

We describe both the terminology and use of symbols introduced by Mendel in his 1866 paper and discuss some misconceptions concerning their interpretation.
Individual and community-level factors associated with caesarean section in Haiti: secondary analysis of data from the 2016–2017 Haitian Demographic and Health Survey
Authors: Jean Simon David , Jean-Baptiste Stanley , Nazaire Roodjmie , Joseph Ghislaine , Carmil Joseph Arcelin , Joseph Fanor , Kondo Tokpovi Vénunyé Claude
Published: April 2023

Introduction

For several decades, the rate of caesarean section (CS) has been increasing in the world. In some countries, the CS rate is below the WHO recommended range (10–15%), while in other countries, it is significantly higher. The aim of this paper was to identify individual and community-level factors associated with CS in Haiti.

Methods

Secondary data analysis was conducted on nationally representative cross-sectional survey data from the 2016–2017 Haitian Demographic and Health Survey (HDHS). The analysis was restricted to 6303 children born in 5 years prior the survey (of the interviewed women). The study population’ characteristics, and the prevalence of CS were analysed using descriptive analysis (univariate/bivariate). In addition, multilevel binary logistic regression analysis was performed to identify factors associated with CS. Both descriptive and multivariate analysis were conducted using STATA 16.0 software (Stata Corp, Tex, USA). Statistical significance was declared at p < 0.05.

Results

The overall prevalence of CS delivery was estimated at 5.4% (95% CI 4.8–6.0) in Haiti. Results also revealed that mothers aged 35 and above (aOR = 1.38; 95% CI 1.00–1.96); who attended secondary (aOR = 1.95; 95% CI 1.39–2.76) and higher education level (aOR = 3.25; 95% CI 1.92–5.49); who were covered by health insurance (aOR = 2.57; 95% CI 1.57–4.19); with less than 3 children (aOR = 4.13; 95% CI 2.18–7.85) or 3–4 children (aOR = 2.07; 95% CI 1.09–3.94); who received 9 or more antenatal visits (aOR = 2.21; 95% CI 1.40–3.50) were significantly more likely to deliver by CS. Children in communities with high preponderance of private health facilities had greater odds to be delivered through CS (aOR = 1.90; 95% CI 1.25–2.85). Furthermore, children with an average birth weight (aOR = 0.66; 95% CI 0.48–0.91) were less likely to be delivered through CS than their counterparts with high birth weight.

Conclusions

While the CS prevalence was low in Haiti, it masks significant geographic, social and economic disparities. To better develop and implement maternal and child health programs that address CS deliveries, the government authorities and NGOs operating in the field of women’s health in Haiti should take these disparities into account.
Effects of influential points and sample size on the selection and replicability of multivariable fractional polynomial models
Authors: Sauerbrei Willi , Kipruto Edwin , Balmford James
Published: April 2023

Background

The multivariable fractional polynomial (MFP) approach combines variable selection using backward elimination with a function selection procedure (FSP) for fractional polynomial (FP) functions. It is a relatively simple approach which can be easily understood without advanced training in statistical modeling. For continuous variables, a closed test procedure is used to decide between no effect, linear, FP1, or FP2 functions. Influential points (IPs) and small sample sizes can both have a strong impact on a selected function and MFP model.

Methods

We used simulated data with six continuous and four categorical predictors to illustrate approaches which can help to identify IPs with an influence on function selection and the MFP model. Approaches use leave-one or two-out and two related techniques for a multivariable assessment. In eight subsamples, we also investigated the effects of sample size and model replicability, the latter by using three non-overlapping subsamples with the same sample size. For better illustration, a structured profile was used to provide an overview of all analyses conducted.

Results

The results showed that one or more IPs can drive the functions and models selected. In addition, with a small sample size, MFP was not able to detect some non-linear functions and the selected model differed substantially from the true underlying model. However, when the sample size was relatively large and regression diagnostics were carefully conducted, MFP selected functions or models that were similar to the underlying true model.

Conclusions

For smaller sample size, IPs and low power are important reasons that the MFP approach may not be able to identify underlying functional relationships for continuous variables and selected models might differ substantially from the true model. However, for larger sample sizes, a carefully conducted MFP analysis is often a suitable way to select a multivariable regression model which includes continuous variables. In such a case, MFP can be the preferred approach to derive a multivariable descriptive model.