bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal–fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon
Authors: Seijas-Chávez Julio Abel , Nolan Melissa S. , Lynn Mary K. , da Rocha Maria José Francalino , da Costa Araújo Muana , Fonseca Fernando Luiz Affonso , Laporta Gabriel Zorello
Published: November 2021

Background

Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth?

Methods

From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children’s Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation.

Results

In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86–12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02–6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever.

Conclusions

While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.
Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia
Authors: Jongdeepaisal Monnaphat , Ean Mom , Heng Chhoeun , Buntau Thoek , Tripura Rupam , Callery James J. , Peto Thomas J. , Conradis-Jansen Franca , von Seidlein Lorenz , Khonputsa Panarasri , Pongsoipetch Kulchada , Soviet Ung , Sovannaroth Siv , Pell Christopher , Maude Richard J.
Published: November 2021

Background

In the Greater Mekong Subregion, adults are at highest risk for malaria, particularly those who visit forests. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria.

Methods

Alongside a clinical trial of anti-malarial chemoprophylaxis in northern Cambodia, qualitative research was conducted, including in-depth interviews and observation, to explore the acceptability of malaria prophylaxis for forest goers, the implementation opportunities, and challenges of this strategy.

Results

Prophylaxis with artemether–lumefantrine for forest goers was found to be acceptable under trial conditions. Three factors played a major role: the community’s awareness and perception of the effectiveness of prophylaxis, their trust in the provider, and malaria as a local health concern. The findings highlight how uptake and adherence to prophylaxis are influenced by the perceived balance between benefits and burden of anti-malarials which are modulated by the seasonality of forest visits and its influence on malaria risk.

Conclusions

The implementation of anti-malarial prophylaxis needs to consider how the preventive medication can be incorporated into existing vector-control measures, malaria testing and treatment services. The next step in the roll out of anti-malarial prophylaxis for forest visitors will require support from local health workers.
Love bites: male frogs (Plectrohyla, Hylidae) use teeth scratching to deliver sodefrin precursor-like factors to females during amplexus
Authors: Schulte Lisa M. , Martel An , Cruz-Elizalde Raciel , Ramírez-Bautista Aurelio , Bossuyt Franky
Published: November 2021

Background

Efficient transfer of chemical signals is important for successful mating in many animal species. Multiple evolutionary lineages of animals evolved direct sex pheromone transmission during traumatic mating—the wounding of the partner with specialized devices—which helps to avoid signal loss to the environment. Although such direct transmission modes of so-called allohormone pheromones are well-documented in invertebrates, they are considered rare in vertebrates. Males of several species of the frog genusPlectrohyla(Hylidae, Anura) have elongated teeth and develop swollen lips during the breeding season. Here we investigated the possibility that these structures are used to scratch the females’ skin and apply allohormone pheromones during traumatic mating in severalPlectrohylaspecies.

Results

Our behavioural observations revealed that males press their upper jaw onto the females’ dorsum during amplexus, leaving small skin scratches with their teeth. Histological examinations of the males’ lips identified specialized mucus glands, resembling known amphibian pheromone glands. Whole-transcriptome sequencing of these breeding glands showed high expression of sodefrin precursor-like factor (SPF) proteins, which are known to have a pheromone function in multiple amphibian species.

Conclusions

Our study suggests SPF delivery via traumatic mating in several anuran species: the males have specialized breeding glands in the lips for production and secretion and use their elongated teeth as wounding devices for application. We hypothesize that these SPF proteins end up in the females’ circulatory system, where understanding their exact function will require further molecular, physiological and behavioural testing.
Effects of endplate coverage and intervertebral height change on heterotopic ossification following cervical disc replacement
Authors: Shen Yi-Wei , Yang Yi , Liu Hao , Rong Xin , Ding Chen , Meng Yang , Wang Bei-Yu , Hong Ying
Published: November 2021

Background

Heterotopic ossification (HO) is a common complication after cervical disc replacement (CDR). Biomechanical factors including endplate coverage and intervertebral disc height change may be related to HO formation. However, there is a dearth of quantitative analysis for endplate coverage, intervertebral height change and their combined effects on HO.

Methods

Patients who underwent single-level or two-level CDR with Prestige-LP were retrospectively reviewed. Clinical outcomes were evaluated through Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, and visual analogue scale (VAS) score. Radiological data, including the prosthesis-endplate depth ratio, intervertebral height change, posterior heterotopic ossification (PHO) and angular parameters, were collected. Logistic regression analysis was used to identify the potential risk factors. Receiver operating characteristic curves were plotted and the cut-off values of each potential factors were calculated.

Results

A total of 138 patients with 174 surgical segments were evaluated. Both the prosthesis-endplate depth ratio (P < 0.001) and post-operative disc height change (P < 0.001) were predictive factors for PHO formation. The area under the curve (AUC) of the prosthesis-endplate depth ratio, disc height change and their combined effects represented by the combined parameter (CP) were 0.728, 0.712 and 0.793, respectively. The risk of PHO significantly increased when the prosthesis-endplate depth ratio < 93.77% (P < 0.001, OR = 6.909, 95% CI 3.521–13.557), the intervertebral height change ≥ 1.8 mm (P < 0.001, OR = 5.303, 95% CI 2.592–10.849), or the CP representing the combined effect < 84.88 (P < 0.001, OR = 10.879, 95% CI 5.142–23.019).

Conclusions

Inadequate endplate coverage and excessive change of intervertebral height are both potential risk factors for the PHO after CDR. Endplate coverage less than 93.8% or intervertebral height change more than 1.8 mm would increase the risk of PHO. The combination of these two factors may exacerbate the non-uniform distribution of stress in the bone-implant interface and promote HO development.
Chronic wasting disease in Europe: new strains on the horizon
Authors: Tranulis Michael Andreas , Gavier-Widén Dolores , Våge Jørn , Nöremark Maria , Korpenfelt Sirkka-Liisa , Hautaniemi Maria , Pirisinu Laura , Nonno Romolo , Benestad Sylvie Lafond
Published: November 2021

Prion diseases are fatal neurodegenerative disorders with known natural occurrence in humans and a few other mammalian species. The diseases are experimentally transmissible, and the agent is derived from the host-encoded cellular prion protein (PrPC), which is misfolded into a pathogenic conformer, designated PrPSc (scrapie). Aggregates of PrPSc molecules, constitute proteinaceous infectious particles, known as prions. Classical scrapie in sheep and goats and chronic wasting disease (CWD) in cervids are known to be infectious under natural conditions. In CWD, infected animals can shed prions via bodily excretions, allowing direct host-to-host transmission or indirectly via prion-contaminated environments. The robustness of prions means that transmission via the latter route can be highly successful and has meant that limiting the spread of CWD has proven difficult. In 2016, CWD was diagnosed for the first time in Europe, in reindeer (Rangifer tarandus) and European moose (Alces alces). Both were diagnosed in Norway, and, subsequently, more cases were detected in a semi-isolated wild reindeer population in the Nordfjella area, in which the first case was identified. This population was culled, and all reindeer (approximately 2400) were tested for CWD; 18 positive animals, in addition to the first diagnosed case, were found. After two years and around 25,900 negative tests from reindeer (about 6500 from wild and 19,400 from semi-domesticated) in Norway, a new case was diagnosed in a wild reindeer buck on Hardangervidda, south of the Nordfjella area, in 2020. Further cases of CWD were also identified in moose, with a total of eight in Norway, four in Sweden, and two cases in Finland. The mean age of these cases is 14.7 years, and the pathological features are different from North American CWD and from the Norwegian reindeer cases, resembling atypical prion diseases such as Nor98/atypical scrapie and H- and L-forms of BSE. In this review, these moose cases are referred to as atypical CWD. In addition, two cases were diagnosed in red deer (Cervus elaphus) in Norway. The emergence of CWD in Europe is a threat to European cervid populations, and, potentially, a food-safety challenge, calling for a swift, evidence-based response. Here, we review data on surveillance, epidemiology, and disease characteristics, including prion strain features of the newly identified European CWD agents.
Epigenetic activation of the elongator complex sensitizes gallbladder cancer to gemcitabine therapy
Authors: Xu Sunwang , Jiang Cen , Lin Ruirong , Wang Xiaopeng , Hu Xiaoqiang , Chen Wei , Chen Xiangjin , Chen Tao
Published: November 2021

Background

Gallbladder cancer (GBC) is known for its high malignancy and multidrug resistance. Previously, we uncovered that impaired integrity and stability of the elongator complex leads to GBC chemotherapy resistance, but whether its restoration can be an efficient therapeutic strategy for GBC remains unknown.

Methods

RT-qPCR, MS-qPCR and ChIP-qPCR were used to evaluate the direct association between ELP5 transcription and DNA methylation in tumour and non-tumour tissues of GBC. EMSA, chromatin accessibility assays, and luciferase assays were utilized to analysis the DNA methylation in interfering PAX5-DNA interactions. The functional experiments in vitro and in vivo were performed to investigate the effects of DNA demethylating agent decitabine (DAC) on the transcription activation of elongator complex and the enhanced sensitivity of gemcitabine in GBC cells. Tissue microarray contains GBC tumour tissues was used to evaluate the association between the expression of ELP5, DNMT3A and PAX5.

Results

We demonstrated that transcriptional repression of ELP5 in GBC was highly correlated with hypermethylation of the promoter. Mechanistically, epigenetic analysis revealed that DNA methyltransferase DNMT3A-catalysed hypermethylation blocked transcription factor PAX5 activation of ELP5 by disrupting PAX5-DNA interaction, resulting in repressed ELP5 transcription. Pharmacologically, the DNA demethylating agent DAC eliminated the hypermethylated CpG dinucleotides in the ELP5 promoter and then facilitated PAX5 binding and reactivated ELP5 transcription, leading to the enhanced function of the elongator complex. To target this mechanism, we employed a sequential combination therapy of DAC and gemcitabine to sensitize GBC cells to gemcitabine-therapy through epigenetic activation of the elongator complex.

Conclusions

Our findings suggest that ELP5 expression in GBC is controlled by DNA methylation-sensitive induction of PAX5. The sequential combination therapy of DAC and gemcitabine could be an efficient therapeutic strategy to overcome chemotherapy resistance in GBC.
Design, implementation, and management of an international medical device registry
Authors: Mauch Herbert , Kaur Jasmin , Irwin Colin , Wyss Josie
Published: November 2021

Background

Registries are powerful clinical investigational tools. Although in hospitals registries may be mandated, industry-sponsored, international registries are voluntary and therefore can require clearer objectives and more planning. The registry also needs sufficient resources and appropriate measurement tools to motivate long-term participation and ensure success.

Methods

We summarize our learnings from 10 years of running a medical device registry that surveys patient-reported benefits of hearing implants.

Results

We enlisted 77 participating clinics globally, who actively recruited a total of more than 1500 hearing implant users. We identified the stages in developing a registry specific to hearing loss. Furthermore, we report the challenges and successes in design and implementation and make recommendations for future registries.

Conclusions

Data collection infrastructure needs to be kept up to date throughout the defined registry lifetime, and it is essential to oversee data quality and completeness. Compliance at registry sites is important for data quality and needs to be weighed against the cost of site monitoring. To motivate sites to enter data accurately and expeditiously, we facilitated easy access to their own data which helped to support their clinical routine.

Trial registration

ClinicalTrials.gov NCT02004353. 9th December 2013.
Salt stress improves thermotolerance and high-temperature bioethanol production of multi-stress-tolerant Pichia kudriavzevii by stimulating intracellular metabolism and inhibiting oxidative damage
Authors: Li Chunsheng , Liu Qiuying , Wang Yueqi , Yang Xianqing , Chen Shengjun , Zhao Yongqiang , Wu Yanyan , Li Laihao
Published: November 2021

Background

High-temperature bioethanol production benefits from yeast thermotolerance. Salt stress could induce obvious cross-protection against heat stress of Pichia kudriavzevii, contributing to the improvement of its thermotolerance and bioethanol fermentation. However, the underlying mechanisms of the cross-protection remain poorly understood.

Results

Salt stress showed obvious cross-protection for thermotolerance and high-temperature ethanol production of P. kudriavzevii observed by biomass, cell morphology and bioethanol production capacity. The biomass and ethanol production of P. kudriavzevii at 45 °C were, respectively, improved by 2.6 and 3.9 times by 300 mmol/L NaCl. Metabolic network map showed that salt stress obviously improved the key enzymes and intermediates in carbohydrate metabolism, contributing to the synthesis of bioethanol, ATP, amino acids, nucleotides, and unsaturated fatty acids, as well as subsequent intracellular metabolisms. The increasing trehalose, glycerol, HSPs, and ergosterol helped maintain the normal function of cell components. Heat stress induced serious oxidative stress that the ROS-positive cell rate and dead cell rate, respectively, rose from 0.5% and 2.4% to 28.2% and 69.2%, with the incubation temperature increasing from 30 to 45 °C. The heat-induced ROS outburst, oxidative damage, and cell death were obviously inhibited by salt stress, especially the dead cell rate which fell to only 20.3% at 300 mmol/L NaCl. The inhibiting oxidative damage mainly resulted from the abundant synthesis of GSH and GST, which, respectively, increased by 4.8 and 76.1 times after addition of 300 mmol/L NaCl. The improved bioethanol production was not only due to the improved thermotolerance, but resulted from the up-regulated alcohol dehydrogenases and down-regulated aldehyde dehydrogenases by salt stress.

Conclusion

The results provide a first insight into the mechanisms of the improved thermotolerance and high-temperature bioethanol production of P. kudriavzevii by salt stress, and provide important information to construct genetic engineering yeasts for high-temperature bioethanol production.

Graphical Abstract
Directed evolution and secretory expression of xylose isomerase for improved utilisation of xylose in Saccharomyces cerevisiae
Authors: Bae Jung-Hoon , Kim Mi-Jin , Sung Bong Hyun , Jin Yong-Su , Sohn Jung-Hoon
Published: November 2021

Background

Xylose contained in lignocellulosic biomass is an attractive carbon substrate for economically viable conversion to bioethanol. Extensive research has been conducted on xylose fermentation using recombinant Saccharomyces cerevisiae expressing xylose isomerase (XI) and xylose reductase/xylitol dehydrogenase (XR/XDH) pathways along with the introduction of a xylose transporter and amplification of the downstream pathway. However, the low utilization of xylose in the presence of glucose, due to the varying preference for cellular uptake, is a lingering challenge. Studies so far have mainly focused on xylose utilization inside the cells, but there have been little trials on the conversion of xylose to xylulose by cell before uptake. We hypothesized that the extracellular conversion of xylose to xylulose before uptake would facilitate better utilization of xylose even in the presence of glucose. To verify this, XI from Piromyces sp. was engineered and hyper-secreted in S. cerevisiae for the extracellular conversion of xylose to xylulose.

Results

The optimal pH of XI was lowered from 7.0 to 5.0 by directed evolution to ensure its high activity under the acidic conditions used for yeast fermentation, and hyper-secretion of an engineered XI-76 mutant (E56A and I252M) was accomplished by employing target protein-specific translational fusion partners. The purified XI-76 showed twofold higher activity than that of the wild type at pH 5. The secretory expression of XI-76 in the previously developed xylose utilizing yeast strain, SR8 increased xylose consumption and ethanol production by approximately 7–20% and 15–20% in xylose fermentation and glucose and xylose co-fermentation, respectively.

Conclusions

Isomerisation of xylose to xylulose before uptake using extracellular XI was found to be effective in xylose fermentation or glucose/xylose co-fermentation. This suggested that glucose competed less with xylulose than with xylose for uptake by the cell. Consequently, the engineered XI secretion system constructed in this study can pave the way for simultaneous utilization of C5/C6 sugars from the sustainable lignocellulosic biomass.
Self-generated peroxyacetic acid in phosphoric acid plus hydrogen peroxide pretreatment mediated lignocellulose deconstruction and delignification
Authors: Tian Dong , Chen Yiyi , Shen Fei , Luo Maoyuan , Huang Mei , Hu Jinguang , Zhang Yanzong , Deng Shihuai , Zhao Li
Published: November 2021

Background

Peroxyacetic acid involved chemical pretreatment is effective in lignocellulose deconstruction and oxidation. However, these peroxyacetic acid are usually artificially added. Our previous work has shown that the newly developed PHP pretreatment (phosphoric acid plus hydrogen peroxide) is promising in lignocellulose biomass fractionation through an aggressive oxidation process, while the information about the synergistic effect between H3PO4 and H2O2 is quite lack, especially whether some strong oxidant intermediates is existed. In this work, we reported the PHP pretreatment system could self-generate peroxyacetic acid oxidant, which mediated the overall lignocellulose deconstruction, and hemicellulose/lignin degradation.

Results

The PHP pretreatment profile on wheat straw and corn stalk were investigated. The pathways/mechanisms of peroxyacetic acid mediated-PHP pretreatment were elucidated through tracing the structural changes of each component. Results showed that hemicellulose was almost completely solubilized and removed, corresponding to about 87.0% cellulose recovery with high digestibility. Rather high degrees of delignification of 83.5% and 90.0% were achieved for wheat straw and corn stalk, respectively, with the aid of peroxyacetic acid oxidation. A clearly positive correlation was found between the concentration of peroxyacetic acid and the extent of lignocellulose deconstruction. Peroxyacetic acid was mainly self-generated through H2O2 oxidation of acetic acid that was produced from hemicellulose deacetylation and lignin degradation. The self-generated peroxyacetic acid then further contributed to lignocellulose deconstruction and delignification.

Conclusions

The synergistic effect of H3PO4 and H2O2 in the PHP solvent system could efficiently deconstruct wheat straw and corn stalk lignocellulose through an oxidation-mediated process. The main function of H3PO4 was to deconstruct biomass recalcitrance and degrade hemicellulose through acid hydrolysis, while the function of H2O2 was to facilitate the formation of peroxyacetic acid. Peroxyacetic acid with stronger oxidation ability was generated through the reaction between H2O2 and acetic acid, which was released from xylan and lignin oxidation/degradation. This work elucidated the generation and function of peroxyacetic acid in the PHP pretreatment system, and also provide useful information to tailor peroxide-involved pretreatment routes, especially at acidic conditions.

Graphical abstract
Inferior vena cava thrombosis as a possible cause of nephrotic-range proteinuria: two case reports
Authors: Apostolova Yana , Mehier Patricia , Qanadli Salah D. , Pruijm Menno
Published: November 2021

Background

Nephrotic-range proteinuria is a common reason for nephrological consultation in clinical practice. The differential diagnosis is wide, and generally focuses on different forms of glomerulonephritis, but other causes should not be overlooked, as illustrated in this article.

Case presentations

We report two female patients with nephrotic-range proteinuria. In the first case, a 46 year old Caucasian patient who suffered from extreme obesity (Body mass index (BMI) 77 kg/m2), acute kidney injury and nephrotic-range proteinuria were discovered during an emergency consultation for acute abdominal pain. The second patient (aged 52, also Caucasian) developed stage 4 chronic kidney disease and nephrotic proteinuria (protein/creatinine ratio 1821 g/mol) after accidental rupture of the inferior vena cava during a gastric bypass operation. On split-urine collection, both had a much higher degree of proteinuria during the day than during the night, compatible with orthostatic proteinuria. At further work-up, inferior vena cava thrombosis was diagnosed in both patients, whereas renal veins were patent.

Discussion

After simple anticoagulation in the first case, and anticoagulation plus endovascular recanalization in the second, there was almost complete resolution of the orthostatic proteinuria and a strong improvement of the estimated glomerular filtration rate in both patients. These cases highlight that nephrotic-range proteinuria can be linked to inferior vena cava thrombosis, and that a split-urine collection may also be very useful in the diagnostic work-up of proteinuria in adults.
Irreversible electroporation for pancreatic cancer using intraprocedural cone-beam computed tomography fusion navigation: a case report
Authors: Rao Sriram , Bui Thanh-Lan , Sasani Ali , Sadeghi Ben , Macherla Anvesh , Houshyar Roozbeh , Abi-Jaoudeh Nadine
Published: November 2021

Background

Patients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer.

Case presentation

The patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized.

Conclusions

Although not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation.
New Delhi metallo-β-lactamase-1 among Escherichia coli strains isolated from leukemia patients in Iran: two case reports
Authors: Roshani Mahdane , Goodarzi Alireza , Dehbashi Sanaz , Afrasiabi Farhad , Goudarzi Hossein , Hashemi Ali , Arabestani Mohammad Reza
Published: November 2021

Background

Escherichia coli has appeared as an important opportunistic pathogen responsible for nosocomial infections in patients with immunodeficiency, particularly in leukemia patients. New Delhi metallo-beta-lactamase is an enzyme originally found in Enterobacteriaceae.

Case presentation

In this study, 80 isolates of Escherichia coli and Klebsiella pneumoniae were collected over the course of 2 years from two medical centers in Tehran, Iran. Production of carbapenemase was detected in the isolates using modified Hodge test. New Delhi metallo-beta-lactamase-1 genes were detected by polymerase chain reaction amplification with specific primers. Two New Delhi metallo-beta-lactamase-1-producing Escherichia coli strains were isolated from two Iranian patients with leukemia. These two patients were 6 and 15 years old, one female and the other male, from two oncology centers in Iran. The isolates were resistant to carbapenems (imipenem, meropenem), and two isolates were positive for carbapenemase production by modified Hodge test.

Conclusions

The emergence of New Delhi metallo-beta-lactamase-1-producing Escherichia coli is a threat for leukemia patients in oncology and hematology departments. We conclude that the incidence of multidrug resistant pathogens has increased among patients with leukemia and is life threatening.
Comparison of test performance on paper-based testing (PBT) and computer-based testing (CBT) by English-majored undergraduate students in China
Authors: Yu Wenjing , Iwashita Noriko
Published: November 2021

Computer-based testing (CBT), which refers to delivering assessments with computers, has been widely used in large English proficiency tests worldwide. Despite an increasing CBT in China, limited research is available concerning whether CBT can be used for the Test for English Majors-Band 4 (TEM 4). The current study investigated whether testing mode impacted TEM 4 score and factors (i.e., computer familiarity level and attitude towards CBT) that might correlate with performance on CBT of TEM 4. Overall 92 Chinese undergraduate students were randomly assigned to one of the groups, i.e., CBT or paper-based testing (PBT), and took the test. A mixed method was employed, including (1) quantitative and qualitative analysis of test performance in two modes, as well as CBT group participants’ computer familiarity and attitudes towards the mode; and (2) thematic analysis of semi-structured interviews. The results revealed that (1) test scores in CBT and PBT were comparable; (2) two items in the computer familiarity questionnaire, i.e., comfort level of reading articles on the computer and forgetting time when using computers, positively correlated with CBT scores; and (3) participants’ attitude towards CBT did not impact test performance.
The effect of biodynamic preparations on growth and fruit quality of giant pumpkin (Cucurbita maxima D.)
Authors: Juknevičienė Edita , Danilčenko Honorata , Jarienė Elvyra , Živatkauskienė Vilma , Zeise Johanna , Fritz Jürgen
Published: November 2021

Background

Food quality of agricultural crops depends on environmental conditions, production system and cultivation method. A plant-based nutrition with food rich in vitamins, minerals and secondary plant compounds with antioxidative properties promotes human health. This investigation was inspired by an increasing global issue on how to improve product quality while using alternative preparations. The main aim of a 3-year study was to investigate the influence of fermented manure and silica products on yield and nutritive components in peel, fruit and seeds of three pumpkin cultivars. In four replicates as block design, the effects of individually as well as combined application of biodynamic horn manure and horn silica preparation were compared to a control variant.

Results

Horn manure application significantly increased total and marketable yield. Marketable yield, contents of macroelements, total carotenoids, single carotenoids (lutein + zeaxanthin, lycopene, ß-carotene) and antioxidants (catechins, total phenols, leuco-anthocyanins) were significantly increased by horn silica use. The combination of both biodynamic preparations had a significantly increasing effect on total and marketable yield, net photosynthetic productivity, dry matter content and total and single carotenoid contents (lutein + zeaxanthin, lycopene, ß-carotene).

Conclusions

The pumpkin trial results indicated a general growth-promoting effect by horn manure, a quality-enhancing effect by horn silica and a compensatory effect through both preparations on a high qualitative level. In accordance with other investigations, these effects did not occur in the same way in all plant species. Therefore, the effects of the biodynamic preparations should be tested in further trials on a plant species-specific basis.

Graphic abstract
Patient advocacy group involvement in health technology assessments: an observational study
Authors: Single Ann , Cabrera Ariana , Fifer Simon , Tsai Jane , Paik Jin-Young , Hope Philip
Published: November 2021

Background

In some jurisdictions, patients and patient groups may be invited to provide input when Health Technology Assessment (HTA) is used to inform decisions about which medicines should be subsidised or funded. This input can help frame the evidence from a patient perspective, address uncertainties in the evidence and interpret it for the local setting. However, there is currently no evidence linking patient involvement with positive reimbursement decisions.

Aim

We aimed to understand the expectations of patient involvement in the reimbursement process, especially among cancer patient advocacy groups (PAGs) in New Zealand (Aotearoa), South Korea and Taiwan.

Methods

We developed an online survey to help understand the role that cancer PAGs play in reimbursement processes and identify knowledge gaps about the processes that might impact the efforts of PAGs. The survey elicited the views of staff and patients affiliated with PAGs (n = 43) on current practices and how the assessment and reimbursement of new cancer drugs might be improved.

Results

There was variability in knowledge of the HTA assessment processes and in experience of being involved in them. Those with HTA experience were more likely to have confidence in the process. Those who had not been involved tended to have little awareness of, or frustration with, decision-making processes. Most identified cost, finances and economic assessments as key considerations in current processes. Some respondents had clear ideas about how their knowledge and involvement could improve processes to determine the value of new medicines. However, for many, a lack of information about the basis for decision making and opportunities to be involved was a barrier to identifying process improvement.

Conclusions

HTA is implemented primarily in countries seeking to have fair and equitable processes for funding medicines. PAGs often recognise the financial challenges of funding new medicines and share the desire for procedural fairness. The connection PAGs make between patient involvement and improved access to new medicines may be based on the belief they can add information to the evidence base, help solve problems, ensure fairness through transparency and/or influence the culture towards increased access to medicines they value.
Systematic review of clinical evidence on postoperative delirium: literature search of original studies based on validated diagnostic scales
Authors: Bilotta F. , Russo G. , Verrengia M. , Sportelli A. , Foti L. , Villa G. , Romagnoli S.
Published: November 2021

Background

Postoperative delirium is a serious complication that can occur within the 5th postoperative day. In 2017, the European Society of Anesthesiologists delivered dedicated guidelines that reported the need for routine monitoring using validated scales.

Objective

Aim of this systematic review is to identify clinical studies related to postoperative delirium that included postoperative monitoring with validated scales.

Design

Systematic review

Methods

Searched keywords included the following terms: postoperative, postsurgical, post anesthesia, anesthesia recovery, delirium, and confusion. Two researchers independently screened retrieved studies using a data extraction form.

Results

Literature search led to retrieve 6475 hits; of these, 260 studies (5.6% of the retrieved), published between 1987 and 2021, included in their methods a diagnostic workup with the use of a postoperative delirium validated scale and monitored patients for more than 24 h, therefore are qualified to be included in the present systematic review.

Conclusion

In conclusion, available clinical literature on postoperative delirium relies on a limited number of studies, that included a validated diagnostic workup based on validated scales, extracted from a large series of studies that used inconsistent diagnostic criteria. In order to extract indications based on reliable evidence-based criteria, these are the studies that should be selectively considered. The analysis of these studies can also serve to design future projects and to test clinical hypothesis with a more standardized methodological approach.
Maximum baryon masses for static neutron stars in f(R) gravity
Authors: Astashenok A. V. , Capozziello S. , Odintsov S. D. , Oikonomou V. K.
Published: November 2021

We investigate the upper mass limit predictions of the baryonic mass for static neutron stars in the context of f(R) gravity. We use the most popular f(R) gravity model, namely the R
2 gravity, and calculate the maximum baryon mass of static neutron stars adopting several realistic equations of state and one ideal equation of state, namely that of causal limit. Our motivation is based on the fact that neutron stars with baryon masses larger than the maximum mass for static neutron star configurations inevitably collapse to black holes. Thus with our analysis, we want further to enlighten the predictions for the maximum baryon masses of static neutron stars in R
2 gravity, which, in turn, further strengthens our understanding of the mysterious mass gap region. As we show, the baryon masses of most of the equations of states studied in this paper lie in the lower limits of the mass gap region

–

, but intriguingly enough, the highest value of the maximum baryon masses we found is of the order of

. This upper mass limit also appears as a maximum static neutron star gravitational mass limit in other contexts. Combining the two results which refer to baryon and gravitational masses, we point out that the gravitational mass of static neutron stars cannot be larger than three solar masses, while based on maximum baryon masses results of the present work, we can conspicuously state that it is highly likely the lower mass limits of astrophysical black holes in the range of

–

. This, in turn, implies that maximum neutron star masses in the context of R
2 gravity are likely to be in the lower limits of the range of

–

. Hence our work further supports the General Relativity claim that neutron stars cannot have gravitational masses larger than

and then, to explain observations comparable or over this limit, we need alternative extensions of General Relativity, other than f(R) gravity.
The spectral line asymmetry of the Doppler effect in relativistic plasmas
Authors: Gossa H. , Meftah M. T. , Chenini K. , Zenkhri D. E. , Amieur B. , Guerrida H.
Published: November 2021

In this work, we present a comparative study between the relativistic and non-relativistic Doppler effects on spectral line profiles in ultra-hot plasmas in a laboratory system. We have established an exact formula of the relativistic Doppler profile in ultra-high-temperature plasma that is not a Gaussian one (unlike the non-relativistic Doppler profile that is Gaussian). We have also derived a new FWHM (Full Width at Half Maximum) formula of the corresponding profile that is different from the non-relativistic FWHM (

). We have also shown that, in the relativistic case, Doppler broadening exhibits an asymmetry of spectral line profile (non-Gaussian profile). To ensure the validity of our investigation, we have compared our theoretical calculation with the experimental results and found a good agreement.
The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration
Authors: Canales Coutiño Brenda , Mayor Roberto
Published: November 2021

Cells are permanently exposed to a multitude of different kinds of signals: however, how cells respond to simultaneous extracellular signals within a complex in vivo environment is poorly understood. Here, we studied the role of the mechanosensitive ion channel Piezo1 on the migration of the neural crest, a multipotent embryonic cell population. We identify that Piezo1 is required for the migration of Xenopus cephalic neural crest. We show that loss of Piezo1 promotes focal adhesion turnover and cytoskeletal dynamics by controlling Rac1 activity, leading to increased speed of migration. Moreover, overactivation of Rac1, due to Piezo1 inhibition, counteracts cell migration inhibitory signals by Semaphorin 3A and Semaphorin 3F, generating aberrant neural crest invasion in vivo. Thus, we find that, for directional migration in vivo, neural crest cells require a tight regulation of Rac1, by semaphorins and Piezo1. We reveal here that a balance between a myriad of signals through Rac1 dictates cell migration in vivo, a mechanism that is likely to be conserved in other cell migration processes.
A 37 kb region upstream of brachyury comprising a notochord enhancer is essential for notochord and tail development
Authors: Schifferl Dennis , Scholze-Wittler Manuela , Wittler Lars , Veenvliet Jesse V. , Koch Frederic , Herrmann Bernhard G.
Published: November 2021

The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor brachyury (T) is essential for both formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail; however, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T that is essential for notochord function and tailbud outgrowth. Within that region, we discovered a T-binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord, allowing proper trunk and tail development.
SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning
Authors: Gamart Julie , Barozzi Iros , Laurent Frédéric , Reinhardt Robert , Martins Laurène Ramos , Oberholzer Thomas , Visel Axel , Zeller Rolf , Zuniga Aimée
Published: November 2021

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds.
The endoplasmic reticulum–plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis
Authors: Xie Beichen , Panagiotou Styliani , Cen Jing , Gilon Patrick , Bergsten Peter , Idevall-Hagren Olof
Published: November 2021

Endoplasmic reticulum (ER)–plasma membrane (PM) contacts are sites of lipid exchange and Ca2+ transport, and both lipid transport proteins and Ca2+ channels specifically accumulate at these locations. In pancreatic β-cells, both lipid and Ca2+ signaling are essential for insulin secretion. The recently characterized lipid transfer protein TMEM24 (also known as C2CD2L) dynamically localizes to ER–PM contact sites and provides phosphatidylinositol, a precursor of phosphatidylinositol-4-phosphate [PI(4)P] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], to the PM. β-cells lacking TMEM24 exhibit markedly suppressed glucose-induced Ca2+ oscillations and insulin secretion, but the underlying mechanism is not known. We now show that TMEM24 only weakly interacts with the PM, and dissociates in response to both diacylglycerol and nanomolar elevations of cytosolic Ca2+. Loss of TMEM24 results in hyper-accumulation of Ca2+ in the ER and in excess Ca2+ entry into mitochondria, with resulting impairment in glucose-stimulated ATP production.
Born without night: The consequence of the no-night environment on reproductive performance in diurnal zebra finches
Authors: Jha Neelu Anand , Taufique S. K. Tahajjul , Kumar Vinod
Published: November 2021

We investigated the consequence of no night environment (constant light, LL) on reproductive performance in zebra finches in the parent (P) and subsequent F1 generation. As a measure of the overall effects on the metabolic reproductive health, we monitored daily activity behaviour, recorded song and cheek patch size in males, and measured body size and hormone levels. As compared to controls under 12 h light: 12 h darkness (12:12 h LD), both P and F1 pairs showed a compromised reproductive success, as evidenced by fewer fledglings and viable offsprings with longer fledging durations, and increased offspring mortality with successive three clutches under LL. The overall negative effect of the no-night environment was increased in the F1generation. As compared to P pairs, F1pairs had more failed nesting and breeding attempts, took longer to initiate reproduction, incubated fewer eggs, produced fewer viable offspring with longer fledging duration, and showed increased offspring mortality. Consistent with negative reproductive effects, P males showed significant changes in the motif duration and other spectral features of song, and both F1 and F2 males copied poorly the song of their parent under LL. Plasma corticosterone and sex hormones (testosterone in males and estradiol in females) levels were significantly lower under LL. Daily plasma melatonin rhythm persisted but with a reduced amplitude under LL. These results demonstrate the importance of night in reproduction in a continuously breeding diurnal species, and give insights into the possible impact on physiology of animals whose surrounding environment is consistently losing the darkness of night.