bluuebunny/crossref_metadata_2025 huggingface dataset:
cAMP activates calcium signalling via phospholipase C to regulate cellulase production in the filamentous fungus Trichoderma reesei
Authors: Chen Yumeng , Fan Xingjia , Zhao Xinqing , Shen Yaling , Xu Xiangyang , Wei Liujing , Wang Wei , Wei Dongzhi
Published: March 2021

Background

The filamentous fungus Trichoderma reesei is one of the best producers of cellulase and has been widely studied for the production of cellulosic ethanol and bio-based products. We previously reported that Mn2+ and N,N-dimethylformamide (DMF) can stimulate cellulase overexpression via Ca2+ bursts and calcium signalling in T. reesei under cellulase-inducing conditions. To further understand the regulatory networks involved in cellulase overexpression in T. reesei, we characterised the Mn2+/DMF-induced calcium signalling pathway involved in the stimulation of cellulase overexpression.

Results

We found that Mn2+/DMF stimulation significantly increased the intracellular levels of cAMP in an adenylate cyclase (ACY1)-dependent manner. Deletion of acy1 confirmed that cAMP is crucial for the Mn2+/DMF-stimulated cellulase overexpression in T. reesei. We further revealed that cAMP elevation induces a cytosolic Ca2+ burst, thereby initiating the Ca2+ signal transduction pathway in T. reesei, and that cAMP signalling causes the Ca2+ signalling pathway to regulate cellulase production in T. reesei. Furthermore, using a phospholipase C encoding gene plc-e deletion strain, we showed that the plc-e gene is vital for cellulase overexpression in response to stimulation by both Mn2+ and DMF, and that cAMP induces a Ca2+ burst through PLC-E.

Conclusions

The findings of this study reveal the presence of a signal transduction pathway in which Mn2+/DMF stimulation produces cAMP. Increase in the levels of cAMP activates the calcium signalling pathway via phospholipase C to regulate cellulase overexpression under cellulase-inducing conditions. These findings provide insights into the molecular mechanism of the cAMP–PLC–calcium signalling pathway underlying cellulase expression in T. reesei and highlight the potential applications of signal transduction in the regulation of gene expression in fungi.
Sex and nest type influence avian blood parasite prevalence in a high-elevation bird community
Authors: Rodriguez Marina D. , Doherty Paul F. , Piaggio Antoinette J. , Huyvaert Kathryn P.
Published: March 2021

Background

The prevalence of avian haemosporidian parasites and the factors influencing infection in the Colorado Rocky Mountains are largely unknown. With climate change expected to promote the expansion of vector and avian blood parasite distributions, baseline knowledge and continued monitoring of the prevalence and diversity of these parasites is needed.

Methods

Using an occupancy modeling framework, we conducted a survey of haemosporidian parasite species infecting an avian community in the Colorado Rocky Mountains in order to estimate the prevalence and diversity of blood parasites and to investigate species-level and individual-level characteristics that may influence infection.

Results

We estimated the prevalence and diversity of avian Haemosporidia across 24 bird species, detecting 39 parasite haplotypes. We found that open-cup nesters have higher Haemoproteus prevalence than cavity or ground nesters. Additionally, we found that male Ruby-crowned Kinglets, White-crowned Sparrows, and Wilson’s Warblers have higher Haemoproteus prevalence compared to other host species. Plasmodium prevalence was relatively low (5%), consistent with the idea that competent vectors may be rare at high altitudes.

Conclusions

Our study presents baseline knowledge of haemosporidian parasite presence, prevalence, and diversity among avian species in the Colorado Rocky Mountains and adds to our knowledge of host–parasite relationships of blood parasites and their avian hosts.

Graphical Abstract
High prevalence, intensity, and genetic diversity of Trichinella spp. in wolverine (Gulo gulo) from Yukon, Canada
Authors: Sharma Rajnish , Harms N. Jane , Kukka Piia M. , Jung Thomas S. , Parker Sarah E. , Ross Sasha , Thompson Peter , Rosenthal Benjamin , Hoberg Eric P. , Jenkins Emily J.
Published: March 2021

Background

Species of Trichinella are globally important foodborne parasites infecting a number of domestic and wild vertebrates, including humans. Free-ranging carnivores can act as sentinel species for detection of Trichinella spp. Knowledge of the epidemiology of these parasites may help prevent Trichinella spp. infections in northern Canadian animals and people. Previous research on Trichinella spp. in wildlife from Yukon did not identify risk factors associated with infection, or the diversity and identity of species of Trichinella in regional circulation, based on geographically extensive sampling with large sample sizes.

Methods

In a cross-sectional study, we determined the prevalence, infection intensity, risk factors, and species or genotypes of Trichinella in wolverine (Gulo gulo) in two regions of Yukon, Canada, from 2013–2017. A double separatory funnel digestion method followed by mutiplex PCR and PCR-RFLP were used to recover and identify species of Trichinella, respectively.

Results

We found larvae of Trichinella in the tongues of 78% (95% CI 73–82) of 338 wolverine sampled. The odds of adult (≥ 2 years) and yearling (1 year) wolverine being Trichinella spp.-positive were four and two times higher, respectively, compared to juveniles (<1 year). The odds of Trichinella spp. presence were three times higher in wolverine from southeast than northwest Yukon. The mean intensity of infection was 22.6 ± 39 (SD, range 0.1–295) larvae per gram. Trichinella T6 was the predominant genotype (76%), followed by T. nativa (8%); mixed infections with Trichinella T6 and T. nativa (12%) were observed. In addition, T. spiralis was detected in one wolverine. Out of 22 isolates initially identified as T. nativa in multiplex PCR, 14 were analyzed by PCR-RFLP to distinguish them from T. chanchalensis, a recently discovered cryptic species, which cannot be distinguished from the T. nativa on multiplex PCR. Ten isolates were identified either as T. chanchalensis alone (n = 7), or mixed infection with T. chanchalensis and T. nativa (n = 2) or T. chanchalensis and Trichinella T6 (n = 1)].

Conclusions

Wolverine hosted high prevalence, high larval intensity, and multiple species of Trichinella, likely due to their scavenging habits, apex position in the food chain, and wide home range. Wolverine (especially adult males) should be considered as a sentinel species for surveys for Trichinella spp. across their distributional range.

Graphical Abstract
Regular swimming exercise improves metabolic syndrome risk factors: a quasi-experimental study
Authors: Omar Jamal Shaker , Jaradat Nidal , Qadoumi Mohammad , Qadoumi Abdel Naser
Published: March 2021

Background

In the past few decades, swimming became one of the most important physical activities within the health system and is considered a practical nonpharmacological approach to managing of type 2 diabetes (T2DM), hyperlipidemia, hypertension (HTN), and obesity. The current study aimed to assess the effect of long-term swimming sessions on glycemic and lipidemic parameters, hemodynamic responses, body fat percent, and body mass index for patients with metabolic risk factors from Palestine.

Methods

Forty participants from both genders with T2DM and HTN (aged 52.4 ± 5.5 yrs) agreed to participate in this quasi-experimental study and were divided into two groups. The first group included the participants who performed long-term swimming sessions and the second group served as the control. The first group exercised for 2 h, 3 times/week in 29–33 °C swimming pool temperature for 16 weeks. Simultaneously, the control group did not participate in any exercise and advised them to keep on with their everyday lifestyle. All the obtained metabolic syndrome risk factors data were analyzed using a two-way ANOVA analysis of variance (2*2) which was applied to determine the differences according group, time, and interaction.

Results

The results showed that there were statistically significant differences at p < 0.05 in the variables of Total Cholesterol (TC), High Density of Lipoprotein (HDL), Low Density of Lipoprotein (LDL), Triglycerides (TG), Blood Glucose (BG), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Body Mass Index (BMI), and body fat percent according to group, time, and interaction for the experimental group.

Conclusions

The findings of the current study suggested that the regular 16 weeks of swimming sessions could be considered nonpharmacological approaches in managing T2DM and HTN.
The effectiveness of manual therapy applied to craniomandibular structures in the treatment of temporomandibular disorders: protocol for a systematic review
Authors: Asquini Giacomo , Rushton Alison , Pitance Laurent , Heneghan Nicola , Falla Deborah
Published: March 2021

Background

The term temporomandibular disorder (TMD) includes disorders of the temporomandibular joints (TMJ), masticatory muscles and adjacent tissues. Several studies have examined the effectiveness of manual therapy (MT) for TMDs by evaluating changes in pain and maximum mouth opening (MMO). Nevertheless, the effectiveness of MT exclusively applied to the craniomandibular structures (craniomandibular manual therapy (CMMT)) on pain and TMJ range of motion remains unclear. This review aims to evaluate the effectiveness of CMMT on pain and TMJ range of motion in people with TMDs.

Methods

This protocol is reported in line with the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P). Databases including MEDLINE, Embase, CINAHL, ZETOC, Web of Science, SCOPUS, PEDro, PubMed, Cochrane Library and Best Evidence, EBM reviews–Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature ChiroAccess and Google Scholar will be searched from inception as well as key journals and grey literature. Randomised controlled trials involving adults with TMD that compare the effect of any type of CMMT (e.g. mobilisation) on pain and range of motion with a placebo intervention, controlled care intervention or other types of treatment will be included. Two reviewers will independently screen articles for inclusion, extract data, assess risk of bias (revised Cochrane risk of bias tool) for included studies and evaluate overall quality of evidence (Grading of Recommendations Assessment, Development and Evaluation). A meta-analysis will be conducted if possible. If not, a narrative synthesis will be conducted reporting the effectiveness of CMMT according to disorder type (TMJ disorders, masticatory muscle disorders and mixed disorders).

Discussion

In this review, the effectiveness of MT applied to craniomandibular structures for the treatment of TMD will be evaluated. Results will be submitted for publication in a peer-reviewed journal and presented at conferences. We expect our findings will facilitate treatment planning for manual therapists managing patients with TMD and provide future clinical research implications.

Systematic review registration

PROSPERO CRD42019160213
Ecological connectivity in fragmented agricultural landscapes and the importance of scattered trees and small patches
Authors: Tiang Darrel Chin Fung , Morris Andrew , Bell Mathew , Gibbins Christopher N. , Azhar Badrul , Lechner Alex M.
Published: March 2021

Background

Fragmentation and habitat loss can restrict species movement and reduce connectivity, negatively impacting biodiversity. Characterising the overall connectivity of an area can inform better management of human modified landscapes. Contemporary connectivity modelling methods seldom incorporate fine-scale movement patterns associated with movement between fine-scaled structural connectivity elements such as scattered trees, roadside corridors and small patches of habitat. This study aims to characterise connectivity within the Karuah-Myall catchments, a typical woodland ecosystem that is fragmented by agriculture, using least-cost path analysis and a graph-theoretic approach; it focuses on how fine-scaled vegetation such as scattered trees support connectivity. We mapped scattered (and paddock) trees within this agricultural landscape where the main human modified land use was pasture. We modelled connectivity for a general representative woodland species using an interpatch dispersal distance and gap crossing threshold, and resistance from different land cover types. The gap crossing distance threshold was used to model movement between fine-scaled vegetation features. We compared the least-cost paths modelled with and without scattered trees.

Results

Our results show that by excluding scattered trees, least-cost paths across the cleared pasture landscape did not reflect the types of movement patterns typically observed from field studies, such as those associated with a foray-search strategy used by small and medium mammals and birds. The modelling also shows that the Karuah-Myall catchments are well connected and provide value to biodiversity beyond the catchment borders, by connecting coastal vegetation to the Great Eastern Ranges national wildlife corridor initiative.

Conclusion

Connectivity models that exclude fine-scale landscape features such as scattered trees and small, linear patches risk misrepresenting connectivity patterns. Models of regional-scale connectivity can be influenced by the presence or absence of even the smallest features, such as scattered trees.
An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases
Authors: Huang Xiaobing , Wong Garry
Published: March 2021

PIWI-interacting RNAs (piRNAs) are small non-coding transcripts that are highly conserved across species and regulate gene expression through pre- and post-transcriptional processes. piRNAs were originally discovered in germline cells and protect against transposable element expression to promote and maintain genome stability. In the recent decade, emerging roles of piRNAs have been revealed, including the roles in sterility, tumorigenesis, metabolic homeostasis, neurodevelopment, and neurodegenerative diseases. In this review, we summarize piRNA biogenesis in C. elegans, Drosophila, and mice, and further elaborate upon how piRNAs mitigate the harmful effects of transposons. Lastly, the most recent findings on piRNA participation in neurological diseases are highlighted. We speculate on the mechanisms of piRNA action in the development and progression of neurodegenerative diseases. Understanding the roles of piRNAs in neurological diseases may facilitate their applications in diagnostic and therapeutic practice.
The application of social innovation in healthcare: a scoping review
Authors: van Niekerk Lindi , Manderson Lenore , Balabanova Dina
Published: March 2021

Background

Social innovation has been applied increasingly to achieve social goals, including improved healthcare delivery, despite a lack of conceptual clarity and consensus on its definition. Beyond its tangible artefacts to address societal and structural needs, social innovation can best be understood as innovation in social relations, in power dynamics and in governance transformations, and may include institutional and systems transformations.

Methods

A scoping review was conducted of empirical studies published in the past 10 years, to identify how social innovation in healthcare has been applied, the enablers and barriers affecting its operation, and gaps in the current literature. A number of disciplinary databases were searched between April and June 2020, including Academic Source Complete, CIHAHL, Business Source Complete Psych INFO, PubMed and Global Health. A 10-year publication time frame was selected and articles limited to English text. Studies for final inclusion was based on a pre-defined criteria.

Results

Of the 27 studies included in this review, the majority adopted a case research methodology. Half of these were from authors outside the health sector working in high-income countries (HIC). Social innovation was seen to provide creative solutions to address barriers associated with access and cost of care in both low- and middle-income countries and HIC settings in a variety of disease focus areas. Compared to studies in other disciplines, health researchers applied social innovation mainly from an instrumental and technocratic standpoint to foster greater patient and beneficiary participation in health programmes. No empirical evidence was presented on whether this process leads to empowerment, and social innovation was not presented as transformative. The studies provided practical insights on how implementing social innovation in health systems and practice can be enhanced.

Conclusions

Based on theoretical literature, social innovation has the potential to mobilise institutional and systems change, yet research in health has not yet fully explored this dimension. Thus far, social innovation has been applied to extend population and financial coverage, principles inherent in universal health coverage and central to SDG 3.8. However, limitations exist in conceptualising social innovation and applying its theoretical and multidisciplinary underpinnings in health research.

Graphic abstract
The Maudsley model of anorexia nervosa treatment for adolescents and young adults (MANTRa): a study protocol for a multi-center cohort study
Authors: Wittek Tanja , Truttmann Stefanie , Zeiler Michael , Philipp Julia , Auer-Welsbach Ellen , Koubek Doris , Ohmann Susanne , Werneck-Rohrer Sonja , Sackl-Pammer Petra , Schöfbeck Gabriele , Mairhofer Dunja , Kahlenberg Leonie , Schmidt Ulrike , Karwautz Andreas F. K. , Wagner Gudrun
Published: March 2021

Background

The treatment of anorexia nervosa (AN) is often challenging due to medical complications as well as high relapse and mortality rates. Studies about effective treatment options for people with AN are particularly scarce in the adolescent population. This paper is a study protocol for a multi-center cohort study assessing the feasibility, acceptability and efficacy of a new, manualized treatment program, the “Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults” (MANTRa) compared to psychotherapeutic treatment as usual (TAU).

Methods/design

One hundred patients between 13 and 21 years who meet the inclusion criteria will receive 24 to 34 individual weekly MANTRa therapy sessions or weekly TAU sessions. Primary outcome variables will be BMI and eating disorder psychopathology 12 months after baseline. Further changes in central coherence, cognitive flexibility, emotion recognition, comorbid psychopathology (e.g. depression, obsessive-compulsive and anxiety disorders, non-suicidal self-injury), personality factors and therapeutic alliance will be assessed.

Discussion

This multi-center study will examine the utility of the treatment program MANTRa for adolescents with AN and, therefore enhances the current knowledge about potential treatments for this patient group.

Trial registration

ClinicalTrials.gov Identifier: NCT03535714. Registered: 24/05/2018 (retrospectively registered, still recruiting).
Establishment of the African Medicines Agency: progress, challenges and regulatory readiness
Authors: Ncube Bakani Mark , Dube Admire , Ward Kim
Published: March 2021

Insufficient access to quality, safe, efficacious and affordable medical products in Africa has posed a significant challenge to public health for decades. In part, this is attributed to weak or absent policies and regulatory systems, a lack of competent regulatory professionals in National Medicines Regulatory Authorities (NMRAs) and ineffective regional collaborations among NMRAs. In response to national regulatory challenges in Africa, a number of regional harmonisation efforts were introduced through the African Medicines Regulatory Harmonisation (AMRH) initiative to, among others, expedite market authorisation of medical products and to facilitate the alignment of national legislative frameworks with the AU Model Law on Medical Products Regulation. The goals of the model law include to increase collaboration across countries and to facilitate the overall regional harmonisation process. The AMRH initiative is proposed to serve as the foundation for the establishment of the African Medicines Agency (AMA). The AMA will, as one of its mandates, coordinate the regional harmonisation systems that are enabled by AU Model Law domestication and implementation. In this paper, we review the key entities involved in regional and continental harmonisation of medicines regulation, the milestones achieved in establishing the AMA as well as the implementation targets and anticipated challenges related to the AU Model Law domestication and the AMA’s establishment. This review shows that implementation targets for the AU Model Law have not been fully met, and the AMA treaty has not been ratified by the minimum required number of countries for its establishment. In spite of the challenges, the AU Model Law and the AMA hold promise to address gaps and inconsistencies in national regulatory legislation as well as to ensure effective medicines regulation by galvanising technical support, regulatory expertise and resources at a continental level. Furthermore, this review provides recommendations for future research.
Posterior-Chain Resistance Training Compared to General Exercise and Walking Programmes for the Treatment of Chronic Low Back Pain in the General Population: A Systematic Review and Meta-Analysis
Authors: Tataryn Nicholas , Simas Vini , Catterall Tailah , Furness James , Keogh Justin W. L.
Published: March 2021

Background

While chronic exercise training has been demonstrated to be an effective non-pharmacological treatment for chronic low back pain (CLBP), there has been a relative lack of evidence or clinical guidelines for whether a posterior chain resistance training programme provides any benefits over general exercise (GE).

Objectives

To determine if chronic posterior chain resistance training (PCRT), defined as exercise programmes of ≥6 weeks duration focused on the thoracic, lumbar and hip extensor musculature, is more effective than GE in improving pain, level of disability, muscular strength and the number of adverse events in recreationally active and sedentary individuals with CLBP.

Methods

Four electronic databases were systematically searched from 25 September 2019 until 30 August 2020. Using the Joanna Briggs Institute (JBI) Critical Appraisal Tools checklist for randomized controlled trials (RCTs), articles were critically appraised and compared against the inclusion/exclusion criteria. Standardized mean difference (SMD), risk difference (RD) and confidence interval (CI) were calculated using Review Manager 5.3.

Results

Eight articles were included, with a total of 408 participants (203 PCRT, 205 GE). Both PCRT and GE were effective in improving a number of CLBP-related outcomes, but these effects were often significantly greater in PCRT than GE, especially with greater training durations (i.e. 12–16 weeks compared to 6–8 weeks). Specifically, when compared to GE, PCRT demonstrated a greater reduction in pain (SMD = − 0.61 (95% CI − 1.21 to 0.00), p = 0.05; I2 = 74%) and level of disability (SMD = − 0.53 (95% CI − 0.97 to − 0.09), p = 0.02; I2 = 52%), as well as a greater increase in muscle strength (SMD = 0.67 (95% CI 0.21 to 1.13), p = 0.004; I2 = 0%). No differences in the number of adverse events were reported between PCRT and GE (RD = − 0.02 (95% CI − 0.10 to 0.05), p = 0.57; I2 = 72%).

Conclusion

Results of the meta-analysis indicated that 12–16 weeks of PCRT had a statistically significantly greater effect than GE on pain, level of disability and muscular strength, with no significant difference in the number of adverse events for recreationally active and sedentary patients with CLBP. Clinicians should strongly consider utilizing PCRT interventions for 12–16 weeks with patients with CLBP to maximize their improvements in pain, disability and muscle strength. Future research should focus on comparing the efficacy and adverse events associated with specific PCRT exercise training and movement patterns (i.e. deadlift, hip lift) in treating this population.

Trial registration

PROSPERO CRD42020155700.
The neotypification of Frontonia vernalis (Ehrenberg, 1833) Ehrenberg, 1838 and the description of Frontonia paravernalis sp. nov. trigger a critical revision of frontoniid systematics
Authors: Serra Valentina , D’Alessandro Aldo , Nitla Venkatamahesh , Gammuto Leandro , Modeo Letizia , Petroni Giulio , Fokin Sergei I.
Published: March 2021

Background

Among Oligohymenophorea (Ciliophora, Alveolata) the subclass Peniculia stands as one of the most well-known groups. Frontonia is the largest genus of Peniculia, and its representatives are spread in any type of water bodies as well as in soil. At a first glance, Frontonia species exhibit an overall similar morphology, and form a well-recognizable taxon of ciliates. Despite the general morphological homogeneity, the phylogenetic analysis based on the 18S rDNA sequencing showed that Frontonia is a non-monophyletic group. The systematics of this genus should be deeply reviewed, although additional issues complicate the task solving. First, type species of the genus is not yet clearly established, and no type material is available. In this context, the situation of F. vernalis, one of the first Frontonia ever described, is somehow puzzled: the description of this ciliate made by Ehrenberg (in 1833 and 1838) contains several inaccuracies and subsequent misidentifications by other authors occurred. Moreover, the 18S rDNA sequence of a putative F. vernalis is available on GenBank, but no morphological description of the correspondent specimens is provided; thus, in our opinion, it should be only prudently associated with F. vernalis or at least indicated as “F. vernalis”.

Results

In the present work, we provide the neotypification of F. vernalis newly found in Italy, presenting its multidisciplinary description and its neotype material. Similarly, we describe a novel species bearing Chlorella-like endosymbionts, Frontonia paravernalis sp. nov., retrieved in two far distant locations (Italy, Russia). A critical discussion on the status of Frontonia taxonomy and phylogeny is also presented, based on the 18S rDNA sequencing of both these two newly collected species and other 14 frontoniids isolated in different parts of the world. Finally, in the present study F. leucas was neotypified and proposed as the type species of the genus.

Conclusions

Green frontoniids form a monophyletic clade of freshwater organisms characterized by having a single contractile vacuole and bearing intracytoplasmatic Chlorella-like symbionts. With the neotypification of F. vernalis and F. leucas a fundamental step in Frontonia systematics was taken, and the bases for further taxonomic studies were laid.
Training registered nurses to conduct pre-implementation assessment to inform program scale-up: an example from the rural Transitions Nurse Program
Authors: Leonard Chelsea , Gilmartin Heather , McCreight Marina , Kelley Lynette , Mayberry Ashlea , Burke Robert E.
Published: March 2021

Objectives

Adapting evidence-based practices to local settings is critical for successful implementation and dissemination. A pre-implementation assessment evaluates local context to inform implementation, but there is little published guidance for clinician-implementers. The rural Transitions Nurse Program (TNP) is a care coordination intervention that facilitates care transitions for rural veterans. In year 1 of TNP, pre-implementation assessments were conducted by a centralized project team through multi-day visits at five sites nationwide. In year 2, we tested if local site TNP nurses could conduct pre-implementation assessments using evidence-based tools and coaching from the TNP team. This required developing a multicomponent pre-implementation strategy bundle to guide data collection and synthesis. We hypothesized that (1) nurses would find the pre-implementation assessment useful for tailoring TNP to local contexts and (2) nurses would identify similar barriers and facilitators to those identified at first year sites.

Methods

The bundle included guides for conducting key informant interviews, brainwriting, process mapping, and reflective journaling. We evaluated TNP nurse satisfaction and perceived utility of the structure and process of the training and bundle through pre-post surveys. To assess the outcome of data collection efforts, we interviewed nurses 4 months after completion of the pre-implementation assessment to determine if and how they used pre-implementation findings to tailor implementation of TNP to local contexts. To further assess outcomes, all data that the nurses collected were analyzed thematically. Themes related to barriers and facilitators were compared across years.

Findings

Five nurses at different VA medical centers used the pre-implementation strategy bundle to collect site-level data and completed pre-post surveys. Findings indicated that the pre-implementation assessment was highly recommended, and the bundle provided adequate training. Nurses felt that pre-implementation work oriented them to the local context and illustrated how to integrate TNP into existing processes. Barriers and facilitators identified by nurses were similar to those collected in year 1 by the TNP research team, including communication challenges, need for buy-in, and logistical concerns.

Conclusions

This proof-of-concept study suggests that evidence-based tools can effectively guide clinician-implementers through the process of conducting a pre-implementation assessment. This approach positively informed TNP implementation and oriented nurses to their local context prior to implementation.
Antibiograms of intensive care units at an Egyptian tertiary care hospital
Authors: Negm Essamedin M. , Mowafy Sherif M. S. , Mohammed Ahmad A. , Amer Marwa G. , Tawfik Ahmed E. , Ibrahim Ashraf E. S. , Hassan Tarek H.
Published: March 2021

Background

Intensive care unit (ICU) infection management is a growing challenge, and physicians should have regularly updated antibiograms. The aim of this study was to find out the prevalence of pathogens and to determine their antibiotic susceptibility in different ICUs of an Egyptian tertiary care hospital. This retrospective record-based cross-sectional study was conducted from the first of January to the last of December 2019 with a total of 45,221 diagnostic first-isolate culture/patient obtained from different ICUs in Zagazig University Hospitals. The antibiogram construction was done according to Clinical and Laboratory Standards Institute instructions and a Web-based antibiogram at Stanford University.

Results

The positive blood isolate was the most prevalent infection site (32.37%) followed by sputum and urine isolates. Gram-negative microorganisms (74.41%) were the most common pathogens, with Klebsiella pneumoniae as the most frequently identified one with an incidence of 33.51% followed by Escherichia coli with 19.3% incidence. Antibiotic sensitivity showed that colistin is the most effective antibiotic with 96.2%, 94.7%, and 89.9% sensitivity for Klebsiella, E. coli, and Acinetobacter, respectively, while carbepenems sensitivity was extremely low, showing 19.5% and 19% imipenem and meropenem sensitivity for Klebsiella, 48% imipenem and 52.7% meropenem sensitivity for E. coli, 20.1% imipenem and 20.3% meropenem sensitivity for Acinetobacter, and 17.3% imipenem and 15.2% meropenem sensitivity for Pseudomonas aeruginosa. Fungal infection in our results represented less than 1%.

Conclusion

Our study provides a local baseline epidemiological data which describes the extent of the ICU infections problem in this tertiary care hospital.

Trial registration

ClinicalTrials.gov (NCT04318613)
Multicenter Prospective Cohort Study of the Patient-Reported Outcome Measures PRO-CTCAE and CAT EORTC QLQ-C30 in Major Abdominal Cancer Surgery (PATRONUS): A Student-Initiated German Medical Audit (SIGMA) Study
Authors:   CHIR-Net SIGMA Study Group*, Mihaljevic André L.
Published: March 2021

Background

The patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the computerized adaptive testing (CAT) version of the EORTC quality-of-life questionnaire QLQ-C30 have been proposed as new PRO measures in oncology; however, their implementation in patients undergoing cancer surgery has not yet been evaluated.

Methods

Patients undergoing elective abdominal cancer surgery were enrolled in a prospective multicenter study, and postoperative complications were recorded according to the Dindo–Clavien classification. Patients reported PRO data using the CAT EORTC QLQ-C30 and the PRO-CTCAE to measure 12 core cancer symptoms. Patients were followed-up for 6 months postoperatively. The study was carried out by medical students of the CHIR-Net SIGMA study network.

Results

Data of 303 patients were obtained and analyzed across 15 sites. PRO-CTCAE symptoms ‘poor appetite’, ‘fatigue’, ‘exhaustion’ and ‘sleeping problems’ increased after surgery and climaxed 10–30 days postoperatively. At 3–6 months postoperatively, no PRO-CTCAE symptom differed significantly to baseline. Patients reported higher ‘social functioning’ (p = 0.021) and overall quality-of-life scores (p < 0.05) 6 months after cancer surgery compared with the baseline level. There was a lack of correlation between postoperative complications or death and any of the PRO items evaluated. Feasibility endpoints for student-led research were met.

Conclusion

The two novel PRO questionnaires were successfully applied in surgical oncology. Postoperative complications do not affect health-reported quality-of-life or common cancer symptoms following major cancer surgery. The feasibility of student-led multicenter clinical research was demonstrated, but might be enhanced by improved student training.
Sampling flying bats with thermal and near-infrared imaging and ultrasound recording: hardware and workflow for bat point counts
Authors: Darras Kevin , Yusti Ellena , Knorr Andreas , Huang Joe Chun-Chia , Kartono Agus Priyono , . Ilham
Published: March 2021

Bat communities can usually only be comprehensively monitored by combining ultrasound recording and trapping techniques. Here, we propose bat point counts, a novel, single method to sample all flying bats. We designed a sampling rig that combines a thermal scope to detect flying bats and their flight patterns, an ultrasound recorder to identify echolocating bat calls, and a near-infrared camera and LED illuminator to photograph bat morphology. We evaluated the usefulness of the flight pattern information, echolocation call recordings, and near-infrared photographs produced by our sampling rig to determine a workflow to process these heterogenous data types. We present a conservative workflow to enable taxonomic discrimination and identification of bat detections. Our sampling rig and workflow allowed us to detect both echolocating and non-echolocating bats and we could assign 84% of the detections to a guild. Subsequent identification can be carried out with established methods such as identification keys and call libraries, based on the visible morphological features and echolocation calls. Currently, a higher near-infrared picture quality is required to resolve more detailed diagnostic morphology, but there is considerable potential to extract more information with higher-intensity illumination. This is the first proof-of-concept for bat point counts, a method that can passively sample all flying bats in their natural environment.
Radishchev’s “Bova” and Its Place in the History of Russian Folkloric Stylization
Authors: Wachtel Michael
Published: March 2021

Aleksandr Radishchev (1749–1802) has long been recognized for the boldness and originality of his writings. The present essay examines a substantial but largely forgotten poetic work (“Bova”), focusing on its experimental metrics. The author considers Radishchev’s possible motivations in creating this unprecedented form and suggests a new means of categorizing it.
Data-Driven Optimization: A Reproducing Kernel Hilbert Space Approach
Authors: Bertsimas Dimitris , Koduri Nihal
Published: March 2021

Data-Driven Optimization Using Reproducing Kernel Hilbert Spaces
Modelling of the Micro Lubricating Gap Geometry Between Valve Plate and Cylinder Block in an Axial Piston Pump
Authors: Zhang Zhiqiang , Yuan Haitao , Song Jianli , Zhou Haibo
Published: March 2021

The paper focuses on the effect of force and torque balance (FTB) of cylinder block, coaxiality error (CE) between main shaft and cylinder block, and other factors, especially eccentric wear (OTEW) of valve plate on wedge angle of the micro lubricating gap between valve plate and cylinder block, and a novel trigonometric function model of the gap geometry and mechanical balance equations of cylinder block are proposed. The three eddy current displacement sensors are used to measure the gap thickness. The results show that, the theoretical wedge angle due to FTB is nearly 1.2E-4, the test wedge angle owing to CE 1.65E-4~4.3E-4, the wedge angle by OTEW about 1.35E-3, therefore, CE and OTEW have a larger impact on the wedge angle. The test results demonstrate the total wedge angle obviously increases with the enlargement of swash plate angle but slightly rises with the increasing working pressure.
Management of acute paediatric fractures treated surgically in the UK: a cross-sectional study
Authors: Rashid MS , Dorman S , Humphry S ,   POTS study collaborators
Published: March 2021

Introduction

The epidemiology of acute paediatric orthopaedic trauma managed surgically across the NHS is poorly described. Compliance against national standards for the management of supracondylar humeral fractures is also unknown at a national level.

Methods

Collaborators in 129 NHS hospitals prospectively collected data on surgically managed acute paediatric orthopaedic trauma cases. Data were collected over a seven-day period and included demographics, injury characteristics, operative details and timing of surgery. A national audit was also undertaken to evaluate compliance with the British Orthopaedic Association Standards for Trauma Guideline 11: Supracondylar Fractures of the Humerus in Children.

Results

Data were captured on 770 surgically treated cases. The three most common injuries were forearm fractures of both bones (n = 235), distal radius fractures (n = 194) and supracondylar elbow fractures (n = 89). The mode day of injury was Friday (n = 136) and the mode day of surgery was Saturday (n = 138). 88% of supracondylar fractures received surgery on the day of presentation or the following day. Only 14% of supracondylar fractures were treated surgically after 8pm; 33/89 used 2.0mm Kirschner wires, 38/89 used 1.6mm wires and 2/89 used 1.2mm wires.

Conclusion

Forearm fractures of both bones, distal radius fractures and supracondylar humeral fractures were the three most common injuries treated surgically. There is wide variation in compliance against national standards in the management of supracondylar humeral fractures with 88% undertaking surgery on the day of or the day following presentation but only 37% using the recommended 2.0mm Kirschner wires.
Early presentation of post-intubation tracheoesophageal fistula with severe tracheal stenosis in COVID-19 patient
Authors: García-Herreros LG , Jiménez A , Cabrera LF , Vinck EE , Pedraza M
Published: March 2021

The current global COVID-19 pandemic is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, acquired tracheoesophageal fistulas are mainly iatrogenic lesions produced by prolonged tracheal intubation. We present a case of tracheoesophageal fistula with severe tracheal stenosis following tracheal intubation in a patient with SARS-CoV-2 infection.
Microvascular reconstruction for head and neck cancers in high risk population: clinical outcomes and complications
Authors: Katna R , Singh S , Bhosale B , Deshpande A , Kalyani N ,   On behalf of Mumbai Oncology Group – Head and Neck
Published: March 2021

Introduction

Microvascular reconstruction is the gold standard for reconstruction in oral cavity cancers. Age and comorbidities determine the type of reconstruction. We aimed to analyse the impact of high-risk comorbidities on perioperative morbidity.

Methods

This is a retrospective study of 317 patients undergoing microvascular reconstruction from January 2014 to December 2017. High risk patients were based on age, American Society of Anaesthesiologists (ASA) grade (III/IV) and Charlson comorbidity index (CCI) score >4; overall, 73 out of 317 patients were evaluated.

Results

Median age was 59 years. Five patients (6.8%) had complete flap failures and seven (9.5%) had minor complications (wound breakdown, bleeding, wound dehiscence, partial flap loss). ASA score of IV was significantly associated with morbidity while age >65 years and CCI >4 was not associated. The overall flap success rate was 93.2%.

Conclusions

A high-risk population has nearly similar outcomes for microvascular reconstruction as a younger age group. High ASA score adversely affects surgery-related outcomes.
Bio-inspired butterfly core-shaped photonic crystal fiber-based refractive index sensor
Authors: Mashrafi Md. , Kamrunnahar Q. M. , Haider Firoz , Haider Rakib , Aoni Rifat Ahmmed , Ahmed Rajib
Published: March 2021

Light controllability, design flexibility, and non-linearity features of photonic crystal fiber (PCF) based surface plasmon resonance (SPR) sensor enable high sensitivity in the field of biosensing. Here, bio-inspired butterfly-core shaped microstructure fiber-based plasmonic sensor is proposed where circular air-holes are arranged to enhance the sensing performance. Butterfly shaped core is designed to confine the incident light into the core by preventing light scattering through the cladding and helps to excite surface electron of plasmonic metal layer. Chemically stable plasmonic material gold is used to produce the SPR phenomenon. The analyte detection layer and the plasmon layer are located externally on the PCF surface to make the detection process more feasible. The sensor performance is studied based on the finite element method (FEM), and the structural parameters are tuned to obtain maximum sensor performance. This modified core-based sensor exhibits the maximum wavelength sensitivity (WS) of 56,000 nm/RIU and the amplitude sensitivity (AS) of 1,584 RIU-1 for the x-polarized mode. It also shows an improved sensor resolution (SR) of 1.8 ×10−6 RIU, along with a decent figure of merit (FOM) of 691 RIU-1. Moreover, this sensor can detect analyte refractive indexes (RI) within a broad RI range of 1.33 to 1.42 in the visible to near-infrared wavelength range (450–2100 nm). Finally, the proposed sensor may have possible application to detect organic chemicals, food quality, and diseases with high accuracy due to outstanding sensitivity and linearity.
A computational study of co-inhibitory immune complex assembly at the interface between T cells and antigen presenting cells
Authors: Su Zhaoqian , Dhusia Kalyani , Wu Yinghao
Published: March 2021

The activation and differentiation of T-cells are mainly directly by their co-regulatory receptors. T lymphocyte-associated protein-4 (CTLA-4) and programed cell death-1 (PD-1) are two of the most important co-regulatory receptors. Binding of PD-1 and CTLA-4 with their corresponding ligands programed cell death-ligand 1 (PD-L1) and B7 on the antigen presenting cells (APC) activates two central co-inhibitory signaling pathways to suppress T cell functions. Interestingly, recent experiments have identified a new cis-interaction between PD-L1 and B7, suggesting that a crosstalk exists between two co-inhibitory receptors and the two pairs of ligand-receptor complexes can undergo dynamic oligomerization. Inspired by these experimental evidences, we developed a coarse-grained model to characterize the assembling of an immune complex consisting of CLTA-4, B7, PD-L1 and PD-1. These four proteins and their interactions form a small network motif. The temporal dynamics and spatial pattern formation of this network was simulated by a diffusion-reaction algorithm. Our simulation method incorporates the membrane confinement of cell surface proteins and geometric arrangement of different binding interfaces between these proteins. A wide range of binding constants was tested for the interactions involved in the network. Interestingly, we show that the CTLA-4/B7 ligand-receptor complexes can first form linear oligomers, while these oligomers further align together into two-dimensional clusters. Similar phenomenon has also been observed in other systems of cell surface proteins. Our test results further indicate that both co-inhibitory signaling pathways activated by B7 and PD-L1 can be down-regulated by the new cis-interaction between these two ligands, consistent with previous experimental evidences. Finally, the simulations also suggest that the dynamic and the spatial properties of the immune complex assembly are highly determined by the energetics of molecular interactions in the network. Our study, therefore, brings new insights to the co-regulatory mechanisms of T cell activation.
A neuroendocrine pathway modulating osmotic stress in Drosophila
Authors: Zandawala Meet , Nguyen Thomas , Balanyà Segura Marta , Johard Helena A. D. , Amcoff Mirjam , Wegener Christian , Paluzzi Jean-Paul , Nässel Dick R.
Published: March 2021

Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown ofCrzand acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs ofCapa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown ofCrzRin Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body inDrosophila.