bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular drivers of insecticide resistance in the Sahelo-Sudanian populations of a major malaria vector Anopheles coluzzii
Authors: Ibrahim Sulaiman S. , Muhammad Abdullahi , Hearn Jack , Weedall Gareth D. , Nagi Sanjay C. , Mukhtar Muhammad M. , Fadel Amen N. , Mugenzi Leon J. , Patterson Edward I. , Irving Helen , Wondji Charles S.
Published: May 2023

Background

Information on common markers of metabolic resistance in malaria vectors from countries sharing similar eco-climatic characteristics can facilitate coordination of malaria control. Here, we characterized populations of the major malaria vector Anopheles coluzzii from Sahel region, spanning four sub-Saharan African countries: Nigeria, Niger, Chad and Cameroon.

Results

Genome-wide transcriptional analysis identified major genes previously implicated in pyrethroid and/or cross-resistance to other insecticides, overexpressed across the Sahel, including CYP450s, glutathione S-transferases, carboxylesterases and cuticular proteins. Several, well-known markers of insecticide resistance were found in high frequencies—including in the voltage-gated sodium channel (V402L, I940T, L995F, I1527T and N1570Y), the acetylcholinesterase-1 gene (G280S) and the CYP4J5-L43F (which is fixed). High frequencies of the epidemiologically important chromosomal inversion polymorphisms, 2La, 2Rb and 2Rc, were observed (~80% for 2Rb and 2Rc). The 2La alternative arrangement is fixed across the Sahel. Low frequencies of these inversions (<10%) were observed in the fully insecticide susceptible laboratory colony of An. coluzzii (Ngoussou). Several of the most commonly overexpressed metabolic resistance genes sit in these three inversions. Two commonly overexpressed genes, GSTe2 and CYP6Z2, were functionally validated. Transgenic Drosophila melanogaster flies expressing GSTe2 exhibited extremely high DDT and permethrin resistance (mortalities <10% in 24h). Serial deletion of the 5′ intergenic region, to identify putative nucleotide(s) associated with GSTe2 overexpression, revealed that simultaneous insertion of adenine nucleotide and a transition (T->C), between Forkhead box L1 and c-EST putative binding sites, were responsible for the high overexpression of GSTe2 in the resistant mosquitoes. Transgenic flies expressing CYP6Z2 exhibited marginal resistance towards 3-phenoxybenzylalcohol (a primary product of pyrethroid hydrolysis by carboxylesterases) and a type II pyrethroid, α-cypermethrin. However, significantly higher mortalities were observed in CYP6Z2 transgenic flies compared with controls, on exposure to the neonicotinoid, clothianidin. This suggests a possible bioactivation of clothianidin into a toxic intermediate, which may make it an ideal insecticide against populations of An. coluzzii overexpressing this P450.

Conclusions

These findings will facilitate regional collaborations within the Sahel region and refine implementation strategies through re-focusing interventions, improving evidence-based, cross-border policies towards local and regional malaria pre-elimination.
Modeling early germline immunization after horizontal transfer of transposable elements reveals internal piRNA cluster heterogeneity
Authors: Asif-Laidin Amna , Casier Karine , Ziriat Zoheir , Boivin Antoine , Viodé Elise , Delmarre Valérie , Ronsseray Stéphane , Carré Clément , Teysset Laure
Published: May 2023

Background

A fraction of all genomes is composed of transposable elements (TEs) whose mobility needs to be carefully controlled. In gonads, TE activity is repressed by PIWI-interacting RNAs (piRNAs), a class of small RNAs synthesized by heterochromatic loci enriched in TE fragments, called piRNA clusters. Maintenance of active piRNA clusters across generations is secured by maternal piRNA inheritance providing the memory for TE repression. On rare occasions, genomes encounter horizontal transfer (HT) of new TEs with no piRNA targeting them, threatening the host genome integrity. Naïve genomes can eventually start to produce new piRNAs against these genomic invaders, but the timing of their emergence remains elusive.

Results

Using a set of TE-derived transgenes inserted in different germline piRNA clusters and functional assays, we have modeled a TE HT in Drosophila melanogaster. We have found that the complete co-option of these transgenes by a germline piRNA cluster can occur within four generations associated with the production of new piRNAs all along the transgenes and the germline silencing of piRNA sensors. Synthesis of new transgenic TE piRNAs is linked to piRNA cluster transcription dependent on Moonshiner and heterochromatin mark deposition that propagates more efficiently on short sequences. Moreover, we found that sequences located within piRNA clusters can have different piRNA profiles and can influence transcript accumulation of nearby sequences.

Conclusions

Our study reveals that genetic and epigenetic properties, such as transcription, piRNA profiles, heterochromatin, and conversion efficiency along piRNA clusters, could be heterogeneous depending on the sequences that compose them. These findings suggest that the capacity of transcriptional signal erasure induced by the chromatin complex specific of the piRNA cluster can be incomplete through the piRNA cluster loci. Finally, these results have revealed an unexpected level of complexity that highlights a new magnitude of piRNA cluster plasticity fundamental for the maintenance of genome integrity.
CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis
Authors: Wang Yujuan , Zhang Yuan , Guo Xinyu , Zheng Yiqiang , Zhang Xinjie , Feng Shanshan , Wu Hui-Yuan
Published: May 2023

Background

The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) — polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis.

Results

In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP — CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation.

Conclusion

These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.
A comparison of point-tracking algorithms in ultrasound videos from the upper limb
Authors: Magana-Salgado Uriel , Namburi Praneeth , Feigin-Almon Micha , Pallares-Lopez Roger , Anthony Brian
Published: May 2023

Tracking points in ultrasound (US) videos can be especially useful to characterize tissues in motion. Tracking algorithms that analyze successive video frames, such as variations of Optical Flow and Lucas–Kanade (LK), exploit frame-to-frame temporal information to track regions of interest. In contrast, convolutional neural-network (CNN) models process each video frame independently of neighboring frames. In this paper, we show that frame-to-frame trackers accumulate error over time. We propose three interpolation-like methods to combat error accumulation and show that all three methods reduce tracking errors in frame-to-frame trackers. On the neural-network end, we show that a CNN-based tracker, DeepLabCut (DLC), outperforms all four frame-to-frame trackers when tracking tissues in motion. DLC is more accurate than the frame-to-frame trackers and less sensitive to variations in types of tissue movement. The only caveat found with DLC comes from its non-temporal tracking strategy, leading to jitter between consecutive frames. Overall, when tracking points in videos of moving tissue, we recommend using DLC when prioritizing accuracy and robustness across movements in videos, and using LK with the proposed error-correction methods for small movements when tracking jitter is unacceptable.
The roles and involvement of global health partners in the health workforce: an exploratory analysis
Authors: Nove Andrea , Ajuebor Onyema , Diallo Khassoum , Campbell James , Cometto Giorgio
Published: May 2023

Development partners and global health initiatives are important actors in financing health systems in many countries. Despite the importance of the health workforce to the attainment of global health targets, the contribution of global health initiatives to health workforce strengthening is unclear. A 2020 milestone in the Global Strategy on Human Resources for Health is that “all bilateral and multilateral agencies have participated in efforts to strengthen health workforce assessments and information exchange in countries.” This milestone exists to encourage strategic investments in the health workforce that are evidence-based and incorporate a health labour market approach as an indication of policy comprehensiveness. To assess progress against this milestone, we reviewed the activities of 23 organizations (11 multilaterals and 12 bilaterals) which provide financial and technical assistance to countries for human resources for health, by mapping grey and peer-reviewed literature published between 2016 and 2021. The Global Strategy states that health workforce assessment involves a “deliberate strategy and accountability mechanisms on how specific programming contributes to health workforce capacity-building efforts” and avoids health labour market distortions. Health workforce investments are widely recognized as essential for the achievement of global health goals, and some partners identify health workforce as a key strategic focus in their policy and strategy documents. However, most do not identify it as a key focus, and few have a published specific policy or strategy to guide health workforce investments. Several partners include optional health workforce indicators in their monitoring and evaluation processes and/or require an impact assessment for issues such as the environment and gender equality. Very few, however, have embedded efforts in their governance mechanisms to strengthen health workforce assessments. On the other hand, most have participated in health workforce information exchange activities, including strengthening information systems and health labour market analyses. Although there is evidence of participation in efforts to strengthen health workforce assessments and (especially) information exchange, the achievement of this milestone of the Global Strategy requires more structured policies for the monitoring and evaluation of health workforce investments to optimize the value of these investments and contribute towards global and national health goals.
Local government policy to facilitate healthy and sustainable diets and the broader policy hierarchy: insights from Milan Urban Food Policy Pact cities
Authors: Barbour Liza R. , Woods Julie L. , Brimblecombe Julie K.
Published: May 2023

Background

Local government authorities are well positioned to change the way food is produced and consumed through the implementation of integrated food policies. By facilitating the uptake of healthy and sustainable diet-related practices, integrated local government food policy can trigger change throughout the food supply chain. This study aimed to provide insights as to how the policy hierarchy surrounding local governments may be influencing local government’s capacity to create integrated food policy.

Methods

Content analysis was conducted on local government food policies (n = 36) from signatory cities of the Milan Urban Food Policy Pact were mapped to seven global regions. A set of 13 predetermined healthy and sustainable diet-related practices, organized into three categories: “where to source food”, “what to eat” and “how to eat”, was used to assess the level of integration of each local government food policy. Additional policies from the broader policy hierarchy that were mentioned in each local government food policy were sourced and then screened for relevancy, charted according to their level of administration (local, national, global region, international) and analysed to consider which diet-related practice(s) each broader policy was likely to promote.

Results

Analysis revealed three key insights: (i) local government food policies across all included global regions (n = 4) mostly promoted practices in the “where to source food” category, (ii) local government food policies across all global regions referred to policies from higher levels of administration (local, national, global region and international) which tended to also promote practices in the “where to source food” category and (iii) regarding the level of integration, local government food policies in Europe and Central Asia targeted the highest number of diet-related practices.

Conclusions

The level of integration of food policy at national, global region and international levels may be influencing that of local governments. Further research is required to understand why local government food policies are referring to some relevant policies and not others, and to determine whether a greater focus on the diet-related practices of “what to eat” and “how to eat” in policies from higher levels of government would support local governments to also prioritize these practices in their food policies.
Mistreatment of women during childbirth and its influencing factors in public maternity hospitals in Tehran, Iran: a multi-stakeholder qualitative study
Authors: Mirzania Marjan , Shakibazadeh Elham , Bohren Meghan A. , Hantoushzadeh Sedigheh , Babaey Farah , Khajavi Abdoljavad , Foroushani Abbas Rahimi
Published: May 2023

Background

Mistreatment during labour and childbirth is a common experience for many women around the world. This study aimed to explore the manifestations of mistreatment and its influencing factors in public maternity hospitals in Tehran.

Methods

A formative qualitative study was conducted using a phenomenological approach in five public hospitals between October 2021 and May 2022. Sixty in-depth face-to-face interviews were conducted with a purposive sample of women, maternity healthcare providers, and managers. Data were analyzed with content analysis using MAXQDA 18.

Results

Mistreatment of women during labour and childbirth was manifested in four form: (1) physical abuse (fundal pressure); (2) verbal abuse (judgmental comments, harsh and rude language, and threats of poor outcomes); (3) failure to meet professional standards of care (painful vaginal exams, neglect and abandonment, and refusal to provide pain relief); and (4) poor rapport between women and providers (lack of supportive care and denial of mobility). Four themes were also identified as influencing factors: (1) individual-level factors (e.g., providers’ perception about women’s limited knowledge on childbirth process), (2) healthcare provider-level factors (e.g., provider stress and stressful working conditions); (3) hospital-level factors (e.g., staff shortages); and (4) national health system-level factors (e.g., lack of access to pain management during labour and childbirth).

Conclusions

Our study showed that women experienced various forms of mistreatment during labour and childbirth. There were also multiple level drivers for mistreatment at individual, healthcare provider, hospital and health system levels. Addressing these factors requires urgent multifaceted interventions.
The artificial intelligence and machine learning in lung cancer immunotherapy
Authors: Gao Qing , Yang Luyu , Lu Mingjun , Jin Renjing , Ye Huan , Ma Teng
Published: May 2023

Since the past decades, more lung cancer patients have been experiencing lasting benefits from immunotherapy. It is imperative to accurately and intelligently select appropriate patients for immunotherapy or predict the immunotherapy efficacy. In recent years, machine learning (ML)-based artificial intelligence (AI) was developed in the area of medical-industrial convergence. AI can help model and predict medical information. A growing number of studies have combined radiology, pathology, genomics, proteomics data in order to predict the expression levels of programmed death-ligand 1 (PD-L1), tumor mutation burden (TMB) and tumor microenvironment (TME) in cancer patients or predict the likelihood of immunotherapy benefits and side effects. Finally, with the advancement of AI and ML, it is believed that "digital biopsy" can replace the traditional single assessment method to benefit more cancer patients and help clinical decision-making in the future. In this review, the applications of AI in PD-L1/TMB prediction, TME prediction and lung cancer immunotherapy are discussed.
Traumatic hemorrhage and chain of survival
Authors: Latif Rana K. , Clifford Sean P. , Baker Jeffery A. , Lenhardt Rainer , Haq Mohammad Z. , Huang Jiapeng , Farah Ian , Businger Jerrad R.
Published: May 2023

Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. Following death related to central nervous system injury, hemorrhage accounts for the majority of remaining traumatic fatalities. Among those with severe trauma that reach the hospital alive, many may survive if the hemorrhage and traumatic injuries are diagnosed and adequately treated in a timely fashion. This article aims to review the recent advances in pathophysiology management following a traumatic hemorrhage as well as the role of diagnostic imaging in identifying the source of hemorrhage. The principles of damage control resuscitation and damage control surgery are also discussed. The chain of survival for severe hemorrhage begins with primary prevention; however, once trauma has occurred, prehospital interventions and hospital care with early injury recognition, resuscitation, definitive hemostasis, and achieving endpoints of resuscitation become paramount. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.
Heterologous expression and characterization of novel GH12 β-glucanase and AA10 lytic polysaccharide monooxygenase from Streptomyces megaspores and their synergistic action in cellulose saccharification
Authors: Qin Xing , Yang Kun , Zou Jiahuan , Wang Xiaolu , Tu Tao , Wang Yuan , Su Xiaoyun , Yao Bin , Huang Huoqing , Luo Huiying
Published: May 2023

Background

The combination of cellulase and lytic polysaccharide monooxygenase (LPMO) is known to boost enzymatic saccharification of cellulose. Although the synergy between cellulases (GH5, 6 or 7) and LPMOs (AA9) has been extensively studied, the interplay between other glycoside hydrolase and LPMO families remains poorly understood.

Results

In this study, two cellulolytic enzyme-encoding genes SmBglu12A and SmLpmo10A from Streptomyces megaspores were identified and heterologously expressed in Escherichia coli. The recombinant SmBglu12A is a non-typical endo-β-1,4-glucanase that preferentially hydrolyzed β-1,3-1,4-glucans and slightly hydrolyzed β-1,4-glucans and belongs to GH12 family. The recombinant SmLpmo10A belongs to a C1-oxidizing cellulose-active LPMO that catalyzed the oxidation of phosphoric acid swollen cellulose to produce celloaldonic acids. Moreover, individual SmBglu12A and SmLpmo10A were both active on barley β-1,3-1,4-glucan, lichenan, sodium carboxymethyl cellulose, phosphoric acid swollen cellulose, as well as Avicel. Furthermore, the combination of SmBglu12A and SmLpmo10A enhanced enzymatic saccharification of phosphoric acid swollen cellulose by improving the native and oxidized cello-oligosaccharides yields.

Conclusions

These results proved for the first time that the AA10 LPMO was able to boost the catalytic efficiency of GH12 glycoside hydrolases on cellulosic substrates, providing another novel combination of glycoside hydrolase and LPMO for cellulose enzymatic saccharification.
An optimized force-triggered density gradient sedimentation method for isolation of pelage follicle dermal papilla cells from neonatal mouse skin
Authors: Du Lijuan , Gan Yuyang , Zheng Bowen , Huang Junfei , Hu Zhiqi , Miao Yong
Published: May 2023

Background

The dermal papilla cells are a specialized population of mesenchymal cells located at the base of the hair follicle (HF), which possess the capacity to regulate HF morphogenesis and regeneration. However, lack of cell-type specific surface markers restricts the isolation of DP cells and application for tissue engineering purposes.

Methods

We describe a novel force-triggered density gradient sedimentation (FDGS) method to efficiently obtain purified follicular DP-spheres cells from neonatal mouse back skin, utilizing only centrifugation and optimized density gradients.

Results

Expression of characteristic DP cell markers, alkaline phosphatase, β-catenin, versican, and neural cell adhesion molecules, were confirmed by immunofluorescence. Further, the patch assays demonstrated that DP cells maintained their hair regenerative capacity in vivo. Compared with current methods, including microdissection and fluorescence-activated cell sorting, the FDGS technique is simpler and more efficient for isolating DP cells from neonatal mouse skin.

Conclusions

The FDGS method will improve the research potential of neonatal mouse pelage-derived DP cells for tissue engineering purposes.
Integrated analysis of robust sex-biased gene signatures in human brain
Authors: Wapeesittipan Pattama , Joshi Anagha
Published: May 2023

Background

Sexual dimorphism is highly prominent in mammals with many physiological and behavioral differences between male and female form of the species. Accordingly, the fundamental social and cultural stratification factors for humans is sex. The sex differences are thought to emerge from a combination of genetic and environmental factors. It distinguishes individuals most prominently on the reproductive traits, but also affects many of the other related traits and manifest in different disease susceptibilities and treatment responses across sexes. Sex differences in brain have raised a lot of controversy due to small and sometimes contradictory sex-specific effects. Many studies have been published to identify sex-biased genes in one or several brain regions, but the assessment of the robustness of these studies is missing. We therefore collected huge amount of publicly available transcriptomic data to first estimate whether consistent sex differences exist and further explore their likely origin and functional significance.

Results and conclusion

In order to systematically characterise sex-specific differences across human brain regions, we collected transcription profiles for more than 16,000 samples from 46 datasets across 11 brain regions. By systematic integration of the data from multiple studies, we identified robust transcription level differences in human brain across to identify male-biased and female-biased genes in each brain region. Firstly, both male and female-biased genes were highly conserved across primates and showed a high overlap with sex-biased genes in other species. Female-biased genes were enriched for neuron-associated processes while male-biased genes were enriched for membranes and nuclear structures. Male-biased genes were enriched on the Y chromosome while female-biased genes were enriched on the X chromosome, which included X chromosome inactivation escapees explaining the origins of some sex differences. Male-biased genes were enriched for mitotic processes while female-biased genes were enriched for synaptic membrane and lumen. Finally, sex-biased genes were enriched for drug-targets and more female-biased genes were affected by adverse drug reactions than male-biased genes. In summary, by building a comprehensive resource of sex differences across human brain regions at gene expression level, we explored their likely origin and functional significance. We have also developed a web resource to make the entire analysis available for the scientific community for further exploration, available at https://joshiapps.cbu.uib.no/SRB_app/
Effect of the identification group size and image resolution on the diagnostic performance of metabolic Alzheimer’s disease-related pattern
Authors: Štokelj Eva , Tomše Petra , Tomanič Tadej , Dhawan Vijay , Eidelberg David , Trošt Maja , Simončič Urban ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2023

Background

Alzheimer’s disease-related pattern (ADRP) is a metabolic brain biomarker of Alzheimer’s disease (AD). While ADRP is being introduced into research, the effect of the size of the identification cohort and the effect of the resolution of identification and validation images on ADRP’s performance need to be clarified.

Methods

240 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography images [120 AD/120 cognitive normals (CN)] were selected from the Alzheimer's disease neuroimaging initiative database. A total of 200 images (100 AD/100 CN) were used to identify different versions of ADRP using a scaled subprofile model/principal component analysis. For this purpose, five identification groups were randomly selected 25 times. The identification groups differed in the number of images (20 AD/20 CN, 30 AD/30 CN, 40 AD/40 CN, 60 AD/60 CN, and 80 AD/80 CN) and image resolutions (6, 8, 10, 12, 15 and 20 mm). A total of 750 ADRPs were identified and validated through the area under the curve (AUC) values on the remaining 20 AD/20 CN with six different image resolutions.

Results

ADRP’s performance for the differentiation between AD patients and CN demonstrated only a marginal average AUC increase, when the number of subjects in the identification group increases (AUC increase for about 0.03 from 20 AD/20 CN to 80 AD/80 CN). However, the average of the lowest five AUC values increased with the increasing number of participants (AUC increase for about 0.07 from 20 AD/20 CN to 30 AD/30 CN and for an additional 0.02 from 30 AD/30 CN to 40 AD/40 CN). The resolution of the identification images affects ADRP’s diagnostic performance only marginally in the range from 8 to 15 mm. ADRP’s performance stayed optimal even when applied to validation images of resolution differing from the identification images.

Conclusions

While small (20 AD/20 CN images) identification cohorts may be adequate in a favorable selection of cases, larger cohorts (at least 30 AD/30 CN images) shall be preferred to overcome possible/random biological differences and improve ADRP’s diagnostic performance. ADRP’s performance stays stable even when applied to the validation images with a resolution different than the resolution of the identification ones.
Knowledge, attitudes and behaviour of Egyptians towards antibiotic use in the community: can we do better?
Authors: Maarouf Lina , Amin Mohamed , Evans Benjamin A. , Abouelfetouh Alaa
Published: May 2023

Background

Infectious diseases are among the leading causes of death worldwide. This is concerning because of the increasing capacity of the pathogens to develop antibiotic resistance. Antibiotic overuse and misuse remain the main drivers of resistance development. In the USA and Europe, annual campaigns raise awareness of antibiotic misuse hazards and promote their judicial use. Similar efforts are lacking in Egypt. This study assessed the knowledge of the public in Alexandria, Egypt of antibiotic misuse risks and their habits towards antibiotic use, in addition to conducting a campaign to increase awareness of the safe use of antibiotics.

Methods

A questionnaire assessing knowledge, attitudes and behaviour towards antibiotics was used to collect responses from study participants at various sports clubs in Alexandria in 2019. An awareness campaign to correct misconceptions and a post awareness survey followed.

Results

Most of the participants were well-educated (85%), in their middle age (51%) and took antibiotics last year (80%). 22% would take an antibiotic for common cold. This dropped to 7% following the awareness. There was a 1.6 time increase in participants who would start an antibiotic on a healthcare professional’s advice following the campaign. A 1.3 time increase in participants who would finish an antibiotic regimen was also observed. The campaign made all participants recognize that unwise antibiotic use is harmful to them or others; and 1.5 more participants would spread the word about antibiotic resistance. Despite learning of the risks of antibiotic use, there was no change in how often participants thought they should take antibiotics.

Conclusions

Although awareness of antibiotic resistance is rising, some wrong perceptions hold fast. This highlights the need for patient and healthcare-tailored awareness sessions as part of a structured and national public health program directed to the Egyptian population.
Dual inhibition of IDO1/TDO2 enhances anti-tumor immunity in platinum-resistant non-small cell lung cancer
Authors: Wu Chunjing , Spector Sydney A. , Theodoropoulos George , Nguyen Dan J. M. , Kim Emily Y. , Garcia Ashley , Savaraj Niramol , Lim Diane C. , Paul Ankita , Feun Lynn G. , Bickerdike Michael , Wangpaichitr Medhi
Published: May 2023

Background

The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production.

Methods

Co-culture, syngeneic, and humanize mice models were utilized. C57BL/6 mice were inoculated with either Lewis lung carcinoma mouse cells (LLC) or their platinum-resistant counterpart (LLC-CR) cells. Humanized mice were inoculated with either A (human CS cells) or ALC (human CR cells). Mice were treated with either IDO1 inhibitor or TDO2 (tryptophan 2,3-dioxygenase-2) inhibitor at 200 mg/kg P.O. once a day for 15 days; or with a new-in-class, IDO1/TDO2 dual inhibitor AT-0174 at 170 mg/kg P.O. once a day for 15 days with and without anti-PD1 antibody (10 mg/kg, every 3 days). Immune profiles and KYN and tryptophan (TRP) production were evaluated.

Results

CR tumors exhibited a more highly immunosuppressive environment that debilitated robust anti-tumor immune responses. IDO1-mediated KYN production from CR cells suppressed NKG2D on immune effector natural killer (NK) and CD8+ T cells and enhanced immunosuppressive populations of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Importantly, while selective IDO1 inhibition attenuated CR tumor growth, it concomitantly upregulated the TDO2 enzyme. To overcome the compensatory induction of TDO2 activity, we employed the IDO1/TDO2 dual inhibitor, AT-0174. Dual inhibition of IDO1/TDO2 in CR mice suppressed tumor growth to a greater degree than IDO1 inhibition alone. Significant enhancement in NKG2D frequency on NK and CD8+ T cells and a reduction in Tregs and MDSCs were observed following AT-1074 treatment. PD-L1 (programmed death-ligand-1) expression was increased in CR cells; therefore, we assessed dual inhibition + PD1 (programmed cell death protein-1) blocking and report profound anti-tumor growth and improved immunity in CR tumors which in turn extended overall survival in mice.

Conclusion

Our study reports the presence of platinum-resistant lung tumors that utilize both IDO1/TDO2 enzymes for survival, and to escape immune surveillance as a consequence of KYN metabolites. We also report early in vivo data in support of the potential therapeutic efficacy of the dual IDO1/TDO2 inhibitor AT-0174 as a part of immuno-therapeutic treatment that disrupts tumor metabolism and enhances anti-tumor immunity.
Context drives movement patterns in a mobile marine predator
Authors: Lubitz Nicolas , Daly Ryan , Filmalter John D , Sheaves Marcus , Cowley Paul D , Naesje Tor F , Barnett Adam
Published: May 2023

Intra-specific variability in movement behaviour occurs in all major taxonomic groups. Despite its common occurrence and ecological consequences, individual variability is often overlooked. As a result, there is a persistent gap in knowledge about drivers of intra-specific variability in movement and its role in fulfilling life history requirements. We apply a context-focused approach to bull sharks (Carcharhinus leucas), a highly mobile marine predator, incorporating intra-specific variability to understand how variable movement patterns arise and how they might be altered under future change scenarios. Spatial analysis of sharks, acoustically tagged both at their distributional limit and the centre of distribution in southern Africa, was combined with spatial analysis of acoustically tagged teleost prey and remote-sensing of environmental variables. The objective was to test the hypothesis that varying resource availability and magnitude of seasonal environmental change in different locations interact to produce variable yet predictable movement behaviours across a species’ distribution. Sharks from both locations showed high seasonal overlap with predictable prey aggregations. Patterns were variable in the centre of distribution, where residency, small- and large-scale movements were all recorded. In contrast, all animals from the distributional limit performed ‘leap-frog migrations’, making long-distance migrations bypassing conspecifics in the centre of distribution. By combining multiple variables related to life history requirements for animals in different environments we identified combinations of key drivers that explain the occurrence of differing movement behaviours across different contexts and delineated the effects of environmental factors and prey dynamics on predator movement. Comparisons with other taxa show striking similarities in patterns of intra-specific variability across terrestrial and marine species, suggesting common drivers.
Exploiting a heterologous construction of the 3-hydroxypropionic acid carbon fixation pathway with mesaconate as an indicator in Saccharomyces cerevisiae
Authors: Xu Shijie , Qiao Weibo , Wang Zuanwen , Fu Xiaoying , Liu Zihe , Shi Shuobo
Published: May 2023

The 3-Hydroxypropionic acid (3-HP) pathway is one of the six known natural carbon fixation pathways, in which the carbon species used is bicarbonate. It has been considered to be the most suitable pathway for aerobic CO2 fixation among the six natural carbon fixation pathways. Mesaconate is a high value-added derivative in the 3-HP pathway and can be used as a co-monomer to produce fire-retardant materials and hydrogels. In this study, we use mesaconate as a reporting compound to evaluate the construction and optimization of the sub-part of the 3-HP pathway in Saccharomyces cerevisiae. Combined with fine-tuning of the malonyl-CoA reductase (MCR-C and MCR-N) expression level and optimization of 3-Hydroxypropionyl-CoA synthase, the 3-HP sub-pathway was optimized using glucose or ethanol as the substrate, with the productions of mesaconate reaching 90.78 and 61.2 mg/L, respectively.

Graphical Abstract
A case report of sigmoid colon cancer with the inferior mesenteric artery directly originating from the superior mesenteric artery
Authors: Mizoguchi Kiyotaka , Nagayoshi Kinuko , Mizuuchi Yusuke , Tamura Koji , Sada Masafumi , Nakata Kohei , Ouchida Kenoki , Nakamura Masafumi
Published: May 2023

Background

There are few reports describing the unusual origin of the inferior mesenteric artery (IMA). We report a rare case of advanced sigmoid colon cancer with the IMA arising from the superior mesenteric artery.

Case presentation

A 59-year-old man with diarrhea and abdominal distention was diagnosed with advanced sigmoid colon cancer. Colonoscopy revealed a semi-circumferential cancer lesion in the sigmoid colon. Enhanced CT scan and CT angiography showed that the IMA directly originated from the superior mesenteric artery at the level of the second lumbar vertebra. PET-CT suggested metastases in the para-intestinal lymph nodes and the liver, but not in the central lymph nodes along the IMA. Preoperative diagnosis was sigmoid colon cancer cT4aN2aM1a cStage IVA(UICC, 8th edition). We performed laparoscopic complete resection as the radical treatment of the primary region prior to resection of the liver metastases. Intraoperative findings showed that the IMA was running parallel to the abdominal aorta; meanwhile, the colonic autonomic nerve was supplied from the lumbar splanchnic nerve at the caudal side of the duodenum. Central lymph nodes around the colonic autonomic nerve were dissected en bloc with the regional lymph nodes. Pathological radical resection including the regional lymph nodes metastasis was achieved. Two months later, complete resection of the liver metastasis was performed. After the adjuvant chemotherapy, no recurrence was observed 1.5 years after the liver resection was performed.

Conclusions

Preoperative confirmation of the anatomy helped us to safely complete radical surgery in a patient with unusual bifurcation of the IMA.
A mixed-method feasibility study of the use of the Complete Vocal Technique (CVT), a pedagogic method to improve the voice and vocal function in singers and actors, in the treatment of patients with muscle tension dysphonia: a study protocol
Authors: McGlashan Julian , Aaen Mathias , White Anna , Sadolin Cathrine
Published: May 2023

Background

Muscle tension dysphonia (MTD) results from inefficient or ineffective voice production and is the cause of voice and throat complaints in up to 40% of patients presenting with hoarseness. Standard treatment is voice therapy (SLT-VT) delivered by specialist speech therapists in voice disorders (SLT-V). The Complete Vocal Technique (CVT) is a structured, pedagogic method which helps healthy singers and other performers optimise their vocal function enabling them to produce any sound required. The aim of this feasibility study is to investigate whether CVT administered by a trained, non-clinical CVT practitioner (CVT-P) can be applied to patients with MTD before progressing to a pilot randomised control study of CVT voice therapy (CVT-VT) versus SLT-VT.

Methods/design

In this feasibility study, we use a mixed-method, single-arm, prospective cohort design. The primary aim is to demonstrate whether CVT-VT can improve the voice and vocal function in patients with MTD in a pilot study using multidimensional assessment methods. Secondary aims are to assess whether (1) a CVT-VT study is feasible to perform; (2) is acceptable to patients, the CVT-P and SLT-VTs; and (3) whether CVT-VT differs from existing SLT-VT techniques. A minimum of 10 consecutive patients with a clinical diagnosis of primary MTD (types I–III) will be recruited over a 6-month period. Up to 6 video sessions of CVT-VT will be delivered by a CVT-P using a video link. The primary outcome will be a change in pre-/post-therapy scores of a self-reported patient questionnaire (Voice Handicap Index (VHI)). Secondary outcomes include changes in throat symptoms (Vocal Tract Discomfort Scale), acoustic/electroglottographic and auditory-perceptual measures of voice. Acceptability of the CVT-VT will be assessed prospectively, concurrently and retrospectively both quantitatively and qualitatively. Differences from SLT-VT will be assessed by performing a deductive thematic analysis of CVT-P transcripts of therapy sessions.

Conclusion

This feasibility study will provide important data to support whether to proceed with a randomised controlled pilot study focusing on the effectiveness of the intervention compared to standard SLT-VT. Progression criteria will be based on demonstrating a positive outcome in treatment, successful delivery of the pilot study protocol, acceptability to all stakeholders and satisfactory recruitment rates.

Trial registration

ClinicalTrials.gov website (NCT05365126 Unique Protocol ID: 19ET004). Registered on 06 May 2022.
Malposition of a pulmonary artery catheter in the left ventricle: a case report
Authors: Nakanishi Toshiyuki , Kato Shohei , Tamura Tetsuya , Kako Eisuke , Sobue Kazuya
Published: May 2023

Background

Placement of pulmonary artery catheters may be associated with a variety of complications. We present a case where a pulmonary artery catheter was accidentally advanced into the left ventricle by perforating the intraventricular septum.

Case presentation

A 73-year-old woman underwent mitral valve dysfunction. A pulmonary artery catheter could not pass the tricuspid valve under general anesthesia, which was manually advanced via the right ventricle during surgery. After valve replacement, systolic pulmonary artery pressure was higher than radial arterial blood pressure. Transesophageal echocardiography (TEE) revealed the tip of the catheter in the left ventricle. The catheter was withdrawn and then advanced to the pulmonary artery under monitoring of TEE. Transseptal shunt flow gradually decreased and finally disappeared. The surgery was completed without additional procedures.

Conclusions

Although ventricular septal perforation is rare, it should be recognized as a potential complication of pulmonary artery catheter insertion.
Framing the fallibility of Computer-Aided Detection aids cancer detection
Authors: Kunar Melina A. , Watson Derrick G.
Published: May 2023

Computer-Aided Detection (CAD) has been proposed to help operators search for cancers in mammograms. Previous studies have found that although accurate CAD leads to an improvement in cancer detection, inaccurate CAD leads to an increase in both missed cancers and false alarms. This is known as the over-reliance effect. We investigated whether providing framing statements of CAD fallibility could keep the benefits of CAD while reducing over-reliance. In Experiment 1, participants were told about the benefits or costs of CAD, prior to the experiment. Experiment 2 was similar, except that participants were given a stronger warning and instruction set in relation to the costs of CAD. The results showed that although there was no effect of framing in Experiment 1, a stronger message in Experiment 2 led to a reduction in the over-reliance effect. A similar result was found in Experiment 3 where the target had a lower prevalence. The results show that although the presence of CAD can result in over-reliance on the technology, these effects can be mitigated by framing and instruction sets in relation to CAD fallibility.
Predictors of severe lupus flare: a prospective follow-up study
Authors: Fatemi Alimohammad , Keivani-Boroujeni Elaheh , Smiley Abbas
Published: May 2023

Background

Flare-up of systemic lupus erythematosus (SLE) is a common characteristic that could have deleterious effects on patients’ outcome and survival. The aim of this study was to identify the predictors of severe lupus flare.

Methods

120 patients with SLE were enrolled and followed-up for 23 months. Demographic, clinical manifestations, laboratory parameters and disease activity were recorded at each visit. In addition, presence of severe lupus flare at each visit was evaluated by using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLE disease activity index (SLEDAI) flare composite index. Predictors of severe lupus flare were obtained by backward logistic regression analyses. Predictors of SLEDAI were obtained by backward linear regression analyses.

Results

During the follow-up period, 47 patients had at least one episode of severe lupus flare. Mean (SD) age of patients with severe flare versus no flare was 31.7 (7.89) and 38.3 (8.24) years, respectively (P = 0.001). Ten (62.5%) out of 16 males and 37 (35.5%) out of 104 females had severe flare (P = 0.04). History of lupus nephritis (LN) was recorded in 76.5% and 44% of patients with severe flare and no severe flare, respectively (P = 0.001). Thirty-five (29.2%) patients with high anti-double-stranded DNA (anti-ds-DNA antibody) and 12 (10%) with negative anti-ds-DNA antibody had severe lupus flare (P = 0.02). By multivariable logistic regression analysis, younger age (OR = 0.87, 95% CI 0.80–0.94, P = 0.0001), history of LN (OR = 4.66, 95% CI 1.55–14.002, P = 0.006) and high SLEDAI at the first visit (OR = 1.19, 95% CI 1.026–1.38) were the main predictors of flare. When severe lupus flare after the first visit was used as the outcome variable, similar findings were observed but, SLEDAI, although left among the final predictors in the model, was not significant. SLEDAIs in future visits were mainly predicted by Anti-ds-DNA antibody, 24-h urine protein and arthritis at the first visit.

Conclusion

SLE patients with younger age, history of previous LN or high baseline SLEDAI, may need closer monitoring and follow up.
“Dancing spree” in breast: a rare case presentation
Authors: Garg Mehak , Padmanabhan Veenashankari , Ingole Sanjivanee , Gnanavel Harini , Dev Bhawna
Published: May 2023

Background

Filariasis is a tropical vector-borne disease seen predominantly in endemic areas, and the most common presentation is a lymphatic disorder in the form of lymphangiectasia. This case describes the breast as one of the uncommon sites of involvement by the filarial worm.

Case presentation

We report an uncommon case of breast filariasis with chief complaints of a nodular lump in the breast.

Conclusions

As symptoms of breast filariasis can mimic breast malignancy, appropriate diagnosis using real-time ultrasound plays a crucial role to reduce psychological stress on the patient and also helps in planning treatment.
Chloride ion erosion of pre-stressed concrete bridges in cold regions
Authors: Cui Hongtao , Zhuo Yi , Ke Dongyuan , Li Zhonglong , Li Shunlong
Published: May 2023

The erosion of chloride ions in concrete bridges will accelerate the corrosion of reinforcement, which is an important reason for the decline of bridge durability. The erosion process of chloride ion, especially deicing salt solution in cold regions, is complex and has many influencing factors. It is very important to use accurate and effective methods to analyze the chloride ion erosion process in concrete. In this study, the pre-stressed concrete bridge retired in the cold region was taken as the research object, and the specimens from the whole bridge are obtained by the method of core drilling sampling. The concentration of chloride ion was measured at different depths of the specimens. The process of chloride ion erosion was simulated in two-dimensional space through COMSOL multi-physical field simulation, and compared with the measured results. The simulation method proposed in this paper has good reliability and accuracy.