bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the truth about mining: Corporate cartography and its contestations
Authors: van Teijlingen Karolien
Published: October 2023

Conflicts over extractive projects often hinge on questions about which and whose knowledge counts, and whose realities and knowledges are ignored in decision-making. This has led scholars to scrutinize ‘corporate science’ and the ways in which mining corporations produce forms of ignorance through the deliberate distortion and manipulation of knowledge on the socio-environmental impacts of mining. In this article, I examine these dynamics through a case study of the expansion of mining in the Ecuadorian Amazon, with a focus on the role of corporate cartography and counter-mapping. Based on an analysis of the ‘lines of becoming’ of various maps and ethnographic engagements with map-makers, I argue that our inquiry into corporate science and ignorance should go beyond the notion of ‘ignorance as strategy’. To fully understand the production of ignorance in the extractive industries, we should look more comprehensively at the ways of knowing and unknowing that have become customary in this sector. Drawing on power/knowledge-ignorance and the work of decolonial critical geographers, I show that a focus on the rather mundane and standardized practices and procedures enriches our understanding of the way in which corporate actors – and in particular their consultants – produce and reproduce colonial forms of (un)knowing.
Fast Estimation of Loader’s Shovel Load Volume by 3D Reconstruction of Material Piles
Authors: Wu Binyun , Wang Shaojie , Lin Haojing , Li Shijiang , Hou Liang
Published: October 2023

Fast and accurate measurement of the volume of earthmoving materials is of great significance for the real-time evaluation of loader operation efficiency and the realization of autonomous operation. Existing methods for volume measurement, such as total station-based methods, cannot measure the volume in real time, while the bucket-based method also has the disadvantage of poor universality. In this study, a fast estimation method for a loader’s shovel load volume by 3D reconstruction of material piles is proposed. First, a dense stereo matching method (QORB–MAPM) was proposed by integrating the improved quadtree ORB algorithm (QORB) and the maximum a posteriori probability model (MAPM), which achieves fast matching of feature points and dense 3D reconstruction of material piles. Second, the 3D point cloud model of the material piles before and after shoveling was registered and segmented to obtain the 3D point cloud model of the shoveling area, and the Alpha-shape algorithm of Delaunay triangulation was used to estimate the volume of the 3D point cloud model. Finally, a shovel loading volume measurement experiment was conducted under loose-soil working conditions. The results show that the shovel loading volume estimation method (QORB–MAPM VE) proposed in this study has higher estimation accuracy and less calculation time in volume estimation and bucket fill factor estimation, and it has significant theoretical research and engineering application value.
Diagnosis and management of elevated intracranial pressure in the emergency department
Authors: Patel Sima , Maria-Rios Jose , Parikh Amay , Okorie Okorie Nduka
Published: October 2023

Background

Elevated intracranial pressure is a devastating complication of catastrophic brain injury. Intracranial hypertension is commonly seen in neurologic injury secondary to traumatic brain injuries. Uncontrolled pressures can lead to permanent neurologic damage, but acute medical management is often overlooked when pursuing surgical management options that may not always be indicated.

Discussion

Traumatic brain injury is the leading cause of death in patients with severe neurologic injury. Diagnosing elevated intracranial pressures is imperative in initiating prompt treatment to reduce secondary central nervous system injury, morbidity, and mortality. Although the initial injury to the brain is typically irreversible, intracranial pressure control can assist in salvaging the remaining brain tissue from additional damage. We will discuss the initial medical and surgical management of traumatic brain injury to prevent further neurologic deterioration and reduce mortality.

Conclusion

Recent literature has reported several methods to detect elevated intracranial pressure easily and studies describing multiple treatment modalities. These investigations suggest that early detection and timely treatment of intracranial hypertension are beneficial in reducing mortality.
The novel developed microsatellite markers revealed potential hybridization among Cymbidium species and the interspecies sub-division of C. goeringii and C. ensifolium
Authors: Ning Hui-Juan , Gui Fang-Fang , Tian En-Wei , Yang Li-Yuan
Published: October 2023

Background

Orchids (Cymbidium spp.) exhibit significant variations in floral morphology, pollinator relations, and ecological habitats. Due to their exceptional economic and ornamental value, Cymbidium spp. have been commercially cultivated for centuries. SSR markers are extensively used genetic tools for biology identification and population genetics analysis.

Result

In this study, nine polymorphic EST-SSR loci were isolated from Cymbidium goeringii using RNA-Seq technology. All nine SSR loci showed transferability in seven other congeneric species, including 51 cultivars. The novel SSR markers detected inter-species gene flow among the Cymbidium species and intra-species sub-division of C. goeringii and C. ensifolium, as revealed by neighborhood-joining and Structure clustering analyses.

Conclusion

In this study, we developed nine microsatellites using RNA-Seq technology. These SSR markers aided in detecting potential gene flow among Cymbidium species and identified the intra-species sub-division of C. goeringii and C. ensifolium.
Why healthcare providers are not vaccinated? A qualitative study during the COVID-19 pandemic in Iran
Authors: Kokabisaghi Fatemeh , Akhtar Fatemeh , Taghipour Ali , Javan-Noughabi Javad , Moghri Javad , Tabatabaee Seyed Saeed
Published: October 2023

Background

Vaccination has been effective in controlling contagious diseases, especially among high-risk groups such as medical staff. Their unwillingness to be vaccinated might adversely affect individual and public health. This study aimed to explore the factors related to the refusal of COVID-19 vaccines among health service providers.

Methods

A qualitative study was conducted on 28 healthcare providers in Mashhad, Northeast of Iran from March to June 2022. The method of data collection was face-to-face interviews. The purposive method was used for sampling. Data collection continued until the saturation was reached. To analyze the data, the content analysis method was applied, and Maxqda (version 10) software was used.

Results

By analyzing interview transcripts, six themes and ten sub-themes were extracted. Factors that explained employees’ reluctance to be vaccinated against COVID-19 were the opinion of peers, lack of trust in vaccines, fear of vaccination, mistrust to the government and health authorities, low perceived risk of coronavirus disease, and the contradictions of traditional and modern medicine in their approach to controlling the disease.

Conclusions

Among healthcare workers, concerns about the side effects of vaccines were the most influential factors in refusing vaccination. Providing reliable information about vaccines and their safety is key to increasing the trust of health workers in vaccination and facilitating its acceptance.
EuCARE-POSTCOVID Study: a multicentre cohort study on long-term post-COVID-19 manifestations
Authors: Varisco Benedetta , Bai Francesca , De Benedittis Sara , Tavelli Alessandro , Cozzi-Lepri Alessandro , Sala Matteo , Miraglia Federica Gaia , Santoro Maria Mercedes , Ceccherini-Silberstein Francesca , Shimoni Yishai , Ravid Sivan , Kozlovski Tal , König Florian , Pfeifer Nico , Shamsara Elham , Parczewski Milosz , Monforte Antonella d’Arminio , Incardona Francesca , Mommo Chiara , Marchetti Giulia
Published: October 2023

Background

Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10–20% of patients and reaching 50–60% in certain cohorts, while the associated risk factors remain poorly understood.

Methods

This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period.

Patients will be followed up at the post-COVID-19 clinic of each centre at 2–3, 6–9, and 12–15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders.

Discussion

This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs.

Trial registration

This study has been registered with ClinicalTrials.gov under the identifier NCT05531773.
Nosocomial infections in the surgical intensive care unit: an observational retrospective study from a large tertiary hospital in Palestine
Authors: Aiesh Banan M. , Qashou Raghad , Shemmessian Genevieve , Swaileh Mamoun W. , Abutaha Shatha A. , Sabateen Ali , Barqawi Abdel-Karim , AbuTaha Adham , Zyoud Sa’ed H.
Published: October 2023

Background

Nosocomial infections or hospital-acquired infections are a growing public health threat that increases patient morbidity and mortality. Patients at the highest risk are those in intensive care units. Therefore, our objective was to provide a pattern analysis of nosocomial infections that occurred in an adult surgical intensive care unit (ICU).

Methods

This study was a retrospective observational study conducted in a 6-bed surgical intensive care unit (SICU) at An-Najah National University Hospital (NNUH) to detect the incidence of nosocomial infections from January 2020 until December 2021. The study group included 157 patients who received antibiotics during their stay in the SICU.

Results

The incidence of nosocomial infections, either suspected or confirmed, in the SICU was 26.9% (95 out of 352 admitted patients). Pneumonia (36.8%) followed by skin and soft tissue infections (35.8%) were the most common causes. The most common causative microorganisms were in the following order: Pseudomonas aeruginosa (26.3%), Acinetobacter baumannii (25.3%), extended-spectrum beta lactamase (ESBL)-Escherichia coli (23.2%) and Klebsiella pneumonia (15.8%). The average hospital stay of patients with nosocomial infections in the SICU was 18.5 days.

Conclusions

The incidence of nosocomial infections is progressively increasing despite the current infection control measures, which accounts for an increased mortality rate among critically ill patients. The findings of this study may be beneficial in raising awareness to implement new strategies for the surveillance and prevention of hospital-acquired infections in Palestinian hospitals and health care centers.
DeepHipp: accurate segmentation of hippocampus using 3D dense-block based on attention mechanism
Authors: Wang Han , Lei Cai , Zhao Di , Gao Liwei , Gao Jingyang
Published: October 2023

Background

The hippocampus is a key area of the brain responsible for learning, memory, and other abilities. Accurately segmenting the hippocampus and precisely calculating the volume of the hippocampus is of great significance for predicting Alzheimer’s disease and amnesia. Most of the segmentation algorithms currently involved are based on templates, such as the more popular FreeSufer.

Methods

This study proposes Deephipp, a deep learning network based on a 3D dense block using an attention mechanism for accurate segmentation of the hippocampus. DeepHipp is based on the following novelties: (i) DeepHipp adopts powerful data augmentation schemes to enhance the segmentation ability. (ii) DeepHipp is designed to incorporate 3D dense-block to capture multiple-scale features of the hippocampus. (iii) DeepHipp creatively uses the attention mechanism in the field of hippocampal image segmentation, extracting useful hippocampus information in a massive feature map, and improving the accuracy and sensitivity of the model.

Conclusions

We describe the illustrative results and show extensive qualitative and quantitative comparisons with other methods. Our achievement demonstrates that the accuracy of DeepHipp can reach 83.63%, which is superior to most existing methods in terms of accuracy and efficiency of hippocampus segmentation. It is noticeable that deep learning can potentially lead to an effective segmentation of medical images.
Dietary potassium liberalization with fruit and vegetables versus potassium restriction in people with chronic kidney disease (DK-Lib CKD): a clinical trial protocol
Authors: Iman Yasmin , Balshaw Robert , Alexiuk Mackenzie , Hingwala Jay , Cahill Leah , Mollard Rebecca , Tangri Navdeep , Mackay Dylan
Published: October 2023

Background

Potassium regulation in the body is primarily done in the kidney. In addition to this, hyperkalemia, occurs in approximately 10% of individuals with chronic kidney disease (CKD) and is associated with elevated all-cause mortality. Individuals with CKD are often told to restrict dietary potassium (K), however, this recommendation is based on low quality evidence. Reduced quality of life, limited dietary choices and nutritional deficiencies are all potential negative outcomes that may occur when restricting dietary K in CKD patients. There is a need for randomized controlled trials investigating the impact of dietary K modification on serum K concentrations in people with CKD.

Methods

A randomized 2-period crossover design comparing a liberalized K fruit and vegetable diet where participants will be required to consume ~ 3500 mg of dietary K daily, to a standard K restricted diet where participants will be required to consume < 2000 mg of dietary K daily. All participants will begin on a liberalized K run-in period for 2 weeks where they will receive fruit and vegetables home deliveries and for safety will have clinical chemistry, including serum potassium measurements taken after 1 week. Participants will then be randomized into either liberalized K or standard K diet for six weeks and then crossover to the other intervention for another 6 weeks after a 2-week washout period.

Discussion

30 male and female CKD outpatients, ≥ 18 years of age, who have an estimated glomerular filtration rate (eGFR) between 15 and 45 ml/min/1.73m2 and serum K between 4.5 and 5.5 mEq/L. This design would have greater than 80% power to detect a difference of 0.35 mEq/L serum K between groups. Anthropometric measurements, clinical chemistry, dietary recalls, physical function assessments, as well as a quality of life assessments will also be measured in this trial. These findings will provide high quality evidence for, or against, recommendations for dietary K restriction in individuals living with CKD. The removal of K restriction could provide individuals living with CKD more dietary choice leading to improved dietary status and quality of life.

Trial Registration

This trial has received approval from the University of Manitoba Research Ethics board (HS25191 (B2021:104)).
Zimmermann-Laband syndrome and infantile systemic hyalinosis: an enigma with two separate terms with overlapping features: a case report
Authors: Owlia Fatemeh , Navabazam Alireza , akhavan-karbasi Mohammad-Hasan , Derakhshan Barjoei Mohammad Moein
Published: October 2023

Background

Zimmermann-Laband Syndrome (ZLS) and infantile systemic hyalinosis (ISH) are rare genetic disorders. They are characterized by various spectrum manifestations. In spite of other case reports, this case with features of both syndromes was reported by oral medicine specialists and oral and maxillofacial surgeons.

Case presentation

In this study, we reported an 18-months old female patient with gingival overgrowth. This phenomenon completely embedded all the erupted teeth. In this case, the presence of multiple papulonodular cutaneous lesions is a newly observed aspect that has rarely been reported in the existing literature. Gingival overgrowth was excised under general anesthesia. At six months of follow-up after surgery, mastication and breathing problems were improved. Aesthetic aspects were ameliorated in terms of gingival appearance.

Conclusions

To date, due to the ambiguous presentations, both syndromes remain an enigma for specialists. A timely diagnosis could be crucial for prognosis and preventing severe further surcharge. Dentists could play an important role in the diagnosis of rare disorders.
Psychosis secondary to thyrotoxicosis that persisted post-thyroidectomy: a case report
Authors: Kothari Shiva , Townsend William , Chaudhry Zuhaib , Kalin Seth , Freeman Kevin
Published: October 2023

Background

This case report is of a patient with psychosis secondary to thyrotoxicosis that persisted and reemerged after definitive treatment of thyroidectomy, which is a unique occurrence in the literature.

Case presentation

This patient is a male between 30 and 35 years of age with a history of Graves Disease and no past psychiatric history who was admitted to the hospital due to psychosis secondary to thyrotoxicosis. The thyrotoxicosis was treated with surgical removal, but the psychotic symptoms persisted after surgery and normalization of standard thyroid functional measures. The symptoms were of sufficient significance for inpatient psychiatric hospitalization, a rare occurrence. Ultimately after an extended stay in the psychiatric unit, the patient’s symptoms stabilized with a second-generation antipsychotic, and the patient was discharged from the psychiatric unit.

Conclusion

This case is evidence that the link between psychosis and hyperthyroidism is still poorly understood due to the patient’s psychotic symptoms persisting after the definitive treatment of thyroidectomy and the fact that it required anti-psychotic medications for normalization.
Identification of the causal relationship between sleep quality, insomnia, and oral ulcers
Authors: Liu Qianxi , Wang Jiongke , Liu Tiannan , Zeng Xin , Zhang Xuefeng
Published: October 2023

Background

Multiple epidemiological studies have posited a potential association between sleep quality and the risk of oral diseases, yet the resulting conclusions have remained contentious, and the presence of a causal link remains equivocal. In this study, we aimed to investigate the causal relationship between sleep duration, insomnia, and common oral diseases.

Methods

We utilized genetic correlation and two-sample Mendelian randomization analyses based on summary statistics from genome-wide association studies of sleep duration (N = 460,099), insomnia (N = 462,341), mouth ulcer (N = 385,026), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652).

Results

Our results revealed a negative genetic correlation between sleep duration and mouth ulcer (genetic correlation: -0.09, P = 0.007), while a positive genetic correlation between insomnia and mouth ulcer was observed (genetic correlation: 0.18, P = 2.51E-06). Furthermore, we demonstrated that longer sleep duration is significantly associated with a reduced risk of mouth ulcers (OR: 0.67, 95% CI: 0.54–0.83, P = 2.84E-04), whereas insomnia is nominally associated with an increased risk of mouth ulcers (OR: 1.40, 95% CI: 1.01–1.95, P = 0.044). In contrast, no significant association was detected between sleep quality and periodontal disease or oral cavity cancer.

Conclusions

This work provides robust evidence to support the notion that enhanced sleep quality may confer a decreased risk of oral ulcers, thereby bearing considerable clinical relevance.
Sense of coherence in a general adult population in Northern Norway and its associations with oral health
Authors: Mathisen Kine Margrethe , Holde Gro Eirin , Torp Steffen , Jönsson Birgitta
Published: October 2023

Background

Sense of coherence (SOC) is a global orientation to life that may affect a person’s way of acting and living within his or her life context, which can have an impact on general and oral health. The aims of this study were (i) to describe the distribution of SOC in a general adult population; (ii) to explore whether sociodemographic characteristics, oral health-related behaviours, self-reported oral health, and clinical oral status were associated with SOC; and (iii) to explore whether SOC was associated with self-reported oral health, controlling for sociodemographic characteristics, oral health-related behaviours, and oral clinical status.

Methods

This study was based on data from the cross-sectional population-based study Oral Health in Northern Norway (N = 1819 individuals, 923 women, mean age 47.1 ± 15.2 years). Data were collected between October 2013 and November 2014 in Troms County. Participants answered a questionnaire that included items on SOC, sociodemographic characteristics, oral health-related behaviours, and self-reported oral health. Clinical oral status (number of teeth, dental caries, and periodontal status) was determined through oral and radiographic examination. Linear regression analysis was used to examine factors associated with SOC. Logistic regression analysis was used to examine SOC and its association with self-reported oral health adjusted for sociodemographic characteristics, behaviours, and clinical oral status.

Results

The mean SOC score was 68.5 (standard deviation 10.5). The younger age groups (20–29 and 30–39 years) had mean SOC scores of 64.0 (95% CI: 62.7,65.3) and 67.2 (95% CI: 66.0,68.5), respectively, and the older age groups (40–79 years) had mean SOC scores between 69.8 and 70.1 (95% CI: 68.2,71.3). A higher mean SOC score was associated with older age, higher education level, higher income (all p < 0.001), being married/cohabiting (p = 0.005), and toothbrushing ≥ 2 times/day (p = 0.008). Approximately 49% of participants reported good oral health. SOC was positively associated with self-reported good oral health in the adjusted model (odds ratio:1.03 [95% CI: 1.02,1.05] p < 0.001).

Conclusions

SOC was associated with sociodemographic characteristics and toothbrushing habits. There was no significant association between SOC and clinical oral status; however, SOC was positively associated with self-reported good oral health. This indicates that a person’s SOC might have an impact on how an individual perceives their oral health, independent of sociodemographic characteristics and the presence of oral diseases.
A systematic review on removal of osseointegrated implants: un update
Authors: Tafuri Giuseppe , Santilli Manlio , Manciocchi Eugenio , Rexhepi Imena , D’Addazio Gianmaria , Caputi Sergio , Sinjari Bruna
Published: October 2023

Background

Today dental implants represent an effective therapy in case of partial or total edentulism, with an excellent success rate. Despite the results obtained, there may be biological or mechanical complications during the therapy, which lead to the loss of the implant. This systematic review aims to evaluate the current state of the art in the literature on techniques used for the removal of dental implants. Various aspects will be analyzed, such as the success of the technique, any complications, and the advantages and disadvantages of their use.

Methods

Two reviewers conducted a literature analysis (PubMed, Embase, Web of Science) of the last 20 years (2003–2023). The main criterion analyzed was the success of the technique, while secondary outcomes such as complications and risks of the technique were also analyzed. 258 articles were identified in the various search databases. 42 eligible articles were subsequently identified after an article screening. Only 18 full texts were subsequently included in the review.

Results

A total of 18 articles were selected and 1142 implants and 595 patients were included. The main techniques used were the Counter-Torque Ratchet Technique (CTRT), Piezoelectric bone surgery (PBS), trephine drills, carbide burs, Erbium, Chromium, Yttrium, Scandium, Gallium, Garnett (Er:Cr:YSGG) laser and carbon dioxide (CO2) laser. Combined uses of techniques have been identified such as: PBS and trephine burs or carbide burs, trephine burs with the use of a 3d-printed guide, CTRT and trephine burs. The technique with the highest success rate, less morbidity for the patient, and less removal of bone appears to be the CTRT.

Conclusions

The use of conservative techniques, especially CTRT, in bone removal is useful to allow for immediate implant placement in the removal area. However, further studies with a high sample size are needed to be performed on all techniques, particularly new randomized controlled trials (RCTs) that allow for the analysis of the success of alternative techniques such as Laser and Piezosurgery, which appear to be very promising.
Negation recognition in clinical natural language processing using a combination of the NegEx algorithm and a convolutional neural network
Authors: Argüello-González Guillermo , Aquino-Esperanza José , Salvador Daniel , Bretón-Romero Rosa , Del Río-Bermudez Carlos , Tello Jorge , Menke Sebastian
Published: October 2023

Background

Important clinical information of patients is present in unstructured free-text fields of Electronic Health Records (EHRs). While this information can be extracted using clinical Natural Language Processing (cNLP), the recognition of negation modifiers represents an important challenge. A wide range of cNLP applications have been developed to detect the negation of medical entities in clinical free-text, however, effective solutions for languages other than English are scarce. This study aimed at developing a solution for negation recognition in Spanish EHRs based on a combination of a customized rule-based NegEx layer and a convolutional neural network (CNN).

Methods

Based on our previous experience in real world evidence (RWE) studies using information embedded in EHRs, negation recognition was simplified into a binary problem (‘affirmative’ vs. ‘non-affirmative’ class). For the NegEx layer, negation rules were obtained from a publicly available Spanish corpus and enriched with custom ones, whereby the CNN binary classifier was trained on EHRs annotated for clinical named entities (cNEs) and negation markers by medical doctors.

Results

The proposed negation recognition pipeline obtained precision, recall, and F1-score of 0.93, 0.94, and 0.94 for the ‘affirmative’ class, and 0.86, 0.84, and 0.85 for the ‘non-affirmative’ class, respectively. To validate the generalization capabilities of our methodology, we applied the negation recognition pipeline on EHRs (6,710 cNEs) from a different data source distribution than the training corpus and obtained consistent performance metrics for the ‘affirmative’ and ‘non-affirmative’ class (0.95, 0.97, and 0.96; and 0.90, 0.83, and 0.86 for precision, recall, and F1-score, respectively). Lastly, we evaluated the pipeline against two publicly available Spanish negation corpora, the IULA and NUBes, obtaining state-of-the-art metrics (1.00, 0.99, and 0.99; and 1.00, 0.93, and 0.96 for precision, recall, and F1-score, respectively).

Conclusion

Negation recognition is a source of low precision in the retrieval of cNEs from EHRs’ free-text. Combining a customized rule-based NegEx layer with a CNN binary classifier outperformed many other current approaches. RWE studies highly benefit from the correct recognition of negation as it reduces false positive detections of cNE which otherwise would undoubtedly reduce the credibility of cNLP systems.
Characterization of essential eggshell proteins from Aedes aegypti mosquitoes
Authors: Isoe Jun , Simington Carter J. , Oscherwitz Max E. , Peterson Alyssa J. , Rascón Alberto A. , Massani Brooke B. , Miesfeld Roger L. , Riehle Michael A.
Published: October 2023

Background

Up to 40% of the world population live in areas where mosquitoes capable of transmitting the dengue virus, including Aedes aegypti, coexist with humans. Understanding how mosquito egg development and oviposition are regulated at the molecular level may provide new insights into novel mosquito control strategies. Previously, we identified a protein named eggshell organizing factor 1 (EOF1) that when knocked down with RNA interference (RNAi) resulted in non-melanized and fragile eggs that did not contain viable embryos.

Results

In this current study, we performed a comprehensive RNAi screen of putative A. aegypti eggshell proteins to identify additional proteins that interact with intracellular EOF1. We identified several proteins essential for eggshell formation in A. aegypti and characterized their phenotypes through a combination of molecular and biochemical approaches. We found that Nasrat, Closca, and Polehole structural proteins, together with the Nudel serine protease, are indispensable for eggshell melanization and egg viability. While all four proteins are predominantly expressed in ovaries of adult females, Nudel messenger RNA (mRNA) expression is highly upregulated in response to blood feeding. Furthermore, we identified four additional secreted eggshell enzymes that regulated mosquito eggshell formation and melanization. These enzymes included three dopachrome-converting enzymes (DCEs) and one cysteine protease. All eight of these eggshell proteins were essential for proper eggshell formation. Interestingly, their eggshell surface topologies in response to RNAi did not phenocopy the effect of RNAi-EOF1, suggesting that additional mechanisms may influence how EOF1 regulates eggshell formation and melanization.

Conclusions

While our studies did not identify a definitive regulator of EOF1, we did identify eight additional proteins involved in mosquito eggshell formation that may be leveraged for future control strategies.
Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review
Authors: Guo Ruolan , Chen Yuanying , Hu Xuyun , Qi Zhan , Guo Jun , Li Yuchuan , Hao Chanjuan
Published: October 2023

Background

Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits (FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction.

Methods

Exome sequencing was used to detect the candidate variants. The in silico prediction and expressional level analysis were performed to evaluate the pathogenicity of the variations. Additionally, we presented the patient’s detailed clinical information and compared the clinical feature with other previously reported patients with FARSA-deficiency.

Results

We identified compound heterozygous rare missense variants (c.1172 T > C/ p.Leu391Pro and c.1211G > A/ p.Arg404His) in FARSA gene in a Chinese male patient. The protein structure prediction and the analysis of levels of FARSA and FARSB subunits indicated both variants pathogenic. Clinical feature review indicated inflammatory symptoms in young infants may be an additional key feature. Thyroid dysfunction should be considered as a phenotype with variable penetrance.

Conclusions

Our results expanded the current phenotypic and genetic spectrum of FARSA-deficiency.
c-Diadem: a constrained dual-input deep learning model to identify novel biomarkers in Alzheimer’s disease
Authors: Jemimah Sherlyn , AlShehhi Aamna ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2023

Background

Alzheimer’s disease (AD) is an incurable, debilitating neurodegenerative disorder. Current biomarkers for AD diagnosis require expensive neuroimaging or invasive cerebrospinal fluid sampling, thus precluding early detection. Blood-based biomarker discovery in Alzheimer’s can facilitate less-invasive, routine diagnostic tests to aid early intervention. Therefore, we propose “c-Diadem” (constrained dual-input Alzheimer’s disease model), a novel deep learning classifier which incorporates KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway constraints on the input genotyping data to predict disease, i.e., mild cognitive impairment (MCI)/AD or cognitively normal (CN). SHAP (SHapley Additive exPlanations) was used to explain the model and identify novel, potential blood-based genetic markers of MCI/AD.

Methods

We developed a novel constrained deep learning neural network which utilizes SNPs (single nucleotide polymorphisms) and microarray data from ADNI (Alzheimer’s Disease Neuroimaging Initiative) to predict the disease status of participants, i.e., CN or with disease (MCI/AD), and identify potential blood-based biomarkers for diagnosis and intervention. The dataset contains samples from 626 participants, of which 212 are CN (average age 74.6 ± 5.4 years) and 414 patients have MCI/AD (average age 72.7 ± 7.6 years). KEGG pathway information was used to generate constraints applied to the input tensors, thus enhancing the interpretability of the model. SHAP scores were used to identify genes which could potentially serve as biomarkers for diagnosis and targets for drug development.

Results

Our model’s performance, with accuracy of 69% and AUC of 70% in the test dataset, is superior to previous models. The SHAP scores show that SNPs in PRKCZ, PLCB1 and ITPR2 as well as expression of HLA-DQB1, EIF1AY, HLA-DQA1, and ZFP57 have more impact on model predictions.

Conclusions

In addition to predicting MCI/AD, our model has been interrogated for potential genetic biomarkers using SHAP. From our analysis, we have identified blood-based genetic markers related to Ca2+ ion release in affected regions of the brain, as well as depression. The findings from our study provides insights into disease mechanisms, and can facilitate innovation in less-invasive, cost-effective diagnostics. To the best of our knowledge, our model is the first to use pathway constraints in a multimodal neural network to identify potential genetic markers for AD.
Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop
Authors: Ceriello Antonio , Rodbard Helena W. , Battelino Tadej , Brosius Frank , Cosentino Francesco , Green Jennifer , Ji Linong , Kellerer Monika , Koob Susan , Kosiborod Mikhail , Lalic Nebojsa , Marx Nikolaus , Nedungadi T. Prashant , Parkin Christopher G. , Rydén Lars , Sheu Wayne Huey-Herng , Standl Eberhard , Vandvik Per Olav , Schnell Oliver ,   for the Taskforce of the Guideline Workshop
Published: October 2023

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.
Development of a counterselectable system for rapid and efficient CRISPR-based genome engineering in Zymomonas mobilis
Authors: Zheng Yanli , Fu Hongmei , Chen Jue , Li Jie , Bian Yuejie , Hu Ping , Lei Lei , Liu Yihan , Yang Jiangke , Peng Wenfang
Published: October 2023

Background

Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis.

Results

We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong Pgap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids.

Conclusions

This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.
Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians
Authors: Deng Kaige , Xing Jiali , Xu Gang , Jin Bao , Wan Xueshuai , Zheng Yongchang , Du Shunda , Sang Xinting
Published: October 2023

Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.
Flexible multilevel nonvolatile biocompatible memristor with high durability
Authors: Chen Xiaoping , Zhao Xu , Huang Xiaozhong , Tang Xiu-Zhi , Sun Ziqi , Ni Da-Long , Hu Hailong , Yue Jianling
Published: October 2023

Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (ICC) for the set process, where the emerging multilevel states show high durability over 103 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.

Graphical Abstract
Low expression of PINK1 and PARK2 predicts poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Lu Xiangyun , Yao Yongkun , Ma Yandi , Zhang Xudong , Peng Hao , Pei Yuhui , Lu Yulin , Wang Lianghai
Published: October 2023

Background

The Parkinson’s disease (PD) gene family expression is strongly linked to tumor development and progression; PINK1 and PARK2 are essential members of the PD gene family. However, the relationship between PINK1 and PARK2 and esophageal squamous cell carcinoma (ESCC) remains unknown. This research aims to clarify the prognostic value of PINK1 and PARK2 in ESCC.

Methods

PINK1 and PARK2 protein levels in 232 ESCC specimens, and 125 matched adjacent normal tissues were detected by immunohistochemistry. The relationship between PINK1 and PARK2 protein expression and clinicopathological features were analyzed. Kaplan–Meier survival analysis was performed to estimate the prognostic value of the PINK1 and PARK2 proteins in patients. Cox univariate and multivariate analyses were used to assess the risk factors affecting the OS for patients with ESCC.

Results

PINK1 and PARK2 had low expression in ESCC. Patients with low PINK1 had worse differentiation and advanced T and TNM stages. Lower PARK2 expression was linked to lymph node metastases and an advanced TNM stage. Furthermore, reduced PINK1 and PARK2 levels were associated with a poor prognosis for ESCC. Cox univariate and multivariate analyses revealed that PINK1, PARK2, and tumor size were closely associated with the prognosis of patients with ESCC, and PARK2 was an independent risk factor for patients with ESCC. Finally, the PINK1 and PARK2 proteins were closely related and shared the same signal pathway.

Conclusions

PINK1 and PARK2 could work as tumor suppressors in ESCC and are likely to become new treatment targets for ESCC.
Behaviour change techniques used in lifestyle interventions that aim to reduce cancer-related fatigue in cancer survivors: a systematic review
Authors: de Vries-ten Have Judith , Winkels Renate M. , Kampman Ellen , Winkens Laura H.H.
Published: October 2023

Background

Lifestyle interventions that target dietary and/or physical activity behaviours may impact cancer-related fatigue in cancer survivors. Changing lifestyle may be especially difficult for cancer survivors suffering from cancer-related fatigue. To increase effectiveness of lifestyle interventions, behaviour change techniques (BCTs) can be applied. The aim of this review is to systematically describe which BCTs are applied in lifestyle interventions targeting cancer-related fatigue among cancer survivors who finished primary treatment.

Methods

PubMed, Scopus, PsycINFO, Cochrane Library and Web of Science were searched to identify randomised controlled trials (RCTs) of dietary and/or physical activity interventions targeting cancer-related fatigue in cancer survivors. The BCT taxonomy was used to code the BCTs that were applied in those interventions. BCTs that were reported in at least 25% of effective interventions were indicated as ‘promising BCT’, but only retained this classification when these BCTs were present in less than 25% of ineffective interventions.

Results

Twenty-nine RCTs were identified, of which 17 were effective in reducing cancer-related fatigue. The most frequently applied BCTs were Goal setting (behaviour), Instruction on how to perform the behaviour, Demonstration of the behaviour, Behavioural practice/rehearsal, and Credible Source. The BCT ‘Generalisation of the target behaviour’ was identified as promising. These results should be interpreted with caution as only three studies screened their participants on level of cancer-related fatigue and most studies focused only on physical activity. Furthermore, many studies did not include a measure for actual behaviour change and had no follow-up period after the intervention ended.

Conclusions

There is a need for studies that screen their participants on level of cancer-related fatigue and a need for studies that focus more on dietary behaviours as a possible intervention to reduce fatigue. Also, studies should include follow-up timepoints after the interventions ends to examine long-term behaviour change. Future lifestyle interventions should describe interventions in detail to allow for easier coding of BCTs, and report on actual behaviour change following the intervention. Interventions may apply the BCT ‘Generalisation of the target behaviour’ to incorporate lifestyle behaviours in daily life. This may increase the chance that interventions will effectively reduce cancer-related fatigue.