bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of dental practices in Jazan of Saudi Arabia: a GIS-based approach
Authors: Shubayr Mosa Ali , Kruger Estie , Majeed Muhammad Mansoor , Hattan Afrah H , Jearan Shoaa Ahmed , Tennant Marc
Published: April 2023

Background

Jazan region in the Kingdom of Saudi Arabia (KSA) has been extensively studied regarding access to dental care services, but there is currently no specific study on the distribution of public (primary healthcare centres (PHCs) and hospitals) and private dental healthcare facilities in the area. This study aimed to evaluate the spatial distribution of public and private dental care facilities in the Jazan region in relation to the population distribution in each governorate of the region.

Methods

The most up-to-date, easily accessible, and anonymous data and information were used for this investigation. The Ministry of Health’s (MOH) Statistical Yearbook 2020 and interactive map were used to identify the locations of healthcare facilities. These locations were plotted on a map using Google Maps, and the data was converted to longitude and latitude with 90% level building accuracy. QGIS’s integrated database was used to develop buffer zones and perform attribute analysis. The data was then exported for analysis in Microsoft Excel, where healthcare facility-to-population ratios were determined.

Results

In Jazan region, consisting of 17 governorates and a population of 1,726,739, there were 275 public and private dental clinics, with a ratio of one dental clinic per 6,279 people in terms of general health services. Only 12.4% of these clinics were located beyond 20 km of the city centre, serving approximately 70% of the region’s population.

Conclusion

The uneven distribution of dental clinics in the Jazan region has hampered access to dental treatments and has led to a significant burden on dental health facilities, reducing the quality of care available in the region. Mapping the distribution of MOH, private, and other health facilities, as well as the burden of oral disease in the Jazan region, is necessary for further research.
Viral predation pressure on coral reefs
Authors: Silveira Cynthia B. , Luque Antoni , Haas Andreas F. , Roach Ty N. F. , George Emma E. , Knowles Ben , Little Mark , Sullivan Christopher J. , Varona Natascha S. , Wegley Kelly Linda , Brainard Russel , Rohwer Forest , Bailey Barbara
Published: April 2023

Background

Predation pressure and herbivory exert cascading effects on coral reef health and stability. However, the extent of these cascading effects can vary considerably across space and time. This variability is likely a result of the complex interactions between coral reefs’ biotic and abiotic dimensions. A major biological component that has been poorly integrated into the reefs' trophic studies is the microbial community, despite its role in coral death and bleaching susceptibility. Viruses that infect bacteria can control microbial densities and may positively affect coral health by controlling microbialization. We hypothesize that viral predation of bacteria has analogous effects to the top-down pressure of macroorganisms on the trophic structure and reef health.

Results

Here, we investigated the relationships between live coral cover and viruses, bacteria, benthic algae, fish biomass, and water chemistry in 110 reefs spanning inhabited and uninhabited islands and atolls across the Pacific Ocean. Statistical learning showed that the abundance of turf algae, viruses, and bacteria, in that order, were the variables best predicting the variance in coral cover. While fish biomass was not a strong predictor of coral cover, the relationship between fish and corals became apparent when analyzed in the context of viral predation: high coral cover (> 50%) occurred on reefs with a combination of high predator fish biomass (sum of sharks and piscivores > 200 g m−2) and high virus-to-bacteria ratios (> 10), an indicator of viral predation pressure. However, these relationships were non-linear, with reefs at the higher and lower ends of the coral cover continuum displaying a narrow combination of abiotic and biotic variables, while reefs at intermediate coral cover showed a wider range of parameter combinations.

Conclusions

The results presented here support the hypothesis that viral predation of bacteria is associated with high coral cover and, thus, coral health and stability. We propose that combined predation pressures from fishes and viruses control energy fluxes, inhibiting the detrimental accumulation of ecosystem energy in the microbial food web.
Proteomics analysis of methionine enkephalin upregulated macrophages against infection by the influenza-A virus
Authors: Fu Wenrui , Xie Zifeng , Bai Mei , Zhang Zhen , Zhao Yuanlong , Tian Jing
Published: April 2023

Macrophages have a vital role in phagocytosis and antiviral effect against invading influenza viruses. Previously, we found that methionine enkephalin (MENK) inhibited influenza virus infection by upregulating the “antiviral state” of macrophages. To investigate the immunoregulatory mechanism of action of MENK on macrophages, we employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages infected with the influenza-A virus and cells infected with the influenza-A virus after pretreatment with MENK. A total of 215 DEPs were identified: 164 proteins had upregulated expression and 51 proteins had downregulated expression. Proteomics analysis showed that DEPs were highly enriched in “cytokine-cytokine receptor interaction”, “phagosome”, and “complement and coagulation cascades pathway”. Proteomics analysis revealed that MENK could be an immune modulator or prophylactic for the prevention and treatment of influenza. MENK promoted the polarization of M1 macrophages, activated inflammatory responses, and enhanced phagocytosis and killing function by upregulating opsonizing receptors.
Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study
Authors: Deng Ya-Ya , Jiang Ding-Yi , Zhu Peng-Fei , Lu Hongrui , Liu Qian , Zhang Xinyue , Pan Shuang-Yue , Chen Zhe-Ling , Yang Liu
Published: April 2023

Background

Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy.

Methods

This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People’s Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy.

Results

A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period.

Conclusions

Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.
Cytokine expression in gingival crevicular fluid around teeth opposing dental implants and 3-unit fixed partial dentures in a cross-sectional study
Authors: Zhu Xin-Rui , Wang Chen-Xi , Chen Chang , Wang Rui-Yong , Zhang Yu
Published: April 2023

Objective

This study aimed to study the cytokines in gingival crevicular fluid (GCF) of the teeth opposing to dental implants and 3-unit fixed partial dentures (FPDs).

Materials and methods

A total of 74 participants were recruited for this cross-sectional study. Based on the status of lower first molars, the participants were divided into dental implants group and 3-unit FPDs group. Social index and oral hygiene were recorded. Occlusal loading was evaluated with a T-scan. GCF was sampled from the upper first molar and assessed with a commercial cytokine assay kit.

Results

Forty three dental implants patients and 31 3-unit FPDs patients received all of the clinical and laboratory evaluation. The dental implants group had a higher occlusion force distribution on first molars region. IL-10, IL-17, RANK had a higher mean in dental implants group and was associated with occlusion force of first molar. There was a weakly association between IL-10 and dental implants in the binary logistic regression analyses.

Conclusions

In this study, the teeth opposing implants have a higher level of cytokines in the GCF than teeth opposing to 3-unit FPDs in periodontal healthy participants because of the poor osseoperception of dental implants. IL-10 might reflect a higher occlusion force in dental implants region.

Clinical relevance

This study provided that different tooth restoration methods could influence the periodontal status of the contact teeth.
The effect of ultrasound-guided intercostal nerve block on postoperative analgesia in thoracoscopic surgery: a randomized, double-blinded, clinical trial
Authors: Li Shuo , Feng Jinteng , Fan Kun , Fan Xiaoe , Cao Shaoning , Zhang Guangjian
Published: April 2023

Background

Intercostal nerve block (ICNB) is a very effective analgesic method. We aimed to explore the effect of preemptive analgesia with ultrasound-guided intercostal nerve block on postoperative analgesia in thoracoscopic surgery.

Methods

126 patients, aged 18–70 years, with American Society of Anesthesiologists (ASA) physical status I-II and scheduled for thoracoscopic pulmonary resection were enrolled in this study. 119 patients were left for final analysis. Patients were randomly allocated to group ICNB and group CONTROL. Patients in CONTROL group were administered sufentanil with patient-controlled analgesia device after operation In group ICNB, patients received ropivacaine ICNB prior to surgery and patient-controlled analgesia device after operation. The primary outcome is visual analog scale pain score (VAS) at rest at 0,4, 8,16,24,48,72 and 168 h postoperatively and they were compared. Surgical outcomes and rescue analgesia requirement were also recorded.

Results

VAS scores were statistically significantly lower for ICNB group compared to control group at 0, 4, 8, 16, 24 and 48 h postoperatively. The duration of insertion of chest tube in ICBN group was shorter than that in control group, and the difference was statistically significant (4.69 ± 2.14 vs. 5.67 ± 2.86, P = 0.036). The postoperative hospital stay, incidence of nausea and vomiting and postoperative pulmonary infection rate in ICBN group were all lower than those in the control group, but there were no statistical differences. The frequency of rescue analgesia during 48 postoperative hours was different between the two groups (ICNB vs. Control; 9.83% vs. 31.03%, P = 0.004).

Conclusions

For patients undergoing thoracoscopic surgery, ultrasound-guided ICNB is simple, safe, and effective for providing acute postoperative pain management during the early postoperative stage.

Trial registration

Chinese clinical trials: chictr.org.cn, ChiCTR1900021017. Registred on 25/01/2019.
Pulmonary placental transmogrification: a difficult pattern in differential diagnosis of pulmonary hamartomas from a tertiary care hospital in Turkey
Authors: Yaprak Bayrak Busra , Vural Cigdem , Yildiz Kursat
Published: April 2023

Objective

Pulmonary placental transmogrification (PT) is a benign lesion curable by resection, represented by an unusual peculiar morphological variation including placentoid bullous change in the pulmonary hamartoma. In this retrospective study, we aimed to examine the histopathological features of pulmonary hamartomas in lung, to evaluate the different histological components, especially PT, and to investigate importance of PT pattern and its relationship with other clinicopathological features.

Methods

Thirty-five cases of pulmonary hamartomas were recruited from the records between 2001 and 2021, divided into two groups according to presence of PT, as PT (-) and PT (+) in pathological examination.

Results

77.1% of all patients were male. There was no significant difference between the two groups in terms of age, sex, comorbidity, presence of symptoms, tumor localization, and radiological findings (P > 0.05). Pulmonary hamartomas were resected totally from 28 patients (80%). Five of these patients (17.9%) had PT components in resection materials with varying degree between 5 and 80%, and all were from male patients. Examination with frozen sections were performed in 15 PT (-) and 5 PT (+) patients but diagnosis with frozen sections was not achieved in any of PT (+) patients. Most of materials included chondroid components (52.22 ± 29.7%) in both groups (P < 0.05).

Conclusion

The placental papillary projections are available patterns associated with a pulmonary hamartoma and these projections observed especially in frozen sections are very crucial to recognize PT pattern in hamartomas, as they can result in confusions in differential diagnosis of malignities.
Risk factors for postoperative cerebral infarction in Lung Cancer patients: a retrospective study
Authors: Maru Natsumi , Hino Haruaki , Utsumi Takahiro , Matsui Hiroshi , Taniguchi Yohei , Saito Tomohito , Murakawa Tomohiro
Published: April 2023

Background

Postoperative cerebral infarction is a rare but serious complication after lung cancer surgery. We aimed to investigate the risk factors and evaluate the efficiency of our devised surgical procedure to prevent cerebral infarction.

Methods

We retrospectively examined 1,189 patients who underwent a single lobectomy for lung cancer at our institution. We identified the risk factors for cerebral infarction and investigated the preventive effects of performing resection of the pulmonary vein as the last step of the surgical procedure during left upper lobectomy.

Results

Among the 1,189 patients, we identified 5 male patients (0.4%) with postoperative cerebral infarction. All five underwent left-sided lobectomy including three upper and two lower lobectomies. Left-sided lobectomy, a lower forced expiratory volume in 1 s, and lower body mass index were associated with postoperative cerebral infarction (Ps < 0.05). The 274 patients who underwent left upper lobectomy were stratified by two procedures: lobectomy with resection of the pulmonary vein as the last step of the surgical procedure (n = 120) and the standard procedure (n = 154). The former procedure significantly shortened the length of the pulmonary vein stump when compared with the standard procedure (mean stump length: 15.1 vs. 18.6 mm, P < 0.01), and the shorter pulmonary vein might possibly prevent postoperative cerebral infarction (frequency: 0.8% vs. 1.3%, Odds ratio: 0.19, P = 0.31).

Conclusions

Resecting the pulmonary vein as the last step during the left upper lobectomy enabled the length of the pulmonary stump to be significantly shorter, which may contribute to preventing cerebral infarction.
Oxygenated right ventricular assist device as part of veno-venopulmonary extracorporeal membrane oxygenation to support the right ventricle and pulmonary vasculature
Authors: Usman Asad Ali , Cevasco Marisa , Maybauer Marc O. , Spelde Audrey Elizabeth , Olia Salim , Bermudez Christian , Ibrahim Michael , Szeto Wilson , Vernick William J. , Gutsche Jacob T.
Published: April 2023

COVID–19 infection can lead to severe acute respiratory distress syndrome (ARDS), right ventricular (RV) failure and pulmonary hypertension. Venovenous extracorporeal membrane oxygenation (V-V ECMO) has been used for patients with refractory hypoxemia. More recently dual-lumen right atrium to pulmonary artery oxygenated right ventricular assist devices (Oxy-RVAD) have been utilized in the severe medical refractory COVID ARDS setting. Historically, animal data has demonstrated that high continuous non-pulsatile RVAD flows, leading to unregulated and unprotected circulation through the pulmonary vessels is associated with an increased risk of pulmonary hemorrhage and increased amount of extravascular lung water. These risks are heightened in the setting of ARDS with fragile capillaries, left ventricular (LV) diastolic failure, COVID cardiomyopathy, and anticoagulation. Concurrently, due to infection, tachycardia, and refractory hypoxemia, high V-V ECMO flows to match high cardiac output are often necessary to maintain systemic oxygenation. Increase in cardiac output without a concurrent increase in VV ECMO flow will result in a higher fraction of deoxygenated blood returning to the right heart and therefore resulting in hypoxemia. Several groups have suggested using a RVAD only strategy in COVID ARDS; however, this exposes the patients to the risk of pulmonary hemorrhage. We present one of the first known cases using an RV mechanical support, partial flow pulmonary circulation, oxygenated Veno-venopulmonary (V-VP) strategy resulting in RV recovery, total renal recovery, awake rehabilitation, and recovery.
World’s first en bloc heart-lung transplantation using the paragonix lungguard donor preservation system
Authors: Neto Daniel , Guenthart Brandon , Shudo Yasuhiro , Currie Maria E.
Published: April 2023

We present the first en bloc heart-lung donor transplant procurement using the Paragonix LUNGguard™ donor preservation system. This system offers reliable static hypothermic conditions designed to prevent major complications such as cold ischemic injury, uneven cooling and physical damage. While this represents a single case, the encouraging results warrant further investigation.
A model for crowdsourcing high-impact research questions for Castleman disease and other rare diseases
Authors: Korsunska Ania , Repasky Mileva , Zuccato Mary , Fajgenbaum David C.
Published: April 2023

Background

There are approximately 10,000 rare diseases that affect around 30,000,000 individuals in the U.S.A., most of which do not have an FDA-approved treatment. This fact highlights the failure of traditional research approaches to overcome the unique challenges of developing rare disease treatments. The Castleman Disease Collaborative Network was founded in 2012 to advance research and treatments for Castleman disease, a rare and deadly disease that involves the immune system attacking the body’s vital organs for an unknown cause. It has spearheaded a novel strategy for advancing biomedical research, the Collaborative Network Approach. This approach consists of eight steps, one of which is to identify and prioritize high-impact research questions through crowdsourcing ideas from the entire community of stakeholders: patients, loved ones, physicians, and researchers. Rather than hoping that the right researcher will apply for the right research project at the right time, crowdsourcing high-priority research projects into a research strategy ensures that the most high-impact, patient-centered studies are prioritized. The Castleman Disease Collaborative Network launched an initiative in 2021 to systematically generate this list of community-directed studies to focus Castleman disease research efforts.

Results

The Castleman Disease Collaborative Network was able to successfully create a patient-centered research agenda through engaging the entire community of stakeholders. The community contributed important questions about Castleman disease, which were prioritized and reviewed by our Scientific Advisory Board, and the result was a finalized list of studies that address these prioritized questions. We were also able to generate a best practices list which can serve as a model that can be utilized for other rare diseases.

Conclusion

Creating a patient-centered research agenda through crowdsourcing research ideas from the community is one of the most important ways that the Castleman Disease Collaborative Network operationalizes its commitment to keeping patients at the center of research and we hope that by sharing these insights we can assist other rare disease organizations to pursue a patient-centric approach.
Hyperthyroidism in pregnancy: design and methodology of a Danish multicenter study
Authors: Torp Nanna Maria Uldall , Pedersen Inge Bülow , Carlé Allan , Karmisholt Jesper Scott , Ebbehøj Eva , Grove-Laugesen Diana , Brix Thomas Heiberg , Bonnema Steen Joop , Schrijvers Bieke F. , Nygaard Birte , Sigurd Lena Bjergved , Feldt-Rasmussen Ulla , Klose Marianne , Rasmussen Åse Krogh , Andersen Stig , Andersen Stine Linding
Published: April 2023

Background

Graves’ disease (GD) is the main cause of hyperthyroidism in women of the fertile age. In pregnant women, the disease should be carefully managed and controlled to prevent maternal and fetal complications. Observational studies provide evidence of the adverse effects of untreated hyperthyroidism in pregnancy and have in more recent years substantiated a risk of teratogenic side effects with the use of antithyroid drugs (ATDs). These findings have challenged the clinical recommendations regarding the choice of treatment when patients become pregnant. To extend observational findings and support future clinical practice, a systematic collection of detailed clinical data in and around pregnancy is needed.

Methods

With the aim of collecting clinical and biochemical data, a Danish multicenter study entitled ‘Pregnancy Investigations on Thyroid Disease’ (PRETHYR) was initiated in 2021. We here describe the design and methodology of the first study part of PRETHYR. This part focuses on maternal hyperthyroidism and recruits female patients in Denmark with a past or present diagnosis of GD, who become pregnant, as well as women who are treated with ATDs in the pregnancy, irrespective of the underlying etiology. The women are included during clinical management from endocrine hospital departments in Denmark, and study participation includes patient questionnaires in pregnancy and postpartum as well as review of medical records from the mother and the child.

Results

Data collection was initiated on November 1, 2021 and covered all five Danish Regions from March 1, 2022. Consecutive study inclusion will continue, and we here report the first status of inclusion. As of November 1, 2022, a total of 62 women have been included in median pregnancy week 19 (interquartile range (IQR): 10–27) with a median maternal age of 31.4 years (IQR: 28.5–35.1). At inclusion, 26 women (41.9%) reported current use of thyroid medication; ATDs (n = 14), Levothyroxine (n = 12).

Conclusion

This report describes a newly established systematic and nationwide collection of detailed clinical data on pregnant women with hyperthyroidism and their offspring. Considering the course and relatively low prevalence of GD in pregnant women, such nationwide design is essential to establish a sufficiently large cohort.
Retraction Note: LncRNA BCAR4 promotes migration, invasion, and chemo-resistance by inhibiting miR-644a in breast cancer
Authors: Wu Tangwei , Li Xiaoyi , Yan Ge , Tan Zheqiong , Zhao Dan , Liu Shuiyi , Wang Hui , Xiang Yuan , Chen Weiqun , Lu Hongda , Liao Xinghua , Li Yong , Lu Zhongxin
Published: April 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-022-02588-8.
Insights into high-grade serous carcinoma pathobiology using three-dimensional culture model systems
Authors: Tomas Emily , Shepherd Trevor G.
Published: April 2023

Epithelial ovarian cancer (EOC) research has become more complex as researchers try to fully understand the metastatic process. Especially as we delve into the concept of tumour dormancy, where cells transition between proliferative and dormant states to survive during disease progression. Thus, the in vitro models used to conduct this research need to reflect this vast biological complexity. The innovation behind the many three-dimensional (3D) spheroid models has been refined to easily generate reproducible spheroids so that we may understand the various molecular signaling changes of cells during metastasis and determine therapeutic efficacy of treatments. This ingenuity was then used to develop the 3D ex vivo patient-derived organoid model, as well as multiple co-culture model systems for EOC research. Although, researchers need to continue to push the boundaries of these current models for in vitro and even in vivo work in the future. In this review, we describe the 3D models already in use, where these models can be developed further and how we can use these models to gain the most knowledge on EOC pathogenesis and discover new targeted therapies.
Clinical risk factors for increased respiratory drive in intubated hypoxemic patients
Authors: Spinelli Elena , Pesenti Antonio , Slobod Douglas , Fornari Carla , Fumagalli Roberto , Grasselli Giacomo , Volta Carlo Alberto , Foti Giuseppe , Navalesi Paolo , Knafelj Rihard , Pelosi Paolo , Mancebo Jordi , Brochard Laurent , Mauri Tommaso
Published: April 2023

Background

There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients.

Methods

We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths).

Results

Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047–1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997–0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267–1.867, p < 0.001); lower pHa (IR 0.104, 95%CI 0.024–0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921–0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1.

Conclusions

Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.
Comprehensive benchmark and architectural analysis of deep learning models for nanopore sequencing basecalling
Authors: Pagès-Gallego Marc , de Ridder Jeroen
Published: April 2023

Background

Nanopore-based DNA sequencing relies on basecalling the electric current signal. Basecalling requires neural networks to achieve competitive accuracies. To improve sequencing accuracy further, new models are continuously proposed with new architectures. However, benchmarking is currently not standardized, and evaluation metrics and datasets used are defined on a per publication basis, impeding progress in the field. This makes it impossible to distinguish data from model driven improvements.

Results

To standardize the process of benchmarking, we unified existing benchmarking datasets and defined a rigorous set of evaluation metrics. We benchmarked the latest seven basecaller models by recreating and analyzing their neural network architectures. Our results show that overall Bonito’s architecture is the best for basecalling. We find, however, that species bias in training can have a large impact on performance. Our comprehensive evaluation of 90 novel architectures demonstrates that different models excel at reducing different types of errors and using recurrent neural networks (long short-term memory) and a conditional random field decoder are the main drivers of high performing models.

Conclusions

We believe that our work can facilitate the benchmarking of new basecaller tools and that the community can further expand on this work.
Effects of advanced glycation end products (AGEs) on the differentiation potential of primary stem cells: a systematic review
Authors: Xu Kuishuai , Zhang Liang , Yu Ning , Ren Zhongkai , Wang Tianrui , Zhang Yingze , Zhao Xia , Yu Tengbo
Published: April 2023

The formation and accumulation of advanced glycation end products (AGEs) have been associated with aging and the development, or worsening, of many degenerative diseases, such as atherosclerosis, chronic kidney disease, and diabetes. AGEs can accumulate in a variety of cells and tissues, and organs in the body, which in turn induces oxidative stress and inflammatory responses and adversely affects human health. In addition, under abnormal pathological conditions, AGEs create conditions that are not conducive to stem cell differentiation. Moreover, an accumulation of AGEs can affect the differentiation of stem cells. This, in turn, leads to impaired tissue repair and further aggravation of diabetic complications. Therefore, this systematic review clearly outlines the effects of AGEs on cell differentiation of various types of primary isolated stem cells and summarizes the possible regulatory mechanisms and interventions. Our study is expected to reveal the mechanism of tissue damage caused by the diabetic microenvironment from a cellular and molecular point of view and provide new ideas for treating complications caused by diabetes.
Exploring expert perceptions about microplastics: from sources to potential solutions
Authors: Grünzner Maja , Pahl Sabine , White Mathew P. , Thompson Richard C.
Published: April 2023

Concern about plastic pollution, including microplastics, is high amongst European citizens, and effective actions are needed to reduce microplastic pollution. However, there is still uncertainty and debate about the major sources, impacts, and in particular the solutions. The aim of the current study was to gather expert perceptions about the risks of different microplastic sources to the natural environment and human health (measured as the likelihood and severity of negative impacts resulting from exposure), as well as the feasibility and effectiveness of different solutions. Experts were identified as scientists working on plastic. Usable responses were received from 73 experts with an average of 5 years’ experience in plastic research. Experts thought that there was currently stronger evidence for microplastic impacts on the natural environment than on human health, that, accordingly, the risks were higher, and they were more worried about impacts on the natural environment than on human health. Experts perceived tyre particles and textile fibres to be the main sources of microplastics presenting risk for both natural environment and human health. Various solutions were rated as relatively effective and feasible overall. Solutions that were rated as above-average in terms of effectiveness and feasibility included education and awareness programmes, washing machine filters, bans of plastic items, simplified design of products, and circular economy approaches. However, experts were uncertain about the effectiveness and feasibility of recovery and clean-up solutions, with overall ratings for these being below-average in comparison to other solutions earlier in the plastic life cycle. An improved understanding of expert views on these matters could inform the distribution of limited research resources and help prioritise research questions, especially with regard to potential solutions and interventions which will be critical for the success of the UN Plastics Treaty.
Reweighted variational full-waveform inversions
Authors: Wang Wenlong , McMechan George A. , Ma Jianwei
Published: April 2023

Starting from an initial model and predefined priors, a variational full-waveform inversion (VFWI) seeks posterior distributions of model parameters via optimization using a Bayesian theorem. Thus, VFWI is useful in estimating uncertainties in full-waveform inversions (FWIs). However, the resolution of the inverted models from VFWIs is usually not as good as those from conventional FWIs. We decompose the loss function in a VFWI into two terms: the complexity cost and the data misfit. The data variance, which balances these two terms, is expected to decrease during an iterative optimization to gradually put higher weight on the data misfit. We develop and compare two reweighting schemes in VFWI that can produce high-resolution velocity models and the associated uncertainties. Inversions are performed efficiently in a deep-learning framework to take advantage of automatic differentiation. Tests using synthetic data and blind data indicate that reweighted VFWIs are less sensitive to initial models and can generate inversion results that have higher resolution than those from conventional FWIs.
High-resolution reflection seismic imaging to reveal subsurface geologic structures of a deep geothermal reservoir
Authors: Zheng Yikang , Wang Yibo
Published: April 2023

Detailed imaging of the subsurface structure, especially the fault system, is necessary for the development of geothermal reservoirs. Among the various geophysical methods, reflection seismic imaging can provide high resolution at depth for the evaluation of drilling positions. Different from the sedimentary environments in hydrocarbon exploration, specialized seismic processing techniques are needed for geothermal cases in hard-rock basements. A 2D surface seismic survey has been conducted to gain a better illustration of the fault system in a deep geothermal project. An optimized processing workflow is applied to the data set and the results generated from different migration methods are compared. The resulting image reveals the geologic structure with different reflection features at the target site, which provides the basis for a comprehensive characterization of the deep geothermal reservoir. This demonstrates the potential of reflection seismic imaging to assess the feasibility of geothermal energy development.
The heterogeneity of depressions: A phenomenological viewpoint
Authors: Stanghellini Giovanni
Published: April 2023

What is commonly referred to as “depression” indicates a heterogeneous complex disorder that includes distinct psychopathological forms. A more accurate classification can be achieved by assessing the individual experiences of depression and tracing back each of these forms to the specific vulnerable structure from which they emerge. Each of these vulnerable forms of existence can be characterized by focusing on their values. I identify four main prototypes. Homo melancholicus is impressive for their over-normality, extreme social adjustment, and conformism; their depressive decomposition is characterized by the experience of loss. The values of homo œconomicus are utility (every action must be directed toward production) and optimization (what costs more than it produces is a dead branch to be cut); their depressive decomposition is marked by insolvency. Homo dissipans’ values are excess (feeling animated by an inexhaustible drive to “pour out” of oneself, especially outside the limits of composure and reasonableness) and expenditure (an ethical attitude that gives its approval to excess and to its metamorphic and destructive power); their depressive decomposition is epitomized by inner incoherence and emptiness. The style of homo nevroticus form of existence is subjugated by the condemnation to limitation and the diktat of prohibition; their depressive decomposition is characterized by frustration and demoralization.
Electron-doping Ruddlesden-Popper nickelate
Authors: Chen X. , Jiang P. , Zhong Z.
Published: April 2023

The discovery of cuprate and iron-based superconductors in the last three decades has stimulated a great enthusiasm in researching high T

C
superconductors. For cuprate, a lot of superconducting compounds were discovered and the superconducting behavior can be tuned by changing the number of the

layer. Currently, a cuprate-like superconductor, i.e., nickelate, is reported, which opens a new era in the field of superconductivity. However, the superconducting behavior is only limited in quite a few nickelate compounds. Here, based on first-principles calculations, we investigate the electronic band structure of Ruddlesden Popper (RP) phase and reduced RP (rRP) phase nickelates, and the electron doping influences on these phases. Our results further indicate that the most effective electron-doping selection for these RP/rRP phases is the fluorine replacing the oxygen sites (FO) of LaO or

layer to control the

electron state. This

doping not only introduces electrons to system but also keeps the effective single

band. Our theoretical predictions would contribute to the discovering of more possible nickelate superconductors.
Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Grotta James C.
Published: April 2023

OBJECTIVE

This article reviews the history of IV thrombolysis, its current indications and implementation, the duality of the “time is brain” versus “tissue clock” approaches, the impact of endovascular thrombectomy on IV thrombolysis, the emergence of tenecteplase, and future research directions.

LATEST DEVELOPMENTS

The growing use of factor Xa inhibitors has increasingly caused patients with stroke to be excluded from treatment with IV thrombolysis. Important geographic, socioeconomic, sex, race, and ethnic disparities have been identified in the implementation of IV thrombolysis and need to be overcome. IV thrombolysis substantially improves outcomes when provided within the first golden hour after stroke onset in patients treated in mobile stroke units, supporting the “time is brain” concept and encouraging the possible value of more widespread implementation of the mobile stroke unit approach. At the same time, other studies have shown that IV thrombolysis can be successful in patients whose “tissue clock” is still ticking up to 9 hours after stroke onset or in patients who awaken with their stroke, as demonstrated by favorable imaging profiles. These considerations, along with the emergence of endovascular thrombectomy, have fostered examination of our care systems, including the “drip and ship” versus direct to comprehensive or endovascular thrombectomy stroke center approaches, as well as the possibility of skipping IV thrombolysis in certain patients treated with endovascular thrombectomy. Data suggesting that tenecteplase is at least noninferior to alteplase, as well as its more convenient dosing, has led to its increased use. Ongoing studies are evaluating newer thrombolytics and adding antithrombotic therapy to IV thrombolysis.

ESSENTIAL POINTS

IV thrombolysis remains the most common acute stroke treatment. Advances in acting faster to treat stroke have increased its efficacy, and advances in imaging have expanded its use. However, implementing these advances and overcoming disparities in IV thrombolysis use remain major challenges.
Diagnosis and Management of Large Artery Atherosclerosis
Authors: Chaturvedi Seemant
Published: April 2023

OBJECTIVE

Ischemic stroke due to large vessel atherosclerosis is a significant cause of stroke globally. With the aging population, the number of people with atherosclerotic stroke will increase in the coming decades. This article reviews the recent developments in the assessment and treatment of extracranial and intracranial atherosclerotic disease.

LATEST DEVELOPMENTS

More intensive dual antiplatelet therapy can now be recommended for patients with transient ischemic attack or stroke. More stringent blood pressure and lipid control is also advised. The need for carotid revascularization will likely decrease in the coming decades because of advances in multimodal medical therapy; in particular, the role of revascularization for treating asymptomatic carotid stenosis is controversial. Patients with symptomatic intracranial stenosis should receive intensive medical therapy. Interest in high-resolution carotid plaque imaging is growing.

ESSENTIAL POINTS

The prevention of stroke due to large vessel atherosclerosis has improved owing to advances in medical therapies. The role of carotid revascularization is unclear for many patient subgroups.
Pediatric Ischemic Stroke
Authors: Fox Christine
Published: April 2023

OBJECTIVE

Pediatric cerebrovascular disease is one of the leading causes of death and disability in children. Survivors of childhood stroke and their families are often left to cope with long-lasting sequelae, such as barriers to school reentry and long-term challenges in attaining independence as adults. Because childhood stroke is rare and providers may not be familiar with the disorder, this article reviews the risk factors, acute management, and sequelae of ischemic stroke in children.

LATEST DEVELOPMENTS

High-quality evidence has resulted in an organized approach to emergent treatment of ischemic stroke in adults, but most front-line providers are less prepared for emergent stroke management in children. The level of evidence for reperfusion therapies in children remains low but is growing. Thrombolysis and thrombectomy are sometimes considered for hyperacute treatment of stroke in children. Readiness for pediatric stroke at regional centers should include an organized approach to pediatric stroke triage and management based on extrapolation from adult stroke trials, expert consensus, and emerging pediatric studies.

ESSENTIAL POINTS

This review provides up-to-date information about ischemic stroke risk factors and management in children. Preparation for rapid stroke diagnosis and management in children may improve outcomes.
Management of Unruptured Intracranial Aneurysms and Brain Arteriovenous Malformations
Authors: Nguyen Thanh Ngoc
Published: April 2023

OBJECTIVE

Managing a patient with an unruptured brain aneurysm or brain arteriovenous malformation (AVM) can lead to uncertainty about preventive treatment. While the bleeding risks are low, the morbidity or mortality associated with a hemorrhagic event is not insignificant. The objective of this article is to review the natural history of these vascular entities, the risk factors for hemorrhage, preventive treatment options, and the risks of treatment.

LATEST DEVELOPMENTS

Randomized trials to inform preventive treatment strategies for unruptured intracranial aneurysms and brain AVMs are ongoing. Higher angiographic obliteration rates of unruptured intracranial aneurysms have been reported with the flow-diversion technique compared with alternative standard techniques. One randomized trial for unruptured brain AVMs showed a higher rate of morbidity and mortality in patients who underwent interventional treatment compared with observation.

ESSENTIAL POINTS

The decision to treat a patient with a brain aneurysm should consider patient factors, the patient’s life expectancy, aneurysm anatomical factors, and treatment risks. Patients with unruptured brain AVMs should be observed in light of recent clinical trial data or enrolled in an ongoing clinical trial.
Hemato-vascular specification requires arnt1 and arnt2 genes in zebrafish embryos
Authors: Edwards Hailey E. , Elizalde Mary Jane , Souder Jaclyn P. , Gorelick Daniel A.
Published: April 2023

During embryonic development, a subset of cells in the mesoderm germ layer are specified as hemato-vascular progenitor cells, which then differentiate into endothelial cells and hematopoietic stem and progenitor cells. In zebrafish, the transcription factor npas4l (cloche) is required for the specification of hemato-vascular progenitor cells. However, it is unclear whether npas4l is the sole factor at the top of the hemato-vascular specification cascade. Here, we show that arnt1 and arnt2 genes are required for hemato-vascular specification. We found that arnt1;arnt2 double mutant zebrafish embryos, but not arnt1 or arnt2 single mutants, lack blood cells and most endothelial cells. arnt1/2 mutants have reduced or absent expression of etsrp and tal1, the earliest known endothelial and hematopoietic transcription factor genes. We found that Npas4l binds both Arnt1 and Arnt2 proteins in vitro, consistent with the idea that PAS domain-containing bHLH transcription factors act in a multimeric complex to regulate gene expression. Our results demonstrate that npas4l, arnt1 and arnt2 act together to regulate endothelial and hematopoietic cell fate, where each gene is necessary, but not sufficient, to drive hemato-vascular specification.
The non-canonical Wnt receptor Ror2 is required for cartilage cell polarity and morphogenesis of the craniofacial skeleton in zebrafish
Authors: Dranow Daniel B. , Le Pabic Pierre , Schilling Thomas F.
Published: April 2023

Non-canonical/β-catenin-independent Wnt signaling plays crucial roles in tissue/cell polarity in epithelia, but its functions have been less well studied in mesenchymal tissues, such as the skeleton. Mutations in non-canonical Wnt signaling pathway genes cause human skeletal diseases such as Robinow syndrome and Brachydactyly Type B1, which disrupt bone growth throughout the endochondral skeleton. Ror2 is one of several non-canonical Wnt receptor/co-receptors. Here, we show that ror2−/− mutant zebrafish have craniofacial skeletal defects, including disruptions of chondrocyte polarity. ror1−/− mutants appear to be phenotypically wild type, but loss of both ror1 and ror2 leads to more severe cartilage defects, indicating partial redundancy. Skeletal defects in ror1/2 double mutants resemble those of wnt5b−/− mutants, suggesting that Wnt5b is the primary Ror ligand in zebrafish. Surprisingly, the proline-rich domain of Ror2, but not its kinase domain, is required to rescue its function in mosaic transgenic experiments in ror2−/− mutants. These results suggest that endochondral bone defects in ROR-related human syndromes reflect defects in cartilage polarity and morphogenesis.