bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety and depression symptoms, albuminuria and risk of acute myocardial infarction in the Norwegian HUNT cohort study
Authors: Gustad Lise Tuset , Myklebust Tor Åge , Bjerkeset Ottar , Williams Lana J. , Laugsand Lars Erik , Dalen Håvard , Berk Michael , Romundstad Solfrid
Published: November 2022

Background

Studies suggest increased risk for an outcome in people with joint exposures that share common causal pathways. The objective of this study was to determine the risk of incident acute myocardial infarction (AMI) following exposure to both albuminuria and/or anxiety and depression symptoms.

Methods

Participants who provided urine samples to the HUNT2 (1995–97) or HUNT3 (2007–2009) surveys were followed until the end of 2016. Albuminuria was measured by Albumin Creatine Ratio (ACR) and participants self-reported mood and anxiety symptoms on the Hospital Anxiety and Depression scale. We used Cox regression to estimate hazard ratios (HRs) for first incident AMI considering interaction between exposures and additive models to calculate the proportion of AMI that were attributable to the synergy of both exposures, adjusted for the Framingham variables.

Results

Eleven thousand fourteen participants free of previous AMI were eligible for participation, with 1234 incident AMIs occurred during a mean 13.7 years of follow-up. For participants who had a healthier CVD risk profile, the HR for AMI of having both albuminuria (3–30 mg/mmol) and depression (≥8) was 2.62 (95% 1.12–6.05) compared with a HR 1.34 (95% CI 1.04–1.74) with raised ACR only (Likelihood Ratio-test 0.03). Adding anxiety (≥8) to albuminuria (3–30) tripled the risk (HR 3.32 95% CI 1.43–7.17). The additive models suggest that these risks are not higher than expected based on each risk factor alone.

Conclusions

This study indicate that the risk of AMI in persons with elevated albuminuria but with an otherwise healthy CVD profile might be amplified by anxiety and depression symptoms. The increased risk with joint risk factors is not higher than expected based on each risk factor alone, which indicate that the risk factors do not share causal pathways.
Short-form development of the specific module of the QLICD-CRF(V2.0) for assessing the quality of life of patients with chronic renal failure
Authors: Xiao Zhengqin , Liu Yuxi , Fong Daniel Yee-Tak , Huang Xinping , Weng Min , Wan Chonghua
Published: November 2022

Background

A short instrument would enhance the viability of a study. Therefore, we aimed to shorten the specific module (SPD-10) of the Quality of Life Instrument for Chronic Diseases - Chronic Renal Failure (QLICD-CRF) for assessing the quality of life of patients with chronic renal failure.

Methods

The 10-item SPD-10 was self-administered to 164 patients with chronic renal failure. A shortened form was first obtained by a tandem use of the classical test theory (CTT), the generalizability theory (GT), and the item response theory (IRT). In addition, we also shortened the SPD-10 by the Optimal Test Assembly (OTA).

Results

Both the tandem use of GT, CTT and IRT, and the OTA derived the same 7-item shortened version (SPD-7). It included items CRF1, CRF2, CRF3, CRF4, CRF6, CRF8, and CRF9 of the SPD-10. The SPD-7 had a Cronbach alpha of 0.78. The correlation coefficients of its total and factor scores with those of the SPD-10 were 0.96 and 0.98, respectively. Confirmatory factor analysis confirmed the unidimensional structure of the SPD-7, with the comparative fit index=0.96, the Tucker-Lewis index=0.94, and the root mean square error of approximation=0.09.

Conclusion

The short-form SPD-7 is reliable and valid for assessing the impact of clinical symptoms and side effects on the quality of life of patients with chronic renal failure. It is an efficient option without compromising the measurement performance of the SPD-10.
Rapid and precise identification of bloodstream infections using a pre-treatment protocol combined with high-throughput multiplex genetic detection system
Authors: Zhang Jinghao , Yang Feng , Sun Zhaoyang , Fang Yi , Zhu Haowei , Zhang Dijun , Zeng Xianping , Liu Wenjian , Liu Tao , Liu Yixin , Chi Wenjing , Wang Su , Ding Li , Wu Yong , Zhang Yanmei , Zhao Hu
Published: November 2022

Background

Bloodstream infection (BSI) is a life-threatening condition with high morbidity and mortality rates worldwide. Early diagnosis of BSI is critical to avoid the unnecessary application of antimicrobial agents and for proper treatment. However, the current standard methods based on blood culture are time-consuming, thus failing to provide a timely etiological diagnosis of BSI, and common PCR-based detection might be inhibited by matrix components.

Methods

The current study explored an integrated pre-analytical treatment protocol for whole blood samples, wherein pathogens are enriched and purified by incubation and concentration, and inhibitors are inactivated and removed. Further, this study developed and evaluated a novel high-throughput multiplex genetic detection system (HMGS) to detect 24 of the most clinically prevalent BSI pathogens in blood culture samples and pre-treated whole blood samples. The specificity and sensitivity were evaluated using related reference strains and quantified bacterial/fungal suspensions. The clinical utility of BSI-HMGS combined with the pre-analytical treatment protocol was verified using blood cultures and whole blood samples.

Results

The combined pre-treatment protocol and BSI-HMGS was highly specific for target pathogens and possessed a low detection limit for clinical whole blood samples. The pre-treatment protocol could deplete the PCR inhibitors effectively. For blood culture samples, the current method showed 100.0% negative percent agreements and > 87.5% positive percent agreements compared to the reference results based on blood culture findings. For whole blood samples, the current method showed 100.0% negative percent agreements and > 80.0% positive percent agreements compared to the reference results for most pathogens. The turnaround time was ≤ 8 h, and all the procedures could be conducted in a general clinical laboratory.

Conclusion

The BSI-HMGS combined with the pre-treatment protocol was a practical and promising method for early and precise detection of BSIs, especially for areas without access to advanced medical facilities.
Low-dose nivolumab in advanced hepatocellular carcinoma
Authors: Chen Yen-Hao , Wang Chih-Chi , Chen Yen-Yang , Wang Jing-Houng , Hung Chao-Hung , Kuo Yuan-Hung
Published: November 2022

Background

The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC).

Methods

We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan–Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Results

In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child–Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1–2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment.

Conclusion

Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice.
Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study
Authors: Min Wenjiao , Zhou Bo , Li Zhengyu , Tang Nie , Zhang Xu , Wang Jinxiang , Chen Yuexin , Zhou Yaling , A Ruhan , Tang Lei , Li Gang , Sun Xueli
Published: November 2022

Objective

Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm.

Methods

In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes were measured.

Results

Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the ‘disease group, the BD + pre-DM group as the ‘mixed period group’, and the pre-DM group as the ‘pre-disease group’. The conscientiousness factor scores of the NEO-FFI in the ‘disease group’ were higher than the norm but lower than the norm in the ‘pre-disease group’. The scores of neurotic factors in the ‘pre-disease’ and ‘mixed period’ groups were both significantly higher than that in the ‘disease group’ (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the ‘pre-disease group’ to the ‘mixed period group’ then to the ‘disease group’, while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%.

Conclusion

This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation.

Trial registration

Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the “stress-dysrhythmia” theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/).
Oral hygiene and oral health behavior, periodontal complaints and oral health-related quality of life in pregnant women
Authors: Schröter Uwe , Ziebolz Dirk , Stepan Holger , Schmalz Gerhard
Published: November 2022

Objectives

This questionnaire-based cross-sectional study aimed in the evaluation of oral hygiene and oral health behavior, periodontal complaints and oral health-related quality of life (OHRQoL) in pregnant women in southwest-Saxony, Germany.

Materials and methods

Consecutive patients attending the clinics for Obstetrics and Gynecology, Heinrich-Braun-Klinikum Zwickau, Germany, were recruited in the years 2020 and 2021. The evaluation consisted of three parts: (I) dental and oral hygiene behavior, (II) periodontal complaints and (III) German short form of oral health impact profile (OHIP G14) to assess OHRQoL.

Results

853 out of 1056 participants were included in the study. The pregnant women reported that they have received information on oral health during pregnancy more often from gynecologists than from dentists. Slightly more than half of the participants (51.5%) rated to regularly undergo a professional tooth cleaning. Similarly, nearly half of the women stated to perform interdental cleaning (55.8%). The most common periodontal complaint was bleeding of the gums (45.4%). The OHIP G14 findings of all questions as well as sum scores showed a median of 0. Regression analysis revealed that regular professional tooth cleaning was a predictor of better OHRQoL (β – 0.698, CI95 0.049–1.299; p < 0.04).

Conclusion

Oral hygiene and oral health behavior of pregnant women in southwest-Saxony requires improvement. While the overall OHRQoL of the cohort was not reduced, professional tooth cleaning and thus professional preventive measures can support OHRQoL during pregnancy. Improved interdisciplinary oral health care concepts for pregnant women should be fostered. These concepts can also positively influence OHRQoL issues.
A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes
Authors: Toh Huishi , Yang Chentao , Formenti Giulio , Raja Kalpana , Yan Lily , Tracey Alan , Chow William , Howe Kerstin , Bergeron Lucie A. , Zhang Guojie , Haase Bettina , Mountcastle Jacquelyn , Fedrigo Olivier , Fogg John , Kirilenko Bogdan , Munegowda Chetan , Hiller Michael , Jain Aashish , Kihara Daisuke , Rhie Arang , Phillippy Adam M. , Swanson Scott A. , Jiang Peng , Clegg Dennis O. , Jarvis Erich D. , Thomson James A. , Stewart Ron , Chaisson Mark J. P. , Bukhman Yury V.
Published: November 2022

Background

The Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely usedMus musculusandRattus norvegicusmodels, holds the promise of better translation of research findings to the clinic.

Results

We report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse.

Conclusions

Our findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism.
Attractive and repulsive effects of sensory history concurrently shape visual perception
Authors: Moon Jongmin , Kwon Oh-Sang
Published: November 2022

Background

Sequential effects of environmental stimuli are ubiquitous in most behavioral tasks involving magnitude estimation, memory, decision making, and emotion. The human visual system exploits continuity in the visual environment, which induces two contrasting perceptual phenomena shaping visual perception. Previous work reported that perceptual estimation of a stimulus may be influenced either by attractive serial dependencies or repulsive aftereffects, with a number of experimental variables suggested as factors determining the direction and magnitude of sequential effects. Recent studies have theorized that these two effects concurrently arise in perceptual processing, but empirical evidence that directly supports this hypothesis is lacking, and it remains unclear whether and how attractive and repulsive sequential effects interact in a trial. Here we show that the two effects concurrently modulate estimation behavior in a typical sequence of perceptual tasks.

Results

We first demonstrate that observers’ estimation error as a function of both the previous stimulus and response cannot be fully described by either attractive or repulsive bias but is instead well captured by a summation of repulsion from the previous stimulus and attraction toward the previous response. We then reveal that the repulsive bias is centered on the observer’s sensory encoding of the previous stimulus, which is again repelled away from its own preceding trial, whereas the attractive bias is centered precisely on the previous response, which is the observer’s best prediction about the incoming stimuli.

Conclusions

Our findings provide strong evidence that sensory encoding is shaped by dynamic tuning of the system to the past stimuli, inducing repulsive aftereffects, and followed by inference incorporating the prediction from the past estimation, leading to attractive serial dependence.
Vicarious trauma on the hemodialysis healthcare workers in the besieged Ethiopia’s Tigray region: a call to action
Authors: Berhe Ephrem , Tesfay Bisrat , Teka Hale
Published: November 2022

Background

The war on Ethiopia’s Tigray broke out on November 4, 2020. Amid the armed conflict, governmental institutions were destroyed, people were displaced, and thousands of civilians were killed. The region was experiencing an on-and-off type of blockade since the war broke out until June 28, 2021, at which time the federal government of Ethiopia imposed a siege cutting off the region from the rest of the world. Due to the shortage of medicines and medical supplies, witnessing deaths that otherwise were preventable under normal conditions has become the daily predicament of healthcare workers. The burden of healthcare disintegration is particularly carried by patients with chronic medical illnesses including patients on dialysis.

Main body

Ayder hospital, Tigray’s flagship healthcare institution, hosts the only hemodialysis center in the entire region. This center is currently unable to give appropriate care to kidney failure patients for a lack of access to dialysis supplies and consumables due to the ongoing war and siege. This has resulted in vicarious trauma manifested with compassion fatigue, irritability, a feeling of bystander guilt; sadness about the patient’s victimization, and hopelessness among healthcare workers caring for dialysis patients.

Conclusion

The suffering of veteran patients and witnessing preventable deaths have continued to haunt and torment healthcare workers in the dialysis unit leading to vicarious trauma. Cognizant of the fact that vicarious trauma has serious health ramifications on healthcare workers; we call up the international community to advocate for a full resumption of access to healthcare and the provision of mental health support and educate and train healthcare workers dealing with end-stage kidney disease patients on hemodialysis.
Lower transmissibility of SARS-CoV-2 among asymptomatic cases: evidence from contact tracing data in Oslo, Norway
Authors: Methi Fredrik , Madslien Elisabeth Henie
Published: November 2022

Background

Asymptomatic COVID-19 cases have complicated the surveillance and tracking of the pandemic. Previous studies have estimated that 15–25% of all infectees remain asymptomatic.

Methods

Based on contact tracing data from Oslo, Norway, we estimated transmission and susceptibility dynamics among symptomatic and asymptomatic cases and their contacts as identified by manual contact tracing between September 1, 2020, and September 1, 2021.

Results

Among 27,473 indexes and 164,153 registered contacts, the secondary attack rate (SAR-14) was estimated to be 28% lower through asymptomatic exposure (13%) compared to symptomatic exposure (18%). Furthermore, those infected by asymptomatic cases were almost three times more likely to be asymptomatic compared to those infected by symptomatic cases.

Conclusions

Symptomatic cases spread the virus to a greater extent than asymptomatic, and infectees are more likely to be asymptomatic if their assumed infector was asymptomatic.
Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy
Authors: Su Wei , Lv Chen , Huang Lingtuo , Zheng XiaoHang , Yang Shengwu
Published: November 2022

Background

Senile osteoporosis (SOP) is one of the most prevalent diseases that afflict the elderly population, which characterized by decreased osteogenic ability. Glucosamine (GlcN) is an over-the-counter dietary supplement. Our previous study reported that GlcN promotes osteoblast proliferation by activating autophagy in vitro. The purpose of this study is to determine the effects and mechanisms of GlcN on senile osteoporosis and osteogenic differentiation in vivo.

Methods

Aging was induced by subcutaneous injection ofd-Galactose (d-Gal), and treated with GlcN or vehicle. The anti-senile-osteoporosis effect of GlcN was explored by examining changes in micro-CT, serum indicators, body weight, protein and gene expression of aging and apoptosis. Additionally, the effects of GlcN on protein and gene expression of osteogenesis and autophagy were observed by inhibiting autophagy with 3-methyladenine (3-MA).

Results

GlcN significantly improved bone mineral density (BMD) and bone micro-architecture, decreased skeletal senescence and apoptosis and increased osteogenesis ind-Gal induced osteoporotic mice. While all effect was reversed with 3-MA.

Conclusion

GlcN effectively delayed the progression of osteoporosis in senile osteoporotic mice by promoting osteoblast autophagy. This study suggested that GlcN may be a prospective candidate drug for the treatment of SOP.
Traditional Chinese medicine injections: where we are after 80-year development
Authors: Zheng Wenwen , Wu Yiyang , Gao Hanlu , Ouyang Defang
Published: November 2022

Traditional Chinese medicine (TCM) injection is the combination of modern pharmaceutical technology and traditional Chinese prescription, which was born in 1941 and played a great role in the backward medical conditions at that time. However, the debate over TCM injections has never stopped due to adverse drug reactions (ADRs). The regulation on TCM injections has been further strengthened since 2017, which has prompted many TCM injections to carry out re-evaluations on quality, safety, efficiency as well as pharmacoeconomics, which made significant changes and progress. This review presented an up-to-date analysis of the types, amounts, and ADRs of TCM injections based on the published data and literature. This review also summarized the potential reasons for the ADRs and re-evaluation strategies. This review will provide some useful clues for TCM injections and their clinical use.
Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial
Authors: Maitre Thomas , Bonnet Maryline , Calmy Alexandra , Raberahona Mihaja , Rakotoarivelo Rivonirina Andry , Rakotosamimanana Niaina , Ambrosioni Juan , Miró José M. , Debeaudrap Pierre , Muzoora Conrad , Davis Angharad , Meintjes Graeme , Wasserman Sean , Wilkinson Robert , Eholié Serge , Nogbou Frédéric Ello , Calvo-Cortes Maria-Camilla , Chazallon Corine , Machault Vanessa , Anglaret Xavier , Bonnet Fabrice
Published: November 2022

Background

Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily).

Methods

This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as “definite,” “probable,” or “possible” using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40.

Discussion

The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries.

Trial registration

ClinicalTrials.gov NCT04145258. Registered on October 30, 2019.
Conducting a supportive oncology clinical trial during the COVID-19 pandemic: challenges and strategies
Authors: Deng Jie , Lukens John N. , Cohn Joy C. , McMenamin Erin , Murphy Barbara , Spinelli Bryan A. , Murphy Niya , Steinmetz Alicia K. , Landriau Megan A. , Lin Alexander
Published: November 2022

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.

Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT 03030859). Registered on 22 January 2017.
Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial
Authors: Ali Shaukat , Shalim Elisha , Farhan Farah , Anjum Fatima , Ali Ayesha , Uddin Syed Muneeb , Shahab Faisal , Haider Mustafa , Ahmed Iqra , Ali Mir Rashid , Khan Sadaf , Rao Sadia , Guriro Kabeer , Elahi Saud , Ali Muhammad , Mushtaq Tehreem , Sayeed Muneeba Ahsan , Muhaymin Sheikh Muhammad , Luxmi Shoba , Saifullah  , Qureshi Saeed
Published: November 2022

Background

COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma.

The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial.

Methods

This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes.

Discussion

This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients.

Trial registration

Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.
dynamAedes: a unified modelling framework for invasive Aedes mosquitoes
Authors: Da Re Daniele , Van Bortel Wim , Reuss Friederike , Müller Ruth , Boyer Sebastien , Montarsi Fabrizio , Ciocchetta Silvia , Arnoldi Daniele , Marini Giovanni , Rizzoli Annapaola , L’Ambert Gregory , Lacour Guillaume , Koenraadt Constantianus J. M. , Vanwambeke Sophie O. , Marcantonio Matteo
Published: November 2022

Mosquito species belonging to the genusAedeshave attracted the interest of scientists and public health officers because of their capacity to transmit viruses that affect humans. Some of these species were brought outside their native range by means of trade and tourism and then colonised new regions thanks to a unique combination of eco-physiological traits. Considering mosquito physiological and behavioural traits to understand and predict their population dynamics is thus a crucial step in developing strategies to mitigate the local densities of invasiveAedespopulations. Here, we synthesised the life cycle of four invasiveAedesspecies (Ae. aegypti,Ae. albopictus,Ae. japonicusandAe. koreicus) in a single multi-scale stochastic modelling framework which we coded in the R package . We designed a stage-based and time-discrete stochastic model driven by temperature, photo-period and inter-specific larval competition that can be applied to three different spatial scales: punctual, local and regional. These spatial scales consider different degrees of spatial complexity and data availability by accounting for both active and passive dispersal of mosquito species as well as for the heterogeneity of the input temperature data. Our overarching aim was to provide a flexible, open-source and user-friendly tool rooted in the most updated knowledge on the species’ biology which could be applied to the management of invasiveAedespopulations as well as to more theoretical ecological inquiries.

Graphical Abstract
A parallel ADMM-based convex clustering method
Authors: Fodor Lidija , Jakovetić Dušan , Boberić Krstićev Danijela , Škrbić Srđan
Published: November 2022

Convex clustering has received recently an increased interest as a valuable method for unsupervised learning. Unlike conventional clustering methods such as k-means, its formulation corresponds to solving a convex optimization problem and hence, alleviates initialization and local minima problems. However, while several algorithms have been proposed to solve convex clustering formulations, including those based on the alternating direction method of multipliers (ADMM), there is currently a limited body of work on developing scalableparallel and distributedalgorithms and solvers for convex clustering. In this paper, we develop a parallel, ADMM-based method, for a modified convex clustering sum-of-norms (SON) formulation for master–worker architectures, where the data to be clustered are partitioned across a number of worker nodes, and we provide its efficient, open-source implementation (available on Parallel ADMM-based convex clustering.https://github.com/lidijaf/Parallel-ADMM-based-convex-clustering. Accessed on 10 June 2022) for high-performance computing (HPC) cluster environments. Extensive numerical evaluations on real and synthetic data sets demonstrate a high degree of scalability and efficiency of the method, when compared with existing alternative solvers for convex clustering.
Dynamics of a fractional plankton–fish model under the influence of toxicity, refuge, and combine-harvesting efforts
Authors: Premakumari R. N. , Baishya Chandrali , Kaabar Mohammed K. A.
Published: November 2022

In this work, we analyze plankton–fish dynamics in the presence of toxicity, refuge, and combine-harvesting efforts by a considering Holling type-II functional response. We have considered phytoplankton, zooplankton, and fish populations, and the interdependent evolution is presented with the help of the Caputo fractional derivative. Since toxicity in phytoplankton spreads to zooplankton and hence to fish, we have introduced toxic terms in all the populations. On the other hand, to save the population from extinction harvesting is an essential tool. Theoretical aspects are studied in terms of nonnegativity, boundedness, existence, and uniqueness of the solution. Sufficient conditions are derived for the stability of various points of equilibrium. The composite behavior is studied by varying the values of different parameters and fractional derivatives. Numerical simulations are carried out to strengthen the theoretical findings.
RHO GTPase family in hepatocellular carcinoma
Authors: Wang Tiantian , Rao Dean , Yu Chengpeng , Sheng Jiaqi , Luo Yiming , Xia Limin , Huang Wenjie
Published: November 2022

RHO GTPases are a subfamily of the RAS superfamily of proteins, which are highly conserved in eukaryotic species and have important biological functions, including actin cytoskeleton reorganization, cell proliferation, cell polarity, and vesicular transport. Recent studies indicate that RHO GTPases participate in the proliferation, migration, invasion and metastasis of cancer, playing an essential role in the tumorigenesis and progression of hepatocellular carcinoma (HCC). This review first introduces the classification, structure, regulators and functions of RHO GTPases, then dissects its role in HCC, especially in migration and metastasis. Finally, we summarize inhibitors targeting RHO GTPases and highlight the issues that should be addressed to improve the potency of these inhibitors.
Targeting Bruton’s tyrosine kinase in vitreoretinal lymphoma: an open-label, prospective, single-center, phase 2 study
Authors: Guan Wenxue , Wang Liang , Peng Xiaoyan
Published: November 2022

Vitreoretinal lymphoma (VRL) is strongly linked to central nervous system (CNS) progression with no standard treatment approaches. Commonly used strategies include repeated intraocular injections of low-dose methotrexate or local radiotherapy, with great inconvenience, long-term side effects, and high risk of CNS relapse. In this study, we evaluated the efficacy and safety of bruton’s tyrosine kinase inhibitors (BTKi) in the treatment of VRL. This prospective single-center study enrolled patients with relapsed or newly diagnosed VRL between October 2020 and April 2022. Patients received BTKi monotherapy until disease progression or unacceptable toxicity. The primary endpoint was the disease control (DC) rate after one month of treatment; secondary endpoints include toxicity, overall survival (OS), and progression-free survival (PFS). Ten consecutive patients with VRL were enrolled into this study. After 1-month treatment, 9 patients (90%) achieved a DC, with 7 patients (70%) achieving a complete response (CR). With a median follow-up of 8.3 (2.5–21.4) months, 4 patients were confirmed to have disease progression, with a PFS of 1.2, 7.5, 9.1, and 11.6 months, respectively. The remaining 6 patients have durable control of disease and were still on treatment at time of the analysis. BTKi were well-tolerated and no patients discontinued the drug because of adverse events. In conclusion, targeting BTK in VRL is viable, and our findings could pave the way for a paradigm change in VRL therapy choices. Further large-scale studies, however, are required to give stronger evidence about the efficacy and safety.
Aligned nanofibrous collagen membranes from fish swim bladder as a tough and acid-resistant suture for pH-regulated stomach perforation and tendon rupture
Authors: Luan Zhaohui , Liu Shuang , Wang Wei , Xu Kaige , Ye Shaosong , Dan Ruijue , Zhang Hong , Shu Zhenzhen , Wang Tongchuan , Fan Chaoqiang , Xing Malcolm , Yang Shiming
Published: November 2022

Background

Wound closure in the complex body environment places higher requirements on suture’s mechanical and biological performance. In the scenario of frequent mechanical gastric motility and extremely low pH, single functional sutures have limitations in dealing with stomach bleeding trauma where the normal healing will get deteriorated in acid. It necessitates to advance suture, which can regulate wounds, resist acid and intelligently sense stomach pH.

Methods

Based on fish swim bladder, a double-stranded drug-loaded suture was fabricated. Its cytotoxicity, histocompatibility, mechanical properties, acid resistance and multiple functions were verified. Also, suture’s performance suturing gastric wounds and Achilles tendon was verified in an in vivo model.

Results

By investigating the swim bladder’s multi-scale structure, the aligned tough collagen fibrous membrane can resist high hydrostatic pressure. We report that the multi-functional sutures on the twisted and aligned collagen fibers have acid resistance and low tissue reaction. Working with an implantable “capsule robot”, the smart suture can inhibit gastric acid secretion, curb the prolonged stomach bleeding and monitor real-time pH changes in rabbits and pigs. The suture can promote stomach healing and is strong enough to stitch the fractured Achilles tendon.

Conclusions

As a drug-loaded absorbable suture, the suture shows excellent performance and good application prospect in clinical work.
Synthesis of Two Macrocyclic Fragments of Manadomanzamine Alkaloids
Authors: Kurihara Yuki , Azuma Atsushi , Yasufuku Haruka , Takikawa Shinsaku , Chida Noritaka , Sato Takaaki
Published: November 2022

The synthesis of two macrocyclic fragments in the manadomanzamine alkaloids based on a strategy using reductive nucleophilic addition to macrolactams is reported. The sequence through the Wittig coupling and macrolactamization gives quick access to both eleven-membered and ten-membered macrolactams. The iridium-catalyzed reductive Strecker reaction of the ten-membered macrolactam takes place via the corresponding unstable imine intermediate.
Anthropogenic landscapes of Ukraine and their reconstruction
Authors: Denysyk Hryhoriy , Kanskyi Volodymyr , Kanska Viktoriia , Denysyk Bohdan
Published: November 2022

The aim of the research was to analyze the structure of Ukraine’s anthropogenic land scape and the directions of its development for the purposes of further reconstruction and rational use. The current state of ten types of anthropogenic landscapes was assessed. In the research based on the maps of natural and contemporary landscapes, use was pri marily made of historical and archaeological methods, including historical and genetic sequences. The present landscape of Ukraine can be described as the coexistence of three types of landscapes: natural, natural-anthropogenic and anthropogenic. Anthropogenic landscapes which are definitely dominating nowadays, started to be formed in the late Pa leolithic. The classification of ten types of anthropogenic landscapes should be improved and supplemented as the new types of anthropogenic landscapes are created, e.g. garden and park landscapes. Anthropogenic landscapes do not exist in isolation, but interact with one another and with natural landscapes. What is particularly noteworthy is the re construction of the anthropogenic landscape of the Forest-Field zone. The restoration of landscapes should begin with the creation of an eco-network. The national ecological net work is ineffective because it does not take into account anthropogenic landscape chang es. The reconstruction of all types of anthropogenic landscapes must allow for their zonal and regional specificity as well as their cultural importance. The cultural landscape will be the basis of the new structure of the national eco-network and will increase its range.
Determinants of Ukraine’s geopolitical orientation
Authors: Kowalski Mariusz
Published: November 2022

The Russian side often talks about the special ties between Russia and Ukraine. This assumption underlies the Russian geopolitical doctrine. Nevertheless, Ukraine does not share this view, wishing to be a sovereign and independent state. Russia cannot understand that, however, being stuck in its imperial myth and one-sided interpretation of former and today’s determinants. Meanwhile, Russians and Ukrainians were moulded by different historical circumstances, which was manifested in the emergence of two distinct languages and national traditions. In addition, historical processes tied Ukrainians more closely to the freedom traditions of the West, while the Russians were much more exposed to the impact of the despotic East, which was one of the main factors behind the distinctive features of both nations. The existence within the borders of one state for 200–300 years did not erase these differences. The emancipation of people’s masses that took place from the mid-19th century made the distinctive features more visible and had to lead to political divisions. For this reason, even the USSR was constituted as a union. This fact, however, did not prevent its dissolution. As a result, Ukraine has been an independent country for three decades. Russian actions counteracting these tendencies, strengthened even more the sense of distinctiveness of Ukrainians and their western civilisational and geopolitical orientation. Owing to this fact, Russia’s integrative actions against Ukraine, carried out by imperial and despotic methods, are doomed to failure.
Αλληλοδιαπλοκή ψηφιακού-ψυχολογικού:
Authors: Σαρλά Νικόλ
Published: November 2022

Παρά τη διεύρυνση της θεωρητικής επεξεργασίας της ψηφιακής συνθήκης τις τελευταίες δεκαετίες, υπάρχουν ακόμα πλευρές που παραμένουν αθέατες ή ελλιπώς διερευνημένες. Εξετάζοντας την ιστορία της διαμόρφωσης της ψηφιακότητας κατά τη διάρκεια του 20ου αιώνα, μια από αυτές τις πλευρές που αναδεικνύεται είναι ο ρόλος των ψυχολογικών μοντέλων στις θεωρίες που θεμελίωσαν την ψηφιακή συνθήκη και στις οποίες βασίστηκε η παραγωγή ψηφιακών τεχνολογιών. Στόχος του άρθρου είναι, αφενός, η σκιαγράφηση του ρόλου των ψυχολογικών μοντέλων στη διαμόρφωση της ψηφιακότητας μέσα από την εξέταση της αντικειμενοποίησης, νευρολογικοποίησης και υπολογιστικοποίησης των νοητικών διαδικασιών. Αφετέρου, βάσει της εξέτασης των παραπάνω διεργασιών, η σκιαγράφηση του πορτραίτου της ψηφιακότητας, μέσα από τον εντοπισμό των ψυχολογικών επιρροών όπως αντανακλώνται στα βασικά χαρακτηριστικά της ψηφιακής συνθήκης.
Οικονομικά κίνητρα για τον εμβολιασμό έναντι της νόσου Covid - 19. Μια βιοηθική προσέγγιση
Authors: Φύτρου Παρασκευή
Published: November 2022

Η θέσπιση οικονομικών κινήτρων στο πλαίσιο της εκστρατείας εμβολιασμού έναντι της νόσου Covid-19, ως μέσο πειθούς του ανεμβολίαστου πληθυσμού παγκοσμίως, εγείρει τον βιοηθικό προβληματισμό αναφορικά με την εναρμόνιση του μέτρου με τις βασικές βιοηθικές αρχές αλλά και ως προς την ηθική του βάση. Στην παρούσα ανάλυση καταρχάς, εισφέρονται επιχειρήματα περί της υπονόμευσης της αρχής της αυτονομίας, καθώς το μέτρο μπορεί να εκληφθεί ως εξωτερική πίεση και έμμεσος εξαναγκασμός που χειραγωγεί την ατομική συναίνεση και φαλκιδεύει την ελεύθερη συνειδητή επιλογή. Ταυτόχρονα, με την εφαρμογή του, αναφύονται ζητήματα εκμετάλλευσης και έλλειψης σεβασμού των υποκειμένων, ενώ αμφισβητείται εκ νέου η συμβατότητά του τόσον με την αρχή της ωφέλειας υπό μια ευρεία έννοια, -εστιάζοντας τόσο στην ηθική όσο και την κοινωνική επισφάλειά του-, όσον και με την αρχή της δικαιοσύνης, καθόσον ανακινεί ζητήματα ανισότητας και συμπεριφοράς που υποκρύπτει διακρίσεις. Η διερεύνηση της συμβατότητας του μέτρου με τις ανωτέρω αρχές διαπλέκεται με την ηθική αποτίμησή του, που καταλήγει να του προσδίδει ηθικά αμφιλεγόμενο χαρακτήρα, καθώς απομακρύνει το υποκείμενο από το ηθικό υπόβαθρο της επωφελούς πράξης του εμβολιασμού. Περαιτέρω, αμφισβητείται η λυσιτέλεια και αποτελεσματικότητα του μέτρου και ως εκ τούτου κρίνεται μη ανεκτή η υιοθέτησή του στο πλαίσιο της ανάσχεσης του πανδημικού κύματος, ενώ παράλληλα προτείνεται η ενεργοποίηση άλλων οδών πλησιέστερων στις βιοηθικές αρχές και το σεβασμό στην αξία του ανθρώπου.
Ηθικά ζητήματα από τη διαλειτουργικότητα στον ηλεκτρονικό φάκελο υγείας
Authors: Χασιώτης Ηρακλής , Χασιώτη Ευαγγελία-Ζωή
Published: November 2022

Η υιοθέτηση ηλεκτρονικών συστημάτων στην υγειονομική περίθαλψη μέσω των Τεχνολογιών Πληροφοριακών Συστημάτων (ΤΠΕ) οδήγησε στην αύξηση της ποιότητας της παρεχόμενης υγείας, τη δημιουργία, συλλογή, μεταφορά και αποθήκευση των δεδομένων υγειονομικής περίθαλψης καθώς και την ανάκτηση τους από εξουσιοδοτημένους επαγγελματίες υγείας. Η χρήση των ΤΠΕ οδηγεί στην μείωση των ιατρικών λαθών, στην μείωση του κόστους, στην άμεση ανάκτηση δεδομένων οποιαδήποτε στιγμή και σε οποιοδήποτε σημείο και τέλος στην ικανοποίηση των ασθενών. Η μετακίνηση των ασθενών μεταξύ διαφορετικών παρόχων υγειονομικής περίθαλψης οδηγεί στην ανάγκη ηλεκτρονικών τρόπων καταγραφής εξετάσεων και αναφορών προκειμένου να μπορούν να ανακτηθούν όποτε κρίνεται αναγκαίο. Η διαλειτουργικότητα των πληροφοριακών συστημάτων μεταξύ τους για την έγκαιρη πρόσβαση σε  πληροφορίες των ασθενών όπως ο Ατομικός Ηλεκτρονικός Φάκελος Ασθενούς (ΑΗΦΥ) που εμπεριέχει πληροφορίες όπως το ιστορικό, τις διαγνώσεις, τις ιατρικές και απεικονιστικές  εξετάσεις κρίνεται αναγκαία για την ασφάλεια των δεδομένων. 

Ωστόσο εγείρονται πολλές ηθικές προκλήσεις όπως η εμπιστευτικότητα της διακίνησης των δεδομένων, ο έλεγχος στην πρόσβαση και ανάκτηση αυτών, η προσβολή της ιδιωτικής ζωής, η αποθήκευση, η διατήρηση και διανομή των δεδομένων.

Η συζήτηση και οι συστάσεις που πρέπει να λαμβάνουν χώρα αφορούν την ενημερωμένη συναίνεση των ασθενών και το δικαίωμα της αυτονομίας, την ασφάλεια των προσωπικών δεδομένων μέσω του Γενικού Κανονισμού Προσωπικών Δεδομένων (GDPR- ν. 2016/679), την εξασφάλιση Ποιότητας καθώς και τον σχεδιασμό ασφαλούς και ολοκληρωμένου τρόπου διαλειτουργικότητας των συστημάτων υγειονομικής περίθαλψης και πώς μπορούν να αντιμετωπιστούν.
How have Japanese primary care physicians carried out vaccinations against COVID-19? : Attempts at making the non-scalable ‘scalable’
Authors: Kimura Shuhei , Horiguchi Sachiko , Goto Ryohei , Iida Junko , Ozone Sachiko , Kaneko Makoto , Teruyama Junko , Hama Yusuke , Haruta Junji , Miyachi Junichiro
Published: November 2022

Vaccine rollouts have been underway to combat the COVID-19 pandemic globally. Based on ongoing interviews with ten primary care physicians ‘in the field’, this paper elucidates how in practice the vaccinations were carried out in Japan in 2021. We examine what the primary care physicians did to prepare for the rollouts, what problems they faced, and how they responded to these problems. Large-scale vaccination projects are supposed to proceed smoothly and quickly, or to have what Anna Tsing calls ‘scalability’. In practice, however, they required a variety of tasks for coordination, information sharing, and promotion. Despite feeling stressed by the lack of information and exhausted by the work overload, the primary care physicians carried out the vaccinations as an important service to their patients and communities. The findings of this paper will provide valuable materials for improving future vaccine rollouts.
Opportunities for additional education in the formation of social competence and self-realization of children and youth
Authors: Ivanova Irina , Makarova Valentina
Published: November 2022

The article is devoted to the study of the pedagogical possibilities of additional education in creating conditions for the formation of the social competence of students and the versatile self-realization of the younger generation. Solving the problems associated with the education of responsible, active and competent citizens today determines the priority lines for the development of educational policy in the Russian Federation. The article reflects the results of the theoretical analysis of modern pedagogical literature on the issues of determining the possibilities of additional education in solving the identified urgent problems and revealing the pedagogical potential of this type of education in the upbringing of the younger generation. The proposed materials can be used in the process of teaching students in the areas of training: "Organization of work with youth", "Pedagogical education", "Psychological and pedagogical education", levels of higher education - bachelor's, master's in the process of mastering students of disciplines based on the study of the subject area associated with further education.