bluuebunny/crossref_metadata_2025 huggingface dataset:
Do organic substances act as a degradable binding matrix in calcium oxalate kidney stones?
Authors: Adelman Adi , Shilo Yaniv , Modai Jonathan , Leibovici Dan , Dror Ishai , Berkowitz Brian
Published: March 2021

Background

Calcium oxalate (CaOx) stones are considered to be highly resistant to chemolysis. While significant organic matter has been identified within these stones, which is presumed to bind (inorganic) CaOx particles and aggregates, most chemolysis efforts have focused on methods to attack the CaOx components of a stone. We examine the feasibility of inducing chemolysis of CaOx kidney stones, within hours, by specifically attacking the organic matrix present in these stones.

Methods

In contrast to previous studies, we focused on the possible “brick and mortar” stone configuration. We systematically tested, via in vitro experiments, the ability of an extensive range of 26 potential chemolysis agents to induce relatively fast disintegration (and/or dissolution) of a large set of natural CaOx stone fragments, extracted during endourological procedures, without regard to immediate clinical application. Each stone fragment was monitored for reduction in weight and other changes over 72 h.

Results

We find that agents known to attack organic material have little, if any, effect on stone chemolysis. Similarly, protein and enzymatic agents, and oral additive medical treatments, have little immediate effect.

Conclusions

These findings suggest that the organic and inorganic constituents present in CaOx stones are not structured as “brick and mortar” configurations in terms of inorganic and organic components.
Diabetes, even newly defined by HbA1c testing, is associated with an increased risk of in-hospital death in adults with COVID-19
Authors: Liu Ye , Lu Ran , Wang Junhong , Cheng Qin , Zhang Ruitao , Zhang Shuisheng , Le Yunyi , Wang Haining , Xiao Wenhua , Gao Hongwei , Zeng Lin , Hong Tianpei
Published: March 2021

Background

Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19.

Methods

This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was ≥6.5% (48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis.

Results

Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs. 5.9%, p <  0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p <  0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥1.0 μg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19.

Conclusions

The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.
Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis
Authors: Liu Bin , Meng Xiang , Ma Yanfang , Li Huizhen , Liu Yuqi , Shi Nannan , Chen Yaolong , Wang Yanping , Lu Cheng
Published: March 2021

Background

Total glucosides of paeony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pallas, has been increasingly used as the adjunctive therapy for rheumatoid arthritis (RA) patients. Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. The objective of this study is to evaluate the clinical safety of TGP adjuvant therapy in the RA treatment.

Methods

PubMed, EMBASE, Web of Science, China Network Knowledge Infrastructure (CNKI), SinoMed and WanFang Data were retrieved for randomized controlled trials (RCTs) and cohort study about TGP adjuvant therapy in patients with RA up to 28 January 2021. Literatures with eligibility criteria and information were screened and extracted by two researchers independently. The RevMan5.3 software was used for data analysis with effect estimates as risk ratio (RR) with 95% confidence interval (CI).

Results

A total of 39 studies involving 3680 RA participants were included. There were 8 comparisons: TGP plus methotrexate (MTX) therapy versus MTX therapy, TGP plus leflunomide (LEF) therapy versus LEF therapy, TGP plus MTX and LEF therapy versus MTX plus LEF therapy, TGP plus tripterygium glycosides (TG) therapy versus TG therapy, TGP plus meloxicam (MLX) therapy versus MLX therapy and TGP plus sulfasalazine (SSZ) therapy versus SSZ therapy, TGP plus iguratimod (IGU) therapy versus IGU therapy, TGP plus prednisone acetate tablets (PAT) therapy versus PAT therapy. The meta-analysis results showed that the occurrence of hepatic adverse effect (RR = 0.31, 95% CI = 0.23–0.41, P < 0.00001) and leukopenia (RR = 0.41, 95% CI = 0.26–0.66, P = 0.0002) in TGP adjuvant therapy was significant decreased compared with non-TGP therapy. However, only TGP plus LEF therapy (RR = 0.22, 95% CI = 0.08–0.60, P = 0.003) and TGP plus MTX and LEF therapy (RR = 0.31, 95% CI = 0.22–0.42, P < 0.00001) had statistical difference in the subgroups of hepatic adverse effect. In leukopenia, TGP plus MTX and LEF therapy (RR = 0.47, 95% CI = 0.25–0.87, P = 0.02) had statistical difference.

Conclusions

This meta-analysis indicated that TGP adjuvant therapy might alleviate the incidence of hepatic adverse effect and leukopenia for the RA treatment compared to non-TGP therapy. The clinical safety of TGP adjuvant therapy warrant further investigation in experimental studies.
Using Mendelian randomization study to assess the renal effects of antihypertensive drugs
Authors: Zhao Jie V. , Schooling C. Mary
Published: March 2021

Background

Angiotensin-converting enzyme (ACE) inhibitors and/or in combination with calcium channel blockers (CCBs) are generally recommended as the first-line antihypertensive therapy for people with hypertension and kidney dysfunction. Evidence from large randomized controlled trials comprehensively comparing renal effects of different classes of antihypertensive drugs is lacking.

Methods

We used a Mendelian randomization study to obtain unconfounded associations of genetic proxies for antihypertensives with kidney function. Specifically, we used published genetic variants in genes regulating target proteins of these drugs and then applied to a meta-analysis of the largest available genome-wide association studies of kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria). Inverse variance weighting was used as the main analysis and to combine estimates from different sources.

Results

Genetically predicted ACE inhibition was associated with higher eGFR (effect size 0.06, 95% confidence interval (CI) 0.008, 0.11), while genetic proxies for beta-blockers were associated with lower eGFR (− 0.02, 95% CI − 0.04, − 0.004) when meta-analyzing the UK Biobank and CKDGen. Genetic proxies for CCBs were associated with lower UACR (− 0.15, 95% CI − 0.28, − 0.02) and lower risk of albuminuria (odds ratio 0.58, 95% CI 0.37, 0.90) in CKDGen. The associations were robust to using different analysis methods and different genetic instruments.

Conclusions

Our findings suggest the reno-protective associations of genetically proxied ACE inhibitors and CCBs, while genetic proxies for beta-blockers may be related to lower eGFR. Understanding the underlying mechanisms would be valuable, with implications for drug development and repositioning of treatments for kidney disease.
Novel biallelic variant in BBS9 causative of Bardet–Biedl syndrome: expanding the spectrum of disease-causing genetic alterations
Authors: Suárez-González Julia , Seidel Verónica , Andrés-Zayas Cristina , Izquierdo Elvira , Buño Ismael
Published: March 2021

Background

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy disorder. Many BBS disease-causing genetic variants have been identified due to the advancement of molecular diagnostic tools. We report on a novel pathogenic variant in a consanguineous Pakistani family with an affected child.

Case presentation

Clinical exome sequencing was used to search for BBS causing variants in the affected individual and identified a novel homozygous splice-site variant in the BBS9 gene (c.702 + 1del). Sanger sequencing was performed for variant validation and segregation studies. Expression analysis using mRNA levels to assess the functional impact of the novel variant demonstrated skipping of exon 7 in the affected alleles, suggesting a truncating effect. Three-dimensional structural modelling was used to predict pathogenicity of the variant residue and the alteration leads to a partial deletion of the PHTB1_N domain and a total deletion of the PHTB1_C domain.

Conclusion

The study of this case expands the spectrum of biallelic variants in the BBS9 gene associated with BBS and increased the knowledge on the molecular consequences of splicing variation c.702 + 1del.
Fibroblasts in cancer dormancy: foe or friend?
Authors: Dai Li , Li Mao , Zhang Wei-long , Tang Ya-Jie , Tang Ya-ling , Liang Xin-hua
Published: March 2021

Cancer dormancy is defined that the residual cancer cells could enter into a state of quiescence and patients remain asymptomatic for years or even decades after anti-tumor therapies. Fibroblasts, which represent a predominant cell type in tumor microenvironment, play a pivotal role in determining the ultimate fate of tumor cells. This review recapitulates the pleiotropic roles of fibroblasts which are divided into normal, senescent, cancer-associated fibroblasts (CAFs) and circulation CAFs in tumor dormancy, relapse, metastasis and resistance to therapy to help the treatment of cancer metastasis.
Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children
Authors: Ahmad Abdullahi , Prom Aurelia , Bradley John , Ndiath Mamadou , Etoketim Blessed , Bah Mamadou , Van Geertruyden Jean-Pierre , Drakeley Chris , Bousema Teun , Achan Jane , D’Alessandro Umberto
Published: March 2021

Background

Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children.

Methods

The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24–59 months old who were eligible to receive SMC (SMC group) and children 5–8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression.

Results

During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14–2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20–4.95; p = 1.0).

Conclusion

In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.
Correction to: A review of health effects associated with exposure to jet engine emissions in and around airports
Authors: Bendtsen Katja M. , Bengtsen Elizabeth , Saber Anne T. , Vogel Ulla
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
The interplay between environmental exposures and COVID-19 risks in the health of children
Authors: Sly Peter D. , Trottier Brittany A. , Bulka Catherine M. , Cormier Stephania A. , Fobil Julius , Fry Rebecca C. , Kim Kyoung-Woong , Kleeberger Steven , Kumar Pushpam , Landrigan Philip J. , Lodrop Carlsen Karin C. , Pascale Antonio , Polack Fernando , Ruchirawat Mathuros , Zar Heather J. , Suk William A.
Published: March 2021

Background

An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution.

Objectives

To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps.

Methods

An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps.

Discussion

Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life.

Conclusion

A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.
A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation
Authors: Zhou Ziheng , Yin Hanrui , Guo Yajie , Fang Yuanyuan , Yuan Feixiang , Chen Shanghai , Guo Feifan
Published: March 2021

Background

Leucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, thus protecting the organism against obesity. However, a complete deprivation of leucine can lead to an extremely rapid fat loss in mice, accompanied by prolonged adverse effects such as weakness and mental fatigue. Therefore, in this study we aimed to seek the optimal concentration of dietary leucine that can reduce fat mass and improve the metabolism without the onset of severe effects.

Methods

To investigate whether there is a better concentration of diet leucine restriction (LR), based on the diet we conducted (A10021B), that can reduce fat mass and improve metabolism status without taking many negative effects, we fed 8 weeks old male C57Bl/6J mice with increasing degrees of leucine restriction diet 0% LR (control group), 25% LR, 50% LR, and 75% LR groups (4–6 mice each group). Fat mass and blood glucose levels were measured. The expression levels of genes involved in lipid metabolism in white adipose tissue (WAT) and liver, and proteins in insulin signaling were assessed in WAT, liver and muscle.

Results

We found that the 50% LR group is the most proper group here at the lowest leucine effective concentration, which reduced fat mass (p < 0.05) and improved glucose regulation in mice over a 90 days feeding. Further studies revealed that lipid synthesis pathway (Fas, Scd1and Srebp1, p < 0.05) was downregulated and lipolysis (Atgl, p < 0.05) was upregulated in WAT in 50% LR group, compared to that in control group. Furthermore, glucose regulation (glucose tolerance test, p < 0.05) was also improved, and insulin signaling (p < 0.05) in the muscle was enhanced in 50% LR group while in WAT and liver were not changed.

Conclusions

Collectively, a 50% LR in mice reduced fat mass and improved glucose regulation, which may function through modulating lipid synthesis and lipolysis pathway in adipose tissue as well as enhancing insulin signaling in muscle. So far, we provide a further consideration for carrying out the diet of leucine restriction to reduce fat and improve metabolism status before clinical study.
Vestibular dose correlates with dizziness after radiosurgery for the treatment of vestibular schwannoma
Authors: Ermiş Ekin , Anschuetz Lukas , Leiser Dominic , Poel Robert , Raabe Andreas , Manser Peter , Aebersold Daniel M. , Caversaccio Marco , Mantokoudis Georgios , Abu-Isa Janine , Wagner Franca , Herrmann Evelyn
Published: March 2021

Background

Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS.

Methods

Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed. No dose constraints were given to the vestibule during optimization in treatment planning. Patient and tumor characteristics, pre- and post-SRS vestibular examination results and patient-reported dizziness were assessed from patient records.

Results

Fifty-three patients were analyzed. Median follow-up was 32 months (range, 6–79). The median minimum, mean and maximum vestibular doses were 2.6 ± 1.6 Gy, 6.7 ± 2.8 Gy, and 11 ± 3.6 Gy, respectively. On univariate analysis, Koos grade (p = 0.04; OR: 3.45; 95% CI 1.01–11.81), tumor volume (median 6.1 cm3; range, 0.8–38; p = 0.01; OR: 4.85; 95% CI 1.43–16.49), presence of pre-SRS dizziness (p = 0.02; OR: 3.98; 95% CI 1.19–13.24) and minimum vestibular dose (p = 0.033; OR: 1.55; 95% CI 1.03–2.32) showed a significant association with patient-reported dizziness. On multivariate analysis, minimum vestibular dose remained significant (p = 0.02; OR: 1.75; 95% CI 1.05–2.89). Patients with improved caloric function had received significantly lower mean (1.5 ± 0.7 Gy, p = 0.01) and maximum doses (4 ± 1.5 Gy, p = 0.01) to the vestibule.

Conclusions

Our results reveal that 5 Gy and above minimum vestibular doses significantly worsened dizziness. Additionally, mean and maximum doses received by the vestibule were significantly lower in patients who had improved caloric function. Further investigations are needed to determine dose-volume parameters and their effects on vestibular toxicity.
More weighted cancellous bone can be harvested from the proximal tibia with less donor site pain than anterior iliac crest corticocancellous bone harvesting: retrospective review
Authors: Kim Hanju , Kar Ajit Kumar , Kaja Aditya , Lim Eic Ju , Choi Wonseok , Son Whee Sung , Oh Jong-Keon , Sakong Seungyeob , Cho Jae-Woo
Published: March 2021

Background

Iliac crest is the most preferred autogenous bone graft harvesting donor site while it has sorts of complications like prolonged pain, hematoma, and fracture. Harvesting cancellous bone from proximal tibia is also increasingly being used because of lower complications and less donor site pain. However, there are lack of studies to compare these two donor sites in detail. Thus, we proposed to investigate the available amount of autogenous bone graft from the proximal tibia.

Methods

Fifty-one patients who underwent simultaneous bone graft harvest from the PT and the AIC to fill up the given critical sized bone defects were enrolled in this study. We prospectively collected data including the weight of the harvested bone, donor site pain using the visual analog scale (VAS) score, and complications between the two sites.

Results

The mean weight of cancellous bone harvested from the PT was greater than AIC (33.2g vs. 27.4g, p = 0.001). The mean VAS score was significantly lesser in the PT up to 60 days after harvesting (p < 0.001). There was persistent pain up to 90 days in four PT patients and in seven AIC patients. The major complication was reported only in AIC patients (11.8%).

Conclusions

Harvesting cancellous bone from the PT is an acceptable alternative to the AIC for autogenous bone grafting owing to availability of more weighted graft bone and less donor site pain.
Humanitarian led community-based surveillance: case study in Ekondo-titi, Cameroon
Authors: Metuge Alain , Omam Lundi-Anne , Jarman Elizabeth , Njomo Esther Omam
Published: March 2021

Background

Community-based surveillance (CBS) has been used successfully in many situations to strengthen existing health systems as well as in humanitarian crises. The Anglophone crisis of Northwest Southwest Cameroon, led to burning of villages, targeting of health personnel and destruction of health facilities which, in combination with distrust for the government services led to a collapse of surveillance for outbreak prone diseases.

Methods

We evaluated the ability of the CBS system to identify suspected cases of outbreak prone diseases (OPD) as compared to the facility-based surveillance, evaluated the timeliness of the CBS system in identifying an OPD, reporting of OPD to District Health Service (DHS) and timeliness in outbreak response. The paper also assessed the collaboration with the DHS and contribution of the CBS system with regards to strengthening the overall surveillance of the health district and also determine the interventions undertaken to contain suspected/confirmed outbreaks.

Results

In total 9 alerts of suspected OPDs were generated by the CBS system as compared to 0 by the DHS, with 8 investigated, 5 responses and 3 confirmed outbreaks. Average time from first symptoms to alert generation by the CBS system was 7.3 days. Average time lag from alert generation from the CBS to the DHS was 0.3 days which was essentially within 24 h. There was extensive and synergistic collaboration with the DHS.

Discussion

CBS generated a higher number of alerts than traditional outbreak reported used in the region, and had timely investigations and if appropriate, responses. Careful selection of CHWs with strong community engagement led to the success of the project, and the use of the mobile health team in situ allowed for rapid responses to potential outbreaks, as well as for feedback to CHWs and communities. CBS was also well utilized for identification of other events, such as displacement and malnutrition.

Conclusion

In conflict settings, CBS can help in outbreak identification as well as other events, and a mobile health team is crucial to the success of the CBS due to the ability to rapidly response to generated alerts. The mobile health team provided timely investigation of 8 of 9 alerts generated. Collaboration with existing DHS structures is important for systems strengthening in such settings.
Assessment of alcohol use disorder and its associated factors among alcohol users of medical and surgical outpatients attending a specialized hospital in Gondar, Ethiopia: a cross-sectional study
Authors: Demilew Demeke , Boru Berhanu , Tesfaw Getachew , Kerebih Habtamu , Salelew Endalamaw
Published: March 2021

Background

Alcohol use disorder increase the risk of physical harm, mental or social consequences for patients and others in the community. Studies on alcohol use disorder and associated factors among medical and surgical outpatients in Ethiopia are limited. Therefore, this study is meant to provide essential data on alcohol use disorder and associated factors among alcohol user medical and surgical outpatients to intervene in the future.

Methods

An institution-based cross-sectional study was conducted by using the systematic random sampling technique. Alcohol use disorders were assessed using the World Health Organization’s 10-item Alcohol Use Disorder Identification Test (AUDIT) questionnaire. Bivariate and multivariate logistic regression analyses were performed, a P-value less than 0.05 were considered statistically significant in the multivariate analysis and the strength of association was measured at a 95% confidence interval.

Results

The prevalence of alcohol use disorder was 34.5% with a 95% CI (29.20, 39.80) among study participants. In the multivariate logistic regression analysis, male sex (AOR = 3.33, 95%CI: 1.40, 7.93), history of mental illness (AOR = 2.68, 95%CI: 1.12, 6.38), drinking for relaxation (AOR = 1.88, 95%CI: 1.02, 3.48) and history of lifetime tobacco use (AOR = 5.64, 95%CI: 1.95, 16.29) were factors significantly associated with alcohol use disorder.

Conclusion

The prevalence of alcohol use disorders among medical and surgical outpatients was found to be high. Male sex, history of mental illness, alcohol use for relaxation and lifetime cigarette smoking need more attention during the assessment of patients in the medical and surgical outpatient departments.
Fujita type theorem for a class of coupled quasilinear convection–diffusion equations
Authors: Zhou Yanan , Leng Yan , Nie Yuanyuan
Published: March 2021

In this paper, we establish the Fujita type theorem for a homogeneous Neumann outer problem of the coupled quasilinear convection–diffusion equations and formulate the critical Fujita exponent. Besides, the influence of diffusion term, reaction term, and convection term on the global existence and the blow-up property of the problem is revealed. Finally, we discuss the large time behavior of the solution to the outer problem in the critical case and describe the asymptotic behavior of the solution.
EuroScore and IL-6 predict the course in ICU after cardiac surgery
Authors: Bauer Andreas , Korten Insa , Juchem Gerd , Kiesewetter Isabel , Kilger Erich , Heyn Jens
Published: March 2021

Background

Despite modern advances in intensive care medicine and surgical techniques, mortality rates in cardiac surgical patients are still about 3%. Considerable efforts were made to predict morbidity and mortality after cardiac surgery. In this study, we analysed the predictive properties of EuroScore and IL-6 for mortality in ICU, prolonged postoperative mechanical ventilation, and prolonged stay in ICU.

Methods

We enrolled 2972 patients undergoing cardiac surgery. The patients either underwent aortic valve surgery (AV), mitral valve surgery (MV), coronary artery bypass grafting (CABG), and combined operations of aortic valve and coronary artery bypass grafting (AV + CABG) or of mitral and tricuspid valve (MV + TV). Different laboratory and clinical parameters were analysed.

Results

EuroScore as well as IL-6 were associated with increased mortality after cardiac surgery. Furthermore, a higher EuroScore and elevated levels of IL-6 were predictors for prolonged mechanical ventilation and a longer stay in ICU. Especially, highly significant elevated IL-6 levels and an increased EuroScore showed a strong association. Statistics suggested superiority when both parameters were combined in a single model.

Conclusion

Our results suggest that EuroScore and IL-6 are helpful in predicting the course in ICU after cardiac surgery, and therefore, the use of intensive care resources. Especially, the combination of highly elevated levels of IL-6 and EuroScore may prove to be excellent predictors for an unfortunate postoperative course in ICU.
What place for virtual reality in the intensive care unit during medical procedures?
Authors: Puel Floriane , Minville Vincent , Vardon-Bounes Fanny
Published: March 2021

In the intensive care unit, patients are subject to discomforts and pain. Their management is essentially based on pharmacologic approaches. Immersive virtual reality could represent an adjunctive non-invasive and non-pharmacological pain control technique. It is based on real-time interaction with an artificial 360° immersive world using interfaces that enable physical and emotional perceptions to make the user feel better trying to reduce pain perception and to limit anxiety. Evaluation of virtual reality in intensive care unit is lacking and further studies are necessary before to introduce this alternative method for critical patients.
A survived case of penetrating neck injury with intrathoracic organ damage
Authors: Kagimoto Atsushi , Mimura Takeshi , Hiraiwa Nanami , Yamashita Yoshinori
Published: March 2021

Background

Thoracic surgeons rarely encounter stab wounds with injury to the intrathoracic organs. However, such sudden and urgent situations could arise; therefore, experiences in managing such cases are invaluable.

Case presentation

An 84-year-old woman with depression who had a stab injury in the neck caused by a broad-bladed kitchen knife was brought to our facility by ambulance. She was stable in the emergency room; however, a computed tomography scan revealed that the blade had penetrated the right thoracic cavity. A right hemopneumothorax was seen. Considering the possibility of injury to the major vessels, a median sternotomy was performed. During the dissection around the blade, the patient started bleeding profusely, which required repair of an injury to the right internal jugular vein. The blade tip had penetrated the dorsal right upper lung lobe; however, it did not reach the hilum, and the knife was carefully removed. The damaged area of the lung was removed by wedge resection.

Conclusion

Patients with deep stab wounds from knives are often hemodynamically stable because the blade acts as tamponade and prevents hemorrhage. Therefore, a surgical approach that allows for good visualization should be considered for the extraction of the blade.
Update on fetal cardiovascular magnetic resonance and utility in congenital heart disease
Authors: Sun Liqun , Lee Fu-Tsuen , van Amerom Joshua F. P. , Freud Lindsay , Jaeggi Edgar , Macgowan Christopher K. , Seed Mike
Published: March 2021

Background

Congenital heart disease (CHD) is the most common birth defect, affecting approximately eight per thousand newborns. Between one and two neonates per thousand have congenital cardiac lesions that require immediate post-natal treatment to stabilize the circulation, and the management of these patients in particular has been greatly enhanced by prenatal detection. The antenatal diagnosis of CHD has been made possible through the development of fetal echocardiography, which provides excellent visualization of cardiac anatomy and physiology and is widely available. However, late gestational fetal echocardiographic imaging can be hampered by suboptimal sonographic windows, particularly in the setting of oligohydramnios or adverse maternal body habitus.

Main body

Recent advances in fetal cardiovascular magnetic resonance (CMR) technology now provide a feasible alternative that could be helpful when echocardiography is inconclusive or limited. Fetal CMR has also been used to study fetal circulatory physiology in human fetuses with CHD, providing new insights into how these common anatomical abnormalities impact the distribution of blood flow and oxygen across the fetal circulation. In combination with conventional fetal and neonatal magnetic resonance imaging (MRI) techniques, fetal CMR can be used to explore the relationship between abnormal cardiovascular physiology and fetal development. Similarly, fetal CMR has been successfully applied in large animal models of the human fetal circulation, aiding in the evaluation of experimental interventions aimed at improving in utero development. With the advent of accelerated image acquisition techniques, post-processing approaches to correcting motion artifacts and commercial MRI compatible cardiotocography units for acquiring gated fetal cardiac imaging, an increasing number of CMR methods including angiography, ventricular volumetry, and the quantification of vessel blood flow and oxygen content are now possible.

Conclusion

Fetal CMR has reached an exciting stage whereby it may now be used to enhance the assessment of cardiac morphology and fetal hemodynamics in the setting of prenatal CHD.
Role of CNTNAP2 in autism manifestation outlines the regulation of signaling between neurons at the synapse
Authors: Agarwala Swati , Ramachandra Nallur B.
Published: March 2021

Background

Autism is characterized by high heritability and a complex genetic mutational landscape with restricted social behavior and impaired social communication. Whole-exome sequencing is a reliable tool to pinpoint variants for unraveling the disease pathophysiology. The present meta-analysis was performed using 222 whole-exome sequences deposited by Simons Simplex Collection (SSC) at the European Nucleotide Archive. This sample cohort was used to identify causal mutations in autism-specific genes to create a mutational landscape focusing on the CNTNAP2 gene.

Results

The authors account for the identification of 15 high confidence genes with 24 variants for autism with Simons Foundation Autism Research Initiative (SFARI) gene scoring. These genes encompass critical autism pathways such as neuron development, synapse complexity, cytoskeleton, and microtubule activation. Among these 15 genes, overlapping variants were present across multiple samples: KMT2C in 167 cases, CNTNAP2 in 192 samples, CACNA1C in 152 cases, and SHANK3 in 124 cases. Pathway analysis identifies clustering and interplay of autism genes—WDFY3, SHANK2, CNTNAP2, HOMER1, SYNGAP1, and ANK2 with CNTNAP2. These genes coincide across autism-relevant pathways, namely abnormal social behavior and intellectual and cognitive impairment. Based on multiple layers of selection criteria, CNTNAP2 was chosen as the master gene for the study. It is an essential gene for autism with speech-language delays, a typical phenotype in most cases under study. It showcases nine variants across multiple samples with one damaging variant, T589P, with a GERP rank score range of 0.065–0.95. This unique variant was present across 86.5% of the samples impairing the epithelial growth factor (EGF) domain. Established microRNA (miRNA) genes hsa-mir-548aq and hsa-mir-548f were mutated within the CNTNAP2 region, adding to the severity. The mutated protein showed reduced stability by 0.25, increased solvent accessibility by 9%, and reduced depth by 0.2, which rendered the protein non-functional. Secondary physical interactors of CNTNAP2 through CNTN2 proteins were mutated in the samples, further intensifying the severity.

Conclusion

CNTNAP2 has been identified as a master gene in autism manifestation responsible for speech-language delay by impairing the EGF protein domain and downstream cascade. The decrease in EGF is correlated with vital autism symptoms, especially language disabilities.
Management of liver disease patients in different clinical situations during COVID-19 pandemic
Authors: Zaky Samy , Alboraie Mohamed , El Badry Mohamed , Metwally Mohamed A. , Abdelaziz Ahmed , Fouad Yasser , Abd-Elsalam Sherief , Mahmoud Abdelmajeed , Shiha Gamal , Baki Amin Abdel , El Kassas Mohamed , Esmat Gamal
Published: March 2021

Chronic liver diseases are common worldwide, especially in developing countries. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) leads to the infection of many patients with underlying chronic liver diseases. As a relatively new disease, management of COVID-19, in the context of chronic liver disease, is mainly based on the experience of the treating physician and the available data. In this review, we summarize the available evidence about the management of liver disease patients, in the context of COVID-19 infection, which can increase the severity of viral hepatitis B. Also, its clearance in HBV patients is delayed. A sixfold increased severity of COVID-19 was reported in obese patients with metabolic associated fatty liver disease (MAFDL). In patients with autoimmune liver disease (AILD), it is not recommended to change their immunosuppressive therapy (as long as they are not infected with COVID-19), in order to avoid a flare of liver disease. However, immunosuppressant drugs should be modified, in the case of infection with COVID-19. To date, no data suggest an increased risk or severity in metabolic liver diseases, such as hemochromatosis, Wilson’s disease, or alpha-1 antitrypsin deficiency. Patients with liver cirrhosis should be carefully managed with minimum exposure to healthcare facilities. Basic investigations for follow-up can be scheduled at wider intervals; if patients need admission, this should be in COVID-19-clean areas. Patients with hepatocellular carcinomas may have a poor prognosis according to preliminary reports from China. The course of COVID-19 in liver transplant recipients on immunosuppression seems to have a benign course, based on few reports in children and adults. The hepatotoxicity of COVID-19 drugs ranges from mild liver enzyme elevation to a flare of underlying liver diseases. Therefore, the decision should be customized. Telemedicine can minimize the exposure of healthcare workers and patients to infection with COVID-19 and decrease the consumption of personal protective equipment.
Sequence phylogenetic analysis and associative genetic diversity of Sarcocystis hirsuta based on 18S rRNA gene
Authors: Sudan Vikrant , Kumar Rahul , Shanker Daya , Singh Amit
Published: March 2021

Background

Sarcocystis hirsuta, a tissue cyst-forming coccidian parasite of cattle, is worldwide in distribution. In spite of its global presence, limited literature is available on its characterization studies. No literature is available from India on molecular aspects ofS. hirsuta.The present study was designed to characterize the isolates ofS. hirsutaon the 18S gene locus. A total of five isolates ofS. hirsutawere characterized. PCR products were cloned, sequenced, and compared with other sequences across the world. A phylogenetic tree was constructed based on the maximum parsimony (MP) method with the tree–bisection–regrafting (TBR) algorithm.

Results

An appreciable genetic variability was noticed between variousS. hirsutaisolates at the 18S gene locus. Sequences generated from the present study (MN121567–MN121571) represented two haplotypes with 99.74–100.00% nucleotide homology within themselves. Alongside, a nucleotide homology of 97.82–99.92% was observed between Indian isolates and isolates across the globe. The two haplotypes were markedly distinct from each other with 3 nucleotide substitutions within themselves. Overall, Indian isolates ofS. hirsutawere close to those from China and Vietnam than to those from New Zealand, Brazil, and Germany.

Conclusion

The present communication describes the first report of phylogenetic characterization ofS. hirsutafrom India. The findings are very much important in delineating the evolutionary phylogenetics ofS. hirsuta.
Where to Start and What to Do Next: The Sequencing of Treatments in Metastatic Esophagogastric Cancer
Authors: Mamdani Hirva , Jalal Shadia I.
Published: March 2021

Esophagogastric cancer is associated with rising incidence and high mortality. Nearly 40% of patients have metastatic disease at the time of diagnosis with poor 5-year overall survival. The treatment of squamous cell carcinoma of the esophagus and gastroesophageal adenocarcinoma has started to bifurcate in recent years, owing to the evolving understanding of the biologic and genomic characteristics of these tumors. Incorporation of HER2-directed therapy in the form of monoclonal antibody and antibody-drug conjugate is now standard of care for patients with HER2-positive disease. The addition of immune checkpoint inhibitors to the therapeutic landscape of metastatic esophagogastric cancer is associated with modest improvement in overall survival, and definition of predictive biomarkers of response to checkpoint inhibition remains imprecise. A number of therapeutic targets including FGFR2b, Claudin 18.2, DKK-1, and DNA repair defects are being explored in clinical trials. Similarly, combination immunotherapy and novel HER2-targeting agents, such as bispecific antibody and small-molecule inhibitors, are at various stages of clinical development. Despite the progress made in the field of targeted therapies and checkpoint inhibition, chemotherapy remains an integral part of treatment of metastatic esophagogastric cancer but is associated with considerable toxicity. Clinical trials focusing on minimizing toxicity of currently available therapeutic agents, development of novel biomarker-driven treatment strategies, and overcoming resistance to immune checkpoint inhibition will define the future of this traditionally indelible disease.
Highlights from the previous volumes
Authors: Nimmagadda Varun , Ying Na , Mikura Y. , Otomo Hiroshi
Published: March 2021

Can quarantine do more than just "flatten the curve"

Rossby-waves--related CO2 concentrations to surface air temperature

Conformal inflation in the metric-affine geometry

A kinetic generator for classical field theories with conservation laws
Cross-channel contributions to vortex patterns in photoionization by a pair of counter-rotating circularly polarized attosecond pulses
Authors: Zhen Q. , Zhang S. Q. , Yang Z. J. , Liu X. S.
Published: March 2021

We theoretically investigate the cross-channel contributions to vortex patterns in photoionization of

by a pair of left-right circularly polarized attosecond pulses by numerically solving the two-dimensional (2D) time-dependent Schrödinger equation (TDSE). It is found that the contribution of the ionization cross-channel only worked with a short time delay and the ionization cross-channel will lead to the difference in the brightness of the vortex patterns. The sensitivity of the vortex pattern to the time delay can be employed to control the ionized electron distributions by adjusting the time delay between two laser pulses. These phenomena can be explained by the attosecond perturbation ionization theory.
Relationship between charge density wave, filamentary superconductivity and bulk superconductivity in ZrTe3
Authors: Nomura A. , Kobayashi S. , Ohta S. , Sakata H.
Published: March 2021

We investigated the relationship between a charge density wave (CDW) with a transition temperature

of

, filamentary superconductivities (SCs) along the a-axis and the b-axis with transition temperatures (

’s) of

, and a bulk SC with a

below 2.5 K in ZrTe3, by measuring electrical resistance and magnetization for several crystals synthesized at different growth temperatures. As the growth temperature increased, the

decreased, the

of the bulk SC increased, and the

’s of the filamentary SCs did not show a clear change. The anisotropy of the upper critical field

was different between the filamentary SCs and the bulk SC. These differences in the growth temperature dependence of

and the anisotropy of

indicate that the filamentary SCs are unrelated to the bulk SC. Moreover, the growth temperature dependence of the transition temperatures indicates that the CDW has a competitive relationship with the bulk SC, but a non-competitive coexistence with the filamentary SCs. Based on the anisotropies of

, we also infer that the filamentary SCs and the bulk SC occur on quasi-one-dimensional Fermi surfaces and a three-dimensional Fermi surface, respectively, and that the relationship between the three states in ZrTe3 cannot be explained solely in terms of conventional competition for a Fermi surface.
Long-Term Results of a Phase II Trial of Apatinib for Progressive Radioiodine Refractory Differentiated Thyroid Cancer
Authors: Lin Yan-Song , Zhang Xin , Wang Chen , Liu Yan-Qing , Guan Wen-Min , Liang Jun
Published: March 2021

Context

Radioiodine refractory differentiated thyroid cancer (RAIR-DTC) has been a global challenge due to its poor prognosis and limited treatment options.

Objective

We report here the long-term results of the phase II clinical trial of apatinib, an anti-angiogenic tyrosine kinase inhibitor, for RAIR-DTC.

Methods

This was an open-label, exploratory phase II clinical trial among progressive RAIR-DTC patients. Apatinib treatment was given once daily until disease progression, unmanageable toxicity, withdrawal, or death. The primary end points were objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS), overall survival (OS), duration of response, long-term safety, and the association between patients with different tumor genotype (BRAFV600E and TERT promotor mutation) and their PFS rates were also assessed.

Results

The ORR was 80%, and the DCR was 95%. The overall median PFS was 18.4 months (95% CI, 9.2-36.8 months) and the median OS was 51.6 months (95% CI, 29.2-not reached [NR]). Patients with BRAFV600E mutation (10 of 18 evaluated) had a longer median PFS compared with patients with BRAF wild-type (NR vs 9.2 months; P = 0.002). The most common adverse events included palmar-plantar erythrodysesthesia syndrome (19/20), proteinuria (18/20), and hypertension (16/20).

Conclusion

In this long-term evaluation, apatinib displayed sustainable efficacy and tolerable safety profile, warranting it as a promising treatment option for progressive RAIR-DTC.