bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and stabilization of CO2 nanobubbles using surfactants for extraction of polyphenols from Camellia oleifera shells
Authors: Javed Miral , Belwal Tarun , Huang Hao , Xu Yanqun , Ettoumi Fatima‐ezzahra , Li Li , Fang Xuezhi , Luo Zisheng
Published: August 2022

Camellia oleifera shells are abundant in polyphenolic compounds. Green extraction methods of polyphenolic compounds are essential to ensure product quality, efficiency, process cost, environment, and safety. This study investigated the effect of Tween 80 and Rhamnolipid surfactants on the production and utilization of stabilized carbon dioxide nanobubbles (CO2‐NBs). The results confirmed the presence of the CO2‐NBs in ultra‐pure water with a concentration of 8.45 ± 1.05 × 108 ml–1, among which the stable CO2‐NBs possessed a mean size of 40–90 nm and a negative zeta potential (−41.6 ± 1.3 mV). Further, the efficiency of CO2‐NBs combined with ultrasonication (CO2‐NBs‐Rh‐UAE) was evaluated to extract polyphenols from Camellia oleifera shells (waste). The CO2‐NBs treatment with ultrasonication showed the highest total phenolic content (TPC) and total flavonoid content (TFC) (36.75 ± 0.22 mg GAE/g DW and 24.06 ± 0.22 mg RE/g DW, respectively). Overall, this study demonstrated an innovative approach for producing, stabilizing, and utilizing biosurfactant stabilized CO2‐NBs to extract polyphenolic compounds from the waste agricultural products. These findings highlighted the potential application of biosurfactant‐stabilized CO2‐NBs.
Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity
Authors: Arneaud Sonja L. B. , McClendon Jacob , Tatge Lexus , Watterson Abigail , Zuurbier Kielen R. , Madhu Bhoomi , Gumienny Tina L. , Douglas Peter M.
Published: August 2022

Aging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF‐1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF‐1 modulates age across tissues remain unclear. Herein, we report a nonautonomous mode of age regulation by HSF‐1 in the Caenorhabditis elegans nervous system that works through the bone morphogenic protein, BMP, signaling pathway to modulate membrane trafficking in peripheral tissues. In particular, HSF‐1 represses the expression of the neuron‐specific BMP ligand, DBL‐1, and initiates a complementary negative feedback loop within the intestine. By reducing receipt of DBL‐1 in the periphery, the SMAD transcriptional coactivator, SMA‐3, represses the expression of critical membrane trafficking regulators including Rab GTPases involved in early (RAB‐5), late (RAB‐7), and recycling (RAB‐11.1) endosomal dynamics and the BMP receptor binding protein, SMA‐10. This reduces cell surface residency and steady‐state levels of the type I BMP receptor, SMA‐6, in the intestine and further dampens signal transmission to the periphery. Thus, the ability of HSF‐1 to coordinate BMP signaling along the gut–brain axis is an important determinate in age progression.
Corticosteroids for patients with vestibular neuritis: An evidence synthesis for guidelines for reasonable and appropriate care in the emergency department
Authors: Oliveira J. e Silva Lucas , Khoujah Danya , Naples James G. , Edlow Jonathan A. , Gerberi Danielle J. , Carpenter Christopher R. , Bellolio Fernanda
Published: August 2022

Background

A short course of corticosteroids is among the management strategies considered by specialists for the treatment of vestibular neuritis (VN). We conducted an umbrella review (systematic review of systematic reviews) to summarize the evidence of corticosteroids use for the treatment of VN.

Methods

We included systematic reviews of randomized controlled trials (RCTs) and observational studies that evaluated the effects of corticosteroids compared to placebo or usual care in adult patients with acute VN. Titles, abstracts, and full texts were screened in duplicate. The quality of reviews was assessed with the A MeaSurement Tool to Assess systematic Reviews (AMSTAR‐2) tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to rate certainty of evidence. No meta‐analysis was performed.

Results

From 149 titles, five systematic reviews were selected for quality assessment, and two reviews were of higher methodological quality and were included. These two reviews included 12 individual studies and 660 patients with VN. In a meta‐analysis of two RCTs including a total of 50 patients, the use of corticosteroids (compared to placebo) was associated with higher complete caloric recovery (risk ratio 2.81, 95% confidence interval [CI] 1.32 to 6.00, low certainty). It is very uncertain whether this translates into clinical improvement as shown by the imprecise effect estimates for outcomes such as patient‐reported vertigo or patient‐reported dizziness disability. There was a wide CI for the outcome of dizziness handicap score (one study, 30 patients, 20.9 points in corticosteroids group vs. 15.8 points in placebo, mean difference +5.1, 95% CI −8.09 to +18.29, very low certainty). Higher rates of minor adverse effects for those receiving corticosteroids were reported, but the certainty in this evidence was very low.

Conclusions

There is limited evidence to support the use of corticosteroids for the treatment of VN in the emergency department.
Fire severity has lasting effects on the distribution of arboreal mammals in a resprouting forest
Authors: Campbell‐Jones Maggie M. , Bassett Michelle , Bennett Andrew F. , Chia Evelyn K. , Leonard Steve , Collins Luke
Published: August 2022

Wildfire severity is assumed to be an important driver of habitat availability and species' distributions in forest ecosystems. Many studies have focused on the immediate or short‐term effects of fire severity in fire‐prone ecosystems, with much less focus on how long the effect of fire severity may persist. We examined the effect of fire severity on the distribution of arboreal mammals at 3 and 10 years post‐fire, in a temperate forest ecosystem dominated by eucalypts that have strong resistance and resilience to low and high severity fire, respectively. The study took place within areas affected by the 2009 Kilmore East‐Murrindindi wildfires in south‐eastern Australia. Sites were established across a gradient of fire severity (unburnt through to canopy consumption) and surveyed at 3 and 10 years following fire. Owing to low detection rates for many species, analyses were limited to greater glider (Petauroides volans) occurrence and arboreal species richness. At both 3 and 10 years post‐fire, the greater glider was restricted to unburnt forest or sites affected only by understorey fire, which acted as fire refugia. Greater gliders were absent from sites affected by high severity, canopy‐consuming fires at both points in time. Greater glider occurrence was associated with high levels of canopy cover (>50%), which were typically those areas that were unburnt or burnt at low severity. The richness of arboreal mammals increased over time and was greater in unburnt or minimally affected forest. Our findings emphasize: (i) that fire severity is an important driver of the distribution of arboreal mammals; and (ii) the importance of recognizing longer‐term effects of fire severity in assessing species distributions, even in highly resilient forest communities. Recent advances in mapping fire severity provide new opportunities to assess the effects of fire severity on the distributional patterns of fauna in eucalypt forests.
Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies*
Authors: Chrimes N. , Higgs A. , Hagberg C. A. , Baker P. A. , Cooper R. M. , Greif R. , Kovacs G. , Law J. A. , Marshall S. D. , Myatra S. N. , O'Sullivan E. P. , Rosenblatt W. H. , Ross C. H. , Sakles J. C. , Sorbello M. , Cook T. M.
Published: August 2022

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co‐ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of ‘sustained exhaled carbon dioxide’ using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.
Pupil diameter during cataract surgery after intracameral injection of the first ready‐to‐use combination of mydriatics and anaesthetic at the beginning of surgery in patients with a preoperative pupil diameter <6 mm
Authors: Kęcik Dariusz , Grabska‐Liberek Iwona , Jurowski Piotr , Mrukwa–Kominek Ewa , Omulecki Wojciech , Romanowska–Dixon Bożena , Szaflik Jacek P. , Romaniuk Wanda , Szaflik Jerzy , Kopacz Dorota , Mianowska Katarzyna
Published: August 2022

Purpose

We evaluated, in a real‐life setting, the effect of Mydrane® (ready‐to‐use combination of tropicamide, phenylephrine hydrochloride and lidocaine, injected into the anterior chamber at the beginning of cataract surgery to induce mydriasis and intraocular anaesthesia) on the pupil diameter during cataract surgery in patients with a preoperative pupil diameter <6 mm after the use of topical mydriatics.

Methods

We collected and analysed the data of 59 consecutive patients whose pupils dilated to a diameter <6 mm after the administration of mydriatic eye drops during the preoperative visit and who received Mydrane® during cataract surgery.

Results

In the group of 59 patients with a preoperative pupil diameter <6 mm after topical mydriatics, cataract surgery was performed in 36 patients (61.0%) using only Mydrane® to obtain mydriasis, with no additional drug or medical device. The mean pupil diameters in this group (36 of 59) during the preoperative assessment after topical mydriatics and just before capsulorhexis when Mydrane® was injected during surgery were 5.1 ± 0.74 and 6.15 ± 1.14 mm. Additional drugs were used in 23 patients (39%). In this group, the mean pupil diameters after topical mydriatics and just before capsulorhexis using Mydrane® were 4.58 ± 1.06 and 5.6 ± 1.26 mm, respectively.

Conclusion

In a real‐life setting, the mean pupil diameter achieved during cataract surgery after the intracameral injection of Mydrane® in patients with a preoperative pupil diameter <6 mm was over 1 mm larger than the mean pupil diameter after topical mydriatics, despite the trauma caused by the operation.
Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis
Authors: Zhao Xiaofang , Wu Jiangfan , Zhu Shenyin
Published: August 2022

Aims

To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin‐like/kexin type 9 (PCSK9) inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods

We conducted a disproportionality analysis of PCSK9 inhibitors in the FAERS (01/2004–12/2021). The association between PCSK9 inhibitors and oAEs was evaluated using the information component (IC) and the reporting odds ratio (ROR), and the difference in oAEs between evolocumab and alirocumab was compared using the ROR. Different sensitivity analyses were conducted to evaluate the robustness of results.

Results

A total of 103 531 reports involving at least 1 PCSK9 inhibitor were found in the FAERS. PCSK9 inhibitors were associated with higher reporting of increased lacrimation (IC 0.27 [95% confidence interval {CI} 0.02–0.45]; ROR 1.21 [95% CI 1.04–1.40]), seasonal allergy (IC 0.39 [95% CI 0.04–0.64]; ROR 1.32 [95% CI 1.07–1.62]) and eye operation (IC 0.66 [95% CI 0.04–1.10]; ROR 1.60 [95% CI 1.11–2.30]) compared with the full database, and there was no difference between evolocumab and alirocumab. Sensitivity analyses showed that the disproportionate signals of increased lacrimation disappeared after excluding cases with other lipid‐lowering agents in the combined drugs. Except for eye operations, most of these adverse events occurred within 30 days of the first dose, and all 3 oAEs were mostly reported in women and individuals >65 years.

Conclusion

This pharmacovigilance study identified a possible signal of ocular disorders associated with PCSK9 inhibitors and encourages paying attention to at‐risk populations in PCSK9 inhibitors medication.
Assessment of the nlmixr R package for population pharmacokinetic modeling: A metformin case study
Authors: Mak Wen Yao , Ooi Qing Xi , Cruz Cintia Valeria , Looi Irene , Yuen Kah Hay , Standing Joseph F.
Published: August 2022

Aim

nlmixr offers first‐order conditional estimation (FOCE), FOCE with interaction (FOCEi) and stochastic approximation estimation‐maximisation (SAEM) to fit nonlinear mixed‐effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates.

Method

Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness‐of‐fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re‐estimated as the initial estimates were perturbed 100 times and resultant changes evaluated.

Results

The absorption kinetics of metformin depend significantly on food status. Under the fasted state, the first‐order absorption into the central compartment was preceded by zero‐order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first‐order absorption from depot into the central compartment. The means of relative mean estimation error (rMEE) (
) and rRMSE (
) were 0.48 and 0.35, respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased. When initial estimates were perturbed, FOCEi estimates were more biased and imprecise.

Discussion

nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations.
The impact of histological grade on outcomes in follicular lymphoma: An analysis of patients in the SEER database in the context of evolving disease classification and treatment
Authors: Naik Anisha , Gooley Ted , Loeb Keith , Soma Lorinda , Smith Stephen D. , Gopal Ajay , Naresh Kikkeri N.
Published: August 2022

Currently, there is no convincing evidence that the grade of follicular lymphoma (FL) impacts patient outcome. We correlated grades in 33 925 patients with nodal FL during 1992–2018 in the SEER database with disease‐specific survival (DSS) and overall survival (OS). Patients with FL grade 3 had lower DSS and OS as compared to FL grades 1–2. During 1992–2005, the 10‐year DSS for patients with FL grades 3 and grades 1–2 were 68.6%, and 71.4%, respectively, and in 2006–2018, they were 77.7% and 82.6%, respectively. The 10‐year OS estimates in 1992–2005 were 49.9% and 54.2% for grade 3 and grades 1–2 respectively, and in 2006–2018, they were 59.1% and 63.5% for grade 3 and grades 1–2, respectively. After adjustment for stage and age, the hazard ratios for death due to FL and death from any cause for patients with FL grade 3 during 1992–2005 were 1.09 (1.02–1.16) and 1.07 (1.02–1.12), respectively, compared to FL grades 1–2; and during 2006–2018, the hazard ratios for death due to FL and death from any cause for patients with FL grade 3 were 1.34 (1.22–1.45) and 1.16 (1.10–1.23), respectively compared to FL grades 1–2. The grade of FL is an important determinant of disease biology.
Plasma exosomal DOK3 reflects immunological states in lung tumor and predicts prognosis of gefitinib treatment
Authors: Ochiai Ryosuke , Hayashi Kentaro , Yamamoto Hiroshi , Fujii Risa , Saichi Naomi , Shinchi Hiroki , Ishida Tsuyoshi , Honda Takeshi , Shimizu Tetsuo , Matsutani Noriyuki , Seki Nobuhiko , Kawamura Masafumi , Ueda Koji
Published: August 2022

To identify liquid biomarkers that predict clinical outcomes of epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI), we enrolled patients with EGFR gene mutation‐positive non–small‐cell lung cancer who were intended to receive gefitinib treatment. Using plasma samples obtained prior to gefitinib treatment from 12 enrolled patients, we performed comprehensive proteomic analysis of plasma exosomes to explore proteins correlating with tumor reduction rate (TRR), progression‐free survival (PFS), or overall survival (OS). Of the detected 1769 proteins, 119, 130, or 119 proteins demonstrated a strong correlation (|r| > 0.5) with TRR, PFS, or OS, respectively. Interestingly, 34 (29%), 41 (32%), or 27 (23%) of them, respectively, were functionally involved in the regulation of the immune response. CD8α chain was consistently listed as a molecule positively correlated with PFS and OS, suggesting that the long‐lasting effects of gefitinib may be due to the antitumor effects of CD8+ T cells, as well as the induction of immunogenic apoptosis of tumor cells by blocking the EGFR signaling pathway. Notably, Doking Protein 3 (DOK3), a molecule involved in B‐cell receptor signaling, and some immunoglobulin and complement molecules exhibited a clear correlation with PFS longevity of gefitinib treatment. Indeed, the strong expression of DOK3 in B cells was confirmed within tertiary lymphoid structures of lung cancer tissues derived from patients with long PFS. These findings suggest that the patients with active B‐cell and T‐cell immunity as a host immunological feature are more likely to benefit from gefitinib therapy. Circulating exosomal DOK3 has the potential as a predictive marker of response to gefitinib indicating this immunological feature.
Learning the rules of the game: The role of generic “you” and “we” in shaping children's interpretations of norms
Authors: Orvell Ariana , Elli Giulia , Umscheid Valerie , Simmons Ella , Kross Ethan , Gelman Susan A.
Published: August 2022

A critical skill of childhood is learning social norms. We examine whether the generic pronouns “you” and “we,” which frame information as applying to people in general rather than to a specific individual, facilitate this process. In one pre‐registered experiment conducted online between 2020 and 2021, children 4‐ to 9‐year‐old primarily living in the midwestern U.S. (N = 146, 75 girls, 71 boys,Mage = 7.14,SD = 1.69, 82% White) interpreted actions described with generic pronouns (vs. “I”) as normatively correct and selected the speaker who used generic pronouns as the rule‐follower, particularly when generic pronouns were presented first. There were no significant effects of age. These results illustrate how generic pronouns influence how children discern unfamiliar norms and form interpersonal judgments.
Regular support provided by dermatological nurses improves outcomes in patients with psoriasis treated with topical drugs: a randomized controlled trial
Authors: Svendsen Mathias Tiedemann , Feldman Steven R. , Mejldal Anna , Möller Sören , Kongstad Line Planck , Andersen Klaus E.
Published: August 2022

Background

Patient adherence to topical antipsoriatic drugs is often poor, leading to poor efficacy. Use of long-term support delivered by dermatological nurses to patients treated with topical drugs may improve outcome.

Aim

To evaluate whether regular support from dermatological nurses improves outcome and treatment adherence in patients with psoriasis receiving topical medications.

Methods

We conducted a randomized controlled trial (RCT) (clinicaltrials.gov registration NCT04220554), in which patients received once-daily topical medications (containing corticosteroids and/or calcipotriol) for as long as their psoriasis was visible. The patients were randomly allocated to standard care by the dermatologist either with (n = 51) or without (n = 52) support from dermatological nurses. The nurse support intervention consisted of a structured dermatological consultation at baseline and Week 1, followed by contact with a nurse each month (in the outpatient clinic or by telephone). The primary outcome was severity of psoriasis, which was measured by the Lattice System Physician's Global Assessment (LS-PGA) and assessed by intention-to-treat analyses using linear mixed regression models for longitudinal data. Secondary outcomes were quality of life (measured by the Dermatology Life Quality Index; DLQI) and good adherence (defined as use of ≥ 80% of recommended doses).

Results

In total, 92 patients (89%) completed the 48-week trial period. The intervention group improved more than the nonintervention group from baseline to Week 24 in LS-PGA (2.21 vs. 1.28, P = 0.001) and in DLQI at Week 12 (6.50 vs. 1.55, P < 0.001). Differences between the two groups in favour of the intervention were observed throughout the study period. More participants in the intervention group had good adherence compared with the nonintervention group (36% vs. 14%, P < 0.001).

Conclusion

Regular, continued patient support from dermatological nurses increased the efficacy of psoriasis treatment, improved quality of life and enhanced long-term adherence to topical antipsoriatic drugs. However, there is still room for more improvement.
Old dog, new tricks: split-thickness skin graft harvesting from the postauricular scalp using a Silver manual dermatome
Authors: Hunt William Thomas Nicholas , Nelson Toby G.
Published: August 2022

Click here for the corresponding questions to this CME article.
Long‐term outcome of cerebral amyloid angiopathy‐related hemorrhage
Authors: Che Ruiwen , Zhang Mengke , Sun Hailiang , Ma Jin , Hu Wenbo , Liu Xin , Ji Xunming
Published: August 2022

Object

The long‐term functional outcome of cerebral amyloid angiopathy‐related hemorrhage (CAAH) patients is unclear. We sought to assess the long‐term functional outcome of CAAH and determine the prognostic factors associated with unfavorable outcomes.

Methods

We enrolled consecutive CAAH patients from 2014 to 2020 in this observational study. Baseline characteristics and clinical outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long‐term outcome.

Results

Among the 141 CAAH patients, 76 (53.9%) achieved favorable outcomes and 28 (19.9%) of them died at 1‐year follow‐up. For the longer‐term follow‐up with a median observation time of 19.0 (interquartile range, 12.0–26.5) months, 71 (50.4%) patients obtained favorable outcomes while 33 (23.4%) died. GCS on admission (OR, 0.109; 95% CI, 0.021–0.556;p = 0.008), recurrence of ICH (OR, 2923.687; 95% CI, 6.282–1360730.14;p = 0.011), WML grade 3–4 (OR, 31.007; 95% CI, 1.041–923.573;p = 0.047), severe central atrophy (OR, 4220.303; 95% CI, 9.135–1949674.84;p = 0.008) assessed by CT was identified as independent predictors for long‐term outcome.

Interpretation

Nearly 50% of CAAH patients achieved favorable outcomes at long‐term follow‐up. GCS, recurrence of ICH, WML grade and cerebral atrophy were identified as independent prognostic factors of long‐term outcome.
Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience
Authors: Das Bibek , Fehervari Matyas , Hamrang‐Yousefi Sahar , Jiao Long R. , Pai Madhava , Jenkins John T. , Spalding Duncan R. C.
Published: August 2022

Aim

Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD‐RC) to achieve curative, margin‐negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low‐volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long‐term outcomes of this procedure at a single high‐volume hepatopancreaticobiliary surgery unit in the UK.

Method

A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD‐RC in a 7‐year period (2013–2020). Clinico‐pathological and outcome data were reviewed.

Results

Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien–Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan–Meier estimated 5‐year overall survival was 83.3% (95% CI 58.3%–100%). Univariate survival analysis identified perineural invasion and extra‐colonic origin as predictors of poor survival (log‐rank P < 0.05).

Conclusion

En bloc PD‐RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin‐negative resections and resultant long‐term survival in carefully selected patients.
Genomewide association study identifies a novel variant associated with tacrolimus trough concentration in Chinese renal transplant recipients
Authors: Yang Siyao , Jiang Haixia , Li Chengcheng , Lu Huijie , Li Chuanjiang , Ye Demei , Qi Huana , Xu Wenbin , Bao Xiaojie , Maseko Nicola , Zhang Siqi , Shao Ruifan , Li Liang
Published: August 2022

Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable interindividual variability in pharmacokinetics (PKs). Genetic and clinical factors play important roles in TAC PKs. We enrolled a total of 251 Chinese renal transplant recipients and conducted a genomewide association study (GWAS), linkage disequilibrium (LD), and one‐way analysis of variance (ANOVA) to find genetic variants affecting log‐transformed TAC trough blood concentration/dose ratio (log[C0/D]). In addition, we performed dual luciferase reporter gene assays and multivariate regression models to evaluate the effect of the genetic variants. The GWAS results showed that all 23 genomewide significant single‐nucleotide polymorphisms (p < 5 × 10−8) were located on chromosome 7, includingCYP3A5*3. LD, conditional association analysis, and one‐way ANOVA showed that rs75125371 T > C independently influenced TAC log(C0/D). Dual luciferase reporter gene assays indicated that rs75125371 minor allele (C) was significantly associated with increased normalized luciferase activity than the major allele (T) in the Huh7 cells (p = 1.2 × 10−5) and HepaRG cells (p = 0.0097). A model inclusive of age, sex, hematocrit,CYP3A5*3, and rs75125371 explained 37.34% variance in TACC0. These results suggest that rs75125371 T > C is a functional and population‐specific variant affecting TACC0in Chinese renal transplant recipients.
The fibrosis‐4 score is associated with long‐term mortality in different phenotypes of acute heart failure
Authors: Tseng Chih‐Hsueh , Huang Wei‐Min , Yu Wen‐Chung , Cheng Hao‐Min , Chang Hao‐Chih , Hsu Pai‐Feng , Chiang Chern‐En , Chen Chen‐Huan , Sung Shih‐Hsien
Published: August 2022

Background

Fibrosis‐4 score (FIB4) was a non‐invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients.

Method

Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All‐cause mortality up to 5 years after discharge was obtained by linking to the national death registry.

Results

Among a total of 1854 participants, 940 patients died during a mean follow‐up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications [hazard ratio and 95% confidence interval of mortality: 1.009 (1.002–1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010–1.031)]. The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts [interaction p‐value <0.001, and 0.004, respectively].

Conclusions

FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD.
Uncovering bias in order assignment
Authors: Grant Darren
Published: August 2022

To mitigate sequencing effects in decision‐making, many situations require a set of items to be considered in a random order. When such orderings are repeated, one can test whether randomization indeed obtains, or whether some orderings have been manipulated in order to achieve a favorable result. This paper articulates the key features of this problem and presents three general tests for randomness. These methods are used to analyze the order in which lottery numbers are drawn in Powerball, contestants perform on American Idol, and candidates are placed on election ballots. This last application features frequent manipulation, with potentially serious consequences.
Numerical simulation of fatigue behavior of flexible metal films in multiphysics fields
Authors: Zheng Yichuan , Huang Xingzhen , Li Zhaoxia
Published: August 2022

The operating ambient of flexible electronics interconnects is a complex environment that includes mechanical deformation, electric current, and temperature. It is a potential threat to the long‐term service reliability of flexible electronic devices. This paper aims to develop a multiphysics fatigue model for flexible metal films. The effect of multiphysics fields is considered in the Coffin–Manson relationship based on reasonable simplification. The fatigue behavior of copper films of various thicknesses on a flexible substrate was investigated when electrical current and mechanical displacement loads were applied simultaneously. The developed model is validated to compare with experimental results. The numerical results show that it can analyze the effect of multiphysics fields and predict the fatigue life of copper films. Therefore, it could be a means to assess the fatigue performance of metal films on flexible substrates in multiphysics fields.
Three‐dimensional fatigue crack growth simulation and fatigue life assessment based on finite element analysis
Authors: Ilie Paul , Ince Ayhan
Published: August 2022

Damage tolerance design allows manufactures to assess fatigue crack propagation of components containing initial defects. A new modeling approach is proposed to carry out a systematic crack growth analysis based on an analytical method using reduced order models and three‐dimensional (3D) finite element (FE)‐based fatigue crack growth (FCG) analysis. 3D FE‐based FCG analysis is adopted as an advanced modeling approach for component geometries without any simplifications with respect to crack front shape or planarity of the crack path. The FE‐based FCG approach was verified and validated in two different stages: Ti‐6Al‐4V plate geometry with three different single elliptical crack configurations and Al 2024‐T3 specimens with two different multiple crack configurations. The analytical FCG approach was developed to estimate crack front evolution and crack growth life for three different elliptical cracks to verify the FE‐based approach. Experimental data of Al 2024‐T3 specimens with multi‐edge cracks was used to further validate the FE‐based FCG approach. The FE‐based FCG approach proved to be both accurate and powerful in assessing crack propagation life and crack paths of structural parts.
Insights into the role of external layers in cyanobacteria at varying temperatures and their regulatory mechanism
Authors: Cheng Yuran , Li Zhe , Xiao Yan , Wu Xinghua , Liu Liming
Published: August 2022

The dominance of cyanobacteria and their adaptability to changing climates might be attributed to their morphological plasticity related to external layers. The content of exopolysaccharides in cyanobacterial external layers has been shown to increase at elevated temperatures. However, the answers to the questions of why and how cyanobacteria adapt to varying temperatures by adjusting the physiological and biophysical properties of their external layers are still not clear.

We cultivated three cyanobacterial strains, Nostoc sp. FACHB‐2009, Dolichospermum sp. FACHB‐82 and Microcystis sp. FACHB‐3296, which are embedded in three typical types of external layers—sheath, capsule and slime, respectively––and each grown at three different temperatures (10°C, 25°C and 35°C).

The results showed that varying the temperature significantly changed the physicochemical properties of the external layers. High temperature conditions promoted increases in colony sizes compared to the control, with the external layers becoming thicker, looser and more adhesive, whereas cell sizes did not significantly change. Additionally, the expression patterns of related genes varied with temperature; it represents several temp dependent genes related to synthesis of nucleotide sugars were upregulated at high temperature but downregulated at low temperature.

As the external layers are wrapped outside cells, we assumed a “spherical shell heat conduction model”. Through that, we inferred that the presence of external layers influenced heat transfer in the cyanobacteria, thereby playing a role in stabilising cell activity at various temperatures.

Transcriptome tests showed that the use of intracellularly stored nucleotide sugars for external layer synthesis was the preferred process for cyanobacteria at low temperature, whereas de novo external layer synthesis was the preferred process for cyanobacteria at high temperature.
Effect of metabolic dysfunction‐associated fatty liver disease on liver cancer risk in a population with chronic hepatitis B virus infection: A nationwide study
Authors: Yun Byungyoon , Ahn Sang Hoon , Oh Juyeon , Yoon Jin‐Ha , Kim Beom Kyung
Published: August 2022

Background

The association between metabolic dysfunction‐associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC) lacks clinical validation in at‐risk populations. We assessed this relationship among chronic hepatitis B (CHB) patients.

Methods

Data was collected from the National Health Insurance System database in South Korea. Chronic hepatitis B patients aged over 40 years receiving health examinations between 2011 and 2012 were recruited. The primary outcome was HCC. Metabolic dysfunction‐associated fatty liver disease was defined as hepatic steatosis in combination with at least one of the following: (i) overweight, (ii) diabetes, or (iii) lean/normal weight with two or more metabolic components. Multivariable Cox regression analysis was used to estimate adjusted hazard ratios (aHRs).

Results

Of 197 346 participants, 66 149 had MAFLD; 19 149, 44 475, and 2525 fulfilled diabetes (regardless of overweight), overweight alone, and lean/normal weight with two or more metabolic components, respectively. During follow‐up (median 7 years), 13 771 developed HCC. Metabolic dysfunction‐associated fatty liver disease was independently associated with increased risk of HCC, with aHR of 1.36 (p < 0.001). Propensity score matching confirmed the same phenomena, with aHR of 1.37 (p < 0.001). Furthermore, when stratified by liver cirrhosis and/or antiviral therapy, independent significances of MAFLD for HCC risk were maintained (all p < 0.001). Compared with the persistent non‐MAFLD subgroup during the entire follow‐up, diagnosis of MAFLD from at least one health examination significantly increased HCC risk with aHRs of 1.41, 1.37, and 1.14 among subgroups with persistent MAFLD, MAFLD to non‐MAFLD, and non‐MAFLD to MAFLD, respectively (all p < 0.05).

Conclusions

Metabolic dysfunction‐associated fatty liver disease consistently increases HCC risk among CHB patients. Further studies are needed to develop an effective preventive strategy through control of metabolic health.
Biblical exegesis as the soul of John Paul II’s Theology of the Body
Authors: Exegesis Biblical , Johnston Eric M.
Published: August 2022

John Paul II is often misread as more of a philosopher than a theologian. But his Theology of the Body, rightly read, is in its entirety an exercise in exegesis. By focusing on the Bible, he gives a more fully theological account of his topic, one focused on the mystery of redemption by grace, rather than on merely human efforts.
Contrasting genetic population structures in acorn weevils (Curculio spp.) in expanding forests: The effects of differences in resource‐tracking strategies
Authors: Ruiz‐Carbayo Helena , Espelta Josep Maria , Pino Joan , Hampe Arndt , Bonal Raul
Published: August 2022

Woody vegetation spread over former croplands in Europe has created new unexploited habitats for forest organisms. Their ability to colonise them and thrive depends on life‐history traits including fecundity, dormancy and dispersal ability.

The effects of these traits on species distribution, abundance and community assembly have been extensively studied in fragmented landscapes. However, their consequences for genetic diversity and connectivity in local populations remain largely unknown.

We investigated the genetic population structure and diversity of Curculio elephas and Curculio glandium (Coleoptera: Curculionidae), two sympatric acorn weevils with contrasting life‐history strategies, in a landscape with mature oak stands and plots of new expanding forests.

Using a fragment of a mitochondrial gene cytochrome oxidase subunit 1 and nuclear DNA (80 single nucleotide polymorphisms [SNPs]), we found that gene flow between populations was significantly weaker in the poor disperser C. elephas, especially in isolated new forests. However, genetic neutrality tests did show population expansion in C. elephas, which suffers frequent population bottlenecks (probably linked to extended dormancy) and is a poor coloniser of isolated new forests. However, its greater fecundity allows it to recovery quickly if the number of reproductive individuals falls. Its populations are thus larger but genetically less diverse than those of C. glandium

Within foraging guilds, the most fecund species will outcompete the others under a context of constrained dispersal. Hence, new landscapes of expanding forests represent a good opportunity for more mobile but less fecund species to colonise new habitats and so be temporarily released from competition.
A comparison of different Malaise trap types
Authors: Uhler Johannes , Haase Peter , Hoffmann Lara , Hothorn Torsten , Schmidl Jürgen , Stoll Stefan , Welti Ellen A. R. , Buse Jörn , Müller Jörg
Published: August 2022

Recent reports on insect decline have highlighted the need for long‐term data on insect communities towards identifying their trends and drivers.

With the launch of many new insect monitoring schemes to investigate insect communities over large spatial and temporal scales, Malaise traps have become one of the most important tools due to the broad spectrum of species collected and reduced capture bias through passive sampling of insects day and night. However, Malaise traps can vary in size, shape, and colour, and it is unknown how these differences affect biomass, species richness, and composition of trap catch, making it difficult to compare results between studies.

We compared five Malaise trap types (three variations of the Townes and two variations of the Bartak Malaise trap) to determine their effects on biomass and species richness as identified by metabarcoding.

Insect biomass varied by 20%–55%, not strictly following trap size but varying with trap type. Total species richness was 20%–38% higher in the three Townes trap models compared to the Bartak traps. Bartak traps captured lower richness of highly mobile taxa but increased richness of ground‐dwelling taxa. The white roofed Townes trap captured a higher richness of pollinators.

We find that biomass, total richness, and taxa group specific richness are all sensitive to Malaise trap type. Trap type should be carefully considered and aligned to match monitoring and research questions. Additionally, our estimates of trap type effects can be used to adjust results to facilitate comparisons across studies.
Case complexity of root canal treatments accepted for training in a secondary care setting assessed by three complexity grading systems: A service evaluation
Authors: Long Ruby , Dutta Arindam , Thomas Matthew B. M. , Vianna Morgana Eli
Published: August 2022

Aims

To evaluate the complexity of root canal treatments accepted for treatment by postgraduate training grades at Cardiff University Dental Hospital (CUDH) using the English Commissioning Standard for Restorative Dentistry (ECS) in comparison with the American Association of Endodontists case complexity form (AAE) and the Restorative Index of Treatment Need (RIOTN).

Methodology

Two hundred case records were evaluated using the AAE, RIOTN and ECS scoring systems. Each case received a score from minimal to high complexity (1–3). Examiners were calibrated and inter‐examiner reliability calculated using the percentage agreement. Frequency of scores were then compared.

Results

Most cases were at level 3 and assessment varied amongst the criteria used (AAE: 99.5%, RIOTN: 65.5% and ECS: 55.5%). The AAE factor ‘endodontic treatment history’ was largely responsible for differing scores when compared with the RIOTN (78%) and ECS (64%). The RIOTN factor regarding post treatment disease (‘endodontic retreatment’) was responsible for increased complexity compared with ECS in most cases (74%). The ECS factor ‘quality of root filling’ was the most common reason (85%) for an increase in complexity compared with RIOTN.

Conclusions

Within the limitations of this service evaluation, it was possible to conclude that a high proportion of cases treated by training grades at CUDH were of a high complexity level (level 3) using the three guidelines (ECS, AAE and RIOTN). These cases were appropriate for postgraduate training under various levels of supervision and substantiated by the findings reported here. The factors responsible for a large part of difference in allocation of scores amongst the systems were ‘endodontic treatment history’, ‘root canal retreatment’ and ‘quality of root filling’.
Effect of high pressure in barium disilicate glass investigated by DTA and Raman spectroscopy
Authors: Evaristo Leonardo , Silveira Rafael , Tissot Matheus , Hippler Gisele , Moulton Benjamin , Buchner Silvio
Published: August 2022

This work aimed to explore the effect of high pressures at room temperature on the vibrational modes and the thermal properties and stability of barium disilicate glass (BaO‐2SiO2) (BS2). The BS2 was prepared through the conventional melting route at atmospheric pressure. After being submitted to different pressure values (2.5 GPa, 4.0 GPa, and 7.7 GPa) and room temperature, the samples were characterized ex situ by Raman spectroscopy and differential thermal analysis. With this, it is possible to see that the pressure modifies the Raman vibrational modes of the glass, in the region associated with the Si‐O‐Si symmetrical bending modes. The Si‐O symmetrical stretching vibrational modes (Qn) remain unchanged, however there are changes on values of glass transition and decrease crystallization temperature, as well as the parameters of thermal stability of the glass.
Factors associated with eHealth use among community dwelling older adults
Authors: Choi MoonKi
Published: August 2022

Background

With the proliferation of the internet and the development of internet‐based healthcare interventions, eHealth is expected to be an effective complement to traditional healthcare services. However, without understanding the characteristics of the user population, eHealth itself can isolate older adults.

Aim

This study aims to identify the characteristics of internet use and the factors associated with eHealth use among older adults.

Methods

A secondary data analysis was conducted from a cross‐sectional descriptive study. A convenience sample of 186 community dwelling older adults was recruited at two senior welfare centres in Korea. The data collected included demographic characteristics, health related characteristics, internet use, eHealth use and eHealth literacy. Multiple linear regression was utilized to determine factors related to eHealth use.

Results

Among 186 respondents, 98 reported that they used the internet. Internet usage was associated with educational attainment, marital status, cognitive function and possession of internet‐enabled devices. The results of multiple regression analysis showed that greater eHealth usage was related to more positive perception of eHealth usability and better eHealth literacy among older adults.

Conclusion

Educational programmes for older adults should be developed to facilitate digital capability and eHealth literacy. Useful and effective online health resources that are easy to use should be also developed.
Insulin antibodies are prevalent in adults with type 1 diabetes referred for islet cell transplantation and are modified by islet transplantation and immunosuppression: an Australian experience
Authors: Hensman Callum J. , Gooley Judith L. , Januszewski Andrzej S. , Lee Melissa H. , MacIsaac Richard J. , Boston Raymond C. ,   Australian Islet Transplant Consortium, Ward Glenn M. , Jenkins Alicia J.
Published: August 2022

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody‐negative post islet cell transplantation.
Locally acquired lymphocytic choriomeningitis virus infections in South‐East Queensland: an outbreak of a pathogen rarely described in Australia
Authors: Aaron Luke , McMahon Jamie , Taylor Carmel , Pyke Alyssa T. , Brischetto Anna , Aminzadeh Zohreh , Beale Mark
Published: August 2022

Lymphocytic choriomeningitis virus (LCMV) is a zoonotic virus that can cause clinically significant illnesses in humans. Although cases of LCMV infection are well described globally, and there is evidence that the virus is present in Australian rodent populations, there has been only one case of domestically acquired LCMV infection published previously. Here, we describe a cluster of LCMV infections in South‐East Queensland identified in early 2021, and the diagnostic testing processes implemented. This identifies LCMV as an under‐recognised human pathogen in Australia.