bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic civil facility degradation prediction for rare defects under imperfect maintenance
Authors: Leu Sou-Sen , Fu Yen-Lin , Wu Pei-Lin
Published: October 2023

Purpose

This paper aims to develop a dynamic civil facility degradation prediction model to forecast the reliability performance tendency and remaining useful life under imperfect maintenance based on the inspection records and the maintenance actions.

Design/methodology/approach

A real-time hidden Markov chain (HMM) model is proposed in this paper to predict the reliability performance tendency and remaining useful life under imperfect maintenance based on rare failure events. The model assumes a Poisson arrival pattern for facility failure events occurrence. HMM is further adopted to establish the transmission probabilities among stages. Finally, the simulation inference is conducted using Particle filter (PF) to estimate the most probable model parameters. Water seals at the spillway hydraulic gate in a Taiwan's reservoir are used to examine the appropriateness of the approach.

Findings

The results of defect probabilities tendency from the real-time HMM model are highly consistent with the real defect trend pattern of civil facilities. The proposed facility degradation prediction model can provide the maintenance division with early warning of potential failure to establish a proper proactive maintenance plan, even under the condition of rare defects.

Originality/value

This model is a new method of civil facility degradation prediction under imperfect maintenance, even with rare failure events. It overcomes several limitations of classical failure pattern prediction approaches and can reliably simulate the occurrence of rare defects under imperfect maintenance and the effect of inspection reliability caused by human error. Based on the degradation trend pattern prediction, effective maintenance management plans can be practically implemented to minimize the frequency of the occurrence and the consequence of civil facility failures.
Multiparameter least‐squares reverse time migration using the viscoacoustic‐wave equation
Authors: Nogueira Peterson , Porsani Milton
Published: October 2023

In viscoacoustic least‐squares reverse time migration methods, the reflectivity image associated with the Q factor is negligible, inverting only the velocity (v) parameter or v‐related variables such as squared slowness or bulk modulus. However, the Q factor influences the amplitude and phase of the seismic data, especially in basins containing gas reservoirs or storing . Therefore, the Q factor and its associated parameters must be considered in the context of viscoacoustic least‐squares reverse time migration. Thus, we propose a multiparameter viscoacoustic least‐squares reverse time migration procedure, which obtains the inverse of bulk modulus (κ) and the Q magnitude (τ) simultaneously. We derive and implement the multiparameter forward and adjoint pair Born operators and the gradient formulas concerning κ and τ parameters. Then, we apply these derivations in our proposed multiparameter approach, which can produce images with better balanced amplitudes and more resolution than conventional reverse time migration images.
In need of age‐appropriate cardiac models: Impact of cell age on extracellular matrix therapy outcomes
Authors: Ozcebe S. Gulberk , Zorlutuna Pinar
Published: October 2023

Aging is the main risk factor for cardiovascular disease (CVD). As the world's population ages rapidly and CVD rates rise, there is a growing need for physiologically relevant models of aging hearts to better understand cardiac aging. Translational research relies heavily on young animal models; however, these models correspond to early ages in human life, therefore cannot fully capture the pathophysiology of age‐related CVD. Here, we first investigated the transcriptomic and proteomic changes that occur with human cardiac aging. We then chronologically aged human induced pluripotent stem cell‐derived cardiomyocytes (iCMs) and showed that 14‐month‐old iCMs exhibited a similar aging profile to the human CMs and recapitulated age‐related disease hallmarks. Using aged iCMs, we studied the effect of cell age on the young extracellular matrix (ECM) therapy, an emerging approach for myocardial infarction (MI) treatment and prevention. Young ECM decreased oxidative stress, improved survival, and post‐MI beating in aged iCMs. In the absence of stress, young ECM improved beating and reversed aging‐associated expressions in 3‐month‐old iCMs while causing the opposite effect on 14‐month‐old iCMs. The same young ECM treatment surprisingly increased SASP and impaired beating in advanced aged iCMs. Overall, we showed that young ECM therapy had a positive effect on post‐MI recovery; however, cell age was determinant in the treatment outcomes without any stress conditions. Therefore, “one‐size‐fits‐all” approaches to ECM treatments fail, and cardiac tissue engineered models with age‐matched human iCMs are valuable in translational basic research for determining the appropriate treatment, particularly for the elderly.
Differential sperm histone retention in normozoospermic ejaculates of infertile men negatively affects sperm functional competence and embryo quality
Authors: Pandya Riddhi Kirit , Jijo Ameya , Cheredath Aswathi , Uppangala Shubhashree , Salian Sujith Raj , Lakshmi Vani R , Kumar Pratap , Kalthur Guruprasad , Gupta Sanjay , Adiga Satish Kumar
Published: October 2023

Background

The unique epigenetic architecture that sperm cells acquire during spermiogenesis by retaining <15% of either canonical or variant histone proteins in their genome is essential for normal embryogenesis. Whilst heterogeneous levels of retained histones are found in morphologically normal spermatozoa, their effect on reproductive outcomes is not fully understood.

Methods

Processed spermatozoa (n = 62) were tested for DNA integrity by sperm chromatin dispersion assay, and retained histones were extracted and subjected to dot‐blot analysis. The impact of retained histone modifications in normozoospermic patients on sperm functional characteristics, embryo quality, metabolic signature in embryo spent culture medium and pregnancy outcome was studied.

Results

Dot‐blot analysis showed heterogeneous levels of retained histones in the genome of normozoospermic ejaculates. Post‐wash sperm yield was affected by an increase in H3K27Me3 and H4K20Me3 levels in the sperm chromatin (p < 0.05). Also, spermatozoa with higher histone H3 retention had increased DNA damage (p < 0.05). Spermatozoa from these cohorts, when injected into donor oocytes, correlated to a significant decrease in the fertilisation rate with an increase in sperm histone H3 (p < 0.05) and H3K27Me3 (p < 0.01). An increase in histone H3 negatively affected embryo quality (p < 0.01) and clinical pregnancy outcome post‐embryo transfer (p < 0.05). On the other hand, spent culture medium metabolites assessed by high‐resolution (800 MHz) nuclear magnetic resonance showed an increased intensity of the amino acid methionine in the non‐pregnant group than in the pregnant group (p < 0.05) and a negative correlation with sperm histone H3 in the pregnant group (p < 0.05).

Discussion and conclusion

Histone retention in spermatozoa can be one of the factors behind the development of idiopathic male infertility. Such spermatozoa may influence embryonic behaviour and thereby affect the success rate of assisted reproductive technology procedures. These results, although descriptive in nature, warrant further research to address the underlying mechanisms behind these clinically important observations.
Can 24 h of ambulatory ECG be used to triage patients to extended monitoring?
Authors: Johnson Linda S. , Måneheim Alexandra , Slusarczyk Magdalena , Grotek Agnieszka , Witkowska Olga , Bacevicius Justinas , Sörnmo Leif , Dziubinski Marek , Bhavnani Sanjeev , Healey Jeffrey S. , Engström Gunnar
Published: October 2023

Background

Access to long‐term ambulatory recording to detect atrial fibrillation (AF) is limited for economical and practical reasons. We aimed to determine whether 24 h ECG (24hECG) data can predict AF detection on extended cardiac monitoring.

Methods

We included all US patients from 2020, aged 17–100 years, who were monitored for 2–30 days using the PocketECG device (MEDICALgorithmics), without AF ≥30 s on the first day (n = 18,220, mean age 64.4 years, 42.4% male). The population was randomly split into equal training and testing datasets. A Lasso model was used to predict AF episodes ≥30 s occurring on days 2–30.

Results

The final model included maximum heart rate, number of premature atrial complexes (PACs), fastest rate during PAC couplets and triplets, fastest rate during premature ventricular couplets and number of ventricular tachycardia runs ≥4 beats, and had good discrimination (ROC statistic 0.7497, 95% CI 0.7336–0.7659) in the testing dataset. Inclusion of age and sex did not improve discrimination. A model based only on age and sex had substantially poorer discrimination, ROC statistic 0.6542 (95% CI 0.6364–0.6720). The prevalence of observed AF in the testing dataset increased by quintile of predicted risk: 0.4% in Q1, 2.7% in Q2, 6.2% in Q3, 11.4% in Q4, and 15.9% in Q5. In Q1, the negative predictive value for AF was 99.6%.

Conclusion

By using 24hECG data, long‐term monitoring for AF can safely be avoided in 20% of an unselected patient population whereas an overall risk of 9% in the remaining 80% of the population warrants repeated or extended monitoring.
The prophylactic value of TNF‐α inhibitors against retinal cell apoptosis and optic nerve axon loss after corneal surgery or trauma
Authors: Paschalis Eleftherios I. , Zhou Chengxin , Sharma Jyoti , Dohlman Thomas H. , Kim Sarah , Lei Fengyang , Chodosh James , Vavvas Demetrios , Urtti Arto , Papaliodis George , Dohlman Claes H.
Published: October 2023

Background and Purpose

Late secondary glaucoma is an often‐severe complication after acute events like anterior segment surgery, trauma and infection. TNF‐α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti‐TNF‐α antibodies are in animals very effective in protecting the retinal cells and the optic nerve—and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF‐α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration.

Methods

For drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub‐set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified.

Results

Subconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50% axon loss as compared to 8% in the adalimumab treatment group.

Conclusions

Subconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long‐term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti‐TNF‐α biologics to reduce inflammation and future secondary glaucoma.
LGBTQ+ new and expectant parents' experiences of perinatal services during the UK's first COVID‐19 lockdown
Authors: Greenfield Mari , Darwin Zoe
Published: October 2023

Background

COVID‐19 created specific challenges for new and expectant parents and perinatal services. Services changed rapidly in the United Kingdom (UK), including the withdrawal of home birth services, birth center closures, and restrictions on the number of birth partners allowed in the birth room. The purpose of this study was to examine how these changes affected the experiences of LGBTQ+ parents in the UK.

Methods

An online survey was conducted in April 2020 to provide real‐time data capture of new and expectant families' experiences. It was open to those in the third trimester, or to those who had given birth since the beginning of the first UK lockdown period, and their partners. The survey asked open‐ended questions about perinatal experiences. Demographic data were also collected, including sexual orientation and gender. Responses were collected from 1754 participants, including 76 who self‐identified as LGBTQ+.

Results

Thematic analysis identified that LGBTQ+ new and expectant parents faced similar issues to cisgendered, heterosexual expectant parents, though additional concerns were also noted relating to support and recognition. Heterocentric policies negatively affect lesbian families. Non‐birthing co‐mothers feared invalidation as parents. Sexual minority pregnant women were more likely than heterosexual pregnant women to consider additional birth supporters and to consider freebirthing.

Discussion

Service changes introduced in the pandemic were cisheteronormative, creating additional challenges for LGBTQ+ new and expectant parents and compounding existing inequalities. When planning, changing, or evaluating perinatal services, specific consideration is needed to include birthing parents who are not mothers and mothers who did not give birth. If appropriate care is not available, consequences may include impaired perinatal wellbeing and restricted birth choices. Including sexual orientation and gender in data collection enables different perspectives to be considered.
Natural history of blood pressure in sickle cell disease pregnancy
Authors: Early Macy L. , Luo Amy , Solow Marissa , Matusiak Kristine , Eke Ahizechukwu C. , Shehata Nadine , August Phyllis , Kuo Kevin H. M. , Lanzkron Sophie , Malinowski Ann Kinga , Pecker Lydia H.
Published: October 2023

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD‐related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non‐SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSβ0 group than in the non‐SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSβ0 group and non‐SCD controls, whereas the mean SBP and DBP in the HbSC/HbSβ+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSβ0.
Exploring dual effects of dinutuximab beta on cell death and proliferation of insulinoma
Authors: Karatug Kacar Ayse
Published: October 2023

Insulinoma INS‐1 cells are pancreatic beta cell tumors. Dinutuximab beta (DB) is a monoclonal antibody used in the treatment of neuroblastoma. The aim of this study is to investigate the effects of DB on pancreatic beta cell tumors at the molecular level. DB (Qarziba®) was available from EUSA Pharma. Streptozotocin (STZ) was used induce to cell cytotoxicity. DB was applied to the cells before or after the STZ application. KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were analyzed by q‐RT‐PCR, and protein levels were analyzed by Western blotting. Analysis of glucose‐stimulated insulin secretion was performed. Ca+2 and CA19‐9 levels were determined by the ELISA kit. PERK, CHOP, HSP90, p‐c‐Jun, p‐Atf2, and p‐Elk1 protein levels were analyzed by simple WES. Decreased KCND3, KCNK1, and PTHrP protein levels and increased KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were observed with DB applied after STZ application. Cell dysfunction was detected with DB applied before and after STZ application. Ca19‐9 and Ca+2 levels were increased with DB applied after STZ application. PERK, CHOP, and p‐Elk1 levels decreased, while HSP90 levels increased with DB applied after STZ application. CHOP, p‐Akt‐2, and p‐c‐Jun levels increased in the DB group. As a result, INS‐1 cells go to cell death via the ERK signaling pathway without ER stress and release insulin with the decrease of K+ channels and an increase in Ca+2 levels with DB applied after STZ application. Moreover, the cells proliferate via JNK signaling with DB application. DB holds promise for the treatment of insulinoma. The study should be supported by in vivo studies.
LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes
Authors: Li Yuqian , Zhang Qiang , Tan Qing , Sha Xuan , Gao Yang , Hua Rong , Zhou Ping , Wei Zhaolian , He Xiaojin , Cao Yunxia , Li Tao , Wu Huan
Published: October 2023

Asthenozoospermia (AZS) is the primary cause of infertility in males. The radial spoke (RS) is an axonemal structure, connecting the peripheral doublet microtubules with the central pair of microtubules. This T‐shaped multiprotein complex functions as a mechanochemical sensor to promote sperm motility. LRRC23 is a novel subunit of the RS complex that is necessary for flagellar assembly and movement in mice. However, the importance of LRRC23 in modulating RS formation in humans remains unclear. Here, we identified a homozygous nonsense mutation in LRRC23 (c.376C>T:p. Arg126X) in an infertile AZS patient whose parents were consanguineous. We verified the adversity of this novel mutation because of its ability to disrupt LRRC23 synthesis and impair RSs integrity. Furthermore, we demonstrated an interaction between LRRC23 and RSPH3 in vitro, indicating that LCCR23 is associated with RS in humans. Meanwhile, the LRRC23‐mutant patient had a good prognosis following intracytoplasmic sperm injection. This study provides strong preliminary evidence that LRRC23 defects are potential causative factors of AZS in humans, which expands our knowledge for improved genetic counseling and better reproductive recommendations for patients with AZS.
Comparison of patient‐centered outcomes measures between low‐speed drilling without irrigation and high‐speed drilling with irrigation: A randomized clinical trial
Authors: Bernabeu‐Mira Juan Carlos , Peñarrocha‐Diago Miguel , Peñarrocha‐Diago María , Romero‐Gavilán Francisco , Camacho‐Alonso Fabio , Peñarrocha‐Oltra David
Published: October 2023

Objective

To compare patient satisfaction during surgery, postoperative pain and inflammation and quality of life between high‐speed drilling with irrigation and low‐speed drilling without irrigation for implant bed preparation.

Materials and Methods

Sixty‐six posterior single edentulous patients were included in a randomized controlled clinical trial. Implant beds were created using high‐speed drilling with irrigation (control group) or low‐speed drilling without irrigation (test group). Patient satisfaction during surgery (in relation to drilling‐time perception, vibration, pressure, noise, comfort, and drowning sensation) and postoperative pain and inflammation were evaluated using a 100‐mm visual analogue scale (VAS)‐based questionnaire. Quality of life was analyzed with a Likert scale (in relation to mouth opening, chewing, speaking, sleeping, daily routine, and job). The follow‐up period was 7 days.

Results

Patient satisfaction in relation to drilling‐time perception, vibration, pressure, and noise did not show statistically significant differences (p > .05). The highest scores of drowning sensation (p < .05) were correlated (moderate correlation (r = .57)) with lowest scores of comfort (p < .005). Both postoperative pain and inflammation means were significantly higher in the control group than in the test group. No significant differences in quality of life were observed during the postoperative period (p > .05).

Conclusion

Low‐speed drilling without irrigation for single implant site preparation was more comfortable for patients than high‐speed drilling with irrigation, due to the correlation between important drowning sensation and low perceived comfort. Postoperative pain and inflammation were lower for low‐speed drilling without irrigation. Further studies are needed to validate or refute these results.
Natural language processing for identification of refractory status epilepticus in children
Authors: Chafjiri Fatemeh Mohammad Alizadeh , Reece Latania , Voke Lillian , Landschaft Assaf , Clark Justice , Kimia Amir A. , Loddenkemper Tobias
Published: October 2023

Objective

Pediatric status epilepticus is one of the most frequent pediatric emergencies, with high mortality and morbidity. Utilizing electronic health records (EHRs) permits analysis of care approaches and disease outcomes at a lower cost than prospective research. However, reviewing EHR manually is time intensive. We aimed to compare refractory status epilepticus (rSE) cases identified by human EHR review with a natural language processing (NLP)‐assisted rSE screen followed by a manual review.

Methods

We used the NLP screening tool Document Review Tool (DrT) to generate regular expressions, trained a bag‐of‐words NLP classifier on EHRs from 2017 to 2019, and then tested our algorithm on data from February to December 2012. We compared results from manual review to NLP‐assisted search followed by manual review.

Results

Our algorithm identified 1528 notes in the test set. After removing notes pertaining to the same event by DrT, the user reviewed a total number of 400 notes to find patients with rSE. Within these 400 notes, we identified 31 rSE cases, including 12 new cases not found in manual review, and 19 of the 20 previously identified cases. The NLP‐assisted model found 31 of 32 cases, with a sensitivity of 96.88% (95% CI = 82%–99.84%), whereas manual review identified 20 of 32 cases, with a sensitivity of 62.5% (95% CI = 43.75%–78.34%).

Significance

DrT provided a highly sensitive model compared to human review and an increase in patient identification through EHRs. The use of DrT is a suitable application of NLP for identifying patients with a history of recent rSE, which ultimately contributes to the implementation of monitoring techniques and treatments in near real time.
Seasonally variable and sex‐specific motivation for cooperative resource defence in a duetting songbird—The Chubb's cisticola
Authors: Budka Michał , Kokociński Patryk , Osiejuk Tomasz Stanisław
Published: October 2023

Duets are one of the most complex forms of acoustic displays, involving two individuals vocalising in a coordinated way to defend resources cooperatively. However, motivation to defend resources may be sex specific and variable in time and space, which should be reflected in the changes in duet singing behaviour. We experimentally examined whether the motivation to defend resources is sex specific and seasonally variable in an Afrotropical, sedentary songbird living in pairs or small groups—the Chubb's cisticola. We broadcasted songs of males, females and duets in a random order, both at the beginning and the end of the breeding season. We quantified the birds' responses from the perspective of the entire group as well as its individual members. We found cooperative responses to each type of intruder, with the birds flying and singing. Groups consisting of two to four individuals responded significantly more strongly towards intrusions by females than pairs, and at the beginning than at the end of breeding season. Solo syllables comprised less than 4% of all recorded syllables, and in most cases were sung within a song also containing duet and chorus syllables (only 12 from 1773 songs analysed were solo songs). Males sang solo syllables more often than females (83% vs. 17% of all solo syllables) and did it significantly more often towards intruding females than males or pairs. The number of solo syllables sung by females was independent of treatment and season. Together, our results suggests that Chubb's cisticola uses duets to cooperatively defend resources located within its territory, but the intensity of reaction is sex specific and seasonally variable. We suggest that defended resources could be mates, group stability or reproductive effort. Looking at the function of duets from the perspective of the group and its particular members, various stages of the season and different resources defended by birds allow for a better understanding of cooperative singing.
Explaining Ukraine's resilience to Russia's invasion: The role of local governance
Authors: Rabinovych Maryna , Brik Tymofii , Darkovich Andrii , Savisko Myroslava , Hatsko Valentyn , Tytiuk Serhii , Piddubnyi Igor
Published: October 2023

Resilience of local communities (territorial hromadas) is an increasingly salient matter in the academic and policy debate on the factors which have determined Ukraine's resilience to Russia's 2022 invasion. Building on existing literature on institutional resilience and its predictors, this article explains the ability of Ukrainian self‐governed municipalities to withstand the threats to institutional stability stemming from the invasion. First, it uses an exploratory qualitative design to operationalize the concept of resilience and its predictors with an account of varying experiences of Ukrainian hromadas during the full‐scale invasion (e.g., hromadas near the frontline and in the rear). Next, it presents data from open sources and the results of a regression analysis to test the impact of various groups of predictors on hromadas' resilience to the full‐scale invasion. Our models show a significant relationship between hromadas' resilience and geographical, politico‐administrative and economic predictors influenced by the outcomes of the decentralization reform conducted in Ukraine since 2014.
Why do students pursue a doctorate in the era of the ‘PhD crisis’? Evidence from Taiwan
Authors: Horta Hugo , Li Huan , Chan Sheng‐Ju
Published: October 2023

Drawing on interviews with nine PhD students and twelve PhD graduates from a research university in Taiwan, this paper explores students' motivational profiles for pursuing a PhD at a time when that degree is increasingly decoupled from academic employment. Using self‐determination theory as a conceptual lens, the paper identifies common enrolment motivations in the PhD crisis era. Amidst the doctoral enrolment crisis in Taiwan, where the traditional employment path for PhD graduates (i.e., academia) is more of a mirage than a reality, the motivations of students to pursue a PhD do not differ much from those found in the literature concerning the era of PhD expansion. Two typical motivational profiles are predominant, one dominated by the accumulation of career advantages and the other by the search for personal growth. The findings show that the first profile tends to be on the minds of most students. The second profile tends to be adopted by those who have few career concerns or those who have a greater need for self‐improvement. We also find that these motivations have unique nuances, meanings and consequences for universities and doctoral education in the PhD crisis era.
Global survey of endodontic practice and adoption of newer technologies
Authors: Cheung Monique Charlene , Peters Ove Andreas , Parashos Peter
Published: October 2023

Aim

To investigate current endodontic practices, adoption of technologies and continuing education attendance within specialist endodontic practice globally and to identify geographic trends.

Methodology

A web‐based survey of endodontic association members in Australia, Britain, Canada, Italy, New Zealand and the USA on routine treatment preferences, armamentarium and education attendance was conducted. Chi‐squared, independent sample t‐tests, Cochran's Q test and McNemar's test were performed.

Results

The survey was completed by 543 endodontists or endodontic post‐graduate students. Almost all respondents used the dental operating microscope (DOM, 91.3%), engine‐driven nickel–titanium instruments (NiTi, 97.6%), electronic apex locators (EAL, 93.0%), cone‐beam computed tomography (CBCT, 91.2%) and calcium silicate‐based materials (CSBMs, 93.7%). Dental dam was always used by 99.1%. Over half used irrigation adjuncts (81.8%), warm vertical compaction (74.6%) and heat‐treated NiTi (60.2%). Geographic comparison between AP (Asia–Pacific, n = 78), AM (Americas, n = 402) and EM (Europe and Middle East, n = 63) was performed. AM and EM preferred single‐visit treatment more (p < .001) and used higher sodium hypochlorite concentrations than AP. AM had more access to CBCT in the workplace (86.6%) than AP (65.4%, p < .001) and used CBCT for routine preoperative assessment (39.6%) more than EM (7.3%, p < .001). Almost all of EM used irrigation adjuncts (95.2%), more than AM (78.1%, p = .001). AP used steroid/antibiotic medicaments most (p < .001) and had the highest attendance at continuing education programmes.

Conclusion

Several endodontic‐specific armamentaria have reached almost complete adoption within global specialist endodontic practice, whilst the continued uptake of newer technologies should be followed over time. Some practising philosophies varied significantly across different geographic regions.
β‐ADRENOCEPTOR AGONIST ACTIVITY OF LABETOLOL ON THE ISOLATED UTERUS OF THE RAT
Authors: CAREY BERNADETTE , WHALLEY E.T.
Published: October 2023

Isoprenaline produced dose‐dependent reductions of responses of the isolated uterus of the rat produced by an EC80 of acetylcholine. Propranolol acted as a competitive antagonist to isoprenaline. Labetolol also reduced the acetylcholine‐induced contractions but was much less potent than isoprenaline. The greatest reduction was smaller than that produced by isoprenaline. Propranolol antagonized the lower doses of labetolol. It is suggested that labetolol possesses partial agonist activity at the β‐adrenoceptors of the rat isolated uterus.
A COMPARISON OF THE ANTI‐ANAPHYLACTIC ACTIVITIES OF SALBUTAMOL AND DISODIUM CROMOGLYCATE IN THE RAT, THE RAT MAST CELL AND IN HUMAN LUNG TISSUE
Authors: BUTCHERS P.R. , FULLARTON J.R. , SKIDMORE I.F. , THOMPSON L.E. , VARDEY C.J. , WHEELDON A.
Published: October 2023

Salbutamol and disodium cromoglycate were compared for anti‐anaphylactic activity against passive anaphylaxis in rat skin and peritoneum in vivo and in rat mast cells and human lung fragments in vitro.

Salbutamol administered intravenously to rats inhibited cutaneous anaphylaxis, but also inhibited cutaneous responses to histamine and 5‐hydroxytryptamine. Salbutamol administered intraperitoneally inhibited the release of slow reacting substance of anaphylaxis (SRS‐A) but not the release of histamine in the peritoneum. It was a very weak inhibitor of histamine release from rat mast cells in vitro.

Disodium cromoglycate administered intravenously to rats inhibited cutaneous anaphylaxis. Disodium cromoglycate administered intraperitoneally to rats inhibited the release of histamine and, to a lesser extent, SRS‐A in the peritoneum. It was an effective but short‐acting inhibitor of histamine release from rat mast cells in vitro.

Salbutamol was a potent inhibitor of the anaphylactic release of histamine and SRS‐A from fragments of human lung.

Disodium cromoglycate was a weak inhibitor of the anaphylactic release of histamine and SRS‐A from fragments of human lung. The inhibition was variable and not dose‐related.

The concentration of salbutamol required to inhibit anaphylaxis in human lung is of the same order as that required to relax human bronchial muscle. It is suggested that salbutamol may be more effective in allergic asthma if given in a prophylactic regimen.
THE EFFECTS OF CALCIUM AND MAGNESIUM IONS, TEMPERATURE AND REPETITIVE STIMULATION ON INHIBITORY JUNCTIONAL TRANSMISSION IN SMOOTH MUSCLE OF GUINEA‐PIG SMALL INTESTINE
Authors: LANG RICHARD J.
Published: October 2023

The effects of calcium and magnesium ions and temperature on the peak amplitude of the nonadrenergic, noncholinergic inhibitory junction potential, evoked by a single stimulus, or paired transmural stimuli, were examined in the circular muscle of guinea‐pig small intestine.

The peak amplitude of the inhibitory junction potential (i.j.p.) could be decreased by lowering the external concentration of calcium or by raising the external magnesium concentration (at 25°C).

At 25°C, the second of a pair of i.j.ps was larger than the first at short intervals (<0.2 s), but smaller at larger intervals (0.2 to 20 s). Enhancement of the second (test) response decayed exponentially with a time constant of 87 ms. Depression of the test i.j.p. was maximal at 0.4 s and then recovered exponentially with a time constant of 11 s.

In low calcium or high magnesium solution, depression of the test i.j.p. decreased without any change in the rate of recovery from depression.

Despite the slow rate of recovery from depression after a single conditioning response, transmitter output could be maintained during low‐frequency repetitive stimulation.

The peak amplitude of the i.j.p. increased as the temperature was raised to 35°C (Q10 = 1.5).

In contrast to the neuromuscular junction, the depression of the second of a pair of i.j.ps decreased as the temperature was raised. At 35°C the test i.j.p. was larger than the conditioning i.j.p. for most stimulus intervals (1 to 20 s).

The results suggest that the rate of replenishment of the store of inhibitory transmitter is sensitive to both temperature and repetitive stimulation.
ANALYSIS OF ANOMALOUS pKB VALUES FOR METIAMIDE AND ATROPINE IN THE ISOLATED STOMACH OF THE MOUSE
Authors: ANGUS J.A. , BLACK J.W.
Published: October 2023

In the isolated, lumen‐perfused, stomach preparation of the mouse, metiamide was found by kinetic analysis to behave like a simple competitive antagonist of histamine‐stimulated acid secretion. However, the pKB estimate of 5.08 was significantly lower than that found in guinea‐pig atrium (6.0) or rat uterus (6.1) suggesting that H2‐receptors might not be homogeneous.

A similar analysis showed that atropine also behaved like a simple competitive antagonist of bethanechol‐stimulated acid secretion and the estimated pKB (7.65) was significantly lower than the standard estimate of this parameter in guinea‐pig ileum (9.0). Either the muscarinic cholinoceptors in mouse stomach were also anomalous or the preparation was introducing a systematic error. Lumen perfusion might distort this type of kinetic analysis by allowing steady‐state conditions but not true equilibrium to develop at the receptor compartment due to loss of antagonist into the gastric secretion. Drug interactions at receptors in the muscle layers of the stomach would be expected to be much less sensitive to this error.

When the atropine‐bethanechol interaction was measured on the contraction of the isolated, lumen‐perfused, stomach of the mouse the necessary conditions for simple competition were not met even though the sensitivity to atropine was obviously increased. The criteria for the expected simple competition were being obscured by events at low antagonist concentrations. Alterations in agonist or antagonist concentrations could be more or less eliminated so that physiological antagonism, perhaps by release of 5‐hydroxytryptamine, was considered. This was supported, to some extent, by finding that, when stomachs from animals pretreated with reserpine were used, the kinetic analysis was normalized and gave a pKB of 8.99. Apparently, the muscarinic receptors in mouse stomach are homogeneous with those in other tissues.

Therefore, we conclude that our results no more point to heterogeneity among histamine receptors than they point to differences in muscarinic cholinoceptors because this type of kinetic analysis can be readily distorted by special features of the measuring system.
THE EFFECTS OF NEUROLEPTICS WITH CENTRAL DOPAMINE AND NORADRENALINE RECEPTOR BLOCKING PROPERTIES IN THE l‐DOPA AND (+)‐ AMPHETAMINE‐INDUCED WAKING EEG IN THE RAT
Authors: MONTI J.M.
Published: October 2023

A study was carried out in rats (prepared for chronic sleep recording) of the effects of pretreatment with neuroleptics differing in their relative antinoradrenaline and antidopamine receptor potencies, on the l‐DOPA and (+)‐amphetamine‐induced increase in waking EEG.

Haloperidol (0.6 mg/kg), which blocks central dopamine and noradrenaline (NA) receptors, reversed the EEG desynchronizing actions of l‐DOPA and (+)‐amphetamine.

Low doses of pimozide (0.4 to 0.8 mg/kg) which block dopamine receptors exclusively, were not able to modify the pharmacologically induced disruption of the sleep‐awake cycle. However, at 1 mg/kg, a dose which also produces blockade of NA receptors, pimozide counteracted the increase in waking elicited by (+)‐amphetamine.

Spiroperidol (1 to 4 mg/kg) which is devoided of NA receptor blocking properties, failed to reverse the l‐DOPA or (+)‐amphetamine‐induced arousal.

Our results suggest that the increased waking time observed after the catecholamine agonists is related to an increased availability of NA rather than dopamine.
MUSCIMOL ANTAGONISM OF MORPHINE ANALGESIA IN RATS
Authors: MANTEGAZZA PAOLO , TAMMISO REMIGIO , VICENTINI LUCIA , ZAMBOTTI FERNANDA , ZONTA NERINA
Published: October 2023

Muscimol, a γ‐aminobutyric acid (GABA) receptor agonist, when injected intraventricularly antagonizes the antinociceptive effect of morphine given either subcutaneously or intraventricularly. The antagonistic effect of muscimol on morphine analgesia appears to be linearly related.

This finding provides support for the view that a GABA‐ergic system is involved in morphine analgesia.
EFFECTS OF THE OESTROUS CYCLE AND EXOGENOUS OVARIAN STEROIDS ON METABOLISM OF β‐PHENYLETHYLAMINE IN RAT LUNG
Authors: BAKHLE Y.S. , BEN‐HARARI R.R.
Published: October 2023

Metabolism of [14C]‐β‐phenylethylamine (PEN), a substrate for monoamine oxidase‐B (MAO‐B), was measured in lung homogenates and in perfused lungs during the 4 day oestrous cycle of the rat.

Metabolism in vitro was high during met‐oestrus and di‐oestrus and low during pro‐oestrus and oestrus; this variation in activity correlated with changes in Vmax of the enzyme without changes in Km.

PEN metabolism in lung homogenates was also altered by treatment of rats with 17β‐oestradiol but not by progesterone treatment.

Metabolism of [14C]‐PEN in perfused lungs was the same during either pro‐oestrus or met‐oestrus. Uptake of [14C]‐PEN in perfused lung measured directly was also the same at these two stages.

These results demonstrate that in lungs MAO‐B activity was affected by endogenous changes in steroid level but that such changes in enzymic activity were not reflected in the metabolic properties of whole lung.
RELAXATION OF ISOLATED TAENIA COLI OF GUINEA‐PIG BY ENANTIOMERS OF 2‐AZIDO ANALOGUES OF ADENOSINE AND ADENINE NUCLEOTIDES
Authors: CUSACK N.J. , PLANKER M.
Published: October 2023

2‐Azido photoaffinity analogues of adenosine 5′‐triphosphate (ATP), adenosine 5′‐diphosphate (ADP), adenosine 5′‐monophosphate (AMP), and adenosine have been synthesized and tested on guinea‐pig taenia coli.

2‐Azido‐ATP and 2‐azido‐ADP were approximately 20 times more potent than ATP as relaxants of taenia coli, and required prolonged washout times before recovery of the muscle.

2‐Azido‐AMP and 2‐azidoadenosine were 2 to 12 times more potent than ATP, but took much longer (up to 100 s) to reach maximal relaxation. This behaviour is different from that of AMP and adenosine which were much less potent than ATP.

l‐Enantiomers of adenosine and adenine nucleotides were also tested. l‐ATP and l‐ADP were 3 to 6 times less potent than ATP and ADP, and l‐AMP and l‐adenosine were inactive. 2‐Azido‐l‐ATP and 2‐azido‐l‐ADP were approximately 120 times less potent than 2‐Azido‐ATP and 6 times less potent than ATP as relaxants of taenia coli. 2‐Azido‐l‐AMP and 2‐azido‐l‐adenosine were almost inactive.

2‐Azido derivatives are photolysed by u.v. irradiation to reactive intermediates. 2‐Azido‐ATP and 2‐azidoadenosine might be suitable photoaffinity ligands for labelling putative P2 and PI purine receptors respectively. 2‐Azido‐l‐ATP and 2‐azido‐l‐adenosine could be useful controls for nonspecific labelling.
Contribution of cuproptosis and Cu metabolism‐associated genes to chronic obstructive pulmonary disease
Authors: Qi Wenchuan , Liu Lu , Zeng Qian , Zhou Ziyang , Chen Daohong , He Bin , Gong Siyao , Gao Lei , Wang Xiao , Xiong Jian , Cai Dingjun , Yu Shuguang , Zhao Ling
Published: October 2023

Airway epithelial cell injury plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, a novel form of Cu‐induced programmed cell death known as cuproptosis has not yet been thoroughly investigated in the context of COPD. Clinical reports have suggested that high copper exposure may increase the risk of COPD. In this study, we aimed to determine the expression and potential functions of cuproptosis‐related genes and genes associated with copper metabolism in COPD. We initially identified 52 copper metabolism‐related genes based on a review of the literature. Subsequently, we calculated the expression levels of these genes using data from four GEO datasets. To gain insights into the activated signalling pathways and underlying mechanisms in COPD patients, we conducted Gene Ontology (GO) and KEGG pathway analyses, examined protein–protein interactions, and performed weighted correlation network analysis. Our findings revealed that 18 key copper metabolism‐related genes, including 5 cuproptosis‐related genes, were significantly enriched in signalling pathways and biological processes associated with the development of COPD. Further analysis of clinical data and animal experiments confirmed the high expression of certain cuproptosis key regulators, such as DLD and CDKN2A, in both healthy smokers and COPD smokers. Additionally, these regulators exhibited abnormal expression in a COPD rat model. Notably, copper content was found to be elevated in the lung tissues of COPD rats, suggesting its potential involvement in cuproptosis. These findings provide an experimental foundation for further research into the role of cuproptosis in COPD. Targeting copper metabolism‐related genes may represent an effective approach for the treatment of COPD.
Recurrent emergency department visits among persons living with dementia: Bending the curve
Authors: Shah Manish N. , Hwang Ula
Published: October 2023

This editorial comments on the article by Jones et al. in this issue.
Novel genomic prognostic biomarkers for dogs with cancer
Authors: Chon Esther , Sakthikumar Sharadha , Tang Min , Hamilton Matthew J. , Vaughan Andrew , Smith Ashley , Sommer Breann , Robat Cecilia , Manley Christina , Mullin Christine , Ohashi Emi , Manor Emily , Custis James , Intile Joanne , Shiu Kai Biu , Parshley Lisa , Bergman Noelle , Sheppard‐Olivares Sabina , Hafeman Scott , Wright Zachary , Haworth David , Hendricks William , Wang Guannan
Published: October 2023

Background

Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery.

Hypothesis

Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value.

Animals

A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available.

Methods

Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression.

Results

Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82,P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05).

Conclusion and Clinical Importance

We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer.
Rainbow in Gethen: Queer utopia and community collectivism in Ursula K. Le Guin's “Coming of Age in Karhide”
Authors: Paul Aleena Achamma , Krishna S. Swathi
Published: October 2023

This essay seeks to examine how Ursula K. Le Guin's science fiction short story “Coming of Age in Karhide” (1995) set in the planet of Gethen in the fictional Hainish universe envisions a political utopia of sequentially hermaphroditic humans to offer a succinct critique of traditional gender roles and conventional sexual customs while celebrating the potential of collective responsibility. While maintaining that the recent scholarship on queer utopias in SF has largely geared toward posthumanist articulations, the present essay argues that Ursula K. Le Guin who laid the genre conventions of queer utopic narratives unabashedly places her short story “Coming of Age in Karhide” within the ideals of humanism by upholding community as a unifying entity, at the same time carefully avoiding the pitfalls of anthropocentrism. Drawing from queer theorists and social scientists, this essay, while exemplifying the implications of a futuristic gender‐neutral society, albeit partially, examines Le Guin's celebration of community collectivism in “Coming of Age in Karhide” to argue that the integration with the values and expectations of the larger community occasions individual growth and identity formation of the teenage protagonist and thereby, attests to the author's humanistic temperament.
Immigrant linguistic justice: The lay of the land
Authors: De Schutter Helder , Song Seunghyun
Published: October 2023

Linguistic justice is concerned with the just way of politically regulating linguistic diversity. Today, the linguistic‐justice debate may be differentiated into three different domains: interlinguistic justice, intralinguistic justice, and global linguistic justice. Each of these domains has, to a significant extent, attracted different authors and debates, although the normative system underlying them is structurally similar. This introductory piece aims to provide context for our symposium dedicated to linguistic justice and migration by, first, giving an overview of linguistic justice, second, linking linguistic justice to migration, and, finally, providing an overview of the various papers in the symposium, situating them against the background developed in the first two sections.