bluuebunny/crossref_metadata_2025 huggingface dataset:
MEFIB‐Index and MAST‐Score in the assessment of hepatic decompensation in metabolic dysfunction‐associated steatosis liver disease—Individual participant data meta‐analyses
Authors: Noureddin Nabil , Ajmera Veeral , Bergstrom Jaclyn , Bettencourt Richele , Huang Daniel Q. , Siddiqi Harris , Majzoub Abdul M. , Nayfeh Tarek , Tamaki Nobuharu , Izumi Namiki , Nakajima Atsushi , Idilman Ramzan , Gumussoy Mesut , Oz Digdem Kuru , Erden Ayse , Loomba Rohit
Published: September 2023

Background

There are limited data regarding the longitudinal association between MEFIB‐Index (MRE combined with FIB‐4) versus MAST‐Score (MRI‐aspartate aminotransferase) and hepatic decompensation.

Aim

To examine the longitudinal association between MEFIB‐Index versus MAST‐Score in predicting hepatic decompensation in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD).

Methods

This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI‐PDFF and were followed for hepatic decompensation. Cox‐proportional hazard analyses were used to assess the association between MEFIB‐Index versus MAST‐Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment.

Results

This meta‐analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB‐Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST‐Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow‐up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB‐Index [HR = 49.22 (95% CI: 6.23–388.64, p < 0.001)] and a positive MAST‐Score [HR = 3.86 (95% CI: 1.46–10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB‐Index (c‐statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST‐Score (c‐statistic: 0.81, SE = 0.03) (p < 0.0001) in predicting hepatic decompensation.

Conclusion

A combination of MRI‐based biomarker and blood tests, MEFIB‐Index and MAST‐Score can predict the risk of hepatic decompensation in patients with MASLD.
Reproductive pattern of the southern bunchgrass lizard (Sceloporus aeneus) from Cuautepec de Hinojosa, Hidalgo, Mexico
Authors: Manríquez‐Morán Norma L. , González‐Espinoza Jorge E. , Domínguez‐Guerrero Saúl F. , de la Rosa‐Cruz Gabino
Published: September 2023

Squamata is one of the groups of sauropsids with the greatest diversity in life histories. The timing and expression of events related to reproductive phenology are considered among the most important components of squamate life histories. Here we studied the male and female reproductive patterns, clutch size, and clutch frequency of the oviparous lizard Sceloporus aeneus from a population in the southeast of Hidalgo State, Mexico, from April 2010 to March 2011. The gonadal analysis showed that the minimum snout‐vent length at sexual maturity in males and females was 46 mm. Both sexes exhibit seasonal reproductive patterns; males present maximum gonadal activity in winter‐spring (February–May), and females are vitellogenic in spring‐summer (May–July). Clutch size averaged 7 eggs (range 5–9) and did not show a relationship with female body size. Females produce at least two clutches per breeding season. The reproductive patterns described in this study were similar to those observed in other populations of S. aeneus, although some events in the reproductive phenology of both sexes appear to be related to local environmental factors.
Do advertisements with a social message elevate subjective well‐being?: An examination of empirical associations
Authors: Manzoor Iqra , ul Haq Zia
Published: September 2023

Advertising, a form of publicity, can pass on a social message so that people understand their sobligation towards society. The purpose of this study was to look into how consumers responded to socially conscious advertisements. This study conceptualizes the antecedents of attitude towards commercial advertisements that incorporate the social message, including advertising creativity, informativeness, and emotional appeal; each one can influence consumers' behavior. This study also examined the relationship between (i) Attitude towards the ad with a social message and purchase intention of the consumer and (ii) Purchase intention of the consumer and subjective well‐being. The interrelationships in the proposed model were investigated using structural equation modeling (SEM). A quantitative survey of university students was conducted in order to gather the data, which was based on an experiment. A field survey of 395 students was conducted to test the hypotheses. The results of the empirical tests confirm that attitude towards the advertisement positively affects the purchase intention of the consumer and that advertising creativity and emotional appeal are the key predictors of attitude towards the advertisement that highlights a social issue. And, purchase intention positively influences the subjective well‐being of the consumers. This paper contributes to the theory by giving new insight into the advertising literature. It also provides the necessary knowledge to marketers and advertisers on commercial advertisements incorporating a social message and the subjective well‐being of consumers.
Pregnancy, delivery and neonatal outcomes among women with hypoparathyroidism—A population‐based study
Authors: Hochberg Alyssa , Pare Aurelie , Badeghiesh Ahmad M. , Baghlaf Haitham A. , Dahan Michael H.
Published: September 2023

Objective

Data are inconclusive regarding pregnancy complications associated with maternal chronic hypoparathyroidism. Therefore, we aimed to compare pregnancy, delivery and neonatal outcomes in patients affected by chronic hypoparathyroidism to those without chronic hypoparathyroidism.

Design

A retrospective population‐based study utilising data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP‐NIS) database over 11 years from 2004 to 2014 inclusively. Multivariate logistic regression was used to control for confounders.

Patients

Patients with chronic hypoparathyroidism compared with those without.

Measurements

Obstetric and neonatal outcomes.

Results

We identified 204 pregnancies in mothers with chronic hypoparathyroidism and 9,096,584 pregnancies without chronic hypoparathyroidism. After adjusting for age, insurance plan type, obesity, chronic hypertension, thyroid disease, pregestational diabetes mellitus, and previous caesarean section, patients in the hypoparathyroidism group, compared with those without hypoparathyroidism, were found to have an increased rate of preterm birth (<37 weeks) (19.1% vs. 7.2%, aOR: 2.49, 95% confidence interval [CI]: 1.74–3.54, p < 0.0001, respectively); and blood transfusions (4.9% vs. 1.0%, aOR: 4.07, 95% CI: 2.15–7.73, p < ‐0.0001). Neonates to mothers with chronic hypoparathyroidism had a higher rate of congenital anomalies (4.4% vs. 0.4%, aOR: 6.50, 95% CI: 3.31–12.75, p < 0.0001), with comparable rates of small‐for‐gestational‐age neonates and intrauterine foetal death.

Conclusion

This is the largest study of chronic hypoparathyroidism in pregnancy to date. We found significant increases in the rates of preterm birth, blood transfusions and congenital anomalies in chronic hypoparathyroidism. Our findings highlight the importance of identifying chronic hypoparathyroidism as a risk factor for pregnancy and neonatal complications, although it remains unknown if maintaining calcium in the target range will mitigate these risks.
Utilization of hepatitis C virus infected donors in heart transplant recipients with elevated MELD‐XI score
Authors: Hirani Rahim , Okumura Kenji , Isath Ameesh , Gregory Vasiliki , Khan Shazli , Dhand Abhay , Lanier Gregg M. , Spielvogel David , Kai Masashi , Ohira Suguru
Published: September 2023

Background

The advent of direct‐acting antivirals has helped to increase the safe utilization of organs from hepatitis C virus positive (HCV+) donors. However, the outcomes of heart transplantation (HT) using an HCV+ donor are unclear in recipients with underlying liver disease represented by an elevated model for end‐stage liver disease excluding international normalized ratio (MELD‐XI).

Methods

The United Network of Organ Sharing database was queried from Jan 2016 to Dec 2021. Post‐transplant outcomes stratified by recipient MELD‐XI score (low <10.37, medium, 10.38–13.39, and high >13.4) was compared between patients with HT from HCV+ (N = 792) and patients with HT from HCV‐negative donors (N = 15,266).

Results

The median MELD‐XI score was comparable (HCV+, 12.1, vs. HCV‐negative, 11.8, p = .37). In the HCV+ group, donors were older (33 vs. 31 years, p < .001). Ischemic time of donor hearts (3.48 vs. 3.28 h, p < .001) and travel distance (250 vs. 157 miles, p < .001) were longer in HCV+ group. In the Kaplan Meier analysis with a median follow‐up of 750 days, survival was comparable between the two groups (2‐year survival, MELD‐XI Low: HCV+, 92.4 ± 3.6% vs. HCV‐negative, 91.1 ±.8%, p = .83, Medium: HCV+ 89.2 ± 4.3% vs. HCV‐negative, 88.2 ± 1.0%, p = .68, and High: HCV+, 84.9 ± 4.5% vs. HCV‐negative, 84.6 ± 1.1%, p = .75) In multivariate Cox hazard models, HCV donors were not associated with mortality in each MELD‐XI subgroup (Low: adjusted hazard ratio (aHR), 1.02, p = .94; Medium: aHR, .95, p = .81; and High: aHR, .93, p = .68).

Conclusion

Utilization of HCV+ hearts was not associated with an increased risk of adverse outcomes in recipients with an elevated MELD‐ XI score.
Low‐density lipoprotein cholesterol and non‐high‐density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German–Austrian diabetes registry
Authors: Brandts Julia , Tittel Sascha R. , Bramlage Peter , Danne Thomas , Brix Johanna M. , Zimny Stefan , Heyer Christoph H. J. , Holl Reinhard W. , Müller‐Wieland Dirk
Published: September 2023

Aim

To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid‐lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022.

Materials and Methods

Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline‐based low‐density lipoprotein cholesterol (LDL‐C) and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) goal attainment was analysed.

Results

In patients with T1D (median age 38.35 [20.51‐57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86‐78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk‐based recommended LDL‐C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk‐based goal of LDL‐C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non‐HDL‐C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively.

Conclusion

Approximately 2 years after publication of the guidelines, LDL‐C and non‐HDL‐C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.
Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 2 diabetes
Authors: Pieber Thomas R. , Asong Marisse , Fluhr Gabriele , Höller Vera , Kristensen Niels R. , Larsen Jonas H. , Ribel‐Madsen Rasmus , Svehlikova Eva , Vinther Siri , Voortman Margarete , Haahr Hanne
Published: September 2023

Aims

To characterize the pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in type 2 diabetes (T2D).

Materials and Methods

In an open‐label trial, 46 individuals with T2D (18‐75 years; body mass index 18.0‐38.0 kg/m2; glycated haemoglobin ≤75 mmol/mol [≤9%]; basal insulin‐treated) received subcutaneous once‐weekly icodec for ≥8 weeks at individualized doses, aiming at a pre‐breakfast plasma glucose concentration of 4.4 to 7.0 mmol/L (80‐126 mg/dL) on the last three mornings of each weekly dosing interval. Frequent blood sampling to assess total serum icodec concentration (ie, albumin‐bound and unbound) occurred from first icodec dose until 35 days after last dose. Icodec trough concentrations following initiation of once‐weekly dosing were predicted by pharmacokinetic modelling. During the final 3 weeks of icodec treatment, while at steady state, the icodec glucose‐lowering effect was assessed in three glucose clamps (target 7.5 mmol/L [135 mg/dL]): 0 to 36, 40 to 64 and 144 to 168 h post‐dose, thus covering the initial, middle and last part of the 1‐week dosing interval. Glucose‐lowering effect during a complete dosing interval was predicted by pharmacokinetic‐pharmacodynamic modelling.

Results

Model‐predicted icodec steady state was attained after 3 to 4 weeks. At steady state, model‐predicted daily proportions of glucose‐lowering effect on days 1 to 7 of the 1‐week dosing interval were 14.1%, 16.1%, 15.8%, 15.0%, 14.0%, 13.0% and 12.0%, respectively. Icodec duration of action was at least 1 week in all participants. Once‐weekly icodec was overall safe and well tolerated in the current trial.

Conclusions

The pharmacokinetic and pharmacodynamic characteristics of icodec in individuals with T2D support its potential as a once‐weekly basal insulin.
Religion and development in Samoa: Time to draw on the strength of local culture?
Authors: Alofaituli Brian
Published: September 2023

Motivation

As in much of the Pacific, Samoans understand their culture through Western religious lenses. Christianity andfa'a‐Samoa(culture and practices) are entangled; they determine Samoa's daily reality of governance, society, and economic development. To discuss Samoa's development over the past two centuries without addressing Samoan agency in maintaining the Christian mantle to navigate their worldviews would be to misrepresent modern Samoa. Policy and investment for economic development, especially foreign aid, is largely determined at national level. Samoa's most vital communities to effect change, however, are local: church congregations and their leaders.

Purpose

I examine the intersections of religiosity and Samoa's development. Should foreign aid donors consider Samoa's religious communities to implement effective education, poverty, and development programmes if religion is regarded as a cultural entity?

Methods and approach

I usedtalanoato collect data from discussions with directors of two leading aid donors in Samoa, the United Nations (UN) and the Asian Development Bank (ADB), and the Aid Coordinator for the Government of Samoa.Talanoais a face‐to‐face dialogue often used in Pacific communities.

Findings

Religion plays a significant role in Samoan society. Samoans view economic development, the improvement of the lives of ordinary citizens, job stability, and education as part of themanuia(blessings) of Samoa's religious and political status and communitytapuaiga(prayers). That said, religion is not considered in formal discussions of aid and development. The interviewees agree that aid donors should understand the role of religion in daily society.

Policy implications

Perhaps it is time for aid donors and Christian Pacific Island countries to use these unorthodox methods for positive economic and social changes. As stated in Samoa's World Summit on Sustainable Development Assessment Report, “the potential influential standing and the extensive outreach of the church within the community makes it a valuable vehicle to drive pro‐harmony strategies” (Government of Samoa, 2000).
Vestibular contribution to spatial encoding
Authors: Zanchi Silvia , Cuturi Luigi F. , Sandini Giulio , Gori Monica , Ferrè Elisa R.
Published: September 2023

Determining the spatial relation between objects and our location in the surroundings is essential for survival. Vestibular inputs provide key information about the position and movement of our head in the three‐dimensional space, contributing to spatial navigation. Yet, their role in encoding spatial localisation of environmental targets remains to be fully understood. We probed the accuracy and precision of healthy participants' representations of environmental space by measuring their ability to encode the spatial location of visual targets (Experiment 1). Participants were asked to detect a visual light and then walk towards it. Vestibular signalling was artificially disrupted using stochastic galvanic vestibular stimulation (sGVS) applied selectively during encoding targets' location. sGVS impaired the accuracy and precision of locating the environmental visual targets. Importantly, this effect was specific to the visual modality. The location of acoustic targets was not influenced by vestibular alterations (Experiment 2). Our findings indicate that the vestibular system plays a role in localising visual targets in the surrounding environment, suggesting a crucial functional interaction between vestibular and visual signals for the encoding of the spatial relationship between our body position and the surrounding objects.
Systematic review of drug therapy for chorea in NXK2‐1‐related disorders: Efficacy and safety evidence from case studies and series
Authors: Nou‐Fontanet Laia , Martín‐Gómez Carmen , Isabel‐Gómez Rebeca , Bachoud‐Lévi Anne‐Catherine , Zorzi Giovanna , Capuano Alessandro ,   NKX2‐1‐Related Disorders Guideline Working Group, Blasco‐Amaro Juan Antonio , Ortigoza‐Escobar Juan Darío
Published: September 2023

Background

The NKX2‐1‐related disorders (NKX2‐1‐RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2‐1‐RD, aiming to provide clinical recommendations for its management.

Methods

A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2‐1‐RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.

Results

Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.

Conclusions

The management of chorea in individuals with NKX2‐1‐RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Deep reinforcement learning‐based precise prediction model for Smart M‐Health system
Authors: Jagannath Duraiswamy Jothinath , Dolly Raveena Judie , Dinesh Peter James
Published: September 2023

The use of Android mobile phones and other wireless technology in the field of healthcare infers to mHealth (mobile health). Modern Science and technological developments have paved way for better and more sophisticated solutions towards Smart mHealth systems and preventive Smart Healthcare services for disease—treatment, surveillance, management of chronic disease and tracking epidemic outbreaks. Thus, the mHealth data can be collected from various end users, deposited in repository, perform analysis and suitable Smart Healthcare services can be made accessible to end users, anytime, anywhere, over the internet. This can be achieved by incorporating the methodologies of advanced Soft Computing methodologies, data communication, cloud storage and cloud computing, big data analysis, artificial intelligence, computer communication/networking and other engineering techniques. However, the analysis of such huge volumes of data and to provide precise Smart Healthcare services is a million‐dollar question. This research article exposes a Deep Reinforcement Learning model for precisely predicting the disease and offer precise Smart m‐Healthcare services to the end users. This research provides an intensive experimental analysis and investigation using synthetic health parameters that were simulated using various mHealth sensors. The dataset includes 15 varieties of mHealth metrics with a total dataset size of 285.
The future of parenting plan evaluations: A view from the trenches
Authors: McNamara Kathleen , Lund Mary
Published: September 2023

As expectations rise for parenting plan evaluators to be well‐trained, skilled, and knowledgeable in numerous subject areas, and scrutiny of evaluators' work intensifies, the pool of qualified evaluators is shrinking nationwide. The future of parenting plan evaluation as a forensic subspecialty relies upon the availability of competent and committed professionals to do this challenging work, yet few are entering the field. Five experienced parenting plan evaluators from various regions of the United States, including the authors, met for a roundtable discussion to ponder the future of parenting plan evaluations. The panel discussed what drew them to the work, their experiences “in the trenches,” and what has kept them committed to doing evaluations despite daunting challenges. Their views of the rewards and risks of doing the work, barriers and disincentives to newcomers entering the field, recommendations to new evaluators, and outlook for the future are presented.
Judicial decision‐making in family court involving children with autism spectrum disorder
Authors: Lahaie Emilie , Poitras Karine , Birnbaum Rachel
Published: September 2023

The prevalence of autism spectrum disorder (ASD) in children and adolescents has increased over the past decade. Consequently, the courts and experts are more likely to be exposed to these children whose needs are highly heterogeneous. The present study aims to document judicial decision‐making about children with autism spectrum as well as the parenting recommendations made by experts involved in these cases. There were 104 court decisions reviewed in Quebec over the past ten years. The results show that 85.6% of the decisions included a child custody assessment and that judges are more likely to order primary care to mother (56%). However, shared parenting (27%) and primary care to the father (17%) were also ordered in disputes involving an autistic child. Bivariate analyses revealed that challenges with parental monitoring and supervision were associated with court‐ordered parenting arrangements. The present study revealed that a child custody assessment as well as father custody are more often observed than in the general population. This study highlights the need for further research to shed light on the best interests of children with ASD following the separation of their parents.
Shoot nitrogen concentrations required for optimal herbage growth of multiple perennial ryegrass (Lolium perenne L.) cultivars relative to modern summer‐active cocksfoot (Dactylis glomerata L.) and tall fescue (Festuca arundinacea Schreb.) cultivars
Authors: Langworthy Adam D. , Corkrey Ross , Rawnsley Richard P. , Hills James L.
Published: September 2023

One possible approach for improving the nitrogen (N)‐use efficiency of perennial ryegrass (Lolium perenne L.) pastures and reducing environmental N losses is to select cultivars or incorporate alternative pasture species with lower shoot N concentrations. Viability of this strategy depends on herbage production not being unduly compromised. A pot experiment compared the shoot N concentration requirements of a diverse range of perennial ryegrass cultivars to achieve 90% and 99% of the herbage yield maxima achievable within a 20 day regrowth cycle. This research was undertaken to quantify if and what effect Australasian breeding programs have had on the N nutrition of perennial ryegrass. Our experiment found minimal genetic variation in the shoot N concentration requirements for vegetative perennial ryegrass swards to achieve near‐maximum herbage yields of living biomass. Across evaluated cultivars, swards achieving 90% and 99% of herbage yield maxima required minimum shoot N concentrations (on a dry matter basis) of 2.56% and 2.87%, respectively. Our experiment also evaluated the shoot N concentration requirements of modern summer‐active cocksfoot (syn. orchardgrass; Dactylis glomerata L.) and tall fescue (Festuca arundinacea Schreb.) ecotypes. We found their shoot N concentration requirements to achieve optimal herbage growth to be similar to those of perennial ryegrass. Taken together, our results suggest that within the perennial ryegrass genome, and among similar high yielding temperate perennial grasses, there may be limited scope for selecting plants with lower shoot N concentration requirements.
δ238U of Coal Reference Materials Determined by MC‐ICP‐MS
Authors: Sheng Jiaru , Li Siqi , Owens Jeremy D. , Wang Xiangli , Wei Yong , Ming Guodong , Huang Fang
Published: September 2023

Uranium (U) associated with coal can be an important source of U and result in environmental pollution during coal combustion. In this study, we developed a method for measurement of U isotope ratios in coals using multiple‐collector inductively coupled plasma‐mass spectrometry. The 233U‐236U double‐spike was utilised to calibrate the instrumental isotopic fractionation. High‐pressure bomb and dry ashing were adopted to digest the coal samples. The δ238UCRM‐145 values obtained from the two different digestion procedures were in good agreement. The δ238UCRM‐145 of seven coal and one fly ash reference materials are reported. Furthermore, the results of fly ash, bottom ash and feed coal samples reveal that the combustion processes lead to relatively small U isotopic fractionation between the samples within the same coal‐fired power plant, indicating that U isotope data can be used as a tracer for heavy metal pollution resulting from coal combustion. The U isotope measurement method of coal established in this study provides technical support to understand the behaviour of U during coal formation and combustion.
Subclinical synovial proliferation in patients with severe haemophilia A: The value of ultrasound screening and biochemical markers
Authors: van Bergen Eline D. P. , van Leeuwen Flora H. P. , Foppen Wouter , Timmer Merel A. , Schutgens Roger E. G. , Mastbergen Simon C. , Lafeber Floris P. J. G. , de Jong Pim A. , Fischer Kathelijn , van Vulpen Lize F. D.
Published: September 2023

Aim

Subclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation.

Methods

This cross‐sectional study included patients with severe haemophilia A born 1970–2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM‐1, Coll2‐1, COMP, CS846, TIMP, and urinary CTX‐II) were compared individually and as combined indexes between patients with and without active synovial proliferation.

Results

This cohort consisted of 79 patients with a median age of 31 years (range 16.5–50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2–1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation.

Conclusion

Subclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation.
Island spider origins show complex vertical stratification patterns in Macaronesia
Authors: Costa R. , Cardoso P. , Rigal F. , Borges P. A. V.
Published: September 2023

Spiders are among the most diverse and yet threatened groups of arthropods in Macaronesia. Found in most habitat types, they occupy the vertical gradient of native forests from ground to canopy level.

We hypothesize that their vertical distribution is influenced by the colonization origin. As introduced species should arrive using shipping containers and similar means, they should mostly occupy the lower levels in the gradient, with potential negative effects on the indigenous epigean fauna.

Spiders were sampled from epigean to arboreal microhabitats (maximum height varying between 2 and 4 m) on 45 sites across five islands belonging to three archipelagos. The mean and range of vertical stratification were obtained for each captured species. These values were then compared between different colonization origins at Macaronesian and archipelagic levels.

Native non‐endemic species were found at significantly higher vertical strata than both endemic and introduced species. Likewise, native non‐endemics had a larger vertical range. These patterns were largely replicated across archipelagos, although there were exceptions.

Overall, introduced species do not seem to occur mostly at lower strata in the native forests of Macaronesia (at least in the studied vertical range) but seem to be vertically restricted in most settings with the exception of Madeira.
Defining the proteomic landscape of cultured macrophages and their polarization continuum
Authors: Oates Tiah CL , Moura Pedro L , Cross Stephen , Roberts Kiren , Baum Holly E , Haydn‐Smith Katy L , Wilson Marieangela C , Heesom Kate J , Severn Charlotte E , Toye Ashley M
Published: September 2023

Macrophages have previously been characterized based on phenotypical and functional differences into suggested simplified subtypes of MØ, M1, M2a and M2c. These macrophage subtypes can be generated in a well‐established primary monocyte culture model that produces cells expressing accepted subtype surface markers. To determine how these subtypes retain functional similarities and better understand their formation, we generated all four subtypes from the same donors. Comparative whole‐cell proteomics confirmed that four distinct macrophage subtypes could be induced from the same donor material, with > 50% of 5435 identified proteins being significantly altered in abundance between subtypes. Functional assessment highlighted that these distinct protein expression profiles are primed to enable specific cell functions, indicating that this shifting proteome is predictive of meaningful changes in cell characteristics. Importantly, the 2552 proteins remained consistent in abundance across all macrophage subtypes examined, demonstrating maintenance of a stable core proteome that likely enables swift polarity changes. We next explored the cross‐polarization capabilities of preactivated M1 macrophages treated with dexamethasone. Importantly, these treated cells undergo a partial repolarization toward the M2c surface markers but still retain the M1 functional phenotype. Our investigation of polarized macrophage subtypes therefore provides evidence of a sliding scale of macrophage functionality, with these data sets providing a valuable benchmark resource for further studies of macrophage polarity, with relevance for cell therapy development and drug discovery.
Factors leading to diagnostic delay in tuberculosis in the tropical north of Australia
Authors: Vigneswaran Nilanthy , Parnis Roger , Lowbridge Christopher , Townsend David , Ralph Anna P.
Published: September 2023

Background

Tuberculosis (TB) incidence is decreasing in the Northern Territory (NT) but still exceeds rates elsewhere in Australia. Deaths and morbidity from advanced TB continue, with delay in diagnosis a contributor to adverse outcomes.

Aims

We aimed to describe the delay in diagnosis of TB, identify risk factors for delay and examine the associations between delay and clinical outcomes.

Methods

We conducted a historical cohort analysis which included adult inpatients diagnosed with TB at the Royal Darwin Hospital from 2010 to 2020. Patient delay was measured as time from symptom onset to first seeking care, and health system delay was quantified as time from first relevant clinical contact to diagnosis. The sum of these two periods was the total delay. Ethics approval was granted by NT HREC (2020‐3852).

Results

Eighty‐four cases were included; the median total delay was 90 days (interquartile range (IQR): 60–121), patient delay was 53 days (IQR: 30–90), and health system delay was 21 days (IQR: 12–45). Patient delay was longer among patients with extrapulmonary (median: 100 days (IQR: 90–105) compared with pulmonary TB patients (39 days (IQR: 27–54), P < 0.0001). Health system delay was longer in those aged ≥45 years (30 days (IQR: 16–51) vs younger patients (14 days (IQR: 8–30), P = 0.007) and among non‐smokers (31 days (IQR: 21–55) vs 21 days (IQR: 10–40), P = 0.048). Median delay was longer among patients with non‐drug‐related complications of disease (P < 0.0001), those admitted to critical care (P < 0.0001), and those with respiratory failure (P = 0.001).

Conclusion

The patient delays we report are longer than reported elsewhere in Australia. The next steps will require concerted efforts to improve community awareness of TB and strategies to strengthen health systems through better resourcing and healthcare provider support.
Flot2 deficiency facilitates B cell‐mediated inflammatory responses and endotoxic shock
Authors: Yang Qin , Zhang Zhenhua , Chen Ziye , Wang Yiyuan , Chen Yan , Zheng Jiehuang , Li Ruopeng , Li Lihong , Mo Lixia , Liang Qinghe , Chen Fengsheng , Wang Junjian , Li Xiaojuan
Published: September 2023

Sepsis is a life‐threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin‐induced septic mice. However, the effects of Flot2 on sepsis and B‐cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2−/−) mice, RNA‐seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL‐6 and unchanged Breg cytokine IL‐10 were shown in B cells from Flot2−/− mice. Similar results were subsequently observed in B cell‐specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis.
Targeted therapy for non‐small‐cell lung cancer: New insights into regulated cell death combined with immunotherapy
Authors: Li Shutong , Wang Aoxue , Wu Yongya , He Shengyuan , Shuai Wen , Zhao Min , Zhu Yumeng , Hu Xiuying , Luo Yubin , Wang Guan
Published: September 2023

Non‐small‐cell lung cancer (NSCLC), which has a high rate of metastatic spread and drug resistance, is the most common subtype of lung cancer. Therefore, NSCLC patients have a very poor prognosis and a very low chance of survival. Human cancers are closely linked to regulated cell death (RCD), such as apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. Currently, small‐molecule compounds targeting various types of RCD have shown potential as anticancer treatments. Moreover, RCD appears to be a specific part of the antitumor immune response; hence, the combination of RCD and immunotherapy might increase the inhibitory effect of therapy on tumor growth. In this review, we summarize small‐molecule compounds used for the treatment of NSCLC by focusing on RCD and pharmacological systems. In addition, we describe the current research status of an immunotherapy combined with an RCD‐based regimen for NSCLC, providing new ideas for targeting RCD pathways in combination with immunotherapy for patients with NSCLC in the future.
Effect of photobiomodulation on the efficacy of anesthesia in maxillary permanent molar teeth with molar incisor hypomineralization: A randomized clinical trial
Authors: Aykanat Berkehan , Elbay Mesut
Published: September 2023

Background

Difficulty in anesthetizing teeth that have been diagnosed with molar incisor hypomineralization (MIH) is a frequently reported clinical problem. The effects of low‐level laser application (photobiomodulation) on the efficacy of anesthesia during the dental treatment of patients with MIH have not yet been studied.

Aim

To assess the effects of photobiomodulation therapy (PBMT) on the efficacy of anesthesia in maxillary permanent molar teeth with MIH.

Design

This prospective, parallel‐arm control, randomized, triple‐blind clinical trial included children aged 7–12 years. Maxillary permanent first molar teeth with MIH that required pulpotomy treatment were included. Seventy participants were randomly divided into two groups: experimental (with PBMT) and control (placebo). In the experimental group, before the administration of local infiltration anesthesia, PBMT (diode laser: 940 nm; continuous mode; 0.5 W; 78 J/cm2) was applied to the oral mucosa for 60 s each. In the control group, the laser probe was channeled toward the mucosa but was not activated. Pain scores were evaluated during the access cavity preparation of the pulpotomy treatment (when using the dentin cutting handpiece and while entering into the pulp) using the Face, Legs, Activity, Cry, Consolability (FLACC) scale. Additional anesthesia requirements were assessed in both groups. The data obtained were analyzed for statistical significance (p < .05). The chi‐squared test was used to determine the effect of PBMT on categorical outcomes.

Results

The no‐pain scores of the experimental group were higher than those of the control group (29% vs. 20%). Moderate‐to‐high pain was more frequent in the control group than in the experimental group (43% vs. 20%). While 31% of the experimental group required supplemental anesthesia, 49% of the control group required supplemental anesthesia during pulpotomy of the tooth with MIH. No statistical difference, however, was found between the two groups in terms of pain scores and the need for supplemental anesthesia (p = .235, p = .143).

Conclusions

Anesthesia with and without PBMT caused no difference in pain during the treatment of maxillary molar teeth with MIH.
Presenting points or rank: The impacts of leaderboard elements on English vocabulary learning through video lectures
Authors: Pi Zhongling , Yu Qiuchen , Zhang Yi , Li Yan , Chen Hui , Yang Jiumin
Published: September 2023

Background

Leaderboards are a highly popular gamification component used in student learning to enhance motivation, attentional engagement, and learning performance. However, few studies have examined the effects of individual leaderboard elements on English vocabulary learning through video lectures.

Objectives

The present study aimed to examine how different leaderboard elements (i.e., points and rank) may affect students' English vocabulary learning through video lectures.

Methods

A total of 34 students were assigned to groups using different leaderboard elements in a counterbalanced order. Participants' motivation, eye movements, and learning performance were measured and analysed.

Results and Conclusions

Students' leaderboard rank was shown to increase their motivation regardless of whether other elements were present. Eye movement tracking revealed that the presence of the leaderboard increased students' saccades between the questions and the options, and lengthened their dwell time on the learning materials while reducing their dwell time on the non‐learning‐related screen areas. Presenting students' rank alone also improved their learning performance.

Implications

Our findings strongly support the use of video lectures for English vocabulary learning, with the following recommendations: (1) Instructors should present students' rank on the leaderboard to enhance students' motivation and engagement; (2) Instructors should present only the students' rank on the leaderboard to also enhance students' learning performance.
Learning from screencast software tutorials: A comparison of cognitive load in dual and single‐monitor learning environments
Authors: Kueker Doug , Moore Joi
Published: September 2023

Background

Learning to use software using screencast videos with worked examples in the corresponding practice files presents a classic split‐attention problem that requires learners to mentally integrate information from the video with a target application. While there is evidence that splitting attention either temporally or spatially adversely impacts learning, it is unclear if there is a meaningful difference in the load imposed by splitting attention in different ways. Furthermore, while much is known about effective screencast design, little is known about how learning environment features, such as the monitor configuration, influence learning from this form of instruction.

Objective

An experiment was conducted with 42 novice learners to compare the effects of two common monitor configurations that divided attention differently on three physiological measures of cognitive load.

Methods

Effects due to the monitor setup were assessed using a 2 × 2 study design that controlled for task order and working memory capacity. In one condition, subjects split attention temporally by toggling back and forth between the video and target application on one monitor. In contrast, the other condition required subjects to split attention spatially by shifting their gaze between the video and target application displayed on two side‐by‐side monitors.

Results and Conclusions

Results indicated that cognitive load as measured through task‐evoked pupil response was significantly higher, p < 0.05, for groups with two monitors during both instruction and testing, even after controlling for working memory capacity.
Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone
Authors: Song Xudong , Que Dongdong , Zhu Yingqi , Yu Wenjie , Xu Haoran , Zhang Xiuli , Yan Jing , Wang Yuxi , Rui Bowen , Yang Yashu , Zhuang Zhenyu , Huang Guanlin , Zhao Xiaoqing , Yang Chaobo , Cai Yanbin , Yang Pingzhen
Published: September 2023

Background

Substrate‐based ablation can treat uninducible or hemodynamically instability scar‐related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown.

Objective

To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR.

Methods

Thirty‐six patients with scar‐related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier.

Results

Forty‐five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels.

Conclusion

Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate‐based ablation strategies for scar‐related VT and shorter procedure times.