bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid‐related ambulance attendances during the first 2 years of the COVID‐19 pandemic in Victoria, Australia
Authors: McGrath Michael , Stare Mark , Chua Phyllis , Ogeil Rowan , Nehme Ziad , Scott Debbie , Lubman Dan I.
Published: October 2023

Background and Aims

Public health measures introduced to contain the spread of the SARS‐CoV‐2 virus likely affected opioid supply and demand, as well as the patterns and contexts of opioid use. We measured opioid‐related harms during the first 2 years of COVID‐19 restrictions in Victoria, Australia.

Design

We adopted an interrupted time series analysis design using interventional autoregressive integrated moving average (ARIMA) models. Opioid‐related ambulance attendance data between January 2015 and March 2022 were extracted from the National Ambulance Surveillance System.

Setting

Victoria, Australia.

Participants

Patients (≥15 years) attended to by an ambulance for opioid‐related harms.

Measurements

Monthly opioid‐related ambulance attendances for three drug types: heroin, prescription opioids and opioid agonist therapy (OAT) medications.

Findings

The monthly rate of heroin‐related attendances fell by 26% immediately after the introduction of COVID‐19 restrictions. A reduced rate of heroin‐related attendances was observed during COVID‐19 restrictions, resulting in 2578 averted heroin‐related attendances. There was no change in the rate of attendances for extra‐medical OAT medications or prescription opioids.

Conclusions

Strict COVID‐19 restrictions in Victoria, Australia appear to have resulted in a substantial reduction in heroin‐related ambulance attendances, perhaps because of border closures and restrictions on movement affecting supply, changing patterns of drug consumption, and efforts to improve access to OAT. Despite policy changes allowing longer OAT prescriptions and an increased number of unsupervised doses, we found no evidence of increased harms related to the extra‐medical use of these medications.
Does a local Alcohol Health Champion programme have a measurable impact on health and crime outcomes? A natural experiment evaluation of Communities in Charge of Alcohol (CICA) based on triangulation of methods
Authors: Scott Lauren J. , Hidajat Mira , Burns Elizabeth J. , Ure Cathy , Hargreaves Suzy C. , Audrey Suzanne , Coffey Margaret , Hare Susan , Siqueira Noemia , Parrott Steve , Cook Penny A. , de Vocht Frank
Published: October 2023

Background and Aim

Drinking alcohol may cause harm to an individual's health and social relationships, while a drinking culture may harm societies as it may increase crime rates and make an area feel less safe. Local councils in Greater Manchester, UK, developed the Communities in Charge of Alcohol (CICA) intervention, in which volunteers were trained to give alcohol‐related advice to the public and taught how to influence policies to restrict when, where and how alcohol is sold. As part of a larger study, the aim of the current project is to measure the impact of CICA on health and crime outcomes at the lower super output (LSOA) geographical aggregation.

Design

Quantitative evaluation using four time series analytic methods (stepped‐wedge design, and comparisons to local controls, national controls and synthetic controls) with findings triangulated across these methods. A cost–benefit analysis was carried out alongside the effectiveness analysis.

Setting and Participants

The general public in Greater Manchester, UK, between 2010 and 2020.

Measurements

The primary outcome of interest was alcohol‐related hospital admissions. Secondary outcomes were accident and emergency (A&E) attendances, ambulance callouts, recorded crimes and anti‐social behaviour incidents.

Findings

Triangulation of the results did not indicate any consistent effect on area‐level alcohol‐related hospital admissions, A&E attendances, ambulance callouts, reported crimes or anti‐social behaviour associated with the implementation of CICA. The primary stepped‐wedge analysis indicated an increase in alcohol‐related hospital admissions following the implementation of CICA of 13.4% (95% confidence interval −3.3%, +30.1%), which was consistent with analyses based on other methods with point estimates ranging from +3.4% to 16.4%.

Conclusion

There is no evidence of a measurable impact of the Communities in Charge of Alcohol (CICA) programme on area‐level health and crime outcomes in Greater Manchester, UK, within 3 years of the programme start. The increase in alcohol‐related hospital admissions was likely the result of other temporal trends rather than the CICA programme. Possible explanations include insufficient follow‐up time, too few volunteers trained, volunteers being unwilling to get involved in licensing decisions or that the intervention has no direct impact on the selected outcomes.
Seasonal adaptation of Mangalica pigs in terms of muscle morphology and metabolism
Authors: Kim Sangwoo , Nakayama Chisato , Kondoh Daisuke , Okazaki Tatsuki , Yoneda Erina , Tomita Kisaki , Sasaki Motoki , Muranishi Yuki
Published: October 2023

The skeletal muscle plays an important role in maintaining body temperature, which is mediated by thermogenesis and glucose or lipid metabolism. Mangalica is a native Hungarian pig that has cold tolerance and can live in grazing environments throughout the year. We evaluated the morphological and genetic aspects of Mangalica using muscle tissues to elucidate the mechanisms underlying the tolerance to seasonal effects in grazing environments. The muscle tissues in each season were analysed using morphological evaluation and electron microscopy. The cross‐sectional area of skeletal muscle cells in summer was significantly larger than that in winter. The thickness of myofibrils in summer was significantly higher than in winter. The thickness of the Z‐line in winter was significantly higher than in summer. The expression of MYH4 and GLUT4 was significantly lower in winter than in summer. The result of ATPase staining indicated significantly increase the muscle fibre ratio of type 1 in winter than that in summer. These findings indicate that the muscle fibre in Mangalica shifts from fast‐twitch to slow‐twitch fibre, and the metabolic physiology of the muscle was adapted to the cold environment. This study demonstrates that Mangalica gained tolerance to both seasonal heat and cold stresses that are caused by significant changes in ambient temperature in a year because of changes in their muscle fibre type and metabolic function. This study may contribute to elucidating the mechanism of thermogenetic adaptation in cold and heat environments among mammals.
A metabolomic perspective on the mechanisms by which environmental pollutants and lifestyle lead to male infertility
Authors: Yang Wen , Hua Rong , Cao Yunxia , He Xiaojin
Published: October 2023

The incidence of male infertility (MI) is rising annually. According to epidemiological studies, environmental pollution (e.g., organic, inorganic, and air pollutants), occupational exposure (e.g., high temperature, organic solvents, and pesticides), and poor lifestyle (e.g., diet, sleep, smoking, alcohol consumption, and exercise) are important non‐genetic causative factors of MI. Due to multiple and complex causative factors, the dose–effect relationship, and the uncertainty of pathogenicity, the pathogenesis of MI is far from fully clarified. Recent data show that the pathogenesis of MI can be monitored by the metabolites in serum, seminal plasma, urine, testicular tissue, sperm, and other biological samples. It is considered that these metabolites are closely related to MI phenotypes and can directly reflect the individual pathological and physiological conditions. Therefore, qualitative and quantitative analysis of the metabolome, the related metabolic pathways, and the identification of biomarkers will help to explore the MI‐related metabolic problems and provide valuable insights into its pathogenic mechanisms. Here, we summarized new findings in MI metabolomics biomarkers research and their abnormal metabolic pathways triggered by the presented non‐genetic risk factors, providing a metabolic landscape of semen and seminal plasma in general MI patients. Then, we compared the similarities and differences in semen and seminal plasma biomarkers between MI patients exposed to environmental and poor lifestyle factors and MI patients in general, and summarized some common biomarkers. We provide a better understanding of the biological underpinnings of MI pathogenesis, which might offer novel diagnostic, prognostic, and precise treatment approaches to MI.
Measurement errors in semi‐parametric generalised regression models
Authors: Hattab Mohammad W. , Ruppert David
Published: October 2023

Regression models that ignore measurement error in predictors may produce highly biased estimates leading to erroneous inferences. It is well known that it is extremely difficult to take measurement error into account in Gaussian non‐parametric regression. This problem becomes even more difficult when considering other families such as binary, Poisson and negative binomial regression. We present a novel method aiming to correct for measurement error when estimating regression functions. Our approach is sufficiently flexible to cover virtually all distributions and link functions regularly considered in generalised linear models. This approach depends on approximating the first and the second moment of the response after integrating out the true unobserved predictors in any semi‐parametric generalised regression model. By the latter is meant a model with both linear and non‐parametric effects that are connected to the mean response by a link function and with a response distribution in an exponential family or quasi‐likelihood model. Unlike previous methods, the method we now propose is not restricted to truncated splines and can utilise various basis functions. Moreover, it can operate without making any distributional assumption about the unobserved predictor. Through extensive simulation studies, we study the performance of our method under many scenarios.
Probability of second live birth after first natural and medically assisted reproduction‐mediated live birth: A historical cohort study
Authors: Esposito Giovanna , Parazzini Fabio , Viganò Paola , Franchi Matteo , Cipriani Sonia , Fedele Francesco , Corrao Giovanni , Somigliana Edgardo
Published: October 2023

Introduction

Evidence on the role of medically assisted reproduction (MAR) in achieving the desired number of children is very limited. The aim of the current investigation was to assess the probability and the mode of conception of a second live birth according to the mode of conception of the first one.

Material and methods

This historical cohort study was based on administrative data from regional healthcare databases. Women hospitalized for childbirth in Lombardy between January 1, 2007 and December 31, 2017 were identified. The probability of a second live birth up to 2021 was estimated using the Kaplan–Meier method. We calculated this probability according to the mode of conception of the first birth, and the analysis was also performed in strata of maternal age at first birth. Cox proportional hazards models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between mode of conception at first live birth and the probability of having a second live birth. Mothers were right‐censored if they moved out of the region, died, or did not have a second live birth by the end of follow‐up.

Results

We identified 431 333 women who had their first live birth after a natural conception and 16 837 who had their first live birth after MAR. The probability of having a second live birth was 58.6% and 32.1%, respectively in the two groups (HR = 0.68, 95% CI: 0.66–0.70). Considering solely women who naturally conceived their first live birth, the probability to have a second child with MAR was 1.1% and to have a second child naturally 59.3%. The corresponding values were 11.5% and 25.2% in the group of women with a first MAR‐mediated live birth.

Conclusions

In our cohort, one woman out of 10 having a first MAR‐mediated live birth underwent MAR programs again. Considering women who had a first natural live birth, this proportion was drastically reduced. In the field of MAR, more attention should be given to the capacity of a couple to achieve the number of desired children.
Systematic review: Scores used to predict outcomes in acute severe ulcerative colitis
Authors: Kayal Maia , Meringer Hadar , Martin Lily , Colombel Jean Frederic
Published: October 2023

Background

Approximately 25% of patients with ulcerative colitis (UC) experience an episode of acute severe ulcerative colitis (ASUC) during their disease course. Management and risk stratification of these patients is a great unmet medical need.

Aim

To review the literature systematically all currently available scores used to predict outcomes in patients with ASUC.

Methods

We executed a comprehensive search comprising both index terms and keywords in MEDLINE, Embase and Cochrane CENTRAL databases. We included observational cohort studies that reported on scoring indices to predict outcomes in patients admitted with ASUC defined by the Truelove and Witts criteria. We excluded studies that reported on risk factors of outcomes in patients with ASUC in isolation, not in the context of a score.

Results

The literature search identified 8729 studies, of which 18 were chosen to report 19 scores. Most scores included clinical and/or laboratory components. Two included imaging assessed by abdominal plain films; five included endoscopy assessed by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) or the Mayo Score. Outcomes included intravenous corticosteroid response and short‐ and long‐term colectomy. The reported positive predictive value of the scores ranged from 70 to 100% for their respective outcome.

Discussion

Multiple scores exist for the prediction of outcomes in patients with ASUC, although each has limitations. A new score that reflects the current standard of care is needed to inform risk stratification in patients with ASUC.
Sites of infrastructure, apprenticeship and possibilities for self: Locating Indonesia's missing women in representative politics
Authors: Siahaan Asima Yanty , Jakimow Tanya , Yumasdaleni  , Harahap Aida Fitria
Published: October 2023

Women are under‐represented in Indonesian legislatures, and those women who are elected are disproportionately from ‘elite’ backgrounds. This research sought to understand the conditions for women to succeed in politics in conditions of patriarchy and clientelist politics. Research in North Sumatera, Indonesia, revealed that many women did not make the conscious decision not to enter politics, but rather found that they had not established the required preconditions earlier enough in life. Patriarchal social norms and a transactional political culture frustrate women's ability to acquire these conditions, yet they are also subject to change. Interviews with women elected representatives and women who had never contested an election revealed three sites that are critical to women either acquiring the preconditions to contest elections, or frustrating that pathway: the household, the ‘community’ and religious/ethnic associations. We demonstrate how women's actions in these sites transform the conditions to make them more conducive to women's political participation.
Geography's lens, landscape architecture, and the green recovery
Authors: Smith Carl A.
Published: October 2023

In this article, I expound upon the recent claim that Geography is well placed to contribute to the global ‘green recovery’ by suggesting that landscape architects have the potential to be highly effective collaborators in this endeavour. Contemporary Geography represents a diverse array of sub‐fields coalescing around scale, space and place. Altogether, Geography provides a disciplinary lens that is multi‐scalar and can focus on any number of critical environmental and cultural concerns that resonate with green recovery discourse. At various times, landscape architecture has shared Geography's multi‐scalar and multifaceted lens, and through this complementary outlook, the disciplines have collaborated within mutual spaces such as ‘geodesign’, and through a to‐and‐fro of methods of practice and disciplinary reflection. However, ongoing discourse within landscape architecture describes self‐doubt around the consistency of its agency and capacity to engage with the critical challenges of the climate crisis and social inequity. Elsewhere, this has been attributed to landscape architecture's loss of professional territory to other practices of spatial design, and a reverse into scenography. Here I articulate the concern that much landscape architectural practice appears to intermittently misplace the scale and scope that is akin to Geography's lens and that, although this has stymied the discipline, there are recent indications that landscape architecture is hungry for relevance and ready to re‐engage with the necessary space, place, and scale. This article, then, looks to provide are a reminder of the potential to be found in landscape architecture and whet the appetite for green recovery collaboration.
Milk as a diagnostic fluid to monitor viral diseases in dairy cattle
Authors: Brito B , Hick P
Published: October 2023

Background

Infectious viral diseases in dairy cattle have substantial implications for milk production, quality and overall animal health. Diagnostic tools providing reliable results are crucial for effective disease control at the farm and industry level. Pooled or bulk tank milk (BTM) can be used as a cost‐effective aggregate sample to assess herd disease status in dairy farms.

Findings

Detection of pathogens or specific antibodies in milk can be used for monitoring endemic diseases within‐farm, region or country‐level disease surveillance and to make informed decisions on farm management. The suitability of assays applied to pooled milk samples relies on validation data of fit‐for‐purpose tests to design an optimal testing strategy. Diverse approaches and variable scope of studies determining test accuracy need to be critically appraised before sourcing the parameters to design sampling strategies and interpreting surveys. Determining if BTM or pooled milk is the best approach for a disease management programme should carefully consider several aspects that will impact the accuracy and interpretation, for example, the size of the lactating herd, the risk of infection in the lactating and non‐lactating groups, the expected within‐herd prevalence, the duration of infection, the duration and concentration of antibodies in milk and use of vaccination.

Conclusions

There are examples of tests on BTM samples providing efficient assessments of the herd disease status and supporting disease control programmes for viral diseases. However, challenges arise in pooled milk testing due to the need for accurate estimates of the imperfect sensitivity and specificity of the assays. Integration of new biotechnologies could enhance multiplexing and data interpretation for comprehensive surveillance. The development of highly sensitive assays is necessary to meet the demands of larger dairy herds and improve disease detection and assessment.
Attitudes towards deprescribing in geriatric psychiatry: A survey among older psychiatric outpatients
Authors: Lundby Carina , Nielsen Marianne , Simonsen Trine , Galsgaard Stine , Haastrup Maija Bruun , Ravn‐Nielsen Lene Vestergaard , Pottegård Anton
Published: October 2023

Understanding the patient perspective is a significant part of the deprescribing process. This study aimed to explore the attitudes of older patients with psychiatric disorders towards deprescribing. A total of 72 of psychiatric outpatients (68% women; median age 76 years) completed the validated Danish version of the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Patients used a median of eight medications (interquartile range 6–12), with 88%, 49% and 24% using antidepressants, antipsychotics and anxiolytics, respectively. Fifty‐one percent of patients reported an intrinsic desire to stop one of their medications, while 92% would be willing to stop one on their physician's advice. Seventy‐five percent of patients would be worried about missing out on future benefits following deprescribing and 37% had previous bad deprescribing experiences. Use of ≥8 regular medications was associated with more concerns about stopping medication and greater perceived burden of using medication, while use of antipsychotics was not associated with any differences in rPATD factor scores. It is crucial for health care professionals to be aware of patients' specific concerns and past experiences to promote a patient‐centred deprescribing approach that takes into account the needs and preferences of older patients with psychiatric disorders.
Effects of metalinguistic corrective feedback on novice EFL students' digital game‐based grammar learning performances, perceptions and behavioural patterns
Authors: Liu Lo‐An , Hwang Gwo‐Jen
Published: October 2023

Learning with digital games has gained considerable popularity. While digital game‐based learning has the potential to improve learners' language learning achievement, engagement and motivation, there still exists a gap when it comes to providing effective feedback to learners within these games. Conventional digital games generally provide learners with immediate error correction, which could be of less help to learners when learning complex language content, such as grammar. In this study, a metalinguistic corrective feedback‐based digital gaming approach is proposed. Moreover, an experiment was conducted to explore how digital games, combined with metalinguistic corrective feedback, affect novice English learners' grammar learning achievement, as well as their perceptions of learning motivation, self‐efficacy and flow experience during learning. Lag sequential analysis was also applied to identify differences in the behavioural patterns of the two groups. A total of 76 university students participated in this study. The experimental group learned the target grammar via digital games combined with metalinguistic corrective feedback, whereas the control group learned with digital games combined with regular feedback, which is immediate error correction. The results suggest that metalinguistic corrective feedback has a positive impact on students' grammar learning, and benefits students who have lower initial intrinsic motivation and self‐efficacy. Different feedback types also lead to diverse learning behaviours.

Practitioner notes

What is already known about this topic

Feedback has substantial potential within the domain of digital game‐based learning.

Proper instructional theories and strategies should be considered when designing digital games to guide language learners to engage in meaningful learning.

What this paper adds

Feedback that directs learners to rectify errors by emphasizing grammatical rules and language structures is referred to as metalinguistic corrective feedback. This study proposed a metalinguistic corrective feedback‐based digital gaming approach to explore the efficacy of such feedback in digital games.

In addition to learning outcomes, learners' learning behaviour patterns were also recorded and analysed in this study.

Implications for practice and/or policy

It is potentially worth integrating metalinguistic corrective feedback into digital games to facilitate language learners' learning performances and perceptions.

Metalinguistic corrective feedback has the potential to support learners with lower self‐efficacy and motivation to learn complicated language content.

Future research can integrate different feedback models into digital games and investigate their effectiveness.
Upgrading financial education by adding Python‐based personalized financial projection: A randomized control trial
Authors: Zhu Alex Yue Feng
Published: October 2023

Research has shown that even though standardized financial education has gained prevalence to promote financial literacy over the past decade, it has had little effect on personal financial planning. The present study used a randomized control trial to examine the effectiveness of a Python‐based personalized financial projection on young working adults in Hong Kong, to examine if and how this approach improves their financial planning. Participants assigned to the experiment group received standardized financial education and Python‐based financial projections, while those in the control group only received standardized financial education. The assessment based on the two‐wave data showed that Python‐based financial projection promoted future time perspectives, reduced temporal discounting, and improved financial planning via the full mediation of promoting financial attitudes. Although numerous applications for personal financial planning exist (such as Wallet, Walnut, Monefy, and Money View), our Python‐based financial projection stands out as the pioneering solution tailored for the hands‐on manipulation of programming code to effectively manage personal finances. Our findings suggest a new track to upgrade personalized financial projection and standardized financial education and contribute generously to the development of personal finance education.

Practitioner notes

What is already known about this topic

Standardized financial education promotes objective financial knowledge.

Standardized financial education has a limited effect on personal financial planning.

Classical personalized financial projection promotes personal financial planning, but the effect is small.

What this paper adds

Introduction of a novel Python‐based personalized financial projection by manipulating projection code.

The evidence that Python‐based personalized financial projection more strongly improves personal financial planning, compared to the classical personalized financial projection.

The evidence why Python‐based personalized financial projection can improve personal financial planning.

Implications for practice and/or policy

Facilitating engagement of young working adults with personalized finance planning through the use of a Python‐based intervention.

Integrating Python‐based personalized financial projection into standardized financial education in the school setting.

Using Python as the platform to design more topic‐specific financial education module.
Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia
Authors: Stimpson Madeleine L. , Wolf Julia , Charbit Bruno , Williams Emily L. , Lait Philippa J. P. , Schewitz‐Bowers Lauren P. , Lee Richard W. J. , Bradbury Charlotte A.
Published: October 2023

Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil). We also demonstrate that glucocorticoid treatment impairs Breg interleukin‐10 production via an indirect T‐cell‐mediated mechanism.
Beyond compliance: harmonising research and husbandry practices to improve experimental reproducibility using fish models
Authors: Paull Gregory C. , Lee Carole J. , Tyler Charles R.
Published: October 2023

Reproducibility in animal research is impacted by the environment, by husbandry practices in the laboratory and by the animals' provenance. These factors, however, are often not adequately considered by researchers. A disconnect between researchers and animal care staff can result in inappropriate housing and husbandry decisions for scientific studies with those animals. This is especially the case for the research in neuro‐behaviour, epigenetics, and the impact of climate change, as heritable phenotypic, behavioural or physiological changes are known to result from the animals' environmental housing, husbandry, provenance and prior experience. This can lead to greater variation (even major differences) in data outcomes among studies, driving scientific uncertainties. Herein, we illustrate some of the endpoints measured in fish studies known to be intrinsically linked to the environment and husbandry conditions and assess the significance of housing and husbandry practice decisions for research adopting these endpoints for different fish species. We highlight the different priorities and challenges faced by researchers and animal care staff and how harmonising their activities and building greater understanding of how husbandry practices affect the fish will improve reproducibility in research outcomes. We furthermore illustrate how improving engagement between stakeholders, including regulatory bodies, can better underpin fish husbandry decisions and where researchers could help to drive best husbandry practices through their own research with fish models.
Convergence and divergence in science and practice of urban and rural forest restoration
Authors: Romanelli João P. , Piana Max R. , Klaus Valentin H. , Brancalion Pedro H. S. , Murcia Carolina , Cardou Françoise , Wallace Kiri Joy , Adams Cristina , Martin Philip A. , Burton Philip J. , Diefenderfer Heida L. , Gornish Elise S. , Stanturf John , Beyene Menilek , Santos João Paulo Bispo , Rodrigues Ricardo R. , Cadotte Marc W.
Published: October 2023

Forest restoration has never been higher on policymakers' agendas. Complex and multi‐dimensional arrangements across the urban–rural continuum challenge restorationists and require integrative approaches to strengthen environmental protection and increase restoration outcomes. It remains unclear if urban and rural forest restoration are moving towards or away from each other in practice and research, and whether comparing research outcomes can help stakeholders to gain a clearer understanding of the interconnectedness between the two fields. This study aims to identify the challenges and opportunities for enhancing forest restoration in both urban and rural systems by reviewing the scientific evidence, engaging with key stakeholders and using an urban–rural forest restoration framework. Using the Society for Ecological Restoration's International Principles as discussion topics, we highlight aspects of convergence and divergence between the two fields to broaden our understanding of forest restoration and promote integrative management approaches to address future forest conditions. Our findings reveal that urban and rural forest restoration have convergent and divergent aspects. We emphasise the importance of tailoring goals and objectives to specific contexts and the need to design different institutions and incentives based on the social and ecological needs and goals of stakeholders in different regions. Additionally, we discuss the challenges of achieving high levels of ecological restoration and the need to go beyond traditional ecology to plan, implement, monitor, and adaptively manage restored forests. We suggest that rivers and watersheds could serve as a common ground linking rural and urban landscapes and that forest restoration could interact with other environmental protection measures. We note the potential for expanding the creative vision associated with increasing tree‐containing environments in cities to generate more diverse and resilient forest restoration outcomes in rural settings. This study underscores the value of integrative management approaches in addressing future forest conditions across the urban–rural continuum. Our framework provides valuable insights for policymakers, researchers, and decision‐makers to advance the field of forest restoration and address the challenges of restoration across the urban–rural continuum. The rural–urban interface serves as a convergence point for forest restoration, and both urban and rural fields can benefit from each other's expertise.
The knockdown of lncRNA DLGAP1‐AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR‐451a/HK2 axis
Authors: Zheng Changjun , Li Ronghang , Zheng Shuang , Fang Hongjuan , Xu Meng , Zhong Lei
Published: October 2023

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1‐AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT‐qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1‐AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial–mesenchymal transition (EMT)‐related markers. The proliferation of OS cells was determined using a CCK‐8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR‐451a, HK2, and DLGAP1‐AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1‐AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1‐AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1‐AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1‐AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1‐AS2 overexpression accelerated the progression of OS. We further found that DLGAP1‐AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1‐AS2 bound to miR‐451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1‐AS2/miR‐451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1‐AS2 upregulated HK2 expression by sponging miR‐451a to accelerate OS development.
Ethyl gallate concurrent administration protects against acetaminophen‐induced acute liver injury in mice: An in vivo and in silico approach
Authors: Ezhilarasan Devaraj , Shree Harini Karthik , Karthick Munusamy , Selvaraj Chandrabose
Published: October 2023

Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti‐inflammatory, and anti‐microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP‐induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N‐acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor‐α, interleukin‐1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5‐trihydroxybenzoic acid region. These effects of EG against APAP‐induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti‐inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.
Current insights and molecular docking studies of HIV‐1 reverse transcriptase inhibitors
Authors: Singh Ankit Kumar , Kumar Adarsh , Arora Sahil , Kumar Raj , Verma Amita , Khalilullah Habibullah , Jaremko Mariusz , Emwas Abdul‐Hamid , Kumar Pradeep
Published: October 2023

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non‐nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti‐HIV drugs. Zidovudine, didanosine, and stavudine are FDA‐approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA‐approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV‐1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA‐approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).
Assessment of testicular function in boys and adolescents
Authors: Lopez Dacal Jimena , Castro Sebastián , Suco Sofía , Correa Brito Lourdes , Grinspon Romina P. , Rey Rodolfo A.
Published: October 2023

Objective

The hypothalamic‐pituitary‐testicular axis is characterised by the existence of major functional changes from its establishment in fetal life until the end of puberty. The assessment of serum testosterone and gonadotrophins and semen analysis, typically used in the adult male, is not applicable during most of infancy and childhood. On the other hand, the disorders of gonadal axis have different clinical consequences depending on the developmental stage at which the dysfunction is established. This review addresses the approaches to evaluate the hypothalamic‐pituitary‐testicular axis in the newborn, during childhood and at pubertal age.

Design

We focused on the hormonal laboratory and genetic studies as well as on the clinical signs and imaging studies that guide the aetiological diagnosis and the functional status of the gonads.

Results

Serum gonadotrophin and testosterone determination is useful in the first 3–6 months after birth and at pubertal age, whereas AMH and inhibin B are useful biomarkers of testis function from birth until the end of puberty. Clinical and imaging signs are helpful to appraise testicular hormone actions during fetal and postnatal life.

Conclusions

The interpretation of results derived from the assessment of hypothalamic‐pituitary‐testicular in paediatric patients requires a comprehensive knowledge of the developmental physiology of the axis to understand its pathophysiology and reach an accurate diagnosis of its disorders.
Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study
Authors: Tarçın Gürkan , Çatlı Gönül , Çetinkaya Semra , Eren Erdal , Kardelen Aslı Derya , Akıncı Ayşehan , Böber Ece , Kara Cengiz , Yıldırım Ruken , Er Eren , Polat Recep , Özhan Bayram , Yıldız Melek , Kor Yılmaz , Evliyaoğlu Olcay , Dündar Bumin , Ercan Oya
Published: October 2023

Objective

Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases.

Design

National, multicenter and retrospective study.

Patients

All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow‐up data of the children with CD between December 2015 and March 2017.

Measurements

Diagnostic tests of CD and tumour size.

Results

Thirty‐four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late‐night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow‐up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure.

Conclusions

Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one‐third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow‐up after surgery.
Prophylactic antibiotics in septoplasty with intranasal septal splints: A comparative analysis
Authors: Zavdy Ofir , Nakache Gabriel , Alkan Uri , Hazan Alain , Reifen Ella , Ritter Amit
Published: October 2023

Objectives

Postoperative antibiotic therapy is a common practice following septoplasty with intra‐septal splints placement (ISS), even though there is a lack of evidence to support it. We sought to investigate the role of antibiotic therapy in septal surgeries with the placement of ISS.

Design

A retrospective comparative study was conducted using the electronic charts of adult patients who underwent septoplasty with the placement of ISS with or without turbinate reduction. Nasal cultures were taken routinely during surgery as part of the department's protocol for monitoring infectious diseases. The ISS were also routinely examined for the presence of bacteria after their removal on the eighth day following surgery.

Setting

A large otolaryngology department in a tertiary medical center.

Participants

Adult patients who underwent septoplasty in our institution.

Main outcome measures

We analyzed all post‐operative infections to search for risk factors in the cohort.

Results

Post‐operative infection rates following septoplasty with ISS were low at 6%, which is consistent with previously published rates. Infection rates were significantly higher in patients who were not treated with antibiotics (OR = 8.2, 95%CI: 1.63–41.1; p = .01, φ = 0.04). Diabetes was associated with an increased risk of postoperative infection regardless of prophylactic antibiotic therapy (OR = 5.2, 95%CI: 1.15–23.5; p = .032, φ = .04). The detection of Klebsiella pneumonia before surgery was associated with an increased rate of postoperative infection (OR = 16.6, 95%CI: 3.02–91.54; p = .001, φ = 0.12).

Conclusions

Patients undergoing septoplasty with the placement of ISS are at increased risk of gram‐negative bacterial colonisation, and development of postoperative nasal infection. A single preoperative dose of IV antibiotic therapy should be considered a potential prophylactic option for septoplasty with ISS.
Prevention and treatment of cisplatin‐induced ototoxicity in adults: A systematic review
Authors: Correa‐Morales Juan Esteban , Giraldo‐Moreno Sara , Mantilla‐Manosalva Nidia , Cuellar‐Valencia Laura , Borja‐Montes Oscar Felipe , Bedoya‐Muñoz Lennis Jazmin , Iriarte‐Aristizábal María Fernanda , Quintero‐Muñoz Elias , Zuluaga‐Liberato Andrea Marcela
Published: October 2023

Objectives

Ototoxicity is a common disabling side effect of platinum‐based chemotherapy. This study aimed to assess the evidence on the management of platinum‐induced ototoxicity in adult cancer patients.

Methods

Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non‐pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.

Results

Nineteen randomised controlled trials and five quasi‐experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non‐pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D‐methionine) showed mild benefits in preventing cisplatin‐induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention‐related adverse effects, thereby limiting safety conclusions.

Conclusions

Current interventions have mild benefits in preventing cisplatin‐induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high‐quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Does broadband affect local economic outcomes less than we thought? Micro evidence from Louisiana
Authors: Wagner Gary A. , Lee Hyun Ji
Published: October 2023

High‐speed internet access is a core tenet of economic development strategies post‐COVID. While expanding access is linked to many positive benefits, evidence associating broadband to job growth and business formation is more mixed. This study expands the literature along several dimensions, most notably exploring how business download speeds affect employment, business formation, and survival at a microscale. Using conventional and Least Absolute Shrinkage and Selection Operator instrumental variables strategies, with terrain features as instruments, we find consistent evidence that broadband speeds stimulate local development. However, our estimates are 60%–65% smaller than those from recent studies, suggesting that broadband may be less beneficial than previously assumed.
The Relative Importance of Target and Judge Characteristics in Shaping the Moral Circle
Authors: Jaeger Bastian , Wilks Matti
Published: October 2023

People's treatment of others (humans, nonhuman animals, or other entities) often depends on whether they think the entity is worthy of moral concern. Recent work has begun to investigate which entities are included in a person's moral circle, examining how certain target characteristics (e.g., species category, perceived intelligence) and judge characteristics (e.g., empathy, political orientation) shape moral inclusion. However, the relative importance of target and judge characteristics in predicting moral inclusion remains unclear. When predicting whether a person will deem an entity worthy of moral consideration, how important is it to know who is making the judgment (i.e., characteristics of the judge), who is being judged (i.e., characteristics of the target), and potential interactions between the two factors? Here, we address this foundational question by conducting a variance component analysis of the moral circle. In two studies with participants from the Netherlands, the United States, the United Kingdom, and Australia (N = 836), we test how much variance in judgments of moral concern is explained by between‐target differences, between‐judge differences, and by the interaction between the two factors. We consistently find that all three components explain substantial amounts of variance in judgments of moral concern. Our findings provide two important insights. First, an increased focus on interactions between target and judge characteristics is needed, as these interactions explain as much variance as target and judge characteristics separately. Second, any theoretical account that aims to provide an accurate description of moral inclusion needs to consider target characteristics, judge characteristics, and their interaction.