bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in characteristics and conservation values of plant communities on abandoned agricultural lands with and without fires
Authors: Abella Scott R. , Schetter Timothy A.
Published: December 2021

Question

Which plant community characteristics most consistently vary with prior land use?

Location

Oak Openings Preserve, Ohio, USA.

Methods

In 2020, we measured plant communities on 22 sites encompassing three prior land uses: (a) contemporary Quercus forests continuously forested since before the 1930s; (b) former agricultural lands, under cultivation in the 1930s and abandoned 70–80 years before our study and that were unburned; and (c) former agricultural lands also abandoned 70–80 years earlier and that were burned in 2013 prescribed fires. Among the three land uses, we compared 12 plant community variables, categorized into four groups characterizing different sets of community properties (structure, diversity, composition, and conservation values).

Results

A multivariate combination of the 12 community variables differed among all three land uses, each of the four categories of variables differed between at least two land uses, and eight of 12 individual variables differed between at least two land uses. Community structure displayed a gradient of decreasing tree canopy and understorey plant cover and increasing lichen–moss cover from continuously forested to unburned and burned formerly cultivated sites. Understorey plant species richness did not vary with land use, but species diversity was higher on cultivated sites, irrespective of fire history. While all three land uses now contain Quercus tree overstories, each land use exhibited unique understorey species composition. Only formerly cultivated sites contained state‐listed endangered species. Cultivated sites had a lower proportion of native species cover than did continuously forested sites, but native species still comprised over 90% of the plant cover on cultivated sites. Compared with continuous forests, the soil organic layer (O horizon) was five times thinner and loss on ignition in the 0–15 cm mineral soil 49% (unburned) and 66% (burned) lower on previously cultivated sites.

Conclusions

Community characteristics varied in their sensitivity to land use history, with species composition among the most sensitive to prior land use. A dense sapling layer of Acer rubrum forming in long‐unburned Quercus forests across much of eastern North America was absent in our study on formerly cultivated sites, possibly due to dry, infertile soil. From a restoration and conservation standpoint of the study region's pre‐settlement, frequently burned and open savannas and woodlands, previously cultivated sites may be easier to keep open via prescribed fire. Moreover, perhaps precisely because much of the flora historically developed in open savannas and woodlands which previously cultivated sites on the contemporary landscape most closely mimicked, previously cultivated sites presently contain higher species diversity and more conservation priority species than do continuously forested sites.
The impact of treatment choices on potential drug–drug interactions in hypertensive patients
Authors: Perić Aneta , Udilović Ana , Dobrić Silva , Vezmar Kovačević Sandra
Published: December 2021

Aims

The aim of this study was to analyse potential drug–drug interactions (pDDIs) and their potential adverse drug reactions (ADRs) among hypertensive patients. Moreover, we investigated the possibility of reducing pDDIs with different treatment choices.

Methods

This was a cross‐sectional study including all outpatients with hypertension and two or more medications, treated in a university hospital in Serbia. Lexicomp Interact (Lexi‐Comp, Inc., Hudson, OH) was used for identification of pDDIs and potential ADRs. Treatment choices were explored according to patient characteristics, treatment guidelines and the interacting potential of drugs. Data were analysed using descriptive analysis and multiple logistic regression.

Results

A total of 350 patients were included in this study, with average age (77 [36–98] years and 6.1 [2.5]) medications. The majority of patients (86.0%) had at least one clinically significant pDDI, and the average was 3.78 (3.90) (range 1–25). Suggestions for treatment change aimed mainly at eliminating drug duplications, reducing the use of thiazide diuretics, sulfonylureas, alpha‐lipoic acid and pentoxifylline and increasing the use of calcium‐channel blockers, when appropriate. pDDIs would have decreased to 2.10 (2.52), P <.001, yet male gender, ≥6 medications, cardiovascular diseases, diabetes, benign prostatic hyperplasia, would be predictive of two or more pDDIs. The main potential adverse outcomes of pDDIs were hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis.

Conclusion

Careful choice of drugs can reduce but not eliminate pDDIs and their potential ADRs in hypertensive patients. Close monitoring for hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis is necessary.
Bipolar disorder and regretted behavior in relation to use of social media and online dating
Authors: Rydahl Klara F. K. , Brund René B. K. , Medici Clara R. , Straarup Krista M. N. , Straszek Sune P. V. , Østergaard Søren D.
Published: December 2021

Objectives

Individuals with bipolar disorder are prone to risk‐taking behavior that is subsequently regretted. Here, we investigated whether this also occurs in relation to the use of social media and online dating.

Methods

A questionnaire‐based survey focusing on the use of social media and online dating was conducted among individuals attending an outpatient clinic for bipolar disorder, and among individuals attending two general practices in the same region (controls). The association between bipolar disorder and self‐reported regretted behavior on social media/online dating sites was investigated using logistic regression with adjustment for age and sex.

Results

A total of 124 individuals with bipolar disorder and 196 individuals without affective disorder from the general practices (controls) formed the study sample. Among the individuals with bipolar disorder who used social media, 66% reported regretted behavior as a consequence of this use, whereas only 31% of the controls reported such behavior. The corresponding numbers for individuals who used online dating were 65% for those with bipolar disorder and 31% for the controls. Following adjustment for age and sex, bipolar disorder was associated with elevated risk of regretted behavior in relation to the use of both social media (adjusted odds ratio: 3.6, 95% CI: 2.2, 5.9) and online dating (adjusted odds ratio: 4.1, 95% CI: 2.1, 8.0).

Conclusions

These findings suggest that risk‐taking behavior and subsequent regret among individuals with bipolar disorder extend to social media and online dating. Cautious use of these platforms may be particularly relevant for individuals with bipolar disorder.
Implementing Essential Coaching for Every Mother during the COVID‐19 pandemic: A pre‐post intervention study
Authors: Dol Justine , Aston Megan , Grant Amy , McMillan Douglas , Tomblin Murphy Gail , Campbell‐Yeo Marsha
Published: December 2021

Objectives

The primary objective of this project was to evaluate the preliminary impact of Essential Coaching for Every Mother on maternal self‐efficacy, social support, postpartum anxiety, and postpartum depression. The secondary objective was to explore the acceptability of the Essential Coaching for Every Mother program provided during the COVID‐19 pandemic.

Methods

A prospective pre‐post study was conducted with first‐time mothers in Nova Scotia, Canada, between July 15 and September 19, 2020. Participants completed a self‐report survey at enrollment (after birth) and 6 weeks postpartum. Various standardized measures were used, and qualitative feedback on the program was also collected. Paired t tests were carried out to determine changes from baseline to follow‐up on psychosocial outcomes, and qualitative feedback was analyzed through thematic analysis.

Results

A total of 88 women enrolled. Maternal self‐efficacy increased between baseline (B) and follow‐up (F) (B: 33.33; F: 37.11, P = 0.000), whereas anxiety (STAI) declined (B: 38.49; F: 34.79, P = 0.004). In terms of acceptability, 89% of participants felt that the number of messages was just right, 84.5% felt the messages contained all the information they needed relative to caring for a newborn, and 98.8% indicated they would recommend this program to other new mothers.

Conclusions

Essential Coaching for Every Mother may play a role in increasing maternal self‐efficacy and decreasing anxiety, although future work with a control group is needed to delineate the true effects of the program. Overall, mothers were satisfied with the Essential Coaching for Every Mother program and would recommend it for other mothers, during the COVID‐19 pandemic and beyond.
Elevated intraocular pressure in children with acute lymphoblastic leukaemia: A prospective study
Authors: Barzilai‐Birenboim Shlomit , Elitzur Sarah , Nirel Ronit , Ehrenberg Miriam , Zahavi Alon , Avrahami Galia , Gabbay Itay E. , Gilad Gil , Dotan Gad , Izraeli Shai , Daood Rabeea Haj , Geffen Noa
Published: December 2021

Most childhood acute lymphoblastic leukaemia (ALL) protocols include high‐dose steroid therapy. However, the known potential of high‐dose steroids to significantly elevate intraocular pressure (IOP) and lead to glaucomatous optic neuropathy has not been intensively investigated in children with ALL. Moreover, as children with ALL do not routinely undergo IOP measurements, the need for IOP monitoring and therapy is unknown. We prospectively measured IOP in 90 children with newly diagnosed ALL attending a tertiary paediatric haematology/oncology centre, at diagnosis and at the middle and end of induction therapy. Ocular hypertension (IOP > 21 mm Hg) at any time point was documented in 64 children (71%), and the prevalence increased during induction. Thirty‐six children (40%) had elevated IOP at ALL diagnosis before therapy initiation, and stratification to non‐standard ALL was a risk factor. IOP reduction therapy was administered to 13 children (14%); none required surgery. Values normalised in all cases. On multivariate logistic regression analysis, dexamethasone therapy was a significant risk factor for ocular hypertension. High body mass index was an additional risk factor in children with elevated IOP at ALL diagnosis. Routine evaluation of IOP during steroid therapy is very important in children with ALL to ensure early intervention which may prevent permanent ocular damage.
Ruthenium 360 and mitoxantrone inhibit mitochondrial calcium uniporter channel to prevent liver steatosis induced by high‐fat diet
Authors: Zhang Zhiwang , Luo Zupeng , Yu Lin , Xiao Yang , Liu Siqi , ALuo Zhier , Ma Zeqiang , Huang Liang , Xiao Lianggui , Jia Mengting , Song Ziyi , Zhang Haojie , Li Yixing , Zhou Lei
Published: December 2021

Background and Purpose

Non‐alcoholic fatty liver disease (NAFLD) affects over 25% of the general population and lacks an effective treatment. Recent evidence implicates disrupted mitochondrial calcium homeostasis in the pathogenesis of hepatic steatosis.

Experimental Approach

In this study, mitochondrial calcium uniporter (MCU) was inhibited through classical genetic approaches, viral vectors or small molecule inhibitors in vivo to study its role in hepatic steatosis induced by high‐fat diet (HFD). In vitro, MCU was overexpressed or inhibited to change mitochondrial calcium homeostasis, endoplasmic reticulum–mitochondrial linker was adopted to increase mitochondria‐associated membranes (MAMs) and MICU1‐EF hand mutant was used to decrease the sensitivity of mitochondrial calcium uptake 1 (MICU1) to calcium and block MCU channel.

Key Results

Here, we found that inhibition of liver MCU by AAV virus and classical genetic approaches can prevent HFD‐induced liver steatosis. MCU regulates mitochondrial calcium homeostasis and affects lipid accumulation in liver cells. In addition, a HFD in mice enlarged the MAM. The high‐calcium environment produced by MAM invalidated the function of MICU1 and led to persistent open of MCU channels. Therefore, it caused mitochondrial calcium overload and liver fat deposition. Inhibition of MAM and MCU alleviated HFD‐induced hepatic steatosis. MCU inhibitors (Ru360 and mitoxantrone) can block MCU channels and reduce mitochondrial calcium levels. Intraperitoneal injection of MCU inhibitors (0.01‐μM·kg−1 bodyweight) can alleviate HFD‐induced hepatic steatosis.

Conclusion and Implications

These findings provide molecular insights into the way HFD disrupts mitochondrial calcium homeostasis and identify MCU as a promising drug target for the treatment of hepatic steatosis.
Amlodipine, an anti‐hypertensive drug, alleviates non‐alcoholic fatty liver disease by modulating gut microbiota
Authors: Li Yang , Zhao Danyang , Qian Minyi , Liu Jun , Pan Chuyue , Zhang Xinxin , Duan Xubin , Zhang Yufei , Jia Wenxin , Wang Lirui
Published: December 2021

Background and Purpose

Non‐alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s.

Experimental Approach

Mice were fed with high‐fat diet (HFD) and 0.05% N‐nitro‐L‐arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum.

Key Results

Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate‐ and amlodipine aspartate‐treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD‐fed hypertensive mice.

Conclusion and Implications

Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.
Wildlife predation by dogs in Madagascar
Authors: Merz Leandra , Kshirsagar Akhil R. , Rafaliarison Radoniaina R. , Rajaonarivelo Tsiky , Farris Zach J. , Randriana Zoavina , Valenta Kim
Published: December 2021

Human–wildlife conflicts are increasing in number and intensity making conflict mitigation and coexistence a top priority for wildlife conservation. Domesticated dogs (Canis lupus familiaris) can mitigate or exacerbate human–wildlife conflict leading to positive and negative impacts on both humans and wildlife. However, the human–dog–wildlife interface is not well understood, particularly in biodiversity hot spots. Madagascar is a tropical biodiversity hot spot with many rare and threatened species of high conservation concern. Here we assess wildlife predation by free‐roaming dogs in communities surrounding Andasibe–Mantadia and Ranomafana National Parks in eastern Madagascar using surveys of dog owners living adjacent to protected areas. Nearly half of survey respondents reported that their dog(s) had killed wildlife. Dogs that spent more time away from home, that traveled to the forest more frequently, that had killed domestic livestock, and that were owned for hunting were more likely to have killed wildlife. Dogs that were fed were approximately 20% less likely to have killed wildlife than dogs that were not fed. Keeping dogs restrained more often and providing food are therefore likely to reduce wildlife predation by dogs provided these are socially acceptable options. Additionally, we found spatial variation in wildlife predation by dogs both between and within our two study regions. These results can help conservation organizations develop targeted, effective interventions appropriately tailored to the local context and prioritize specific areas with higher wildlife predation by dogs.

Abstract in French is available with online material.
Hydroxamates as a potent skeleton for the development of metallo‐β‐lactamase inhibitors
Authors: Chigan Jia‐Zhu , Li Jia‐Qi , Ding Huan‐Huan , Xu Yin‐Sui , Liu Lu , Chen Cheng , Yang Ke‐Wu
Published: December 2021

Bacterial resistance caused by metallo‐β‐lactamases (MβLs) has become an emerging public health threat, and the development of MβLs inhibitor is an effective way to overcome the resistance. In this study, thirteen novel O‐aryloxycarbonyl hydroxamates were constructed and assayed against MβLs. The obtained molecules specifically inhibited imipenemase‐1 (IMP‐1) and New Delhi metallo‐β‐lactamase‐1, exhibiting an IC50 value in the range of 0.10–18.42 and 0.23–22.33 μM, respectively. The hydroxamate 5 was found to be the most potent inhibitor, with an IC50 of 0.1 and 0.23 μM using meropenem and cefazolin as substrates. ICP‐MS analysis showed that 5 did not coordinate to the Zn(II) ions at the active site of IMP‐1, while the rapid dilution, thermal shift and MALDI‐TOF assays revealed that the hydroxamate formed a covalent bond with the enzyme. Cytotoxicity assays indicated that the hydroxamates have low toxicity in MCF‐7 cells. This work provided a potent scaffold for the development of MβLs inhibitors.
How frequent is burnout among informal caregivers of disabled children? Findings from a cross‐sectional study in Karachi, Pakistan
Authors: Zeeshan Mehwish , Shaikh Shiraz , Ahmer Zaeema
Published: December 2021

Background

Informal caregivers are those who care for children without getting paid. They are often more prone to stress due to their extra daily tasks which leads to burnout. This study aimed to determine the frequency and associated risk factors of burnout among informal caregivers of children with disabilities in Karachi.

Methodology

A cross‐sectional study was done in 10 rehabilitation institutes of Karachi with 310 mothers of children with disabilities from infancy till 18 years of age in 2019. Pretested questionnaire was administered to collect data in which 31 mothers were interviewed through convenience sampling from each rehabilitation institute. To assess burnout, the Maslach Burnout Inventory (MBI) was used. Association of different variables of study participants with the scores of its three subdimensions, Emotional Exhaustion (EE), Depersonalization (DP) and Personal Accomplishment (PA), were analysed using linear regression modelling.

Results

Mean EE score was high in 6.5% of the mothers while PA scores were low in 58.7% of the mothers. High EE with low PA (defined by our team as ‘burnout’) was found in 4.2% of the mothers, with none of them reporting high levels of DP. Linear regression analysis significantly predicted higher EE scores of mothers with more than one disabled child while lower EE scores were significantly predicted in highly educated mothers and mothers who spent more time in caregiving. Higher PA scores were also significantly predicted for highly educated mothers. DP scores were significantly predicted to be higher in mothers who had highly educated husband/guardian, employed mothers and those living in joint families whereas they were significantly predicted to be lower in highly educated mothers.

Conclusion

We have identified that mothers who are less educated, have more than one child with disability and who live in joint families will need extra support and input to prevent burnout.
Kynurenic acid in neurodegenerative disorders—unique neuroprotection or double‐edged sword?
Authors: Ostapiuk Aleksandra , Urbanska Ewa M.
Published: December 2021

Aims

The family of kynurenine pathway (KP) metabolites includes compounds produced along two arms of the path and acting in clearly opposite ways. The equilibrium between neurotoxic kynurenines, such as 3‐hydroxykynurenine (3‐HK) or quinolinic acid (QUIN), and neuroprotective kynurenic acid (KYNA) profoundly impacts the function and survival of neurons. This comprehensive review summarizes accumulated evidence on the role of KYNA in Alzheimer's, Parkinson's and Huntington's diseases, and discusses future directions of potential pharmacological manipulations aimed to modulate brain KYNA.

Discussion

The synthesis of specific KP metabolites is tightly regulated and may considerably vary under physiological and pathological conditions. Experimental data consistently imply that shift of the KP to neurotoxic branch producing 3‐HK and QUIN formation, with a relative or absolute deficiency of KYNA, is an important factor contributing to neurodegeneration. Targeting specific brain regions to maintain adequate KYNA levels seems vital; however, it requires the development of precise pharmacological tools, allowing to avoid the potential cognitive adverse effects.

Conclusions

Boosting KYNA levels, through interference with the KP enzymes or through application of prodrugs/analogs with high bioavailability and potency, is a promising clinical approach. The use of KYNA, alone or in combination with other compounds precisely influencing specific populations of neurons, is awaiting to become a significant therapy for neurodegenerative disorders.
Perception of Happening: How the Brain Deals with the No‐History Problem
Authors: White Peter A.
Published: December 2021

In physics, the temporal dimension has units of infinitesimally brief duration. Given this, how is it possible to perceive things, such as motion, music, and vibrotactile stimulation, that involve extension across many units of time? To address this problem, it is proposed that there is what is termed an “information construct of happening” (ICOH), a simultaneous representation of recent, temporally differentiated perceptual information on the millisecond time scale. The main features of the ICOH are (i) time marking, semantic labeling of all information in the ICOH with ordinal temporal information and distance from what is informationally identified as the present moment, (ii) vector informational features that specify kind, direction, and rate of change for every feature in a percept, and (iii) connectives, information relating vector informational features at adjacent temporal locations in the ICOH. The ICOH integrates products of perceptual processing with recent historical information in sensory memory on the subsecond time scale. Perceptual information about happening in informational sensory memory is encoded in semantic form that preserves connected semantic trails of vector and timing information. The basic properties of the ICOH must be supported by a general and widespread timing mechanism that generates ordinal and interval timing information and it is suggested that state‐dependent networks may suffice for that purpose. Happening, therefore, is perceived at a moment and is constituted by an information structure of connected recent historical information.
Endogenous metabolic markers for predicting the activity of dihydropyrimidine dehydrogenase
Authors: Kang Jihyun , Kim Andrew HyoungJin , Jeon Inseung , Oh Jaeseong , Jang In‐Jin , Lee SeungHwan , Cho Joo‐Youn
Published: December 2021

Five‐fluorouracil (5‐FU) is a chemotherapeutic agent that is mainly metabolized by the rate‐limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5‐FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into two groups based on DHU/U ratio. The calculated DHU/U ratios ranged from 0.52 to 7.12, and the two groups were classified into the 10th percentile and 90th percentile for untargeted metabolomics analysis using liquid chromatography‐quantitative time‐of‐flight‐mass spectrometry. A total of 4440 compounds were detected and filtered out based on a coefficient of variation below 30%. Our results revealed that six metabolites differed significantly between the high activity group and low activity group (false discovery rate q‐value < 0.05). Uridine was significantly higher in the low DPD activity group and is a precursor of U involved in pyrimidine metabolism; therefore, we speculated that DPD deficiency can influence uridine levels in plasma. Furthermore, the cutoff values for detecting DPD deficient patients from previous studies were unsuitable for Koreans. Our metabolomics approach is the first study that reported the DHU/U ratio distribution in healthy Korean subjects and identified a new biomarker of DPD deficiency.
The role of the IAC Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy and the ACR Breast Imaging‐Reporting and Data System in the evaluation of breast lesions
Authors: Sundar Preethi Muthusamy , Shanmugasundaram Sakthisankari , Nagappan Elango
Published: December 2021

Background

Stratification of breast lesions for appropriate management is achieved through an integration of clinical examination, imaging, and fine needle aspiration biopsy (FNAB). The current study aimed to evaluate the combined effectiveness of the widely used Breast Imaging‐Reporting and Data System (BI‐RADS) with the recently proposed International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology.

Methods

A retrospective analysis was done on all breast FNABs from 2016 through 2020. The cases were categorised according to the IAC Yokohama System. Histopathological correlation of the BI‐RADS and IAC Yokohama System was performed. The rate of malignancy (ROM) for each category of the BI‐RADS and IAC Yokohama System was calculated.

Results

The ROM values for categories I to V were 38%, 0.6%, 21.9%, 100%, and 97%, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of FNAB with category III assumed as malignant were 98.9%, 85%, 76.1%, 99.3%, and 89.5%, respectively. With category III assumed as benign, these indices were 90.8%, 98.9%, 97.5%, 95.7%, and 96.2%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of BI‐RADS were 91.5%, 81.9%, 72%, 95%, and 85.1%, respectively.

Conclusions

FNAB is still an indispensable test in the evaluation of breast lesions. The utilisation of the IAC Yokohama reporting system for breast cytology in conjunction with ACR BI‐RADS aids in better stratification of lesions.
Mutualistic coupling of vocabulary and non‐verbal reasoning in children with and without language disorder
Authors: Griffiths Sarah , Kievit Rogier A. , Norbury Courtenay
Published: December 2021

Mutualism is a developmental theory that posits positive reciprocal relationships between distinct cognitive abilities during development. It predicts that abilities such as language and reasoning will influence each other's rates of growth. This may explain why children with Language Disorders also tend to have lower than average non‐verbal cognitive abilities, as poor language would limit the rate of growth of other cognitive skills. The current study tests whether language and non‐verbal reasoning show mutualistic coupling in children with and without language disorder using three waves of data from a longitudinal cohort study that over‐sampled children with poor language at school entry (N = 501, 7–13 years). Bivariate Latent Change Score models were used to determine whether early receptive vocabulary predicted change in non‐verbal reasoning and vice‐versa. Models that included mutualistic coupling parameters between vocabulary and non‐verbal reasoning showed superior fit to models without these parameters, replicating previous findings. Specifically, children with higher initial language abilities showed greater growth in non‐verbal ability and vice versa. Multi‐group models suggested that coupling between language and non‐verbal reasoning was equally strong in children with language disorder and those without. This indicates that language has downstream effects on other cognitive abilities, challenging the existence of selective language impairments. Future intervention studies should test whether improving language skills in children with language disorder has positive impacts on other cognitive abilities (and vice versa), and low non‐verbal IQ should not be a barrier to accessing such intervention.
Current provision and HCP experiences of remote care delivery and diabetes technology training for people with type 1 diabetes in the UK during the COVID‐19 pandemic
Authors: Forde Hannah , Choudhary Pratik , Lumb Alistair , Wilmot Emma , Hussain Sufyan
Published: December 2021

Background

The COVID‐19 pandemic has led to the rapid implementation of remote care delivery in type 1 diabetes. We studied current modes of care delivery, healthcare professional experiences and impact on insulin pump training in type 1 diabetes care in the United Kingdom (UK).

Methods

The UK Diabetes Technology Network designed a 48‐question survey aimed at healthcare professionals providing care in type 1 diabetes.

Results

One hundred and forty‐three healthcare professionals (48% diabetes physicians, 52% diabetes educators and 88% working in adult services) from approximately 75 UK centres (52% university hospitals, 46% general and community hospitals), responded to the survey. Telephone consultations were the main modality of care delivery. There was a higher reported time taken for video consultations versus telephone (p < 0.001). Common barriers to remote consultations were patient familiarity with technology (72%) and access to patient device data (67%). We assessed the impact on insulin pump training. A reduction in total new pump starts (73%) and renewals (61%) was highlighted. Common barriers included patient digital literacy (61%), limited healthcare professional experience (46%) and time required per patient (44%). When grouped according to size of insulin pump service, pump starts and renewals in larger services were less impacted by the pandemic compared to smaller services.

Conclusion

This survey highlights UK healthcare professional experiences of remote care delivery. While supportive of virtual care models, a number of factors highlighted, especially patient digital literacy, need to be addressed to improve virtual care delivery and device training.
‘Is insulin right for me?’: Feasibility of a pilot randomised controlled trial and acceptability of a web‐based intervention to reduce psychological barriers to insulin therapy among adults with type 2 diabetes
Authors: Holmes‐Truscott Elizabeth , Holloway Edith E. , Husin Hanafi M. , Furler John , Hagger Virginia , Skinner Timothy C. , Speight Jane
Published: December 2021

Aims

Acceptable and accessible interventions are needed to address ‘psychological insulin resistance’, which is a common barrier to insulin uptake among adults with type 2 diabetes (T2D). Our aim was to test the feasibility of a randomised controlled trial (RCT) study design and acceptability of a theoretically grounded, psycho‐educational, web‐based resource to reduce negative insulin appraisals among adults with T2D.

Methods

A double‐blinded, parallel group, two‐arm pilot RCT (1:1), comparing intervention with active control (existing online information about insulin). Eligible participants were Australian adults with T2D, taking oral diabetes medications. Exclusion criteria: prior use of injectable medicines; being ‘very willing’ to commence insulin. Primary outcomes: study feasibility (recruitment ease, protocol fulfilment, attrition, data completeness); secondary outcomes: intervention acceptability (intervention engagement, user feedback) and likely efficacy (negative Insulin Treatment Appraisal Scale [ITAS] scores at follow‐up). Online surveys completed at baseline and 2 weeks.

Results

During 4‐week recruitment, 76 people expressed interest: 51 eligible and 35 enrolled (intervention = 17, control = 18; median[interquartile range] age = 62[53, 69] years; 17 women). Protocol fulfilment achieved by 26 (74%) participants (n = 13 per arm), with low participant attrition (n = 6, 17%). Intervention acceptability was high (>80% endorsement, except format preference = 60%). ITAS negative scores differed between‐groups at follow‐up (M diff = −6.5, 95% confidence interval: −10.7 to −2.4), favouring the intervention.

Conclusions

This novel web‐based resource (“Is insulin right for me?”) is acceptable and associated with a likely reduction in negative insulin appraisals, relative to existing resources. This pilot shows the study design is feasible and supports conduct of a fully powered RCT.
A morphological approach to evaluating the nature of vineyard soils in semiarid Mediterranean environment
Authors: Jiménez‐Ballesta Raimundo , Bravo Sandra , Amorós Jose A. , Pérez‐de‐los‐Reyes Caridad , García‐Pradas Jesús , Sanchez Monica , García‐Navarro Francisco J.
Published: December 2021

La Mancha (Central Spain) is one of the most extensive vineyard regions in the world, and ‘Valdepeñas’ is a representative Protected Denomination of Origin (PDO) in this region. However, what are their main soil types? what kind of horizons are the most common? and what is the role of the geomorphological positions in their pedodiversity? After describing and sampling 90 soil profiles in this area, Alfisols, Inceptisols and Entisols were mainly identified in Soil Taxonomy terms; in other words, Luvisols, Cambisols, Regosols, Leptosols and a highly significant proportion of Calcisols according to FAO‐UNESCO‐ISSS. The accumulation of carbonate, the thickness of which varies from a diffuse or powdery form to crusted forms, appear sometimes like polycyclic. The presence of red soils, with or without a calcic or petrocalcic horizon, indicates the most representative edaphic stages in this region. Consequently, the morphological signature is calcic or petrocalcic, followed by argillic and/or cambic horizons, under ochric horizons. It can be concluded that the nature of soils in Valdepeñas can be considered a differential factor to bear in mind for quality viticultural production.

Highlights

There are unknown conceptual zones in support production of wine.

A comprehensive study in a local case was performed due to its traditional production of vineyards.

This study highlights the importance and uniqueness of the calcic and petrocalcic horizons.

A disconnect exists between some tradicional viticultural zones with low reputation and the real value of their soils.
Evaluating methods for controlling feral cats that minimise non‐target impacts at Taunton National Park (Scientific)
Authors: Augusteyn John , Nolan Barry
Published: December 2021

Feral Cat (Felis catus) (cat) is a predator of the Bridled Nail‐Tailed Wallaby (BNTW) (Onychogalea frenata) living at Taunton National Park (Scientific) (Taunton). The aim of this study was to determine if traps and poison baits could be used to control feral cats without impacting non‐target species at Taunton. The techniques trialled included poison fresh meat baits and several types of traps presented in different ways and with various lures. Thirty‐one percent of fresh meat baits was taken during bait uptake trials; corvids removed 40% of these and dogs removed 16%. Cats were not detected, on camera traps, taking a bait. The elevated soft‐jaw traps (81 trap nights/cat) and single‐entry cage traps (98 trap nights/cat) were found to be the most successful of all the trap types trialled and had low amounts of by‐catch. Other trap types trialled took more than 166 trap nights to catch a cat. The elevated soft‐jaw trap configurations had the lowest amount of by‐catch (avg. 0.33%), and the log trap had the highest amount of by‐catch (1%). Ground‐set traps successfully trapped cats (305 trap nights/cat) but caught more by‐catch (0.9%) compared to the elevated soft‐jaw trap types and most wallabies caught in these traps had to be euthanised.
The severity of neuropsychiatric symptoms is higher in early‐onset than late‐onset Alzheimer’s disease
Authors: Falgàs Neus , Allen Isabel E. , Spina Salvatore , Grant Harli , Piña Escudero Stefanie D. , Merrilees Jennifer , Gearhart Rosalie , Rosen Howard J. , Kramer Joel H. , Seeley William W. , Neylan Thomas C. , Miller Bruce L. , Rabinovici Gil D. , Grinberg Lea T. , Walsh Christine M.
Published: December 2021

Background and purpose

The faster rates of cognitive decline and predominance of atypical forms in early‐onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late‐onset AD (LOAD); however, prior studies based on non‐biomarker‐diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem‐confirmed diagnoses. Additionally, the contribution of co‐pathologies was explored.

Methods

In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory—Questionnaire (NPI‐Q) was assessed at baseline and during follow‐up. The NPI‐Q mean comparisons and regression models adjusted by cognitive (Mini‐Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non‐amnestic diagnosis on NPI‐Q. Regression models assessing the effect of co‐pathologies on NPI‐Q were performed.

Results

At baseline, the NPI‐Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI‐Q total, anxiety, motor disturbances and night‐time behavior scores (p < 0.05). No differences between amnestics/non‐amnestics were found. Argyrophilic grain disease co‐pathology predicted a higher severity of NPI‐Q scores in LOAD.

Conclusions

Anxiety, night‐time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co‐pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.
Effect of thickness on shrinkage stress and bottom‐to‐top hardness ratio of conventional and bulk‐fill composites
Authors: Santin Daniella Cristo , Velo Marilia Mattar de Amoêdo Campos , Camim Francielly da Silva , Brondino Nair Cristina Margarido , Honório Heitor Marques , Mondelli Rafael Francisco Lia
Published: December 2021

This study evaluated the effect of the material thickness on shrinkage stress and bottom‐to‐top hardness ratio of conventional and bulk‐fill composites. Six commercial composites were selected based on their different technologies: Two conventional (C1, C2), two high‐viscosity bulk‐fill (HVB1, HVB2), and two low‐viscosity bulk‐fill (LVB1, LVB2). Shrinkage stress was analyzed for five specimens with 2 mm thickness (C‐factor 0.75 and volume 24 mm3) and five specimens with 4 mm thickness (C‐factor 0.375 and volume 48 mm3) for 300 s in a universal testing machine. Bottom‐to‐top hardness ratio values were obtained from Knoop microhardness measurements in specimens with 2‐ and 4‐mm thickness (n = 5). Thickness increase resulted in significantly higher shrinkage stress for all materials with the exception of HVB2 and LVB1. C1, C2, HVB2, and LVB1 showed lower bottom‐to‐top hardness ratios at 4 mm than at 2 mm. Only LVB2 presented a bottom‐to‐top hardness ratio lower than 80% at 2 mm, while HVB1 surpassed this threshold at 4 mm of depth. The results suggest that the increase of composite thickness affected the shrinkage stress values. Also, thickness increase resulted in lower bottom‐to‐top hardness ratio. HVB1 showed better behavior than other bulk‐fill materials, with low stress and adequate bottom‐to‐top hardness ratio at 4 mm thickness.
Long‐term effect of curcuminoid treatment on resin‐to‐dentin bond strength
Authors: Tekbas Atay Meltem , Seseogullari‐Dirihan Roda , Mutluay Mustafa Murat , Tezvergil‐Mutluay Arzu
Published: December 2021

Endogenous dentin proteases contribute to the degradation of collagen fibrils in the hybrid layer. Recently, inhibition of host‐derived proteases by curcuminoids has shown promising results. The aim of this study was to evaluate the effect of curcuminoid treatment on the microtensile bond strength (μTBS) after 24 h or 12 months of storage. Fifty‐four extracted sound human molars were flattened to mid‐coronal dentin and divided into nine groups. After phosphoric acid‐etching for 15 s, the dentin was experimentally treated for 60 s using 100 μM or 200 μM of curcumin, diflourobenzocurcumin, or demethoxycurcumin dissolved in 1% and 2% dimethyl sulfoxide (DMSO)/water solutions. Untreated and DMSO‐treated groups served as controls. After bonding agent application, each tooth was restored with dental composite. The molars were sectioned into 0.9 × 0.9 × 6 mm beams. The μTBS testing was performed after 24 h and 12 months of storage in artificial saliva. Data were analyzed using regression analyses. Failure patterns were evaluated using scanning electron microscopy. Dentin treatment with curcuminoids did not adversely affect 24‐h μTBS compared to controls. After 12 months, the μTBS of curcuminoid groups was statistically significantly higher than the controls. This study indicates the feasibility of using curcuminoids as protease inhibitors.
Tranexamic acid inhibits melanogenesis partially via stimulation of TGF‐β1 expression in human epidermal keratinocytes
Authors: Xing Xiaoxue , Xu Zhongyi , Chen Li , Jin Shanglin , Zhang Chengfeng , Xiang Leihong
Published: December 2021

Oral tranexamic acid (TA) has been an effective treatment for melasma with unclear mechanism. The present study aimed to demonstrate the effect of TA on melanogenesis via regulation of TGF‐β1 expression in keratinocytes. We firstly determined the expression level of TGF‐β1 in TA‐treated keratinocyte‐conditioned medium (KCM). Then, the mRNA and protein levels of microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase‐related protein 1 (TRP‐1) of human epidermal melanocytes (NHEMs) in the presence of TA‐treated KCM were evaluated via RT‐PCR and western blot analysis. Moreover, melanin content and tyrosinase activity were quantified. TGF‐β1 gene was knocked down by small interfering RNA (siRNA) in keratinocytes. The mRNA and protein levels of TGF‐β1 in keratinocytes were significantly increased after TA treatment. Melanin contents, tyrosinase activity, protein and mRNA levels of TYR, MITF and TRP‐1 were downregulated in NHEMs in the presence of TA‐treated KCM. Knockdown of TGF‐β1 in keratinocytes could attenuate the inhibitory effect of TA‐treated KCM on melanogenesis. TA could stimulate TGF‐β1 expression in keratinocytes, which further inhibits melanogenesis through the paracrine signalling.
Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non‐syndromic basal cell carcinomas: The paradigm of oncogenic synergy
Authors: Dasgeb Bahar , Pajouhanfar Sara , Jazayeri Ali , Schoenberg Elizabeth , Kumar Gaurav , Fortina Paolo , Berger Adam C. , Uitto Jouni
Published: December 2021

There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of genetic markers that can lead to earlier and closer observation of patients at high risk for development of multiple BCCs. The overall goal is to decrease the morbidity and the economic burden of diagnosis and treatment of recurring and/or advanced BCCs. Four patients with numerous BCCs, some of them exceptionally large, were included in this study. A sample of representative BCCs, normal non–sun‐exposed skin and blood samples were obtained from each patient. Whole‐exome sequencing of DNA was conducted on all samples, and a series of bioinformatics filtering was performed to identify potentially pathogenic sequence variants. The analysis of the data resulted in detection of oncogenic mutations in PTCH1, two of which being novel, and concurrent mutations in TP53 in BCC tumours of all four patients. Such mutations may explain the numerous and postexcision recurring nature of the BCCs of exceptionally large size observed in all these patients, and they can be suggested to serve as a genetic marker for high‐risk patients for early detection, prognostication and close follow‐up.
The dual roles of three MMPs and TIMP in innate immunity and metamorphosis in the silkworm, Bombyx mori
Authors: Liu Tai‐Hang , Wei Yi , Dong Xiao‐Long , Chen Peng , Wang Ling , Yang Xi , Lu Cheng , Pan Min‐Hui
Published: December 2021

The matrix metalloproteinases (MMPs) and their endogenous inhibitory factors, tissue inhibitors of metalloproteinases (TIMPs), are implicated in many diseases. However, the mammalian MMPs (> 20) and TIMPs (> 3) are larger in number, and so little is known about their individual roles in organisms. Hence, we have systematically studied the roles of all three MMPs and one TIMP in silkworm innate immunity and metamorphosis. We observed that MMPs and TIMP are highly expressed during the pupation stage of the silkworms, and TIMP could interact with each MMPs. High‐activity MMPs and low‐activity TIMP may enhance the infection of B. mori nucleopolyhedrovirus in both in vitro and in vivo. MMPs’ knockout and TIMP overexpression delayed silkworm development and even caused death. Interestingly, different MMPs’ knockout led to different tubular tissue dysplasia. These findings provide insights into the conserved functions of MMPs and TIMP in human organogenesis and immunoregulation.