bluuebunny/crossref_metadata_2025 huggingface dataset:
A dsRNA‐degrading nuclease (dsRNase2) limits RNAi efficiency in the Asian corn borer (Ostrinia furnacalis)
Authors: Fan Yun‐He , Song Hui‐Fang , Abbas Mureed , Wang Yan‐Li , Li Tao , Ma En‐Bo , Cooper Anastasia M.W. , Silver Kristopher , Zhu Kun Yan , Zhang Jian‐Zhen
Published: November 2020

The efficiency of RNA interference (RNAi) varies substantially among different insect species. Rapid degradation of double‐stranded RNA (dsRNA) by dsRNA‐degrading nucleases (dsRNases) has been implicated to cause low RNAi efficiency in several insect species. In this study, we identified four dsRNase genes (OfdsRNase1, OfdsRNase2, OfdsRNase3 and OfdsRNase4) from the Asian corn borer (Ostrinia furnacalis) transcriptome database. Bioinformatic analyses showed that each deduced protein sequence contained endonuclease NS domains and signal peptides. Gene expression analysis revealed that OfdsRNase2 was exclusively expressed in the midgut of larvae. RNAi efficiency was investigated in 2‐d‐old fifth‐instar larvae (high expression of dsRNase2) and 2‐d‐old pupae (low expression of dsRNase2) by feeding or injecting dsRNA targeting a marker gene that encodes the lethal giant larvae protein (OfLgl). Our results showed that OfLgl only partially silenced the expression of OfLgl in pupae, but not in larvae, suggesting that OfdsRNase2 could contribute to lower RNAi efficiency in larval stages. This hypothesis was supported by our RNAi‐of‐RNAi experiment using a tissue culture technique where the silencing efficiency against the reporter gene, OfHex1, was significantly improved after knockdown of OfdsRNase2. When double luciferase assays were performed to evaluate the role of the four dsRNases in vitro, only OfdsRNase2 expressed in S2 cells significantly affected RNAi efficiency by degrading dsRNA. Taken together, our results suggested that the degradation of dsRNA by OfdsRNase2 in the midgut contributed to low RNAi efficiency in O. furnacalis larvae.
Matrix metalloproteinase‐14 (MMP‐14) downregulation inhibits esophageal squamous cell carcinoma cell migration, invasion, and proliferation
Authors: Chen Nanzheng , Zhang Guangjian , Fu Junke , Wu Qifei
Published: November 2020

Background

Matrix metalloproteinase‐14 (MMP‐14) is known to be a key regulator of oncogenesis and tumor progression. The present study was designed to assess the relationship between the downregulation of MMP‐14 and the in vitro proliferative, migratory, and invasive activity of esophageal squamous cell carcinoma (ESCC) cells.

Methods

MMP‐14 expression in human ESCC and paracancerous normal esophageal tissue samples was evaluated via immunohistochemistry, and correlations between MMP‐14 staining and patient clinicopathological features were examined. In addition, siRNA was used to knockdown MMP‐14 in ESCC cells, and the proliferation and invasive activity of these cells were then evaluated via MTT and Transwell assays, respectively. Flow cytometry was additionally used to assess cell cycle progression, while Western blotting was employed to measure protein levels within these cells.

Results

ESCC samples were found to exhibit MMP‐14 overexpression relative to paracancerous tissue samples, and this overexpression was positively correlated with tumor T classification (T1‐2 vs. T3; P < 0.05), N classification (negative vs. positive; P < 0.001), degree of differentiation (G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05) and clinical stage (I–IIA vs. IIB–III; P < 0.05). When MMP‐14 was knocked down in ESCC cells, this induced cell cycle arrest, impairing their proliferative and invasive activity.

Conclusions

MMP‐14 is a key regulator of the proliferation and invasion of ESCC cells, making it a viable therapeutic target for the treatment of this cancer.
Clinical application of ultrasound‐guided mediastinal lymph node biopsy through cervical mediastinoscopy
Authors: Fu Yili , Chen Qingshan , Yu Zexing , Dong Honghong , Li Xin , Chen Qirui , Hu Bin , Li Hui , Miao Jinbai
Published: November 2020

Background

Cervical mediastinoscopy is useful for diagnosing lung and mediastinal disease. Ultrasound is a safe real‐time diagnostic tool widely employed in many surgical fields. Ultrasound was used in cervical mediastinoscopy in our cohort with satisfactory results. This study investigated the safety, feasibility, and availability of video‐assisted mediastinoscopy (VAM) combined with ultrasound for mediastinal lymph node biopsy.

Methods

A total of 87 cases involving cervical mediastinal lymph node biopsy performed from November 2015 to May 2020, with complete clinical and pathological information, were retrospectively analyzed in the Department of Thoracic Surgery at Beijing Chaoyang Hospital. The cohort was divided into two groups: ultrasound‐guided biopsy under video‐assisted mediastinoscopy (UVAM) (44 cases) and routine VAM (43 cases). Operation time, biopsy number and nodal stations, postoperative complications, pathological conditions, and surgical difficulty were compared between the two nodal stations.

Results

UVAM was significantly shorter and more lymph node specimens were obtained than with VAM. There was one case of fatal bleeding and two cases of right recurrent laryngeal nerve injury in the VAM group, and no postoperative complications in the UVAM group.

Conclusions

When used with cervical VAM, ultrasound guidance assists physicians assess the space between lymph nodes, surrounding tissues, and large vessels systematically, making biopsy safer and easier, improving lymph node sampling, and decreasing postoperative complications. Furthermore, surgeons can easily learn and master this method.

Key points

Significant findings of the study: Ultrasound was used in combination with cervical mediastinoscopy and the results showed that ultrasound guidance makes biopsy in patients safer and easier, improves lymph node sampling, and decreases postoperative complications.

What this study adds: Surgeons can easily learn and master this method.
Combining machine learning algorithms for prediction of antidepressant treatment response
Authors: Kautzky Alexander , Möller Hans‐Juergen , Dold Markus , Bartova Lucie , Seemüller Florian , Laux Gerd , Riedel Michael , Gaebel Wolfgang , Kasper Siegfried
Published: November 2020

Objectives

Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho‐sociodemographic variables and their predictive impact on treatment outcome phenotypes.

Experimental Procedures

Treatment response was defined by a change of HAM‐D 17‐item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross‐center validation design. In total, 88 predictors were implemented.

Results

Clustering revealed four distinct HAM‐D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability.

Conclusion

Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment‐ and symptom‐specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic.
Impaired hypothalamic feedback dysregulates brain glucocorticoid signaling in genetically‐selected Marchigian Sardinian alcohol‐preferring rats
Authors: Natividad Luis A. , Steinman Michael Q. , McGinn M. Adrienne , Sureshchandra Suhas , Kerr Tony M. , Ciccocioppo Roberto , Messaoudi Ilhem , Edwards Scott , Roberto Marisa
Published: November 2020

Genetically‐selected Marchigian Sardinian alcohol‐preferring (msP) rats display comorbid symptoms of increased alcohol preference and elevated anxiety‐like behavior. Heightened stress sensitivity in msPs is influenced by genetic polymorphisms of the corticotropin‐releasing factor receptor in the central nucleus of the amygdala (CeA), as well as reduced influence of anti‐stress mechanisms that normally constrain the stress response. Given this propensity for stress dysregulation, in this study, we expand on the possibility that msPs may display differences in neuroendocrine processes that normally terminate the stress response. We utilized behavioral, biochemical, and molecular assays to compare basal and restraint stress‐induced changes in the hypothalamic–pituitary–adrenal (HPA) axis of male and female msPs relative to their nonselected Wistar counterparts. The results showed that msPs display deficits in marble‐burying behavior influenced by environmental factors and procedures that modulate arousal states in a sex‐dependent manner. Whereas male msPs display evidence of dysregulated neuroendocrine function (higher adrenocorticotropic hormone levels and subthreshold reductions in corticosterone), females display restraint‐induced elevations in corticosterone levels that were persistently higher in msPs. A dexamethasone challenge reduced the circulation of these stress hormones, although the reduction in corticosterone was generally attenuated in msP versus Wistar rats. Finally, we found evidence of diminished stress‐induced glucocorticoid receptor (GR) phosphorylation in the hypothalamic paraventricular nucleus of msPs, as well as innate increases in phosphorylated GR levels in the CeA of male msPs. Collectively, these findings suggest that negative feedback processes regulating HPA responsiveness are diminished in msP rats, possibly underlying differences in the expression of anxiety‐like behaviors.
Assessing effect of long‐term abstinence on coupling of three core brain networks in male heroin addicts: A resting‐state functional magnetic resonance imaging study
Authors: Chen Jiajie , Wang Fan , Zhu Jia , Li Yongbin , Liu Wei , Xue Jiuhua , Shi Hong , Li Wei , Li Qiang , Wang Wei
Published: November 2020

Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long‐term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty‐three heroin addicts with LA, 27 heroin addicts with short‐term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting‐state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue‐induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex‐precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.
Tobacco use disorder and the lungs
Authors: McRobbie Hayden , Kwan Benjamin
Published: November 2020

This narrative review provides a summary of the impact of tobacco smoking on the respiratory system and the benefits of smoking cessation. Tobacco smoking is one of the leading preventable causes of death world‐wide and a major risk factor for lung cancer and chronic obstructive pulmonary disease. Smoking is also associated with an increased risk of respiratory infections and appears to be related to poorer outcomes among those with COVID‐19. Non‐smokers with second‐hand smoke exposure also experience significant adverse respiratory effects. Smoking imposes enormous health‐ and non‐health‐related costs to societies. The benefits of smoking cessation, in both prevention and management of respiratory disease, have been known for decades and, to this day, cessation support remains one of the most important cost‐effective interventions that health professionals can provide to people who smoke. Cessation at any age confers substantial health benefits, even in smokers with established morbidities. As other treatments for chronic respiratory disease advance and survival rates increase, smoking cessation treatment will become even more relevant. While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited.
Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in Texas, USA
Authors: Hill Lucas G. , Loera Lindsey J. , Evoy Kirk E. , Renfro Mandy L. , Torrez Sorina B. , Zagorski Claire M. , Perez Joshua C. , Jones Shaun M. , Reveles Kelly R.
Published: November 2020

Background and Aims

Patients with opioid use disorder (OUD) must be able to obtain prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) from a pharmacy promptly to reduce risk for a recurrence of use and subsequent morbidity and mortality. Telephone audits have identified concerning gaps in availability of NNS within US pharmacies, but the availability of BUP/NX has not been rigorously evaluated. This study estimated the availability of BUP/NX and NNS in the US state of Texas and compared availability by pharmacy type and metropolitan status.

Design

A cross‐sectional telephone audit with a secret shopper approach conducted from 18 May 2020 to 7 June 2020.

Setting and Participants

A random sample of 800 of 5078 (16%) community pharmacies licensed with the Texas State Board of Pharmacy.

Measurements

Primary outcomes included availability of a 1‐week supply of generic BUP/NX 8/2 mg films and a single unit of NNS 4 mg, overall and by pharmacy type. Secondary outcomes included willingness and estimated time‐frame to order BUP/NX if unavailable.

Findings

Data from 704 pharmacies (471 chain, 233 independent) were included for analyses. Of these, 34.1% of pharmacies (45.0% of chains versus 12.0% of independents, P < 0.0001) were willing and able to dispense a 1‐week supply of generic BUP/NX and a single unit of NNS. BUP/NX alone was available in 42.2% of pharmacies (52.4% of chains versus 21.5% of independents, P < 0.0001). NNS alone was available in 60.1% of pharmacies (77.9% of chains versus 24.0% of independents, P < 0.0001). Of the 397 pharmacies with generic BUP/NX unavailable, 62.2% of pharmacies (73.9% of chains versus 48.0% of independents, P < 0.0001) indicated willingness to order.

Conclusions

Most pharmacies in Texas do not appear to be willing and able to dispense prescribed buprenorphine/naloxone films and naloxone nasal spray to patients with opioid use disorder in a timely manner. Deficiencies in availability are markedly more pronounced in independent pharmacies compared with chain pharmacies.
Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta‐analysis
Authors: Ferraro Claire F. , Stewart Daniel E. , Grebely Jason , Tran Lucy T. , Zhou Shally , Puca Carla , Hajarizadeh Behzad , Larney Sarah , Santo Thomas , Higgins Julian P. T. , Vickerman Peter , Degenhardt Louisa , Hickman Matthew , French Clare E.
Published: November 2020

Background and aim

Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID.

Methods

We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand‐searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non‐Randomised Studies of Interventions (ROBINS‐I) tool. Meta‐analyses were conducted using random‐effects models.

Results

Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28–2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96–4.95.

Conclusions

Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.
Mapping genes for phosphorus utilization and correlated traits using a 4k SNP linkage map in Japanese quail (Coturnix japonica)
Authors: Vollmar S. , Haas V. , Schmid M. , Preuß S. , Joshi R. , Rodehutscord M. , Bennewitz J.
Published: November 2020

A large F2 cross with 920 Japanese quail was used to map QTL for phosphorus utilization, calcium utilization, feed per gain and body weight gain. In addition, four bone ash traits were included, because it is known that they are genetically correlated with the focal trait of phosphorus utilization. Trait recording was done at the juvenile stage of the birds. The individuals were genotyped genome‐wide for about 4k SNPs and a linkage map constructed, which agreed well with the reference genome. QTL linkage mapping was performed using multimarker regression analysis in a line cross model. Single marker association mapping was done within the mapped QTL regions. The results revealed several genome‐wide significant QTL. For the focal trait phosphorus utilization, a QTL on chromosome CJA3 could be detected by linkage mapping, which was substantiated by the results of the SNP association mapping. Four candidate genes were identified for this QTL, which should be investigated in future functional studies. Some overlap of QTL regions for different traits was detected, which is in agreement with the corresponding genetic correlations. It seems that all traits investigated are polygenic in nature with some significant QTL and probably many other small‐effect QTL that were not detectable in this study.
Patients with ventricular assist device and cerebral entrapment—Supporting skullcap reimplantation
Authors: Gyoten Takayuki , Rojas Sebastian V. , Irimie Anca , Schramm René , Morshuis Michiel , Gummert Jan F. , Sitzer Matthias , Fox Henrik
Published: November 2020

Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device (LVAD) support as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP when aiming for transplantation. Data were collected from our prospective institutional database including all patients undergoing LVAD implantation between 2010 and 2019. Six patients needed CP procedures and were included. Our analysis focused on postoperative outcome, survival, and facilitation of heart transplantation. Study endpoints included also all‐cause mortality. From a total of 1010 LVAD implantations during analysis period in our center, six bridge‐to‐transplantation LVAD patients [median age at LVAD implantation: 32.5 years (IQR: 24.8‐39.5 years); four male, HVAD, n = 3; HM II, n = 1; HM 3, n = 2] underwent CP with imminent entrapment secondary to cerebral hemorrhage or malignant infarction. Primary heart failure etiology was myocarditis (n = 2), dilated (n = 2), or ischemic (n = 2). Median INTERMACS class was 1.5 (IQR; 1.0‐2.8). Median time on LVAD support to DC procedure was 33 months (IQR: 16‐48 months). The indication for DC was intraparenchymal hemorrhage (n = 4), subdural hematoma (n = 1), and malignant middle cerebral artery infarction (n = 1). After a median time of 4 months (IQR: 3.3‐4.0 months, range; 2.0‐10 months) post DC procedure, CP was subsequently performed without profound neurologic disabilities in all patients. After median time of 26 months (IQR: 21‐42 months) follow‐up, three patients successfully received heart transplantation, one patient could undergo LVAD explantation for myocardial recovery, and the remaining two patients are still on the list awaiting heart transplantation. CP procedure with skullcap reimplantation is feasible and can be safely performed in LVAD patients, which subsequently may even be eligible for heart transplantation with beneficial prognosis.
Complex raw materials and the supply system: Mineralogical and geochemical study of the jade artefacts of the Longshan Culture (2400–2000 bce) from Sujiacun site in coastal Shandong, China
Authors: Zhang B. S. , Wu X. T. , Sun Y. F. , Ritchey M. , Fan A. C. , Zhang Y. Y. , Yu G. , Song Y. B.
Published: November 2020

X‐ray fluorescence (XRF), X‐ray diffraction (XRD) and Raman spectroscopy were employed to analyse the chemical compositions and phase structures of nine pieces of jade artefacts unearthed from Sujiacun, a Longshan Culture (2400–2000 bce) site in coastal Shandong, eastern China. The results of the analyses indicated these samples were primarily made from multiple raw mineral materials, including antigorite, actinolite, clinochlore, turquoise and muscovite. No nephrite was recovered from the Sujiacun site. This is strikingly different from other top‐ranking settlements of Longshan Culture, such as Dantu, Liangchengzhen and Xizhufeng, in which nephrite was the main material of jade artefacts. This may reflect the distinctions in the supply system of jade raw materials among different rankings of Longshan period sites. In addition, laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) was used to analyse the composition of the rare earth elements of serpentine jade. These preliminary results were compared with published data on the composition of serpentine jade and it was found that the Sujiacun serpentine jade artefacts were likely sourced from the Taishan jade deposit.
Changes in plant species richness after cessation of forest disturbance
Authors: Vetaas Ole R. , Shrestha Krishna B. , Sharma Lila N.
Published: November 2020

Questions

What will happen to species diversity in a forest when exploitation of the canopy foliage terminates? The foliage of the main canopy tree of a mountain evergreen oak forest was harvested at different intensities prior to a forest survey in 1993 and resampled in 2013 after the harvest of canopy foliage ceased (1995). We predict a decrease in herbaceous species richness with increasing canopy cover, and an opposite trend for vines and woody species. We hypothesise that plant species’ alpha and beta diversity will change most in the plots where foliage was most intensively harvested while showing less change in the plots that underwent almost no harvesting.

Location

Temperate evergreen laurel–oak forest in the Himalaya, Nepal.

Methods

We resampled all non‐epiphytic vascular plants in 64 plots of 10 m × 10 m in 2013, following the same protocol used in 1993. Plant species were categorised into three life forms; woody (except woody vines), herbaceous, and vines. Uni‐ and multivariate numerical methods were used to assess the significance of the changes in species diversity for different life forms.

Results

Vines and woody species increased, whereas herbaceous species decreased, but overall gamma diversity remained unchanged. The overall alpha richness for herbaceous species decreased, while the opposite is true for woody and vine richness. Herbaceous richness decreased and woody richness increased in the areas with low and intermediate disturbance (in 1993), whereas vines remained unchanged. Only vine richness increased in the area that was very disturbed in 1993. Total species richness as well as herbaceous and vine richness decreased with increasing tree canopy cover.

Conclusions

Plots that were intensively harvested in 1993 did not recover their richness because vines dominated the forest floor. Management should prevent overexploitation, and only allow low‐intensity canopy disturbance, which may facilitate habitat diversity and thereby enhance species richness.
Prescription medicine misuse in the Asia–Pacific region: An evolving issue?
Authors: Chan Wui Ling , Wood David M. , Dargan Paul I.
Published: November 2020

Prescription medicine misuse, especially misuse of opioids has become a major public healthcare issue in many developed countries such as the USA and Australia where this is associated with significant morbidity (Emergency Department visits due to acute toxicity) and mortality. In this review, we looked at the available data obtained from peer‐reviewed articles and population surveys to gain an insight into the current situation in the Asia–Pacific region. There is currently limited information available, but data from subpopulation surveys in a number of countries suggests that prescription medicine misuse is likely to be an issue of concern from a public health perspective in the Asia–Pacific region. The available data suggest that misuse prevalence rates and the medicines that are commonly misused are similar to countries such as the USA and UK. Further studies are required to determine the overall prevalence of misuse, the harms associated with this and the sources of drugs being misused so that appropriate interventions can be implemented to tackle issues related to prescription medicine misuse in this region.
Analysis of clustered interval‐censored data using a class of semiparametric partly linear frailty transformation models
Authors: Lee Chun Yin , Wong Kin Yau , Lam K. F. , Xu Jinfeng
Published: November 2020

A flexible class of semiparametric partly linear frailty transformation models is considered for analyzing clustered interval‐censored data, which arise naturally in complex diseases and dental research. This class of models features two nonparametric components, resulting in a nonparametric baseline survival function and a potential nonlinear effect of a continuous covariate. The dependence among failure times within a cluster is induced by a shared, unobserved frailty term. A sieve maximum likelihood estimation method based on piecewise linear functions is proposed. The proposed estimators of the regression, dependence, and transformation parameters are shown to be strongly consistent and asymptotically normal, whereas the estimators of the two nonparametric functions are strongly consistent with optimal rates of convergence. An extensive simulation study is conducted to study the finite‐sample performance of the proposed estimators. We provide an application to a dental study for illustration.
‘Just knowing’ and the challenges of giving medicines to children with severe and profound intellectual disabilities: A hermeneutic inquiry
Authors: Doyle Carmel
Published: November 2020

Accessible summary

I asked mothers to speak to me about their experience of giving medicines to their child with severe and profound intellectual disabilities.

Mothers told me their instincts often tell them how their child is and they also talked about the challenges in giving medicines every day.

The findings from this study show how important it is that professionals understand how difficult it can be.

It is essential that we support mothers to "give medicines."

Background

Children with severe and profound intellectual disabilities experience multiple chronic health conditions requiring a variety of medications. The aim of this study was to explore mothers' lived experience of giving medicines to children with severe and profound intellectual disabilities.

Materials and Methods

A hermeneutic phenomenological approach was adopted with a purposeful sample of 15 mothers adopted. Face‐to‐face interviews and participant diaries were utilised for data collection.

Results

Themes were identified with one being that of "lived body" exploring how mothers "just know" or use their instincts and also the challenges they encountered in daily life when giving medicines.

Conclusions

This paper provides insight into the complexity of giving medicines to children with severe and profound intellectual disabilities and the level of support required by mothers.
DGT, a novel heterocyclic diterpenoid, effectively suppresses psoriasis via inhibition of STAT3 phosphorylation
Authors: Bian Gang , Wang Lidan , Xie Qing , Wang Yanping , Feng Haimei , Yu Yunhui , Chen Zijun , Deng Shiping , Li Yunsen
Published: November 2020

Background and Purpose

Psoriasis is a chronic immune‐mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses.

Experimental Approach

We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol‐induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)‐induced psoriasis‐like model.

Key Results

DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ‐induced psoriasis‐like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL‐17‐related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation.

Conclusion and Implications

DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease.
Awareness and knowledge of developmental coordination disorder: A survey of caregivers, teachers, allied health professionals and medical professionals in Australia
Authors: Hunt Jacqui , Zwicker Jill G , Godecke Erin , Raynor Annette
Published: November 2020

Background

To allow for accurate and timely diagnosis of developmental coordination disorder (DCD) key stakeholders must be familiar with and be able to identify features of this disorder. No studies to date have investigated the awareness of DCD among key stakeholders in Australia.

Methods

An online survey was complete by 494 Australian participants: primary caregivers (n = 153), teachers (n = 149), allied health professionals (n = 165) and medical professionals (n = 27).

Results

DCD and related terms were among the least known childhood disorders. Approximately half of the sample were familiar with the term DCD but every stakeholder group were more familiar with the term dyspraxia. Allied health professionals demonstrated greater knowledge of the features of DCD, particularly motor features. Every stakeholder group showed poor recognition of the social and psychological effects of DCD. A relatively low percentage of allied health (53%) and medical (33%) professionals reported they had identified or diagnosed DCD and less than 20% of these felt that the DSM‐5 contained adequate information to make a DCD diagnosis. Most teachers (82%) believed they should play a role in identifying early warning signs of this disorder, and 80% believed there are children in the school system who were labelled as lazy or defiant when they have motor skills impairments. Primary caregivers were supportive of a diagnosis of DCD being provided; however, only 16% were confident that a physician would provide an accurate and timely diagnosis.

Conclusion

Key stakeholders play a unique and important role in the identification of children with DCD. Though most participants acknowledge the role that they play, all stakeholder groups demonstrated poor familiarity with the term DCD and low levels of knowledge about the features of this disorder. Improved familiarity and knowledge of the disorder is needed for access to appropriate services and improved long‐term outcomes for this condition.
Bos d 11 in baked milk poses a risk for adverse reactions in milk‐allergic patients
Authors: Hindley James P. , Oliver Maria A. , Thorpe Cathy , Cullinane Angharad , Wuenschmann Sabina , Chapman Martin D.
Published: November 2020

Background

Patients are commonly challenged with foods containing baked milk, for example muffins, yet little is known about the specific allergen content of muffins used in milk challenges or of the effect that baking has on allergenicity.

Objective

Our objective was to compare the levels of major milk allergens in uncooked and baked muffins using monoclonal immunoassays and IgE antibody binding before and after baking.

Methods

Uncooked and baked muffins were prepared using recipes from Mount Sinai and Imperial College. Allergen levels were compared by ELISA for Bos d 5 (β‐lactoglobulin) and Bos d 11 (β‐casein). IgE reactivity was assessed using sera from milk‐sensitized donors in direct binding and inhibition ELISA.

Results

Bos d 5 was reduced from 680 µg/g in uncooked muffin mix to 0.17 µg/g in baked muffins, representing a >99% decrease after baking. Conversely, Bos d 11 levels in baked muffin remained high and only decreased by 30% from a mean of 4249 µg/g in uncooked muffin mix to 2961 µg/g when baked (~181 mg Bos d 11 per muffin). Baked muffins retained ~70% of the IgE binding to uncooked muffin mix. Baked muffin extract inhibited IgE binding to uncooked muffin mix by up to 80%, demonstrating retention of in vitro IgE reactivity.

Conclusions and Clinical Relevance

High levels of Bos d 11 in baked muffins pose a risk for adverse reactions, especially in patients who have high anti‐casein IgE antibodies.
Identification of the third FGF9 variant in a girl with multiple synostosis–comparison of the genotype:phenotype of FGF9 variants in humans and mice
Authors: Sentchordi‐Montané Lucia , Diaz‐Gonzalez Francisca , Cátedra‐Vallés Elena V. , Heath Karen E.
Published: November 2020

Multiple synostosis syndrome (SYNS) is a heterogeneous group of genetic disorders mainly characterized by multiple joint synostosis due to variants in either NOG, GDF5, FGF9 or GDF6. To date, only two FGF9 variants have been associated with SYNS, characterized with hand and feet joint synostosis and fusion of the elbow and vertebral lumbar joints. Craniosynostosis was also observed in one family. Here, we report the clinical and radiological description of a young girl with a third heterozygous FGF9 variant, NM_002010.2:c.427A>T;p.(Asn143Tyr), which interestingly, is located at the same amino acid as the well characterized spontaneous Eks mouse variant. We also compare the genotype: phenotypes observed between humans and mice with SYNS.
Wavelet‐based Heat Kernel Derivatives: Towards Informative Localized Shape Analysis
Authors: Kirgo Maxime , Melzi Simone , Patanè Giuseppe , Rodolà Emanuele , Ovsjanikov Maks
Published: November 2020

In this paper, we propose a new construction for the Mexican hat wavelets on shapes with applications to partial shape matching. Our approach takes its main inspiration from the well‐established methodology of diffusion wavelets. This novel construction allows us to rapidly compute a multi‐scale family of Mexican hat wavelet functions, by approximating the derivative of the heat kernel. We demonstrate that this leads to a family of functions that inherit many attractive properties of the heat kernel (e.g. local support, ability to recover isometries from a single point, efficient computation). Due to its natural ability to encode high‐frequency details on a shape, the proposed method reconstructs and transfers ‐functions more accurately than the Laplace‐Beltrami eigenfunction basis and other related bases. Finally, we apply our method to the challenging problems of partial and large‐scale shape matching. An extensive comparison to the state‐of‐the‐art shows that it is comparable in performance, while both simpler and much faster than competing approaches.
Survey to define informational needs of patients undergoing surgery for Crohn’s anal fistula
Authors: Lee Matthew J. , Jones Georgina L. , Lobo Alan J. , Brown Steven R. ,   the pCD collaborators
Published: November 2020

Aim

There are many surgical treatments used in Crohn's anal fistula, although none is perfect. Decisions about surgery in this condition may be preference sensitive. The aim of this study was to identify what information patients would like in order to make treatment decisions and to explore experiences of making decisions in this setting.

Method

A survey was designed based upon qualitative interviews and input from patients and clinicians. It included a long list of informational items to be ranked on a scale of importance, a control preference scale, the decision regret scale, and items exploring preferred information formats. This was distributed through 10 English hospitals to patients with recent surgical treatment for Crohn's anal fistula. Results were analysed using principal component analysis, to identify key informational needs, and other appropriate descriptive statistics.

Results

In total 92 questionnaires were returned (response rate 41.8%); 48 (52.5%) respondents were women and 54 (58.7%) had undergone seton insertion. Principal component analysis identified three information needs: wound and aftercare, effect on perianal symptoms, severity of surgery. Decision‐making preferences showed a desire to participate in decision‐making. Median decision regret score was 25/100 (i.e., low). The preferred format for sharing information to support decision‐making was from the surgeon, 80/92 (87.0%), and from a booklet, 58/92 (63.0%).

Conclusion

Key informational needs in this condition are wound and after care, effect on perianal symptoms, and severity of surgery. Patients would like this information to help engage in shared decision‐making.
Holographic Declarative Memory: Distributional Semantics as the Architecture of Memory
Authors: Kelly Mary Alexandria , Arora Nipun , West Robert L. , Reitter David
Published: November 2020

We demonstrate that the key components of cognitive architectures (declarative and procedural memory) and their key capabilities (learning, memory retrieval, probability judgment, and utility estimation) can be implemented as algebraic operations on vectors and tensors in a high‐dimensional space using a distributional semantics model. High‐dimensional vector spaces underlie the success of modern machine learning techniques based on deep learning. However, while neural networks have an impressive ability to process data to find patterns, they do not typically model high‐level cognition, and it is often unclear how they work. Symbolic cognitive architectures can capture the complexities of high‐level cognition and provide human‐readable, explainable models, but scale poorly to naturalistic, non‐symbolic, or big data. Vector‐symbolic architectures, where symbols are represented as vectors, bridge the gap between the two approaches. We posit that cognitive architectures, if implemented in a vector‐space model, represent a useful, explanatory model of the internal representations of otherwise opaque neural architectures. Our proposed model, Holographic Declarative Memory (HDM), is a vector‐space model based on distributional semantics. HDM accounts for primacy and recency effects in free recall, the fan effect in recognition, probability judgments, and human performance on an iterated decision task. HDM provides a flexible, scalable alternative to symbolic cognitive architectures at a level of description that bridges symbolic, quantum, and neural models of cognition.
Using Theory of Change to improve post‐2020 conservation: A proposed framework and recommendations for use
Authors: Rice Wayne Stanley , Sowman Merle R. , Bavinck Maarten
Published: November 2020

Contemporary conservation must address social well‐being while still protecting biodiversity. Accordingly, the objective of the Convention on Biological Diversity's recent Zero Draft Post‐2020 Global Biodiversity Framework is to sustainably meet the needs of people while reducing biodiversity loss. However, frequent “failures” in achieving this social‐ecological balance necessitates more holistic, systematic, and adaptive post‐2020 conservation interventions. The Theory of Change (ToC) approach provides a useful and flexible tool to support this endeavor. However, debate persists over its usefulness, and “best” manner of use. This paper explores the elements of, and proposes a framework for developing robust conservation ToC pathways. The framework emphasizes the importance of producing a shared vision of desired results and actions, and associated causal assumptions, among actors. Furthermore, evaluation is considered key to informing required ongoing adaptation to better achieve desired results. The paper also critically explores the challenges associated with ToC, and makes recommendations for its improved use in post‐2020 conservation. In particular, we aim to inform the implementation and mainstreaming of the Post‐2020 Global Biodiversity Framework, especially at a national‐ and local‐level. The framework and discussion should be relevant to a broad range of conservation actors at various scales that must address linked social and ecological objectives.
Role for Drug Transporters in Chemotherapy‐Induced Peripheral Neuropathy
Authors: Stage Tore B. , Hu Shuiying , Sparreboom Alex , Kroetz Deanna L.
Published: November 2020

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common and dose‐limiting toxicity to widely used chemotherapeutics. Although the exact molecular mechanism of chemotherapy‐induced peripheral neuropathy remains elusive, there is consensus that it is caused by damage to the peripheral nervous system leading to sensory symptoms. Recently developed methodologies have provided evidence of expression of drug transporters in the peripheral nervous system. In this literature review, we explore the role for drug transporters in CIPN. First, we assessed the transport of chemotherapeutics that cause CIPN (taxanes, platins, vincristine, bortezomib, epothilones, and thalidomide). Second, we cross‐referenced the transporters implicated in genetic or functional studies with CIPN with their expression in the peripheral nervous system. Several drug transporters are involved in the transport of chemotherapeutics that cause peripheral neuropathy and particularly efflux transporters, such as ABCB1 and ABCC1, are expressed in the peripheral nervous system. Previous literature has linked genetic variants in efflux transporters to higher risk of peripheral neuropathy with the taxanes paclitaxel and docetaxel and the vinca alkaloid vincristine. We propose that this might be due to accumulation of the chemotherapeutics in the peripheral nervous system due to reduced neuronal efflux capacity. Thus, concomitant administration of efflux transporter inhibitors may lead to higher risk of adverse events of drugs that cause CIPN. This might prove valuable in drug development where screening new drugs for neurotoxicity might also require drug transporter consideration. There are ongoing efforts targeting drug transporters in the peripheral nervous system to reduce intraneuronal concentrations of chemotherapeutics that cause CIPN, which might ultimately protect against this dose‐limiting adverse event.
Habitat amount and ambient temperature dictate patterns of anuran diversity along a subtropical elevational gradient
Authors: Carvalho‐Rocha Vítor , Peres Carlos A. , Neckel‐Oliveira Selvino
Published: November 2020

Aim

Patterns of diversity along elevational gradients are driven by species characteristics but remain poorly understood. Filling this gap is imperative given the deteriorating conservation status of anurans worldwide. Here, we examine frog diversity and species composition along a sharp subtropical elevational gradient and assess the degree to which these are determined by environmental and spatial predictors.

Location

An extensive southern Brazilian Atlantic Forest elevational gradient ranging from 300 to 1,800 m above sea level.

Methods

We sampled 38 ponds and used structural equation modelling to examine the direct and indirect effects of area, climate, habitat amount, habitat complexity and productivity on frog species richness and abundance. We also applied joint species distribution models to investigate the importance of these predictors on frog species composition using species distribution and co‐occurrence along the elevational gradient.

Results

We recorded 12,636 individuals of 41 frog species. Frog species richness was highest at intermediate elevations, showing a hump‐shaped pattern. Frog abundance was highest at lowlands and decreased towards higher elevations. We found support for only the habitat amount hypothesis in explaining overall species richness. Although temperature had a positive influence on productivity and frog abundance, neither predictors were related to species richness. Species composition diverged markedly between lowland and highland frog assemblages, which was mainly attributed to differences in ambient temperature.

Main conclusion

Elevations containing more extensive natural habitat areas retained the most species‐rich frog assemblages. The mid‐elevational peak is likely attributed to lowland habitat (<800 masl) heterogeneity and extreme climatic conditions in highland areas (>1,400 masl). The entire elevational gradient is, however, critical in maintaining anuran species diversity as lowland assemblages are distinct from those at mid‐ to high elevations. Our study also shows that anthropogenic habitat loss has a decisive effect on montane frog diversity, reinforcing the need to effectively protect these areas.