bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated intraocular pressure induces neuron‐specific β‐III‐tubulin expression in non‐neuronal vascular cells
Authors: Prokosch Verena , Brockhaus Kathrin , Anders Fabian , Liu Hanhan , Mercieca Karl , Gericke Adrian , Melkonyan Harut , Thanos Solon
Published: December 2019

Purpose

Pathological alterations within optic nerve axons and progressive loss of the parental retinal ganglion cell (RGC) bodies are characteristics of glaucomatous neuropathy. Abnormally elevated intraocular pressure (IOP) is thought to be the major risk factor for most forms of glaucomatous changes, while lowering of the IOP is the mainstream of treatment. However, the pathophysiological mechanisms involved in neurodegenerative changes are poorly understood. It remains still a matter of debate whether elevated IOP harms the neurons directly or indirectly through alterations in the retinal vascularization.

Methods

We analysed morphological and molecular changes within the retina exposed to elevated IOP in an animal model of glaucoma in vivo, in retinal explants and in cultured dissociated retinal cells each incubated under elevated air pressure in vitro, imitating elevated IOP.

Results

Although ß‐III‐tubulin expressing RGCs decreased within the course of the disease, total amount of ß‐III‐tubulin protein within the retina increased, leading to the assumption that other cells than RGCs abnormally express ß‐III‐tubulin due to elevated IOP. Surprisingly, we found that β‐III‐tubulin, a marker developmentally regulated and specifically expressed in neurons under normal conditions, was strongly up‐regulated in desmin‐, PDGFR‐β‐ and α‐SMA‐positive pericytes as well as in endothelin‐1‐positive endothelial cells both in vivo under elevated IOP and in vitro under elevated culture atmosphere pressure that simulated IOP elevation. Beta‐III‐tubulin‐driven signalling pathways (ERK 1/2, pERK1/2 and cdc42/Rac) were also regulated.

Conclusion

The unprecedented regulation of neuron‐specific β‐III‐tubulin in pericytes and endothelial cells is likely associated with a role of the retinal vasculature in the IOP‐induced development and manifestation of glaucomatous degenerative optic nerve response.
Determinants and effects of fluid status changes in caesarean delivered neonates
Authors: Zanardo Vincenzo , Tortora Domenico , Parotto Matteo , Severino Lorenzo , Simbi Alphonse , Guerrini Pietro , Straface Gianluca
Published: December 2019

Aim

Evidence suggests that caesarean section is associated with a reduced placental transfusion and poor iron‐related haematological indices, both in cord and peripheral blood, compared with vaginal delivery. We assessed determinants and effects of fluid status changes on placental transfusion in neonates delivered by elective (ElCD) and emergency (EmCD) caesarean section.

Methods

Placental transfusion was estimated by ∆ haematocrit (Hct) increase from birth to 48 hours of life, accounting for contemporaneous ∆ body weight decrease, in 143 women/infant pairs, 62 who underwent ElCD and 81 EmCD, respectively.

Results

Cord blood Hct levels at birth of ElCS neonates were significantly lower than those of EmCD neonates (44.58 + 4.87vs 49.93 + 4.29, P = .01). At 48 hours of life, capillary heel Hct levels of ElCD and of EmCD neonates were comparable. ElCD had a higher ∆ body weight decrease (ElCD −7.25 ± 1.74% vs EmCD −6.31 ± 2.34% [P: .011]) and ∆ Hct increase ([ElCD + 5.93 ± 4.92 vs EmCD + 3.59 ± 5.29, [P: .011]). In a linear regression model analysis, gestational age in ElCD neonates had a significant effect on the differences in arterial cord blood Hct, body weight at birth and body weight decrease at 48 hours after birth.

Conclusion

Early‐term surgical delivery is a determinant of transient dilutional anaemia in ElCD neonates, lacking neuroendocrine response of labour and delivery.
The hypoxia tolerance of eight related African mole‐rat species rivals that of naked mole‐rats, despite divergent ventilatory and metabolic strategies in severe hypoxia
Authors: Ivy Catherine M. , Sprenger Ryan J. , Bennett Nigel C. , van Jaarsveld Barry , Hart Daniel W. , Kirby Alexia M. , Yaghoubi Dadmehr , Storey Kenneth B. , Milsom William K. , Pamenter Matthew E.
Published: December 2019

Aims

Burrowing mammals tend to be more hypoxia tolerant than non‐burrowing mammals and rely less on increases in ventilation and more on decreases in metabolic rate to tolerate hypoxia. Naked mole‐rats (Heterocephalus glaber, NMRs), eusocial mammals that live in large colonies, are among the most hypoxia‐tolerant mammals, and rely almost solely on decreases in metabolism with little change in ventilation during hypoxia. We hypothesized that the remarkable hypoxia tolerance of NMRs is an evolutionarily conserved trait derived from repeated exposure to severe hypoxia owing to their burrow environment and eusocial colony organization.

Methods

We used whole‐body plethysmography and indirect calorimetry to measure the hypoxic ventilatory and metabolic responses of eight mole‐rat species closely related to the NMR.

Results

We found that all eight species examined had a strong tolerance to hypoxia, with most species tolerating 3 kPa O2, Heliophobius emini tolerating 2 kPa O2 and Bathyergus suillus tolerating 5 kPa O2. All species examined employed a combination of increases in ventilation and decreases in metabolism in hypoxia, a response midway between that of the NMR and that of other fossorial species (larger ventilatory responses, lesser reductions in metabolism). We found that eusociality is not fundamental to the physiological response to hypoxia of NMRs as Fukomys damarensis, another eusocial species, was among this group.

Conclusions

Our data suggest that, while the NMR is unique in the pattern of their physiological response to hypoxia, eight closely related mole‐rat species share the ability to tolerate hypoxia like the current “hypoxia‐tolerant champion,” the NMR.
Drive and Direction: Empathy with Intended Targets Moderates the Proactive Personality–Job Performance Relationship via Work Engagement
Authors: Chong SinHui , Van Dyne Linn , Kim You Jin , Oh Jo K.
Published: December 2019

Proactive employees are self‐starting and driven. Thus, they typically exhibit high levels of work engagement. While work engagement reflects the degree to which employees are attentive and absorbed when performing their work tasks, it does not guarantee effective job performance unless their actions are strategic. We draw on Grant and Ashford’s (2008) proactivity framework to develop a drive and direction contingency model that expands our understanding of how and when proactive personality predicts job performance via work engagement. We argue that employee’s drive (represented by the positive relation of proactive personality with work engagement) predicts job performance only when the employee also has high (vs. low) empathy with their intended targets, such as customers. Empathy with intended targets allows employees to understand and feel their targets’ concerns and feelings, thus providing a direction that guides their work engagement to address their targets’ interests and predict job performance. Results from a multiple‐source (employees, supervisors, and organizational records) lagged (T1–T2) field study and a lab experiment support our model. We discuss the implications, limitations, and future directions of our findings.
Effect of different implant placement depths on crestal bone levels and soft tissue behavior: A 5‐year randomized clinical trial
Authors: de Siqueira Rafael Amorim Cavalcanti , Savaget Gonçalves Junior Robson , dos Santos Paulo Gustavo Freitas , de Mattias Sartori Ivete Aparecida , Wang Hom‐Lay , Fontão Flavia Noemy Gasparini Kiatake
Published: December 2019

Objectives

This randomized clinical trial analyzed the long‐term (5‐year) crestal bone changes and soft tissue dimensions surrounding implants with an internal tapered connection placed in the anterior mandibular region at different depths (equi‐ and subcrestal).

Materials and methods

Eleven edentulous patients were randomly divided in a split‐mouth design: 28 equicrestal implants (G1) and 27 subcrestal (1–3 mm) implants (G2). Five implants were placed per patient. All implants were immediately loaded. Standardized intraoral radiographs were used to evaluate crestal bone (CB) changes. Patients were assessed immediately, 4, 8, and 60 months after implant placement. The correlation between vertical mucosal thickness (VMT) and soft tissue recession was analyzed. Sub‐group analysis was also performed to evaluate the correlation between VMT and CB loss. Rank‐based ANOVA was used for comparison between groups (α = .05).

Results

Fifty‐five implants (G1 = 28 and G2 = 27) were assessed. Implant and prosthetic survival rate were 100%. Subcrestal positioning resulted in less CB loss (−0.80 mm) when compared to equicrestal position (−0.99 mm), although the difference was not statistically significant (p > .05). Significant CB loss was found within the G1 and G2 groups at two different measurement times (T4 and T60) (p < .05). Implant placement depths and VMT had no effect on soft tissue recession (p > .05).

Conclusions

There was no statistically significant difference in CB changes between subcrestal and equicrestal implant positioning; however, subcrestal position resulted in higher bone levels. Neither mucosal recession nor vertical mucosa thickness was influenced by different implant placement depths.
Deproteinized bovine bone mineral is non‐inferior to deproteinized bovine bone mineral with 10% collagen in maintaining the soft tissue contour post‐extraction: A randomized trial
Authors: Sapata Vítor M. , Llanos Alexandre H. , Cesar Neto João B. , Jung Ronald E. , Thoma Daniel S. , Hämmerle Christoph H. F. , Pannuti Cláudio M. , Romito Giuseppe A.
Published: December 2019

Objectives

To test the non‐inferiority of demineralized bovine bone mineral (DBBM) compared to demineralized bovine bone mineral with 10% collagen (DBBM‐C) for the maintenance of the soft tissue contour after tooth extraction in the esthetic zone.

Material and Methods

Sixty‐five patients randomly received ridge preservation at a single site in the anterior maxilla with DBBM or DBBM‐C. Both, DBBM and DBBM‐C, were covered with a collagen matrix. Profilometric analyses were performed at baseline (BL), immediately after treatment (PO), and at 4 months (FU; day of implant placement). The main outcome was the horizontal mean change (HC) at the buccal aspect. The measurements also included changes of the estimated soft tissue thickness (eTT) at 1, 3, and 5 mm below the buccal gingival margin. Descriptive analysis was performed, and differences between groups were analyzed using independent samples t test. The non‐inferiority test was performed for HC.

Results

At 4 months, the horizontal mean change (HC) was −1.43 mm (±0.53 mm) (DBBM‐C) and −1.32 mm (±0.53 mm) (DBBM). Change of the estimated soft tissue thickness (eTT) between baseline (BL) and four months of follow‐up (FU) at 1, 3, and 5 mm amounted to −4.58 mm (±2.02 mm), −2.40 mm (±0.97 mm), and −1.37 mm (±0.78 mm) for DBBM‐C and to −4.12 mm (±1.80 mm), −2.09 mm (±0.91 mm), and −1.23 mm (±0.72 mm) for DBBM. The differences between the groups were not statistically significantly for any of the outcome measures (p > .05).

Conclusions

DBBM is non‐inferior to DBBM‐C for the maintenance of the soft tissue contour 4 months after tooth extraction.
Expanding the differential of superficial tumors with round‐cell morphology: Report of three cases of CIC‐rearranged sarcoma, a potentially under‐recognized entity
Authors: Maloney Nolan , Smith Stephen M. , Peters Sara B. , Batistatou Anna , Evangelou Zoi , Harms Paul W. , Chan May P. , Antonescu Cristina R. , Linos Konstantinos
Published: December 2019

Among sarcomas with a round‐cell morphology that lack rearrangement of the EWSR1 gene, rearrangements involving the CIC gene are the most common. In comparison with Ewing Sarcoma, CIC‐rearranged sarcomas present at an older average age, arise almost exclusively in soft tissues, are clinically more aggressive, and are more likely to be resistant to the chemotherapy regimens used for Ewing sarcoma. CIC‐rearranged sarcomas present more commonly in a deep location, and we suspect that superficial presentations may be under‐recognized. In this case series, we report three of such cases. Overall, the morphology is similar to CIC‐rearranged sarcomas of deeper locations. We hope to raise awareness among the dermatopathology community by expanding the differential of superficial tumors with round cell morphology.
Estimating prevalence and incidence of skin cancer in Germany
Authors: Krensel Magdalene , Petersen Jana , Mohr Peter , Weishaupt Carsten , Augustin Jobst , Schäfer Ines
Published: December 2019

Background and objectives

The aim of the present study was to determine the prevalence and incidence of skin cancer.

Patients and methods

We calculated prevalence and incidence for cutaneous melanoma (CM) and non‐melanoma skin cancer (NMSC) in 2012 in Germany, using claims data of 2.1 million insured persons. In order to allow statements concerning differences between subgroups, we calculated 95 % confidence intervals. Finally, we standardized prevalence and incidence with regard to the German population.

Results

The prevalence and incidence of CM amounted to 0.12 % and 0.04 % and increased with age. For NMSC these measures were 0.65 % and 0.15 %. Of the prevalent and incident patients, 88.9 % and 87.4 % (CM) and 99.4 % and 98.8 % (NMSC) respectively were at early stages. A projection on the whole population resulted in 75,419 persons affected by CM and 376,004 persons affected by NMSC, including 24,075 (CM) and 84,618 (NMSC) incident patients.

Conclusions

In this study, we defined epidemiological measures according to the number of patients affected by skin cancer and having a medical consultation indicating a need for treatment. These results can serve in future research as a data basis for analysis of health service demand in skin cancer patients and the associated costs.
Climate change jointly with migration ability affect future range shifts of dominant fir species in Southwest China
Authors: Liao Ziyan , Zhang Lin , Nobis Michael P. , Wu Xiaogang , Pan Kaiwen , Wang Keqing , Dakhil Mohammed A. , Du Mingxi , Xiong Qinli , Pandey Bikram , Tian Xianglin
Published: December 2019

Aim

As a prominent geographical distribution centre for the dark coniferous forests, mountains of Southwest China (MSWC) is experiencing an unprecedented warming trend, posing severe challenges to the survival of dominant fir (Abies) species. Although plant's migration ability is a prerequisite for its survival in changing environments, it has often been ignored in species distribution models (SDMs). This study aimed to quantify the magnitude and direction of range changes by the year 2080 for six dominant fir species, that isAbies recurvata,Abies faxoniana,Abies squamata,Abies ernestii,Abies forrestiiandAbies georgei, with an emphasis on exploring the relationship between migration ability and projected distributions.

Location

The mountains of Southwest China.

Methods

We applied the Maximum Entropy (Maxent) algorithm to calibrate ecological niche models and to project the climatically suitable areas (CSAs) of each species under two emission scenarios (RCP 4.5 and RCP 8.5). Additionally, we delimited future species ranges by three migration scenarios (full‐, no‐ and partial‐migration scenarios).

Results

The simulations showed the distinctive responses of the six fir species to anthropogenic climate change (ACC). By 2080, the distribution areas ofAbies recurvatawere projected to decline only in the no‐migration scenario but increase under the full‐ and partial‐migration scenarios, while the other five species were projected to decline in the majority of emission × migration scenarios. Fir species in the southern region were predicted to be more vulnerable to ACC due to the larger losses in CSAs and a stronger effect of the partial‐migration scenario on the newly colonized areas of this group. The studied species showed a simulated migration trend (northward and westward) to the interior Qinghai‐Tibet Plateau under ACC.

Main conclusions

Benefits or losses for species under ACC depended on the geographical location, their ecological niches and migration abilities, which provide essential insights for a spatial conservation assessment of biodiversity hotspots in the future.
Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high‐fat diet‐induced nonalcoholic fatty liver in rats
Authors: El‐Deen Reham M. , Heeba Gehan H. , Abdel‐latif Rania G. , Khalifa Mohamed M.A.
Published: December 2019

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease linked to insulin resistance, oxidative stress, and cytokine imbalance. Phosphodiesterase (PDE) inhibitors have shown remarkable antioxidant and anti‐inflammatory potential in different disease sets including liver diseases. This study aimed to compare the ameliorative effect of different PDE inhibitors on a high‐fat diet (HFD)‐induced NAFLD. Male Wistar rats were fed a HFD for 16 weeks to induce NAFLD, and then, oral treatments of a vehicle or different PDE inhibitors (pentoxifylline (50 mg/kg), cilostazol (20 mg/kg), or sildenafil (5 mg/kg)) were started in the last four weeks and given on a daily basis. Rats’ body composition and liver indices were recorded. Serum levels of liver enzymes, glucose, insulin, bilirubin, total cholesterol, triglycerides, and nitric oxide were measured. Liver tissues were used for histopathological examination and detecting oxidative stress and inflammatory markers. Results showed that different PDE inhibitors exhibited different efficacy against liver injury and metabolic disorders associated with HFD‐induced NAFLD in rodents evident by different strength‐ameliorated effects on the aforementioned parameters. Compared to cilostazol and sildenafil, insulin resistance, hepatic oxidative stress, and inflammatory markers were significantly reduced by pentoxifylline treatment. Furthermore, pentoxifylline nearly completely reversed hepatocyte steatosis and exhibited superior rectifying effect on the rats’ liver status compared with other PDE inhibitors. This investigation highlighted the potential role of PDE inhibitors in NAFLD treatment. Pentoxifylline had the most remarkable ameliorative effects against NAFLD, while sildenafil was the least effective.
Contribution of GPD2/mGPDH to an alternative respiratory chain of the mitochondrial energy metabolism and the stemness in CD133‐positive HuH‐7 cells
Authors: Mikeli Maimaiti , Fujikawa Makoto , Nagahisa Kai , Yasuda Shuhei , Yamada Natsuhiko , Tanabe Tsutomu
Published: December 2019

HuH‐7 cells, derived from human hepatocarcinoma, are known to contain the CD133‐positive cancer stem cell populations. HuH‐7 cells showed higher ATP synthesis activity through the respiratory chain compared to another human hepatocarcinoma cell line HepG2 and showed an especially higher glycerol‐3‐phosphate (G3P)‐driven ATP synthesis (G3P‐ATPase) activity. We found that the CD133‐positive HuH‐7 cells expressed high levels of GPD2 (glycerol‐3‐phosphate dehydrogenase or mGPDH) and showed high G3P‐ATPase activity. Next, to elucidate the relationship between CD133 and GPD2, we inhibited downstream factors of CD133 and found that a p38 inhibitor decreased the expression of GPD2 and decreased the G3P‐ATPase activity. Furthermore, GPD2‐knockdown (GPD2‐KD) cells exhibited strong reduction of the G3P‐ATPase activity and reduction of lactic acid secretion. Finally, we validated the effect of GPD2‐KD on tumorigenicity. GPD2‐KD cells were found to show decreased anchorage‐independent cell proliferation, suggesting the linkage of G3P‐ATPase activity to the tumorigenicity of the CD133‐positive HuH‐7 cells. Inhibition of G3P‐ATPase disrupts the homeostasis of energy metabolism and blocks cancer development and progression. Our results suggest inhibitors, targeting GPD2 may be potential new anticancer agents.
Effect of low‐dose factor VIII prophylaxis therapy on bone mineral density and 25(OH) vitamin D level in children with severe haemophilia A
Authors: Gamal Andrawes Nevine , Hashem Fayek Manal , Salah El‐Din Nouran , Atef Mostafa Raguia
Published: December 2019

Background

Decreased bone mineral density (BMD) is a significant morbidity in haemophilia. Vitamin D is important for the bone health of people with haemophilia. Regular factor VIII prophylaxis can prevent bleeding and arthropathy.

Aim

To determine the 25(OH) vitamin D level in severe haemophilia A patients and correlate it to their Hemophilia Joint Health Score (HJHS) and dual‐energy X‐ray absorptiometry (DEXA). We also compared the 25(OH) vitamin D and DEXA in haemophilia A and healthy children and in haemophilia A children on prophylaxis versus on‐demand therapy.

Methods

Fifty severe haemophilia A patients were compared to 50 age‐matched healthy boys. Patients were recruited from the Pediatric Hematology Clinic, Ain Shams University from May 2017 to April 2018. Full medical history was taken with emphasis on frequency of bleeding episodes, duration and amplitude of pain assessed by the pain score. Weight, height, body mass index and HJHS were assessed. 25(OH) vit‐D3, calcium, phosphorus and alkaline phosphatase were measured. BMD was assessed using Lunar DEXA, paediatric software.

Results

People with haemophilia had significantly lower 25(OH) vit‐D3 (P < .001) and DEXA z‐score (P < .001) than controls. Seventy per cent of patients were on factor VIII prophylaxis twice weekly (15U/kg/dose). Significant difference was found regarding DEXA z‐score (P = .012), 25(OH) vit‐D3 (P = .033) and HJHS (P = .022) among patients on prophylaxis and on‐demand therapy.

Conclusion

Severe haemophilia A patients showed significantly lower 25(OH) vit‐D3 and DEXA than controls. Hence, vitamin D deficiency should be tested in all people with haemophilia for early diagnosis and treatment. Low‐dose prophylaxis in severe haemophilia preserves BMD and increases vitamin D. Further studies are required to evaluate the effect of different prophylaxis protocols on BMD and haemophilic arthropathy.
Participation and consultation engagement strategies have complementary roles: A case study of patient and public involvement in clinical practice guideline development
Authors: Armstrong Melissa J. , Gronseth Gary S. , Gagliardi Anna R. , Mullins C. Daniel
Published: December 2019

Background

Patient and public involvement (PPI) is recommended when developing high‐quality clinical practice guidelines, but the effects of different PPI strategies are largely unstudied.

Objective

To assess the impact of participation and consultation strategies on guideline question development.

Design

Instrumental case study design.

Setting and participants

This study used a clinical practice guideline in development by the American Academy of Neurology. A patient, two caregivers and a dementia advocate participated in the guideline development group alongside clinicians. The guideline protocol was posted for public consultation for 30 days.

Interventions studied

Participation (patient representatives on the guideline development group) and consultation (public comment, survey) PPI strategies.

Main outcome measures

Public comment responses and guideline development group meeting transcripts were analysed descriptively. Transcript quotes were compared to the conceptual model of PPI in guideline development. The effects of participation and consultation strategies within the guideline case were compared.

Results

Participation strategies shaped discussions, set a patient‐centred scope, highlighted personal aspects of disease, affected how professionals viewed PPI, identified issues overlooked by medical professionals, and contributed to selecting patient‐relevant guideline populations and outcomes. Professionals responded to public comment more than patient representatives. Patient survey participants confirmed the priorities voiced by patient representatives on the guideline development group. Final guideline questions included populations and outcomes promoted by patient representatives despite negative feedback from professional public commenters.

Discussion and conclusions

Participation and consultation PPI strategies have different advantages. Congruence between strategies increases the strength of the patient voice. Guideline developers should prioritize using both strategies for successful PPI.
Effect of a pharmacist-led intervention on adherence among patients with a first-time prescription for a cardiovascular medicine: a randomized controlled trial in Norwegian pharmacies†
Authors: Hovland Ragnar , Bremer Sara , Frigaard Christine , Henjum Solveig , Faksvåg Per Kristian , Sæther Erik Magnus , Kristiansen Ivar Sønbø
Published: December 2019

Objective

To examine whether a pharmacist-led intervention improves medication adherence among patients who have filled a first-time prescription for a cardiovascular medicine.

Methods

Design: Unblinded randomized controlled trial. Setting: 67 Norwegian pharmacies, October 2014–June 2015. Participants: 1480 adults with a first-time prescription for a cardiovascular medicine. Intervention: Participants in the intervention group received two consultations with a pharmacist 1–2 and 3–5 weeks after filling the prescription. Participants in the control group received care according to usual practice. Main outcome measure: The primary outcome was self-reported adherence as measured by the 8-item Morisky Medication Adherence Scale (MMAS-8), at 7 and 18 weeks after filling the prescription. Adherence from baseline to week 52 was estimated using data from the Norwegian Prescription Database (NPD).

Key Findings

Data from MMAS-8 showed that 91.3% of the patients in the intervention group were adherent after 7 weeks versus 86.8% in the control group (4.5% difference, 95% CI 0.8–8.2, P = 0.017). The corresponding proportions were 88.7% versus 83.7% after 18 weeks (5.0% difference, 95% CI 0.8–9.2, P = 0.021). NPD data (n = 1294) showed no significant difference in adherence after 52 weeks (95% CI −2.0 to 7.8, P = 0.24). However, adherence among statin users (n = 182) was 66.5% in the intervention group versus 57.4% among new statin users in the general population (n = 1500) (difference 9.1%, 95% CI 1.5–16.0, P = 0.019).

Conclusion

The main outcome measure indicates that a short, structured pharmacist-led intervention may increase medication adherence for patients starting on chronic cardiovascular medication. However, these findings could not be confirmed by the NPD data analysis.
Properties of h‐Likelihood Estimators in Clustered Data
Authors: Youngjo Lee , Kim Gwangsu
Published: December 2019

We study properties of the maximum h‐likelihood estimators for random effects in clustered data. To define optimality in random effects predictions, several foundational concepts of statistics such as likelihood, unbiasedness, consistency, confidence distribution and the Cramer–Rao lower bound are extended. Exact probability statements about interval estimators for random effects can be made asymptotically without a prior assumption. Using the binary‐matched pair example, we illustrated that the use of random effects recover information, leading to the boon on estimating treatment effects.
A facile pathway to prepare molybdenum boride powder from molybdenum and boron carbide
Authors: Wang Yu , Zhang He , Jiao Shuqiang , Chou Kuo‐Chih , Zhang Guo‐Hua
Published: December 2019

Molybdenum boride is an ideal hard and wear‐resistant material. In this study, a new method is proposed for preparing molybdenum boride, by which Mo first reacts with B4C to generate the mixture of molybdenum boride and C, and then the product is decarburized by molten Ca to generate CaC2. Pure molybdenum boride could be obtained after acid leaching to remove the by‐product CaC2. According to the experimental and thermodynamic calculation results, it is concluded that the single‐phase MoB could be successfully prepared, while Mo2B, Mo2B5, and MoB4 could not be synthesized by this method. Moreover, it was found that the particle size of finally prepared MoB is determined by particle size of raw Mo powder. The residual carbon content of the product could be decreased to 0.10 wt% after first reaction at 1673 K for 6 hours and then decarburization reaction at 1673 K for 6 hours.
Divergent effects of canonical and non‐canonical TGF‐β signalling on mixed contractile‐synthetic smooth muscle cell phenotype in human Marfan syndrome aortic root aneurysms
Authors: Pedroza Albert J. , Koyano Tiffany , Trojan Jeffrey , Rubin Adam , Palmon Itai , Jaatinen Kevin , Burdon Grayson , Chang Paul , Tashima Yasushi , Cui Jason Z. , Berry Gerry , Iosef Cristiana , Fischbein Michael P.
Published: December 2019

Aortic root aneurysm formation is a cardinal feature of Marfan syndrome (MFS) and likely TGF‐β driven via Smad (canonical) and ERK (non‐canonical) signalling. The current study assesses human MFS vascular smooth muscle cell (SMC) phenotype, focusing on individual contributions by Smad and ERK, with Notch3 signalling identified as a novel compensatory mechanism against TGF‐β‐driven pathology. Although significant ERK activation and mixed contractile gene expression patterns were observed by traditional analysis, this did not directly correlate with the anatomic site of the aneurysm. Smooth muscle cell phenotypic changes were TGF‐β‐dependent and opposed by ERK in vitro, implicating the canonical Smad pathway. Bulk SMC RNA sequencing after ERK inhibition showed that ERK modulates cell proliferation, apoptosis, inflammation, and Notch signalling via Notch3 in MFS. Reversing Notch3 overexpression with siRNA demonstrated that Notch3 promotes several protective remodelling pathways, including increased SMC proliferation, decreased apoptosis and reduced matrix metalloproteinase activity, in vitro. In conclusion, in human MFS aortic SMCs: (a) ERK activation is enhanced but not specific to the site of aneurysm formation; (b) ERK opposes TGF‐β‐dependent negative effects on SMC phenotype; (c) multiple distinct SMC subtypes contribute to a ‘mixed’ contractile‐synthetic phenotype in MFS aortic aneurysm; and (d) ERK drives Notch3 overexpression, a potential pathway for tissue remodelling in response to aneurysm formation.
Histopathological kidney changes and myoglobinuria in neotropical non‐human primates attacked by dogs, Brazil
Authors: Fernandes Natália Coelho Couto de Azevedo , do Nascimento Paloma Martins , Sánchez‐Sarmiento Angélica M. , Ressio Rodrigo A. , dos Santos Cirqueira Cinthya , Kanamura Cristina Takami , de Carvalho Júlia , da Silva Silvana Mello Pereira , Peruchi Amanda Rezende , de Souza Junior Julio César , Hirano Zelinda Maria Braga , Catão‐Dias José Luiz
Published: December 2019

Background

Non‐human primates (NHPs) are susceptible to dogs’ attacks, events that may cause muscle damage along with stress, and could be in some extent compatible with capture myopathy, a syndrome that results in myoglobinuria and renal damage.

Methods

We aimed to evaluate by histopathology pre‐existing lesions and subsequent sequelae related to dogs’ attacks, acute tubular necrosis (ATN) and myoglobinuria, as well as the usefulness of Pearls Stain and IHC to diagnose it. Histopathology was performed in available organs, and sections of kidney submitted to Prussian blue stain and myoglobin immunohistochemistry.

Results

During January 2014—June 2016, 16/145 (11%) of NHPs received by Adolfo Lutz Institute, Brazil were reported as attacked by dogs. A high frequency of young and debilitated animals was found. Myoglobinuria was observed in more than half animals (9/16; 56.2%), from which (5/9; 55.5%) presented ATN.

Conclusions

Kidney lesions are plausible findings in NHPs attacked by dogs.
Tinkering and overruling the computer decision support system: Working strategies of telephone triage nurses who assess the urgency of callers suspected of having an acute cardiac event
Authors: Wouters Loes T. , Zwart Dorien L. , Erkelens Daphne C. , Huijsmans Marlies , Hoes Arno W. , Damoiseaux Roger A. , Rutten Frans H. , de Groot Esther
Published: December 2019

Aims and objectives

To understand clinical reasoning and decision‐making of triage nurses during telephone conversations with callers suspected of having acute cardiac events, and support from a computer decision support system (CDSS) herewith.

Background

In telephone triage, nurses assess the urgency of callers’ conditions with clinical reasoning, often supported by CDSS. The use of CDSS may trigger interactional workability dilemmas.

Design

Qualitative study using principles of a grounded theory approach following COREQ criteria for qualitative research.

Methods

Audio‐stimulated recall interviews were conducted amongst twenty‐four telephone triage nurses at nine out‐of‐hours primary care centres (OHS‐PC).

Results

Telephone triage nurses use clinical reasoning elements for urgency assessment. Typically in telephone triage, they interpret the vocal—but not worded—elements in communication (paralanguage) such as tone of voice and shortness of breath and create a mental image to compensate for lack of visual information. We confirmed that interactional workability dilemmas occur. Congruence, established when the CDSS supports the triage nurses’ decision‐making, is essential for the CDSS’ value. If congruence is absent, triage nurses may apply four working strategies: (a) tinker to make CDSS final recommendation align with their own assessment, (b) overrule the CDSS recommendation, (c) comply with the CDSS recommendation or (d) transfer responsibility to the GP.

Conclusion

Triage nurses who assess urgency may experience absence of congruence between the CDSS and their decision‐making. Awareness of how triage nurses reason and make decisions about urgency and what aspects influence their working strategies can help in achieving optimal triage of callers suspected of acute cardiac events at OHS‐PC.

Relevance to clinical practice

Triage nurses’ reasoning and their working strategies are vital for outcome of triage decisions. Understanding these processes is essential for CDSS developers and OHS‐PC managers, who should value how triage nurses interact with the CDSS, while they have the benefit of callers in mind.
Intaglio Surface Dimension and Guide Tube Deviations of Implant Surgical Guides Influenced by Printing Layer Thickness and Angulation Setting
Authors: Dalal Nishchal , Ammoun Rami , Abdulmajeed Aous A. , Deeb George R. , Bencharit Sompop
Published: December 2019

Purpose

To measure overall intaglio dimensional and tube deviations of implant guides printed at 50 and 100 µm layer thickness at 0°, 45°, and 90° angulation using a stereolithographic (SLA) printer.

Materials and Methods

A surgical implant guide design from a subject missing a maxillary right central incisor, used as the original standard tessellation language (STL) were stereolithographically fabricated at each thickness and angulation, 50 and 100 µm layer thickness at 0°, 45°, and 90° angulation (n = 10 each group). The guide was then scanned using cone beam computed tomography. The digital imaging and communications in medicine (DICOM) scanned files were then converted to an STL format. The overall dimensional deviations of the intaglio surface and the positioning of the implant guide tube were then superimposed onto the original designed STL file using best‐fitting alignment. A t‐test and an F‐test as well as ANOVA followed by a post hoc t‐test were used to determine statistical significant differences (α = 0.05) for the intaglio surface and guide tube deviation, respectively.

Results

The overall intaglio surface discrepancies (µm) printed at 0°, 45°, and 90° were 55.07 ± 1.36, 52.39 ± 2.09, and 61.02 ± 15.96 for 50 µm layer; and 98.38 ± 10.55, 84.47 ± 10.61, and 90.26 ± 5 for 100 µm layer with statistically significant differences for both t‐test and F‐test, p < 0.001. The maximal guide tube linear deviations (µm) printed at 0°, 45°, and 90° were 10.78 ± 3.84, 8.16 ± 3.68, and 12.57 ± 5.39 for 50 µm layer (ANOVA, p = 0.096); and 10.95 ± 5.23, 16.79 ± 4.97, and 22.63 ± 2.81 for 100 µm layer (ANOVA, p < 0.001). The maximal guide tube angular deviations (°) printed at 0°, 45°, and 90° were 1.29 ± 0.30, 0.64 ± 0.13, and 0.56 ± 0.21 for 50 µm layer (ANOVA, p < 0.001); and 1.57 ± 0.29, 0.86 ± 0.14, and 1.02 ± 0.31 for 100 µm layer (ANOVA, p = 0.034). There was a statistical difference in the deviations between 50 and 100 µm layer printing in all printed angulations except at 0° (t‐test, p = 0.05, p = 0.03, and p = 0.001 for 0°, 45°, and 90°) and linear deviations (t‐test, p < 0.001, p = 0.009, and p = 0.001 for 0°, 45°, and 90°).

Conclusion

Printing at 50 µm layer reduces dimensional intaglio deviations in general and reduces tube angular deviations with different angulations of printing. However, the deviations were only ∼60 to 100 µm for the intaglio dimension deviations; and ∼0.04 to 0.26 mm and ∼0.25° to ∼2° for tube deviations.
Characterization of body knotting behavior used for escape in a diversity of hagfishes
Authors: Haney W. A. , Clark A. J. , Uyeno T. A.
Published: December 2019

Hagfishes possess flexible bodies that allow them to tie and manipulate body knots. These knots are used to remove mucous from the body, escape tight spaces, pull prey from burrows and, since they lack opposable jaws, to create leverage during feeding events. Despite its importance, knotting is poorly understood because this fast and three‐dimensionally complex behavior is difficult to study both in the laboratory and in their natural benthic habitats. To consistently stimulate analyzable knotting behaviors, we developed a novel restraint device to record high‐speed, biplanar video in three species of hagfish from two major taxa (Eptatretinae and Myxininae): Eptatretus stoutii, Eptatretus springeri and Myxine glutinosa. These data were analyzed to characterize knot type and kinematics of knot formation. We found that despite reduced radii of curvature and strain associated with more complex knots, all species of hagfish preferred the simplest overhand knots. While all species were physically capable of tying more complex knots, E. stoutii exhibited a lower ‘behavioral’ stiffness by tying complex knots more frequently and coiling when at rest. The hyper‐flexible, hyper‐redundant hagfish body may require a high level of neural input for control. However, analyses of knotting motions indicate that hagfish seem to employ only four movements (body bends, twists, surface contacts and tail insertions into body loops) but in different combinations depending on the knot being tied. Furthermore, these movements and combinations are conserved across all species tested. We hypothesize that control of knotting in hagfish may employ motor primitives to reduce neural input.
Clinical utility of hepatocellular carcinoma risk scores in chronic hepatitis B
Authors: Voulgaris Thodoris , Papatheodoridi Margarita , Lampertico Pietro , Papatheodoridis George V.
Published: December 2019

Background

Several risk scores have been recently developed to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. We systematically assessed the performance of the available HCC risk scores.

Methods

Literature search was performed to identify all published studies reporting development or external validation of HCC risk scores in CHB patients.

Results

Until March 2019, 12 scores were developed in untreated Asian and 7 scores in treated Asian (n = 6) or Caucasian (n = 1) patients. All scores provided significant predictions for HCC development in the derivation and validation cohorts of their original studies (c‐statistic: 0.76‐0.95) and usually classified patients into low, medium and high HCC risk groups. Eleven independent studies and three studies developing their own scores have validated externally some scores in Asian (GAG‐HCC:5, CU‐HCC:6, REACH‐B:6, REACH‐Bm:4, LSM‐HCC:3, PAGE‐B:5) or Caucasian/mixed origin patients (GAG‐HCC:4, CU‐HCC:4, REACH‐B:4, PAGE‐B:2). All scores offered acceptable predictability in almost all independent Asian cohorts (c‐statistic: 0.70‐0.86), but only PAGE‐B and recently modified PAGE‐B (mPAGE‐B) offered good predictability in all independent Caucasian and/or Asian cohorts. Negative predictive values for 5‐year HCC prediction were ≤99% (95%‐99%) in most independent cohorts assessing Asian risk scores and 99%‐100% in all independent cohorts (Caucasian/mixed origin:2; Asian:3) assessing PAGE‐B and/or recently mPAGE‐B.

Conclusions

Direct comparison of the newest HCC risk scores in independent patient cohorts of different origin remains intriguing, although statistical associations may not be directly transferable to clinical practice. PAGE‐B and recently mPAGE‐B score seem to offer persistently high predictability for Caucasian and/or Asian treated patients with low HCC risk who require no surveillance.
Congenital antithrombin deficiency in patients with splanchnic vein thrombosis
Authors: Baiges Anna , de la Morena‐Barrio María Eugenia , Turon Fanny , Miñano Antonia , Alberto Ferrusquía Jose , Magaz Marta , Reverter Juan Carlos , Vicente Vicente , Hernández‐Gea Virginia , Corral Javier , García‐Pagán Juan Carlos
Published: December 2019

Background and aims

Splanchnic vein thromboses (SVT) are a rare condition that can be life‐threatening. The most severe thrombophilia associated to SVT is antithrombin (AT) deficiency, usually caused by SERPINC1 mutations. Although transitory AT deficiencies and congenital disorders of the N‐glycosylation pathways (CDG) have been recently reported as causes of AT deficiency, the current AT clinical screening still only includes anti‐FXa activity. This study aims to (a) improve the detection of AT deficiency in SVT and (b) characterize the features of AT deficiency associated with SVT.

Methods

The study was performed in 2 cohorts: (a) 89 SVT patients with different underlying etiologies but in whom AT deficiency had been ruled out by classical diagnostic methods; and (b) 271 unrelated patients with confirmed AT deficiency and venous thrombosis. AT was evaluated by functional (anti‐FXa and anti‐FIIa) and immunological methods (ELISA, crossed immunoelectrophoresis, western blot), and SERPINC1 sequencing was performed.

Results

In 4/89 patients (4.5%) additional alterations in AT were found (two had SERPINC1 mutations, one had a specific variant causing transient AT deficiency and one patient had CDG). In 11 of the 271 patients (4.1%) with AT deficiency and thrombosis, thrombosis was located at the splanchnic venous territory.

Conclusions

Antithrombin deficiency may be underdiagnosed by current clinical screening techniques. Therefore, a comprehensive AT evaluation should be considered in cases of rethrombosis or doubtful interpretation of anti‐FXa activity levels. SVT is a relatively common localization of the thrombotic event in patients with congenital AT deficiency.
Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis
Authors: Sangnes Dag A. , Søfteland Eirik , Bekkelund Mattis , Frey Jakub , Biermann Martin , Gilja Odd Helge , Dimcevski Georg
Published: December 2019

Background

Gastroparesis is a potentially severe late complication of diabetes mellitus. Today, delayed gastric emptying (GE) is mandatory for establishing the diagnosis. In this study, we compared wireless motility capsule (WMC) with gastric emptying scintigraphy (GES).

Methods

Seventy‐two patients (49 women) with diabetes mellitus (59 type 1) and symptoms compatible with gastroparesis were prospectively included between 2014 and 2018. Patients were simultaneously examined with GES and WMC. Symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI‐SYM) questionnaire. All patients were on intravenous glucose‐insulin infusion during testing.

Key Results

WMC and GES correlated r = .74, P < .001. Compared to GES, WMC at ordinary cutoff for delayed GE (300 minutes) had a sensitivity of 0.92, specificity 0.73, accuracy 0.80, and Cohen's kappa κ = 0.61 (P < .001). By receiver operating characteristics (ROC), the area under the curve was 0.95 (P < .001). A cutoff value for delayed GE of 385 minutes produced sensitivity 0.92, specificity 0.83, accuracy 0.86, and Cohen's kappa κ = 0.72 (P < .001). Inter‐rater reliability for GE time with WMC was r = .996, κ = 0.97, both P < .001. There was no difference in symptom severity between patients with normal and delayed GE.

Conclusions & Inferences

Our findings demonstrate the applicability of WMC as a reliable test to assess gastric emptying in diabetic gastroparesis showing very high inter‐observer correlation. By elevating the cutoff value for delayed emptying from 300 to 385 minutes, we found higher specificity without reducing sensitivity.
Prediction of postoperative lower respiratory tract infections in tongue cancer patients based on pretreatment swallowing function
Authors: Deng Wei , Yang Le , Xie Chunqing , Lu Huanzi , Xiao Yudong , Zeng Bin , Liang Yujie , Liao Guiqing
Published: December 2019

Objectives

This study investigated the predictive role of pretreatment swallowing function and surgical factors on postoperative and nosocomial lower respiratory tract infections (PN‐LRTIs).

Subjects and methods

A retrospective study for predicting PN‐LRTIs from January 2017 to December 2018 at Hospital of Stomatology, Sun Yat‐sen University. Patients who were newly diagnosed with tongue squamous cell carcinoma (TSCC) were enrolled. Presurgical swallowing function was assessed using water swallow test (WST) and the M.D. Anderson Dysphagia Inventory (MDADI).

Results

A total of 83 patients were recruited to the study. Of which 54 were men (65.1%) and 29 were women (34.9%), with the mean age of 51 years old. Thirteen (15.7%) developed PN‐LRTIs. On univariate analysis, the outcomes of WST, the MDADI scores, T stage, tongue resection range, operative time, segmental mandibulectomy, and type of neck dissection exhibited a statistical significance (p < .05). On multivariate analysis, abnormal group of WST (odds ratio [OR], 15.88; 95% CI, 2.13–118.64) and total glossectomy (OR, 12.20; 95% CI, 2.01–68.32) was demonstrated to be independent risk factors.

Conclusions

The WST together with the resection range of tongue can predict the postoperative risk of PN‐LRTIs collaboratively. Clinically, preventive measures and intensified care should be taken for patients with abnormal WST outcome before surgery and management of total glossectomy.