bluuebunny/crossref_metadata_2025 huggingface dataset:
We collaborate with everyone, but with some more than others: evidence of stakeholder collaboration among internal security professional higher education institutions
Authors: Valk Anne , Kratovitš Mairit
Published: February 2021

The aim of this article is to identify the main stakeholders of institutions of professional higher education in the field of internal security in selected countries, and the most important collaboration practices, and the factors that affect collaboration. Within the framework of a qualitative phenomenographic study, interviews were conducted with representatives of Estonian, German, Finnish, and Norwegian institutions of professional education in the field of internal security. The results showed that institutions of professional higher education differ from traditional universities in prioritizing their main stakeholders, putting employers first, and not students. In addition, the ministries under whose government they operate, and other higher education institutions were named as the main stakeholders. Collaboration with stakeholders is mostly based on common interests and personal relationships (e.g., mediation, networking, joint reputation building, collaboration councils), on some kind of formal basis (e.g., feedback system, collaboration councils) or subordination (e.g., execution of orders and instructions, trading). The aspects most influencing collaboration were considered to be the aspects related to trust and professionalism, and in particular informal collaboration was valued. The results of this study enabled the author to supplement a framework from a previous study, which originally described the theoretical collaboration of the stakeholders of an institution of higher education in the field of internal security; this was supplemented by adding the dimension of collaboration diversity.
Repeated triggered ruptures on a distributed secondary fault system: an example from the 2016 Kumamoto earthquake, southwest Japan
Authors: Ishimura Daisuke , Tsutsumi Hiroyuki , Toda Shinji , Fukushima Yo , Kumahara Yasuhiro , Takahashi Naoya , Ichihara Toshihiko , Takada Keita
Published: February 2021

The Mw7.0 2016 Kumamoto earthquake occurred on the previously mapped Futagawa–Hinagu fault causing significant strong ground motions. A ~ 30-km-long dextral surface rupture appeared on the major fault zone and dextral slip was up to 2–3 m. However, the surface ruptures were also broadly and remotely distributed approximately 10 km away from the primary rupture zone. These numerous distributed secondary surface slips with vertical displacement of less than a few tens of centimeters were detected by the interferometric synthetic aperture radar (InSAR) technology in previous studies. Such displacements occurred not only on previously mapped faults but also on unknown traces. Here, we addressed the following fundamental issues: whether the broadly distributed faults were involved in the past major earthquakes in the neighborhood, and how the fault topography of such secondary faults develops, seismically or aseismically. To find clues for understanding these issues, we show the results of field measurements of surface slips and paleoseismic trenching on distributed secondary faults called the Miyaji faults inside the Aso caldera, 10 km away from the eastern end of the primary rupture zone. Field observations revealed small but well-defined dextral slip surface ruptures that were consistent with vertical and dextral offsets derived from InSAR. On the trench walls, the penultimate event with vertical displacements almost similar to the 2016 event was identified. The timing of the penultimate event was around 2 ka, which was consistent with that of the primary fault and archeological information of the caldera. Considering the paleo-slip event and fault models of the Miyaji faults, they were presumed not to be source faults, and slip on these faults have been triggered by large earthquakes along major adjacent active faults. The results provide important insights into the seismic hazard assessment of low-slip-rate active faults and fault topography development due to triggered displacement along secondary faults.
Different solutions lead to similar life history traits across the great divides of the amniote tree of life
Authors: Meiri Shai , Murali Gopal , Zimin Anna , Shak Lior , Itescu Yuval , Caetano Gabriel , Roll Uri
Published: February 2021

Amniote vertebrates share a suite of extra-embryonic membranes that distinguish them from anamniotes. Other than that, however, their reproductive characteristics could not be more different. They differ in basic ectothermic vs endothermic physiology, in that two clades evolved powered flight, and one clade evolved a protective shell. In terms of reproductive strategies, some produce eggs and others give birth to live young, at various degrees of development. Crucially, endotherms provide lengthy parental care, including thermal and food provisioning—whereas ectotherms seldom do. These differences could be expected to manifest themselves in major differences between clades in quantitative reproductive traits. We review the reproductive characteristics, and the distributions of brood sizes, breeding frequencies, offspring sizes and their derivatives (yearly fecundity and biomass production rates) of the four major amniote clades (mammals, birds, turtles and squamates), and several major subclades (birds: Palaeognathae, Galloanserae, Neoaves; mammals: Metatheria and Eutheria). While there are differences between these clades in some of these traits, they generally show similar ranges, distribution shapes and central tendencies across birds, placental mammals and squamates. Marsupials and turtles, however, differ in having smaller offspring, a strategy which subsequently influences other traits.
A clinical and radiographic study of implants placed in autogenous bone grafts covered by either a platelet-rich fibrin membrane or deproteinised bovine bone mineral and a collagen membrane: a pilot randomised controlled clinical trial with a 2-year follow-up
Authors: Hartlev Jens , Schou Søren , Isidor Flemming , Nørholt Sven Erik
Published: February 2021

Purpose

To compare the survival and clinical performance of implants placed in sites previously augmented with autogenous bone grafts covered by either a platelet-rich fibrin (PRF) membrane (PRF group) or a standard procedure (gold standard) involving coverage of the autogenous bone graft with deproteinised bovine bone mineral and a resorbable collagen membrane (control group).

Methods

A total of 27 partially edentulous patients (test n = 14, control n = 13) with indication for staged lateral bone block augmentation and dental implant placement were included. Twenty-four months after crown placement (range: 14–32 months), patients were recalled for a final clinical and radiographic follow-up. Outcome measures were implant survival, implant crown survival, clinical parameters of the implant, peri-implant marginal bone level, marginal bone level of adjacent tooth surfaces, biological and technical complications and patient-related outcome measures.

Results

Two implants were lost in the control group (85% survival rate); none were lost in the PRF group (100% survival rate). None of the 26 initially placed implant crowns were lost, but one implant and therefore one implant crown were lost after 20 months. Consequently, the definitive implant crown survival was 92% (95% confidence interval (CI): 73–110%) in the control group and 100% in the PRF group. No statistical difference in implant survival rate (p = 0.13) or implant crown survival was seen between the groups (p = 0.28). The mean marginal bone level at the follow-up was 0.26 mm (95% CI: 0.01–0.50 mm) in the PRF group and 0.68 mm (95% CI: 0.41–0.96 mm) in the control group. The difference between the groups was − 0.43 mm (95% CI: − 0.80 to − 0.05 mm, p = 0.03), which was statistically significant (p = 0.03). Both groups demonstrated similar healthy peri-implant soft tissue values at the final follow-up.

Conclusion

Although the current study is based on a small sample of participants, the findings suggest that the methodology of the PRF and the control group approach can both be used for bone augmentation with a similar outcome. A significant, but clinically irrelevant, higher peri-implant marginal bone level was registered in the PRF group than in the control group. Patients in both groups were highly satisfied with the treatment.

Trial registration

ClinicalTrials.gov Identifier: NCT04350749. Registered 17 April 2020. Retrospectively registered.
A classroom intervention targeting working memory, attention and language skills: a cluster randomised feasibility trial
Authors: Rowe Anita , Titterington Jill , Holmes Joni , Henry Lucy , Taggart Laurence
Published: February 2021

Background

International debate around the best models of speech and language therapy provision for children with language disorders has highlighted the need for research into classroom-based approaches and intervention dosage. Working memory (WM) is a cognitive skill linked to attention and language. ‘Recall to Enhance Children’s Attention, Language and Learning’ (RECALL) is a novel, 6-week, classroom-based intervention delivered by health professionals (HPs) and teachers. It is designed to target WM and enhance attention and language skills in 4–5 year olds.

Methods

A cluster randomised feasibility trial was conducted to investigate aspects of the feasibility of a definitive trial to evaluate RECALL: (i) recruitment and sampling procedures; (ii) compliance and fidelity; (iii) the acceptability of RECALL to HPs and teachers; (iv) the appropriateness of the outcome measures. Six classes of 4–5 year olds participated: two received RECALL, two received an existing intervention targeting attention skills (not underpinned by WM theory), and two received education as usual (no intervention). Ten children in each class (n = 60) were sampled to assess the appropriateness of the outcome measures. Classroom observations were conducted to measure fidelity and semi-structured interviews with HPs, and teachers explored the acceptability of RECALL.

Results

The recruitment targets were met, and all six schools completed the trial, but the sampling procedures require modification. Compliance was good (95% of RECALL sessions were delivered), but fidelity to the intervention protocol varied between 76% and 45% across the two schools. This was influenced by large class sizes, child factors, and facilitator factors, e.g., their understanding of the theory underpinning the intervention. The lack of fidelity reduced the dose (number of practice items) accessed by individual children, particularly those most at risk. There were mixed findings regarding the acceptability of RECALL and the appropriateness of the outcome measures.

Conclusions

The trial protocol could be easily scaled-up in a future definitive trial, with an amended sampling procedure. RECALL should be repackaged as a small group intervention to enhance the fidelity of its delivery and its acceptability to HPs and teachers. This study highlights the need for thorough training for professionals who deliver classroom-based interventions for children with language disorders.

Trial registration

ISRCTN13633886. Registered on 7 September 2018
Successful removal of a central venous catheter misplaced in the right subclavian artery using an intravascular stent: a case report
Authors: Yoshida Haruka , Ikemoto Shinichiro , Tokinaga Yasuyuki , Ejiri Kanako , Kawamata Tomoyuki
Published: February 2021

Background

Cannulation of a central venous catheter is sometimes associated with serious complications. When arterial cannulation occurs, attention must be given to removal of a catheter.

Case presentation

A 62-year-old man was planned for emergency thoracic endovascular aortic repair. After the induction of anesthesia, a central venous catheter was unintentionally inserted into the right subclavian artery. We planned to remove the catheter. Since we considered that surgical repair would be highly invasive for the patient, we decided to remove it using a percutaneous intravascular stent. A stent was inserted through the right axillary artery. The stent was expanded immediately after the catheter was removed. Post-procedural angiography revealed no leakage from the catheter insertion site and no occlusion of the right subclavian and vertebral arteries. There were no obvious hematoma or thrombotic complications.

Conclusions

A catheter that has been misplaced into the right subclavian artery was safely removed using an intravascular stent.
Filter lifetimes of different hemodiafiltration membrane materials in dogs: reevaluation of the optimal anticoagulant dosage
Authors: Yuzawa Hiroko , Hirose Yousuke , Kimura Tomonori , Shinozaki Keisuke , Oguchi Moe , Morito Tomohiro , Sadahiro Tomohito
Published: February 2021

Background

In continuous renal replacement therapy (CRRT), administration of anticoagulants is necessary for achieving a certain level of filter lifetime. Generally, anticoagulant doses are controlled to keep activated partial thromboplastin time and other indicators within a certain target range, regardless of the membrane materials used for the filter. However, in actual clinical practice, the filter lifetime varies significantly depending on the membrane material used. The objective of this study was to demonstrate that the minimum anticoagulant dose necessary for prolonging the filter lifetime while reducing the risk of hemorrhagic complications varies depending on the type of membrane.

Methods

In three beagles, hemodiafiltration was performed with hemofilters using polysulfone (PS), polymethylmethacrylate (PMMA), and AN69ST membranes separately. The minimum dose of nafamostat mesylate (NM) that would allow for 6 h of hemodiafiltration (required dose) was investigated for each membrane material.

Results

The NM doses required for 6 h of hemodiafiltration were 2 mg/kg/h for the PS membrane, 6 mg/kg/h for the PMMA membrane, and 6 mg/kg/h for the AN69ST membrane.

Conclusion

For hemodiafiltration performed in beagles, the required NM dose varied for each filter membrane material. Using the optimal anticoagulant dose for each membrane material would allow for safer CRRT performance.
Policy implications for awareness gaps in antimicrobial resistance (AMR) and antimicrobial use among commercial Nepalese poultry producers
Authors: Lambrou Anastasia S. , Innes Gabriel K. , O’Sullivan Laura , Luitel Himal , Bhattarai Rebanta K. , Basnet Hom B. , Heaney Christopher D.
Published: February 2021

Background

Nepal’s poultry industry has increased with a growing middle class, which has translated to an increase in antimicrobial consumption and thus a rise in antimicrobial resistance (AMR). Describing and understanding antimicrobial use practices among commercial poultry producers in Nepal may help minimize the risks of AMR development in both humans and animals and determine the effectiveness of relevant policies.

Methods

From July to August 2018, poultry farmers were randomly recruited from Nepal’s Chitwan District to participate in a cross-sectional study. The lead producer in each poultry operation was administered a quantitative structured-survey via a 30-min interview. Participants were asked to provide demographics, production practices, and knowledge about their antimicrobial use practices. Descriptive data analysis was performed to obtain frequencies and compare practices.

Results

In total, 150 commercial poultry producers of whom raised between 300 and 40,000 birds completed the interviews. Only 33% (n = 49) of producers reported knowing what AMR was, and among them only 50% (n = 25) consulted a veterinarian for treatment options. Antimicrobial administration for growth promotion was still employed by 13% of poultry producers. Similarly, critically important antimicrobial drugs, specifically colistin, were identified at 35% of participating operations. Producers reported low overall understanding and compliance of withdrawal periods (n = 41; 27%), which may result in both AMR development and adverse health reactions among consumers who ingest antimicrobial residues. Although Nepal has publicized antimicrobial use policies and awareness campaigns to instill healthy production practices, most producers (82%) were unaware of them.

Conclusion

Many Nepalese poultry producers lack overall antimicrobial use and AMR awareness, which is evidenced by low antimicrobial withdrawal period compliance, use of antimicrobials for growth promotion, and the sustained use of critically important antimicrobials. Improved outreach and educational capacities, paired with increased veterinary resources and extensive monitoring in operations and retail meat products, may increase AMR awareness and policy enforcement.
Morphological and molecular identification of four Purpureocillium isolates and evaluating their efficacy against the sweet potato whitefly, Bemisia tabaci (Genn.) (Hemiptera: Aleyrodidae)
Authors: Sun Tingfei , Wu Jianhui , Ali Shaukat
Published: February 2021

Background

Entomopathogenic fungi are widely distributed and well described within the fungal kingdom. This study reports the isolation, characterization, and virulence of 4 Purpureocillium lilacinum isolates against the sweet potato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae).

Results

Four strains of Purpureocillium lilacinum (XI-1, XI-4, XI-5, and J27) were isolated from soil samples from different localities of China. The morphological studies observed that four strains showed essentially the same morphological characteristics. After 7 days of cultivation, the colonies were purple, round, and bulged. Conidia were single-celled, oval to spindle-shaped, chain-like, and the spore size was about 2.0–2.3 × 3.1–4.0 μm. The genome-based identification results showed that ITS sequences of XI-1 (GenBank accession # MW386433), XI-4 (GenBank accession # MW386434), XI-5 (GenBank accession # MW386435), and J27 (GenBank accession # MW386436) were similar to another P. lilacinum. The newly identified strains of P. lilacinum proved pathogenicity to B. tabaci under laboratory conditions. In addition, the P. lilacinum isolate XI-5 was the most virulent one against different nymphal instars of whitefly having median lethal concentration (LC50) values of 4.99 × 106, 4.82 × 105, and 2.85 × 106 conidia/ml, respectively, 7 days post application.

Conclusion

The newly isolated strains of P. lilacinum can be developed as a potential biopesticide against the whitefly although extensive field bioassays as well as development of proper formulation are still required.
The efficacy of repetitive transcranial magnetic stimulation in treating patients with chronic daily headache
Authors: AbdElkader Ann Ali , Fahmy Ebtesam Mohammed , Ahmad Ayat Allah Farouk , Labib Amira A. , El-Mekkawy Leqaa Ali , El Razek Shaimaa shaheen Mohammed Abd
Published: February 2021

Background

Headache is the most commonpain disorder, affecting around 66% of the global population. This study aimed to investigate the efficacy of high-frequencyrepetitive transcranial magnetic stimulation(rTMS) in treating patients with primary chronic daily headaches (chronictension-type headacheand chronic migraine).

Methods

Twenty-seven patients participated in the study, divided into 2 groups: a study group (16 patients) and a control group (11 patients). Treatment consisted of 12 high-frequency (5 Hz) real rTMS sessions, delivered over the left dorsolateral prefrontal cortex (DLPFC), whereas sham rTMS was used for the control group.

Results

Patients of the study group, after real rTMS stimulation, showed a high statistically significant reduction of the measured headache parameters compared to the control group (Pvalue < 0.001), and the percentage of improvement was 94.5%. No significant reduction of headache parameters, after sham rTMS stimulation, was observed in the control group (Pvalue > 0.05) and the percentage of improvement was 7.9%.

Conclusion

High-frequency rTMS is effective in reducing chronic tension headaches andchronic migraines. This finding runs with the approval of the suggested role of DLPFC in pain control. This might open opinions for new treatment strategies in tension-type headache and migraine prevention.
Prevalence of obsessive-compulsive disorder (OCD) among Iraqi undergraduate medical students in time of COVID-19 pandemic
Authors: Taher Taqi Mohammed Jwad , Al-fadhul Shaymaa Abdul Lateef , Abutiheen Ali A. , Ghazi Hasanain Faisal , Abood Naeem Shami
Published: February 2021

Background

Obsessive-compulsive disorder (OCD) is a common mental disorder affecting millions of people. Its onset and peak are during late teens making university students a priority target. Medical student perhaps is at greater risk for developing OCD while corona COVID-19 is expected to more exaggerate symptoms mainly with extra hygiene and cleanliness practices. The aim of the study was to estimate the prevalence of OCD symptoms among Iraqi medical students, and to assess the associated psychological symptoms and its correlates. An analytic cross-sectional study was conducted among Iraqi medical students during the period from August to October 2020. An online anonymous, voluntary, and self-administered questionnaire based on the 18 questions Obsessive-Compulsive Inventory-Revised scale (OCI-R) was used to collect the data.

Results

A total of 1644 students had filled the questionnaire. Females were 1116 (67.9%), while 1153 (70.1%) had reported accompanying mental symptoms. Of which worry and stress were the most prevalent with 674 (25.9%) and 617 (23.7%) respectively. However, 707 (43%) have probable OCD symptoms that need further assessment. Unpleasant thoughts were the most prevalent symptoms with 51.8%. Surprisingly, the washing and contamination scales were low at 14% and 19.4% while repeating certain numbers was the least with 8%. OCD symptoms were significantly related to younger age and earlier years of study. Further, all accompanied mental symptoms were significantly associated with probable OCD status.

Conclusion

High prevalence of OCD among medical students during the COVID-19 pandemic. No association of OCD with gender and family history. Younger students and early years of study were more likely to suffer from OCD symptoms.
Psychological distress and its risk factors during COVID-19 pandemic in Saudi Arabia: a cross-sectional study
Authors: Elhessewi Ghada Moh Samir , Almoayad Fatmah , Mahboub Samira , Alhashem Anwar Mohammed , Fiala Lamiaa
Published: February 2021

Background

The control measures during COVID-19 such as curfew, lockdown, and social distancing had observed differences in controlling the spread of the disease around the Kingdom of Saudi Arabia; however, they might contribute to psychological illnesses such as anxiety, depression, panic disorder, and distress. A cross-sectional descriptive study was conducted to assess psychological distress and the factors affecting it among general population in the Kingdom of Saudi Arabia during the COVID-19 pandemic.

Results

Seven hundred and thirty-nine people completed an online questionnaire which included the Kessler Psychological Distress Scale (K10). Psychological distress was found among 35% of the study sample. Western and northern regions reported higher rates of distress. In addition, higher rates were found among younger and unmarried individuals. Distress was significantly positively correlated with perceptions of susceptibility and severity of COVID-19 infection, and the fear to lose a job as a result of the pandemic and the related precautions.

Conclusion

Psychological support programs should be provided targeting high-risk groups of younger and unmarried population. Further research should be conducted to evaluate the effectiveness of psychological support interventions.
Drug delivery nanocarriers and recent advances ventured to improve therapeutic efficacy against osteosarcoma: an overview
Authors: Desai Sujit Arun , Manjappa Arehalli , Khulbe Preeti
Published: February 2021

Background

Osteosarcoma (OS) is one of the key cancers affecting the bone tissues, primarily occurred in children and adolescence. Recently, chemotherapy followed by surgery and then post-operative adjuvant chemotherapy is widely used for the treatment of OS. However, the lack of selectivity and sensitivity to tumor cells, the development of multi-drug resistance (MDR), and dangerous side effects have restricted the use of chemotherapeutics.

Main body

There is an unmet need for novel drug delivery strategies for effective treatment and management of OS. Advances in nanotechnology have led to momentous progress in the design of tumor-targeted drug delivery nanocarriers (NCs) as well as functionalized smart NCs to achieve targeting and to treat OS effectively. The present review summarizes the drug delivery challenges in OS, and how organic nanoparticulate approaches are useful in overcoming barriers will be explained. The present review describes the various organic nanoparticulate approaches such as conventional nanocarriers, stimuli-responsive NCs, and ligand-based active targeting strategies tested against OS. The drug conjugates prepared with copolymer and ligand having bone affinity, and advanced promising approaches such as gene therapy, gene-directed enzyme prodrug therapy, and T cell therapy tested against OS along with their reported limitations are also briefed in this review.

Conclusion

The nanoparticulate drugs, drug conjugates, and advanced therapies such as gene therapy, and T cell therapy have promising and potential application in the effective treatment of OS. However, many of the above approaches are still at the preclinical stage, and there is a long transitional period before their clinical application.
Medulloblastoma: clinicopathological parameters, risk stratification, and survival analysis of immunohistochemically validated molecular subgroups
Authors: Eid Asmaa Mustafa , Heabah Nehal Abd El-Ghaffar
Published: February 2021

Background

Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular subgrouping using surrogate immunohistochemistry and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) and progression-free survival (PFS) of MB patients. This study included 40 MBs; immunohistochemical staining, using β-catenin and GRB2-Associated Binding Protein 1 (GAB1) antibodies, was used to classify MB cases into wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/SHH molecular subgroups. Nuclear morphometric analysis (for assessment of degree of anaplasia) and Kaplan-Meier survival curves were done.

Results

MB cases were classified into WNT (10%), SHH (30%), and non-WNT/SHH (60%) subgroups. Histopathological types differed significantly according to tumor location (p< 0.001), degree of anaplasia (p = 0.014), molecular subgroups (p < 0.001), and risk stratification (p = 0.008). Molecular subgroups differed significantly in age distribution (p = 0.031), tumor location (p< 0.001), histopathological variants (p < 0.001), and risk stratification (p < 0.001). OS was 77.5% and 50% after 1 and 2 years, while PFS was 65% and 27.5% after 1 and 2 years, respectively. OS and PFS were associated significantly with histopathological variants (p < 0.001 and 0.001), molecular subgroups (p = 0.012 and 0.005), and risk stratification (p < 0.001 and < 0.001), respectively.

Conclusions

Medulloblastoma classification based on molecular subgroups, together with clinicopathological indicators, mainly histopathological types; accurately risk stratifies MB patients and predicts their survival.
COVID-19 causing acute deterioration of interstitial lung disease: a case report
Authors: Kathar Hussain Mohamed Rafi , Kulasekaran N. , Anand A. M. , Danassegarane Padma Reka
Published: February 2021

Background

Interstitial lung disease (ILD) comprises a heterogeneous group of disorders characterized by multifocal diffuse lung involvement. Similarly, COVID-19 has varied multispectral organ involvement. Patients with underlying ILD and coexistent COVID-19 infection may lead to an acute blow to the already deceased lung.

Case presentation

A 58-year-old man presented with fever and cough with expectoration for the past 4 days associated with breathlessness. He was a smoker and alcoholic for the past 20 years. His saturation was low in room air around 84% and improved to 98% with 10 l/min of nasal oxygen. Further investigation shows acute deterioration of ILD.

Conclusion

COVID-19 infection has a spectrum of manifestations. Acute deterioration of ILD is rarely reported in the literature. Etiology should be investigated further.
A practice facilitation-guided intervention in primary care settings to reduce cardiovascular disease risk: a cost analysis
Authors: Gold Heather T. , Siman Nina , Cuthel Allison M. , Nguyen Ann M. , Pham-Singer Hang , Berry Carolyn A. , Shelley Donna R.
Published: February 2021

Background

A stepped-wedge, cluster randomized controlled trial assessed the effectiveness of practice facilitation (PF) for adoption of guidelines for prevention and treatment of cardiovascular disease risk factors. This study estimated the associated cost of PF for guideline adoption in small, private primary care practices.

Methods

The cost analysis included categories for start-up costs, intervention costs, and practice staff costs for the implemented PF-guided intervention. We estimated the total 1-year costs to operate the program and calculated the mean and range of the cost-per-practice by quarter of the intervention. We estimated the lower and upper bounds for all salary expenses, rounding to the nearest $100.

Results

Total 1-year intervention costs for all 261 practices ranged from $7,900,000 to $10,200,000, with program and practice salaries comprising $6,600,000–$8,400,000 of the total. Start-up costs were a small proportion (3%) of the total 1-year costs. Excluding start-up costs, quarter 1 cost-per-practice was the most expensive at $20,400–$26,700, and quarter 4 was the least expensive at about $10,000. Practice staff time (compared with program staff time) was the majority of the staffing costs at 75–84%.

Conclusions

The PF strategy costs approximately $10,000 per practice per quarter for program and practice costs, once implemented and running at highest efficiency. Whether this program is “worth it” to the decision-maker depends on the relative costs and effectiveness of their other options for improving cardiovascular risk reduction.

Trial registration

This study is retrospectively registered on January 5, 2016, atwww.clinicaltrials.govasNCT02646488.
Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy
Authors: Shalaby Kholoud , Bahriz Rania , Mahsoub Nancy , El-Arman Mohammed M. , El-Said Ghada
Published: February 2021

Background

Matrix metalloproteinase 9 (MMP-9) is an important inflammatory marker in diabetic nephropathy. Many studies assessed the association between MMP-9 gene polymorphism and different microvascular complications of type 2 diabetes mellitus, though the results were inconclusive and need further exploration. Our study aimed to assess the association between MMP-9 -1562C/T gene polymorphism and diabetic nephropathy in patients with type 2 diabetes mellitus.

Results

Taking CC genotype of rs3918242 (MMP-9-1562C/T SNP) as the reference genotype and C as the reference allele, TT genotype, T allele showed significantly lower frequency in diabetic nephropathy group than without nephropathy (2.9% versus 20%, 20% versus 35.7% respectively), with the possible significant protective effect against diabetic nephropathy development (OR = 0.269, 0.450 respectively); it was considered as an independent predictor for diabetic nephropathy occurrence.

Conclusions

This study suggested that T allele of MMP-9 -1562C/T single nucleotide polymorphism had a protective role against diabetic nephropathy development and also had a role for early prediction of patients susceptible to this complication, so it helps in prevention and management of those patients.
Evaluating Readability Scores of Treatment Summaries and Cancer Survivorship Care Plans
Authors: Kue Jennifer , Klemanski Dori L. , Browning Kristine K.
Published: February 2021

PURPOSE:

Treatment Summaries and Survivorship Care Plans (TS/SCPs) may be difficult for patients to comprehend because of readability, magnitude of information, and complex medical verbiage.

METHODS:

Readability scores were calculated for TS/SCP templates including ASCO, Oncolink, Journey Forward, and the authors' institution. The Simple Measure of Gobbledygook (SMOG) index, Flesch-Kincaid reading grade level, Coleman-Liau Index, and Gunning Fog index were used to assess readability.

RESULTS:

The Flesch-Kincaid reading ease scores for the blank ASCO templates ranged from 47.4 to 53.3, requiring a reading grade level of 10-12. Coleman-Liau and Gunning Fog scores showed that an 11th grade reading level is essential, and SMOG required a college education to comprehend the ASCO templates. For the colorectal case exemplar, Oncolink's template resulted in the lowest SMOG score (11.3; 11th grade), Flesch-Kincaid reading grade level (11; 11th grade), and Coleman-Liau score (12; 12th grade). Journey Forward's TS/SCP template scored the highest on the SMOG (21.2; college graduate), Flesch-Kincaid reading grade level (18.3; college graduate), and Gunning-Fog index (25.8; college graduate) compared with other TS/SCPs.

CONCLUSION:

The existing TS/SCP templates used by US cancer centers are written at a grade level beyond the comprehension of most adults. Cancer care teams should assess TS/SCP content for readability and use of plain language and reduce medical jargon.
Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review
Authors: Perlman Jordan E , Johnston Philip C , Hui Ferdinand , Mulligan Guy , Weil Robert J , Recinos Pablo F , Yogi-Morren Divya , Salvatori Roberto , Mukherjee Debraj , Gallia Gary , Kennedy Laurence , Hamrahian Amir H
Published: February 2021

Context

Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases.

Evidence Acquisition

We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977.

Evidence Synthesis

IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation.

Conclusion

A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure.
Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer
Authors: Zhang Lingyun , Ren Zhixiang , Su Zhengzheng , Liu Yang , Yang Tian , Cao Minyuan , Jiang Yong , Tang Ying , Chen Haining , Zhang Weihan , Gong Rixiang , Wei Tao , Peng Yong , Liu Bo , Zhang Wei , Yang Li , Hu Yiguo , Li Zhihui , Zhu Jingqiang , Xu Heng , Shu Yang , Luo Han
Published: February 2021

Background

Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.

Methods

Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.

Results

The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.

Conclusions

This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.
In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover
Authors: Vigevano Francesca , Gregori Giulia , Colleluori Georgia , Chen Rui , Autemrongsawat Vimlin , Napoli Nicola , Qualls Clifford , Villareal Dennis T , Armamento-Villareal Reina
Published: February 2021

Introduction

Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

Methods

Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) with and without T2D and between obese without and with T2D.

Results

Compared to MHO and MUHO without T2D, MUHO with T2D had significantly lower levels of osteocalcin ((7.49 ± 3.0 and 6.03 ± 2.47 vs 4.24 ± 2.72 ng/mL, respectively, P = 0.003) and C-terminal telopeptide of type I collagen (CTx) (0.28 ± 0.10 and 0.29 ± 0.13 vs 0.21 ± 0.15 ng/mL, respectively, P = 0.02). Dividing our subjects simply into those with and without T2D showed that obese men with T2D had significantly lower levels of osteocalcin (P = 0.003) and CTx (P = 0.005), greater trabecular separation at the tibia and radius (P = 0.03 and P = 0.04, respectively), and lower tibial failure load and stiffness (both P = 0.04), relative to obese men without T2D.

Conclusion

In men, the combination of obesity and T2D is associated with reduced bone turnover and poorer trabecular bone microarchitecture and bone strength compared to those who are obese but without T2D, suggesting worse bone disease.
The Influence of Prepubertal Onset of Type 1 Diabetes and Age of Menarche on Polycystic Ovary Syndrome Diagnosis
Authors: Łebkowska Agnieszka , Adamska Agnieszka , Krentowska Anna , Uruska Aleksandra , Rogowicz-Frontczak Anita , Araszkiewicz Aleksandra , Ożegowska Katarzyna , Hryniewicka Justyna , Leśniewska Monika , Wender-Ożegowska Ewa , Zozulińska-Ziółkiewicz Dorota , Kowalska Irina
Published: February 2021

Context

Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty.

Objective

The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM.

Design, Setting, and Patients

We studied 83 women with T1DM (age 26 ± 5 years, BMI 24 ± 3 kg/m2) 36 with premenarchal (PM) onset of T1DM [17 with PCOS diagnosed (PCOS+PM) and 19 without PCOS (noPCOS+PM)] and 47 women with postmenarchal onset of T1DM [24 with PCOS (PCOS-noPM) and 23 without PCOS (noPCOS-noPM)].

Outcome Measurements

Clinical examination, assessment of serum sex hormones, glycated hemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women.

Results

Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24 h and U/kg bw/24 h than T1DM-noPM (P-values = 0.014 and 0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24 h in comparison to PCOS-noPM (P-values = 0.004 and = 0.006, respectively). In multivariable logistic regression analysis, age of menarche [odds ratio (OR): 0.672; 95% confidence interval (CI): 0.465-0.971] and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS.

Conclusions

There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.
Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial
Authors: Riddle Matthew C , Gerstein Hertzel C , Xavier Denis , Cushman William C , Leiter Lawrence A , Raubenheimer Peter J , Atisso Charles M , Raha Sohini , Varnado Oralee J , Konig Manige , Lakshmanan Mark , Franek Edward
Published: February 2021

Context

Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.

Objective

This work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and < 65 years).

Methods

A post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Participants included type 2 diabetes patients aged 50 years or older with established cardiovascular (CV) disease or multiple CV risk factors, and a wide range of glycemic control. Patients were randomly assigned (1:1) to dulaglutide 1.5 mg or placebo as an add-on to country-specific standard of care. Main outcomes measures included MACE (first occurrence of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unknown causes).

Results

There were 5256 randomly assigned patients who were 65 years or older (mean = 71.0), and 4645 were younger than 65 years (mean = 60.7). Baseline characteristics were similar in randomized treatment groups. Dulaglutide treatment showed a similar reduction in the incidence (11% vs 13%) of MACE in older vs younger patients. The rate of permanent study drug discontinuation, incidence of all-cause mortality, hospitalizations for heart failure, severe hypoglycemia, severe renal or urinary events, and serious gastrointestinal events were similar between randomized treatment groups within each age subgroup. The incidence rate of serious cardiac conduction disorders was numerically higher in the dulaglutide group compared to placebo within each age subgroup but the difference was not statistically significant.

Conclusion

Dulaglutide had similar efficacy and safety in REWIND in patients65 years and older and those younger than 65 years.
Stem cell quiescence: the challenging path to activation
Authors: Urbán Noelia , Cheung Tom H.
Published: February 2021

Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity. Quiescence has long been viewed as an inactive state but recent studies have shown that it is in fact an actively regulated process and that adult stem cells are highly reactive to extrinsic stimuli. This has fuelled hopes of boosting the reactivation potential of adult stem cells to improve tissue function during ageing. In this Review, we provide a perspective of the quiescent state and discuss how quiescent adult stem cells transition into the cell cycle. We also discuss current challenges in the field, highlighting recent technical advances that could help overcome some of these challenges.
TRIP6 is required for tension at adherens junctions
Authors: Venkatramanan Srividya , Ibar Consuelo , Irvine Kenneth D.
Published: February 2021

Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6 and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown, we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for the recruitment of vinculin and VASP to adherens junctions. Knockdown of TRIP6 or vinculin, but not of LIMD1, also influences the localization of myosin and F-actin. In TRIP6 knockdown cells, actin stress fibers are lost apically but increased basally, and there is a corresponding increase in the recruitment of vinculin and VASP to basal focal adhesions. Our observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.
Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process
Authors: Mela Alexander , Momany Michelle
Published: February 2021

Septins colocalize with membrane sterol-rich regions and facilitate recruitment of cell wall synthases during wall remodeling. We show that null mutants missing an Aspergillus nidulans core septin present in hexamers and octamers (ΔaspAcdc11, ΔaspBcdc3 or ΔaspCcdc12) are sensitive to multiple cell wall-disturbing agents that activate the cell wall integrity MAPK pathway. The null mutant missing the octamer-exclusive core septin (ΔaspDcdc10) showed similar sensitivity, but only to a single cell wall-disturbing agent and the null mutant missing the noncore septin (ΔaspE) showed only very mild sensitivity to a different single agent. Core septin mutants showed changes in wall polysaccharide composition and chitin synthase localization. Mutants missing any of the five septins resisted ergosterol-disrupting agents. Hexamer mutants showed increased sensitivity to sphingolipid-disrupting agents. Core septins mislocalized after treatment with sphingolipid-disrupting agents, but not after ergosterol-disrupting agents. Our data suggest that the core septins are involved in cell wall integrity signaling, that all five septins are involved in monitoring ergosterol metabolism, that the hexamer septins are required for sphingolipid metabolism and that septins require sphingolipids to coordinate the cell wall integrity response.