bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial
Authors:   On behalf of the CRASH-3 trial collaborators, Brenner Amy , Belli Antonio , Chaudhri Rizwana , Coats Timothy , Frimley Lauren , Jamaluddin Sabariah Faizah , Jooma Rashid , Mansukhani Raoul , Sandercock Peter , Shakur-Still Haleema , Shokunbi Temitayo , Roberts Ian
Published: November 2020

Background

The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death.

Methods

The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis.

Results

There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94).

Conclusions

Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury.

Trial registration

ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011.
A live-online mindfulness-based intervention for children living with epilepsy and their families: protocol for a randomized controlled trial of Making Mindfulness Matter©
Authors: Puka Klajdi , Bax Karen , Andrade Andrea , Devries-Rizzo Margo , Gangam Hema , Levin Simon , Nouri Maryam N. , Prasad Asuri N. , Secco Mary , Zou Guangyong , Speechley Kathy N.
Published: November 2020

Background

Epilepsy extends far beyond seizures; up to 80% of children with epilepsy (CWE) may have comorbid cognitive or mental health problems, and up to 50% of parents of CWE are at risk for major depression. Past research has also shown that family environment has a greater influence on children’s and parents’ health-related quality of life (HRQOL) and mental health than epilepsy-related factors. There is a pressing need for low-cost, innovative interventions to improve HRQOL and mental health for CWE and their parents. The aim of this randomized controlled trial (RCT) is to evaluate whether an interactive online mindfulness-based intervention program, Making Mindfulness Matter (M3), can be feasibly implemented and whether it positively affects CWE’s and parents’ HRQOL and mental health (specifically, stress, behavioral, depressive, and anxiety symptoms).

Methods

This parallel RCT was planned to recruit 100 child-parent dyads to be randomized 1:1 to the 8-week intervention or waitlist control and followed over 20 weeks. The intervention, M3, will be delivered online and separately to parents and children (ages 4–10 years) in groups of 4–8 by non-clinician staff of a local community epilepsy agency. The intervention incorporates mindful awareness, social-emotional learning skills, and positive psychology. It is modeled after the validated school-based MindUP program and adapted for provision online and to include a parent component.

Discussion

This RCT will determine whether this online mindfulness-based intervention is feasible and effective for CWE and their parents. The proposed intervention may be an ideal vector to significantly improve HRQOL and mental health for CWE and their parents given its low cost and implementation by community epilepsy agencies.

Trial registration

ClinicalTrials.govNCT04020484. Registered on July 16, 2019.
Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: a single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM)
Authors: Mohamad Safiai Nabil Izzaatie , Amir Nur Ain , Basri Hamidon , Inche Mat Liyana Najwa , Hoo Fan Kee , Yusof Khan Abdul Hanif Khan , Loh Wei Chao , Chia Peck Kee , Ramachandran Vasudevan , Mat Din Hazwan , Samsudin Intan Nureslyna , Fernandez Aaron , Mohamed Mohd Hazmi , Ching Siew Mooi , Hashim Hasnur Zaman , Wan Sulaiman Wan Aliaa
Published: November 2020

Background

This is a phase II randomised, double-blind, sham-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine amongst migraine subjects.

Methods

Subjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions.

Discussion

Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration.

Trial registration

ClinicalTrials.govNCT03556722. Registered on 14 June 2018
Local persistence of novel regional variants of La Crosse virus in the Northeast USA
Authors: Eastwood Gillian , Shepard John J. , Misencik Michael J. , Andreadis Theodore G. , Armstrong Philip M.
Published: November 2020

Background

La Crosse virus (LACV) (genus Orthobunyavirus, family Peribunyaviridae) is a mosquito-borne virus that causes pediatric encephalitis and accounts for 50–150 human cases annually in the USA. Human cases occur primarily in the Midwest and Appalachian regions whereas documented human cases occur very rarely in the northeastern USA.

Methods

Following detection of a LACV isolate from a field-collected mosquito in Connecticut during 2005, we evaluated the prevalence of LACV infection in local mosquito populations and genetically characterized virus isolates to determine whether the virus is maintained focally in this region.

Results

During 2018, we detected LACV in multiple species of mosquitoes, including those not previously associated with the virus. We also evaluated the phylogenetic relationship of LACV strains isolated from 2005–2018 in Connecticut and found that they formed a genetically homogeneous clade that was most similar to strains from New York State.

Conclusion

Our analysis argues for local isolation and long-term persistence of a genetically distinct lineage of LACV within this region. We highlight the need to determine more about the phenotypic behavior of these isolates, and whether this virus lineage poses a threat to public health.
Probiotics supplementation and insulin resistance: a systematic review
Authors: Salles Bárbara Izabel Moraes , Cioffi Débora , Ferreira Sandra Roberta G.
Published: November 2020

Background

Research on intestinal microbiota has grown considerably, as well as the interest on probiotics’ supplementation effects on metabolism. Considering high prevalence rates of metabolic diseases linked by insulin resistance, we performed a systematic review of existing literature which addressed the role of probiotics in modulating insulin sensitivity in animals and humans.

Methods

This systematic review was based on PRISMA guidelines. Searches for original articles published in English from 1990 to January 2020 were made in the electronic database of PubMed from the National Library of Medicine, using Medical Subject Headings to identify longitudinal studies conducted in animals and humans which reported effects of probiotics in a variety of insulin resistance parameters.

Results

Overall, results from 27 probiotic interventions (Lactobacillus, Bifidobacterium, Clostridium and Akkermansia) indicated significant beneficial changes in insulin resistance measures in animal studies. Additionally, they improved lipid profile, inflammatory and oxidative markers, short-chain fatty acids production and microbiota composition. In seven clinical trials, samples and designs were heterogeneous. Five showed benefits in insulin resistance parameters and in two others no effect was detected.

Conclusion

Available data regarding the effects of certain probiotics do not guarantee sustained amelioration of insulin resistance in humans. Consistent beneficial results for intestinal barrier function, immune system and metabolism were reported in animals may encourage long-term randomized clinical trials in people with obesity and cardiometabolic risk. Whether supplementation with probiotics in combination with medications and/or prebiotics, associated with a healthy lifestyle, will prove useful to attenuate insulin resistance requires further investigation.
Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report
Authors: Trovik Linn Hereide , Sandnes Miriam , Blomberg Bjørn , Holmaas Gunhild , Ahmed Aymen Bushra , Tvedt Tor Henrik Anderson , Vintermyr Olav , Reikvam Håkon
Published: November 2020

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases.

Case presentation

The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae.

Conclusions

We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality.
Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rodent hind-limb allotransplantation model
Authors: Chen Chien-Chang , Chen Rong-Fu , Shao Jheng-Syuan , Li Yun-Ting , Wang Yu-Chi , Brandacher Gerald , Chuang Jiin-Haur , Kuo Yur-Ren
Published: November 2020

Background

Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation.

Methods

B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis.

Result

An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin.

Conclusion

ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.
Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head
Authors: Li Lu , Wang Yikai , Yu Xiaobing , Bao Yongming , An Lijia , Wei Xiaowei , Yu Weiting , Liu Baoyi , Li Junlei , Yang Jiahui , Xia Yan , Liu Ge , Cao Fang , Zhang Xiuzhi , Zhao Dewei
Published: November 2020

Background

Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH.

Methods

To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes.

Results

The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1.

Conclusions

This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.
LigGrep: a tool for filtering docked poses to improve virtual-screening hit rates
Authors: Ha Emily J. , Lwin Cara T. , Durrant Jacob D.
Published: November 2020

Structure-based virtual screening (VS) uses computer docking to prioritize candidate small-molecule ligands for subsequent experimental testing. Docking programs evaluate molecular binding in part by predicting the geometry with which a given compound might bind a target receptor (e.g., the docked “pose” relative to a protein target). Candidate ligands predicted to participate in the same intermolecular interactions typical of known ligands (or ligands that bind related proteins) are arguably more likely to be true binders. Some docking programs allow users to apply constraints during the docking process with the goal of prioritizing these critical interactions. But these programs often have restrictive and/or expensive licenses, and many popular open-source docking programs (e.g., AutoDock Vina) lack this important functionality. We present LigGrep, a free, open-source program that addresses this limitation. As input, LigGrep accepts a protein receptor file, a directory containing many docked-compound files, and a list of user-specified filters describing critical receptor/ligand interactions. LigGrep evaluates each docked pose and outputs the names of the compounds with poses that pass all filters. To demonstrate utility, we show that LigGrep can improve the hit rates of test VS targetingH. sapienspoly(ADPribose) polymerase 1 (HsPARP1),H. sapienspeptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (HsPin1p), andS. cerevisiaehexokinase-2 (ScHxk2p). We hope that LigGrep will be a useful tool for the computational biology community. A copy is available free of charge athttp://durrantlab.com/liggrep/.
On a new structure of the pantograph inclusion problem in the Caputo conformable setting
Authors: Thabet Sabri T. M. , Etemad Sina , Rezapour Shahram
Published: November 2020

In this work, we reformulate and investigate the well-known pantograph differential equation by applying newly-defined conformable operators in both Caputo and Riemann–Liouville settings simultaneously for the first time. In fact, we derive the required existence criteria of solutions corresponding to the inclusion version of the three-point Caputo conformable pantograph BVP subject to Riemann–Liouville conformable integral conditions. To achieve this aim, we establish our main results in some cases including the lower semi-continuous, the upper semi-continuous and the Lipschitz set-valued maps. Eventually, the last part of the present research is devoted to proposing two numerical simulative examples to confirm the consistency of our findings.
New post quantum analogues of Ostrowski-type inequalities using new definitions of left–right $(p,q)$-derivatives and definite integrals
Authors: Chu Yu-Ming , Awan Muhammad Uzair , Talib Sadia , Noor Muhammad Aslam , Noor Khalida Inayat
Published: November 2020

The main objective of this paper is to introduce a new more elegant notion of left–right$(p,q)$(p,q)-derivative and definite integrals. To show the significance of these concepts, we discuss some of their basic properties. A new generalized$(p,q)$(p,q)-integral identity is also obtained. Utilizing this identity as an auxiliary result we then obtain our main results using the concept ofn-polynomial convex functions.
Inflammatory breast cancer associated with amyopathic dermatomyositis: a case report
Authors: Inaguma Gaku , Shimada Akihiko , Tsunoda Junya , Matsuzaki Tomohiko , Nishi Tomohiko , Seki Hiroaki , Matsumoto Hidetoshi
Published: November 2020

Background

Dermatomyositis is associated with malignant tumors including breast cancer, and inflammatory breast cancer is considered to have a poorer prognosis than most breast cancers.

Case presentation

A 74-year-old Asian woman, developed erythema on her face, back, and the back of her hands, 3 weeks before attending our department. At the same time, she had noticed a right breast mass and redness of the skin of the breast. The clinical findings and vacuum aspiration biopsy diagnosed inflammatory breast cancer and neoadjuvant chemotherapy was performed. The mass and enlarged axillary lymph nodes had shrunk, therefore a total mastectomy was performed. The sentinel lymph node biopsy was negative. She was discharged 7 days after surgery without any complications. She has received a postoperative aromatase inhibitor and is alive without recurrence. The dermatomyositis also began to improve with the start of her chemotherapy and has not recurred since the surgery.

Conclusions

Neoadjuvant chemotherapy was performed for inflammatory breast cancer with dermatomyositis, and tumor shrinkage was confirmed. A total mastectomy without axillary lymph node dissection was performed. Dermatomyositis and breast cancer have not recurred. Dermatomyositis may have been a paraneoplastic syndrome due to breast cancer.
The role of clockwork orange in the circadian clock of the cricket Gryllus bimaculatus
Authors: Tomiyama Yasuaki , Shinohara Tsugumichi , Matsuka Mirai , Bando Tetsuya , Mito Taro , Tomioka Kenji
Published: November 2020

The circadian clock generates rhythms of approximately 24 h through periodic expression of the clock genes. In insects, the major clock genes period (per) and timeless (tim) are rhythmically expressed upon their transactivation by CLOCK/CYCLE, with peak levels in the early night. In Drosophila, clockwork orange (cwo) is known to inhibit the transcription of per and tim during the daytime to enhance the amplitude of the rhythm, but its function in other insects is largely unknown. In this study, we investigated the role of cwo in the clock mechanism of the cricket Gryllus bimaculatus. The results of quantitative RT-PCR showed that under a light/dark (LD) cycle, cwo is rhythmically expressed in the optic lobe (lamina-medulla complex) and peaks during the night. When cwo was knocked down via RNA interference (RNAi), some crickets lost their locomotor rhythm, while others maintained a rhythm but exhibited a longer free-running period under constant darkness (DD). In cwoRNAi crickets, all clock genes except for cryptochrome 2 (cry2) showed arrhythmic expression under DD; under LD, some of the clock genes showed higher mRNA levels, and tim showed rhythmic expression with a delayed phase. Based on these results, we propose that cwo plays an important role in the cricket circadian clock.
A comparative study of executive functions among children with attention deficit and hyperactivity disorder and those with learning disabilities
Authors: El Wafa Heba Essam Abou , Ghobashy Soha Abd El Latif , Hamza Aya Maged
Published: November 2020

Background

Both ADHD and learning disorders have been found to be associated with executive dysfunctions; the executive functions’ (EFs) construct generally involves a series of components—planning, cognitive flexibility, inhibition, attention control, and verbal and visuo-spatial working memory—that work independently in many ways but are closely related. There were no significant studies comparing both disorders and excluding the drug’s effects on executive functions. In our study, we used BDEFS-CA to assess executive functions among a sample of 340 children divided in to four groups: group 1 (100 children), ADHD only; group II (80 children), LD only; group III (60 children), combined ADHD and LD; and group IV (100 children), control group. We included children aged from 6 to 13 of both sexes of average IQ and all had to be drug naive with no sensory impairment or disabling neurological disorder and after their parents’ consent.

Results

The results showed that there was significant higher affection of the five executive functions domains in the first three groups more than the fourth control group. Furthermore, the self-restraint (response-inhibition) executive dysfunction was the most commonly affected EF in group I while time management EF and self-regulation and problem solving EF were the most commonly affected EF in the LD group.

Conclusions

Complete executive function profile assessment should be done for children diagnosed with ADHD or learning disability and EF intervention program should be included in the management plan for better outcomes mainly self-restraint EF in case of ADHD and problem solving and self-organization EF in case of learning disabilities
The effect of power lines on time-domain airborne electromagnetic data
Authors: Kang Seogi , Dewar Noah , Knight Rosemary
Published: November 2020

The acquisition of airborne electromagnetic (AEM) data colocated with water well data provides an essential data set for constructing an accurate rock-physics relationship between resistivity from AEM and lithology from wells. Results from an AEM survey in Butte and Glenn Counties, California, USA, where 41 water wells are located within 100 m of the AEM flight lines, provide a unique opportunity to investigate the effect of water wells on AEM data. Based on systematic numerical analyses and examination of the field data, we find that the only noise source related to the wells that affects the AEM signals in our study area is the power lines; the effect of the steel casings in the study area is negligible. Our numerical simulations yield two important findings: (1) the effect of the power line is mainly dependent upon the resistivity of the ground pathway between the base of the power-line poles, and (2) for the resistivity structure in the study area, when the ground contact resistance is sufficiently low, the effect of the power line will be observed in the AEM data until there is a separation distance of 174 m from the power line; the total power-line percentage effect less than 3% has been considered to be negligible. However, we find that, in the field data, an average separation distance between the power line and high-quality AEM data (i.e., no impact from the power lines) is only 60% of this predicted distance. We attribute this to the high ground contact resistance caused by degradation of the grounded electrodes located at the bottom of the power-line poles. For our 41 wells, after removing any soundings contaminated by power-line noise, we are left with high-quality soundings located 0–160 m from the water wells, with an average distance of 77 m.
Quantifying hydraulically induced fracture height and density from rapid time-lapse distributed acoustic sensing vertical seismic profile data
Authors: Zhao Xiaomin , Willis Mark E. , Inks Tanya , Wilson Glenn A.
Published: November 2020

Several recent studies have advanced the use of time-lapse distributed acoustic sensing vertical seismic profile data in horizontal wells for determining hydraulically stimulated fracture properties. Hydraulic fracturing in a horizontal well typically generates vertical fractures in the rock medium around each stage. We have modeled the hydraulically stimulated formation with vertical fracture sets about the lateral wellbore as a horizontally transverse isotropic medium. Rock-physics modeling is used to relate the anisotropy parameters to the fracture properties. This modeling is used to develop an inversion for compressional wave time delay to the fracture height and density of each stage. Field data from two horizontal wells are analyzed, and the fracture height evaluated using this technique is consistent with the microseismic analysis.
Role of Age at Diagnosis in Defining Potential Familial Nonmedullary Thyroid Cancer in Kindreds With Two Affected Members
Authors: Capezzone Marco , Sagnella Alfonso , Pilli Tania , Maino Fabio , Forleo Raffaella , Cantara Silvia , Cartocci Alessandra , Castagna Maria Grazia
Published: November 2020

Context

The definition of familial nonmedullary thyroid cancer (FNMTC) in 2 or more first-degree relatives is controversial due to the high probability of observing a sporadic association when only 2 members of first-degree relatives are affected.

Objective

To evaluate the role of age at diagnosis in differentiating the true cases of FNMTC.

Design, Setting, Participants, and Main Outcome

From a group of 721 papillary thyroid cancer (PTC) patients, 95 familial PTC (FPTC) patients with 2 first-degree relatives have been identified. They were split in 2 groups: Group 1 consisted of both the proband and the affected relative, with age at diagnosis ≤ 45 years; Group 2 consisted of proband and/or the affected family member, with age at diagnosis > 45 years. The clinical-pathological features and outcome of both FPTC groups were compared with 626 sporadic PTC patients (SPTC).

Results

Familial PTC patients with age at diagnosis ≤ 45 years, compared with the matched group of sporadic PTCs, had a more frequent multifocal, bilateral, and extrathyroidal extension of tumor and showed worse outcome. No differences were found between FPTC and SPTC patients with age > 45 years. At multivariate analysis, distant metastases, American Thyroid Association (ATA) risk, and FPTC ≤ 45 years were independent predictors of outcome.

Conclusions

Based on the observation that PTC is more aggressive when the diagnosis is made in 2 family members, both with age < 45years, we suggest that the definition of FPTC in kindreds with 2 affected members should also take into account the age at diagnosis as a key element of familial cancer.
Kazuo Ishiguro's Nonactors
Authors: Christou Maria
Published: November 2020

At center stage in Kazuo Ishiguro's work is the figure of the nonactor: a character type that confronts us time and again with scenarios in which action is devalued. This essay shows that, despite finding themselves in situations that mandate action, Ishiguro's characters opt instead for risk-averse and mechanical-like behaviors that are antonymous to change. This, however, is not a solely aesthetic phenomenon, and the essay examines the figure of the nonactor in Ishiguro's novels as part of a broader turn toward nonaction. It does so by considering this figure in relation to a distinctly twentieth-century context within which, as Hannah Arendt has it, human action came to be seen as more dangerous than ever before. Ishiguro's nonactors can be seen as the legacy, but also as the mutations, of this understanding in our own era and in the contemporary novel. This legacy, the essay demonstrates, reveals an underexamined aspect of the neoliberal mind-set that dominates the post–Cold War world. Rather than promote the worthiness of individual, self-serving action, Ishiguro's novels bring to the forefront something different though no less pernicious: a wholescale devaluation of the individual's capacity to act.
Growing Up Against Allegory: The Late Works of J. M. Coetzee
Authors: Davies Benjamin R.
Published: November 2020

The first two books of J. M. Coetzee's recent trilogy, The Childhood of Jesus (2013) and The Schooldays of Jesus (2016), are extremely strange. Just when “the Australian fiction,” following the works set in South Africa and various international locations, was thought to be the last phase of Coetzee's career, the Nobel laureate changed tack. The Jesus books challenge readers and critics with their sparse tone, lengthy philosophical dialogues, and allegorical obscurity. Their difficulty seems to shed little light on some of the most intriguing questions about Coetzee's writing: namely, its form and its interaction with allegory. Beginning with a reappraisal of a classic work of Coetzee studies, this essay then lays out a theory about the connection between reading and writing allegory within traditions of what constitutes a “novel.” In the second section, examples from Coetzee's earlier fiction are analyzed, with focus on In the Heart of the Country (1977) and Boyhood (1997). Parental roles are found to be vital in the connections between the novel form and allegory. The third section applies these analyses to Childhood and Schooldays. Focus on the books’ references to Plato and Don Quixote helps scrutinize their philosophy and reach the thesis of this essay: that with these books, Coetzee experiments with a form that goes beyond the novel.
Paper-based Electrochemical Flow Biosensor Using Enzyme-modified Polystyrene Particles
Authors: Loew Noya , Shitanda Isao , Kishiro Kanako , Hoshi Yoshinao , Itagaki Masayuki
Published: November 2020

Paper-based electrochemical biosensors are a promising alternative to conventional biosensors. Herein, a screen-printed paper-based electrochemical flow biosensor was developed. The sensor comprised carbon-based working and counter electrodes and an Ag/AgCl reference electrode that was printed directly on paper, thereby forming a flow path. Glucose oxidase (GOx) was immobilized on polystyrene (PS) beads and a mediator tetrathiafulvalene was introduced upstream of the electrodes. The response current of the biosensor increased linearly with the glucose concentration, up to 100 mM of glucose.
Moodle E-Learning Environment as an Effective Tool for Descriptive Geometry Teaching Organization in the COVID-19 Pandemic Conditions
Authors: Ignat'ev S. , Folomkin A. , Tret'yakova Z. , Glazunov K.
Published: November 2020

The COVID-19 pandemic caused a serious crisis in the Russia’s education system, associated with the simultaneous universal transition to distance learning, which required the mobilization of all information and communication resources, and intensification of efforts to create conditions for e-distance learning implementation. In this paper the organizational and pedagogical conditions for the effectiveness of high educational institutions’ students distance work in the Moodle e-learning environment when studying "Descriptive Geometry" course have been theory-based and defined. Has been performed generalization of pedagogical experience and analysis of scientific literature on education informatization. Have been presented the concept and algorithm of the developed electronic course, which includes interactive lectures, practical studies and test tasks. The system of statistical indicators used to optimize test tasks, whose calculation incorporated into the Moodle system, has been considered: the ease index of test tasks, standard deviation, discrimination index, and discrimination coefficient. Have been presented the results of survey findings for students on the peculiarities of working with "Descriptive Geometry" electronic course. Effective organizational and pedagogical conditions for the widespread introduction of "Descriptive Geometry" electronic course during the pandemic have been identified. In the paper’s postlude have been presented ways for further development and improvement of the electronic course. In particular, for educational process’s quality improvement, it is proposed the follows:

- to transfer the input control and assessment of students' subject readiness to study graphic disciplines in the Moodle system;

- to create appropriate materials for repeating geometry and drawing school courses, to which a student will be redirected depending on test results;

- to develop an e-course working algorithm, building a certain trajectory of learning adapted to a particular student.
Condicionantes de la desigualdad en el acceso al mercado laboral y remuneración en profesionales de la salud del Perú
Authors: Pacovilca-Alejo Olga Vicentina , Zea-Montesinos César Cipriano , Reginaldo-Huamaní Rafael , Guerra-Olivares Tula Susana , Ordóñez-Ccora Gabriela , Pacovilca-Alejo Gelber Sebasti , Quispe-Ilanzo Melisa Pamela , Oyola-García Alfredo Enrique
Published: November 2020

Introducción: el objetivo de este estudio fue identificar los factores condicionantes de la desigualdad en el acceso al mercado laboral y remuneración en los profesionales de salud del Perú. Materiales y métodos: estudio observacional basado en el análisis secundario de los principales resultados de la Encuesta Nacional a Egresados Universitarios y Universidades, 2014 con una muestra de 1974 profesionales de la salud sometida a expansión para calcular chi cuadrado, odds ratio crudo (ORC) y odds ratio ajustado (ORA) mediante regresión logística, con sus intervalos de confianza al 95%. Resultados: existió mayor riesgo de desocupación en mujeres (ORA: 1.574; IC95%: 1.456-1.702), en universidades públicas (ORA: 1.137; IC95 %: 1.068-1.210) o ubicadas en provincias diferentes a Lima y Callao (ORA: 1.552; IC95 %: 1.452-1.661). La autoidentificación como mestizos (ORA: 0.704; IC95 %: 0.621-0.798), quechuas (ORA: 0.653; IC95 %: 0.556-0.767), aymaras (ORA: 0.679; IC95 %: 0.511-0.902) y otros (ORA: 0.549; IC95 %: 0.432-0.698) tuvo un efecto protector frente a la desocupación. Las mujeres (ora: 1.580; IC95%: 1.484- 1.682), los quechuas (ORA: 1.259; IC95 %: 1.092-1.451) y los egresados de universidades ubicadas fuera de Lima y Callao (ORA: 2.601; IC95 %: 2.455-2.756) presentaron mayor riesgo de remuneración inferior a los 1000 soles; en cambio, el egreso de una universidad pública (ORA: 0.784; IC95%: 0.744-0.828) disminuyó la probabilidad de remuneración menor a 1000 soles. Conclusión: el sexo, la etnia, el centralismo y el nivel socioeconómico condicionarían la desigualdad en el mercado laboral, a pesar del mayor nivel de instrucción obtenido por los profesionales de salud.
The surgical repair of proximal hamstring avulsions
Authors: Wood David , French Sofie R. , Munir Selin , Kaila Rajiv
Published: November 2020

Aims

Despite the increase in the surgical repair of proximal hamstring tears, there exists a lack of consensus in the optimal timing for surgery. There is also disagreement on how partial tears managed surgically compare with complete tears repaired surgically. This study aims to compare the mid-term functional outcomes in, and operating time required for, complete and partial proximal hamstring avulsions, that are repaired both acutely and chronically.

Methods

This is a prospective series of 156 proximal hamstring surgical repairs, with a mean age of 48.9 years (21.5 to 78). Functional outcomes were assessed preinjury, preoperatively, and postoperatively (six months and minimum three years) using the Sydney Hamstring Origin Rupture Evaluation (SHORE) score. Operating time was recorded for every patient.

Results

Overall, significant improvements in SHORE scores were seen at both six months and mid-term follow-up. Preoperatively, acute patients (median score 27.1 (interquartile range (IQR) 22.9)) reported significantly poorer SHORE scores than chronic patients (median score 42.9 (IQR 22.1); p < 0.001). However, this difference was not maintained postoperatively. For partial tears, acutely repaired patients reported significantly lower preoperative SHORE scores compared to chronically reapired partial tears (median score 24.3 (IQR 15.7) vs median score 40.0 (IQR 25.0); p < 0.001) but also significantly higher SHORE scores at six-month follow-up compared to chronically repaired partial tears (median score 92.9 (IQR 10.7) vs. median score 82.9 (IQR 14.3); p < 0.001). For complete tears, there was only a difference in preoperative SHORE scores between acute and chronic groups. Overall, acute repairs had a significantly shorter operating time (mean 64.67 minutes (standard deviation (SD) 12.99)) compared to chronic repairs (mean 74.71 minutes (SD = 12.0); t = 5.12, p < 0.001).

Conclusion

Surgical repair of proximal hamstring avulsions successfully improves patient reported functional outcomes in the majority of patients, irrespective of the timing of their surgery or injury classification. However, reducing the time from injury to surgery is associated with greater improvement in patient outcomes and an increased likelihood of returning to preinjury functional status. Acute repair appears to be a technically less complex procedure, as indicated by reduced operating times, postoperative neurological symptoms and number of patients requiring bracing. Acute repair is therefore a preference among many surgeons. Cite this article: Bone Joint J 2020;102-B(10):1419–1427.
Fasciectomy under local anaesthetic and adrenaline for Dupuytren’s contracture in a community setting in the UK with a cost analysis
Authors: Noureddine Hussein , Vejsbjerg Karen , Harrop Jennifer E. , White Martin J. , Chakravarthy Jagganath , Harrison John W. K.
Published: November 2020

Aims

In the UK, fasciectomy for Dupuytren’s contracture is generally performed under general or regional anaesthetic, with an arm tourniquet and in a hospital setting. We have changed our practice to use local anaesthetic with adrenaline, no arm tourniquet, and perform the surgery in a community setting. We present the outcome of a consecutive series of 30 patients.

Methods

Prospective data were collected for 30 patients undergoing open fasciectomy on 36 digits (six having two digits affected), over a one-year period and under the care of two surgeons. In total, 10 ml to 20 ml volume of 1% lidocaine with 1:100,000 adrenaline was used. A standard postoperative rehabilitation regime was used. Preoperative health scores, goniometer measurements of metacarpophalangeal (MCP), proximal interphalangeal (PIP) contractures, and Unité Rheumatologique des Affections de la Main (URAM) scores were measured pre- and postoperatively at six and 12 weeks.

Results

The mean preoperative contractures were 35.3° (0° to 90°) at the metacarpophalangeal joint (MCPJ), 32.5° (0° to 90°) at proximal interphalangeal joint (PIPJ) (a combined deformity of 67.8°). The mean correction was 33.6° (0° to 90°) for the MCPJ and 18.2° (0° to 70°) for the PIPJ leading to a combined correction of 51.8°. There was a complete deformity correction in 21 fingers (59.5%) and partial correction in 14 digits (37.8%) with no correction in one finger. The mean residual deformities for the partial/uncorrected group were MCP 4.2° (0° to 30°), and PIP 26.1° (0° to 85°). For those achieving a full correction the mean preoperative contracture was less particularly at the PIP joint (15.45° (0° to 60°) vs 55.33° (0° to 90°)). Mean preoperative URAM scores were higher in the fully corrected group (17.4 (4 to 31) vs 14.0 (0 to 28)), but lower at three months post-surgery (0.5 (0 to 3) vs 4.40 (0 to 18)), with both groups showing improvements. Infections occurred in two patients (three digits) and both were successfully treated with oral antibiotics. No other complications were noted. The estimated cost of a fasciectomy under local anaesthetic in the community was £184.82 per patient. The estimated hospital theatre costs for a fasciectomy was £1,146.62 under general anaesthetic (GA), and £1,085.30 under an axillary block.

Conclusion

This study suggests that a fasciectomy performed under local anaesthetic with adrenaline and without an arm tourniquet and in a community setting is safe, and results in favourable outcomes regarding the degree of correction of contracture achieved, functional scores, and short-term complications. Local anaesthetic fasciectomy in a community setting achieves a saving of £961.80 for a GA and £900.48 for an axillary block per case. Cite this article: Bone Joint J 2020;102-B(10):1354–1358.
Comparison of plaster-of-Paris casts and Woodcast splints for immobilization of the limb during serial manipulation and casting for idiopathic clubfoot in infants
Authors: Singh Kumar Amerender , Shah Hitesh , Joseph Benjamin
Published: November 2020

Aims

The study was undertaken to compare the efficacy of Woodcast splints and plaster-of-Paris casts in maintaining correction following sequential manipulation of idiopathic clubfeet.

Methods

In this randomized prospective trial, 23 idiopathic clubfeet were immobilized with plaster-of-Paris casts and 23 clubfeet were immobilized with a splint made of Woodcast that encircled only two-thirds the circumference of the limb. The number of casts or splints needed to obtain full correction, the frequency of cast or splint-related complications, and the time taken for application and removal of the casts and splints were compared.

Results

The mean number of casts required to obtain full correction of the deformity (Pirani Score 0) was 4.35 (95% confidence interval (CI) 3.74 to 4.95) when plaster-of-Paris was used and 4.87 (95% CI 4.33 to 5.41) when the Woodcast splint was used (p = 0.190). The time required for application and removal of the Woodcast splint were significantly less than that required for application and removal of plaster-of-Paris casts (p < 0.001). Woodcast splint-related complications were not more frequent than plaster-of-Paris cast related complications.

Conclusion

Though Woodcast splints covering two-thirds of the circumference of the lower limbs of infants were effective in maintaining the correction of clubfoot deformity during serial manipulation and casting treatment, the superiority of Woodcasts over plaster-of-Paris could not be established. Cite this article: Bone Joint J 2020;102-B(10):1399–1404.
Systematic investigation of metallosis associated with magnetically controlled growing rod implantation for early-onset scoliosis
Authors: Zhang Teng , Sze K. Y. , Peng Z. W. , Cheung Kenneth M. C. , Lui Y. F. , Wong Y. W. , Kwan Kenny Y. H. , Cheung Jason P. Y.
Published: November 2020

Aims

To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod.

Methods

This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining.

Results

Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues.

Conclusion

Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: Bone Joint J 2020;102-B(10):1375–1383.