bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances and challenges of neoadjuvant therapy in pancreatic cancer
Authors: Yu Yang , Zheng Peng , Chen Yajing , Wang Bofang , Paul Maswikiti Ewetse , Tao Pengxian , Wang Dengfeng , Li Haiyuan , Gu Baohong , Gao Lei , Wang Dan , Chen Hao
Published: November 2020

Pancreatic cancer has been becoming the second cause of cancer death in the western world, and its disease burden has increased. Neoadjuvant therapy is one of the current research hotspots in the field of pancreatic cancer, aiming to improve the surgical rate and prognosis of pancreatic cancer. Based on the latest evidence, this review discussed neoadjuvant therapy in pancreatic cancer from the following three aspects: patient selection, protocols selection of neoadjuvant therapy, and treatment response evaluation and resectability prediction. A big controversy existed on the indications of neoadjuvant treatment, but it was agreed that any patient who is likely to achieve R0 resection due to neoadjuvant therapy should be the targeted population. A variety of chemotherapy regimens were tried for neoadjuvant therapy in pancreatic cancer, and FOLFIRINOX and Nab‐Paclitaxel plus Gemcitabine are two preferred regimens at present. It was challenging to evaluate treatment response and predict resectability after neoadjuvant therapy, although imaging by CT is widely used. Based on new findings of the remarkable performance of several chemotherapy regimens with or without radiotherapy, the neoadjuvant indications of pancreatic cancer have extended in recent years. However, it is still a challenge to assess the neoadjuvant treatment response and determine the timing of surgery.
Does composite repair of giant paraoesophageal hernia improve patient outcomes?
Authors: Lee Felix , Khoma Oleksandr , Mendu Maite , Falk Gregory
Published: November 2020

Background

Paraoesophageal hernia (PEH) is often symptomatic and reduces patients' quality of life (QoL). There is ongoing debate regarding the most effective surgical technique to repair giant PEH. This study aimed to see if an elective laparoscopic non‐mesh composite technique of giant PEH repair offered an advantage in symptom control, hernia recurrence, QoL, morbidity and mortality.

Methods

Data were extracted from a prospectively maintained database of patients undergoing hiatal hernia repair. Composite hernia repairs from inception for giant PEH between March 2009 and December 2015 were included. Perioperative mortality, complications, hernia recurrence rates, prevalence, recurrence of symptoms and QoL were included in analysis.

Results

Inclusion criteria were met by 218 patients. Mean age was 70 (49–93). The average hernia size was 62% (range 30–100%; SD 21). There was one perioperative death and three significant complications (Clavien–Dindo grade III and IV). Recurrence rate was 24.8%. Without recurrence, QoL improved significantly across all domains. Recurrence of hiatus hernia reduced QoL. Surgery resulted in resolution of symptoms other than dysphagia which was incompletely improved. Patients' overall satisfaction with surgery was high.

Conclusion

Composite repair of giant PEH is safe with overall good outcomes. Majority of hernia recurrence are small and asymptomatic. Hernia recurrence negatively affected long‐term QoL scores.
Laparoscopic mediastinal approach for retrosternal gastric conduit cancer after esophagectomy
Authors: Hayashi Masato , Fujita Takeshi , Matsushita Hisayuki
Published: November 2020

The prognosis of esophageal cancer has improved, but the incidence of gastric conduit cancer has increased. Gastric conduit cancer is difficult to treat because current treatment options are highly invasive; in particular, surgical procedures have high mortality and modality. Treatment through the retrosternal route usually requires sternotomy, which often causes lethal osteomyelitis. To prevent lethal complications and reduce invasiveness, we used the laparoscopic mediastinal approach. Here, we report a successful case using the laparoscopic mediastinal approach for the treatment of gastric conduit cancer through the retrosternal route. Despite a few concerns, this approach can be a treatment option for gastric conduit cancer through the retrosternal route.
Pathogen‐mediated modulation of host metabolism and trophic interactions in Spodoptera littoralis larvae
Authors: Shaurub El‐Sayed H. , Reyad Naglaa F. , Mohamed Amr A.
Published: November 2020

The success and sustainability of entomopathogens in insect control depend on their stress potential and ability to modulate certain physiological aspects of their insect hosts. In the present study, newly moulted fourth instars of Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae) were incubated for 24 h with the median lethal dose (LD50) of Steinernema riobrave, Heterorhabditis bacteriophora, or Beauveria bassiana to determine their effects on certain metabolic activities and nutritional physiology compared to those of uninfected (control) larvae. Infection decreased total protein, lipid, and carbohydrate contents. Carbohydrase activity was found to be pathogen and enzyme dependent, with S. riobrave and H. bacteriophora infection increasing amylase, invertase, and trehalase activities. Beauveria bassiana infection decreased amylase and invertase activities but increased that of trehalase. Infection with the three pathogens also enhanced phosphatase activity. All pathogens reduced transaminase activity. Changes in the nutritional indices varied not only with the variation in the candidate entomopathogen and surviving instar but also with the variation in the age of the same instar, with a profound change in late last instars (3‐day‐old sixth instars). The link between the metabolic activities and nutritional indices was discussed. Overall, the entomopathogen‐host interaction appears to be primarily nutritional. The pleiotropic effects of the median lethal infections on the insect pest might eventually help in the biological control potential of the entomopathogens tested.
Changes in flight period predict trends in abundance of Massachusetts butterflies
Authors: Michielini James P. , Dopman Erik B. , Crone Elizabeth E.
Published: November 2020

Phenological shifts are well‐documented in the ecological literature. However, their significance for changes in demography and abundance is less clear. We used 27 years of citizen science monitoring to quantify trends in phenology and relative abundance across 89 butterfly species. We calculated shifts in phenology using quantile regression and shifts in relative abundance using list length analysis and counts from field trips. Elongated activity periods within a year were the strongest predictor of increases in relative abundance. These changes may be driven in part by changes in voltinism, as this association was stronger in multivoltine species. Some species appear to be adding a late‐season generation, whereas other species appear to be adding a spring generation, revealing a possible shift from vagrant to resident. Our results emphasise the importance of evaluating phenological changes throughout species’ flight period and understanding the consequences for such climate‐related changes on viability or population dynamics.
Contextual Metrics a Mathematical Definition for a Comprehensive Approach of Geographical Distances
Authors: Kloeckner Benoît R. , L’Hostis Alain , Richard Thomas
Published: November 2020

Our goal is to establish a mathematical framework for the description of geographical distance in a comprehensive way. Geographical distance always refer to potential or realized movement between places, and these displacements obey the least effort rule. While this optimization of effort is well known to imply the Triangle Inequality in many situation, breaks in movement generate a paradox: effort optimization, taking into account the need to rest, results in apparent violations of the Triangle Inequality. In order to solve this issue, we introduce contextual metrics that consider space but also any contextual information relevant to travel, such as resources used for moving. Our approach permits to build a subjective space where distances are affected by the characteristics of the individual on the move. Contextual metrics frame the optimization problem in a space enriched by the context that the traveler has to take into account, making apparent that the violation of the Triangle Inequality in case of break was only an artifact of a model lacking crucial information. The range of geographical situations that can be modeled with this framework underline the level of generalization that can be expected from this approach.
Peripheral eco‐morphology predicts restricted lineage diversification and endemism among corvoid passerine birds
Authors: Kennedy Jonathan D. , Marki Petter Z. , Fjeldså Jon , Rahbek Carsten
Published: November 2020

Aim

Across a variety of taxonomic scales, species diversity is unevenly distributed among its constituent units, and clades with few species are more common than expected assuming homogeneous rates of speciation and extinction among lineages. In order to explain the prevalence of species‐poor families among a global and species‐rich radiation of passerine birds, we test whether these groups share common eco‐morphological, geographical and phylogenetic attributes.

Location

Global.

Time period

Late Oligocene to the present day.

Major taxa studied

The Corvides (c. 790 species).

Methods

We obtained 10 linear measurements of external morphology for 782 species of corvoid passerines. Using these measurements as a proxy for species ecology, we assessed the positioning of corvoid families in eco‐morphological trait space and how these factors were associated with their species richness and rates of lineage diversification. Subsequently, we compared these same characteristics (species richness, morphological positioning and rates of lineage diversification) between families that are currently endemic to the Australasian ancestral area of the Corvides with those that have dispersed and diversified throughout other continental and insular landmasses.

Results

Families with low species richness and rates of diversification tend to occupy the most peripheral positions in eco‐morphological trait space, with almost all of these groups being endemic to Australasia. The peripheral eco‐morphological positioning of the Australasian groupings is generally greater than expected upon accounting for differences in phylogenetic isolation and heterogeneity in rates of trait evolution, implying that species‐poor corvoid families repeatedly evolved towards marginal areas of morphospace.

Main conclusions

The over‐representation of species‐poor clades across diverse sets of organismal groups is consistent with their evolution towards, and the maintenance in, marginal areas of ecological niche space. The evolution of peripheral eco‐morphological characters represents a potentially significant limit to rates of range expansion and lineage diversification.
Mimics of melanoma in reflectance confocal microscopy
Authors: Pogorzelska‐Antkowiak Anna , Calik Jacek
Published: November 2020

The diagnosis of melanoma is challenging for both dermatologists and oncologists. Incidence of melanoma increases at a rate of 3–7% per year. Usage of modern tools such as dermoscopy and in vivo reflectance confocal microscopy improve early diagnosis and can save a life. There are a few melanoma simulators which can cause confusion and mislead in the differential diagnosis. This study aims to present skin lesions which can be similar to melanoma in confocal microscopy and to emphasize the importance of a detailed differential diagnosis. We describe five melanocytic lesions similar to melanoma and misleading confocal features. Although in vivo reflectance confocal microscopy is very useful in differentiating melanocytic lesions, histopathology evaluation in cases of melanoma mimics is definitive.
Roasting Ethics
Authors: ANDERSON LUVELL
Published: November 2020

What are the rules of the comedic roast? Initially, there might seem to be a tension between “the comedic” and “roasting” or “insult.” The comedic is concerned with the funny or mirth while insults are mean-spirited in nature, tools of injury. So how can the two be combined to produce something fun? In this article, I entertain a few views that attempt a resolution of this apparent tension. I conclude with a proposal that suggests when they are successful, roasts employ mechanisms that redirect attention from the joke's content to its formal properties; it is when those mechanisms fail that roasting becomes disagreeable.
The Comic in the Midst of Tragedy's Grief with Tig Notaro, Hannah Gadsby, and Others
Authors: WILLETT CYNTHIA , WILLETT JULIE
Published: November 2020

The function of the comic in the midst of tragedy is not clear. After all, is it simply comic relief that wounded nations, communities, or individuals seek? Tragedy has long been cast as memory and mourning while comedy offers for the masses a Nietzschean moment of joyful forgetting and for the Stoic mind a measure of transcendence from our grief. The latter view came into prominence for modern American culture with the nineteenth-century satirist Mark Twain, who wrote that “the secret source of humor itself is not joy but sorrow,” which has been interpreted through the often-quoted formula: comedy is tragedy plus time. The assumption is that we need some distance emotionally in order to mock or transcend the tragic. While we grant the humor of transcendence can produce some momentary relief through emotional distance, we wonder if there might be another way that humor can deal with suffering? Popular psychology often speaks of five stages of grief, and while that progression seems too linear and simplistic, we find that the now much more inclusive comic stage has something to offer their audiences struggling to make sense of a volatile world.
Climate‐related geographical variation in performance traits across the invasion front of a widespread non‐native insect
Authors: Thompson Lily M. , Powers Sean D. , Appolon Ashley , Hafker Petra , Milner Lelia , Parry Dylan , Agosta Salvatore J. , Grayson Kristine L.
Published: November 2020

Aim

Invasive species are ideal systems for testing geographical differences in performance traits and measuring evolutionary responses as a species spreads across divergent climates and habitats. The European gypsy moth,Lymantria dispar disparL. (Lepidoptera: Erebidae), is a generalist forest defoliator introduced to Medford, Massachusetts, USA in 1869. The invasion front extends from Minnesota to North Carolina and the ability of this species to adapt to local climate may contribute to its continuing spread. We evaluated the performance of populations along the climatic gradient of the invasion front to test for a relationship between climate and ecologically important performance traits.

Location

Eastern United States of America

Taxon

Lymantria dispar disparL. (Lepidoptera: Erebidae)

Methods

Insects from 14 populations across the US invasion front and interior of the invasive range were reared from hatch to adult emergence in six constant temperature treatments. The responses of survival, pupal mass and larval development time were analysed as a function of source climate (annual mean normal temperature), rearing temperature and their interaction using multiple polynomial regression.

Results

With the exception of female development time, there were no significant interactions between source climate and rearing temperature, indicating little divergence in the shape of thermal reaction norms among populations. Source population and rearing temperature were significant predictors of survival and pupal mass. Independent of rearing temperature, populations from warmer climates had lower survival than those from colder climates, but attained larger body size despite similar development times. Larval development time was dependent on rearing temperature, but there were not consistent relationships with source climate.

Main Conclusions

Thermal adaptation can be an important factor shaping the spread of invasive species, particularly in the context of climate change. Our results suggest thatL. d. disparis highly plastic, but has undergone climate‐related adaptation in thermal performance and life‐history traits as it spread across North America.
Effects of salt intervention on serum levels of Klotho influenced by salt sensitivity
Authors: Hu Jia‐Wen , Chu Chao , Shi Tao , Yan Yang , Mu Jian‐Jun
Published: November 2020

Klotho was involved in sodium reabsorption and the regulation of blood pressure. Animal studies indicated Klotho deficiency could mediate the development of salt‐sensitive hypertension, indicating its correlation with salt sensitivity. We aimed to explore the responses of Klotho to salt intake through dietary intervention in Chinese adults. Forty‐four participants were enrolled from Lantian county of Shaanxi, China. All participants sequentially underwent a 3‐day normal diet, a 7‐day low‐Na+ diet, and a 7‐day high‐Na+ diet. The concentrations of serum Klotho were assessed by using ELISA kits. Serum level of Klotho was 360.44 ± 93.89 pg/mL at baseline and increased while changed to low‐salt diet (478.65 ± 183.25 vs 360.44 ± 93.89 pg/mL, P < .001). During high‐salt diet, serum Klotho decreased to 354.37 ± 98.16 pg/mL (P < .001, compared to low‐salt diet). The overall responses of Klotho were more prominent in salt‐resistant participants. Serum Klotho of salt‐resistant group changed from 353.92 ± 97.65 pg/mL to 496.76 ± 196.21 pg/mL while changed from normal diet to low‐salt diet (P < .001) and decreased to 350.37 ± 99.50 pg/mL during high‐salt intake (P < .001). Furthermore, the response of serum Klotho to low‐salt intervention was much greater in salt‐resistant individuals than in salt‐sensitive ones. The responses of serum Klotho to dietary salt intervention were influenced by salt sensitivity, which was more prominent in salt‐resistant participants.
Investigating associations between birth order and autism diagnostic phenotypes
Authors: Alvares Gail A. , Licari Melissa K. , Stevenson Paul G. , Bebbington Keely , Cooper Matthew N. , Glasson Emma J. , Tan Diana W. , Uljarević Mirko , Varcin Kandice J. , Wray John , Whitehouse Andrew J. O.
Published: November 2020

Background

Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First‐ and later‐born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample.

Methods

Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1–18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling’s birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity.

Results

Adaptive functioning and intelligence scores decreased with increasing birth order, with later‐born children more likely to have an intellectual disability. Compared to first‐born children with siblings, first‐born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning.

Conclusions

These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.
Conflicting roles for humans in learning health systems and AI‐enabled healthcare
Authors: Kasperbauer T. J.
Published: November 2020

The goals of learning health systems (LHS) and of AI in medicine overlap in many respects. Both require significant improvements in data sharing and IT infrastructure, aim to provide more personalized care for patients, and strive to break down traditional barriers between research and care. However, the defining features of LHS and AI diverge when it comes to the people involved in medicine, both patients and providers. LHS aim to enhance physician‐patient relationships while developments in AI emphasize a physicianless experience. LHS also encourage better coordination of specialists across the health system, but AI aims to replace many specialists with technology and algorithms. This paper argues that these points of conflict may require a reconsideration of the role of humans in medical decision making. Although it is currently unclear to what extent machines will replace humans in healthcare, the parallel development of LHS and AI raises important questions about the exact role for humans within AI‐enabled healthcare.
Impact of feed restriction, chloroquine and deoxynivalenol on viral haemorrhagic septicaemia virus IVb in fathead minnow Pimephales promelas Rafinesque
Authors: Liu Juan‐Ting , Lumsden John S.
Published: November 2020

Autophagy can markedly alter host response to infectious disease, and several studies have demonstrated that a restricted diet or deoxynivalenol modulates autophagy and reduces mortality of fish due to bacterial disease. The picture is less clear for viral diseases of fish. Duplicate tanks of fathead minnow, Pimephales promelas Rafinesque, were fed a replete diet (control), 100 µM chloroquine, 5 µM deoxynivalenol, 10% (fasted) or 40% of a replete diet (pair‐fed) for 2 weeks and then experimentally infected by intraperitoneal injection with 2 × 105 viral haemorrhagic septicaemia virus IVb. Survival from highest to lowest for the different treatments was as follows: deoxynivalenol (average 43.3%); control (40.0%); pair‐fed (35.0%); fasted (33.3%); and chloroquine (21.7%). No treatment significantly altered the survival rate of fathead minnow after VHSV IVb infection when compared to controls; however, the fish fed with chloroquine had significantly lower survival rate than the fish fed deoxynivalenol (p < .05).
How Do Claims‐Based Measures of End‐of‐Life Care Compare to Family Ratings of Care Quality?
Authors: Christian Thomas J. , Hassol Andrea , Brooks Gabriel A. , Gu Qian , Kim Seyoun , Landrum Mary Beth , Keating Nancy L.
Published: November 2020

OBJECTIVES

Assess whether frequently‐used claims‐based end‐of‐life (EOL) measures are associated with higher ratings of care quality.

DESIGN

Retrospective cohort study.

SETTING/PARTICIPANTS

Deceased fee‐for‐service Medicare beneficiaries with cancer who underwent chemotherapy during July 2016 to January 2017 and died within 12 months and their caregiver respondents to an after‐death survey (n = 2,559).

MEASUREMENTS

We examined claims‐based measures of EOL care: chemotherapy 14 days or more before death; inpatient admissions, intensive care unit (ICU) use, and emergency department (ED) visits 30 days or more before death; hospice election and the timing of election before death. Primary outcomes are family ratings of “excellent” care in the last month of life and reports that hospice care began “at the right time.” Associations were assessed with logistic regression, adjusted by patient characteristics.

RESULTS

Family rated EOL care as excellent less often, if within 30 days before death the cancer patient had inpatient admissions (1 hospitalization = 41.5% vs 51.5% none, adjusted difference −10.1 percentage points), ICU use (38.6% for any ICU use vs 47.4% none; adjusted difference −8.8 percentage points), ED visits (41.0% 1 visit vs 51.6% no visits; adjusted difference −10.6 percentage points), or elected hospice within 7 days before death. Among hospice enrollees, family more often reported that hospice began at the right time if it started at least 7 days before death (hospice 1–2 days before death 60.2% vs hospice 7–13 days 74.9%; adjusted difference +14.7 percentage points).

CONCLUSIONS

Claims‐based measures of EOL care for cancer patients that reflect avoidance of hospital‐based care and earlier hospice enrollment are associated with higher ratings of care quality by bereaved family members.
Effects of running exercises on reaction time and working memory in individuals with intellectual disability
Authors: Affes S. , Borji R. , Zarrouk N. , Sahli S. , Rebai H.
Published: November 2020

Background

This study explored the effect of running exercises at low [30% heart rate reserve (HRR)] and moderate (60%HRR) intensities on cognitive performances in individuals with intellectual disability (ID).

Methods

Participants performed randomly reaction time (RT) tests: visual RT [simple RT (SRT) and choice RT (CRT)], auditory SRT (ASRT) and working memory (WM) (Corsi test) before and after the exercises.

Results

The results showed that after both exercises, SRT decreased significantly (P < 0.001) in both groups with higher extent (P < 0.05) at 60%HRR compared with 30%HRR. CRT decreased (P < 0.01), similarly, after the both exercises in both groups with higher (P < 0.001) extent in the intellectual disability group (IDG). ASRT decreased significantly, at 30%HRR, in IDG (P < 0.001) and in control group (CG) (P < 0.01) with greater extent in IDG (P < 0.001). At 60%HRR, ASRT decreased significantly in both groups (P < 0.001) with greater extent in IDG (P < 0.001). The ΔASRT% was significantly (P < 0.05) higher at 30%HRR compared with 60%HRR in IDG. In CG, no significant (P = 0.21) difference was reported between intensities. The Corsi forward and the Corsi backward scores increased significantly (P < 0.01) in both groups after both intensities with higher extent in IDG (P < 0.01).

Conclusions

Our results suggest that low and moderate running exercises improve similarly simple and choice visual RT as well as WM in individuals with ID. Furthermore, low‐intensity exercise could be more appropriate to enhance ASRT compared the moderate one in these individuals. Therefore, low‐intensity exercise seems to be an efficient strategy to improve cognitive performances in individuals with ID.
The role of knowledge and self‐efficacy on dental consultation behavior of patients with type 2 diabetes
Authors: Kudoh Rie , Shibayama Taiga , Hidaka Kikue
Published: November 2020

Aim

This study aimed to examine the association of knowledge and self‐efficacy as variables for behavior related to dental consultations among patients with type 2 diabetes, depending on the diagnosis of periodontal disease at a general hospital in Japan.

Methods

A cross‐sectional survey was conducted with 198 patients with type 2 diabetes (mean age: 66.1 ± 10.1 years, men: 56.6%, mean glycated hemoglobin: 7.3 ± 1.0%). The self‐efficacy of patients with periodontal disease was assessed using the Self‐Efficacy Scale for Self‐Care. Knowledge was measured using five dichotomous items based on reference to clinical guidelines. Dental consultation behavior was assessed from regular dental checkup behavior.

Results

In total, 31.8% of participants attended their regular dental checkup in the last year. Logistic regression analysis revealed that dental consultation behavior was positively associated with self‐efficacy among patients diagnosed with periodontal disease (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.10–1.45), and positively associated with the knowledge among patients not diagnosed with periodontal disease (OR = 1.54, 95%, CI: 1.09 − 2.16).

Conclusion

Patients without periodontal disease need to learn about accurate knowledge regarding periodontal disease as a complication of diabetes and its prevention via dental checkups. Supportive consultation to improve self‐efficacy with respect to dental consultations should be offered to patients with periodontal disease. Medical professionals will be able to support each patient with type 2 diabetes by changing the educational approach for promoting regular dental checkups at the time of diabetes consultations.
Role of Ten eleven translocation‐2 (Tet2) in modulating neuronal morphology and cognition in a mouse model of Alzheimer's disease
Authors: Li Liping , Miao Miao , Chen Jiarui , Liu Zhitao , Li Wanyi , Qiu Yisha , Xu Shujun , Wang Qinwen
Published: November 2020

Abnormal expression of Ten eleven translocation‐2 (Tet2) contributes to the pathogenesis of Alzheimer's disease (AD). However, to date, the role of Tet2 in modulating neuronal morphology upon amyloid‐β (Aβ)‐induced neurotoxicity has not been shown in a mouse model of AD. Here, we have developed a model of injured mouse hippocampal neurons induced by Aβ42oligomers in vitro. We also investigated the role of Tet2 in injured neurons using recombinant plasmids‐induced Tet2 inhibition or over‐expression. We found that the reduced expression of Tet2 exacerbated neuronal damage, whereas the increased expression of Tet2 was sufficient to protect neurons against Aβ42toxicity. Our results indicate that the brains of aged APPswe/PSEN1 double‐transgenic (2 × Tg‐AD) mice exhibit an increase in Aβ plaque accumulation and a decrease in Tet2 expression. As a result, we have also explored the underlying mechanisms of Tet2 in cognition and amyloid load in 2 × Tg‐AD mice via adeno‐associated virus‐mediated Tet2 knockdown or over‐expression. Recombinant adeno‐associated virus was microinjected into bilateral dentate gyrus regions of the hippocampus of the mice. Knocking down Tet2 in young 2 × Tg‐AD mice resulted in the same extent of cognitive dysfunction as aged 2 × Tg‐AD mice. Importantly, in middle‐aged 2 × Tg‐AD mice, knocking down Tet2 accelerated the accumulation of Aβ plaques, whereas over‐expressing Tet2 alleviated amyloid burden and memory loss. Furthermore, our hippocampal RNA‐seq data, from young 2 × Tg‐AD mice, were enriched with aberrantly expressed lncRNAs and miRNAs that are modulated by Tet2. Tet2‐modulated lncRNAs (Malat1, Meg3, Sox2ot, Gm15477, Snhg1) and miRNAs (miR‐764, miR‐211, and miR‐34a) may play a role in neuron formation. Overall, these results indicate that Tet2 may be a potential therapeutic target for repairing neuronal damage and cognitive impairment in AD.

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Clinical Effectiveness of a Self‐Regulation Theory–Based Self‐Management Intervention for Adults With Knee Osteoarthritis: A Long‐Term Follow‐Up
Authors: Kao Mei‐Hua , Tsai Yun‐Fang
Published: November 2020

Purpose

To determine if there are long‐term effects of a self‐management intervention guided by self‐regulation theory for adults with knee osteoarthritis at 6 and 12 months after completing the intervention.

Design

This long‐term follow‐up study used a longitudinal quasi‐experimental design with repeated measures.

Methods

A convenience sample of 127 patients with knee osteoarthritis who were 45 to 64 years of age were recruited from outpatient clinics in Taiwan. The Self‐Management Needs of Knee Osteoarthritis Scale was used to assess self‐management needs at enrollment (baseline). To evaluate the long‐term effects, participants were reassessed at 6 and 12 months after the intervention using the following questionnaires: The Knee Injury and Osteoarthritis Outcome Score, Healthcare Outcomes, and the Short‐Form Health Survey. Generalized estimating equations compared assessments at baseline with scores at 6 and 12 months following completion of the intervention. Multiple regression was used to examine significant factors associated with the assessments.

Findings

Participants had moderate levels of self‐management needs. When assessments at 6 months were compared with baseline, scores for knee symptoms and physical function and quality of life showed significant improvements; significant reductions were seen in body mass index, unplanned medical consultations, and pain medication doses. Assessments at 12 months compared with baseline measures indicated these improvements were maintained. These improvements were significant from baseline measures at both 6 months and 12 months after adjustments were made for time and other significant variables.

Conclusions

Twelve months after completion of the intervention, the significant improvements seen at 6 months were maintained. Our findings demonstrate that the self‐management intervention had significant long‐term effects on knee symptoms and physical function, body mass index and pain medication doses, and overall quality of life for patients with moderate self‐management needs of knee osteoarthritis.

Clinical Relevance

Clinical care of knee osteoarthritis that includes a self‐regulation theory–based self‐management intervention could provide long‐term benefits to patients.
Sacral co‐ossification in dinosaurs: The oldest record of fused sacral vertebrae in Dinosauria and the diversity of sacral co‐ossification patterns in the group
Authors: Moro Débora , Kerber Leonardo , Müller Rodrigo T. , Pretto Flávio A.
Published: November 2020

The fusion of the sacrum occurs in the major dinosaur lineages, i.e. ornithischians, theropods, and sauropodomorphs, but it is unclear if this trait is a common ancestral condition, or if it evolved independently in each lineage, or even how or if it is related to ontogeny. In addition, the order in which the different structures of the sacrum are fused, as well as the causes that lead to this co‐ossification, are poorly understood. Herein, we described the oldest record of fused sacral vertebrae within dinosaurs, based on two primordial sacral vertebrae from the Late Triassic of Candelária Sequence, southern Brazil. We used computed microtomography (micro‐CT) to analyze the extent of vertebral fusion, which revealed that it occurred only between the centra. We also assessed the occurrence of sacral fusion in Dinosauria and close relatives. The degree of fusion observed in representatives of the major dinosaur lineages suggested that there may be a sequential pattern of fusion of the elements of the sacrum, more clearly observed in Sauropodomorpha. Our analyses suggest that primordial sacral vertebrae fuse earlier in the lineage (as seen in Norian sauropodomorphs). Intervertebral fusion is observed to encompass progressively more vertebral units as sauropodomorphs evolve, reaching up to five or more fully fused sacrals in Neosauropoda. Furthermore, the new specimen described here indicates that the fusion of sacral elements occurred early in the evolution of dinosaurs. Factors such as ontogeny and the increase in body size, combined with the incorporation of vertebrae to the sacrum may have a significant role in the process and in the variation of sacral fusion observed.
Simple method to distinguish the type of fetal premature contraction using arterial Doppler time interval measurements
Authors: Teramachi Yozo , Maeno Yasuki , Hirose Akiko , Horinouchi Takashi , Kozuma Yutaka , Yoshizato Toshiyuki , Suda Kenji
Published: November 2020

Aim

The purpose of this study was to establish a simple method to distinguish premature ventricular contractions (PVC) from premature atrial contractions (PAC) using a fetal Doppler ultrasound arterial pulse waveform to measure time intervals between sinus node restarting.

Methods

We retrospectively identified 14 fetuses with premature contraction (8 with PAC, 6 with PVC). We measured two distinct parts of time intervals using an arterial pulsed‐wave Doppler: the two consecutive waveforms just before the premature contraction (2‐V interval) and two consecutive waveforms including the premature contraction (XV interval) to measure time intervals between sinus node restarting. We then evaluated the time difference between the 2‐V and XV intervals in PVC compared to PAC.

Results

For PVC, the difference between the 2‐V interval and the XV interval was significantly shorter than that for PAC. A cut‐off point of 33 ms, where a difference ≤33 ms was clearly shown to be associated with a PVC and a difference more than 33 ms signified a PAC was demonstrated.

Conclusion

The 2‐V and XV interval measurements, used to measure time intervals between sinus node restarting, could easily distinguish PVC from PAC in utero. Therefore, this study could potentially be a feasible and effective method for obstetricians or sonographers to employ usefully.
Mental Health Services in the United States Public High Schools
Authors: Shelton Andrea J. , Owens Emiel W.
Published: November 2020

BACKGROUND

Mental health services in the United States public schools are an important component of the academic success of a student. Not all schools, however, have the necessary personnel and funding to offer such services.

METHODS

In this paper, we provide an analysis of data collected from schools in 3 geographic locations. Comparisons were made of the availability of personnel to assess and treat mental health disorders in students enrolled in city, urban, and suburban schools, with over 10,000 schools represented. The data were part of the 2015 to 2016 School Survey on Crime and Safety.

RESULTS

Accessibility of mental health practitioners and reasons that limited efforts of a school to provide the services were assessed. Statistically significant differences were identified by school location, demonstrating that those in rural communities were most challenged providing diagnostic assessment and treatment for students by school mental health professionals, for several reasons.

CONCLUSIONS

Increased state and county funding to support mental health practitioners in public high schools is one suggestion to address mental health disorders in students. Other strategies are offered for timely and appropriate diagnoses and treatment for mental health disorders that may impact the quality of life of a student for a lifetime.
Midazolam oxidation in cattle liver microsomes: The role of cytochrome P450 3A
Authors: Nassi Alberto , Quintieri Luigi , Merlanti Roberta , Pezzato Francesca , Capolongo Francesca , Pauletto Marianna , Dacasto Mauro , Giantin Mery
Published: November 2020

In humans, the cytochrome P450 3A (CYP3A) subfamily is involved in midazolam (MDZ) biotransformation into 1′‐ and 4‐hydroxy metabolites, and the former serves as a probe for CYP3A catalytic activity. In veterinary species is still crucial to identify enzyme‐ and species‐specific CYP substrates; thus, the aim of this study was to characterize MDZ oxidation in cattle liver. A HPLC‐UV method was used to measure 1′‐ and 4‐hydroxy MDZ (1′‐ and 4‐OHMDZ, respectively) formation in cattle liver microsomes and assess the role of CYP3A by an immunoinhibition study. Moreover, MDZ hydroxylation was evaluated in 300 cattle liver samples and results were correlated with testosterone hydroxylation. Formation of both metabolites conformed to a single‐enzyme Michaelis–Menten kinetics. Values ofVmaxandKmwere 0.67 nmol/min/mg protein and 6.16 μM for 4‐OHMDZ, and 0.06 nmol/min/mg protein and 10.08 μM for 1′‐OHMDZ. An anti‐rat CYP3A1 polyclonal antibody inhibited up to 50% and 94% 1′‐ and 4‐OHMDZ formation, respectively. MDZ oxidation in liver microsomes was poorly correlated with testosterone hydroxylation. In conclusion, cattle metabolized MDZ to 1′‐OHMDZ and 4‐OHMDZ. The immunoinhibition results indicated a major contribution of CYP3As to 4‐OHMDZ formation and the involvement of other CYPs in 1′‐OHMDZ production, paving the way for further investigations.
A two‐country, three‐commodity Ricardian trade model with Keynesian unemployment
Authors: Sato Hideo
Published: November 2020

Conventional trade models either assume full employment or suppose imperfect labor markets and attribute unemployment to the imperfectness. Needless to say, Keynesian unemployment arising from a shortage of effective demand has not been considered. In this paper, our two‐country, three‐commodity trade model determines patterns of the international division of labor, commodity terms of trade, relative wage rates and employment quantities in each country simultaneously, given the production techniques, labor endowments and effective demand. Furthermore, the model argues the significance of link commodities commonly produced in both countries and quantity adjustments without price changes in the face of demand changes.
Thoracic impedance measurement in heart stimulation and cardiac arrhythmias
Authors: Ząbek Andrzej , Boczar Krzysztof , Nowosielska‐Ząbek Ewa , Holcman Katarzyna , Ulman Mateusz , Lelakowski Jacek , Małecka Barbara
Published: November 2020

The electrocardiogram (ECG) interpretation in patients with implantable cardioverter defibrillator (ICD) is often a puzzling problem. The difficulty of the device function evaluation further increases in the presence of unfamiliar timing cycles and additional functions.

We present an interesting ECG with a special function of a Biotronik ICD devices called the thoracic impedance monitoring, and demonstrate its behavior in a patient with atrial fibrillation, pacing beats, ventricular ectopic beats, and couple of ventricular beats. This report shows unexceptional occurrence of tricky ECG finding in patient with Biotronik ICDs.
Device related thrombus after left atrial appendage closure: State of the art
Authors: Yu Jiangtao , Bai Yuan , Jiang Li‐Sheng
Published: November 2020

Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Patients with AF are at higher risk of stroke with the left atrial appendage (LAA) being the most common site for thrombus formation. Although oral anticoagulation (OAC) remains the standard of care for stroke prevention in AF patients, there are still several limitations, including increased risk of bleeding and noncompliance. LAA closure (LAAC) has been found to be non‐inferior to OAC in preventing all‐cause strokes and systemic embolisms in randomized clinical trials, and is increasingly performed for stroke prevention in patients with nonvalvular AF (NVAF). However, device‐related thrombus (DRT) after LAAC and a potentially increased risk of stroke related to DRT were observed in several registered studies, and attract wide concern. This review provides a comprehensive update on the incidence, mechanism, risk factors, prevention, diagnosis, and treatment of DRT after LAAC in patients with NVAF.
Pulmonary Daoyin as a traditional Chinese medicine rehabilitation programme for patients with IPF: A randomized controlled trial
Authors: Zhou Miao , Zhang Hailong , Li Fenglei , Yu Zhefeng , Yuan Chengbo , Oliver Brian , Li Jiansheng
Published: November 2020

Background and objective

IPF is a chronic progressive lung disease in which PR provides benefit for patients. PD, a TCM PR programme, has known effectiveness in COPD, but its utility in IPF is unknown. We investigated its effectiveness and safety in patients with IPF.

Methods

A 6‐month randomized controlled trial (RCT) was conducted in three Chinese clinics. Ninety‐six participants diagnosed with IPF were randomly assigned to one of the three groups: the PD group received a PD programme two times a day, 5 days/week for 2 months, and the exercise group exercised via a stationary cycle ergometer, 30 min/day, 5 days/week for 2 months. Volunteers in the control group were advised to maintain their usual activities. Primary outcomes were changes from baseline in the 6MWD and HRQoL score on the SGRQ‐I at 1 and 2 months (at the end of the intervention) and at 6 months (4 months after the intervention). Secondary outcomes measures included FVC, DLCO (% predicted) and the changes in mMRC.

Results

The 6MWD was increased in the PD group compared to exercise and control groups. 6MWD increased by 60.44 m in the PD group, 32.16 m in the exercise group and 12.42 m in controls after the 2 months of rehabilitation programme. The between‐group differences in the change from baseline were 28.78 m (95% CI: 0.54 to 56.01; P = 0.044) and 48.02 m (95% CI: 23.04 to 73.00; P < 0.001) at 2 months, and 25.61 m (95% CI: −0.67 to 51.89; P = 0.058) and 50.93 m (95% CI: 25.47 to 76.40; P < 0.001) at 6 months, respectively, including a difference exceeding the MCID. There was no significant change in the SGRQ‐I score, the mMRC dyspnoea score, FVC and DLCO (% predicted) in either the PD or exercise groups.

Conclusion

Two months after the intervention, a clinically meaningful difference in 6MWD was observed favouring the PD programme. The PD programme is safe and effective as a rehabilitation intervention designed to increase exercise tolerance and is an appropriate substitute for PR.
Evolution of lived experience of dementia caregivers after a psycho‐educational group: an interpretative phenomenological analysis
Authors: Dovi Eliane , Bier Jean‐Christophe , Fantini‐Hauwel Carole
Published: November 2020

The ‘Help and Support for Caregivers and Patients’ psycho‐education group aims to educate and support dementia caregivers. Fourteen spousal caregivers were interviewed before (T1) and after (T2) psycho‐education participation. Intrapersonal processes and the potential evolution of lived experience were explored using longitudinal interpretative phenomenological analysis. Three trajectory groups were identified at T1: proactive help‐seekers, passive but hopeful caregivers and ambivalent caregivers. T2 interviews revealed that caregivers experienced growth in their role, benefitted from peer interactions, feelings of guilt were addressed and they were using out‐of‐home dementia‐specific services. Identifying beliefs or attitudes that might prevent caregivers from getting help or support is important. Caregiver well‐being remains a public health priority and furthering our knowledge about their complex and changing needs is paramount to provide well‐designed and tailored resources.
The relationship between malnutrition and TH2 immune markers: a study in school‐aged children of different socio‐economic backgrounds in Makassar, Indonesia
Authors: Wahyuni Sitti , van Dorst Marloes M.A.R. , Amaruddin Aldian I. , Muhammad Munawir , Yazdanbakhsh Maria , Hamid Firdaus , Koopman Jan Pieter R. , Sartono Erliyani
Published: November 2020

Objective

The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TH2 immune markers in school‐aged children in Makassar, Indonesia.

Methods

A cross‐sectional study was performed in five schools where socio‐demographic characteristics were recorded. Children’s standardised z‐scores of body mass index (z‐BMI) and age‐standardised z‐scores of height (z‐HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin‐like growth factor (IGF‐1) and TH2 immune markers were measured.

Results

In total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99–4.23) and IGF‐1 (GMR 1.45, 95% CI: 1.15–1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49–0.66 and GMR 0.78, 95% CI: 0.63–0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64–0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50–4.78) but no relationship was found with the other TH2 immune markers.

Conclusion

Malnutrition is prominent in school‐aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.