bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of Hacking and Blunt Force Skeletal Trauma
Authors: Peace Breana N. , Pokines James T. , Cummings Peter M. , Harbaugh Allen G.
Published: June 2020

Hacking trauma is prevalent in forensic cases involving genocide and dismemberment, but research into the identification of this type of trauma is lacking. The present study examines characteristics of hacking and blunt force skeletal trauma in order to determine if there is a point at which blunt force trauma becomes distinguishable from hacking trauma. Ten implements with a range of blade angles (i.e., the striking surface of the implement) were used in conjunction with a controlled‐force hacking device to impact 100 limb bones of white‐tailed deer (Odocoileus virginianus). Observations of the trauma included the occurrence and degree of fragmentation, the entrance widths of the impacts, and composite scores of six hacking characteristics, especially the distinctive V‐shaped kerf. ANOVA tests and regression analyses were used to assess the relationships between these characteristics and the blade angles. A significant relationship (p‐value = 0.011) was found between the composite hacking scores and the blade angles, indicating that blunt force and hacking trauma can be distinguished. The entrance widths of the impacts exhibited a significant relationship with the blade angles (p‐value = 0.037). There was also a significant relationship between the visibility of a V‐shaped kerf in the bones (p‐value = 0.003), with visibility decreasing around the 60° blade angle. These data should assist in establishing guidelines to differentiate hacking and blunt force skeletal trauma in cases where the implement is on a spectrum between sharp and blunt.
Epstein‐Barr virus positive inflammatory pseudotumours (IPT) and IPT‐like tumours
Authors: Cheung Alyson , Leung Howard Ho‐Wai , Lee Kit‐Fai , Lai Paul Bo‐San , Chong Charing Ching‐Ning
Published: June 2020

Inflammatory pseudotumour (IPT) is a spectrum of lesions which mimic malignancies in various organs. Preoperative diagnosis is often challenging. In this case report, we present two rare cases of Epstein‐Barr virus (EBV) associated IPTs and discuss the clinico‐pathological characteristics of these two entities.
Long‐term results from a series of patients managed with breast conservation surgery and hypofractionated radiotherapy in Christchurch: What is the recurrence rate and how do we detect recurrences
Authors: Mohamad Hanib Mohamad Firdaus Bin , Robinson Bridget A , Frampton Chris , James Melissa L
Published: June 2020

Aims

Hypofractionated radiation treatment (HFRT) following breast conservation surgery (BCS) has similar efficacy to conventionally fractionated radiation treatment (CFRT). This study updates outcomes for patients treated with HFRT in Christchurch, New Zealand, and reports on the pattern, timing and method of detection of recurrences to inform follow‐up practice.

Methods

Between 2004 and 2006, 273 women with early breast cancer were treated with HFRT (42.5 Gray (Gy) in 16 fractions). Details of demographics, tumour characteristics, treatments, any recurrence (local, nodal or distant), follow‐ups and date of death were collected. The primary endpoint was local recurrence rate (LRR); secondary endpoints were local recurrence‐free survival (LRFS) and overall survival (OS).

Results

With a median follow‐up of 12.9 years, 17 women developed a local recurrence. LRR at 5 and 10 years were 3.1% and 5.3%, respectively. Five‐year LRFS was 91.7% and ten‐year LRFS was 83.5%. The OS at five years was 93.7% and at ten years was 87.7%. For the 41 patients with a first recurrence at any site, 75.6% were symptomatic, 22% were screen detected with radiology and 2.4% were incidental findings. None of the first recurrences were detected when asymptomatic on clinical examination in follow‐up clinics.

Conclusions

The rate of local recurrence following HFRT for BCS is low. No asymptomatic recurrence was detected by routine clinic follow‐up. The utility of regular clinical examination for the detection of recurrence is low and this should inform follow‐up strategies.
Spondylodiscitis and spinal epidural abscess related to long‐term placement of an airway stent for malignant central airway obstruction
Authors: Shikano Kohei , Ishii Daisuke , Umimura Tomotaka , Rakuman Shintaro , Maki Satoshi , Kasai Hajime , Orita Sumihisa , Iwasawa Shunichiro , Sugiura Toshihiko , Ohtori Seiji , Tatsumi Koichiro
Published: June 2020

A 70‐year‐old male was referred to our hospital with lower limb muscle weakness and numbness of the left hand. The patient had previously been diagnosed seven years ago with lung cancer accompanied by central airway obstruction and had received chemoradiotherapy following placement of a metallic stent. Computed tomography (CT) scan revealed an osteolytic lesion which was adjacent to the fractured stent. T2‐weighted magnetic resonance imaging (MRI) demonstrated high signal intensity in the disc space. The patient was diagnosed with spondylodiscitis and spinal epidural abscess related to the airway stent. Despite hemilaminectomy, laminectomy and long‐term antibiotic therapy, the infection was uncontrolled. Moreover, osteolytic destruction and kyphotic deformity progressed. Removal of the airway stent was necessary; however, it was impossible because bronchial resection was required and the risk of mediastinal injury was considered to be high. The patient subsequently received palliative care. Long‐term airway stenting can cause spondylodiscitis and spinal epidural abscess. Indications for the placement of metallic stents for malignant central airway obstruction should be carefully evaluated after considering the difficulty in removal and the long‐term risk of severe complications.

Key points

Significant findings of the study

Long‐term placement and fracture of the airway stent can cause spondylodiscitis and spinal epidural abscess.

What this study adds

The indication of placement of a metallic stent for malignant central airway obstruction should be considered with caution, especially if long‐term survival can be expected.
Analysis of targeted somatic mutations in pleomorphic carcinoma of the lung using next‐generation sequencing technique
Authors: Manabe Saki , Kasajima Rika , Murakami Shuji , Miyagi Yohei , Yokose Tomoyuki , Kondo Tetsuro , Saito Haruhiro , Ito Hiroyuki , Kaneko Takeshi , Yamada Kouzo
Published: June 2020

Background

Pleomorphic carcinoma (PC) of the lung is a rare type of lung cancer with aggressive characteristics and a poor prognosis. Because it is rare, the molecular characteristics of PC remain unclear.

Methods

A gene mutation analysis was performed using next‐generation sequencing (NGS) in patients with PC of the lung who had undergone surgical resection.

Results

A total of nine patients were enrolled in the study. All the patients were male and eight had a history of smoking. Eight tumors contained spindle cells and three contained giant cells. Mutations considered significant were found in eight of the nine patients: in TP53 in five patients, in MET in two patients, and in ALK, ERBB2, PIK3CA, APC, NF1, and CDKN2A in one patient each. No EGFR mutation was detected in our analysis. Co‐mutations were detected in three patients: TP53 with MET and NF1, TP53 with ERBB2, and PIK3CA with CDKN2A.

Conclusions

TP53 mutations were detected most frequently in PC of the lung with NGS analysis. Different co‐mutations were seen in several specimens.

Key points

Significant findings of the study

This study demonstrates that mutations in the TP53 gene are frequently found and co‐mutations are sometimes found in pleomorphic carcinoma of the lung using genomic profiling analysis.

What this study adds

Our results will help to analogize the genetic characteristics and potential target of molecular‐targeted agents of pleomorphic carcinoma of the lung.
Right upper lobectomy in lung cancer with double aortic arch: A case report
Authors: Kawamoto Nobutaka , Okita Riki , Inokawa Hidetoshi , Hayashi Masataro , Furukawa Masashi , Okada Masanori , Okabe Kazunori
Published: June 2020

Double aortic arch (DAA) is a rare congenital anomaly of the heart and aorta in which a vascular ring that surrounds the trachea and esophagus is formed. In most patients, respiratory distress and dysphagia develop in childhood, and asymptomatic adult patients are rarely known. Herein, we describe a patient with lung cancer and DAA. A 66‐year‐old man who had DAA underwent video‐assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection for primary lung cancer. Lymph node dissection of the right upper mediastinum revealed that the right recurrent laryngeal nerve branched from the right vagus nerve just beneath the right aortic arch. Additionally, the right aortic arch narrowed the space surrounding the trachea, superior vena cava, and arch of the azygos vein, impeding the stapling of the truncus anterior artery and right upper lobe pulmonary vein with the video‐assisted thoracoscopic approach.

Key points

Significant findings of the study

In double aortic arch, the recurrent laryngeal nerve branches from the vagus nerve just beneath the ipsilateral aortic arch.

The right aortic arch narrows the space surrounding the trachea, superior vena cava, and arch of the azygos vein.

What this study adds

The anatomy of a double aortic arch impedes mediastinal lymph node dissection on the ventral side of the trachea. Handling autosuture devices for stapling pulmonary arteries and veins is also difficult.
Common Institutional Ownership and Earnings Management*
Authors: Ramalingegowda Santhosh , Utke Steven , Yu Yong
Published: June 2020

This study examines the relation between earnings management and block ownership of same‐industry peer firms by a common set of institutional investors (common institutional ownership). This relation is important given the tremendous growth of common institutional ownership and the significant influence of blockholders on financial reporting. We hypothesize that common institutional ownership mitigates earnings management by enhancing institutions' monitoring efficiency and by encouraging institutions to internalize the negative externality of a firm's earnings management on peer firms' investments. Consistent with our hypothesis, we find that higher common institutional ownership is related to less earnings management. Analyses of a quasi‐natural experiment based on financial institution mergers show that this negative relation is unlikely to be driven by the endogeneity of common institutional ownership. Cross‐sectional tests provide evidence that the negative relation is stronger among firms for which common institutional ownership is likely to generate a greater reduction in institutions' information acquisition and processing costs, and among firms whose severe financial misstatements are more likely to distort co‐owned peer firms' investments, supporting both mechanisms underlying our hypothesis. Our findings inform the ongoing debate on the costs and benefits of common institutional ownership by highlighting an important benefit: the enhanced monitoring of financial reporting.
Growth rate of clinically diagnosed superficial basal cell carcinoma and changes in dermoscopic features over time
Authors: Sykes Adrian Jonathan , Wlodek Christina , Trickey Adam , Clayton Gemma L , Oakley Amanda
Published: June 2020

Background/Objectives

Basal cell carcinoma (BCC) is the most commonly occurring skin cancer. BCCs have been found to generally grow slowly. Data are limited on how the dermoscopic characteristics of BCCs evolve. We set out to determine the growth rate of superficial BCCs (sBCC) and assess the change in dermoscopic features over time.

Methods

A retrospective review was performed of clinically diagnosed sBCC. Images, demographic and dermoscopic data were collected by a melanographer. Mixed effects linear regression models were used to investigate sBCC growth and associations between size and dermoscopic/demographic variables. We tested differences in trends over time in dermoscopic features using non‐parametric trend tests.

Results

100 individual sBCC were evaluated in 70 patients (mean age 62; 59% male), 69% had Fitzpatrick skin phototype 1 or 2, and 81% had some degree of actinic damage. sBCC were present on the back in 58% and 22% of men and women, respectively. The median surface area was 41.9 mm2 with a growth rate of 0.81 mm2/month. Males had larger sBCC than females. There was no association between sBCC size and Fitzpatrick skin phototype, history of skin cancer or family history of melanoma. There is some evidence larger sBCC gain shiny white structures (P = 0.053) over time.

Conclusions

sBCC grow at a rate unlikely to adversely affect patient outcomes associated with long wait times. Our data suggest that dermoscopy can aid in appropriate treatment selection for sBCC.
Real‐time intraoperative ultrasound biomicroscopy for determining graft orientation during Descemet's membrane endothelial keratoplasty
Authors: Nahum Yoav , Galor Orly , Atar Maya , Bahar Irit , Livny Eitan
Published: June 2020

Purpose

To evaluate the intraoperative use of ultrasound biomicroscopy (UBM) during Descemet's membrane endothelial keratoplasty (DMEK) to determine graft's orientation.

Methods

Prospective interventional study of eight eyes of seven patients who underwent DMEK. Following the identification of correct graft orientation using 'Blue cannula tip' sign during DMEK surgery, UBM was used to ascertain graft's orientation. The rate of successful DMEK graft orientation determined by the UBM was registered and verified postoperatively by anterior segment‐optical coherence tomography (OCT). Intra‐ and postoperative complications, postoperative clearance of the cornea, corrected distance visual acuity and endothelial cell loss were also noted.

Results

The study included five males and two females aged 54–82 years with corneal oedema due to Pseudophakic bullous keratopathy (n = 5), Fuchs’ endothelial dystrophy (n = 2). In all cases, the technique allowed proper determination of the graft's orientation. In one case, ‘blue cannula tip’ sign showed correct orientation while UBM identified an upside–down graft. The graft was inverted in the anterior chamber using fluid jets, and repeat ‘blue cannula tip’ sign and UBM examination both showed correct orientation. In all cases, postoperative anterior segment‐OCT demonstrated correct graft orientation.

Conclusions

Use of intraoperative UBM to determine graft orientation during DMEK correlated with proper graft orientation, as was verified postoperatively by anterior segment‐OCT. The use of UBM can be particularly helpful in cases of poor graft visibility due to opaque corneal stroma, pigment or blood in the anterior chamber during surgery, or when the blue tint of the graft fades rapidly, which may preclude proper determination of graft's orientation.
Testing the Associations among Social Axioms, School Belonging, and Flourishing in University Students: A Two‐Year Longitudinal Study
Authors: Li Yun , Tong Kwok Kit , Tao Vivienne Y. K. , Zhang Meng Xuan , Wu Anise M. S.
Published: June 2020

Background

This longitudinal study investigated the temporal stability of social axioms, which are generalised social beliefs, and tested their prospective effects on individuals' flourishing, among students, as well as the extent to which they can be potentially mediated by perceived sense of belonging at school.

Methods

Participants were 195 Chinese university students, who voluntarily completed a questionnaire measuring social axioms (at baseline, 1‐year follow‐up, and 2‐year follow‐up studies), school belonging (at 1‐year follow‐up study), and flourishing (at baseline and 2‐year follow‐up studies).

Results

Results showed supportive evidence for five types of social axioms being generally stable across these time intervals. After controlling for baseline flourishing, high baseline social cynicism significantly predicted a lower level of follow‐up flourishing, whereas high baseline reward for application predicted a higher level of follow‐up flourishing. Furthermore, higher levels of social cynicism predicted lower levels of school belonging, and the latter partially mediated the effect of social cynicism on follow‐up flourishing.

Conclusions

All social axioms are relatively stable across time. Social cynicism, reward for applications, and school belonging are the most salient predictors for flourishing among Chinese university students.
Subtyping of male breast cancer by PAM50 and immunohistochemistry: a pilot study of a consecutive Danish cohort
Authors: Christensen Lene Gaarsmand , Lautrup Marianne Djernes , Lyng Maria Bibi , Möller Sören , Jylling Anne Marie Bak
Published: June 2020

Male breast cancer (MBC) is a rare disease that is still to be fully understood. In female breast cancer, molecular subtyping by gene expression has proven its significance. In this study, we characterize a consecutive cohort of MBC patients surgically treated from 1997 to 2017, identified at our institution (N = 37), and report the association between molecular subtypes found by a surrogate panel of immunohistochemical (IHC) markers, and the PAM50 signature, as well as risk of recurrence score and overall survival for the different subtypes. PAM50 subtypes were determined using the nCounter FLEX system instrument and software. The distribution of molecular subtypes according to the PAM50 signature was as follows: 56% luminal B, 39% luminal A, and 5% basal‐like. None of the tumors were HER2‐enriched. Using IHC surrogate markers, we found 80% luminal B‐like, 15% luminal A‐like, and 5% basal‐like. None were HER2‐positive (non‐luminal). We found a strong statistical association between subtypes found by PAM50 signature and the IHC surrogate markers (p < 0.001). Furthermore, we found luminal A tumors to be smaller in size compared to luminal B tumors (p = 0.04). Patients with luminal A subtype tumors had the lowest ROR scores with a mean of 39, whereas patients with luminal B subtype tumors had a mean ROR score of 69. Significant worse overall survival for luminal B tumors compared to luminal A tumors was seen (p = 0.02). Male breast cancer seems to be a mainly luminal disease, with luminal B being the most frequent subtype. Further studies are needed to ensure correct therapeutic strategies for this select group of patients.
Effects of intramammary infusion of Bifidobacterium breve on mastitis pathogens and somatic cell response in quarters from dairy cows with chronic subclinical mastitis
Authors: Nagahata Hajime , Mukai Takuma , Natsume Yo , Okuda Miyuki , Ando Tatsuya , Hisaeda Keiichi , Gondaira Satoshi , Higuchi Hidetoshi
Published: June 2020

The present study assessed the effects of intramammary infusion of Bifidobacterium breve (B. breve) on mastitis‐causing pathogens and on the somatic cell counts (SCC) in lactating cows with chronic subclinical mastitis. The bacteriological cure rates of 42 quarters from 42 cows infected with Staphylococcus aureus, Corynebacterium bovis, coagulase‐negative staphylococci, and environmental streptococci were 18.2% (2/11), 14.3% (1/7), 58.8% (10/17), and 28.6% (2/7), respectively, on day 14 after B. breve infusion. In a second trial, B. breve was infused into 18 quarters from 18 cows with chronic subclinical mastitis from which pathogens had not been isolated; the rates of quarters showing SCC > 50 × 104 cells/ml prior to B. breve infusion that decreased to < 30 × 104 cells/ml after infusion were significantly (p < .01) increased to 61.1% (11/18) on day 14 compared to that prior to infusion (0/18). The intramammary infusion of B. breve appears to be a non‐antibiotic approach for elimination of minor pathogens and decreasing SCC in quarters with chronic subclinical mastitis in dairy cows.
Pluripotency‐associated genes reposition during early embryonic developmental stages in pigs
Authors: Nguyen Hiep Thi , Nghia Nguyen Trong , Lien Nghiem Thi Ha , Dang‐Nguyen Thanh Quang , Men Nguyen Thi , Viet Linh Nguyen , Xuan Nguyen Bui , Noguchi Junko , Kaneko Hiroyuki , Kikuchi Kazuhiro
Published: June 2020

We examined the allelic expression and positioning of two pluripotency‐associated genes, OCT4 and SOX2, and two housekeeping genes, ACTB and TUBA, in 4‐ and 8‐cell porcine embryos utilizing RNA and DNA fluorescence in situ hybridization (FISH) in single blastomeres. The proportion of blastomeres expressing SOX2 bi‐allelically increased from 45% at the 4‐cell stage to 60% at the 8‐cell stage. Moreover, in 8‐cell embryos, SOX2 was expressed bi‐allelically in significantly more blastomeres than was the case for OCT4, and this was associated with a tendency for SOX2 alleles to move toward the nuclear interior during 4‐ to 8‐cell transition. However, the radial location of OCT4 alleles did not change significantly during this transition. The locations of active and inactive alleles based on DNA and RNA FISH signals were also calculated. Inactive OCT4 alleles were located in very close proximity to the nuclear membrane, whereas active OCT4 alleles were more centrally disposed in the nucleus. Nevertheless, the nuclear location of active and inactive SOX2 alleles did not change in either 4‐ or 8‐cell blastomeres. Our RNA and DNA FISH data provide novel information on the allelic expression patterns and positioning of pluripotency‐associated genes, OCT4 and SOX2, during embryonic genome activation in pigs.
A canine distemper virus seroprevalence study of dogs on three islands in the Torres Strait region, Australia
Authors: Ruffalo G , Byers M , Ward MP
Published: June 2020

Canine distemper virus (CDV) can cause mortality in domestic dogs, which is easily prevented by the consistent application of vaccination protocols. The aim of this study was to determine if the dog populations of three strategically located islands in the Torres Strait of Australia, adjacent to Papua New Guinea, are infected by CDV. Eighty‐four serum samples were collected from 70 dogs resident on Saibai, Dauan and Boigu Islands during 2017–2018. Sera were tested for CDV antibodies by a virus neutralization test (VNT). Overall, 7 (8.3%) sera from 6 (8.6%) dogs resident on all three islands were test positive. VNT titres ranged from 20 to >1280. Male adult dogs were more commonly seropositive than female and juvenile dogs. Considering the origin and age of test positive dogs, and veterinary visits to these islands, it was concluded that there is evidence of exposure to a field strain of CDV – rather than previous vaccination – in 4 of the 70 dogs (5.7%) tested in this study. Given the strategic location of these islands in a zone of high biosecurity risk, ongoing surveillance of pathogens such as CDV could inform on potential disease spread pathways in this region. In addition, the presence of high serological titres in the apparent absence of clinical disease requires further investigation.
Transurethral en bloc submucosal hydrodissection vs conventional resection for resection of non‐muscle‐invasive bladder cancer (HYBRIDBLUE): a randomised, multicentre trial
Authors: Gakis Georgios , Karl Alexander , Bertz Simone , Burger Maximillian , Fritsche Hans‐Martin , Hartmann Arndt , Jokisch Friedrich , Kempkensteffen Carsten , Miller Kurt , Mundhenk Jens , Schneevoigt Birte‐Swantje , Schubert Tina , Schwentner Christian , Wullich Bernd , Stenzl Arnulf
Published: June 2020

Objective

To determine whether transurethral en bloc submucosal hydrodissection of bladder tumours (TUEB) improves the quality of the resection compared to conventional transurethral resection of bladder tumour (TURBT) in patients with non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

A randomised, multicentre trial (HYBRIDBLUE) was conducted with a superiority design. Six German academic centres participated between September 2012 and August 2015. Based on literature analysis, a sample size for accurate histopathological assessment concerning muscle invasion was assumed to be feasible in 50% (P0 = 0.5) of TURBT and 80% of TUEB cases. After pre‐screening of a total of 305 patients, participants were allocated to two study arms: Group I: hexaminolevulinate (HAL)‐guided TUEB; Group II: conventional HAL‐guided TURBT. The primary endpoint was the proportion of specimens that could be reliably evaluated pathologically concerning muscle invasiveness. Secondary endpoints included rates of histopathological completeness of the resection, muscularis propria content, recurrence, and complication rates.

Results

A total of 115 patients (TUEB 56; TURBT 59) were eligible for final analysis. Adequate histopathological assessment, which included muscularis propria content and tumour margins (R0 vs R1), was present in 48/56 (86%) TUEB patients compared to 37/59 (63%; P = 0.006) in the TURBT group. R0 was confirmed in 30/56 TUEB patients (57%) and five of 59 TURBT patients (9%; P < 0.001). No complications of Grade ≥III were observed in both arms. At 3 and 12 months, three and 19 patients recurred in the TUEB group vs seven and 11 patients in the TURBT group, respectively (P = 0.33 and P = 0.08).

Conclusions

In this randomised study, TUEB was shown to be clinically safe regarding perioperative endpoints. An adequate histopathological assessment concerning muscle invasion was significantly better assessable in the TUEB arm compared to standard TURBT. This finding indicates the clinical potential for reducing the rate of early re‐resections. Yet, a larger study with recurrence‐free survival as the primary endpoint is needed to assess the oncological efficacy between both techniques.
Abnormal scaffold attachment factor 1 expression and localization in spinocerebellar ataxias and Huntington’s chorea
Authors: Buckner Nicola , Kemp Kevin C. , Scott Helen L. , Shi Gongyu , Rivers Caroline , Gialeli Andriana , Wong Liang-Fong , Cordero-LLana Oscar , Allen Nicholas , Wilkins Alastair , Uney James B.
Published: June 2020

SAFB1 is a DNA and RNA binding protein that is highly expressed in the cerebellum and hippocampus and is involved in the processing of coding and non‐coding RNAs, splicing and dendritic function. We analyzed SAFB1 expression in the post‐mortem brain tissue of spinocerebellar ataxia (SCA), Huntington’s disease (HD), Multiple sclerosis (MS), Parkinson’s disease patients and controls. In SCA cases, the expression of SAFB1 in the nucleus was increased and there was abnormal and extensive expression in the cytoplasm where it co‐localized with the markers of Purkinje cell injury. Significantly, no SAFB1 expression was found in the cerebellar neurons of the dentate nucleus in control or MS patients; however, in SCA patients, SAFB1 expression was increased significantly in both the nucleus and cytoplasm of dentate neurons. In HD, we found that SAFB1 expression was increased in the nucleus and cytoplasm of striatal neurons; however, there was no SAFB1 staining in the striatal neurons of controls. In PD substantia nigra, we did not see any changes in neuronal SAFB1 expression. iCLIP analysis found that SAFB1 crosslink sites within ATXN1 RNA were adjacent to the start and within the glutamine repeat sequence. Further investigation found increased binding of SAFB1 to pathogenic ATXN1‐85Q mRNA. These novel data strongly suggest SAFB1 contributes to the etiology of SCA and Huntington’s chorea and that it may be a pathological marker of polyglutamine repeat expansion diseases.
Regulation of smooth muscle contraction by monomeric non‐RhoA GTPases
Authors: Li Bingsheng , Wang Ruixiao , Wang Yiming , Stief Christian G. , Hennenberg Martin
Published: June 2020

Smooth muscle contraction in the cardiovascular system, airways, prostate and lower urinary tract is involved in the pathophysiology of many diseases, including cardiovascular and obstructive lung disease plus lower urinary tract symptoms, which are associated with high prevalence of morbidity and mortality. This prominent clinical role of smooth muscle tone has led to the molecular mechanisms involved being subjected to extensive research. In general smooth muscle contraction is promoted by three major signalling pathways, including the monomeric GTPase RhoA pathway. However, emerging evidence suggests that monomeric GTPases other than RhoA may be involved in signal transduction in smooth muscle contraction, including Rac GTPases, cell division control protein 42 homologue, adenosine ribosylation factor 6, Ras, Rap1b and Rab GTPases. Here, we review these emerging functions of non‐RhoA GTPases in smooth muscle contraction, which has now become increasingly more evident and constitutes an emerging and innovative research area of high clinical relevance.
Sensitization of glutamate receptor‐mediated pain behaviour via nerve growth factor‐dependent phosphorylation of transient receptor potential V1 under inflammatory conditions
Authors: Masuoka Takayoshi , Yamashita Yuka , Yoshida Junko , Nakano Katsuya , Tawa Masashi , Nishio Matomo , Ishibashi Takaharu
Published: June 2020

Background and Purpose

Glutamate and metabotropic glutamate (mGlu) receptors on primary sensory neurons are crucial in modulating pain sensitivity. However, it is unclear how inflammation affects mGlu receptor‐mediated nociceptive responses. We therefore investigated the effects of mGlu1/5 receptor agonists on pain‐related behaviour during persistent inflammation and their underlying mechanisms.

Experimental Approach

Effects of a mGlu1/5 receptor agonist on pain‐related behaviour during inflammation was assessed in mice. Intracellular calcium responses, membrane current responses, and protein expression in primary sensory neurons were examined using cultured dorsal root ganglion (DRG) neurons, dissociated from wild‐type and gene knockout mice.

Key Results

Persistent inflammation induced by complete Freund's adjuvant increased the duration of mGlu1/5 receptor‐mediated pain behaviour, which was antagonized by inhibition of nerve growth factor (NGF)–tropomyosin receptor kinase A (TrkA) signalling. Calcium imaging revealed that NGF treatment increased the number of cultured DRG neurons responding to mGlu1/5 receptor activation. Stimulation of mGlu1/5 receptors in NGF‐treated DRG neurons induced inward currents through TRPV1 channels in association with PLC but not with IP3 receptors. NGF treatment also increased the number of neurons responding to a DAG analogue via TRPV1 channel activation. Furthermore, NGF up‐regulated expression of TRPV1 and A‐kinase anchoring protein 5 (AKAP5), resulting in increased AKAP5‐dependent TRPV1 phosphorylation. AKAP5 knockout mice did not exhibit mGlu1/5 receptor‐mediated excitation in NGF‐treated DRG neurons or pain response facilitation under inflammatory conditions.

Conclusions and Implications

NGF augments glutamate‐ and mGlu1/5 receptor‐mediated excitation of nociceptive neurons by AKAP5‐dependent phosphorylation of TRPV1 channels, potentiating hypersensitivity to glutamate in inflamed tissues.
Dental implant‐based oral rehabilitation in patients reconstructed with free fibula flaps: Clinical study with a follow‐up 3 to 6 years
Authors: Goker Funda , Baj Alessandro , Bolzoni Alessandro Remigio , Maiorana Carlo , Giannì Aldo Bruno , Del Fabbro Massimo
Published: June 2020

Background

Oral rehabilitation of patients after maxillofacial reconstructive surgery represents a challenge and stable prosthetic retention can be achieved with the use of dental implants.

Purpose

This retrospective report aimed to evaluate implant‐based oral rehabilitation following maxillofacial reconstruction with free fibula flaps.

Materials and Methods

A total of 14 patients who had reconstruction with fibula flaps either by CAD/CAM or conventional surgery were included in this study. A total of 56 implants (40 in flaps, 16 in native bone) were evaluated. Follow‐up after reconstructive surgery ranged between 3.25 and 6.3 years. Follow‐up after implant surgery ranged between 1.5 and 3.8 years.

Results

Overall survival rate was 85.7% in free fibula flaps and 85.6% in dental implants. Eight implants were lost in three patients and all of these failures were in dental implants inserted in free flaps. According to the results on patient basis, the implant survival was not influenced by any variable.

Conclusions

The maxillofacial reconstruction with free fibula flap and oral rehabilitation with implant‐supported prostheses after ablative surgery can be considered as an effective and safe procedure with successful aesthetic and functional outcomes.
Histopathological evaluation of nail lichen planus: A cross‐sectional study
Authors: Kharghoria Geetali , Grover Chander , Bhattacharya Sambit Nath , Sharma Sonal
Published: June 2020

Introduction

Up to 10% of patients with lichen planus (LP) have nail involvement; still there is a paucity of studies on histopathological features. Nevertheless, nail biopsy is the diagnostic standard, especially for isolated nail LP.

Methodology

Nails of 45 patients with nail LP were evaluated clinically and biopsies taken from most involved nail (25 nail bed and 20 matrix biopsies). Correlation of clinical and histopathological features was also done.

Results

The mean age of the study group participants was 36.91 ± 18.27 years with a M:F ratio of 1.81:1. The most common clinical variant of LP seen was oral LP (51%), with isolated nail involvement in 29%. Clinically, major features were onychorrhexis (92.3%), longitudinal melanonychia (74.3%), and nail bed erythema (54%). Histopathologically, hypergranulosis of nail matrix and bed epithelium (51.1%), followed by sawtooth acanthosis (44.4%) and lichenoid band (24.4%) were most common. A diagnosis using prevalent diagnostic criteria was confirmed in 51.1% biopsies. Distinctive “fraying of nail plate,” a change not previously described, was noted in 33.3% cases.

Conclusion

Histopathology of nail LP has been attributed a diagnostic role; however, existing diagnostic criteria are not sensitive enough and need refinement. Not hitherto described features like fraying of nail plate are seen in a significant number of cases.
Human impact overrides bioclimatic drivers of red fox home range size globally
Authors: Main Michael T. , Davis Robert A. , Blake David , Mills Harriet , Doherty Tim S.
Published: June 2020

Aim

Identifying the variables that influence animal home range size is important for understanding the biological requirements of individuals and their social interactions. Given their often broad distributions, carnivores are model organisms for studying range‐wide determinants of home range size. Here, we test predictions about environmental determinants of home range size for one of the world's most widely distributed carnivores, the red fox (Vulpes vulpes).

Location

Global.

Methods

We compiled a database of 70 mean home range estimates from 62 studies and four continents, which we analysed according to site‐based temperature, precipitation, environmental productivity and human influence variables.

Results

We found a very strong negative effect of the Human Footprint Index (HFI), with fox home range size decreasing as the level of human impact increased. When analysing the constituent components of the HFI separately, we found that human population density was the only well‐supported variable (cf. built environments, croplands, pasture lands, nightlights, railways, roads and navigable waterways). Predicted home range size at the highest human population densities (0.75 km2) was 93% lower than at the lowest population densities (10.83 km2). We also found that home range size increased as mean annual temperature and temperature seasonality increased. The analyses did not support our prediction that home ranges would be smaller in areas of higher environmental productivity or precipitation.

Main conclusions

Smaller home range sizes observed in highly disturbed areas can be attributed to increased food availability from anthropogenic sources. The lack of an effect of environmental productivity contrasts with previous studies that have shown a negative relationship with carnivore home range size. It may be that anthropogenic food sources have negated the impacts that low‐productivity environments have on fox home ranges. Our results emphasize the strong potential for human activities to transform animal space use across the globe.
Is endoscopic resection appropriate for type 3 gastric neuroendocrine tumors? Retrospective multicenter study
Authors: Hirasawa Toshiaki , Yamamoto Noriko , Sano Takeshi
Published: June 2020

Background

Gastrectomy with lymphadenectomy is recommended for type 3 gastric neuroendocrine tumors (G‐NETs). This study aimed to identify the risk factors for lymph node metastasis (LNM) arising from G‐NETs to assess the suitability of endoscopic resection (ER).

Methods

Nationwide clinicopathological data of patients with type 3 G‐NETs who underwent surgery or ER were collected. A single pathologist graded the histological tumor specimens.

Results

Among 176 cases from 53 institutions, 144 were eligible for analysis (90 NET‐G1 and 54 NET‐G2 grade, 8‐mm median‐size tumors). Of these, 63 patients had undergone ER (15 with additional surgeries). Histological data regarding LNM were available for 93 surgical patients. LNM was confirmed in 15 (16%) tumors and was correlated with tumor diameter, invasion depth, and tumor grade. LNM was negative in six tumors ≤5 mm, confined to the mucosa or submucosa, with a grade of G1, and without lymphovascular invasion, but the number of cases was too small to propose ER indications. Among 48 patients treated with ER alone, only one developed recurrence; no mortality was observed at follow‐up, although many patients were classified with SM2/NET‐G2/tumors >5 mm. This suggests that not all LNMs arising from small G‐NETs are fatal.

Conclusion

Gastrectomy with lymphadenectomy for type 3 G‐NETs is recommended on the basis of LNM. However, ER for type 3 G‐NETs ≤10 mm, confined to the mucosa or submucosa, with a grade of G1 has shown excellent survival outcomes despite the risk of LNM, and therefore, could be an alternative treatment option.
Biopsychosocial factors associated with a current depressive episode in diabetes: the ELSA‐Brasil study
Authors: van Duinkerken E. , Moreno A. B. , Eto F. N. , Lotufo P. , Barreto S. M. , Giatti L. , Viana M. C. , Nunes M. A. , Chor D. , Griep R. H.
Published: June 2020

Aims

Depression is more prevalent in people with diabetes, and is associated with worse diabetes outcomes. Depression in diabetes is more treatment resistant, and as underlying mechanisms are unknown, development of more effective treatment strategies is complicated. A biopsychosocial model may improve our understanding of the pathophysiology, and therewith help improving treatment options.

Methods

Diabetes was diagnosed according to American Diabetes Association (ADA) criteria and a current depressive episode according to the International Classification of Diseases (ICD‐10), based on the Clinical Interview Schedule Revised (CIS‐R). From the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil), we included 455 participants without diabetes with a current depressive episode and 10 900 without either diabetes or a current depressive episode. Furthermore, 2183 participants had diabetes alone and 106 had both diabetes and a current depressive episode. Variable selection was based on their relationship with depression and/or diabetes. Multinomial multivariate logistic regression was used to determine how the models differed between participants with and without diabetes.

Results

A current depressive episode in diabetes was related to being older and female, having poorer education, financial problems, experiencing discrimination at work, home and school, higher waist circumference, albumin to creatinine ratio and insulin resistance, and the presence of hypertension and cardiovascular disease. In non‐diabetes, a current depressive disorder was related to being female, not being black, low income, psychological and social factors, non‐current alcohol use, lower HDL cholesterol, higher insulin resistance and the presence of cardiovascular disease.

Conclusions

A current depressive episode in the presence compared with the absence of diabetes was related more to biological than to psychosocial factors.
Increased sugar concentration in response to a wide range of pollinator sounds can be adaptive for the plant: answer to Raguso et al
Authors: Veits Marine , Khait Itzhak , Boonman Arjan , Sharabi Gayl , Sapir Yuval , Yovel Yossi , Hadany Lilach
Published: June 2020

In Veits et al., we showed that flowers respond to a range of pollinator sounds by increased nectar sugar concentration. Here we clarify that (1) our argument is relevant to most pollinators, and not limited to bees (2) specifically, bees do access Oenothera Drumondii nectar in this area.
Targeting Wnt/β‐catenin by anthelmintic drug niclosamide overcomes paclitaxel resistance in esophageal cancer
Authors: Wei Wei , Liu Hongfang , Yuan Jia , Yao Yang
Published: June 2020

Esophageal cancer is an aggressive malignancy, and its current treatment strategies are plagued with high rates of recurrence. In this work, we demonstrate that niclosamide, an anthelmintic drug, is a potential sensitizing candidate for overcoming chemoresistance in esophageal cancer. Using a panel of esophageal cancer cell lines and normal cells, we show that niclosamide has anti‐esophageal cancer activity and is likely to be less effective against normal esophageal epithelial and fibroblast cells. The combination of niclosamide with paclitaxel results in much greater efficacy than paclitaxel alone, suggesting that niclosamide is active against esophageal cancer cells that are resistant to paclitaxel. This is further confirmed by our results that niclosamide is effective in inhibiting proliferation and inducing apoptosis in paclitaxel‐resistant esophageal cancer cells. In line with the findings obtained from in vitro cell culture system, niclosamide augments the in vivo efficacy of paclitaxel and significantly arrests paclitaxel‐resistant esophageal cancer growth without causing toxicity in mice. Mechanistically, we show that niclosamide decreases β‐catenin level and activity, and inhibits phosphorylation of STAT3 and mTORC1 substrate 70S6K. Stabilization of β‐catenin level by Wnt activator lithium chloride (LiCl) significantly abolishes the inhibitory effects of niclosamide in inhibiting proliferation and survival but not suppressing phosphorylation of STAT3 and 70S6K in paclitaxel‐resistant esophageal cancer cells, suggesting that niclosamide sensitizes esophageal cancer cell to paclitaxel mainly through inhibiting Wnt/β‐catenin. Our work demonstrates the efficacy of niclosamide and its underlying mechanism in paclitaxel‐resistant esophageal cancer. Our work emphasizes that Wnt/β‐catenin inhibition is a sensitizing strategy in esophageal cancer.
Fatty acid‐binding protein 3 regulates differentiation of IgM‐producing plasma cells
Authors: Kobayashi Shuhei , Phung Hai The , Tayama Shunichi , Kagawa Yoshiteru , Miyazaki Hirofumi , Yamamoto Yui , Maruyama Takashi , Ishii Naoto , Owada Yuji
Published: June 2020

Plasma cells (PCs), which aim to protect host health, produce various subsets of immunoglobulin (Ig) in response to extracellular pathogens. Blimp‐1 (encoded by Prdm1)—a protein that is highly expressed by PCs—is important for PC functions, including the generation of Igs. Fatty acid‐binding protein 3 (FABP3) is a carrier protein of polyunsaturated fatty acids (PUFAs) and participates in multiple cellular functions. Although the functions of FABP3 in neurons and cardiac myocytes are well‐noted, their roles in immune cells remain to be fully elucidated. In this study, we demonstrate that FABP3 is expressed in activated B cells and that FABP3 promotes PC development and IgM secretion. Moreover, we provide the first evidence that FABP3 is necessary for Blimp‐1 expression, by regulating the histone modification of its promoter region. Taken together, our findings reveal that FABP3 acts as a positive regulator of B‐cell activation by controlling histone acetylation of the Blimp‐1 gene, thereby playing a role in host defense against pathogens.
Location dependence of breathing mechanism for a slant crack in a shaft
Authors: Mobarak Hossain Mohammad , Wu Helen , Yang Chunhui
Published: June 2020

Periodic stresses are always imposed on a rotor, and thus, a crack due to fatigue is unavoidable. Machinery must be properly diagnosed to avoid tragic accidents. Vibration detection is the most important tool for such a diagnosis system. It is important to know the vibration characteristics of a cracked rotor in order to develop a monitoring system which can detect a crack in an early stage of propagation. In this study, to explore the crack breathing mechanism, a three‐dimensional finite element model is simulated by using a commercial analysis solver—Abaqus/Standard. A two‐disc rotor system with a slant crack is used under the coupling effect of rotor weight and unbalance force. Unlike crack breathing under rotor weight‐only, a crack opens and closes differently under the effects of unbalance forces. Crack breathing depends on its location along the length of the shaft and individual parameters of the rotor system. A few crack locations are recognised along shaft length where the crack may stay fully closed or open during shaft rotation under certain loading circumstances. These locations also split the shaft into different areas based on the orientation of the unbalance force, crack size and location, where shaft stiffness may be higher or lower. Presented findings indicate that predicting the dynamic response of cracked rotors can be anticipated much accurately. Therefore, the impacts of unbalance forces and individual rotor physical characteristics on crack breathing must be taking into consideration.
Minimum wage, trade and unemployment in general equilibrium
Authors: Marjit Sugata , Ganguly Shrimoyee , Acharyya Rajat
Published: June 2020

The path‐breaking work of Card and Krueger, showing that a higher minimum wage can increase employment, turned the age‐old conventional wisdom on its head. This paper demonstrates that this apparently paradoxical result is perfectly plausible in a competitive general equilibrium production structure of a small open economy with a non‐traded good, without recourse to monopsony, spatial heterogeneity, heterogeneity of consumers and so on, the usual theoretical drivers behind the result. Following Jones and Marjit, we build a simple general equilibrium model with production complementarity and we show that a higher minimum wage can raise aggregate employment. Expansion in the non‐traded sector following a wage hike may be consistent with the overall expansion of the export sector in a multi‐good framework, an unlikely outcome in a conventional two‐good model which cannot accommodate with production complementarity.
Challenging times: ethics, nursing and the COVID‐19 pandemic
Authors: Turale Sue , Meechamnan Chutima , Kunaviktikul Wipada
Published: June 2020

Globally nurses and midwives are working hard to detect cases of COVID‐19, to save lives or give comfort in the face of death, to educate themselves and the public about protective measures to stop the viral spread, while still caring for those not infected with the virus. In many countries nurses are working under virtual siege from this pandemic, with not enough resources or personal protective equipment, overwhelming numbers of patients, staff shortages, underprepared health systems and supply chain failures. Nurses and other health and emergency workers are suffering physical and emotional stress, and moral distress from conflicting professional values. They are faced with unpalatable and complex ethical issues in practice, with moral conflicts, high levels of acuity and patient deaths, and long working hours. A rising number of nurses are infected with SARS‐CoV‐2 or dying in the line of duty. Nurses need strong moral courage, stamina and resilience to work on the front lines of the pandemic, often while separated from their loved ones.