bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of intestinal microbiota and fecal cortisol, T3, and IgA in forest musk deer (Moschus berezovskii) from birth to weaning
Authors: LI Yimeng , ZHANG Tianxiang , SHI Minghui , ZHANG Baofeng , HU Xin , XU Shanghua , DING Jianhong , LIU Shuqiang , HU Defu , RUBENSTEIN Daniel
Published: January 2021

Analysis of the intestinal microbiota and physiological parameters in mammalian infancy can reveal health status. In this study, we used a combination of molecular and immunochemical approaches to assess fecal microbiota as well as Cortisol (Cor), Triiodothyronine (T3), and immunoglobulin A (IgA) levels of young forest musk deer (FMD), from birth to one month after weaning (7 days of age–110 days of age). During development as the diet of FMD changes from consuming milk to eating plants, the richness and diversity of intestinal microbiota of young FMD increased significantly. Cor levels remained unchanged throughout early development while significantly increased after weaning, T3 and IgA initially were derived from milk during lactation, significantly decreased after weaning. Correlation network analysis showed that the community of food‐oriented microbes were highly structured and that many genera were correlated. Overall, this study provides scientific insights into effective management strategies for the protection of FMD population.
Octopus vulgaris ink extracts exhibit antioxidant, antimutagenic, cytoprotective, antiproliferative, and proapoptotic effects in selected human cancer cell lines
Authors: Hernández‐Zazueta Martin Samuel , García‐Romo Joel Said , Noguera‐Artiaga Luis , Luzardo‐Ocampo Iván , Carbonell‐Barrachina Ángel Antonio , Taboada‐Antelo Pablo , Campos‐Vega Rocio , Rosas‐Burgos Ema Carina , Burboa‐Zazueta María Guadalupe , Ezquerra‐Brauer Josafat Marina , Martínez‐Soto Juan Manuel , Santacruz‐Ortega Hisila del Carmen , Burgos‐Hernández Armando
Published: January 2021

Cancer is a noncommunicable disease of rising worldwide concern. Marine food products such as Octopus vulgaris ink (OI) could be sources of compounds addressing these concerns. This study aimed to evaluate the antimutagenic, cytoprotective, antiproliferative, proapoptotic, and antioxidant capacity of OI extracts on human cancer cell lines (22Rv1, HeLa, A549). The ARPE‐19 cell line was used as a reference human cell line to evaluate the ink's cytotoxicity. The water extract exhibited the highest antimutagenic and cytoprotective effect, but the dichloromethane extract (DM) showed the lowest half lethal concentration against 22Rv1 cells. Structural elucidation of purified DM fractions (F1, F2, F3) identified an unreported compound, N‐(2‐ozoazepan‐3‐yl)‐pyrrolidine‐2‐carboxamide (OPC). DM‐F2 showed high antiproliferative effect (LC50 = 27.6 µg/mL), reactive species modulation, early‐apoptosis induction (42.9%), and nuclei disruption in 22Rv1 cells. In silico analysis predicted high OPC affinity with Cyclin D1 (−6.70 kcal/mol), suggesting its potential impact on cell cycle arrest. These results highlight the antimutagenic, cytoprotective, and antiproliferative potential health benefits derived from underutilized marine food products such as OI. Further investigations at in vitro or in vivo levels are required to elucidate mechanisms and health benefits from OI.

Practical Application

O. vulgaris ink is an underutilized marine natural product that could be a source of biological compounds with potential health benefits such as antioxidant activity and cancer prevention.
Predicting sample success for large‐scale ancient DNA studies on marine mammals
Authors: Keighley Xénia , Bro‐Jørgensen Maiken Hemme , Ahlgren Hans , Szpak Paul , Ciucani Marta Maria , Sánchez Barreiro Fátima , Howse Lesley , Gotfredsen Anne Birgitte , Glykou Aikaterini , Jordan Peter , Lidén Kerstin , Olsen Morten Tange
Published: January 2021

In recent years, nonhuman ancient DNA studies have begun to focus on larger sample sizes and whole genomes, offering the potential to reveal exciting and hitherto unknown answers to ongoing biological and archaeological questions. However, one major limitation to such studies is the substantial financial and time investments still required during sample screening, due to uncertainty regarding successful sample selection. This study investigates the effect of a wide range of sample properties including latitude, sample age, skeletal element, collagen preservation, and context on endogenous content and DNA damage profiles for 317 ancient and historic pinniped samples collected from across the North Atlantic and surrounding regions. Using generalised linear and mixed‐effect models, we found that a range of factors affected DNA preservation within each of the species under consideration. The most important findings were that endogenous content varied significantly within species according to context, the type of skeletal element, the collagen content and collection year. There also appears to be an effect of the sample's geographic origin, with samples from the Arctic generally showing higher endogenous content and lower damage rates. Both latitude and sample age were found to have significant relationships with damage levels, but only for walrus samples. Sex, ontogenetic age and extraction material preparation were not found to have any significant relationship with DNA preservation. Overall, skeletal element and sample context were found to be the most influential factors and should therefore be considered when selecting samples for large‐scale ancient genome studies.
Non‐GAAP Earnings: A Consistency and Comparability Crisis?*
Authors: Black Dirk E. , Christensen Theodore E. , Ciesielski Jack T. , Whipple Benjamin C.
Published: January 2021

We use a novel data set to examine the across‐time consistency and across‐firm comparability of firms' non‐GAAP earnings disclosures. Given widespread concern about non‐GAAP reporting among regulators, standard setters, the investor community, and academics, our investigation provides timely evidence on how managers' deviations from their own non‐GAAP disclosure history, or the reporting of industry peers, affects how well earnings inform on firm performance. We begin by identifying firms that change their non‐GAAP earnings definition from one year to the next. These deviations are uncommon, but when managers change the items they exclude in calculating non‐GAAP earnings, the changes generally enhance the information in earnings about firms' core performance. We also examine whether non‐GAAP earnings are more comparable than GAAP earnings and find that firms' non‐GAAP adjustments result in greater earnings comparability. Finally, we examine instances in which firms deviate from common sector‐wide definitions of non‐GAAP earnings. We find that these deviations also result in earnings metrics that better represent firms' core operations. Overall, our results suggest that when managers vary their non‐GAAP calculations, either across time or across firms, the resulting non‐GAAP metrics generally enhance the information in earnings about firms' ongoing performance. Thus, our analysis helps mitigate concerns about why managers might vary their non‐GAAP reporting calculations.
Knowledge, experiences and attitudes of dental health professionals towards reporting child abuse in Western Australia
Authors: Kugananthan S , Nguyen T , Patel J , Anthonappa R
Published: January 2021

Background

Up to 50% of child abuse (CA) victims exhibit evidence of traumatic facial or intraoral injuries. Dental health professionals (DHPs) are therefore well‐positioned to detect and report incidences of CA. This study aimed to assess the knowledge and attitudes of Western Australian DHPs towards identifying and reporting CA.

Methods

General dentists, specialists, hygienists and oral health therapists completed an online questionnaire which assessed their knowledge and experience in identifying and reporting CA.

Results

A total of 228 participants completed the questionnaire (representing 7% of DHPs, 60% of paediatric dentists and 11% of all dental hygienists and therapists in Western Australia). The majority of participants (66.2%, P < 0.05) felt that they were unlikely to recognize a patient with physical abuse, or detect signs of sexual abuse (90.8%, P < 0.001). Uncertainty around diagnosing abuse was a barrier towards reporting cases (86.4%, P < 0.05) and most participants (78.0%, P < 0.05) felt that they did not have adequate safeguarding training to report CA.

Conclusions

Self‐reported confidence in identifying and reporting CA cases was low; with the majority of the dental professionals participating in this study unlikely to recognize signs of CA. Inadequate training and knowledge around correct reporting protocols were identified as barriers, which warrants an appropriate change to improve child safeguarding.
Validity evidence and measurement equivalence for the Dutch translation of the conditional reasoning test for aggression
Authors: LeBreton James M. , Reichin Sydney L. , te Nijenhuis Jan , Cremers Myckel , van der Heijden‐Lek Kitty
Published: January 2021

The Conditional Reasoning Test for Aggression (CRT‐A) indirectly measures the implicit motive to aggress by engaging respondents in inductive reasoning tasks. Most research involving the CRT‐A has been based on the original English version of the test with most data being collected in the United States. The purpose of the current paper is to evaluate the psychometric properties of a Dutch translation of this test and to examine if it could be used to predict measures of integrity. In the first of two studies, we evaluated the psychometric properties and measurement equivalence of the CRT‐A across US and Dutch samples. In the second study, we examined validity evidence for the Dutch version of the CRT‐A. Results from Study 1 indicated that the test was mostly equivalent across cultures (i.e. limited differential item functioning was detected). Results from Study 2 demonstrated that the Dutch version of the CRT‐A was correlated with measures of behavioral integrity and provided incremental prediction of integrity over and above traditional self‐report measures of explicit personality traits. We discuss the implications for using CRTs across different cultures and languages.
Randomised clinical trial: exclusive enteral nutrition versus standard of care for acute severe ulcerative colitis
Authors: Sahu Pabitra , Kedia Saurabh , Vuyyuru Sudheer K. , Bajaj Aditya , Markandey Manasvini , Singh Namrata , Singh Mukesh , Kante Bhaskar , Kumar Peeyush , Ranjan Mukesh , Sahni Peush , Panwar Rajesh , Sharma Raju , Das Prasenjit , Makharia Govind , Travis Simon P. L. , Ahuja Vineet
Published: January 2021

Background

Intravenous corticosteroids are the mainstay of therapy for acute severe ulcerative colitis (ASUC), but 30%‐40% of patients fail to respond.

Aim

To investigate the effectiveness of exclusive enteral nutrition (EEN) as adjunctive therapy to intravenous corticosteroids in patients with ASUC.

Methods

This was an open‐label randomised controlled trial, in which patients who were admitted with ASUC between August 2018 and May 2020 were randomised 1:1 to EEN or standard of care (SOC). Patients on EEN received a semi‐elemental formula for 7 days along with SOC. The primary outcome was corticosteroid failure, defined by the need for salvage medical therapy or colectomy. Faecal microbial analysis was performed on day 1 and day 7 by 16s ribosomal RNA sequencing in some patients.

Results

Of 62 patients (mean age 35.3 ± 12.1 years, 40% male), 32 were randomised to EEN and 30 to SOC. Corticosteroid failure was lower on EEN compared to SOC (intention‐to‐treat analysis 25% vs 43%, P = 0.051; per protocol analysis 19% vs 43%, P = 0.04), without any difference in colectomy rate (9% vs 13%; P = 0.41). Patients on EEN had a shorter hospital stay [median (range) 10 (8‐17) vs 13 (8‐24) days; P = 0.04], higher day 7 albumin level (34 ± 4 vs 29 ± 3 g/L, P < 0.01), greater reduction in serum C‐reactive protein and faecal calprotectin levels (both P = 0.04) and a lower composite outcome of colectomy/hospitalisation at 6 months (16% vs 39%; P = 0.045) compared to SOC. Patients on EEN showed increased abundance of Erysipelotrichaceae on day 7, with reduced Bifidobacterium and Veillonellaceae compared to SOC.

Conclusions

EEN for 7 days may augment corticosteroid responsiveness in patients with ASUC. (REF/2018/05/019844; CTRI/2020/06/025989).
ONO‐7684 a novel oral FXIa inhibitor: Safety, tolerability, pharmacokinetics and pharmacodynamics in a first‐in‐human study
Authors: Beale Dominic , Dennison Jeremy , Boyce Malcolm , Mazzo Francesca , Honda Naoki , Smith Paul , Bruce Mark
Published: January 2021

Aims

The objectives of this study were to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of ONO‐7684, a novel activated factor XI (FXIa) inhibitor, in healthy subjects.

Methods

This was a first‐in‐human (FIH), randomised, placebo‐controlled, double‐blind, single and multiple dose study in healthy subjects under fed and fasted conditions. This study consisted of two parts: single ascending dose (Part A; 1, 5, 20, 80, 150 or 300 mg ONO‐7684 or placebo) and multiple ascending doses (Part B; 80, 150 or 250 mg ONO‐7684 or placebo daily for 14 days). In both parts, subjects were randomised in a 3:1 ratio to receive ONO‐7684 or placebo.

Results

ONO‐7684 was well tolerated at all dose levels tested following both single and repeated doses, with a low overall incidence of treatment‐emergent adverse events. There was no evidence to suggest a bleeding risk. Dose proportionality in exposure was observed for the range of 1–300 mg ONO‐7684 in Part A. In Part A, the half‐life of ONO‐7684 administered in the fasted state ranged from 16.0 to 19.8 hours. In Part B, the half‐life of ONO‐7684 administered in the fed state ranged from 22.1 to 27.9 hours, supporting once daily oral dosing. ONO‐7684 strongly inhibited factor XI coagulation activity (FXI:C) and increased activated partial thromboplastin time (aPTT), with a mean maximum on treatment percentage inhibition versus baseline of 92% and a mean maximum on treatment ratio‐to‐baseline of 2.78, respectively, at 250 mg ONO‐7684 daily.

Conclusions

The data generated in this FIH study demonstrate the promising potential of oral FXIa inhibition and ONO‐7684 for indications requiring anticoagulation.
Vascular hitch for paediatric pelvi‐ureteric junction obstruction with crossing vessels: institutional analysis and systematic review with meta‐analysis
Authors: Kim Jin K. , Keefe Daniel T. , Rickard Mandy , Milford Karen , Lorenzo Armando J. , Chua Michael E.
Published: January 2021

Objective

To compare the outcomes for laparoscopic vascular hitch (VH) and dismembered pyeloplasty in patients with pelvi‐ureteric junction obstruction (PUJO) secondary to crossing vessels (CV).

Patients and Methods

Patients who underwent laparoscopic management of CV at our institution were identified between 2008 and 2020. Baseline characteristics and outcome measures were compared between those who underwent VH and those who underwent dismembered pyeloplasty. Those who underwent VH were selected intraoperatively by identifying CV in the absence of intrinsic obstruction by assessing resolution of hydronephrosis after cranially displacing the CV away from the PUJ, followed by intraoperative fluid bolus and diuretic test. In addition, a systematic search and meta‐analysis were performed in June 2020 (International Prospective Register of Systematic Reviews [PROSPERO] ID CRD42020195833).

Results

A total of 20 patients underwent VH and 74 dismembered pyeloplasty. On multivariate analysis, VH was associated with: shorter operative time (P = 0.001; odds ratio [OR] 0.455, 95% confidence interval [CI] 0.294–0.705) and length of stay (P = 0.012; OR 0.383, 95% CI 0.183–0.803), lower use of stents (P < 0.001; OR 0.024, 95% CI 0.004–0.141) and opioid administration (P = 0.005; OR 0.157, 95% CI 0.044–0.567). From our literature search, 194 records were identified and 18 records were included (three comparative and 16 non‐comparative). Meta‐analysis of the comparative studies and our institutional data showed similar success rates (relative risk [RR] 1.77, 95% CI 0.33–9.52) and complication rates (RR 0.75, 95% CI 0.20–2.82). VH was associated with shorter operative time (standardised mean difference [SMD] −1.65, 95% CI −2.58 to −0.72 h) and hospital stay (SMD −1.41, 95% CI −2.36 to –0.47 days). The VH success rates ranged from 87.5% to 100% in the identified studies. Failure of VH was associated with unrecognised concomitant intrinsic obstruction in addition to CV.

Conclusions

A VH, for well‐selected patients with CV without concomitant intrinsic obstruction, offers a high success rate with shorter operative times.
Emerging benefits and drawbacks of α2‐adrenoceptor agonists in the management of sepsis and critical illness
Authors: Lankadeva Yugeesh R. , Shehabi Yahya , Deane Adam M. , Plummer Mark P. , Bellomo Rinaldo , May Clive N.
Published: January 2021

Agonists of α2‐adrenoceptors are increasingly being used for the provision of comfort, sedation and the management of delirium in critically ill patients, with and without sepsis. In this context, increased sympathetic and inflammatory activity are common pathophysiological features linked to multi‐organ dysfunction, particularly in patients with sepsis or those undergoing cardiac surgery requiring cardiopulmonary bypass. Experimental and clinical studies support the notion that the α2‐adrenoceptor agonists, dexmedetomidine and clonidine, mitigate sympathetic and inflammatory overactivity in sepsis and cardiac surgery requiring cardiopulmonary bypass. These effects can protect vital organs, including the cardiovascular system, kidneys, heart and brain. We review the pharmacodynamic mechanisms by which α2‐adrenoceptor agonists might mitigate multi‐organ dysfunction arising from pathophysiological conditions associated with excessive inflammatory and adrenergic stress in experimental studies. We also outline recent clinical trials that have examined the use of dexmedetomidine in critically ill patients with and without sepsis and in patients undergoing cardiac surgery.
From widespread faulting to localised rifting: Evidence from K‐Ar fault gouge dates from the Norwegian North Sea rift shoulder
Authors: Fossen Haakon , Ksienzyk Anna K. , Rotevatn Atle , Bauck Marit S. , Wemmer Klaus
Published: January 2021

Although seismic and stratigraphic well information put tight constraints on rift basin evolution, eroded rift shoulders commonly expose polydeformed prerift basement whose deformation history may be difficult to constrain. In this work, we apply K‐Ar dating of fault gouge samples from 18 faults to explore the brittle deformation of the well‐exposed eastern rift margin to the northern North Sea rift. We find evidence of clay gouge formation since the Late Devonian, with distinct Permian and Jurassic fault activity peaks that closely match early stages of the two well‐established North Sea rift phases. A marked decay in fault density away from the rift margin confirms a close relationship between rifting and onshore faulting. The results show that initial rift‐related extension affected a much wider area than the resulting offshore rift. Hence our data support a rift model where strain is initially distributed over a several 100 km wide region, as a prelude to the development of the ~150–200 km wide Permo‐Triassic northern North Sea rift as defined by large marginal faults. Towards the end of the second rift phase, strain localises even more strongly to the 25–50 km wide Viking Graben. Interestingly, a period of early widespread extension is seen for both phases of North Sea rifting and may be a general characteristic of continental rifting. The documented prerift faulting and fracturing of the basement since the Devonian weakened the basement and probably facilitated the widespread initial extension that subsequently localised to form the northern North Sea rift, with further localisation to its relatively narrow central part (Viking Graben).
Non‐governmental organisations and universities as transition intermediaries in sustainability transformations building on grassroots initiatives
Authors: Wolf Patricia , Harboe Julie , Sudbrack Rothbarth Catherine , Gaudenz Urs , Arsan Leyla , Obrist Chris , van Leeuwen Manon
Published: January 2021

Although niche grassroots initiatives can push bottom‐up sustainability transitions, they can face problems in forming a more global niche and in scaling their innovative solutions to a regime level. A thorough literature review shows scholarly agreement on the assumption that universities and non‐governmental organisations (NGOs) can support sustainability transition in the acceleration phase by intermediating within niches and between niches and regimes. As in‐depth research and a reality check on successful intermediary strategies in this context are still lacking, this paper aims to contribute to a conceptual framework that integrates the NGOs and universities expected activities in existing literature and relates them to one another. We develop such a framework and test it in three case studies from the plastic revaluation field, comparing and drawing on the perspectives of niche, intermediary and regime actors. Findings confirm the conceptual framework and suggest changes and extensions. We enhance existing knowledge by providing detailed insights into successful intermediary activities in these innovation systems and draw conclusions for policymakers.
Thin Cloud Removal for Single RGB Aerial Image
Authors: Song Chengfang , Xiao Chunxia , Zhang Yeting , Sui Haigang
Published: January 2021

Acquired above variable clouds, aerial images contain the components of ground reflection and cloud effect. Due to the non‐uniformity, clouds in aerial images are even harder to remove than haze in terrestrial images. This paper proposes a divide‐and‐conquer scheme to remove the thin translucent clouds in a single RGB aerial image. Based on colour attenuation prior, we design a kind of veiling metric that indicates the local concentration of clouds effectively. By this metric, an aerial image containing thickness‐varied clouds is segmented into multiple regions. Each region is veiled by clouds of nearly‐equal concentration, and hence subject to common assumptions, such as boundary constraint on transmission. The atmospheric light in each region is estimated by the modified local colour‐line model and composed into a spatially‐varying airlight map for the entire image. Then scene transmission is estimated and further refined by a weighted ‐norm based contextual regularization. Finally, we recover ground reflection via the atmospheric scattering model. We verify our cloud removal method on a number of aerial images containing thin clouds and compare our results with classical single‐image dehazing methods and the state‐of‐the‐art learning‐based declouding method, respectively.
Outcome of peri‐implant maintenance care in patients with an implant‐supported lower denture—A 3.5‐year retrospective analysis
Authors: van der Moolen Pieter Leo , Post Ben Jeroen , Slot Dagmar Else , van der Weijden Fridus August
Published: January 2021

Background

Implant‐supported overdentures represent a successful treatment for edentulous patients. As early diagnosis, detection and supportive care are considered key factors for the prevention of peri‐implant diseases, consistent maintenance of these implants is becoming increasingly relevant.

Purpose

This retrospective analysis evaluated a cohort of edentulous patients with a mandibular implant‐supported overdenture over a period of 3.5 years during which the peri‐implant tissues were assessed.

Materials and Methods

A total of 108 patients that had consistently adhered to the annual maintenance appointments was selected. The clinical peri‐implant pocket probing depth (PiPPD) and peri‐implant bleeding on probing score (PiBOP) were investigated. Data from the 3.5‐year follow‐up were compared to data from the baseline assessment.

Results

A 100% implant survival was reported after 3.5 years. The mean PiBOP showed a significant decrease over time (P = .028). The mean PiPPD was found significantly deeper for male patients both at baseline (P = .004) and 3.5‐year follow‐up (P < .001). Besides, the PiPPD for locator anchorages was found significantly deeper compared to ball anchorages at the 3.5‐year follow‐up (P = .026).

Conclusion

In those patients that adhered to the annual maintenance visits during the 3.5 years after implant surgery a stable peri‐implant condition was observed. As future consideration, the comparison of the clinical outcomes of patients participating in the maintenance program with those that did not would make this observation even more meaningful.
On marginal bone level changes around dental implants
Authors: Coli Pierluigi , Jemt Torsten
Published: January 2021

Background

Peri‐implant bone level values have been used as the clinical standard of reference to describe the status of a dental implant, despite the fact that their significance for the long‐term survival of the implant has never been properly assessed.

Purpose

To challenge the assumption that the natural course of peri‐implant bone loss is the loss of the implant.

Materials and methods

This article is a narrative review on reasons and interpretations of marginal bone level changes around dental implants.

Results and conclusions

Different views regarding the pattern and progression of marginal bone loss depending on dental specialties have been identified. However, the present finding of a negative correlation between an increasing cumulative marginal bone loss and a decreasing risk of implant failures over time indicates that peri‐implant marginal bone loss does not necessarily represent a condition of disease. Reduction of marginal bone levels may be observed in a majority of patients during follow‐up time, with only a minority of those patients losing implants and implant‐supported prostheses in the long term. Bone level changes seem often to occur as a consequence of physiological processes and/or as an adaptation to altered external as well as host response factors. Periodical radiological assessments of implant‐restorations remain a valid diagnostic tool for the detection of potential implant fractures, loss of osseointegration, screws working loose and for the detection of the few cases with advanced, continuously progressing marginal bone loss during time. The detection of peri‐implant marginal bone loss at one time point should not be immediately considered as a sign of ongoing pathology and of an increased risk of future loss of the implant in question.
Impact of COVID‐19 pandemic on functioning of cytopathology laboratory: Experience and perspective from an academic centre in New York
Authors: Virk Renu K. , Wood Teresa , Tiscornia‐Wasserman Patricia G.
Published: January 2021

COVID‐19 has extraordinarily impacted every facet of the health care facilities’ operations. Various strategies and policies were implemented promptly to preserve resources, not only to provide medical care to the expected massive numbers of COVID‐19 patients, but also to mitigate the contagion spread at the workplace to ensure safety of healthcare workers. All routine, non‐essential medical services and procedures were ramped down and workers deemed non‐essential were directed to work remotely from home to reduce the number of people at hospital premises and preserve much needed personal protective equipment that were in short supply at the outset of the pandemic. The laboratories did not remain unscathed and were under immense pressure to maintain workplace safety while being operational and provide best patient care with limited resources. In this paper, we share our experience and challenges that we faced in a cytopathology laboratory at a major academic centre in New York, USA during the peak of infection.
Predicting mood decline following temporal lobe epilepsy surgery in adults
Authors: Doherty Christine , Nowacki Amy S. , Pat McAndrews Mary , McDonald Carrie R. , Reyes Anny , Kim Michelle S. , Hamberger Marla , Najm Imad , Bingaman William , Jehi Lara , Busch Robyn M.
Published: January 2021

Objective

To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy.

Methods

Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory–Second Edition score and a postoperative raw score > 11.

Results

Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism‐adjusted c‐statistic of .70 and good calibration, with slight probability overestimation in higher risk patients.

Significance

Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.
Curcumin nanoparticles as a photoprotective adjuvant
Authors: Adusumilli Nagasai C. , Mordorski Breanne , Nosanchuk Joshua , Friedman Joel M. , Friedman Adam J.
Published: January 2021

With rising skin cancer rates and interest in preventing photoaging, adjuvants for sunscreens are in high demand. The potential of curcumin has been posited due to its anti‐inflammatory, antioxidant and wound healing properties. In prior studies, curcumin decreased UV‐induced inflammation, apoptotic changes in human keratinocytes and dermal fibroblasts, and the expression of matrix metalloproteinases. However, curcumin's utility has been hindered by poor aqueous solubility and rapid degradation in vivo. To overcome these limitations, we synthesized curcumin nanoparticles (curc‐np), which offer sustained topical delivery and enhanced bioavailability. Curc‐np and controls were applied to the skin of BALB/c mice prior to UVB irradiation. Twenty‐four hours later, mice pretreated with curc‐np showed less erythema, induration and scale compared to controls. Histopathology showed fewer sunburn cells, and TUNEL assay indicated decreased apoptosis in curc‐np treated mice. Immunohistochemistry illustrated less p53 expression in skin pretreated with curc‐np. Furthermore, cytokine analysis revealed significantly less IL‐6 and significantly greater anti‐inflammatory IL‐10 in skin of curc‐np‐treated mice as compared to controls. Taken together, our results reinforce curcumin's established anti‐inflammatory effects in the skin and highlight its potential as a photoprotective adjuvant when delivered through nanoparticles. Further investigation alongside sunscreens against UV‐induced damage is warranted.
Centrally acting antihypertensives change the psychogenic cardiovascular reactivity
Authors: Mendonça Michelle M. , Costa Amanda N. , Moraes Gean C.A. , Martins Gustavo M. , Almeida Aline F. , Rincon Gabriel C.N. , Siqueira João P.R. , Padilha Daniella M. , Moya Marcela I. , Ferreira‐Neto Marcos L. , Gomes Rodrigo Mello , Pedrino Gustavo Rodrigues , Fontes Marco Antônio Peliky , Colombari Eduardo , Crestani Carlos C. , Fajemiroye James O. , Xavier Carlos Henrique
Published: January 2021

Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT – normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control ‐ CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air‐jet (10 L/min – restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR; (ii) different stimuli evoked pressor and tachycardic responses; (iii) CL and RI reduced pressor response to sound; (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR; (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI; (vi) air‐jet increased pressure and heart rate; (vii) CL or RI attenuated the pressor responses to air‐jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air‐jet‐induced tachycardia.
Statins attenuate antiviral IFN‐β and ISG expression via inhibition of IRF3 and JAK/STAT signaling in poly(I:C)‐treated hyperlipidemic mice and macrophages
Authors: Koike Atsushi , Tsujinaka Kaito , Fujimori Ko
Published: January 2021

Viral infection is a significant burden to health care worldwide. Statins, 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase inhibitors, are widely used as cholesterol‐lowering drugs. Recently, long‐term statin therapy was shown to reduce the antiviral immune response; however, the underlying molecular mechanisms are unclear. Here, we found that simvastatin decreased polyinosinic–polycytidylic acid [poly(I:C)]‐induced expression of antiviral interferon (IFN)‐β and IFN‐stimulated genes (ISGs) in the bronchoalveolar lavage fluid (BALF) and lungs of mice with high‐fat diet‐induced hyperlipidemia. Macrophages were the dominant cell type in the BALF of poly(I:C)‐treated mice. We examined the effects of simvastatin in primary lung macrophages and found that simvastatin suppressed poly(I:C)‐induced expression of IFN‐β and ISGs. We examined the molecular mechanisms of statin‐mediated inhibition of antiviral gene expression using murine macrophage‐like cell line, J774.1/JA‐4. Simvastatin and pitavastatin decreased poly(I:C)‐induced expression of IFN‐β and ISGs. Moreover, they repressed poly(I:C)‐induced phosphorylation of IFN regulatory factor (IRF) 3 and signal transducers and activators of transcription (STAT) 1, which is involved in Janus kinase (JAK)/STAT signaling. Mevalonate and geranylgeranyl pyrophosphate (GGPP), but not cholesterol, counteracted the negative effect of statins on IFN‐β and ISG expression and phosphorylation of IRF3 and STAT1. The geranylgeranyltransferase inhibitor suppressed poly(I:C)‐induced expression of IFN‐β and ISGs and phosphorylation of IRF3 and STAT1. These results suggest that statins suppressed the expression of IFN‐β and ISGs in poly(I:C)‐treated hyperlipidemic mice and murine macrophages and that these effects occurred through the inhibition of IRF3 and JAK/STAT signaling in macrophages. Furthermore, GGPP recovered the statin‐suppressed IRF3 and JAK/STAT signaling in poly(I:C)‐treated macrophages.
The effect of needle size on cerebrospinal fluid collection time and post‐dural puncture headache: A retrospective cohort study
Authors: van Dongen Robin M. , Onderwater Gerrit L. J. , Pelzer Nadine , Zielman Ronald , van Oosterhout Willibrordus P. J. , van Zwet Erik W. , Ferrari Michel D. , Terwindt Gisela M.
Published: January 2021

Objective

The main objective of this study was to compare cerebrospinal fluid (CSF) collection time and patient's discomfort between 20G (a)traumatic and 22G atraumatic needles.

Background

Risk of post‐dural puncture headache (PDPH) is decreased using atraumatic needles. Smaller needles may give lower risk but possibly at the cost of increased CSF collection time (due to lower flow), leading to additional patient's discomfort.

Methods

We performed a retrospective study of lumbar puncture data from a research program on CSF metabolomics and compared traumatic 20G (n = 210) with atraumatic 20G (n = 39) and 22G (n = 105) needles. In this cohort, incidence of PDPH was prospectively registered with other procedure details. Primary outcome was CSF collection time (time to fill the tube). Secondary outcomes were pain and stress scores during procedure, and incidence of PDPH.

Results

The time to collect 10 mL of CSF was longer for 22G needles (6.1 minutes; 95% CI 5.8–6.5) than for 20G traumatic (2.2 minutes; 95% CI 2.1–2.2) and 20G atraumatic needles (2.9 minutes; 95% CI 2.8–3.1). There were no differences in pain and stress scores. PDPH was lower for 22G atraumatic needles: odds ratio 0.41 (95% CI 0.25–0.66) versus 20G traumatic needles and 0.53 (95% CI 0.40–0.69) versus 20G atraumatic needles. Absolute PDPH rates were 69/210 (32.9%) for 20G traumatic, 13/39 (33.3%) for 20G atraumatic, and 19/105 (18.1%) for 22G atraumatic needles.

Conclusions

CSF collection time is slightly longer for smaller 22G needles, but this does not lead to more discomfort for the patient.
Severity of liver fibrosis using shear wave elastography is influenced by hepatic necroinflammation in chronic hepatitis patients, but not in cirrhotic patients
Authors: Nakano Chikage , Nishimura Takashi , Tada Toshifumi , Yoshida Masahiro , Takashima Tomoyuki , Aizawa Nobuhiro , Ikeda Naoto , Nishikawa Hiroki , Enomoto Hirayuki , Hatano Etsuro , Yano Hirohisa , Hirota Seiichi , Hachiya Hiroyuki , Iijima Hiroko
Published: January 2021

Aim

Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically.

Methods

A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically.

Results

The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p < 0.001). In patients with F0–1, F2, and F3, TE and VTQ values of A2 or A3 were significantly higher than those of A0 or A1 (p value, all <0.05), but not in patients with F4. The median alanine aminotransferase (ALT) values increased significantly with the progression of liver inflammation (p < 0.001). Moreover, TE and VTQ in patients with ALT ≥70 IU/L were significantly higher than those in patients with ALT <70 IU/L (p < 0.01), but not in patients with F4.

Conclusion

Shear wave elastography can be affected by hepatic necroinflammation in F0–F3 fibrosis, but not in F4.
DNA damage‐inducible transcript 3 immunohistochemistry is highly sensitive for the diagnosis of myxoid liposarcoma but care is required in interpreting the significance of focal expression
Authors: Vargas Ana Cristina , Chan Noni L , Wong Daniel D , Zaborowski Matthew , Fuchs Talia L , Ahadi Mahsa , Clarkson Adele , Sioson Loretta , Sheen Amy , Maclean Fiona , Bonar Fiona , Cheah Alison , Jones Martin , Chou Angela , Gill Anthony J
Published: January 2021

Aims

Myxoid liposarcoma (MLPS) is characterised by DNA damage‐inducible transcript 3 (DDIT3) gene rearrangements, confirmation of which is commonly used diagnostically. Recently, DDIT3 immunohistochemistry (IHC) has been reported to be highly sensitive and, when strict criteria are employed, specific for the diagnosis of MLPS. The aim of this study was to independently investigate DDIT3 IHC as a diagnostic marker for MLPS.

Methods and results

DDIT3 IHC was performed on 52 MLPS and on 152 mimics on whole sections, and on 515 non‐MLPS sarcomas in tissue microarray format. Only one MLPS (which had undergone acid‐based decalcification) was completely negative. With inclusion of this case if any nuclear expression is considered to indicate positivity, the overall sensitivity of DDIT3 is 98% (51 of 52 cases) and the specificity is 94% (633 of 667 non‐MLPS cases are negative). If a cut‐off of >10% of neoplastic cells is required for positivity, then the sensitivity remains 98% (51/52) and the specificity is 98.5% (657 of 667 non‐MLPS cases are negative). If a cut‐off of >50% of cells is required for positivity, then the sensitivity is 96% (50 of 52 cases) but the specificity improves to 100%.

Conclusions

Diffuse nuclear DDIT3 expression occurs in the overwhelming majority of MLPSs, and can be used to confirm the diagnosis in most cases without the need for molecular testing. A complete absence of expression argues strongly against MLPS, and almost completely excludes this diagnosis, particularly if there is consideration of technical factors such as decalcification. The significance of focal DDIT3 expression should be interpreted in the morphological and clinical context, although most tumours showing only focal expression are not MLPS.
ABO and Rhesus D blood groups in the Northern Territory of Australia
Authors: McLean Antonia , Szabo Ferenc , Wang Zhiqiang
Published: January 2021

Background

There are no contemporary published data on the frequency of the ABO and Rhesus D (RhD) blood groups in the Northern Territory (NT) of Australia, particularly for the large Aboriginal population.

Aims

To establish the frequencies of ABO and RhD blood groups in the NT Aboriginal and non‐Aboriginal populations in order to aid transfusion inventory management and clinical practice.

Methods

Retrospective data were collected from 1 January 2012 to 31 December 2012. All patients with a blood group sample processed by the NT public hospital laboratories and a recorded ABO and RhD report were included. Results were analysed using Stata 14.

Results

The Aboriginal and non‐Aboriginal populations had significantly different ABO and RhD distributions (P < 0.001). For Aboriginal individuals, 955/1686 (56.6%) were group O and 669/1686 (39.7%) were group A. In non‐Aboriginal individuals, 1201/2657 (45.2%) were group O and 986/2657 (37.1%) were group A. We found that 1646/1686 (97.6%) of Aboriginal individuals were RhD positive, compared with 2225/2657 (83.7%) of non‐Aboriginal individuals. Only 62/1686 (3.7%) of Aboriginal individuals were group B or AB, compared with 470/2657 (17.7%) of non‐Aboriginal individuals. In Aboriginal individuals we found that group O was more common than A in the ‘Northern’ NT, whereas there was similar distribution of the groups in ‘Central Australia’.

Conclusions

We found a significant difference in ABO and RhD blood groups between Aboriginal and non‐Aboriginal individuals in the NT (P < 0.001). These findings will aid transfusion inventory management, allowing us to plan supply of blood products and reduce waste.
A Retrospective observational cohort study of the effect of antenatal influenza vaccination on birth outcomes in Cape Town, South Africa, 2015‐2016
Authors: McMorrow Meredith L. , Rossi Liza , Meiring Susan , Bishop Katherine , Itzikowitz Raphaela , Isaacs Washiefa , Stellenboom Faakhiera , Walaza Sibongile , Hellferscee Orienka , Treurnicht Florette K. , Zar Heather J. , Tempia Stefano , Cohen Cheryl
Published: January 2021

Background

There are conflicting data concerning the impact of antenatal influenza vaccination on birth outcomes including low birthweight (LBW), preterm birth, small for gestational age (SGA), and stillbirth.

Methods

We conducted a retrospective observational cohort study of infants born to women residing in Mitchells Plain, Cape Town. Infants were born at 4 health facilities during May 28 – December 31, 2015 and April 15 – December 31, 2016. We performed crude and multivariable logistic regression, propensity score (PS) matching logistic regression, and inverse probability of treatment weighted (IPTW) regression to assess vaccine effectiveness (VE) against LBW, preterm birth, SGA, and stillbirth adjusting for measured confounders.

Results

Maternal vaccination status, antenatal history, and ≥1 birth outcome(s) were available for 4084/5333 (76.6%) pregnancies, 2109 (51.6%) vaccinated, and 1975 (48.4%) unvaccinated. The proportion LBW was lower in vaccinated (6.9%) vs. unvaccinated (12.5%) in multivariable [VE 0.27 (95% CI 0.07‐0.42)], PS [VE 0.30 (95% CI 0.09‐0.51)], and IPTW [VE 0.24 (95% CI 0.04‐0.45)]. Preterm birth was less frequent in vaccinated (8.6%) than unvaccinated (16.4%) in multivariable [VE 0.26 (0.09‐0.40)], PS [VE 0.25 (95% CI 0.09‐0.41)], and IPTW [VE 0.34 (95% CI 0.18‐0.51)]. The proportion SGA was lower in vaccinated (6.0%) than unvaccinated (8.8%) but not in adjusted models. There were few stillbirths in our study population, 30/4084 (0.7%).

Conclusions

Using multiple analytic approaches, we found that influenza vaccination was associated with lower prevalence of LBW (24‐30%) and preterm birth (25‐34%) in Cape Town during 2015‐2016.
Determining the impact of age and sex on the psychophysical and neurophysiological response to thermal pain across the adult lifespan
Authors: Atalla Sebastian W. , Cowan Ronald L. , Anderson Alison R. , Dietrich Mary S. , Iversen Larkin , Beth Kalvas Laura , Moss Karen O. , Wright Kathy , Monroe Todd B.
Published: January 2021

Aims

Determine sex‐ and age‐associated psychophysical and neurophysiological differences in the processing of pain across the adult lifespan.

Design

Preliminary, exploratory, cross‐sectional study.

Methods

Using psychophysics (to measure intensity and unpleasantness) and functional magnetic resonance imaging blood oxygenation level dependent methods (to measure stimulus‐evoked brain activation), we will examine sex‐ and age‐associated differences in thermal pain processing and their underlying neurophysiology in a broad range of healthy adults (ages 30–89). We will acquire resting state functional connectivity data for secondary analyses exploring whether resting state connectivity predicts psychophysical and neurophysiological responses to thermal pain. To examine the effects of altered blood flow, we will acquire resting‐state arterial spin labeling magnetic resonance imaging data to quantify resting cerebral blood flow. We will interpret findings in the context of a proposed neural model of pain, ageing, and sex. Study funding was received in June of 2014. Ethical approval was obtained from the Vanderbilt University IRB prior to study initiation.

Conclusion

Exploring the biological reasons for age‐ and sex‐associated differences in pain processing will increase our understanding of pain in older adults. The paucity of neurobiological evidence to support best practice pain management in older adults places these individuals at risk for poor pain management.

Impact

Poorly treated pain in older adults is a critical public health problem associated with a poor quality of life and increased healthcare costs. Understanding how age and sex have an impact on central processing of pain across the lifespan is a critical step toward improving personalized pain medicine.