bluuebunny/crossref_metadata_2025 huggingface dataset:
Research End-User Perspectives about Using Social Work Research in Policy and Practice
Authors: Tilbury Clare , Hughes Mark , Bigby Christine , Fisher Mike
Published: January 2021

Research funding and assessment initiatives that foster engagement between researchers and research end-users have been adopted by governments in many countries. They aim to orient research towards achieving measurable impacts that improve economic and social well-being beyond academia. This has long been regarded as important in social work research, as it has in many fields of applied research. This study examined research engagement and impact from the perspective of research end-users working in human services. In-person or telephone interviews were conducted with forty-three research end-users about how they used research and interacted with researchers. Content analysis was undertaken to identify engagement strategies and thematic coding was employed to examine underpinning ideas about research translation into practice. Participants were involved in many types of formal and informal research engagements. They viewed research translation as a mutual responsibility but indicated that researchers should do more to improve the utility of their research for industry. The findings highlight the iterative nature of engagement and impact and raise questions about the infrastructure for scaling up impact beyond relationships between individual researchers and their industry partners.
The Role of Self-efficacy in the Recovery Trajectory of Mental Health Consumers
Authors: Wu Hui-Ching , Yang Chiao-Yu , Chen Yi-Ching
Published: January 2021

This study examined the relative contributions of consumer–provider trust, health care choice, empowerment as well as possible mediation by self-efficacy, to a recovery trajectory model in an Asian collective cultural context. We interviewed 310 adults with severe mental illnesses referred from community rehabilitation centers in Taiwan. They were administered six scales, including the Satisfaction with Services (SS), Quality of Life (QL), Self-Efficacy Scale, Working Alliance Inventory-Short Form, Information and Advice Scale and Personal Empowerment Scale. Quantitative path analysis was used to evaluate the effects of the predictors on the QL and SS. The study revealed a satisfactory model fit. Self-efficacy and trust had significant direct effects and empowerment had a significant indirect effect on subjective QL, while empowerment, health care choices, and trust had significant direct effects on SS. Self-efficacy mediated the influence of empowerment on the QL. In conclusion, SS might be improved by building a trusting relationship, providing information regarding health care choices, and improving consumer empowerment and QL can be improved by strengthening self-efficacy and empowerment. The recovery-promoting competitive model should take cultural characteristics including traditional dependence on authority figures, into consideration in an Asian context.
On the 400th anniversary of the birth of Thomas Willis
Authors: Molnár Zoltán
Published: January 2021

Zoltan Molnar marks the 400th anniversary of the birth of one of the great neuroanatomists, Thomas Willis. While Willis’ name is usually associated with ‘the circle’ and the word ‘neurologia’, his work also formed the foundation of modern translational research and clinical medicine.
A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement
Authors: Rebelo Adriana P , Cortese Andrea , Abraham Amit , Eshed-Eisenbach Yael , Shner Gal , Vainshtein Anna , Buglo Elena , Camarena Vladimir , Gaidosh Gabriel , Shiekhattar Ramin , Abreu Lisa , Courel Steve , Burns Dennis K , Bai Yunhong , Bacon Chelsea , Feely Shawna M E , Castro Diana , Peles Elior , Reilly Mary M , Shy Michael E , Zuchner Stephan
Published: January 2021

The CADM family of proteins consists of four neuronal specific adhesion molecules (CADM1, CADM2, CADM3 and CADM4) that mediate the direct contact and interaction between axons and glia. In the peripheral nerve, axon-Schwann cell interaction is essential for the structural organization of myelinated fibres and is primarily mediated by the binding of CADM3, expressed in axons, to CADM4, expressed by myelinating Schwann cells. We have identified—by whole exome sequencing—three unrelated families, including one de novo patient, with axonal Charcot-Marie-Tooth disease (CMT2) sharing the same private variant in CADM3, Tyr172Cys. This variant is absent in 230 000 control chromosomes from gnomAD and predicted to be pathogenic. Most CADM3 patients share a similar phenotype consisting of autosomal dominant CMT2 with marked upper limb involvement. High resolution mass spectrometry analysis detected a newly created disulphide bond in the mutant CADM3 potentially modifying the native protein conformation. Our data support a retention of the mutant protein in the endoplasmic reticulum and reduced cell surface expression in vitro. Stochastic optical reconstruction microscopy imaging revealed decreased co-localization of the mutant with CADM4 at intercellular contact sites. Mice carrying the corresponding human mutation (Cadm3Y170C) showed reduced expression of the mutant protein in axons. Cadm3Y170C mice showed normal nerve conduction and myelin morphology, but exhibited abnormal axonal organization, including abnormal distribution of Kv1.2 channels and Caspr along myelinated axons. Our findings indicate the involvement of abnormal axon-glia interaction as a disease-causing mechanism in CMT patients with CADM3 mutations.
Metabolic and Hemodynamic Resting-State Connectivity of the Human Brain: A High-Temporal Resolution Simultaneous BOLD-fMRI and FDG-fPET Multimodality Study
Authors: Jamadar Sharna D , Ward Phillip G D , Liang Emma X , Orchard Edwina R , Chen Zhaolin , Egan Gary F
Published: January 2021

Simultaneous [18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging (FDG-PET/fMRI) provides the capacity to image 2 sources of energetic dynamics in the brain—glucose metabolism and the hemodynamic response. fMRI connectivity has been enormously useful for characterizing interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease, but FDG-sPET cannot be used to estimate subject-level measures of “connectivity,” only across-subject “covariance.” Here, we applied high-temporal resolution constant infusion functional positron emission tomography (fPET) to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterized by frontoparietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with FDG-sPET metabolic covariance, indicating that metabolic brain connectivity is a nonergodic process whereby individual brain connectivity cannot be inferred from group-level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain and open up the opportunity for novel fundamental studies of human brain connectivity as well as multimodality biomarkers of neurological diseases.
Developmental Differences Between the Limbic and Neocortical Telencephalic Wall: An Intrasubject Slice-Matched 3 T MRI-Histological Correlative Study in Humans
Authors: Bobić-Rasonja Mihaela , Pogledić Ivana , Mitter Christian , Štajduhar Andrija , Milković-Periša Marija , Trnski Sara , Bettelheim Dieter , Hainfellner Johannes A , Judaš Miloš , Prayer Daniela , Jovanov-Milošević Nataša
Published: January 2021

The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15–35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones’ proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.
Outcomes of open and endovascular repair of Kommerell diverticulum
Authors: Bloom Jordan P , Attia Rizwan Q , Sundt Thoralf M , Cameron Duke E , Hedgire Sandeep S , Bhatt Ami B , Isselbacher Eric M , Srivastava Sunita D , Kwolek Christopher J , Eagleton Matthew J , Mohebali Jahan , Jassar Arminder S
Published: January 2021

OBJECTIVES

Kommerell diverticulum (KD) is a rare congenital vascular anomaly often associated with an aberrant subclavian artery (ASCA). Definitive indications for intervention remain unclear. We present open and endovascular (EV) operative outcomes in a large contemporary series and propose a management algorithm.

METHODS

Between 2004 and 2020, 224 patients presented with ASCA and associated KD to our institution. Of the 43 (19.2%) patients who underwent operative repair, 31 (72.1%) had open surgical (OS) repair via thoracotomy and 12 (27.9%) had EV repair. Univariable and bivariable statistical analyses were conducted stratified by approach. The median follow-up time was 5.4 years (IQR, 2.9–9.7).

RESULTS

Patients in EV group were older (68 years vs 47 years, P < 0.001) and had larger aneurysms (base diameter 3.2 cm vs 21.5 cm, P = 0.007). All patients with dysphagia lusoria were treated with open surgery (n = 20). Asymptomatic patients with incidentally detected KD (50% vs 16.1%), those with chest or back pain (50% vs 19.4%) and patients who presented with an aortic emergency (25% vs 6.5%) were more likely to be treated endovascularly (P = 0.001). Carotid-to-subclavian bypass was used in 38 (88.4%) patients. There were no operative mortalities. In-hospital mortality was similar between groups (3.2% vs 16.7%, P = 0.121). Mid-term mortality was higher in the EV group [4 (33.8%) vs 0, P < 0.001]. There were 2 (15.4%) postoperative strokes in the EV group. There were no statistically significant differences in other postoperative complications or hospital length of stay between groups.

CONCLUSIONS

KD can be managed using open or EV approaches with low morbidity and mortality. Treatment strategy should depend on clinical presentation and patient factors.
Prevalence of cardiac arrhythmias in cannabis use disorder related hospitalizations in teenagers from 2003 to 2016 in the United States
Authors: Umapathi Krishna Kishore , Thavamani Aravind , Dhanpalreddy Harshitha , Nguyen Hoang H
Published: January 2021

Aims

Cannabis is an increasingly common recreational substance used by teenagers. However, there is limited data probing association of cardiac arrhythmias with marijuana use in this population.

Methods and Results

We provide prevalence trends, disease burden and healthcare utilization of cardiac arrhythmias associated with cannabis use disorder (CUD) in hospitalized teenagers (13–20 years) using a large national administrative database in the United States from 2003–2016. We used partial least square regression analysis for assessing trends in prevalence of cardiac arrhythmias and multiple logistic regression to elucidate independent predictors of arrhythmias associated with CUD. Among all CUD related hospitalizations (n = 876, 431), 0.5% had arrhythmias. Prevalence trends of arrhythmias among CUD increased six-fold during the study period (P < 0.001). CUD was more prevalent in males and older teens (both P < 0.001). There was a significant risk for mortality when CUD was associated with arrhythmia (7.4% vs. 0.1%, P < 0.001). While mean length-of-stay (LOS) was shorter (4.4 vs. 5.4 days, P < 0.001) for patients with CUD, they incurred three times higher mean hospitalization charges when compared to CUD patients without arrhythmia ($45 959 vs. $18 986, P < 0.001). Both LOS and hospitalization charges showed an uptrend during the study period (P < 0.001). Congenital heart disease, congestive heart failure, hypertension, and obesity independently predicted arrhythmias in CUD while other substance abuse did not change the risk of arrhythmia in CUD.

Conclusion

Arrhythmia burden is increasing among teenagers with CUD, and co-occurrence of arrhythmia and CUD worsens hospital outcomes.
Mitochondrial P2X7 Receptor Localization Modulates Energy Metabolism Enhancing Physical Performance
Authors: Sarti Alba Clara , Vultaggio-Poma Valentina , Falzoni Simonetta , Missiroli Sonia , Giuliani Anna Lisa , Boldrini Paola , Bonora Massimo , Faita Francesco , Di Lascio Nicole , Kusmic Claudia , Solini Anna , Novello Salvatore , Morari Michele , Rossato Marco , Wieckowski Mariusz R , Giorgi Carlotta , Pinton Paolo , Di Virgilio Francesco
Published: January 2021

Basal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, Adenosine 5′-triphosphate (ATP) synthesis, and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia, and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack (1) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca2+ level, (2) modifies expression pattern of oxidative phosphorylation enzymes, and (3) severely affects cardiac performance. Hearts from P2rx7-deleted versus wild-type mice are larger, heart mitochondria smaller, and stroke volume, ejection fraction, fractional shortening, and cardiac output, are significantly decreased. Accordingly, the physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.
Models of care for patients with hypertension and diabetes in humanitarian crises: a systematic review
Authors: Jaung Michael S , Willis Ruth , Sharma Piyu , Aebischer Perone Sigiriya , Frederiksen Signe , Truppa Claudia , Roberts Bayard , Perel Pablo , Blanchet Karl , Ansbro Éimhín
Published: January 2021

Care for non-communicable diseases, including hypertension and diabetes (HTN/DM), is recognized as a growing challenge in humanitarian crises, particularly in low- and middle-income countries (LMICs) where most crises occur. There is little evidence to support humanitarian actors and governments in designing efficient, effective, and context-adapted models of care for HTN/DM in such settings. This article aimed to systematically review the evidence on models of care targeting people with HTN/DM affected by humanitarian crises in LMICs. A search of the MEDLINE, Embase, Global Health, Global Indexus Medicus, Web of Science, and EconLit bibliographic databases and grey literature sources was performed. Studies were selected that described models of care for HTN/DM in humanitarian crises in LMICs. We descriptively analysed and compared models of care using a conceptual framework and evaluated study quality using the Mixed Methods Appraisal Tool. We report our findings according to PRISMA guidelines. The search yielded 10 645 citations, of which 45 were eligible for this review. Quantitative methods were most commonly used (n = 34), with four qualitative, three mixed methods, and four descriptive reviews of specific care models were also included. Most studies detailed primary care facility-based services for HTN/DM, focusing on health system inputs. More limited references were made to community-based services. Health care workforce and treatment protocols were commonly described framework components, whereas few studies described patient centredness, quality of care, financing and governance, broader health policy, and sociocultural contexts. There were few programme evaluations or effectiveness studies, and only one study reported costs. Most studies were of low quality. We concluded that an increasing body of literature describing models of care for patients with HTN/DM in humanitarian crises demonstrated the development of context-adapted services but showed little evidence of impact. Our conceptual framework could be used for further research and development of NCD models of care.
Twin Peaks: more twinning in humans than ever before
Authors: Monden Christiaan , Pison Gilles , Smits Jeroen
Published: January 2021

STUDY QUESTION

How many twins are born in human populations and how has this changed over recent decades?

SUMMARY ANSWER

Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year.

WHAT IS KNOWN ALREADY

It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing.

STUDY DESIGN, SIZE, DURATION

We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980–1985 and the 2010–2015 periods.

PARTICIPANTS/MATERIALS, SETTING, METHODS

For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010–2015 period. For 112 countries, we were also able to obtain twinning rates for 1980–1985.

MAIN RESULTS AND THE ROLE OF CHANCE

Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world.

LIMITATIONS, REASONS FOR CAUTION

For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys.

WIDER IMPLICATIONS OF THE FINDINGS

The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery.

STUDY FUNDING/COMPETING INTEREST(S)

The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest.

TRIAL REGISTRATION NUMBER

N/A.
Seeing Is Disbelieving: The Depths and Limits of Factual Misinformation in War
Authors: Silverman Daniel , Kaltenthaler Karl , Dagher Munqith
Published: January 2021

Misinformation, lies, and fake news are pervasive in war. But when are they actually believed by the people who live in war zones, and when are they not? This question is key, as their spread can spark greater violence and spoil efforts to make peace. In this study, we advance a new argument about lies in war. Building on existing research that links people's factual beliefs in conflict to their psychological and informational biases, we argue that they also hinge on their exposure and proximity to relevant events. While war is rife with lies, those close to the action have the means and the motives to see through them. We test this argument with a unique combination of survey and event data from the Coalition air campaign against the Islamic State of Iraq and the Levant in contemporary Iraq, finding support for our theory. Ultimately, the results help enhance our understanding of the dynamics of modern armed conflict and the reach of misinformation in contemporary world politics.
Invasive infections withPurpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature
Authors: Sprute Rosanne , Salmanton-García Jon , Sal Ertan , Malaj Xhorxha , Ráčil Zdeněk , Ruiz de Alegría Puig Carlos , Falces-Romero Iker , Barać Aleksandra , Desoubeaux Guillaume , Kindo Anupma Jyoti , Morris Arthur J , Pelletier René , Steinmann Joerg , Thompson George R , Cornely Oliver A , Seidel Danila , Stemler Jannik ,   the FungiScope® ECMM/ISHAM Working Group
Published: January 2021

Objectives

To provide a basis for clinical management decisions in Purpureocillium lilacinum infection.

Methods

Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed.

Results

We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22).

Conclusions

P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.
Derivation of Pheromone-Based Larval Thresholds in Spruce Budworm Accounting for Distance to Defoliated Forest Stands
Authors: Rhainds Marc , DeMerchant Ian , Therrien Pierre
Published: January 2021

Spruce budworm, Choristoneura fumiferana Clem. (Lepidoptera: Tortricidae), is the most severe defoliator of Pinaceae in Nearctic boreal forests. Three tools widely used to guide large-scale management decisions (year-to-year defoliation maps; density of overwintering second instars [L2]; number of males at pheromone traps) were integrated to derive pheromone-based thresholds corresponding to specific intergenerational transitions in larval densities (L2i → L2i+1), taking into account the novel finding that threshold estimates decline with distance to defoliated forest stands (DIST). Estimates of thresholds were highly variable between years, both numerically and in terms of interactive effects of L2i and DIST, which limit their heuristic value. In the context of early intervention strategy (L2i+1 > 6.5 individuals per branch), however, thresholds fluctuated within relatively narrow intervals across wide ranges of L2i and DIST, and values of 40–200 males per trap may thus be used as general guideline.
Institutions and the productivity challenge for European regions
Authors: Rodríguez-Pose Andrés , Ganau Roberto
Published: January 2021

Europe has witnessed a considerable labour productivity slowdown in recent decades. Many potential explanations have been proposed to address this productivity ‘puzzle’. However, how the quality of local institutions influences labour productivity has been overlooked by the literature. This article addresses this gap by evaluating how institutional quality affects labour productivity growth and, particularly, its determinants at the regional level during the period 2003–2015. The results indicate that institutional quality influences regions’ labour productivity growth both directly—as improvements in institutional quality drive productivity growth—and indirectly—as the short- and long-run returns of human capital and innovation on labour productivity growth are affected by regional variations in institutional quality.
The prognostic impact of tumour location and first-line chemotherapy regimen in locally advanced pancreatic cancer
Authors: Takeda Tsuyoshi , Sasaki Takashi , Mie Takafumi , Furukawa Takaaki , Yamada Yuto , Kasuga Akiyoshi , Matsuyama Masato , Ozaka Masato , Sasahira Naoki
Published: January 2021

Background

The prognostic impact of tumour location (pancreatic head vs. pancreatic body/tail) and first-line chemotherapy regimen (gemcitabine plus nab-paclitaxel vs. modified FOLFIRINOX) has not been fully elucidated in locally advanced pancreatic cancer. Therefore, we conducted this study to examine the prognostic impact of tumour location and first-line chemotherapy regimen.

Methods

We retrospectively investigated locally advanced pancreatic cancer patients who initiated first-line chemotherapy (gemcitabine plus nab-paclitaxel or modified FOLFIRINOX) between March 2014 and December 2019. We compared clinical characteristics and survival outcomes according to chemotherapy regimen and tumour location. Furthermore, we examined the prognostic factors associated with overall survival using cox proportional hazards model. Distant metastasis pattern was also compared according to tumour location.

Results

A total of 128 patients were included (GnP 95, mFFX 33; Ph 66, Pbt 62). Distribution of chemotherapy regimen was balanced between pancreatic head and pancreatic body/tail cancers. Eight patients underwent conversion surgery and 81 patients (63%) developed distant metastasis. Although patients receiving modified FOLFIRINOX were significantly younger and tended to have better performance status compared to patients receiving gemcitabine plus nab-paclitaxel, radiological tumour response, progression-free survival, overall survival and chemotherapy-related adverse events were similar between the two groups except for grades 3–4 anorexia (9% vs. 1%, P = 0.05). Furthermore, overall survival was similar between pancreatic head and pancreatic body/tail cancers. Conversion surgery and radiation therapy were identified as independent prognostic factors for overall survival. The most common site of distant metastasis was liver metastasis in both groups and pattern of distant metastasis was not different between the two groups.

Conclusions

In our experience, tumour location and first-line chemotherapy regimen were not a prognostic factor for overall survival in locally advanced pancreatic cancer.
A novel radiolytic rotenone derivative, rotenoisin A, displays potent anticarcinogenic activity in breast cancer cells
Authors: Bak Dong-ho , Kang Seong Hee , Park Chul-hong , Chung Byung Yeoup , Bai Hyoung-Woo
Published: January 2021

Chemotherapy for cancer treatment has therapeutic limitations, such as drug resistance, excessive toxic effects and undesirable adverse effects. Therefore, efforts to improve the safety and efficacy of chemotherapeutic agents are essential. Ionizing radiation can improve physiological and pharmacological properties by transforming structural modifications of the drug. In this study, in order to reduce the adverse effects of rotenone and increase anticancer activity, a new radiolytic rotenone derivative called rotenoisin A was generated through radiolytic transformation. Our findings showed that rotenoisin A inhibited the proliferation of breast cancer cells and increased the rate of apoptosis, whereas it had no inhibitory effect on primary epidermal keratinocytes compared with rotenone. Moreover, rotenoisin A-induced DNA damage by increasing reactive oxygen species (ROS) accumulation. It was also confirmed not only to alter the composition ratio of mitochondrial proteins, but also to result in structural and functional changes. The anticancer effect and molecular signalling mechanisms of rotenoisin A were consistent with those of rotenone, as previously reported. Our study suggests that radiolytic transformation of highly toxic compounds may be an alternative strategy for maintaining anticancer effects and reducing the toxicity of the parent compound.
JASMONATE RESISTANT 1 negatively regulates root growth under boron deficiency in Arabidopsis
Authors: Huang Yupu , Wang Sheliang , Shi Lei , Xu Fangsen
Published: January 2021

Boron (B) is an essential micronutrient for plant growth and development. Jasmonic acid (JA) plays pivotal roles in plant growth, but the underlying molecular mechanism of JA involvement in B-deficiency-induced root growth inhibition is yet to be explored. In this study, we investigated the response of JA to B deficiency and the mechanism of JAR1-dependent JA signaling in root growth inhibition under B deficiency in Arabidopsis. B deficiency enhanced JA signaling in roots, and root growth inhibition was partially restored by JA biosynthesis inhibition. The jar1-1 (jasmonate-resistant 1, JAR1) mutant, and mutants of coronatine-insensitive 1 (coi1-2) and myc2 defective in JA signaling showed insensitivity to B deficiency. The ethylene-overproduction mutant eto1 and ethylene-insensitive mutant etr1 showed sensitivity and insensitivity to B deficiency, respectively, suggesting that ethylene is involved in the inhibition of primary root growth under B deficiency. Furthermore, after a decline in levels of EIN3, which may contribute to root growth, ethylene signaling was weakened in the jar1-1 mutant root under B deficiency. Under B deficiency, B concentrations were increased in the roots and shoots of the jar1-1 mutant, owing to the large root system and its activity. Therefore, our findings revealed that JA, which is involved in the inhibition of root growth under B deficiency, is regulated by JAR1-activated JA and ethylene signaling pathways.
Herbicide Selection Promotes Antibiotic Resistance in Soil Microbiomes
Authors: Liao Hanpeng , Li Xi , Yang Qiue , Bai Yudan , Cui Peng , Wen Chang , Liu Chen , Chen Zhi , Tang Jiahuan , Che Jiangang , Yu Zhen , Geisen Stefan , Zhou Shungui , Friman Ville-Petri , Zhu Yong-Guan
Published: January 2021

Herbicides are one of the most widely used chemicals in agriculture. While they are known to be harmful to nontarget organisms, the effects of herbicides on the composition and functioning of soil microbial communities remain unclear. Here we show that application of three widely used herbicides—glyphosate, glufosinate, and dicamba—increase the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in soil microbiomes without clear changes in the abundance, diversity and composition of bacterial communities. Mechanistically, these results could be explained by a positive selection for more tolerant genotypes that acquired several mutations in previously well-characterized herbicide and ARGs. Moreover, herbicide exposure increased cell membrane permeability and conjugation frequency of multidrug resistance plasmids, promoting ARG movement between bacteria. A similar pattern was found in agricultural soils across 11 provinces in China, where herbicide application, and the levels of glyphosate residues in soils, were associated with increased ARG and MGE abundances relative to herbicide-free control sites. Together, our results show that herbicide application can enrich ARGs and MGEs by changing the genetic composition of soil microbiomes, potentially contributing to the global antimicrobial resistance problem in agricultural environments.
Relax, Keep Walking — A Practical Guide to Continuous Phylogeographic Inference with BEAST
Authors: Dellicour Simon , Gill Mandev S , Faria Nuno R , Rambaut Andrew , Pybus Oliver G , Suchard Marc A , Lemey Philippe
Published: January 2021

Spatially explicit phylogeographic analyses can be performed with an inference framework that employs relaxed random walks to reconstruct phylogenetic dispersal histories in continuous space. This core model was first implemented 10 years ago and has opened up new opportunities in the field of phylodynamics, allowing researchers to map and analyze the spatial dissemination of rapidly evolving pathogens. We here provide a detailed and step-by-step guide on how to set up, run, and interpret continuous phylogeographic analyses using the programs BEAUti, BEAST, Tracer, and TreeAnnotator.
Optimal Distribution of Iron to Sink Organs via Autophagy Is Important for Tolerance to Excess Zinc in Arabidopsis
Authors: Shinozaki Daiki , Tanoi Keitaro , Yoshimoto Kohki
Published: January 2021

Zinc (Zn) is nutritionally an essential metal element, but excess Zn in the environment is toxic to plants. Autophagy is a major pathway responsible for intracellular degradation. Here, we demonstrate the important role of autophagy in adaptation to excess Zn stress. We found that autophagy-defective Arabidopsis thaliana (atg2 and atg5) exhibited marked excess Zn-induced chlorosis and growth defects relative to wild-type (WT). Imaging and biochemical analyses revealed that autophagic activity was elevated under excess Zn. Interestingly, the excess Zn symptoms of atg5 were alleviated by supplementation of high levels of iron (Fe) to the media. Under excess Zn, in atg5, Fe starvation was especially severe in juvenile true leaves. Consistent with this, accumulation levels of Fe3+ near the shoot apical meristem remarkably reduced in atg5. Furthermore, excision of cotyledons induced severe excess Zn symptoms in WT, similar to those observed in atg5. Our data suggest that Fe3+ supplied from source leaves (cotyledons) via autophagy is distributed to sink leaves (true leaves) to promote healthy growth under excess Zn, revealing a new dimension, the importance of heavy-metal stress responses by the intracellular recycling.
Compositions and Classification of Fractionated Boninite Series Melts from the Izu–Bonin–Mariana Arc: A Machine Learning Approach
Authors: Valetich Matthew J , Le Losq Charles , Arculus Richard J , Umino Susumu , Mavrogenes John
Published: January 2021

Much of the boninite magmatism in the Izu–Bonin–Mariana arc is preserved as evolved boninite series compositions wherein extensive fractional crystallization of pyroxene and spinel have obscured the diagnostic geochemical indicators of boninite parentage, such as high Mg and low Ti at intermediate silica contents. As a result, the usual geochemical discriminants used for the classification of the broad range of parental boninites are inapplicable to such highly fractionated melts. These issues are compounded by the mixing of demonstrably different whole-rock and glass analyses in classification schemes and petrological interpretations based thereon. Whole-rock compositions are compromised by entrainment of variable proportions of crystalline phases resulting in inconsistent differences from corresponding in situ glass analyses, which arguably better reflect prior melt compositions. To circumvent such issues, we herein present a robust method for the classification of highly fractionated boninite series glasses. This new classification leverages the analysis of trace elements, which are much more sensitive to evolutionary processes than major elements, and benefits from the use of unsupervised machine learning as a classification tool. The results show that the most fractionated boninite series melts preserve geochemical indicators of their parentage, and highlight the pitfalls of interpreting whole-rock and glass analyses interchangeably.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults
Authors: Hijma Hemme J , Siebenga Pieter S , de Kam Marieke L , Groeneveld Geert Jan
Published: January 2021

Objective

To evaluate the analgesic potential, safety, tolerability, and pharmacokinetics of VX-150, a pro-drug of a highly selective NaV1.8 inhibitor, in healthy subjects.

Design

This was a randomized, double-blind, placebo-controlled, crossover study in healthy subjects.

Subjects

Twenty healthy male subjects with an age of 18–55 years, inclusive, were enrolled. Eligibility was based on general fitness, absence of current or previous medical conditions that could compromise subject safety, and a training assessment of pain tolerance across pain tests to exclude highly tolerant individuals whose tolerance could compromise the ability to detect analgesic responses. All dosed subjects completed the study.

Methods

Subjects were randomized 1:1 to one of two sequences receiving a single VX-150 dose and subsequently placebo, or vice versa, with at least 7 days between dosing. A battery of pain tests (pressure, electrical stair, [capsaicin-induced] heat, and cold pressor) was administered before dosing and repetitively up to 10 h after dosing, with blood sampling up to 24 h after dosing. Safety was monitored throughout the study. Data were analyzed with a repeated-measures mixed-effects model.

Results

VX-150 induced analgesia in a variety of evoked pain tests, without affecting subject safety. Significant effects were reported for the cold pressor and heat pain thresholds. Maximum median concentration for the active moiety was 4.30 µg/mL at 4 h after dosing.

Conclusion

Results of this proof-of-mechanism study are supportive of the potential of VX-150, a highly selective NaV1.8 channel inhibitor, to treat various pain indications.
Hypnotherapy for Procedural Pain and Distress in Children: A Scoping Review Protocol
Authors: Geagea Daly , Tyack Zephanie , Kimble Roy , Eriksson Lars , Polito Vince , Griffin Bronwyn
Published: January 2021

Objective

Inadequately treated pain and distress elicited by medical procedures can put children at higher risk of acute and chronic biopsychosocial sequelae. Children can benefit from hypnotherapy, a psychologically tailored intervention, as an adjunct to pharmacological agents to address the multiple components of pain and distress. Despite providing evidence on the effectiveness and potential superiority of hypnotherapy to other psychological interventions, research on hypnotherapy for pediatric procedural pain and distress has been predominantly limited to oncology and needle procedures. Plus, there is a lack of reporting of intervention manuals, factors influencing hypnotic responding, pain unpleasantness outcomes, theoretical frameworks, adverse events, as well as barriers and facilitators to the feasibility of delivering the intervention and study procedures. The proposed review aims to map the range and nature of the evidence on hypnotherapy for procedural pain and distress in children to identify gaps in literature and areas requiring further investigation.

Methods

This review will follow the Arksey and O‘Malley (2005) methodology and incorporate additional scoping review recommendations by the Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses. Relevant studies will be identified through searching published literature databases (PubMed, Cochrane Library, PsycINFO, Embase, CINAHL, Scopus and Web of Science) and grey literature in addition to hand-searching of reference lists and key journals. Two authors will independently screen titles and abstracts of search results followed by full-texts review against eligibility criteria.

Conclusion

Findings are anticipated to guide future research and inform the development of tailored hypnotic interventions in children.
Phenotype and treatment of elderly onset compared with younger onset rheumatoid arthritis patients in international daily practice
Authors: Maassen Johanna M , Bergstra Sytske Anne , Chopra Arvind , Govind Nimmisha , Murphy Elizabeth A , Vega-Morales David , Huizinga Tom W J , Allaart Cornelia F
Published: January 2021

Objective

To identify possible differences in baseline characteristics, initial treatment and treatment response between RA patient subgroups based on age at disease onset.

Methods

Daily practice data from the worldwide METEOR registry were used. Patients (7912) were stratified into three age-groups (age at disease diagnosis <45 years, 45–65 years, >65 years). Initial treatment was compared between the different age-groups. With Cox regression analyses the effect of age-group on time-to-switch from first to second treatment was investigated, and with linear mixed models differences in response to treatment (DAS and HAQ) between the age-groups were assessed, after correction for potential confounders.

Results

The >65 years age-group included more men, and more seronegative RA with somewhat higher inflammatory markers. Initial treatment choices differed only slightly between the age-groups, and the time-to-switch from initial treatment to the next was similar. DAS and HAQ improvement were dependent on the age-group, reflected by a significant interaction between age-group and outcome. The stratified analysis showed a difference of −0.02 and −0.05 DAS points and, −0.01 and 0.02 HAQ points per month in the <45 and 45–65 years age-groups as compared with the >65 year age group, a difference that did not seem clinically relevant.

Conclusion

In this international study on worldwide clinical practice, patients with RA onset >65 years include more men and seronegative arthritis, and were initially treated slightly differently than younger patients. We observed no clinically relevant differences in timing of a next treatment step, or response to treatment measured by DAS and HAQ.
Effect of Planting Population on Stem Diseases of Soybean in Iowa and Wisconsin
Authors: Kandel Yuba R. , Phillips Xavier A. , Gaska John M. , Conley Shawn P. , Mueller Daren S.
Published: January 2021

Farmers may adjust seeding rate across or within fields for a variety of reasons. The objectives of this study were to determine if seeding rate affected two late-season stem diseases, anthracnose stem blight (ASB) and pod and stem blight (PSB), and yield of soybean. Disease incidence, severity, and yield were collected from eight field trials in Iowa and Wisconsin during 2016 to 2018. ASB incidence exceeded 80% in most of the trials and significantly differed across years with the highest incidence in 2016 and 2018 compared with 2017, the year with the least precipitation. A similar trend across years was observed for ASB severity. The incidence and severity of PSB also differed across years, although PSB incidence and severity were always less than ASB. PSB was greatest in 2017 compared with the other two years. Seeding rate did not affect either disease. A seeding rate of 198,000 to 395,000 seeds/ha provided statistically similar yield. Weather conditions each year affected late-season stem diseases.
Impact of the United States Department of Agriculture, Agricultural Research Service on Plant Pathology: 2015–2020
Authors: Widmer Timothy L. , Costa José M.
Published: January 2021

There is an increasing need to supply the world with more food as the population continues to grow. Research on mitigating the effects of plant diseases to improve crop yield and quality can help provide more food without increasing the land area devoted to farming. National Program 303 (NP 303) within the U.S. Department of Agriculture, Agricultural Research Service is dedicated to research across multiple fields in plant pathology. This review article highlights the research impact within NP 303 between 2015 and 2020, including case studies on wheat and citrus diseases and the National Plant Disease Recovery System, which provide specific examples of this impact.
Case Management in a Time of Uncertainties
Authors: Powell Suzanne K.
Published: January 2021

The year 2020 was a time of uncertainties and unpredictability. In this issue of Professional Case Management Journal, 2 articles discuss the issues of prolonged grief, complicated grief, and self-care.
Emergence of carbapenem-resistant Klebsiella pneumoniae harbouring bla
OXA-48-like genes in China
Authors: Chen Ying , Fang Li , Yang Yunxing , Yan Rushuang , Fu Ying , Shen Ping , Zhao Dongdong , Chen Yan , Hua Xiaoting , Jiang Yan , Moran Robert A. , van Schaik Willem , Yu Yunsong
Published: January 2021

Klebsiella pneumoniae

strains carrying OXA-48-like carbapenemases are increasingly prevalent across the globe. There is thus an urgent need to better understand the mechanisms that underpin the dissemination of bla
OXA-48-like carbapenemases. To this end, four ertapenem-resistant

K. pneumoniae

isolates producing OXA-48-like carbapenemases were isolated from two patients. Genome sequencing revealed that one sequence type (ST) 17 isolate carried bla
OXA-181, whilst three isolates from a single patient, two ST76 and one ST15, carried bla
OXA-232. The 50514 bp bla
OXA-181-harbouring plasmid, pOXA-181_YML0508, was X3-type with a conjugation frequency to

Escherichia coli

of 1.94×10−4 transconjugants per donor. The bla
OXA-232 gene was located on a 6141 bp ColKP3-type plasmid, pOXA-232_WSD, that was identical in the ST76 and ST15

K. pneumoniae

isolates. This plasmid could be transferred from

K. pneumoniae

to

E. coli

at low frequency, 8.13×10−6 transconjugants per donor. Comparative analysis revealed that the X3 plasmid acquired the bla
OXA-48-like gene via IS3000-mediated co-integration of the ColKP3-type plasmid. Our study highlights how plasmid integration and rearrangements can contribute to the spread of bla
OXA-48-like genes, which provides important clues for clinical prevention of the dissemination of

K. pneumoniae

strains carrying bla
OXA-48-like carbapenemases.