bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of the Syphilis Health Check in Clinic and Laboratory-Based Settings
Authors: Fakile Yetunde F. , Brinson Myra , Mobley Victoria , Park Ina U. , Gaynor Anne M.
Published: January 2019

Background

In this study, we evaluate the performance of the Syphilis Health Check (SHC) in clinical and laboratory settings using fingerstick whole blood and serum.

Methods

Fingerstick whole blood and serum specimens from adult patients (n = 562) without prior syphilis history presenting at 2 county health department STD clinics in North Carolina were tested. Fingerstick specimens were tested with the SHC in clinic, and serum specimens were tested at the North Carolina State Laboratory of Public Health with: (1) qualitative rapid plasma reagin, (2) treponemal EIA, and (3) SHC. Sensitivity and specificity were calculated with 95% confidence intervals.

Results

The fingerstick whole blood had a sensitivity of 100% (7 of 7) and specificity of 95.7% (531 of 555), compared with consensus reference testing (CRT) (rapid plasma reagin and EIA reactive), but a sensitivity of 50% (8 of 16), and specificity of 95.9% (523 of 546), when compared with the treponemal EIA. Both laboratory-based SHC on serum and whole-blood SHC performed similarly, compared with CRT, and the treponemal EIA alone. Twenty-four specimens SHC reactive on whole blood were nonreactive by CRT. In 8 of these 24 cases, STD clinic staff reported difficulty reading the test line for the SHC. Of the fingerstick whole-blood SHC reactive specimens, only 14 of 31 were also serum SHC reactive.

Conclusions

The SHC on whole blood appears to be sensitive at detecting patients likely to have syphilis and could be an option for testing among high-risk populations. However, given challenges in interpreting SHC test results, adequate training of persons performing testing and ongoing quality assurance measures are key.
Is There Evidence of Gender Bias in the Oral Examination for Initial Certification by the American Board of Physical Medicine & Rehabilitation?
Authors: Driscoll Sherilyn W. , Robinson Lawrence R. , Raddatz Mikaela M. , Kinney Carolyn L.
Published: January 2019

Objective

Unconscious bias may result in a prejudicial evaluation of another person and lead to unfair treatment. Potential gender bias risk exists in the scoring process on the American Board of Physical Medicine and Rehabilitation oral examination (Part II) because of the face-to-face interactions between candidates and examiners. This study was undertaken to determine whether performance on the American Board of Physical Medicine and Rehabilitation Part II examination differed based on candidate gender or configuration of examiner/candidate gender pairings. The impact of examiner unconscious bias training on candidate performance was also assessed.

Design

This is a retrospective observational study of first-time Part II physical medicine and rehabilitation certification examination test takers between 2013 and 2018.

Results

There were significant differences in pass rates (men 84%, women 89%) and mean scaled scores (men 6.56, women 6.81) between men and women (P < 0.001) with the biggest domain score differences in data acquisition and interpersonal and communication skills. Implementation of examiner unconscious bias training did not impact candidate performance.

Conclusions

Women candidates scored higher and had a higher pass rate than men candidates overall on the American Board of Physical Medicine and Rehabilitation Part II examination. This difference does not seem to be due to scoring gender bias by the Part II examiners or due to candidate aptitude as measured on the Part I examination.
Analysis of H-index in Assessing Gender Differences in Academic Rank and Leadership in Physical Medicine and Rehabilitation in the United States and Canada
Authors: Yang Hsin Yun , Rhee Gaeun , Xuan Lisa , Silver Julie K. , Jalal Sabeena , Khosa Faisal
Published: January 2019

Objectives

The aims of the study were (1) to establish potential gender differences in academic physical medicine and rehabilitation faculty across the United States and Canada and (2) to evaluate associations between physician gender, leadership position, and research productivity.

Design

Physical medicine and rehabilitation programs enlisted in Fellowship and Residency Electronic Interactive Database (n = 72) and Canadian Resident Matching Service (n = 9) were searched for academic faculty with Doctor of Medicine degrees to generate a database of gender and academic profiles. Bibliometric data were collected using Elsevier's Scopus and analyzed by Strata v14.2.

Results

Of 1045 faculty meeting the inclusion criteria, 653 were men and 392 were women. Men were found in greater numbers across all academic ranks, with professors as most conspicuous (79.14%), and held most (85.54%) leadership positions. The study's prediction model assessed for gender differences in academic rank and leadership roles and found that odds of men having higher h-index as 0.78 (95% confidence interval = 0.24–0.87), indicating that women were not significantly inferior in academic performance.

Conclusions

A significantly greater number of men make up physical medicine and rehabilitation faculty in all academic ranks and leadership positions. H-index based on gender and adjusted for covariates is comparable between men and women, suggesting that more complex, multifactorial issues are likely influencing the gender differences.
A Patient-Centered Multicomponent Strategy for Accelerated Linkage to Care Following Community-Wide HIV Testing in Rural Uganda and Kenya
Authors: Ayieko James , Petersen Maya L. , Charlebois Edwin D. , Brown Lillian B. , Clark Tamara D. , Kwarisiima Dalsone , Kamya Moses R. , Cohen Craig R. , Bukusi Elizabeth A. , Havlir Diane V. , Van Rie Annelies
Published: January 2019

Introduction:

As countries move toward universal HIV treatment, many individuals fail to link to care after diagnosis of HIV. Efficient and effective linkage strategies are needed.

Methods:

We implemented a patient-centered, multicomponent linkage strategy in the SEARCH “test-and-treat” trial (NCT 01864603) in Kenya and Uganda. After population-based, community-wide HIV testing, eligible participants were (1) introduced to clinic staff after testing, (2) provided a telephone “hot-line” for enquiries, (3) provided an appointment reminder phone call, (4) given transport reimbursement on linkage, and (5) tracked if linkage appointment was missed. We estimated the proportion linked to care within 1 year and evaluated factors associated with linkage at 7, 30, and 365 days after diagnosis.

Results:

Among 71,308 adults tested, 6811 (9.6%) were HIV-infected; of these, 4760 (69.9%) were already in HIV care, and 30.1% were not. Among 2051 not in care, 58% were female, median age was 32 (interquartile range 26–40) years, and median CD4 count was 493 (interquartile range 331–683) cells/µL. Half (49.7%) linked within 1 week, and 73.4% linked within 1 year. Individuals who were younger [15–34 vs. >35 years, adjusted Risk Ratio (aRR) 0.83, 95% confidence interval (CI): 0.74 to 0.94], tested at home vs. community campaign (aRR = 0.87, 95% CI: 0.81 to 0.94), had a high HIV-risk vs. low-risk occupation (aRR = 0.81, 95% CI: 0.75 to 0.88), and were wealthier (aRR 0.90, 95% CI: 0.83 to 0.97) were less likely to link. Linkage did not differ by marital status, stable residence, level of education, or having a phone contact.

Conclusions:

Using a multicomponent linkage strategy, high proportions of people living with HIV but not in care linked rapidly after HIV testing.
Modified Mandibular Sagittal Split Osteotomy
Authors: Ferri Joël , Schlund Matthias , Roland-Billecart Thomas , Nicot Romain
Published: January 2019

Introduction:

Mandibular osteotomies aim to displace the dental arch to the necessary position, ideally without limitation, while preserving inferior alveolar nerve (IAN) function. Supraforaminal osteotomies offer nerve safety but limit the extent of advancement, whereas Epker and Obwegeser–Dal Pont osteotomies enable unchallenged mandibular advancement but are associated with an inferior border notch. Here, we describe a new technique to avoid such disadvantages.

Technical note:

The beginning of the procedure was similar to Epker's technique, with sectioning of the lingual cortex up to the level of the lingula. Sectioning of the buccal cortex was stopped 3 to 4 mm above the inferior border and then performed horizontally up to the gonial angle in total thickness. The inferior border periosteum and muscles attachments were conserved and hence, appropriately vascularized.

Discussion:

This technique offers 4 advantages: absence of the inferior border notch, lower risk of damage to the IAN than with Epker's technique, sufficiently large bony surface to obtain bone healing as in Epker's technique, and no limitation to setback movement in contrast to Obwegeser–Dal Pont's or the supraforaminal osteotomy techniques.
Effects of Different Levels of Restraint Stress on Bone–Implant Contact
Authors: Bozoglan Alihan , Dundar Serkan , Yildirim Tuba T. , Bulmus Ozgur , Ertugrul Abdullah Seckin , Bozoglan Merve Y. , Tekin Samet , Toy Vesile Elif
Published: January 2019

This study examined the effects of different levels of chronic restraint stress on bone–titanium implant contact in rats. This study included 32 adult female Sprague–Dawley rats. The machined surface titanium implants were surgically placed into the metaphyseal region of the rat tibias. Next, the rats were divided randomly into 4 groups, namely, control (CNT) (n = 8), low-restraint stress (LRS) (n = 8), medium-restraint stress (MRS) (n = 8), and high-restraint stress (HRS) (n = 8) groups. The rats in the CNT group received only the titanium implants surgically but did not receive any further treatment during the experimental period of 30 days. The rats in the LRS, MRS, and HRS groups were applied restraint stress for 1, 2, and 4 hours, respectively, daily for 28 days starting from day 2 after the surgery. At the end of the study period, the rats were sacrificed and their implants and the surrounding bone tissues were harvested for performing nondecalcified histological analysis. Moreover, blood samples were collected from the rats and were centrifuged for analyzing serum cortisol levels. Serum cortisol levels of the rats in the LRS, MRS, and HRS groups were higher than those of the rats in the CNT group (P < 0.05). Moreover, serum cortisol levels of the rats in the HRS group were higher than those of the rats in the MRS and LRS groups (P < 0.05). The extent of bone–implant contact was lower in the rats in the HRS group than in the rats in the CNT and LRS groups (P < 0.05). These data suggest that the application of 4-hour chronic restraint stress during the 28-day experimental period impaired the bone–implant contact.
Granulomatous Inflammation of the Upper Eyelid After Autologous Fat Injection
Authors: Huh Jungah , Yang Sungwon , Park Jinhwan , Lee Hwa , Baek Sehyun
Published: January 2019

A 45-year-old female came to the clinic complaining of periorbital swelling and ptosis on the left upper eyelid that had started 6 months previously. She had received an autologous fat injection in the forehead 6 months prior, and there was no other ophthalmologic history. There were no abnormal findings, including pupil, extraocular movement, or fundus examination. There was eyebrow elevation of the left upper eyelid, and the marginal reflex distance 1 was 1 mm on the left eye compared to 4 mm on the right eye. There were a 2-cm-sized round and firm mass on the left upper eyelid that was not accompanied by tenderness. Orbital computed tomography showed heterogeneous infiltration with an ill-defined margin. Excisional biopsy and levator advancement were performed on the left upper eyelid, and histological findings showed chronic granulomatous inflammation with foreign body reaction and fat necrosis.

A complete history for patient presentation with autologous fat injection is important when a periorbital mass is encountered clinically because granulomatous inflammation of the eyelid may occur after autologous fat injection in the forehead and can be related to migration of the injected fat.
Impact of Cardiac Risk Factors on Complications Following Cranial Vault Remodeling: Analysis of the 2012 to 2016 National Safety Quality Improvement Program-Pediatric Database
Authors: Bartz-Kurycki Marisa , Wei Shuyan , Bernardi Karla , Moffitt Joseph K. , Greives Matthew R.
Published: January 2019

Congenital cardiac malformations have been reported in 8% of patients with craniosynostosis undergoing cranial vault remodeling (CVR), but associations with surgical outcomes are unknown. This study evaluated postoperative complications in patients who underwent CVR for craniosynostosis with or without cardiac risk factors (CRF) using the National Safety Quality Improvement Program-Pediatric (NSQIP-P) database. NSQIP-P database was queried for patients <2 years with craniosynostosis who underwent CVR from 2012 to 2016 based on diagnosis and procedure codes. The primary outcome was a composite of available NSQIP-P complications. Analysis compared patients with craniosynostosis based on the presence or absence of CRF. Univariate and multiple logistic regression identified risk factors associated with postoperative complications. A total of 3293 patients met inclusion criteria (8% with CRF). Two-thirds of patients experienced at least 1 complication, though patients with CRF experienced a greater proportion (74% vs 66%, P = 0.001). Univariate analysis identified associations between post-operative complications and age, ASA class, supplemental oxygen, neuromuscular disorders, preoperative nutritional supplementation, interventricular hemorrhage, and CRF. On multivariate regression, only older age (OR 1.17, 95% CI 1.01–1.36) and longer operative duration (OR 1.01, 95% CI 1.01–1.01) were associated with greater odds of postoperative complications. The most common complication in patients with craniosynostosis who undergo CVR is bleeding requiring transfusion. Older age and longer operative duration were associated with postoperative complications. Although patients with CRF have more postoperative complications, CRF was not a risk factor on adjusted analysis.
Catheter Aspiration With Recanalization for Budd-Chiari Syndrome With Inferior Vena Cava Thrombosis
Authors: Yang Fang , Huang Ping-Chao , Yan Lei-Lei , Zhang Ze-Dong , Fu Yu-Fei , Xia Feng-Fei
Published: January 2019

Purpose:

To assess the safety and clinical effectiveness of catheter aspiration with recanalization in patients with Budd-Chiari syndrome (BCS) and inferior vena cava (IVC) thrombosis.

Materials and Methods:

Between January 2010 and December 2017, 33 patients with BCS and IVC thrombosis were treated by catheter aspiration with IVC recanalization in our center. A 12 F angled-tip guiding catheter was used for the aspiration of thrombi in the IVC. Recanalization was conducted following thrombi aspiration. Rates of technical success, clinical success and long-term patency were calculated.

Results:

Catheter aspiration with IVC recanalization was technically successful in all patients. After aspiration, no thrombi were detectable by IVC venography in 21 patients, while residual mural thrombi were found in 12 patients. IVC balloon dilation was performed in 18 patients, while stent insertion was performed in 15 patients. We also achieved clinical success in all patients. Symptomatic and asymptomatic pulmonary embolism were found in 1 patient each, respectively. The cumulative 1-, 3-, and 5-year patency rates were 93.6%, 93.6%, and 83.2%, respectively. All patients remained alive during the follow-up.

Conclusions:

Catheter aspiration with recanalization is a safe and efficacious approach to treating patients with BCS and IVC thrombosis.
Communication in cancer: its impact on the experience of cancer care: communicating with the angry patient and the patient in denial
Authors: Pene Christopher Tino Hamana , Kissane David
Published: January 2019

Purpose of review

This review aims to describe the recent literature on communication between cancer care clinicians and angry patients and patients in denial.

Recent findings

Clinicians had improved perceived self-efficacy in responding to patient anger after completing anger management training, with a focus on reframing anger as a normative response to unmet needs. Psychosocial and mindfulness programmes for cancer patients were found to be useful for modifying anger response to stressors. Existing clinician communication guidelines may not meet the complex needs of adolescents and individuals with anger-prone personality expressing anger. The detrimental effects of avoiding communication about cancer and dying in patients and families include increased stress and emotional burden, patient depression and anxiety and regret in bereaved family members. Further understanding of the complex interplay between the expression of instrumental and emotional concerns of patients may lead to improved clinician communication.

Anger and maladaptive denial in patients with cancer have detrimental effects that can be seen across a wide range of cultural contexts, in not only the patient but also in their families and the involved clinicians. Training interventions for both patients and clinicians can benefit patient emotional response and perceived clinician self-efficacy.
Oncologists communicating with patients about assisted dying
Authors: Selby Debbie , Bean Sally
Published: January 2019

Purpose of review

Across all jurisdictions in which assisted dying is legally permissible, cancer is the primary reported underlying diagnosis. Therefore, oncologists are likely to be asked about assisted dying and should be equipped to respond to inquiries or requests for assisted dying. Because Medical Assistance in Dying was legalized in Canada in 2016, it is a relatively new end-of-life practice and has prompted the need to revisit the academic literature to inform communication with patients about assisted dying.

Recent findings

We reviewed applicable literature published in the past 5 years, pertaining to assisted dying and communication. In total, 86 articles were identified, 21 were flagged as relevant to review in detail, and six were included in the review. Key themes included perceived barriers and benefits to communicating with patients on the topic, pragmatic approaches for facilitating the conversation with patients, and the issue of proactively discussing assisted dying by broaching it as an option with patients.

These findings indicate that there is still discomfort around having conversations about assisted dying with patients but new tools and approaches are being developed to support the practice.
Cancer and fertility: optimizing communication between patients and healthcare providers
Authors: Shen Shiyang , Zelkowitz Phyllis , Rosberger Zeev
Published: January 2019

Purpose of review

This article reviews the status of guidelines and recommendations for communication between patients with cancer and healthcare providers (HCPs) concerning fertility issues.

Recent findings

The timing, the type of information provided, and the openness of HCPs can all affect how patients with cancer perceive discussions regarding fertility concerns and preservation. In addition, whether such discussions occur is associated with intrinsic factors, such as age and sex of the patients as well as HCP's knowledge level. It has also been found that the patients have different needs for information regarding fertility preservation and preferences for types of communication strategies regarding the impact of their disease and treatments on options for family planning.

Although discussions about fertility concerns in the context of cancer between physicians and patients are occurring more frequently, there are inconsistent findings regarding satisfaction with these discussions. Recent research has found that the timing, type of information given, and level of openness of the HCP can impact how patients perceive communications regarding the risks of cancer treatment on fertility preservation options and future family planning. Age, sex, and HCP's knowledge of fertility risks and fertility preservation services are also notable factors associated with whether and how extensively discussions about fertility take place. More women than men report having a fertility discussion with an HCP. However, men are more likely to report satisfaction with the fertility discussion than women.
The oriental armyworm (
Mythimna separata
) feeding induces systemic defence responses within and between maize leaves
Authors: Malook Saif ul , Qi Jinfeng , Hettenhausen Christian , Xu Yuxing , Zhang Cuiping , Zhang Jingxiong , Lu Chengkai , Li Jing , Wang Lei , Wu Jianqiang
Published: January 2019

Maize (
Zea mays
) is a staple cereal crop cultivated all over the world but that is threatened by various insects. Feeding of the lepidopteran insect
Mythimna separata
triggers defence signalling and increases anti-herbivore benzoxazinoids (Bxs) in the insect-damaged maize leaves. However, the herbivory-elicited within-leaf and leaf-to-leaf systemic signalling in maize remains largely unexplored. Here, we show that simulated
M. separata
herbivory and mechanical wounding elicited increased levels of jasmonic acid (JA), JA–Ile (JA–isoleucine conjugate) and Bxs in the damaged areas and in specific systemic regions within a leaf. Importantly, increased contents of Bxs were detected in a systemic leaf, and consistently, this leaf exhibited increased defence against
M. separata
. Increased JA/JA–Ile and altered transcriptome, including Bx biosynthesis genes, were detected in systemic leaves after wounding or simulated herbivory treatments, although only simulated herbivory induced increase of the contents of Bxs systemically. Promoter and co-expression analysis revealed that transcription factors
bHLH57
and
WRKY34
may regulate Bx biosynthesis genes in systemic leaves. Moreover, leaf ablation experiment indicated that the systemic signal rapidly exited the local leaves within 30 min after elicitation. This study provides new insight into the temporal and spatial regulation of defence responses of maize against lepidopteran insects.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
A fungal milRNA mediates epigenetic repression of a virulence gene in
Verticillium dahliae
Authors: Jin Yun , Zhao Jian-Hua , Zhao Pan , Zhang Tao , Wang Sheng , Guo Hui-Shan
Published: January 2019

MiRNAs in animals and plants play crucial roles in diverse developmental processes under both normal and stress conditions. miRNA-like small RNAs (milRNAs) identified in some fungi remain functionally uncharacterized. Here, we identified a number of milRNAs in
Verticillium dahliae
, a soil-borne fungal pathogen responsible for devastating wilt diseases in many crops. Accumulation of a
V. dahliae
milRNA1, named VdmilR1, was detected by RNA gel blotting. We show that the precursor gene
VdMILR1
is transcribed by RNA polymerase II and is able to produce the mature VdmilR1, in a process independent of
V. dahliae
DCL (Dicer-like) and AGO (Argonaute) proteins. We found that an RNaseIII domain-containing protein, VdR3, is essential for
V. dahliae
and participates in VdmilR1 biogenesis. VdmilR1 targets a hypothetical protein-coding gene,
VdHy1
, at the 3′UTR for transcriptional repression through increased histone H3K9 methylation of
VdHy1
. Pathogenicity analysis reveals that
VdHy1
is essential for fungal virulence. Together with the time difference in the expression patterns of VdmilR1 and
VdHy1
during fungal infection in cotton plants, our findings identify a novel milRNA, VdmilR1, in
V. dahliae
synthesized by a noncanonical pathway that plays a regulatory role in pathogenicity and uncover an epigenetic mechanism for VdmilR1 in regulating a virulence target gene.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Early signalling mechanisms underlying receptor kinase-mediated immunity in plants
Authors: Zhou Zhaoyang , Zhao Yan , Bi Guozhi , Liang Xiangxiu , Zhou Jian-Min
Published: January 2019

Pattern-recognition receptors (PRRs), which are single transmembrane proteins belonging to the receptor-like kinase (RLK) and receptor-like protein (RLP) super families, sense microbe- and host-derived molecular patterns to activate immune responses in plants. PRRs associate with co-receptors, scaffold proteins and receptor-like cytoplasmic kinases (RLCKs) to form immune receptor complexes at the cell surface, allowing activation of cellular responses upon perception of extracellular ligands. Recent advances have uncovered new mechanisms by which these immune receptor complexes are regulated at the levels of composition, stability and activity. It has become clear that RLCKs are central components directly linking PRRs to multiple downstream signalling modules. Furthermore, new studies have provided important insights into the regulation of reactive oxygen species, mitogen-activated protein (MAP) kinase cascades and heterotrimeric G proteins, which has not only deepened our understanding of immunity, but also expanded our view of transmembrane signalling in general.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Rice black-streaked dwarf virus P10 suppresses protein kinase C in insect vector through changing the subcellular localization of LsRACK1
Authors: Lu Lina , Wang Qi , Huang Deqing , Xu Qiufang , Zhou Xueping , Wu Jianxiang
Published: January 2019

Rice black-streaked dwarf virus (RBSDV) was known to be transmitted by the small brown planthopper (SBPH) in a persistent, circulative and propagative manner in nature. Here, we show that RBSDV major outer capsid protein (also known as P10) suppresses the protein kinase C (PKC) activity of SBPH through interacting with the receptor for activated protein kinase C 1 (LsRACK1). The N terminal of P10 (amino acids (aa) 1–270) and C terminal of LsRACK1 (aa 268–315) were mapped as crucial for the interaction. Confocal microscopy and subcellular fractionation showed that RBSDV P10 fused to enhanced green fluorescent protein formed vesicular structures associated with endoplasmic reticulum (ER) membranes in
Spodoptera frugiperda
nine cells. Our results also indicated that RBSDV P10 retargeted the initial subcellular localization of LsRACK1 from cytoplasm and cell membrane to ER and affected the function of LsRACKs to activate PKC. Inhibition of RACK1 by double stranded RNA-induced gene silencing significantly promoted the replication of RBSDV in SBPH. In addition, the PKC pathway participates in the antivirus innate immune response of SBPH. This study highlights that RACK1 negatively regulates the accumulation of RBSDV in SBPH through activating the PKC signalling pathway, and RBSDV P10 changes the subcellular localization of LsRACK1 and affects its function to activate PKC.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Signal pathways involved in microbe–nematode interactions provide new insights into the biocontrol of plant-parasitic nematodes
Authors: Liang Lian-Ming , Zou Cheng-Gang , Xu Jianping , Zhang Ke-Qin
Published: January 2019

Plant-parasitic nematodes (PPNs) cause severe damage to agricultural crops worldwide. As most chemical nematicides have negative environmental side effects, there is a pressing need for developing efficient biocontrol methods. Nematophagous microbes, the natural enemies of nematodes, are potential biocontrol agents against PPNs. These natural enemies include both bacteria and fungi and they use diverse methods to infect and kill nematodes. For instance, nematode-trapping fungi can sense host signals and produce special trapping devices to capture nematodes, whereas endo-parasitic fungi can kill nematodes by spore adhesion and invasive growth to break the nematode cuticle. By contrast, nematophagous bacteria can secrete virulence factors to kill nematodes. In addition, some bacteria can mobilize nematode-trapping fungi to kill nematodes. In response, nematodes can also sense and defend against the microbial pathogens using strategies such as producing anti-microbial peptides regulated by the innate immunity system. Recent progresses in our understanding of the signal pathways involved in microbe–nematode interactions are providing new insights in developing efficient biological control strategies against PPNs.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management'.
Unveiling the function and regulation control of the DUF3129 family proteins in fungal infection of hosts
Authors: Huang Wei , Hong Song , Tang Guirong , Lu Yuzhen , Wang Chengshu
Published: January 2019

Many prokaryotic and eukaryotic proteins contain domains of unknown function (DUFs). A DUF3129 family of proteins is widely encoded in the genomes of fungal pathogens. A few studies in plant and insect pathogens indicated that the DUF3129 genes are required for fungal penetration of host cuticles with an unclear mechanism. We found that a varied number of DUF3129 proteins is present in different fungal species and the proteins are evolutionarily diverged from each other at the inter- and intra-specific levels. By using the insect pathogenic fungus
Metarhizium robertsii
as a model, we performed experiments and found that the seven DUF3129 proteins encoded by this fungus are localized to cellular lipid droplets (LDs). Individual deletion of these genes did not affect fungal formation of the infection structure appressoria and the accumulation of LDs in fungal conidia. When compared with the wild-type (WT) strain, insect bioassays revealed that the virulence of most null mutants were significantly impaired during topical infection but not during injection of insects. Carbon starvation and the subsequent Western blot analysis indicated that the LD-specific perilipin protein was completely degraded in the WT cells whereas varied levels of perilipin could be detected in the mutant cells, which signified that depletion of LD content was delayed in mutant cells, and DUF3129 proteins are therefore involved in LD degradation. We also provided biochemical evidence that these DUF3129 genes are transcriptionally regulated by a yeast Ste12-like transcription factor. The findings of this study not only unveil the function of DUF3129 proteins but also better understand the diverse mechanism of fungus–host interactions.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Enhancement of oxidative stress contributes to increased pathogenicity of the invasive pine wood nematode
Authors: Zhang Wei , Zhao Lilin , Zhou Jiao , Yu Haiying , Zhang Chi , Lv Yunxue , Lin Zhe , Hu Songnian , Zou Zhen , Sun Jianghua
Published: January 2019

Reactive oxygen species (ROS) play important roles in defence response of host plants versus pathogens. While generation and detoxification of ROS is well understood, how varied ability of different isolates of pathogens to overcome host ROS, or ROS contribution to a particular isolate's pathogenicity, remains largely unexplored. Here, we report that transcriptional regulation of the ROS pathway, in combination with the insulin pathway, increases the pathogenicity of invasive species
Bursaphelenchus xylophilus
. The results showed a positive correlation between fecundity and pathogenicity of different nematode isolates. The virulent isolates from introduced populations in Japan, China and Europe had significantly higher fecundity than native avirulent isolates from the USA. Increased expression of
Mn-SOD
and reduced expression of
catalase
/
GPX-5
and H
2
O
2
accumulation during invasion are associated with virulent strains. Additional H
2
O
2
could improve fecundity of
Bu. xylophilus
. Furthermore, depletion of
Mn-SOD
decreased fecundity and virulence of
Bu. xylophilus
, while the insulin pathway is significantly affected. Thus, we propose that destructive pathogenicity of
Bu. xylophilus
to pines is partly owing to upregulated fecundity modulated by the insulin pathway in association with the ROS pathway and further enhanced by H
2
O
2
oxidative stress. These findings provide a better understanding of pathogenic mechanisms in plant–pathogen interactions and adaptive evolution of invasive species.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Cross-talking between baculoviruses and host insects towards a successful infection
Authors: Wang Manli , Hu Zhihong
Published: January 2019

Baculoviridae is a family of large DNA viruses that infect insects. They have been extensively used as safe and efficient biological agents for the control of insect pests. As a result of coevolution with their hosts, baculoviruses developed unique life cycles characterized by the production of two distinctive virion phenotypes, occlusion-derived virus and budded virus, which are responsible for mediating primary infection in insect midgut epithelia and spreading systemic infection within infected insects, respectively. In this article, advances associated with virus–host interactions during the baculovirus life cycle are reviewed. We mainly focus on how baculoviruses exploit versatile strategies to overcome diverse host barriers and establish successful infections. For example, in the midgut, baculoviruses encode enzymes to degrade peritrophic membranes and use a series of
per os
infectivity factors to initiate primary infection. A viral fibroblast growth factor is expressed to attract tracheoblasts that spread the virus for systemic infection. Baculoviruses use different strategies to suppress host defence systems, including apoptosis, melanization and RNA interference. Additionally, baculoviruses can manipulate host physiology and induce ‘tree-top disease’ for optimal virus replication and dispersal. These advances in our understanding of baculoviruses will greatly inform the development of more effective baculoviral pesticides.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Genetic variants of calcium and vitamin D metabolism in kidney stone disease
Authors: Howles Sarah A. , Wiberg Akira , Goldsworthy Michelle , Bayliss Asha L. , Grout Emily , Tanikawa Chizu , Kamatani Yoichiro , Terao Chikashi , Takahashi Atsushi , Kubo Michiaki , Matsuda Koichi , Thakker Rajesh V. , Turney Benjamin W. , Furniss Dominic
Published: January 2019

Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden1,2 with a heritability of ~45-60%3. To identify genetic variants associated with nephrolithiasis we performed genome-wide association studies (GWAS) and meta-analysis in British and Japanese populations, including 12,123 nephrolithiasis cases and 416,928 controls. Twenty loci associated with nephrolithiasis were identified, ten of which are novel. A novel CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of nephrolithiasis patients the CYP24A1-associated locus correlated with serum calcium concentration and number of kidney stone episodes, and the DGKD-associated locus correlated with urinary calcium excretion. Moreover, DGKD knockdown impaired CaSR-signal transduction in vitro, an effect that was rectifiable with the calcimimetic cinacalcet. Our findings indicate that genotyping may inform risk of incident kidney stone disease prior to vitamin D supplementation and facilitate precision-medicine approaches, by targeting CaSR-signaling or vitamin D activation pathways in patients with recurrent kidney stones.
A GWAS-Derived Polygenic Score for Interleukin-1β is Associated with Hippocampal Volume in Two Samples
Authors: Avinun Reut , Nevo Adam , Knodt Annchen R. , Elliott Maxwell L. , Hariri Ahmad R.
Published: January 2019

Accumulating research suggests that the pro-inflammatory cytokine interleukin-1β (IL-1β) has a modulatory effect on the hippocampus, a brain structure important for learning and memory as well as linked with both psychiatric and neurodegenerative disorders. Here, we use an imaging genetics strategy to test an association between an IL-1β polygenic score, derived from summary statistics of a recent genome-wide association study (GWAS) of circulating cytokines, and hippocampal volume, in two independent samples. In the first sample of 512 non-Hispanic Caucasian university students (274 women, mean age 19.78 ± 1.24 years) from the Duke Neurogenetics Study, we identified a significant positive correlation between higher polygenic scores, which presumably reflect higher circulating IL-1β levels, and average hippocampal volume. This positive association was successfully replicated in a second sample of 7,960 white British volunteers (4,158 women, mean age 62.63±7.45 years) from the UK Biobank. Collectively, our results suggest that a functional GWAS-derived score of IL-1β blood circulating levels affects hippocampal volume, and lend further support in humans, to the link between IL-1β and the structure of the hippocampus.
Antitumor effects of Tv1 venom peptide in liver cancer
Authors: Anand Prachi , Filipenko Petr , Huaman Jeannette , Lyudmer Michael , Hossain Marouf , Santamaria Carolina , Huang Kelly , Ogunwobi Olorunseun O. , Holford Mandë
Published: January 2019

A strategy for treating the most common type of liver cancer, hepatocellular carcinoma (HCC) applies a targeted therapy using venom peptides that are selective for ion channels and transporters overexpressed in tumor cells. Here, we report selective anti-HCC properties of Tv1, a venom peptide from the predatory marine terebrid snail,Terebra variegata.Tv1 was appliedin vitroto liver cancer cells and administeredin vivoto allograft tumor mouse models. Tv1 inhibited the proliferation of murine HCC cells via calcium dependent apoptosis resulting from down-regulation of the cyclooxygenase-2 (COX-2) pathway. Additionally, tumor sizes were significantly reduced in Tv1-treated syngeneic tumor-bearing mice. Tv1’s mechanism of action involves binding to specific transient receptor potential (TRP) cation channels that are overexpressed in HCC cell models. Our findings demonstrate the unique potential of venom peptides to function as tumor specific ligands in the quest for targeted cancer therapies.
Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy
Authors: Ross Jacob A , Levy Yotam , Ripolone Michela , Kolb Justin S , Turmaine Mark , Holt Mark , Moggio Maurizio , Fiorillo Chiara , Lindqvist Johan , Figeac Nicolas , Zammit Peter S , Jungbluth Heinz , Vissing John , Witting Nanna , Granzier Henk , Zanoteli Edmar , Hardeman Edna C , Wallgren-Pettersson Carina , Ochala Julien
Published: January 2019

Nemaline myopathy (NM) is a genetically heterogeneous skeletal muscle disorder caused by mutations predominately affecting contractile filaments, in particular thin filament structure and/or regulation. The underlying cellular pathophysiology of this disease remains largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mice and patients with NM, including disrupted nuclear envelope, altered chromatin arrangement, and disorganisation of the cortical cytoskeleton. We demonstrate that such nuclear defects are caused by impairment of muscle fibre contractility, and that cytoskeletal organisation determines nuclear morphology. Our results overlap with findings in diseases caused by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to underlie some of the hallmarks of NM, which include broad transcriptional alterations, arrested muscle fibre growth, contractile filament disarray and altered mechanical properties.
A novel blaSIM-1-carrying megaplasmid pSIM-1-BJ01 isolated from clinical Klebsiella pneumonia
Authors: Lü Yang , Liang Hui , Zhang Wei , Liu Jia , Wang Shiwei , Hu Hongyan
Published: January 2019

A rare carbapenem-resistant gene blaSIM-1 was found in a 316-kb megaplasmid designated pSIM-1-BJ01 isolated from a clinical strain Klebsiella pneumonia 13624. The plasmid pSIM-1-BJ01 was fully sequenced and analyzed. Its length is 316,557 bp and it has 342 putative open reading frames with two multidrug-resistant regions and a total of 19 resistant genes. Its backbone was highly homologous to the newly reported plasmid pRJA166a, which was isolated from a clinical third-generation cephalosporin-resistant hypervirulen strain K. pneumonia ST23. The plasmid pSIM-1-BJ01 was verified to be able to transfer to Escherichia coli. The emergency of the transferable blaSIM-1-carrying multidrug-resistant plasmid pSIM-1-BJ01 suggests the spread of blaSIM among Enterobacteriaceae is possible. Therefore, the data presented herein provided insights into the genomic diversity and evolution of blaSIM-carrying plasmids, as well as the dissemination and epidemiology of blaSIM among Enterobacteriaceae in public health system.
Semantic Integration of Clinical Laboratory Tests from Electronic Health Records for Deep Phenotyping and Biomarker Discovery
Authors: Zhang Xingmin Aaron , Yates Amy , Vasilevsky Nicole , Gourdine JP , Carmody Leigh C. , Danis Daniel , Joachimiak Marcin P. , Ravanmehr Vida , Pfaff Emily R. , Champion James , Robasky Kimberly , Xu Hao , Fecho Karamarie , Walton Nephi A. , Zhu Richard , Ramsdill Justin , Mungall Chris , Köhler Sebastian , Haendel Melissa A. , McDonald Clem , Vreeman Daniel J. , Peden David B. , Chute Christopher G. , Robinson Peter N.
Published: January 2019

Electronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to the Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2421 commonly used laboratory tests with HPO terms. Using these annotations, a software assesses laboratory test results and converts each into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows reusing readily available laboratory tests in EHR for deep phenotyping and using the hierarchical structure of HPO for association studies with medical outcomes and genomics.

One Sentence Summary

We present an approach to semantically integrating LOINC-encoded laboratory data with the Human Phenotype Ontology and show that the integrated LOINC data can be used to identify biomarkers for asthma from electronic health record data.
A brainstem-central amygdala circuit underlies defensive responses to learned threats
Authors: Gu Yiran , Vazey Elena M. , Aston-Jones Gary , Lin Longnian , LeDoux Joseph E. , Sears Robert M
Published: January 2019

Norepinephrine (NE) plays a central role in the acquisition of aversive learning via actions in the lateral nucleus of the amygdala (LA)1,2. However, the function of NE in expression of aversively-conditioned responses has not been established. Given the role of the central nucleus of the amygdala (CeA) in the expression of such behaviors3, and the presence of NE projections in this brain nucleus, we assessed the effects of NE activity in the CeA on behavioral expression using receptor-specific pharmacology and cell-and projection-specific chemogenetic manipulations. We found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively. We then show that locally inhibiting or activating LC terminals in CeA is sufficient to achieve this bidirectional modulation of defensive reactions. These findings support the hypothesis that LC projections to CeA are required for the expression of defensive responses elicited by conditioned threats.
Olfactory Co-Stimulation Influences Intranasal Somatosensory Perception
Authors: Karunanayaka Prasanna R. , Lu Jiaming , Yang Qing X. , Sathian K.
Published: January 2019

Olfactory sensitivity is influenced by intranasal trigeminal sensation. For instance, sniffing is central to how humans and animals perceive odorants. Here, we investigated the influence of olfactory co-stimulation on the perception of intranasal somatosensory stimulation. In this study, twenty-two healthy human subjects, with normal olfactory function, performed a localization task for weak air-puff stimuli, in the presence or absence of a pure odorant, phenyl ethyl alcohol (PEA; rose odor). Visual cues were used to inform participants to briefly hold their breath while weak, poorly localizable, air-puffs and/or PEA were delivered to either nostril. Although PEA alone could not be localized, when accompanied by a weak air-puff in the ipsilateral nostril, localization accuracy significantly improved, relative to presentation of the air-puff without the odorant. The enhancement of localization was absent when the air-puff and PEA were presented to opposite nostril. Since ipsilateral but not contralateral co-stimulation with PEA increased the accuracy of weak air-puff localization, the results argue against a non-specific alerting effect of PEA. These findings suggest an interaction between the olfactory and somatosensory trigeminal systems.
Memory-driven computing accelerates genomic data processing
Authors: Becker Matthias , Chabbi Milind , Warnat-Herresthal Stefanie , Klee Kathrin , Schulte-Schrepping Jonas , Biernat Pawel , Günther Patrick , Baβler Kevin , Craig Rocky , Schultze Hartmut , Singhal Sharad , Ulas Thomas , Schultze Joachim L.
Published: January 2019

Next generation sequencing (NGS) is the driving force behind precision medicine and is revolutionizing most, if not all, areas of the life sciences. Particularly when targeting the major common diseases, an exponential growth of NGS data is foreseen for the next decades. This enormous increase of NGS data and the need to process the data quickly for real-world applications requires to rethink our current compute infrastructures. Here we provide evidence that memory-driven computing (MDC), a novel memory-centric hardware architecture, is an attractive alternative to current processor-centric compute infrastructures. To illustrate how MDC can change NGS data handling, we used RNA-seq assembly and pseudoalignment followed by quantification as two first examples. Adapting transcriptome assembly pipelines for MDC reduced compute time by 5.9-fold for the first step (SAMtools). Even more impressive, pseudoalignment by near-optimal probabilistic RNA-seq quantification (kallisto) was accelerated by more than two orders of magnitude with identical accuracy and indicated 66% reduced energy consumption. One billion RNA-seq reads were processed in just 92 seconds. Clearly, MDC simultaneously reduces data processing time and energy consumption. Together with the MDC-inherent solutions for local data privacy, a new compute model can be projected pushing large scale NGS data processing and primary data analytics closer to the edge by directly combining high-end sequencers with local MDC, thereby also reducing movement of large raw data to central cloud storage. We further envision that other data-rich areas will similarly benefit from this new memory-centric compute architecture.