bluuebunny/crossref_metadata_2025 huggingface dataset:
VDJbase: an adaptive immune receptor genotype and haplotype database
Authors: Omer Aviv , Shemesh Or , Peres Ayelet , Polak Pazit , Shepherd Adrian J , Watson Corey T , Boyd Scott D , Collins Andrew M , Lees William , Yaari Gur
Published: October 2019

VDJbase is a publicly available database that offers easy searching of data describing the complete sets of gene sequences (genotypes and haplotypes) inferred from adaptive immune receptor repertoire sequencing datasets. VDJbase is designed to act as a resource that will allow the scientific community to explore the genetic variability of the immunoglobulin (Ig) and T cell receptor (TR) gene loci. It can also assist in the investigation of Ig- and TR-related genetic predispositions to diseases. Our database includes web-based query and online tools to assist in visualization and analysis of the genotype and haplotype data. It enables users to detect those alleles and genes that are significantly over-represented in a particular population, in terms of genotype, haplotype and gene expression. The database website can be freely accessed at https://www.vdjbase.org/, and no login is required. The data and code use creative common licenses and are freely downloadable from https://bitbucket.org/account/user/yaarilab/projects/GPHP.
APAatlas: decoding alternative polyadenylation across human tissues
Authors: Hong Wei , Ruan Hang , Zhang Zhao , Ye Youqiong , Liu Yaoming , Li Shengli , Jing Ying , Zhang Huiwen , Diao Lixia , Liang Han , Han Leng
Published: September 2019

Alternative polyadenylation (APA) is an RNA-processing mechanism on the 3′ terminus that generates distinct isoforms of mRNAs and/or other RNA polymerase II transcripts with different 3′UTR lengths. Widespread APA affects post-transcriptional gene regulation in mRNA translation, stability, and localization, and exhibits strong tissue specificity. However, no existing database provides comprehensive information about APA events in a large number of human normal tissues. Using the RNA-seq data from the Genotype-Tissue Expression project, we systematically identified APA events from 9475 samples across 53 human tissues and examined their associations with multiple traits and gene expression across tissues. We further developed APAatlas, a user-friendly database (https://hanlab.uth.edu/apa/) for searching, browsing and downloading related information. APAatlas will help the biomedical research community elucidate the functions and mechanisms of APA events in human tissues.
DNAproDB: an expanded database and web-based tool for structural analysis of DNA–protein complexes
Authors: Sagendorf Jared M , Markarian Nicholas , Berman Helen M , Rohs Remo
Published: October 2019

DNAproDB (https://dnaprodb.usc.edu) is a web-based database and structural analysis tool that offers a combination of data visualization, data processing and search functionality that improves the speed and ease with which researchers can analyze, access and visualize structural data of DNA–protein complexes. In this paper, we report significant improvements made to DNAproDB since its initial release. DNAproDB now supports any DNA secondary structure from typical B-form DNA to single-stranded DNA to G-quadruplexes. We have updated the structure of our data files to support complex DNA conformations, multiple DNA–protein complexes within a DNAproDB entry and model indexing for analysis of ensemble data. Support for chemically modified residues and nucleotides has been significantly improved along with the addition of new structural features, improved structural moiety assignment and use of more sequence-based annotations. We have redesigned our report pages and search forms to support these enhancements, and the DNAproDB website has been improved to be more responsive and user-friendly. DNAproDB is now integrated with the Nucleic Acid Database, and we have increased our coverage of available Protein Data Bank entries. Our database now contains 95% of all available DNA–protein complexes, making our tools for analysis of these structures accessible to a broad community.
A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes
Authors: Mostajo Nelly F , Lataretu Marie , Krautwurst Sebastian , Mock Florian , Desirò Daniel , Lamkiewicz Kevin , Collatz Maximilian , Schoen Andreas , Weber Friedemann , Marz Manja , Hölzer Martin
Published: October 2019

Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.
Charitable giving when donors are constrained to give a minimum amount
Authors: Cartwright Edward J , Mirza Zarak
Published: October 2019

In some instances charities insist on donors giving more than a minimum amount. In other instances charities frame appeals for funds in a way that suggests there is a minimum donation. So, what are the effects on charitable giving if a minimum donation is required? We first provide a simple theoretical model that shows the effects are ambiguous. We then report the results of two lab experiments that consider very different settings. In the first experiment the only incentive to give is intrinsic motivation. Here we find that a minimum constraint lowers giving. The second experiment involves group interaction with extrinsic incentives to give. Here we find that a minimum constraint increases giving. Our results suggest that the effects of a minimum constraint may depend critically on the mix of intrinsic and extrinsic incentives.
Establishment of xenografts of urological cancers on chicken chorioallantoic membrane (CAM) to study metastasis
Authors: Hu Junhui , Ishihara Moe , Chin Arnold I , Wu Lily
Published: October 2019

Cancer of the urological system commonly occurs in the kidney, bladder, and prostate gland. The clear cell subtype of renal cell carcinoma (ccRCC) constitutes the great majority of kidney cancer. Metastatic ccRCC portends a very poor outcome with no effective treatment available. Prostate cancer is the most common cancer in males in the US. Despite recent advances in selective kinase inhibitors and immunotherapies, the rate of developing new treatment from bench to bedside is slow. A time-consuming step is at the animal drug testing stage, in which the mouse model is the gold standard. In the pursuit to streamline the in vivo cancer biology research and drug development, we explored the feasibility of the chicken chorioallantoic membrane (CAM) model to establish xenografts. The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice. We generated CAM xenografts from ccRCC, bladder and prostate cancer, with established cancer cell lines and freshly isolated patient-derived tissues, either as primary tumor cells or small pieces of tumors. The successful CAM engraftment rate from the different tumor sources is 70% or above. Using our previously established metastatic ccRCC mouse model, we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice. Taken together, CAM can serve as a valuable platform to establish new patient-derived xenografts (PDXs) to study tumor biology, thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.
Interaction among inflammasome, autophagy and non-coding RNAs: new horizons for drug
Authors: Pu Qinqin , Lin Ping , Wang Zhihan , Gao Pan , Qin Shugang , Cui Luqing , Wu Min
Published: October 2019

Autophagy and inflammasomes are shown to interact in various situations including infectious disease, cancer, diabetes and neurodegeneration. Since multiple layers of molecular regulators contribute to the interplay between autophagy and inflammasome activation, the detail of such interplay remains largely unknown. Non-coding RNAs (ncRNAs), which have been implicated in regulating an expanding list of cellular processes including immune defense against pathogens and inflammatory response in cancer and metabolic diseases, may join in the crosstalk between inflammasomes and autophagy in physiological or disease conditions. In this review, we summarize the latest research on the interlink among ncRNAs, inflammasomes and autophagy and discuss the emerging role of these three in multiple signaling transduction pathways involved in clinical conditions. By analyzing these intriguing interconnections, we hope to unveil the mechanism inter-regulating these multiple processes and ultimately discover potential drug targets for some refractory diseases.
Opioid Exposure Negatively Affects Antidepressant Response to Venlafaxine in Older Adults with Chronic Low Back Pain and Depression
Authors: Stahl Sarah T , Jung Changgi , Weiner Debra K , Peciña Marta , Karp Jordan F
Published: October 2019

Objective

Serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly co-prescribed with opioids for chronic pain. The purpose of this study was to describe pain and mood response to venlafaxine among older adults with chronic low back pain (CLBP) and depression relative to opioid exposure.

Design

Secondary analyses were collected from a randomized clinical trial testing a stepped-care approach to comorbid pain and depression in older patients: the Addressing Depression and Pain Together study (ADAPT: 2010–2016).

Setting

University-based late-life mental health research clinic.

Subjects

Two hundred twenty-seven adults aged 65+ years with CLBP and depression.

Methods

Participants received six weeks of lower-dose venlafaxine (≤150 mg/d). Pain and depression were measured each week. Response for both pain and depression at the end of six weeks was defined by a ≥30% improvement on a 0–20 numeric rating scale for low back pain and a Patient Health Questionnaire-9 score ≤5. Opioid exposure was analyzed as prescribed (yes or no) and by morphine equivalent dosing (MED).

Results

Patients co-prescribed an opioid were less likely to report a pain response to venlafaxine. MED was negatively correlated with pain response. Depression response was not impacted.

Conclusions

Opioids are negatively associated with older adults’ early analgesic response to lower-dose venlafaxine. These findings suggest that clinicians may wish to consider either nonopioid or alternative antidepressant approaches to pain management in these complex patients. It is reassuring that opioids do not prevent depression response. Future research should examine both longer duration of treatment and a wider range of doses.
NICE UpdateNICE public health guidance update
Authors: Winchester Sarah , Haynes Charlotte , Owen Lesley , Leng Gillian
Published: October 2019

This article covers recent National Institute for Health and Care Excellence guidance and standards relevant to public health with a focus on behaviour change. The article summarizes recommendations for local commissioners and providers to help them tackle a range of behaviours including smoking, poor eating patterns, lack of physical activity and alcohol misuse.
P35 Prevalence of chronic kidney disease in patients with juvenile systemic lupus erythematosus: a single centre study
Authors: Mahfouz Yasmin , Madenidou Anastasia-Vasiliki , Ciurtin Coziana
Published: September 2019

Background

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disorder that can affect any organ system. An estimated 10- 20% of all patients with SLE develop clinical disease before the age of 16 years and are therefore classified as juvenile-onset SLE (JSLE). JSLE is characterised by more severe clinical manifestations, such as lupus nephritis, more complications and less favourable outcomes compared to adult-onset SLE. Chronic kidney disease (CKD) refers to a state of irreversible kidney damage and/or reduction of kidney function that is associated with progressive loss of function over time. Lupus nephritis does not always lead to CKD. However, when it does it is associated with increased morbidity and mortality. It is important to identify clinical and laboratory predictors of CKD development in JSLE patients, as a more aggressive treatment approach could be advocated for these patients. In this study we compared the baseline characteristics of JSLE patients with and without chronic kidney disease to ascertain if there are any significant differences between the two groups.

Methods

This is a single-centre retrospective study, who included patients reviewed in our young adult and adolescent clinics. All data were analysed descriptively. Mann-Whitney U or Chi-Square tests were performed to compare the characteristics between the patients with and without CKD. We used the Pearson’s (r) or Kendall’s τ (tau) correlation to examine if there is any association between the CKD and the baseline characteristics.

Results

We identified 44 JSLE patients, out of which 17 (39%) fulfilled the diagnostic criteria for CKD at their last clinical review. The stages of CKD varied from 2 to 5. All patients with CKD also had lupus nephritis, while 5/44 patients (11%) had lupus nephritis without CKD. There were statistical significant differences in the treatments used for patients with and without CKD. As expected, the highest dsDNAlevels were higher in patients with CKD (p = 0.03). There was also a positive moderate correlation (ρ = 0.32) between raised levels of dsDNAand the development of CKD (p = 0.008). We also found a negative moderate correlation (τ= -0.439) between the presence of RF and CKD (p = 0.04).

Conclusion

We found a negative moderate correlation between the presence of RF and CKD, which has also been reported in the literature before. Further research using a large JSLE cohort is suggested to explore further if RF exerts a protective effect against renal disease in SLE. dsDNA is a serological marker of lupus nephritis and it is reasonable that the highest dsDNA correlates with CKD.

Conflicts of Interest

The authors declare no conflicts of interest.
P62 Getting to know you: a quality improvement project designed to enhance paediatric inpatient rehabilitation for those with non-inflammatory musculoskeletal pain
Authors: McKenna Dearbhla , Rooney Madeline , Jackson Paul , Harkness Cathyrn
Published: October 2019

Background

In November 2018 the paediatric rheumatology team in Belfast attended the Bridges self-management course. Bridges reflects on what works well as a team and how you can build upon current practice, with an emphasis upon a self-management approach. There are eleven Bridges principles aiming to help interdisciplinary team’s co-ordinate their service around the patient. Bridges believes that the language we use can improve our clinical practice, especially with regards to problem solving, encouraging self-discovery, encouraging patients to reflect and enabling them to take action.

Our team felt that we should use this approach to enhance our inpatient rehabilitation service. We chose this group of patients as we felt that this can be a challenging group to treat and it can take a long time to build supportive and trusting relationships.

Methods

Prior to commencing this project each member of the multidisciplinary team assessed the patient individually on the first day of admission. In retrospect we discovered that this led to repetition for the patient and this assessment was very clinician led. It also focused on clinician led (SMART) goals and achieving these. We furthermore realised we did not separately ask patients and parents what they wanted to gain from our service.

Our method of improvement was to devise three questionnaires. One for a parent, one for a child under fourteen and over fourteen. These are distributed prior to being assessed by the team, allowing us to gather information and negating the need for repetition. The questionnaire gathers information regarding family members, education, school attendance, additional educational assistance, past medical history. For the patient we ask, what are their main concerns, what has helped so far, what support the patient has, what activities they enjoy as a family and what they hope to gain from their inpatient stay. The patient must fill out a description of their typical day, including their mood. Questions specifically for the parents are asking why their child has been referred, what their main concerns are, to outline their typical day, what do they feel has helped and what do they aim to gain from our team.

Results

We have utilised the questionnaires for every inpatient since January 2019. All team members feel that this new approach allows us to gain valuable information from patients and their parents thus encouraging them to adopt a self-management approach and to prioritise the patient’s story. As a team we feel that we learn a lot about our patients using this method and that it is more time effective. It allows us to identify unrealistic hopes and discuss these.

Conclusion

We believe that using the Bridges approach and by mainly adapting our language skills and organisation we have improved this service.

Conflicts of Interest

The authors declare no conflicts of interest.
Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study
Authors: Jaeger Veronika K , Tikly Mohammed , Xu Dong , Siegert Elise , Hachulla Eric , Airò Paolo , Valentini Gabriele , Matucci Cerinic Marco , Distler Oliver , Cozzi Franco , Carreira Patricia , Allanore Yannick , Müller-Ladner Ulf , Ananieva Lidia P , Balbir-Gurman Alexandra , Distler Jörg H W , Czirják Laszlo , Li Mengtao , Henes Jörg , Jimenez Sergio A , Smith Vanessa , Damjanov Nemanja , Denton Christopher P , DelGaldo Francesco , Saketkoo Lesley Ann , Walker Ulrich A ,   and EUSTAR co-authors
Published: October 2019

Objectives

Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.

Methods

SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.

Results

The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].

Conclusion

Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.
HUMAN EXPOSURE TO BACKGROUND RADIATION IN ORTUM, KENYA
Authors: Wanjala F O , Hashim N O , Otwoma D , Nyambura C , Kebwaro J , Mauring A , Bartilol J , Chege M
Published: October 2019

The activity concentration of radionuclides 238U, 232Th and 40K in soil and the absorbed dose rate (ADRA) at 1 m above the ground in Ortum was determined. The activity concentration in soils ranged from 33 to 85, 20 to 67 and 148–1019 Bq kg–1, respectively with an average of 40 ± 1.43, 56 ± 1.46 and 425 ± 19.24 Bq kg–1, respectively. The activity concentration of 232Th and 238U was found to reduce with increasing depth while that of 40K increased with increasing depth. The average activity concentration in soil was higher than the world average values. The average ADRA in air at 1 m above the ground was found to be 112 ± 29.6 nGy h–1. The soil and rocks in Ortum are recommended for use because the activity concentration of the terrestrial radionuclides is lower than the recommended threshold values.
Long-term Dextromethorphan Use and Acute Intoxication Results in an Episode of Mania and Autoenucleation
Authors: Bernstein Laura B. , Albert David , Baguer Carlos , Popiel Maryann
Published: October 2019

The pharmacologic and neuropsychiatric sequelae of long-term dextromethorphan use and acute dextromethorphan intoxication are reviewed in this case report. Dextromethorphan ingestion at the high end of toxicity, although rare, can cause violence to oneself and others, even in those previously without any history of such behaviors. In this article, the neuropsychiatric consequences of dextromethorphan toxicity are highlighted in a case report of a 37-year-old woman who had been using dextromethorphan for 5 years. She presented to a large urban emergency department in a psychotic and manic state after attempting autoenucleation. She reported to consult liaison psychiatry staff that she had taken a total of 1400 mg of dextromethorphan over the course of 3 days with intent to experience altered state of consciousness. Toxicology screens on admission did not reveal any other substances in her system. She had no formal psychiatric history and no history of mania, psychosis, or self-harm. To our knowledge, this is the first case of autoenucleation resulting from dextromethorphan-induced mania with psychotic features.
Healthcare Satisfaction and Unmet Needs Among Bereaved Parents in the NICU
Authors: Baughcum Amy E. , Fortney Christine A. , Winning Adrien M. , Dunnells Zackery D. O. , Humphrey Lisa M. , Gerhardt Cynthia A.
Published: September 2019

Background:

Learning directly from bereaved parents about their experiences in the neonatal intensive care unit (NICU) can improve services at end-of-life (EOL) care. Parents who perceive that their infant suffered may report less satisfaction with care and may be at greater risk for distress after the death. Despite calls to improve EOL care for children, limited research has examined the EOL experiences of families in the NICU.

Purpose:

We examined parent perceptions of their infant's EOL experience (eg, symptom burden and suffering) and satisfaction with care in the NICU.

Methods/Search Strategy:

Forty-two mothers and 27 fathers (representing 42 infants) participated in a mixed-methods study between 3 months and 5 years after their infant's death (mean = 39.45 months, SD = 17.19). Parents reported on healthcare satisfaction, unmet needs, and infant symptoms and suffering in the final week of life.

Findings/Results:

Parents reported high levels of healthcare satisfaction, with relative strengths in providers' technical skills and inclusion of the family. Greater perceived infant suffering was associated with lower healthcare satisfaction and fewer well-met needs at EOL. Parents' understanding of their infant's condition, emotional support, communication, symptom management, and bereavement care were identified as areas for improvement.

Implications for Practice:

Parents value comprehensive, family-centered care in the NICU. Additionally, monitoring and alleviating infant symptoms contribute to greater parental satisfaction with care. Improving staff knowledge about EOL care and developing structured bereavement follow-up programs may enhance healthcare satisfaction and family outcomes.

Implications for Research:

Prospective studies are needed to better understand parental perceptions of EOL care and the influence on later parental adjustment.
Number (of Whom?) Needed to Treat (with What?)
Authors: Westreich Daniel , Mooney Stephen J.
Published: October 2019

The number needed to treat (NNT) is a widely used measure of the potential impact of a treatment or intervention, but it is often calculated and discussed in ways which oversimplify critical issues. Specifically, the NNT itself depends on the population under study and the specific form that “treatment” would take in that population. We discuss how understanding the difference between the effect of removing a harmful exposure and the effect of deploying a specific intervention to remove that harmful exposure can affect the calculation and interpretation of an NNT. Our discussion extends a previously described framework distinguishing exposure effects from population intervention effects.
A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort
Authors: Lin Yuan , Zhu Yeyi , Wu Jing , Hinkle Stefanie N. , Rawal Shristi , Han Jiali , Weir Natalie L. , Tsai Michael Y. , Zhang Cuilin
Published: October 2019

Background:

Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown.

Methods:

We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case–control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10–14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors.

Results:

Overall, TL was not significantly associated with GDM risk. The TL–GDM association was significantly modified by age (P
interaction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years.

Conclusion:

Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.
Delayed Hypersensitivity Reaction after Nipple Tattooing: A Novel Case Report
Authors: Joseph Walter J. , Roy Eva , Stofman Guy M.
Published: October 2019

We present a patient who underwent bilateral 3-dimensional (3D) nipple tattooing for nipple areolar reconstruction after implant-based breast reconstruction for breast cancer. Several weeks after nipple tattooing, the patient developed a delayed hypersensitivity reaction around both of her tattooed nipple areolar complexes. This is the first case reported in the literature of a hypersensitivity reaction from 3D nipple tattooing.
Fire Ant Punctate Keratopathy: A Novel Diagnosis Based on Clinical and Anterior Segment Optical Coherence Tomography Findings
Authors: Patael Yael Yohai , Segal Ori , Segev Fani
Published: September 2019

Purpose:

To describe the ocular findings and the long-term outcomes of patients diagnosed with corneal injury due to little fire ants (LFAs).

Methods:

This is a retrospective case series of patients evaluated with corneal injury due to LFAs from October 2015 to January 2018 at the Cornea Clinic in Meir Medical Center. Patients underwent anterior segment optical coherence tomography (AS-OCT) imaging during the follow-up.

Results:

Four patients reported ocular contact with LFAs and presented to our department with unilateral, scattered, small, dense, round, bright white opacities in the anterior corneal stroma, which remained unchanged in appearance over time, despite topical antibiotic and steroid treatment. No inflammatory signs were noted in the anterior chamber. Follow-up was performed clinically using AS-OCT for periods of 9 to 26 months after the incidents. AS-OCT findings demonstrated small, subepithelial, hyperreflective foci at the level of the anterior stroma to a depth of 145 to 250 μm, with posterior shadowing that remained unchanged over time. These findings were well-correlated with biomicroscopy findings.

Conclusions:

LFA bites can cause long-lasting corneal injury in humans with characteristic clinical biomicroscopic findings. The corneal lesions do not respond to conventional topical treatment. AS-OCT imaging can be a useful modality for diagnosis and follow-up. Awareness by both patients and ophthalmologists of this clinical entity may be helpful in diagnosis and management.
Upregulation of cortical GABAA receptor concentration in fibromyalgia
Authors: Pomares Florence B. , Roy Steve , Funck Thomas , Feier Natasha A. , Thiel Alexander , Fitzcharles Mary-Ann , Schweinhardt Petra
Published: September 2019

An imbalance between excitatory and inhibitory neurotransmission has been linked to fibromyalgia (FM). Magnetic resonance spectroscopy has shown increased levels of glutamate in the insula and posterior cingulate cortex in FM as well as reduced insular levels of gamma-aminobutyric acid (GABA). Both of these changes have been associated with increased pain sensitivity. However, it is not clear whether excitatory and/or inhibitory neurotransmission is altered across the brain. Therefore, the aim of this study was to quantify GABAA receptor concentration on the whole brain level in FM to investigate a potential dysregulation of the GABAergic system. Fifty-one postmenopausal women (26 FM, 25 matched controls) underwent assessments of pain sensitivity, attention and memory, psychological status and function, as well as positron emission tomography imaging using a tracer for GABAA receptors, [18F]flumazenil. Patients showed increased pain sensitivity, impaired immediate memory, and increased cortical GABAA receptor concentration in the attention and default-mode networks. No decrease of GABAA receptor concentration was observed. Across the 2 groups, GABAA receptor concentration correlated positively with functional scores and current pain in areas overlapping with regions of increased GABAA receptor concentration. This study shows increased GABAA receptor concentration in FM, associated with pain symptoms and impaired function. The changes were widespread and not restricted to pain-processing regions. These findings suggest that the GABAergic system is altered, possibly indicating an imbalance between excitatory and inhibitory neurotransmission. Future studies should try to understand the nature of the dysregulation of the GABAergic system in FM and in other pain syndromes.
Two successful insertions of peripherally inserted central catheters in a patient with persistent left superior vena cava
Authors: Kang Junren , Liu Bing , Sun Wenyan
Published: October 2019

Rationale:

Peripherally inserted central catheters (PICC), normally located at the lower 1/3rd of the superior vena cava (SVC) and cavo-atrial junction, are commonly used in cancer patients. Persistent left superior vena cava (PLSVC) is a vascular anomaly, in patients with which seldom research was reported about PICC implanted. After obtaining written informed consent, we present a case where two successful insertions of PICC were performed in a 50-year-old female patient with PLSVC and right SVC.

Patients concerns:

The patient had ovarian cancer and was admitted for chemotherapy using PICC.

Diagnoses:

Ovarian cancer and PLSVC.

Interventions and Outcomes:

Following insertion of PICC in PLSVC, thrombosis developed. PICC was removed after routine anticoagulation therapy. Owing to tumor recurrence, a second PICC was inserted in the right SVC without any complications.

Lessons:

PICC insertion in PLSVC for chemotherapy may be associated with an increased risk of deep venous thrombosis of the upper extremity. A right catheter insertion in patient with PLSVC was preferred.
Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility
Authors: Zhang Yijian , Zhang Junxin , Liu Hao , He Fan , Chen Angela , Yang Huilin , Pi Bin
Published: October 2019

Background

Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS.

Methods

Pubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS.

Results

A total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians.

Conclusion

FOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies.

Level of evidence

Level III diagnostic study.
Inclusion of Nursing Homes and Long-term Residents in Medicare ACOs
Authors: Chang Chiang-Hua , Mainor Alexander , Raymond Stephanie , Peck Kristen , Colla Carrie , Bynum Julie
Published: September 2019

Background:

Long-term nursing home residents have complex needs that often require services from acute care settings. The accountable care organization (ACO) model provides an opportunity to improve care by creating payment incentives for more coordinated, higher quality care.

Objectives:

To assess the extent of nursing home participation in ACOs, and the characteristics of residents and their nursing homes connected to ACOs.

Research Design:

This was a cross-sectional study.

Subjects:

Medicare nursing home residents identified from 2014 Minimum Data Set assessments. Residents were attributed to ACOs based on Medicare methods.

Measures:

Individuals’ demographics, clinical characteristics, health care utilization, and nursing home characteristics.

Results:

Among 660,780 nursing home residents, a quarter of them were attributed to ACOs. ACO residents had only small differences from non-ACO residents: age 85 years and older (47.1% vs. 45.3%), % black (10.5% vs. 12.7%), % dual eligible (74.3% vs. 75.8%), and emergency department visits (55.1 vs. 57.3 per 100). Of the 14,868 nursing homes with study residents, few were ACO providers (N=222, 1.6% of total residents) yet many had at least one ACO resident (N=8077, 76.4% of total residents); one-fifth had at least 20 (N=2839, 33.4% of total residents). ACO-provider homes were more likely than other homes to have a 5-star rating, be hospital-based and have Medicare as the primary payer.

Conclusions:

With a quarter of long-term nursing home residents attributed to an ACO, and one-fifth of nursing homes caring for a large number of ACO residents, outcomes and spending in this setting are important for ACOs to consider when designing patient care strategies.
Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan
Authors: Rashid Muhammad U. , Naeemi Humaira , Qazi Abid Q. , Muhammad Noor , Ahmad Mansoor , Akhtar Noreen , Rahman Nazneen
Published: October 2019

Background and Aim:

Wilms tumor (WT) is the most common childhood malignant renal tumor. Germline mutations in several WT predisposition genes have been identified. However, the fundamental cause of most WT patients remains unexplained. Recently, a founder mutation, c.1060C>T (p. Arg254X) in a mitotic spindle checkpoint gene, TRIP13, was reported in 5 unrelated children with WT from the United Kingdom, of Pakistani descent from Azad Kashmir region. This observation suggests other children with WT in Pakistan may also harbor this mutation. We conducted the first study to assess the contribution of TRIP13 c.1060C>T mutation to WT in Pakistan.

Materials and Methods:

Constitutional genomic DNA from 68 Pakistani individuals including unrelated WT cases (n=26) and one (n=10) or both (n=32) of their parent(s) were screened for the TRIP13 c.1060C>T mutation using DNA sequence analysis. We also included positive controls in the analyses.

Results:

The median age of WT diagnosis was 3.0 years (range, 0.75 to 10). The TRIP13 c.1060C>T mutation was not found in any WT patient (n=26) or their parents (n=42). Twenty-four patients (92.4%) presented with unilateral tumor and 2 patients (7.7%) were diagnosed with synchronous bilateral WT. Thirteen patients (50%) reported parental consanguinity. Thirteen patients (50.0%) belonged to the Punjabi ethnicity and 1 patient (3.8%) had a Kashmiri background. Four patients (16.7%) reported a family history of WT or other malignancies. The predominant histologic subtype was stromal (46.2%). The majority of patients presented with >5 cm of tumor size (81%). None of the patients had a personal or family history of congenital anomalies, or associated genetic syndromes.

Conclusions:

Our findings suggest that TRIP13 c.1060C>T mutation may be infrequent in Pakistani WT cases. Further evaluation of this mutation in a large number of WT patients of Kashmiri heritage and various ethnic backgrounds from Pakistan is warranted.
Buprenorphine Use in Palliative Care
Authors: Jones Katie Fitzgerald
Published: October 2019

Palliative care is encountering an increasing number of patients with opioid use disorder who are managed on medication-assisted treatment. Buprenorphine is US Food and Drug Administration approved for office-based management of opioid use disorder. As a partial opioid agonist, it can be used to manage pain in the palliative care setting but can also pose inherent challenges to the management of pain that necessitates full opioid agonists. This article uses a case example to highlight the management of substance use disorder and pain in a patient on buprenorphine along the full illness trajectory. In addition, an overview of buprenorphine pharmacology, unique aspects of the prescribing waiver, and pain management will be discussed.
Disease-Related Worries in Persons With Crohn Disease
Authors: Wåhlin Monica , Stjernman Henrik , Munck Berit
Published: October 2019

Crohn disease, a chronic inflammatory bowel disease, affects everyday life, impairs quality of life, and creates worries. This study explored disease-related worries in persons with Crohn disease to gain deeper insight into how this worry is experienced and handled. Eight women and 4 men with Crohn disease who reported their disease-related worries as high or very high in a questionnaire were interviewed. The interviews were evaluated by qualitative content analysis, generating 3 categories: worries about the disease itself; feelings related to the worries; and management of the worries. The unpredictable course of the disease, impaired function due to fatigue, and lack of bowel control were the most prominent causes of worry. The worries created feelings of stress, guilt, and frustration. The participants expressed a need to talk about their worries, to make them visible and recognized, and to be understood. The participants found individual ways to handle the worries. Actively gaining control by changing focus, performing relaxation exercises, and seeking information were important self-care strategies. In addition, a strong and partially unmet need for expressing and venting concerns to one's caregiver was identified.
Integrin α6β4 signaling switches DNA repair from homologous recombination to non-homologous end-joining pathway to sensitize breast cancer cells to cisplatin
Authors: Chen Min , Marrs Brock , Qi Lei , Knifley Teresa , Jarrett Stuart G. , Weiss Heidi L. , Stewart Rachel L. , D’Orazio John A. , O’Connor Kathleen L.
Published: September 2019

Integrin α6β4 is highly expressed in triple negative breast cancer (TNBC) and drives aggressiveness by stimulating proliferation, angiogenesis, cell migration, invasion and metastasis. Signaling from this integrin stimulates DNA repair and apoptosis resistance, suggesting that it could contribute to therapeutic resistance. Upon testing this hypothesis, we found that integrin α6β4 signaling promoted a three-fold greater sensitivity to cisplatin but exhibited no difference in response to other chemotherapies tested. Mechanistic investigations revealed that integrin α6β4 stimulated quicker and higher amplitude of activation of ATM, Chk2, p53, and 53BP1, which required the integrin β4 signaling domain. Genetic manipulation of gene expression demonstrated that mutant p53 cooperated with integrin α6β4 for cisplatin sensitivity and was necessary for downstream phosphorylation of 53BP1 and enhanced ATM activation. Additionally, we discovered that integrin α6β4 preferentially activated DNA-PKc in response to cisplatin, which led to formation of DNA-PKc-p53 complexes and 53BP1 activation. As a result, integrin α6β4 shifted double strand break repair from homologous recombination (HR) to non-homologous end joining (NHEJ). In summary, we discovered a novel function of integrin α6β4 in switching DSB repair from HR to NHEJ that results in cisplatin sensitivity in TNBC.
Neural reinstatement guides context-dependent emotional memory retrieval
Authors: Hennings Augustin C. , McClay Mason , Lewis-Peacock Jarrod A. , Dunsmoor Joseph E.
Published: October 2019

Reactivating the memory of a context improves retrieval of information learned in that context. But does context reactivation resolve memory competition between related but conflicting emotional experiences? Here, we asked whether spontaneously retrieved episodic context disambiguates competing memories of fear and safety in the healthy brain and in posttraumatic stress disorder. During fMRI, subjects learned that items from an object category were a threat, and then learned that different items from the same category were safe in a unique context. The next day, subjects viewed new threat ambiguous stimuli from the same category and reported their expectation of threat. Multivoxel pattern analysis (MVPA) was used to identify and decode neural patterns unique to the context of safety learning. We show that in healthy adults the degree of neural reinstatement of the safe context predicted activity to threat ambiguous stimuli in the ventromedial prefrontal cortex (vmPFC) and hippocampus, regions important for contextual modulation of emotional memory retrieval. The degree of context reinstatement also disambiguated subjects’ feelings of threat versus safety. In contrast, context reinstatement did not resolve emotional memory retrieval in subjects with PTSD, indicating a contextual processing deficit in this group. Finally, multivoxel pattern similarity between safe and threat ambiguous stimuli overlapped in the vmPFC in healthy adults but not in PTSD. These findings reveal how neural reinstatement helps resolve context-dependent memory retrieval between opposing sources of emotional information. Understanding how the human brain separately encodes and retrieves competing memories of related events has broad implications for the study of emotional memory, associative learning, and the neuropathophysiology of affective disorders.
ITC and SPR Analysis Using Dynamic Approach
Authors: Krishnamoorthy Ganesh Kumar , Alluvada Prashanth , Hameed Shahul , Kwa Timothy , Krishnamoorthy Janarthanan
Published: October 2019

Biophysical techniques such as Isothermal Calorimetry (ITC) and Surface Plasmon Resonance (SPR) are routinely used to ascertain the global binding mechanisms of protein-protein or protein-ligand interaction. Recently, Dumas etal, have explicitly modelled the instrument response of the ligand dilution and analysed the ITC thermogram to obtain kinetic rate constants. Adopting a similar approach, we have integrated the dynamic instrument response with the binding mechanism to simulate the ITC profiles of equivalent and independent binding sites, equivalent and sequential binding sites and aggregating systems. The results were benchmarked against the standard commercial software Origin-ITC. Further, the experimental ITC chromatograms of 2’-CMP + RNASE and BH3I-1 + hBCLXLinteractions were analysed and shown to be comparable with that of the conventional analysis. Dynamic approach was applied to simulate the SPR profiles of a two-state model, and could reproduce the experimental profile accurately.
Ways to unwind with HROB, a new player in homologous recombination
Authors: Saredi Giulia , Rouse John
Published: October 2019

Homologous recombination (HR) is an important route for repairing DNA double-strand breaks (DSBs). The early stages of HR are well understood, but later stages remain mysterious. In this issue of Genes & Development, Hustedt and colleagues (pp. 1397–1415) reveal HROB as a new player in HR required for recruitment of the MCM8–9 complex, which is paralogous to the MCM2–7 replicative helicase. HROB functions closely with MCM8–9 to promote postsynaptic DNA repair synthesis. This study sheds valuable light on late events in HR and suggests that HROB may load MCM8–9 onto HR intermediates to facilitate the DNA unwinding required for DNA repair synthesis.