bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate Population III stellar complex at z = 6.629 in the MUSE Deep Lensed Field
Authors: Vanzella E , Meneghetti M , Caminha G B , Castellano M , Calura F , Rosati P , Grillo C , Dijkstra M , Gronke M , Sani E , Mercurio A , Tozzi P , Nonino M , Cristiani S , Mignoli M , Pentericci L , Gilli R , Treu T , Caputi K , Cupani G , Fontana A , Grazian A , Balestra I 
Published: March 2020

ABSTRACT
We discovered a strongly lensed (μ ≳ 40) Ly α emission at z = 6.629 (S/N ≃ 18) in the MUSE Deep Lensed Field (MDLF) targeting the Hubble Frontier Field (HFF) galaxy cluster MACS J0416. Dedicated lensing simulations imply that the Ly α emitting region necessarily crosses the caustic. The arc-like shape of the Ly α extends 3 arcsec on the observed plane and is the result of two merged multiple images, each one with a de-lensed Ly α luminosity L ≲ 2.8 × 1040 erg s−1 arising from a confined region (≲150 pc effective radius). A spatially unresolved Hubble Space Telescope(HST) counterpart is barely detected at S/N ≃ 2 after stacking the near-infrared bands, corresponding to an observed (intrinsic) magnitude m1500 ≳ 30.8 (≳35.0). The inferred rest-frame Ly α equivalent width is EW0 &gt; 1120 Å if the IGM transmission is TIGM &lt; 0.5. The low luminosities and the extremely large Ly α EW0 match the case of a Population III (Pop III) star complex made of several dozens stars (∼104 M⊙) that irradiate an H ii region crossing the caustic. While the Ly α and stellar continuum are among the faintest ever observed at this redshift, the continuum and the Ly α emissions could be affected by differential magnification, possibly biasing the EW0 estimate. The aforementioned tentative HST detection tends to favour a large EW0, making such a faint Pop III candidate a key target for the James Webb Space Telescope and Extremely Large Telescopes.
Chimeric siRNAs with chemically modified pentofuranose and hexopyranose nucleotides: altritol-nucleotide (ANA) containing GalNAc–siRNA conjugates: in vitro and in vivo RNAi activity and resistance to 5′-exonuclease
Authors: Kumar Pawan , Degaonkar Rohan , Guenther Dale C , Abramov Mikhail , Schepers Guy , Capobianco Marie , Jiang Yongfeng , Harp Joel , Kaittanis Charalambos , Janas Maja M , Castoreno Adam , Zlatev Ivan , Schlegel Mark K , Herdewijn Piet , Egli Martin , Manoharan Muthiah 
Published: March 2020

Abstract
In this report, we investigated the hexopyranose chemical modification Altriol Nucleic Acid (ANA) within small interfering RNA (siRNA) duplexes that were otherwise fully modified with the 2′-deoxy-2′-fluoro and 2′-O-methyl pentofuranose chemical modifications. The siRNAs were designed to silence the transthyretin (Ttr) gene and were conjugated to a trivalent N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. Sense and antisense strands of the parent duplex were synthesized with single ANA residues at each position on the strand, and the resulting siRNAs were evaluated for their ability to inhibit Ttr mRNA expression in vitro. Although ANA residues were detrimental at the 5′ end of the antisense strand, the siRNAs with ANA at position 6 or 7 in the seed region had activity comparable to the parent. The siRNA with ANA at position 7 in the seed region was active in a mouse model. An Oligonucleotide with ANA at the 5′ end was more stable in the presence of 5′-exonuclease than an oligonucleotide of the same sequence and chemical composition without the ANA modification. Modeling studies provide insight into the origins of regiospecific changes in potency of siRNAs and the increased protection against 5′-exonuclease degradation afforded by the ANA modification.
Mechanisms of palmitic acid-conjugated antisense oligonucleotide distribution in mice
Authors: Chappell Alfred E , Gaus Hans J , Berdeja Andres , Gupta Ruchi , Jo Minji , Prakash Thazha P , Oestergaard Michael , Swayze Eric E , Seth Punit P 
Published: March 2020

AbstractConjugation of antisense oligonucleotide (ASO) with a variety of distinct lipophilic moieties like fatty acids and cholesterol increases ASO accumulation and activity in multiple tissues. While lipid conjugation increases tissue exposure in mice and reduces excretion of ASO in urine, histological review of skeletal and cardiac muscle indicates that the increased tissue accumulation of lipid conjugated ASO is isolated to the interstitium. Administration of palmitic acid-conjugated ASO (Palm-ASO) in mice results in a rapid and substantial accumulation in the interstitium of muscle tissue followed by relatively rapid clearance and only slight increases in intracellular accumulation in myocytes. We propose a model whereby increased affinity for lipid particles, albumin, and other plasma proteins by lipid-conjugation facilitates ASO transport across endothelial barriers into tissue interstitium. However, this increased affinity for lipid particles and plasma proteins also facilitates the transport of ASO from the interstitium to the lymph and back into circulation. The cumulative effect is only a slight (∼2-fold) increase in tissue accumulation and similar increase in ASO activity. To support this proposal, we demonstrate that the activity of lipid conjugated ASO was reduced in two mouse models with defects in endothelial transport of macromolecules: caveolin-1 knockout (Cav1−/−) and FcRn knockout (FcRn−/−).
SuperCYPsPred—a web server for the prediction of cytochrome activity
Authors: Banerjee Priyanka , Dunkel Mathias , Kemmler Emanuel , Preissner Robert 
Published: March 2020

Abstract
Cytochrome P450 enzymes (CYPs)-mediated drug metabolism influences drug pharmacokinetics and results in adverse outcomes in patients through drug–drug interactions (DDIs). Absorption, distribution, metabolism, excretion and toxicity (ADMET) issues are the leading causes for the failure of a drug in the clinical trials. As details on their metabolism are known for just half of the approved drugs, a tool for reliable prediction of CYPs specificity is needed. The SuperCYPsPred web server is currently focused on five major CYPs isoenzymes, which includes CYP1A2, CYP2C19, CYP2D6, CYP2C9 and CYP3A4 that are responsible for more than 80% of the metabolism of clinical drugs. The prediction models for classification of the CYPs inhibition are based on well-established machine learning methods. The models were validated both on cross-validation and external validation sets and achieved good performance. The web server takes a 2D chemical structure as input and reports the CYP inhibition profile of the chemical for 10 models using different molecular fingerprints, along with confidence scores, similar compounds, known CYPs information of drugs—published in literature, detailed interaction profile of individual cytochromes including a DDIs table and an overall CYPs prediction radar chart (http://insilico-cyp.charite.de/SuperCYPsPred/). The web server does not require log in or registration and is free to use.
Immune Checkpoint Inhibitors for Brain Metastases: A Primer for Neurosurgeons
Authors: Aquilanti Elisa , Brastianos Priscilla K 
Published: March 2020

Abstract
Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brain metastases from melanoma and nonsmall cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones. In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities. We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.
Rules versus Discretion in Bank Resolution
Authors: Walther Ansgar , White Lucy 
Published: March 2020

Abstract
Recent reforms have given regulators broad powers to “bail-in” bank creditors during financial crises. We analyze efficient bail-ins and their implementation. To preserve liquidity, regulators must avoid signaling negative private information to creditors. Therefore, optimal bail-ins in bad times only depend on public information. As a result, the optimal policy cannot be implemented if regulators have wide discretion, due to an informational time-inconsistency problem. Rules mandating tough bail-ins after bad public signals, or contingent convertible (co-co) bonds, improve welfare. We further show that bail-in and bailout policies are complementary: if bailouts are possible, then discretionary bail-ins are more effective.
Love Carefully and Without ‘Over-bearing Fears’: The Persuasive Power of Authenticity in Late 1980s British AIDS Education Material for Adolescents
Authors: Elizabeth Hannah J 
Published: March 2020

Summary
This article examines the 1987 British AIDS education leaflet Love Carefully: Use a condom, drawing on methodologies from both the history of emotion and literary analysis. The informative leaflet, produced collaboratively by the sexual health charities Brook and the Family Planning Association, was intended to prevent the spread of HIV among heterosexual adolescents, a group increasingly viewed as ‘at risk’ by adult producers of health education globally. Steeped in British teenage popular culture, it deployed an introduction from well-known teenage agony aunt Melanie McFadyean, a cartoon strip, and statements from celebrities. The cartoon offered a representation of the difficulties experienced by heterosexual teenagers negotiating the prospect of penetrative sex with a new partner, offering a successful example of condom negotiation, while sympathetically examining why some found condom use and AIDS difficult subjects to broach. The article argues the leaflet deployed emotions and authenticity to persuade teenagers to practise safer sex.
The Mother-Based Intervention: Policy, Social Work, and the Absence of Fathers in the Social Services in Israel
Authors: Perez-Vaisvidovsky Nadav , Mizrahi Reli , Halpern Ayana 
Published: March 2020

AbstractThe increasing scholarly interest in the absence of fathers from family-focused interventions by the social services tends to focus on the role of fathers, mothers, and social workers in this absence. The role of policymakers, however, has been neglected. This article examines the case study of policymakers in the Israeli social services to fill in this gap and examine the role of policy and policymakers in fathers’ absence. The findings reveal that policy is based on the ‘mother-based intervention’ assumption—the services are built around the assumption that interventions include only mothers, and therefore make engaging fathers an exception.
Effect of combinations of feed-grade urea and slow-release urea in a finishing beef diet on fermentation in an artificial rumen system
Authors: Alipour Daryoush , Saleem Atef Mohamed , Sanderson Haley , Brand Tassilo , Santos Laize V , Mahmoudi-Abyane Mahdi , Marami Mohammad Reza , McAllister Tim Angus 
Published: March 2020

AbstractThis study evaluated the effect of combinations of feed-grade urea and slow-release urea (SRU) on fermentation and microbial protein synthesis within two artificial rumens (Rusitec) fed a finishing concentrate diet. The experiment was a completely randomized, dose–response design with SRU substituted at levels of 0% (control), 0.5%, 1%, or 1.75% of dry matter (DM) in place of feed-grade urea, with four replicate fermenters per dosage. The diet consisted of 90% concentrate and 10% forage (DM basis). The experiment was conducted over 15 d, with 8 d of adaptation and 7 d of sampling. Dry matter and organic matter disappearances were determined after 48 h of incubation from day 9 to 12, and daily ammonia (NH3) and volatile fatty acid (VFA) production were measured from day 9 to 12. Microbial protein synthesis was determined on days 13–15. Increasing the level of SRU quadratically affected total VFA (Q, P = 0.031) and ammonia (Q, P = 0.034), with a linear increment in acetate (L, P = 0.01) and isovalerate (L, P = 0.05) and reduction in butyrate (L, P = 0.05). Disappearance of neutral detergent fiber (NDF) and acid detergent fiber (ADF) was quadratically affected by levels of SRU, plateauing at 1% SRU. Inclusion of 1% SRU resulted in the highest amount of microbial nitrogen associated with feed particles (Q, P = 0.037). Responses in the efficiency of microbial protein synthesis fluctuated (L, P = 0.002; Q, P = 0.001) and were the highest for 1% SRU. In general, the result of this study showed that 1% SRU in combination with 0.6% urea increased NDF and ADF digestibility and total volatile fatty acid (TVFA) production.
Association Between Patterns of Alcohol Use and Short-Term Risk of Suicide Attempt Among Patients With and Without Reported Suicidal Ideation
Authors: Richards Julie E. , Shortreed Susan M. , Simon Greg E. , Penfold Robert B. , Glass Joseph E. , Ziebell Rebecca , Williams Emily C. 
Published: March 2020

Objective:
To evaluate the association between patterns of alcohol use and short-term risk of suicide attempt among patients with and without reported suicidal ideation.

Methods:
Kaiser Permanente Washington electronic health record data were used to identify mental health visits (1/1/2010-6/30/2015) with documented assessments for unhealthy alcohol use (AUDIT-C) and suicidal ideation (PHQ-9 ninth question). Logistic regression fit using generalized estimating equations were used to conduct visit-level analyses, accounting for correlation between individuals’ assessments. Separate models evaluated the association between (1) level of alcohol consumption and (2) frequency of heavy episodic drinking (HED), in combination with suicidal ideation (any vs none), with suicide attempt within 90 days following each visit. Primary models adjusted for age, gender, race/ethnicity and visit year.

Results:
Of 59,705 visits (43,706 unique patients), 372 (0.62%) were followed by a suicide attempt within 90 days. The risk of suicide attempt was significantly higher for patients reporting suicidal ideation across all levels of alcohol consumption compared to patients reporting low-level alcohol use and no suicidal ideation, particularly high-level use (OR 9.77, 95% CI, 6.23–15.34). Similarly, risk of suicide attempt was higher for patients reporting suicidal ideation across all levels of HED relative to those reporting no HED or suicidal ideation, particularly HED monthly or more (OR 6.80, 95% CI 4.77–9.72). Among patients reporting no suicidal ideation, no associations were observed.

Conclusions:
Findings underscore the potential value of offering alcohol-related care to patient reporting suicidal ideation. Additional strategies are needed to identify suicide risk among those reporting no suicidal ideation.
Challenges for hepatitis B virus cure in resource-limited settings in sub-Saharan Africa
Authors: Kramvis Anna 
Published: March 2020

Purpose of review
The aim of this article is to highlight the unique challenges for hepatitis B virus (HBV) cure faced in resource-limited settings (RLS) in sub-Saharan Africa (SSA), where access to disease prevention measures, medical testing, and treatment are limited.

Recent findings
SSA RLS face challenges, which need to be anticipated as HBV cure research advances. There is a paucity of data because of lack of HBV surveillance and limited access to laboratories. Interruption of transfusion-transmitted infections, perinatal mother-to-child-transmissions, and transmission in people-who-infect-drug networks has not been achieved fully. Although RLS in SSA are within the epicenter of the HIV pandemic, unlike for HIV, there is no population-based testing for HBV. Public health response to HBV is inadequate with concomitant political inertia in combatting HBV infection.

Summary
A functional HBV cure will improve the diagnosis/treatment cascade, decrease costs and accelerate HBV elimination. There is a concerted effort to find a HBV cure, which will be finite, not require life-long treatment, adherence, and continued monitoring. Increased research, improved financial, infrastructural and human resources will positively impact on implementation of HBV cure, when available. We can emulate major strides made in tackling HIV and the strength of advocacy groups in soliciting policymakers to take action.
Ursolic Acid Improves Monocrotaline-Induced Right Ventricular Remodeling by Regulating Metabolism
Authors: Gao Xiaojian , Zhang Zeyu , Li Xin , Wei Qingxia , Li Hanlu , Li Chen , Chen Haixu , Liu Chunlei , He Kunlun 
Published: March 2020

Abstract:
Pulmonary arterial hypertension (PAH) is a progressive and malignant disease characterized by pulmonary small arteries and right ventricle (RV) remodeling that can lead to severe RV dysfunction and death. The current therapeutic targets for RV dysfunction, which is strongly linked to mortality, are far from adequate. Therefore, we investigated the effect of ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, on PAH-induced RV remodeling and its underlying mechanism. We established a PAH model by injecting Sprague Dawley rats with monocrotaline (MCT, 60 mg/kg, ip), as verified by echocardiography and hemodynamic examination. Proteomic analysis was performed on RV samples using a Q Exactive high-field mass spectrometer, followed by KEGG enrichment analysis. The effect of 4 weeks of UA (50 mg/kg) treatment on RV remodeling was explored based on ultrasound, hemodynamic parameters, and histological changes, with the mechanism verified in vivo and in vitro by qRT-PCR and western blotting. RV hypertrophy, fibrosis, increased apoptosis, and abnormal metabolism were induced by MCT and suppressed by UA via a mechanism that changed the expression of key markers. UA also attenuated the Phenylephrine-induced hypertrophy of neonatal rat ventricular myocytes and upregulated peroxisome proliferator-activated receptor-alpha (PPARα), a key fatty acid metabolism regulator, and its downstream factor carnitine palmitoyl transferase 1b. In conclusion, UA exerts beneficial effects on PAH-induced RV dysfunction and remodeling by regulating PPARα-dependent fatty acid metabolism.
The prevalence of masked hypertension in relation to cigarette smoking in a Chinese male population
Authors: Zhang Dong-Yan , Huang Jian-Feng , Kang Yuan-Yuan , Dou Yu , Su Yan-Lun , Zhang Li-Juan , Cheng Yi-Bang , Guo Qian-Hui , Huang Qi-Fang , Li Yan , Wang Ji-Guang 
Published: March 2020

Background:
Smokers may smoke cigarettes during ambulatory or home blood pressure (BP) monitoring but not clinic measurement. We investigated the prevalence of masked hypertension in relation to cigarette smoking in Chinese outpatients enrolled in a multicenter registry.

Methods:
Our study included 1646 men [494 (30.0%) current smokers]. We defined masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and elevated daytime (≥135/85 mmHg) or night-time (≥120/70 mmHg) ambulatory or morning or evening home SBP/DBP (≥135/85 mmHg).

Results:
In all men, multiple logistic regression showed that current cigarette smoking was significantly associated with daytime [prevalence 18.7%, odds ratio (OR) 1.69, 95% confidence interval 1.27–2.25, P = 0.0003] but not night-time (prevalence 27.1%, P = 0.32) ambulatory masked hypertension and associated with evening (prevalence 14.6%, OR 1.81, confidence interval 1.33–2.47, P = 0.0002) but not morning (prevalence 17.6%, P = 0.29) home masked hypertension. The associations were more pronounced for heavy smoking (≥20 cigarettes/day) relative to never smoking for both masked daytime ambulatory (OR 1.97, P = 0.001) and evening home hypertension (OR 2.40, P < 0.0001) or in patients over 55 years of age (P for interaction in relation to daytime ambulatory masked hypertension = 0.005). In men with clinic normotension (n = 742), the associations were also significant (P < 0.01), particularly in those with a normal to high-normal clinic BP (n = 619, P < 0.04).

Conclusion:
Cigarette smoking was associated with increased odds of masked daytime ambulatory and evening home hypertension, especially in heavy smoking or older men.
Clinical Profile of Bilateral Microsporidial Keratoconjunctivitis in Healthy Individuals—A Case Series With Long-term Follow-up
Authors: Mohanty Amrita , Mitra Sanchita , Das Sujata , Priyadarshini Smrutirekha , Sahu Srikant K. 
Published: March 2020

Purpose:
To describe bilateral microsporidial keratoconjunctivitis in healthy individuals with long-term follow-up.

Methods:
Six cases of smear-positive bilateral microsporidial keratoconjunctivitis were diagnosed and followed up during the study period August 2017 to January 2019. Associated risk factors, clinical features, coexistence with adenovirus, clinical course, and recurrence were studied.

Results:
The mean age was 36.6 years (range: 10–65 years). The mean duration of symptoms was 13.6 days (range: 7–60 days). Predisposing risk factors were present in 4 of 6 cases. The best-corrected visual acuity at presentation was ≥20/30 in all eyes except in one. Typical microsporidial epithelial lesions were seen in only one case. Persistent lesions, clinically resembling Thygeson superficial punctate keratitis in both eyes, were observed in 3 cases. The lesions in 5 eyes resolved with topical lubricants, and the remaining 7 eyes were treated with topical steroids and tacrolimus 0.03%. Complete resolution was seen in 5 eyes at the end of 1 month, and superficial scarring at the last follow-up was seen in 5 eyes. The best-corrected visual acuity was ≤20/30 in 3 eyes at the last follow-up. The mean duration of follow-up was 7.3 months (range: 3–12 mo).

Conclusions:
Bilateral microsporidial keratoconjunctivitis in healthy patients has an atypical presentation with prolonged course. Microsporidia could be implicated as potential candidates in the etiopathogenesis of Thygeson superficial punctate keratitis.
Epithelial Plaque Formation Secondary to Recombinant Human Nerve Growth Factor
Authors: Weinlander Eric , Ling Jennifer , Reddy Aparna , Nallasamy Nambi 
Published: March 2020

Purpose:
To report a case of corneal epithelial plaque formation associated with recombinant human nerve growth factor (cenegermin 0.002%; Oxervate, Dompé US Inc., Boston, MA), an as-yet unreported adverse event.

Methods:
A case report and review of literature.

Results:
A 45-year-old woman presented with a nonhealing 3.25- × 4.25-mm corneal epithelial defect secondary to multifactorial neurotrophic keratitis in the right eye. The epithelial defect was resistant to maximal medical therapy, and so cenegermin 0.002% was initiated, resulting in resolution of the corneal epithelial defect. After 6.5 weeks of treatment, she developed an unusual corneal epithelial plaque, decreased visual acuity, and eye pain. Cenegermin was ceased, after which the lesion resolved, visual acuity improved, and eye pain resolved.

Conclusions:
Cenegermin 0.002% has emerged as a promising treatment for neurotrophic keratitis. Reported adverse events with this agent have been minor and typically not vision threatening. Here, we describe corneal epithelial plaque formation as a visually significant adverse event that resolved with cessation of cenegermin 0.002%. Although the underlying mechanism is unknown, clinicians should be alerted to the possibility of epithelial plaque formation in patients being treated with recombinant human nerve growth factor for neurotrophic keratitis.