bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal signal and the phylodynamic threshold of SARS-CoV-2
Authors: Duchene Sebastian , Featherstone Leo , Haritopoulou-Sinanidou Melina , Rambaut Andrew , Lemey Philippe , Baele Guy 
Published: August 2020

AbstractThe ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus’s evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 × 10−3 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.
Anaphylaxis and alternative medicine: an unexpected association
Authors: Diaz Sandra Gonzalez , Furci Fabiana , Olivieri Bianca , Ansotegui Ignacio J. 
Published: August 2020

Purpose of reviewThe present review aims to evaluate the use of complementary medicine among patients with allergic disorders, highlighting the risk of adverse reactions, which are often not considered and referred by patients to specialists.Recent findingsComplementary medicine is often used in clinical practice and preferred by patients as it is considered a natural therapy compared to traditional medicine. This choice is because of various cultural and socioeconomics aspects.SummaryThe use of complementary medicine and its adverse reactions, often as severe as anaphylaxis, is frequently reported in atopic patients, in which a cross reactivity between the natural herbs used and the pollen to which they are sensitized is possible.Therefore, a personalized approach in atopic patients before the use of natural products is crucial to prevent any adverse reactions.
Pediatric Provider Experiences with Implementation of Routine Mental Health Screening
Authors: Godoy Leandra , Gordon Sara , Druskin Lindsay , Long Melissa , Kelly Katherine Patterson , Beers Lee 
Published: August 2020

ABSTRACT:

Objective:
Despite the utility of universal screening, most pediatric providers rarely use mental health (MH) screening tools. As such, provider descriptions of their experiences with universal screening are limited. The goal of this study was to describe barriers to, and facilitators of, universal MH screening implementation, the perceived impact of such screening, impressions of a screening-focused quality improvement (QI) Learning Collaborative, and lessons learned.

Method:
We invited primary care clinicians participating in a large-scale QI Learning Collaborative on MH screening (n = 107) to complete postproject interviews. Interviews were transcribed and analyzed using constant comparative qualitative analysis, an inductive, iterative process.

Results:
Eleven interviews were completed and analyzed. Practice sites included academic health centers, a private practice, and a federally qualified health center. Providers described the positive impact of screening (increased identification of MH concerns) and barriers and facilitators of screening at the practice level (clinic and leadership buy-in and electronic medical record integration), the provider level (provider beliefs about the importance of screening), and the patient level (parent literacy). Challenges of linking families with care after screening included lack of adequate referrals, long wait lists, limited bilingual providers, insurance gaps, and inadequate feedback loops. Access to on-site MH clinicians and participation in the Learning Collaborative were described as beneficial.

Conclusion:
Findings elucidate how universal MH screening can be sustainably integrated into real-world primary care settings and may facilitate the uptake of American Academy of Pediatrics recommendations for best practices in screening for MH concerns.
OUTCOMES OF NONCONFLUENT DIODE LASER PANRETINAL PHOTOCOAGULATION FOR AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY AFTER INTRAVITREAL BEVACIZUMAB
Authors: Mammo Danny A. , Rubino Shaina M. , Quiram Polly A. 
Published: August 2020

Purpose:
To assess the safety and efficacy of less dense panretinal photocoagulation after intravitreal bevacizumab in aggressive posterior retinopathy of prematurity infants.

Methods:
Retrospective consecutive case series of premature infants diagnosed with aggressive posterior retinopathy of prematurity between August 2012 and November 2015 who received intravitreal bevacizumab with subsequent modified indirect diode laser panretinal photocoagulation for reactivation or incomplete vascularization. Main outcome measures included postprocedural reactivation, retinal detachments, or anterior segment ischemia.

Results:
Sixty-one eyes of 31 premature infants were identified. The average gestational age was 24 ± 2.2 weeks (range 22–27), and the average birth weight was 661.5 ± 167.1 g (range 340.0–930.5 g). The average follow-up was 3.9 ± 1.3 years (range 1.3–5.4 years). At the last follow-up, no patient had experienced postlaser reactivation, retinal detachments, anterior segment ischemia, or other laser complications.

Conclusion:
This study suggests that nonconfluent panretinal photocoagulation for aggressive posterior retinopathy of prematurity infants who have received intravitreal bevacizumab may be safe and effective. This study's strengths include a sizeable sample size, long-term follow-up of nearly 4 years, and consistency in treatment among patients by a single, experienced retinopathy of prematurity specialist.
MICROSTRUCTURAL CHANGES IN CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA AFTER INTRAVITREAL DEXAMETHASONE IMPLANT INJECTION
Authors: Park Un Chul , Park Jung Hyun , Yoon Chang Ki , Yu Hyeong Gon 
Published: August 2020

Purpose:
To evaluate microstructural changes in cystoid macular edema in retinitis pigmentosa after intravitreal dexamethasone implant injection.

Methods:
In an extended cohort of a randomized trial of intravitreal dexamethasone implant for the management of retinitis pigmentosa-associated cystoid macular edema, microstructural changes during six months after the treatment were evaluated using spectral-domain optical coherence tomography.

Results:
Forty-two eyes were included, and all had cystoid space in the inner nuclear layer (INL) at baseline. No eyes showed subretinal fluid, and 28.6% showed hyperreflective foci. Among 38 eyes with cystoid space both in the INL and outer nuclear layer/Henle's layer, 13 (34.2%) showed complete resolution and 12 (31.6%) showed cystoid space only in the INL at 2 months after injection, whereas others showed persistent cystoid space in both layers. After complete resolution, cystoid space recurrence was earlier in the INL than in the outer nuclear layer/Henle's layer. Multivariable analysis showed that greater cystoid space area in the INL and outer nuclear layer/Henle's layer, presence of macular leakage, and longer intact external limiting membrane at baseline were associated with greater cystoid space area decrease after the treatment.

Conclusion:
Resolution and recurrence pattern of retinitis pigmentosa-associated cystoid macular edema after dexamethasone treatment showed that the INL is the primary layer of cystic change, and this suggests its pathogenesis is most likely caused by Müller cell dysfunction.
Accelerated Epi-On Versus Standard Epi-Off Corneal Collagen Cross-Linking for Progressive Keratoconus in Pediatric Patients: Five Years of Follow-Up
Authors: Henriquez Maria A. , Hernandez-Sahagun Gustavo , Camargo Jorge , Izquierdo Luis 
Published: August 2020

Purpose:
The purpose of this study was to evaluate and compare the 5-year efficacy and safety of accelerated transepithelial (A-epi-on) corneal collagen cross-linking (CXL) with standard CXL (epi-off) in children with progressive keratoconus (KC).

Methods:
This prospective cohort study included 78 eyes of patients aged 18 years old or younger with progressive KC who underwent CXL at the Oftalmosalud Institute of Eyes, Lima, Peru. A-epi-on CXL was performed in 32 eyes (30′ of impregnation/5′ of irradiation at 18 mW/cm2) and epi-off CXL was performed in 46 eyes (30′of impregnation/30′ minutes of irradiation at 3 mW/cm2). Visual acuity, refraction, and the Scheimpflug imaging parameters were evaluated preoperatively and postoperatively at 1 and 5 years.

Results:
The best corrected visual acuity improved to 0.06 logarithm of the minimum angle of resolution (SD: 0.19, P = 0.03) and 0.09 logarithm of the minimum angle of resolution (SD: 0.13, P < 0.001) in the A-epi-on and epi-off groups, respectively. The mean flattening in the mean keratometry was 0.09 diopters (D) (SD: 0.68, P = 0.33) and 3.18 D (SD: 5.17, P < 0.001) in the A-epi-on CXL and Epi-off groups at the 5-year follow-up. Significant differences were found in the change at 1 and 5 years between the groups for cylinder reduction, flat and mean K, and pachymetry (all P < 0.05). The KC progression rate was 9.37% (3/32) in the A-epi-on CXL; no progression was found in the epi-off CXL group at the 5-year follow-up.

Conclusions:
Both procedures halted the progression of KC at the 5-year follow-up; however, epi-off CXL was safer and more effective when compared with A-epi-on CXL.
Sex- and cell-dependent contribution of peripheral high mobility group box 1 and TLR4 in arthritis-induced pain
Authors: Rudjito Resti , Agalave Nilesh M. , Farinotti Alex Bersellini , Lundbäck Peter , Szabo-Pardi Thomas A. , Price Theodore J. , Harris Helena Erlandsson , Burton Michael D. , Svensson Camilla I. 
Published: August 2020

Abstract
Spinal high mobility group box 1 protein (HMGB1) plays crucial roles in arthritis-induced pain; however, the involvement of peripheral HMGB1 has not been examined previously. In this study, we addressed the role of peripheral HMGB1 and explored if sex contributes differentially to nociception in arthritis. We found Hmgb1 expression to be elevated in the ankle joints of male and female mice subjected to collagen antibody-induced arthritis. Blocking the action of peripheral HMGB1, however, only reversed collagen antibody-induced arthritis-mediated hypersensitivity in males. Intra-articular injection of the toll-like receptor (TLR)4-activating, partially reduced disulfide, but not the fully reduced all-thiol, HMGB1 evoked mechanical hypersensitivity in both sexes. A sex-dependent temporal profile in expression of inflammatory factors in the ankle joint was observed in response to intra-articular injection of disulfide HMGB1, with male mice showing a delayed, yet longer-lasting increase in mRNA levels for several of the investigated factors. Intra-articular HMGB1 did not induce cellular infiltration in the ankle joint suggesting its action on tissue resident cells. To further explore possible sex differences in cellular involvement, we used the macrophage inhibitor, minocycline, and mice with specific TLR4 depletion in myeloid cells or nociceptors. We found that inhibition of resident macrophages attenuated HMGB1-induced pain-like behavior only in male mice. Interestingly, although the contribution of TLR4 on myeloid cells to nociception was minimal in females compared to males, TLR4 on nociceptors are important for HMGB1-induced pain in both sexes. Collectively, our work highlights sex- and cellular location-dependent roles of HMGB1 and TLR4 in peripheral pain mechanisms.
Reliability and validity of the severe impairment battery in Taiwanese patients with moderate to severe Alzheimer’s disease
Authors: Huang Mao-Hsuan , Tsai Chia-Fen , Hu Chaur-Jong , Lin Yu-Te , Yang Yuan-Han , Wang Wen-Fu , Lee Wei-Ju , Fuh Jong-Ling 
Published: August 2020

Background:
The severe impairment battery (SIB) was developed to evaluate cognitive functions in moderate to severe dementia patients. We aimed to examine the reliability and validity of the Taiwanese version of the SIB (T-SIB) in patients with moderate to severe Alzheimer’s disease (AD).

Methods:
AD patients with clinical dementia rating (CDR) stage 2 (n = 79) or 3 (n = 21) and scores <15 on the Taiwanese version of mini mental state examination (T-MMSE) were recruited from six hospitals in Taiwan. Cronbach’s alpha was used to evaluate the internal consistency of the T-SIB. The CDR and functional assessment staging (FAST) scores were used to assess dementia severity.

Results:
We recruited 100 AD patients (73 women and 27 men; mean T-SIB score, 56.4 ± 24.8). The mean T-SIB total score for patients with CDR 2 and 3 were 60.3 ± 23.3 and 41.2 ± 24.9, respectively. The internal consistency of the T-SIB was 0.96. The T-SIB was moderately correlated with the T-MMSE (Pearson’s correlation coefficient = 0.76). The areas under the curve for discriminating between CDR 2 and CDR 3 were 0.81 (95% CI = 0.91–0.71) and 0.72 (95% CI = 0.84–0.61), respectively. Using a cut-off score of 59, the T-SIB had a sensitivity of 80% and specificity of 61% for discriminating between CDR 2 and CDR 3. Using a cut-off score of 45, the T-SIB had a sensitivity of 83.3% and specificity of 73.1% for discriminating between the FAST stage 7c.

Conclusion:
T-SIB is a reliable and valid instrument for measuring cognition of severely demented Taiwanese AD patients.
Adjunctive Raloxifene and Isradipine Improve Cognitive Functioning in Patients With Schizophrenia
Authors: Vahdani Bita , Armani Kian Alireza , Esmaeilzadeh Abdolreza , Zenoozian Saeedeh , Yousefi Vida , Mazloomzadeh Saeideh 
Published: August 2020

Abstract

Background
Cognitive impairment is the most important feature of schizophrenia leading to severe functional disability. To identify pathways that improve pathophysiological neurocognition in schizophrenia is a current challenge for the development of goal-directed clinical interventions. In the present study, we investigated the effects of raloxifene (a selective estrogen modulator) and isradipine (a voltage-gated L-type calcium channel blocker) on cognitive deficits in patients with schizophrenia.

Method
We designed a double-blind, randomized, parallel, placebo-controlled trial. We randomized 60 patients with schizophrenia into 3 groups including isradipine 5 mg, raloxifine 60 mg, and placebo for 6 consequent weeks, all in the same shape capsules, 2 times a day, along with treatment as usual. The initial and final results of blood tests, electrocardiograms, and cognitive tests in specific domains, such as attention, processing speed, executive function, and verbal memory were evaluated.

Results
Our findings revealed a remarkable association between adjunctive raloxifene treatment and the alleviation of verbal memory deficits. Isradipine treatment significantly improved the verbal memory and attention dysfunction in some variables of the Stroop test, compared with the placebo. However, no effect was observed in processing speed and executive function deficits.

Conclusions
To the best of our knowledge, this study provides the first evidence that isradipine is a novel therapy option improving verbal memory and attention, both related to its activity in the hippocampus and the cerebellum. Further investigations are necessary to elucidate the mechanisms of action for both drugs in schizophrenia.
Patient Satisfaction With Human Papillomavirus Self-Sampling in a Cohort of Ethnically Diverse and Rural Women in Yunnan Province, China
Authors: Goldstein Andrew , Plafker Benjamin , Stamper Sarah , Goldstein Lena , Lipson Roberta , Bedell Sarah , Wang Jue , Brenner Gal , Goldstein Gail , O'Keefe Karen , O'Keefe Casey , O'Keefe McKenna , O'Keefe Tierney , Goldstein Amelia , Zhao Anna 
Published: August 2020

Objective
Rural Yunnan Province is one of the most ethnically, culturally, and religiously diverse regions in China. The majority of its women have never been screened for cervical cancer. It is not known whether women would feel comfortable and ultimately even prefer using a human papillomavirus (HPV) self-swabbing method.

Methods
In a 6-day period, 3,600 women were taught the role of HPV in cervical cancer. They were then given self-swabbing instructions. After obtaining their specimens, 600 women were interviewed about their experience with HPV self-testing. The women were of the Yi, Hui, Dai, and Han ethnicities.

Results
The overwhelming majority of the women surveyed understood the self-sampling instructions (588/600, 98%) and felt comfortable carrying out the self-sampling procedure (584/600, 97%). Significantly more women (389/600, 64.8%) preferred self-sampling to having the provider (211/600, 35.2%) obtain the sample (χ2 = 105.61, p < .05). Women who preferred self-sampling did so primarily because they felt capable of obtaining the specimens (n = 80) or that it was a more convenient way to be tested (n = 79). The medical expertise of the provider (n = 74) and concerns over the accuracy of the test (n = 88) shifted some women's preference toward a provider-obtained sample.

Conclusions
There are 400+ million Chinese women who have never had a cervical cancer screening. Self-testing has the potential to significantly increase the number of women tested. Despite the diversity of the women screened, the majority felt comfortable self-sampling and preferred self-swabbing to provider testing.
Microtechnologies for inner ear drug delivery
Authors: Forouzandeh Farzad , Borkholder David A. 
Published: August 2020

Purpose of review
Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field for clinical and animal research environments.

Recent findings
Micropump technologies are being developed for dynamic control of flow rates with refillable reservoirs enabling timed delivery of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or round window membrane (RWM) delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active research area with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged for controlled microperforation of the RWM for significant enhancement in permeability, combinable with emerging matrix formulations that optimize biological interaction and drug release kinetics.

Summary
Microsystem technologies are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.
Insulin-like growth factor 1: role in the auditory system and therapeutic potential in otology
Authors: Gao Li , Nakagawa Takayuki 
Published: August 2020

Purpose of review
Insulin-like growth factor 1 (IGF-1) is a hormone necessary for the development, growth, and maintenance of various organs, and has been used as a therapeutic agent in clinical settings. This review aimed to illustrate its role in the auditory systems and its potential use as a therapeutic in the field of otology.

Recent findings
Previous animal studies have indicated the critical role of IGF-1 in the development and maintenance of the auditory system, especially in the cochlea. A clinical study demonstrated a close relationship between the serum level of IGF-1 and the progression of age-related hearing impairment, suggesting its importance in the maintenance of hearing in humans. More recently, its effect on the regeneration of cochlear synapses has been reported using explant cultures, which could explain the course of hearing recovery in patients who underwent topical IGF-1 application for the treatment of sudden sensorineural hearing loss.

Summary
Recent advances in experimental and clinical investigations have revealed the importance of IGF-1 in the maintenance of the auditory function. On the basis of broad targets, its clinical application will expand to the field of otology in the future.
Progress towards xenogenic tolerance
Authors: Duggan Erin M. , Griesemer Adam 
Published: August 2020

Purpose of review
To describe the most recent progress towards tolerance in xenotransplantation.

Recent findings
Mixed chimerism and thymic transplantation have been used to promote tolerance in xenotransplantation models. Intra-bone bone marrow transplantation is a recent advance for mixed chimerism, which promotes longer lasting chimerism and early graft function of subsequent organ transplantation. The hybrid thymus, an advancement to the vascularized thymokidney and vascularized thymic lobe, is being developed to allow for both donor and recipient T-cell selection in the chimeric thymus, encouraging tolerance to self and donor while maintaining appropriate immune function. Regulatory T cells show promise to promote tolerance by suppressing effector T cells and by supporting mixed chimerism. Monoclonal antibodies such as anti-CD2 may promote tolerance through suppression of CD2+ effector and memory T cells whereas Tregs, which express lower numbers of CD2, are relatively spared and might be used to promote tolerance.

Summary
These findings contribute major advances to tolerance in xenotransplantation. A combination of many of these mechanisms will likely be needed to have long-term tolerance maintained without the use of immunosuppression.