bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy: Republication
Authors: Shah Shahini , Hill Andrew 
Published: February 2021

Purpose of review
A growing body of evidence suggests that integrase inhibitors (INSTIs) are significantly associated with weight gain and obesity. Obesity is a significant risk factor for metabolic syndrome and diabetes. This article comprehensively reviews recent available evidence weight gain and the risks of metabolic syndrome and diabetes associated with INSTIs.

Recent findings
Recent evidence continues to contribute to the evidence for weight gain associated with INSTIs, especially when used with newer nucleoside reverse transcriptase inhibitor, tenofovir alafenamide (TAF). Although the literature suggests a neutral effect on lipids, there is evidence that INSTIs are associated with metabolic syndrome due to treatment-emergent obesity. The literature for short-term treatment-emergent diabetes and insulin resistance remains inconsistent, but there is some evidence that weight gain could lead to an increased risk of developing diabetes in the future.

Summary
Longer term studies are required to understand the metabolic impact of INSTIs, secondary to weight gain. Evidence suggests that INSTIs, when used with TAF, contribute to metabolic syndrome and may have long-term risks of diabetes. INSTIs, when used with tenofovir disoproxil fumarate, have fewer metabolic implications. Clinicians must monitor for weight gain and metabolic effects, especially in those with underlying risk factors.
Association of genetic polymorphisms NCF4 rs1883112, CBR3 rs1056892, and ABCC1 rs3743527 with the cardiotoxic effects of doxorubicin in children with acute lymphoblastic leukemia
Authors: Gándara-Mireles Jesús Alonso , Lares-Asseff Ismael , Reyes Espinoza Elio Aarón , Blanco Javier G. , González Font Antonio Emilio , Córdova Hurtado Lourdes Patricia , Castañeda Verónica Loera , Fierro Ignacio Villanueva , Romero Leslie Patrón , Reyes Horacio Almanza 
Published: February 2021

Objectives
Cardiotoxicity is a frequent complication secondary to the use of anthracyclines for cancer chemotherapy. Evidence suggests that certain polymorphic genetic variants modify the risk for anthracycline-related cardiotoxicity. Reports documenting the impact of genetic polymorphisms on anthracycline-cardiotoxicity risk in pediatric patients with cancers from Latin American countries are scarce. The objective of this study was to evaluate associations between NCF4 rs1883112, CBR3 rs1056892 and ABCC1 rs3743527 genotype status and echocardiographic parameters indicative of anthracycline-cardiotoxicity in a group of Mexican children with acute lymphoblastic leukemia (ALL).

Methods
Sixty-seven children (2–18 years old) with ALL were treated at the State Cancer Center in Durango, Mexico. NCF4, CBR3, and ABCC1 genotypes were examined by real-time PCR. Left ventricular ejection fraction and diastolic filling ratio were examined as markers of systolic and diastolic anthracycline-toxicity.

Results

NCF4 rs1883112 genotype status was significantly associated with the risk of doxorubicin cardiotoxicity [odds ratio (OR) = 10.80, 95% confidence interval (CI) 1.69–68.98, P = 0.01]. There was a significant association between heterozygous CBR3 rs1056892 genotype status and anthracycline-cardiotoxicity risk (OR = 9.91, 95% CI 1.07–91.47, P = 0.04). Heterozygosis for the ABCC1 rs3743527 allele was associated with protection from anthracycline-cardiotoxicity (OR = 0.30, 95% CI 0.09–0.91, P = 0.03).

Conclusion
This pilot study suggests that selected polymorphic variants may impact the risk for anthracycline-cardiotoxicity in pediatric patients with ALL treated with a contemporary chemotherapeutic regimen in Mexico.
Postpartum headaches after epidural or spinal anesthesia
Authors: Joudi Noor , Ansari Jessica 
Published: February 2021

Purpose of review
Postpartum headache is a common occurrence with various obstetric, neurologic, and anesthetic etiologies. Post dural puncture headache (PDPH) after neuraxial anesthesia is a culprit that may be less familiar to obstetricians. In this review, authors will discuss the differential diagnosis and management of postpartum headache, review PDPH, and explore evidence suggesting that PDPH may have greater implications than previously considered.

Recent findings
Emerging evidence suggests that PDPH, previously believed to be benign and self-limited, is associated with significant acute and chronic sequelae. A recent large database study links PDPH to subdural hematoma and cerebral venous sinus thrombosis. The authors also identified associations between PDPH and bacterial meningitis, depression, and back pain. A growing body of literature also links PDPH or unintentional dural puncture with an epidural needle (UDP) with development of chronic headaches.

Summary
Patients who experience UDP or PDPH should be counseled to return for evaluation for new or worsening headache. In the immediate postpartum setting, clinicians assessing these patients should have a low threshold to obtain brain imaging. In addition, obstetricians should be alerted that patients who suffer UDP may be prone to develop chronic headache disorders and consider referral to pain specialists.
Genetics of recurrent pregnancy loss: a review
Authors: Tise Christina G. , Byers Heather M. 
Published: February 2021

Purpose of review
Human reproduction is remarkably inefficient; with pregnancy loss occurring in 10–30% of clinically recognized pregnancies. Of those, 3–5% of couples experience recurrent pregnancy loss (RPL), more than 50% of who never receive an underlying diagnosis. Herein, we review evidence that genetic changes, including pathogenic variant(s) in highly penetrant genes, may provide an explanation for a proportion of couples with pregnancy loss.

Recent findings
Genetic abnormalities that may predispose to pregnancy loss include chromosomal aneuploidy, copy number variants, single-gene changes and others. Although previously limited by the need for hypothesis-driven assessment, advancement of various molecular technologies have sheparded in the opportunity to identify molecular cause of highly heterogeneous conditions, including RPL. The identification of causative genetic aberrations associated with RPL demonstrates a promising area of further research.

Summary
The journey of human development from a single-cell zygote to a term infant is complex process. Early research into copy number variants and highly penetrant single-gene changes may provide diagnosis for a proportion of couples with RPL as well as inform genes critical for early human development.
The Divine Proportion: Origins and Usage in Plastic Surgery
Authors: Hwang Kun , Park Chan Yong 
Published: February 2021

Background:
The aim of this study was to summarize the existing literature on the origin of the concept of the divine proportion and its usage in the plastic surgery field.

Methods:
In PubMed, the search terms [golden ratio AND (plastic surgery OR aesthetic surgery OR face)] were used, resulting in 65 articles. Among them, 15 articles were excluded and 50 abstracts were reviewed, of which 45 were excluded. The remaining 5 full articles and 11 other mined articles were reviewed.

Results:
No evidence was found that the golden ratio had been used in any architecture or paintings before Pacioli’s Divina proportione (Divine proportion) (1509), after which painters begin to use this ratio in their art. Fechner (1876) found that the golden ratio (1:1.618) was more aesthetically pleasing than any other proportion of rectangles. Recently Marquardt invented a facial mask containing decagons and pentagons that embody φ in all dimensions, and claimed that this mask yielded the most beautiful shape of the human face. However, it did not fit the average facial features of northwestern Europeans or their perceptions of ideal femininity.

Conclusions:
Mathematical regularity can be found in nature and in the human body. However, this does not necessarily mean that a “formula of beauty” exists in mathematics. From the contributions of modern aestheticians, we now know that the so-called “essence of beauty” cannot be derived from the mathematical “formula of beauty” in the object itself. Therefore, it is suggested that beauty is based on biology, rather than on mathematics.
Getting Better Results in Flexor Tendon Surgery and Therapy
Authors: Ayhan Egemen , Tuna Zeynep , Oksuz Cigdem 
Published: February 2021

Summary
Recently, better outcomes have been reported when up-to-date developments in flexor tendon surgery and therapy were followed. Slightly tensioned multistrand repairs, judicious venting of pulleys, and early active motion are widely accepted principles. In addition to these principles, tailoring of the repair according to intraoperative active movement with wide awake local anesthesia no tourniquet (WALANT) surgical setting is recommended for better results. We aimed to describe our up-to-date approach to flexor tendon surgery and therapy with the help of visual communication tools of this age. The ideal primary repair of flexor tendons, the management of delayed presentation flexor tendon injuries, the key steps to achieve better results with flexor tendon therapy, and the tele-rehabilitation experience during COVID-19 pandemic will be highlighted. Zone 2 flexor tendon injuries are the most demanding part and will be focused on.
Emergent expansion of clinical epigenetics in patients with cardiovascular diseases
Authors: Napoli Claudio , Coscioni Enrico , de Nigris Filomena , Donatelli Francesco 
Published: February 2021

Purpose of review
Cardiovascular diseases (CVDs) are typically caused by multifactorial events including mutations in a large number of genes. Epigenetic-derived modifications in the cells are normal but can be amended by aging, lifestyle, and exposure to toxic substances. Major epigenetic modifications are DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs. These pivotal players are involved in the epigenetic-induced modifications observed during CVDs. Nevertheless, despite impressive efforts capitalized in epigenetic research in the last 50 years, clinical applications are still not satisfactory.

Recent findings
Briefly, we present some of the recent steps forward in the epigenetic studies of CVDs. There is an increased appreciation for the contribution of epigenetic alterations in the development of CVDs. Now, we have novel epigenetic biomarkers and therapeutic trials with the use of statins, metformin, and some compounds affecting epigenetic pathways including a BET inhibitor apabetalone. The new knowledge of epigenetic regulation is also discussed in the light of precision medicine of CVDs.

Summary
Epigenetic studies of CVDs have the promise to yield both mechanistic insights as well as adjunct treatments (repurposed drugs and apabetalone). The overall concept of precision medicine is not widely recognized in routine medical practice and the so-called reductionist approach remains the most used way to treat CVD patients.
Radiation and the Skeptical Public: Tips and Tools for Communicating Effectively
Authors: Caffrey Emily 
Published: February 2021

Abstract
Public communication about radiation is tricky business. Members of the public are frequently skeptical about messages from scientific sources, particularly when it comes to radiation. As radiation protection professionals, it is our job to relay scientifically sound information in a simple, clear, and concise manner. This paper discusses the Health Physics Society’s “Ask The Experts” feature, the society’s most successful public education endeavor with over one million visitors annually. The keys to effective communication of technical information are demonstrating empathy and compassion, keeping the language simple and concise, and offering sources of additional information to empower the individual to learn more on their own. The two most common categories of questions—radiation exposures from diagnostic imaging procedures and radiation exposures to the fetus—are discussed in detail, and some general information on how to respond to these types of questions is provided. A template for responding to public questions is provided, along with some examples.
Trends, Associations, and Impact of Atrial Fibrillation in Patients With Light-chain Cardiac Amyloidosis
Authors: Abe Temidayo , Olanipekun Titilope , Khoury Mtanis , Egbuche Obiora , Effoe Valery , Ghali Jalal 
Published: February 2021

Background:
In this study, we investigated the temporal trends in the prevalence and prognostic implication of atrial fibrillation (AF) in patient with light-chain cardiac amyloidosis (AL-CA).

Methods:
We identified 3030 patients with AL-CA from the 2015 to 2017 National Inpatient Sample, of which 1577 (52%) had AF. We used trend analysis to assess the temporal trends in the prevalence of AF by subtype from 2015 to 2017. We compared inhospital mortality, acute on chronic heart failure, stroke, length of stay (LOS), and total cost in patients with to those without AF, stratified by subtype of AF.

Results:
The prevalence of AF among patients with AL-CA was unchanged from 2015 to 2017 (50%–53%; adjusted odds ratio, 1.1 [0.9–1.5]; P = 0.3). The trend was unchanged in the stratified analysis by subtype of AF. Patients with AF were older and had more comorbidities. After propensity matching, acute on chronic heart failure was significantly higher in patients with AL-CA and AF, compared with those with AL-CA alone (55.6% vs. 48.3%; P < 0.0001). There was no difference in inhospital mortality (7.5% vs. 7.5%; P = 0.9), stroke (2.0% vs. 2.5%; P = 0.5), median LOS (5 [3–9] vs. 5 [3–8]; P = 0.3), and median total hospital cost $42,469 ([$21,309–$92,855] vs. $44,008 [$22,889–$94,200]; P = 0.6). In the stratified analysis, acute on chronic heart failure remained significant higher in patients with paroxysmal and nonparoxysmal AF, while LOS became significantly longer in patients with paroxysmal AF.

Conclusions:
Among patients with AL-CA, AF is associated with a higher risk of acute on chronic heart failure.
BASELINE PREDICTORS ASSOCIATED WITH 3-YEAR CHANGES IN DARK ADAPTATION IN AGE-RELATED MACULAR DEGENERATION
Authors: Lains Ines , Pundlik Shrinivas J. , Nigalye Archana , Katz Raviv , Luo Gang , Kim Ivana K. , Vavvas Demetrios G. , Miller Joan W. , Miller John B. , Husain Deeba 
Published: February 2021

Purpose:
To assess the relationship between baseline age-related macular degeneration (AMD) and disease stage, as well as optical coherence tomography features seen in AMD, with 3-year changes in dark adaptation (DA).

Methods:
Prospective longitudinal study including patients with AMD and a comparison group (n = 42 eyes, 27 patients). At baseline and 3 years, we obtained color fundus photographs, spectral-domain optical coherence tomography, and rod-mediated DA (20 minutes protocol). Multilevel mixed-effect models were used for analyses, with changes in rod intercept time at 3 years as the primary outcome. As some eyes (n = 11) reached the DA testing ceiling value at baseline, we used 3-year changes in area under the DA curve as an additional outcome.

Results:
Baseline AMD, AMD stage, and hyperreflective foci on optical coherence tomography were associated with larger changes in rod intercept time at 3 years. When change in area under the DA curve was used as an outcome, in addition to these features, the presence of retinal atrophy and drusenoid pigment epithelial detachment had significant associations. New subretinal drusenoid deposits at 3 years were also associated with more pronounced changes in rod intercept time and area under the DA curve.

Conclusion:
Specific optical coherence tomography features are associated with DA impairments over time, which supports that structural changes predict functional loss over 3 years.
Metabolic syndrome and the aging retina
Authors: Roddy Gavin W. 
Published: February 2021

Purpose of review
This review explores metabolic syndrome (MetS) as a risk factor that accelerates aging in retinal neurons and may contribute to the neurodegeneration seen in glaucomatous optic neuropathy (GON) and age-related macular degeneration (AMD).

Recent findings
Both animal model experiments and epidemiologic studies suggest that metabolic stress may lead to aberrant regulation of a number of cellular pathways that ultimately lead to premature aging of the cell, including those of a neuronal lineage.

Summary
GON and AMD are each leading causes of irreversible blindness worldwide. Aging is a significant risk factor in the specific retinal neuron loss that is seen with each condition. Though aging at a cellular level is difficult to define, there are many mechanistic modifiers of aging. Metabolic-related stresses induce inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, alterations to the unfolded protein response, defects in autophagy, alterations to the microbiome, and deposition of advanced glycation end products that can all hasten the aging process. Due to the number of variables related to metabolic health, defining criteria to enable the study of risk factors at a population level is challenging. MetS is a definable constellation of related metabolic risk factors that includes enlarged waist circumference, dyslipidemia, systemic hypertension, and hyperglycemia. MetS has been associated with both GON and AMD and may contribute to disease onset and/or progression in each disease.
Current and future therapies for persistent corneal epithelial defects and neurotrophic keratopathy
Authors: Ong Erin S. , Jeng Bennie H. 
Published: February 2021

Purpose of review
The corneal epithelium is a crucial barrier against pathogens, and when disrupted in the setting of certain underlying risk factors such as neurotrophic keratopathy (NK), may result in persistent epithelial defects (PEDs) of the cornea. Management is challenging and may require a variety of different approaches ranging from conservative medical therapy to surgical intervention. The purpose of this review is to provide an update on current and potential future therapeutic options for PEDs and NK.

Recent findings
Recent research has yielded promising results for numerous novel therapies aimed at treating PEDs. Many of these attempt to stimulate healing at the cellular level, via signaling of corneal epithelial differentiation, migration, and proliferation. Considerable advances have also been made regarding medical and surgical promotion of corneal re-innervation and restoration of corneal sensitivity to directly address the underlying NK condition.

Summary
Together with the current well established therapeutic options available for PEDs and NK, growing research on newer alternatives suggest increasing potential for both more effective and more convenient therapies for these difficult situations.
Childhood Outcomes Following Parechovirus Infections in a US Young Infant Cohort
Authors: Kilbride Howard , Jackson Mary Anne , Selvarangan Rangaraj 
Published: February 2021

Background:
Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort.

Methods:
Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate.

Results:
Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness.

Conclusions:
Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted.
Intrapartum Cesarean Delivery Due to Nonreassuring Fetal Heart Rate and the Risk of Pediatric Infectious Morbidity-related Hospitalizations of the Offspring
Authors: Leybovitz-Haleluya Noa , Wainstock Tamar , Pariente Gali , Sheiner Eyal 
Published: February 2021

Objectives:
One of the most common indications for intrapartum cesarean delivery (CD) is nonreassuring fetal heart rate (NRFHR) patterns. We aimed to study the long-term effect of CD due to NRFHR on the risk for subsequent childhood infectious morbidity-related hospitalizations of the offspring.

Study Design:
A population-based cohort study was performed, comparing total and different subtypes of infectious morbidity-related pediatric hospitalizations among offspring born by CD due to NRFHR versus labor dystocia (failure of labor to progress during the 1st or 2nd stage). The analysis included all singletons born between the years 1999–2014 at a single tertiary regional medical center. Infectious-related morbidities included hospitalizations involving a predefined set of International Classification of Diseases, 9th revision codes, as recorded in hospital computerized files. Infants with congenital malformations, multiple gestations, vaginal deliveries and vacuum failure were excluded from the analysis. Perinatal mortality cases were excluded from the long-term analysis. A Kaplan-Meier survival curve was used to compare the cumulative morbidity, and a Cox proportional hazards model was constructed to adjust for confounders.

Results:
The study population included 9956 newborns who met inclusion criteria; among them, 5810 (58%) were born by CD due to NRFHR, and 4146 (42%) were born via CD following labor dystocia with normal fetal heart rate (comparison group). Offspring born following NRFHR had higher rates of infectious morbidity-related hospitalizations (11.4% vs. 9.1%; odds ratio, 1.3; 95% confidence interval, 1.1–1.5; P < 0.01; Kaplan-Meier survival curve P < 0.01). The association remained significant and independent while adjusting for gestational age, maternal age and comorbidities, using a Cox proportional hazards model (adjusted hazard ratio, 1.3; 95% confidence interval, 1.2–1.4; P < 0.01).

Conclusions:
In our population, CD due to NRFHR is a risk factor for pediatric infectious morbidity-related hospitalizations of the offspring.