bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex
Authors: Ravichandran Subramaniyam , Razzaq Maria , Parveen Nazia , Ghosh Ambarnil , Kim Kyeong Kyu 
Published: August 2021

AbstractG-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.
Reconciling psychological and neuroscientific accounts of reduced motivation in aging
Authors: Soutschek Alexander , Bagaïni Alexandra , Hare Todd A , Tobler Philippe N 
Published: August 2021

Abstract
Motivation is a hallmark of healthy aging, but the motivation to engage in effortful behavior diminishes with increasing age. Most neurobiological accounts of altered motivation in older adults assume that these deficits are caused by a gradual decline in brain tissue, while some psychological theories posit a switch from gain orientation to loss avoidance in motivational goals. Here, we contribute to reconcile the psychological and neural perspectives by providing evidence that the frontopolar cortex (FPC), a brain region involved in cost–benefit weighting, increasingly underpins effort avoidance rather than engagement with age. Using anodal transcranial direct current stimulation together with effort–reward trade-offs, we find that the FPC’s function in effort-based decisions remains focused on cost–benefit calculations but appears to switch from reward-seeking to cost avoidance with increasing age. This is further evidenced by the exploratory, independent analysis of structural brain changes, showing that the relationship between the density of the frontopolar neural tissue and the willingness to exert effort differs in young vs older adults. Our results inform aging-related models of decision-making by providing preliminary evidence that, in addition to cortical thinning, changes in goal orientation need to be considered in order to understand alterations in decision-making over the life span.
Safety Profile for Microneedling: A Systematic Review
Authors: Chu Sherman , Foulad Delila P. , Atanaskova Mesinkovska Natasha 
Published: August 2021

BACKGROUND
Microneedling is a minimally invasive procedure that stimulates collagen and elastin proliferation. It is used in the treatment of various skin pathologies, that is, scarring, photodamage, and hair loss; however, its safety profile has yet to be comprehensively reviewed.

OBJECTIVE
This review will discuss the reported side effects of microneedling in the current literature and delineate factors that increase the risk of complications.

MATERIALS AND METHODS
A literature search in August 2019 was conducted using the PubMed database to identify studies reporting adverse events (AEs) after microneedling therapy.

RESULTS
Eighty-five articles were included in this systematic review. The most common reported AEs are transient procedural events that are expected postprocedure lasting up to 7 days, such as transient erythema/edema and pain, postinflammatory hyperpigmentation (PIH), dry skin/exfoliation, lymphadenopathy, and irritant contact dermatitis. Persistent serious adverse effects included PIH, tram-track scarring, and granulomatous reactions. Factors that increase the risk of events are active infections, darker skin, and metal allergies.

CONCLUSION
Microneedling is a relatively safe therapy. Most reported AEs are minimal, resolving quickly and spontaneously. Caution should be taken in patients with active infection, darker skin types, metal allergies, and when used in conjunction with products not approved for intradermal use.
Depression, burnout, and professional outcomes among PAs
Authors: Blackstone Sarah R. , Johnson Aimee K. , Smith Noël E. , McCall Timothy C. , Simmons Whitney R. , Skelly Ashley W. 
Published: August 2021

ABSTRACT

Objective:
This study examined the effect of depression and burnout on PA professional fulfillment and medical errors.

Methods:
Eight hundred eighty PAs completed an online survey containing the Professional Fulfillment Index, PHQ-2, GAD-7, and demographic questions. Two serial mediation models examined the relationship between depression, burnout, and professional outcomes.

Results:
Burnout fully mediated the relationship between depression and outcomes in both models and the present research indicates that burnout plays a stronger role in job satisfaction than symptoms of depression.

Conclusions:
Understanding the underpinnings of professional satisfaction may mitigate clinician turnover, which in turn may lead to cost savings for the organization, better resilience and mental health for clinicians, and potentially better patient outcomes.
Knockdown of Circular Ubiquitin-specific Peptidase 9 X-Linked Alleviates Oxidized Low-density Lipoprotein-induced Injuries of Human Umbilical Vein Endothelial Cells by Mediating the miR-148b-3p/KLF5 Signaling Pathway
Authors: Jiang Xiaowen , Chen Lei , Wu Hao , Chen Yuegao , Lu Weiqin , Lu Kaiping 
Published: August 2021

Abstract:
There is evidence that the development of atherosclerosis (AS) involves the dysregulation of circular RNAs. This study aimed to investigate the role of circular ubiquitin-specific peptidase 9 X-linked (circUSP9X) in AS cell models. Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) were used as cell models of AS. The expression of circUSP9X, miR-148b-3p, and Kruppel-like factor 5 (KLF5) messenger RNA was measured using quantitative polymerase chain reaction. Cell viability was assessed by Cell Counting Kit-8 assay. Lactate dehydrogenase leakage, malonaldehyde content, and superoxide dismutase activity were investigated using matched commercial kits. Cell apoptosis was detected using flow cytometry assay. The protein levels of apoptosis-related markers and KLF5 were detected by western blot. The release of proinflammatory factors was monitored by enzyme-linked immunosorbent assay. The predicted relationship between miR-148b-3p and circUSP9X or KLF5 was confirmed by dual-luciferase reporter assay or RNA immunoprecipitation assay. CircUSP9X was highly expressed in ox-LDL–treated HUVECs. CircUSP9X knockdown inhibited ox-LDL–induced lactate dehydrogenase leakage, apoptosis, inflammation, and oxidative stress in HUVECs. CircUSP9X directly bound to miR-148b-3p, and KLF5 was a target of miR-148b-3p. CircUSP9X could regulate KLF5 expression by competitively targeting miR-148b-3p. Rescue experiments indicated that circUSP9X knockdown inhibited ox-LDL–induced HUVEC injuries by enriching miR-148b-3p, and miR-148b-3p restoration alleviated ox-LDL–induced HUVEC injuries by degrading KLF5. In conclusion, circUSP9X knockdown relieved ox-LDL–triggered HUVEC injuries during AS progression partly by mediating the miR-148b-3p/KLF5 network.
Nischarin Is Not the Functional I1 Imidazoline Receptor Involved in Blood Pressure Regulation
Authors: Arnoux Alizée , Aubertin Gaëlle , Da Silva Sylvia , Weiss Maud , Bousquet Pascal , Monassier Laurent , Niederhoffer Nathalie 
Published: August 2021

Abstract:
Imidazoline receptor antisera selected/Nischarin was proposed several years ago as the functional entity for the I1 medullary receptors (I1Rs) targeted, together with α2-adrenoceptors, by the centrally acting antihypertensive drugs, such as clonidine. The objective of this study was to test this assumption using a pyrroline analog of clonidine, LNP599, which, unlike clonidine and related compounds, displays high selectivity toward I1Rs. Cardiovascular effects of LNP599 (3 mg/kg intravenous) were evaluated in anesthetized, artificially ventilated nischarin mutant rats expressing a truncated form of nischarin lacking the putative imidazoline binding site. LNP599 induced a rapid and pronounced fall in arterial blood pressure in wild-type animals (−42.7% ± 11.0% after 15 minutes), associated with a ≈30% heart rate reduction. Similar effects were obtained in homozygous and heterozygous nischarin mutant rats. The observation that the hypotensive response to I1R activation is not affected by the absence of the putative imidazoline binding site on nischarin strongly suggests that nischarin cannot be regarded as the functional I1R. Carbohydrate regulation was improved in nischarin mutant rats, further supporting the conclusion that nischarin and I1R are 2 distinct molecular entities.
The American Contact Dermatitis Society Core Allergen Series
Authors: Towery Laura E. , Marion Tyler , Montañez-Wiscovich Marjorie 
Published: August 2021

ABSTRACT
Allergic contact dermatitis has been increasing in prevalence with the growing complexity of the ingredients in commercial products. The gold standard for the diagnosis of allergic contact dermatitis is patch testing. Patch testing allows for identification of relevant allergens that can then guide treatment with targeted avoidance. Although patch testing initially required clinicians to handpick suspected allergens, the development of a standard allergen panel in 1995 called the Thin-Layer Rapid Epicutaneous Test transformed the way patch testing is performed. In recent years, more comprehensive series have been developed, including the American Contact Dermatitis Society (ACDS) Core Allergen Series, which tests for 80 allergens rather than 36 allergens. The benefits of using the ACDS Series include (a) a greater likelihood of detecting relevant allergen(s), (b) a decreased need for repeat testing and subsequently fewer clinic appointments and less patient travel, and (c) an ability to update and modify the series of allergens based on consumer trends and patient data. Important/relevant allergens found in the ACDS Series but not the Thin-Layer Rapid Epicutaneous Test include many preservatives, adhesives, fragrances, and propylene glycol. We propose that patch testing with extended series of allergens be considered for first-line use when evaluating patients with suspected allergic contact dermatitis.
Lice Infestations in the Pediatric Population
Authors: Vassantachart Janna M. , Florentino Abigail , Admani Shehla 
Published: August 2021

ABSTRACT
Lice cause a common pruritic condition known as pediculosis, which can cause significant psychosocial distress and embarrassment. The infestations can present differently in the pediatric population compared with the adult population, and certain infestations such as head lice are found more commonly in children. To avoid delayed diagnosis, healthcare providers should be knowledgeable of these differences. This article provides an overview of epidemiology and pathophysiology, clinical presentation and diagnosis, and management of lice infestations, specifically addressing the infant and children population.
Decision-Making in Sport During a Pandemic
Authors: Hamilton Bruce , Burt Peter , Anderson Lynley 
Published: August 2021

Objective:
The COVID-19 pandemic has affected all elements of global society, and sport is not exempt. Many sporting events have been either postponed or canceled, and national sporting organizations have had to make highly complex decisions in the face of scientific uncertainty and risk. This article applies these lessons to the world of sport with the goal of assisting sporting organizations to make sound and reasoned decisions during a pandemic.

Data Sources:
A narrative approach using both academic literature sources and live examples from the authors' experience. We use Daniels and Sabin's accountability for reasonableness framework to facilitate decision-making in the face of such uncertainty.

Main Results:
Decision-making in the context of uncertainty has the potential to create conflict and disengagement from key stakeholders. Evidence from recent pandemics has illustrated that an ethical approach to decision-making results in reasoned decision-making and confers a legitimacy to decisions that ultimately supports engagement and satisfaction from stakeholders.

Conclusions:
The incorporation of ethical considerations into risk assessment and management when making complex decisions, which incorporate high levels of uncertainty, will assist sporting organizations have positive outcomes.
Long-term survival following radiofrequency ablation of lung metastases in an elderly patient with calcaneal osteosarcoma
Authors: Futani Hiroyuki , Takaki Haruyuki , Sawai Tatsuo , Taniguchi Junichi , Kako Yasukazu , Ide Yoshi-Hiro , Yamakado Koichiro , Tachibana Toshiya 
Published: August 2021

Abstract

Rationale:
Recently, the number of osteosarcomas has been increasing in elderly patients due to human longevity. Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete resection in elderly patients is often difficult due to high risk of operative complications. Computed tomography (CT) guided radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. In this report, we present the first case older than 65 years applying RFA for lung metastases due to osteosarcoma.

Patient concerns:
A 74-year-old male presented with 1-year history of heel pain. A conventional high-grade osteosarcoma in his calcaneus was diagnosed. Below-knee amputation was performed. However, lung metastases were found in both lungs 1 year after amputation. CT-guided lung RFA was chosen since surgical intervention for lung metastases was abandoned because of tumor multiplicity and medical comorbidities. A total of 18 lung metastases were treated by CT-guided RFA. The most frequent complication was pneumothoraxes in 4 of 8 (50%) procedures and chest tube drainage was required in 2 of these (2 of 8 (25%) procedures).

Diagnoses:
Six lung metastases of osteosaroma were found in both lungs at 1 year after surgery.

Interventions:
CT-guided lung RFA was performed. A total of 18 lung metastases were treated in 8 lung RF procedures.

Outcomes:
The patient has been alive with disease for 5.5 years after the initial surgery.

Lessons:
CT-guided lung RFA is effective for elderly patients with osteosarcoma lung metastases in spite of discouragement of lung metastasectomy due to multiplicity of metastases and medical-comorbidities.
The prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy
Authors: Zhang Kai-Ping , Fang Xiang , Zhang Yin , Chao Min 
Published: August 2021

Abstract

Background:
It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.

Methods:
A detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software.

Results:
Consequently, 26 studies including 7943 patients were satisfied in current analysis. There were no significant differences between liposomal and conventional chemotherapy in OS (HR = 0.98, 95%CI: 0.93–1.04, P = .544) and PFS (HR = 1.00, 95%CI: 0.92–1.10, P = .945). Likewise, subgroup-analysis regarding country, cancer type, and sample sizes also showed the similar results of the 2 paired groups.

Conclusion:
Taken together, our finding has demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm our conclusion.
Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy
Authors: Tanito Masaki , Ishida Akiko , Ichioka Sho , Takayanagi Yuji , Tsutsui Aika , Manabe Kaoru , Shirakami Tomoki , Sugihara Kazunobu , Matsuo Masato 
Published: August 2021

Abstract
The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ± standard deviation, 69.9 ± 14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ± 5.4 mm Hg) than grades 0 (15.0 ± 5.1 mm Hg, P = .032) and 1 (14.5 ± 4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ± 3.2 mm Hg) than the other 3 grades (1.3–1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ± 0.8) and bimatoprost (2.0 ± 0.7) than latanoprost (1.0 ± 0.8, P < .001 for both comparisons) and tafluprost (1.0 ± 0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ± 0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard β = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (−0.18) and omidenepag (−0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.
The cognitive dysfunction related to Alzheimer disease or cerebral small vessel disease
Authors: Liang Zhenhong , Wu Lijuan , Gong Shumei , Liu Xiaohong 
Published: August 2021

Abstract
Alzheimer disease (AD) and sporadic cerebral small vessel disease (CSVD) are common cognitive disorders. Both AD and CSVD have mental symptoms including chronic progressive cognitive impairment, dysfunction, and behavioral abnormalities. However, the differences on the cognitive dysfunction of AD and CSVD remain unclear. It is necessary to elucidate the cognitive dysfunction differences of AD and CSVD, and to identify the potential risk factors.
AD or sporadic CSVD patients treated in our hospital from December 1, 2018 to May 31, 2019 were included. And we selected healthy participants as controls. The mini-mental state examination and Montreal Cognitive Assessment Scale were used for neuropsychological assessment, and related medical information were collected and compared.
A total of 190 patients were included. The total mini-mental state examination scores in AD, CSVD group were significantly less than that of control group, there were significant differences in the domains of directional ability, attention and computing ability, delayed recall, and visual perception (all P < .05); the total Montreal Cognitive Assessment Scale scores in AD, CSVD group were significantly less than that of control group. There were significant differences in the domains of visual space and execution, immediate remember, attention and computing ability, language, delayed recall, and directional ability (all P < .05); diabetes was a risk factor both for AD (hazard ratio = 1.63, 95% confidence interval: 1.35–1.97) and CSVD (hazard ratio = 1.15, 95% confidence interval: 1.08–1.27).
The cognitive dysfunctions of AD are difference to that of CSVD patients, and diabetes is the risk factor both for AD and CSVD, future studies are needed to further identify the prevention and treatment of AD and CSVD.
Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history
Authors: Wu Jingjing , He Huimin , Zhang Qi , Zhang Yan 
Published: August 2021

Abstract
Fasting plasma glucose level was linearly associated with colorectal cancer (CRC) risk. However, the dose–response relationship between fasting blood glucose (FBG) and CRC risk was still uncertain.
A total of 11,632 patients without self-reported diabetes mellitus and colorectal polyps’ history were identified in the Korean Multicenter Cancer Cohort (1993–2005). The nonlinear relationship was estimated through a restricted cubic spline regression, and a two-piece-wise Cox proportional hazards model was further performed to calculate the threshold effect. Multiple imputation was used to control the bias from missing data.
Overall, 1.1% (n = 132) of participants were diagnosed with CRC in the follow-up duration. With a median follow-up duration of 12.0 years, participants with FBG ≥126 mg/dL were associated with higher CRC risk (adjusted hazard ratio [HR], 1.67; 95% confidence interval [CI]: 1.01, 2.76). Landmark analyses limited to long-term survivors demonstrated increased CRC risk with FBG ≥ 126 mg/dL in all subsets (≥3years: HR,1.93 (95% CI: 1.13–3.29); ≥5years: HR, 2.04 (95% CI: 1.–3.63); ≥10years: HR, 2.50 (95% CI: 1.19–5.25)). With FBG smoothly increasing before, the latter increased dramatically after the turning point (P for nonlinearity = 0.283). When FBG was increasing per mmol/L, HR was 1.07(95% CI: 0.90, 1.29) for FBG < 126 mg/dL and 1.27 (95% CI: 1.06, 1.53) for FBG ≥ 126 mg/dL. Besides, HR was 1.09 (95% CI: 1.02, 1.16) for the CRC risk.
In the population without self-reported diabetes mellitus and colorectal polyps’ history. FBG was linearly associated with CRC risk, especially for FBG over 126 mg/dL.