bluuebunny/crossref_metadata_2025_split huggingface dataset:
DICER1 platform domain missense variants inhibit miRNA biogenesis and lead to tumor susceptibility
Authors: Pelletier Dylan , Chong Anne-Laure , Wu Mona , Witkowski Leora , Albert Sophie , Sabbaghian Nelly , Fabian Marc R , Foulkes William D 
Published: June 2023

Abstract
The endoribonuclease DICER1 plays an essential role in the microRNA (miRNA) biogenesis pathway, cleaving precursor miRNA (pre-miRNA) stem-loops to generate mature single-stranded miRNAs. Germline pathogenic variants (GPVs) in DICER1 result in DICER1 tumor predisposition syndrome (DTPS), a mainly childhood-onset tumor susceptibility disorder. Most DTPS-causing GPVs are nonsense or frameshifting, with tumor development requiring a second somatic missense hit that impairs the DICER1 RNase IIIb domain. Interestingly, germline DICER1 missense variants that cluster in the DICER1 Platform domain have been identified in some persons affected by tumors that also associate with DTPS. Here, we demonstrate that four of these Platform domain variants prevent DICER1 from producing mature miRNAs and as a result impair miRNA-mediated gene silencing. Importantly, we show that in contrast to canonical somatic missense variants that alter DICER1 cleavage activity, DICER1 proteins harboring these Platform variants fail to bind to pre-miRNA stem-loops. Taken together, this work sheds light upon a unique subset of GPVs causing DTPS and provides new insights into how alterations in the DICER1 Platform domain can impact miRNA biogenesis.
Watching the clock in glioblastoma
Authors: Chan Priscilla , Rich Jeremy N , Kay Steve A 
Published: June 2023

Abstract
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 14.2% of all diagnosed tumors and 50.1% of all malignant tumors, and the median survival time is approximately 8 months irrespective of whether a patient receives treatment without significant improvement despite expansive research (Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015–2019. Neurooncology. 2022; 24(suppl 5):v1–v95.). Recently, important roles for the circadian clock in GBM tumorigenesis have been reported. Positive regulators of circadian-controlled transcription, brain and muscle ARNT-like 1 (BMAL1), and circadian locomotor output cycles kaput (CLOCK), are highly expressed also in GBM and correlated with poor patient prognosis. BMAL1 and CLOCK promote the maintenance of GBM stem cells (GSCs) and the establishment of a pro-tumorigenic tumor microenvironment (TME), suggesting that targeting the core clock proteins may augment GBM treatment. Here, we review findings that highlight the critical role the circadian clock plays in GBM biology and the strategies by which the circadian clock can be leveraged for GBM treatment in the clinic moving forward.
Tufted Puffins exhibit low levels of genetic differentiation among breeding colonies in North America
Authors: Graham Brendan A , Hipfner J Mark , Rojek Nora A , Stephensen Shawn W , Burg Theresa M 
Published: June 2023

Abstract
Tufted Puffins (Fratercula cirrhata) are experiencing population declines in some parts of their distribution, making this a species of increased conservation interest. Genetic data will help to identify Tufted Puffin populations of conservation importance and provide an important tool for developing conservation management plans. This species is broadly distributed across the North Pacific Ocean but little is known about the extent of genetic variation and differentiation across their range. In this study, we examine mitochondrial DNA (mtDNA), 8 microsatellite loci and 1,260 single nucleotide polymorphisms (SNPs) to determine the extent of gene flow among 7 breeding colonies (Oregon to the western Aleutians) in the North American breeding range of the species and identify potential barriers to dispersal. Our results show that most breeding colonies form a single genetic cluster, and mtDNA data show substantial historical gene flow among populations. For the microsatellite dataset, all FST comparisons that include St. Lazaria, in southeast Alaska, except Oregon, which had a small sample size, were significant as were comparisons between Triangle Island and the two westernmost sampling sites of Buldir and Aiktak. For the SNP dataset, FST comparisons were low and nonsignificant, further suggesting that breeding colonies form a single panmictic population. Individuals were more closely related to individuals from the same colony, and we found a weak relationship between genetic and geographic distance. This suggests that dispersal among colonies is high, likely facilitated by an overlap in wintering ranges among colonies. The high connectivity among breeding colonies indicates that Tufted Puffins form a single conservation unit, although future genetic studies should incorporate a whole genome sequencing approach to assessing how functional genetic diversity varies across their distribution.
How welfare wins: Discursive institutionalism, the politics of the poor, and the expansion of social welfare in India during the early 21st century
Authors: Roy Indrajit 
Published: June 2023

AbstractThe worldwide explosion of social welfare has been described as the “quiet revolution” of our time. This paper analyses the expansion of social welfare in India during the early part of the 2000s. What explains this expansion of encompassing social welfare in India, following a history of disparate and fragmented social policies? The answer, I argue, lies in recognizing the importance of the “politics of the poor,” the ensemble of negotiations that encompass both electoral participation and contentious politics vis-à-vis the political institutions in India. The paper develops this argument by drawing together insights from discursive institutionalism, Indian politics, and the politics of welfare literature. Doing so enables me to examine the ways in which poor people’s political practices were interpreted by India’s parliamentarians to justify the legislation of India’s flagship social welfare program the National Rural Employment Guarantee Act. I analyze the discourses communicated through 78 parliamentary debates in English and Hindi to enact the law. I blend this analysis with process tracing of electoral behavior of India’s poor and the Maoist insurrection that exploded in the country’s poorest districts at the turn of the century.
Discontinuation rate of sulfasalazine, leflunomide and methotrexate due to adverse events in a real-life setting (NOR-DMARD)
Authors: Mielnik Pawel , Sexton Joseph , Fagerli Karen M , Bakland Gunnstein , Hu Yi , Kristianslund Eirik K , Hoff Mari , Wierød Ada , Kvien Tore K 
Published: June 2023

Abstract

Objectives
MTX, LEF and SSZ are conventional synthetic DMARDs (csDMARDs) with a well-established role in the treatment of RA. We aimed to estimate and compare the relative risks for adverse events (AEs) and the discontinuation of these drugs owing to AEs.

Methods
We included all 3339 patients from the NOR-DMARD study treated with MTX, LEF or SSZ in monotherapy. All reported AEs were compared between treatment groups using quasi-Poisson regression. In addition, drug retention rates were analysed using Kaplan–Meier estimates with Cox regression to control for possible confounders. We analysed drug retention rates and cumulative risk of discontinuation attributable to AEs using the Kaplan–Meier estimator. We assessed age, sex, baseline DAS in 28 joints with ESR (DAS28-ESR), seropositivity, prednisolone use, previous DMARD use, year of inclusion and co-morbidity as possible cofounders.

Results
We found that the discontinuation rate attributable to AEs was significantly higher for LEF and SSZ than for MTX. After the first year, it was 13.7% (95% CI 12.2, 15.2), 39.6% (95% CI 34.8, 44) and 43.4% (95% CI 38.2, 48.1) for MTX, SSZ and LEF, respectively. Similar results were found when adjusting for confounders. The overall AEs were comparable across the treatment groups. The AE profile was as expected for each drug.

Conclusion
Our work has shown a similar AE profile of csDMARDs to previous data. However, higher discontinuation rates for SSZ and LEF cannot be explained easily from AE profiles.
Evidence on Buprenorphine Dose Limits: A Review
Authors: Grande Lucinda A. , Cundiff Dave , Greenwald Mark K. , Murray MaryAnne , Wright Tricia E. , Martin Stephen A. 
Published: June 2023

Objectives
As overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly effective medication for reducing the risk of overdose death, but only if a patient remains in treatment. Shared decision making between prescribers and patients is important to establish a dose that meets each patient’s treatment needs. However, patients frequently face a dose limit of 16 or 24 mg/d based on dosing guidelines on the Food and Drug Administration’s package label.

Methods
This review discusses patient-centered goals and clinical criteria for determining dose adequacy, reviews the history of buprenorphine dose regulation in the United States, examines pharmacological and clinical research results with buprenorphine doses up to 32 mg/d, and evaluates whether diversion concerns justify maintaining a low buprenorphine dose limit.

Results
Pharmacological and clinical research results consistently demonstrate buprenorphine’s dose-dependent benefits up to at least 32 mg/d, including reductions in withdrawal symptoms, craving, opioid reward, and illicit use while improving retention in care. Diverted buprenorphine is most often used to treat withdrawal symptoms and reduce illicit opioid use when legal access to it is limited.

Conclusions
In light of established research and profound harms from fentanyl, the Food and Drug Administration’s current recommendations on target dose and dose limit are outdated and causing harm. An update to the buprenorphine package label with recommended dosing up to 32 mg/d and elimination of the 16 mg/d target dose would improve treatment effectiveness and save lives.
Reconstruction of High-Tension Scalp Defects by the Twizzler Technique: A Retrospective Case Series
Authors: Riopelle Alexandria M. , Jeong Daehee , Boyd Alexandra Y. , Schanbacher Carl F. 
Published: June 2023

BACKGROUND
Scalp wounds are difficult to close primarily because of the inelasticity of the galea, often requiring adjacent tissue transfer or grafting. It is still debated whether intraoperative tissue expansion can occur on the scalp.

OBJECTIVE
We report our experience with the Twizzler technique, a form of intraoperative tissue expansion and load cycling, to achieve primary closure of high-tension scalp wounds.

MATERIALS AND METHODS
In this case series, scalp defects repaired by the Twizzler were identified and those with minimum 3 month follow-up underwent assessment by physicians and patients.

RESULTS
All 50 scalp defects that could not be otherwise closed primarily were repaired successfully with the Twizzler. The average defect width was 2.0 cm (range 0.9–3.9 cm), the average physician aesthetic rating was 3.71 on a 5-point scale (very good; n = 25), and most patients rated the scars as “near normal skin” on the Patient and Observer Scar Assessment Scale 3.0 (n = 32).

CONCLUSION
Based on the findings of this case series, the Twizzler can be used to repair small and medium high-tension scalp defects after Mohs micrographic surgery. Intraoperative tissue expansion and creep deformation on the scalp is limited, but seemingly possible.
Safety of recent ophthalmic drugs and devices for wet macular degeneration
Authors: Timtim Elise , Weng Christina Y. , Finn Avni P. 
Published: June 2023

Purpose of review
With frequent antivascular endothelial growth factors (VEGF) injections well established as the standard of care in neovascular age-related macular degeneration (nAMD), focus has now shifted towards decreasing treatment burden without compromising safety and efficacy. This review summarizes clinical stage and recently approved drugs and devices for nAMD, with an emphasis paid to safety concerns and their implications for product adoption.

Recent findings
Three strategies have emerged to decrease the treatment burden associated with the current standard of care: more durable intravitreal agents, sustained-release modalities and gene therapy. The appearance of biosimilars will further impact drug availability and cost. As patterns of adverse events emerge from clinical trial or postmarketing surveillance data, manufacturers have proactively responded by appointing independent review committees or issuing voluntary recalls. However, the example of one biosimilar approved outside of the USA and European Union demonstrates how early safety concerns, even when addressed by substantive data, can generate lingering uncertainty.

Summary
As the number of promising new treatments in nAMD continues to grow, so too does the amount of data that providers must sift through. The perception of safety surrounding first movers in each new therapeutic area is sure to affect adoption of that modality more broadly.
Outcomes of iStent Inject Versus Kahook Dual Blade Surgery in Glaucoma Patients Undergoing Cataract Surgery
Authors: Barkander Anna , Economou M A , Jóhannesson Gauti 
Published: June 2023

Précis:
iStent Inject implantation (iStent) or Kahook Dual Blade goniotomy (KDB) in combination with phacoemulsification have a similar IOP-lowering effect in all stages of glaucoma, and medications are significantly reduced, especially after KDB.

Purpose:
To compare the 2-year efficacy and safety of iStent or KDB in combination with phacoemulsification in eyes with mild to advanced open angle glaucoma.

Methods:
A retrospective chart review of 153 patients that received iStent or KDB in combination with phacoemulsification at a single center between March 2019 and August 2020. The main outcome parameters at 2 years were: (1) intraocular pressure (IOP)-reduction ≥20%, with a postoperative IOP ≤18 mm Hg, and (2) a reduction of ≥1 medication. Results were stratified by glaucoma grade.

Results:
After 2 years, mean IOP was reduced from 20.3±6.1 to 14.2±4.1 mm Hg in the phaco-iStent group (P<0.001) and from 20.1±6.1 to 14.7±3.6 mm Hg in the phaco-KDB group (P<0.001). The mean number of medications was reduced from 3.0±0.9 to 2.6±1.1 in the Phaco-iStent group (P=0.001) and from 2.3±1.0 to 1.5±1.3 in the Phaco-KDB group (P<0.001). Success regarding IOP-reduction ≥20% with a postoperative IOP ≤18 mm Hg was met by 46% in the phaco-iStent group and by 51% in the phaco-KDB group. A reduction of ≥1 medication was met by 32% in the phaco-iStent group and by 53% in the phaco-KDB group (P=0.013). Eyes with mild to moderate and advanced glaucoma responded equally well to the success criteria.

Conclusions:
iStent and KDB, in combination with phacoemulsification, both lowered IOP effectively in all stages of glaucoma. More medications were reduced after KDB, suggesting that it may be a more effective procedure compared with iStent.
Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures
Authors: Sluka Kathleen A. , Wager Tor D. , Sutherland Stephani P. , Labosky Patricia A. , Balach Tessa , Bayman Emine O. , Berardi Giovanni , Brummett Chad M. , Burns John , Buvanendran Asokumar , Caffo Brian , Calhoun Vince D. , Clauw Daniel , Chang Andrew , Coffey Christopher S. , Dailey Dana L. , Ecklund Dixie , Fiehn Oliver , Fisch Kathleen M. , Frey Law Laura A. , Harris Richard E. , Harte Steven E. , Howard Timothy D. , Jacobs Joshua , Jacobs Jon M. , Jepsen Kristen , Johnston Nicolas , Langefeld Carl D. , Laurent Louise C. , Lenzi Rebecca , Lindquist Martin A. , Lokshin Anna , Kahn Ari , McCarthy Robert J. , Olivier Michael , Porter Linda , Qian Wei-Jun , Sankar Cheryse A. , Satterlee John , Swensen Adam C. , Vance Carol G.T. , Waljee Jennifer , Wandner Laura D. , Williams David A. , Wixson Richard L. , Zhou Xiaohong Joe ,   the A2CPS Consortium
Published: June 2023

Abstract
Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.
Learning pain from others: a systematic review and meta-analysis of studies on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning
Authors: Meeuwis Stefanie H. , Wasylewski Mateusz T. , Bajcar Elżbieta A. , Bieniek Helena , Adamczyk Wacław M. , Honcharova Sofiia , Di Nardo Marianna , Mazzoni Giuliana , Bąbel Przemysław 
Published: June 2023

Abstract
Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that contribute to these effects could help in the development of strategies for optimizing treatment of chronic pain conditions. We systematically reviewed and meta-analyzed the literature on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning (OL). A systematic literature search was conducted in the databases PubMed, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus, and Academic Search Ultimate. Twenty-one studies were included in the systematic review, 17 of which were suitable for meta-analysis (18 experiments; n = 764 healthy individuals). The primary end point was the standardized mean difference (SMD) for pain following placebo cues associated during OL with low vs high pain. Observational learning had a small-to-medium effect on pain ratings (SMD 0.44; 95% confidence interval [CI] 0.21-0.68; P < 0.01) and a large effect on pain expectancy (SMD 1.11; 95% CI 0.49-2.04; P < 0.01). The type of observation (in-person vs videotaped) modulated the magnitude of placebo hypoalgesia/nocebo hyperalgesia (P < 0.01), whereas placebo type did not (P = 0.23). Finally, OL was more effective when observers' empathic concern (but no other empathy-related factors) was higher (r = 0.14; 95% CI 0.01-0.27; P = 0.03). Overall, the meta-analysis demonstrates that OL can shape placebo hypoalgesia and nocebo hyperalgesia. More research is needed to identify predictors of these effects and to study them in clinical populations. In the future, OL could be an important tool to help maximize placebo hypoalgesia in clinical settings.
Interpretation bias in endometriosis-related pain
Authors: Pickup Brydee , Sharpe Louise , Todd Jemma 
Published: June 2023

Abstract
Endometriosis-related pain has been predominantly medically managed, which has hindered understanding of psychological factors involved in these pain experiences. Models of chronic pain highlight the biased interpretation of ambiguous information as health threat related (interpretation bias) as an important process in the development and maintenance of chronic pain. Whether interpretation bias may also be similarly implicated in endometriosis-related pain is unclear. The current study aimed to address this gap in the literature by (1) comparing interpretation biases between a sample of participants with endometriosis and a control sample of participants without medical conditions and pain, (2) exploring relationships between interpretation bias and endometriosis-related pain outcomes, and (3) exploring whether interpretation bias moderated the relationship between endometriosis-related pain severity and pain interference. The endometriosis and healthy control samples comprised 873 and 197 participants, respectively. Participants completed online surveys assessing demographics, interpretation bias, and pain-related outcomes. Analyses revealed that interpretation bias was significantly stronger among individuals with endometriosis relative to controls, with a large effect size. Within the endometriosis sample, interpretation bias was significantly associated with increases in pain-related interference, however, interpretation bias was not associated with any other pain outcomes and did not moderate the relationship between pain severity and pain interference. This study is the first to evidence biased interpretation styles among individuals with endometriosis and to show this bias is associated with pain interference. Whether interpretation bias varies over time and whether this bias can be modified through scalable and accessible interventions to alleviate pain-related interference are avenues for future research.
Investigation of exacerbating factors for postpartum hair loss: a questionnaire-based cross-sectional study
Authors: Hirose Asuka , Terauchi Masakazu , Odai Tamami , Fudono Ayako , Tsurane Kotoi , Sekiguchi Masaki , Iwata Misako , Anzai Tatsuhiko , Takahashi Kunihiko , Miyasaka Naoyuki 
Published: June 2023

Background:
Although postpartum hair loss is believed to be common, there is little reliable information.

Objective:
We sought to examine the factors that were associated with postpartum hair loss and to elucidate factors correlated with its pathogenesis.

Methods:
We carried out a questionnaire-based cross-sectional study. The study participants were women who delivered at 2 facilities and filled the questionnaire 10–18 months after delivery. The survey questionnaire included baseline characteristics, pregnancy details, delivery, childcare, and extent of postpartum hair loss. We divided participants into 2 groups according to the absence or presence of postpartum hair loss and performed logistic regression analyses.

Results:
A total of 331 (21.0%) responses were analyzed; among these 304 (91.8%) women had postpartum hair loss. The average time for the start, peak, and end of hair loss was 2.9, 5.1, and 8.1 months, respectively. Women with hair loss had an earlier time of delivery, a lower birth weight, a higher preterm labor rate, and longer-term breastfeeding. Logistical regression analyses revealed that longer-term breastfeeding and preterm labor were independent predictors of postpartum hair loss. The adjusted odds ratio for postpartum hair loss in women who ended breastfeeding 6–12 months postpartum versus those who ended it after 12 months or more was 5.96 (95% confidence interval [CI] [1.68, 21.09]) and 6.37 (95% CI [1.95, 20.76]) compared with those who stopped breastfeeding within 6 months postpartum.

Limitations:
Finer details such as pregnancy complications and delivery information may not be accurate since all results are based on questionnaire responses. There may be a sampling bias because women who suffer from postpartum hair loss may tend to participate more frequently.

Conclusion:
Over 90% of women experienced postpartum hair loss. Our data show that long-term breastfeeding and preterm labor correlate with postpartum hair loss.