bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Office of Parliamentary Legal Advisers (opla) in the Houses of the Oireachtas – History, Functions and Recent Key Parliamentary Legal Issues
Authors: Kennedy Oisín , English Mellissa 
Published: December 2021

Abstract
The Office of Parliamentary Legal Advisers (opla) is the in-house legal team in the Irish national parliament. It provides specialist, non-partisan legal advice to Parliament on a broad range of parliamentary, constitutional and corporate legal issues. In recent years, the opla has been assigned additional functions within the legislative process, now providing legal policy analysis and legislative drafting services to non-Government Members in respect of private legislative proposals and advising Members in respect of Government Bills. This article will provide a history of the opla, will outline some recent key parliamentary legal issues and will elaborate on the recent development of legislative drafting and advisory services within the Office.
Making the Void Fruitful
Authors: Keane Patrick J. 
Published: December 2021

Shedding fresh light on the life and work of William Butler Yeats—widely acclaimed as the major English-language poet of the twentieth century—this new study by leading scholar Patrick J. Keane questions established understandings of the Irish poet’s long fascination with the occult: a fixation that repelled literary contemporaries T.S. Eliot and W.H. Auden, but which enhanced Yeats’s vision of life and death.
Through close reading of selected poems, the first section of Making the Void Fruitful assesses Yeats’s spiritualised treatment of corporeal themes, exploring sex and eroticism as the expression of a duality inherent to his ontological and supernatural convictions. The power-producing tension in Yeats’s work is not only intellectual but emotional. At its vital centre is his Muse: the beautiful political firebrand, Maud Gonne, whose activist Republican politics he considered his one real rival. Through close engagement with the poems and plays she inspired, the second section explores Yeats’s complex relationship with Maud, an obsessive and unrequited love which he sublimated and transformed into the greatest body of Muse poetry since Petrarch, in whose tradition of spiritualized eroticism Yeats, perhaps the last of the great Romantics, was consciously writing.
Shaped by the conviction that no modern poet exceeded Yeats in animating the enduring themes of love and spirituality through poetry, this book emphasises the influence, of Blake, Nietzsche, and John Donne, on what Yeats called ‘the thinking of the body’. Grounded firmly in the textual materiality of Yeats’s oeuvre, this book will be of interest to researchers and students of W.B. Yeats, as well as to those in the fields of Anglophone literatures and cultures, and philosophy.
Sociodemographic Differences in Care Plans and Time to Treatment Among Children Being Considered for Adenotonsillectomy
Authors: Knaus Maria E. , Koppera Swapna , Lind Meredith N. , Cooper Jennifer N. 
Published: December 2021

ObjectiveTo assess sociodemographic differences in care plans and time to evaluation or treatment after otolaryngologic consultation among children with obstructive sleep‐disordered breathing (oSDB).Study DesignRetrospective cohort study.SettingSingle tertiary children’s hospital.MethodsWe included children aged 2 to 9 years with oSDB seen from June to December 2018 as new otolaryngology clinic patients. Logistic regression was used to examine whether sociodemographic factors were associated with having adenotonsillectomy or polysomnography planned at the end of the visit. Kaplan‐Meier analyses and Cox proportional hazards models were used to compare times to these events.ResultsAn overall 1020 children were included, of whom 65% were White and 18% were Black. Approximately 77% were metropolitan residents, 52% were publicly insured, and 88% of caregivers spoke primarily English. Treatment plans included adenotonsillectomy for 62% of patients, polysomnography for 15%, and new medication therapy for 13%. In multivariable analyses, there were no significant differences by child race/ethnicity, metropolitan/nonmetropolitan residence, type of health insurance, or caregiver primary language in the likelihood of having adenotonsillectomy or polysomnography planned. Among children for whom adenotonsillectomy was planned, children from metropolitan areas had greater times to surgery than children from nonmetropolitan areas (hazard ratio, 0.81 [95% CI, 0.66‐0.99]; P =. 04). This was explained by a difference between Black children from metropolitan areas and White children from nonmetropolitan areas (hazard ratio, 0.65 [95% CI, 0.49‐0.86]; P =. 003); there were no racial/ethnic differences in time to surgery among metropolitan‐residing children (P =. 09).ConclusionsAfter initial otolaryngology consultation, children with oSDB from metropolitan areas have longer times to adenotonsillectomy than those from nonmetropolitan areas.
Independent Role of Nasal Congestion in Positive Airway Pressure Compliance for OSA Treatment
Authors: Wu Hao , Fang Fang , Guo Yaxin , Wu Chan , Wei Yongxiang 
Published: December 2021

ObjectiveTo determine the independent role of nasal congestion in positive airway pressure (PAP) therapy compliance and factors associated with an unfavorable shift of PAP compliance.Study DesignProspective cohort study.SettingTertiary care center.MethodsThis follow‐up study comprised 174 patients with newly diagnosed obstructive sleep apnea (OSA) who accepted PAP therapy from January 2017 to June 2019. Information was collected on basic demographics, comorbidities, sleep‐related symptoms, nasal symptoms, and upper airway assessment. PAP adherence data were collected at the end of the first week and the third month.ResultsAfter 3 months of follow‐up, 147 participants were included for final data analysis. The proportion of nasal congestion (29.2% vs 52.0%, P =. 005) and its severity (mean rank, 58.5 vs 75.1; P =. 007) were significantly higher in the noncompliance group as compared with the compliance group. After adjustment for basic demographics, comorbidities, sleep‐related symptoms or sleep study parameters, and Friedman clinical staging, multinomial logistic regression models showed that nasal congestion (all odds ratios >2.0, P <. 05) was independently associated with a higher odds of PAP noncompliance. Patients with an unfavorable shift of PAP compliance were younger (mean ± SD, 47.5 ± 10.6 vs 53.1 ± 12.6 years; P =. 021) and had a lower body mass index (27.2 ± 3.7 vs 29.3 ± 5.0, P =. 027) than those who consistently complied. OSA severity was associated with PAP compliance, initially and in the long term.ConclusionNasal congestion is an independent predictor of PAP noncompliance. Younger patients with lower BMI were more likely to have an unfavorable shift of PAP compliance. Initial and long‐term adherence to PAP therapy was affected by OSA severity.
The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies—A perspective from US Medicaid data
Authors: Chow Wing , Hardy Hélène , Song Ji , Connolly Nancy , Wu Bingcao 
Published: December 2021

Background People with human immunodeficiency virus (HIV)-1 face challenges with treatment adherence for various reasons, including consideration of neuropsychiatric disorders and neuropsychiatric adverse reactions associated with antiretroviral therapy (ART). Methods A retrospective cohort study was conducted using administrative claims data from the IBM MarketScan® Multi-State Medicaid Database (1/1/2014–12/31/2017). Adults (≥18 years) diagnosed with HIV-1 and newly initiated on antiretroviral therapy with continuous health plan enrollment were included. Primary outcome was the 6-month period prevalence of neuropsychiatric events (NPEs) of interest after ART initiation. Results Among 1971 newly treated patients included in the study, mean age (standard deviation [SD]) was 38.5 (12.7) years, and 41.4% were female. During the 6 months after ART initiation, 51.4% of patients had a claim for ≥1 NPE versus 30.3% of matched patients without HIV. Among newly treated patients, the most common (≥10%) NPE claims were for depression (42.2%), anxiety (15.8%), headache (11.9%), and bipolar/manic depression (10.1%). Also in this group, the mean (SD) total all-cause healthcare cost during the 6-month post-ART initiation was $16,632 ($33,928), of which $2914 ($18,233) was NPE-related. Conclusions In summary, in this Medicaid study of people newly initiated on ART, there was a high prevalence of NPEs, and incremental NPE-associated costs were considerable.
What are you looking at? Gaze following with and without target objects in ASD and typical development
Authors: Thorup Emilia , Nyström Pär , Bölte Sven , Falck-Ytter Terje 
Published: December 2021

Children with autism spectrum disorder (ASD) display difficulties with response to joint attention in natural settings but often perform comparably to typically developing (TD) children in experimental studies of gaze following. Previous work comparing infants at elevated likelihood for ASD versus TD infants has manipulated aspects of the gaze cueing stimulus (e.g. eyes only versus head and eyes together), but the role the peripheral object being attended to is not known. In this study of infants at elevated likelihood of ASD ( N = 97) and TD infants ( N = 29), we manipulated whether or not a target object was present in the cued area. Performance was assessed at 10, 14, and 18 months, and diagnostic assessment was conducted at age 3 years. The results showed that although infants with later ASD followed gaze to the same extent as TD infants in all conditions, they displayed faster latencies back to the model’s face when (and only when) a peripheral object was absent. These subtle atypicalities in the gaze behaviors directly after gaze following may implicate a different appreciation of the communicative situation in infants with later ASD, despite their ostensively typical gaze following ability. Lay abstract During the first year of life, infants start to align their attention with that of other people. This ability is called joint attention and facilitates social learning and language development. Although children with autism spectrum disorder (ASD) are known to engage less in joint attention compared to other children, several experimental studies have shown that they follow other’s gaze (a requirement for visual joint attention) to the same extent as other children. In this study, infants’ eye movements were measured at age 10, 14, and 18 months while watching another person look in a certain direction. A target object was either present or absent in the direction of the other person’s gaze. Some of the infants were at elevated likelihood of ASD, due to having an older autistic sibling. At age 3 years, infants were assessed for a diagnosis of ASD. Results showed that infants who met diagnostic criteria at 3 years followed gaze to the same extent as other infants. However, they then looked back at the model faster than typically developing infants when no target object was present. When a target object was present, there was no difference between groups. These results may be in line with the view that directly after gaze following, infants with later ASD are less influenced by other people’s gaze when processing the common attentional focus. The study adds to our understanding of both the similarities and differences in looking behaviors between infants who later receive an ASD diagnosis and other infants.
Hypofibrinogenemia with preserved hemostasis and protection from thrombosis in mice with an Fga truncation mutation
Authors: Hur Woosuk S. , Paul David S. , Bouck Emma G. , Negrón Oscar A. , Mwiza Jean-Marie , Poole Lauren G. , Cline-Fedewa Holly M. , Clark Emily G. , Juang Lih Jiin , Leung Jerry , Kastrup Christian J. , Ugarova Tatiana P. , Wolberg Alisa S. , Luyendyk James P. , Bergmeier Wolfgang , Flick Matthew J. 
Published: December 2021

Abstract
Genetic variants within the fibrinogen Aα chain encoding the αC-region commonly result in hypodysfibrinogenemia in patients. However, the (patho)physiological consequences and underlying mechanisms of such mutations remain undefined. Here, we generated Fga270 mice carrying a premature termination codon within the Fga gene at residue 271. The Fga270 mutation was compatible with Mendelian inheritance for offspring of heterozygous crosses. Adult Fga270/270 mice were hypofibrinogenemic with ∼10% plasma fibrinogen levels relative to FgaWT/WT mice, linked to 90% reduction in hepatic Fga messenger RNA (mRNA) because of nonsense-mediated decay of the mutant mRNA. Fga270/270 mice had preserved hemostatic potential in vitro and in vivo in models of tail bleeding and laser-induced saphenous vein injury, whereas Fga−/− mice had continuous bleeding. Platelets from FgaWT/WT and Fga270/270 mice displayed comparable initial aggregation following adenosine 5′-diphosphate stimulation, but Fga270/270 platelets quickly disaggregated. Despite ∼10% plasma fibrinogen, the fibrinogen level in Fga270/270 platelets was ∼30% of FgaWT/WT platelets with a compensatory increase in fibronectin. Notably, Fga270/270 mice showed complete protection from thrombosis in the inferior vena cava stasis model. In a model of Staphylococcus aureus peritonitis, Fga270/270 mice supported local, fibrinogen-mediated bacterial clearance and host survival comparable to FgaWT/WT, unlike Fga−/− mice. Decreasing the normal fibrinogen levels to ∼10% with small interfering RNA in mice also provided significant protection from venous thrombosis without compromising hemostatic potential and antimicrobial function. These findings both reveal novel molecular mechanisms underpinning fibrinogen αC-region truncation mutations and highlight the concept that selective fibrinogen reduction may be efficacious for limiting thrombosis while preserving hemostatic and immune protective functions.
OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfash mice, and govern susceptibility to RNA-based therapies
Authors: Sacchetto Claudia , Peretto Laura , Baralle Francisco , Maestri Iva , Tassi Francesca , Bernardi Francesco , van de Graaf Stan F. J. , Pagani Franco , Pinotti Mirko , Balestra Dario 
Published: December 2021

Abstract
Background
Aberrant splicing is a common outcome in the presence of exonic or intronic variants that might hamper the intricate network of interactions defining an exon in a specific gene context. Therefore, the evaluation of the functional, and potentially pathological, role of nucleotide changes remains one of the major challenges in the modern genomic era. This aspect has also to be taken into account during the pre-clinical evaluation of innovative therapeutic approaches in animal models of human diseases. This is of particular relevance when developing therapeutics acting on splicing, an intriguing and expanding research area for several disorders. Here, we addressed species-specific splicing mechanisms triggered by the OTC c.386G>A mutation, relatively frequent in humans, leading to Ornithine TransCarbamylase Deficiency (OTCD) in patients and spfash mice, and its differential susceptibility to RNA therapeutics based on engineered U1snRNA.

Methods
Creation and co-expression of engineered U1snRNAs with human and mouse minigenes, either wild-type or harbouring different nucleotide changes, in human (HepG2) and mouse (Hepa1-6) hepatoma cells followed by analysis of splicing pattern. RNA pulldown studies to evaluate binding of specific splicing factors.

Results
Comparative nucleotide analysis suggested a role for the intronic +10-11 nucleotides, and pull-down assays showed that they confer preferential binding to the TIA1 splicing factor in the mouse context, where TIA1 overexpression further increases correct splicing. Consistently, the splicing profile of the human minigene with mouse +10-11 nucleotides overlapped that of mouse minigene, and restored responsiveness to TIA1 overexpression and to compensatory U1snRNA. Swapping the human +10-11 nucleotides into the mouse context had opposite effects.
Moreover, the interplay between the authentic and the adjacent cryptic 5′ss in the human OTC dictates pathogenic mechanisms of several OTCD-causing 5′ss mutations, and only the c.386+5G>A change, abrogating the cryptic 5′ss, was rescuable by engineered U1snRNA.

Conclusions
Subtle intronic variations explain species-specific OTC splicing patterns driven by the c.386G>A mutation, and the responsiveness to engineered U1snRNAs, which suggests careful elucidation of molecular mechanisms before proposing translation of tailored therapeutics from animal models to humans.
A novel biplanar medial opening-wedge high tibial osteotomy: the Z-shaped technique. A case series at 7.2 years follow-up
Authors: Presutti Marcello , Goderecci Remo , Palumbo Pietro , Giannetti Alessio , Mazzoleni Manuel Giovanni , Randelli Filippo Maria Nicola , Angelozzi Massimo , Calvisi Vittorio , Fidanza Andrea 
Published: December 2021

Abstract
Background
High tibial osteotomy (HTO) provides reliable and good long-term results, if performed with correct indications, but different techniques and types of fixation have been described. The purpose of this study is to present a novel modified biplanar medial opening-wedge (MOW) HTO technique where the osteotomies are performed in a Z-shaped fashion, and to present the medium-term clinical and radiographic results.

Materials and methods
We present a case series of 75 patients (80 knees) with mean age of 45.8 years, affected by isolated medial knee osteoarthritis and symptomatic varus knee malalignment, who underwent novel biplanar Z-shaped MOWHTO. Clinical and radiological outcomes were collected, retrospectively before surgery and at median follow-up of 7.2 years (95% CI 5.6–9.2 months) after surgery. Clinical results and satisfaction were assessed by visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Likert scale. Radiological assessment involved the evaluation of the medial proximal tibial angle (MPTA), tibial slope (TS), Caton–Deschamps index, and knee osteoarthritis grade according to Ahlbäck classification. Pre- and postoperative results were compared using the two-tailed t-test or Wilcoxon’s test of independent samples for paired data or nonparametric analog. P < 0.05 was considered significant.

Results
At medium-term follow-up, Z-shaped MOWHTO showed a survival rate of 95 ± 1.7% with failure occurring in four knees due to symptom recurrence and osteoarthritis progression. No perioperative complications were observed (intraarticular fracture, delayed union or nonunion, and neurological injury). Mean bone healing time was 12 weeks. Clinical scores showed significant improvement at last follow-up and a good grade of satisfaction. MPTA increased significantly, while Caton–Deschamps index decreased significantly. No significant TS increase was found.

Conclusions
Modified biplanar Z-shaped MOWHTO is a safe and reliable technique that offers satisfactory clinical and radiological medium-term outcomes with low knee arthroplasty conversion rate. The unique three-dimensional geometrical conformation potentially provides a favorable environment for bone healing, increased anteroposterior and rotational stability, and safer opening-wedge loading force application with low lateral hinge fracture risk.

Level of evidence
Level IV, retrospective observational case series study.
Trial registration The study protocol was approved by the Internal Review Board of our Institution (authorization number 54/2019, 20 November 2019).
Identification and validation of a regulatory mutation upstream of the BMP2 gene associated with carcass length in pigs
Authors: Li Jing , Peng Song , Zhong Liepeng , Zhou Lisheng , Yan Guorong , Xiao Shijun , Ma Junwu , Huang Lusheng 
Published: December 2021

Abstract
Background
Carcass length is very important for body size and meat production for swine, thus understanding the genetic mechanisms that underly this trait is of great significance in genetic improvement programs for pigs. Although many quantitative trait loci (QTL) have been detected in pigs, very few have been fine-mapped to the level of the causal mutations. The aim of this study was to identify potential causal single nucleotide polymorphisms (SNPs) for carcass length by integrating a genome-wide association study (GWAS) and functional assays.

Results
Here, we present a GWAS in a commercial Duroc × (Landrace × Yorkshire) (DLY) population that reveals a prominent association signal (P = 4.49E−07) on pig chromosome 17 for carcass length, which was further validated in two other DLY populations. Within the detected 1 Mb region, the BMP2 gene stood out as the most likely causal candidate because of its functions in bone growth and development. Whole-genome gene expression studies showed that the BMP2 gene was differentially expressed in the cartilage tissues of pigs with extreme carcass length. Then, we genotyped an additional 267 SNPs in 500 selected DLY pigs, followed by further whole-genome SNP imputation, combined with deep genome resequencing data on multiple pig breeds. Reassociation analyses using genotyped and imputed SNP data revealed that the rs320706814 SNP, located approximately 123 kb upstream of the BMP2 gene, was the strongest candidate causal mutation, with a large association with carcass length, with a ~ 4.2 cm difference in length across all three DLY populations (N = 1501; P = 3.66E−29). This SNP segregated in all parental lines of the DLY (Duroc, Large White and Landrace) and was also associated with a significant effect on body length in 299 pure Yorkshire pigs (P = 9.2E−4), which indicates that it has a major value for commercial breeding. Functional assays showed that this SNP is likely located within an enhancer and may affect the binding affinity of transcription factors, thereby regulating BMP2 gene expression.

Conclusions
Taken together, these results suggest that the rs320706814 SNP on pig chromosome 17 is a putative causal mutation for carcass length in the widely used DLY pigs and has great value in breeding for body size in pigs.