bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizer’s dilemma: optimization strongly influences model selection in transcriptomic prediction
Authors: Crawford Jake , Chikina Maria , Greene Casey S 
Published: January 2024

AbstractMotivationMost models can be fit to data using various optimization approaches. While model choice is frequently reported in machine-learning-based research, optimizers are not often noted. We applied two different implementations of LASSO logistic regression implemented in Python’s scikit-learn package, using two different optimization approaches (coordinate descent, implemented in the liblinear library, and stochastic gradient descent, or SGD), to predict mutation status and gene essentiality from gene expression across a variety of pan-cancer driver genes. For varying levels of regularization, we compared performance and model sparsity between optimizers.ResultsAfter model selection and tuning, we found that liblinear and SGD tended to perform comparably. liblinear models required more extensive tuning of regularization strength, performing best for high model sparsities (more nonzero coefficients), but did not require selection of a learning rate parameter. SGD models required tuning of the learning rate to perform well, but generally performed more robustly across different model sparsities as regularization strength decreased. Given these tradeoffs, we believe that the choice of optimizers should be clearly reported as a part of the model selection and validation process, to allow readers and reviewers to better understand the context in which results have been generated.Availability and implementationThe code used to carry out the analyses in this study is available at https://github.com/greenelab/pancancer-evaluation/tree/master/01_stratified_classification. Performance/regularization strength curves for all genes in the Vogelstein et al. (2013) dataset are available at https://doi.org/10.6084/m9.figshare.22728644.
HiPhase: jointly phasing small, structural, and tandem repeat variants from HiFi sequencing
Authors: Holt James M , Saunders Christopher T , Rowell William J , Kronenberg Zev , Wenger Aaron M , Eberle Michael 
Published: January 2024

Abstract

Motivation
In diploid organisms, phasing is the problem of assigning the alleles at heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation, such as structural or tandem repeat variants. However, current phasing tools typically only phase small variants, leaving larger variants unphased.

Results
We developed HiPhase, a tool that jointly phases SNVs, indels, structural, and tandem repeat variants. The main benefits of HiPhase are (i) dual mode allele assignment for detecting large variants, (ii) a novel application of the A*-algorithm to phasing, and (iii) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions. In our assessment, HiPhase produced an average phase block NG50 of 480 kb with 929 switchflip errors and fully phased 93.8% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, structural, and tandem repeat variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.

Availability and implementation
HiPhase is available as source code and a pre-compiled Linux binary with a user guide at https://github.com/PacificBiosciences/HiPhase.
Statistical framework to determine indel-length distribution
Authors: Wygoda Elya , Loewenthal Gil , Moshe Asher , Alburquerque Michael , Mayrose Itay , Pupko Tal 
Published: January 2024

Abstract

Motivation
Insertions and deletions (indels) of short DNA segments, along with substitutions, are the most frequent molecular evolutionary events. Indels were shown to affect numerous macro-evolutionary processes. Because indels may span multiple positions, their impact is a product of both their rate and their length distribution. An accurate inference of indel-length distribution is important for multiple evolutionary and bioinformatics applications, most notably for alignment software. Previous studies counted the number of continuous gap characters in alignments to determine the best-fitting length distribution. However, gap-counting methods are not statistically rigorous, as gap blocks are not synonymous with indels. Furthermore, such methods rely on alignments that regularly contain errors and are biased due to the assumption of alignment methods that indels lengths follow a geometric distribution.

Results
We aimed to determine which indel-length distribution best characterizes alignments using statistical rigorous methodologies. To this end, we reduced the alignment bias using a machine-learning algorithm and applied an Approximate Bayesian Computation methodology for model selection. Moreover, we developed a novel method to test if current indel models provide an adequate representation of the evolutionary process. We found that the best-fitting model varies among alignments, with a Zipf length distribution fitting the vast majority of them.

Availability and implementation
The data underlying this article are available in Github, at https://github.com/elyawy/SpartaSim and https://github.com/elyawy/SpartaPipeline.
Job Polarisation, Labour Market Fluidity and the Flattening of the Phillips Curve
Authors: Siena Daniele , Zago Riccardo 
Published: January 2024

Abstract
This paper shows that job polarisation—i.e., the disappearance of routine jobs—is changing the characteristics of the labour market. This has structural implications for the relationship between inflation and unemployment, the price Phillips curve. Using data from the European Monetary Union and exploiting the fact that job polarisation accelerates during recessions, we obtain two empirical results. First, countries experiencing a bigger shift in the occupational structure during a downturn exhibit a flatter Phillips curve afterwards. Second, the occupational shifts experienced during the Great Recession and the Sovereign Debt Crisis explain more than a fourth of the flattening of the curve in the 2002–18 period. Then, using a New Keynesian model with unemployment and search and matching frictions, we highlight a channel through which labour market characteristics operate on the slope of the Phillips curve. Increasing labour market fluidity—i.e., a higher separation and hiring rate—decreases the slope of the Phillips curve. Using micro-data, we find that in the European Monetary Union non-routine jobs are more fluid. We conclude that job polarisation flattened the Phillips curve.
Impact of congenital heart disease on personality disorders in adulthood
Authors: Stapel Britta , Winter Lotta , Heitland Ivo , Löffler Friederike , Bauersachs Johann , Westhoff-Bleck Mechthild , Kahl Kai G 
Published: January 2024

Abstract

Aims
Adults with congenital heart disease (ACHD) constitute an ever-growing patient population characterized by high risks for cardiovascular- and mental disorders. Personality disorders (PDs) are associated with adverse physical and mental health. Studies assessing PD prevalence in ACHD are lacking.

Methods and results
Personality disorder point prevalence was assessed in 210 ACHD by Structured Clinical Interview for Axis-II Personality Disorders (SCID-II) and compared to meta-analytical data from the general population (GP). Depression and anxiety were measured by self-report (Hospital Anxiety and Depression Scale, HADS) and clinician rating (Montgomery–Åsberg depression rating scale, MADRS). Childhood maltreatment was assessed with the Childhood Trauma Questionnaire and quality-of-life (QOL) with the World Health Organization QOL Scale. PD prevalence was markedly higher in ACHD compared to GP (28.1 vs. 7.7%). Particularly borderline (4.8 vs. 0.9%) and cluster C (i.e. anxious or fearful; 17.1 vs. 3.0%) PDs were overrepresented. PD diagnosis was associated with a surgery age ≤12 years (χ²(1) = 7.861, ϕ = 0.195, P = 0.005) and higher childhood trauma levels (U = 2583.5, Z = −3.585, P &lt; 0.001). ACHD with PD reported higher anxiety (HADS-A: U = 2116.0, Z = −5.723, P &lt; 0.001) and depression (HADS-D: U = 2254.5, Z = −5.392, P &lt; 0.001; MADRS: U = 2645.0, Z = −4.554, P &lt; 0.001) levels and lower QOL (U = 2538.5, Z = −4.723, P &lt; 0.001).

Conclusion
Personality disorders, particularly borderline- and cluster C, are significantly more frequent in ACHD compared to GP and associated with depression, anxiety, and decreased QOL. Data from the GP suggest an association with adverse cardiometabolic and mental health. To ensure guideline-based treatment, clinicians should be aware of the increased PD risk in ACHD.
Exploring Social Determinants of Mental Health of Older Unforced Migrants: A Systematic Review
Authors: Bhatia Pankhuri , McLaren Helen , Huang Yunong 
Published: January 2024

Abstract

Background and Objectives
Although the vulnerabilities stemming from the intersection of aging and migration are widely recognized, the migration contexts and the factors influencing the mental health of older unforced migrants have received scant attention. This review explores the drivers of unforced migrations in later life and the individual, relational, and structural factors influencing their mental health and well-being.

Research Design and Methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of 7 databases for English peer-reviewed journal articles was conducted. A total of 21 studies were identified and analyzed inductively.

Results
The review classified motivations for migration as push factors and pull factors: push factors such as escaping structural inequities in the homeland and pull factors included seeking better lifestyle opportunities and reuniting with family. The positive determinants of mental health included cordial family relationships, paid employment, the presence of a partner, and strong support networks. Advanced age, absence of a partner, lifestyle changes, lack of intergenerational support, poor language proficiency, unfavorable policies, lack of access to resources, and systemic biases negatively affected the mental health of older unforced migrants.

Discussion and Implications
The review highlights the need to recognize the diversity among older migrants to develop policies and programs that address their specific circumstances. Recognizing their strengths, rather than focusing solely on their vulnerabilities will help create a more positive and supportive environment, enabling them to thrive in their new communities.
Nurturing Attentiveness: A Naturalistic Observation Study of Personal Care Interactions Between People With Advanced Dementia and Their Caregivers
Authors: Backhouse Tamara , Jeon Yun-Hee , Killett Anne , Green Jessica , Khondoker Mizanur , Mioshi Eneida 
Published: January 2024

Abstract

Background and Objectives
Personal care interactions can provide vital opportunities for caregivers to engage with a person living with advanced dementia. However, interactions may also be a contentious experience, what makes this so is not fully understood. We aimed to examine features of personal care interactions between caregivers and people with advanced dementia to understand how care may be improved.

Research Design and Methods
This was a naturalistic observation study using one-off video-recorded observations of personal care interactions between 14 people with advanced dementia and 12 caregivers (n = 7 care-home staff, n = 5 family carers) in the United Kingdom (total observation time 03:01:52). Observations were analyzed with observational video coding to determine the frequency of actions of people with dementia and qualitative content analysis for in-depth examination.

Results
Refusals of care were present in 32% of video sections. Active engagement of people with dementia was observed in 66% of sections. Rare contentious interactional components were characterized by the person with dementia appearing to show uneasiness and caregivers being flustered and uncertain. However, caregivers typically emanated a nurturing attentiveness, were attuned to the person, and skilled in seamlessly supporting them through care activities.

Discussion and Implications
Findings draw on real-world empirical evidence to reinvigorate the notion of person-centeredness in dementia care. The findings provide much needed insight into practical ways to improve care interactions for people with advanced dementia and enhance their personhood. Appropriate training/guidance for caregivers could support positive personal care experiences for both the person with dementia and caregiver.
IMPACT OF TREATMENT RESPONSE WITH ADALIMUMAB ON RISK OF SERIOUS INFECTIONS IN PATIENTS WITH CROHN’S DISEASE: SECONDARY ANALYSIS OF THE PYRAMID REGISTRY
Authors: Ahuja Dhruv , Luo Jiyu , Qi Yuchen , Syal Gaurav , Boland Brigid , Chang John , Ma Christopher , Jairath Vipul , Xu Ronghui , Singh Siddharth 
Published: January 2024

Abstract

BACKGROUND AND AIMS
Treatment efficacy and safety are primary factors in choosing therapies in patients with Crohn’s disease (CD). However, they can be perceived to be at odds with each other with more potent therapies associated with increased risk of infections. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry.

METHODS
We included patients with CD who newly started adalimumab in the prospective PYRAMID registry (NCT00524537) and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs. non-responders (not in steroid-free clinical remission) at 6m after treatment initiation (landmark). We compared the risk of serious infections between responders vs. non-responders between 6-36m after treatment initiation, through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model.

RESULTS
Of 1515 adalimumab-treated patients with complete data at 6m, 763 (50.4%) were classified as responders (37±13y, 56% female, disease duration, 9.5y). At time of starting adalimumab (baseline), as compared with non-responders, responders were less likely to have moderate to severe symptoms (55.6% vs. 33%), require steroids (45.5% vs. 17.3%) or opiates (6.6% vs. 1.3%), have had prior CD-related surgery (46.5% vs. 35.1%), without any differences in disease location, perianal disease, and prior CD complications. On follow-up, between 6-36m (observation period after 6m landmark), 123 patients experienced a total of 162 serious infections. Of these, 52 responders (6.8%) experienced a serious infection vs. 71 non-responders (9.4%). Approximately, 58% infections were classified as gastrointestinal in origin. On stabilized IPTW through generalized boosting model, responders were 34% less likely to experience serious infections on follow-up compared with non-responders (HR, 0.66; 95% CI, 0.46-0.96). There was no significant difference in risk of serious infections between responders vs. non-responders based on organ site (gastrointestinal infections: HR, 0.61; 95% CI, 0.38-0.99; extra-intestinal infections: HR, 0.61; 95% CI, 0.46-1.30) (p-value for difference in groups = 1.00). Responders were significantly less likely to require corticosteroids on follow-up (1y: 4.4%, 2y: 8.9%, 3y: 9.6%), compared with non-responders (1y: 50.7%, 2y: 51.6% vs. 3y: 51%).

CONCLUSIONS
Patients with CD who respond to adalimumab have lower risk of developing serious infections, compared with non-responders, after accounting for disease severity. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.
ARGINASE 2 AMELIORATES EXPERIMENTAL COLITIS THROUGH ANTIOXIDANT EFFECTS VIA SPERMIDINE PRODUCTION
Authors: Imazu Noriyuki , Torisu Takehiro , Yokote Akihito , Umeno Junji , Kawasaki Keisuke , Fujioka Shin , Matsuno Yuichi , Nagasue Tomohiro , Kawatoko Shinichiro , Moriyama Tomohiko , Nitahata Tomoki , Uchida Yushi , Aihara Seishi , Kitazono Takanari 
Published: January 2024

Abstract

BACKGROUND
Spermidine which is a type of polyamine, shows elevated levels in patients with ulcerative colitis and is implicated in the pathogenesis of ulcerative colitis (UC). Arginase 2 (ARG2) plays a critical role in spermidine production. This study aimed to determine the role and mechanism of endogenous spermidine by using ARG2-deficient mice.

METHODS
The protective role of spermidine against oxidative stress was examined by intracellular reactive oxygen species levels and cell viability. The physiological role of spermidine was investigated using Arg2 knockdown cells with reduced spermidine. The importance of ARG2 in inflammation was examined in the dextran sulfate sodium-induced colitis model. Protein expression levels of ARG2 and accumulation of spermidine in patients with UC were evaluated by immunohistochemistry of the rectum.

RESULTS
ARG2 protein expression and the accumulation of spermidine were upregulated in the rectum of mice with dextran sulfate sodium colitis. Spermidine upregulated antioxidant genes in the cells. Arg2 knockdown cells showed reduced antioxidant activity. Dextran sulfate sodium colitis was more severe in Arg2-deficient mice, and organoids derived from Arg2-deficient mice showed diminished tolerance to oxidative stress. Furthermore, in the rectum of patients with UC, ARG2 and spermidine expression levels were higher in the active phase than in the remission phase.

CONCLUSIONS
Endogenous spermidine in the intestinal epithelium induced by ARG2 has a protective role in colitis. Spermidine may be a promising new therapeutic target for inflammatory bowel disease.
MULTIPLE BIOSIMILAR INFLIXIMAB SWITCHING IS NOT ASSOCIATED WITH DISEASE FLARE IN INFLAMMATORY BOWEL DISEASE: A REAL-WORLD EFFECTIVENESS ANALYSES IN A NATIONAL U.S. COHORT
Authors: Hou Jason , Pham Codey , Xu Anthony , Sansgiry Shubhada , Modi Varsha , Waljee Akbar 
Published: January 2024

Abstract

BACKGROUND
Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD.

METHODS
We conducted a retrospective cohort study of IBD patients who received maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. All cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from IFX originator to one biosimilar, or Double Switch (DS)- switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate logistic regression models adjusting for patient and non-patient factors.

RESULTS
A total of 789 patients (487 CD, 298 UC, 4 IBDU) on maintenance IFX originator were identified during the study period. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In multivariate (MV) logistic regression including age, race, gender, concomitant medication, comorbidity, and VA priority status, no significant differences in flares at 12 months was observed between the DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82).

CONCLUSION
In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, double switch was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.
NETWORK META-ANALYSIS TO EVALUATE THE COMPARATIVE EFFICACY OF BIOLOGICS FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH CROHN’S DISEASE
Authors: Schreiber Stefan , Danese Silvio , Colombel Jean-Frederic , Hisamatsu Tadakazu , Irving Peter , Park Hyunsoo , Kim Dong-Hyeon , Lee Young Nam , Hanauer Stephen 
Published: January 2024

Abstract

INTRODUCTION
While the therapeutic armamentarium for Crohn’s disease (CD) is rapidly expanding, direct evidence on comparative efficacy of various treatments is lacking. CT-P13 subcutaneous (SC) provides patients with a new opportunity for maintenance treatment of their disease.

METHODS
A network meta-analysis (NMA) was conducted to evaluate comparative efficacy of licensed biologics. Phase 3 randomized controlled-trials (RCTs) evaluating biologics approved by the European Medicines Agency or United States Food and Drug Administration as of 31 March 2023 for maintenance treatment of adult patients with moderate-to-severe CD were included, i.e. infliximab (IFX) intravenous (IV) and SC, adalimumab (ADL) SC, vedolizumab (VDZ) IV and SC, ustekinumab (UST) SC, and risankizumab (RZB) SC. Eligible studies evaluated the efficacy of maintenance therapy with follow-up periods of 52–64 weeks in patients who responded to induction treatment. Each study was controlled with placebo (PBO) or an active comparator. Head-to-head studies directly comparing efficacy of licensed biologics in CD (including those with treat-through designs) were also considered for inclusion. Clinical remission rates following the maintenance treatment were compared in a Bayesian NMA fixed-effect model.

RESULTS
Overall, 8 RCTs were identified and included in the analysis (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY). Most studies enrolled both naïve and biologic- and/or Janus kinase inhibitor-exposed patients, apart from ACCENT-1 and SEAVUE which enrolled only anti-tumor necrosis factor- and biologic-naïve patients, respectively. Among 8 comparator arms, IFX SC 120 mg every 2 weeks (Q2W) showed the highest odds ratio (95% credible interval) vs. PBO for clinical remission during the maintenance phase (3.52 [2.18–5.65]), followed by ADL SC 40 mg Q2W (2.92 [1.90–4.47]), UST SC 90 mg every 8 weeks (Q8W) (2.79 [1.85–4.21]), IFX IV 5 mg/kg Q8W (2.55 [1.29–5.27]), VDZ IV 300 mg Q8W (2.33 [1.43–3.86]), RZB SC 180 mg Q8W (1.80 [1.15–2.84]), VDZ SC 108 mg Q2W (1.76 [1.14–2.70]), and RZB SC 360 mg Q8W (1.60 [1.00–2.52]). In addition, IFX SC 120 mg Q2W showed the highest surface under the cumulative ranking curve (SUCRA) values (0.887), followed by ADL SC 40 mg Q2W (0.763), UST SC 90 mg Q8W (0.718), IFX IV 5 mg/kg Q8W (0.630), VDZ IV 300 mg Q8W (0.566), RZB SC 180 mg Q8W (0.353), VDZ SC 108 mg Q2W (0.327), RZB SC 360 mg Q8W (0.252), and PBO (0.005).

CONCLUSION
In this updated NMA on the comparative efficacy of licensed biologics, IFX SC 120 mg Q2W showed favorable efficacy in terms of clinical remission during maintenance treatment of 52–64 weeks’ duration in patients with moderate-to-severe CD.