bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy
Authors: von Drygalski Annette , Gomez Esteban , Giermasz Adam , Castaman Giancarlo , Key Nigel S. , Lattimore Susan U. , Leebeek Frank W. G. , Miesbach Wolfgang A. , Recht Michael , Gut Robert , Dolmetsch Ricardo , Monahan Paul E. , Le Quellec Sandra , Pipe Steven W. 
Published: December 2022

Abstract
Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here, we report 3-year outcomes from a phase 2b, open-label, single-dose, single-arm, multicenter trial conducted among adults with severe or moderately severe hemophilia B (FIX ≤2%). All participants (n = 3) received a single intravenous dose (2 × 1013 gene copies per kg) and will be followed up for 5 years. The primary end point of FIX activity ≥5% at 6 weeks was met. Secondary end points included bleed frequency, FIX concentrate use, joint health, and adverse events (AEs). All participants required routine FIX prophylaxis and had neutralizing antibodies to AAV5 before etranacogene dezaparvovec treatment. After administration, FIX activity rose to a mean of 40.8% in year 1 and was sustained in year 3 at 36.9%. All participants discontinued FIX prophylaxis. Bleeding was completely eliminated in 2 out of 3 participants. One participant required on-demand FIX replacement therapy per protocol because of elective surgical procedures, for 2 reported bleeding episodes, and twice for a single self-administered infusion because of an unreported reason. One participant experienced 2 mild, self-limiting AEs shortly after dosing. During the 3-year study period, there were no clinically significant elevations in liver enzymes, no requirement for steroids, no FIX inhibitor development, and no late-emergent safety events in any participant. Etranacogene dezaparvovec was safe and effective in adults with hemophilia B over 3 years after administration. This trial was registered at www.clinicaltrials.gov as #NCT03489291.
Selecting initial therapy in CLL
Authors: Ahn Inhye E. , Brown Jennifer R. 
Published: December 2022

Abstract
Targeted therapy is a powerful treatment option in chronic lymphocytic leukemia (CLL) that has outperformed conventional chemoimmunotherapy in most clinical settings. Except for selected young, fit patients with a mutated immunoglobulin heavy chain variable region gene, most patients benefit from targeted therapy with either a continuous BTK inhibitor or 1-year fixed-duration venetoclax-obinutuzumab as first-line treatment of CLL. Treatment selection is driven by patient-, treatment-, and disease-related factors, encompassing patient preference, concomitant medications, comorbidities, safety profile of the regimen, and TP53 aberration. Clinical trials are actively investigating the simultaneous inhibition of Bruton’s tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) proteins with or without a CD20 monoclonal antibody, which can achieve deep response in most patients (52%-89% undetectable minimal residual disease in bone marrow).
Fitness and frailty in myeloma
Authors: Pawlyn Charlotte , Khan Abdullah M. , Freeman Ciara L. 
Published: December 2022

Abstract
As the aging population grows, so too does the number of well-tolerated antimyeloma therapies. Physicians will see an increasing volume of patients for subsequent lines of therapy, which could now extend this relationship for over a decade. For younger patients, treatment choices are infrequently impacted by concerns of fitness, but instead about effecting the deepest, most durable response. Older adults, in contrast, are more likely to experience under- than overtreatment, and therefore more objective (and ideally straightforward) ways to evaluate their fitness and ability to tolerate therapy will increasingly assist in decision-making. Post hoc analyses categorizing the fitness of trial patients in the modern treatment era globally demonstrate that even in highly selected populations, those that are recategorized as less fit or frail are consistently at higher risk of inferior outcomes and increased toxicities. Real-world data are comparatively lacking but do demonstrate that most patients with myeloma are not representative of those enrolled on clinical trials, generally more heavily burdened by comorbidities and more likely to be categorized as “less than fit.” Simultaneously, the number of therapeutic options open to patients in the relapsed setting continues to grow, now including T-cell engagers and cellular therapies, with their unique toxicity profiles. The aim of this review is to summarize the available data, highlight some of the approaches possible to easily assess fitness and how results might inform treatment selection, and illustrate ways that patients' condition can be optimized rather than lead to exclusion from the more complex therapies newly available.
Approach to the patient with suspected hypereosinophilic syndrome
Authors: Klion Amy D. 
Published: December 2022

Abstract
Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders with clinical manifestations ranging from fatigue to life-threatening endomyocardial fibrosis and thromboembolic events. Given the broad differential diagnosis of HES, a comprehensive approach is needed to identify potential secondary (treatable) causes and define end-organ manifestations. Classification by clinical HES subtype is also useful in terms of assessing prognosis and guiding therapy. Corticosteroids remain the mainstay of initial therapy in the setting of acute, life-threatening PDGFR mutation-negative HES. Whereas the recent availability of eosinophil-targeted therapies with extraordinary efficacy and little apparent toxicity is changing the treatment paradigm, especially for idiopathic HES and overlap syndromes, questions remain unanswered regarding the choice of agent, impact of combination therapies, and long-term effects of eosinophil depletion. This review provides a case-based discussion of the differential diagnosis of HES, including the classification by clinical HES subtype. Treatment options are reviewed, including novel eosinophil-targeted agents recently approved for the treatment of HES and/or other eosinophil-associated disorders. Primary (myeloid) disorders associated with hypereosinophilia are not be addressed in depth in this review.
At-home noninvasive ventilation initiation with telemonitoring in amyotrophic lateral sclerosis patients: a retrospective study
Authors: Réginault Thomas , Bouteleux Benoit , Wibart Philippe , Mathis Stéphane , Le Masson Gwendal , Pillet Odile , Grassion Léo 
Published: December 2022

BackgroundNoninvasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. NIV initiation is mostly conducted at hospital, but a recurrent lack of hospital beds led to the necessity of exploring an at-home initiation process. Here, we report data from our NIV initiation cohort of ALS patients. Could our at-home NIV initiation process with telemonitoring in ALS patients be an efficient solution for adherence and nocturnal hypoxaemia correction?MethodsWe performed a retrospective analysis of data collected from 265 ALS patients treated at the Bordeaux ALS Centre for whom NIV initiation was carried out between September 2017 and June 2021, with two modalities: at-home initiation or in-hospital initiation. The primary outcome was adherence to NIV at 30 days. The secondary outcome was at-home NIV initiation process efficiency of nocturnal hypoxaemia correction.ResultsAt 30 days, NIV adherence (mean >4 h·day−1) was 66% of the total population, 70% of the at-home NIV initiation subgroup and 52% of the in-hospital NIV initiation subgroup. Nocturnal hypoxaemia correction was observed in 79% of adherent patients in the at-home NIV initiation subgroup. Mean delay of NIV prescription and at-home NIV initiation was 8.7 days (+/−6.5)versus29.5 days in hospital.ConclusionOur study shows that our at-home NIV initiation process in ALS patients is a good option to provide rapid access to NIV with good adherence and efficiency. Further literature on the benefits of at-home NIV initiation is welcomed, especially to evaluate long-term efficiency and global cost analysis.
A Poisson reduced-rank regression model for association mapping in sequencing data
Authors: Fitzgerald Tiana , Jones Andrew , Engelhardt Barbara E. 
Published: December 2022

AbstractBackgroundSingle-cell RNA-sequencing (scRNA-seq) technologies allow for the study of gene expression in individual cells. Often, it is of interest to understand how transcriptional activity is associated with cell-specific covariates, such as cell type, genotype, or measures of cell health. Traditional approaches for this type of association mapping assume independence between the outcome variables (or genes), and perform a separate regression for each. However, these methods are computationally costly and ignore the substantial correlation structure of gene expression. Furthermore, count-based scRNA-seq data pose challenges for traditional models based on Gaussian assumptions.ResultsWe aim to resolve these issues by developing a reduced-rank regression model that identifies low-dimensional linear associations between a large number of cell-specific covariates and high-dimensional gene expression readouts. Our probabilistic model uses a Poisson likelihood in order to account for the unique structure of scRNA-seq counts. We demonstrate the performance of our model using simulations, and we apply our model to a scRNA-seq dataset, a spatial gene expression dataset, and a bulk RNA-seq dataset to show its behavior in three distinct analyses.ConclusionWe show that our statistical modeling approach, which is based on reduced-rank regression, captures associations between gene expression and cell- and sample-specific covariates by leveraging low-dimensional representations of transcriptional states.
Pattern recognition of topologically associating domains using deep learning
Authors: Yang Jhen Yuan , Chang Jia-Ming 
Published: December 2022

Abstract
Background
Recent increasing evidence indicates that three-dimensional chromosome structure plays an important role in genomic function. Topologically associating domains (TADs) are self-interacting regions that have been shown to be a chromosomal structural unit. During evolution, these are conserved based on checking synteny block cross species. Are there common TAD patterns across species or cell lines?

Results
To address the above question, we propose a novel task—TAD recognition—as opposed to traditional TAD identification. Specifically, we treat Hi-C maps as images, thus re-casting TAD recognition as image pattern recognition, for which we use a convolutional neural network and a residual neural network. In addition, we propose an elegant way to generate non-TAD data for binary classification. We demonstrate deep learning performance which is quite promising, AUC > 0.80, through cross-species and cell-type validation.

Conclusions
TADs have been shown to be conserved during evolution. Interestingly, our results confirm that the TAD recognition model is practical across species, which indicates that TADs between human and mouse show common patterns from an image classification point of view. Our approach could be a new way to identify TAD variations or patterns among Hi-C maps. For example, TADs of two Hi-C maps are conserved if the two classification models are exchangeable.
Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial
Authors: de la Rocha Carmen , Cid-López Marco A. , Venegas-López Blanca I. , Gómez-Méndez Sandra C. , Sánchez-Ortiz Adriana , Pérez-Ríos Alma M. , Llamas-Velázquez Ricardo A. , Meza-Acuña Aidé I. , Vargas-Íñiguez Bárbara , Rosales-Galván Daniela , Tavares-Váldez Alejandra , Luna-Gudiño Nizdali , Hernández-Puente Cinthia V. , Milenkovic Jovana , Iglesias-Palomares Cecilia , Méndez-del Villar Miriam , Gutiérrez-Dieck Gerardo A. , Valderrábano-Roldán Carlos G. , Mercado-Cerda Jennefer , Robles-Bojórquez Jocelyn G. , Mercado-Sesma Arieh R. 
Published: December 2022

Abstract
Background
Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo.

Methods
A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days.

Results
None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group.

Conclusions
At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19.
Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.
Insulin resistance in women with recurrent miscarriage: a systematic review and meta-analysis
Authors: Cai Wang-Yu , Luo Xi , Lv Hou-Yi , Fu Kai-You , Xu Jian 
Published: December 2022

AbstractPurposeThis review aimed to investigate the association of insulin resistance (IR) in women with recurrent pregnancy loss compared to women with normal pregnancy history.MethodsPubMed, EMBASE, the Web of Science and Google Scholar databases were accessed to collect published observational studies that compared IR of recurrent pregnancy loss women with healthy women until the 6thof October 2022. Outcomes assessed in this review and meta-analysis included fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, glucose to insulin ratio. Mean differences, odds ratios with 95% confidence interval were pooled using the fixed or random effect models. Sensitivity analyses were performed to validate the robustness of the results. Review Manager version 5.4.1 and Stata version 8.0 were used.ResultsA total of nineteen studies involving 4453 individuals were included. Recurrent pregnancy loss patients presented significantly higher fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, and lower glucose to insulin ratios. Additionally, recurrent pregnancy loss patients had higher rates of IR as defined by abnormal fasting plasma insulin, homeostasis model assessment for IR, and glucose to insulin ratio. Sensitivity analyses validated the robustness of the results.ConclusionIn the current review, we show that recurrent pregnancy loss is associated with a higher degree of IR and highlight the importance of screening and treatment of IR.
Simplification of dosimetry in 90Y-radioembolization therapy by dual planar images
Authors: Abuqbeitah Mohammad , Akdağ Özgür Taylan , Demir Mustafa , Asa Sertaç , Sönmezoğlu Kerim 
Published: December 2022

Abstract
Aim
The purpose was to provide a practical and effective method for performing reliable 90Y dosimetry based on 99mTc-MAA and SPEC/CT. The impact of scatter correction (SC) and attenuation correction (AC) on the injected 90Y activity, lung shunt fraction (LSF) and the delivered dose to lung and liver compartments was investigated within the scope of the study.

Material and methods
Eighteen eligible patients (F: 3, M: 15) were subjected to 90Y therapy. 99mTc-MAA (111-222 MBq) was injected into the targeted liver, followed by whole-body scan (WBS) with peak-window at 140 keV (15% width) and one down-scatter window. SPECT/CT scan was subsequently acquired encompassing lung and liver regions. The LSFs were fashioned from standard WBS LSFwb (St), scatter corrected WBS LSFwb (Sc), only scatter corrected SPECT LSFspect (NoAC-SC) and SPECT/CT with attenuation and scatter correction LSFspect (AC-SC). The absorbed doses that would be delivered to tumor and injected healthy liver were estimated using different calculation modes involving AC-SC (SPECT/CT), NoAC-SC (SPECT), NoAC-NoSC+LSFwb (SC), AC-SC + LSFwb (St), and NoAC-NoSC+LSFwb (St).

Results
The average deviations (range) in LSF values between standard LSFwb (St) and those from SPECT/CT (AC-SC), SPECT (NoAC-SC), and LSFwb (SC) were − 50% (− 29/− 71), − 32% (− 8/− 67), and − 45% (− 13/80), respectively. The suggested 90Y activity (GBq/Gy) was decreased within a range of 2-11%, 1-9%, and 2-7% by using LSFspect (AC-SC), LSFspect (NoAC-SC), and LSFwb (SC), respectively. Overall, two-sample t-test yielded no statistically significant difference (p < 0.05) in the absorbed doses to tumor and injected healthy liver between AC-SC (SPECT) and the rest of approaches with/and without AC and SC. However, a statistically significant difference (p < 0.05) was demonstrated in the lung shunt fractions and lung doses due to AC and SC. The LSFs from scatter corrected planar images LSFwb (SC) exhibited well agreement (R2 = 0.92) with SPECT/CT (AC-SC) and there was no statistically significant difference (Pvalue > 0.05) between both methods.

Conclusion
It was deduced that SPECT/CT with attenuation and scatter correction plays a crucial role in the measurements of lung shunt fraction and dose as well as the total number of 90Y treatments. However, the absorbed dose to tumors and injected healthy liver was minimally affected by AC and SC. Besides, a good agreement was observed between LSF datasets from SPECT/CT versus scatter corrected WBS that can be alternatively and effectively used in 90Y dosimetry.
Factors associated with allergy traits around the 2nd year of life: a brazilian cohort study
Authors: Muniz Alessandra Karla Oliveira Amorim , Ribeiro Cecilia Claudia Costa , Vianna Elcio Oliveira , Serra Hellen Cristina Oliveira Amorim , Nascimento Joelma Ximenes Prado Teixeira , Cardoso Viviane Cunha , Barbieri Marco Antonio , da Silva Antonio Augusto Moura , Bettiol Heloisa 
Published: December 2022

Abstract
Background
Allergic status has been strongly influenced by early exposures; however, allergic diseases are hard to measure in early life. Thus, this study proposed a latent variable allergy traits around the second year of life and analyzed pre- and perinatal factors associated with this phenomenon.

Methods
The study used data from the BRISA birth cohort, Ribeirão Preto, Brazil (n = 3644). The theoretical model included: family allergy (history of allergic rhinitis, atopic dermatitis, and asthma); gestational period variables (socioeconomic status, mother’s skin color, pregestational body mass index – BMI, smoking, gestational diabetes, and hypertension); birth variables (gestational age, 5-minute Apgar score, birth weight, type of delivery), and early life factor (exclusive breast feeding). The outcome was allergy traits around the 2nd year of life, a latent variable deduced from the shared variance among medical diagnosis of allergic rhinitis, atopic dermatitis, and food allergy. The model was analyzed by structural equation modeling.

Results
Higher socioeconomic status (SC = 0.256; p < 0.001) and higher family allergy values (SC = 1.224; p < 0.001) were associated with higher allergy trait values. Hypertension during pregnancy was associated with higher values (SC = 0.170; p = 0.022) and exclusive breast feeding (SC = -0.192; p < 0.001) with low allergy trait values.

Conclusion
Although socioeconomic and environmental factors were associated with allergy traits around the 2nd year of life, the family component of allergy was the exposure that best explained this outcome.
Counseling parents about child feeding: a qualitative evaluation of French doctors and health/childcare professionals’ experiences and perception of a brochure containing new recommendations
Authors: De Rosso Sofia , Riera-Navarro Camille , Ducrot Pauline , Schwartz Camille , Nicklaus Sophie 
Published: December 2022

AbstractBackgroundParents are crucial in establishing their children’s eating habits, and doctors and health/childcare professionals (HCCPs) can provide meaningful and trusted guidance on feeding, especially in the 0-3-year-old period. With the upcoming release of the official brochure containing the new child feeding recommendations in France, this study aims to: (1) assess professionals’ practices and perceptions regarding their communication with parents on child feeding and (2) evaluate their perception of the draft of the new brochure.MethodsA 15-page draft brochure (without pictures) containing updated child feeding recommendations for children 0–3 years old was developed by Santé publique France (the French public health agency). Online semi-structured interviews were conducted with professionals (n = 21), including 13 pediatricians and general practitioners (doctors) and eight healthcare or childcare professionals (HCCPs) two weeks after they were provided with this draft brochure to read. The interview guide was developed and piloted with other professionals (n = 3) prior to these interviews. Interview data were transcribed verbatim and analyzed thematically using an inductive approach.ResultsWhile doctors and HCCPs mostly communicate orally with parents, both acknowledged that the brochure might be a helpful supplement, especially for HCCPs to legitimize their advice to parents. For doctors, giving the brochure to parents may help provide systematic advice and save time during consultations. Professionals serving parents of lower socioeconomic status would prefer a supplement with less text and more illustrations. In general, the messages were perceived to be easily understandable but providing detachable cards to distribute according to the child’s age would facilitate information dissemination and might be more useful to parents. Professionals reported that lack of training, the circulation of contradictory information, and language barriers were common challenges.ConclusionFrench professionals welcomed the new official brochure as a means to spread updated child feeding recommendations. However, this brochure could be modified and specific tools developed to better adapt to professionals’ needs of communication with parents and to facilitate the relay of information. Providing updated and consistent information to parents should be considered a priority for public health stakeholders toward increased adherence to new recommendations.