bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Longitudinal Patient-Reported Satisfaction and Health-Related Quality of Life following DIEP Flap Breast Reconstruction: Effects of Reconstruction Timing
Authors: Ochoa Oscar , Garza Ramon , Pisano Steven , Chrysopoulo Minas , Ledoux Peter , Arishita Gary , Ketchum Norma , Michalek Joel E. , Nastala Chet 
Published: March 2022

Background:
Without reconstruction, mastectomy alone can produce significant detrimental effects on health-related quality of life. The magnitude of quality-of-life benefits following breast reconstruction may be unique based on timing of reconstruction. Facilitated by the BREAST-Q questionnaire, characterization of how reconstruction timing differentially affects patient-reported quality of life is essential for improved evidence-based clinical practice.

Methods:
Consecutive DIEP flap breast reconstruction patients prospectively completed BREAST-Q questionnaires preoperatively and at two different time intervals postoperatively. The first (postoperative time point A) and second (postoperative time point B) postoperative questionnaires were completed 1 month postoperatively and following breast revision/symmetry procedures, respectively. Postoperative flap and donor-site complications were recorded prospectively. Stratified by timing (immediate versus delayed) of reconstruction, preoperative clinical data, operative morbidity, and BREAST-Q scores were compared at all time points.

Results:
Between July of 2012 and August of 2016, 73 patients underwent 130 DIEP flap breast reconstructions. Collectively, breast satisfaction, psychosocial well-being, and sexual well-being scores significantly (p < 0.001) increased postoperatively versus baseline. Chest and abdominal physical well-being scores returned to baseline levels by postoperative time point B. Preoperatively, patients undergoing delayed breast reconstruction reported significantly (p < 0.05) lower breast satisfaction, psychosocial well-being, and sexual well-being scores compared to immediate reconstruction patients. Postoperatively, delayed and immediate reconstruction patients reported similar quality-of-life scores. Outcome satisfaction and flap and donor-site morbidity were similar between groups irrespective of timing of reconstruction.

Conclusions:
In this prospective study, patient-reported outcomes demonstrate significant improvements in breast satisfaction, psychosocial well-being, and sexual well-being among patients following DIEP flap reconstruction. Moreover, preoperative differences in quality-of-life scores among delayed/immediate reconstruction patients were eliminated postoperatively.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Ultrarare missense and frameshift variants in the TECTA gene may involve tectorial membrane in familial Meniere disease
Authors: Román-Naranjo Pablo , Parra-Perez Alberto M. , Escalera-Balsera Alba , Soto-Varela Andrés , Gallego-Martinez Alvaro , Aran Ismael , Perez-Fernandez Nicolas , Bächinger David , Eckhard Andreas H. , Gonzalez-Aguado Rocio , Frejo Lidia , Lopez-Escamez Jose A. 
Published: March 2022

ABSTRACTBackgroundMeniere’s disease (MD) is an inner ear disease defined by episodes of vertigo associated with sensorineural hearing loss initially affecting low- to medium frequencies, tinnitus, and aural fullness. Familial aggregation has been reported in 9-10% of MD patients showing, mostly, an autosomal dominant inheritance pattern with incomplete penetrance. However, familial MD is a genetically heterogeneous disorder and other inheritance patterns have been recently proposed, such as recessive and digenic inheritance involving rare variants in OTOG and MYO7A genes, respectively. In this study, a familial MD cohort was recruited to identify new candidate genes.MethodsExome sequencing was performed in 99 individuals (from 77 families) diagnosed with MD according to the diagnostic criteria defined by the Barany Society. Candidate variants were classified based on the ACMG/AMP guidelines, and their effects were evaluated by protein modeling. Standard audiometric evaluations were retrieved, and a case report was made of each family to assess the genotype-phenotype correlations.ResultsThe TECTA gene, which encodes α-tectorin, was highlighted as a candidate for four multicase MD families carrying rare missense heterozygous variants and a short deletion in this gene. Variants in α-tectorin were also found in two additional families with one MD patient and relatives with partial syndromes carrying a missense heterozygous variant and a short deletion. According to the predicted protein model, these variants could affect the stability of α-tectorin.ConclusionsSeveral MD families were identified carrying rare variants and deletions in the TECTA gene, which encodes one of the main proteins of the tectorial membrane (TM). The TM is an extracellular matrix localized over the sensory epithelium mediating the mechanical stimulation of cochlear hair cells, a critical role in the process of hearing. Modifications on the TM stability and the micromechanics involved in the sound-evoked motion of stereocilia might be involved in familial MD.
A Progeroid Syndrome Caused by RAF1 deficiency Underscores the importance of RTK signaling for Human Development
Authors: Wong Samantha , Tan Yu Xuan , Tan Kiat Yi , Loh Abigail , Aziz Zainab , Özkan Engin , Kayserili Hülya , Escande-Beillard Nathalie , Reversade Bruno 
Published: March 2022

AbstractSomatic and germline gain-of-function point mutations in RAF, the first oncogene to be discovered in humans, delineate a group of tumor-prone syndromes known as RASopathies. In this study, we document the first human phenotype resulting from the germline loss of function of the proto-oncogene RAF1 (a.k.a. CRAF). In a consanguineous family, we uncovered a homozygous p.Thr543Met mutation segregating with a neonatal lethal progeroid syndrome with cutaneous, craniofacial, cardiac and limb anomalies. Structure-based prediction and functional tests using human knock-in cells showed that threonine 543 is essential to: 1) ensure RAF1’s stability and phosphorylation, 2) maintain its kinase activity towards substrates of the MAPK pathway and 3) protect from stress-induced apoptosis. When injected in Xenopus embryos mutant RAF1T543M failed to phenocopy the effects of overactive FGF/MAPK signaling confirming its hypomorphic activity. Collectively, our data disclose the genetic and molecular etiology of a novel segmental progeroid syndrome which highlights the importance of RTK signaling for human development and homeostasis.Short summaryA germline homozygous recessive loss-of-function mutation p.T453M in RAF1 causes a neonatal lethal progeroid syndrome. In vitro and in vivo tests demonstrate that Thr543 is necessary for RAF1’s protein stability, to transduce signaling to the MAPK pathway and to respond to stress-induced apoptosis.
Deep learning based electrocardiographic screening for chronic kidney disease
Authors: Holmstrom Lauri , Christensen Matthew , Yuan Neal , Hughes J. Weston , Theurer John , Jujjavarapu Melvin , Fatehi Pedram , Kwan Alan , Sandhu Roopinder K. , Ebinger Joseph , Cheng Susan , Zou James , Chugh Sumeet S. , Ouyang David 
Published: March 2022

AbstractBackgroundUndiagnosed chronic kidney disease (CKD) is a common and usually asymptomatic disorder that causes a high burden of morbidity and early mortality worldwide. We developed a deep learning model for CKD screening from routinely acquired ECGs.MethodsWe collected data from a primary cohort with 111,370 patients which had 247,655 ECGs between 2005 and 2019. Using this data, we developed, trained, validated, and tested a deep learning model to predict whether an ECG was taken within one year of the patient receiving a CKD diagnosis. The model was additionally validated using an external cohort from another healthcare system which had 312,145 patients with 896,620 ECGs from between 2005 and 2018.ResultsUsing 12-lead ECG waveforms, our deep learning algorithm achieved discrimination for CKD of any stage with an AUC of 0.77 (95% CI 0.76-0.77) in a held-out test set and an AUC of 0.71 (0.71-0.71) in the external cohort. Our 12-lead ECG-based model performance was consistent across the severity of CKD, with an AUC of 0.75 (0.0.74-0.77) for mild CKD, AUC of 0.76 (0.75-0.77) for moderate-severe CKD, and an AUC of 0.78 (0.77-0.79) for ESRD. In our internal health system with 1-lead ECG waveform data, our model achieved an AUC of 0.74 (0.74-0.75) in detecting any stage CKD. In the external cohort, our 1-lead ECG-based model achieved an AUC of 0.70 (0.70-0.70). In patients under 60 years old, our model achieved high performance in detecting any stage CKD with both 12-lead (AUC 0.84 [0.84-0.85]) and 1-lead ECG waveform (0.82 [0.81-0.83]).ConclusionsOur deep learning algorithm was able to detect CKD using ECG waveforms, with particularly strong performance in younger patients and patients with more severe stages of CKD. Given the high global burden of undiagnosed CKD, further studies are warranted to evaluate the clinical utility of ECG-based CKD screening.
An antisense oligonucleotide-based strategy to ameliorate cognitive dysfunction in the 22q11.2 Deletion Syndrome
Authors: Thakur Pratibha , Lackinger Martin , Diamantopoulou Anastasia , Rao Sneha , Chen Yijing , Khalizova Khakima , Ferng Annie , Mazur Curt , Kordasiewicz Holly , Shprintzen Robert J. , Markx Sander , Xu Bin , Gogos Joseph A. 
Published: March 2022

AbstractAdults and children with the 22q11.2 Deletion Syndrome demonstrate cognitive, social and emotional impairments and high risk for schizophrenia. Work in mouse model of the 22q11.2 deletion provided compelling evidence for abnormal expression and processing of microRNAs. A major transcriptional effect of the microRNA dysregulation is up-regulation ofEmc10,a component of the ER membrane complex, which promotes membrane insertion of a subset of polytopic and tail-anchored membrane proteins. We previously uncovered a key contribution of EMC10 in mediating the behavioral phenotypes observed in 22q11.2 deletion mouse models. Here we show that expression and processing of miRNAs is abnormal andEMC10expression is elevated in neurons derived from 22q11.2 deletion carriers. Reduction ofEMC10 levelsrestores defects in neurite outgrowth and calcium signaling in patient neurons. Furthermore, antisense oligonucleotide administration and normalization ofEmc10in the adult mouse brain not only alleviates cognitive deficits in social and spatial memory but remarkably sustains these improvements for over two months post injection, indicating its therapeutic potential. Broadly, our study integrates findings from both animal models and human neurons to elucidate the translational potential of modulatingEMC10levels and downstream targets as a specific venue to ameliorate disease progression in 22q11.2 Deletion Syndrome.
Early life pain experience changes adult functional pain connectivity in the rat somatosensory and the medial prefrontal cortex
Authors: Chang Pishan , Fabrizi Lorenzo , Fitzgerald Maria 
Published: March 2022

AbstractEarly life pain experience (ELP) alters adult pain behaviour and increases injury induced pain hypersensitivity, but the effect of ELP upon adult functional brain connectivity is not known. We have performed continuous local field potential (LFP) recording in the awake adult male rats to test the effect of ELP upon functional cortical connectivity related to pain behaviour. Somatosensory cortex (S1) and medial prefrontal cortex (mPFC) LFPs evoked by mechanical hindpaw stimulation were recorded simultaneously with pain reflex behaviour for 10 days after adult skin injury. We show that, post adult injury, S1 LFP delta and gamma energy and S1 LFP delta/gamma frequency modulation are significantly increased in ELP rats compared to controls. Adult injury also induces increases in S1-mPFC functional connectivity which is significantly prolonged in ELP rats, lasting 4 days compared to 1 day in controls. Importantly, the increases in LFP energy and connectivity in ELP rats were directly correlated with increased behavioural pain hypersensitivity. Thus, early life pain (ELP) alters adult brain functional connectivity, both within and between cortical areas involved in sensory and affective dimensions of pain. The results reveal altered brain connectivity as a mechanism underlying the effects of early life pain upon adult pain perception.Significance StatementPain and stress in early life has a lasting impact upon pain behaviour and may increase vulnerability to chronic pain in adults. Here we record pain-related cortical activity and simultaneous pain behaviour in awake adult male rats previously exposed to pain in early life. We show that functional connectivity within and between the somatosensory cortex and the medial prefrontal cortex is increased in these rats and that these increases are correlated with their behavioural pain hypersensitivity. The results reveal that early life pain alters adult brain connectivity, which may explain the impact of childhood pain upon adult chronic pain vulnerability.
Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI
Authors: Rosa Francesco La , Beck Erin S. , Maranzano Josefina , Todea Ramona-Alexandra , van Gelderen Peter , de Zwart Jacco A. , Luciano Nicholas J. , Duyn Jeff H. , Thiran Jean-Philippe , Granziera Cristina , Reich Daniel S. , Sati Pascal , Cuadra Meritxell Bach 
Published: March 2022

AbstractManually segmenting multiple sclerosis (MS) cortical lesions (CL) is extremely time-consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep learning-based framework (CLAIMS: Cortical Lesion Artificial Intelligence-based assessment in Multiple Sclerosis) for the automated detection and classification of MS CL with 7T MRI.Two 7T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5mm isotropic MP2RAGE acquired 4 times (MP2RAGEx4), 0.7mm MP2RAGE, 0.5mm T2*-weighted GRE, and 0.5mm T2*-weighted EPI. The second dataset consisted of 20 scans including only 0.75×0.75×0.9 mm MP2RAGE. CLAIMS was first evaluated using 6-fold cross-validation with single and multi-contrast 0.5mm MRI input. Second, performance of the model was tested on 0.7mm MP2RAGE images after training with either 0.5mm MP2RAGEx4, 0.7mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state-of-the-art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGEx4 achieved comparable results to the multi-contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain-scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6μL (lesion-wise detection rate of 71% vs 48%).The proposed framework outperforms previous state-of-the-art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7T MRI, especially in the field of diagnosis and differential diagnosis of multiple sclerosis patients.
Altered brain reward response to monetary incentives in fibromyalgia: A replication study
Authors: Park Su Hyoun , Deng Eden Z. , Baker Anne K. , MacNiven Kelly H. , Knutson Brian , Martucci Katherine T. 
Published: March 2022

AbstractDysregulated brain reward systems have been observed in chronic pain. Using functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task, Martucci et al. (2018) showed that neural responses to reward anticipation and outcome are altered in patients with fibromyalgia. The current study aimed to replicate these results in a separate cohort of patients with fibromyalgia recruited at a new location using a similar study design. Twenty patients with fibromyalgia and 20 healthy controls were included in the replication study. Group fMRI analyses revealed a solid and consistent trend of main findings similar to the previous results. Specifically, in the replication cohort of patients with fibromyalgia, medial prefrontal cortex (MPFC) activity was reduced during gain anticipation and increased during no-loss (non-punishment) outcomes, as compared to controls. Similar to the Martucci et al. results, again in the replication cohort, nucleus accumbens activity during gain anticipation did not differ in patients compared to controls. The same behavioral, correlational, and exploratory analyses that were conducted in the Martucci et al. study were conducted in the present replication study, with prior results largely replicated here. Thus, the present replication study results solidify observations of altered cortico-striatal processing to monetary rewards in chronic pain, which underscore relevance of altered brain reward circuits, particularly as related to the MPFC in patients with fibromyalgia.
Differences in Genetic Correlations between Posttraumatic Stress Disorder and Alcohol Use Disorder-Related Phenotypes Compared to Alcohol Consumption-Related Phenotypes
Authors: Bountress Kaitlin E. , Bustamante Daniel , de Viteri Stacey Subbie-Saenz , Chatzinakos Chris , Sheerin Christina , Peterson Roseann E. , Webb Bradley T. , Daskalakis Nikolaos P. , Edenberg Howard ,   The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, Meyers Jackie , Amstadter Ananda 
Published: March 2022

AbstractBackgroundPosttraumatic Stress Disorder (PTSD) tends to co-occur with greater alcohol consumption as well as alcohol use disorder (AUD). However, it is unknown whether the same etiologic factors that underlie PTSD-AUD comorbidity also contribute to PTSD-alcohol consumption.MethodsWe used summary statistics from large-scale genome-wide association studies (GWAS) of European-ancestry (EA) and African-ancestry (AA) participants to estimate genetic correlations between PTSD (both the diagnosis and re-experiencing symptoms) and a range of alcohol consumption-related and AUD-related phenotypes (e.g., drinks per week, max drinks, consumption, AUD).ResultsIn EAs, there were positive genetic correlations between PTSD phenotypes and AUD-related phenotypes (i.e., Alcohol Use Disorders Identification Test (AUDIT) problem score, maximum alcohol intake, AUD, and alcohol dependence) (rGs: .132-.533, all FDR adjusted p<.05). However, the genetic correlations between PTSD phenotypes and alcohol consumption -related phenotypes (i.e., drinks per week, AUDIT consumption score, AUDIT total score, and a combination of consumption and problems) were negatively associated or non-significant (rGs: -.417- -.042, FDR adjusted p: <.05-NS). For AAs, the direction of correlations was sometimes consistent and sometimes inconsistent with that in EAs, and the ranges were larger (rGs for AUD--related: -.275 -.266, FDR adjusted p: NS, alcohol consumption-related: .145-.699, FDR adjusted p: NS).ConclusionsThese findings illustrate that the genetic associations between consumption and problem alcohol phenotypes and PTSD differ in both strength and direction. Thus, the genetic factors that may lead someone to develop PTSD and consume large quantities of alcohol are not the same as those that lead someone to develop PTSD-AUD.
A predictive model for hospitalization and survival to COVID-19 in a retrospective population-based study
Authors: Cisterna-García Alejandro , Guillén-Teruel Antonio , Caracena Marcos , Pérez Enrique , Jiménez Fernando , Francisco-Verdú Francisco J. , Reina Gabriel , González-Billalabeitia Enrique , Palma José T. , Sánchez Álvaro , Botía Juan A. 
Published: March 2022

AbstractThe severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is highly transmissible and has been responsible for a pandemic associated with a high number of deaths. The clinical management of patients and the optimal use of resources are two important factors in reducing this mortality, especially in scenarios of high incidence. To this end, it is necessary to develop tools that allow early triage of patients with the minimal use of diagnostic tests and based on readily accessible data, such as electronic medical records. This work proposes the use of a machine learning model that allows the prediction of mortality and risk of hospitalization using simple demographic characteristics and comorbidities, using a COVID-19 dataset of 86867 patients. In addition, we developed a new method designed to deal with data imbalance problems. The model was able to predict with high accuracy (89-93%, ROC-AUC = 0.94) the patient’s final status (expired/discharged) and with medium accuracy the risk of hospitalization (71-73%, ROC-AUC = 0.75). These models were obtained by assembling and using easily obtainable clinical characteristics (2 demographic characteristics and 19 predictors of comorbidities). The most relevant features of these models were the following patient characteristics: age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure.
Cost-effectiveness of digital therapeutics for essential hypertension
Authors: Nomura Akihiro , Tanigawa Tomoyuki , Kario Kazuomi , Igarashi Ataru 
Published: March 2022

AbstractBackgroundHypertension increases the risk of cardiovascular and other diseases. Lifestyle modification is a significant component of nonpharmacological treatments for hypertension. We previously reported the clinical efficacy of digital therapeutics (DTx) in the HERB-DH1 trial. However, there is still a lack of cost-effectiveness assessments evaluating the impact of prescription DTx. This study aimed to analyze the cost-effectiveness of using prescription DTx in treating hypertension.MethodsWe developed a monthly cycle Markov model and conducted Monte Carlo simulations using the HERB-DH1 trial data to investigate quality-adjusted life-years (QALYs) and the cost of DTx for hypertension plus guideline-based lifestyle modification consultation treatment as usual (TAU), comparing DTx+TAU and TAU-only groups with a lifetime horizon. The model inputs were obtained from the HERB-DH1 trial, published or publicly available data, and expert assumptions. The incremental cost-effectiveness ratio (ICER) per QALY was used as the benchmark for cost-effectiveness. We performed probabilistic sensitivity analyses (PSAs) using the Monte Carlo simulation with 2 million sets.ResultsThe DTx+TAU strategy produced 18.778 QALY and was associated with ¥3,924,075 ($34,122) expected costs, compared with 18.686 QALY and ¥3,813,358 ($33,160) generated by the TAU-only strategy over a lifetime horizon, resulting in an ICER of ¥1,199,880 ($10,434)/QALY gained for DTx+TAU. The monthly cost and attrition rate of DTx for hypertension have a significant impact on ICERs. In the PSA, the probability of the DTx arm being a cost-effective option was 87.8% at a threshold value of ¥5 million ($43,478)/QALY gained.ConclusionsThe DTx+TAU strategy was more cost-effective than the TAU-only strategy.