bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auricular Cartilage Graft for Lengthening Levator Muscle Aponeurosis With Ectropion Correction for Paralytic Lagophthalmos
Authors: Lowndes Correa Francalacci Renata , Lessa Sérgio , da Costa Aboudib José Horácio 
Published: July 2022

Abstract

Background
Paralytic lagophthalmos can have devastating consequences for vision if left untreated. Several surgical techniques have been described, including the utilization of alloplastic and autologous materials.

Objectives
The authors sought to evaluate the effectiveness of the surgical treatment of paralytic lagophthalmos with combined techniques employing autologous material and involving the upper and lower eyelids.

Methods
Patients with paralytic lagophthalmos underwent stretching of the levator aponeurosis with interposition of conchal cartilage in the upper eyelid associated with sectioning of the orbitomalar ligament and lateral canthoplasty in the lower eyelid. The effectiveness of the technique was evaluated employing subjective (symptomatology) and objective parameters (ophthalmologic evaluation and measurements of lagophthalmos and marginal reflex distances 1 and 2).

Results
Eight patients with paralytic lagophthalmos were subjected to the proposed technique. In the postoperative period, 85.7% reported complete improvement of symptoms and 62.5% presented a normal eye examination. The mean lagophthalmos measurement was reduced by 5.93 mm, the mean marginal reflex distance 2 was reduced by 2.61 mm, and the mean marginal reflex distance 1 was reduced by 0.69 mm.

Conclusions
The technique presented herein, employing autologous material associated with sectioning of the orbitomalar ligament and lateral canthoplasty, was effective in the treatment of paralytic lagophthalmos and did not present significant complications, such as extrusion.

Level of Evidence: 4
Application of non-negative matrix factorization in oncology: one approach for establishing precision medicine
Authors: Hamamoto Ryuji , Takasawa Ken , Machino Hidenori , Kobayashi Kazuma , Takahashi Satoshi , Bolatkan Amina , Shinkai Norio , Sakai Akira , Aoyama Rina , Yamada Masayoshi , Asada Ken , Komatsu Masaaki , Okamoto Koji , Kameoka Hirokazu , Kaneko Syuzo 
Published: July 2022

AbstractThe increase in the expectations of artificial intelligence (AI) technology has led to machine learning technology being actively used in the medical field. Non-negative matrix factorization (NMF) is a machine learning technique used for image analysis, speech recognition, and language processing; recently, it is being applied to medical research. Precision medicine, wherein important information is extracted from large-scale medical data to provide optimal medical care for every individual, is considered important in medical policies globally, and the application of machine learning techniques to this end is being handled in several ways. NMF is also introduced differently because of the characteristics of its algorithms. In this review, the importance of NMF in the field of medicine, with a focus on the field of oncology, is described by explaining the mathematical science of NMF and the characteristics of the algorithm, providing examples of how NMF can be used to establish precision medicine, and presenting the challenges of NMF. Finally, the direction regarding the effective use of NMF in the field of oncology is also discussed.
LRLoop: a method to predict feedback loops in cell–cell communication
Authors: Xin Ying , Lyu Pin , Jiang Junyao , Zhou Fengquan , Wang Jie , Blackshaw Seth , Qian Jiang 
Published: July 2022

AbstractMotivationIntercellular communication (i.e. cell–cell communication) plays an essential role in multicellular organisms coordinating various biological processes. Previous studies discovered that feedback loops between two cell types are a widespread and vital signaling motif regulating development, regeneration and cancer progression. While many computational methods have been developed to predict cell–cell communication based on gene expression datasets, these methods often predict one-directional ligand–receptor interactions from sender to receiver cells and are not suitable to identify feedback loops.ResultsHere, we describe ligand–receptor loop (LRLoop), a new method for analyzing cell–cell communication based on bi-directional ligand–receptor interactions, where two pairs of ligand–receptor interactions are identified that are responsive to each other and thereby form a closed feedback loop. We first assessed LRLoop using bulk datasets and found our method significantly reduces the false positive rate seen with existing methods. Furthermore, we developed a new strategy to assess the performance of these methods in single-cell datasets. We used the between-tissue interactions as an indicator of potential false-positive prediction and found that LRLoop produced a lower fraction of between-tissue interactions than traditional methods. Finally, we applied LRLoop to the single-cell datasets obtained from retinal development. We discovered many new bi-directional ligand–receptor interactions among individual cell types that potentially control proliferation, neurogenesis and/or cell fate specification.Availability and implementationAn R package is available at https://github.com/Pinlyu3/LRLoop. The source code can be found at figshare (https://doi.org/10.6084/m9.figshare.20126138.v1). The datasets can be found at figshare (https://doi.org/10.6084/m9.figshare.20126021.v1).Supplementary informationSupplementary data are available at Bioinformatics online.
Activation of Wnt/β-catenin pathway mitigates blood–brain barrier dysfunction in Alzheimer’s disease
Authors: Wang Qi , Huang Xiaomin , Su Yixun , Yin Guowei , Wang Shouyu , Yu Bin , Li Hui , Qi Junhua , Chen Hui , Zeng Wen , Zhang Kai , Verkhratsky Alexei , Niu Jianqin , Yi Chenju 
Published: July 2022

Abstract
Alzheimer’s disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for Alzheimer’s disease pose a significant challenge, because the mechanisms of disease are not being fully understood. Malfunction of the blood–brain barrier is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease, especially at the early stages of the disease. However, the underlying mechanisms remain poorly characterized, while few molecules can directly target and improve blood–brain barrier function in the context of Alzheimer’s disease. Here, we showed dysfunctional blood–brain barrier in patients with Alzheimer’s disease reflected by perivascular accumulation of blood-derived fibrinogen in the hippocampus and cortex, accompanied by decreased tight junction proteins Claudin-5 and glucose transporter Glut-1 in the brain endothelial cells. In the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer’s disease, blood–brain barrier dysfunction started at 4 months of age and became severe at 9 months of age. In the cerebral microvessels of APP/PS1 mice and amyloid-β-treated brain endothelial cells, we found suppressed Wnt/β-catenin signalling triggered by an increase of GSK3β activation, but not an inhibition of the AKT pathway or switching to the Wnt/planar cell polarity pathway. Furthermore, using our newly developed optogenetic tool for controlled regulation of LRP6 (upstream regulator of the Wnt signalling) to activate Wnt/β-catenin pathway, blood–brain barrier malfunction was restored by preventing amyloid-β-induced brain endothelial cells impairments and promoting the barrier repair. In conclusion, targeting LRP6 in the Wnt/β-catenin pathway in the brain endothelium can alleviate blood–brain barrier malfunction induced by amyloid-β, which may be a potential treatment strategy for Alzheimer’s disease.
Localized chemogenetic silencing of inhibitory neurons: a novel mouse model of focal cortical epileptic activity
Authors: Goldenberg Adi Miriam , Schmidt Sarah , Mitelman Rea , Levy Dana Rubi , Prigge Matthias , Katz Yonatan , Yizhar Ofer , Beck Heinz , Lampl Ilan 
Published: July 2022

AbstractFocal cortical epilepsies are frequently refractory to available anticonvulsant drug therapies. One key factor contributing to this state is the limited availability of animal models that allow to reliably study focal cortical seizures and how they recruit surrounding brain areas in vivo. In this study, we selectively expressed the inhibitory chemogenetic receptor, hM4D, in GABAergic neurons in focal cortical areas using viral gene transfer. GABAergic silencing using Clozapine-N-Oxide (CNO) demonstrated reliable induction of local epileptiform events in the electroencephalogram signal of awake freely moving mice. Anesthetized mice experiments showed consistent induction of focal epileptiform-events in both the barrel cortex (BC) and the medial prefrontal cortex (mPFC), accompanied by high-frequency oscillations, a known characteristic of human seizures. Epileptiform-events showed propagation indication with favored propagation pathways: from the BC on 1 hemisphere to its counterpart and from the BC to the mPFC, but not vice-versa. Lastly, sensory whisker-pad stimulation evoked BC epileptiform events post-CNO, highlighting the potential use of this model in studying sensory-evoked seizures. Combined, our results show that targeted chemogenetic inhibition of GABAergic neurons using hM4D can serve as a novel, versatile, and reliable model of focal cortical epileptic activity suitable for systematically studying cortical ictogenesis in different cortical areas.
Tailoring brain–machine interface rehabilitation training based on neural reorganization: towards personalized treatment for stroke patients
Authors: Jia Tianyu , Li Chong , Mo Linhong , Qian Chao , Li Wei , Xu Quan , Pan Yu , Liu Aixian , Ji Linhong 
Published: July 2022

AbstractElectroencephalogram (EEG)-based brain–machine interface (BMI) has the potential to enhance rehabilitation training efficiency, but it still remains elusive regarding how to design BMI training for heterogeneous stroke patients with varied neural reorganization. Here, we hypothesize that tailoring BMI training according to different patterns of neural reorganization can contribute to a personalized rehabilitation trajectory. Thirteen stroke patients were recruited in a 2-week personalized BMI training experiment. Clinical and behavioral measurements, as well as cortical and muscular activities, were assessed before and after training. Following treatment, significant improvements were found in motor function assessment. Three types of brain activation patterns were identified during BMI tasks, namely, bilateral widespread activation, ipsilesional focusing activation, and contralesional recruitment activation. Patients with either ipsilesional dominance or contralesional dominance can achieve recovery through personalized BMI training. Results indicate that personalized BMI training tends to connect the potentially reorganized brain areas with event-contingent proprioceptive feedback. It can also be inferred that personalization plays an important role in establishing the sensorimotor loop in BMI training. With further understanding of neural rehabilitation mechanisms, personalized treatment strategy is a promising way to improve the rehabilitation efficacy and promote the clinical use of rehabilitation robots and other neurotechnologies.
Connectome-based individualized prediction of reciprocity propensity and sensitivity to framing: a resting-state functional magnetic resonance imaging study
Authors: Fang Huihua , Liao Chong , Fu Zhao , Tian Shuang , Luo Yuejia , Xu Pengfei , Krueger Frank 
Published: July 2022

AbstractBackgroundThe social representation theory states that individual differences in reciprocity decisions are composed of a stable central core (i.e., reciprocity propensity, RP) and a contextual-dependent periphery (i.e., sensitivity to the framing effect; SFE, the effect by how the decision is presented). However, the neural underpinnings that explain RP and SFE are still unknown.MethodHere, we employed prediction and lesion models to decode resting-state functional connectivity (RSFC) of RP and SFE for reciprocity decisions of healthy volunteers who underwent RS functional magnetic resonance imaging and completed one-shot trust (give frame) and distrust (take frame) games as trustees.ResultsRegarding the central core, reciprocity rates were positively associated between the give and take frame. Neuroimaging results showed that inter-network RSFC between the default-mode network (DMN; associated with mentalizing) and cingulo-opercular network (associated with cognitive control) contributed to the prediction of reciprocity under both frames. Regarding the periphery, behavioral results demonstrated a significant framing effect-people reciprocated more in the give than in the take frame. Our neuroimaging results revealed that intra-network RSFC of DMN (associated with mentalizing) contributed dominantly to the prediction of SFE.ConclusionOur findings provide evidence for distinct neural mechanisms of RP and SFE in reciprocity decisions.
Tuberculosis Treatment Outcomes in Brazil: Different Predictors for Each Type of Unsuccessful Outcome
Authors: Ridolfi Felipe , Peetluk Lauren , Amorim Gustavo , Turner Megan , Figueiredo Marina , Cordeiro-Santos Marcelo , Cavalcante Solange , Kritski Afrânio , Durovni Betina , Andrade Bruno , Sterling Timothy R , Rolla Valeria ,   for the Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil Consortium
Published: July 2022

Abstract

Background
Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors.

Methods
Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015–2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome.

Results
Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0–9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7–4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1–3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2–6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1–4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4–19.7), diabetes (aOR = 3.1; 95% CI, 1.4–6.7), and PWH (aOR = 3.9; 95% CI, 1.3–11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3–.9) and death (aOR = 0.5; 95% CI, .2–1.0).

Conclusions
The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes.
Congenital Tuberculosis After In Vitro Fertilization: A Case for Tuberculosis Screening of Women Evaluated for Infertility
Authors: Sands Ashley , Santiago Maria T , Uduwana Shanika , Glater-Welt Lily , Ezhuthachan Idil D , Coscia Gina , Hayes Lisa , Berry Gregory J , Rubin Lorry G , Hagmann Stefan H F 
Published: July 2022

Abstract
We report a case of multidrug-resistant congenital tuberculosis (TB) in an infant conceived by in vitro fertilization and review 22 additional infant–mother pairs in the literature. Females evaluated for infertility should be screened for TB risk, and those at risk require a TB-specific diagnostic evaluation before receiving assisted reproductive treatment.
Magnitude and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission: A Longitudinal Cohort Study
Authors: Kelly J Daniel , Lu Scott , Anglin Khamal , Garcia-Knight Miguel , Pineda-Ramirez Jesus , Goldberg Sarah A , Tassetto Michel , Zhang Amethyst , Donohue Kevin , Davidson Michelle C , Romero Mariela , Diaz Sanchez Ruth , Djomaleu Manuella , Mathur Sujata , Chen Jessica Y , Forman Carrie A , Servellita Venice , Montejano Rubi D , Shak Joshua R , Rutherford George W , Deeks Steven G , Abedi Glen R , Rolfes Melissa A , Saydah Sharon , Briggs-Hagen Melissa , Peluso Michael J , Chiu Charles , Midgley Claire M , Andino Raul , Martin Jeffrey N 
Published: July 2022

Abstract

Background
Households have emerged as important venues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations.

Methods
From September 2020 to January 2022, symptomatic nonhospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least 1 other SARS-CoV-2–uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts.

Results
We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case’s symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45% [95% confidence interval {CI}, 29%–62%]), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41% [95% CI, 25%–59%]) among all contacts and 12/29 (41% [95% CI, 24%–61%]) among vaccinated contacts. At least 1 comorbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts.

Conclusions
Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection.
Non-actionable Results, Accuracy, and Effect of First- and Second-line Line Probe Assays for Diagnosing Drug-Resistant Tuberculosis, Including on Smear-Negative Specimens, in a High-Volume Laboratory
Authors: Pillay Samantha , de Vos Margaretha , Derendinger Brigitta , Streicher Elizabeth Maria , Dolby Tania , Scott Leeré Ann , Steinhobel Amy Debra , Warren Rob Mark , Theron Grant 
Published: July 2022

Abstract

Background
Rapid tuberculosis (TB) drug susceptibility testing (DST) is crucial. Genotype MTBDRsl is a widely deployed World Health Organization (WHO)–endorsed assay. Programmatic performance data, including non-actionable results from smear-negative sputum, are scarce.

Methods
Sputa from Xpert MTB/RIF individuals (n = 951) were routinely-tested using Genotype MTBDRplus and MTBDRsl (both version 2). Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing.

Findings
89% (849 of 951) of individuals were culture-positive (56%, 476 of 849 smear-negative). MTBDRplus had at least 1 nonactionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92 of 476) of smear-negatives; for MTBDRsl, 40% (171 of 427) were nonactionable (28%, 120 of 427 false-negative TB; 17%, 51 of 427 indeterminate). In smear-negatives, MTBDRsl sensitivity for fluoroquinolones was 84% (95% confidence interval, 67%–93), 81% (54%–95%) for second-line injectable drugs, and 57% (28%–82%) for both. Specificities were 93% (89%–98%), 88% (81%–93%), and 97% (91%–99%), respectively. Twenty-three percent (172 of 746) of Xpert rifampicin-resistant specimens were MTBDRplus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDRsl improved (6 [5–7] vs 37 [35–46]; P &lt; .001).

Conclusions
MTBDRsl did not generate a result in 4 of 10 smear-negatives, resulting in substantial missed resistance. However, if MTBDRsl generates an actionable result, that is accurate in ruling-in resistance. Isoniazid DST remains crucial. This study provides real-world, direct, second-line susceptibility testing performance data on non-actionable results (that, if unaccounted for, cause an overestimation of test utility), accuracy, and care cascade impact.
The Ross procedure in adult patients: a single-centre analysis of long-term results up to 28 years
Authors: Oeser Claudia , Uyanik-Uenal Keziban , Kocher Alfred , Laufer Guenther , Andreas Martin 
Published: July 2022

Abstract

OBJECTIVES
This study aimed to provide an in-depth insight into our single-centre experience with the Ross procedure.

METHODS
All adults who underwent the Ross procedure between 1991 and 2014 were included. Based on the total number of Ross procedures performed by each surgeon at our centre during this 24-year period, surgeon volume was classified as low (&lt;25 procedures), intermediate (25–44 procedures) and high (≥45 procedures). Survival, complications and reinterventions were evaluated. A single cardiologist assessed the pulmonary autograft’s function and the neoaortic root diameter by echocardiography.

RESULTS
The outcomes of 224 patients {176 men, 48 women; mean age 37.2 [standard deviation (SD) 10.0] years} were analysed. Patients operated on by a low-volume surgeon had 7.22 times higher odds (P &lt; 0.001) for a serious adverse event during the intraoperative or early postoperative course than patients operated on by a high-volume surgeon. Early mortality was 1.8%. Overall survival was 87.3% at 20 years. Compared with the demographically matched general population, the patients’ survival was significantly lower (P = 0.002). The cumulative incidence of autograft and right ventricular outflow tract conduit reintervention was 21.5% and 5.9% at 20 years, respectively. Patients with preoperative aortic regurgitation had 6.25 times the subdistribution hazard of autograft reintervention (Bonferroni-adjusted P = 0.042) and a higher neoaortic root z-score [1.37 (SD 2.04) vs 0.17 (SD 1.81), P = 0.004] than patients with aortic stenosis. In patients with preoperative aortic regurgitation, autograft wrapping (remnant aortic wall and/or Vicryl® mesh) was associated with a 74% reduction in the subdistribution hazard of autograft reintervention (Bonferroni-adjusted P = 0.002) and with a reduced incidence of neoaortic root dilatation (P = 0.037).

CONCLUSIONS
The Ross procedure performed by a specialized surgeon provides very satisfying long-term results. The higher risk of autograft reintervention in preoperative aortic regurgitation may be counteracted by supporting the autograft.