bluuebunny/crossref_metadata_2025_split huggingface dataset:
An economy of details: standards and data reusability
Authors: Delgado Ana 
Published: December 2022

Abstract
Reusability has been a key issue since the origins of the parts-based approach to synthetic biology. Starting with the BioBrick™ standard part, multiple efforts have aimed to make biology more exchangeable. The reusability of parts and other deoxyribonucleic acid-based data has proven over time to be challenging, however. Drawing on a series of qualitative interviews and an international workshop, this article explores the challenges of reusability in real laboratory practice. It shows particular ways that standards are experienced as presenting shortcomings for capturing the kinds of contextual information crucial for scientists to be able to reuse biological parts and data. I argue that researchers in specific laboratories develop a sense of how much circumstantial detail they need to share for others to be able to make sense of their data and possibly reuse it. When choosing particular reporting formats, recharacterizing data to gain closer knowledge or requesting additional information, researchers enact an ‘economy of details’. The farther apart two laboratories are in disciplinary, epistemological, technical and geographical terms, the more detailed information needs to be captured for data to be reusable across contexts. In synthetic biology, disciplinary distance between computing science and engineering researchers and experimentalist biologists is reflected in diverging views on standards: what kind of information should be included to enable reusability, what kind of information can be captured by standards at all and how they may serve to produce and circulate knowledge. I argue that such interdisciplinary tensions lie at the core of difficulties in setting standards in synthetic biology.
Sural Nerve Vertical Cross-Face Graft for Lacrimal Gland Neurotization to Improve Tear Secretion in Neurodeprivative Dry Eye
Authors: Giannaccare Giuseppe , Bolognesi Federico , Fogagnolo Paolo , Allevi Fabiana , Ruggiero Federica , Filipov Iulian , Marchetti Claudio , Scorcia Vincenzo , Biglioli Federico 
Published: December 2022

Purpose:
No specific interventions have been reported for the treatment of severe neurodeprivative dry eye disease owing to facial nerve palsy. We describe herein the feasibility of a novel surgical procedure to reinnervate the lacrimal gland and report the preliminary outcomes of the first series of patients who were treated accordingly.

Methods:
Prospective interventional case series including consecutive patients affected by facial palsy with absolute deficiency of tear secretion who underwent lacrimal gland neurotization. A sural nerve vertical cross-face graft was used to connect the lacrimal gland with the parasympathetic branch of the lingual nerve directed to the contralateral submandibular gland.

Results:
Lacrimal neurotization was performed uneventfully in 10 patients (4 M, 6 F; mean age 47.1 ± 17.1 years). In all cases, the procedure was combined with facial reanimation, while corneal neurotization was performed in 4 cases. One year postoperatively, mean values of a Schirmer test increased significantly compared with baseline values (7.56 ± 7.84 vs. 0 ± 0 mm/5 min; P = 0.02), while the mean daily number of instillation of tear substitutes decreased significantly (21.8 ± 4.5 vs. 7.1 ± 2.2; P = 0.009). Overall, all patients were satisfied with surgery (very satisfied: n = 7 and satisfied: n = 2). No major postoperative complications occurred.

Conclusions:
Vertical cross-face using a sural nerve graft to connect the lacrimal gland with the contralateral submandibular gland is a novel technique for treating patients with facial nerve palsy and severe neurodeprivative dry eye disease. This surgery both performed alone and combined with corneal neurotization is able to improve tear secretion and decrease the need for frequent instillations of tear substitutes.
Clinically Based Automated Tracing and Tortuosity Estimation of Corneal Nerve Fibers From Confocal Microscopy Images
Authors: Colonna Alessia , Scarpa Fabio 
Published: December 2022

Purpose:
The purpose of this study was the development of an algorithm able to automatically trace corneal nerves and to estimate a nerve tortuosity index that is useful in clinical practice.

Methods:
In vivo confocal microscopy is an imaging technique that allows the clinical assessment of corneal and systemic diseases. Many studies have demonstrated a correlation between the tortuosity level of nerve fibers in the subbasal plexus layer and some pathologies. We developed an algorithm that provides fully automatic tracing of nerve fibers. It also includes a new way of dealing with bifurcations, separating the main paths from the secondary ones. Based on this automated tracing, the tortuosity was estimated as the absolute curvature, tortuosity density, and fractal dimension. These metrics were considered first individually and then as a linear combination of 2 or 3 of them. We investigated the capability of the estimated tortuosity to emulate the clinical classification into low, mid, and high tortuosity levels. Furthermore, we investigated its ability to distinguish healthy subjects from pathological subjects.

Results:
Excellent agreement between manual and automated grouping of tortuosity (96.6% accuracy) was obtained. Moreover, the proposed algorithm could differentiate between healthy and pathological subjects with an accuracy of 77.1% by analyzing each image individually. The accuracy improved to 86.31% by considering 3 images of the same subject simultaneously.

Conclusions:
The proposed framework provides completely automated analysis of corneal nerve images. The results demonstrate the ability of our method to emulate the clinical classification of tortuosity levels and its potential for identifying healthy and pathological subjects.
Vergence and Accommodation Deficits in Children and Adolescents with Vestibular Disorders
Authors: Chinn Ryan N. , Marusic Sophia , Wang Alicia , Vyas Neerali , Staffa Steven J. , Brodsky Jacob R. , Raghuram Aparna 
Published: December 2022

ABSTRACT

Significance
The high frequency of vergence and accommodation deficits coexisting in patients with a vestibular diagnosis merits a detailed visual function examination.

Purpose
Deficits in vergence and saccades have been reported in patients with vestibular symptomatology. We retrospectively evaluated visual function deficits in adolescents with vestibular diagnoses and concussion.

Methods
Inclusion criteria: vestibular and optometric evaluations between 2014 and 2020; 6 to <22 years old; 20/25 best-corrected vision or better. Clinical criteria assigned vestibular diagnoses and concussion diagnoses. Vestibular diagnoses included vestibular migraine, benign paroxysmal positional vertigo, and persistent postural perceptual dizziness. Visual function deficits were compared to a pediatric control group (30). Non-parametric statistics assessed differences in group distribution.

Results
153 patients were included: 18 had vestibular diagnoses only, 62 had vestibular diagnoses related to concussion, and 73 had concussion only. Vergence deficits were more frequent in patients with vestibular diagnoses and concussion (42%) and concussion only (34%) compared to controls (3%; all P = .02). Accommodation deficits were more frequent in patients with vestibular diagnoses only (67%), vestibular diagnoses and concussion (71%), and concussion (58%) compared to controls (13%; all P = .002). Patients with vestibular migraine and concussion (21) had more vergence deficits (62%) and accommodation insufficiency (52%) than concussion only patients (47%; P = .02; 29%; P = .04). Patients with benign paroxysmal positional vertigo and concussion (20) had lower positive fusional vergence and failed near vergence facility (35%) more than concussion only patients (16%; P = .03).

Conclusions
Visual function deficits were observed at a high frequency in patients with a vestibular diagnosis with or without a concussion and particularly in vestibular migraine or benign paroxysmal positional vertigo. Visual function assessments may be important for patients with vestibular diagnoses.
Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis
Authors: Curtis Jeffrey R. , Stolshek Bradley , Emery Paul , Haraoui Boulos , Karis Elaine , Kricorian Greg , Collier David H. , Yen Priscilla K. , Bykerk Vivian P. 
Published: December 2022

Background/Objective
The effect of treatment withdrawal on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) whose disease is in sustained remission has not been well described. This analysis aimed to compare PRO changes in patients with RA following medication withdrawal and disease worsening.

Methods
SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis) was a phase 3, multicenter, randomized withdrawal, double-blind controlled study in patients with RA taking methotrexate plus etanercept and in remission (Simple Disease Activity Index ≤3.3). Patient's Global Assessment of Disease Activity, Patient's Assessment of Joint Pain, Health Assessment Questionnaire–Disability Index, and 36-Item Short-Form Health Survey were evaluated for 48 weeks following methotrexate or etanercept withdrawal. Treatment differences for patients with versus without disease worsening were evaluated using a 2-sample t test for continuous end points and log-rank test for time-to-event end points.

Results
Of 253 patients, 121 experienced disease worsening and 132 did not. All PRO scores were similar to those of a general population at baseline and deteriorated over time across the study population. The PtGA and Patient's Assessment of Joint Pain values deteriorated less in those on etanercept monotherapy compared with methotrexate monotherapy. More patients with versus without disease worsening experienced deterioration that was greater than the minimal clinically important difference (MCID) for all PROs tested. In patients with disease worsening, PtGA deterioration more than the MCID preceded Simple Disease Activity Index disease worsening.

Conclusions
Etanercept monotherapy showed benefit over methotrexate in maintaining PRO scores. Patients with disease worsening experienced a more rapid worsening of PtGA beyond the MCID versus patients without disease worsening.

Categories: autoinflammatory disease, biological therapy, DMARDs, rheumatoid arthritis
Bacteriophage and antibiotic combination therapy for recurrentEnterococcus faeciumbacteremia
Authors: Stellfox Madison E. , Fernandes Carolyn , Shields Ryan K. , Haidar Ghady , Hughes Kramer Kailey , Dembinski Emily , Mangalea Mihnea R. , Canfield Gregory S. , Duerkop Breck A. , Van Tyne Daria 
Published: December 2022

AbstractEnterococcus faeciumis a member of the human gastrointestinal (GI) tract microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinicalE. faeciumisolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistantE. faecium(VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrentE. faeciumbloodstream infections (BSIs) of increasing severity that ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole genome sequencing (WGS) showed that the patient was colonized with closely relatedE. faeciumstrains for at least two years, and that invasive isolates likely emerged from a largeE. faeciumpopulation in the patient’s GI tract. The addition of bacteriophage (phage) therapy to the patient’s antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE andE. faecium. Eventual recurrence ofE. faeciumBSI was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage neutralizing antibody response occurred simultaneously with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections.ImportancePhage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrentE. faeciuminfections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient’s quality of life. Combination phage and antibiotic therapy reducedE. faeciumand VRE abundance in the patient’s stool. Eventually an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.
Synergizing algorithmic design, photoclick chemistry and multi-material volumetric printing for accelerating complex shape engineering
Authors: Chansoria Parth , Rütsche Dominic , Wang Anny , Liu Hao , D’Angella Davide , Rizzo Riccardo , Hasenauer Amelia , Weber Patrick , Ibrahim Nafeesah Bte Mohamed , Korshunova Nina , Zenobi-Wong Marcy 
Published: December 2022

AbstractAccelerating the designing and manufacturing of complex shapes has been a driving factor of modern industrialization. This has led to numerous advances in computational design and modeling and novel additive manufacturing (AM) techniques that can create complex shapes for bespoke applications. By combining a new coding-based design approach with high-throughput volumetric printing, we envision a new approach to transform the way we design and fabricate complex shapes. Here, we demonstrate an algorithmic voxel-based approach, which can rapidly generate and analyze porous structures, auxetic meshes and cylinders, or perfusable constructs. We use this design scheme in conjunction with new approaches for multi-material volumetric printing based on thiol-ene photoclick chemistry to rapidly fabricate complex heterogeneous structures. Collectively, the new design and fabrication technique we demonstrate can be used across a wide-spectrum of products such as actuators, biomedical implants and grafts, or tissue and disease models.TeaserA new scheme of rapidly designing and printing complex multi-material structures for implant and tissue graft applications.
Single cell gene set scoring with nearest neighbor graph smoothed data (gssnng)
Authors: Gibbs David L , Strasser Michael K , Huang Sui 
Published: December 2022

AbstractGene set scoring (or enrichment) is a common dimension reduction task in bioinformatics that can be focused on differences between groups or at the single sample level. Gene sets can represent biological functions, molecular pathways, cell identities, and more. Gene set scores are context dependent values that are useful for interpreting biological changes following experiments or perturbations. Single sample scoring produces a set of scores, one for each member of a group, which can be analyzed with statistical models that can include additional clinically important factors such as gender or age. However, the sparsity and technical noise of single cell expression measures create difficulties for these methods, which were originally designed for bulk expression profiling (microarrays, RNAseq). This can be greatly remedied by first applying a smoothing transformation that shares gene measure information within transcriptomic neighborhoods. In this work, we use the nearest neighbor graph of cells for matrix smoothing to produce high quality gene set scores on a per-cell, per-group, level which is useful for visualization and statistical analysis.Availability and implementationThe gssnng software is available using the python package index (PyPI) and works with Scanpy AnnData objects. It can be installed using ‘pip install gssnng’. More information and demo notebooks: Seehttps://github.com/IlyaLab/gssnng
High frequency monitoring of feeding activity in benthic suspension feeders
Authors: Agüera Antonio , Strohmeier Tore , Krogness Cathinka , Strand Øivind 
Published: December 2022

AbstractSuspension feeders ecosystem role and services are mainly driven by their efficiency in clearing particles from the water column. As such there is an interest on suspension feeders feeding activity and how they interact with the ecosystem. Advancing research on feeding response requires experimental designs where individuals can be exposed to continuously changing environments and where feeding activity can be monitored at a high frequency and at different time scales. There are several methods to monitor feeding activity (as clearance rate (CR) and particle capture efficiency (CE)) of suspension feeders. Among them, the flow-through method is most often used and it allows individuals to be exposed to changing conditions. However, as with the other existing methods, the flow-through method is labor intensive and time consuming limiting both the number of individuals that could be observed simultaneously and the resolution at which measurements can be taken. The flow-through method is constrained by the need to measure the flow rate through the chambers and to take samples to determine particle concentration in the water. In this work we automated the standard flow-through method using micro-controller based prototyping. The result is a methodological approach that continuously monitor feeding at high frequency and on a larger number of individuals while reducing handling and measurement errors. This work provides the description and assessment of the automated set-up, which is an end to end solution that can readily assembled and configured.
Nigral-specific increase in ser31 tyrosine hydroxylase phosphorylation offsets dopamine loss and forestalls hypokinesia onset during progressive nigrostriatal neuron loss
Authors: Kasanga Ella A. , Han Yoonhee , Shifflet Marla K. , Navarrete Walter , McManus Robert , Parry Caleb , Barahona Arturo , Nejtek Vicki A. , Richardson Jason R. , Salvatore Michael F. 
Published: December 2022

AbstractMechanisms that augment dopamine (DA) signaling to compensate for tyrosine hydroxylase (TH) loss and delay motor impairment in Parkinson’s disease remain unidentified. The rat nigrostriatal pathway was unilaterally-lesioned by 6-OHDA to determine whether differences in DA content, TH protein, TH phosphorylation, or D1receptor expression in striatum or substantia nigra (SN) aligned with onset of hypokinesia at two time points. At 7 days, DA and TH loss in striatum exceeded 95%, whereas DA was unaffected in SN, despite ∼60% TH loss. At 28 days, hypokinesia was established. At both time points, ser31 TH phosphorylation increased only in SN, corresponding to less DA versus TH loss. ser40 TH phosphorylation was unaffected in striatum or SN. By day 28, D1receptor expression increased only in lesioned SN. These results indicate that increased ser31 TH phosphorylation and D1receptor in the SN, not striatum, augment DA signaling against TH loss to mitigate hypokinesia.Highlights–Despite >90% TH and DA loss in striatum, open-field locomotor activity did not decrease–Early after lesion, DA and TH loss in striatum exceeded 90%. In contrast, DA loss did not occur despite 60% TH loss in substantia nigra (SN).–TH loss was progressive in the SN, with loss also spreading contralateral to lesion.–Loss of TH protein in SN preceded cell loss ipsilateral and contralateral to lesion, indicating first stages of nigrostriatal neuron loss begin with loss of TH protein loss.–TH phosphorylation at ser31 in SN was associated with less, if any, DA loss compared to TH protein loss.–TH phosphorylation at ser40 did not change in either region and at any time during TH loss, suggesting no contribution to differences in DA loss against TH loss.–Expression of the D1 receptor increased 2.5-fold in the SN late, but not early, after lesion, suggesting a post-synaptic receptor response to offset DA loss in SN.–No increases in TH phosphorylation or D1 receptor expression in striatum at any time after lesion induction, indicating that compensatory mechanisms occur only in substantia nigra, but not in striatum, to delay onset of hypokinesia.
Does Inter-Protein Contact Prediction Benefit from Multi-Modal Data and Auxiliary Tasks?
Authors: Talukder Arghamitra , Yin Rujie , Sun Yuanfei , Shen Yang , You Yuning 
Published: December 2022

AbstractApproaches toin silicoprediction of protein structures have been revolutionized by AlphaFold2, while those topredict interfaces between proteinsare relatively underdeveloped, owing to the overly complicated yet relatively limited data of protein–protein complexes. In short, proteins are 1D sequences of amino acids folding into 3D structures, and interact to form assemblies to function. We believe that such intricate scenarios are better modeled with additional indicative information that reflects their multi-modality nature and multi-scale functionality. To improve binary prediction of inter-protein residue-residue contacts, we propose to augment input features with multi-modal representations and to synergize the objective with auxiliary predictive tasks. (i) We first progressively add three protein modalities into models: protein sequences, sequences with evolutionary information, and structure-aware intra-protein residue contact maps. We observe thatutilizing all data modalities delivers the best prediction precision. Analysis reveals that evolutionary and structural information benefit predictions on the difficult and rigid protein complexes, respectively, assessed by the resemblance to native residue contacts in bound complex structures. (ii) We next introduce three auxiliary tasks via self-supervised pre-training (binary prediction of protein-protein interaction (PPI)) and multi-task learning (prediction of inter-protein residue–residue distances and angles). Although PPI prediction is reported to benefit from predicting inter-contacts (as causal interpretations), it is not found vice versa in our study. Similarly, the finer-grained distance and angle predictions did not appear to uniformly improve contact prediction either. This again reflects the high complexity of protein–protein complex data, for whichdesigning and incorporating synergistic auxiliary tasks remains challenging.