bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Year Efficacy and Safety of the PAUL Glaucoma Implant Using a Standardized Surgical Protocol
Authors: José Patrícia , Barão Rafael C. , Teixeira Filipa J. , Marques Raquel E. , Peschiera Riccardo , Barata André , Abegão Pinto Luís 
Published: December 2021

Précis:
The PAUL Glaucoma Implant is an effective intraocular pressure (IOP)-lowering device with an acceptable safety profile. Its design as a nonvalved device with a small tube diameter using a vicryl ligation suture around the tube that is posteriorly reabsorbed instead of an ab luminal stent makes it an option in cases selected for glaucoma drainage device implantation.

Purpose:
The aim was to determine the 1-year efficacy and safety of PAUL Glaucoma Implant using a uniform, standardized surgical procedure.

Materials and Methods:
Retrospective, cohort study. Patient charts were screened between December 2018 and January 2020, with inclusion requiring a minimum follow-up of 12 months. Primary outcome was IOP-lowering at 12 months, with surgical success defined as ≤18 mm Hg and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and qualified success if otherwise. Safety outcomes were also analyzed. A standardized protocol was followed in all cases, which included mitomycin C application and 1 vicryl ligation of the tube.

Results:
A total of 24 eyes from 21 patients fulfilled inclusion criteria. Median patient age at time of surgery was 42 years (range: 1 to 76 y). IOP decreased from 31.4 (10.0) mm Hg in preoperative period to 12.5 (4.3) mm Hg in the last follow-up (P<0.001). Qualified success criteria were fulfilled by 75% of cases, while absolute success was 33%. The mean number of IOP-lowering drugs used before surgery was 3.0 and 0.9 at the 12-month visit (P<0.001). No postoperative hypotony requiring intervention was recorded.

Conclusions:
PAUL Glaucoma Implant appears to be a safe and effective glaucoma drainage implant for the treatment of moderate and advanced glaucoma.
Outcomes of Baerveldt Glaucoma Drainage Devices in Pediatric Eyes
Authors: Jacobson Adam , Besirli Cagri G. , Bohnsack Brenda L. 
Published: December 2021

Précis:
In children, Baerveldt implants showed 84% success at 1 year, but decreased to 32% at 8 years. Age, race, and glaucoma type were not risk factors for failure. Concurrent intraocular surgery was associated with complications.

Purpose:
Evaluate success and risk factors for failure and complications of Baerveldt glaucoma implants in children.

Methods:
Retrospective case series of children who underwent Baerveldt implant placement (2012-2019 by single surgeon) with ≥1 year follow-up. Ocular examination and surgical details were collected. Failure defined as intraocular pressure (IOP) <5 mm Hg or >21 mm Hg for 2 consecutive visits, need for IOP related surgery, or visually significant complication.

Results:
One hundred-six eyes of 76 patients underwent 110 Baerveldt placement at median 6.4 years. Baerveldt placement was combined with additional procedures in 49% with vitrectomy most common (30%). Success of first Baerveldt (per patient) was 64% at final follow-up (median 4.7 y). One-, 5-, and 8-year survival rates were 84%, 60%, and 32%, respectively. There was no difference (P=0.97) in survival between first Baerveldt and all Baerveldt surgeries. Failure of first Baerveldt was not associated with sex, age, ethnicity, prior IOP-lowering surgery, concurrent intraocular surgery, or glaucoma type. Complications occurred in 14% and were associated with concurrent surgery. Twenty-six percent required additional IOP-lowering surgery. At final follow-up, IOP and glaucoma medications were significantly decreased (P<0.0001). Eyes underwent an average of 3.8±2.3 ocular surgeries and 3.0±2.0 glaucoma surgeries.

Conclusions:
Baerveldt implants showed good success initially, but survival rates declined over time. No risk factors for failure of first implanted Baerveldt were identified. Concurrent surgery was associated with complications. Majority of eyes required multiple surgeries to achieve IOP control and preserve vision.
Nutrition priorities in obese critically ill patients
Authors: Al-Dorzi Hasan M. , Stapleton Renee D. , Arabi Yaseen M. 
Published: December 2021

Purpose of review
During critical illness, several neuroendocrine, inflammatory, immune, adipokine, and gastrointestinal tract hormone pathways are activated; some of which are more intensified among obese compared with nonobese patients. Nutrition support may mitigate some of these effects. Nutrition priorities in obese critically ill patients include screening for nutritional risk, estimation of energy and protein requirement, and provision of macronutrients and micronutrients.

Recent findings
Estimation of energy requirement in obese critically ill patients is challenging because of variations in body composition among obese patients and absence of reliable predictive equations for energy expenditure. Whereas hypocaloric nutrition with high protein has been advocated in obese critically ill patients, supporting data are scarce. Recent studies did not show differences in outcomes between hypocaloric and eucaloric nutrition, except for better glycemic control. Sarcopenia is common among obese patients, and the provision of increased protein intake has been suggested to mitigate catabolic changes especially after the acute phase of critical illness. However, high-quality data on high protein intake in these patients are lacking. Micronutrient deficiencies among obese critically ill patients are common but the role of their routine supplementation requires further study.

Summary
An individualized approach for nutritional support may be needed for obese critically ill patients but high-quality evidence is lacking. Future studies should focus on nutrition priorities in this population, with efficient and adequately powered studies.
Toward a Standardized and Individualized Laboratory-Based Protocol for Wheelchair-Specific Exercise Capacity Testing in Wheelchair Athletes
Authors: Janssen Rowie J. F. , de Groot Sonja , Van der Woude Lucas H. V. , Houdijk Han , Vegter Riemer J. K. 
Published: December 2021

AbstractPrevious studies on handrim wheelchair–specific (an)aerobic exercise capacity in wheelchair athletes have used a diversity of participants, equipment, and protocols. Therefore, test results are difficult to compare among studies. The first aim of this scoping review is to provide an overview of the populations studied, the equipment and protocols used, and the reported outcomes from all laboratory-based studies on wheelchair-specific exercise capacity in wheelchair athletes. The second aim is to synthesize these findings into a standardized, yet individualized protocol. A scoping literature search resulted in 10 anaerobic and 38 aerobic protocols. A large variety in equipment, protocol design, and reported outcomes was found. Studies that systematically investigated the influence of protocol features are lacking, which makes it difficult to interpret and compare test outcomes among the heterogeneous group of wheelchair athletes. Protocol design was often dependent on a priori participant knowledge. However, specific guidelines for individualization were missing. However, the common protocol features of the different studies were united into guidelines that could be followed when performing standardized and individualized wheelchair-specific exercise capacity tests in wheelchair athletes. Together with guidelines regarding reporting of participant characteristics, used equipment, and outcome measures, we hope to work toward more international agreement in future testing.
Treatment of Sagittal Craniosynostosis Using Osteoplastic Parietal Craniotomy Flap With Distraction Osteogenesis: A Variation on Technique
Authors: Habarth-Morales Theodore E. , Piatt Joseph H. , Caterson Edward J. 
Published: December 2021

Abstract:
Late presentation sagittal craniosynostosis presents a unique challenge due to the decreased ability of the skull to repair the bony defects created by standard of care techniques. Distraction osteogenesis is a viable strategy to correct this defect in late presenting cases. The authors describe a variation in technique in which the temporalis muscle origin is retained, creating an osteoplastic bone flap with retained vascularity through the tem-poralis muscle. This may improve postoperative bony healing of bony defects in this compromised population. The authors present two patients who presented to them late with sagittal synostosis who were treated with distraction osteogenesis in which vascular continuity to the parietal bones is preserved through the temporalis muscle.
Drug Induced Sleep Endoscopy Versus Awake Endoscopy in Retrolingual Obstruction Assessment in Obstructive Sleep Apnea Patients: A Comparative Study
Authors: Pérez-Martín Nuria , Bosco Gabriela , Navarro Andrés , Morato Marta , Racionero Miguel A. , Fernandez-Sanjuan Patricia , O’Connor-Reina Carlos , Plaza Guillermo 
Published: December 2021

Abstract:
The aim of this study is to evaluate the correlation of retrolingual obstruction determined by drug induced sleep endoscopy (DISE) and awake endoscopy evaluation of Muller maneuver (MM) and lingual tonsil hypertrophy (LTH) in patients with obstructive sleep apnea.
A prospective cohort of 100 patients with obstructive sleep apnea who underwent DISE was assessed. The inclusion criteria were age between 18 and 70 years, and apnea-hypopnea index higher than 5. Friedman staging, LTH and MM were determined by awake endoscopy, as other physical findings. The authors evaluated the correlation of retrolingual obstruction determined by DISE using velum oropharynx tongue, epiglottis (VOTE) and nose, oropharynx, hypopharynx, larynx (NOHL) classification.
When retrolingual MM was assessed, significant changes between awake and DISE were observed (P = 0.000). Conversely, Friedman stage had no significant changes to DISE retrolingual findings (P = 0.868). Analyzing LTH and DISE retrolingual findings according to NOHL and VOTE, if a cutoff value was established at 50%, DISE findings differ from awake: NOHL (P<0.001) and VOTE (P = 0.004). Nevertheless, if a restrictive cutoff at 75% was attached, DISE findings were similar to awake: NOHL (P = 0.124) and VOTE (P = 0.123).
This study demonstrates that awake endoscopy determining LTH and Friedman stage is a mild predictor of collapse at retrolingual level, showing significant correlation to DISE only when severe retrolingual collapse is present. Our findings suggest that in-office awake endoscopy may have certain predictive value to select surgical patients.
Correlation Between Sports-Related Maxillofacial Injuries and Head Injuries: A Five-Year Retrospective Study
Authors: Park Han-Kyul , Shriya Jaiswai M. , Jeon Min-A. , Choi Na-Rae , Chen Chun-Ming , Park Jin-Young , Hwang Dae-Seok 
Published: December 2021

Purpose:
As sports have become more diverse and demanding, the number of patients with a maxillofacial injury accompanied by a cranial injury or neurological symptoms has increased. This study examined the correlation between sports-related maxillofacial injuries and head injuries.

Patients and Methods:
Among the patients who visited the emergency department of Pusan National University Dental Hospital due to a maxillofacial injury from sporting activities between 2014 and 2018, those who additionally had head injuries were retrospectively examined. Sporting activities were classified according to the American Academy of Pediatrics classification, and severity of injuries was determined using the Facial Injury Severity Scale (FISS). Patients whose medical records showed neurological symptoms and who underwent brain computed tomography for concomitant head injury were selected. The association between each of these variables, including age and gender, was statistically analyzed.

Results:
A total of 95 patients were included in this study, most of whom were male teenagers, and cycling was the most common cause of injuries. The meanFISS score was 0.79. Brain computed tomography was conducted for 91 patients, and 28 patients reported neurological symptoms. Only 11 patients underwent advanced evaluation in the neurology or neurosurgery department. Most patients were diagnosed with contusion and concussion and were monitored without any treatment.

Conclusions:
Higher FISS values did not reflect the severity of maxillofacial and head injury. In this study, there were some patients with cranial fracture and cerebral hemorrhage with mild neurosurgical symptoms of facial trauma. Although the incidence of head trauma is not high, the necessity of wearing protective equipment cannot be overemphasized because severe trauma is permanent. Neurological signs and symptoms of patients with maxillofacial trauma should not be overlooked and require a thorough evaluation.
Seminal Studies in Facial Reanimation Surgery: Consensus and Controversies in the Top 50 Most Cited Articles
Authors: Boonipat Thanapoom , Asaad Malke , Al-Mouakeh Ahmad , Muro-Cardenas Jose , Mardini Samir , Stotland Mitchell A. , Glass Graeme E. 
Published: December 2021

Abstract
Facial paralysis can impair one's ability to form facial expressions that are congruent with internal emotion. This hinders communication and the cognitive processing of emotional experience. Facial reanimation surgery, which aims to restore full facial expressivity is a relatively recent undertaking which is still evolving. Due in large part to published techniques, refinements, and clinical outcomes in the scientific literature, consensus on best practice is gradually emerging, whereas controversies still exist.
Taking stock of how the discipline reached its current state can help delineate areas of agreement and debate, and more clearly reveal a path forward. To do this, the authors have analyzed the 50 seminal publications pertaining to facial reanimation surgery. In longstanding cases, the free gracilis transfer emerges as a clear muscle of choice but the nerve selection remains controversial with prevailing philosophies advocating cross facial nerve grafts (with or without the support of an ipsilateral motor donor) or an ipsilateral motor donor only, of which the hypoglossal and nerve to masseter predominate. The alternative orthodoxy has refined the approach popularized by Gillies in 1934 and does not require the deployment of microsurgical principles. Although this citation analysis does not tell the whole story, surgeons with an interest in facial reanimation will find that this is a good place to start.
The MLL3/4 complexes and MiDAC act antagonistically as genome-wide regulators of H4K20ac to control a specific gene expression program
Authors: Wang Xiaokang , Rosikiewicz Wojciech , Sedkov Yurii , Mondal Baisakhi , Kallappagoudar Satish , Tvardovskiy Andrey , Bajpai Richa , Xu Beisi , Pruett-Miller Shondra M , Schneider Robert , Herz Hans-Martin 
Published: December 2021

AbstractThe mitotic deacetylase complex MiDAC has recently been shown to play a vital physiological role in embryonic development and neurite outgrowth. However, how MiDAC functionally intersects with other chromatin-modifying regulators is poorly understood. Here, we describe a physical interaction between the histone H3K27 demethylase UTX, a complex-specific subunit of the enhancer-associated MLL3/4 complexes, and MiDAC. We demonstrate that UTX bridges the association of the MLL3/4 complexes and MiDAC by interacting with ELMSAN1, a scaffolding subunit of MiDAC. Our data shows that MiDAC constitutes a negative genome-wide regulator of H4K20ac, an activity which is counteracted by the MLL3/4 complexes. MiDAC and the MLL3/4 complexes co-localize at many genomic regions, that are enriched for H4K20ac and the enhancer marks H3K4me1, H3K4me2 and H3K27ac. We find that MiDAC antagonizes the recruitment of the MLL3/4 complexes to negatively regulate H4K20ac, H3K4me2 and H3K27ac resulting in transcriptional attenuation of associated genes. In summary, our findings provide a paradigm how the opposing roles of chromatin-modifying components, such as MiDAC and the MLL3/4 complexes, balance the transcriptional output of specific gene expression programs.
Agonists to ions: Efficiency suggests ‘zipper’ mechanism for nicotinic receptor activation
Authors: Auerbach Anthony 
Published: December 2021

ABSTRACTAgonists are classified by the strength at which they bind to their target sites (affinity) and their ability to activate receptors once bound to those sites (efficacy). Efficiency is a third fundamental agonist property that is a measure of the correlation between affinity and efficacy. Efficiency is the percent of agonist binding energy that is converted into energy for receptor activation (‘gating’). In the muscle nicotinic acetylcholine receptor, agonists belong to families having discrete efficiencies of 54%, 51%, 42% or 35%. Efficiency depends on the size and composition of both the agonist and binding site, and can be estimated from, and used to interpret, concentration-response curves. A correlation between affinity and efficacy indicates that the agonist’s energy changes that take place within binding and gating processes are linked. Efficiency suggests that receptors turn on and off by progressing through a sequence of energy-linked domain rearrangements, as in a zipper.
A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors
Authors: Chen KY , Krischuns T , Varga L Ortega , Harigua-Souiai E , Paisant S , Zettor A , Chiaravalli J , Courtney D , O’Brien A , Baker SC , Isel C , Agou F , Jacob Y , Blondel A , Naffakh N 
Published: December 2021

AbstractEffective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC50 values in the 4-21 µM range. The here described assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.
The P3 O-Tert-Butyl-Threonine is Key to High Cellular and Antiviral Potency for Aldehyde-Based SARS-CoV-2 Main Protease Inhibitors
Authors: Ma Yuying , Yang Kai S. , Geng Zhi Zachary , Alugubelli Yugendar R. , Shaabani Namir , Vatansever Erol C. , Ma Xinyu R. , Cho Chia-Chuan , Khatua Kaustav , Blankenship Lauren , Yu Ge , Sankaran Banumathi , Li Pingwei , Allen Robert , Ji Henry , Xu Shiqing , Liu Wenshe Ray 
Published: December 2021

ABSTRACTAs an essential enzyme to SARS-CoV-2, main protease (MPro) is a viable target to develop antivirals for the treatment of COVID-19. By varying chemical compositions at both P2 and P3 sites and the N-terminal protection group, we synthesized a series of MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal at the P1 site. These inhibitors have a large variation of determined IC50 values that range from 4.8 to 650 nM. The determined IC50 values reveal that relatively small side chains at both P2 and P3 sites are favorable for achieving high in vitro MPro inhibition potency, the P3 site is tolerable toward unnatural amino acids with two alkyl substituents on the α-carbon, and the inhibition potency is sensitive toward the N-terminal protection group. X-ray crystal structures of MPro bound with 16 inhibitors were determined. All structures show similar binding patterns of inhibitors at the MPro active site. A covalent interaction between the active site cysteine and a bound inhibitor was observed in all structures. In MPro, large structural variations were observed on residues N142 and Q189. All inhibitors were also characterized on their inhibition of MPro in 293T cells, which revealed their in cellulo potency that is drastically different from their in vitro enzyme inhibition potency. Inhibitors that showed high in cellulo potency all contain O-tert-butyl-threonine at the P3 site. Based on the current and a previous study, we conclude that O-tert-butyl-threonine at the P3 site is a key component to achieve high cellular and antiviral potency for peptidyl aldehyde inhibitors of MPro. This finding will be critical to the development of novel antivirals to address the current global emergency of concerning the COVID-19 pandemic.
The N-Terminal Carbamate is Key to High Cellular and Antiviral Potency for Boceprevir-Based SARS-CoV-2 Main Protease Inhibitors
Authors: Alugubelli Yugendar R. , Geng Zhi Zachary , Yang Kai S. , Shaabani Namir , Khatua Kaustav , Ma Xinyu R. , Vatansever Erol C. , Cho Chia-Chuan , Ma Yuying , Blankenship Lauren , Yu Ge , Sankaran Banumathi , Li Pingwei , Allen Robert , Ji Henry , Xu Shiqing , Liu Wenshe Ray 
Published: December 2021

ABSTRACTBoceprevir is an HCV NSP3 inhibitor that has been explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (MPro) and contains an α-ketoamide warhead, a P1 β-cyclobutylalanyl moiety, a P2 dimethylcyclopropylproline, a P3 tert-butyl-glycine, and a P4 N-terminal tert-butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based MPro inhibitors including PF-07321332 and characterized their MPro inhibition potency in test tubes (in vitro) and human host cells (in cellulo). Crystal structures of MPro bound with 10 inhibitors and antiviral potency of 4 inhibitors were characterized as well. Replacing the P1 site with a β-(S-2-oxopyrrolidin-3-yl)-alanyl (opal) residue and the warhead with an aldehyde leads to high in vitro potency. The original moieties at P2, P3 and the P4 N-terminal cap positions in boceprevir are better than other tested chemical moieties for high in vitro potency. In crystal structures, all inhibitors form a covalent adduct with the MPro active site cysteine. The P1 opal residue, P2 dimethylcyclopropylproline and P4 N-terminal tert-butylcarbamide make strong hydrophobic interactions with MPro, explaining high in vitro potency of inhibitors that contain these moieties. A unique observation was made with an inhibitor that contains an P4 N-terminal isovaleramide. In its MPro complex structure, the P4 N-terminal isovaleramide is tucked deep in a small pocket of MPro that originally recognizes a P4 alanine side chain in a substrate. Although all inhibitors show high in vitro potency, they have drastically different in cellulo potency in inhibiting ectopically expressed MPro in human 293T cells. All inhibitors including PF-07321332 with a P4 N-terminal carbamide or amide have low in cellulo potency. This trend is reversed when the P4 N-terminal cap is changed to a carbamate. The installation of a P3 O-tert-butyl-threonine improves in cellulo potency. Three molecules that contain a P4 N-terminal carbamate were advanced to antiviral tests on three SARS-CoV-2 variants. They all have high potency with EC50 values around 1 μM. A control compound with a nitrile warhead and a P4 N-terminal amide has undetectable antiviral potency. Based on all observations, we conclude that a P4 N-terminal carbamate in a boceprevir derivative is key for high antiviral potency against SARS-CoV-2.