bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Functional Outcomes Following Modified Intervastus Approach
Authors: Sartawi Muthana , Rahman Hafizur , Kohlmann James 
Published: May 2021

Background:
The modified intervastus (MIV) approach is a new muscle and tendon sparing approach to the knee that is easy to perform and compatible with more extensile approaches such as a quadriceps snip. The study reports the clinical and functional outcomes of patients undergoing total knee arthroplasty (TKA) using the MIV approach. These results will be compared with published results of TKA done utilizing the subvastus approach.

Methods:
A total of 84 patients underwent TKA using the MIV approach from 2017 to 2019. Clinical and functional outcomes were assessed by recording the knee injury and osteoarthritis outcomes score, visual analog scale for pain, and knee range of motion (ROM). Outcome data was collected preoperatively, on the day of surgery, and postoperatively at 2, 6 weeks, 3, 6 months, 1, and 2 years. Paired sample t tests were conducted to assess the statistical significance observed in the outcomes between different time intervals.

Results:
All patients were able to walk on the day of surgery. The knee ROM increased significantly by 2 weeks after surgery (9.36%) and a net improvement for knee ROM of 37.89% was observed by the end of 2 years (P<0.001). Knee injury and osteoarthritis outcomes score improved by 226.35% and visual analog scale for pain decreased by 82.34% following 2 years of surgery (Ps<0.001).

Conclusion:
The study reports impressive clinical and functional outcomes using the MIV approach. The approach is safe and affords adequate exposure for the majority of primary TKA cases.
Exploring the Experiences of Families of Latino Children Newly Diagnosed With Autism Spectrum Disorder
Authors: Coffield Caroline N. , Spitalnik Deborah M. , Harris Jill F. , Jimenez Manuel E. 
Published: May 2021

ABSTRACT:

Objective:
Understanding families' experiences from their initial developmental concerns through the first several months after autism spectrum disorder (ASD) diagnosis might help explain persistent disparities in age of diagnosis for low-income Latino children and those whose parents speak a primary language other than English. We explored these experiences among Latino parents of children recently diagnosed with ASD to develop a richer understanding of this critical juncture.

Method:
We conducted semistructured interviews with Latino parents of children diagnosed with ASD in the previous 3 months who were receiving follow-up care through a large, hospital-based outpatient practice. Interviews were recorded, transcribed verbatim, translated, and analyzed using an iterative process.

Results:
Twenty parents participated in a semistructured interview approximately 3 months after their child was diagnosed with ASD. All respondents were female and Latina, 90% spoke Spanish, and 95% of children received Medicaid. We identified the following 3 themes from their experiences: (1) When parents first shared their concerns about their child's development with professionals, they felt unheard. (2) Parents were surprised that the diagnostic process for ASD relied on parental description of child development and behavior and observation of the child, not on medical tests. (3) Receiving an ASD diagnosis was a life-altering event for parents, and how that diagnosis was communicated by clinicians had a significant impact on families.

Conclusion:
Parents of young Latino children identified several barriers throughout the process of ASD identification and diagnosis that have important implications for improving clinician communication with families.
The dual role of ferroptosis in pancreatic cancer: a narrative review
Authors: Tang Daolin , Chen Xin , Comish Paul B. , Kang Rui 
Published: May 2021

Abstract
Pancreatic ductal adenocarcinoma is the main cause of cancer-related mortality, with a lack of effective treatments and overall survival rates far lower than other solid cancers. This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis. Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance. In particular, recent studies have suggested that ferroptosis, a type of iron-dependent nonapoptotic cell death, is a promising target for pancreatic ductal adenocarcinoma. Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways, mediated by extrinsic/membrane transports (e.g., solute carrier family 7 member 11) or intrinsic/enzymes (e.g., glutathione peroxidase 4). Although the exact effector molecule remains obscure, reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death. While treatment-induced ferroptosis is beneficial to suppress tumor growth, inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma. In this review, we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.
Nonabducent Cranial Neuropathies in Cerebral Venous Sinus Thrombosis
Authors: Nagaraja Nandakumar , Sabu Sibiya 
Published: May 2021

Introduction:
Cerebral venous sinus thrombosis (CVST) can rarely present with cranial neuropathies other than abducent nerve palsy. The authors report a case and review the literature for nonabducent cranial neuropathies in CVST.

Case Report:
A 22-year-old woman with a history of oral contraceptive use developed right-sided headache, blurred vision, and dizziness for 4 days. Magnetic resonance venogram showed complete thrombosis of the right transverse sinus, sigmoid sinus, and internal jugular vein, and partial thrombosis of the superior sagittal sinus, left transverse sinus, and superior part of the left internal jugular vein. Hypercoagulable workup revealed heterozygous factor V Leiden mutation. About 2 weeks after symptom onset, she developed right facial droop and left eye ptosis. Examination revealed bilateral papilledema, partial left ptosis, complete right abducent, and right peripheral facial palsies. Acetazolamide 250 mg 2 times per day was initiated for the treatment of headache. Three days after starting acetazolamide left ptosis, right facial and abducent palsies improved that continued to get better with only slight deficits at discharge 4 weeks from symptom onset. Follow-up computed tomography venogram on day 24 showed partial recanalization of CVST.

Conclusion:
A systematic review identified 26 patients from 21 articles with nonabducent cranial neuropathies. Seven patients had lower motor neuron facial palsy, 13 patients had hearing loss or vertigo with vestibulocochlear involvement, and 6 patients had other mixed cranial nerve palsies with CVST. They are usually associated with transverse sinus and/or sigmoid sinus thrombosis. They have a good prognosis with improvement and complete resolution of cranial neuropathies in most cases usually in 1 month.
Concurrent Stroke and Myocardial Infarction After Mild COVID-19 Infection
Authors: Ruiz-Ares Gerardo , Jimenez-Valero Santiago , Fernández-Prieto Andrés , Arbas-Redondo Emilio , Díaz-Pollán Beatriz , Navia Pedro , Meras Pablo , Alonso de Leciñana Maria , de Donebún Jorge R.P. , Rigual Ricardo , Fuentes Blanca , Díez-Tejedor Exuperio 
Published: May 2021

Introduction:
The concurrency of both, acute stroke and acute myocardial infarction in normal conditions, outside the pandemic is rare. Coagulopathy has been associated with the inflammatory phase of coronavirus disease (COVID-19) and might be involved in this concurrency.

Cases Report:
We describe 2 patients with previous mild or no symptoms of COVID-19, admitted for acute stroke with recent/simultaneous myocardial infarction in whom admission polymerase chain reaction was negative but serologic testing diagnosed COVID-19. In these patients, concurrent stroke and myocardial infarction could have been promoted by COVID-19 infection. Management and evolution are detailed, and their contacts to confirm the COVID-19 infection. Pathogenic analysis of possible hypercoagulation state is described suggesting the hypothesis of endothelial dysfunction as the strongest mechanism involved in thrombus formation after the acute phase of COVID-19 infection.

Conclusions:
Our experience with these cases suggests that patients with mild symptoms can also present thromboembolic complications once the acute phase of COVID-19 infection has passed.
Aβ-related Angiitis (ABRA)—A Rare Paraneoplastic Cause of Cerebral Vasculitis in a Young Patient
Authors: Rill Constantin , Scheerer Lukas , Iorgu Ana-Maria , Bonmann Eckhard 
Published: May 2021

Introduction:
Aβ-related angiitis (ABRA) is a very rare disease entity with combined features of cerebral amyloid angiopathy and primary angiitis of the CNS. However, the pathogenesis has not been conclusively described yet. Interestingly though, a possible paraneoplastic origin has been reported in the past. ABRA leads to severe encephalopathy with a broad spectrum of unspecific neurological symptoms and usually occurs in older patients. Because of the response to immunological treatment, it is important to confirm the diagnosis as fast as possible. Unfortunately, the pathway to a definite diagnosis is often complicated and prolonged.

Case Report:
Here, we describe a 48-year-old-female patient presenting headache, behavioral changes as well as subacute fatigue and epileptic seizures in the recent past. The initial neuroradiological examination demonstrated extended lesions in the left hemisphere compatible with an inflammatory or neoplastic disease. After extensive investigations, initially without a definite result, we finally validated the diagnosis of ABRA by brain biopsy. Shortly afterwards a routine check-up revealed an invasive mammary carcinoma. Owing to a mandatory mastectomy and chemotherapy, an immunosuppressive therapy was not implemented.

Conclusions:
The reported case demonstrates our diagnostic approach and the clinical difficulties in validating a rare cause of encephalopathy in a young patient with nonspecific clinical and neuroradiological findings. Because of the possibility of an effective treatment, it is important to consider ABRA in the differential diagnosis especially when blood tests, analysis of cerebrospinal fluid, and angiography show normal results. Since a paraneoplastic genesis is presumed, a search for an underlying tumor disease should be considered.
Prevalence of postamputation pain and its subtypes: a meta-analysis with meta-regression
Authors: Schwingler Paul M. , Moman Rajat N. , Hunt Christy , Ashmore Zachary , Ogletree Sandra P. , Uvodich Mason E. , Murad M. Hassan , Hooten W. Michael 
Published: May 2021

Abstract

Introduction:
The inconsistent use of standardized approaches for classifying postamputation pain (PAP) has been a barrier to establishing its prevalence.

Objectives:
The primary objective of this systematic review and meta-analysis is to determine the prevalence of nontraumatic lower-extremity PAP using an established taxonomy. The secondary objective is to determine the prevalence of PAP subtypes, including phantom limb pain and residual limb pain (RLP).

Methods:
An a priori protocol was registered, and a database search was conducted by a reference librarian. Randomized trials and uncontrolled studies were eligible for inclusion. The risk of bias was assessed using a tool developed for uncontrolled studies. A total of 2679 studies were screened, and 13 studies met inclusion criteria (n = 1063).

Results:
The sources of risk of bias included selection bias and, to a lesser extent, whether the outcome was adequately ascertained. Two studies reported the prevalence of PAP and the pooled prevalence was 61% (95% confidence interval [CI], 33%–86%) with high heterogeneity (I2 = 93%). Thirteen studies reported the prevalence of phantom limb pain and the pooled prevalence was 53% (95% CI, 40%–66%) with high heterogeneity (I2 = 93%). Eight studies reported the prevalence of RLP and the pooled prevalence was 32% (95% CI 24%–41%) with high heterogeneity (I2 = 76%). Clinical subtypes of RLP were not reported.

Conclusions:
The prevalence of PAP is high in patients with nontraumatic lower-extremity amputations. Ongoing research that uses a taxonomy for PAP is needed to fully delineate the prevalence of PAP subtypes.
Combination of Crossbar and Let-Down Techniques for Dorsal Hump and Septal Correction in Rhinoplasty
Authors: Öztürk Güncel 
Published: May 2021

Abstract
Rhinoplasty is one of the most common and challenging surgeries in aesthetic plastic surgery. Among rhinoplasty operations, dorsal hump reduction and septal deviation surgeries are quite common. In the present research, the author describes new approaches in which let-down and crossbar techniques are used in patients with simultaneous dorsal hump and septal deviation deformations. The records of the patients were accessed from a private practice. According to the inclusion and exclusion criteria, 36 patients were included. Two approaches were defined according to patients' needs. Patients were evaluated using the “Rhinoplasty Outcome Evaluation” (ROE) questionnaire before and 12 months after surgery. The follow-up periods ranged between 14 and 21 months. The ROE scores ranged between 80 and 100 points after 1 year. The initial median ROE score was 55.5, and it increased to 90.5 points at 12 months after surgery (P < 0.001). Patient satisfaction was excellent for 90% of the included patients. The present research is the first to demonstrate the successful results of the combination of crossbar and let-down techniques in patients with septal deviation and nasal hump. Plastic surgeons will be able to solve these challenging problems without relapse with the combination of crossbar and let-down techniques.
Preliminary Immunogenicity of a Pan-COVID-19 T Cell Vaccine in HLA-A*02:01 Mice
Authors: Carter Brandon , Chen Jinjin , Kaseke Clarety , Dimitrakakis Alexander , Gaiha Gaurav D. , Xu Qiaobing , Gifford David K. 
Published: May 2021

AbstractNew strains of SARS-CoV-2 have emerged, including B.1.351 and P.1, that demonstrate increased transmissibility and the potential of rendering current SARS-CoV-2 vaccines less effective. A concern is that existing SARS-CoV-2 spike subunit vaccines produce neutralizing antibodies to three dimensional spike epitopes that are subject to change during viral drift. Here we provide an initial report on the hypothesis that adaptive T cell based immunity may provide a path for a pan-COVID-19 vaccine that is resilient to viral drift. T cell based adaptive immunity can be based on short peptide sequences selected from the viral proteome that are less subject to drift, and can utilize multiple such epitopes to provide redundancy in the event of drift. We find that SARS-CoV-2 peptides contained in a mRNA-LNP T cell vaccine for SARS-CoV-2 are immunogenic in mice transgenic for the human HLA-A*02:01 gene. We plan to test the efficacy of this vaccine with SARS-CoV-2 B.1.351 challenge trials with HLA-A*02:01 mice.
Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals
Authors: Chen Elaine C. , Gilchuk Pavlo , Zost Seth J. , Suryadevara Naveenchandra , Winkler Emma S. , Cabel Carly R. , Binshtein Elad , Sutton Rachel E. , Rodriguez Jessica , Day Samuel , Myers Luke , Trivette Andrew , Williams Jazmean K. , Davidson Edgar , Li Shuaizhi , Doranz Benjamin J. , Campos Samuel K. , Carnahan Robert H. , Thorne Curtis A. , Diamond Michael S. , Crowe James E. 
Published: May 2021

ABSTRACTUnrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of SARS-CoV-2 infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identified 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, ACE2-blocking clone that protectsin vivo), and others recognizing non-RBD epitopes that bound the heptad repeat 1 region of the S2 domain. Germline-revertant forms of some public clonotypes bound efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.
The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)
Authors: Ebrahim Ali , Riley Blake T. , Kumaran Desigan , Andi Babak , Fuchs Martin R. , McSweeney Sean , Keedy Daniel A. 
Published: May 2021

AbstractThe COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mprowere obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mproacross multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including mobile solvent interleaved between the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to counter-punch COVID-19 and combat future coronavirus pandemics.SynopsisX-ray crystallography at variable temperature for SARS-CoV-2 Mproreveals a complex conformational landscape, including mobile solvent at the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and an intramolecular network bridging the active site and dimer interface.
Structural visualization of de novo initiation of RNA polymerase II transcription
Authors: Yang Chun , Fujiwara Rina , Kim Hee Jong , Colón Jose J. Gorbea , Steimle Stefan , Garcia Benjamin A. , Murakami Kenji 
Published: May 2021

SummaryStructural studies of the initiation-elongation transition of RNA polymerase II (pol II) transcription were previously facilitated by the use of synthetic oligonucleotides. Here we report structures of initiation complexesde novoconverted from pre-initiation complex (PIC) through catalytic activities and stalled at different template positions. Contrary to previous models, the closed-to-open promoter transition was accompanied by a large positional change of the general transcription factor TFIIH which became in closer proximity to TFIIE for the active delivery of the downstream DNA to the pol II active center. The initially-transcribing complex (ITC) reeled over 80 base pairs of the downstream DNA by scrunching, while retaining the fixed upstream contact, and underwent the transition to elongation when it encountered promoter-proximal pol II from a preceding round of transcription. TFIIH is therefore conducive to promoter melting, TSS scanning, and promoter escape, extending far beyond synthesis of a short transcript.
SARS -CoV-2 T-cell immunity to variants of concern following vaccination
Authors: Gallagher Kathleen M.E. , Leick Mark B. , Larson Rebecca C. , Berger Trisha R. , Katsis Katelin , Yam Jennifer Y. , Brini Gabrielle , Grauwet Korneel ,   MGH COVID-19 Collection & Processing Team, Maus Marcela V. 
Published: May 2021

SUMMARYRecently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence1–6. A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein7, 8, which is required for viral entry to host cells9. Immunity to SARS-CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants10–12, investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants.
Fixed or random? On the reliability of mixed-effects models for a small number of levels in grouping variables
Authors: Oberpriller Johannes , de Souza Leite Melina , Pichler Maximilian 
Published: May 2021

AbstractBiological data are often intrinsically hierarchical. Due to their ability to account for such dependencies, mixed-effects models have become a common analysis technique in ecology and evolution. While many questions around their theoretical foundations and practical applications are solved, one fundamental question is still highly debated: When facing a low number of levels should we model a grouping (blocking, clustering) variable as a random or fixed effect? In such situation, the variance of the random effect is imprecise, but whether this affects the statistical properties of the population effect is unclear.Here, we analyzed the consequences of including a grouping variable as fixed or random effect in the correctly specified and other possible miss-specified models (too simple or too complex models) for data with small number of levels (2 - 8). For all these options, we calculated type I error rates and power. Moreover, we show how these statistical properties change with the study design.We found that the model choice does not influence the statistical properties of the population effect when the effect is the same at all levels However, if an ecological effect differs among levels, using a random slope and intercept model, and switching to a fixed-effect model only in case of a singular fit, avoids overconfidence in the results. Additionally, power and type I error are strongly influenced by the number of and difference between levels.We conclude that inferring the correct random effect structure is of high importance to get correct statistical properties. When in doubt, we recommend starting with the simpler model and using model diagnostics to identify missing components. When having identified the correct structure, we encourage to start with a mixed-effects model independent of the number of levels and switch to a fixed-effect model only in case of a singular fit. With these recommendations, we allow for more informative choices about study design and data analysis and thus make ecological inference with mixed-effects models more robust for small number of levels.