bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Lumbar Disk Herniation on Performance Outcomes and New Contracts in the National Football League
Authors: Dupont Marcel M. , Fourman Mitchell S. , Iyer Sravisht , Qureshi Sheeraz A. , Sheha Evan D. , Rhie-Lee Julia , Dowdell James 
Published: September 2022

Study Design:
This was a retrospective cohort study.

Objective:
To determine performance outcomes and the contract-signing ability for the most recent cohort of professional football players treated for lumbar disk herniation (LDH).

Summary of Background Data:
LDH can have a significant impact on the career of a National Football League (NFL) player. Previous studies have found favorable return to play (RTP) and performance outcomes for players with LDH, but the impact on the ability to sign new contracts (an important surrogate to assess continued success) has not previously been studied.

Materials and Methods:
NFL players treated for LDH from 2000 to 2020 were identified from a public records search. Age, position, type of treatment, and RTP measures were collected. Pro Football Focus (PFF) performance grade and contract values were compared before the injury and after treatment. Multivariable logistic regression was used to identify independent risk factors associated with the ability to RTP and sign high-value contracts.

Results:
One hundred one players were treated for an LDH, of which 75 returned to play. Posttreatment performance as measured by PFF was similar to preinjury levels (P=0.2). However, both total and guaranteed contract values were significantly reduced (P<0.01). In multivariable analysis, both lower age and higher preinjury PFF grade were independent predictors of RTP and ability to sign a new contract. A preinjury contract that contained a high proportion of guaranteed money was found to be an independent predictor of the ability to sign a contract that was >20% guaranteed.

Conclusion:
Although the majority of players were able to RTP at preserved performance levels following LDH treatment, their contract values were significantly reduced. RTP and contract-signing ability were not associated with the type of treatment, but rather baseline factors such as the player’s age, performance, and preinjury compensation.

Level of Evidence:
Level IV.
Corticosteroid-resistant Sweet’s syndrome as the first manifestation of myelodysplastic/ myeloproliferative neoplasm-unclassifiable: a case report
Authors: Pan Lina , Zhang Jingru , Li Peng , Zhao Chuanli , Zang Shaolei , Ji Min , Lu Fei , Ye Jingjing , Zhang Chunqing , Ji Chunyan 
Published: September 2022

Abstract
A middle-aged man was diagnosed with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U), with severe and extensive corticosteroid-resistant Sweet’s syndrome (SS) as the first manifestation, with evidence of clinical manifestations, pathological description, and laboratory evaluation. The skin lesions continued to spread despite treatment with systemic corticosteroids but were successfully treated with intravenous immunoglobulin (IVIG).
Optimizing Therapeutic Drug Monitoring in Pregnant Women: A Critical Literature Review
Authors: Moreira Fernanda de Lima , Benzi Jhohann Richard de Lima , Pinto Leonardo , Thomaz Matheus de Lucca , Duarte Geraldo , Lanchote Vera Lucia 
Published: September 2022

Background:
More than 90% of pregnant women take at least one drug during pregnancy. Drug dose adjustments during pregnancy are sometimes necessary due to various pregnancy-induced physiological alterations frequently associated with lower plasma concentrations. However, the clinical relevance or benefits of therapeutic drug monitoring (TDM) in pregnant women have not been specifically studied. Clinical pharmacokinetic studies in pregnant women are incredibly challenging for many reasons. Despite this, regulatory agencies have made efforts to encourage the inclusion of this population in clinical trials to achieve more information on the pharmacotherapy of pregnant women. This review aims to provide support for TDM recommendations and dose adjustments in pregnant women.

Methods:
The search was conducted after a predetermined strategy on PubMed and Scopus databases using the MeSH term “pregnancy” alongside other terms such as “Pregnancy and dose adjustment,” “Pregnancy and therapeutic drug monitoring,” “Pregnancy and PBPK,” “Pregnancy and pharmacokinetics,” and “Pregnancy and physiological changes.”

Results:
The main information on TDM in pregnant women is available for antiepileptics, antipsychotics, antidepressants, antibiotics, antimalarials, and oncologic and immunosuppressive drugs.

Conclusions:
More data are needed to support informed benefit–risk decision making for the administration of drugs to pregnant women. TDM and/or pharmacokinetic studies could ensure that pregnant women receive an adequate dosage of an active drug. Mechanistic modeling approaches potentially could increase our knowledge about the pharmacotherapy of this special population, and they could be used to better design dosage regimens.
Risk factors and prognostic significance of platelet count abnormalities in children with HIV infection on antiretroviral therapy
Authors: Lubega Joseph , Kim Taylor O. , Airewele Gladstone , Grimes Amanda , Bulsara Shaun , Peckham Erin , Wanless Sebastian R. , Haq Heather , Elyanu Peter , Musoke Philippa , Lumumba Mwita , Kekitiinwa Adeodata , Matshaba Mogomotsi , Scheurer Michael , Despotovic Jenny 
Published: September 2022

Objectives:
To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

Design:
A retrospective nested case control study of patients 0–18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004–2014.

Methods:
Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with selected clinical variables. We constructed Kaplan–Meier curves and a Cox proportional hazards model to evaluate the impact of T/T on survival.

Results:
Two thousand, one hundred and nine children were sampled. The incidence density of thrombocytopenia was 1 per 57.9 (95% confidence interval [CI] 50.3–66.8) CWH-years. Thrombocytopenia was higher in children with WHO Stage III/IV, lower in children on zidovudine, and had no association with use of lamivudine or nevirapine, CD4+ suppression, age, and nutrition status. Thrombocytopenia was independently associated with 2.2-fold higher mortality (95% CI 1.62–3.08). The incidence density of thrombocytosis was 1 per 11.4 (95% CI 10.7–12.1) CWH-years. Thrombocytosis was associated with higher CD4+ cell count, younger age, and use of lamivudine or nevirapine, and did not impact survival.

Conclusions:
Platelet count is a clinically valuable biomarker of HIV clinical progression and mortality. Laboratory studies are necessary to elucidate the mechanisms of T/T.
64Cu-DOTA-Rituximab PET/CT of B-Cell Non-Hodgkin Lymphoma for Imaging the CD20 Expression
Authors: Lee Inki , Lim Ilhan , Lee Kyo Chul , Kang Hye Jin , Lim Sang Moo 
Published: September 2022

Abstract

64Cu-DOTA-rituximab PET/CT was performed on a 62-year-old and a 71-year-old men diagnosed with B-cell non-Hodgkin lymphoma. Compared with 18F-FDG PET/CT, lesions could be detected more sensitively, and it was confirmed that there was no discernible 64Cu-DOTA-rituximab uptake in the tumor other than lymphoma. 64Cu-DOTA-rituximab PET/CT could be a powerful tool for the diagnosis and monitoring treatment response of lymphoma because of imaging the CD20 expression.
Monitoring the Progression of a Calcifying Uterine Leiomyoma
Authors: Resto David A. , Park Peter Sang Uk , Werner Thomas J. , Høilund-Carlsen Poul F. , Alavi Abass 
Published: September 2022

Abstract
Uterine leiomyomas (fibroids) are common and benign hormone-dependent tumors of the uterus, often coinciding with atypical menstrual bleeding, urinary incontinence, and lower abdominal pain. The PET tracer 18F-NaF has been used to study metastatic and benign bone disorders, but its potential use in investigating the molecular alterations of extraosseous tissues and tumors has not been fully investigated. In this report, we present a calcifying uterine leiomyoma incidentally detected on 18F-NaF PET/CT scans in a postmenopausal 61-year-old woman and follow-up image 2 years after, highlighting the potential of 18F-NaF in monitoring both the molecular and structural progression of uterine leiomyomas.
Exact global alignment using A* with chaining seed heuristic and match pruning
Authors: Groot Koerkamp Ragnar , Ivanov Pesho 
Published: September 2022

AbstractMotivationSequence alignment has been at the core of computational biology for half a century. Still, it is an open problem to design a practical algorithm for exact alignment of a pair of related sequences in linear-like time (Medvedev, 2022b).MethodsWe solve exact global pairwise alignment with respect to edit distance by using the A* shortest path algorithm. In order to efficiently align long sequences with high divergence, we extend the recently proposedseed heuristic(Ivanovet al., 2022) withmatch chaining, gap costs, andinexact matches. We additionally integrate the novelmatch pruningtechnique and diagonal transition (Ukkonen, 1985) to improve the A* search. We prove the correctness of our algorithm, implement it in the A*PA aligner, and justify our extensions intuitively and empirically.ResultsOn random sequences of divergenced=4% and lengthn, the empirical runtime of A*PA scales near-linearly with length (best fitn1.06,n≤107bp). A similar scaling remains up tod=12% (best fitn1.24,n≤107bp). Forn=107bp andd=4%, A*PA reaches >500× speedup compared to the leading exact aligners EDLIB and BIWFA. The performance of A*PA is highly influenced by long gaps. On long (n>500 kbp) ONT reads of a human sample it efficiently aligns sequences withd<10%, leading to 3× median speedup compared to EDLIB and BIWFA. When the sequences come from different human samples, A*PA performs 1.7× faster than EDLIB and BIWFA.Availabilitygithub.com/RagnarGrootKoerkamp/astar-pairwise-alignerContactragnar.grootkoerkamp@inf.ethz.ch,pesho@inf.ethz.ch
Myonuclear alterations associated with exercise are independent of age in humans
Authors: Battey E. , Ross J.A , Hoang A. , Wilson D.G.S. , Han Y. , Levy Y. , Pollock R.D. , Kalakoutis M. , Pugh J.N. , Close G.L. , Ellison-Hughes G. M. , Lazarus N.R. , Iskratsch T. , Harridge S.D.R. , Ochala J. , Stroud M.J. 
Published: September 2022

AbstractAge-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with nuclear lamina protein Lamin A regulating nuclear shape, nuclear mechanics, and ultimately gene expression. Defective Lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals. Complementary to this, exercise resulted in increased levels of Lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan.Key pointsThe nucleus plays an active role in translating forces into biochemical signalsMyonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function.Here, we present striking differences in myonuclear shape and mechanics associated with exercise, in both young and old humans.Myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals.We conclude that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.
Structural basis of bacteriophage T5 infection trigger and E. coli cell wall perforation
Authors: Linares Romain , Arnaud Charles-Adrien , Effantin Grégory , Darnault Claudine , Epalle Nathan Hugo , Erba Elisabetta Boeri , Schoehn Guy , Breyton Cécile 
Published: September 2022

AbstractThe vast majority of bacteriophages (phages) - bacterial viruses - present a tail that allows host recognition, cell wall perforation and safe channelling of the viral DNA from the capsid to the cytoplasm of the infected bacterium. The majority of tailed phages bears a long flexible tail (Siphoviridae) at the distal end of which a tip complex, often called baseplate, harbours one or more Receptor Binding Protein·s (RBPs). Interaction between the RBPs and the host surface triggers cell wall perforation and DNA ejection, but little is known on these mechanisms for Siphoviridae. Here, we present the structure of siphophage T5 tip at high resolution, determined by electron cryo-microscopy, allowing to trace most of its constituting proteins, including 35 C-terminal residues of the Tape Measure Protein. We also present the structure of T5 tip after interaction with its E. coli receptor FhuA reconstituted into nanodisc. It brings out the dramatic conformational changes underwent by T5 tip upon infection, i.e. bending of the central fibre on the side, opening of the tail tube and its anchoring to the membrane, and formation of a transmembrane channel. These new structures shed light on the mechanisms of host recognition and activation of the viral entry for Siphoviridae.
Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans
Authors: Ridley Amanda JL , Ou Yaqing , Karlsson Richard , Pun Nabina , Birchenough Holly L , Jowitt Thomas A , Lawless Craig , Miller Rebecca L , Dyer Douglas P 
Published: September 2022

AbstractChemokine driven leukocyte recruitment is a key component of the immune response and is central to a wide range of diseases. However, there has yet to be a clinically successful therapeutic approach that targets the chemokine system during inflammatory disease; possibly due to the supposed redundancy of the chemokine system. A range of recent studies have demonstrated that the chemokine system is in fact based on specificity of function. Here we have generated a resource to analyse chemokine gene (ligand and receptor) expression across different species, tissues and diseases; revealing complex expression patterns whereby multiple chemokine ligands that mediate recruitment of the same leukocyte type are expressed in the same context, e.g. the CXCR3 ligands CXCL9, 10 and 11. We use biophysical approaches to show that CXCL9, 10 and 11 have very different interactions with extracellular matrix glycosaminoglycans (GAGs) which is exacerbated by specific GAG sulphation. Finally, in vivo approaches demonstrate that GAG-binding is critical for CXCL9 driven recruitment of specific T cell subsets (e.g. CD4+) but not others (e.g. CD8+), independent of CXCR3 expression. Our data demonstrate that chemokine expression is complex and that multiple ligands are likely needed for robust leukocyte recruitment across tissues and diseases. We also demonstrate that ECM GAGs facilitate decoding of these complex chemokine signals so that they are either primarily presented on GAG-coated cell surfaces or remain more soluble. Our findings represent a new mechanistic understanding of chemokine mediated immune cell recruitment and identify novel avenues to target specific chemokines during inflammatory disease.
Single-cell analysis of megakaryopoiesis in peripheral CD34+ cells: insights into ETV6-related thrombocytopenia
Authors: Bigot Timothée , Gabinaud Elisa , Hannouche Laurent , Sbarra Véronique , Andersen Elisa , Bastelica Delphine , Falaise Céline , Ibrahim-Kosta Manal , Loosveld Marie , Saultier Paul , Payet-Bornet Dominique , Alessi Marie-Christine , Potier Delphine , Poggi Marjorie 
Published: September 2022

AbstractExpansion of human megakaryoblasts from peripheral blood-derived CD34+ cells is commonly used to characterize inherited or acquired thrombocytopenia and evaluate defects in megakaryocyte (MK) differentiation, MK maturation and proplatelet formation. We applied single-cell RNA sequencing to understand local gene expression changes during megakaryopoiesis (days 6 and 11 of differentiation) in peripheral CD34+ cells from healthy controls and patients with ETV6-related thrombocytopenia.Analysis of gene expression and regulon activity revealed distinct clusters partitioned into seven major cell stages: hematopoietic stem/progenitor cells (HSPC), common-myeloid progenitors (CMP), MK-primed CMP, granulocyte-monocyte progenitors, megakaryocyte-erythroid progenitors (MEP), MK progenitor /mature MK (MKP/MK) and platelets. We observed a subpopulation of MEP that arose directly from HSPC, deviating from the canonical MK differentiation pathway.ETV6 deficiency was characterized by an increase in HSPC, a decrease in MKP/MK, and a lack of platelets. ETV6 deficiency also led to the development of aberrant MEP and MKP/MK cell populations. Genes involved in “mitochondrial” and “DNA repair” pathways were downregulated, while genes involved in “translation” pathways were upregulated. Analysis of patient samples and hematopoietic cell lines transduced with an ETV6 variant revealed increased translation in MK. Ribosomal protein small 6 (RPS6) levels in MK, platelets and peripheral blood mononuclear cells was consistent with the translation findings.Our results provide a framework to understand peripheral CD34+ cell-derived megakaryocytic cultures. Our observations also shed light on ETV6-variant pathology and reveal potential targets for diagnostic and therapeutic purposes.Key points-scRNAseq gain insight into in vitro megakaryopoiesis, identify MK-primed CMP, and a differentiation trajectory that bypasses the CMP.-ETV6 variants led to the development of aberrant MEP and MK cell populations.
Staining of human skin with RGB trichrome unveils a proteoglycan-enriched zone in the hair dermal sheath
Authors: Serrano-Garrido Clara , Gaytán Francisco 
Published: September 2022

AbstractThe skin is the largest organ in the body and plays several essential functions acting as a barrier that protects us from physical and chemical insults, prevents the entrance of pathogens and the loss of water, besides playing an esential role in the regulation of body temperature. The skin displays a high regenerative capacity, evidenced by its self-renewing activity and the process of wound healing, driven by the existence of several resident stem cell populations. Due to the high prevalence of skin pathology, and their anatomical accessibility, skin biopsies and their subsequent microscopic observation constitute a powerfull tool for the study of primary skin diseases, as well as cutaneous manifestations of systemic diseases. This gave rise to dermatopathology as a specific discipline that unifies dermatology and pathology. In this setting, staining with hematoxylin and eosin constitutes the gold standard method for microscopic observation and diagnosis. Yet, several additional stains are used for specific purposes, such as trichrome stains for the staining of collagens in the extracellular matrix. We have applied a recently developed stain (RGB trichrome, acronym for picrosirius Red, fast Green and alcian Blue) to human samples to assess the staining outcomes in normal skin tissues. RGB staining provides a high contrasted interface between epidermis and dermis, and a comprehensible staining of the different dermal structures such as blood vessels, nerves, and sweat and sebaceous glands. The specific staining of collagens by picrosirius red can be useful for the objective quantification of these proteins under polarized light microscopy. In hair follicles, RGB staining resulted in specific staining of the epidermal sheaths and the encasing connective tissue (i.e., dermal sheath). Interestingly, the dermal sheath show two domains in which blue predominates over red staining, thus indicating that proteoglycans prevail in these areas. These two zones are the dermal papilla and an uncharacterized zone located at the upper isthmus, that we have denominated as proteoglycan-enriched belt (PEB). While the role of the papilla in the induction and regulation of hair growth is clearly established, the possible role of PEB remains to be determined and merits additional investigation.
Golden Standard: A complete standard, portable, and interoperative MoClo tool for model and non-model bacterial hosts
Authors: Blázquez Blas , Torres-Bacete Jesús , Leon David San , Kniewel Ryan , Martinez Igor , Sordon Sandra , Wilczak Aleksandra , Salgado Sergio , Huszcza Ewa , Popłoński Jarosław , Prieto M. Auxiliadora , Nogales Juan 
Published: September 2022

ABSTRACTModular cloning assembly has become a benchmark technology in synthetic biology. However, there is a mismatch between its impressive development and the standardization required to promote interoperability between the different systems available. The full development of the field is thus hampered by a surge of oftentimes incompatible organism-specific systems. To overcome these issues, we present Golden Standard (GS), a Type IIS assembly method underpinned by the Standard European Vector Architecture (SEVA). GS unlocks modular cloning applications with any type of microorganism and delivers consistent combinatorial multi-part assembly of standardized genetic elements to create genetic circuits of up to twenty transcription units. Reliance on the Golden Gate syntax renders GS fully compatible with many existing tools and it sets the path towards efficient reusability of available part libraries and assembled TUs. GS was fully validated in terms of DNA assembly performance, portability and phenotype engineering in model and non-model bacteria. In order to facilitate the widespread adoption and future community-driven development of GS, we provide a web-portal featuring: i) a repository of parts and vectors, ii) a SBOLHub for exchange and analysis of constructs and iii) Wizard and Setup tools to guide the design of constructs using stored and user-specific parts.