bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastid phylogenomic insights into relationships of all flowering plant families
Authors: Li Hong-Tao , Luo Yang , Gan Lu , Ma Peng-Fei , Gao Lian-Ming , Yang Jun-Bo , Cai Jie , Gitzendanner Matthew A. , Fritsch Peter W. , Zhang Ting , Jin Jian-Jun , Zeng Chun-Xia , Wang Hong , Yu Wen-Bin , Zhang Rong , van der Bank Michelle , Olmstead Richard G. , Hollingsworth Peter M. , Chase Mark W. , Soltis Douglas E. , Soltis Pamela S. , Yi Ting-Shuang , Li De-Zhu 
Published: October 2021

AbstractBackgroundFlowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades.ResultsHere, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all otherMesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades ofMesangiospermaeremain intractable despite increased sampling, probably due to an ancient rapid radiation.ConclusionsWe provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants.
Mechanical behaviour of healthy versus alkali-lesioned corneas by a porcine organ culture model
Authors: Fontanella Chiara Giulia , Carniel Emanuele Luigi , Corain Livio , Peruffo Antonella , Iacopetti Ilaria , Pavan Piero G. , Todros Silvia , Perazzi Anna 
Published: October 2021

Abstract
Background
Cornea is a composite tissue exhibiting nonlinear and time-dependent mechanical properties. Corneal ulcers are one of the main pathologies that affect this tissue, disrupting its structural integrity and leading to impaired functions. In this study, uniaxial tensile and stress-relaxation tests are developed to evaluate stress-strain and time-dependent mechanical behaviour of porcine corneas.

Results
The samples are split in two groups: some corneas are analysed in an unaltered state (healthy samples), while others are injured with alkaline solution to create an experimental ulcer (lesioned samples). Furthermore, within each group, corneas are examined in two conditions: few hours after the enucleation (fresh samples) or after 7 days in a specific culture medium for the tissue (cultured samples). Finally, another condition is added: corneas from all the groups undergo or not a cross-linking treatment. In both stress-strain and stress-relaxation tests, a weakening of the tissue is observed due to the imposed conditions (lesion, culture and treatment), represented by a lower stiffness and increased stress-relaxation.

Conclusions
Alkali-induced corneal stromal melting determines changes in the mechanical response that can be related to a damage at microstructural level. The results of the present study represent the basis for the investigation of traditional and innovative corneal therapies.
Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial
Authors: Vogelmeier Claus F. , Jones Paul W. , Kerwin Edward M. , Boucot Isabelle H. , Maltais François , Tombs Lee , Compton Chris , Lipson David A. , Bjermer Leif H. 
Published: October 2021

Abstract
Background
In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids.

Methods
The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10−30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21–24, and rescue medication use (puffs/day) over Weeks 1–24. Analyses were conducted across the full range of reversibility (−850–896 mL); however, results are presented for the range −100–400 mL because there were few participants with values outside this range.

Results
The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range.

Conclusions
FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.
Dysfunctional lactate metabolism in human alveolar type II cells from idiopathic pulmonary fibrosis lung explant tissue
Authors: Newton Danforth A. , Lottes Robyn G. , Ryan Rita M. , Spyropoulos Demetri D. , Baatz John E. 
Published: October 2021

Abstract
Background
Idiopathic Pulmonary Fibrosis (IPF) is the most common and progressive form of the interstitial lung diseases, leading most patients to require lung transplants to survive. Despite the relatively well-defined role of the fibroblast in the progression of IPF, it is the alveolar type II epithelial cell (AEC2) that is now considered the initiation site of damage, driver of disease, and the most efficacious therapeutic target for long-term resolution. Based on our previous studies, we hypothesize that altered lactate metabolism in AEC2 plays a pivotal role in IPF development and progression, affecting key cellular and molecular interactions within the pulmonary microenvironment.

Methods
AEC2s isolated from human patient specimens of non-fibrotic and IPF lungs were used for metabolic measurements, lactate dehydrogenase (LDH) analyses and siRNA-mediated knockdown experiments.

Results
AEC2s isolated from human IPF lung explant tissues had lower rates of oxidative metabolism and were more glycolytic lactate-producing cells than were AEC2 from control, non-fibrotic lung explant tissues. Consistent with this shift in metabolism, patient-derived IPF AEC2s exhibited LDH tetramers that have higher ratios of LDHA:LDHB (i.e., favoring pyruvate to lactate conversion) than control AEC2s. Experimental manipulation of LDHA subunit expression in IPF AEC2s restored the bioenergetic profile characteristic of AEC2 from non-fibrotic lungs.

Conclusions
These results are consistent with the concept that altered lactate metabolism may be an underlying feature of AEC2 dysfunction in IPF and may be a novel and important target for therapeutic treatment.
A systematic review of proteomic biomarkers in oral squamous cell cancer
Authors: Pillai Jyotsnaa , Chincholkar Tanvi , Dixit Ruhi , Pandey Manoj 
Published: October 2021

Abstract
Background
Head and neck squamous cell cancer (HNSCC) is the most common cancer associated with chewing tobacco, in the world. As this is divided in to sites and subsites, it does not make it to top 10 cancers. The most common subsite is the oral cancer. At the time of diagnosis, more than 50% of patients with oral squamous cell cancers (OSCC) had advanced disease, indicating the lack of availability of early detection and risk assessment biomarkers. The new protein biomarker development and discovery will aid in early diagnosis and treatment which lead to targeted treatment and ultimately a good prognosis.

Methods
This systematic review was performed as per PRISMA guidelines. All relevant studies assessing characteristics of oral cancer and proteomics were considered for analysis. Only human studies published in English were included, and abstracts, incomplete articles, and cell line or animal studies were excluded.

Results
A total of 308 articles were found, of which 112 were found to be relevant after exclusion. The present review focuses on techniques of cancer proteomics and discovery of biomarkers using these techniques. The signature of protein expression may be used to predict drug response and clinical course of disease and could be used to individualize therapy with such knowledge.

Conclusions
Prospective use of these markers in the clinical setting will enable early detection, prediction of response to treatment, improvement in treatment selection, and early detection of tumor recurrence for disease monitoring. However, most of these markers for OSCC are yet to be validated.
Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China
Authors: Chen Hongbin , Yin Yuyao , van Dorp Lucy , Shaw Liam P. , Gao Hua , Acman Mislav , Yuan Jizhen , Chen Fengning , Sun Shijun , Wang Xiaojuan , Li Shuguang , Zhang Yawei , Farrer Rhys A. , Wang Hui , Balloux Francois 
Published: October 2021

AbstractBackgroundMethicillin-resistantStaphylococcus aureus(MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear.MethodsHere, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes.ResultsST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role ofchpin increasing the virulence potential of ST59 by creating Δchpknockout mutants, confirming that ST59 can carrychpwithout a measurable impact on fitness.ConclusionsOur results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of thechpgene.
Atypical involvement of central nervous system in classic Hodgkin lymphoma: a case report
Authors: Ahmed Shanila , Irfan Babar , Raza Muhammad , Haider Ghulam 
Published: October 2021

Abstract
Background
Hodgkin lymphoma is a systemic disease that commonly involves the cervical, supraclavicular, and mediastinal lymph nodes. The involvement of central nervous system in Hodgkin lymphoma is extremely rare, and diagnosis is usually established using distinct morphological and immunohistochemical staining on the tissue biopsied. Extranodal presentation of HL is a rare occurrence. It has been evident that prognosis is encouraging in patients with disease that is limited to just central nervous system initially or as relapse, compared with involvement of multiple sites of relapse.

Case presentation
We herein report a case of a 35-year-old South-East Asian male with relapsed Hodgkin lymphoma. The patient developed a parotid gland lesion, cervical lymphadenopathy with significant weight loss, and intermittent night sweats. Along with spread to the central nervous system, there was a high suspicion of tuberculosis. Upon biopsy of his cervical lymph node, the patient was confirmed to have Hodgkin lymphoma. Immediate treatment began with six cycles of chemotherapy consisting of adriamycin, bleomycin, vinblastine, and dacarbazine. The patient received three cycles of chemotherapy consisting of ifosfamide, carboplatin, and etoposide but then was lost to follow-up. Five years later, the patient suffered a road traffic accident. Upon work-up, a right parietal space-occupying lesion with moderate cerebral edema and midline shift was found on computed tomography of the brain. The patient underwent resection of the space-occupying lesion of brain, with features consistent with classical Hodgkin lymphoma on histopathology examination. It is crucial for such lesions to be investigated meticulously to rule out any secondary disease process.

Conclusion
Relapsed Hodgkin lymphoma with central nervous system involvement is relatively rare with just over two dozen cases reported to date and is observed infrequently in developing nations. Therefore, space-occupying lesion should always be investigated, and biopsy of such lesions is gold standard to establish diagnosis. With timely appropriate therapy, complete remission can be achieved. However, large-scale studies would be prudent to explore the presentation, survival, and treatment options for patients with Hodgkin lymphoma involving the central nervous system.
Ocular adverse events from pharmacological treatment in patients with multiple sclerosis—A systematic review of the literature
Authors: Muñoz-Ortiz Juliana , Reyes-Guanes Juliana , Zapata-Bravo Estefanía , Mora-Muñoz Laura , Reyes-Hurtado Juan Antonio , Tierradentro-García Luis Octavio , Rojas-Carabali William , Gómez-Suarez Marcela , de-la-Torre Alejandra 
Published: October 2021

Abstract
Purpose
The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.

Methods
A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.

Results
A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.

Conclusions
Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.

Systematic review registration
PROSPERO ID CRD42020106886
Alteration of the gut microbiome in mycophenolate-induced enteropathy: impacts on the profile of short-chain fatty acids in a mouse model
Authors: Jardou Manon , Provost Quentin , Brossier Clarisse , Pinault Émilie , Sauvage François-Ludovic , Lawson Roland 
Published: October 2021

AbstractBackgroundMycophenolic acid (MPA) is the most widely used immunosuppressive drug in transplantation and for autoimmune diseases. Unfortunately, more than 30% of patients experience a typical gastrointestinal adverse effect also referred to as mycophenolate-induced enteropathy. Due to its antibacterial, antifungal, and antiviral properties, MPA exposure is associated with intestinal dysbiosis characterized by a decrease in density and diversity of the microbiome regarding the main bacterial phyla (Firmicutes and Bacteroidetes). These bacterial phyla are known for their metabolic role in maintaining the homeostasis of the digestive tract, particularly through the production of short-chain fatty acids (SCFA) that could contribute to the pathophysiology of mycophenolate-induced enteropathy. Our study aimed at deciphering short-chain fatty acids (SCFA) profile alterations associated with gastrointestinal toxicity of MPA at the digestive and systemic levels in a mouse model.MethodsTen-week old C57BL/6 (SOPF) mice were randomly assigned in 2 groups of 9 subjects: control, and mycophenolate mofetil (MMF, 900 mg/kg/day). All mice were daily treated by oral gavage for 7 days. Individual faecal pellets were collected at days 0, 4 and 8 as well as plasma at day 8 for SCFA profiling. Additionally, after the sacrifice on day 8, the caecum was weighted, and colon length was measured. The proximal colon was cut for histological analysis.ResultsMMF treatment induced around 10% weight loss at the end of the protocol associated with a significant decrease in caecum weight and a slight reduction in colon length. Histological analysis showed significant architectural changes in colon epithelium. Moreover, we observed an overall decrease in SCFA concentrations in faecal samples, especially regarding acetate (at day 8, control 1040.6 ± 278.161 μM versus MMF 384.7 ± 80.5 μM,p< 0.01) and propionate (at day 8, control 185.94 ± 51.96 μM versus MMF 44.07 ± 14.66 μM,p< 0.001), and in plasma samples for butyrate (at day 8, control 0.91 ± 0.1 μM versus MMF 0.46 ± 0.1 μM,p <0.01).ConclusionsThese results are consistent with functional impairment of the gut microbiome linked with digestive or systemic defects during MMF treatment.
Effects of low temperature on electrophysiology and mechanophysiology of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)
Authors: Kanade Pooja P. , Oyunbaatar Nomin-Erdene , Lee Dong-Weon 
Published: October 2021

AbstractStudies related to low temperature and their effect on cardiomyocytes are essential as hypothermia—like situations have been known to induce arrhythmia or ventricular fibrillation. Till date, several studies have been carried out on animals and their electrophysiological responses have been studied in the form of action potential. However, for a complete assessment of the effect of low temperature, mechanophysiological changes along with electrophysiological changes need to be investigated, at the tissue level. In this study, the effect of culture temperature on cell growth has been studied by measuring the field potential and contractility of human induced pluripotent stem cell-derived cardiomyocytes. This study has the potential to further improve the understanding of low temperature on human cells.