Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-Component Signal Transduction Systems in the Human Pathogen Streptococcus agalactiae

Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. ABSTRACT Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. These signal transducing systems are necessary for metabolic regulation, resistance to antibiotics and antimicrobials, pathogenesis, and adhesion to the mucosal surfaces to colonize the host. This minireview discusses the structures of these TCSs in GBS as well as how selected systems regulate essential cellular processes such as survival and colonization. GBS contains almost double the number of TCSs compared to the closely related Streptococcus pyogenes and Streptococcus pneumoniae, and while research on GBS TCSs has been increasing in recent years, no comprehensive reviews of these TCSs exist, making this review especially relevant.
Intraoperative Primary Tumor Identification and Margin Assessment in Head and Neck Unknown Primary Tumors

Objective Surgical management of the unknown primary head and neck squamous cell carcinoma (UP HNSCC) remains controversial due to challenging clinical diagnosis. This study compares positron emission tomography–computed tomography (PET-CT) findings with intraoperative identification of primary tumors and compares intraoperative frozen-section margins to final histopathology. In addition, adjuvant therapy indications are provided. Study Design Prospective cohort study. Setting Academic university hospital. Subjects and Methods Sixty-one patients with UP HNSCC were included. Patients received PET-CT, followed by oropharyngeal transoral laser microsurgery (TLM). Margins were assessed intraoperatively using frozen sections and afterward by final histopathology. Adjuvant treatment was based on final histopathology. Results The sensitivity of localizing the primary tumor with PET-CT was 50.9% with a specificity of 82.5%. The primary tumor was found intraoperatively on frozen sections in 82% (n = 50) of patients. Five more tumors were identified on final histopathology, leading to a total of 90% (n = 55). Of the 50 intraoperatively found tumors, 98% (n = 49) had negative margins on frozen sections, and 90% (n = 45) were truly negative on final histopathology. Eighteen patients (29.5%) avoided adjuvant treatment. Conclusion PET-CT localized the primary tumor in fewer than half the cases. This protocol identified 90% of primary tumors. Intraoperative frozen-section margin assessment has shown potential with a specificity of 92% compared to final histopathology. As a result, adjuvant therapy was avoided in almost one-third of our patients.
Socioeconomic Status in Relation to Risks of Major Gastrointestinal Cancers in Chinese Adults: A Prospective Study of 0.5 Million People

Background: Low socioeconomic status (SES) is associated with higher risk of certain gastrointestinal (e.g., colorectal, pancreatic, and liver) cancers in Western populations. Evidence is very limited in China, where correlates and determinants of SES differ from those in the West. Methods: The prospective China Kadoorie Biobank recruited 512,715 adults (59% women, mean age 51 years) from 10 (5 urban, 5 rural) regions. During 10 years of follow-up, 27,940 incident cancers (including 3,061 colorectal, 805 pancreatic, and 2,904 liver) were recorded among 510,131 participants without prior cancer at baseline. Cox regression was used to estimate adjusted HRs for specific cancers associated with area-level (e.g., per capita gross domestic product, disposable income) and individual-level (e.g., education, household income) SES. Results: Area-level SES and household income showed positive associations with incident colorectal and pancreatic cancers and inverse associations with liver cancer (Ptrend < 0.05). Education showed no association with colorectal cancer but inverse associations with pancreatic and liver cancers, with adjusted HRs comparing university to no formal schooling being 1.05 [95% confidence interval (CI), 0.85–1.29], 0.49 (95% CI, 0.28–0.85), and 0.61 (95% CI, 0.47–0.81), respectively. Potential risk factors (e.g., smoking, alcohol) partly explained the inverse associations of education with pancreatic and liver cancers (17.6% and 60.4%), respectively. Conclusions: Among Chinese adults, the associations of SES with gastrointestinal cancers differed by cancer type and SES indicator. Potential risk factors partially explained the inverse associations of education with pancreatic and liver cancers. Impact: The different associations between SES with gastrointestinal cancers may inform cancer prevention strategies.
The OPR Protein MTHI1 Controls the Expression of Two Different Subunits of ATP Synthase CFo in Chlamydomonas reinhardtii

The OPR protein MTHI1 is a major actor in the biogenesis of chloroplast ATP synthase in green algae that coregulates the expression of AtpH and AtpI, the two subunits of the proton channel. In the green alga Chlamydomonas (Chlamydomonas reinhardtii), chloroplast gene expression is tightly regulated posttranscriptionally by gene-specific trans-acting protein factors. Here, we report the identification of the octotricopeptide repeat protein MTHI1, which is critical for the biogenesis of chloroplast ATP synthase oligomycin-sensitive chloroplast coupling factor. Unlike most trans-acting factors characterized so far in Chlamydomonas, which control the expression of a single gene, MTHI1 targets two distinct transcripts: it is required for the accumulation and translation of atpH mRNA, encoding a subunit of the selective proton channel, but it also enhances the translation of atpI mRNA, which encodes the other subunit of the channel. MTHI1 targets the 5′ untranslated regions of both the atpH and atpI genes. Coimmunoprecipitation and small RNA sequencing revealed that MTHI1 binds specifically a sequence highly conserved among Chlorophyceae and the Ulvale clade of Ulvophyceae at the 5′ end of triphosphorylated atpH mRNA. A very similar sequence, located ∼60 nucleotides upstream of the atpI initiation codon, was also found in some Chlorophyceae and Ulvale algae species and is essential for atpI mRNA translation in Chlamydomonas. Such a dual-targeted trans-acting factor provides a means to coregulate the expression of the two proton hemi-channels.
Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer: Results from the Phase 2 KEYNOTE-100 Study.

BACKGROUND Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. PATIENTS AND METHODS This phase 2 study of pembrolizumab (NCT02674061) examined 2 patient cohorts with ROC: cohort A received 1-3 prior lines of treatment with a platinum-free (PFI) or treatment-free interval (TFI) between 3-12 months and cohort B received 4-6 prior lines with a PFI/TFI of ≥ 3 months. Pembrolizumab 200 mg was administered intravenously every 3 weeks until cancer progression, toxicity, or completion of 2 years. Primary endpoints were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. RESULTS Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2 months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS<1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1 months for both cohorts. Median OS was not reached for cohort A and was 17.6 months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. CONCLUSIONS Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response. CLINICAL TRIAL NUMBER Clinicaltrials.gov, NCT02674061.
Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus

Key Points CSR and somatic hypermutation are required for the progression of lupus nephritis in BXSB mice. AID deficient BXSB mice have prolonged survival with improved renal function. Almost a decade has passed since the approval of belimumab, an mAb directed against B lymphocyte stimulation and the first targeted therapy approved for systemic lupus erythematous (SLE) in over 50 y. Although well tolerated, the efficacy of belimumab remains limited and is not labeled for patients suffering from nephritis, the leading cause of patient mortality. We sought to explore alternative targets of autoreactive B lymphocytes through manipulation of affinity maturation. The BXSB/MpJ mouse, a well-established model of human SLE, develops elevated antinuclear Abs and immune complex–mediated nephritis along with other manifestations of SLE-like disease. To limit interfering with critical background genetics, we used CRISPR-Cas9 to disrupt activation-induced cytidine deaminase (AID; Aicda) directly in BXSB zygotes. Homozygous null mice demonstrated significantly prolonged survival compared with wild-type. Although mice continued to develop plasma cells, splenic follicular structure was restored, and renal pathology was reduced. Mice developed expanded germinal center B lymphocyte populations as in other models of AID deficiency as well as increased populations of CD73+ B lymphocytes. Treatment with the small molecule inhibitor of RAD51, 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid, resulted in minimal changes in disease markers in BXSB mice. The prolonged survival in AID-deficient BXSB mice appears attributed primarily to the reduced renal pathology, warranting further exploration, as current therapeutics targeting lupus nephritis are limited and, thus, in great demand.
Effects of the mycorrhizal fungus Ceratobasidium sp. AR2 on growth and flavonoid accumulation in Anoectochilus roxburghii

Background Anoectochilus roxburghii is a traditional Chinese medicine with potent medicinal activity owing to the presence of secondary metabolites, particularly flavonoids. A. roxburghii also maintains a symbiotic relationship with mycorrhizal fungi. Moreover, mycorrhizal fungi can induce metabolite synthesis in host plants. However, little is known about the role of mycorrhizal fungi in promoting the accumulation of flavonoid metabolites in A. roxburghii. Methods A. roxburghii and the isolated fungus Ceratobasidium sp. AR2 were cocultured. The portion of A. roxburghii above the medium treated with or without AR2 was studied by transcriptome and target metabolome analyses. Results AR2 promoted the growth and development of A. roxburghii. The contents of total flavonoid, rutin, isorhamnetin, and cyanidin-3-glucoside chloride were increased compared with those in uninoculated cultures. Transcriptome analysis suggested that 109 unigenes encoding key enzymes were potentially associated with changes in flavonoids. Quantitative real-time polymerase chain reaction of fourteen flavonoid-related unigenes showed that most flavonoid biosynthetic genes were significantly differentially expressed between inoculated and uninoculated plantlets. Conclusion The isolate AR2 could significantly promote the growth and development of A. roxburghii and the accumulation of flavonoids. Overall, our findings highlighted the molecular basis of the effects of mycorrhizal fungi on flavonoid biosynthesis in A. roxburghii and provided novel insights into methods to improve the yield and quality of A. roxburghii.
Factors associated with hemolysis during extracorporeal membrane oxygenation (ECMO)—Comparison of VA- versus VV ECMO

Venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO) are effective support modalities to treat critically ill patients. ECMO-associated hemolysis remains a serious complication. The aim was to disclose similarities and differences in VA- and VV ECMO-associated hemolysis. This is a retrospective single-center analysis (January 2012 to September 2018) including 1,063 adult consecutive patients (VA, n = 606; VV, n = 457). Severe hemolysis (free plasma hemoglobin, fHb > 500 mg/l) during therapy occurred in 4% (VA) and 2% (VV) (p≤0.001). VV ECMO showed significantly more hemolysis by pump head thrombosis (PHT) compared to VA ECMO (9% vs. 2%; p≤0.001). Pretreatments (ECPR, cardiac surgery) of patients who required VA ECMO caused high fHb pre levels which aggravates the proof of ECMO-induced hemolysis (median (interquartile range), VA: fHb pre: 225.0 (89.3–458.0); VV: fHb pre: 72.0 (42.0–138.0); p≤0.001). The survival rate to discharge from hospital differed depending on ECMO type (40% (VA) vs. 63% (VV); p≤0.001). Hemolysis was dominant in VA ECMO patients, mainly caused by different indications and not by the ECMO support itself. PHT was the most severe form of ECMO-induced hemolysis that occurs in both therapies with low frequency, but more commonly in VV ECMO due to prolonged support time.
Far-red photons have equivalent efficiency to traditional photosynthetic photons: implications for re-defining photosynthetically active radiation.

Far-red photons (701-750 nm) are abundant in sunlight but are considered inactive for photosynthesis and are thus excluded from the definition of photosynthetically active radiation (PAR; 400 to 700 nm). Several recent studies have shown that far-red photons synergistically interact with shorter wavelength photons to increase leaf photochemical efficiency. The value of far-red photons in canopy photosynthesis has not been studied. Here we report the effects of far-red photons on single leaf and canopy photosynthesis in 14 diverse crop species. Adding far-red photons (up to 40%) to a background of shorter wavelength photons caused an increase in canopy photosynthesis equal to adding 400-700 nm photons. Far-red alone minimally increased photosynthesis. This indicates that far-red photons are equally efficient at driving canopy photosynthesis when acting synergistically with traditionally defined photosynthetic photons. Measurements made using LEDs with peak wavelength of 711, 723, or 746 nm showed that the magnitude of the effect was less at longer wavelengths. The consistent response among diverse species indicates that the mechanism is common in higher plants. These results suggest that far-red photons (701-750 nm) should be included in the definition of photosynthetically active radiation. This article is protected by copyright. All rights reserved.
The Left Atrial Appendage Morphology Improves Prediction of Stagnant Flow and Stroke Risk in Atrial Fibrillation.

The left atrial appendage (LAA) is the most common site of thrombus formation in patients with atrial fibrillation. Therefore, better knowledge of the morphology, physiology, and function of the LAA may provide a better estimate of stroke risk. The LAA morphology is currently classified into 4 categories: chicken-wing (CW), windsock, cauliflower, and cactus. Chicken-wing is the most common and carries lower risk. This classification system, however, lacks consistent inter-rater reliability and correlation with stroke risk.
Why Are Women with Fibromyalgia so Stigmatized?

INTRODUCTION Many female pain sufferers with medically unexplained pain are at risk of being stigmatized in our Western society. Fibromyalgia is offered as the exemplar condition. AIM To understand why these women are being stigmatized. METHODS A review of the recent literature was conducted with a focus on the perceptions of women with a diagnosis of fibromyalgia who have been stigmatized. RESULTS Three intertwined themes emerged as contributing to their stigmatization: moralizing attitudes, disbelief as to the reality of pain, and pain's invisibility. CONCLUSION Given how embedded the factors responsible for the stigmatization of women with fibromyalgia in Western society are, the realistic prospects for addressing this issue are poor.
DSC perfusion-based collateral imaging and quantitative T2 mapping to assess regional recruitment of leptomeningeal collaterals and microstructural cortical tissue damage in unilateral steno-occlusive vasculopathy

Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values (P = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased (P = 0.0001) and correlated negatively with increase of qT2 (P < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased (P < 0.01) and negatively correlated with changes of parenchymal rCPP (P = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy.
Anorectal manometry in children with defecation disorders BSPGHAN Motility Working Group consensus statement

Defecatory disorders in children, including chronic constipation (CC) and fecal incontinence (FI), are common conditions worldwide and have a significant impact on children, their families, and the healthcare system. Anorectal manometry (ARM) and high‐resolution anorectal manometry (HRAM) are relatively novel tools for the assessment of anal sphincter function and rectal sensation and have contributed significantly to improving the understanding of the anorectum as a functional unit. ARM has been recognized as the investigation of choice for adults with symptoms of defecation disorders, including fecal incontinence (FI), evacuation difficulties, and constipation. Although it is the gold standard tool in adults, it has yet to be formally accepted as a standardized diagnostic tool in the pediatric age, with limited knowledge regarding indications, protocol, and normal values. ARM/HRAM is slowly becoming recognized among pediatricians, but given that there are currently no agreed guidelines there is a risk that will lead to diversity in practice. The British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN)—Motility Working Group (MWG) therefore has taken the opportunity to provide guidance on the use of ARM/HRAM in children with CC and/or FI.
In Situ Construction of Hierarchical Diamond Supported on Carbon Nanowalls/Diamond for Enhanced Electron Field Emission.

The integration of sp2/sp3-bonded carbon has aroused increasing attentions on attaining a great electron field emission (EFE) performance. Herein, a novel hierarchical diamond@carbon nanowalls/diamond (D@C/D) architecture is facilely prepared through the growth of hybrid carbon nanowalls/diamond (C/D) film followed by the in situ hydrogen plasma treatment using microwave plasma chemical vapor deposition. The hierarchical D@C/D architecture is composed of thin diamond nanoplatelets sandwiched into carbon nanowalls (CNWs) as the bottom layer and the thickened nanoplatelets constituted by diamond nanograins as the upper layer. The hydrogen plasma plays an effective role in the transformation of sacrificial sp2-bonded CNWs to sp3-bonded diamond, eventually leading to the template thickening of diamond nanoplatelets in the upper layer. Impressively, the D@C/D-90 film demonstrates much better EFE behaviors of low turn-on potential (Eo = 4.3 V μm-1), high current density (Je@8 V μm-1 = 20.81 mA cm-1), and superior long-term stability, in comparison with pristine C/D film (Eo = 6 V μm-1, Je@8 V μm-1 = 0.33 mA cm-1). The enhanced EFE performance of hierarchical D@C/D film is ascribed to the well-established graphite pathway for electron transporting from the bottom to the up and the increased diamond emitting sites with negative-electron-affinity and robust nature at the top. This work will promote the development of high-performance cathode EFE material based on hybrid sp2/sp3-bonded carbon, and the method proposed here also provides an effective strategy to construct diamond nanostructure for various applications.
Recent Advances in Chain Conformation and Bioactivities of Triple-helix Polysaccharides.

Natural polysaccharides derive from renewable biomass sources, and are regarded as environmentally friendly and sustainable polymers. As the third abundant biomacromolecule after protein and nucleic acid in nature, polysaccharides are also closely related to many different life activities. It is worth noting that β-glucans are one of the most widely reported active polysaccharides, and usually are considered as biological response modifiers (BRMs). Among them, β-glucans with triple-helix conformation have been the hottest and most well-researched polysaccharides at present, especially lentinan (LNT) and schizophyllan (SPG), which have already been used as commercial clinic antitumor drugs in some Asian countries. Thus, creation of these active triple-helix polysaccharides will be beneficial to the research and development of sustainable "green" biopolymers in the fields of the food and life sciences. Therefore, full fundamental research of triple-helix polysaccharides is essential to discovery more polysaccharide-applications. In this review, the recent research progress of chain conformation, bioactivities and structure-function relationship of β-glucans with triple-helix conformation are summarized, with 247 references from 1949 to 2019. The main contents can be divided as follows: the characterization methods of the macromolecular conformation, proof of triple helices, bioactivities and structure-function relationship. We believe that the governments, enterprises, universities and institutes, which are dealing with the survival and health of human beings, will expect the development of the natural bioproducts in the future. Hence, a deep understanding of β-glucans with triple-helix chain conformation is essential for the successful applications of the natural medicines and biologics for a sustainable world.