Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single‐cell RNA sequencing

PE is a pregnancy‐specific syndrome that affects 3%–5% of pregnant women. It often presents as new‐onset hypertension and proteinuria during the third trimester. PE progresses rapidly and may lead to serious complications, including the death of both mother and fetus. In low‐income countries, PE is one of the main causes of maternal and child mortality. While the cause of PE is still debated, clinical and pathological studies suggest that the placenta plays an important role in the pathogenesis of PE.
A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu2+-Mediated Aβ Aggregation

Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu2+-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu2+-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu2+-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD.
Socio-Demographic Characteristics, Body Weight Status and Energy Intake among Users and Non-Users of Dietary Supplements among Government Employees in Putrajaya, Malaysia

The use of dietary supplements is prevalent among many groups worldwide. However, few studies have examined their use among government employees. The aim of this cross-sectional study was to determine the association among sociodemographic characteristics, body weight status, and energy intake with dietary supplement use among government employees in Putrajaya, Malaysia. Simple random sampling was used to select a sample of 460 government employees from six ministries in Putrajaya, Malaysia. The data used in this study were collected through anthropometric measurements (height, weight, % body fat, waist and hip circumferences), a self-administered questionnaire (sociodemographic characteristics and dietary supplements use), and an interviewer-administered questionnaire (24-hour dietary recall; fruit and vegetable intake). The results indicated that the prevalence of dietary supplement use was 55.4%, with vitamin C (38.4%) being the most popular type of dietary supplement. Health issues (80.8%) were the most common reason for usage, internet (59.2%) was the main source of information, and pharmacies (71.8%) were the most indicated places to purchase dietary supplements. A multivariate analysis showed that participants who were female, married, had better monthly income, lived within a smaller household size, had a normal body mass index, classified as having unhealthily high body fat percentage, did not skip breakfast, and consumed at least five servings of fruits and vegetables per day were significantly more likely to use dietary supplements. In conclusion, health-conscious groups were more prone to consume dietary supplements, and due to the high prevalence of dietary supplement use, dissemination of accurate scientific information regarding dietary supplements is highly recommended among government employees.
Androgenic-Induced Transposable Elements Dependent Sequence Variation in Barley

A plant genome usually encompasses different families of transposable elements (TEs) that may constitute up to 85% of nuclear DNA. Under stressful conditions, some of them may activate, leading to sequence variation. In vitro plant regeneration may induce either phenotypic or genetic and epigenetic changes. While DNA methylation alternations might be related, i.e., to the Yang cycle problems, DNA pattern changes, especially DNA demethylation, may activate TEs that could result in point mutations in DNA sequence changes. Thus, TEs have the highest input into sequence variation (SV). A set of barley regenerants were derived via in vitro anther culture. High Performance Liquid Chromatography (RP-HPLC), used to study the global DNA methylation of donor plants and their regenerants, showed that the level of DNA methylation increased in regenerants by 1.45% compared to the donors. The Methyl-Sensitive Transposon Display (MSTD) based on methylation-sensitive Amplified Fragment Length Polymorphism (metAFLP) approach demonstrated that, depending on the selected elements belonging to the TEs family analyzed, varying levels of sequence variation were evaluated. DNA sequence contexts may have a different impact on SV generated by distinct mobile elements belonged to various TE families. Based on the presented study, some of the selected mobile elements contribute differently to TE-related SV. The surrounding context of the TEs DNA sequence is possibly important here, and the study explained some part of SV related to those contexts.
The Risk Factors for Radiation Pneumonitis after Single-Fraction Carbon-Ion Radiotherapy for Lung Cancer or Metastasis

Simple Summary There was no reports about the risk factors of high dose single-fraction carbon-ion radiotherapy. Although there were only small number of patients with symptomatic radiation pneumonitis after this treatment, we showed that the risk factors of radiation pneumonitis include the dose–volume parameter. Abstract There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose–volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed. Treatment was planned using Xio-N. The median follow-up duration was 53 months, and the median clinical target volume was 32.3 mL. Three patients developed grade 2 RP, and one patient developed grade 3 interstitial pneumonitis. None of the patients developed grade 4 or 5 RP. The dose-volume parameters of the normal lung irradiated at least with 5–30 Gy (RBE), and the mean lung dose was significantly lower in patients with grade 0–1 RP than in those with grade 2–3 RP. Pretreatment with higher SP-D and interstitial pneumonitis were significant factors for the occurrence of symptomatic RP. The present study showed a certain standard for single-fraction carbon-ion radiotherapy that does not increase the risk of RP; however, further validation studies are needed.
Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.
Exploring Codon Adjustment Strategies towards Escherichia coli-Based Production of Viral Proteins Encoded by HTH1, a Novel Prophage of the Marine Bacterium Hypnocyclicus thermotrophus

Marine viral sequence space is immense and presents a promising resource for the discovery of new enzymes interesting for research and biotechnology. However, bottlenecks in the functional annotation of viral genes and soluble heterologous production of proteins hinder access to downstream characterization, subsequently impeding the discovery process. While commonly utilized for the heterologous expression of prokaryotic genes, codon adjustment approaches have not been fully explored for viral genes. Herein, the sequence-based identification of a putative prophage is reported from within the genome of Hypnocyclicus thermotrophus, a Gram-negative, moderately thermophilic bacterium isolated from the Seven Sisters hydrothermal vent field. A prophage-associated gene cluster, consisting of 46 protein coding genes, was identified and given the proposed name Hypnocyclicus thermotrophus phage H1 (HTH1). HTH1 was taxonomically assigned to the viral family Siphoviridae, by lowest common ancestor analysis of its genome and phylogeny analyses based on proteins predicted as holin and DNA polymerase. The gene neighbourhood around the HTH1 lytic cassette was found most similar to viruses infecting Gram-positive bacteria. In the HTH1 lytic cassette, an N-acetylmuramoyl-L-alanine amidase (Amidase_2) with a peptidoglycan binding motif (LysM) was identified. A total of nine genes coding for enzymes putatively related to lysis, nucleic acid modification and of unknown function were subjected to heterologous expression in Escherichia coli. Codon optimization and codon harmonization approaches were applied in parallel to compare their effects on produced proteins. Comparison of protein yields and thermostability demonstrated that codon optimization yielded higher levels of soluble protein, but codon harmonization led to proteins with higher thermostability, implying a higher folding quality. Altogether, our study suggests that both codon optimization and codon harmonization are valuable approaches for successful heterologous expression of viral genes in E. coli, but codon harmonization may be preferable in obtaining recombinant viral proteins of higher folding quality.
Small-Molecule Inhibition of Viral Fusion Glycoproteins.

Viral fusion glycoproteins catalyze membrane fusion during viral entry. Unlike most enzymes, however, they lack a conventional active site in which formation or scission of a specific covalent bond is catalyzed. Instead, they drive the membrane fusion reaction by cojoining highly regulated changes in conformation to membrane deformation. Despite the challenges in applying inhibitor design approaches to these proteins, recent advances in knowledge of the structures and mechanisms of viral fusogens have enabled the development of small-molecule inhibitors of both class I and class II viral fusion proteins. Here, we review well-validated inhibitors, including their discovery, targets, and mechanism(s) of action, while highlighting mechanistic similarities and differences. Together, these examples make a compelling case for small-molecule inhibitors as tools for probing the mechanisms of viral glycoprotein-mediated fusion and for viral glycoproteins as druggable targets. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer with very limited therapeutic options. Cancer stem cells (CSCs) are essential for propagation of PDAC, but also for its metastatic activity and chemoresistance. To date, it is still unclear how cancer stem cells (CSCs) regulate their ‘stemness’ and self-renewal properties, and to what extent they share common features with normal stem cells. Telomerase regulation is a key factor in stem cell maintenance. Here, we investigate how telomerase regulation affects CSC biology in PDAC, and delineate the mechanisms by which telomerase activity and CSC properties are linked. Abstract To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.
Systematic Review on Healthcare and Societal Costs of Tinnitus

Tinnitus disability is a heterogeneous and complex condition, affecting more than 10% and compromising the quality of life of 2% of the population, with multiple contributors, often unknown, and enigmatic pathophysiology. The available treatment options are unsatisfactory, as they can, at best, reduce tinnitus severity, but not eliminate its perception. Given the spread of tinnitus and the lack of a standardized treatment, it is crucial to understand the economic burden of this condition. We conducted a systematic review of the literature on PubMed/MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR) and Google Scholar, in order to identify all the articles published on the economic burden of tinnitus before 1 April 2021 (PROSPERO—International prospective register of systematic reviews—No: CRD42020180438). Out of 273 articles identified through our search strategy, only five articles from studies conducted in the United States of America (USA), the Netherlands and the United Kingdom (UK) provided data on tinnitus’s economic costs. Three studies provided mean annual estimates per patient ranging between EUR 1544 and EUR 3429 for healthcare costs, between EUR 69 and EUR 115 for patient and family costs and between EUR 2565 and EUR 3702 for indirect costs, including productivity loss. The other two studies reported an annual mean cost of EUR 564 per patient for tinnitus-related clinical visits, and total costs of EUR 1388 and EUR 3725 for patients treated with a sound generator and Neuromonics Tinnitus Treatment, respectively. Our comprehensive review shows a gap in the knowledge about the economic burden of tinnitus on healthcare systems, patients and society. The few available studies show considerable expenses due to healthcare and indirect costs, while out-of-pocket costs appear to be less financially burdensome. Comprehensive health economic evaluations are needed to fill the gaps in current knowledge, using a unified method with reliable and standardized tools.
Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH

In this work, we have investigated the binding conformations of the substrate in the active site of 5-HIU hydrolase kpHIUH and its catalytic hydrolysis mechanism. Docking calculations revealed that the substrate adopts a conformation in the active site with its molecular plane laying parallel to the binding interface of the protein dimer of kpHIUH, in which His7 and His92 are located adjacent to the hydrolysis site C6 and have hydrogen bond interactions with the lytic water. Based on this binding conformation, density functional theory calculations indicated that the optimal catalytic mechanism consists of two stages: (1) the lytic water molecule is deprotonated by His92 and carries out nucleophilic attack on C6=O of 5-HIU, resulting in an oxyanion intermediate; (2) by accepting a proton transferred from His92, C6–N5 bond is cleaved to completes the catalytic cycle. The roles of His7, His92, Ser108 and Arg49 in the catalytic reaction were revealed and discussed in detail.
Successful Smoking Cessation among Women Smokers Based on Utilizing National Smoking Cessation Service Type in Korea

Background: This study aimed to evaluate the successful smoking cessation across different national smoking cessation services. Methods: This study included data that had been previously entered into the integrated information system for smoking cessation services and comprised 144,688 participants after excluding missing data. These clinics provide face-to-face counseling, phone calls, text messages, and e-mail services for six months and nine sessions. Results: The women-only program had the lowest success rate (11.3%). Compared with the women-only program, the six-month success rate of smoking cessation clinic at public health centers (OR = 3.72, CI = [3.52, 3.92]), visiting-type smoking cessation clinics (OR = 2.97, CI = [2.79, 3.16]), the residential 4 -night 5-day program (OR = 7.79, CI = [6.49, 9.35]), and a program for inpatients (OR = 2.36, CI = [1.89, 2.94]) showed a significant increase. Conclusions: Emotional labor workers who participated in the women-only program had low smoking cessation success rates, while those who participated in the residential 4-night 5-day program had high success rates.
Marital Stability Over 10 Years Following Traumatic Brain Injury

Supplemental Digital Content is Available in the Text. Objective: To examine the stability of marriage from the time of traumatic brain injury (TBI) to 10 years postinjury. Design: Retrospective cohort. Setting: TBI Model Systems centers. Participants: In total, 1423 participants in the TBI Model Systems National Database who experienced TBI 10 years prior and were married at the time of injury. Interventions: Not applicable. Main Outcome Measure: Remaining married to the same partner from the time of injury to 10-year follow-up. Results: At 10 years, 66% (938) remained married to the same person. Significant associations were found with age at injury (P < .0001), sex (P = .0028), and preinjury problematic substance use (P = .0092). Marital stability over the 10-year period was higher for those who were older, were female, and had no problematic substance use history. Marital instability was greatest in the first year postinjury. Conclusions: Most married adults who received inpatient rehabilitation for TBI remained married to the same individual 10 years later. Those who were younger, were male, and had a history of problematic substance use were at a highest risk for relationship dissolution. Findings have implications for content, timing, and delivery of marital interventions. Substance use education and prevention appear to be important aspects of marital support.
The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment

Simple Summary Cancer cells are the target of most approved therapies. A growing body of evidence suggests that these agents have important roles in modulating the biology of host cells and their interactions with cancer cells, including blood vessels, fibroblasts, immune and fat cells, among others. This review provides an overview of potential roles of commonly used therapeutics in the tumor microenvironment, with a focus on cancer-associated fibroblasts. This includes an emphasis on therapies commonly used for the treatment of high-grade serous ovarian cancers (e.g., platinum, taxanes, PARP inhibitors, and anti-angiogenic agents). In vitro, in vivo, and clinical studies are included, and perspectives offered on how to best interpret the influence of therapeutics on normal cells. Abstract High-grade serous ovarian cancer (HGSOC) is characterized by a complex and dynamic tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and adipocytes. Although most approved therapies target cancer cells, a growing body of evidence suggests that chemotherapeutic agents have an important role in regulating the biology of the diverse cells that compose the TME. Understanding how non-transformed cells respond and adapt to established therapeutics is necessary to completely comprehend their action and develop novel therapeutics that interrupt undesired tumor–stroma interactions. Here, we review the effects of chemotherapeutic agents on normal cellular components of the host-derived TME focusing on CAFs. We concentrate on therapies used in the treatment of HGSOC and synthesize findings from studies focusing on other cancer types and benign tissues. Agents such as platinum derivatives, taxanes, and PARP inhibitors broadly affect the TME and promote or inhibit the pro-tumorigenic roles of CAFs by modifying the bidirectional cross-talk between tumor and stromal cells in the tumor organ. While most chemotherapy research focuses on cancer cells, these studies emphasize the need to consider all cell types within the tumor organ when evaluating chemotherapeutics.
Perception of risk of exposure in the management of hazardous drugs in home hospitalization and hospital units

Objective To assess the perception of risk of exposure in the management of hazardous drugs (HDs) through home hospitalization and hospital units. Material and methods A questionnaire was released, at the national level, to health professionals with HD management expertise. Questionnaire included 21 questions that were scored using a Likert scale: 0 (null probability) to 4 (very high probability). The internal consistency and reliability of the questionnaire were calculated using Cronbach’s alpha and the intraclass correlation coefficient, respectively. Results 144 questionnaires (response rate 70.2%) were obtained: 65 (45.1%) were nurses, 42 (28.9%) occupational physicians, and 37 (26.1%) were pharmacists. Cronbach’s alpha was 0.93, and intraclass correlation coefficient was 0.94 (95% CI 0.91–0.97; p-value < 0.001). The mean probability was 1.95 ± 1.02 (median 1.9; minimum: 0.05; 1st quartile 1.1; 3rd quartile 2.6; and maximum 4). Differences were observed in scoring among professional groups (occupational physicians versus nurses (1.6/2.1, p = 0.044); pharmacists versus nurses (1.7/2.1, p = 0.05); and occupational physicians versus pharmacists (1.6/1.7, p = 0.785), due mainly to the administration stage (p = 0.015). Conclusions The perception of risk of exposure was moderate, being higher for nurses. It would be advisable to integrate HDs into a standardized management system (risk management model applicable to any healthcare center) to improve the safety of health professionals.