bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Shumian capsules in treating insomnia
Authors: Wang Cuiying , Yang Yuying , Ding Xiao , Li Jiamin , Zhou Xue , Teng Jing , Qi Xianghua 
Published: December 2021

Abstract

Background:
It is known to all that the incidence of insomnia is becoming higher and higher with the increase of people's life stress. To some extent, it has brought about bad effects on people's life, work, study, and health, such as mental exhaustion, low work efficiency, and mood irritability. Now there are medications and non-medications methods for insomnia. As one of the treatments for insomnia, western medicine is to prolong the sleeping time and improve the anxious mood. However, taking western medicine to treat insomnia can also be accompanied by some adverse reactions at the same time, such as drug dependence, an allergic reaction, and so on. Traditional Chinese medicine therapy is based on syndrome differentiation and holistic concept. Shumian capsules (SM) are a kind of proprietary Chinese medicine for insomnia, which have the effect of relieving depression and calming the mind. But there are no studies on the efficacy and safety of SM in the treatment of insomnia. Therefore, I will provide a systematic review and meta-analysis to evaluate the efficacy and safety of SM for insomnia.

Methods:
All the studies searched were from PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang databases, and the studies types included in the analysis were all randomized controlled trials. All the retrieval contents were completed independently by 2 researchers, and a third reviewer would be involved when there existed any disagreement. The eligible studies were screened out according to the inclusion criteria and exclusion criteria, and some useful information was extracted and made into a feature table, including the year of the included studies, the age, and disease course of the participants in the studies and intervention methods, etc. Cochrane risk-of-bias tool was used to evaluate the quality of literature and meta-analysis was conducted by RevMan 5.4 software.

Results:
A total of 9 articles including 709 participants were included in the study after screening out. The primary outcomes of statistical analysis were cure rate and total effective rate, while the secondary outcomes included Pittsburgh sleep quality index score and incidence of adverse reactions. The results showed that Pittsburgh sleep quality index score of the SM group and Western medicine group were statistically significant (MD = –0.50, 95% confidence interval [CI] = [–0.78, –0.22], P = .0005). The total effective rate of the SM group was slightly higher than that of the Western medicine group, but there was no statistical significance (relative risk [RR] = 1.03, 95% CI = [0.95,1.13], P = .43).

Conclusion:
This meta-analysis provides evidence for the efficacy and safety of SM in the treatment of insomnia, and provides a new idea for the clinical treatment of insomnia. But more research is needed to support further evidence.
The blood-brain barrier disruption after syncope: a dynamic contrast-enhanced magnetic resonance imaging study
Authors: Huh Hyungkyu , Lee Eun-Hee , Oh Sung Suk , Kim Jong-Hoon , Seo Young Beom , Choo Yoo Jin , Park Juyoung , Chang Min Cheol 
Published: December 2021

Abstract

Rationale:
Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we demonstrated blood-brain barrier (BBB) disruption following syncope.

Patient concerns:
A 45-year-old man experienced syncope with a chief complaint of syncope (duration: 1 minutes), 1 day before visiting a university hospital for examination. He had no history of medical problems and was not taking any medications. This episode was the first in his lifetime.

Diagnoses:
After syncope, the patient did not have any illnesses or symptoms, such as headache, cognitive deficits, or somnolence.

Interventions:
Cardiac evaluation did not reveal any abnormal findings. In addition, in conventional brain and chest computed tomography and brain MRI, no abnormal lesions were observed.

Outcomes:
DCE-MRI of the patient showed bright blue colored lines within the sulci throughout the cerebral cortex. The regions of interest, including bright blue colored lines, had significantly higher Ktrans values (6.86 times higher) than those in healthy control participants. These findings are indicative of BBB disruption of the vessels in the sulci.

Lessons:
Using DCE-MRI, we demonstrated BBB disruption following syncope. DCE-MRI is a useful tool for the detection of BBB disruption following syncope.
Efficacy, safety, and retention rate of extended-release divalproex versus conventional delayed-release divalproex
Authors: Zhang Chen Qi , Bai Xue Yang , Wan Yong , Li Hong Yan , Sun Hongbin 
Published: December 2021

Abstract

Background:
A novel once-daily divalproex-extended release (VPA-ER) dose formulation has been developed, which prolongs therapeutic serum levels compared with that of twice-daily conventional divalproex-delayed release (VPA-DR). Currently, there is lack of meta-analysis focusing on drug retention rate between VPA-ER and VPA-DR. Thus, our study is the first one that aims to systematically examine and compare the efficacy, safety, and retention rate of VPA-ER and VPA-DR.

Methods:
Online databases including MEDLINE via PubMed, Cochrane Library, Embase (up to October 30, 2021) will be applied for literature screen. We will conduct meta-analysis by using Stata16.0 software.

Results:
This study aims to evaluate the efficacy, safety, and drug retention rate of VPA-ER versus conventional VPA-DR

Conclusion:
Once-daily VPA-ER may present a positive efficacy and not increase the incidence of AEs and has a higher retention rate for patients, which can be used as a substitute for conventional VPA-DR.
INPLASY registration number: INPLASY2021110090
(DOI: 10.37766/inplasy2021.11.0090).
Outcomes of 2-octyl cyanoacrylate skin adhesives following musculoskeletal oncology surgery
Authors: Chobpenthai Thanapon , Poosiripinyo Thanate , Tuntarattanapong Pakjai , Thanindratarn Pichaya , Trathitephun Warayos 
Published: December 2021

Abstract
2-octyl cyanoacrylate (2OCA) is a high-viscosity medical-grade tissue adhesive that is routinely used. However, no studies have evaluated its use in musculoskeletal surgery.
We enrolled 99 patients who underwent musculoskeletal surgery. 2OCA was chosen for wound closure and was performed by a specific surgeon for all patients. The drying times for the adhesive were recorded, and photographs were obtained intra-operatively. Posttreatment follow-up consisted of queries regarding pain level and recording incisional dehiscence, wound infection, hematoma, and incisional bleeding. Data collection was performed postoperatively at 48 hours, 5 to 10 days, 14 days, and 30 days. Other adverse events were documented.
2OCA was applied to 110 incisions in 99 patients, comprising 62 female and 37 male patients. The mean age of patients was 50.41 (±16.83) years; mean incision length was 10.24 (±5.7) cm, and the mean pain score using a visual analogue scale was 2.37 on a postoperative day 7. The mean drying time was 1.81 (±0.59) minutes; 91 (91%) patients reported excellent and superior satisfaction, and the remaining patients reported “good” (6%) and “fair” (2%) satisfaction. The percentages of dehiscence, hematoma and keloid formation were considerably low.
In this study, 2OCA was safe for musculoskeletal oncology surgical incisions. The incidence of postoperative adverse events was low. However, some patients develop hematomas. Postoperative pain was low, and patient satisfaction was high. 2OCA can be a practical alternative to traditional suture closure for skin incisions after musculoskeletal surgery.
Analysis of the 2012 Canadian Community Health Survey-Mental Health demonstrates employment insecurity to be associated with mental illness
Authors: Kim Il-Ho , Choi Cyu-Chul , Urbanoski Karen , Park Jungwee , Kim Ji Man 
Published: December 2021

Abstract
A growing number of people depend on flexible employment, characterized by outsider employment and lower levels of job security. This study investigated whether there was a synergistic effect of employment status and job insecurity on mental disorders.
This study used data from the 2012 Canadian Community Health Survey-Mental Health (CCHS) of 13,722 Canada's labor force population aged 20 to 70. Data were collected from January to December, 2012, using computer-assisted personal interviewing. As combining employment status with perceived job insecurity, we formed five job categories: secure full-time, full-time insecure, part-time secure, part-time insecure employment, and unemployment.
Results showed that, regardless of employment status (full-time vs part-time), insecure employment was significantly associated with high risk of mental disorders. Furthermore, the odds ratios for insecure employment were similar to those for unemployment. Male workers who are full-time, but with insecure jobs, were more likely to experience mental disorders than female workers.
This study's findings imply that while perceived job insecurity may be a critical factor for developing mental health problems among workers, providing effective health care services can mitigate an excessive health risk for the most vulnerable employment, especially for insecure part-time employment and unemployment.
Drug tolerance facilitates the evolution of drug resistance in Candida albicans
Authors: Massahi Samira , Bettauer Van , Khurdia Sanny , Khosravi Nasim , Simpson Shawn , Harb Mathieu , Dumeaux Vanessa , Whiteway Malcolm , Hallett Michael 
Published: December 2021

Background
For Candida albicans and Candidiasis, drug resistance is sometimes due to the pre-existence of genetic polymorphisms that bypass the mode of action of the drug, thus conferring a long-term survival benefit. In other cases, resistance is acquired via the evolution of de novo genetic polymorphisms. There is evidence that C. albicans possess a drug tolerance response which “buys time” for individuals to evolve beneficial mutations. Our goal here is to characterize this poorly understood epigenetic cytoprotective program at the single cell molecular level.

Methods
We developed a nano-litre droplet based Candida single cell sequencing platform capable of transcriptionally profiling several thousand individual cells in an efficient manner. We exploit this platform to profile both untreated and drug exposed (incl. fluconazole, caspofungin and nystatin) populations at early time points post-treatment (tolerance) and late time points (resistance) in order to understand survival trajectories. The profile are compared with the matched sequenced genomes.

Results
We show that untreated Candida populations exhibit “bet hedging”, stochastically expressing cytoprotective transcriptional programs, and drug tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different transcriptional programs. We observe a burst of chromosomal aberrations at two days post-treatment that differ between survivor subpopulation.

Discussion
Our single cell approach highlights that survivor subpopulations pass through a tolerance phase that involves a multivariate transcriptional response including upregulation of efflux pumps, chaperones and transport mechanisms, and cell wall maintenance. Together this suggests that targeting the tolerance response concomitantly with standard therapies could represent an efficient approach to ablating clinical persistence.
Tell me what type of extracellular vesicles you secrete, and I will tell you who you are: yeast or hypha
Authors: Martínez-López Raquel , Vaz Catarina , Redondo Esther , Calvo Guillermo , Hernáez María Luisa , Gil Concha , Monteoliva Lucía 
Published: December 2021

The transition between yeast and hyphal morphologies plays a crucial role in the pathogenicity of Candida albicans. Recent studies have pointed out the great relevance of extracellular vesicles (EVs) secreted by microorganisms in a wide variety of biological processes including interaction with the host. Therefore, the main objective of this work was to compare the EVs secreted by yeast and hyphal forms to shed light on C. albicans-host interaction.
EVs were obtained by ultracentrifugation of the culture medium supernatant and analysed by mass spectrometry. They were characterized by transmission electronic microscopy (TEM) and dynamic light scattering (DLS).
DLS and TEM analysis showed that yeast EVs were significantly bigger than hyphal EVs, being most of them in the range between 400 to 500nm while hyphal EVs were ranged mostly around 100-200nm.
Proteomic analysis showed greater protein diversity in hyphal EVs when compared to yeast EVs (up to 1700 different proteins identified versus 300), although less amount of total protein was obtained. Gene Ontology (GO) analysis showed that yeast EVs were enriched in surface proteins while hyphal EVs, although containing also most of these surface proteins, were also significantly and exclusively enriched in proteins involved in protein metabolism (ribosomal proteins, many aminoacid-pathway enzymes and proteasome) and cellular transport. The differences between YEVs and HEVs also prompted a different immune host response, as tested with macrophage cell cultures and human sera from patients with invasive candidiasis.
All these differences point out a possible different biogenesis and roles of EVs secreted by both morphologies.
Candida glabrata MSH2 deletion increases antifungal tolerance in vitro and during intra-abdominal candidiasis (IAC), it does not impact pathogenesis of peritonitis or intra-abdominal abscesses
Authors: Cheng Shaoji , Liu Guojun , Clancy Cornelius Joseph , Thi Nguyen Minh Hong 
Published: December 2021

Background:
IAC is the second most common type of invasive Candidiasis, but its pathogenesis is poorly understood. We have shown that Candida albicans DNA damage response genes are strongly induced within intra-abdominal abscesses. Deletion of C. glabrata MSH2, A DNA mismatch repair (MMR) gene, results in a mutator phenotype that facilitates multidrug resistance in vitro and in mouse gastrointestinal tracts. Our goal was to determine if CGMSH2 Contributed to pathogenesis or resistance to the new antifungal rezafungin during IAC.

Methods:
We createdΔMSH2 in BG2 using SAT-Flipper, and tested virulence and rezafungin responses in a mouse model of IAC.

Results:
ΔMSH2 displayed no growth defects at 30°C in liquid (YPD, Ypglycerol) or solid media (YPD+0.02% MMS, 1MM H2O2, 1M NACL, 20 UG/ML CW, 250 UG/ML OR 0.02% SDS). ΔMSH2 longevity in YPD was comparable to BG2. Caspofungin-, Rezafungin- and Fluconazole-resistant mutants arose 24-, 16- and 3-fold more often, respectively, for ΔMSH2 than BG2 (108-106 CFU overnight in YPD, selected on 8XMIC-Containing plates). However, respective minimum inhibitory concentrations (MICS) were not different, nor were rezafungin time-kills.ΔMSH2 was comparable to BG2 in peritonitis and abscess burdens in mouse IAC.ΔMSH2 demonstrated significantly greater caspofungin- and fluconazole-tolerance than BG2 in abscesses. Rezafungin reduced peritonitis and abscess burdens ofΔMSH2,BG2 ANDFKS mutant strains to similar extents.

Conclusions:
CgMSH2 deletionincreased the frequency of spontaneously-arising echinocandin- and fluconazole-resistant colonies in vitro and tolerance in intra-abdominal abscesses, but it did not attenuate virulence or rezafungin responses during IAC.
A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis via altered secretion of candidalysin
Authors: Liu Junyan , Sansevere Emily , Barker Katherine , Willems Hubertine , Lowes David , Peters Brian 
Published: December 2021

Background:

Candida albicans is the primary etiological agent of vulvovaginal candidiasis (VVC) and exerts its pathogenicity through secretion of the peptide toxin candidalysin encoded by the ECE1 gene. A highly conserved variant ECE1 sequence exists across a diverse set of clinical isolates. Thus, we sought to determine the relative pathogenicity and mechanism(s) associated with this alternative ECE1 allele.

Methods:
Isogenic strains harboring WT or variant ECE1 sequences were engineered in an Δ/Δece1 background. After confirmation of equivalent expression by qPCR, pathogenicity of strains were tested using in vitro epithelial cell and in vivo VVC models of infection and LDH, IL-1β, neutrophil levels monitored. Follow up studies using synthetic candidalysin peptide were also performed. Lastly, a panel of ECE1 chimeras were constructed to assess potential processing defects and detected by a novel HiBiT-tagging approach.

Results:
Strains transformed with either the variant full length ECE1 or candidalysin allele, as compared to the WT sequence, demonstrated significantly reduced immunopathogenicity during in vitro or in vivo infection despite equivalent fungal burden. Interestingly, epithelial challenge with WT or variant synthetic peptide revealed similar capacity to elicit damage and IL-1β. Allele profiling and ECE1 chimera experiments demonstrated that defects in pathogenicity are at least partly due to inefficient ECE1 processing at the peptide 2-peptide 3 junction.

Discussion:
The ECE1 gene displays conserved polymorphisms that alter candidalysin secretion and strain pathogenicity. Future work is focused on determining specific amino acid sequences that contribute to these affects across clinical isolates and disease states.
Preliminary study into the effects of tobacco smoke on Candida albicans
Authors: Williams Megan , Edwards Siôn , Fallis Ian , Wilson Melanie , Bradshaw David , Williams David W 
Published: December 2021

Background:
Denture-stomatitis (DS) is the most common form of oral candidosis with increased prevalence in cigarette smokers (Akram et al. 2018). Interestingly, tobacco condensate (TC) increases Candida albicans adhesion, growth, biofilm-formation, virulence gene expression (Semlali et al. 2014)and hyphal production (Awad and Karuppayil 2018). We hypothesised that TC-treated denture acrylic would therefore affect C. albicans within acrylic biofilms.

Methods:
Acrylic discs (pre-conditioned with TC, artificial saliva (AS) or water) were incubated at 37°C with C. albicans (n=6) for 90 min or 24 h. Adherent Candida were stained with calcofluor white and confocal laser scanning microscopy (CLSM) used to assess levels of adherence, biofilm and hyphal numbers. Expressed virulence genes (n=7) were measured by qPCR.

Results:
CLSM showed that effects of TC-treatment were strain dependent. Adherence of C. albicans PTR/94 to TC-treated surfaces was significantly (P<0.002) lower than on the untreated control. Biofilm levels of PTR/94 after 24 h were found to be significantly higher on AS-treated acrylic than the TC-treated and untreated control. Five strains had significantly fewer filamentous forms after 90 min on TC-treated surfaces. TC-treatment promoted hyphal levels for strain 705/93 after 24h.

Conclusion:
TC pre-conditioning altered adherence and biofilm coverage of C. albicans to acrylic surfaces and influenced hyphal development. Work is ongoing to ascertain the significance of these effects on C. albicans pathogenicity.
Akram et al. (2018). Journal of Oral Science 60(1):115–120.
Awad and Karuppayil (2018). American Journal of Clinical Microbiology and Antimicrobials1(3):1–6.
Semlali et al. (2014). BMC Microbiology. 14:61
Evaluation of antifungal activity of Terminalia subspathulata bark and fruit extracts against azole-resistant Candida isolates
Authors: Yahaya Hassan , Abdullahi Sharif Alhassan , Yakubu Yahaya 
Published: December 2021

Background:
Emerging resistant Candida species become a severe problem for public health. The study aims to examine the efficacy of Terminalia subspathulata bark and fruit extracts as an alternative source of antifungals for resistant strains of Candida species.

Methodology:

Candida albicans was isolated between 4–5th interdigital foot space and C. parapsilosis were isolated from the left-hand third finger of male patients. Morphological and molecular methods identified the isolates. Antifungal susceptibility testing (AFST) was determined using azole derivatives, amphotericin B (AmpB) and echinocandins based on E-test and broth microdilution (BMD) methods. The AFST activity of the 10 μL methanolic extracts with concentrations between 1.25–10 mg/mL was assessed by disk diffusion method according to CLSI guidelines.

Results:
The AFST results showed total resistance to all azoles (FLU, MIC ≥ 256 μg/ml and VOR, ITR and POS each with MIC ≥ 32 μg/ml). The BMD method agreed with E-test MICs. The T. subspathulata bark extract tested indicated activity on the C. albicans lawn with the zone of inhibition between 9–13 mm. The fruit extract indicated zone between 8–10 mm. Candida parapsilosis indicated susceptibility to bark extract with the zone of inhibition between 10–15 mm, while the fruit extract showed zone between 8–13 mm.

Conclusion:
Despite azole resistance, the extracts showed good activity against the isolates. Findings showed alternatives to AmpB and echinocandins because of toxicity and parenteral administration, respectively. Based on our findings, our study first reports the medicinal value of T. subspathulata.
The gut commensal Bacteroides vulgatus mpk reduces Candida albicans pathogenicity towards epithelial cells
Authors: Hammer Merle Lisa , Niemiec Maria Joanna , Auge Isabel , van Leeuwen Pim , Gorki Friederike , Steimle Alexander , Frick Julia-Stefanie , Denise Jacobsen Ilse 
Published: December 2021

The human body is colonized by various microbes, among them the yeast Candida albicans. Mostly harmless, this opportunist causes also disease, ranging from superficial infections to sepsis. Risk factors are disturbed host defenses, mucosal barrier breakdown, and antibiotic-induced dysbiosis. Hence, residing bacteria are important to protect from Candida-mediated damage or inflammation. Bacteroides vulgatus mpk, e.g., is described as positively immunomodulatory in mouse models of inflammatory bowel disease, but its effect on the mycobiota is unknown.
In this study we aimed to determine if B. vulgatus mpk affects C. albicans pathogenicity.
Therefore, intestinal and oral epithelial cellswere pre-infectedin vitrowith B. vulgatus mpk and then challenged with C. albicans SC5314. The role of soluble factors was investigated by spatial separation or use of Bacteroides-conditioned medium (BCM).
Preincubation of host cells with B. vulgatus mpk strongly reduced C. albicans-mediated damage while fungal burden and hyphal length were unaffected by the bacterium. The protective effect did not depend on direct contact of Bacteroidesto host cellsor Candida and could be mimicked using BCM. Contact independency suggests that diffusible factors modulate host cell susceptibility.
Ongoing experiments aim to identifykey soluble Bacteroides mediators as well as subsequent host cell signaling. Additionally, co-colonization experiments of germ-free mice are planned to investigate B. vulgatus mpk’s potential to mediate colonization resistance towards C. albicans. This will contribute to our understanding of how commensal bacteria affect C. albicans and host protection.