bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bifunctional protein ArsRM contributes to arsenite methylation and resistance in Brevundimonas sp. M20
Authors: Li Congcong , Zong Gongli , Chen Xi , Tan Meixia , Gao Wenhui , Fu Jiafang , Zhang Peipei , Wang Bing , Cao Guangxiang 
Published: May 2023

Abstract
Background
Arsenic (As) with various chemical forms, including inorganic arsenic and organic arsenic, is the most prevalent water and environmental toxin. This metalloid occurs worldwide and many of its forms, especially arsenite [As(III)], cause various diseases including cancer. Organification of arsenite is an effective way for organisms to cope with arsenic toxicity. Microbial communities are vital contributors to the global arsenic biocycle and represent a promising way to reduce arsenite toxicity.

Methods
Brevundimonas sp. M20 with arsenite and roxarsone resistance was isolated from aquaculture sewage. The arsHRNBC cluster and the metRFHH operon of M20 were identified by sequencing. The gene encoding ArsR/methyltransferase fusion protein, arsRM, was amplified and expressed in Escherichia coli BL21 (DE3), and this strain showed resistance to arsenic in the present of 0.25–6 mM As(III), aresenate, or pentavalent roxarsone. The methylation activity and regulatory action of ArsRM were analyzed using Discovery Studio 2.0, and its functions were confirmed by methyltransferase activity analysis and electrophoretic mobility shift assays.

Results
The minimum inhibitory concentration of the roxarsone resistant strain Brevundimonas sp. M20 to arsenite was 4.5 mM. A 3,011-bp arsenite resistance ars cluster arsHRNBC and a 5649-bp methionine biosynthesis met operon were found on the 3.315-Mb chromosome. Functional prediction analyses suggested that ArsRM is a difunctional protein with transcriptional regulation and methyltransferase activities. Expression of ArsRM in E. coli increased its arsenite resistance to 1.5 mM. The arsenite methylation activity of ArsRM and its ability to bind to its own gene promoter were confirmed. The As(III)-binding site (ABS) and S-adenosylmethionine-binding motif are responsible for the difunctional characteristic of ArsRM.

Conclusions
We conclude that ArsRM promotes arsenite methylation and is able to bind to its own promoter region to regulate transcription. This difunctional characteristic directly connects methionine and arsenic metabolism. Our findings contribute important new knowledge about microbial arsenic resistance and detoxification. Future work should further explore how ArsRM regulates the met operon and the ars cluster.
Titer improvement of mycophenolic acid in the novel producer strain Penicillium arizonense and expression analysis of its biosynthetic genes
Authors: Ammar Hala A. , Ezzat Saeid M. , Elshourbagi Ebrahim , Elshahat Hind 
Published: May 2023

AbstractMycophenolic acid (MPA) is the active ingredient in the most important immunosuppressive pharmaceuticals. It has antifungal, antibacterial, antiviral, anti-psoriasis, and antitumor activities. Therefore, its overproduction in addition to gene expression analysis was our main target. Through this study, we isolated a novel potent mycophenolic acid (MPA) producer strain of the genusPenicilliumfrom the refrigerated Mozzarella cheese and it was identified with the molecular marker ITS andbenAgenes asP. arizonenseHEWt1. Three MPA overproducer mutants were isolated by exposing the wild type to different doses of gamma-rays, and the fermentation conditions for the highest production of MPA were optimized. The results indicated that MPA amounts produced by the mutants MT1, MT2, and MT3 were increased by 2.1, 1.7, and 1.6-fold, respectively, compared with the wild-type. The growth of both mutant and wild-type strains on PD broth, adjusted to pH 6 and incubated at 25 °C for 15 d, were the best conditions for maximum production of MPA. In a silico study, five orthologs genes of MPA biosynthesizing gene clusters inP. brevicompactumwere predicted from the genome ofP. arizonense. Sequencing and bioinformatic analyses proved the presence of five putative genes namelympaA, mpaC, mpaF, mpaG, andmpaHin theP. arizonenseHEWt1 genome. Gene expression analysis by qRT-PCR indicated an increase in the transcription value of all annotated genes in the three mutants over the wild type. A highly significant increase in the gene expression ofmpaC, mpaF, andmpaHwas observed inP. arizonense-MT1 compared with wild-type. These results confirmed the positive correlation of these genes in MPA biosynthesis and are the first report regarding the production of MPA byP. arizonense.Kew word.Mycophenolic acid,Penicillium arizonense, mutagenesis, gene expression.
Mortality risk factors in community-dwelling, subjectively healthy, Swiss older adults: update after 8-years follow-up
Authors: Gutzwiller Jean-Pierre , Müller-Bolla Krisztina , Ferrari Carlo , Stanga Zeno , Nydegger Urs E. , Risch Lorenz , Risch Martin 
Published: May 2023

Abstract
Background
Worldwide population is ageing, but little is known regarding risk factors associated with increased mortality in subjectively healthy, community-dwelling older adults. We present the updated results of the longest follow-up carried out on Swiss pensioners and we provide results on potential risk factors associated with mortality before the onset of the COVID-19 pandemic.

Materials and methods
Within the SENIORLAB study, we collected demographic data, anthropometric measures, medical history, and laboratory parameters of 1467 subjectively healthy, community-dwelling, Swiss adults aged ≥ 60 years over a median follow-up of 8.79 years. The variables considered in the multivariable Cox-proportional hazard model for mortality during follow-up were selected based on prior knowledge. Two separate models for males and females were calculated; moreover, we fitted the old model obtained in 2018 to the complete follow-up data to highlight differences and similarities.

Results
The population sample included 680 males and 787 females. Age of participants ranged between 60 and 99 years. We experienced 208 deaths throughout the entire follow-up period; no patients were lost at follow-up. The Cox-proportional hazard regression model included female gender, age, albumin levels, smoking status, hypertension, osteoporosis and history of cancer within predictors of mortality over the follow-up period. Consistent findings were obtained also after gender stratification. After fitting the old model, female gender, hypertension, and osteoporosis still showed statistically significant independent associations with all-cause mortality.

Conclusions
Understanding the predictors of a healthy survival can improve the overall quality of life of the ageing population and simultaneously reduce their global economic burden.

Trial registration
The present study was registered in the International Standard Randomized Controlled Trial Number registry: https://www.isrctn.com/ISRCTN53778569 (registration date: 27/05/2015).
Prognostic significance of frailty in hospitalized elderly patients with community-acquired pneumonia: a retrospective cohort study
Authors: Zhao Hongye , Tu Junlan , She Quan , Li Min , Wang Kai , Zhao Weihong , Huang Peng , Chen Bo , Wu Jianqing 
Published: May 2023

Abstract
Background
Frailty is associated with poor prognosis in a wide range of illnesses. However, its prognostic implications for older patients with community-acquired pneumonia (CAP) are not adequately addressed.

Methods
In this study, patients were classified into 3 groups according to the frailty index based on standard laboratory tests (FI-Lab) score: robust (FI-Lab < 0.2), pre-frail (FI-Lab 0.2–0.35), and frail (FI-Lab ≥ 0.35). The relationships between frailty and all-cause mortality and short-term clinical outcomes (length of stay, duration of antibiotic therapy, in-hospital mortality) were examined.

Results
Finally, 1164 patients were included, the median age was 75 years (interquartile range: 69, 82), and 438 patients (37.6%) were women. According to FI-Lab, 261(22.4%), 395(33.9%), and 508(43.6%) were robust, pre-frail, and frail. After adjustment for confounding variables, frailty was independently associated with prolonged antibiotic treatment (p = 0.037); pre-frailty and frailty were independently associated with longer inpatient days (p < 0.05 for both). The risk of in-hospital mortality was independently increased in frail patients (HR = 5.01, 95% CI = 1.51–16.57, p = 0.008) but not pre-frail patients (HR = 2.87, 95% CI = 0.86–9.63, p = 0.088) compared to robust patients. During a median follow-up of 33.9 months (interquartile range: 32.8 to 35.1 months), 408 (35.1%) patients died, of whom 29 (7.1%) were robust, 112 (27.5%) were pre-frail, and 267 (65.9%) were frail. Compared to robust patients, frail and pre-frail were significantly associated with increased risk for all-cause death (HR = 4.29, 95%CI: 1.78–10.35 and HR = 2.42 95%CI: 1.01–5.82, respectively).

Conclusions
Frailty is common among older patients with CAP and is strongly associated with increased mortality, longer length of stay, and duration of antibiotics. A routine frail assessment at the admission of elderly patients with CAP is necessary as the first step for appropriate multidisciplinary interventions.
Preoperative chemoradiotherapy using tegafur/uracil, oral leucovorin, and irinotecan (TEGAFIRI) followed by oxaliplatin-based chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: the study protocol for a phase II trial
Authors: Abe Shinya , Kawai Kazushige , Nozawa Hiroaki , Sasaki Kazuhito , Murono Koji , Emoto Shigenobu , Yokoyama Yuichiro , Matsuzaki Hiroyuki , Nagai Yuzo , Yoshioka Yuichiro , Shinagawa Takahide , Sonoda Hirofumi , Yamamoto Yoko , Oba Koji , Ishihara Soichiro 
Published: May 2023

Abstract
Background
Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol.

Methods
Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery.

Discussion
Since previous findings showed a high percentage of grade 3–4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC.

Trial Registration
Japan Registry of Clinical Trials jRCTs031210660.
The relationship between rurality, travel time to care and death by suicide
Authors: Barry Rebecca , Rehm Jürgen , de Oliveira Claire , Gozdyra Peter , Chen Simon , Kurdyak Paul 
Published: May 2023

Abstract
Background
We previously found an association between rurality and death by suicide, where those living in rural areas were more likely to die by suicide. One potential reason why this relationship exists might be travel time to care. This paper examines the relationship between travel time to both psychiatric and general hospitals and suicide, and then determine whether travel time to care mediates the relationship between rurality and suicide.

Methods
This is a population-based nested case-control study. Data from 2007 to 2017 were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario. Suicides were captured using vital statistics. Travel time to care was calculated from the resident’s home to the nearest hospital based on the postal codes of both locations. Rurality was measured using Metropolitan Influence Zones.

Results
For every hour in travel time a male resides from a general hospital, their risk of death by suicide doubles (AOR = 2.08, 95% CI = 1.61–2.69). Longer travel times to psychiatric hospitals also increases risk of suicide among males (AOR = 1.03, 95%CI = 1.02–1.05). Travel time to general hospitals is a significant mediator of the relationship between rurality and suicide among males, accounting for 6.52% of the relationship between rurality and increased risk of suicide. However, we also found that there is effect modification, where the relationship between travel time and suicide is only significant among males living in urban areas.

Conclusions
Overall, these findings suggest that males who must travel longer to hospitals are at a greater risk of suicide compared to those who travel a shorter time. Furthermore, travel time to care is a mediator of the association between rurality and suicide among males.
Advance Statements for Black African and Caribbean people (AdStAC): protocol for an implementation study
Authors: Babatunde Abigail , Ruck Keene Alex , Simpson Alan , Gilbert Steven , Stephenson Lucy , Chua Kia-Chong , Owen Gareth , Simpson Adelabu Jonathan , Smith Shubulade , Henderson Claire 
Published: May 2023

Abstract
Background
The UK government committed to legislating for Advance Choice Documents/Advance Statements (ACD/AS) following their recommendation by the Independent Review of the MHA (2018). ACDs/AS are yet to be implemented in routine practice despite evidence and high demand; they are associated with improved therapeutic relationships and a reduction (25%, RR 0.75, CI 0.61–0.93) in compulsory psychiatric admission. Barriers to their implementation are well documented, ranging from low knowledge levels to logistical challenges in accessing the content during episodes of acute care. In the UK this is an issue for Black people, who experience detention rates disproportionately (over three times) higher than those of White British people and have poorer care experiences and outcomes. ACDs/AS allow for Black people to have their concerns heard by mental health professionals in a care system where they often feel their views are ignored. AdStAC aims to improve Black service users’ experiences in mental health services in South London by co-producing and testing an ACD/AS implementation resource with Black service users, mental health professionals and carers/supporters of Black service users.

Methods/design
The study will take place in South London, England over three phases: 1) formative work through stakeholder workshops; 2) co-production of resources through a consensus development exercise and working groups; and 3) testing of the resources using quality improvement (QI) methods. A lived experience advisory group, staff advisory group and project steering committee will support the study throughout. The implementation resources will comprise: advance choice document/advance statement (ACD/AS) documentation, stakeholder trainings, a manual for mental health professionals to facilitate the processes of creating and revising advance statements, and informatics development.

Discussion
The implementation resources will help increase the likelihood of the new mental health legislation in England being implemented effectively; through aligning evidence-based medicine, policy and law to effectively provide positive clinical, social and financial outcomes for Black people, the National Health Service (NHS) and wider society. This study will likely benefit a wider group of people with severe mental illness, as when marginalised groups who are least engaged, can be supported with these strategies, then the strategies are likely to work for others.
The value of mesenteric closure after laparoscopic right hemicolectomy: a scoping review
Authors: Xu Weimin , Zhou Jianping 
Published: May 2023

Abstract
Objective
To evaluate the prognostic impact and describe suturing tools of mesenteric closure after laparoscopic right hemicolectomy (LRH).

Methods
PubMed, Embase, Cochrane library, Web of Science, and Scopus databases, were searched and publications relating to mesenteric closure data and tools were extracted. Search terms: “Mesenteric Defects” and “Mesenteric Closure” were used, and manual searches of eligible articles from literature reference lists performed.

Result
A total of 7 publications were identified. 5 focused on prognostic impact and 4 referred to tools for mesenteric closure, two of which concerned both prognostic data and tools. All studies related to prognostic impact were single center with “low” modified GRADE quality. A high degree of heterogeneous was found.

Conclusion
The evidence from current research does not support routine closure of mesenteric defects. Use of a polymer ligation clip has produced favorable results in a small sample size trial and further investigation is merited. A large randomized controlled trial is still warranted.
Indocyanine green combined with methylene blue versus methylene blue alone for sentinel lymph node biopsy in breast cancer: a retrospective study
Authors: Yang Qiu-hui , Zhang Xiang-jian 
Published: May 2023

Abstract
Background
Recent studies have shown that near-infrared (NIR) fluorescence imaging using Indocyanine green (ICG) may improve the efficiency of sentinel lymph node biopsy (SLNB). This study aimed to assess the effectiveness of the combination of ICG and methylene blue (MB) in breast cancer patients undergoing SLNB.

Patients and method
We evaluated ICG plus MB (ICG + MB) identification effectiveness with MB alone using retrospective analysis. From 2016 to 2020, we collected data on 300 eligible breast cancer patients who got SLNB treatment in our institution by ICG + MB or MB alone. By comparing the distribution of clinicopathological characteristics, the detection rate of sentinel lymph nodes (SLNs) and metastatic SLNs, as well as the total number of SLNs in the two groups, we were able to assess the imaging efficiency.

Results
Fluorescence imaging allowed 131 out of 136 patients in the ICG + MB group to find SLNs. ICG + MB group and MB group had detection rates of 98.5% and 91.5% (P = 0.007, χ2 = 7.352), respectively. Besides, the ICG + MB approach was able to produce improved recognition outcomes. What’s more, compared with the MB group, the ICG + MB group can identify more lymph nodes (LNs) (3.1 to 2.6, P = 0.000, t = 4.447). Additionally, in the ICG + MB group, ICG could identify more LNs than MB (3.1 vs 2.6, P = 0.004, t = 2.884).

Conclusion
ICG has high detection effectiveness for SLNs, and when paired with MB, the detection efficiency can be increased even further. Furthermore, the ICG + MB tracing mode does not involve radioisotopes, which has a lot of promise for clinical use and can take the place of conventional standard detection methods.
Evaluation of the dislodgement force of splinted restorations with engaging conical abutments over multiple nonparallel implants (in-vitro study)
Authors: Khamis Mohamed Moataz , Zakaria Niveen Hazem , Farrag Khaled Mohamed , Abolgheit Salma 
Published: May 2023

Abstract
Background
Splinted multiunit cement-retained restorations with screw access channels over engaging abutments are viable implant prosthetic options. However, information regarding the maximum degree of divergence between multiple implants is lacking. The purpose of this in vitro study was to determine the maximum degree of divergence between 2 adjacent implants with conical connections that allows insertion and removal of splinted restorations with engaging preparable abutments or titanium base abutments.

Methods
Two implants were aligned in a stone base, one straight and the other at an angle ranging from 0 to 20 degrees. The implants represented an implant system that had an internal conical connection and a hexed abutment engaging the base of the connection. Two straight preparable engaging cement retained abutments were screwed onto the implants and splinted together using acrylic resin. A total of 11 angles were tested, with 7 specimens for every angle. Evaluation of dislodging force was performed by pulling out the splinted abutments after unscrewing them. This was performed subjectively by 3 blinded investigators who applied a tactile pulling force. A scale of 0–10 was used to estimate the pulling force. Objectively the dislodging force was measured in Newtons using a universal testing machine. A statistical correlation was made between the subjective and objective dislodging force values using Spearman’s rank correlation coefficient.

Results
The mean subjective values increased gradually from 0 to 16 degrees. A sudden rise was noticed at 18 degrees (9.71 ± 0.23) and, at 20 degrees, the investigators were not able to remove the splinted abutments from the implants. The mean objective dislodgement force values increased gradually from 0 to16 degrees and abruptly from 16 degrees (13.57 ± 0.45 N) to 18 degrees (25.40 ± 0.66 N) and 20 degrees (35.22 ± 0.64). The correlation between the subjective and the objective evaluations assessed using the Spearman’s rank correlation coefficient was 0.98 indicating a statistically significant correlation (P < .001). As the objective dislodging force increased, the subjective dislodgement difficulty increased.

Conclusions
Splinting cement retained restorations with screw access channels on engaging abutments is possible when multiple implants with conical connections having an internal flare angle of 8 degrees are used, with implant divergence of up to 16 degrees.
Exploring diagnosis and treatment of premenstrual dysphoric disorder in the U.S. healthcare system: a qualitative investigation
Authors: Chan Kiera , Rubtsova Anna A. , Clark Cari Jo 
Published: May 2023

Abstract
Background
Premenstrual Dysphoric Disorder (PMDD) is a premenstrual condition that affects 3–8% of the US population, yet knowledge on treatment and consistent diagnostic testing is lacking. While research concerning the epidemiology and pharmaceutical treatments for this condition has increased, there is a lack of qualitative studies on the experiences of patients who live with this condition. The aim of this study was to explore the diagnostic and treatment experiences of PMDD patients in the U.S. healthcare system and identify barriers to diagnosis and treatment.

Methods
This study uses a feminist framework with qualitative phenomenological methods. We recruited participants who identified as having PMDD, regardless of official diagnosis, through online forums within the U.S. PMDD community. The study conducted 32 in depth interviews with participants on their experiences with PMDD diagnosis and treatment. Thematic analysis methods revealed key barriers within the diagnostic and care process including patient, provider, and societal barriers.

Results
This study presents a PMDD Care Continuum that represents the timeline of participant experiences beginning from symptom onset towards official diagnosis, treatments, and ongoing management of the condition. Participant experiences demonstrated that much of the diagnostic and treatment processes were burdened on the patient, and that successful navigation within the healthcare system was dependent on high levels of self-advocacy.

Conclusions
This was the first study to describe the qualitative experiences of patients who identified as having PMDD in the U.S. Further research is needed to refine and operationalize diagnostic criteria and treatment guidelines for PMDD.