bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of a Decision-Making Capacity Assessment Model at the Grey Nuns Community Hospital
Authors: Charles Lesley , Kothavade Utkarsha , Brémault-Phillips Suzette , Chan Karenn , Dobbs Bonnie , Tian Peter George Jaminal , Polard Sharna , Parmar Jasneet
Published: January 2022

BACKGROUND. With an increasing elderly population, the number of persons with dementia is expected to increase and, consequently, the number of persons needing decision-making capacity assessments (DMCA) is too. However, many healthcare professionals do not feel ready to provide DMCAs. Since 2006, we implemented a DMCA Model that includes a care pathway, worksheets, education, and mentoring. The objective of this study was to assess the impact of the utilization of this patient-centered DMCA model on the need for Capacity Interviews. METHODS. This was a retrospective quality assurance chart review of patients referred for DMCA to the Geriatric Service at the Grey Nuns Community Hospital from 2006–2020. The Geriatric Service is run by Family Physicians with extra training in Care of the Elderly. We extracted patient demographics, elements of the DMCA process, and whether Capacity Interviews were performed. We used descriptive statistics to summarize the data. RESULTS. Eighty-eight patients were referred for DMCAs, with a mean age of 76 years (SD = 10.5). Dementia affected 43.2% (38/88) of patients. Valid reasons for conducting a DMCA were evident in 93% (80/86) of referrals, and DMCAs were performed in 72.6% (61/84). 85.3% (58/68) of referrals identified the need for DMCA in two to four domains, most commonly accommodation, healthcare, and finances. Two to three disciplines, frequently social workers and occupational therapists, were involved in conducting the DMCAs for 67.2% (39/58) of patients. The Capacity Assessment Process Worksheet was used 63.2% of the time. Capacity Interviews were conducted in only 20.7% of referrals. Following the DMCAs, 48.2% (41/85) of those assessed were deemed to lack capacity. CONCLUSION. This study suggests that the DMCA Model implemented has decreased the need for Capacity Interviews while simultaneously respecting patient autonomy. This is an important finding as DMCAs carried out following this process reduced the need for both a Capacity Interview and declarations of incapacity while simultaneously respecting patient autonomy and supporting patients in their decisions in accordance with the legislation.
“Keeping the Light On”: A Qualitative Study on Hope Perceptions at the End of Life in Portuguese Family Dyads
Authors: Laranjeira Carlos , Dixe Maria Anjos , Semeão Isabel , Rijo Sara , Faria Catarina , Querido Ana
Published: January 2022

Hope performs an important role in how patients and their families cope with suffering and stressful events. To better inform practice and theory on hope, palliative care research should include both patients and their family carers, given their strong interdependence. The aim of this study was to explore how hope is experienced in dyads formed by end-of-life patients and their family carers. In this qualitative study, data were collected by in-depth interviews with seven Portuguese family dyads. Analysis followed a thematic analysis approach. The analysis of the interviews shed light on the importance of hope for all participants, and the challenges involved. Family dyads noted several barriers and facilitators to perceptions of hope. Barriers to hope included limitations imposed by illness, feelings of anguish and helplessness, and poor communication with clinicians. Hope facilitators included supportive others, positive thinking and sense of humour, connection with nature, faith in religion and science, and a sense of compassion with others and altruism. Given the multidimensional scope of hope, the main challenge for family dyads is to look beyond the disease itself. Thus, palliative care teams should be encouraged to support and foster realistic hope, helping families prepare for death, in the context of advanced cancer.
Dental Implants in People with Osteogenesis Imperfecta: A Systematic Review
Authors: Oelerich Ole , Kleinheinz Johannes , Bohner Lauren , Wiesmüller Vera , Hanisch Marcel
Published: January 2022

The aim of this systematic review was to answer the question of whether patients with osteogenesis imperfecta can be prosthetically rehabilitated with dental implants. A protocol was prospectively registered in PROSPERO (CRD42021286368). The inclusion criteria were the presence of osteogenesis imperfecta and the use of implants for prosthetic restorations. Cases in which the inclusion criteria were not met were excluded. PubMed, Web of Science, and Scopus were last searched on 22 August 2021. Quality assessment was performed using the Methodological Quality and Synthesis of Case Series and Case Reports tool. The primary outcome was implant survival. Supporting data were analyzed descriptively. Twelve studies were included. Twenty-three patients received a total number of 116 implants, with 5.0 (±3.8) implants placed per patient. The implant survival rate was 94.0% with a mean follow-up of 59.1 months (±36.1). A limitation of this review was the relatively short follow-up time in some of the included studies; therefore, the survival rate may be overestimated. Nevertheless, the available data showed the loss of only seven implants, with two implants lost due to implant fractures not attributable to the patient. With the limitations of this review and based on the available data, dental implants have a high survival rate in patients with osteogenesis imperfecta. Therefore, dental implants may be a viable treatment option for replacing missing teeth. This research was not funded by external resources.
Profiguration, Active Ageing, and Creativity: Keys for Quality of Life and Overcoming Ageism
Authors: Molina-Luque Fidel , Stončikaitė Ieva , Torres-González Teresa , Sanvicen-Torné Paquita
Published: January 2022

This article is based on qualitative analysis of interviews and focus groups conducted with participants enrolled in the Senior Programme of the University of Lleida, the City Council of Lleida, and care homes, as well as professional workers in the field of gerontology and related areas. It presents the analysis of interviews focused on the participants’ life trajectories, ageing, creativity, self-perception, and quality of life. The study aimed to examine how creativity influences the maintenance and improvement of a sense of wellbeing in older adults, and to reflect on how the perception of old age and of oneself changes through creative activity and active engagement across the life span. The article is framed within a new concept in sociology and the social sciences—‘profiguration’, which is the key element in the promotion and strengthening of intergenerational interdependence, education, wellbeing, social participation, and active ageing.
Patient Factors Associated with Different Hospice Programs in Korea: Analyzing Healthcare Big Data
Authors: Park Young-Taek , Kim Daekyun , Koh Su-Jin , Kim Yeon Sook , Kim Sang Mi
Published: January 2022

The Korean government has implemented a pilot project that introduces a new type of hospice care program called “Consultative Hospice Care” (COHC) since August 2017. The COHC is a new type of hospice program for terminally ill patients in acute care wards, which is different from the Independent Hospice Unit (IHU) care. This study aimed to compare the characteristics of two groups of hospice patients: COHC care only and both IHU care and COHC groups. Healthcare claim data from 1 April 2018 to 31 March 2020 were retrieved from the HIRA data warehouse system. The main outcome variable was patients receiving COHC only or both COHC and IHU care. The total number of hospice patients was 6482. A multivariate logistic regression analysis was used. Of 6482 hospice care recipients, 3789 (58.5%) received both COHC and IHU care. Those who received both COHC and IHU care were significantly associated with several factors: period from the first evaluation to death (adjusted odds ratio (aOR), 1.026; 95% confidence internal (CI), 1.024–1.029; p < 0.0001), disease severity measured by the Charlson Comorbidity Index (aOR, 1.032; CI, 1.017–1.047; p < 0.0001), consciousness (aOR, 3.654; CI, 3.269–4.085; p < 0.0001), and awareness of end-stage disease (aOR, 1.422; CI, 1.226–1.650; p < 0.0001). The COHC program had a critical role in hospice delivery to terminally ill patients. Policymakers on hospice care need to establish plans that promote efficient hospice care delivery systems.
The Contraindications to Combined Oral Contraceptives among Reproductive-Aged Women in an Obstetrics and Gynaecology Clinic: A Single-Centre Cross-Sectional Study
Authors: Assiri Ghadah A. , Bannan Douha F. , Alshehri Ghadah H. , Alshyhani Manal , Almatri Walaa , Mahmoud Mansour A.
Published: January 2022

This study aimed to determine the estimated proportion of contraindications among women taking combined oral contraceptives (COCs) and to assess the risk factors associated with their contraindications. This study was cross-sectional. Reproductive-aged women (18–49 years) on any COCs between 2018 and 2020 were recruited from one obstetrics–gynaecology clinic in a university-affiliated hospital and were included. Contraindications were defined using the World Health Organization (WHO) Medical Eligibility Criteria (MEC) for Contraceptive Use. Data were collected from electronic medical records for all included women, as well as a standardised, pretested, structured survey for one-third of the women. In this cross-sectional study, 380 women using COCs were included. Their mean age was 31.645 ± 7.366 years. Among them, 131 (34.5%) participated via a survey and electronic records, while the other 249 (65.5%) participated via electronic records only. The majority of the participants had a Bachelor’s degree (59.0%) and were married (62.1%). The overall estimated proportion of patients with at least one contraindication to COCs according to category 3 (relative contraindications) or 4 (absolute contraindications) was 31.3% (95% CI 26.63–35.99). The most common contraindications observed were controlled hypertension, category 3 (12.1%); major surgery with prolonged immobilisation, category 4 (4.7%); migraine with aura at any age, category 4 (4.2%); breastfeeding from six weeks to less than six months postpartum, category 3 (4.0%); and diabetes mellitus with complications, category 4 (3.2%). Significant factors associated with contraindications to COCs were married women (OR 2.19, 95% CI 1.38–3.46), those aged 35 years or more (OR 2.33, 95% CI 1.49–3.66), and those with one or more live births (OR 2.19, 95% CI 1.38–3.46). Ensuring proper assessment prior to prescribing and considering alternatives suitable for long-term use among women taking an oral contraceptive regularly is recommended.
Impact of Entrepreneurship on the Quality of Public Health Sector Institutions and Policies
Authors: Rastoka Jelica , Petković Saša , Radicic Dragana
Published: January 2022

The purpose of this paper is to investigate whether public health entrepreneurship principles implementation in the public health sector are alternative ways of promoting an immediate improvement of healthcare infrastructure. To contribute to the literature on the impact of public health entrepreneurship on public healthcare infrastructure, we estimate two empirical models, with the first model having institutions and the second model having public healthcare policies as the dependent variable. Our empirical analysis is based on the WHO international health regulation data for all WHO member countries (in order to achieve a balanced panel, we decided to retain 192 of them), covering the period from 2010 through to 2019. The main results obtained using a Poisson panel regression indicate a positive relationship between employing more entrepreneurship within public healthcare and the quality of public healthcare infrastructure represented through institutions and policies. This study produces several contributions to the stream of research on public health entrepreneurship. First, it makes a theoretical contribution in the way that it fills the lacking literature on the relationship between entrepreneurship within the public health sector and efficiency of country-specific public healthcare infrastructure. Second, it offers an empirical quantitative analysis of entrepreneurship that is generally lacking. Concerning policy implications, the third contribution of this paper is the provision of evidence showing alternative ways to improve healthcare infrastructure other than traditionally observed investments in physical infrastructure.
Knowledge, Awareness, and Prevention of Norovirus Infection among Kindergarten Parents in Chengdu, China
Authors: Li Yuanyuan , Cheng Wenyu
Published: January 2022

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis among children in China. However, little is known about parents’ knowledge of HuNoV infection and their understanding of how to prevent and control the disease. Therefore, we performed an exploratory survey to assess the level of knowledge of HuNoV infection among kindergarten parents. A cross-sectional survey was conducted by investigating kindergarteners’ parents through an online self-administered questionnaire between October 2020 and November 2020 in Chengdu, China. A total of 771 questionnaires were received with valid responses, and 81.97% of respondents had heard about NoV before. Among parents who had heard about HuNoV before, they had a poor awareness of incubation period, duration, and high-incidence seasons of HuNoV infection. The respondents also had a low-level awareness of how to clean the places contaminated by vomitus or stool. The multiple-regression analysis confirmed that factors associated with good knowledge regarding HuNoV infection were level of education, occupation, history of infection, and HuNoV learning experience. The most expected approach to learn about HuNoV among parents was the internet, followed by knowledge training in kindergartens, community information, and television. This is the first study to assess kindergarten parents’ knowledge and awareness of HuNoV infection. The survey results provide insights that would help in developing effective strategies and educational materials to prevent and control the disease.
Exploring the Effects of Land Use Changes on the Landscape Pattern and Soil Erosion of Western Hubei Province from 2000 to 2020
Authors: Li Jiyun , Zhou Yong , Li Qing , Yi Siqi , Peng Lina
Published: January 2022

Accelerated land use and land cover changes affect regional landscape patterns and change the ecological environment, including soil conservation capabilities. This is not conducive to the sustainable development of human society. In this research, we explored the land use change pattern and landscape change pattern in western Hubei from 2000 to 2020. Using the Chinese soil loss equation and stepwise regression, we measure how landscape patterns affect soil erosion under land use and cover changes in western Hubei Province. The results show that average soil erosion in the mountainous areas of western Hubei tended to increase from 2000 to 2010 and decrease from 2010 to 2020; soil erosion was higher in the western than in the eastern part of the study area. The land in areas with high-intensity and low-intensity soil erosion was mainly waterfront/grassland and cropland/forestland, respectively, and the area of moderate to severe soil erosion was greatest when the slope was 10–20°. When the slope exceeded 20°, the soil erosion area of each grade tended to decrease; thus, 20° is the critical slope for soil erosion in the study area. The landscape pattern in mountainous areas changed dramatically from 2000 to 2020. At the landscape level, landscape fragmentation increased and connectivity decreased, but the area of landscape diversity was stable. Soil erosion in western Hubei was positively correlated with the contiguity index, aggregation index and largest patch index but negatively correlated with the Shannon evenness index. The higher the landscape fragmentation and the greater the accumulation of single land-use types, the more severe the soil erosion is, while the higher the landscape connectivity and the richer the landscape diversity, the less severe the soil erosion is. The results can inform regional landscape management and soil conservation research.
Clinician Perspectives of Communication with Aboriginal and Torres Strait Islanders Managing Pain: Needs and Preferences
Authors: Bernardes Christina M. , Ekberg Stuart , Birch Stephen , Meuter Renata F. I. , Claus Andrew , Bryant Matthew , Isua Jermaine , Gray Paul , Kluver Joseph P. , Williamson Daniel , Jones Corey , Houkamau Kushla , Taylor Marayah , Malacova Eva , Lin Ivan , Pratt Gregory
Published: January 2022

Poor communication is an important factor contributing to health disparity. This study sought to investigate clinicians’ perspectives about communicating with Aboriginal and Torres Strait Islander patients with pain. This multi-site and mixed-methods study involved clinicians from three pain management services in Queensland, Australia. Clinicians completed a survey and participated in focus groups. Clinicians rated the importance of communication training, their knowledge, ability, and confidence in communicating with Aboriginal and Torres Strait Islander patients using a 5-point Likert scale. Rating scores were combined into low (scores 1–2); moderate (score 3) and high (scores 4–5). Informed by an interpretive description methodology, thematic analysis of focus group data was used to identify the communication needs and training preferences of clinicians. Overall (N = 64), 88% of clinicians rated the importance of communication training when supporting Aboriginal and Torres Strait Islander patients as “high”. In contrast, far fewer clinicians rated as “high” their knowledge (28%), ability (25%) and confidence (28%) in effectively communicating with Aboriginal and Torres Strait Islander patients. Thematic analysis identified three areas of need: knowledge of Aboriginal and Torres Strait Islander cultures, health beliefs, and understanding cross-cultural cues. Communication skills can be learned and training, in the form of a tailored intervention to support quality engagement with Aboriginal and Torres Strait Islander patients, should combine cultural and communication aspects with biomedical knowledge.
Challenges Faced in Large-Scale Nucleic Acid Testing during the Sudden Outbreak of the B.1.617.2 (Delta)
Authors: Zhu Pingting , Qian Meiyan , Wu Qiwei , Liu Xinyi
Published: January 2022

The Delta variant (B.1.617.2) has dominated in many countries over the world. Its sudden outbreak in China has led the government to quickly carry out large-scale nucleic acid testing to curb its spread. This qualitative study aims to find the challenges based on empirical evidence from the perspectives of the different groups of people involved in the testing, and further explore possible strategies to improve the efficiency of large-scale nucleic acid testing. Using a phenomenological approach, we selected 35 participants (seven managers, eight health professionals, six community volunteers and 14 residents) by purposive sampling. The interviews were conducted by in-depth semi-structured interviews and the data were analyzed by Colaizzi’s seven-step method. Qualitative analysis revealed three main themes: unreasonable and unsafe testing points layout settings, human and medical resources challenges, and potential infection risk. From the different angles, participants all experienced challenges during large-scale nucleic acid testing, making positive planning and adequate preparation important parts of the smooth development of testing. Large-scale nucleic acid testing relies on the cooperation and efforts of all to support containment of the spread of the virus. Local governments should improve their ability to respond to and deal with public health emergencies.
Assessment of Factors Associated with Unfavorable Outcomes among Drug-Resistant TB Patients: A 6-Year Retrospective Study from Pakistan
Authors: Khan Farman Ullah , Rehman Asim ur , Khan Faiz Ullah , Hayat Khezar , Khan Amjad , Ahmad Nafees , Chang Jie , Malik Usman Rashid , Fang Yu
Published: January 2022

The spread of drug-resistant tuberculosis (DR TB) poses significant challenges to the control and successful eradication of TB globally. The current retrospective study was designed to evaluate the treatment outcomes and identify the risk factors associated with unsuccessful outcomes among DR TB patients. A total of 277/308 eligible DR TB patients were enrolled for treatment at the programmatic management unit of DR TB at the Pakistan Institute of Medical Sciences, Islamabad between January 2014 and July 2019. Treatment outcomes were defined according to the WHO recommendations. Death, treatment failure, and lost to follow-up (LTFU) were collectively grouped as unsuccessful treatment outcomes, whereas cured and treatment completed were summed up together as successful treatment outcomes. Out of the total 277 patients, 265 (95.67%) were multidrug/rifampicin-resistant TB (MDR/RR-TB) cases, 8 (2.89%) were isoniazid resistant cases, and 4 (1.44%) were extensively drug-resistant ones. In the current cohort, a total of 177 (63.9%) achieved successful treatment outcomes. Among them, 153 (55.2%) were declared cured and 24 (8.7%) completed their treatment. Of the remaining 100 (36.1%) patients with unsuccessful outcomes, 60 (21.7%) died, 32 (11.5%) were LTFU, and 8 (2.9%) had failed treatment. The proportion of male patients was relatively higher (55.2%), within the age group of 21–40 years (47.3%) and lived in rural areas (66.8%). The multivariate analysis revealed that unsuccessful outcomes had a statistically significant association with being male (adjusted odds ratio, AOR: 1.92, 95% confidence interval (CI): 1.10–3.36), being in an age group above 60 years (AOR: 3.34, 95% CI: 1.09–10.1), suffering from any comorbidity (AOR: 2.69, 95% CI: 1.35–5.38), and the history of use of second-line drugs (AOR; 3.51, 95% CI 1.35–9.12). In conclusion, treatment outcomes among DR TB patients at the study site were poor and did not achieve the treatment success target (≥75%) set by the World Health Organization.
Arterial Hypertension in Morbid Obesity after Bariatric Surgery: Five Years of Follow-Up, a Before-And-After Study
Authors: Arias Angeles , Rodríguez-Álvarez Cristobalina , González-Dávila Enrique , Acosta-Torrecilla Alfonso , Novo-Muñoz M. Mercedes , Rodríguez-Novo Natalia
Published: January 2022

Background: Arterial hypertension (HTN) is common among morbidly obese patients undergoing bariatric surgery. The aim of this study is to analyse the prevalence and evolution of HTN and weight loss in patients suffering from morbid obesity before and after bariatric surgery, during a follow-up period of five years. Methods: A before-and-after study was carried out on severely obese patients undergoing Laparoscopic Roux-En-Y Gastric Bypass (LRYGB). Criteria for HTN diagnosis were current treatment with antihypertensive agents and/or systolic blood pressure (SBP) > 140 mmHg and/or diastolic (DBP) > 90 mmHg. HTN remission was defined as normalisation of blood pressure (BP) maintained after discontinuation of medical treatment, and HTN recurrence was considered when HTN diagnostic criteria reappeared after remission. Weight loss during the study period was evaluated for each patient, calculating excess weight loss percentage (% EWL) and BMI loss percentage (% BMIL) with reference to the baseline value. Results: A total of 273 patients were included in the study. HTN was present in 48.2%; 29.4% of hypertensive patients showed HTN remission two years after the surgical procedure, 30.3% of them had relapsed at five years. Conclusion: LRYGB in obese patients is associated with a remission of HTN, and no weight loss differences were observed between the group of patients showing HTN remission at two years and the group who did not. However, differences were observed after the second follow-up year, with an increased weight loss in the remission group, which could indicate that sustained weight loss favours the control of HTN.
Salicylic Acid Manipulates Ion Accumulation and Distribution in Favor of Salinity Tolerance in Chenopodium quinoa
Authors: Mohammadi Hamid , Rahimpour Bahareh , Pirasteh-Anosheh Hadi , Race Marco
Published: January 2022

Although the effects of salicylic acid (SA) on increasing plant growth in saline conditions have been well known, the mechanisms of induction of salinity tolerance, especially in quinoa (Chenopodium quinoa Willd.), are not fully understood. In the present work, two quinoa genotypes (Titicaca and Giza1) were treated with different SA concentrations (0, 0.75, and 1.5 mM) under varied irrigation water salinities (0, 7, 14, and 21 dS m−1). Salinity decreased shoot and root growth, potassium (K+) concentration, and potassium to sodium ratio (K/Na) and increased sodium (Na+) and chlorine (Cl−) concentrations in both cultivars. Calcium (Ca2+) and magnesium (Mg2+) concentrations increased in 7 dS m−1 but decreased in higher salinities. The growth and salinity tolerance of Giza1 were higher, while the growth of Giza1 increased and of Titicaca decreased in high salinity. Salicylic acid at 0.75-mM concentration increased shoot and root growth and improved the ions concentration in favor of the plant, while the 1.5-mM concentration either had no significant effect or had a negative impact. The ions distribution estimated by K/Na selectivity and storage factor (SF) indicated quinoa accumulated more ions in roots under saline conditions. Salicylic acid increased NaSF, ClSF, and MgSF and decreased KSF and CaSF, meaning less Na+, Cl−, and Mg2+ and more K+ and Ca2+ transferred to shoots in SA-treated plants. Importantly, Giza1, as the more tolerant cultivar, had higher NaSF and ClSF and lower KSF, CaSF, and MgSF. In general, the concentrations of ions in roots were higher than in shoots. The results indicated more ions accumulation in the root could be one of the most important mechanisms of salinity tolerance in quinoa, and the more tolerant cultivar (Giza1) transferred less Na+ and Cl− and more K+ and Ca2+ and Mg2+ to the shoot.
Neighborhood Poverty in Combination with Older Housing Is Associated with Adverse Birth Outcomes: A Study on Ubiquitous Lead Risk among 1 Million Births in Texas
Authors: Wood Bethany Marie , Cubbin Catherine
Published: January 2022

The purpose of this study was to determine whether housing age in combination with neighborhood poverty, as a proxy for fetal exposure to heavy metal lead, is associated with adverse birth outcomes. We linked population-level birth certificate data for Black, Hispanic, White and Other women, stratified by nativity, from 2009–2011 in Texas (n = 1,040,642) to census the tract-level median housing age/poverty level from the American Community Survey, 2007–2011. Tracts with median housing age values before 1975 with a poverty level of 20% or more were considered to be neighborhoods with a high risk of exposure to deteriorating lead-based paint. We estimated multilevel models to examine the relationship between neighborhood housing age/poverty level and each dependent variable (preterm birth, low birth weight, small-for-gestational age). The odds of adverse birth outcomes were significantly higher for mothers living in high-poverty neighborhoods with median housing built before the lead-based paint ban. Increased awareness of—and improved methods of alleviating— ubiquitous lead-based paint exposure in Texas may be necessary interventions for positive developmental trajectories of children. Allocating federal funds for place-based interventions, including universal lead paint mitigation, in older, high-poverty neighborhoods may reduce the disproportionate risk of adverse birth outcomes.
Assessment of the Microbiological Quality of Ready-to-Eat Salads—Are There Any Reasons for Concern about Public Health?
Authors: Łepecka Anna , Zielińska Dorota , Szymański Piotr , Buras Izabela , Kołożyn-Krajewska Danuta
Published: January 2022

Ready-to-eat food products can be readily consumed without further preparation and are convenient for busy on-the-go consumers. The objective of the study was to assess the microbiological quality of ready-to-eat salads. Thirty RTE salads were tested for the presence of bacteria, yeasts, and molds using the TEMPO and agar plate method. The study demonstrated that most of the tested products were characterized by varying microbiological quality. The total number of mesophilic microbiotas was about 6 log CFU g−1. The high number of microorganisms was due to yeast and molds or Enterobacteriaceae. Half of the salads were contaminated with E. coli and three salads were contaminated with S. aureus. LAB were also found, which can be explained mainly by a dairy ingredient. In some salads, Salmonella spp. and L. monocytogenes were detected (26.7% and 33.3% of the samples, respectively). Based on the conducted tests, it was found that the microbiological quality was not satisfactory. The results presented in this study indicate that there is a significant problem of the presence of pathogens. Manufacturers should strive to reduce the possibility of microbial contamination through the use of widely understood hygiene of the production process, using hurdle technology, including the modified atmosphere and refrigerated storage.
Genetic and Epigenetic Markers of Lithium Response
Authors: Pisanu Claudia , Meloni Anna , Severino Giovanni , Squassina Alessio
Published: January 2022

The mood stabilizer lithium represents a cornerstone in the long term treatment of bipolar disorder (BD), although with substantial interindividual variability in clinical response. This variability appears to be modulated by genetics, which has been significantly investigated in the last two decades with some promising findings. In addition, recently, the interest in the role of epigenetics has grown significantly, since the exploration of these mechanisms might allow the elucidation of the gene–environment interactions and explanation of missing heritability. In this article, we provide an overview of the most relevant findings regarding the pharmacogenomics and pharmacoepigenomics of lithium response in BD. We describe the most replicated findings among candidate gene studies, results from genome-wide association studies (GWAS) as well as post-GWAS approaches supporting an association between high genetic load for schizophrenia, major depressive disorder or attention deficit/hyperactivity disorder and poor lithium response. Next, we describe results from studies investigating epigenetic mechanisms, such as changes in methylation or noncoding RNA levels, which play a relevant role as regulators of gene expression. Finally, we discuss challenges related to the search for the molecular determinants of lithium response and potential future research directions to pave the path towards a biomarker guided approach in lithium treatment.
Sorption and Magnetic Properties of Oxalato-Based Trimetallic Open Framework Stabilized by Charge-Assisted Hydrogen Bonds
Authors: Muzioł Tadeusz Mikołaj , Tereba Natalia , Podgajny Robert , Pełka Robert , Czernia Dominik , Wiśniewski Marek , Koter Stanisław , Wrzeszcz Grzegorz
Published: January 2022

We report a new structure of {[Co(bpy)2(ox)][{Cu2(bpy)2(ox)}Fe(ox)3]}n·8.5nH2O NCU-1 presenting a rare ladder topology among oxalate-based coordination polymers with anionic chains composed of alternately arranged [Cu2(bpy)2(ox)]2+ and [Fe(ox)3]3− moieties. Along the a axis, they are separated by Co(III) units to give porous material with voids of 963.7 Å3 (16.9% of cell volume). The stability of this structure is assured by a network of stacking interactions and charge-assisted C-H…O hydrogen bonds formed between adjacent chains, adjacent cobalt(III) units, and alternately arranged cobalt(III) and chain motifs. The soaking experiment with acetonitrile and bromobenzene showed that water molecules (8.5 water molecules dispersed over 15 positions) are bonded tightly, despite partial occupancy. Water adsorption experiments are described by a D’arcy and Watt model being the sum of Langmuir and Dubinin–Serpinski isotherms. The amount of primary adsorption sites calculated from this model is equal 8.2 mol H2O/mol, being very close to the value obtained from the XRD experiments and indicates that water was adsorbed mainly on the primary sites. The antiferromagnetic properties could be only approximately described with the simple CuII-ox-CuII dimer using H = −J·S1·S2, thus, considering non-trivial topology of the whole Cu-Fe chain, we developed our own general approach, based on the semiclassical model (SC) and molecular field (MF) model, to describe precisely the magnetic superexchange interactions in NCU-1. We established that Cu(II)-Cu(II) coupling dominates over multiple Cu(II)-Fe(III) interactions, with JCuCu = −275(29) and JCuFe = −3.8(1.6) cm−1 and discussed the obtained values against the literature data.
The T850D Phosphomimetic Mutation in the Androgen Receptor Ligand Binding Domain Enhances Recruitment at Activation Function 2
Authors: Helsen Christine , Nguyen Tien , Vercruysse Thomas , Wouters Staf , Daelemans Dirk , Voet Arnout , Claessens Frank
Published: January 2022

Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity syndrome and prostate cancer. Here, we describe a gain-of-function mutation of the surface-exposed threonine at position 850, located at the amino-terminus of Helix 10 (H10) in the AR LBD. Since T850 phosphorylation was reported to affect AR function, we created the phosphomimetic mutation T850D. The AR T850D variant has a 1.5- to 2-fold increased transcriptional activity with no effect on ligand affinity. In the androgen responsive LNCaP cell line grown in medium with low androgen levels, we observed a growth advantage for cells in which the endogenous AR was replaced by AR T850D. Despite the distance to the AF2 site, the AR T850D LBD displayed an increased affinity for coactivator peptides as well as the 23FQNLF27 motif of AR itself. Molecular Dynamics simulations confirm allosteric transmission of the T850D mutation towards the AF2 site via extended hydrogen bond formation between coactivator peptide and AF2 site. This mechanistic study thus confirms the gain-of-function character of T850D and T850 phosphorylation for AR activity and reveals details of the allosteric communications within the LBD.
Genome-Wide ChIPseq Analysis of AhR, COUP-TF, and HNF4 Enrichment in TCDD-Treated Mouse Liver
Authors: Cholico Giovan N. , Nault Rance , Zacharewski Tim R.
Published: January 2022

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known for mediating the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Although the canonical mechanism of AhR activation involves heterodimerization with the aryl hydrocarbon receptor nuclear translocator, other transcriptional regulators that interact with AhR have been identified. Enrichment analysis of motifs in AhR-bound genomic regions implicated co-operation with COUP transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF4). The present study investigated AhR, HNF4α and COUP-TFII genomic binding and effects on gene expression associated with liver-specific function and cell differentiation in response to TCDD. Hepatic ChIPseq data from male C57BL/6 mice at 2 h after oral gavage with 30 µg/kg TCDD were integrated with bulk RNA-sequencing (RNAseq) time-course (2–72 h) and dose–response (0.01–30 µg/kg) datasets to assess putative AhR, HNF4α and COUP-TFII interactions associated with differential gene expression. Functional enrichment analysis of differentially expressed genes (DEGs) identified differential binding enrichment for AhR, COUP-TFII, and HNF4α to regions within liver-specific genes, suggesting intersections associated with the loss of liver-specific functions and hepatocyte differentiation. Analysis found that the repression of liver-specific, HNF4α target and hepatocyte differentiation genes, involved increased AhR and HNF4α binding with decreased COUP-TFII binding. Collectively, these results suggested TCDD-elicited loss of liver-specific functions and markers of hepatocyte differentiation involved interactions between AhR, COUP-TFII and HNF4α.
Rare Hereditary Gynecological Cancer Syndromes
Authors: Watanabe Takafumi , Soeda Shu , Endo Yuta , Okabe Chikako , Sato Tetsu , Kamo Norihito , Ueda Makiko , Kojima Manabu , Furukawa Shigenori , Nishigori Hidekazu , Takahashi Toshifumi , Fujimori Keiya
Published: January 2022

Hereditary cancer syndromes, which are characterized by onset at an early age and an increased risk of developing certain tumors, are caused by germline pathogenic variants in tumor suppressor genes and are mostly inherited in an autosomal dominant manner. Therefore, hereditary cancer syndromes have been used as powerful models to identify and characterize susceptibility genes associated with cancer. Furthermore, clarification of the association between genotypes and phenotypes in one disease has provided insights into the etiology of other seemingly different diseases. Molecular genetic discoveries from the study of hereditary cancer syndrome have not only changed the methods of diagnosis and management, but have also shed light on the molecular regulatory pathways that are important in the development and treatment of sporadic tumors. The main cancer susceptibility syndromes that involve gynecologic cancers include hereditary breast and ovarian cancer syndrome as well as Lynch syndrome. However, in addition to these two hereditary cancer syndromes, there are several other hereditary syndromes associated with gynecologic cancers. In the present review, we provide an overview of the clinical features, and discuss the molecular genetics, of four rare hereditary gynecological cancer syndromes; Cowden syndrome, Peutz-Jeghers syndrome, DICER1 syndrome and rhabdoid tumor predisposition syndrome 2.
Contribution of the STAT Family of Transcription Factors to the Expression of the Serotonin 2B (HTR2B) Receptor in Human Uveal Melanoma
Authors: Benhassine Manel , Le-Bel Gaëtan , Guérin Sylvain L.
Published: January 2022

Uveal melanoma (UM) remains the most common intraocular malignancy among diseases affecting the adult eye. The primary tumor disseminates to the liver in half of patients and leads to a 6 to 12-month survival rate, making UM a particularly aggressive type of cancer. Genomic analyses have led to the development of gene-expression profiles that can efficiently predict metastatic progression. Among these genes, that encoding the serotonin receptor 2B (HTR2B) represents the most discriminant from this molecular signature, its aberrant expression being the hallmark of UM metastatic progression. Recent evidence suggests that expression of HTR2B might be regulated through the Janus kinase/Signal Transducer and Activator of Transcription proteins (JAK/STAT) intracellular signalization pathway. However, little is actually known about the molecular mechanisms involved in the abnormally elevated expression of the HTR2B gene in metastatic UM and whether activated STAT proteins participates to this mechanism. In this study, we determined the pattern of STAT family members expressed in both primary tumors and UM cell-lines, and evaluated their contribution to HTR2B gene expression. Examination of the HTR2B promoter sequence revealed the presence of a STAT putative target site (5′-TTC (N)3 GAA3′) located 280 bp upstream of the mRNA start site that is completely identical to the high affinity binding site recognized by these TFs. Gene profiling on microarrays provided evidence that metastatic UM cell lines with high levels of HTR2B also express high levels of STAT proteins whereas low levels of these TFs are observed in non-metastatic UM cells with low levels of HTR2B, suggesting that STAT proteins contribute to HTR2B gene expression in UM cells. All UM cell lines tested were found to express their own pattern of STAT proteins in Western blot analyses. Furthermore, T142 and T143 UM cells responded to interleukins IL-4 and IL-6 by increasing the phosphorylation status of STAT1. Most of all, expression of HTR2B also considerably increased in response to both IL-4 and IL-6 therefore providing evidence that HTR2B gene expression is modulated by STAT proteins in UM cells. The binding of STAT proteins to the −280 HTR2B/STAT site was also demonstrated by electrophoretic mobility shift assay (EMSA) analyses and site-directed mutation of that STAT site also abolished both IL-4 and IL-6 responsiveness in in vitro transfection analyses. The results of this study therefore demonstrate that members from the STAT family of TFs positively contribute to the expression of HTR2B in uveal melanoma.
CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer
Authors: Cao Lu , Bridle Kim R. , Shrestha Ritu , Prithviraj Prashanth , Crawford Darrell H. G. , Jayachandran Aparna
Published: January 2022

Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating a few selected immune checkpoint inhibitors (ICIs) as monotherapy for the treatment of GBC patients. However, only a subset of patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to immune checkpoint (IC) blockade needs to be explored. Epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs) have been implicated as key processes that confer ICI treatment resistance. However, in GBC the EMT-CSC-IC axis has not yet been clearly elucidated. This study aims to examine the aberrant expression of ICs associated with CSC and EMT. We successfully enriched CSCs by utilizing a 3-dimensional culture system and established a reversible EMT model with human GBC NOZ cell line. Notably, ICs CD73 and PD-L1 were closely associated with both CSC and EMT phenotypes. Knockdown of CD73 or PD-L1 reduced the proliferative and motile abilities of both adherent monolayers and anchorage-free spheroids. In conclusion, blocking CD73 and PD-L1 offer a promising therapeutic strategy for targeting highly aggressive populations with CSC and EMT phenotype to improve GBC patient prognosis.
The Cumulative Formation of R-loop Interacts with Histone Modifications to Shape Cell Reprogramming
Authors: Li Hanshuang , Long Chunshen , Hong Yan , Chao Lemuge , Peng Yong , Zuo Yongchun
Published: January 2022

R-loop, a three-stranded RNA/DNA structure, plays important roles in modulating genome stability and gene expression, but the molecular mechanism of R-loops in cell reprogramming remains elusive. Here, we comprehensively profiled the genome-wide landscape of R-loops during cell reprogramming. The results showed that the R-loop formation on most different types of repetitive elements is stage-specific in cell reprogramming. We unveiled that the cumulative deposition of an R-loop subset is positively correlated with gene expression during reprogramming. More importantly, the dynamic turnover of this R-loop subset is accompanied by the activation of the pluripotent transcriptional regulatory network (TRN). Moreover, the large accumulation of the active histone marker H3K4me3 and the reduction in H3K27me3 were also observed in these R-loop regions. Finally, we characterized the dynamic network of R-loops that facilitates cell fate transitions in reprogramming. Together, our study provides a new clue for deciphering the interplay mechanism between R-loops and HMs to control cell reprogramming.
Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids
Authors: Montano Luigi , Maugeri Alessandro , Volpe Maria Grazia , Micali Salvatore , Mirone Vincenzo , Mantovani Alberto , Navarra Michele , Piscopo Marina
Published: January 2022

The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine particles, produced by human activities put a strain on the body’s entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.
Secondary Structures of Proteins Follow Menzerath–Altmann Law
Authors: Matlach Vladimír , Dostál Daniel , Novotný Marian
Published: January 2022

This article examines the presence of the empirical tendency known as the Menzerath–Altmann Law (MAL) on protein secondary structures. MAL is related to optimization principles observed in natural languages and in genetic information on chromosomes or protein domains. The presence of MAL is examined on a non-redundant dataset of 4728 proteins by verifying significant, negative correlations and testing classical and newly proposed formulas by fitting the observed trend. We conclude that the lengths of secondary structures are specifically dependent on their number inside the protein sequence, while possibly reflecting the formula proposed in this paper. This behavior is observed on average but is individually avoidable and possibly driven by a latent cost function. The data suggest that MAL could provide a useful guiding principle in protein design.
New Insights into the Chloroplast Outer Membrane Proteome and Associated Targeting Pathways
Authors: Fish Michael , Nash Delaney , German Alexandru , Overton Alyssa , Jelokhani-Niaraki Masoud , Chuong Simon D. X. , Smith Matthew D.
Published: January 2022

Plastids are a dynamic class of organelle in plant cells that arose from an ancient cyanobacterial endosymbiont. Over the course of evolution, most genes encoding plastid proteins were transferred to the nuclear genome. In parallel, eukaryotic cells evolved a series of targeting pathways and complex proteinaceous machinery at the plastid surface to direct these proteins back to their target organelle. Chloroplasts are the most well-characterized plastids, responsible for photosynthesis and other important metabolic functions. The biogenesis and function of chloroplasts rely heavily on the fidelity of intracellular protein trafficking pathways. Therefore, understanding these pathways and their regulation is essential. Furthermore, the chloroplast outer membrane proteome remains relatively uncharted territory in our understanding of protein targeting. Many key players in the cytosol, receptors at the organelle surface, and insertases that facilitate insertion into the chloroplast outer membrane remain elusive for this group of proteins. In this review, we summarize recent advances in the understanding of well-characterized chloroplast outer membrane protein targeting pathways as well as provide new insights into novel targeting signals and pathways more recently identified using a bioinformatic approach. As a result of our analyses, we expand the known number of chloroplast outer membrane proteins from 117 to 138.