bluuebunny/crossref_metadata_2025 huggingface dataset:
The meaning of losing a child in older adults: a qualitative study
Authors: Safa Azade , Adib-Hajbaghery Mohsen , Rezaei Mahboubeh , Araban Marzieh
Published: November 2021

Background

After losing their child, elderly parents look for a meaning in this phenomenon. This meaning comes out from their experiences, and their responses to and actions in life are shaped based on this meaning. Therefore, this study was conducted with the aim of “understanding the meaning of losing a child in older adults.”

Methods

This qualitative study was conducted using conventional content analysis method. Using semi-structured face-to-face interviews, data were collected from 15 older adults who had experienced of losing their adult child. Data analysis was performed according to the steps proposed by Graneheim and Lundman, 2004. To prove the trustworthiness of the data, credibility, dependability, confirmability and transferability were used.

Results

The age range of participants was between 61 and 83 years and 73.3% of them were female. The two main categories of “tasting the bitter flavor of life” and “searching for a positive meaning in losing a child” together with the theme of “finding hope in the heart of darkness” were extracted from the participants’ experiences.

Conclusions

Despite the grief of losing a child, which had cast a dark shadow over the parents’ lives, the child’s liberation from worldly sufferings, his/her presence in a better world, and being hopeful about the grace of God had caused the elderly parents to find hope in the heart of darkness. After identifying the parents with a deceased child, they should be helped through psychological counseling and care of the healthcare team so that they can adapt to this situation by finding a positive meaning in losing their child.
A survey of personnel and services offered in 32 outpatient US clozapine clinics
Authors: Cotes Robert O. , Rolin Donna , Meyer Jonathan M. , Young Alexander S. , Cohen Amy N. , Gorrindo Tristan
Published: November 2021

Background

Clozapine clinics can facilitate greater access to clozapine, but there is a paucity of data on their structure in the US.

Methods

A 23-item survey was administered to participants recruited from the SMI Adviser Clozapine Center of Excellence listserv to understand characteristics of clozapine clinics.

Results

Clozapine clinics (N = 32) had a median caseload of 45 (IQR = 21–88) patients and utilized a median of 5 (IQR = 4–6) interdisciplinary roles. The most common roles included psychiatrists (100%), pharmacists (65.6%), nurses (65.6%), psychiatric nurse practitioners (53.1%), and case managers (53.1%). The majority of clinics outreached to patients who were overdue for labs (78.1%) and had access to on-site phlebotomy (62.5%). Less than half had on call services (46.9%).

Conclusions

In this first systematic description of clozapine clinics in the US, there was variation in the size, staffing, and services offered. These findings may serve as a window into configurations of clozapine teams.
Perceived influences on reducing prolonged sitting in police staff: a qualitative investigation using the Theoretical Domains Framework and COM-B model
Authors: Brierley Marsha L. , Smith Lindsey R. , Bailey Daniel P. , Every Sofie A. , Staines Taylor A. , Chater Angel M.
Published: November 2021

Background

Workplace interventions have shown promise for reducing sitting in office workers. Police office staff remain an understudied population group that work within a disciplined organisation with distinctive work tasks around public safety, potentially affecting their capability, opportunity, and motivation to change sitting behaviour. This study aimed to assess the perceived influences on reducing workplace sitting in non-operational, desk-based police staff in order to derive theoretical determinants for behaviour change.

Methods

Ten police staff from a single police force in Bedfordshire, England [eight female; 39.5 ± 11.5 years] took part in face-to-face semi-structured interviews lasting 46 ± 11 min on average. Thematic analysis identified key themes which were then mapped onto the Theoretical Domains Framework (TDF) and linked to the Capability, Opportunity, Motivation-Behaviour (COM-B) model.

Results

Seven themes were identified:‘Work tasks are seated’, ‘Social norm is to sit’, ‘Belief in ability to regulate behaviour’, ‘Knowledge of health risks’, ‘Organisational support’, ‘Impact on productivity’, and ‘Perceived autonomy for sitting reduction’.

Conclusions

Awareness of behaviour and health impacts (Capability), social and physical support to sit less (Opportunity), and habit formation techniques (Motivation) are recommended considerations in sitting reduction workplace interventions for police staff.
Assessing the quality of shared decision making for elective orthopedic surgery across a large healthcare system: cross-sectional survey study
Authors: Valentine K. D. , Cha Tom , Giardina John C. , Marques Felisha , Atlas Steven J. , Bedair Hany , Chen Antonia F. , Doorly Terence , Kang James , Leavitt Lauren , Licurse Adam , O’Brien Todd , Sequist Thomas , Sepucha Karen
Published: November 2021

Background

Clinical guidelines recommend engaging patients in shared decision making for common orthopedic procedures; however, limited work has assessed what is occurring in practice. This study assessed the quality of shared decision making for elective hip and knee replacement and spine surgery at four network-affiliated hospitals.

Methods

A cross-sectional sample of 875 adult patients undergoing total hip or knee joint replacement (TJR) for osteoarthritis or spine surgery for lumbar herniated disc or lumbar spinal stenosis was selected. Patients were mailed a survey including measures of Shared Decision Making (SDMP scale) and Informed, Patient-Centered (IPC) decisions. We examined decision-making across sites, surgeons, and conditions, and whether the decision-making measures were associated with better health outcomes. Analyses were adjusted for clustering of patients within surgeons.

Results

Six hundred forty-six surveys (74% response rate) were returned with sufficient responses for analysis. Patients who had TJR reported lower SDMP scores than patients who had spine surgery (2.2 vs. 2.8; p < 0.001). Patients who had TJR were more likely to make IPC decisions (OA = 70%, Spine = 41%; p < 0.001). SDMP and IPC scores varied widely across surgeons, but the site was not predictive of SDMP scores or IPC decisions (all p > 0.09). Higher SDMP scores and IPC decisions were associated with larger improvements in global health outcomes for patients who had TJR, but not patients who had spine surgery.

Conclusions

Measures of shared decision making and decision quality varied among patients undergoing common elective orthopedic procedures. Routine measurement of shared decision making provides insight into areas of strength across these different orthopedic conditions as well as areas in need of improvement.
Clinicopathological features, clinical efficacy on 101 cases of rectal gastrointestinal stromal tumors, and the significance of neoadjuvant therapy
Authors: Yang Hongxin , Shen Chaoyong , Yin Xiaonan , Cai Zhaolun , Wang Qian , Zhang Bo
Published: November 2021

Objective

To investigate the clinicopathological features and clinical efficacy among 101 cases of rectal gastrointestinal stromal tumors (GISTs) and to investigate the significance of imatinib mesylate (IM) neoadjuvant therapy.

Methods

The clinicopathological features, treatment methods, perioperative data, and prognosis of the patients were summarized and analysed in 101 patients with rectal GISTs who received treatment in the Gastrointestinal Surgery of West China Hospital of Sichuan University and the Affiliated Hospital of Guizhou Medical University from August 2002 to November 2020 in China.

Results

A total of 101 patients, including 64 males and 37 females, were aged from 22 to 79 years (55.4 ± 12.2 years). Among the 70 patients who underwent direct surgery, 8 were very low risk cases, 10 were low risk cases, 7 were intermediate risk cases, and 45 were high risk cases. Cox regression analysis showed that postoperative IM adjuvant treatment improved the disease-free survival (DFS) and overall survival (OS) of 52 intermediate and high risk patients. Among the 31 patients who received neoadjuvant therapy, the objective response rate (ORR) was 83.9% (26/31), and the disease control rate (DCR) reached 96.8% (30/31). Subgroup analysis was also conducted based on the tumour diameter. (1) Among the 36 patients with a diameter ≤ 5 cm, two patients received IM neoadjuvant therapy, while 34 patients received direct surgery. Neither univariate nor Cox regression analysis found that neoadjuvant therapy affected DFS and OS. (2) Among the 65 patients with a diameter > 5 cm, 29 received IM neoadjuvant therapy, and 36 received direct surgery. Patients who underwent neoadjuvant therapy had less blood loss (P = 0.022), shorter postoperative hospital stay (P = 0.001), increased anal retention rate (93.1% vs. 72.2%, P = 0.031), and decreased enterostomy rate (10.3% vs. 33.3%, P = 0.037) than those who underwent direct surgery. Cox regression analysis suggested that neoadjuvant therapy and postoperative IM adjuvant therapy improved DFS.

Conclusion

Rectal GISTs are relatively rare and highly malignant tumors. Postoperative oral IM therapy can improve the DFS and OS of intermediate and high risk patients. In patients with rectal GISTs with diameters > 5 cm, IM neoadjuvant therapy can improve anal retention rate, preserve the structure and function of the organs, reduce enterostomy rate, and improve prognosis.
Living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria: outcome of expanded criteria in tumor size
Authors: Liang Hsin-Rou , Hsieh Chia-En , Lin Kuo-Hua , Ko Chih-Jan , Hung Yu-Ju , Hsu Ya-Lan , Chen Yao-Li
Published: November 2021

Background

The Milan criteria are the universal standard of liver transplantation for hepatocellular carcinoma (HCC). Numerous expanded criteria have shown outcomes as good as the Milan criteria. In Taiwan, living donor liver transplant (LDLT) accounts for the majority of transplantations due to organ shortages.

Methods

We retrospectively enrolled 155 patients who underwent LDLT for HCC from July 2005 to June 2017 and were followed up for at least 2 years. Patients beyond the Milan criteria (n = 78) were grouped as recurrent or nonrecurrent, and we established new expanded criteria based on these data.

Results

Patients beyond the Milan criteria with recurrence (n = 31) had a significantly larger maximal tumor diameter (4.13 ± 1.96 cm versus 6.10 ± 3.41 cm, p = 0.006) and total tumor diameter (7.19 ± 4.13 cm versus 10.21 ± 5.01 cm, p = 0.005). Therefore, we established expanded criteria involving maximal tumor diameter ≤ 6 cm and total tumor diameter < 10 cm. The 5-year survival rate of patients who met these criteria (n = 134) was 77.3%, and the 5-year recurrence rate was 20.5%; both showed no significant differences from those of the Milan criteria. Under the expanded criteria, the pool of eligible recipients was 35% larger than that of the Milan criteria.

Conclusion

Currently, patients with HCC who undergo LDLT can achieve good outcomes even when they are beyond the Milan criteria. Under the new expanded criteria, patients can achieve outcomes as good as those with the Milan criteria and more patients can benefit.
Sudden cardiac arrest associated with myxedema coma due to undiagnosed hypothyroidism: a case report
Authors: Yoshinaka Asami , Akatsuka Masayuki , Yamamoto Shuji , Yamakage Michiaki
Published: November 2021

Background

Myxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest.

Case presentation

A 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction.

Conclusions

This case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.
Associations of streptococci and fungi amounts in the oral cavity with nutritional and oral health status in institutionalized elders: a cross sectional study
Authors: Sato Hanako , Yano Akira , Shimoyama Yu , Sato Toshiro , Sugiyama Yukiko , Kishi Mitsuo
Published: November 2021

Background

Disruption of the indigenous microbiota is likely related to frailty caused by undernutrition. However, the relationship between undernutrition and the oral microbiota, especially normal bacteria, is not obvious. The aim of this study was to elucidate the associations of nutritional and oral health conditions with prevalence of bacteria and fungi in the oral cavity of older individuals.

Methods

Forty-one institutionalized older individuals with an average age ± standard deviation of 84.6 ± 8.3 years were enrolled as participants. Body mass index (BMI) and oral health assessment tool (OHAT) scores were used to represent nutritional and oral health status. Amounts of total bacteria, streptococci, and fungi in oral specimens collected from the tongue dorsum were determined by quantitative polymerase chain reaction (PCR) assay results. This study followed the STROBE statement for reports of observational studies.

Results

There was a significant correlation between BMI and streptococcal amount (ρ = 0.526, p < 0.001). The undernutrition group (BMI < 20) showed a significantly lower average number of oral streptococci (p = 0.003). In logistic regression models, streptococcal amount was a significant variable accounting for “not undernutrition” [odds ratio 5.68, 95% confidential interval (CI) 1.64–19.7 (p = 0.06)]. On the other hand, participants with a poor oral health condition (OHAT ≥ 5) harbored significantly higher levels of fungi (p = 0.028).

Conclusion

Oral streptococci were found to be associated with systemic nutritional condition and oral fungi with oral health condition. Thus, in order to understand the relationship of frailty with the oral microbiota in older individuals, it is necessary to examine oral indigenous bacteria as well as etiological microorganisms.
Comparison the effect of charcoal-containing, hydrogen peroxide-containing, and abrasive whitening toothpastes on color stability of a resin composite; an in vitro study
Authors: Mehrgan Sara , Kermanshah Hamid , Omrani Ladan Ranjbar , Ahmadi Elham , Rafeie Niyousha
Published: November 2021

Background

This study aimed to compare the effects of charcoal-containing, hydrogen peroxide-containing, and abrasive whitening toothpastes on color stability of a resin composite.

Methods

Forty-five specimens were fabricated of spectrum TPH3 composite resin and stored in artificial saliva for 24 h. Baseline color assessment was performed using a spectrophotometer device. Then, the specimens were randomly assigned into 5 experimental groups, namely distilled water (GC), Bencer (GB), colgate optic white (GO), perfect white black (GP) and colgate total whitening (GT) toothpastes. The specimens immersed in coffee solution for 10 min and brushed for 1 min with respective toothpaste and then stored in artificial saliva until the next day. This cycle was repeated for 30 days. After 30 days, the final color assessment was performed using the spectrophotometer. Data were analyzed using one-way ANOVA and Tukey tests.

Results

Experimental groups were not significantly different in terms of Δa and ΔE values. However, ΔL and Δb values showed significant difference among the groups. Regarding Δa, GT and GC groups showed red color shift while the other groups showed green color shift. Regarding Δb, all groups showed blue color shift except GT group which showed yellow color shift.

Conclusion

None of the whitening toothpastes could decrease discoloration caused by the coffee solution to the level below the perceptibility threshold except Colgate Optic White which reduced discoloration within the clinically acceptable perceptibility range.
Effect of exposure to etidronic acid on the bond strength of calcium silicate-based cements after 1 and 21 days: an in vitro study
Authors: Rebolloso de Barrio Elena , Pérez-Higueras Juan José , García-Barbero Ernesto , Gancedo-Caravia Lucía
Published: November 2021

Background

After reparation of root perforations with calcium silicate-based cements (CSBC), the surface of the material is expected to be exposed to root canal irrigants (RCI) while resuming the root canal treatment.

Methods

The aim of this study was to compare the effect of exposure to a mixture of sodium hypochlorite (NaOCl) and etidronic acid (HEBP) or other irrigants on the Push Out Bond Strength (POBS) of CSBC after two different setting times. 240 root slices 1 mm thick were obtained from single-rooted human teeth. A 1.4 mm diameter perforation was performed on each slice and filled with Biodentine (BD) or ProRoot MTA (PMTA). After 1 or 21 days they were exposed to 17% ethylenediaminetetraacetic acid, 5.25% NaOCl, a mixture of 5.25% NaOCl and 9% HEBP (NaOCl + HEBP) or saline (n = 15) and submitted to a push-out test. POBS results were analysed with ANOVA and Tukey tests.

Results

BD showed higher POBS than PMTA after 1 day (p < .05). After 21 days no differences were found between materials. After 1 day exposure to NaOCl + HEBP resulted in higher POBS, compared to the other irrigants (p < .05).

Conclusion

POBS results are influenced by the cement, the setting time and the exposure to irrigants.
Effect of cranberry supplementation on liver enzymes and cardiometabolic risk factors in patients with NAFLD: a randomized clinical trial
Authors: Masnadi Shirazi Kourosh , Shirinpour Elham , Masnadi Shirazi Arman , Nikniaz Zeinab
Published: November 2021

Background

We aimed to evaluate the effect of cranberry supplementation on serum liver enzymes, hepatic steatosis, and cardiometabolic risk factors in patients with non-alcoholic fatty liver (NAFLD).

Methods

In the present parallel-designed randomized controlled clinical trial, 110 patients with NAFLD were enrolled. The patients were randomized to receive 144 mg cranberry capsule or placebo for 6 months. The primary efficacy of the treatment was lipid profile, glycemic measurements, and liver enzyme levels.

Results

The data were reported for 46 in the supplementation group and 48 in the placebo group. The patient’s mean (SD) age was 43.16 (11.08) years. No significant differences between groups were observed regarding the post-intervention level of liver enzyme. The mean after-intervention levels of total cholesterol (p < 0.001) and triglyceride (p = 0.01) were significantly lower in the intervention group compared with the placebo group. At the end of the study, the mean insulin and HOMA-IR levels were significantly lower in the cranberry group compared with the placebo group. Significantly more patients in the cranberry group experienced a decrease in steatosis level compared with the control group.

Conclusion

The results of the present study showed that cranberry supplementation had a positive effect on some lipid profiles, insulin resistance, and hepatic steatosis in patients with NAFLD.

Trial registration

IRCT20200725048200N1; first registration date: 11.8.2020.
Ethical challenges faced by French military doctors deployed in the Sahel (Operation Barkhane): a qualitative study
Authors: Lamblin Antoine , Derkenne Clément , Trousselard Marion , Einaudi Marie-Ange
Published: November 2021

Background

French military doctors are currently deployed in the Sahel to support the armed forces of Operation Barkhane, in medical or surgical units. As well as supporting French soldiers, their other missions are diverse and complex: medical assistance to civilians and persons under control (PUC), advice to commanding officers. These tasks can create ethical dilemmas when decisions are forced upon doctors that may be in conflict with medical values or fundamental principles. Little is known about the specific dilemmas experienced by French military doctors in overseas operations. We therefore conducted a qualitative study among doctors and surgeons recently deployed to the Sahel to explore and better understand this question.

Method

Semi-structured, face-to-face interviews were conducted with 20 French military doctors or surgeons deployed since January 2016 in medical or surgical facilities in Mali and Chad.

Results

All interviewed doctors reported having faced several ethical dilemmas during missions. All reported dilemmas involved the treatment of civilians (while delivering community medical assistance) or of PUC. The dilemmas involved choices as to which patients to treat, the use of care as a means to an end by military authorities, and the level of care attainable in the absence of any possible hospital follow-up. Questions of delivering care at the risk of their own safety or the mission’s and of treating openly hostile patients were also brought up. Several dilemmas stemmed from the dual loyalty problem, namely the conflict between military doctors’ duty of care to patients and to the military institution, but this was not the only factor involved. Contextual factors (restricted resources and security constraints) and psychological factors (especially hostility towards the enemy) were also associated with many of the reported dilemmas.

Conclusion

This is the first reported study focusing on the ethical dilemmas encountered by French military doctors in overseas operations. It provides unique insights into their ethical experiences and should prove useful in improving operational training for healthcare personnel deployed on overseas missions.
Cost and consequences of using 7.1 % chlorhexidine gel for newborn umbilical cord care in Kenya
Authors: Brown Lecia , Martin Alan , Were Christopher , Biswas Nandita , Liakos Alexander , DeAngelis Elena , Evitt Lee Alexandra
Published: November 2021

Background

Omphalitis is an important contributor to neonatal mortality in Kenya. Chlorhexidine digluconate 7.1 % w/w (CHX; equivalent to 4 % w/w chlorhexidine) was identified as a life-saving commodity for newborn cord care by the United Nations and is included on World Health Organization and Kenyan Essential Medicines Lists. This pilot study assessed the potential resource savings and breakeven price of implementing CHX for neonatal umbilical cord care versus dry cord care (DCC) in Kenya.

Methods

We employed a cost-consequence model in a Kenyan birth cohort. Firstly, the number of omphalitis cases and cases avoided by healthcare sector were estimated. Incidence rates and treatment effect inputs were calculated from a Cochrane meta-analysis of randomised clinical trials (RCTs) (base case) and 2 other RCTs. Economic outcomes associated with omphalitis cases avoided were determined, including direct, indirect and total cost of care associated with omphalitis, resource use (outpatient visits and bed days) and societal impact (caregiver workdays lost). Costs and other inputs were sourced from literature and supplemented by expert clinical opinion/informed inputs, making necessary assumptions.

Results

The model estimated that, over 1 year, ~ 23,000 omphalitis cases per 500,000 births could be avoided through CHX application versus DCC, circumventing ~ 13,000 outpatient visits, ~ 43,000 bed days and preserving ~ 114,000 workdays. CHX was associated with annual direct cost savings of ~ 590,000 US dollars (USD) versus DCC (not including drug-acquisition cost), increasing to ~ 2.5 million USD after including indirect costs (productivity, notional salary loss). The most-influential model parameter was relative risk of omphalitis with CHX versus DCC. Breakeven analysis identified a budget-neutral price for CHX use of 1.18 USD/course when accounting for direct cost savings only, and 5.43 USD/course when including indirect cost savings. The estimated breakeven price was robust to parameter input changes. DCC does not necessarily represent standard of care in Kenya; other, potentially harmful, approaches may be used, meaning cost savings may be understated.

Conclusions

Estimated healthcare cost savings and potential health benefits provide compelling evidence to implement CHX for umbilical cord care in Kenya. We encourage comprehensive data collection to make future models and estimates of impacts of upscaling CHX use more robust.
Community-based support for children who are next-of-kin for a parent experiencing illness or disability – a scoping review
Authors: Steffenak Anne Kjersti Myhrene , Anderzén-Carlsson Agneta , Opheim Elin , Sandsdalen Tuva
Published: November 2021

Introduction

Children who are next-of-kin, for a parent who experience illness or disability, need support. In Norway, guidelines, routines and structured approaches in the community health services are lacking regarding involving children in the care of a parent and for services when supporting children as next-of-kin. Additionally, no existing international review has focused on support from community health and social services for children who are next-of-kin to a parent regardless of the specific illness or disability.

Aims

This scoping review examined the current knowledge regarding the types of community health and social services support to children 0 to 17 years old living with a parent experiencing illness or disability. The review also identified children’s support preferences and needs.

Methods

The scoping review involved five stages; identifying research question; identifying relevant articles; selecting articles; charting the data and finally, collating, summarizing and reporting the results.

Results

Articles which included community health and social services interventions and children’s preferences or needs for support were included. The foci of interventions included preventive education, peer support, psychosocial support, and interventions focusing on family communication and recovery planning. Articles focusing on children’s preferences or need for support described their wish to be recognized as a next-of-kin, having someone to talk to and professional and peer support.

Conclusion

The review highlighted the importance of children receiving support according to their preferences. It is important to elicit children’s voices, to ensure community health and social services are developed for and tailored to this population.
Selection shapes the landscape of functional variation in wild house mice
Authors: Lawal Raman Akinyanju , Arora Uma P. , Dumont Beth L.
Published: November 2021

Background

Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood.

Results

Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans.

Conclusions

Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.
Early inflammatory events of mastitis—a pilot study with the isolated perfused bovine udder
Authors: Brand Kathrin Susanne , Filor Viviane , Bäumer Wolfgang
Published: November 2021

Background

Bovine mastitis is an important health and cost factor in the milk industry. To elucidate whether isolated perfused bovine udders can be used to study early inflammatory events of mastitis, 1 mg of lipopolysaccharide (LPS) was instilled into quarters of 10 isolated perfused bovine udders. Three hours and 6 h after LPS instillation, tissue samples were taken from the gland cistern and base of the udder, subsequently stored in RNAlater and processed for the determination of inflammation-dependent gene regulation by real-time RT-qPCR. Gene expression analysis was performed using delta-delta Ct method. To translate mRNA results to protein, IL-1ß and IL-6 were determined in tissue homogenate by ELISA.

Results

The instillation of 1 mg LPS lead to an increased expression of pro-inflammatory cytokines and chemokines like TNF-α, CCL20, CXCL8 as well as of IL-1 ß, IL-6 and IL-10, lingual antimicrobial peptide (LAP) and S100A9. However, the degree of elevation differed slightly between gland cistern and udder base and markedly between 3 and 6 h after instillation, with a distinct increase in mediator expression after 6 h. IL-1β protein increased in a time-dependent manner, whereas IL-6 was unchanged within 6 h of LPS instillation.

Conclusion

Compared to in vivo studies with instillation of LPS into udders of living cows, a similar inflammation-dependent gene regulation profile can be mimicked in the isolated perfused bovine udder, indicating a supplementation of animal experiments.

Graphical abstract
Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals
Authors: Bozack Anne K. , Rifas-Shiman Sheryl L. , Coull Brent A. , Baccarelli Andrea A. , Wright Robert O. , Amarasiriwardena Chitra , Gold Diane R. , Oken Emily , Hivert Marie-France , Cardenas Andres
Published: November 2021

Background

Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6–10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs usingcomb-p(Sidakp < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses.

Results

Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10–6). Both associations remained significant but attenuated in blood DNAm collected at mid-childhood (p < 0.01). Two and nine Mn-associated DMPs were identified in male and female infants, respectively (FDR < 0.05), with two and six persisting in mid-childhood (p < 0.05). All metals except Ba and Pb were associated with ≥ 1 DMR among all infants (Sidak p < 0.05). Overlapping DMRs annotated to genes in the human leukocyte antigen (HLA) region were identified for Cr, Cs, Cu, Hg, Mg, and Mn.

Conclusions

Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.
Ground state solutions and infinitely many solutions for a nonlinear Choquard equation
Authors: Wang Tianfang , Zhang Wen
Published: November 2021

In this paper we study the existence and multiplicity of solutions for the following nonlinear Choquard equation:
$$\begin{aligned} -\Delta u+V(x)u=\bigl[ \vert x \vert ^{-\mu }\ast \vert u \vert ^{p}\bigr] \vert u \vert ^{p-2}u,\quad x \in \mathbb{R}^{N}, \end{aligned}$$
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where $N\geq 3$
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, ∗ represents the convolution between two functions. We assume that the potential function $V(x)$
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satisfies general periodic condition. Moreover, by using variational tools from the Nehari manifold method developed by Szulkin and Weth, we obtain the existence results of ground state solutions and infinitely many pairs of geometrically distinct solutions for the above problem.
The nutriRECIPE-Index – development and validation of a nutrient-weighted index for the evaluation of recipes
Authors: Forner Frank , Volkhardt Ina , Meier Toni , Christen Olaf , Stangl Gabriele I.
Published: November 2021

Background

Our objective was to develop a nutrient-based index for evaluating and improving menus in public catering. The nutriRECIPE-Index comprises 24 nutrients and nutrient groups. In developing the index, the following steps were included: setting the goals of the index, nutrient selection, target metrics and scaling, weighting, proof of concept and validation of the index. Furthermore, a unique database was created to integrate bioactive plant compounds in the assessment. An assessment of standard recipes and supposedly healthy recipes should show a significant difference in the results of the nutriRECIPE-Index. Finally, the nutriRECIPE-Index should generate similar or more specific results than existing indices such as the Nutri-Score and the Healthy Meal Index.

Methods

A whole meal cycle (comprising 6 weeks, 106 recipes and including different menu lines, partially with different side dishes) at a university canteen was analysed with the Federal Food Code (BLS) and the nutriRECIPE-Index. The Healthy Meal Index (comprising 3 nutritionally relevant items) and the Nutri-Score algorithm (comprising 7 items) were used to validate the nutrient composition and the results of the nutriRECIPE-Index.

Results

The resulting scores of the recipes and menu lines showed substantial differences, wherein the meals of a health-promoting menu line usually received higher scores than the standard recipes. A correlation between the nutriRECIPE-Index and the Healthy Meal Index (0.604) and the Nutri-Score (0.591) was observed. The nutriRECIPE-Index was better at identifying the worst menus and could better separate mediocre menus from good menus.

Conclusion

The nutriRECIPE-Index is a useful and comprehensive tool for evaluating the nutritional value of recipes and is the first to consider bioactive plant compounds. Further adjustments to different target populations, settings, and cultural backgrounds are possible.
A prediction model for the decline in renal function in people with type 2 diabetes mellitus: study protocol
Authors: Gregorich Mariella , Heinzel Andreas , Kammer Michael , Meiselbach Heike , Böger Carsten , Eckardt Kai-Uwe , Mayer Gert , Heinze Georg , Oberbauer Rainer
Published: November 2021

Background

Chronic kidney disease (CKD) is a well-established complication in people with diabetes mellitus. Roughly one quarter of prevalent patients with diabetes exhibit a CKD stage of 3 or higher and the individual course of progression is highly variable. Therefore, there is a clear need to identify patients at high risk for fast progression and the implementation of preventative strategies. Existing prediction models of renal function decline, however, aim to assess the risk by artificially grouped patients prior to model building into risk strata defined by the categorization of the least-squares slope through the longitudinally fluctuating eGFR values, resulting in a loss of predictive precision and accuracy.

Methods

This study protocol describes the development and validation of a prediction model for the longitudinal progression of renal function decline in Caucasian patients with type 2 diabetes mellitus (DM2). For development and internal-external validation, two prospective multicenter observational studies will be used (PROVALID and GCKD). The estimated glomerular filtration rate (eGFR) obtained at baseline and at all planned follow-up visits will be the longitudinal outcome. Demographics, clinical information and laboratory measurements available at a baseline visit will be used as predictors in addition to random country-specific intercepts to account for the clustered data. A multivariable mixed-effects model including the main effects of the clinical variables and their interactions with time will be fitted. In application, this model can be used to obtain personalized predictions of an eGFR trajectory conditional on baseline eGFR values. The final model will then undergo external validation using a third prospective cohort (DIACORE). The final prediction model will be made publicly available through the implementation of an R shiny web application.

Discussion

Our proposed state-of-the-art methodology will be developed using multiple multicentre study cohorts of people with DM2 in various CKD stages at baseline, who have received modern therapeutic treatment strategies of diabetic kidney disease in contrast to previous models. Hence, we anticipate that the multivariable prediction model will aid as an additional informative tool to determine the patient-specific progression of renal function and provide a useful guide to early on identify individuals with DM2 at high risk for rapid progression.
Urban form and economic sustainability in housing projects
Authors: Ghaffar Mohamed Mahmoud Ahmed Abdel , El Aziz Noha Ahmed Abd
Published: November 2021

Urban areas in metropolitan cities like Cairo suffer from economic, social, and environmental predicaments. Urban economic sustainability is an approach that reforms the urban performance to gain direct benefits such as minimizing costs and maximizing profits and indirect benefits as better social, environmental, and cultural aspects. This research suggests applying such an approach to enhance Egyptian housing projects. The main research question is how to evaluate the economic sustainability of urban forms?. The study presents a “Sustainable Urban Economy model” (SUE model) linking urban fabric, land use pattern, transportation, and street network design with economic sustainability. Research methods and tools include interviews (Delphi method) with 25 urban planning/design and urban economic experts to refine the model. Results show the most effective components of the urban form on economic sustainability (accessibility and degree of permeability, population density, built, and the impact of sub-indicators on the main components. Moreover, results indicate that the seven most influential indicators are the built-up to total space ratio, mixed-use ratio, built-up ratio, population density, floor area ratio, degree of accessibility, and public transportation. Experts suggested values for the seven indicators to measure how the urban form can achieve high economic, environmental, and social performance in the Egyptian context.
Oncologic Home-Hospitalization Delivers a High-Quality and Patient-Centered Alternative to Standard Ambulatory Care: Results of a Randomized-Controlled Equivalence Trial
Authors: Cool Lieselot , Missiaen Jana , Debruyne Philip , Pottel Hans , Foulon Veerle , Lefebvre Tessa , Tack Laura , Archie Petra , Vandijck Dominique , Van Eygen Koen
Published: November 2021

PURPOSE

Given the increasing burden of cancer on patients, health care providers, and payers, the shift of certain outpatient procedures to the patients' homes (further indicated as oncologic home-hospitalization [OHH]) might be a high-quality, patient-centered, and cost-effective alternative to standard ambulatory cancer care (SOC).

METHODS

A randomized-controlled trial was conducted to evaluate the quality of a locally implemented model for OHH (n = 74) compared with SOC (n = 74). The model for OHH consisted of home administration of certain subcutaneous cancer drugs (full OHH) and home nursing assessments before ambulatory systemic cancer therapy (partial OHH). Quality was evaluated based on patient-reported quality of life (QoL) and related end points; service use and cost data; safety data; patient-reported satisfaction and preferences; and model efficiency. An equivalence design was used for primary end point analysis. Participants were followed during 12 weeks of systemic cancer treatment.

RESULTS

This trial demonstrated equivalence of both models (OHH v SOC) in terms of patient-reported QoL (95% CI not exceeding the equivalence margin of 10%). Full OHH resulted in significantly less hospital visits (mean of 5.6 ± 3.0 v 13.2 ± 4.6; P = .011). Partial OHH reduced waiting times for therapy administration at the day care unit with 45% per visit (2 hours 36 minutes ± 1 hour 4 minutes v 4 hours ± 1 hour 4 minutes; P < .001). No safety issues were detected. Of the intervention group, 88% reported to be highly satisfied with the OHH model, and 77% reported a positive impact on their QoL. At study end, 60% of both study arms preferred OHH above SOC.

CONCLUSION

The shift of particular procedures from the outpatient clinic to the patients' homes offers a high-quality and patient-centered alternative for a large proportion of patients with cancer. Further research is needed to evaluate potential cost-efficiency.
Real-Life Long-Term Cohort of Patients With Stage IIIA Non–Small-Cell Lung Cancer: Overall Survival Related to Patients' Characteristics and Multiple Treatment Models
Authors: Abrão Fernando Conrado , Moreira Frederico Rafael , de Abreu Igor Renato Louro Bruno , Marciano Marcelo Giovanni , Younes Riad Naim
Published: November 2021

PURPOSE

This real-life cohort of patients describes the treatment patterns and compares the overall survival (OS) and hazard risk of utilization of multiple therapies.

MATERIALS AND METHODS

Electronic medical registries of patients with stage III non–small-cell lung cancer (NSCLC) regularly attended in 72 hospitals were included. Univariate and multivariate analyses were conducted to evaluate the primary patients' characteristics leading to better OS and cancer-specific survival.

RESULTS

A total of 3,363 patients with stage III NSCLC followed over 19 years were included in this study. The median age was 66.00 (58.00-72.00) years, 65% male, and 41.2% with squamous cell carcinoma followed by adenocarcinoma (34.6%) and undifferentiated carcinoma (13.1%) in clinical stage T3 (50.3%), T2 (29.3%), and T4 (12.3%). The median survival (in months) was 18.4 (95% CI, 16.9 to 19.5) in patients submitted to radiotherapy plus chemotherapy, 11.2 (95% CI, 10.5 to 12.1) to chemotherapy, 31.5 (95% CI, 25.9 to 37.7) to surgery plus chemotherapy, and 33.8 (95% CI, 28.3 to 47.8) to chemotherapy plus radiotherapy plus surgery. The median cancer-specific survival (in months) was 19.3 (95% CI, 17.9 to 20.9) in patients submitted to radiotherapy plus chemotherapy, 12.1 (95% CI, 11.1 to 12.9) to chemotherapy, 36.9 (95% CI, 29.6 to 43.2) to surgery plus chemotherapy, and 41.3 (95% CI, 32.1 to 61.3) to chemotherapy plus radiotherapy plus surgery. The patients treated with multiple chemotherapy plus radiotherapy followed by surgery had significantly better OS and lower mortality rates than those treated with other treatments (adjusted hazard ratio, 0.55; 95% CI, 0.45 to 0.66; P < .001). At the end of the study, 11.2% and 10.7% of the patients were living with and without cancer, respectively.

CONCLUSION

Our real-life 19-year cohort study has shown that only 30.3% of the total patients with stage III NSCLC have been submitted to standard chemotherapy and radiotherapy treatment. This may show a substantial difference between the recruited clinical trials' patients and the real-life patients' characteristics in daily routine treatment.
3-Azidoarynes: Generation and Regioselective Reactions
Authors: Taguchi Jumpei , Kimura Kota , Igawa Kazunobu , Tomooka Katsuhiko , Hosoya Takamitsu
Published: November 2021

The generation of 3-azidoarynes from o-iodoaryl triflate-type precursors was achieved using a silylmethyl Grignard reagent as the activator. The azido group served to control the regioselectivity of the reaction of 3-azidoarynes with arynophiles. The remaining azido group in the adduct also served as a transformable functional group, enabling further derivatization to various nitrogen-containing compounds.