bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features and imaging examination assessment of cervical lymph nodes for thyroid carcinoma
Authors: Wei Bei , Yao Jincao , Peng Chanjuan , Zhao Shanshan , Wang Hui , Wang Liping , Zhu Xi , Kong Yuting , Chen Liyu , Xu Dong
Published: December 2023

Backgrounds

The purpose of this study is to investigate the relationship between clinical characteristics and cervical lymph node metastasis (LNM) in patients with thyroid carcinoma, as well as estimate the preoperative diagnosis values of ultrasound (US) and contrast enhanced computed tomography (CECT) examinations on the neck for detection of cervical LNM in thyroid carcinoma.

Methods

A retrospective analysis of 3 026 patients with surgically proven thyroid carcinoma was conducted. Patients’ clinical characteristics, including gender, age, tumor size, bilateral lesions, multifocality, adenomatous nodules, Hashimoto’s thyroiditis (HT), and extrathyroidal extension, were collected to explore their association with cervical LNM in thyroid carcinoma. Preoperative assessments for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were conducted through US and CECT. The diagnostic value of US, CECT and US combined with CECT for detection of LNM located in various cervical compartments was estimated based on the pathological results.

Results

The risk of cervical LNM was higher in thyroid cancer patients who were male, age < 55 years old, tumor size > 10 mm, bilateral lesions, and extrathyroidal extension, while multifocality, adenomatous nodules and HT had no significant effect on LNM. US, CECT and US combined with CECT all had a higher sensitivity to LLNM (93.1%, 57.8%, 95.4%) than to CLNM (32.3%, 29.0%, 43.4%). US and CECT had a high specificity to both CLNM and LLNM (94.3–97.8%).

Conclusion

Preoperative clinical characteristics and imaging examinations on patients with thyroid carcinoma are crucial to the evaluation of cervical lymph nodes and conducive to individualizing surgical treatments by clinicians. US combined with CECT are superior to single US or CECT alone in detection of CLNM and LLNM.
What happens after forensic psychiatric care? A latent class analysis of dimensions of welfare for former forensic psychiatric patients
Authors: Noland Ebba , Klötz Logan Fia , Sjöström Stefan , Strandh Mattias
Published: December 2023

Background

Mentally disordered offenders are a heterogenous group regarding psychopathology as well as background factors, which makes it likely that more than one stereotypical life situation will apply to all forensic psychiatric patients following discharge. Knowledge about typical life situations would be valuable for optimising support for improving the overall life situation of these individuals. This paper investigates life situations from the perspective of level of living research and resources in terms of different welfare dimensions.

Methods

Included were all all individuals (n = 1146) who had been discharged from forensic psychiatric care in Sweden during 2009–2018 and were included in the Swedish National Forensic Psychiatric Register. Follow-up time varied from 4 to 3644 days, (m = 1697, Md = 1685). Register data from several different registers was combined. Data was analysed using latent class analysis, and multinominal logistic regression analysis investigated what background factors were associated with class membership.

Results

The results show that there are four subgroups of post-discharge life situations: the high support group, the general psychiatric needs group, the working group, and the family group. The high support group was the largest, representing 54% of the entire sample. There are background factors associated with group membership, including both age at discharge, length of stay in forensic psychiatric care and pre-index crime historical factors.

Conclusions

This study contributes to the understanding of the post-discharge lives of former forensic psychiatric patients and shows that for several subgroups, negative outcomes are rare. Knowledge about these subgroups could be drawn upon to make informed decisions about in- and outpatient forensic psychiatric care, discharge from forensic psychiatric services, and what support is offered to former forensic psychiatric patients.
The action logic of the older adults about health-seeking in South Rural China
Authors: Lin Jianqiang , Yang Dan , Zhao Xinyu , Xie Liqiong , Xiong Kun , Hu Lei , Xu Yue , Yu ShanShan , Huang Wenyong , Gong Ni , Liang Xiaoling
Published: December 2023

Background

The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active.

Methods

Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis.

Results

Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) ‘unpredictable’ troubles: they tended to favor the ‘optimal’ solution of keeping their lives in order rather than the best medical treatment options.

Conclusion

This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the ‘inaccessibility’ of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.
The role of community pharmacists in primary and secondary prevention of skin cancer: an evaluation of a Flemish skin cancer prevention campaign
Authors: Proesmans Kristiaan , Van Vaerenbergh Frauke , Lahousse Lies
Published: December 2023

Background

Skin cancer is a leading form of cancer in Belgium. Prevention of skin cancer by community pharmacists can play a role in increasing awareness and promoting sun protection. However, which persons could be reached by community pharmacists for skin cancer awareness in Belgium and whether this increased awareness is associated with increased sun protection and early detection remains unclear.

Methods

Demographics of approached persons in Flemish community pharmacies during the months of May-June 2022 and the content of the skin cancer counseling were retrieved from the pharmacy database. Sunscreen purchases and dermatologist visits were evaluated up to 180 days after the skin cancer counseling.

Results

Community pharmacists provided skin cancer counseling to a broad population of visitors (n = 822, 69% females, median age of 59 years Q1-Q3: 44–71 years). During the campaign, 822 visitors received a leaflet with skin cancer prevalence and sunscreen importance. On top of that, 335 visitors (41%) received additional counseling: skin type sensitivity was checked for 198 visitors (24%), typical characteristics of melanoma were discussed with 100 visitors (12%) and 37 visitors (5%) were referred to a physician for further information or concerns regarding a skin spot. Overall, one out of three visitors purchased sunscreen on the day of the counseling (33%, increasing up to 38% after 180 days). Among people under 20 years, this was even higher (51%). Additional counseling increased the likelihood of a dermatologist visit within 180 days (OR = 1.80; 95%CI: 1.12–2.88).

Conclusions

By providing skin cancer counseling in Belgian community pharmacies, a broad range of citizens was reached and triggered to purchase sunscreen, often on the same day as the counseling. Notably, young people were likely to purchase sunscreen. Citizens receiving additional counseling were more likely to visit a dermatologist within 180 days.
The postgraduate medical educational climate assessed by the Danish Residency Educational Climate Test (DK-RECT): a validation and cross-sectional observational study
Authors: Jacobsen Rikke Borre , Boor Klarke , Christensen Karl Bang , Ung Vilde Hansteen , Carlsen Jørn , Kirk Ole , Hanefeld Dziegiel Morten , Østergaard Elsebet , Rochat Per , Albrecht-Beste Elisabeth , Droogh Marjoes , Lapperre Therese S. , Scheele Fedde , Sørensen Jette Led
Published: December 2023

Background

A good educational climate is essential for delivering high-quality training for medical trainees, professional development, and patient care. The aim of this study was to (1) validate the Dutch Residency Educational Climate Test (D-RECT) in a Danish setting and (2) describe and evaluate the educational climate among medical trainees.

Methods

D-RECT was adopted in a three-step process: translation of D-RECT into Danish (DK-RECT), psychometric validation, and evaluation of educational climate. Trainees from 31 medical specialties at Copenhagen University Hospital – Rigshospitalet, Denmark were asked to complete an online survey in a cross-sectional study.

Results

We performed a forward-backward translation from Dutch to Danish. Confirmatory factor analysis showed that DK-RECT was robust and valid. The reliability analysis showed that only seven trainees from one specialty were needed for a reliable result. With 304 trainees completing DK-RECT, the response rate was 68%. The subsequent analysis indicated a positive overall educational climate, with a median score of 4.0 (interquartile range (IQR): 3.0–5.0) on a five-point Likert scale. Analysis of the subscales showed that the subscale Feedback received the lowest ratings, while Supervision and Peer collaboration were evaluated highest.

Conclusions

Psychometric validation of D-RECT in a Danish context demonstrated valid results on the educational climate in specialist training. DK-RECT can be used to evaluate the effectiveness of interventions in the future and can facilitate the conversation on the educational climate.
Information-seeking process and clinical scenario solving: introduction of a new tool in nursing education
Authors: Vahedparast Hakimeh , Ganjoo Mahasty , Ghasemi Farkhondeh , Dehghani Leila
Published: December 2023

Background

Nursing education has recently undergone changes to improve care. These changes require innovative and transformative strategies in nursing education. Search as learning is one of the educational methods this study was conducted to determine the effect of the information searching process on scenario-based learning in nursing students.

Methods

This study is a single group semi-experimental study that was conducted on 38 nursing students in 2021. Students first drew a concept map according to their existing knowledge about two scenarios (diabetes and trauma). The students then searched the medical databases and drew another concept map after the search. Data were analyzed using descriptive statistics, paired mean tests and Pearson correlation coefficients.

Results

The results showed that the mean scores of the participants in the diabetes scenario before and after the search were 18.32 ± 5.50 and 19.13 ± 7.54, respectively, and those in the trauma scenario were 18.58 ± 7.69 and 29.61 ± 7, respectively (P < 0.01). The mean scores of the details of the conceptual map before and after the search in terms of themes, number of levels and relationships were statistically significant. In both scenarios, there was a positive correlation (p < 0.01) between learning and the number of correct webpages (r = 0.74 for trauma and r = 0.64 for diabetes), as well as between search time and the amount of learning (r = 0.77 for trauma and 0.64 for diabetes).

Conclusions

The results showed that search as learning in nursing education scenarios led to student learning. It is recommended that nurse educators use this method as a tool in nursing education to increase students’ awareness and develop their thinking skills. Further research is recommended to determine the effectiveness of this method with other educational methods.
The association between electronic health information usage and patient-centered communication: a cross sectional analysis from the Health Information National Trends Survey (HINTS)
Authors: Knowles Heidi , Swoboda Thomas K. , Sandlin Devin , Huggins Charles , Takami Trevor , Johnson Garrett , Wang Hao
Published: December 2023

Background

Patient-provider communication can be assessed by the patient-centered communication (PCC) score. With rapid development of electronic health (eHealth) information usage, we are uncertain of their role in PCC. Our study aims to determine the association between PCC and eHealth usage with the analysis of national representative survey data.

Methods

This is a cross sectional analysis using the Health Information National Trends Survey 5 (HINTS 5) cycle 1 to cycle 4 data (2017–2020). Seven specific questions were used for PCC assessment, and eHealth usage was divided into two types (private-eHealth and public-eHealth usage). A multivariate logistic regression was performed to determine the association between PCC and eHealth usage after the adjustment of other social, demographic, and clinical variables.

Results

Our study analyzed a total of 13,055 unweighted participants representing a weighted population of 791,877,728. Approximately 43% of individuals used private eHealth and 19% used public eHealth. The adjusted odds ratio (AOR) of private-eHealth usage associated with positive PCC was 1.17 (95% CI 1.02–1.35, p = 0.027). The AOR of public-eHealth usage associated with positive PCC was 0.84 (95% CI 0.71–0.99, p = 0.043).

Conclusion

Our study found that eHealth usage association with PCC varies. Private-eHealth usage was positively associated with PCC, whereas public-eHealth usage was negatively associated with PCC.
Finding social need-les in a haystack: ascertaining social needs of Medicare patients recorded in the notes of care managers
Authors: Shafer Paul R. , Davis Amanda , Clark Jack A.
Published: December 2023

Background

Unmet social needs may impair health and access to health care, and intervening on these holds particular promise in high-risk patient populations, such as those with multiple chronic conditions. Our objective was to identify social needs in a patient population at significant risk—Medicare enrollees with multiple chronic illnesses enrolled in care management services—and measure their prevalence prior to any systematic screening.

Methods

We partnered with Renova Health, an independent Medicare Chronic Care Management (CCM) provider with patients in 10 states during our study period (January 2017 through August 2020). Our data included over 3,000 Medicare CCM patients, representing nearly 20,000 encounters. We used a dictionary-based natural language processing approach to ascertain the prevalence of six domains of barriers to care (food insecurity, housing instability, utility hardship) and unmet social needs (health care affordability, need for supportive services, transportation) in notes taken during telephonic Medicare CCM patient encounters.

Results

Barriers to care, specifically need for supportive services (2.4%) and health care affordability (0.8%), were the most prevalent domains identified. Transportation as a barrier to care came up relatively less frequently in CCM encounters (0.1%). Unmet social needs were identified at a comparatively lower rate, with potential housing instability (0.3%) flagged most followed by potential utility hardship (0.2%) and food insecurity (0.1%).

Conclusions

There is substantial untapped opportunity to systematically screen for social determinants of health and unmet social needs in care management.
Readiness of managers and health care workers for e-Health: a cross-sectional study in Khartoum primary health care centers, Sudan
Authors: Yassen Eilaf , Atia Ibrahim A. , Manhal Gaffar Alemam A. , Elzein Mohammedelhadi , Mohamed Mozan , Siddig Musab , Eltayeb Raghad , Asmally Rofida , Mohammed Sara , Elhassan Sujood
Published: December 2023

Background

e-Health is defined as “the use, in the health sector, of digital data— transmitted, stored and retrieved electronically—for clinical, educational and administrative purposes, both at the local site and at a distance”. In Primary health care (PHC), the role of e-Health in promoting PHC systems defines its need to achieve the PHC aims. This literary work aims to study the readiness of managers and healthcare workers for e-Health at Khartoum state PHC centers.

Methods

This was a facility-based cross-sectional study that took place between February and August 2022. A sample size of 327 was calculated, and multistage cluster sampling was used. A validated questionnaire was used, and the generated data were analyzed using the Statistical Package for Social Sciences (SPSS). Variables were described as n (%) and mean ± SD. Non-parametric tests and Spearman’s correlation were used to investigate the association of readiness scores with different categorical and numerical variables, respectively. A standard multiple regression model was used to model the associations.

Results

A total of 262 forms were completed. The overall readiness percentages were low for both managers (52.8%) and healthcare workers (55.3%). Factors associated with e-Health readiness included occupation, doctors’ level of expertise, PHC center, and PHC center type.

Conclusions

This study reports low levels of e-Health readiness as reflected by managers and HCWs in Khartoum State PHC. Project planners need to be aware of the obstacles and threats faced by e-Health initiatives if they are not carefully planned, executed, and monitored. Special attention must be given to addressing health inequities and inequalities to ensure that these projects will contribute to fostering accessibility to health services and narrowing the digital divide.
Genetic study of the causal effect of lipid profiles on insomnia risk: a Mendelian randomization trial
Authors: Gong Quancai , Guo Canshou
Published: December 2023

Objectives

In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze lipid profiles, including triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and lipoprotein A (LPA), in a European population to further assess the causal relationship between these lipid types and insomnia.

Materials and methods

This study explores the causal effect of lipid profiles on insomnia based on a genome-wide association study (GWAS)-derived public dataset using two-sample and multivariate Mendelian randomization (MVMR) analysis. The main MR analyses used inverse variance weighting (IVW) odds ratio (OR), and the sensitivity analyses included weighted median (WM) and MR‒Egger.

Results

Both MR and MVMR showed that lowering ApoA-1 and LPA levels had causal effects on the risk of insomnia [MR: per 10 units, ApoA-1: OR: 0.7546, 95% CI: 0.6075–0.9372, P = 0.011; LPA: OR: 0.8392, 95% CI: 0.7202–0.9778, P = 0.025; MVMR: per 10 units, ApoA-1: OR: 0.7600, 95% CI: 0.6362–0.9079, P = 0.002; LPA, OR: 0.903, 95% CI: 0.8283–0.9845, P = 0.021]. There were no causal effects of TG or ApoB on insomnia (all P > 0.05). The MR‒Egger intercept test, funnel plot, and IVW methods all suggested an absence of strong directional pleiotropy, and leave-one-out permutation analysis did not detect any single single-nucleotide polymorphism that had a strong influence on the results.

Conclusion

Elevated levels of ApoA-1 and LPA were independently and causally associated with the risk of insomnia, suggesting that elevated ApoA-1 and LPA levels may contribute to a reduced risk of insomnia.
Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer
Authors: Sheikhnia Farhad , Rashidi Vahid , Maghsoudi Hossein , Majidinia Maryam
Published: December 2023

Colorectal neoplasms are one of the deadliest diseases among all cancers worldwide. Thymoquinone (TQ) is a natural compound of Nigella sativa that has been used in traditional medicine against a variety of acute/chronic diseases such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders. This review aims to present a detailed report on the studies conducted on the anti-cancer properties of TQ against colorectal cancer, both in vitro and in vivo. TQ stands as a promising natural therapeutic agent that can enhance the efficacy of existing cancer treatments while minimizing the associated adverse effects. The combination of TQ with other anti-neoplastic agents promoted the efficacy of existing cancer treatments. Further research is needed to acquire a more comprehensive understanding of its exact molecular targets and pathways and maximize its clinical usefulness. These investigations may potentially aid in the development of novel techniques to combat drug resistance and surmount the obstacles presented by chemotherapy and radiotherapy.

Graphical Abstract
Trend and disparities in authorship of healthcare-related publications on the ongoing Russia-Ukraine war
Authors: Alagbo Habib Olatunji , Mitra Saloni , Madueke Karen , Azuwike Uchechi Blessing , Dos Santos Rocha Ferreira Samantha , Ademuyiwa Alimat Temitope , Adeleke Oluwaseun , Ejinkeonye Chigozirim , Onyebuchi David Izuchukwu , Atowoju Inioluwa , Odelola Faith Inioluwa , Kumari Jyoti , Sowunmi Marvellous , Al-Inaya Yana , Abdul-Rahman Toufik , Shlobin Nathan A.
Published: December 2023

Background

The Russia-Ukraine war has undeniably impacted global science and healthcare in Ukraine. Many Ukrainian researchers have had their projects disrupted by this war, either due to loss of life, displacement, or destruction of resources. Despite these challenges, these researchers have sought to make their voices heard. This scoping review highlights the trend of healthcare-related publications on the current Russia-Ukraine war and characterizes the contribution of Ukrainian authors to these publications.

Method

A comprehensive literature search was performed using two databases (Scopus and Pubmed) for publications related to the ongoing Russia-Ukraine war. We included articles only related to healthcare. We then extracted and analyzed bibliometric data.

Result

One hundred and eighty-three articles were identified, including 12 (6.6%) original articles, 26 (14.2%) cross-sectional studies, 19 (10.4%) letters to the editor, 10 (5.5%) commentaries, 5 (2.7%) perspectives, 35 (19.1%) editorials, 2 (1.1%) randomized controlled trials, 11(6.0%) correspondences, 13 (7.1%) opinions, 8 (4.4%) reviews and 42 (23.0%) are identified as others. 180 (98.4%) studies were in English, and 3 (1.7%) were in German. 54 (29.5%) papers on the war had at least one author affiliated with a Ukrainian institution, and 29 (15.9%) studies had authors with Ukrainian affiliation as first authors.

Conclusion

our study shows that there has been a significant number of publications on the Russia-Ukraine war and only a small portion of first authors, co-authors, and last authors of these publications are affiliated to an institution in Ukraine. Therefore, despite the relatively high number of publications, most publications do not arise from the perspective of Ukrainian authors.
Assessing the impact of transplant site on ovarian tissue transplantation: a single-arm meta-analysis
Authors: Xie Baoli , Li Jiaxu , Huang Yingqin , Hang Fu , Hu Qianwen , Yu Jiaxin , Qin Aiping
Published: December 2023

Background

Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered.

Objective

This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes.

Methods

We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English.

Results

Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6–40, I2: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20–40, I2: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11–36, I2: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0–17, I2: 0.00%, fixed effect).

Conclusion

Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation.

Registration Number

INPLASY202390008.
Toxoplasma gondii seroprevalence in reindeer (Rangifer tarandus tarandus L.) in northern Sweden: a cross-sectional study from 2014
Authors: Kautto Arja Helena , Olsen Abbey , Wallander Camilla , Vågsholm Ivar
Published: December 2023

Background

Toxoplasma gondii is a parasitic protozoan that can infect a wide range of warm-blooded animals, including humans. The infection with T. gondii, is of particular concern due to its potential impact on human and animal health. In Sweden, semi-domesticated reindeer (Rangifer tarandus tarandus L.) is an important species both economically and culturally, but susceptibility to Toxoplasma infection and seroprevalence in reindeer herds remain relatively understudied.

Results

A total of 528 reindeer, sampled at two slaughterhouses in Sweden in 2014, were investigated for antibodies to T. gondii. Specific antibodies to T. gondii were found in 5 of 209 (2.3%) tested adult reindeer and in 6 of 308 (1.9%) tested calves, giving an apparent total prevalence of 2.1% (95% confidence interval 1.1–3.8%). None of four putative risk factors studied (sex, age, type of grazing area, county) were statistically associated with T. gondii seroprevalence.

Conclusions

Swedish semi-domesticated reindeer are exposed to T. gondii and may harbour infectious tissue cysts. To mitigate the risk of T. gondii infection in consumers, reindeer meat should be frozen or cooked thoroughly before consumption. The global climate change may influence the seroprevalence and possible associated risk factors for T. gondii in reindeer. To be able to manage the risk and get better advice to the consumers there is a need for further investigations covering the whole spectra of herding conditions for reindeer.
A protocol for a single center, randomized, controlled trial comparing the clinical efficacy of 3% diquafosol and 0.1% hyaluronic acid in diabetic patients with dry eye disease
Authors: Chen Jiayan , Chen Yimeng , Qin Guanghao , Li Liangzhe , Li Mingze , Cheng Yuan , Zhuang Shuting , Li Zhihui , Zhang Qing , Wu Yi , Yang Lanting , Moutari Salissou , Moore Jonathan E. , Xu Ling , He Wei , Yu Sile , Pazo Emmanuel Eric , He Xingru
Published: December 2023

Background

The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients.

Methods

This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8.

Discussion

This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment.

Trial registration

ClinicalTrials.govNCT05682547. Registered on December 05, 2022.
Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis
Authors: Vélez-Pinto J. F. , Garcia-Arranz M. , García-Bernal D. , García Gómez-Heras S. , Villarejo-Campos P. , García-Hernández A. M. , Vega-Clemente L. , Jiménez-Galanes S. , Guadalajara H. , Moraleda J. M. , García-Olmo D.
Published: December 2023

Background

The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.

Methods

We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.

Results

One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.

Conclusions

Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
SARS-CoV-2-infected hiPSC-derived cardiomyocytes reveal dynamic changes in the COVID-19 hearts
Authors: Li Xiao , Hu Hengrui , Liu Wanlin , Zhang Qiyu , Wang Yujie , Chen Xingjuan , Zhu Yunping , Hu Zhihong , Wang Manli , Ma Jie , Leng Ling
Published: December 2023

Background

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease’s extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients.

Methods

In this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection.

Results

To this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern.

Conclusions

Our findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease.
On measure of noncompactness in variable exponent Lebesgue spaces and applications to integral equations
Authors: Metwali Mohamed M. A.
Published: December 2023

A novel measure of noncompactness is defined in variable exponent Lebesgue spaces $L^{p(\cdot )}$

L

p
(
⋅
)

on an unbounded domain $\mathbb{R}^{+}$

R
+

and its properties are examined. Using the fixed point method, we apply that measure to study the existence theorem for nonlinear integral equations. Our results can be handily applied in studying various types of (differential, integral, functional, and partial differential) equations in $L^{p(\cdot )}$

L

p
(
⋅
)

-spaces. The $L^{p(\cdot )} $

L

p
(
⋅
)

-spaces are natural extensions of classical constant exponent Lebesgue spaces $L_{p}$

L
p

, which allows us to bypass several restrictions that were previously discussed in the literature.
Current status and challenges of breast cancer prevention~DNA methylation would lead to groundbreaking progress in breast cancer prevention~
Authors: Tsukioki Takahiro , Khan Seema A. , Shien Tadahiko
Published: December 2023

The number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer. However, the effects of lifestyle habits on the human body are complexly intertwined with various factors, and the effects vary from person to person depending on their constitution, etc., so there is no basis for this. Therefore, primary prevention of breast cancer is still not being implemented appropriately and efficiently. Furthermore, advances in genomic technology make it possible to assess the risk of developing breast cancer in some individuals. As a result, the establishment of breast cancer prevention methods has become a health priority for high-risk individuals.

Drugs such as tamoxifen and raloxifene are known to prevent the development of breast cancer, based on the results of multiple randomized controlled trials, but there are concerns regarding the side effects of these powerful agents. In addition, several clinical studies have shown that prophylactic mastectomy for women who have BRCA mutations or who are identified as being at high risk reduces the incidence of breast cancer development. However, many issues, such as changes in long-term quality of life after preventive surgery, the optimal timing of surgery and the identification of women who are at high risk but will not develop breast cancer, remain uncertain. In other words, although many researchers have focused on chemoprevention and surgical prevention and clear preventive effects of these strategies have been confirmed, it cannot be said that they are widely accepted. Therefore, the current evidence for chemoprevention and surgical prevention, as well as highlights of several interesting lines of research currently underway, are summarized in this article.
Inter-organ communication involved in metabolic regulation at the whole-body level
Authors: Katagiri Hideki
Published: December 2023

Metabolism in each organ of multi-organ organisms, including humans, is regulated in a coordinated manner to dynamically maintain whole-body homeostasis. Metabolic information exchange among organs/tissues, i.e., inter-organ communication, which is necessary for this purpose, has been a subject of ongoing research. In particular, it has become clear that metabolism of energy, glucose, lipids, and amino acids is dynamically regulated at the whole-body level mediated by the nervous system, including afferent, central, and efferent nerves. These findings imply that the central nervous system obtains metabolic information from peripheral organs at all times and sends signals selectively to peripheral organs/tissues to maintain metabolic homeostasis, and that the liver plays an important role in sensing and transmitting information on the metabolic status of the body. Furthermore, the utilization of these endogenous mechanisms is expected to lead to the development of novel preventive/curative therapies for metabolic diseases such as diabetes and obesity.

(This is a summarized version of the subject matter presented at Symposium 7 presented at the 43rd Annual Meeting of the Japanese Society of Inflammation and Regeneration.)
A country report: impact of COVID-19 lockdowns on involuntary psychiatric treatment in Austria
Authors: Fellinger Matthäus , Waldhör Thomas , Vyssoki Benjamin , Amering Michaela , Leutgeb Lisa , Gschaider Andreas , Rappert Bernhard , König Daniel , Fugger Gernot , Knasmüller Philipp , Gmeiner Andrea
Published: December 2023

Background

Coercive measures such as involuntary psychiatric admission are considered a last resort in the treatment of people with psychiatric disorders. So far, numerous factors have been identified that influence their use. However, the link between a pandemic – in particular, restrictions such as lockdowns – and the use of involuntary psychiatric admission is unclear.

Aim

To examine the association between COVID-19 lockdowns and involuntary psychiatric admissions in Austria.

Method

This retrospective exploratory study assessed all involuntary psychiatric admissions and use of mechanical restraint in Austria, except for the federal state of Vorarlberg, between 1 January 2018 and 31 December 2020. Descriptive statistics and regression models were used.

Results

During the 3-year study period, 40 012 individuals (45.9% females, mean age 51.3 years) had 66 124 involuntary psychiatric admissions for an average of 10.9 days. Mechanical restraint was used during 33.9% of these admissions. In weeks of nationwide COVID-19 lockdowns (2020 v. 2018/2019), involuntary psychiatric admissions were significantly fewer (odds ratio = 0.93, P = 0.0001) but longer (11.6 (s.d.: 16) v. 10.9 (s.d.: 15.8) days). The likelihood of involuntary admission during lockdowns was associated with year (2020 v. 2018–2019; adjusted odds ratio = 0.92; P = 0.0002) but not with sex (P = 0.814), age (P = 0.310), use of mechanical restraint (P = 0.653) or type of ward (P = 0.843).

Conclusions

Restrictions such as lockdowns affect coercive measures and resulted in fewer but longer involuntary psychiatric admissions during weeks of lockdown in Austria. These results strengthen previous findings that showed the dependence of coercive measures on external factors, highlighting the need to further clarify causality and desired prevention effects when using coercive measures.
Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing
Authors: Sharma Ankur , Liu Xin , Chandra Vishal , Rai Rajani , Benbrook Doris M. , Woo Sukyung
Published: December 2023

SHetA2 is a promising, orally active small molecule with anticancer properties that target heat shock proteins. In this study, we aimed to investigate the pharmacodynamic (PD) effects of SHetA2 using preclinical in vitro and in vivo models of ovarian cancer and establish a physiologically based pharmacokinetic (PBPK)/PD model to describe their relationships with SHetA2 concentrations in mice. We found that daily oral administration of 60 mg/kg SHetA2 for 7 days resulted in consistent plasma PK and tissue distribution, achieving tumor drug concentrations required for growth inhibition in ovarian cancer cell lines. SHetA2 effectively induced cyclin D1 degradation in cancer cells in a dose-dependent manner, with up to 70% reduction observed and an IC50 of 4~5 µM. We identified cyclin D1 as a potential PD marker for SHetA2, based on a well-correlated time profile with SHetA2 PK. Additionally, we examined circulating levels of ccK18 as a non-invasive PD marker for SHetA2-induced apoptotic activity and found it unsuitable due to high variability. Using a PBPK/PD model, we depicted SHetA2 levels and their promoting effects on cyclin D1 degradation in tumors following multiple oral doses. The model suggested that twice-daily dosing regimens would be effective for sustained reduction in cyclin D1 protein. Our study provides valuable insights into the PK/PD of SHetA2, facilitating future clinical trial designs and dosing schedules.
Noninstrumented Free Fibula Flap for Cervical Osteomyelitis
Authors: Bindal Shivani , Fairchild Berry , Lamaris Gregory A. , Cochran Joseph A.
Published: December 2023

BACKGROUND AND IMPORTANCE:

Severe cases of cervical vertebral osteomyelitis can pose a challenge regarding reconstruction, stability/alignment, and infection eradication. Here we describe the application of vascularized free fibula (FF) flaps to reconstruct the cervical spine without instrumentation in the setting of severe osteomyelitis.

CLINICAL PRESENTATION:

Two patients presented with symptomatic multilevel cervical osteomyelitis. Both patients were treated with corpectomy and FF flap without instrumentation using a novel wedging and distraction technique to secure the flap into position. Clinical outcomes were based on neurological recovery and infection management. Computed tomography (CT) and CT angiography with 3-dimensional reconstruction were used to measure fusion status and patency of the anastomoses. CT of the cervical spine completed 8 weeks postoperatively demonstrated robust fusion of the fibula flaps to adjacent cervical vertebrae. In both patients, CT angiography demonstrated patency of the arterial anastomoses. Both flaps maintained persistent deformity correction. Both patients made full neurological recovery.

DISCUSSION:

This reconstructive approach represents a salvage technique that offers advantages in cases of prior hardware failure or unfavorable host factors with rapid fusion and definitive treatment with a single surgery.

CONCLUSION:

The use of FF flap without instrumentation seems to be a safe and effective option for cervical spine reconstruction in the setting of severe osteomyelitis.
Who Benefits from State Corporate Tax Cuts? A Local Labor Market Approach with Heterogeneous Firms: Reply
Authors: Suárez Serrato Juan Carlos , Zidar Owen
Published: December 2023

In Suárez Serrato and Zidar (2016), we estimate the incidence of state corporate taxes. Malgouyres, Mayer, and Mazet-Sonilhac (2023) highlight two errors, ignoring effects on firm composition and characterizing capital costs inconsistently. This reply corrects the structural model and corresponding incidence estimates. The incidence results are similar to the originally reported estimates and the confidence intervals widen for some estimates. In the corrected structural model, the firm owner incidence share estimate changes by 1.6 percentage points relative to the original version (i.e., 38.1 percent versus 36.5 percent). The worker share estimate is 35.0 percent. Landowners bear the remaining 26.8 percent. (JEL H22, H25, H32, H71, R23, R51)
The Impact of Host Language Proficiency on Migrants’ Employment Outcomes
Authors: Schmid Lukas
Published: December 2023

This paper estimates the economic gains from proficiency in the host country’s language on migrants’ employment outcomes by exploiting the exogenous placement of refugees to Swiss cantons and a sharp language border dividing German- and French-speaking regions. Using administrative data on African refugees who applied for Swiss asylum between 2008 and 2017, I compare French-speaking refugees assigned to the French-speaking region to French-speaking refugees assigned to the German-speaking region and adjust for common regional differences with outcomes from English-speaking African refugees. The results suggest that language proficiency more than doubles the employment level in the first five years after arrival. (JEL J15, J24, J31, J82, R23)
Herd Design
Authors: Arieli Itai , Gradwohl Ronen , Smorodinsky Rann
Published: December 2023

The classic herding model examines the asymptotic behavior of agents who observe their predecessors’ actions as well as a private signal from an exogenous information structure. In this paper, we introduce a self-interested sender into the model and study her problem of designing this information structure. If agents cannot observe each other, the model reduces to Bayesian persuasion. However, when agents observe predecessors’ actions, they may learn from them, potentially harming the sender. We identify necessary and sufficient conditions under which the sender can nevertheless obtain the same utility as when the agents are unable to observe each other. (JEL D82, D83, D91)
Mistakes in Future Consumption, High MPCs Now
Authors: Lian Chen
Published: December 2023

In a canonical intertemporal consumption model, future consumption mistakes (in response to saving changes) lead to higher current marginal propensities to consume (MPCs). These mistakes increase the value of changing current consumption relative to changing saving, as additional saving will not be spent optimally. Various behavioral biases can cause these mistakes, such as inattention, present bias, diagnostic expectations, and near-rationality (epsilon-mistakes). This result helps explain the empirical puzzle of high-liquidity consumers’ high MPCs. In my approach, predictions of sophistication (anticipation of future mistakes) can be derived independently of the underlying biases. (JEL D15, D91, E21)