bluuebunny/crossref_metadata_2025 huggingface dataset:
Ground-motion model for Housner’s spectrum intensity based on a novel hybrid-scenario approach
Authors: Campbell Kenneth W , Bozorgnia Yousef
Published: June 2023

We use a novel hybrid-scenario approach to develop a ground-motion model (GMM) for Housner’s spectrum intensity ( SI) using estimates of pseudo-spectral acceleration ( PSA) from the authors existing GMMs based on a scenario approach proposed in the literature and predictor variables from the same database used to develop the PSA GMMs. These estimates of SI are used together with the predictor variables to develop a hybrid-scenario GMM using mixed-effects regression analysis. Because the GMM is based on predicted values of PSA, the aleatory variability from the regression is not indicative of the actual variability of observed values of SI. Instead, a hybrid-scenario model for magnitude-dependent between-event, within-event, and total aleatory standard deviations is derived from the PSA GMMs using the scenario approach. The predicted values of SI and its standard deviations from the hybrid-scenario model are found to be relatively consistent with the residuals between these predictions and estimates of SI from the database (i.e. the observations). However, the values of SI predicted from a purely empirical GMM developed directly from the observations are different than those from the hybrid-scenario model by up to a few tens of percent. These differences are the result of an insufficient number of observations resulting from bandwidth limitations of the database that lead to a bias in the empirical results. The near-source standard deviations from the hybrid-scenario GMM are found to be generally consistent with both those from the empirical model and those from the residuals between the hybrid-scenario model and the observations. However, the far-source standard deviations of the hybrid-scenario model are smaller than those from these other methods.
Deep learning classification of uveal melanoma based on histopathological images and identification of a novel indicator for prognosis of patients
Authors: Wan Qi , Ren Xiang , Wei Ran , Yue Shali , Wang Lixiang , Yin Hongbo , Tang Jing , Zhang Ming , Ma Ke , Deng Ying-ping
Published: June 2023

Background

Deep learning has been extensively used in digital histopathology. The purpose of this study was to test deep learning (DL) algorithms for predicting the vital status of whole-slide image (WSI) of uveal melanoma (UM).

Methods

We developed a deep learning model (Google-net) to predict the vital status of UM patients from histopathological images in TCGA-UVM cohort and validated it in an internal cohort. The histopathological DL features extracted from the model and then were applied to classify UM patients into two subtypes. The differences between two subtypes in clinical outcomes, tumor mutation, and microenvironment, and probability of drug therapeutic response were investigated further.

Results

We observed that the developed DL model can achieve a high accuracy of >  = 90% for patches and WSIs prediction. Using 14 histopathological DL features, we successfully classified UM patients into Cluster1 and Cluster2 subtypes. Compared to Cluster2, patients in the Cluster1 subtype have a poor survival outcome, increased expression levels of immune-checkpoint genes, higher immune-infiltration of CD8 + T cell and CD4 + T cells, and more sensitivity to anti-PD-1 therapy. Besides, we established and verified prognostic histopathological DL-signature and gene-signature which outperformed the traditional clinical features. Finally, a well-performed nomogram combining the DL-signature and gene-signature was constructed to predict the mortality of UM patients.

Conclusions

Our findings suggest that DL model can accurately predict vital status in UM patents just using histopathological images. We found out two subgroups based on histopathological DL features, which may in favor of immunotherapy and chemotherapy. Finally, a well-performing nomogram that combines DL-signature and gene-signature was constructed to give a more straightforward and reliable prognosis for UM patients in treatment and management.
Administrative burden in Swiss nursing homes and its association with care workers’ outcomes—a multicenter cross-sectional study
Authors: Ausserhofer Dietmar , Tappeiner Waltraud , Wieser Heike , Serdaly Christine , Simon Michael , Zúñiga Franziska , Favez Lauriane
Published: June 2023

Background

Care workers in nursing homes often perform tasks that are rather related to organizational or management activities than ‘direct patient care’. ‘Indirect care activities’, such as documentation or other administrative tasks are often considered by care workers as a burden, as they increase overall workload and keep them away from caring for residents. So far, there is little investigation into what kind of administrative tasks are being performed in nursing homes, by which type of care workers, and to which extent, nor how administrative burden is associated with care workers’ outcomes.

Purpose

The objective of this study was to describe care workers’ administrative burden in Swiss nursing homes and to explore the association with four care worker outcomes (i.e., job dissatisfaction, emotional exhaustion, intention to leave the current job and the profession).

Methods

This multicenter cross-sectional study used survey data from the Swiss Nursing Homes Human Resources Project 2018. It included a convenience sample of 118 nursing homes and 2′207 care workers (i.e., registered nurses, licensed practical nurses) from Switzerland’s German- and French-speaking regions. Care workers completed questionnaires assessing the administrative tasks and burden, staffing and resource adequacy, leadership ability, implicit rationing of nursing care and care worker characteristics and outcomes. For the analysis, we applied generalized linear mixed models, including individual-level nurse survey data and data on unit and facility characteristics.

Results

Overall, 73.9% (n = 1′561) of care workers felt strongly or rather strongly burdened, with one third (36.6%, n = 787) reporting to spend 2 h or more during a "normal" day performing administrative tasks. Ratings for administrative burden ranged from 42.6% (n = 884; ordering supplies and managing stocks) to 75.3% (n = 1′621; filling out the resident’s health record). One out of four care workers (25.5%, n = 561) intended to leave the profession, whereby care workers reporting higher administrative task burden (OR = 1.24; 95%CI: 1.02–1.50) were more likely to intend to leave the profession.

Conclusion

This study provides first insights on care workers’ administrative burden in nursing homes. By limiting care workers’ burdensome administrative tasks and/or shifting such tasks from higher to lower educated care workers or administrative personnel when appropriate, nursing home managers could reduce care workers’ workload and improve their job satisfaction and retention in the profession.
The effects of sildenafil citrate on intrauterine growth restriction: a systematic review and meta-analysis
Authors: Rakhanova Yenlik , Almawi Wassim Y. , Aimagambetova Gulzhanat , Riethmacher Dieter
Published: June 2023

Background

An increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies.

Methods

Meta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model.

Results

Nine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups.

Conclusion

Sildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission.

Trial registration

The study was registered in PROSPERO on September 18, 2021 (CRD42021271992).
How frail is frail in oncology studies? A scoping review
Authors: Fletcher James A. , Logan Benignus , Reid Natasha , Gordon Emily H. , Ladwa Rahul , Hubbard Ruth E.
Published: June 2023

Aims

The frailty index (FI) is one way in which frailty can be quantified. While it is measured as a continuous variable, various cut-off points have been used to categorise older adults as frail or non-frail, and these have largely been validated in the acute care or community settings for older adults without cancer. This review aimed to explore which FI categories have been applied to older adults with cancer and to determine why these categories were selected by study authors.

Methods

This scoping review searched Medline, EMBASE, Cochrane, CINAHL, and Web of Science databases for studies which measured and categorised an FI in adults with cancer. Of the 1994 screened, 41 were eligible for inclusion. Data including oncological setting, FI categories, and the references or rationale for categorisation were extracted and analysed.

Results

The FI score used to categorise participants as frail ranged from 0.06 to 0.35, with 0.35 being the most frequently used, followed by 0.25 and 0.20. The rationale for FI categories was provided in most studies but was not always relevant. Three of the included studies using an FI > 0.35 to define frailty were frequently referenced as the rationale for subsequent studies, however, the original rationale for this categorisation was unclear. Few studies sought to determine or validate optimum FI categorises in this population.

Conclusion

There is significant variability in how studies have categorised the FI in older adults with cancer. An FI ≥ 0.35 to categorise frailty was used most frequently, however an FI in this range has often represented at least moderate to severe frailty in other highly-cited studies. These findings contrast with a scoping review of highly-cited studies categorising FI in older adults without cancer, where an FI ≥ 0.25 was most common. Maintaining the FI as a continuous variable is likely to be beneficial until further validation studies determine optimum FI categories in this population. Differences in how the FI has been categorised, and indeed how older adults have been labelled as ‘frail’, limits our ability to synthesise results and to understand the impact of frailty in cancer care.
College students’ learning stress, psychological resilience and learning burnout: status quo and coping strategies
Authors: Gong Zhen , Wang Huadi , Zhong Mingxia , Shao Yuling
Published: June 2023

Background

The relationships of college students’ learning stress, psychological resilience and learning burnout remain unclear. We aimed to investigate the status quo and relationship of college students’ learning stress, psychological resilience and learning burnout, to provide insights to the management and nursing care of college students.

Methods

From September 1 to October 31, 2022, students in our college were selected by stratified cluster sampling and underwent survey with the learning stress scale, college students’ learning burnout scale and the psychological resilience scale of college students.

Results

A total of 1680 college students were surveyed in this study. The score of learning burnout was positively correlated with the score of learning stress (r = 0.69), and negatively correlated with the score of psychological resilience (r = 0.59), and the score of learning stress was negatively correlated with the score of psychological resilience (r = 0.61). Learning pressure was correlated with the age(r=-0.60) and monthly family income(r=-0.56), the burnout was correlated with the monthly family income(r=-0.61), and psychological resilience was correlated with the age(r = 0.66) (all P < 0.05). Psychological resilience played an intermediary role in the prediction of learning burnout by learning stress, with an total intermediary role of-0.48, accounting for 75.94% of the total effect.

Conclusions

Psychological resilience is the mediating variable of the influence of learning stress on learning burnout. College managers should take various effective measures to improve college students’ psychological resilience to reduce college students’ learning burnout.
Predictors of suicide attempt within 30 days of first medically documented major depression diagnosis in U.S. army soldiers with no prior suicidal ideation
Authors: Mash Holly B. Herberman , Ursano Robert J. , Kessler Ronald C. , Naifeh James A. , Fullerton Carol S. , Aliaga Pablo A. , Dinh Hieu M. , Sampson Nancy A. , Kao Tzu-Cheg , Stein Murray B.
Published: June 2023

Background

Understanding mental health predictors of imminent suicide attempt (SA; within 30 days) among soldiers with depression and no prior suicide ideation (SI) can inform prevention and treatment. The current study aimed to identify sociodemographic and service-related characteristics and mental disorder predictors associated with imminent SA among U.S. Army soldiers following first documented major depression diagnosis (MDD) with no history of SI.

Methods

In this case-control study using Army Study to Assess Risk and Resilience in Servicemembers (STARRS) administrative data, we identified 101,046 active-duty Regular Army enlisted soldiers (2010–2016) with medically-documented MDD and no prior SI (MDD/No-SI). We examined risk factors for SA within 30 days of first MDD/No-SI using logistic regression analyses, including socio-demographic/service-related characteristics and psychiatric diagnoses.

Results

The 101,046 soldiers with documented MDD/No-SI were primarily male (78.0%), < 29 years old (63.9%), White (58.1%), high school-educated (74.5%), currently married (62.0%) and < 21 when first entering the Army (56.9%). Among soldiers with MDD/No-SI, 2,600 (2.6%) subsequently attempted suicide, 16.2% (n = 421) within 30 days (rate: 416.6/100,000). Our final multivariable model identified: Soldiers with less than high school education (χ23 = 11.21, OR = 1.5[95%CI = 1.2–1.9]); combat medics (χ22 = 8.95, OR = 1.5[95%CI = 1.1–2.2]); bipolar disorder (OR = 3.1[95%CI = 1.5–6.3]), traumatic stress (i.e., acute reaction to stress/not PTSD; OR = 2.6[95%CI = 1.4–4.8]), and “other” diagnosis (e.g., unspecified mental disorder: OR = 5.5[95%CI = 3.8-8.0]) diagnosed same day as MDD; and those with alcohol use disorder (OR = 1.4[95%CI = 1.0-1.8]) and somatoform/dissociative disorders (OR = 1.7[95%CI = 1.0-2.8]) diagnosed before MDD were more likely to attempt suicide within 30 days. Currently married soldiers (χ22 = 6.68, OR = 0.7[95%CI = 0.6–0.9]), those in service 10 + years (χ23 = 10.06, OR = 0.4[95%CI = 0.2–0.7]), and a sleep disorder diagnosed same day as MDD (OR = 0.3[95%CI = 0.1–0.9]) were less likely.

Conclusions

SA risk within 30 days following first MDD is more likely among soldiers with less education, combat medics, and bipolar disorder, traumatic stress, and “other” disorder the same day as MDD, and alcohol use disorder and somatoform/dissociative disorders before MDD. These factors identify imminent SA risk and can be indicators for early intervention.
Psychiatric morbidity among women in Norwegian prisons, 2010–2019: a register-based study
Authors: Svendsen Vegard G , Stavseth Marianne Riksheim , Skardhamar Torbjørn , Bukten Anne
Published: June 2023

Purpose

Research suggests that women in prison have more mental health problems than men and are prone to suffer from more severe psychiatric disorders. This study utilizes national registry data to describe demographic and psychiatric gender differences in Norwegian prisons, and to investigate comorbid psychiatric disorders and time trends in psychiatric morbidity among women.

Methods

Longitudinal data from the Norwegian Prison Release Study linked with the Norwegian Patient Registry and data from Statistics Norway provided information on health care utilization, socioeconomic status, and history of psychiatric disorders among all individuals (nwomen = 5,429; nmen = 45,432) who were incarcerated in a Norwegian prison between 2010 and 2019.

Results

Women were more likely than men to have a history of any psychiatric disorder (75% vs. 59%). Substance use disorders and dual disorders were highly prevalent in both genders, yet highest among women (56 and 38% respectively, versus 43 and 24% among men). From 2010 to 2019, we found a considerable increase in the 12-month prevalence of most diagnostic categories among women entering prison.

Conclusion

Psychiatric and dual disorders are highly prevalent in Norwegian prisons, and especially among women. The proportion of women entering prison with a recent history of mental health problems has increased rapidly over the last decade. Women’s prison institutions need to adjust health and social services, and awareness about substance use and other psychiatric disorders in order to meet the increasing proportion of women facing these challenges.
Risk factors for hamstring strain injury in male college American football players -a preliminary prospective cohort study-
Authors: Mizutani Yuri , Taketomi Shuji , Kawaguchi Kohei , Takei Seira , Yamagami Ryota , Kono Kenichi , Kage Tomofumi , Sameshima Shin , Inui Hiroshi , Fujiwara Sayaka , Tanaka Sakae , Ogata Toru
Published: June 2023

Background

Given the frequency of hamstring strain injuries (HSI) among male college American football players, several studies have attempted to determine whether certain risk factors can predict their occurrence. However, no consensus on modifiable risk factors for HSIs in male college American football players has yet been reached to prevent these injuries. This study aimed to clarify risk factors for HSI prospectively in college male American football players.

Methods

A total of 78 male college American football players, whose positions were limited to skill positions, were medically assessed for potential risk factors of HSI. The preseason medical assessment included anthropometric measurements, joint laxity and flexibility, muscle flexibility, muscle strength, and balance ability.

Results

HSI occurred in a total of 25 thighs from 25 players (32.1%). Injured players had significantly lower hamstring flexibility (p = 0.02) and hamstring to quadriceps strength ratio (H/Q) (p = 0.047) compared to uninjured players. Additionally, injured players had significantly lower general joint laxity scores, especially for the total (p = 0.04), hip (p = 0.007), and elbow (p = 0.04) scores, compared to uninjured players.

Conclusions

Lower hamstring flexibility, lower hamstring to quadriceps strength ratio, and lower general joint laxity score were identified as risk factors for HSI in male college American football players placed in skill positions. The muscle flexibility and H/Q ratio could be useful in preventing HSI in such players.
Economic impact of a more extensive use of FENO testing on the Italian population with asthma
Authors: Rognoni Carla , Milano Carlo , Heffler Enrico , Bonini Matteo , Brussino Luisa , Carpagnano Giovanna Elisiana , Ricciardolo Fabio Luigi Massimo , Costa Francesco , Armeni Patrizio
Published: June 2023

Background

Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called “type 2 inflammation”. Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations.

Methods

A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs.

Results

Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC.

Conclusions

Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.
Synergistic apoptosis by combination of metformin and an O-GlcNAcylation inhibitor in colon cancer cells
Authors: Lee Da Eun , Lee Geun Yong , Lee Hae Min , Choi Soo Young , Lee Su Jin , Kwon Oh-Shin
Published: June 2023

Background

Although autophagy is an important mediator of metformin antitumor activity, the role of metformin in the crosstalk between autophagy and apoptosis remains unclear. The aim was to confirm the anticancer effect by inducing apoptosis by co-treatment with metformin and OSMI-1, an inhibitor of O-GlcNAcylation, in colon cancer cells.

Methods

Cell viability was measured by MTT in colon cancer cell lines HCT116 and SW620 cells. Co-treatment with metformin and OSMI-1 induced autophagy and apoptosis, which was analyzed using western blot, reverse transcription-polymerase chain reaction (RT-PCR) analysis, and fluorescence-activated cell sorting (FACS). Combined treatment with metformin and OSMI-1 synergistically inhibit the growth of HCT116 was confirmed by xenograft tumors.

Results

We showed that metformin inhibited mammalian target of rapamycin (mTOR) activity by inducing high levels of C/EBP homologous protein (CHOP) expression through endoplasmic reticulum (ER) stress and activating adenosine monophosphate-activated protein kinase (AMPK) to induce autophagy in HCT116 cells. Interestingly, metformin increased O-GlcNAcylation and glutamine:fructose-6-phosphate amidotransferase (GFAT) levels in HCT116 cells. Thus, metformin also blocks autophagy by enhancing O-GlcNAcylation, whereas OSMI-1 increases autophagy via ER stress. In contrast, combined metformin and OSMI-1 treatment resulted in continuous induction of autophagy and disruption of O-GlcNAcylation homeostasis, resulting in excessive autophagic flux, which synergistically induced apoptosis. Downregulation of Bcl2 promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and CHOP overexpression, synergistically inducing apoptosis. The activation of IRE1α/JNK signaling by OSMI-1 and PERK/CHOP signaling by metformin combined to inhibit Bcl2 activity, ultimately leading to the upregulation of cytochrome c release and activation of caspase-3.

Conclusions

In conclusion, combinatorial treatment of HCT116 cells with metformin and OSMI-1 resulted in more synergistic apoptosis being induced by enhancement of signal activation through ER stress-induced signaling rather than the cell protective autophagy function. These results in HCT116 cells were also confirmed in xenograft models, suggesting that this combination strategy could be utilized for colon cancer treatment.
Going deeper with health equity measurement: how much more can surveys reveal about inequalities in health intervention coverage and mortality in Zambia?
Authors: Blanchard Andrea K. , Jacobs Choolwe , Musukuma Mwiche , Chooye Ovost , Sikapande Brivine , Michelo Charles , Boerma Ties , Wehrmeister Fernando C.
Published: June 2023

Background

Although Zambia has achieved notable improvements in reproductive, maternal, newborn and child health (RMNCH), continued efforts to address gaps are essential to reach the Sustainable Development Goals by 2030. Research to better uncover who is being most left behind with poor health outcomes is crucial. This study aimed to understand how much more demographic health surveys can reveal about Zambia’s progress in reducing inequalities in under-five mortality rates and RMNCH intervention coverage.

Methods

Using four nationally-representative Zambia Demographic Health Surveys (2001/2, 2007, 2013/14, 2018), we estimated under-five mortality rates (U5MR) and RMNCH composite coverage indices (CCI) comparing wealth quintiles, urban‐rural residence and provinces. We further used multi-tier measures including wealth deciles and double disaggregation between wealth and region (urban residence, then provinces). These were summarised using slope indices of inequality, weighted mean differences from overall mean, Theil and concentration indices.

Results

Inequalities in RMNCH coverage and under-five mortality narrowed between wealth groups, residence and provinces over time, but in different ways. Comparing measures of inequalities over time, disaggregation with multiple socio-economic and geographic stratifiers was often valuable and provided additional insights compared to conventional measures. Wealth quintiles were sufficient in revealing mortality inequalities compared to deciles, but comparing CCI by deciles provided more nuance by showing that the poorest 10% were left behind by 2018. Examining wealth in only urban areas helped reveal closing gaps in under-five mortality and CCI between the poorest and richest quintiles. Though challenged by lower precision, wealth gaps appeared to close in every province for both mortality and CCI. Still, inequalities remained higher in provinces with worse outcomes.

Conclusions

Multi-tier equity measures provided similarly plausible and precise estimates as conventional measures for most comparisons, except mortality among some wealth deciles, and wealth tertiles by province. This suggests that related research could readily use these multi-tier measures to gain deeper insights on inequality patterns for both health coverage and impact indicators, given sufficient samples. Future household survey analyses using fit-for-purpose equity measures are needed to uncover intersecting inequalities and target efforts towards effective coverage that will leave no woman or child behind in Zambia and beyond.
Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study
Authors: Li Yubin , Chang Qiyuan , Mai Qingyun
Published: June 2023

Background

Monozygotic twins (MZTs) are associated with high risks of maternal and fetal complications. Even with the widely used elective single embryo transfer (SET), the risk of MZTs following assisted reproductive technology (ART) treatments remains. However, most studies of MZTs focused on the relevant etiology, with few studies describing pregnancy and neonatal outcomes.

Methods

This retrospective cohort study included 19,081 SET cycles resulting from in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) and testicular sperm aspiration (TESA) performed between January 2010 and July 2020 in a single university-based center. A total of 187 MZTs were included in this investigation. The main outcome measures were the incidence, pregnancy and neonatal outcomes of MZTs. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy loss.

Results

The overall rate of MZTs from ART treatment in SET cycles was 0.98%. No significant difference was found in the incidence of MZTs among the four groups (p = 0.259). The live birth rate of MZTs in the ICSI group (88.5%) was significantly more favorable than in the IVF, PGT and TESA groups (60.5%, 77.2% and 80%, respectively). IVF resulted in a significantly increased risk of pregnancy loss (39.4%) and early miscarriage (29.5%) in MZT pregnancies compared to ICSI (11.4%, 8.5%), PGT (22.7%, 16.6%) and TESA (20%, 13.3%). The total rate of twin-to-twin transfusion syndrome (TTTS) in MZTs was 2.7% (5/187); however, the TESA group had the highest rate at 20% and was significantly higher than the PGT group (p = 0.005). The four ART groups had no significant effect on the occurrence of congenital abnormalities or other neonatal outcomes in newborns from MZT pregnancies. Multivariate logistic regression analysis revealed that infertility duration, cause of infertility, the total dose of Gn used, history of miscarriages, and the number of miscarriages were not related to the risk of pregnancy loss (p > 0.05).

Conclusions

The rate of MZTs was similar among the four ART groups. The pregnancy loss and the early miscarriage rate of MZTs was increased in IVF patients. Neither the cause of infertility nor the history of miscarriage was correlated with the risk of pregnancy loss. MZTs in the TESA group had a higher risk of TTTS, placental effects influenced by sperm and paternally expressed genes may play a role. However, due to the small total number, studies with larger sample sizes are still needed to validate these result. Pregnancy and neonatal outcomes of MZTs after PGT treatment seem to be reassuring but the duration of the study was short, and long-term follow-up of the children is needed.
LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathways under hypoxic-ischemic conditions
Authors: Aoki Yoshinori , Dai Hongmei , Furuta Fumika , Akamatsu Tomohisa , Oshima Takuya , Takahashi Naoto , Goto Yu-ichi , Oka Akira , Itoh Masayuki
Published: June 2023

Background

Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 and the molecular mechanism of LOX-1 gene transcription microglial cells under hypoxic and ischemic conditions.

Methods

We isolated primary rat microglial cells from 3-day-old rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positivity with immunocytochemistry. We treated primary rat microglial cells with oxygen glucose deprivation (OGD) as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines in cells treated with or without siRNA and inhibitors compared with those of cells that did not receive OGD-treatment. To confirm transcription factor binding to the OLR-1 gene promoter under the OGD conditions, we performed a luciferase reporter assay and chromatin immunoprecipitation assay. In addition, we analyzed reactive oxygen species and cell viability.

Results

We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1β, IL-6 and TNF-α; the chemokines CCL2, CCL5 and CCL3; and reactive oxygen/nitrogen species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of inflammatory mediators. We found that NF-κB and HIF-1α bind to the promoter region of the OLR-1 gene. Based on the results of the luciferase reporter assay, NF-κB has strong transcriptional activity. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway.

Conclusion

The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated the immune system. LOX-1 and its related molecules or chemicals may be major therapeutic candidates.
Increasing access to psychological services within pediatric rheumatology care
Authors: Goldstein-Leever Alana , Bearer Christine , Sivaraman Vidya , Akoghlanian Shoghik , Gallup James , Ardoin Stacy
Published: June 2023

Background

Given the impact of psychological factors on rheumatic disease, pediatric psychologists serve a vital role in promoting quality of life and managing common problems among youth with rheumatic disease. The aim of this project was to increase access to psychological services among youth with rheumatic disease at a children’s hospital.

Methods

A quality improvement (QI) team identified key drivers and interventions aimed to increase access to psychological services for youth with rheumatic disease. Data was collected for a 6-month baseline period and 4-year intervention period. We applied the Plan-Do-Study Act method of QI and the American Society for Quality criteria to adjust the center line and control limits.

Results

There were two statistically significant center line shifts in the number of patients seen by psychology and one statistically significant shift in referrals to psychology over time with applied stepwise interventions. Patients seen by a psychologist increased by 3,173% from a baseline average of 1.8 to 59.9 patients seen per month (p < 0.03). Psychology referrals increased by 48% from a baseline average of 9.85 to 14.58 referrals per month over the intervention period (p < .01).

Conclusions

Youth with rheumatic disease received increased access to mental health treatment when psychological services were imbedded within rheumatology care. Psychology referrals also increased significantly, suggesting that psychology integration within a medical clinic can increase identification of needs. Results suggest that psychology integration into rheumatology care may increase access to mental health treatment and identification of psychological needs in this at-risk population.
Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort
Authors: Huang Chung-Feng , Jang Tyng-Yuan , Wu Ping-Hsun , Kuo Mei-Chuan , Yeh Ming-Lun , Wang Chih-Wen , Liang Po-Cheng , Wei Yu-Ju , Hsu Po-Yao , Huang Ching-I , Hsieh Ming-Yen , Lin Yi-Hung , Hsiao Hui-Hua , Hsu Chin-Mu , Huang Chien-Tzu , Lee Chun-Yuan , Chen Yen-Hsu , Chen Tun-Chieh , Lin Kun-Der , Wang Shuo-Hung , Wang Sheng-Fan , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung
Published: June 2023

Background/Aims

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive.

Methods

Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities.

Results

A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0–1, 2–3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ–AZ–Moderna (39.2%), followed by Moderna–Moderna–Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34–0.72, P < 0.001), female sex (OR/CI: 1.85/1.30–2.63, P = 0.001), Moderna–Moderna-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 6.49/3.90–10.83, P < 0.001), BNT–BNT-based vaccination (compared to AZ–AZ-based vaccination, OR/CI: 7.91/1.82–34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34–0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (β: − 0.083; 95% CI: − 0.094–0.011, P = 0.014) independently correlated with low IgG spike antibody levels.

Conclusions

Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.
Functional mechanism of miR-92b-3p in osteogenic differentiation of fibroblasts in patients with ankylosing spondylitis via the TOB1/BMP/Smad pathway
Authors: Lu Liansong , Sun Shaohua , Li Haojie , Xie Yingzhi
Published: June 2023

Background

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis. Upregulation of microRNA (miR)-92b-3p is associated with enhanced osteoblastic differentiation. The current study sought to investigate the functional mechanism of miR-92b-3p in osteogenic differentiation of AS fibroblasts.

Methods

First, fibroblasts were isolated from AS and non-AS patients and cultured. Next, cell morphology was observed, cell proliferation was assessed and the vimentin expression pattern was determined. Alkaline phosphatase (ALP) activity and levels of osteogenic markers RUNX2, OPN, OSX, and COL I were additionally measured, followed by determination of miR-92b-3p and TOB1 levels. The binding site of miR-92b-3p and TOB1 was predicted, and their target relationship was validated. Lastly, miR-92b-3p inhibitor, si-TOB1, and the BMP/Smad signaling pathway inhibitor LDN193189 were delivered into AS fibroblasts to evaluate the osteogenic differentiation of AS fibroblasts and the activation of the BMP/Smad pathway.

Results

miR-92b-3p was highly expressed in AS fibroblasts. AS fibroblasts showed enhanced osteogenic differentiation and proliferation, while inhibition of miR-92b-3p suppressed osteogenic differentiation and proliferation of AS fibroblasts. miR-92b-3p targeted TOB1, and TOB1 was poorly expressed in AS fibroblasts. The concurrent downregulation of TOB1 and inhibition of miR-92b-3p elevated the levels of RUNX2, OPN, OSX, and COL I and ALP activity and further enhanced the proliferation of AS fibroblasts. The BMP/Smad pathway was activated in AS fibroblasts. Silencing miR-92b-3p could inhibit the activation of the BMP/Smad pathway by upregulating TOB1. Inhibition of the BMP/Smad pathway reduced the number of calcified nodules and hindered the osteogenic differentiation and proliferation of AS fibroblasts.

Conclusion

Our findings highlighted that silencing miR-92b-3p inhibited the osteogenic differentiation and proliferation of AS fibroblasts by upregulation of TOB1 and inhibition of the BMP/Smad pathway.

Graphical abstract
The challenges of classical galactosemia: HRQoL in pediatric and adult patients
Authors: Hermans Merel E. , van Oers Hedy A. , Geurtsen Gert J. , Haverman Lotte , Hollak Carla E. M. , Rubio-Gozalbo M. Estela , Bosch Annet M.
Published: June 2023

Background

Classical galactosemia (CG), an inborn error of galactose metabolism, results in long-term complications including cognitive impairment and movement disorders, despite early diagnosis and dietary treatment. Two decades ago, lower motor-, cognitive- and social health related quality of life (HRQoL) was demonstrated in pediatric and adult patients. Since then, the diet has been relaxed, newborn screening was implemented and new international guidelines resulted in major changes in follow-up. The aim of this study was to assess HRQoL of CG by means of online self- and/or proxy-HRQoL-questionnaires focusing on the main areas of concern of CG (i.e. anxiety, depression, cognition, fatigue, social- and upper extremity function) within the patient-reported outcomes measurement information system (PROMIS®) and generic HRQoL-questionnaires (TAPQOL, TACQOL, TAAQOL).

Results

Data of 61 Dutch patients (aged 1–52 years) were collected and compared to available Dutch or US reference populations. On the PROMIS-questionnaires, children reported more fatigue (P = 0.044), lower function in upper extremities (P = 0.021), more cognitive difficulties (P = 0.055, d = 0.56) and higher anxiety (P = 0.063, d = 0.52) than reference children although the latter findings remained non-significant. Parents of CG patients reported lower quality of peer relationships of their children (P < 0.001). Both children and parents reported lower cognitive functioning (P = 0.005, P = 0.010) on the TACQOL. Adults reported on PROMIS domains lower cognitive functioning (P = 0.030), higher anxiety (P = 0.004) and more fatigue (P = 0.026). Cognitive difficulties were reported on the TAAQOL by adults (P < 0.001), as well as physical-, sleeping and social difficulties.

Conclusions

CG remains to impact the HRQoL of pediatric and adult patients negatively on several domains including cognition, anxiety, motor function and fatigue. A lower social health was mainly reported by parents, and not by patients themselves. The Covid-19 pandemic might have amplified the results on anxiety although higher levels of anxiety fit pre-pandemic findings. The reported fatigue is a new finding in CG. Because the effect of lockdown fatigue could not be eliminated and fatigue is a frequent finding in patients with chronic disorders, future studies are warranted. Clinicians and researchers should be attentive to both pediatric and adult patients, and the age-dependent difficulties they might encounter.
The clinical effects of modified tinnitus relieving sound (MTRS) for chronic tinnitus: protocol for a randomized controlled trial
Authors: Tang Dongmei , Wang Jinghan , Yu Xiaopei , Yu Huiqian
Published: June 2023

Introduction

Chronic subjective tinnitus has become an increasingly serious hazard that affects the health-related quality of life for millions of people. Due to the lack of curative treatment strategies, this study aims to introduce a novel acoustic therapy named the modified tinnitus relieving sound (MTRS) for tinnitus and to evaluate the efficacy of MTRS in comparison with unmodified music (UM) which served as a control.

Methods and analysis

A randomized, double-blinded, controlled, clinical trial will be carried out. Sixty-eight patients with subjective tinnitus will be recruited and randomly allocated into two groups in 1:1 ratio. The primary outcome is Tinnitus Handicapped Inventory (THI); the secondary outcomes are the Hospital Anxiety and Distress Scale (HADS; HADS subscales for Anxiety (HADS-A) and Depression (HADS-D)), Athens Insomnia Scale (AIS), the visual analog scale (VAS) for tinnitus, and tinnitus loudness matched by sensation level (SL). Assessment will be performed at baseline and at 1, 3, 9, and 12 months post-randomization. The sound stimulus will be persistent until 9 months after randomization, and be interdictory in the last three months. Data collected during the intervention process will be analyzed and compared to baseline.

Ethics and dissemination

This trial received ethical approval from the Institutional Review Board (IRB) of Eye & ENT Hospital of Fudan University (No. 2017048). The study results will be disseminated via academic journals and conferences.

Funding

This study is supported by the Shanghai Shenkang Development Program (SHDC12019119), the Excellent Doctors-Excellent Clinical Researchers Program (SYB202008), the Shanghai Rising-Star Program (23QC1401200), the Shanghai Rising Stars of Medical Talent Youth Development Program (2021–99), the National Natural Science Foundation of China (81800912), and the National Natural Science Foundation of Shanghai (21ZR1411800).

Trial registration

ClinicalTrials.gov NCT04026932. Registered on 18 July 2019.
Molecular pathogen screening of louse flies (Diptera: Hippoboscidae) from domestic and wild ruminants in Austria
Authors: Peña-Espinoza Miguel , Em Daniel , Shahi-Barogh Bita , Berer Dominik , Duscher Georg G. , van der Vloedt Lara , Glawischnig Walter , Rehbein Steffen , Harl Josef , Unterköfler Maria S. , Fuehrer Hans-Peter
Published: June 2023

Background

Hippoboscid flies (Diptera: Hippoboscidae), also known as louse flies or keds, are obligate blood-sucking ectoparasites of animals, and accidentally of humans. The potential role of hippoboscids as vectors of human and veterinary pathogens is being increasingly investigated, but the presence and distribution of infectious agents in louse flies is still unknown in parts of Europe. Here, we report the use of molecular genetics to detect and characterize vector-borne pathogens in hippoboscid flies infesting domestic and wild animals in Austria.

Methods

Louse flies were collected from naturally infested cattle (n = 25), sheep (n = 3), and red deer (n = 12) across Austria between 2015 and 2019. Individual insects were morphologically identified to species level and subjected to DNA extraction for molecular pathogen screening and barcoding. Genomic DNA from each louse fly was screened forBorreliaspp.,Bartonellaspp., Trypanosomatida, Anaplasmataceae, Filarioidea and Piroplasmida. Obtained sequences of Trypanosomatida andBartonellaspp. were further characterized by phylogenetic and haplotype networking analyses.

Results

A total of 282 hippoboscid flies corresponding to three species were identified:Hippobosca equina(n = 62) collected from cattle,Melophagus ovinus(n = 100) from sheep andLipoptena cervi(n = 120) from red deer (Cervus elaphus). Molecular screening revealed pathogen DNA in 54.3% of hippoboscids, including infections with single (63.39%), two (30.71%) and up to three (5.90%) distinct pathogens in the same individual.BartonellaDNA was detected in 36.9% of the louse flies.Lipoptena cerviwere infected with 10 distinct and previously unreportedBartonellasp. haplotypes, some closely associated with strains of zoonotic potential. DNA of trypanosomatids was identified in 34% of hippoboscids, including the first description ofTrypanosomasp. inH. equina. Anaplasmataceae DNA (Wolbachiaspp.) was detected only inM. ovinus(16%), while < 1% of the louse flies were positive forBorreliaspp. and Filarioidea. All hippoboscids were negative for Piroplasmida.

Conclusions

Molecular genetic screening confirmed the presence of several pathogens in hippoboscids infesting domestic and wild ruminants in Austria, including novel pathogen haplotypes of zoonotic potential (e.g.Bartonellaspp.) and the first report ofTrypanosomasp. inH. equina, suggesting a potential role of this louse fly as vector of animal trypanosomatids. Experimental transmission studies and expanded monitoring of hippoboscid flies and hippoboscid-associated pathogens are warranted to clarify the competence of these ectoparasites as vectors of infectious agents in a One-Health context.

Graphical Abstract