bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential diagnosis and feature visualization for thyroid nodules using computer-aided ultrasonic diagnosis system: initial clinical assessment
Authors: Xie Fang , Luo Yu-Kun , Lan Yu , Tian Xiao-Qi , Zhu Ya-Qiong , Jin Zhuang , Zhang Ying , Zhang Ming-Bo , Song Qing , Zhang Yan
Published: August 2022

Background

To assess the diagnostic efficacy of the computer-aided ultrasonic diagnosis system (CAD system) in differentiating benign and malignant thyroid nodules.

Methods

The images of 296 thyroid nodules were included in validation sets. The diagnostic efficacy of the CAD system was compared with that of junior physicians and senior physicians, as well as that of the combination diagnosis of the CAD system with junior physicians. The diagnostic efficacy of the CAD system for different sizes of thyroid nodules was compared.

Results

The diagnostic sensitivity and accuracy of the CAD system were higher than those of junior physicians (83.4% vs. 72.2%, 73.0% vs. 69.6%), but the diagnostic specificity of the CAD system was lower than that of junior physicians (62.1% vs. 66.9%). The diagnostic accuracy of the CAD system was lower than that of senior physicians (73.0% vs. 83.8%). However, the combination diagnosis of the CAD system with junior physicians had higher accuracy (81.8%) and AUC (0.842) than those of either the CAD system or junior physicians alone, and comparable diagnostic performance with those of senior physicians. The Kappa was 0.635 in the combination diagnosis of the CAD system with junior physicians, showing good consistency with the pathological results. The accuracy (76.4%) of the CAD system was the highest for nodules of 1–2 cm.

Conclusion

The CAD system can effectively assist physicians to identify malignant and benign thyroid nodules, reduce the overdiagnosis and overtreatment of thyroid nodules, avoid unnecessary invasive fine needle aspiration, and improve the diagnostic accuracy of junior physicians.
Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study
Authors: Rodo Carlota , de la Calle María , Maroto Anna , Maiz Nerea , Arévalo Silvia , Garcia-Manau Pablo , Mendoza Manel , Bartha José Luis , Carreras Elena
Published: August 2022

Objectives

To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively.

Methods

Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded.

Results

Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively.

Conclusions

In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18–20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.
Clinical application of low-level laser therapy (Photo-biomodulation therapy) in the management of breast cancer-related lymphedema: a systematic review
Authors: Mahmood Dania , Ahmad Ashfaq , Sharif Faiza , Arslan Syed Asadullah
Published: August 2022

Background

Breast cancer-related lymphedema (BCRL) is a frequent issue that arises after mastectomy surgery in women and compromises physical and mental function. Previously published studies have shown positive effects with the use of Low-level laser therapy in another term Photo-biomodulation therapy (PBM). This research investigated the efficacy of clinical use of LLLT (PBM) in the treatment of metastatic breast cancer-related lymphedema.

Methods

PubMed, PEDro, Medline, and the Cochrane Library were searched for LLLT clinical trials published before October 2021. The methodological quality of randomized trials and the effectiveness of Laser Therapy for BCRL were evaluated. The primary objectives were arm circumference or arm volume, whereas the secondary goals were to assess shoulder mobility and pain severity.

Results

Eight clinical trials were analyzed in total. Typically, the included RCTs had good research quality. At four weeks, there was a considerable reduction in arm circumference/volume, and this continued with long-term follow-up. However, no statistically significant change in shoulder mobility or pain severity was seen between the laser and placebo groups at 0-, 1-, 2-, and 3-month short-term follow-up.

Conclusions

The findings of this comprehensive study demonstrated that LLLT (PBM) was successful in diminishing arm circumference and volume than improving shoulder mobility and pain. Data indicates that laser therapy (PBM) may be a beneficial treatment option for females with PML. Because of the scarcity of evidence, there is a strong need for well-conducted and longer-duration trials in this field.

Trial registration

Details of the protocol for this systematic review were registered on PROSPERO and can be accessed at www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42022315076.
Pharmacogenomic biomarkers as source of evidence of the effectiveness and safety of antidepressant therapy
Authors: Correia Catarina , Alcobia Luciano , Lopes Manuel José , Advinha Ana Margarida
Published: August 2022

Objective

The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in antidepressant treatment.

Methods

The work was developed in two phases: i) a search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) a systematic literature review based on the data obtained in the first phase, with the main objective of finding international literature that could describe and characterize previously reported biomarkers and identify other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified.

Results

Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The most widely studied pharmacogenomic biomarker was CYP2D6. These results were mostly supported by the systematic literature review, which yielded 103 papers, 63 of which were ultimately included in the review. The systematic literature review also revealed the existence of other relevant biomarkers. Most of the included studies show a good level of evidence, which guarantees reliability and good recommendation grades. For the database (built during phase i), the results were informative but resulted in no specific recommendations.

Conclusions

Most pharmacogenomic variants are not studied or acknowledged by genetic tests, and more scientific research is needed to confirm their usefulness. Therefore, only a small number of variants are considered when prescribing antidepressant drugs. In addition, genotyping of patients is not common in clinical practice.
Does the perception of HIV risk among Female sex workers affect HIV prevention behavior? application of the Health Belief Model (HBM)
Authors: Asefa Adane , Midaksa Gachana , Qanche Qaro , Wondimu Wondimagegn , Nigussie Tadesse , Bogale Biruk , Birhanu Frehiwot , Asaye Zufan , Mohammed Nuredin , Yosef Tewodros
Published: August 2022

Background

High prevalence of Human Immune virus/Acquired immunodeficiency syndrome (HIV/AIDS) in Female Sex Workers (FSWs) is identified as a bottleneck in fighting against HIV/AIDS. To this end, the international community planned a strategy of 'Ending inequality' and 'Ending the AIDS epidemic' by 2030. This could not be achieved without due attention to FSWs. Thus, this study attempted to assess HIV prevention behavior and associated factors among FSWs in Dima district of Gambella region, Ethiopia by using the Health Belief Model.

Methods

A community-based cross-sectional study was conducted from March to May 2019 among 449 FSWs selected using the snowball sampling technique. Socio-demographic features, knowledge about HIV, attitude toward HIV prevention methods, and Health Belief Model (HBM) constructs (perceived susceptibility to and severity of HIV, perceived barriers, and benefits of performing the recommended HIV prevention methods, self-efficacy, and cues to practice HIV prevention methods) were collected using face to face interview. Data were entered into Epi-data 3.1 and analyzed using SPSS version 23. Bivariable and multivariable binary logistic regression analysis was done to identify the association between dependent and independent variables. P-value < 5% with 95 CI was used as a cutoff point to decide statistical significance of independent variables.

Results

In this study, 449 FSWs participated making a response rate of 98.90%. Of these, 64.8% had high HIV prevention behavior. Age (AOR = 1.911, 95% CI: 1.100, 3.320), knowledge of HIV (AOR = 1.632, 95% CI: 1.083, 2.458), attitude towards HIV prevention methods (AOR = 2.335, 95% CI: 1.547, 3.523), perceived barriers (AOR = .627, 95% CI: .423, .930), and self-efficacy (AOR = 1.667, 95% CI: 1.107, 2.511) were significantly associated with high HIV prevention behavior.

Conclusion

The study identified that about two third of FSWs practiced the recommended HIV prevention methods. Age of respondents, knowledge of HIV, favorable attitude towards the recommended HIV prevention methods, high self-efficacy, and low perceived barrier were associated with high HIV prevention behavior. Therefore, focusing on these factors would be instrumental for improving effectiveness of the ongoing HIV prevention efforts and attaining the 'Sustainable Development Goals of 'Ending inequality' and 'Ending the AIDS epidemic' by 2030.
Potential interstitial lung abnormalities on chest X-rays prior to symptoms of idiopathic pulmonary fibrosis
Authors: Hoffman T. W. , van Es H. W. , Biesma D. H. , Grutters J. C.
Published: August 2022

Background

Idiopathic pulmonary fibrosis (IPF) often has significant diagnostic delay. At present it is not well-known what factors associate with time to diagnosis and if this is associated with survival after the diagnosis. There has also been increasing attention for interstitial lung abnormalities on chest CT-scans. In this study we assessed what factors associate with time to diagnosis in patients with IPF, and whether early stages of pulmonary fibrosis can be seen on chest X-rays prior to the start of symptoms.

Methods

In this retrospective study, 409 Dutch patients with IPF were included. Clinical characteristics, including patient demographics, medical history, time of start of symptoms, time of first visit to pulmonologist, and any previous radiographic imaging reports were collected from patient records.

Results

In 96 patients (23%) a chest X-ray was available that had been made prior to the start of symptoms (median of 50.5 months (IQR 26.3–83.3 months)), and this showed potential interstitial lung abnormalities in 56 patients (58%). The median time from the start of symptoms to the final diagnosis was 24.0 months (interquartile range 9.0–48.0 months). In a multivariate model that corrected for diffusion capacity of the lung for carbon monoxide, forced vital capacity, sex, and age at diagnosis, time to diagnosis did not associate with survival (hazard ratio 1.051 (95% CI 0.800–1.380; p = 0.72)).

Conclusions

There is a significant diagnostic delay for patients with IPF, but longer time to diagnosis did not associate with survival. Interstitial lung abnormalities were seen in more than half of the patients in whom a chest X-ray had been made prior to the start of symptoms. This illustrates that a computed tomography scan should be strongly considered for analysis of unexplained abnormalities on a chest X-ray. This could facilitate early detection and possibly prevention of disease progression for patients with pulmonary fibrosis.
Effects of walking speeds and durations on the plantar pressure gradient and pressure gradient angle
Authors: Lung Chi-Wen , Mo Pu-Chun , Cao Chunmei , Zhang Keying , Wu Fu-Lien , Liau Ben-Yi , Jan Yih-Kuen
Published: August 2022

Background

Walking exercise has been demonstrated to improve health in people with diabetes. However, it is largely unknown the influences of various walking intensities such as walking speeds and durations on dynamic plantar pressure distributions in non-diabetics and diabetics. Traditional methods ignoring time-series changes of plantar pressure patterns may not fully capture the effect of walking intensities on plantar tissues. The purpose of this study was to investigate the effect of various walking intensities on the dynamic plantar pressure distributions. In this study, we introduced the peak pressure gradient (PPG) and its dynamic patterns defined as the pressure gradient angle (PGA) to quantify dynamic changes of plantar pressure distributions during walking at various intensities.

Methods

Twelve healthy participants (5 males and 7 females) were recruited in this study. The demographic data were: age, 27.1 ± 5.8 years; height, 1.7 ± 0.1 m; and weight, 63.5 ± 13.5 kg (mean ± standard deviation). An insole plantar pressure measurement system was used to measure plantar pressures during walking at three walking speeds (slow walking 1.8 mph, brisk walking 3.6 mph, and slow running 5.4 mph) for two durations (10 and 20 min). The gradient at a location is defined as the unique vector field in the two-dimensional Cartesian coordinate system with a Euclidean metric. PGA was calculated by quantifying the directional variation of the instantaneous peak gradient vector during stance phase of walking. PPG and PGA were calculated in the plantar regions of the first toe, first metatarsal head, second metatarsal head, and heel at higher risk for foot ulcers. Two-way ANOVA with Fisher’s post-hoc analysis was used to examine the speed and duration factors on PPG and PGA.

Results

The results showed that the walking speeds significantly affect PPG (P < 0.05) and PGA (P < 0.05), and the walking durations does not. No interaction between the walking duration and speed was observed. PPG in the first toe region after 5.4 mph for either 10 or 20 min was significantly higher than 1.8 mph. Meanwhile, after 3.6 mph for 20 min, PPG in the heel region was significantly higher than 1.8 mph. Results also indicate that PGA in the forefoot region after 3.6 mph for 20 min was significantly narrower than 1.8 mph.

Conclusions

Our findings indicate that people may walk at a slow speed at 1.8 mph for reducing PPG and preventing PGA concentrated over a small area compared to brisk walking at 3.6 mph and slow running at 5.4 mph.
Correlation between carpal rotational alignment and postoperative wrist range of motion following total wrist arthroplasty
Authors: Ota Mitsutoshi , Matsui Yuichiro , Kawamura Daisuke , Urita Atsushi , Endo Takeshi , Iwasaki Norimasa
Published: August 2022

Background

Although total wrist arthroplasty (TWA) has become a common treatment option for wrists with damage due to rheumatoid arthritis (RA), the optimal implant axial alignment for TWA has been inadequately studied. This study was performed to investigate the relationships between implant alignment and carpal rotational alignment and the wrist range of motion (ROM) following TWA.

Methods

This study included 18 patients who underwent TWA using a DARTS® Total Wrist System (Teijin Nakashima Medical, Okayama, Japan) for wrist RA. Pre- and 6-month postoperative computed tomography scans were performed, including the radial volar line (Rv), capitohamate axis (CH), and Rv-CH angle in axial scans. The wrist ROM was also measured. The relationship between the Rv-CH angle and ROM was examined.

Results

The mean Rv-CH angle showed significant wrist pronation from 73.0° to 83.4° postoperatively. We observed a significant positive correlation (0.58) between the postoperative Rv-CH angle and extension and a significant negative correlation (− 0.56) between the postoperative Rv-CH angle and flexion.

Conclusions

Implantation of the DARTS® TWA prosthesis resulted in pronation of the carpal axial alignment, which was correlated with postoperative wrist extension. The volar cortex of the distal radius can be a novel reference axis for adequate implant placement.
Comparison of intranasal and intraperitoneal administration of Eugenia caryophyllata (clove) essential oil on spatial memory, anxiety-like behavior and locomotor activity in a pilocarpine-induced status epilepticus rat model
Authors: Parvizi Fatemeh , Mehrabi Soraya , Naghizadeh Ayeh , Kamalinejad‬ Mohammad , Goudarzi Sepide , Farahmandfar ‬‬‬‬‬‬‬‬‬‬ Maryam
Published: August 2022

Background

Epilepsy induces behavioral effects and histological changes in the hippocampus. Eugenol, the main component of clove essential oil, has modulatory effects on seizure. We aimed to investigate the effect of intraperitoneal (IP) and intranasal (IN) clove essential oil on cognitive and histological changes during the chronic phase of temporal lope epilepsy.

Methods

Male Wistar rats were divided into eight groups of seven including control, pilocarpine (PLC), clove oil (IP and IN), sesame oil (IP and IN), phenobarbital (positive control) and saline. Rats were injected with 350 mg/kg PLC to induce status epilepticus (SE). We evaluated the effects of 14 days IP (0.1 ml/kg) and IN (0.02 ml/kg) administration of clove essential oil on locomotor/explorative activity, anxiety-like behavior, spatial recognition memory, and hyperexcitability, as well as hippocampal cell survival in PLC-treated rats.

Results

Our findings indicated that clove oil could effectively ameliorate PLC-induced behavioral deficits, and also alleviate neuronal death in the cornu ammonis 1 (CA1) region of the hippocampus. Behavioral results as in the Y-maze, Open field and elevated plus maze featured significant differences between control and treated groups. Post-seizure behavioral battery (PBSS) results explicated that behavioral hyperexcitability were less in clove oil groups (both IN and IP) compared to PLC-treated rats. Moreover, results of this study demonstrated that IN administration of clove oil was more potent in alleviating behavioral impairment at a lower dosage than by IP route. The results of this study, also demonstrated that intranasal administration of clove oil could reduce duration of recurrent seizures.

Conclusion

In summary, clove oil treatment ameliorated histopathological and behavioral consequences of PLC-induced SE.
Navigating uncertain illness trajectories for young children with serious infectious illness: a modified grounded theory study
Authors: Neill Sarah , Bray Lucy , Carter Bernie , Roland Damian , Carrol Enitan D. , Bayes Natasha , Riches Lucie , Hughes Joanne , Pandey Poornima , O’Donnell Jennifer , Palmer-Hill Sue
Published: August 2022

Background

Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital.

The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII).

Methods

An explanatory modified grounded theory design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory.

Results

The core category was ‘navigating uncertain illness trajectories for young children with serious infectious illness’. Uncertainty was prevalent throughout the parents’ and HPs’ stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children’s, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments.

Conclusions

Parents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.
Experience of learning from everyday work in daily safety huddles—a multi-method study
Authors: Wahl Karina , Stenmarker Margaretha , Ros Axel
Published: August 2022

Background

To reduce patient harm, healthcare has focused on improvement based on learning from errors and adverse events (Safety-I). Daily huddles with staff are used to support incident reporting and learning in healthcare. It is proposed that learning for improvement should also be based on situations where work goes well (Safety-II); daily safety huddles should also reflect this approach. A Safety-II-inspired model for safety huddles was developed and implemented at the Neonatal Care Unit at a regional hospital in Sweden. This study followed the implementation with the research questions:

Do patient safety huddles with a focus on Safety-II affect the results of measurements of the patient safety culture? What are the experiences of these huddles amongst staff? What experiences of everyday work arise in the patient safety huddles?

Methods

A multi-method approach was used. The quantitative part consisted of a questionnaire (151 items), submitted on four different occasions, and analysed using Mann Whitney U-test and Kruskal Wallis ANOVA-test. The qualitative data were analysed using thematic content analyses of interviews with staff (n = 14), as well as answers to open questions in the questionnaires.

Results

There were 151 individual responses to the questionnaires. The response rates were 44% to 59%. For most comparisons, there were no differences. There were minor changes in patient safety culture measurements. A lower rating was found in December 2020, compared to October 2019 (p < 0.05), regarding whether the employees pointed out when something was about to go wrong. The interviews revealed that, even though most respondents were generally positive towards the huddles (supporting factors), there were problems (hindering factors) in introducing Safety-II concepts in daily safety huddles. There was a challenge to understanding and describing things that go well.

Conclusions

For patient safety huddles aimed at exploring everyday work to be experienced as a base for learning, including both negative and positive events (Safety-II); there is a need for an open and permissive climate, that all professions participate and stable conditions in management. Support from managers and knowledge of the underpinning Safety-II theories of those who lead the huddles, may also be of importance.
Circulating ceramides and sphingomyelins and the risk of incident cardiovascular disease among people with diabetes: the strong heart study
Authors: Jensen Paul N. , Fretts Amanda M. , Hoofnagle Andrew N. , McKnight Barbara , Howard Barbara V. , Umans Jason G. , Sitlani Colleen M. , Siscovick David S. , King Irena B. , Sotoodehnia Nona , Lemaitre Rozenn N.
Published: August 2022

Background

Plasma ceramides and sphingomyelins have been independently linked to diabetes risk, glucose and insulin levels, and the risk of several cardiovascular (CVD) outcomes. However, whether individual ceramide and sphingomyelin species contribute to CVD risk among people with type 2 diabetes is uncertain. Our goal was to evaluate associations of 4 ceramide and 4 sphingomyelin species with incident CVD in a longitudinal population-based study among American Indians with diabetes.

Methods

This analysis included participants with prevalent type 2 diabetes from two cohorts: a prospective cohort of 597 participants in the Strong Heart Family Study (116 incident CVD cases; mean age: 49 years; average length of follow-up: 14 years), and a nested case–control sample of 267 participants in the Strong Heart Study (78 cases of CVD and 189 controls; mean age: 61 years; average time until incident CVD in cases: 3.8 years). The average onset of diabetes was 7 years prior to sphingolipid measurement. Sphingolipid species were measured using liquid chromatography and mass spectrometry. Cox regression and logistic regression were used to assess associations of sphingolipid species with incident CVD; results were combined across cohorts using inverse-variance weighted meta-analysis.

Results

There were 194 cases of incident CVD in the two cohorts. In meta-analysis of the 2 cohort results, higher plasma levels of Cer-16 (ceramide with acylated palmitic acid) were associated with higher CVD risk (HR per two-fold higher Cer-16: 1.85; 95% CI 1.05–3.25), and higher plasma levels of sphingomyelin species with a very long chain saturated fatty acid were associated with lower CVD risk (HR per two-fold higher SM-22: 0.48; 95% CI 0.26–0.87), although none of the associations met our pre-specified threshold for statistical significance of p = 0.006.

Conclusions

While replication of the findings from the SHS in other populations is warranted, our findings add to a growing body of research suggesting that ceramides, in particular Cer-16, not only are associated with higher diabetes risk, but may also be associated with higher CVD risk after diabetes onset. We also find support for the hypothesis that sphingomyelins with a very long chain saturated fatty acid are associated with lower CVD risk among adults with type 2 diabetes.
Effect of different surgical approaches on the prognosis of patients with postoperative radiotherapy for stage IIB–IVA esophageal squamous cancer
Authors: Gao Mingcheng , Zhu Yulin , Gu Yan , Shi Zhan , Wu Jixiang , Chang Huiwen , Song Jianxiang
Published: August 2022

Objective

To investigate the effect and clinical significance of different thoracic surgical approaches for patients with stage IIB–IVA esophageal squamous cell carcinoma on the survival and prognosis of postoperative radiotherapy patients.

Methods

One hundred thirty-two patients with stage IIB–IVA esophageal squamous cancer who received radiotherapy after surgery were screened for baseline characteristics and survival analysis. The Kaplan-Meier method was used to draw the survival curve for the follow-up data, and the log-rank test was used to compare the difference in survival rate between the two groups. The Cox regression model was used for multivariate survival analysis.

Result

For stage IIB–IVA esophageal squamous cell carcinoma, the results of multivariate analysis showed that different surgical methods and clinical staging were independent factors affecting the survival and prognosis of patients after radiotherapy. The 1-, 3-, and 5-year survival rates of patients with advanced esophageal cancer through the left chest approach were 84.2%, 61.4%, and 36.8% respectively. The 1-, 3-, and 5-year survival rates of patients with advanced esophageal cancer through the right chest approach were 73.3%, 40.0%, and 21.3% respectively. There was no significant difference in the 1-year survival rate (P = 0.135) between the two surgical procedures. The 3-year survival rate (P < 0.05) and the 5-year survival rate (P < 0.05) were significantly different.

Conclusion

For patients with stage IIB–IVA esophageal squamous cell carcinoma undergoing radiotherapy after surgery, the long-term survival prognosis of patients after the left thoracic approach is significantly higher than that of the right thoracic approach.
Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression
Authors: Baarz Bastian Robinson , Laurentius Thea , Wolf Jana , Wessels Inga , Bollheimer Leo Cornelius , Rink Lothar
Published: August 2022

Background

Aging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM)$$\alpha$$αplays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated.

Results

Comparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM$$\alpha$$α. For the first time in humans, we report a mutual relationship between low zinc levels, high CREM$$\alpha$$αexpression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM$$\alpha$$αoverexpression, and counteract subsequent low IL-2 production rates.

Conclusions

Our ex vivo and in vivo data identify zinc deficiency-mediated CREM$$\alpha$$αoverexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy.

Graphical abstract

During the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM$$\mathrm{\alpha }$$αin peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults.
Unified primal-dual active set method for dynamic frictional contact problems
Authors: Abide Stéphane , Barboteu Mikaël , Cherkaoui Soufiane , Dumont Serge
Published: August 2022

In this paper, we propose a semi-smooth Newton method and a primal-dual active set strategy to solve dynamical contact problems with friction. The conditions of contact with Coulomb’s friction can be formulated in the form of a fixed point problem related to a quasi-optimization one thanks to the semi-smooth Newton method. This method is based on the use of the primal-dual active set (PDAS) strategy. The main idea here is to find the correct subset $\mathcal{A}$
A
of nodes that are in contact (active) opposed to those which are not in contact (inactive). For each case, the nonlinear boundary condition is replaced by a suitable linear one. Numerical experiments on both hyper-elastic problems and rigid granular materials are presented to show the efficiency of the proposed method.
The dietary risk assessment of perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS) in the root crops from the survey of the residue in agricultural soil and the crops
Authors: Choi Geun-Hyoung , Lee Deuk-Yeong , Song A-Reum , Moon Bo-Yeon , Kim Jin-Hyo
Published: August 2022

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are persistent organic pollutants (POPs) that are prohibited from being produced and used. However, they remain in the agricultural environment and are transferred to crops. In addition, PFOA is classified as possibly carcinogenic to humans. To fully understand the exposure and risk of PFOA and PFOS for human in crops, a residue survey and estimation of dietary exposure assessment are needed. Therefore, we investigated the residues of PFOA and PFOS in upland soil and cultivated root crops. The average residues of PFOA and PFOS in the soil were < 0.054–0.541 μg kg–1 and 0.024–0.111 μg kg–1, and 0.067–0.193 μg kg–1 and < 0.02 μg kg–1 in the crops, respectively. The average PFOA residues were higher than PFOS in the soil and crops. The estimated daily intakes of PFOA and PFOS in the crops were 0.284 ng kgbw–1 day–1 and 0.023 ng kgbw–1 day–1, and the estimated hazard quotients were 0.355 and 0.013, respectively. In addition, the excess cancer risk of PFOA was calculated to be 1.99 × 10–8. Thus, the non–carcinogenic and carcinogenic risks of PFOA and PFOS were not notable from the surveyed residues in the crops. However, the risks may be higher when the residues in other food crops are considered.
Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy
Authors: Cai Hongzhen , Li Man , Deng Ruiyi , Wang Mopei , Shi Yanyan
Published: August 2022

Gastric cancer is characterized by high morbidity and mortality worldwide. Early-stage gastric cancer is mainly treated with surgery, while for advanced gastric cancer, the current treatment options remain insufficient. In the 2022 NCCN Guidelines for Gastric Cancer, immunotherapy is listed as a first-line option for certain conditions. Immunotherapy for gastric cancer mainly targets the PD-1 molecule and achieves therapeutic effects by activating T cells. In addition, therapeutic strategies targeting other molecules, such as CTLA4, LAG3, Tim3, TIGIT, and OX40, have also been developed to improve the treatment efficacy of gastric cancer immunotherapy. This review summarizes the molecular biomarkers of gastric cancer immunotherapy and their clinical trials.
Using the English GSAT for placement into EFL classes: accuracy and validity concerns
Authors: Liao Yen-Fen
Published: August 2022

The English General Scholastic Ability Test (GSAT), a nationwide high-stakes college entrance exam in Taiwan, has commonly served as a placement test for streaming college freshmen into EFL classes. There has, however, been scant research reported on the feasibility of using an admission test for EFL placement. This study aims to investigate the accuracy and validity of placement decisions being made using the English GSAT scores, with a focus on its relations with the General English Proficiency Test (GEPT) and students’ subsequent performance in class. Quantitative data, including the English GSAT scores, the GEPT High-Intermediate Listening and Reading scores, and the English final course grades, were collected and statistically analyzed from four EFL classes with a total of 100 students at a university in Taiwan. The English GSAT was found to function well to place students into distinctively lower or higher level of EFL classes but did not discriminate well for the borderline cohort. A three-level placement using the English GSAT appeared to be a better differentiation between each proficiency cluster. High achievers in the English GSAT appeared to perform better on the GEPT listening and reading tests than did low achievers. Yet, apart from the GEPT reading test, the English GSAT yielded weak predictive power of student course attainment, which seemingly varied across classes, hinging on course designs and grading policies. Implications drawn from the results of the investigation were further discussed.
Feasibility of a peer-led, after-school physical activity intervention for disadvantaged adolescent females during the COVID-19 pandemic: results from the Girls Active Project (GAP)
Authors: McQuinn Sara , Belton Sarahjane , Staines Anthony , Sweeney Mary Rose
Published: August 2022

Introduction

There is a critical need for interventions that can be feasibly implemented and are effective in successfully engaging adolescent females in physical activity (PA). A theory-based, peer-led, after-school PA intervention, the Girls Active Project (GAP), was codesigned with adolescent females. This study aimed to assess the feasibility of implementing and evaluating the GAP programme.

Setting

One single-sex, female-only, designated disadvantaged postprimary school (students aged 12–18) in Dublin, Ireland.

Methods

Mixed methods were applied with multiple stakeholders over a 12-week trial (March to May 2021). A single-arm study design was used to examine intervention: reach, dose, fidelity, acceptability, compatibility and context. Feasibility of using proposed self-reported outcome measures (moderate-to-vigorous PA levels, self-rated health, life satisfaction, PA self-efficacy and PA enjoyment) was also explored. Due to school closure resulting from the COVID-19 pandemic, the intervention was delivered both online and in person in the school setting.

Results

Eight exercise classes were peer delivered by project leaders (n = 6, students aged 15–17) to intervention recipients (students aged 13-14). Recruitment was low (n = 8, 10% of eligible students, mean age: 13.3 SD: 0.46), yet retention was high (n = 7/8, 88%). Attendance rates were satisfactory (68%), and the intervention was implemented with high fidelity (87%). Data completion rates suggested proposed self-reported outcome measures were deemed appropriate (≥ 95%), except for weight (50%) and height data (80%). Despite COVID-19 hindering intervention implementation, both quantitative and qualitative data suggested that stakeholders were satisfied and perceived the in-person delivered intervention to be compatible with the school setting. Recommended refinements included extending class duration, introducing different rewards, and boosting programme awareness.

Conclusions

Further thought must be given on how to increase recruitment. Overall, the in-person delivered after-school PA programme was well-received by stakeholders and shows promise as an intervention that can be feasibly implemented and evaluated. Suggested improvements to the GAP intervention programme are recommended, before continuing to a more robust evaluation.

Trial registration

10.17605/OSF.IO/75HWJ (prospectively registered, date of registration: 9th December 2020)
Slow recruitment in the HIMALAIA study: lessons for future clinical trials in patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on feasibility data
Authors: Gathier Celine S. , van der Jagt Mathieu , van den Bergh Walter M. , Dankbaar Jan Willem , Rinkel Gabriel J. E. , Slooter Arjen J. C. ,   for the HIMALAIA Study Group, Algra Ale , Dankbaar Jan-Willem , Gathier Celine S. , Kesecioglu Jozef , Rinkel Gabriel J. E. , van der Schaaf Irene C. , Slooter Arjen J. C. , Verweij Bon H. , Dammers Ruben , Dippel Diederik W. J. , Dirven Clemens M. F. , van der Jagt Mathieu , van Kooten Fop , van der Lugt Aad , van den Bergh Walter M. , Coert Bert A. , Müller Marcella C. , Vandertop W. Peter , Beute Guus N. , Oldenbeuving Annemarie W. , van der Pol Bram , Roks Gerwin , van Rooij Willem Jan J. , Sluzewski Menno
Published: August 2022

Background

Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories.

Methods

Efficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized.

Results

Of the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment.

Conclusions

Enrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment.

Trial registration

The original trial was prospectively registered withClinicalTrials.gov(NCT01613235), date of registration 07-06-2012.
Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report
Authors: Zakaria Zaitun , Raja Mohd Rasi Raja Zubaidah , Rahman Noor Azman A.
Published: August 2022

Background

Cerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1).

Case presentation

A 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma.

Conclusions

A careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.
Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease
Authors: Kumar G. Santhana , Tirgar Pravin , Dalal Mittal
Published: August 2022

Background

Polycystic ovary syndrome is a most common female reproductive disorder, involving endocrine and metabolic disorders with unclear etiology. Androgen-based rodent animal models like DHEA and DHT are most suitable for PCOS induction, but still, these models fail to produce non-lean PCOS phenotypes such as hyperandrogenism, hyperinsulinemia, elevated estrogen levels, and ovary weight. Excess fructose consumption leads to hyperandrogenism, hyperinsulinemia, and insulin resistance. The purpose of this study is to investigate, whether fructose consumption along with androgens in rats, could develop all metabolic and endocrine phenotypes of non-lean human PCOS disease. 

Methods

Prepubertal SD rats were administered with DHT (83ug, s.c.) and fructose (20%, p.o.) for 90 days whereas DHEA (7 mg/kg, s.c) and fructose (20%, p.o.) for 30 days. During study duration, the blood glucose level for oral glucose tolerance test, estrus cyclicity, and ultrasonography was observed. Reproductive hormones LH, FSH, insulin, testosterone, and estradiol levels were assessed using ELISA. The ovary, uterus, abdominal fat, and subcutaneous fat were collected and weighed, and histopathology was done for any anomaly’s findings.

Results

DHT + fructose-treated rats showed significant (p < 0.05) increase in serum testosterone, LH, estradiol, decreased FSH levels, and caused multiple cystic follicles. Abdominal fat, subcutaneous fat, ovary, and uterine weight were higher in DHT + F and DHEA + F when compared to control groups. OGTT reveals impaired insulin sensitivity and glucose tolerance in both model groups. Ovarian histopathology of DHT + F shows more cysts than the DHEA + F groups. No significant changes in uterine histology of DHT + F and DHEA + F-treated rats.

Conclusion

DHT + F-treated rats mimic all clinical phenotypes and could be used as novel rodent model for non-lean type PCOS.
Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer
Authors: Hoimes Christopher J. , Flaig Thomas W. , Milowsky Matthew I. , Friedlander Terence W. , Bilen Mehmet Asim , Gupta Shilpa , Srinivas Sandy , Merchan Jaime R. , McKay Rana R. , Petrylak Daniel P. , Sasse Carolyn , Moreno Blanca Homet , Yu Yao , Carret Anne-Sophie , Rosenberg Jonathan E.
Published: August 2022

PURPOSE

Cisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many patients with la/mUC are ineligible. Each enfortumab vedotin and pembrolizumab have shown a survival benefit versus chemotherapy in UC, are not restricted by cisplatin eligibility, and warrant investigation as a first-line (1L) combination therapy in patients ineligible for cisplatin.

METHODS

In this ongoing phase Ib/II, multicenter, open-label study, 1L cisplatin-ineligible patients with la/mUC received enfortumab vedotin 1.25 mg/kg once daily on days 1 and 8 and pembrolizumab 200 mg (day 1) intravenously once daily in 3-week cycles. The primary end point was safety. Key secondary end points included confirmed objective response rate, duration of response (DOR), and overall survival (OS).

RESULTS

Forty-five patients received enfortumab vedotin plus pembrolizumab. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (55.6%), fatigue (51.1%), and alopecia (48.9%). Twenty-nine patients (64.4%) had grade 3 or higher TRAEs; the most common were increased lipase (17.8%), maculopapular rash (11.1%), and fatigue (11.1%). One death (2.2%) was classified as a TRAE. The confirmed objective response rate after a median of nine cycles was 73.3% with a complete response rate of 15.6%. The median DOR and median OS were 25.6 months and 26.1 months, respectively.

CONCLUSION

Enfortumab vedotin plus pembrolizumab showed a manageable safety profile. Most patients experienced tumor shrinkage. The median DOR and median OS exceeding 2 years in a cisplatin-ineligible patient population make this a promising combination currently under investigation in a phase III study (ClinicalTrials.gov identifier: NCT04223856 ).