bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of mutations in the cysteine desulfurase IscS (Pfnfs1) gene in recurrent Plasmodium falciparum infections following artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) treatment in Matayos, Western Kenya
Authors: Gachie Beatrice , Thiong’o Kelvin , Muriithi Brenda , Chepngetich Jean , Onchieku Noah , Gathirwa Jeremiah , Mwitari Peter , Magoma Gabriel , Kiboi Daniel , Kimani Francis
Published: May 2023

Background

Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya.

Methods

Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections.

Results

The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample.

Conclusions

The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.
Anti-malarial resistance in Mozambique: Absence of Plasmodium falciparum Kelch 13 (K13) propeller domain polymorphisms associated with resistance to artemisinins
Authors: da Silva Clemente , Matias Daniela , Dias Brigite , Cancio Beatriz , Silva Miguel , Viegas Ruben , Chivale Nordino , Luis Sonia , Salvador Crizolgo , Duarte Denise , Arnaldo Paulo , Enosse Sonia , Nogueira Fatima
Published: May 2023

Background

Malaria remains one of the most serious public health problems in sub-Saharan Africa and Mozambique is the world's fourth largest contributor, with 4.7% of disease cases and 3.6% of total deaths due to malaria. Its control relies on the fight against the vector and treatment of confirmed cases with anti-malarial drugs. Molecular surveillance is an important tool for monitoring the spread of anti-malarial drug resistance.

Methods

A cross-sectional study recruited 450 participants with malaria infection detected by Rapid Diagnostic Tests, from three different study sites (Niassa, Manica and Maputo) between April and August 2021. Correspondent blood samples were collected on filter paper (Whatman® FTA® cards), parasite DNA extracted and pfk13 gene sequenced using Sanger method. SIFT software (Sorting Intolerant From Tolerant) was used, predict whether an amino acid substitution affects protein function.

Results

No pfkelch13-mediated artemisinin resistance gene mutation was detected in this study settings. However, non-synonymous mutations were detected at prevalence of 10.2%, 6% and 5% in Niassa, Manica and Maputo, respectively. Most (56.3%) of the reported non-synonymous mutations were due to substitution at the first base of the codon, 25% at the second base and 18.8% at the third base. Additionally, 50% of non-synonymous mutations showed a SIFTscore bellow cut off value of 0.05, therefore, they were predicted to be deleterious.

Conclusion

These results do not show an emergence of artemisinin resistance cases in Mozambique. However, the increased number of novel non-synonymous mutations highlights the relevance of increasing the number of studies focused on the molecular surveillance of artemisinin resistance markers, for its early detection.
Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice
Authors: Xiang Du , Zhou Encheng , Wang Mei , Wang Kan , Zhou Shujun , Ma Qing , Zhong Zibiao , Ye Qifa , Chen Yun , Fan Xiaoli , Wang Yanfeng
Published: May 2023

Background

Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix.

Methods

In vitro, follicles isolated from 10–12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10–12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination.

Results

The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts.

Conclusions

Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms.
Disease relapse rate in children with autoimmune rheumatic diseases after COVID-19 infection and vaccination
Authors: Šinkovec Savšek Tjaša , Zajc Avramovič Mojca , Avčin Tadej , Korva Miša , Avšič Županc Tatjana , Toplak Nataša
Published: May 2023

Background

Paediatric patients with autoimmune rheumatic diseases (pARD) are often immunocompromised because of the disease and/or the therapy they receive. At the beginning of COVID-19 pandemic there was a great concern about the possibility of severe SARS-CoV-2 infection in these patients. The best method of protection is vaccination, so as soon as vaccine was licenced, we aimed to vaccinate them. Data on disease relapse rate after COVID-19 infection and vaccination are scarce, but they play important role in everyday clinical decisions.

Methods

The aim of this study was to determine the relapse rate of autoimmune rheumatic disease (ARD) after COVID-19 infection and vaccination. Data on demographic, diagnosis, disease activity, therapy, clinical presentation of the infection and serology were collected from pARD who had COVID-19 and from pARD who were vaccinated against COVID-19, from March 2020 to April 2022. All vaccinated patients received two doses of the BNT162b2 BioNTech vaccine, on average, 3.7 (S.D.=1.4) weeks apart. Activity of the ARD was followed prospectively. Relapse was defined as a worsening of the ARD in a time frame of 8 weeks after infection or vaccination. For statistical analysis, Fisher’s exact test and Mann-Whitney U test were used.

Results

We collected data from 115 pARD, which we divided into two groups. We included 92 pARD after infection and 47 after vaccination, with 24 in both groups (they were infected before/after vaccination). In 92 pARD we registered 103 SARS-CoV-2 infections. Infection was asymptomatic in 14%, mild in 67% and moderate in 18%, 1% required hospitalization; 10% had a relapse of ARD after infection and 6% after vaccination. There was a trend towards higher disease relapse rate after infection compared to vaccination, but the difference was not statistically significant (p = 0.76). No statistically significant difference was detected in the relapse rate depending on the clinical presentation of the infection (p = 0.25) or the severity of the clinical presentation of COVID-19 between vaccinated and unvaccinated pARD (p = 0.31).

Conclusions

There is a trend towards a higher relapse rate in pARD after infection compared to vaccination and connection between the severity of COVID-19 and vaccination status is plausible. Our results were, however, not statistically significant.
Evaluation of optimal single-photon emission computed tomography reference value and three-dimensional mandibular growth pattern in 54 Chinese unilateral condylar hyperplasia patients
Authors: Ouyang Ningjuan , Zhang Chenglong , Xu Feng , Chen Tiantian , Shen Guofang , Si Jiawen , Yu Hongbo
Published: May 2023

Background

The research aimed to evaluate the optimal Single-Photon Emission Computed Tomography (SPECT) cut-off value in differentiating condylar growth activeness, to observe 3-dimensional (3D) mandibular growth pattern, and to explore the potential correlation between 3D measurement parameters and SPECT uptake ratios in Chinese unilateral condylar hyperplasia (UCH) patients.

Methods

 Data of fifty-four Chinese UCH patients were analyzed retrospectively. All patients underwent SPECT within 1 month before or after the first CT examination (CT1); and received a second CT examination at least 12 months later (CT2). Data from CT scans were analyzed by comparing bilateral differences between CT1 and CT2. The sensitivity and specificity of SPECT were calculated by the receiver operating characteristic (ROC) curve. Pearson’s correlation analysis was performed to investigate whether the mandibular growth was correlated with SPECT value.

Results

SPECT had a sensitivity of 68.00% and a specificity of 72.41%, with an area under the ROC curve being 0.709. The optimal SPECT cut-off value for evaluating condylar activity has been determined to be 13%. In patients with an active growing condyle, there was a significant increase in Co-Gn and Co-Go, but not in Go-Gn, Go-MF, or MF-Gn. Pearson’s correlation analysis revealed no correlation between 3D measurement parameters and differences in relative condylar uptake ratios.

Conclusion

SPECT showed good diagnostic performance in UCH with the cut-off value of 13%. For those with an active growing condyle, the mandible grows diagonally and vertically, while the relative condylar uptake ratio was not directly related to mandibular growth.
Nonanatomic healing of the greater tuberosity after plating in proximal humeral fractures: a case control study
Authors: Sheng Ning , Shi Tingwang , Wang Qiuke , Wang Lei , Chen Yunfeng
Published: May 2023

Background

Open reduction and plate internal fixation (ORIF) is one of the most common treatment methods for proximal humeral fractures. Complications associated with the greater tuberosity (GT) are rarely reported, therefore, the purpose of this study was to analyze the complications associated with the GT and the risk factors after locked-plate internal fixation.

Methods

We retrospectively analyzed the medical and radiographic data of patients with proximal humeral fractures involving the GT treated with locking plates between January 2016 and July 2019. We divided all patients into two groups, the anatomic GT healing group and the nonanatomic GT healing group, depending on the radiographic outcomes of the GT. Clinical outcome was assessed by the Constant scoring system. Potential risk factors included preoperative and intraoperative factors. Preoperative factors included sex, age, body mass index, fracture type, fracture-dislocation, proximal humeral bone mineral density, humeral head extension, hinge integrity, comminuted GT, volume and surface area of the main GT fragment, and displacement of the main GT fragment. Intraoperative factors were adequate medial support, residual head-shaft displacement, head-shaft angle and residual GT displacement. Univariate logistic regression and multivariate logistic regression were used to identify risk factors.

Results

There were 207 patients (130 women and 77 men; mean age, 55 years). GT anatomic healing was observed in 139 (67.1%) patients and nonanatomic healing in 68 (32.9%). Patients with GT nonanatomic healing had significantly inferior Constant scores than those with GT anatomic healing (75.0 ± 13.9 vs. 83.9 ± 11.8, P < 0.001). Patients with high GT malposition had worse Constant scores than patients with low GT malposition (73.3 ± 12.7 vs. 81.1 ± 11.4, P = 0.039). The multivariate logistic model showed that GT fracture characteristics were not risk factors for nonanatomic GT healing, while residual GT displacement was.

Conclusions

Nonanatomic healing of the GT is a high-rate complication of proximal humeral fractures, resulting in inferior clinical outcomes, especially for high GT malposition. Fracture characteristics of the GT are not risk factors for GT nonanatomic healing and GT comminution should not be regarded as a contraindication to ORIF for proximal humeral fractures.
Review on risk factors, classification, and treatment of sternal wound infection
Authors: Song Yaoyao , Chu Wanli , Sun Jiachen , Liu Xinzhu , Zhu Hongjuan , Yu Hongli , Shen Chuan’an
Published: May 2023

Sternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.
Fatigue in patients with syndromic heritable thoracic aortic disease: a systematic review of the literature and a qualitative study of patients’ experiences and perceptions
Authors: Velvin Gry , Johansen Heidi , Østertun-Geirdal Amy , Bathen Trine
Published: May 2023

Introduction

The purpose of this study was to explore the literature on fatigue in patients with syndromic heritable thoracic aortic disease (sHTAD), including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers Danlos syndrome (vEDS) and other sHTADs, critically appraise and synthesize the relevant literature. We also aimed to investigate how adults with sHTAD experience and perceive fatigue, and to discuss clinical implications and direction for further research.

Methods

First, a systematic review was performed by searching the published literature in all relevant databases and other sources until 20th October 2022. Second, a qualitative focus group interview study was conducted of 36 adults with sHTADs (LDS n = 11, MFS n = 14, vEDS n = 11).

Results

In the systematic review, 33 articles satisfied the eligibility criteria (3 reviews and 30 primary studies). Of the primary studies: 25 dealt with adults (MFS n = 17, MFS/EDS n = 1, EDS n = 2, LDS/vEDS n = 3, different sHTADs n = 2), 5 with children (MFS n = 4, different sHTADs n = 1). Twenty-two were cross-sectional quantitative studies, 4 prospective and 4 qualitative studies. The quality of the included studies was mostly good, but many had small sample sizes, low response rates and/or participants without verified diagnosis. Despite these limitations, studies indicated high prevalence of fatigue (ranging from 37 to 89%), and fatigue was associated with both health and psychosocial aspects. Few studies found that fatigue was associated with disease-related symptoms. In the qualitative focus groups most of the participants reported that they had experienced fatigue which influenced several aspects of life. Four themes related to fatigue were elucidated: (1) different diagnoses–different fatigue?, (2) the nature of fatigue, (3) searches for causes of fatigue, (4) dealing with fatigue in daily life. The four themes seemed mutually interrelated in terms of barriers, strategies and facilitators for dealing with fatigue. The participants experienced fatigue as a consistent dilemma between self-assertion and inadequacy. Fatigue seems to influence several aspects of daily life and may be one of the most debilitating symptoms of having a sHTAD.

Conclusion

Fatigue seems to negatively impact the lives of people with sHTADs and should be recognized as an important aspect in the lifelong follow-up of these patients. The life-threatening complications of sHTADs may result in emotional stress, including fatigue and the risk of developing a sedentary lifestyle. Research and clinical initiatives should consider rehabilitation interventions aiming at postponing the onset or reducing symptoms of fatigue.
A short-term bioreactor assay to assess the effect of essential oils on a microbiota derived from piglet’s intestinal content
Authors: Bellerose Mathieu , Fravalo Philippe , Mainville Isabelle , Arcand Yves , Thibodeau Alexandre
Published: May 2023

Background

Modulating the microbiota is an emerging way to improve pig health. In-vitro bioreactor systems can be used to reproduce intestinal microbiota to study modulating avenues. In this study, a continuous feeding system to support a microbiota derived from piglet colonic contents, over 72 h, was developed. The microbiota from piglets was collected and used as inoculum. The culture media was derived from an artificial digestion of piglet feed. The microbiota diversity in time, the reproducibility between replicates and the diversity of the bioreactor microbiota compared to the inoculum was assessed. Essential oils were used as a proof of concept to assess the in vitro microbiota modulation. The microbiota diversity was assessed by 16S rRNA amplicon sequencing. Quantitative PCR was also used for total bacteria, lactobacilli and Enterobacteria.

Results

At the start of the assay, the bioreactor microbiota diversity was similar to the inoculum. Time and replication affected the bioreactor microbiota diversity. Between 48 and 72 h, no statistical variation of the microbiota diversity was observable. After a 48 h running period, thymol and carvacrol were added at 200 ppm or 1000 ppm for 24 h. No microbiota modification was observed by sequencing. Quantitative PCR results showed a significant growth of lactobacilli when thymol was used at 1000 ppm, where only a trend was observed with the 16S analysis.

Conclusions

This study presents a bioreactor assay that can be used as a tool for rapid screening of additives and suggests that the effects of essential oils on the microbiota are subtle, acting against a few bacterial genera.
Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity – a randomized controlled trial
Authors: Bhargava Mudit , Kopp Chirag Rajkumar , Naidu Shankar , Dhibar Deba Prasad , Saroch Atul , Khadwal Alka , Narang Tarun , Jain Siddharth , Khullar Aastha , Leishangthem Bidya , Sharma Aman , Kumar Susheel , Sharma Shefali , Jain Sanjay , Dhir Varun
Published: May 2023

Background

Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h.

Methods

Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. Trial Registration number: CTRI/2019/09/021152.

Results

Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan–Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups.

Conclusion

There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.
High-normal serum bilirubin decreased the risk of lower limb atherosclerosis in type 2 diabetes: a real-world study
Authors: Zhao Cui-Chun , Wang Jun-Wei , Chen Ming-Yun , Ke Jiang-Feng , Li Mei-Fang , Li Lian-Xi
Published: May 2023

Background

Bilirubin has been found to protect against overt atherosclerotic diseases, but to date, few studies have investigated the effects of bilirubin especially within the normal range on lower limb atherosclerosis. Therefore, we aimed to assess the associations of bilirubin within normal limits including total bilirubin (TB), conjugated bilirubin (CB) and unconjugated bilirubin (UCB) with lower limb atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods

7284 T2DM patients with normal levels of serum bilirubin were included in this cross-sectional, real-world study. Patients were divided into quintiles by TB levels (< 8.7, 8.7-10.19, 10.20-11.99, 12-13.99, > 13.99 µmol/L). Lower limb ultrasonography was conducted to detect lower limb plaque and stenosis. The association between serum bilirubin and lower limb atherosclerosis was explored by multiple logistic regression.

Results

A remarkable decrease in the prevalence of lower limb plaque (77.5, 75.3, 70.7, 71.7 and 67.9%) and stenosis (21.1, 17.2, 13.3, 13.0 and 12.0%) was observed across the TB quintiles. Multivariable regression analysis showed that serum TB levels were negatively correlated with higher risks of lower limb plaque and stenosis, both as a continuous variable [OR (95%CI): 0.870 (0.784–0.964), p = 0.008 for plaque; and 0.835 (0.737–0.946), p = 0.005 for stenosis] and as categorized in quintiles (p = 0.015 and 0.016 for plaque and stenosis). Interestingly, serum CB levels were only negatively correlated with lower limb stenosis [OR (95%CI): 0.767 (0.685–0.858), p < 0.001], whereas serum UCB levels were only negatively associated with lower limb plaque [ OR (95%CI): 0.864 (0.784–0.952), p = 0.003] after a fully-adjusted analysis. Furthermore, serum CRP was significantly decreased across the TB quintiles and negatively associated with serum TB (r = -0.107, p < 0.001), CB (r = -0.054, p < 0.001), and UCB (r = -0.103, p < 0.001).

Conclusions

High-normal serum bilirubin levels were independently and significantly related to reduced risks of lower limb atherosclerosis in T2DM patients. Furthermore, serum bilirubin levels including TB, CB and UCB were inversely correlated with CRP. These results suggested that higher-normal serum bilirubin may exhibit an anti-inflammatory and protective effect against lower limb atherosclerotic progression in T2DM subjects.
Reduced-order modeling for stochastic large-scale and time-dependent flow problems using deep spatial and temporal convolutional autoencoders
Authors: Abdedou Azzedine , Soulaimani Azzeddine
Published: May 2023

A non-intrusive reduced-order model based on convolutional autoencoders is proposed as a data-driven tool to build an efficient nonlinear reduced-order model for stochastic spatiotemporal large-scale flow problems. The objective is to perform accurate and rapid uncertainty analyses of the flow outputs of interest for which the input parameters are deemed uncertain. The data are constituted from a set of high-fidelity snapshots, collected using an inhouse high-fidelity flow solver, which correspond to a sample of the uncertain input parameters. The method uses a 1D-convolutional autoencoder to reduce the spatial dimension of the unstructured meshes used by the flow solver. Another convolutional autoencoder is used for the time compression. The encoded latent vectors, generated from the two compression levels, are then mapped to the input parameters using a regression-based multilayer perceptron. The proposed model allows for rapid predictions for unseen parameter values, allowing the output statistical moments to be computed efficiently. The accuracy of the proposed approach is compared to that of the linear reduced-order technique based on an artificial neural network through two benchmark tests (the one-dimensional Burgers and Stoker’s solutions) and a hypothetical dam break flow problem, with an unstructured mesh and over a complex bathymetry river. The numerical results show that the proposed methods present strong predictive capabilities to accurately approximate the statistical moments of the outputs. In particular, the predicted statistical moments are oscillations-free, unlike those obtained with the traditional proper orthogonal decomposition method. The proposed reduction framework is simple to implement and can be applied to other parametric and time-dependent problems governed by partial differential equations, which are commonly encountered in many engineering and science problems.
Reliability and validity of the brief version of the difficulties in emotion regulation scale in a sample of Turkish adolescents
Authors: Demirpence Secinti Dilara , Sen Ezgi
Published: May 2023

Background

Difficulty in regulating emotions increases during adolescence and can be associated with psychopathology. It is thus crucial to develop tools to identify adolescents at risk of having emotional difficulties. This study aimed to investigate the reliability and validity of a brief questionnaire in a sample of Turkish adolescents.

Methods

A total of 256 participants (mean age = 15.51 ± 0.85) were recruited. They completed the original form of the Difficulties in Emotion Regulation Scale (DERS-36), a brief version of DERS (DERS-16), the Barrett Impulsivity Scale (BIS-11), and the Toronto Alexithymia Scale (TAS). Psychometric properties of DERS-16 were investigated by confirmatory factor analysis, Cronbach’s alpha, and Pearson correlational analysis.

Results

A five-factor model and second-order bifactor model of DERS-16 were confirmed. Cronbach’s alpha values for the subscales varied between 0.69 and 0.88, while the reliability of the factors Difficulties in Emotional Processing and Difficulties in Emotion Regulation were 0.75 and 0.90, respectively. DERS-16 subscales were positively correlated with the BIS-11 and TAS. In addition, there were only minimal differences between the DERS-16 and DERS-36.

Conclusion

The DERS-16 is a valid and reliable scale for Turkish adolescents. The fact that it has fewer items than DERS-36, but has similar reliability and validity and can be used as two factors, provides significant advantages in terms of applicability.
Best Time of Day for Strength and Endurance Training to Improve Health and Performance? A Systematic Review with Meta-analysis
Authors: Bruggisser Fabienne , Knaier Raphael , Roth Ralf , Wang Wei , Qian Jingyi , Scheer Frank A. J. L.
Published: May 2023

Background

Current recommendations for physical exercise include information about the frequency, intensity, type, and duration of exercise. However, to date, there are no recommendations on what time of day one should exercise. The aim was to perform a systematic review with meta-analysis to investigate if the time of day of exercise training in intervention studies influences the degree of improvements in physical performance or health-related outcomes.

Methods

The databases EMBASE, PubMed, Cochrane Library, and SPORTDiscus were searched from inception to January 2023. Eligibility criteria were that the studies conducted structured endurance and/or strength training with a minimum of two exercise sessions per week for at least 2 weeks and compared exercise training between at least two different times of the day using a randomized crossover or parallel group design.

Results

From 14,125 screened articles, 26 articles were included in the systematic review of which seven were also included in the meta-analyses. Both the qualitative synthesis and the quantitative synthesis (i.e., meta-analysis) provide little evidence for or against the hypothesis that training at a specific time of day leads to more improvements in performance-related or health-related outcomes compared to other times. There was some evidence that there is a benefit when training and testing occur at the same time of day, mainly for performance-related outcomes. Overall, the risk of bias in most studies was high.

Conclusions

The current state of research provides evidence neither for nor against a specific time of the day being more beneficial, but provides evidence for larger effects when there is congruency between training and testing times. This review provides recommendations to improve the design and execution of future studies on this topic.

Registration: PROSPERO (CRD42021246468).
The association of QTc prolongation with cardiovascular events in cancer patients taking tyrosine kinase inhibitors (TKIs)
Authors: Ghafary Ismail , Kim Chang-Kyung , Roth Eric , Lu Michael , Taub Erin M. , Lee Susan , Cohen Ira , Lu Zhongju
Published: May 2023

Objective

To investigate the association between stages of QTc prolongation and the risk of cardiac events among patients on TKIs.

Methods

This was a retrospective cohort study performed at an academic tertiary care center of cancer patients who were taking TKIs or not taking TKIs. Patients with two recorded ECGs between January 1, 2009, and December 31, 2019, were selected from an electronic database. The QTc duration > 450ms was determined as prolonged. The association between QTc prolongation progression and events of cardiovascular disease were compared.

Results

This study included a total of 451 patients with 41.2% of patients taking TKIs. During a median follow up period of 3.1 years, 49.5% subjects developed CVD and 5.4% subjects suffered cardiac death in patient using TKIs (n = 186); the corresponding rates are 64.2% and 1.2% for patients not on TKIs (n = 265), respectively. Among patient on TKIs, 4.8% of subjects developed stroke, 20.4% of subjects suffered from heart failure (HF) and 24.2% of subjects had myocardial infarction (MI); corresponding incidence are 6.8%, 26.8% and 30.6% in non-TKIs. When patients were regrouped to TKIs versus non-TKIs with and without diabetes, there was no significant difference in the incidence of cardiac events among all groups. Adjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). There is a significant increased risk of HF events (HR, 95% CI: 2.12, 1.36–3.32) and MI events (HR, 95% CI: 1.78, 1.16–2.73) during the 1st visit. There are also trends for an increased incidence of cardiac adverse events associated with QTc prolongation among patient with QTc > 450ms, however the difference is not statistically significant. Increased cardiac adverse events in patients with QTc prolongation were reproduced during the 2nd visit and the incidence of heart failure was significantly associated with QTc prolongation(HR, 95% CI: 2.94, 1.73-5.0).

Conclusion

There is a significant increased QTc prolongation in patients taking TKIs. QTc prolongation caused by TKIs is associated with an increased risk of cardiac events.
Excitatory amino acids, possible causative agents of nodding syndrome in eastern Africa
Authors: Miyauchi Yasushi , Shiraishi Ayaka , Abe Konami , Sato Yasuaki , Kita Kiyoshi
Published: May 2023

Background

Nodding syndrome (NS) is one type of epilepsy and a progressive disease characterized by nodding symptoms with children in sub-Saharan Africa. The burden for NS children is heavy, not only mentally but financially for themselves and their families, and yet, the cause and cure of NS remain unknown. The kainic acid-induced model in experimental animals is a well-known epilepsy model that is useful for studying human diseases. In this study, we examined similarities of clinical symptoms and histological brain changes between NS patients and kainic acid-treated rats. In addition, we argued for kainic acid agonist as one of the causes of NS.

Methods

Clinical signs in rats were studied after kainic acid administration, and histological lesions including the expression of tau protein and gliosis, were examined at 24 h, 8 days, and 28 days after dosing.

Results

Kainic acid-induced epileptic symptoms were observed in rats, including nodding accompanied by drooling and bilateral neuronal cell death in the hippocampus and piriform cortex regions. In the regions that exhibited neuronal cell death, an increase in tau protein expression and gliosis were found immunohistochemically. The symptoms and brain histology were similar in the NS and kainic acid-induced rat models.

Conclusion

The results suggest that kainic acid agonist may be one of the causative substances for NS.
Biocontrol potential of entomopathogenic nematodes against the Khapra beetle Trogoderma granarium (Everts) (Coleoptera: Dermestidae)
Authors: Nawab Bushra , Javed Salma
Published: May 2023

Background

The Khapra beetle, Trogoderma granarium (Everts) (Coleoptera: Dermestidae) is one of the most destructive pests of stored wheat and barley worldwide. The broad practice of insecticides has been connected with insect resistance development coupled with the renaissance treated primary insects, environmental contamination, and toxicity to animals, man and other non-target organisms. These harms have invigorated the usage of alternative methods of managing this insect pest.

Results

For biocontrol potential, four species of entomopathogenic nematodes (EPN) were tested: Steinernema pakistanense PCSIR-10, S. bifurcatum PCSIR-39, S. saimkayai PCSIR-6 and S. abbasi PCSIR-17, against adult and larval stages of Khapra beetle under laboratory conditions. At 250 IJs/ml, S. pakistanense and S. bifurcatum caused 100 and 90% at larval stages and 92 and 89% against adult beetles, respectively.

Conclusion

This study documented that EPNs had a potential to control stored grain pest and could be utilized as alternatives of insecticides, which provide an adequate control of insect pest at postharvest stage, but in future more experiment will be required in commercial storage conditions.
The footprint of large wildfires on the multifunctionality of fire-prone pine ecosystems is driven by the interaction of fire regime attributes
Authors: Fernández-Guisuraga José Manuel , Marcos Elena , Calvo Leonor
Published: May 2023

Background

Mediterranean ecosystems dominated byPinus pinasterAit. (maritime pine) are subject to a shift from fuel-limited to drought-driven fire regimes, characterized by an increasing wildfire extent, recurrence, and severity. Previous studies have not addressed the interacting effects of fire recurrence and severity on the ecosystem multifunctionality (EMF) of maritime pine forests, although complex relationships between such fire regime attributes are expected. Here, we evaluated the medium-term effects of fire recurrence and severity on the EMF response of unmanaged, native pine ecosystems dominated byPinus pinasterin the western Mediterranean Basin. We considered four key ecosystem functions computed from functional indicators (carbon regulation, decomposition, soil fertility, and plant production), which were pooled into an EMF construct. The fire regime effects on the trade-offs and synergies between the considered ecosystem functions were also analyzed.

Results

Multiple ecosystem functions responded differentially to fire recurrence and severity. Fire recurrence had a strong effect on soil fertility, decomposition, and plant production functions. No significant effects of fire severity on any of the individual functions were detected. However, both fire regime attributes interacted to determine soil fertility and decomposition functions, suggesting that their performance is only impaired by fire severity when fire recurrence is low. The differing responses to the fire regime attributes among ecosystem functions fostered a significant EMF response to fire severity and its interaction with fire recurrence, indicating that the effect of fire severity on EMF was stronger under low fire recurrence scenarios, even when relationships between individual functions and fire severity were weak. Fire recurrence caused significant trade-offs between functions to emerge. However, these trade-offs were not strong enough to differ significantly from the intrinsic trade-offs (i.e., regardless of the fire regime) of maritime pine ecosystems.

Conclusions

Our results indicated the need to use an integrative approach to assess the response of ecosystem functioning to the fire regime in maritime pine ecosystems. Adaptive management responses are necessary towards the minimization of repeated burnings and the reduction of the fuel load in unmanaged maritime pine stands of the western Mediterranean Basin with similar characteristics to those analyzed in this study.
Conceptual design of the optical system of the 6.5m wide field multiplexed survey telescope with excellent image quality
Authors: Zhang Yifan , Jiang Haijiao , Shectman Stephen , Yang Dehua , Cai Zheng , Shi Yong , Huang Song , Lu Lu , Zheng Yamin , Kang Shaonan , Mao Shude , Huang Lei
Published: May 2023

Astrophysics and cosmology in the coming decades urgently need a large field-of-view (FOV), highly multiplexed spectroscopic survey telescope satisfying challenging image quality and stability requirements. The 6.5 m MUltiplexed Survey Telescope (MUST) proposed by Tsinghua University will be constructed on the Saishiteng Mountain of Northwest China to improve the spectroscopic survey capability of ground-based optical telescopes. In this paper, we demonstrate the conceptual design of the optical system of MUST. MUST will adopt a 6.5 m primary mirror, a 2.45 m secondary mirror, and a multiple-element widefield corrector (WFC) to ensure excellent image quality with an 80% encircled energy size of image spots less than ~ 0.6 arcsec in diameter for the entire 3° FOV and the whole 50° zenith angle range. Thanks to its compact 6.5 m Ritchey-Chretien system and 20,000 optical fibers on its Cassegrain focus, MUST will carry out state-of-the-art wide-field spectroscopic surveys with efficiency ~ 19 times higher than the Dark Energy Spectroscopic Instrument (DESI) using a measure proposed by Ellis et al. Upon completion around 2029, MUST will be one of the world's most advanced wide-field spectroscopic survey telescopes and a new essential reference for the future development of wide-field survey telescopes. It will enable significant advances in many fields in astrophysics and cosmology.
Evaluation of the growth, yield traits and the genetic diversity of some Brassica napus genotypes under Egyptian conditions
Authors: Shafey Sanaa , El-Maaty Shereen Abu , El Habbasha S. F. , Elarabi Nagwa I.
Published: May 2023

Background

Canola (Brassica napus L.) is considered an alternate oilseed plant. Therefore, this study aimed to evaluate some growth parameters, yield, chemical parameters and genetic diversity among thirteen canola genotypes including a collection of Chinese, German, French, and local genotypes under Egyptian conditions.

Result

Trapper genotype recorded the highest values of plant height (47.12 and 89.75 cm) and dry weight/plant (8.54 and 28.19 dry weight/plant) at 60 and 90 days from sowing, respectively. Data from the field experiments showed that significant differences were recorded among tested genotypes for all yield and its component parameters (i.e., plant height (cm), branches/no. plant, siliquas and seed weight (g/plant) and seed oil %. The genetic diversity and the relationships among the thirteen canola genotypes were evaluated utilizing sequence-related amplified polymorphism (SRAP) and simple-sequence repeats (SSRs) markers. The allelic frequency of the different SRAP and SSR markers tested has differed among the thirteen canola genotypes. The SRAP and SSR analyses showed 659 out of 742 and 15 out of 45 markers, respectively, were detected as polymorphic markers (88.8% and 33.33%) among the tested wheat cultivars In addition, the polymorphism information content (PIC), marker index (MI) and resolving power (RP) parameters were computed to assess the effectiveness of the markers. The results indicated the occurrence of a considerable genetic variation between Chinese, European and Egyptian genotypes.

Conclusion

These markers are of considerable value and can be utilized to screen large canola populations. The results of the comparison between the two molecular markers showed that the most effective marker that showed the genetic diversity between canola genotypes was SRAP (88.8%) polymorphism. It could be concluded that the tested canola genotypes could be cultivated under the Egyptian condition with high performance especially Trapper, Agamax and Topas genotypes. Therefore, it could be suggested that these three genotypes seem to be promising for oil gap reduction and need further evaluation for the expansion under new reclaimed regions.
Triplet Strategies in Metastatic Clear Cell Renal Cell Carcinoma: A Worthy Option in the First-Line Setting?
Authors: Fahey Catherine C. , Shevach Jeffrey W. , Flippot Ronan , Albiges Laurence , Haas Naomi B. , Beckermann Kathryn E.
Published: May 2023

Significant strides have been made in the frontline treatment of patients with advanced clear cell renal cell carcinoma (ccRCC). There are multiple standard-of-care doublet regimens consisting of either the combined dual immune checkpoint inhibitors, ipilimumab and nivolumab, or combinations of a vascular endothelial growth factor receptor tyrosine kinase inhibitor and an immune checkpoint inhibitor. Currently, there is an emergence of clinical trials examining triplet combinations. In COSMIC-313, a randomized phase III trial for patients with untreated advanced ccRCC, the triplet combination of ipilimumab, nivolumab, and cabozantinib was compared with a contemporary control arm of ipilimumab and nivolumab. While patients receiving the triplet regimen demonstrated improved progression-free survival, these patients also experienced greater toxicity and the overall survival data are still maturing. In this article, we discuss the role of doublet therapy as standard of care, the current data available for the promise of triplet therapy, the rationale to continue pursuing trials with triplet combinations, and factors for clinicians and patients to consider when choosing among frontline treatments. We present ongoing trials with an adaptive design that may serve as alternative methods for escalating from doublet to triplet regimens in the frontline setting and explore clinical factors and emerging predictive biomarkers (both baseline and dynamic) that may guide future trial design and frontline treatment for patients with advanced ccRCC.
Detecting and Managing T-DXd–Related Interstitial Lung Disease: The Five “S” Rules
Authors: Tarantino Paolo , Tolaney Sara M.
Published: May 2023

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Effects of Sleep Fragmentation and Estradiol Decline on Cortisol in a Human Experimental Model of Menopause
Authors: Cohn Aviva Y , Grant Leilah K , Nathan Margo D , Wiley Aleta , Abramson Mathena , Harder Jessica A , Crawford Sybil , Klerman Elizabeth B , Scheer Frank A J L , Kaiser Ursula B , Rahman Shadab A , Joffe Hadine
Published: May 2023

Context

Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase postmenopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline disturb the HPA axis.

Objective

We examined the effect of experimental fragmentation of sleep and suppression of estradiol as a model of menopause on cortisol levels in healthy young women.

Methods

Twenty-two women completed a 5-night inpatient study during the mid-to-late follicular phase (estrogenized). A subset (n = 14) repeated the protocol after gonadotropin-releasing hormone agonist-induced estradiol suppression. Each inpatient study included 2 unfragmented sleep nights followed by 3 experimental sleep fragmentation nights. This study took place with premenopausal women at an academic medical center. Interventions included sleep fragmentation and pharmacological hypoestrogenism, and main outcome measures were serum bedtime cortisol levels and cortisol awakening response (CAR).

Results

Bedtime cortisol increased 27% (P = .03) and CAR decreased 57% (P = .01) following sleep fragmentation compared to unfragmented sleep. Polysomnographic-derived wake after sleep-onset (WASO) was positively associated with bedtime cortisol levels (P = .047) and negatively associated with CAR (P < .01). Bedtime cortisol levels were 22% lower in the hypoestrogenized state compared to the estrogenized state (P = .02), while CAR was similar in both estradiol conditions (P = .38).

Conclusion

Estradiol suppression and modifiable menopause-related sleep fragmentation both independently perturb HPA axis activity. Sleep fragmentation, commonly seen in menopausal women, may disrupt the HPA axis, which in turn may lead to adverse health effects as women age.