bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-traumatic stress disorders, anxiety, and depression in college students during the COVID-19 pandemic: a cross-sectional study
Authors: Quan Lijuan , Lu Wei , Zhen Rui , Zhou Xiao
Published: April 2023

Objectives

The COVID-19 pandemic has caused an increase in psychiatric disorders in college students, particularly posttraumatic stress disorders (PTSD), depression, and anxiety. While existing studies assess the prevalence of these disorders and their predictors, they overlook potential complications caused by comorbidity between these disorders. To fill this gap, this study examined the prevalence of PTSD, depression, anxiety, and their comorbidity to inform targeted intervention for college students during the COVID-19 pandemic.

Design

Self-report questionnaires were used to assess 6,898 college students about six months after the COVID-19 outbreak.

Results

The results found that the prevalence of PTSD, depression, and anxiety were 15.5%, 32.2%, and 32.1% respectively, and the prevalence of comorbid PTSD and depression, comorbid PTSD and anxiety, comorbid depression and anxiety, and comorbid PTSD, depression, and anxiety symptoms were 11.5%, 11.6%, 20.4%, and 9.4% respectively. Moreover, left-behind status, lower economic status, previous trauma experiences, exposure to the pandemic, and rumination were risk factors of psychological distress, but self-disclosure was a protective factor for these disorders.

Conclusion

These results indicate that distinct psychiatric disorders may be comorbid in individuals, and are further influenced by pre-, within-, and post-disaster factors. Furthermore, psychological service targeted at college students should pay attention to comorbid symptoms rather than only symptoms of single disorders.
Aggregate index of systemic inflammation (AISI) in admission as a reliable predictor of mortality in COPD patients with COVID-19
Authors: Hosseninia Saeed , Ghobadi Hassan , Garjani Kara , Hosseini Seyed Amir Hossein , Aslani Mohammad Reza
Published: April 2023

Background

The role of leukocytes and systemic inflammation indicators in predicting the severity and mortality of inflammatory diseases has been well reported, such as the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), neutrophil/lymphocyte*platelet ratio (NLPR), derived neutrophil/lymphocyte ratio (dNLR), aggregate index of systemic inflammation (AISI), as well as systemic inflammation response index (SIRI) and systemic inflammation index (SII). The purpose of the present study was to investigate the prognostic role of systemic inflammatory indicators in the mortality of chronic obstructive pulmonary disease (COPD) patients with COVID-19.

Methods

This retrospective study included 169 COPD patients hospitalized with COVID-19. Demographic, clinical, and laboratory data were obtained from the patients’ electronic records. The ability of systemic inflammation indeces to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan–Meier curves, with the endpoint being death.

Results

ROC curves showed that the AUD level was significant for WBC, MLR, SIRI, and AISI. Interestingly, Kaplan-Meier survival curves revealed that survival was lower with higher MLR (HR = 2.022, 95% CI = 1.030 to 3.968, P < 0.05) and AISI (HR = 2.010, 95% CI = 1.048 to 3.855, P < 0.05) values. However, the multivariate Cox regression model showed that only AISI was significantly associated with survival.

Conclusion

AISI in COPD patients with COVID-19 was a reliable predictor of mortality.
Cooled radiofrequency ablation of the sacroiliac joint a retrospective case series
Authors: Maalouly Joseph , Rao Prashanth J
Published: April 2023

Background

Sacroiliac (SI) joint dysfunction is a common source of back pain. Recent evidence from different parts of the world suggest that cooled radiofrequency ablation of sacral nerves supplying the SI joints has superior pain alleviating properties than currently available treatment options for SI joint dysfunction.

Patients and methods

After obtaining institutional review board approval, the medical records of 81 patients who underwent cooled radiofrequency ablation in a single institution and by a single surgeon were analyzed retrospectively. The recurrence of pain, progression to fusion and functional outcomes were noted. The patients were operated on between June 2020 and December 2021, they include 59 females and 22 males, the average age was 55.4 ± 17.3. Follow up was at least 6 months postoperative.

Results

22 of the patients had previously underwent lumbar fusions. Follow up period ranged from 6 to 18 months. After radiofrequency ablation, 7 patients progressed to fusions, and 6 patients had to have the procedure done again to relieve their pain. Student t-test was used to compare between preoperative and postoperative values of NPRS (numerical pain rating score) and ODI (Oswestry disability index). It showed significance with P-value < 0.001 in both.

Conclusions

Sacroiliac joint radiofrequency ablation is a good option in the treatment of SI joint pain showing good results in the short term follow up period. It is a simple procedure that can be done in less than 30 min and is capable of providing significant pain relief for patients with sacroiliac joint dysfunction.
Pectoralis major rupture in body builders: a case series including anabolic steroid use
Authors: Stefanou Nikolaos , Karamanis Nikolaos , Bompou Effrosyni , Vasdeki Dionysia , Mellos Thomas , Dailiana Zoe H.
Published: April 2023

Background

Rupture of the pectoralis major (PM) muscle is a rare injury, with increasing incidence over the last decades, mainly due to participation in weightlifting and contact sports. Surgical management of PM injuries has been related with superior functional outcome, faster return to activities, better cosmesis and higher level of patients’ satisfaction. The aim of the study is to present our experience in the management of this rare clinical entity and to correlate the use of anabolic steroids in the occurrence of the injury and the impact of type of injury, method of reconstruction and anabolic steroids on the post-operative outcome.

Cases

We present a series of six male bodybuilding athletes who sustained PM rupture during weightlifting. We recorded the location & type of injury, the history and type of anabolic steroids use, the method of repair and the post-operative outcome.

Treatment and outcomes

The mean follow-up period was 16 (12–24) months. All patients treated surgically had excellent results according to Bak criteria and returned to full activity within 5.4 (5–7) months following surgical reconstruction. No post-operative complications were recorded, despite the continued use of anabolic steroids, however one patient died from myocardial infarction within a year of surgical treatment.

Conclusions

PM rupture is an injury with increasing incidence within bodybuilding athletes probably not related to the dominance of the limb. Fixation of the tendon with suture anchors results in excellent clinical outcome and patient’s satisfaction postoperatively regardless the chronicity of the repair. Our observations in these cases suggest that anabolic steroids use may contribute to the injury due to an excessive upward adjustment of the athlete's goals in lifting weights and moreover the continuation of administration even in the recovery period does not seem to have a negative effect either on the time or on the level of adequate functional recovery postoperatively.
Greenhouse test of spraying dsRNA to control the western flower thrips, Frankliniella occidentalis, infesting hot peppers
Authors: Khan Falguni , Kim Minlee , Kim Yonggyun
Published: April 2023

Background

The western flower thrips Frankliniella occidentalis is an insect pest that damages various crops, including hot peppers. It is a vector of a plant pathogen, tomato spotted wilt virus. To control this pest, chemical insecticides have been used in the past, but the control efficacy is unsatisfactory owing to rapid resistance development by F. occidentalis.

Methodology

: This study reports a novel control technology against this insect pest using RNA interference (RNAi) of the vacuolar-type ATPase (vATPase) expression. Eight subunit genes (vATPase-A ∼ vATPase-H) of vATPase were obtained from the F. occidentalis genome and confirmed for their expressions at all developmental stages.

Results

Double-stranded RNAs (dsRNAs) specific to the eight subunit genes were fed to larvae and adults, which significantly suppressed the corresponding gene expressions after 24-h feeding treatment. These RNAi treatments resulted in significant mortalities, in which the dsRNA treatments at ∼2,000 ppm specific to vATPase-A or vATPase-B allowed complete control efficacy near 100% mortality in 7 days after treatment. To prevent dsRNA degradation by the digestive proteases during oral feeding, dsRNAs were formulated in a liposome and led to an enhanced mortality of the larvae and adults of F. occidentalis. The dsRNAs were then sprayed at 2,000 ppm on F. occidentalis infesting hot peppers in a greenhouse, which resulted in 53.5–55.9% control efficacy in 7 days after treatment. Even though the vATPases are conserved in different organisms, the dsRNA treatment was relatively safe for non-target insects owing to the presence of mismatch sequences compared to the dsRNA region of F. occidentalis.

Conclusion

These results demonstrate the practical feasibility of spraying dsRNA to control F. occidentalis infesting crops.
Transcriptomic profiling of the yeast Komagataella phaffii in response to environmental alkalinization
Authors: Albacar Marcel , Zekhnini Abdelghani , Pérez-Valle Jorge , Martínez José L. , Casamayor Antonio , Ariño Joaquín
Published: April 2023

Background

Adaptation to alkalinization of the medium in fungi involves an extensive remodeling of gene expression. Komagataella phaffii is an ascomycetous yeast that has become an organism widely used for heterologous protein expression. We explore here the transcriptional impact of moderate alkalinization in this yeast, in search of suitable novel promoters able to drive transcription in response to the pH signal.

Results

In spite of a minor effect on growth, shifting the cultures from pH 5.5 to 8.0 or 8.2 provokes significant changes in the mRNA levels of over 700 genes. Functional categories such as arginine and methionine biosynthesis, non-reductive iron uptake and phosphate metabolism are enriched in induced genes, whereas many genes encoding iron-sulfur proteins or members of the respirasome were repressed. We also show that alkalinization is accompanied by oxidative stress and we propose this circumstance as a common trigger of a subset of the observed changes. PHO89, encoding a Na+/Pi cotransporter, appears among the most potently induced genes by high pH. We demonstrate that this response is mainly based on two calcineurin-dependent response elements located in its promoter, thus indicating that alkalinization triggers a calcium-mediated signal in K. phaffii.

Conclusions

This work defines in K. phaffii a subset of genes and diverse cellular pathways that are altered in response to moderate alkalinization of the medium, thus setting the basis for developing novel pH-controlled systems for heterologous protein expression in this fungus.
CAR T-Cell therapy for the management of mantle cell lymphoma
Authors: Huang Zoufang , Chavda Vivek P. , Bezbaruah Rajashri , Dhamne Hemant , Yang Dong-Hua , Zhao Hong-Bing
Published: April 2023

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. Although with the progress in our knowledge of the causes for MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL. Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed. The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.
Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy
Authors: Qiao Xuehan , Hu Zhangmin , Xiong Fen , Yang Yufei , Peng Chen , Wang Deqiang , Li Xiaoqin
Published: April 2023

The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy.
Cost-effectiveness analysis of sorafenib, lenvatinib, atezolizumab plus bevacizumab and sintilimab plus bevacizumab for the treatment of advanced hepatocellular carcinoma in China
Authors: Gong Hongyu , Ong Siew Chin , Li Fan , Weng Zhiying , Zhao Keying , Jiang Zhengyou
Published: April 2023

Background and Objective

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, especially in China. According to the 2021 Chinese Society of Clinical Oncology guidelines, sorafenib, lenvatinib, atezolizumab combined with bevacizumab, and sintilimab combined with bevacizumab are recommended as first-line treatment options for advanced HCC. This study provides a cost-effectiveness analysis of these treatments from the patient perspective.

Methods

A partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.

Results

All compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.

Conclusions

In this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.
HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity
Authors: Naicker Delon , Sonela Nelson , Jin Steven W. , Mulaudzi Takalani , Ojwach Doty , Reddy Tarylee , Brockman Mark A. , Brumme Zabrina L. , Ndung’u Thumbi , Mann Jaclyn K.
Published: April 2023

Background

Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed.

Results

No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4+ T cell decline (p = 0.45). CD4 down-regulation (p = 0.02) and SERINC5 down-regulation (p = 0.003) were significant determinants of E values in univariate analyses, with the greatest relative contribution for SERINC5 down-regulation, and only SERINC5 down-regulation remained significant in the multivariate analysis (p = 0.003). Using a codon-by-codon analysis, several amino acids were significantly associated with increased (10I, 11V, 38D, 51T, 65D, 101V, 188H and, 191H) or decreased (10K, 38E, 65E, 135F, 173T, 176T and, 191R) SERINC5 down-regulation activity. Site-directed mutagenesis experiments of selected mutants confirmed a substantial reduction in SERINC5 down-regulation activity associated with the mutation 173T, while mutations 10K, 135F, and 176T were associated with more modest reductions in activity that were not statistically significant.

Conclusions

These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.
Screening for thyroid disease in pregnancy: a study of Danish clinical practice
Authors: Hatting Line Cleman , Kristensen Marie Østergaard , Lundgaard Maja Hjelm , Sørensen Anne , Andersen Stine Linding
Published: April 2023

Background

Thyroid disease in pregnant women is a matter of clinical awareness, and current clinical guidelines recommend a risk-based screening strategy. This study aimed to evaluate current clinical practice regarding screening for thyroid disease in pregnancy in Denmark.

Methods

A cross-sectional study was performed in the North Denmark Region with consecutive inclusion of 150 pregnant women from Aalborg University Hospital each year in 2020 and 2021. Medical records were reviewed according to the recommended risk-based screening criteria for thyroid disease in pregnancy. Any measurement of thyroid-stimulating hormone (TSH) was assessed 3 months prior to and in pregnancy.

Results

Altogether 292 pregnant women who received no current treatment for thyroid disease were included. A total of 81 (27.7%) had a measurement of TSH before or during the pregnancy, and 30 women (10.3%) in the early pregnancy specifically. One or more of the screening criteria for thyroid disease recommended in the Danish clinical practice guideline were fulfilled in 37 of the 81 women (45.7%) with thyroid function tested and among 41 of the 211 (19.4%) women who did not have thyroid function tested before or during pregnancy.

Conclusion

In a Danish regional investigation, 1 in 4 women had their thyroid function tested in relation to a pregnancy. However, recommended risk-based screening criteria for thyroid disease in pregnancy were heterogeneously distributed. Results encourage considerations on the current practice for the screening of thyroid function in Danish pregnant women and inform the general debate.
Methylglyoxal: a novel upstream regulator of DNA methylation
Authors: Dube Gaurav , Tiamiou Assia , Bizet Martin , Boumahd Yasmine , Gasmi Imène , Crake Rebekah , Bellier Justine , Nokin Marie-Julie , Calonne Emilie , Deplus Rachel , Wissocq Tom , Peulen Olivier , Castronovo Vincent , Fuks François , Bellahcène Akeila
Published: April 2023

Background

Aerobic glycolysis, also known as the Warburg effect, is predominantly upregulated in a variety of solid tumors, including breast cancer. We have previously reported that methylglyoxal (MG), a very reactive by-product of glycolysis, unexpectedly enhanced the metastatic potential in triple negative breast cancer (TNBC) cells. MG and MG-derived glycation products have been associated with various diseases, such as diabetes, neurodegenerative disorders, and cancer. Glyoxalase 1 (GLO1) exerts an anti-glycation defense by detoxifying MG to D-lactate.

Methods

Here, we used our validated model consisting of stable GLO1 depletion to induce MG stress in TNBC cells. Using genome-scale DNA methylation analysis, we report that this condition resulted in DNA hypermethylation in TNBC cells and xenografts.

Results

GLO1-depleted breast cancer cells showed elevated expression of DNMT3B methyltransferase and significant loss of metastasis-related tumor suppressor genes, as assessed using integrated analysis of methylome and transcriptome data. Interestingly, MG scavengers revealed to be as potent as typical DNA demethylating agents at triggering the re-expression of representative silenced genes. Importantly, we delineated an epigenomic MG signature that effectively stratified TNBC patients based on survival.

Conclusion

This study emphasizes the importance of MG oncometabolite, occurring downstream of the Warburg effect, as a novel epigenetic regulator and proposes MG scavengers to reverse altered patterns of gene expression in TNBC.
FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer
Authors: Peng SanFei , Yin YuHan , Zhang YiZheng , Zhu Feng , Yang Ge , Fu Yang
Published: April 2023

Background

FYN is a nonreceptor tyrosine kinase that regulates diverse pathological processes. The pro-cancer role of FYN in multiple malignancies has been elucidated. However, the mechanisms that FYN promotes gastric cancer (GC) progression remain largely unknown.

Methods

In vitro and in vivo assays were used to investigate the function of FYN. FYN, TOPK, p-TOPK expression in GC specimens were detected by immunohistochemistry. Phosphoproteomics assays identify TOPK downstream substrate molecules. The molecular mechanism was determined using COIP assays, pull-down assays, immunofluorescence co-localization assays, western blotting,32p-labeled isotope radioautography assays, vitro kinase assays, and TOPK knockout mice.

Results

FYN was found to be significantly upregulated in GC tissues as well as in GC cells. Knockdown of FYN expression markedly attenuated the malignant phenotype of GC cells in vitro and in vivo. Mechanistically, we identified TOPK/PBK as a novel downstream substrate of FYN, FYN directly phosphorylates TOPK at Y272. One phosphospecific antibodies against Y272 was developed to validate the phosphorylation of TOPK by FYN. Moreover, the TOPK-272F mutation impaired the interaction between TOPK and FYN, leading to disappeared TOPK phosphorylation. Consistently, human GC tissues displayed increased p-TOPK(Y272), which correlated with poor survival. Phosphoproteomics results showed a significant downregulation of both HSPB1 and p-HSPB1(ser15) in TOPK-knockdown cells, which was confirmed by TOPK-konckout mice.

Conclusions

FYN directly binds to TOPK in GC cells and phosphorylates TOPK at the Y272, which leads to proliferation and metastasis of GC. FYN-TOPK axis facilitates GC progression by phosphorylating HSPB1. Collectively, our study elucidates the pivotal role of the FYN-TOPK-HSPB1 cascade in GC.
Unicompartmental knee arthroplasty vs. high tibial osteotomy for medial knee osteoarthritis (UNIKORN): a study protocol of a randomized controlled trial
Authors: Siren Juuso , Rämö Lasse , Rantasalo Mikko , Komulainen Olli , Skants Noora , Reito Aleksi , Kosola Jussi , Lindahl Jan
Published: April 2023

Background

Medial knee osteoarthritis (OA) is a common health problem resulting in knee pain and limiting patients’ physical activity. After failed conservative treatment, unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are possible surgical treatment options for this condition. There is a paucity of high-quality evidence in the literature comparing objective and subjective outcomes of these procedures. Also, there is no common agreement on whether these procedures provide comparable results in late-stage medial knee OA patients.

Methods

We will perform a prospective randomized controlled trial comparing HTO and UKA in patients with late-stage medial knee OA. 100 patients with isolated medial knee OA (KL III–IV) are assigned to either UKA (n = 50) or HTO (n = 50) procedure in patients 45–65 years of age. Our primary outcome will be KOOS5 at one year postoperatively. Secondary outcomes include OARSI physical assessment, length of stay, wearable activity watch, radiographs (OA progression according to Kellgren-Lawrence classification), patient-reported outcomes (KOOS subscales, pain visual analog scale [VAS], Lysholm, and Oxford knee scores), and adverse events (conversion to total knee arthroplasty, surgery-related complications, need for revision surgery) outcomes. Our hypothesis is that neither of the interventions is superior as measured with KOOS5 at 12 months.

Ethics and dissemination

The institutional review board of the Helsinki and Uusimaa Hospital District has approved the protocol. We will disseminate the findings through peer-reviewed publications.

Trial registration

ClinicalTrials.gov/TooloH NCT05442242. Registered on 7/1/2022.
Stratified distribution of Th17 and Treg cells in patients with multi-stage rheumatoid arthritis
Authors: Su Rui , Li Baochen , Wu Ruihe , Xie Yuhuan , Gao Anqi , Gao Chong , Li Xiaofeng , Wang Caihong
Published: April 2023

Objective

Rheumatoid arthritis (RA) is a typical, progressive autoimmune disease. Its occurrence and development are associated with dysregulation of T and B cell numbers. However, the specific immune characteristics of different RA courses remain incompletely defined. Here, we describe the peripheral blood lymphocyte subsets, particularly CD4 + T subsets, of different RA courses with a focus on early RA (Ea-RA).

Methods

In all, 131 patients with Ea-RA, 117 with advanced RA (Ad-RA), and 109 with treated RA (Tr-RA) were enrolled. We collected general clinical data. Whole blood samples obtained from the patients and 97 healthy controls (HCs) were analysed via flow cytometry.

Results

Decreased absolute NK cell numbers and increased CD4/CD8 T cell ratios were observed in different RA groups, including Ea-RA, compared to healthy controls. In Ea-RA patients, the Th17 and Treg cell numbers were similar to those in HCs. We performed k-means clustering based on the profiles of Th17 and Treg cells for patients with multi-stage of RA. We identified three patient types: type A characterised by relatively low Treg and Th17 cell numbers, type B with moderate levels of Treg cells and levels of Th17 cells similar to that of type C patients, and type C with high levels of Treg cells and levels of Th17 cells similar to that of type B patients.

Conclusion

The immune characteristics of Ea-RA patients differ from those of HCs; an immune system disorder is apparent although no differences in Th17 and Treg levels were evident between Ea-RA patients and HCs. We found distributional heterogeneities of Th17 and Treg cells in patients with multi-stage of RA. Stratified management based on such heterogeneity may serve as a useful novel immunotherapy allowing of early intervention.
Effect of interval and continuous small-sided games training on the bio-motor abilities of young soccer players: a comparative study
Authors: Daryanoosh Farhad , Alishavandi Hossein , Nemati Javad , Basereh Aref , Jowhari Alireza , Asad-manesh Enayatollah , Oliveira Rafael , Brito João Paulo , Prieto-González Pablo , García-Calvo Tomás , Khoramipour Kayvan , Nobari Hadi
Published: April 2023

Objective

The present study compared the effects of two different small-sided game (SSG) training methods, interval (ISSG) and continuous (CSSG) on the bio-motor abilities of young soccer players.

Methods

Sixteen young soccer players (age: 19.5 ± 0.5 years; height: 177 ± 4.72 cm) were ranked based on the result of a running-based anaerobic sprint test (RAST) and randomly divided into two groups: CSSG (n = 8) and ISSG (n = 8). The training protocols were performed for eight weeks, three sessions per week. Participants were assessed twice (pre- and post-intervention) to estimate their anaerobic capacity with the RAST, aerobic capacity with Yo-Yo intermittent recovery test, body fat percentage with a bioimpedance analysis, speed with a 30-meter run test, and agility with the Illinois agility test. During the training session, the rating of the perceived exertion (RPE) and heart rate (mean and maximum) were recorded to assess the training load.

Results

In general, aerobic and anaerobic capacities improved after ISSG (p < 0.05, for all). The between-group analysis with repeated measures ANOVA revealed higher values for ISSG than CSSG groups post-intervention in anaerobic power (p = 0.042, ηp2 = 0.264). In addition, the independent t-test results indicated that ISSG presented lower values of mean heart rate (p = 0.023, effect size [ES] = 0.85) and RPE (p < 0.05, ES = 0.88) than CSSG. Moreover, higher values for maximum heart rate were revealed for ISSG than for the CSSG group (p = 0.004, ES = 0.85).

Conclusion

In conclusion, the findings of this study suggests that ISSG can lead to better improvements in anaerobic power and aerobic capacity than CSSG. Additionally, the ISSG led to a lower mean heart rate and RPE than the CSSG. Therefore, coaches and trainers may want to consider incorporating ISSG into their training programs for young soccer players to enhance their bio-motor abilities.
It all depends on which side of the fence you are standing: agent and recipient perspectives are differently linked with job crafting
Authors: Roczniewska Marta , Marszałek Magdalena
Published: April 2023

Background

In social contexts, people may view themselves as agents, who are in control of the environment, or recipients, who succumb to what others have decided. Here, we investigated how these perspectives determine job crafting (JC)—self-initiated employee behaviors targeted at altering job characteristics to fit them with one’s needs.

Methods

Study 1 tested the relationships between chronic agent–recipient tendencies and JC in a cross-lagged panel design. Study 2 was a randomized experiment where agent–recipient perspectives were manipulated to predict JC intentions in the week to follow.

Results

Supporting our predictions, while agents sought structural job resources and increased challenging demands, recipients resorted to reducing hindering demands (Study 1). Study 2 revealed that activating an agent perspective led to stronger intentions to increase structural job resources and challenging demands.

Conclusions

We conclude that agent and recipient perspectives are linked with differential patterns of JC behaviors. Strengthening agency is a vital step in forming job redesign goals during JC interventions.
Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents
Authors: Moreno Lucas , DuBois Steven G. , Glade Bender Julia , Mauguen Audrey , Bird Nick , Buenger Vickie , Casanova Michela , Doz François , Fox Elizabeth , Gore Lia , Hawkins Douglas S. , Izraeli Shai , Jones David T.W. , Kearns Pamela R. , Molenaar Jan J. , Nysom Karsten , Pfister Stefan , Reaman Gregory , Smith Malcolm , Weigel Brenda , Vassal Gilles , Zwaan Christian Michel , Paoletti Xavier , Iasonos Alexia , Pearson Andrew D.J.
Published: April 2023

PURPOSE

There is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.

METHODS

After a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.

RESULTS

Combinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.

CONCLUSION

An optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer.
Tracheostomy, Feeding-Tube, and In-Hospital Postoperative Mortality in Children: A Retrospective Cohort Study
Authors: Brown Sydney E. S. , Hall Matt , Cassidy Ruth B. , Zhao Xinyi , Kheterpal Sachin , Feudtner Chris
Published: April 2023

BACKGROUND:

Neuromuscular/neurologic disease confers increased risk of perioperative mortality in children. Some patients require tracheostomy and/or feeding tubes to ameliorate upper airway obstruction or respiratory failure and reduce aspiration risk. Empiric differences between patients with and without these devices and their association with postoperative mortality have not been previously assessed.

METHODS:

This retrospective cohort study using the Pediatric Health Information System measured 3- and 30-day in-hospital postsurgical mortality among children 1 month to 18 years of age with neuromuscular/neurologic disease at 44 US children’s hospitals, from April 2016 to October 2018. We summarized differences between patients presenting for surgery with and without these devices using standardized differences. Then, we calculated 3- and 30-day mortality among patients with tracheostomy, feeding tube, both, and neither device, overall and stratified by important exposures, using Fisher exact test to test whether differences were significant.

RESULTS:

There were 43,193 eligible patients. Unadjusted 3-day mortality was 1.3% (549/43,193); 30-day mortality was 2.7% (1168/43,193). Most (79.1%) used neither a feeding tube or tracheostomy, 1.2% had tracheostomy only, 15.5% had feeding tube only, and 4.2% used both devices. Compared to children with neither device, children using either or both devices were more likely to have multiple CCCs, dysphagia, chronic pulmonary disease, cerebral palsy, obstructive sleep apnea, or malnutrition, and a prolonged intensive care unit (ICU) stay within the previous year. They were less likely to present for high-risk surgeries (33% vs 57%). Having a feeding tube was associated with decreased 3-day mortality overall compared to having neither device (0.9% vs 1.3%, P = .003), and among children having low-risk surgery, and surgery during urgent or emergent hospitalizations. Having both devices was associated with decreased 3-day mortality among children having low-risk surgery (0.8% vs 1.9%; P = .013), and during urgent or emergent hospitalizations (1.6% vs 2.9%; P = .023). For 30-day mortality, having a feeding tube or both devices was associated with lower mortality when the data were stratified by the number of CCCs.

CONCLUSIONS:

Patients requiring tracheostomy, feeding tube, or both are generally sicker than patients without these devices. Despite this, having a feeding tube was associated with lower 3-day mortality overall and lower 30-day mortality when the data were stratified by the number of CCCs. Having both devices was associated with lower 3-day mortality in patients presenting for low-risk surgery, and surgery during urgent or emergent hospitalizations.
Restricted Polypharmacy Compared to Usual Care in Mechanically Ventilated Patients: A Retrospective Cohort Study
Authors: Bose Somnath , Lehman Li-Wei , Talmor Daniel , Shahn Zachary
Published: April 2023

BACKGROUND:

Adverse effects of excessive sedation in critically ill mechanically ventilated patients are well described. Although guidelines strongly recommend minimizing sedative use, additional agents are added as infusions, often empirically. The tradeoffs associated with such decisions remain unclear.

METHODS:

To test the hypothesis that a pragmatic propofol-based sedation regimen with restricted polypharmacy (RP; ie, prohibits additional infusions unless a predefined propofol dosage threshold is exceeded) would increase coma-and ventilator-free days compared with usual care (UC), we performed a retrospective cohort study of adults admitted to intensive care units (ICUs) of a tertiary-level medical center who were mechanically ventilated, initiated on propofol infusion, and had >50% probability of need for continued ventilation for the next 24 hours. We compared RP to UC, adjusting for baseline and time-varying confounding (demographics, care unit, calendar time of admission, vitals, laboratories, other interventions such as vasopressors and fluids, and more) through inverse probability weighting in a target trial framework. Ventilator-free days and coma-free days within 30 days of intubation and in-hospital mortality were the outcomes of interest.

RESULTS:

A total of 7974 patients were included in the analysis, of which 3765 followed the RP strategy until extubation. In the full cohort under UC, mean coma-free days were 23.5 (95% confidence interval [CI], [23.3–23.7]), mean ventilator-free days were 20.6 (95% CI, [20.4–20.8]), and the in-hospital mortality rate was 22.0% (95% CI, [21.2–22.8]). We estimated that an RP strategy would increase mean coma-free days by 1.0 days (95% CI, [0.7–1.3]) and ventilator-free days by 1.0 days (95% CI, [0.7–1.3]) relative to UC in our cohort. Our estimate of the confounding-adjusted association between RP and in-hospital mortality was uninformative (−0.5%; 95% CI, [−3.0 to 1.9]).

CONCLUSIONS:

Compared with UC, RP was associated with more coma- and ventilator-free days. Restricting addition of adjunct infusions to propofol may represent a viable strategy to reduce duration of coma and mechanical ventilation. These hypothesis-generating findings should be confirmed in a randomized control trial.
Age-Related Differences between Old and Very Old Men in Performance and Fatigability Are Evident after Cycling but Not Isometric or Concentric Single-Limb Tasks
Authors: VARESCO GIORGIO , LUNEAU ERIC , MILLET GUILLAUME Y. , FÉASSON LÉONARD , LAPOLE THOMAS , ROZAND VIANNEY
Published: April 2023

Purpose

This study aimed to compare performance and fatigability between young (n = 13; 18–30 yr), old (n = 13; 60–80 yr), and very old (n = 12; >80 yr) men during a single-joint isometric (ISO) and concentric (CON) task performed on an isokinetic dynamometer and a cycling (BIKE) task.

Methods

Participants randomly performed incremental tasks consisting of stages of 75 contractions (i.e., 120 s, 0.8 s on/0.8 s off) for ISO and CON and 120 s at 37.5 rpm (similar duty cycle) for BIKE. Increments were set as a percentage of body weight. Knee extensor maximal force, voluntary activation, and twitch amplitude were measured at baseline, after each stage, and at task failure (five out of eight contractions below the target force or 6 s in a row at a cadence <37.5 rpm).

Results

Compared with young men, performance (number of stages) was 24% and 40% lower in old and very old men in ISO, 54% and 59% lower in CON, and 36% and 60% lower in BIKE (all P < 0.05). Performance of old and very old differed only in BIKE (P < 0.01). For the last common stages performed, compared with young, force loss was greater for very old men in ISO and for old and very old men in BIKE (all P < 0.05). Overall, for the last common stage performed and task failure, old and very old men presented similar force loss, alterations in voluntary activation, and twitch amplitude.

Conclusions

Our findings reveal that, with workloads relative to body weight, differences in performance between old and very old men could only be observed during BIKE (i.e., the more ecologically valid task). Results from isometric or concentric conditions might not be transferable to dynamic exercise with large muscle masses.
Cinematic rendering to improve visualization of supplementary and ectopic teeth using CT datasets
Authors: Willershausen Ines , Necker Fabian , Kloeckner Roman , Seidel Corinna Lesley , Paulsen Friedrich , Gölz Lina , Scholz Michael
Published: April 2023

Objectives:

Ectopic, impacted, and supplementary teeth are the number one reason for cross-sectional imaging in pediatric dentistry. The accurate post-processing of acquired data sets is crucial to obtain precise, yet also intuitively understandable three-dimensional (3D) models, which facilitate clinical decision-making and improve treatment outcomes. Cinematic rendering (CR) is anovel visualization technique using physically based volume rendering to create photorealistic images from DICOM data. The aim of the present study was to tailor pre-existing CR reconstruction parameters for use in dental imaging with the example of the diagnostic 3D visualization of ectopic, impacted, and supplementary teeth.

Methods:

CR was employed for the volumetric image visualization of midface CT data sets. Predefined reconstruction parameters were specifically modified to visualize the presented dental pathologies, dentulous jaw, and isolated teeth. The 3D spatial relationship of the teeth, as well as their structural relationship with the antagonizing dentition, could immediately be investigated and highlighted by separate, interactive 3D visualization after segmentation through windowing.

Results:

To the best of our knowledge, CR has not been implemented for the visualization of supplementary and ectopic teeth segmented from the surrounding bone because the software has not yet provided appropriate customized reconstruction parameters for dental imaging. When employing our new, modified reconstruction parameters, its application presents a fast approach to obtain realistic visualizations of both dental and osseous structures.

Conclusions:

CR enables dentists and oral surgeons to gain an improved 3D understanding of anatomical structures, allowing for more intuitive treatment planning and patient communication.
Analysis of differences in Muscle Power for female university students majoring in sports according to BMI levels
Authors: Mocanu George-Danut
Published: April 2023

Muscle Power (often expressed in terms of explosive strength or explosive force) is required in most sports activities that involve intense and rapid contractions. Purpose: Identifying the dif-ferences and their significance, between the muscle strength values for the female students of the Faculty of Physical Education and Sports, according to their classification by BMI levels. Materi-al and method: 77 female students of the Faculty of Physical Education and Sport from Galati were evaluated through 6 upper body muscle power tests (30s Plyometric Push-Ups, Shot put, Medicine ball chest throw, Overhead Medicine Ball Throw-forward, Overhead, Medicine Ball Throw-backward, Overhand ball throw) and 7 lower body muscle power tests (Speed Test 10m, Standing Long Jump Test, Vertical Jump Test, 3-Hop Test, 30s Continuous vertical jumps, 30s Lateral double leg hop test, The multiple 5 bounds test). The groups were divided according to BMI levels (underweight 11 cases, normal weight 53 cases and overweight 13 cases). The non-parametric Kruskal–Wallis and Mann-Whitney U tests were used to assess the differences be-tween groups. Results: Arithmetic average values indicate the superiority of underweight and normal-weight women for lower-body strength and overweight and normal-weight women for upper-body strength, especially for heavy objects throw variants. However, performance differ-ences (assessed by ranks) are in most cases insignificant (Z values correspond to thresholds P>0.05). The only exceptions with significant differences (P<0.05) are for Overhead Medicine Ball Throw-forward (with the superiority of the overweight over the underweight) and Shot put - track and field (with the superiority of the overweight over the underweight). Conclusion: The constant involvement of female students in curricular and sports physical activities mitigates the differences between the muscle power of the 3 BMI categories. However, the small numerical composition - for the underweight and overweight groups - does not allow the generalization of the results, as studies on larger samples are needed and have common concerns related to the specifics of the sports practiced.