bluuebunny/crossref_metadata_2025 huggingface dataset:
Agro-morphological genetic diversity assessment of Amaranthus genotypes from Ethiopia based on qualitative traits
Authors: Yeshitila Mekonnen , Gedebo Andargachew , Tesfaye Bizuayehu , Degu Hewan Demissie
Published: October 2024

Amaranths are a promising plant in the family of Amaranthaceae because of their nutritional and functional properties, such as their high antioxidant content and dietary fiber content. However, it's being disregarded for several reasons, such as ignorance, a lack of in-depth research, and the plant's long-term genetic growth in Ethiopia, among other factors. In the current work, we described the genetic diversity of 120 amaranth genotypes using qualitative criteria. The experiment, which was configured with an alpha lattice design and duplicated twice, was run for two seasons in 2020 and 2021. Twenty qualitative descriptors were looked for in the gathered data. Among the 20 qualitative variables that were assessed, the chi-square test result indicated the presence of prevailing phenotypic variation. The results of the agro-morphological characterization also revealed a significant amount of variance. The overall mean of the Shannon diversity indices (H') was 0.61. The indices for germination rate, leaf margin, prominence of leaf veins, and the existence of auxiliary inflorescence varied from 0.12 to 0.99. The estimated diversity indices showed more intra-regional diversity (0.66) than inter-regional diversity (0.34), demonstrating the existence of gene flow between growing regions. Shannon–Weaver Diversity Index, ranged from 0.00 for auxiliary inflorescence to 1.94 for leaf coloration, with an overall mean of 19 characters (95%) that were found to have high diversity (> 0.76) while auxiliary inflorescence was invariant. Except for auxiliary inflorescence, all qualitative features showed a lot of variation. Additionally,
Amaranthus hybridus L. subsp. cruentus
(L.) Theil recorded the greatest Shannon diversity index (0.47) while Amaranthus spinosus L. recorded the lowest (0.00). The hierarchical clustering grouped all the genotypes into three clusters. The first cluster included the most genotypes (58), followed by the second (47), and the third cluster contained the fewest (15). Principal component analysis showed that the first six principal components with eigenvalues greater than one contributed 72% of the variability among genotypes. The study unequivocally demonstrated that, even when the genotypes were grouped into a small number of clusters, there was still enough divergence within the clusters to demonstrate the genotypes of amaranth to have a high genetic diversity. These results indicate that there is substantial genetic diversity among Ethiopian amaranth genotypes, which should be safeguarded and may be utilized in breeding in the future.
Associations between C-reactive protein and individual symptoms of depression in a lower-middle income country
Authors: Fellows Elise , Jones Brett D. M. , Hodsoll John , Husain Nusrat , Khoso Ameer B. , Young Allan H. , Chaudhry Imran B. , Husain M. Ishrat
Published: October 2024

Background

Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs).

Aims

We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms.

Method

This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n= 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms.

Results

High plasma CRP (≥3 mg/L) was detected in 87% (n= 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16–5.25), early morning waking (odds ratio 2.65, 95% CI 1.29–6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39–21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14–0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14–0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation.

Conclusions

The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.
Cancer Care in Resource-Limited Countries: Jordan as an Example
Authors: Abdel-Razeq Hikmat , Al-Ibraheem Akram , Al-Rabi Kamal , Shamiah Omar , Al-Husaini Maysa , Mansour Asem
Published: October 2024

Jordan, a lower- to middle-income country, is relatively small, but with rapidly growing population and a challenged economy. Cancer is a growing health care problem and currently ranked second, after cardiovascular diseases, as a cause of death. Jordan's national cancer registry continues to suffer from problems mostly related to long lag time in reporting, absence of outcome data, and accurate staging. The number of new patients with cancer diagnosed in Jordan is increasing at an expected, none disturbing rate, fueled by population growth, improving life expectancy, changing population structure that hosts more older population, high rate of obesity, smoking, and lack of adequate exercise. However, age-standardized rate for cancer incidence is significantly lower than Western societies, yet, mortality rate is higher. Despite efforts, cancer is still diagnosed at more advanced stages and at younger age. The Jordan breast cancer program represents a great example of opportunistic screening that led to significant downstaging of breast cancer. Efforts to evaluate the feasibility of screening programs for colorectal and lung cancers are underway. Tremendous efforts resulted in the execution of the largest clinical cancer genetics program in the region that helps identify patients and at-risk relatives for hereditary cancers. Low-resourced countries, including Jordan, will not be able to keep up with the rapidly increasing cost of cancer care. A better access to clinical trials and moving cancer care to ambulatory settings should offset some of this cost. A cancer control program that addresses all issues of cancer care from screening and early detection, through active cost-effective treatment that assures wider access to palliative care, hospice, and survivorship programs under an expanded universal health coverage, is an urgent national health priority.
Nimotuzumab plus chemoradiotherapy versus placebo plus chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC): A prospective, randomized-controlled, double-blinded, multicenter phase III clinical trial.
Authors: Sun Yan , Hu Chaosu , Lin Qin , Gao Li , Wang Jianhua , Zhu Xiaodong , Hao Junfang , Lang Jin Yi , Wang Peiguo , Ye Ming , Li Xia , Xu Benhua , Wu Rong , Bai Chunmei , You Qingshan , Chen Xiaozhong , Wang Jun , Hu Desheng , Wu Gang , Pan Jian-ji
Published: October 2024

6001

Background:
Epidermal growth factor receptor (EGFR) is highly expressed in most NPC, and it is also an essential factor of prognosis for NPC. nimotuzumab is a humanized anti-EGFR monoclonal antibody. Retrospective clinical studies showed that nimotuzumab combined with chemo-radiotherapy had better survival benefits in locally advanced NPC. The present study is a confirmatory study that aims to assess the clinical efficacy of long-term survival and safety of nimotuzumab combined with chemo-radiotherapy in locally advanced NPC patients.
Methods:
Patients with locally advanced NPC were randomized (3:1) to receive nimotuzumab (200 mg, weekly, 7-8 weeks) plus chemo-radiotherapy (Arm A) versus chemo-radiotherapy (intensity-modulated radiation therapy or conventional radiotherapy, cisplatin100mg/m
2
/d, 21days/cycle, three cycles) plus placebo (Arm B) as front-line therapy. The primary endpoint was a 5-year OS rate, and the secondary endpoints included disease-free survival and safety.
Results:
482 patients in 24 study sites were enrolled (361 in Arm A vs. 121 in Arm B). Both groups were well balanced regarding age, gender, race and ethnicity. The 5-year OS rate was 76.9% in Arm A compared to 64.3% in Arm B (log-rank=4.125, p=0.042). The median DFS was 50.6 months and 42.6 months in Arm A and B, respectively. The 5-year DFS rate was 40.0% in Arm A compared to 14.4% in Arm B (log-rank=1.701, p=0.192). The combination of nimotuzumab plus chemo-radiotherapy was well tolerated. The incidence of adverse drug reactions (ADRs) in Arm A was similar to Arm B (35.7% vs. 42.1%, p=0.207), and the grade 3-5 ADRs as well (17.7% vs.15.7%, p=0.609).
Conclusions:
Nimotuzumab plus chemo-radiotherapy increase 5-year OS of NPC patients with good safety profile.
Clinical trial information: 01074021.
Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open-label, single-arm, phase Ib clinical trial.
Authors: Liu Zhigang , Huang Xiaotao , Liang Jun , Zhong Guihua , Liu Ye , Liang Lizhong , Hong Haiyu , Feng Weineng , Yang Shuang , Zhang Yaqin , Peng Yingpeng , Liu Qiandan , Zhou Yuling , Zhang Zhaoyuan
Published: October 2024

6023

Background:
The positive outcome of first-line programmed death receptor-1 (PD-1) inhibitors has been revealed in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Researches about neoadjuvant immunotherapy for resectable locally advanced HNSCC have been proceeding continuously, however the optimal regimen was inconclusive. Here, we combined a powerful chemotherapy regime, gemcitabine plus cisplatin (GP), and a PD-1 inhibitor to treat the potentially resectable locally advanced HNSCC followed by operation for exploring the safety and efficacy of the combination regime in this phase I trial.
Methods:
This was an open-label, single-arm, phase Ib clinical trial. Untreated patients, aged 18-70, with histologically confirmed localized advanced HNSCC (stage III-IVB), were enrolled. The eligible patients are scheduled to administered PD-1 inhibitor (Toripalimab) 240 mg on day 1, gemcitabine 1000 mg/m
2
on days 1 and 8, and cisplatin 80 mg/m
2
on day 1 every 21 days for two cycles. Radical resection was performed in 4-6 weeks after the first day of the second cycle. The primary endpoints were safety and no surgical-delay rate. Safety evaluation was performed in total participants in 90 days from the first day of treatment (or 30 days after surgery). The second endpoints consisted pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR) and R0 resection rate.
Results:
By December 10, 2021, twenty-three patients were enrolled. Up to now, 18 out of 23 patients successfully finished the operation on schedule. Grade 3/4 adverse events (AEs) occurred in totally 3 patients (13.0%), 2 (8.7%) case of neutropenia, and one each of fatigue (4.3%), hyperglycemia (4.3%), vomiting (4.3%) and diarrhea (4.3%). The most shared adverse events of grade 1/2 were anorexia (30.4%), fatigue (21.7%), vomitting (17.4%) and hyperglycemia (17.4%). The median interval between second administration and surgery was 33 days. For the 20 patients with available radiological examination at pre- and post-neoadjuvant therapy, the assessment per RESCIST criteria was as follow: 1 (5.0%) CR, 7 (35.0%) PR, 12 (60.0%) SD. R0 resection rate reached 100% in a total of 18 patients with complete surgical resection. Three patients achieved pCR at primary site (viable tumor = 0), 5 achieved MPR (0 < viable tumor≤10%) and 2 among 5 were near-pCR (viable tumor = 1%), and the other 11 patient did not reach MPR.
Conclusions:
Triweekly neoadjuvant Toripalimab plus GP was generally tolerated by the locally advanced HNSCC and contributed to a major pathological response in 44.4% patients at present. Research Sponsor: Shanghai Junshi Biosciences Co., Ltd.
Clinical trial information: NCT04947241.
Efficacy and safety of chemotherapy plus subsequent locoregional radiotherapy and toripalimab in de novo metastatic nasopharyngeal carcinoma.
Authors: Chen Si-Yuan , Chen Mingyuan , Rui You , Hua Yijun , Zou Xiong , Wang Zhi-Qiang
Published: October 2024

6025

Background:
Approximately 50% of primary metastatic nasopharyngeal carcinoma (mNPC) patients who received sequential chemoradiotherapy experience disease progression within one year. Improvements in therapy are greatly needed. This phase II study aimed to investigate the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitor combined with sequential chemoradiotherapy in de novo mNPC.
Methods:
Patients who demonstrated complete or partial response following 3 cycles of cisplatin and fluorouracil (PF) were enrolled. Eligible patients received 3 more cycles of PF and subsequent radiotherapy plus toripalimab every three weeks at a fixed dose of 240 mg. The primary end point was objective response rate (ORR) at three months after radiotherapy, and the secondary end points were progression-free survival (PFS), disease control rate (DCR) and safety profiles. Exploratory study included biomarker analysis and efficacy comparation based on a historical cohort. A Simon’s two-stage optimal design with one-sided type I error rate of 5% and power of 80% was utilized to compare a null hypothesis ORR of 54% against an alternative of 80%. Target accrual was a minimum of 22 patients (stage 1 and 2 combined).
Results:
Of the 22 enrolled patients (7 women and 15 men; median age of 54.5 years [IQR 40.5-57.5 years]), the ORR at three months after radiotherapy was 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the DCR was 81.8%. The median PFS was 19.4 months (95% CI 10.8-NR). Grade 3-4 adverse events occurred in 15 (68.2%) patients; two patients (9.1%) had grade 2 or 3 immune-related adverse events and discontinued toripalimab. This trial met its primary objective of demonstrating a significant ORR versus historical controls (81.8% vs. 54%,
P
= 0.024). Elevation of plasma EBV DNA post radiation was associated with worse median PFS (10.5 vs. 19.4 months; hazard ratio = 4.23, 95% CI 1.0-17.9;
P
= 0.033).
Conclusions:
The addition of toripalimab to sequential chemoradiotherapy displayed promising tumor response and manageable safety profile in primary mNPC. These results support a potential role of PD-1 inhibition as consolidation therapy in the first-line treatment of primary mNPC.
Clinical trial information: NCT04398056.
Four-year result of diffusion-weighted, MRI-guided, dose-painting radiotherapy following induction chemotherapy in patients with locally advanced recurrent nasopharyngeal carcinoma: A randomized controlled trial.
Authors: Liu Feng , Jiang Cuihong , Wu Xiangwei , Liu Wen , Fan Changgen , He Lili , Xiao Shuai , Li Yanxian , Ye Xu , Wu Wenqiong , Zhao Qi , Wang Hui
Published: October 2024

6033

Background:
We hypothesized that diffusion-weighted MR imaging (DWI) guided dose-painting radiotherapy (DP-RT) following induction chemotherapy (IC)was associated with improved local tumor control and progression-free survival compared with conventional MRI-based radiotherapy (RT) in locally advanced recurrentnasopharyngeal carcinoma (rNPC). The purpose of this randomized phase II trial was to compare the efficacy and toxicity of DWI guided DP-RT following IC versus standard conventional MRI-based radiotherapy following IC in locally advanced rNPC.
Methods:
Tow hundred and four patients with locally recurrent T3 to T4 NPC were randomly assigned to receive DWI-guided dose-painting radiotherapy (DP-RT) or conventional MRI-based radiotherapy. Patients in both groups received reirradiation using intensity modulated radiation therapy (IMRT) following cisplatin-based induction chemotherapy. In DP-RT group (group A, n = 102), subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). The dose to GTVnx-DWI was escalated to DT 65.4 Gy/30 Fx in 2.18 Gy per fraction. In conventional MRI-based RT group (group B), PGTVnx was irradiated at DT 60.0 Gy/30 Fx in 2.0 Gy per fraction. This trial is registered with chictr.org.cn, number ChiCTR2100052340.
Results:
Compared with conventional MRI-based radiotherapy, DWI-guided DP-RT significantly improved 4-year progression-free survival (PFS, 48.0% vs. 33.3%; P = 0.033), local control rate (LC, 85.3% vs. 69.6%; P = 0.007), and overall survival (OS, 52.0% vs. 37.3%; P = 0.035). No statistically significant differences in acute and late toxic effects (mucosal necrosis, trismus, temporal lobe necrosis, and cranial nerve palsy) were observed between the two groups. Dose painting (DWI-guided DP-RT vs conventional MRI-based RT) was a significant independent prognostic factor for PFS and LC (P = 0.035 and P = 0.020, respectively).
Conclusions:
Diffusion-weighted MRI guided dose-painting radiotherapy following induction chemotherapy is associated with a considerable progression-free survival and local control benefit, without increasing toxicity, as compared with standard conventional MRI-based RT following IC, among patients with locally recurrent T3 to T4 nasopharyngeal carcinoma.
Clinical trial information: ChiCTR2100052340.
Benefit of Whole-Pelvis Radiation for Patients With Muscle-Invasive Bladder Cancer: An Inverse Probability Treatment Weighted Analysis
Authors: Marcq Gautier , Kool Ronald , Dragomir Alice , Kulkarni Girish S. , Breau Rodney H. , Kim Michael , Busca Ionut , Abdi Hamidreza , Dawidek Mark , Uy Michael , Fervaha Gagan , Alimohamed Nimira , Izawa Jonathan , Jeldres Claudio , Rendon Ricardo , Shayegan Bobby , Siemens Robert , Black Peter C. , Cury Fabio L. , Kassouf Wassim
Published: October 2024

PURPOSE

The value of pelvic lymph node irradiation is debated for patients with muscle-invasive bladder cancer (MIBC) undergoing curative-intent radiation therapy (RT). We sought to compare the oncologic outcomes between bladder-only (BO)-RT and whole-pelvis (WP)-RT using a large Canadian multicenter collaborative database.

PATIENTS AND METHODS

The study cohort consisted of 809 patients with MIBC (cT2-4aN0-2M0) who underwent curative RT at academic centers across Canada. Patients were divided into two groups on the basis of the RT volume: WP-RT versus BO-RT. Inverse probability of treatment weighting (IPTW) and absolute standardized differences (ASDs) were used to balance covariates across treatment groups. Regression models were used to assess the effect of the RT volume on the rates of complete response (CR), cancer-specific survival (CSS), and overall survival (OS).

RESULTS

After exclusion criteria, 599 patients were included, of whom 369 (61.6%) underwent WP-RT. Patients receiving WP-RT were younger (ASD, 0.41) and more likely to have an Eastern Cooperative Oncology Group performance status of 0-1 (ASD, 0.21), clinical node-positive disease (ASD, 0.40), and lymphovascular invasion (ASD, 0.25). In addition, WP-RT patients were more commonly treated with neoadjuvant chemotherapy (ASD, 0.29) and concurrent chemotherapy (ASD, 0.44). In the IPTW cohort, BO-RT and WP-RT groups were well balanced (all pretreatment parameters with an ASD <0.10). In multivariable analysis, WP-RT was not associated with CR rates post-RT (odds ratio, 1.14 [95 CI, 0.76 to 1.72];
P
= .526) but was associated with both CSS (hazard ratio [HR], 0.66 [95% CI, 0.47 to 0.93];
P
= .016) and OS (HR, 0.68 [95% CI, 0.54 to 0.87];
P
= .002), independent of other prognostic factors.

CONCLUSION

Our study demonstrated that WP radiation was associated with better survival compared with bladder radiation alone after adjusted analysis. Additional randomized controlled trials are needed to confirm our findings.
Diagnostic Performance of Ultrasound vs Ultrasound-Guided FNAC in Thyroid Nodules: Data From the ElaTION Trial
Authors: Mehanna Hisham , Nankivell Paul , Boelaert Kristien , Woolley Rebecca , Sharma Neil , Sidhu Paul S , Madani Gitta , Da Forno Philip , Moreman Catherine , Palmer Andrew , Fulton-Lieuw Tessa , Taylor Judith , Rajaguru Kanchana , Bekker Jasper , Vaidhyanath Ram , Rehman Thaj , Deeks Jon
Published: October 2024

Introduction

ElaTION is a large multicenter pragmatic randomized controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound alone (US) compared with US-FNAC to inform and update current practice guidelines.

Methods

Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) vs US-FNAC.

Results

Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US alone was the same as US-FNAC (0.91 [95% CI, 0.85-0.97] vs 0.87 [95% CI, 0.80-0.95] P = .37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, P < .0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%), respectively (P < .0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (nondiagnostic) FNAC and no definitive diagnosis.

Malignancy risk was higher in smaller nodules: < 10 mm 23/60 (38.3%), 10-20 mm 46/162 (28.4%), and >20 mm 80/466 (17.2%) (P < .0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) vs 42/113 (37.2%) respectively (P = .18).

Conclusion

Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the British Thyroid Association classification. However, findings also suggest caution regarding existing recommendations for conservative management of nondiagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-U5) features may help identify high-risk subgroups for more proactive management.
Overexpression of NR1D1 Portends Disease Recurrence in Thyroid Cancer
Authors: Hsu Yi-Chiung , Kuo Chi-Yu , Chien Ming-Nan , Jhuang Jie-Yang , Huang Shih-Yuan , Chang Shao-Chiang , Cheng Shih-Ping
Published: October 2024

Context

Dysregulation of circadian rhythms has been linked to cancer susceptibility. Thyroid cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts.

Objective

Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid cancer and explore its prognostic and translational implications.

Methods

We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms.

Results

Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid cancer cells. The invasion-promoting effect of NR1D1 was regulated by the β-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo.

Conclusion

NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid cancer.
Short Stature in Klinefelter Syndrome From Aggrecan Mutation
Authors: Farrell Antoinette , Sura Sunitha R
Published: October 2024

Despite tall stature being a characteristic feature of Klinefelter syndrome, occasional cases of short stature have been reported. These cases are often attributed to GH deficiency. This case report details a unique case of a 16-year-old male with Klinefelter syndrome exhibiting proportionate short stature resulting from a heterozygous, likely pathogenic, variant in the ACAN gene c.7141G > A (p.Asp2381Asn). This specific variant, previously identified once in a family with a recessive inheritance pattern is reported here for the first time in an individual with Klinefelter syndrome. This report emphasizes the importance of a thorough evaluation and consideration of genetic testing for an underlying diagnosis in short-statured individuals with Klinefelter syndrome. Timely detection would enable appropriate therapeutic interventions.
Ablation of PC1/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity
Authors: Moeller Jana , Meier Daniel T
Published: October 2024

Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neuropeptide and endocrine peptide precursors; it is expressed in neuroendocrine tissues as well as in immune cells. In response to endotoxemia, global PC1/3 knockout mice mount a cytokine storm and die rapidly. Further, immune cells isolated from these mice have a pro-inflammatory signature, suggesting that PC1/3 activates an unknown anti-inflammatory peptide precursor in immune cells. Here, we tested this hypothesis using tissue-specific PC1/3 ablation models. Knocking out PC1/3 in the myeloid or the hematopoietic compartment did not induce any phenotype. In contrast, proopiomelanocortin (POMC)-specific PC1/3 knockout mice phenocopied global PC1/3 knockout mice, including an enlarged spleen size and a hyperinflammatory sepsis phenotype in response to mild endotoxemia. This phenotype was prevented by steroid therapy and mimicked by blocking corticoid receptors in wild-type mice. Thus, our data suggest that sepsis hypersensitivity in PC1/3 deficiency is uncoupled from immune cell intrinsic PC1/3 expression and is driven by a lack of anti-inflammatory glucocorticoids due to an impairment in the hypothalamic-pituitary-adrenal axis.
Curriculum Development for the South African Essential Steps in Managing Obstetric Emergencies (ESMOE) Anesthesiology Training Module: A Delphi Study
Authors: Kuün Engela , Spijkerman Sandra
Published: October 2024

BACKGROUND:

The United Nations Sustainable Development Goal 3 (SDG3) for 2030 aims at <70 maternal deaths per 100,000 live births. South Africa (SA) falls short of this goal and most deaths occur in district and regional hospitals. Due to low anesthesiologist (specialist anesthetist) numbers in the public sector, the anesthetic workforce in these hospitals consists mainly of nonspecialist (general practitioner) junior doctors with limited supervision. The Essential Steps in Managing Obstetric Emergencies (ESMOE) training program for interns was introduced in 2008 to reduce maternal deaths in SA. Training is not consistently offered at all intern-training institutions and it has not been recently revised. This study sought expert suggestions to guide a revision of the regulation, pedagogy, and content of the ESMOE anesthetic module.

METHODS:

A 3-round consensus-seeking modified Delphi technique was used whereby experts rated current and suggested learning outcomes as well as pedagogical- and regulatory aspects of the ESMOE anesthetic module in an anonymous, online, Likert-scale questionnaire. Consensus was defined as ≥70% agreement. Open-ended questions sought motivations for decisions and further suggestions for program improvement.

RESULTS:

Between March 4, 2021 and August 18, 2021, a total of 17/24 (71%), 16/17 (94%), and 15/16 (94%) consenting experts completed the first, second, and third rounds, respectively. During the 3 rounds, the panel achieved consensus on all but 2 questionnaire items. The panel agreed that ESMOE anesthesia training should be mandatory and that it should be offered through a blended learning model. They further concurred that the current learning outcomes should be retained, and suggested additional outcomes based on the most common causes of maternal mortality in SA.

CONCLUSIONS:

Attendance of the ESMOE anesthesia module should be mandatory. Its pedagogy should be updated to a blended learning style to benefit the current digital native intern generation. The content should be updated to address the main causes of maternal mortality in SA in line with SDG3. A national obstetric anesthesia guideline should be considered, and lea-dership and collaboration are required to improve the alignment of undergraduate, internship, and junior doctor anesthesia training in SA. The content, process, and stakeholder engagement suggestions in this study can assist short-course-based anesthesia workforce training in similar global contexts.
Παιδική λογοτεχνία και οντολογικός επαναπροσδιορισμός του υλικού κόσμου. Ο φιλοσοφικός λόγος και η εικονοποιητική μεταφορά ως μέσα για τη διάσπαση της διχοτόμησης φύσης-πολιτισμού
Authors: Αγγελάκη Ρόζη-Τριανταφυλλιά
Published: October 2024

Στο πλαίσιο της παγκόσμιας κινητοποίησης για μια νέα, ηθική προσέγγιση του περιβάλλοντος από τον άνθρωπο, συγγραφείς για παιδιά ευαισθητοποιήθηκαν και επιχείρησαν να ενσταλάξουν στους μικρούς αναγνώστες μια μετα-ανθρωπιστική φιλοσοφία, αποστασιοποιημένη από τις οντολογικές και επιστημολογικές παραδοχές που αντιλαμβάνονται τον άνθρωπο ως τον μοναδικό διαμορφωτή του κόσμου. Βασιζόμενοι στο ότι η εικονογράφηση εξυπηρετεί αισθητικούς, εκπαιδευτικούς και πρακτικούς σκοπούς, συγγραφείς για παιδιά επιλέγουν να βασιστούν στη συλλειτουργία του κειμενικού κώδικα με τον εικονιστικό και στη χρήση εικονοποιητικών μεταφορών, προκειμένου να μυήσουν τους αναγνώστες τους στην έκφραση της Περιβαλλοντικής Ηθικής μέσα από την εκτίμηση της Φύσης. Για τις ανάγκες του παρόντος άρθρου επιλέχθηκε ένα εικονοβιβλίο για παιδιά και ένα εικονογραφημένο παιδικό βιβλίο γνώσεων βραχείας φόρμας, που, μέσα από το μοτίβο του «ριζώματος», υποδεικνύουν στο κοινό τη σχέση των ανθρώπινων σωμάτων με τον μη-ανθρώπινο κόσμο και την εγγενή αξία των γονιδίων όλων των όντων. Σκοπός του άρθρου είναι να συγκρίνει ποιο από τα δυο είδη κατορθώνει να μεταλαμπαδεύσει περισσότερο εύληπτα στα παιδιά σύνθετες έννοιες που αφορούν στην Ύπαρξη και το οικοσύστημα, βοηθώντας τα να προβούν σε συνδέσεις του Εαυτού και της Φύσης. Θα ερευνηθεί η σχέση-κειμένου εικόνας στα επιλεγμένα έργα, το ιδεολογικό υπόβαθρο των συγγραφέων και των εικονογράφων, αν έλαβαν υπόψη το γνωστικό φορτίο και την εμπειρία των αναγνωστών τους και θα αναζητηθούν οι μεταφορές του φιλοσοφικού λόγου που δημιουργούν συνθήκες οπτικής ανάγνωσης και ευνοούν τη σύλληψη βαθύτερων νοημάτων.
Study of neutron induced reaction cross sections on Fe isotopes at the GELINA facility relevant to reactor applications
Authors: Γκάτης Γεώργιος
Published: October 2024

Οι μελέτες των αντιδράσεων νετρονίων παρουσιάζουν σημαντικό ενδιαφέρον, όχι μόνο για τη θεμελιώδη έρευνα στη Πυρηνική Φυσική αλλά και για πρακτικές εφαρμογές. Ο σίδηρος είναι ένα σημαντικό δομικό υλικό, που χρησιμοποιείται ευρέως σε εφαρμογές πυρηνικής τεχνολογίας, ειδικά σε πυρηνικούς αντιδραστήρες όπου τα εξαρτήματα από κράμα σιδήρου χρησιμοποιούνται για την κατασκευή της δομικής υποστήριξης του πυρήνα και ως ανακλαστήρες. Για το λόγο αυτό, ακριβή πυρηνικά δεδομένα για τις αντιδράσεις νετρονίων στο σίδηρο είναι απαραίτητα για το σχεδιασμό και την αξιόπιστη λειτουργία τέτοιων εγκαταστάσεων. Η έλλειψη πειραματικών δεδομένων, ειδικά στην ενεργειακή περιοχή των ταχέων νετρονίων, έχει δημιουργήσει διαφορές μεταξύ των πυρηνικών δεδομένων στις διάφορες αξιολογημένες βιβλιοθήκες.Νέες μετρήσεις ενεργών διατομών αντιδράσεων νετρονίων στο Fe πραγματοποιήθηκαν στην εγκατάσταση χρόνου πτήσης GELINA. Αρχικά, πραγματοποιήθηκαν πειράματα σκέδασης για τον προσδιορισμό της διαφορικής ενεργού διατομής της ελαστικής και ανελαστικής σκέδασης νετρονίων στο 54Fe και 56Fe στην ενεργειακή περιοχή των ταχέων νετρονίων (1-8 MeV), χρησιμοποιώντας εμπλουτισμένα δείγματα και για τα δύο ισότοπα. Για την ανίχνευση των σκεδαζόμενων νετρονίων, χρησιμοποιήθηκε το φασματόμετρο ELISA (ELastic and Inelastic Scattering Array). Το ανιχνευτικό σύστημα αποτελείται από 32 οργανικούς υγρούς σπινθηριστές για την ανίχνευση των σκεδαζόμενων νετρονίων και έναν θάλαμο σχάσης 235U για τη μέτρηση της ροής νετρονίων. Επιπλέον, πειράματα διέλευσης σε natFe πραγματοποιήθηκαν στο σταθμό μέτρησης των 50m της διαδρομής πτήσης 4. Τα νετρόνια ανιχνεύθηκαν από έναν σπινθηριστή γυαλιού λιθίου εμπλουτισμένο σε 6Li. Μετρήθηκαν δύο δείγματα φυσικού σιδήρου 1.2cm και 4.5cm.Τέλος, πραγματοποιήθηκαν θεωρητικοί υπολογισμοί για τη μελέτη της άμεσης σύλληψης στον 56Fe σε μια προσπάθεια να παρασχεθεί φυσική ερμηνεία πίσω από τις αλλαγές που έγιναν στην ενεργό διατομή της αντίδρασης σύλληψης στο 56Fe. Συγκεκριμένα, πραγματοποιήθηκαν δύο κύριες αλλαγές στα δεδομένα των αξιολογημένων βιβλιοθηκών. Προστέθηκε ένα τεχνητό υπόβαθρο στην χαμηλοενεργειακή περιοχή, ώστε να αναπαραχθούν μετρήσεις πειραμάτων integral σε αυτό το ενεργειακό εύρος. Η ενεργός διατομή πάνω από τα 850keV επίσης αυξήθηκε βάσει πειραματικών δεδομένων που παρέχονται από το εργαστήριο Rensselaer Polytechnic Institute (RPI).Ο στόχος της παρούσας εργασίας είναι η πραγματοποίηση νέων πειραμάτων και θεωρητικών υπολογισμών για τη μελέτη των ενεργών διατομών αντιδράσεων που προκαλούνται από νετρόνια στον σίδηρο σε μια προσπάθεια να αντιμετωπιστούν τα ζητήματα που αναφέρονται στις αξιολογημένες βιβλιοθήκες παρέχοντας νέα πειραματικά/θεωρητικά δεδομένα για βασικές αντιδράσεις και ενεργειακές περιοχές νετρονίων.
Σεξουαλική κακοποίηση μέσω εικόνας ως μορφή έμφυλης βίας στο διαδίκτυο. Ανάδυση στοιχείων σεξισμού και ενοχοποίησης θύματος στον αφηγηματικό λόγο των ανήλικων δραστών
Authors: Μπράνη Αναστασία
Published: October 2024

Η σεξουαλική κακοποίηση μέσω εικόνας, αποτελεί μια αναδυόμενη μορφή κυβερνοβίας με βάση το φύλο, η οποία απασχολεί την επιστημονική κοινότητα παγκοσμίως. Το φαινόμενο έχει επηρεάσει και τους εφήβους, με τα αγόρια να εμφανίζονται συχνότερα ως δράστες και τα κορίτσια ως θύματα. Οι πληροφορίες όμως για την εκδήλωση της συγκεκριμένης συμπεριφοράς, προέρχονται κυρίως από την πλευρά των θυμάτων, ενώ απουσιάζουν σχετικές μελέτες από την πλευρά των δραστών. Η  παρούσα μελέτη προσπαθεί να διαχειριστεί αυτό το κενό σχετικά με την έμφυλη βία, που προκύπτει από την μέχρι σήμερα έλλειψη μελετών σε στοχευμένο δείγμα εφήβων δραστών. Πιο συγκεκριμένα, αναφέρεται στην διερεύνηση στοιχείων σεξιστικής ιδεολογίας καθώς και ενοχοποίησης θύματος στον αφηγηματικό λόγο ανήλικων αγοριών, δραστών σεξουαλικής κακοποίησης μέσω εικόνας, ηλικίας 15-17, αξιοποιώντας ημιδομημένες συνεντεύξεις. Οι δράστες έχουν τη τάση να υποτιμούν τις πράξεις τους και να μην αναγνωρίζουν τη σοβαρότητα του προβλήματος. Στοιχεία σεξισμού και στερεοτύπων φύλου κυριαρχούν στο λόγο τους, ενώ τα κορίτσια αποδέκτες της διαδικτυακής κακοποίησης, σχετίζονταν με τους δράστες κυρίως ως σύντροφοι, αναδεικνύοντας ότι η βία στον κυβερνοχώρο σχετίζεται με τη βία στο φυσικό κόσμο. Η παρούσα μελέτη συνέβαλε στην ανάδειξη και κατανόηση  συμπεριφορών έμφυλης βίας από τους εφήβους στο κυβερνοχώρο.
More value and less waste in research on primary cam morphology and its natural history: a qualitative interview study of stakeholders' perspectives
Authors: Dijkstra H Paul , McAuliffe Sean , Boersma Jolanda , Clarke Mike , Khan Karim , Glyn-Jones Sion , Greenhalgh Trisha
Published: October 2024

Background Primary cam morphology, an acquired bony prominence at the head-neck junction of the femur, is highly prevalent in athlete populations, and causally associated with femoroacetabular impingement syndrome and early hip osteoarthritis. Experts agreed on key elements for primary cam morphology and a prioritised research agenda for the field. This research agenda will require higher-quality research to achieve meaningful progress on the aetiology, prognosis and treatment of primary cam morphology in athletes. Aim To explore stakeholders’ perspectives of high-quality research in the research field of primary cam morphology and its natural history. Methods Grounded in interpretive description, we used semi-structured interviews to explore stakeholders’ perspectives of high-quality research in the primary cam morphology research field. The framework for INcreasing QUality In patient-orientated academic clinical REsearch (INQUIRE) informed the interview guide. Audio-recorded interviews were transcribed and analysed using thematic analysis. We recruited a heterogenous and purposive maximum variation sample, drawing from a network of research contacts. Results Fifteen individuals, several with multiple perspectives on research quality in the field, participated. Exploring stakeholders’ perspectives on research quality through an established research quality framework (INQUIRE) illuminated areas for immediate action for research communities in the field of primary cam morphology and its natural history. We crafted five action inviting themes: research communities should: partner with athletes/patients; champion equity, diversity and inclusion; collaborate with one another; pursue open science; and nurture young scholars. Conclusion The findings of this study could inform concrete actions by research communities to pursue higher quality research—more research value and less waste—in the field of primary cam morphology and its natural history. Although the five action-inviting themes reflect contemporary trends in research, and could therefore be transferable to other areas of research, their practical application remains context- and field-specific.
Altered subcellular reactions to stress after a long-term human exposure to antarctic condition
Authors: Moiseyenko Ye. , Rozova K.
Published: October 2024

Medical research in Antarctica opens up new horizons to study individual health and reactions under stress and unusual environmental conditions. A long stay in Antarctica can evoke reactions associated with adaptation to hypoxia and mitochondrial dysfunction, determined by a set of molecular-genetic mechanisms. The aim was to study the changes in platelet ultrastructure in Antarctic winterers under hypoxic loading, and the ultrastructure of mitochondria (MT) of leukocytes in winterers, depending on the length of exposure to Antarctic conditions and number of expeditions participated. We included to the study 24 winterers, who once stayed in Antarctica during 1 year (group 1), 3-4 one-year stays (group 2), and 5-7 one-year stays (group 3). The control group included 8 men, who were not exposed to adverse environmental factors and never visited Antarctica.  We assessed the ultrastructure of platelet and leukocytes before and after the hypoxic loading. The background characteristics of the ultrastructure of platelets and leukocytes of winterers. Significant changes developed in the platelet and leukocytes mitochondria ultrastructure after hypoxic loading. The severity of changes in leukocyte mitochondria correlated with number of expeditions participated, and manifested by development of autophagy, apoptosis up to irreversible organelle changes, a partial or complete vacuolization, excessive swelling of organelles after 1 year stay, 3-4, and 5-7 one-year expeditions respectively. So, a long exposure to Antarctic conditions is associated with mitochondrial dysfunction.
Los derechos de la naturaleza y su repercusión en la defensa de katsa su del pueblo awá en Nariño (Colombia)
Authors: Sánchez Jaramillo Johana Fernanda
Published: October 2024

Esta obra estudia, desde una mirada interdisciplinaria e intercultural, las vías utilizadas para declarar a la Madre Tierra como sujeto de derechos en Colombia y otros países. El tema central son los paradigmas en los cuales se inscribe este cambio de estatus y la posibilidad de que se haga desde un enfoque intercultural. El libro devela si estas declaratorias son útiles, complementarias o irrelevantes en la lucha por la defensa del territorio. El objetivo fue establecer si ese cambio de estatus jurídico ha brindado una mayor protección o ha sido ineficaz. Lo anterior se desarrolla a través de una metodología cualitativa usando la doc- trina, la normatividad, la jurisprudencia, una encuesta a personas de Europa, Norteamérica y Latinoamérica, trabajo de campo en Nariño, testimonios de los awás y entrevistas a expertos ecuatorianos. En estas páginas, los lectores encontrarán un análisis profundo, una mirada fresca e intercultural que tiende puentes entre el conocimiento occidental y ancestral.
The comparison of novel serious games in ADHD screening and early diagnosis
Authors: Ściseł Alicja , Szymańska Kinga , Szyprowski Karol , Trześniowska Agata , Soroka Ewelina
Published: October 2024

Introduction: Despite the increasing global prevalence of ADHD in children, research predominantly focuses on treatment rather than on screening. There is a pressing need for practical tools to identify this disorder. The objective of this review was to conduct a detailed analysis of the novel games used for ADHD screening and early diagnosis.

Material and methods: Our interest was focused on comparing various aspects, such as effectiveness, types of parameters tested, characteristics of the research group, time consumption, and the kind of equipment necessary to conduct the game. Sources were gathered by exploring terms related to ADHD screening and diagnosis in gaming contexts via several databases. Inclusion criteria focused on papers from 2020 to 2024 in English and openly accessible. Ten clinical studies meeting the criteria were identified, analyzed, and compared in subsequent sections.

Results: Our analysis has revealed that the games under discussion are characterized by distinct mechanics and measure different parameters related to ADHD. The methods of their validation are not standardized. These aspects make it challenging to compare them. Certain games incorporate advanced technologies to enhance the objectivity of the screening process.

Conclusions: The results of our review confirm that the screening effectiveness comparable to that acquired by standardized tests could be obtained using serious games. Individuals with ADHD are at higher risk of addiction, though tailored video games can aid in the treatment of ADHD. However, there is a need to standardize the methodology for assessing the effectiveness of the games under analysis.

Keywords: attention-deficit/hyperactivity disorder, serious games, video games, screening, diagnosis
Ten-year clinical and radiological outcomes with a vitamin E-infused highly cross-linked polyethylene acetabular cup
Authors: Afghanyar Yama , Afghanyar Bedjan , Loweg Lennard , Drees Philipp , Gercek Erol , Dargel Jens , Rehbein Philipp , Kutzner Karl P.
Published: October 2024

Aims

Limited implant survival due to aseptic cup loosening is most commonly responsible for revision total hip arthroplasty (THA). Advances in implant designs and materials have been crucial in addressing those challenges. Vitamin E-infused highly cross-linked polyethylene (VEPE) promises strong wear resistance, high oxidative stability, and superior mechanical strength. Although VEPE monoblock cups have shown good mid-term performance and excellent wear patterns, long-term results remain unclear. This study evaluated migration and wear patterns and clinical and radiological outcomes at a minimum of ten years’ follow-up.

Methods

This prospective observational study investigated 101 cases of primary THA over a mean duration of 129 months (120 to 149). At last follow-up, 57 cases with complete clinical and radiological outcomes were evaluated. In all cases, the acetabular component comprised an uncemented titanium particle-coated VEPE monoblock cup. Patients were assessed clinically and radiologically using the Harris Hip Score, visual analogue scale (pain and satisfaction), and an anteroposterior radiograph. Cup migration and polyethylene wear were measured using Einzel-Bild-Röntgen-Analyze software. All complications and associated treatments were documented until final follow-up.

Results

Clinical assessment showed persistent major improvement in all scores. On radiological assessment, only one case showed a lucent line (without symptoms). At last follow-up, wear and migration were below the critical thresholds. No cup-related revisions were needed, indicating an outstanding survival rate of 100%.

Conclusion

Isoelastic VEPE cups offer high success rates and may prevent osteolysis, aseptic loosening, and the need for revision surgeries in the long term. However, longer follow-up is needed to validate our findings and confirm the advantages offered by this cup.

Cite this article: Bone Jt Open 2024;5(10):825–831.
Digital Badging for Information Literacy Instruction: Diffusion of Innovations Analysis and Case Study
Authors: Young Lauren M.
Published: October 2024

Abstract: Digital badging has seen widespread adoption within the US higher education sector with continued growth predicted. Might digital badging present an underrealized opportunity for libraries seeking new vehicles through which to deliver information literacy instructional content? This paper offers an analysis of badging in higher education and considers the strengths and weaknesses of digital badging for asynchronous information literacy instruction by employing Dr. Everett Rogers' Diffusion of Innovations theoretical lens. Current evidence is presented and a case study is provided, detailing Samford University Library's development of an information literacy digital badging pathway incorporating the ACRL Framework and the institution's Christian mission.
Academic Libraries, Counter-Storytelling, and Minoritized Students' Scholarly Identity Development
Authors: Ilett Darren
Published: October 2024

Abstract: This study uses the critical race theory approach of counter-storytelling to explore scholarly identity development among first-generation, low-income, BIPOC (Black, Indigenous, and People of Color), and women students transitioning to graduate school. Data included interview transcripts, observation notes, and student assignments from a program that supports students in completing an original research project and applying for graduate school. Findings show the frequent negative stereotypes about students that circulate in higher education as well as students' own counter-stories that reimagine academia and their place in it. Implications include ways that libraries can better support students' scholarly identity development.