bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering the Genomic Regions Associated with Yield Maintenance in Rice Under Drought Stress Using an Integrated Meta-Analysis Approach
Authors: Daryani Parisa , Amirbakhtiar Nazanin , Soorni Jahad , Loni Fatemeh , Darzi Ramandi Hadi , Shobbar Zahra-Sadat
Published: January 2024

The complex trait of yield is controlled by several quantitative trait loci (QTLs). Given the global water deficit issue, the development of rice varieties suitable for non-flooded cultivation holds significant importance in breeding programs. The powerful approach of Meta-QTL (MQTL) analysis can be used for the genetic dissection of complicated quantitative traits. In the current study, a comprehensive MQTL analysis was conducted to identify consistent QTL regions associated with drought tolerance and yield-related traits under water deficit conditions in rice. In total, 1087 QTLs from 134 rice populations, published between 2000 to 2021, were utilized in the analysis. Distinct MQTL analysis of the relevant traits resulted in the identification of 213 stable MQTLs. The confidence interval (CI) for the detected MQTLs was between 0.12 and 19.7 cM. The average CI of the identified MQTLs (4.68 cM) was 2.74 times narrower compared to the average CI of the initial QTLs. Interestingly, 63 MQTLs coincided with SNP peak positions detected by genome-wide association studies for yield and drought tolerance-associated traits under water deficit conditions in rice. Considering the genes located both in the QTL-overview peaks and the SNP peak positions, 19 novel candidate genes were introduced, which are associated with drought response index, plant height, panicle number, biomass, and grain yield. Moreover, an inclusive MQTL analysis was performed on all the traits to obtain “Breeding MQTLs”. This analysis resulted in the identification of 96 MQTLs with a CI ranging from 0.01 to 9.0 cM. The mean CI of the obtained MQTLs (2.33 cM) was 4.66 times less than the mean CI of the original QTLs. Thirteen MQTLs fulfilling the criteria of having more than 10 initial QTLs, CI < 1 cM, and an average phenotypic variance explained greater than 10%, were designated as “Breeding MQTLs”. These findings hold promise for assisting breeders in enhancing rice yield under drought stress conditions.
Genome-scale metabolic network model and phenome of solvent-tolerant Pseudomonas putida S12
Authors: Han Sol , Kim Dohyeon , Kim Youngshin , Yoon Sung Ho
Published: January 2024

Background

Pseudomonas putida S12 is a gram-negative bacterium renowned for its high tolerance to organic solvents and metabolic versatility, making it attractive for various applications, including bioremediation and the production of aromatic compounds, bioplastics, biofuels, and value-added compounds. However, a metabolic model of S12 has yet to be developed.

Results

In this study, we present a comprehensive and highly curated genome-scale metabolic network model of S12 (iSH1474), containing 1,474 genes, 1,436 unique metabolites, and 2,938 metabolic reactions. The model was constructed by leveraging existing metabolic models and conducting comparative analyses of genomes and phenomes. Approximately 2,000 different phenotypes were measured for S12 and its closely related KT2440 strain under various nutritional and environmental conditions. These phenotypic data, combined with the reported experimental data, were used to refine and validate the reconstruction. Model predictions quantitatively agreed well with in vivo flux measurements and the batch cultivation of S12, which demonstrated that iSH1474 accurately represents the metabolic capabilities of S12. Furthermore, the model was simulated to investigate the maximum theoretical metabolic capacity of S12 growing on toxic organic solvents.

Conclusions

iSH1474 represents a significant advancement in our understanding of the cellular metabolism of P. putida S12. The combined results of metabolic simulation and comparative genome and phenome analyses identified the genetic and metabolic determinants of the characteristic phenotypes of S12. This study could accelerate the development of this versatile organism as an efficient cell factory for various biotechnological applications.
Genome-wide characterization of COMT family and regulatory role of CsCOMT19 in melatonin synthesis in Camellia sinensis
Authors: Pham Thanh Huyen , Tian Xingyu , Zhao Huimin , Li Tong , Lu Litang
Published: January 2024

Background

Caffeic acid O-methyltransferase (COMT) is a key enzyme that regulates melatonin synthesis and is involved in regulating the growth, development, and response to abiotic stress in plants. Tea plant is a popular beverage consumed worldwide, has been used for centuries for its medicinal properties, including its ability to reduce inflammation, improve digestion, and boost immune function. By analyzing genetic variation within the COMT family, while helping tea plants resist adversity, it is also possible to gain a deeper understanding of how different tea varieties produce and metabolize catechins, then be used to develop new tea cultivars with desired flavor profiles and health benefits.

Results

In this study, a total of 25 CsCOMT genes were identified based on the high-quality tea (Camellia sinensis) plant genome database. Phylogenetic tree analysis of CsCOMTs with COMTs from other species showed that COMTs divided into four subfamilies (Class I, II, III, IV), and CsCOMTs was distributed in Class I, Class II, Class III. CsCOMTs not only undergoes large-scale gene recombination in pairs internally in tea plant, but also shares 2 and 7 collinear genes with Arabidopsis thaliana and poplar (Populus trichocarpa), respectively. The promoter region of CsCOMTs was found to be rich in cis-acting elements associated with plant growth and stress response. By analyzing the previously transcriptome data, it was found that some members of CsCOMT family exhibited significant tissue-specific expression and differential expression under different stress treatments. Subsequently, we selected six CsCOMTs to further validated their expression levels in different tissues organ using qRT-PCR. In addition, we silenced the CsCOMT19 through virus-induced gene silencing (VIGS) method and found that CsCOMT19 positively regulates the synthesis of melatonin in tea plant.

Conclusion

These results will contribute to the understanding the functions of CsCOMT gene family and provide valuable information for further research on the role of CsCOMT genes in regulating tea plant growth, development, and response to abiotic stress.
Molecular evolution analysis of MYB5 in Brassicaceae with specific focus on seed coat color of Brassica napus
Authors: Dai Guoqiang , Liu Yi , Shen Wenjie , Zhu Bo , Chen Lunlin , Chen Daozong , Tan Chen
Published: January 2024

Background

MYB transcription factors are splay a vital role in plant biology, with previous research highlighting the significant impact of the R2R3-MYB-like transcription factor MYB5 on seed mucilage biosynthesis, trichome branching, and seed coat development. However, there is a dearth of studies investigating its role in the regulation of proanthocyanidin (PA) biosynthesis.

Results

In this study, a total of 51 MYB5 homologous genes were identified across 31 species belonging to the Brassicaceae family, with particular emphasis on Brassica napus for subsequent investigation. Through phylogenetic analysis, these genes were categorized into four distinct subclasses. Protein sequence similarity and identity analysis demonstrated a high degree of conservation of MYB5 among species within the Brassicaceae family. Additionally, the examination of selection pressure revealed that MYB5 predominantly underwent purifying selection during its evolutionary history, as indicated by the Ka/Ks values of all MYB5 homologous gene pairs being less than one. Notably, we observed a higher rate of non-synonymous mutations in orthologous genes compared to paralogous genes, and the Ka/Ks value displayed a stronger correlation with Ka. In B. napus, an examination of expression patterns in five tissues revealed that MYB5 exhibited particularly high expression in the black seed coat. The findings from the WGCNA demonstrated a robust correlation between MYB5 and BAN(ANR) associated with PA biosynthesis in the black seed coat, providing further evidence of their close association and co-expression. Furthermore, the results obtained from of the analysis of protein interaction networks offer supplementary support for the proposition that MYB5 possesses the capability to interact with transcriptional regulatory proteins, specifically TT8 and TT2, alongside catalytic enzymes implicated in the synthesis of PAs, thereby making a contribution to the biosynthesis of PAs. These findings imply a plausible and significant correlation between the nuique expression pattern of MYB5 and the pigmentation of rapeseed coats. Nevertheless, additional research endeavors are imperative to authenticate and substantiate these findings.

Conclusions

This study offers valuable insights into the genetic evolution of Brassicaceae plants, thereby serving as a significant reference for the genetic enhancement of Brassicaceae seed coat color.
Relationship between serum soluble suppression of tumorigenicity (ST) 2 and global longitudinal strain in early onset preeclampsia
Authors: Prameswari Hawani Sasmaya , Effendi Cut Azlina , Khalid Achmad Fitrah , Irianti Setyorini , Fatati Ita , Akbar Mohammad Rizki
Published: January 2024

Background

Preeclampsia is one of the leading causes of death in childbearing women worldwide. Hemodynamic changes in preeclampsia can trigger cardiac remodeling as indicated by increase of soluble-ST2 (sST2). Global longitudinal strain were able to detect systolic dysfunction better than the ejection fraction. This study aims to evaluate the correlation between serum levels of sST2 towards GLS in patients with early-onset preeclampsia.

Methods

This is a cross-sectional observational study with correlation analysis. Subjects were patients with severe preeclampsia with gestational age before 34 weeks at Dr. Hasan Sadikin Central General Hospital Bandung and Bandung Kiwari Regional General Hospital from June to August 2022. Examination of sST2 was carried out through blood samples using the ELISA method. sST2 was measured using Presage ST2 Assay reagent. GLS examination was carried out using speckle tracking technique with EchoPAC. Correlation analysis was conducted using the Pearson test if normally distributed, otherwise Spearman’s correlation was conducted. Correlation analysis was followed by linear regression.

Results

A total of 30 patients met the inclusion criteria. The mean age was 30.83 ± 7.09, with 17 (56.7%) multiparous patients. The median sST2 was 145.75 ng/mL, and the median GLS was − 17.4%. Spearman correlation analysis showed that there was a significant positive correlation with moderate strength between sST2 and GLS (r = 0.583; p < 0.002). Linear regression showed that every 1 ng/ml increase in sST2 would give an increase in GLS of 0.014%.

Conclusion

There is a significant correlation between sST2 and GLS in patients with early onset severe preeclampsia.
The association between serum uric acid / serum creatinine ratio and in-hospital outcomes in elderly patients with acute myocardial infarction
Authors: Jiang Lujing , Jin JunGuo , He Xuyu , Hu Xiangming , Guo Lan , Chen Guo , Zhou Yingling
Published: January 2024

Background

The role of Serum uric acid (SUA) in acute myocardial infarction (AMI) was controversial, which might be influenced by the renal clearance function of the patients. The present study aimed to explore the association between serum uric acid to serum creatinine ratio (SUA/Scr), reflecting a net production of SUA, and the in-hospital outcomes of elderly patients with AMI.

Methods

In this retrospective study, a total of 330 elderly AMI patients (≥ 75 years) were enrolled. Data of SUA and Scr on admission were collected to calculate SUA/Scr ratio. Logistic regression analysis and receiver-operating curves were performed to assess the association between SUA/Scr ratio and in-hospital major adverse cardiovascular events (MACEs) and all-cause death.

Results

Among the 330 patients, 68 patients had MACEs and 44 patients died. Patients with MACEs or died had lower SUA/Scr values compared with those without MACEs or survival (P < 0.05). Univariate logistic analysis showed that a lower value of SUA/Scr (< 3.45) was significantly associated with in-hospital MACEs (odd ratios (OR): 2.359, 95% confidential interval (CI): 1.369–4.065, P = 0.002) and death (OR: 2.424, 95% CI: 1.275–4.608, P = 0.007). After correcting for confounding factors, a lower SUA/Scr value was still independently associated with in-hospital MACEs (OR: 2.144, 95% CI: 1.169–3.934, P = 0.014) and death (OR: 2.125, 95% CI: 1.050–4.302, P = 0.036). Subgroup analysis showed that the association between a lower SUA/Scr ratio and increased risk of in-hospital outcomes could observed only in males (OR: 2.511, 95%CI: 1.211–5.207, P = 0.013 for MACEs; OR: 2.730, 95% CI: 1.146–6.502, P = 0.023 for death).

Conclusions

A lower SUA/Scr ratio was associated with an increased risk of in-hospital adverse events in elderly patients with AMI, especially in males, which maybe a marker of poor outcomes for elderly AMI patients.
The mode of delivery does not influence the occurrence of post-partum perianal disease flares in patients with inflammatory bowel disease
Authors: Otero-Piñerio Ana M. , Aykun N. , Maspero M. , Holubar Stefan , Hull Tracy , Lipman Jeremy , Steele Scott R. , Lightner Amy L.
Published: January 2024

Introduction

Perianal disease occurs in up to 34% of inflammatory bowel disease (IBD) patients. An estimated 25% of women will become pregnant after the initial diagnosis, thus introducing the dilemma of whether mode of delivery affects perianal disease. The aim of our study was to analyze whether a cesarean section (C-section) or vaginal delivery influence perianal involvement. We hypothesized the delivery route would not alter post-partum perianal manifestations in the setting of previously healed perianal disease.

Methods

All consecutive eligible IBD female patients between 1997 and 2022 who delivered were included. Prior perianal involvement, perianal flare after delivery and delivery method were noted.

Results

We identified 190 patients with IBD who had a total of 322 deliveries; 169 (52%) were vaginal and 153 (48%) were by C-section. Nineteen women (10%) experienced 21/322 (6%) post-partum perianal flares. Independent predictors were previous abdominal surgery for IBD (OR, 2.7; 95% CI, 1–7.2; p = 0.042), ileocolonic involvement (OR, 3.3; 95% CI, 1.1–9.4; p = 0.030), previous perianal disease (OR, 22; 95% CI, 7–69; p < 0.001), active perianal disease (OR, 96; 95% CI, 21–446; p < 0.001) and biologic (OR, 4.4; 95% CI,1.4–13.6; p < 0.011) or antibiotic (OR, 19.6; 95% CI, 7–54; p < 0.001) treatment. Negative association was found for vaginal delivery (OR, 0.19; 95% CI, 0.06–0.61; p < 0.005). Number of post-partum flares was higher in the C-section group [17 (11%) vs. 4 (2%), p = 0.002].

Conclusions

Delivery by C-section section was not protective of ongoing perianal disease activity post-delivery, but should be recommended for women with active perianal involvement.
Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study
Authors: Stylianou-Riga Paraskevi , Boutsikou Theodora , Kouis Panayiotis , Michailidou Kyriaki , Kinni Paraskevi , Sokou Rozeta , Iliodromiti Zoi , Pitsios Constantinos , Yiallouros Panayiotis K. , Iacovidou Nicoletta
Published: January 2024

Background

Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition.

Methods

The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as “Confirmed LOS”: positive blood culture - microorganism isolated and LOS symptoms, “Unconfirmed LOS”: negative blood culture and LOS symptoms, and “Controls” group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression.

Results

A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as “Confirmed LOS”, and “unconfirmed LOS” cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01–1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07–1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13–10.25).

Conclusions

The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.
The correlation between lung ultrasound scores and outcomes of high-flow nasal cannula therapy in infants with severe pneumonia
Authors: Zheng Li-Ling , Chen Rou , Zheng Chan-Hua , Dai Xiao-Juan , Zheng Wei-Da , Zhang Jia-Xiang
Published: January 2024

Objective

The study aimed to explore the effectiveness of bedside lung ultrasound (LUS) combined with the PaO2/FiO2 (P/F) ratio in evaluating the outcomes of high-flow nasal cannula (HFNC) therapy in infants with severe pneumonia.

Methods

This retrospective study analyzed the clinical data of 150 infants diagnosed with severe pneumonia and treated with HFNC therapy at our hospital from January 2021 to December 2021. These patients were divided into two groups based on their treatment outcomes: the HFNC success group (n = 112) and the HFNC failure group (n = 38). LUS was utilized to evaluate the patients’ lung conditions, and blood gas results were recorded for both groups upon admission and after 12 h of HFNC therapy.

Results

At admission, no significant differences were observed between the two groups in terms of age, gender, respiratory rate, partial pressure of oxygen, and partial pressure of carbon dioxide. However, the P/F ratios at admission and after 12 h of HFNC therapy were significantly lower in the HFNC failure group (193.08 ± 49.14, 228.63 ± 80.17, respectively) compared to the HFNC success group (248.51 ± 64.44, 288.93 ± 57.17, respectively) (p < 0.05). Likewise, LUS scores at admission and after 12 h were significantly higher in the failure group (18.42 ± 5.3, 18.03 ± 5.36, respectively) than in the success group (15.09 ± 4.66, 10.71 ± 3.78, respectively) (p < 0.05). Notably, in the success group, both P/F ratios and LUS scores showed significant improvement after 12 h of HFNC therapy, a trend not observed in the failure group. Multivariate regression analysis indicated that lower P/F ratios and higher LUS scores at admission and after 12 h were predictive of a greater risk of HFNC failure. ROC analysis demonstrated that an LUS score > 20.5 at admission predicted HFNC therapy failure with an AUC of 0.695, a sensitivity of 44.7%, and a specificity of 91.1%. A LUS score > 15.5 after 12 h of HFNC therapy had an AUC of 0.874, with 65.8% sensitivity and 89.3% specificity. An admission P/F ratio < 225.5 predicted HFNC therapy failure with an AUC of 0.739, 60.7% sensitivity, and 71.1% specificity, while a P/F ratio < 256.5 after 12 h of HFNC therapy had an AUC of 0.811, 74.1% sensitivity, and 73.7% specificity.

Conclusion

Decreased LUS scores and increased P/F ratio demonstrate a strong correlation with successful HFNC treatment outcomes in infants with severe pneumonia. These findings may provide valuable support for clinicians in managing such cases.
The complex intervention day hospice — a quality-assured study on the implementation, realization, and benefits with model character for Germany (IMPULS) using the example of “Day hospice Adiuvantes”
Authors: Kaiser Ulrich , Vehling-Kaiser Ursula , Hoffmann Ana , Fiedler Moritz , Hofbauer Alexandra , Rechenmacher Michael , Benning Anne , Koller Michael , Kaiser Florian
Published: January 2024

Background

Currently, a conclusive experience on the uniform implementation and benefits of day hospice structures and interventions is lacking in Germany. The following questions should be clarified: (1) Which structural conditions and interventional measures should be established in day hospices from the point of view of patients, relatives, and specialist staff?; (2) Are the planned structures or interventions feasible and implementable under real conditions and accepted by patients, relatives, and staff?; (3) How can a final implementation and intervention catalog for day hospices be designed?; (4) Is this final catalog of services feasible, reasonable, economical, and effective under everyday conditions in day hospices?

Methods

We planned to perform a multistage investigation, guided by the Medical Research Council Framework for the development and evaluation of complex interventions. In Stage 1, an initial theoretical construct on structures and interventions will be established through an extensive literature and guideline review on day hospices and through qualitative interviews. In a nominal group process, we will create a catalog of offers. In Stage 2, feasibility testing is conducted in a single-day hospice under real-life conditions using quantitative quality indicators and qualitative interviews. Structures and interventions can be adapted here if necessary. In a second nominal group process, a final structure and offer catalog is created, which is then implemented in Stage 3 in the day hospice under investigation and evaluated under real daily conditions through a process and effectiveness test. For this purpose, qualitative and quantitative quality indicators will be used and a comparative cohort of patients who are not cared for in the day hospice – but in the same network structure (oncology–palliative care network Lower Bavaria) – is examined.

Discussion

Finally, the initial statements on the reasonable and realizable structures or interventions in day hospices and their benefits in daily real-life conditions as well as possible optimization processes shall be made.

Trial registration

The study was retrospectively registered in the German Clinical Trials Register (DRKS-ID DRKS00031613, registration date April 04, 2023) and the display portal of the Center for Clinical Trials of the University Hospital Regensburg (Z-2022-1734-6, registration date July 01, 2023).
Effectiveness of undergraduate medical students training on LGBTQIA + people health: a systematic review and meta-analysis
Authors: Macedo Ana , Aurindo Maria , Febra Cláudia
Published: January 2024

Background

Adequacy of learning models and their ability to engage students and match session’s objectives are critical factors in achieving the desired outcome. In this systematic review and meta-analysis, we assess the methodological approach, content, and effectiveness of training initiatives addressing medical students’ knowledge, attitudes, confidence and discrimination perception towards LGBTQIA + people.

Method

PubMed, Web of Science, Medline and Scopus were searched to identify published studies, from 2013 to 2023, on effectiveness of training initiatives addressing medical students’ knowledge, attitudes, confidence and discrimination perception towards LGBTQIA + people. The risk of bias of the selected studies was assessed by the Medical Education Research Study Quality Instrument. Overall effect sizes were calculated using a Mantel–Haenszel method, fixed effect meta-analyses.

Results

A total of 22 studies were included, representing 2,164 medical students. The interventions were highly diverse and included seminars, lectures, videos, real-case discussions, roleplay, and group discussions with people from the LGBTQIA + community. After the interventions, there was a significant improvement in self-confidence and comfort interacting with patients and in the understanding of the unique and specific health concerns experienced by LGBTQIA + patients.

Conclusion

Our findings indicated that the outcomes of interventions training actions for medical students that promote knowledge and equity regarding LGBTQIA + people, regardless of their scope, methodology and duration, result in a considerable increase in students’ self-confidence and comfort interacting with LGBTQIA + patients, highlight the need for more actions and programs in this area promoting a more inclusive society and greater equity.
Advancing accuracy in breath testing for lung cancer: strategies for improving diagnostic precision in imbalanced data
Authors: Chen Ke-Cheng , Kuo Shuenn-Wen , Shie Ruei-Hao , Yang Hsiao-Yu
Published: January 2024

Background

Breath testing using an electronic nose has been recognized as a promising new technique for the early detection of lung cancer. Imbalanced data are commonly observed in electronic nose studies, but methods to address them are rarely reported.

Objective

The objectives of this study were to assess the accuracy of electronic nose screening for lung cancer with imbalanced learning and to select the best mechanical learning algorithm.

Methods

We conducted a case‒control study that included patients with lung cancer and healthy controls and analyzed metabolites in exhaled breath using a carbon nanotube sensor array. The study used five machine learning algorithms to build predictive models and a synthetic minority oversampling technique to address imbalanced data. The diagnostic accuracy of lung cancer was assessed using pathology reports as the gold standard.

Results

We enrolled 190 subjects between 2020 and 2023. A total of 155 subjects were used in the final analysis, which included 111 lung cancer patients and 44 healthy controls. We randomly divided samples into one training set, one internal validation set, and one external validation set. In the external validation set, the summary sensitivity was 0.88 (95% CI 0.84–0.91), the summary specificity was 1.00 (95% CI 0.85–1.00), the AUC was 0.96 (95% CI 0.94–0.98), the pAUC was 0.92 (95% CI 0.89–0.96), and the DOR was 207.62 (95% CI 24.62–924.64).

Conclusion

Electronic nose screening for lung cancer is highly accurate. The support vector machine algorithm is more suitable for analyzing chemical sensor data from electronic noses.
The radiation- and chemo-sensitizing capacity of diclofenac can be predicted by a decreased lactate metabolism and stress response
Authors: Schwab Melissa , Dezfouli Ali Bashiri , Khosravi Mohammad , Alkotub Bayan , Bauer Lisa , Birgani Mohammad Javed Tahmasebi , Multhoff Gabriele
Published: January 2024

Background

An enhanced aerobic glycolysis (“Warburg effect”) associated with an increase in lactic acid in the tumor microenvironment contributes to tumor aggressiveness and resistance to radiation and chemotherapy. We investigated the radiation- and chemo-sensitizing effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac in different cancer cell types.

Methods

The effects of a non-lethal concentration of diclofenac was investigated on c-MYC and Lactate Dehydrogenase (LDH) protein expression/activity and the Heat shock Protein (HSP)/stress response in human colorectal (LS174T, LoVo), lung (A549), breast (MDA-MB-231) and pancreatic (COLO357) carcinoma cells. Radiation- and chemo-sensitization of diclofenac was determined using clonogenic cell survival assays and a murine xenograft tumor model.

Results

A non-lethal concentration of diclofenac decreases c-MYC protein expression and LDH activity, reduces cytosolic Heat Shock Factor 1 (HSF1), Hsp70 and Hsp27 levels and membrane Hsp70 positivity in LS174T and LoVo colorectal cancer cells, but not in A549 lung carcinoma cells, MDA-MB-231 breast cancer cells and COLO357 pancreatic adenocarcinoma cells. The impaired lactate metabolism and stress response in diclofenac-sensitive colorectal cancer cells was associated with a significantly increased sensitivity to radiation and 5Fluorouracil in vitro, and in a human colorectal cancer xenograft mouse model diclofenac causes radiosensitization.

Conclusion

These findings suggest that a decrease in the LDH activity and/or stress response upon diclofenac treatment predicts its radiation/chemo-sensitizing capacity.
Effectiveness of suture anchor and transosseous suture technique in arthroscopic foveal repair of the triangular fibrocartilage complex: a systematic review
Authors: Ma Hsuan-Hsiao , Wang Jung-Pan , Yang Chen-Yuan
Published: January 2024

Background

Currently, there were two major surgical methods for arthroscopic triangular fibrocartilage complex (TFCC) foveal repair: suture anchor (SA) and transosseous suture (TOS). The purpose of this systematic review is to examine the relevant outcome improvement and safety of SA and TOS technique.

Methods

Literature review of electronic databases for studies investigating the effects of SA and TOS in patients undergoing arthroscopic TFCC foveal repair was performed. We compared the pre-operative and postoperative functional outcomes, clinical outcomes [pain, range of motion (ROM) and grip strength], and complications of two methods. Minimal clinically important difference (MCID) was used to determine clinically meaningful improvement.

Results

There were 1263 distinct studies identified, with 26 (904 patients) meeting the inclusion criteria. The mean age of participants ranged from 21.4 to 41 years, and the mean follow-up time ranged from 6 to 106 months. Both SA and TOS groups reported significant improvement in the modified mayo wrist score, the disabilities of the arm, shoulder, and hand (DASH) score, quick DASH score, patient-reported wrist evaluation (PRWE) score, and the visual analog scale (VAS) score. According to MCID, all the studies from both groups reporting DASH, quick DASH, PRWE and VAS score achieved clinically meaningful improvement. (MCID: 10 for DASH, 14 for quick DASH, 14 for PRWE and 1.6–18 for VAS). The ROM changes in both groups varied from improvement to deterioration. Grip strength improved in both SA and TOS group. Most complications were self-limited. The reoperation rates in SA and TOS ranged from 0 to 20% and 0 to 27.3%, respectively.

Conclusions

Both SA and TOS technique for arthroscopic TFCC foveal repair could achieve improvement in postoperative functional outcomes, pain, and grip strength with low reoperation rate. However, the ROM improvement was still inconclusive.

Level of evidence IV

Systematic review of level III and IV studies.
Augmented reality-based surgical navigation of pelvic screw placement: an ex-vivo experimental feasibility study
Authors: Heining Sandro-Michael , Raykov Vladislav , Wolff Oliver , Alkadhi Hatem , Pape Hans-Christoph , Wanner Guido A.
Published: January 2024

Background

Minimally invasive surgical treatment of pelvic trauma requires a significant level of surgical training and technical expertise. Novel imaging and navigation technologies have always driven surgical technique, and with head-mounted displays being commercially available nowadays, the assessment of such Augmented Reality (AR) devices in a specific surgical setting is appropriate.

Methods

In this ex-vivo feasibility study, an AR-based surgical navigation system was assessed in a specific clinical scenario with standard pelvic and acetabular screw pathways. The system has the following components: an optical-see-through Head Mounted Display, a specifically designed modular AR software, and surgical tool tracking using pose estimation with synthetic square markers.

Results

The success rate for entry point navigation was 93.8%, the overall translational deviation of drill pathways was 3.99 ± 1.77 mm, and the overall rotational deviation of drill pathways was 4.3 ± 1.8°. There was no relevant theoretic screw perforation, as shown by 88.7% Grade 0–1 and 100% Grade 0–2 rating in our pelvic screw perforation score. Regarding screw length, 103 ± 8% of the planned pathway length could be realized successfully.

Conclusion

The novel innovative system assessed in this experimental study provided proof-of-concept for the feasibility of percutaneous screw placement in the pelvis and, thus, could easily be adapted to a specific clinical scenario. The system showed comparable performance with other computer-aided solutions while providing specific advantages such as true 3D vision without intraoperative radiation; however, it needs further improvement and must still undergo regulatory body approval. Future endeavors include intraoperative registration and optimized tool tracking.
Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET
Authors: Singh Simron , Ferone Diego , Capdevila Jaume , Chan Jennifer Ang , de Herder Wouter W. , Halperin Daniel , Mailman Josh , Hellström Lisa , Liedman Hanna , Svedberg Agneta , Tiberg Fredrik
Published: January 2024

Background

The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG).

Methods

SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events.

Discussion

This is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population.

Trial registration

ClinicalTrials.gov NCT05050942. Registered on 21st September 2021.
Evaluation of the efficiency of nanomicellar formulation of fat-soluble vitamins in patients with cystic fibrosis: the study protocol for a randomized controlled trial
Authors: Soleimanzadeh Mahsa , Talebi Saeedeh , Jaafari Mahmoud Reza , Sayedi Seyed Javad , Emadzadeh Maryam , Kianifar Hamid Reza
Published: January 2024

Background

Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins.

Methods

This prospective, single-blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months.

Discussion

Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis.

Trial registration

Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.
Former Soviet Union middle class: how entrepreneurs are shaping a new stratum and pattern of socio-economic behavior
Authors: Otar Elmira , Salikzhanov Rinat , Akhmetova Aigul , Issakhanova Assel , Mukhambetova Kuralay
Published: January 2024

The purpose of this study is to create a representative socio-economic profile of entrepreneurs operating in the former Soviet Union (FSU) states as a pillar of the new middle-class stratum. This study explored middle-class entrepreneurship from multiple perspectives, encompassing statistical analysis of microdata about households and firms. The aim was to gauge entrepreneurship within a national framework and examine its associations with social and economic factors. The study adopted the Doing Business tool as a novel paradigm to establish a quantitative correlation between the economic system in the post-Soviet space and the investigated variables. The analysis revealed that prospective entrepreneurs are members of the younger generation between the ages of 25 and 34; a critical factor in the development of entrepreneurship is highly educated human capital; and typical representatives of entrepreneurship intending to operate in the FSU states establish their own business as a means of subsistence, not as a means of advancement in the social stratum. In general, an entrepreneur of the middle class in the new economies of the post-Soviet space does not demonstrate a high level of entrepreneurial activity and, as a pillar of the middle-class stratum, is in the formation stage.
Structural Performance Assessment of Derailment Containment Provision for Railway using a Grid Steel Frame
Authors: Kim Tae-Hoon , Kang Yun-Suk , Bang Choon-Seok
Published: January 2024

The structural performance of derailment containment provision (DCP) was investigated using a grid steel frame. The DCP which was installed within the gauge of a track was capable of resisting the impact loading in the case of derailed wheels. It was also possible to control the excessive lateral movement of the derailed train. In this study, the structural performance of DCP with a post-installed anchor to a railway concrete sleeper was evaluated. For this purpose, a total of nine specimens were manufactured and static tests were conducted to investigate the structural performance. Furthermore, the shear resistance of the connecting anchor was also evaluated using grid steel frame specimens. The initial test indicated that the developed DCP for railway using grid steel frames had sufficient load-carrying capacity and performance equivalent to about 150% of the design load. The developed DCP also demonstrated sufficient load-carrying capacity up to about 140% of the designed load in combination tests that simulated conceivable boundary conditions. As analytical results, the overall DCP behavior for the specimen railway that utilized grid steel frames was appropriately tracked, and detailed information was presented.
Weather-dependent changes in habitat use by Alpine chamois
Authors: Anderwald Pia , Buchmann Sven , Rempfler Thomas , Filli Flurin
Published: January 2024

Background

Alterations in weather patterns due to climate change are accelerated in alpine environments, but mountains also provide a wide range of niches and potential refuge areas. In order to identify future critical habitat for mountain ungulates for effective protection, it is important to understand their spatial responses to changing weather conditions without movement constraints by human disturbance.

Methods

Using integrated step selection functions, we investigated fine-scale changes in seasonal habitat use in response to weather and time of day for 55 GPS-collared adult Alpine chamois in summer and 42 individuals in winter in a strictly protected area.

Results

Chamois reacted to increasing precipitation and wind speeds primarily by moving to lower elevations in summer and winter. However, reactions to high summer temperatures predominantly involved preferences for increasing tree cover density and northerly slopes. Snow depth had little effect on habitat choice, and southerly slopes were preferred in winter regardless of temperature. At night, chamois moved to steeper slopes and lower elevations than during daytime in both seasons, and to more open areas in summer. Steeper slopes were also preferred with increasing tree cover density.

Conclusions

Chamois employ adaptive fine-scale adjustments in their habitat choice consistent with respect to efficient thermoregulation and protection from both weather extremes and predation risk in summer and winter. Movement responses to climate change are therefore expected to be far more complex than simple altitudinal changes in distribution. Particularly the role of forest cover must not be underestimated, as it appears to provide important thermal refuge habitat from high summer temperatures.
Unclassifiable CNS tumors in DNA methylation-based classification: clinical challenges and prognostic impact
Authors: Drexler Richard , Brembach Florian , Sauvigny Jennifer , Ricklefs Franz L. , Eckhardt Alicia , Bode Helena , Gempt Jens , Lamszus Katrin , Westphal Manfred , Schüller Ulrich , Mohme Malte
Published: January 2024

DNA methylation analysis has become a powerful tool in neuropathology. Although DNA methylation-based classification usually shows high accuracy, certain samples cannot be classified and remain clinically challenging. We aimed to gain insight into these cases from a clinical perspective. To address, central nervous system (CNS) tumors were subjected to DNA methylation profiling and classified according to their calibrated score using the DKFZ brain tumor classifier (V11.4) as “≥ 0.84” (score ≥ 0.84), “0.3–0.84” (score 0.3–0.84), or “< 0.3” (score < 0.3). Histopathology, patient characteristics, DNA input amount, and tumor purity were correlated. Clinical outcome parameters were time to treatment decision, progression-free, and overall survival. In 1481 patients, the classifier identified 69 (4.6%) tumors with an unreliable score as “< 0.3”. Younger age (P < 0.01) and lower tumor purity (P < 0.01) compromised accurate classification. A clinical impact was demonstrated as unclassifiable cases (“< 0.3”) had a longer time to treatment decision (P < 0.0001). In a subset of glioblastomas, these cases experienced an increased time to adjuvant treatment start (P < 0.001) and unfavorable survival (P < 0.025). Although DNA methylation profiling adds an important contribution to CNS tumor diagnostics, clinicians should be aware of a potentially longer time to treatment initiation, especially in malignant brain tumors.
Limitation of life sustaining measures in neurocritical care: sex, timing, and advance directive
Authors: Bögli Stefan Yu , Stretti Federica , Utebay Didar , Hitz Ladina , Hertler Caroline , Brandi Giovanna
Published: January 2024

Background

The limitation of life sustaining treatments (LLST) causes ethical dilemmas even in patients faced with poor prognosis, which applies to many patients admitted to a Neurocritical Care Unit (NCCU). The effects of social and cultural aspects on LLST in an NCCU population remain poorly studied.

Methods

All NCCU patients between 01.2018 and 08.2021 were included. Medical records were reviewed for: demographics, diagnosis, severity of disease, and outcome. Advance directives (AD) and LLST discussions were reviewed evaluating timing, degree, and reason for LLST. Social/cultural factors (nationality, language spoken, religion, marital status, relationship to/sex of legal representative) were noted. Associations between these factors and the patients’ sex, LLST timing, and presence of AD were evaluated.

Results

Out of 2975 patients, 12% of men and 10.5% of women underwent LLST (p = 0.30). Women, compared to men, more commonly received withdrawal instead of withholding of life sustaining treatments (57.5 vs. 45.1%, p = 0.028) despite comparable disease severity. Women receiving LLST were older (73 ± 11.7 vs. 69 ± 14.9 years, p = 0.005) and often without a partner (43.8 vs. 25.8%, p = 0.001) compared to men. AD were associated with female sex and early LLST, but not with an increased in-hospital mortality (57.1 vs. 75.2% of patients with and without AD respectively).

Conclusions

In patients receiving LLST, the presence of an AD was associated with an increase of early LLST, but not with an increased in-hospital mortality. This supports the notion that the presence of an AD is primarily an expression of the patients’ will but does not per se predestine the patient for an unfavorable outcome.