bluuebunny/crossref_metadata_2025 huggingface dataset:
The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability
Authors: Abad Etna , Sandoz Jérémy , Romero Gerard , Zadra Ivan , Urgel-Solas Julia , Borredat Pablo , Kourtis Savvas , Ortet Laura , Martínez Carlos M. , Weghorn Donate , Sdelci Sara , Janic Ana
Published: April 2024

Background

TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like the recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity in murine Eμ Myc-driven lymphoma, emphasizing its significance in the TP53 network. However, little is known about its targets and its role in cancer development, requiring further exploration. In this work, we investigate RNF144B's impact on tumor suppression beyond the hematopoietic compartment in human cancers.

Methods

Employing TP53 wild-type cells, we generated models lacking RNF144B in both non-transformed and cancerous cells of human and mouse origin. By using proteomics, transcriptomics, and functional analysis, we assessed RNF144B's impact in cellular proliferation and transformation. Through in vitro and in vivo experiments, we explored proliferation, DNA repair, cell cycle control, mitotic progression, and treatment resistance. Findings were contrasted with clinical datasets and bioinformatics analysis.

Results

Our research underscores RNF144B's pivotal role as a tumor suppressor, particularly in lung adenocarcinoma. In both human and mouse oncogene-expressing cells, RNF144B deficiency heightened cellular proliferation and transformation. Proteomic and transcriptomic analysis revealed RNF144B's novel function in mediating protein degradation associated with cell cycle progression, DNA damage response and genomic stability. RNF144B deficiency induced chromosomal instability, mitotic defects, and correlated with elevated aneuploidy and worse prognosis in human tumors. Furthermore, RNF144B-deficient lung adenocarcinoma cells exhibited resistance to cell cycle inhibitors that induce chromosomal instability.

Conclusions

Supported by clinical data, our study suggests that RNF144B plays a pivotal role in maintaining genomic stability during tumor suppression.

Graphical Abstract
Development of a trigger tool to identify harmful incidents, no harm incidents, and near misses in prehospital emergency care
Authors: Packendorff Niclas , Magnusson Carl , Wibring Kristoffer , Axelsson Christer , Hagiwara Magnus Andersson
Published: April 2024

Background

Emergency Medical Services (EMS) are a unique setting because care for the chief complaint is given across all ages in a complex and high-risk environment that may pose a threat to patient safety. Traditionally, a reporting system is commonly used to raise awareness of adverse events (AEs); however, it could fail to detect an AE. Several methods are needed to evaluate patient safety in EMS. In this light, this study was conducted to (1) develop a national ambulance trigger tool (ATT) with a guide containing descriptions of triggers, examples of use, and categorization of near misses (NMs), no harm incidents (NHIs), and harmful incidents (HIs) and (2) use the ATT on randomly selected ambulance records.

Methods

The ambulance trigger tool was developed in a stepwise manner through (1) a literature review; (2) three sessions of structured group discussions with an expert panel having knowledge of emergency medical service, patient safety, and development of trigger tools; (3) a retrospective record review of 900 randomly selected journals with three review teams from different geographical locations; and (4) inter-rater reliability testing between reviewers.

Results

From the literature review, 34 triggers were derived. After removing clinically irrelevant ones and combining others through three sessions of structured discussions, 19 remained. The most common triggers identified in the 900 randomly selected records were deviation from treatment guidelines (30.4%), the patient is non conveyed after EMS assessment (20.8%), and incomplete documentation (14.4%). The positive triggers were categorized as a near miss (40.9%), no harm (3.7%), and harmful incident (0.2%). Inter-rater reliability testing showed good agreement in both sessions.

Conclusion

This study shows that a trigger tool together with a retrospective record review can be used as a method to measure the frequency of harmful incidents, no harm incidents, and near misses in the EMS, thus complementing the traditional reporting system to realize increased patient safety.
Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype
Authors: Hussein Mahitab Morsy , Fouda Eman Mahmoud , Shehab Yasmine , Nabih Enas Samir , Osman Ahmed Mohamed , Ishak Sally Raafat
Published: April 2024

Background

Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.

Methods

This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.

Results

There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53–5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6–1510) ng/ml compared to controls, median (IQR) of 1675 (536.8–2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).

Conclusions

Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
Anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy versus trabeculectomy for treating neovascular glaucoma: protocol for a randomized controlled trial
Authors: Zhu Shuqing , Zhou Mengtian , Li Haoyu , Zhang Shaodan , Xu Shuxia , Lin Haishuang , Xie Yanqie , Le Rongrong , Liang Yuanbo
Published: April 2024

Background

Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy.

Methods

AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time.

Discussion

This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies.

Trial registration

ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255.
Improved consolidated bioprocessing for itaconic acid production by simultaneous optimization of cellulase and metabolic pathway of Neurospora crassa
Authors: Zhao Chen , Zhao Jiajia , Han Jingjing , Mei Yaojie , Fang Hao
Published: April 2024

Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.
Predicting epidermal growth factor receptor mutations in non-small cell lung cancer through dual-layer spectral CT: a prospective study
Authors: Li Fenglan , Qi Linlin , Cheng Sainan , Liu Jianing , Chen Jiaqi , Cui Shulei , Dong Shushan , Wang Jianwei
Published: April 2024

Objective

To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC).

Methods

Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion.

Results

Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]).

Conclusion

Quantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC.

Critical relevance statement

Quantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them.

Key Points

Determining EGFR mutation status in patients with NSCLC before starting therapy is essential.

Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients.

NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.

Graphical Abstract
Does the introduction of an infliximab biosimilar always result in savings for hospitals? A descriptive study using real-world data
Authors: Krstic Marko , Devaud Jean-Christophe , Sadeghipour Farshid , Marti Joachim
Published: April 2024

Background

Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13.

Methods

Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping.

Results

Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal.

Conclusions

The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.
Epidemiology of hyperglycemia during pregnancy in Ethiopia: prevalence, associated factors, and feto-maternal outcomes: systematic review and meta-analysis
Authors: Tola Assefa , Assefa Nega , Dessie Yadeta , Oljira Lemessa , Regassa Lemma Demissie , Gure Tadesse , Gobena Tesfaye
Published: April 2024

Background

Hyperglycemia in pregnancy (HIP) is a significant medical complication affecting pregnant women globally and is considered a public health burden due to the negative outcomes it can cause for both mother and infant. The aim of this systematic review and meta-analysis was to examine the prevalence, risk factors, and feto-maternal outcomes of HIP in Ethiopia.

Methods

To gather relevant information for this study, both published and unpublished studies were searched for in several major databases, including PubMed, Embase, HINARI, Web of Science direct, and Google Scholar, as well as other sources. The Joanna Briggs Institute (JBI) tool was used to evaluate the methodological quality of the findings from these studies. Data was then extracted and summarized using a template in Microsoft Excel software, and the extracted data was analyzed using Stata software version 16.0. If significant heterogeneity was found between studies, subgroup analyses were conducted to further examine the data.

Result

Eighteen studies were included in this systematic review and meta-analysis, involving a total sample size of 50,816 pregnant women in Ethiopia. The prevalence of HIP among pregnant women varied considerably across the primary studies, ranging from 0.4 to 26.2%. The pooled prevalence of HIP among pregnant women in Ethiopia was found to be 6.9% (95% C 2.2–11.6). Pregnant women with a family history of diabetes had 2.5 times higher odds of developing HIP compared to those without a family history of diabetes (OR = 2.49; 95% CI = 2.02, 2.96). However, there was no significant association found between HIP and maternal obesity (OR 2.31, 95% CI = 0.85, 3.78) or previous history of abortion (OR 3.89; 95% CI 0.85, 6.94). The common fetal outcomes associated with HIP were admission to the intensive care unit (46.2; 95% CI 27.4, 65.1), macrosomia (27.3%; 95% CI 9.4%, 45.1%), and preterm birth (16.9; 95% CI 12.5, 21.3). Additionally, hypertensive disorders of pregnancy (28.0%; 95% CI 15.2, 40.8) and operative delivery (51.4%; 95% CI 35.9, 66.8) were more common among women with HIP in Ethiopia.

Conclusion

Although there was some variation between studies, the meta-analysis revealed that approximately seven out of 100 pregnant women in Ethiopia had HIP. A family history of diabetes was found to be a significant predictor of HIP in Ethiopia. Additionally, HIP was associated with various serious adverse outcomes for both mothers and infants in Ethiopia. These findings highlight the need for national guidelines to ensure that pregnant women are uniformly screened for HIP.
Mathematical analysis and optimal control of Dengue fever epidemic model
Authors: Yoda Yacouba , Ouedraogo Harouna , Ouedraogo Dramane , Guiro Aboudramane
Published: April 2024

In this article, we are working on an SEIR-SI type model for dengue disease in order to better observe the dynamics of infection in human beings. We calculate the basic reproduction number $\mathcal{R}_{0}$

R
0

and determine the equilibrium points. We then show the existence of global stability in each of the different states depending on the value of $\mathcal{R}_{0}$

R
0

. Moreover, to support the theoretical work, we present numerical simulations obtained using Python. We also study the sensitivity of the parameters included in the expression of $\mathcal{R}_{0}$

R
0

with the aim of identifying the most influential parameters in the dynamics of dengue disease spread. Finally, we introduce two functions u and v, respectively indicating the treatment of the infected people and any prevention system minimizing contact between humans and the disease causing vectors. We present the curves of the controlled system after calculating the optimal pair of controls capable of reducing the dynamics of the disease spread, still using Python.
Influence of pain duration and severity on oral health-related quality of life and patient satisfaction during adult treatment with clear aligners
Authors: Caldas Waleska , Bonin Fabiana Aparecida , Vianna Camila Pereira , Shimizu Roberto Hideo , Trojan Larissa Carvalho
Published: April 2024

Background

This study aims to compare the impact of pain on quality of life and patient satisfaction during treatment with aligners.

Methods

Ninety-four subjects in active treatment were invited to answer self-reported questions concerning pain severity and duration, occurrence of other signs and symptoms, and level of satisfaction with their treatment. Also, the OHIP-14 questionnaire was applied to assess patients’ OHRQoL.

Results

Ninety-four patients (49 women and 45 men) answered the survey. Pain duration of 1–3 days was reported by 69.1% of patients (n = 60). For those who reported pain (n = 84), it was considered mild severity by 42.9% and moderate by 52.4%. Almost sixty-four percent of the sample were very satisfied with the aligner’s aesthetics (n = 60) and forty-nine percent were satisfied with treatment in general (n = 46). Mean OHIP-14 score was 3.36 ± 2.54. OHRQoL was significantly associated with pain severity, whereas patients who reported having experienced moderate pain presented a significantly higher mean OHIP-14 score than those who reported having experienced mild pain (3.92 ± 1.93 and 2.69 ± 2.83, respectively; p = 0.036). The “psychological discomfort” OHIP-14’s domain was the most influenced by the level of pain.

Conclusion

Pain severity significantly influenced OHRQoL, in adult patients under treatment with clear aligners. However, high levels of patient satisfaction were reported, regardless of pain duration or severity.
Zebrafish nampt-a mutants are viable despite perturbed primitive hematopoiesis
Authors: Pomreinke Autumn Penecilla , Müller Patrick
Published: April 2024

Background

Nicotinamide phosphoribosyltransferase (Nampt) is required for recycling NAD+ in numerous cellular contexts. Morpholino-based knockdown of zebrafish nampt-a has been shown to cause abnormal development and defective hematopoiesis concomitant with decreased NAD+ levels. However, surprisingly, nampt-a mutant zebrafish were recently found to be viable, suggesting a discrepancy between the phenotypes in knockdown and knockout conditions. Here, we address this discrepancy by directly comparing loss-of-function approaches that result in identical defective transcripts in morphants and mutants.

Results

Using CRISPR/Cas9-mediated mutagenesis, we generated nampt-a mutant lines that carry the same mis-spliced mRNA as nampt-a morphants. Despite reduced NAD+ levels and perturbed expression of specific blood markers, nampt-a mutants did not display obvious developmental defects and were found to be viable. In contrast, injection of nampt-a morpholinos into wild-type or mutant nampt-a embryos caused aberrant phenotypes. Moreover, nampt-a morpholinos caused additional reduction of blood-related markers in nampt-a mutants, suggesting that the defects observed in nampt-a morphants can be partially attributed to off-target effects of the morpholinos.

Conclusions

Our findings show that zebrafish nampt-a mutants are viable despite reduced NAD+ levels and a perturbed hematopoietic gene expression program, indicating strong robustness of primitive hematopoiesis during early embryogenesis.
Effectiveness of secukinumab in patients with psoriasis and psoriatic arthritis in a Saudi real-world setting
Authors: Al-Homood Ibrahim A. , Alajlan Mohammed , Alberdisi Majid , Alturki Mohammad , Ahmed Ahmed Ali , Zakaria Nancy
Published: April 2024

Introduction

Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient’s quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period.

Methods

This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks.

Results

The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%.

Conclusion

In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.
A preliminary study on the impact of nutrient stress induction on drug cytotoxicity in glioblastoma cells and fibroblasts
Authors: Hassan Siti Nazihahasma , Yusoff Abdul Aziz Mohamed , Idris Zamzuri , Redzwan Norhanani Mohd , Ahmad Farizan
Published: April 2024

Background

Nutrient stress (NS), one of the hallmarks of the tumour microenvironment, can render cancer cells tolerant to cytotoxicity. Fibroblasts, on the other hand, have cancer cell-like traits, such as plasticity and resiliency. Hence, this study aimed to evaluate the cytotoxicity of the drug on reseeded human U87 glioblastoma (GBM) cells as well as on mouse L929 fibroblasts in the form of monolayer and colonies that grew after NS induction.

Results

No treatment for 48 h showed a statistically significant difference in U87 cell viability when compared to the 50% hypothetical value. However, temozolomide (TMZ) (151.0 µg/ml) and azithromycin (AZI) (92.0 µg/ml) significantly diminished the number of U87 cell colonies compared to the untreated control, and AZI also outperformed doxycycline (DOXY) (147.0 µg/ml). L929 fibroblasts survived NS, but the cytotoxicity of AZI, DOXY, and AZI + DOXY (92.0 + 147.0 µg/ml) substantially increased than in L929 fibroblasts without NS induction.

Conclusions

The present findings suggest that NS does not inevitably contribute to cytotoxic drug tolerance in GBM cells. In addition, although fibroblasts can withstand NS, they can also become susceptible to cytotoxic drug-induced death; nevertheless, the type of drug may play a role.

Graphical Abstract
The effects of contour-based rainwater harvesting and integrated nutrient management on maize yields in semi-arid regions of Zimbabwe
Authors: Chiturike Pasipanodya , Gotosa Jephta , Nyakudya Innocent Wadzanai , Madamombe Sandra M. , Mandumbu Ronald , Chirinda Ngonidzashe , Kugedera Andrew Tapiwa , Nyamadzawo George
Published: April 2024

In the smallholder farming areas located in semi-arid regions of Zimbabwe, low and unreliable rainfall distribution and poor soil fertility are the major factors limiting crop production. The negative effects of these biophysical factors have been worsened by climate change. However, the major challenges have been the lack of sustainable, low-cost water and nutrient management technologies for these semi-arid regions. The objectives of this study were to evaluate the effects of contour-based rainwater harvesting (RWH) namely tied contours (TC), infiltration pits (IP) which were compared with the standard contour (STDC), and intergrated nutrient management (INM) where cattle manure was used as basal fertiliser and Ammonium Nitrate (AN) as top dressing, on maize yields. Results showed that fields with RWH had higher yields compared to STDC. Average maize yields were 2210 and 1792 kg ha
−1
for TC and IP which were 88% and 52% above STDC (1176 kg ha
−1
) respectively. Increasing nitrogen (N) levels resulted in a further increase in maize yields. Return on investment was negative during drier years and was significantly higher in RWH systems compared with STDC during wet seasons. Farmers need to reduce mineral fertiliser application during dry seasons since little rainwater is captured. We conclude that contour based RWH and INM can be used as sustainable low cost methods of crop production. Higher fertiliser application rates when rainfall is limiting, do not result in increased return on investiment.
Endobronchial electrocautery wire snare prior to right middle sleeve lobectomy for adenoid cystic carcinoma of the lung: a case report
Authors: Kawasaki Hidenori , Hoshino Hironobu , Nakasone Shoko , Kawabata Hiroki , Yohena Tomofumi , Atsumi Eriko
Published: April 2024

Background

Adenoid cystic carcinoma of the lung grows gradually, and spreads along the bronchial wall, often requiring tracheobronchoplastic procedure during surgery; however, incomplete resection occasionally occurs due to positive surgical margins. To avoid incomplete resection, effort should be exerted to confirm the extent of airway invasion of the tumor before surgery. Herein, we present the utility of combined treatment with bronchoscopic electrocautery wire snare for the endobronchial tumor prior to sleeve lobectomy with curative resection for patients with adenoid cystic carcinoma of the lung.

Case presentation

A 56-year-old woman experienced a persistent cough 6 months prior. On an annual medical checkup, an abnormal lung shadow was noted. Chest computed tomography (CT) scan demonstrated right middle lobe atelectasis, and a round tumor shadow at the orifice of the right middle lobe bronchus, which protruded into the right intermediate bronchus, was observed. On bronchoscopy, a pedunculated endobronchial tumor in the intermediate bronchus was shown, and the middle lobe bronchus was completely obstructed. Initially, tumor resection via bronchoscopy was performed using an electrocautery wire snare under general anesthesia, and the tumor was pathologically diagnosed as adenoid cystic carcinoma of cT1aN0M0 stage IA. After tumor resection, the extent of tumor progression in the airway was assessed; subsequently, the patient underwent elective right middle sleeve lobectomy and lymphadenectomy. She survived without recurrence 7 years after surgery.

Conclusion

We present a useful combined treatment strategy of bronchoscopic electrocautery wire snare prior to sleeve lobectomy for patients with endobronchial adenoid cystic carcinoma of the lung.
Simultaneous transmediastinal esophagectomy and thoracoscopic lobectomy for synchronous double cancers of the esophagus and lung: a case report
Authors: Kameyama Kenji , Takao Koji , Shiozaki Atsushi , Fujiwara Hitoshi , Ii Tsunehiro
Published: April 2024

Background

Simultaneous surgery for synchronous double cancers of the esophagus and lung is so invasive that minimally invasive surgical procedures are preferred. For left lung cancer, there are few reports on simultaneous surgery due to the difficulty of performing radical esophagectomy only via the left thoracic approach and the high invasiveness of bilateral thoracotomy.

Case presentation

A 65-year-old man who was diagnosed with synchronous double cancer of the esophagus and left lung underwent transmediastinal esophagectomy (TME) and thoracoscopic lobectomy (TSL) simultaneously. This procedure is advantageous because radical esophagectomy can be completed regardless of the side affected by the lung cancer, and respiratory function can be preserved by shortening the duration of differential lung ventilation and avoiding thoracotomy.

Conclusion

This surgery could be a good treatment option for synchronous double cancers of the esophagus and lung in a highly proficient hospital.
The Genetic Pathophysiology and Clinical Management of the TADopathy, X-Linked Acrogigantism
Authors: Daly Adrian F , Beckers Albert
Published: April 2024

Pituitary gigantism is a rare manifestation of chronic growth hormone (GH) excess that begins before closure of the growth plates. Nearly half of patients with pituitary gigantism have an identifiable genetic cause. X-linked acrogigantism (X-LAG; 10% of pituitary gigantism) typically begins during infancy and can lead to the tallest individuals described. In the 10 years since its discovery, about 40 patients have been identified. Patients with X-LAG usually develop mixed GH and prolactin macroadenomas with occasional hyperplasia that secrete copious amounts of GH, and frequently prolactin. Circulating GH-releasing hormone is also elevated in a proportion of patients. X-LAG is caused by constitutive or sporadic mosaic duplications at chromosome Xq26.3 that disrupt the normal chromatin architecture of a topologically associating domain (TAD) around the orphan G-protein–coupled receptor, GPR101. This leads to the formation of a neo-TAD in which GPR101 overexpression is driven by ectopic enhancers (“TADopathy”). X-LAG has been seen in 3 families due to transmission of the duplication from affected mothers to sons. GPR101 is a constitutively active receptor with an unknown natural ligand that signals via multiple G proteins and protein kinases A and C to promote GH/prolactin hypersecretion. Treatment of X-LAG is challenging due to the young patient population and resistance to somatostatin analogs; the GH receptor antagonist pegvisomant is often an effective option. GH, insulin-like growth factor 1, and prolactin hypersecretion and physical overgrowth can be controlled before definitive adult gigantism occurs, often at the cost of permanent hypopituitarism.
Elective Versus Nonelective Spinal Fusions: Surgical and Financial Outcomes in a Bundled Payment Reimbursement Model
Authors: Shahin Maryam N. , Weidenkopf Thérèse , Smith Spencer , Ryu Won Hyung A. , Yoo Jung U. , Orina Josiah N.
Published: April 2024

BACKGROUND AND OBJECTIVES:

Bundled payment for care improvement advanced (BPCIA) is a voluntary alternative payment model administered by the Centers for Medicare and Medicaid Services using value-based care to reduce costs by incentivizing care coordination and improved quality. We aimed to identify drivers of negative financial performance in BPCIA among patients undergoing spinal fusion surgery.

METHODS:

This is a single-institution retrospective review of patients enrolled in BPCIA undergoing spinal fusion with DRGs 453, 454, 455, 459, and 460 from 2018 to 2022. Univariate and multivariable logistic regression analyses were used to identify factors associated with negative financial performance and compare nonelective vs elective surgeries.

RESULTS:

We identified 172 cases, of which 24% (n = 41) had negative financial performance and 9% (n = 16) were nonelective cases. Nonelective surgery (P < .001, odds ratios 19.81), greater levels instrumented (P < .001), and no anterior procedure (P = .001) were associated with negative financial performance. Surgical outcomes associated with negative financial performance and factors more common in nonelective cases respectively included higher hospital length of stay (P < .001, P = .005), nonhome discharge (P < .001, P < .001), 90-day hospital readmission (P < .001, P < .001), 90-day additional nonspine surgery (P = .01, P < .001), and less days at home of the 90 days (P < .001, P = .01). Nonelective surgeries had higher total spend (P = .01), readmission spend (P = .03), skilled nursing facility spend (P = .02), durable medical equipment spend (P = .003), and professional billing spend (P = .04) despite similar target pricing (P = .60), all of which resulted in greater financial loss compared with elective surgeries (P = .001).

CONCLUSION:

Nonelective spinal surgery is an independent preoperative predictor of negative financial performance in BPCIA. Nonelective spinal surgeries are more likely than elective surgeries to have higher length of stay, nonhome discharge, 90-day hospital readmission, 90-day additional nonspine surgeries, and less time spent at home during the bundled period, all of which contribute to higher health care utilization. The Centers for Medicare and Medicaid Services should consider incorporating nonelective spine surgery into risk-adjustment models.
Microsurgical Removal of an Anterior Clinoid Meningioma With Extensive Vascular Encasement: 2-Dimensional Operative Video
Authors: Aldea Sorin , Le Guérinel Caroline
Published: April 2024

Anterior clinoid meningiomas are challenging skull base lesions especially when they encase the internal carotid artery and its branches. According to the Al-Mefty classification, type I can originate in the subclinoid dura, type II on the superolateral aspect of the anterior clinoid process, and type III at the optic foramen, with type I being the most often associated with vascular encasement.
1,2
We present the case of a 70-year-old patient who presented with visual disturbances revealing a large type I anterior clinoid meningioma encasing the internal carotid artery and its branches. The extended pterional approach with removal of the posterior part of the superior and lateral walls of the orbit
3
was offered to the patient given the size of the tumor and the visual impairment. We present the main steps of the surgery: extended pterional approach with postero-lateral orbitotomy, extradural removal of the anterior clinoid process, and hyperosthosis. The meningioma is removed in a stepwise fashion starting in the less dangerous frontal sector of the tumor and ending in the supra cavernous and supra diaphragmatic sectors of the meningioma. The postoperative course was favorable, and at 3-month follow-up, the patient showed a significant visual improvement. Brain MRI showed a subtotal resection of the meningioma and no postoperative complications. We present the nuances and the surgical technique for anterior clinoid meningiomas with extensive vascular encasement. We discuss the factors predicting the preservation of the arachnoid planes reported in the literature.
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The patient consented to the procedure and to the publication of the images. Our Institutional Review Board ethics committee does not require an approval for this type of publication.
Hansenula polymorpha cells lacking the ER-localized peroxins Pex23 or Pex29 show defects in mitochondrial function and morphology
Authors: Chen Haiqiong , de Boer Rinse , Krikken Arjen M. , Wu Fei , van der Klei Ida
Published: April 2024

Pex23 family proteins localize to the endoplasmic reticulum and play a role in peroxisome and lipid body formation. The yeast Hansenula polymorpha contains four members: Pex23, Pex24, Pex29 and Pex32. We previously showed that loss of Pex24 or Pex32 results in severe peroxisomal defects, caused by reduced peroxisome-endoplasmic reticulum contact sites. We now analyzed the effect of the absence of all four Pex23 family proteins on other cell organelles. Vacuoles were normal in all four deletion strains. The number of lipid droplets was reduced in pex23 and pex29, but not in pex24 and pex32 cells, indicating that peroxisome and lipid droplet formation require different Pex23 family proteins in H. polymorpha. In pex23 and pex29 cells mitochondria were fragmented and clustered accompanied by reduced levels of the fusion protein Fzo1. Deletion of DNM1 suppressed the morphological phenotype of pex23 and pex29 cells, suggesting that mitochondrial fusion is affected. pex23 and pex29 cells showed retarded growth and reduced mitochondrial activities. The growth defect was partially suppressed by DNM1 deletion as well as by an artificial mitochondrion-endoplasmic reticulum tether. Hence, the absence of Pex23 family proteins may influence mitochondrion-endoplasmic reticulum contact sites.
Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant
Authors: Ambekar Yogeshwari S. , Caiaffa Carlo Donato , Wlodarczyk Bogdan J. , Singh Manmohan , Schill Alexander W. , Steele John W. , Zhang Jitao , Aglyamov Salavat R. , Scarcelli Giuliano , Finnell Richard H. , Larin Kirill V.
Published: April 2024

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos was significantly lower than that of wild-type embryos. Additionally, exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness in normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development.
The polarity protein Yurt associates with the plasma membrane via basic and hydrophobic motifs embedded in its FERM domain
Authors: Gamblin Clémence L. , Alende Charles , Corriveau François , Jetté Alexandra , Parent-Prévost Frédérique , Biehler Cornélia , Majeau Nathalie , Laurin Mélanie , Laprise Patrick
Published: April 2024

The subcellular distribution of the polarity protein Yurt (Yrt) is subjected to a spatio-temporal regulation in Drosophila melanogaster embryonic epithelia. After cellularization, Yrt binds to the lateral membrane of ectodermal cells and maintains this localization throughout embryogenesis. During terminal differentiation of the epidermis, Yrt accumulates at septate junctions and is also recruited to the apical domain. Although the mechanisms through which Yrt associates with septate junctions and the apical domain have been deciphered, how Yrt binds to the lateral membrane remains as an outstanding puzzle. Here, we show that the FERM domain of Yrt is necessary and sufficient for membrane localization. Our data also establish that the FERM domain of Yrt directly binds negatively charged phospholipids. Moreover, we demonstrate that positively charged amino acid motifs embedded within the FERM domain mediates Yrt membrane association. Finally, we provide evidence suggesting that Yrt membrane association is functionally important. Overall, our study highlights the molecular basis of how Yrt associates with the lateral membrane during the developmental time window where it is required for segregation of lateral and apical domains.
Pulsation waves along the Ciona heart tube reverse by bimodal rhythms expressed by a remote pair of pacemakers
Authors: Fujikake Yuma , Fukuda Kéita , Matsushita Katsuyoshi , Iwatani Yasushi , Fujimoto Koichi , Nishino Atsuo S.
Published: April 2024

The heart of ascidians (marine invertebrate chordates) has a tubular structure, and heartbeats propagate from one end to the other. The direction of pulsation waves intermittently reverses in the heart of ascidians and their relatives; however, the underlying mechanisms remain unclear. We herein performed a series of experiments to characterize the pacemaker systems in isolated hearts and their fragments, and applied a mathematical model to examine the conditions leading to heart reversals. The isolated heart of Ciona robusta autonomously generated pulsation waves at ∼20 to 25 beats min−1 with reversals at ∼1 to 10 min intervals. Experimental bisections of isolated hearts revealed that independent pacemakers resided on each side and also that their beating frequencies periodically changed as they expressed bimodal rhythms, which comprised an ∼1.25 to 5.5 min acceleration/deceleration cycle of a beating rate of between 0 and 25 beats min−1. Only fragments including 5% or shorter terminal regions of the heart tube maintained autonomous pulsation rhythms, whereas other regions did not. Our mathematical model, based on FitzHugh–Nagumo equations applied to a one-dimensional alignment of cells, demonstrated that the difference between frequencies expressed by the two independent terminal pacemakers determined the direction of propagated waves. Changes in the statuses of terminal pacemakers between the excitatory and oscillatory modes as well as in their endogenous oscillation frequencies were sufficient to lead to heart reversals. These results suggest that the directions of pulsation waves in the Ciona heart reverse according to the changing rhythms independently expressed by remotely coupled terminal pacemakers.
The role of vision and lateral line sensing for schooling in giant danios (Devario aequipinnatus)
Authors: Tidswell Ben K. , Veliko-Shapko Annushka , Tytell Eric D.
Published: April 2024

Schooling is a collective behavior that relies on a fish's ability to sense and respond to the other fish around it. Previous work has identified ‘rules’ of schooling – attraction to neighbors that are far away, repulsion from neighbors that are too close and alignment with neighbors at the correct distance – but we do not understand well how these rules emerge from the sensory physiology and behavior of individual fish. In particular, fish use both vision and their lateral lines to sense each other, but it is unclear how much they rely on information from these sensory modalities to coordinate schooling behavior. To address this question, we studied how the schooling of giant danios (Devario aequipinnatus) changes when they are unable to see or use their lateral lines. We found that giant danios were able to school without their lateral lines but did not school in darkness. Surprisingly, giant danios in darkness had the same attraction properties as fish in light when they were in close proximity, indicating that they could sense nearby fish with their lateral lines. However, they were not attracted to more distant fish, suggesting that long-distance attraction through vision is important for maintaining a cohesive school. These results help us expand our understanding of the roles that vision and the lateral line play in the schooling of some fish species.
Investigating the thermal sensitivity of key enzymes involved in the energetic metabolism of three insect species
Authors: Léger Adèle , Cormier Simon B. , Blanchard Arianne , Menail Hichem A. , Pichaud Nicolas
Published: April 2024

The metabolic responses of insects to high temperatures have been linked to their mitochondrial substrate oxidation capacity. However, the mechanism behind this mitochondrial flexibility is not well understood. Here, we used three insect species with different thermal tolerances (the honey bee, Apis mellifera; the fruit fly, Drosophila melanogaster; and the potato beetle, Leptinotarsa decemlineata) to characterize the thermal sensitivity of different metabolic enzymes. Specifically, we measured activity of enzymes involved in glycolysis (hexokinase, HK; pyruvate kinase, PK; and lactate dehydrogenase, LDH), pyruvate oxidation and the tricarboxylic acid cycle (pyruvate dehydrogenase, PDH; citrate synthase, CS; malate dehydrogenase, MDH; and aspartate aminotransferase, AAT), and the electron transport system (Complex I, CI; Complex II, CII; mitochondrial glycerol-3-phosphate dehydrogenase, mG3PDH; proline dehydrogenase, ProDH; and Complex IV, CIV), as well as that of ATP synthase (CV) at 18, 24, 30, 36, 42 and 45°C. Our results show that at high temperature, all three species have significantly increased activity of enzymes linked to FADH2 oxidation, specifically CII and mG3PDH. In fruit flies and honey bees, this coincides with a significant decrease of PDH and CS activity, respectively, that would limit NADH production. This is in line with the switch from NADH-linked substrates to FADH2-linked substrates previously observed with mitochondrial oxygen consumption. Thus, we demonstrate that even though the three insect species have a different metabolic regulation, a similar response to high temperature involving CII and mG3PDH is observed, denoting the importance of these proteins for thermal tolerance in insects.