bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel therapeutic approaches in thalassemias, sickle cell disease, and other red cell disorders
Authors: Pinto Valeria Maria , Mazzi Filippo , De Franceschi Lucia
Published: May 2024

In this last decade, a deeper understanding of the pathophysiology of hereditary red cell disorders and the development of novel classes of pharmacologic agents have provided novel therapeutic approaches to thalassemias, sickle cell disease (SCD), and other red cell disorders. Here, we analyze and discuss the novel therapeutic options according to their targets, taking into consideration the complex process of erythroid differentiation, maturation, and survival of erythrocytes in the peripheral circulation. We focus on active clinical exploratory and confirmatory trials on thalassemias, SCD, and other red cell disorders. Beside β-thalassemia and SCD, we found that the development of new therapeutic strategies has allowed for the design of clinic studies for hereditary red cell disorders still lacking valuable therapeutic alternative such as α-thalassemias, congenital dyserythropoietic anemia, or Diamond-Blackfan anemia. In addition, reduction of heme synthesis, which can be achieved by the repurposed antipsychotic drug bitopertin, might affect not only hematological disorders but multiorgan diseases such as erythropoietic protoporphyria. Finally, our review highlights the current state of therapeutic scenarios, in which multiple indications targeting different red cell disorders are being considered for a single agent. This is a welcome change that will hopefully expand therapeutic option for patients affected by thalassemias, SCD, and other red cell disorders.
Heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice
Authors: Chen Qiyang , Hazra Rimi , Crosby Danielle , Lenhart Diane , Lenhart Shane C. , Mondal Paritosh , Zhang Yingze , Nouraie Seyed M. , Tan Roderick J. , Esmon Charles T. , Rao L. Vijay Mohan , Kim Kang , Ghosh Samit
Published: May 2024

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in sickle cell disease (SCD). Anemia, induced by chronic persistent hemolysis, is associated with the progressive deterioration of renal health, resulting in CKD. Moreover, patients with SCD experience acute kidney injury (AKI), a risk factor for CKD, often during vaso-occlusive crisis associated with acute intravascular hemolysis. However, the mechanisms of hemolysis-driven pathogenesis of the AKI-to-CKD transition in SCD remain elusive. Here, we investigated the role of increased renovascular rarefaction and the resulting substantial loss of the vascular endothelial protein C receptor (EPCR) in the progressive deterioration of renal function in transgenic SCD mice. Multiple hemolytic events raised circulating levels of soluble EPCR (sEPCR), indicating loss of EPCR from the cell surface. Using bone marrow transplantation and super-resolution ultrasound imaging, we demonstrated that SCD mice overexpressing EPCR were protective against heme-induced CKD development. In a cohort of patients with SCD, plasma sEPCR was significantly higher in individuals with CKD than in those without CKD. This study concludes that multiple hemolytic events may trigger CKD in SCD through the gradual loss of renovascular EPCR. Thus, the restoration of EPCR may be a therapeutic target, and plasma sEPCR can be developed as a prognostic marker for sickle CKD.
Interleukin-1–mediated hyperinflammation in XIAP deficiency is associated with defective autophagy
Authors: Dissanayake Dilan , Firouzabady Ashkan , Massumi Mohammad , de Paz Linares Guillermo A. , Marshall Christian , Freeman Spencer A. , Laxer Ronald M. , Yeung Rae S. M.
Published: May 2024

Deficiency of X-linked inhibitor of apoptosis protein (XIAP) is a rare genetic condition that can present with recurrent episodes of hemophagocytic lymphohistiocytosis (HLH), though the exact mechanisms leading to this hyperinflammatory disorder are unclear. Understanding its biology is critical to developing targeted therapies for this potentially fatal disease. Here, we report on a novel multiexonic intragenic duplication leading to XIAP deficiency with recurrent HLH that demonstrated complete response to interleukin (IL)-1β blockade. We further demonstrate using both primary patient cells and genetically modified THP-1 monocyte cell lines that, contrary to what has previously been shown in mouse cells, XIAP-deficient human macrophages do not produce excess IL-1β when stimulated under standard conditions. Instead, nucleotide-binding oligomerization domain–like receptor family pyrin domain containing 3 (NLRP3) inflammasome–mediated hyperproduction of IL-1β is observed only when the XIAP-deficient cells are stimulated under autophagy-promoting conditions and this correlates with defective autophagic flux as measured by decreased accumulation of the early autophagy marker LC3-II. This work, therefore, highlights IL-1β blockade as a therapeutic option for patients with XIAP deficiency experiencing recurrent HLH and identifies a critical role for XIAP in promoting autophagy as a means of limiting IL-1β–mediated hyperinflammation during periods of cellular stress.
Pattern of uveitis in a referral ophthalmology center in Northeastern Thailand
Authors: Wannapanich Trakanta , Chuenchaem Waraporn , Luanratanakorn Patanaree , Laovirojjanakul Wipada
Published: May 2024

Purpose

To report the characteristics and epidemiology of uveitis in a university-based referral center in northeastern Thailand and review the uveitis patterns present in various regions worldwide.

Methods

A retrospective review of all medical records for new patients visiting the uveitis clinic at Srinagarind hospital, Khon Kaen University, between August 2016 and June 2021, was conducted.

Results

A total of 522 uveitis patients were included in this study. Disease etiologies were categorized as non-infectious 35.8% (187/522), infectious 32.8% (171/522), and undetermined cause 31.4% (164/522). Specific diagnoses were established in 68.6% of cases. Vogt-Koyanagi-Harada (VKH) (14.2%) was identified as the most common specific diagnosis, and tuberculosis (6.7%) ranked highest among infectious causes.

Conclusions

Although non-infectious uveitis is observed predominantly in this region, the proportion of infectious uveitis is relatively more common than in developed countries. We have found no cause for one-third of our patients despite the utilization of PCR and serology for diagnostic purposes.
Identification of key genes controlling monoterpene biosynthesis of Citral-type Cinnamomum bodinieri Levl. Based on transcriptome and metabolite profiling
Authors: Ling Qingyan , Zhang Beihong , Wang Yanbo , Xiao Zufei , Hou Jiexi , Liu Qingqing , Zhang Jie , Xiao Changlong , Jin Zhinong , Liu Yuanqiu
Published: May 2024

The citral-type is the most common chemotype in Cinnamomum bodinieri Levl (C. bodinieri), which has been widely used in the daily necessities, cosmetics, biomedicine, and aromatic areas due to their high citral content. Despite of this economic prospect, the possible gene-regulatory roles of citral biosynthesis in the same geographic environment remains unknown. In this study, the essential oils (EOs) of three citral type (B1, B2, B3) and one non-citral type (B0) varieties of C. bodinieri were identified by GC-MS after hydrodistillation extraction in July. 43 components more than 0.10% were identified in the EOs, mainly composed of monoterpenes (75.8–91.84%), and high content citral (80.63–86.33%) were identified in citral-type. Combined transcriptome and metabolite profiling analysis, plant-pathogen interaction(ko04626), MAPK signaling pathway-plant(ko04016), starch and sucrose metabolism(ko00500), plant hormone signal transduction(ko04075), terpenoid backbone biosynthesis (ko00900) and monoterpenoid biosynthesis (ko00902) pathways were enriched significantly. The gene expression of differential genes were linked to the monoterpene content, and the geraniol synthase (CbGES), alcohol dehydrogenase (CbADH), geraniol 8-hydroxylase-like (CbCYP76B6-like) and 8-hydroxygeraniol dehydrogenase (Cb10HGO) were upregulated in the citral-type, indicating that they were associated with high content of geraniol and citral. The activities of CbGES and CbADH in citral type were higher than in non-citral type, which was corroborated by enzyme-linked immunosorbent assay (ELISA). This study on the accumulation mechanism of citral provides a theoretical basis for the development of essential oil of C. bodinieri.
Proteome profiling of Campylobacter jejuni 81–176 at 37 °C and 42 °C by label-free mass spectrometry
Authors: Dreyer Annika , Masanta Wycliffe O. , Lugert Raimond , Bohne Wolfgang , Groß Uwe , Leha Andreas , Dakna Mohammed , Lenz Christof , Zautner Andreas E.
Published: May 2024

Background

The main natural reservoir for Campylobacter jejuni is the avian intestinal tract. There, C. jejuni multiplies optimally at 42 °C – the avian body temperature. After infecting humans through oral intake, the bacterium encounters the lower temperature of 37 °C in the human intestinal tract. Proteome profiling by label-free mass spectrometry (DIA-MS) was performed to examine the processes which enable C. jejuni 81–176 to thrive at 37 °C in comparison to 42 °C. In total, four states were compared with each other: incubation for 12 h at 37 °C, for 24 h at 37 °C, for 12 h at 42 °C and 24 h at 42 °C.

Results

It was shown that the proteomic changes not only according to the different incubation temperature but also to the length of the incubation period were evident when comparing 37 °C and 42 °C as well as 12 h and 24 h of incubation. Altogether, the expression of 957 proteins was quantifiable. 37.1 − 47.3% of the proteins analyzed showed significant differential regulation, with at least a 1.5-fold change in either direction (i.e. log2 FC ≥ 0.585 or log2 FC ≤ -0.585) and an FDR-adjusted p-value of less than 0.05. The significantly differentially expressed proteins could be arranged in 4 different clusters and 16 functional categories.

Conclusions

The C. jejuni proteome at 42 °C is better adapted to high replication rates than that at 37 °C, which was in particular indicated by the up-regulation of proteins belonging to the functional categories “replication” (e.g. Obg, ParABS, and NapL), “DNA synthesis and repair factors” (e.g. DNA-polymerase III, DnaB, and DnaE), “lipid and carbohydrate biosynthesis” (e.g. capsular biosynthesis sugar kinase, PrsA, AccA, and AccP) and “vitamin synthesis, metabolism, cofactor biosynthesis” (e.g. MobB, BioA, and ThiE). The relative up-regulation of proteins with chaperone function (GroL, DnaK, ClpB, HslU, GroS, DnaJ, DnaJ-1, and NapD) at 37 °C in comparison to 42 °C after 12 h incubation indicates a temporary lower-temperature proteomic response. Additionally the up-regulation of factors for DNA uptake (ComEA and RecA) at 37 °C compared to 42 °C indicate a higher competence for the acquisition of extraneous DNA at human body temperature.
Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis
Authors: Keyvanfar Amirreza , Najafiarab Hanieh , Talebian Niki , Tafti Mahdi Falah , Adeli Gelareh , Ghasemi Zahra , Tehrani Shabnam
Published: May 2024

Background

Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.

Methods

Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.

Results

Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1–35.8%), fluconazole (24.8%, 95% CI: 17.4–32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0–26.0%), voriconazole (20.0%, 95% CI: 1.9–38.0%), miconazole (15.0%, 95% CI: 5.1–26.0%), clotrimazole (13.4%, 95% CI: 2.3–24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5–5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I2 > 50.00%, P < 0.01), except for caspofungin (I2 = 0.00%, P = 0.65).

Conclusions

Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.

Registration

The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
De novo engineering riboflavin production Bacillus subtilis by overexpressing the downstream genes in the purine biosynthesis pathway
Authors: Liu Chuan , Xia Miaomiao , Fang Huan , Xu Fan , Wang Sijia , Zhang Dawei
Published: May 2024

Background

Bacillus subtilis is widely used in industrial-scale riboflavin production. Previous studies have shown that targeted mutagenesis of the ribulose 5-phosphate 3-epimerase in B. subtilis can significantly enhance riboflavin production. This modification also leads to an increase in purine intermediate concentrations in the medium. Interestingly, B. subtilis exhibits remarkable efficiency in purine nucleoside synthesis, often exceeding riboflavin yields. These observations highlight the importance of the conversion steps from inosine-5’-monophosphate (IMP) to 2,5-diamino-6-ribosylamino-4(3 H)-pyrimidinone-5’-phosphate (DARPP) in riboflavin production by B. subtilis. However, research elucidating the specific impact of these reactions on riboflavin production remains limited.

Result

We expressed the genes encoding enzymes involved in these reactions (guaB, guaA, gmk, ndk, ribA) using a synthetic operon. Introduction of the plasmid carrying this synthetic operon led to a 3.09-fold increase in riboflavin production compared to the control strain. Exclusion of gmk from the synthetic operon resulted in a 36% decrease in riboflavin production, which was further reduced when guaB and guaA were not co-expressed. By integrating the synthetic operon into the genome and employing additional engineering strategies, we achieved riboflavin production levels of 2702 mg/L. Medium optimization further increased production to 3477 mg/L, with a yield of 0.0869 g riboflavin per g of sucrose.

Conclusion

The conversion steps from IMP to DARPP play a critical role in riboflavin production by B. subtilis. Our overexpression strategies have demonstrated their effectiveness in overcoming these limiting factors and enhancing riboflavin production.
Methylosinus trichosporium OB3b bioaugmentation unleashes polyhydroxybutyrate-accumulating potential in waste-activated sludge
Authors: Eam Hyerim , Ko Dayoung , Lee Changsoo , Myung Jaewook
Published: May 2024

Background

Wastewater treatment plants contribute approximately 6% of anthropogenic methane emissions. Methanotrophs, capable of converting methane into polyhydroxybutyrate (PHB), offer a promising solution for utilizing methane as a carbon source, using activated sludge as a seed culture for PHB production. However, maintaining and enriching PHB-accumulating methanotrophic communities poses challenges.

Results

This study investigated the potential of Methylosinus trichosporium OB3b to bioaugment PHB-accumulating methanotrophic consortium within activated sludge to enhance PHB production. Waste-activated sludges with varying ratios of M. trichosporium OB3b (1:0, 1:1, 1:4, and 0:1) were cultivated. The results revealed substantial growth and methane consumption in waste-activated sludge with M. trichosporium OB3b-amended cultures, particularly in a 1:1 ratio. Enhanced PHB accumulation, reaching 37.1% in the same ratio culture, indicates the dominance of Type II methanotrophs. Quantification of methanotrophs by digital polymerase chain reaction showed gradual increases in Type II methanotrophs, correlating with increased PHB production. However, while initial bioaugmentation of M. trichosporium OB3b was observed, its presence decreased in subsequent cycles, indicating the dominance of other Type II methanotrophs. Microbial community analysis highlighted the successful enrichment of Type II methanotrophs-dominated cultures due to the addition of M. trichosporium OB3b, outcompeting Type I methanotrophs. Methylocystis and Methylophilus spp. were the most abundant in M. trichosporium OB3b-amended cultures.

Conclusions

Bioaugmentation strategies, leveraging M. trichosporium OB3b could significantly enhance PHB production and foster the enrichment of PHB-accumulating methanotrophs in activated sludge. These findings contribute to integrating PHB production in wastewater treatment plants, providing a sustainable solution for resource recovery.

Graphical abstract
Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers
Authors: Zhao Kun , Zhao Qi , Dai Xinzhi , Wen Xue , Luo Xing , Duan Yi , Yang Zhihui , Dai Qiong
Published: May 2024

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.
LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
Authors: Lin Chao , Jiang Tao , E Changyong , Wang Lun , Chen Tong , Wang Xia , Xiang Yien
Published: May 2024

Background

LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC).

Method

qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis.

Results

Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism.

Conclusion

CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.
Tumor-matched and unmatched cancer associated fibroblasts exhibit differential effect on proliferation and FMOD and MMP9 gene expression in head and neck squamous cell carcinoma cells when cocultured in spheroids
Authors: Rademaekers Max , Johansson Emil Oliver , Johansson Ellen , Roberg Karin , Wiechec Emilia
Published: May 2024

Background

Cancer-associated fibroblasts (CAFs) are the major cellular component of the tumor microenvironment and are known to affect tumor growth and response to various treatments. This study was undertaken to investigate the crosstalk between tumor-matched or unmatched CAFs and head and neck squamous cell carcinoma (HNSCC) cells regarding tumor growth and treatment response.

Methods

Three HNSCC cell lines (LK0412, LK0902 and LK0923), were cocultured in 2D or in 3D with their tumor-matched CAFs, site matched CAFs from other tumors or normal oral fibroblasts (NOFs). Cell proliferation was assessed as the amount of Ki67 positive cells/ spheroid area in formalin-fixed- paraffin-embedded 3D spheroids stained with Ki67 antibody. Viability after seven days of cisplatin treatment was measured with CellTiter-Glo 3D Viability Assay. The mRNA expression of CAF-associated markers (ACTA2, COL1A2, FAP, PDGFRα, PDGFRβ, PDPN, POSTN and S100A4) in CAFs before and after coculture with tumor cells as well as mRNA expression of CAF-induced genes (MMP1, MMP9 and FMOD) in tumor cells separated from CAFs after co-culture was measured with RT-qPCR. The expression of selected protein biomarkers was validated with immunohistochemistry based on previous mRNA expression results.

Results

The proliferation of the LK0412 and LK0902 tumor spheroids varied significantly when cocultured with different CAFs and NOFs as shown by Ki-67 positive cells. RT‒qPCR analysis revealed different molecular profile of the analyzed HNSCC-derived CAFs concerning the expression of CAF-associated markers. The interaction between CAFs and HNSCC cells was more pronounced after coculture with unmatched CAFs as shown by changes in mRNA expression pattern of CAF-specific markers. Additionally, the unmatched CAFs significantly upregulated the mRNA expression of MMP1, MMP9 and FMOD in tumor cells compared to tumor-matched CAFs.

Conclusion

Our results indicate that tumor-matched CAFs are unique for each tumor and affect the proliferation and the gene/protein expression of tumor cells in a distinct manner. The interaction between tumor unmatched CAFs and HNSCC cells in the tumor spheroids is associated with significant changes in the mRNA expression of CAF-specific markers and significant increases in FMOD and MMP9 in tumor cells compared to when cocultured with tumor-matched CAFs. Taken together, our results show how important the selection of CAFs is to get a reliable in vitro model that mimics the patients’ tumor.
Long-term survival outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of hepatocellular carcinoma patients
Authors: Yan Guojun , Zhang Kai , Yan Lijun , Zhang Yanbin
Published: May 2024

Background

Hepatocellular carcinoma with peritoneal metastasis (HCC-PM) has a poor outlook. Traditional treatments have limited effect on survival. The safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) have been shown in other peritoneal cancers. This study evaluates the role of CRS + HIPEC in HCC-PM.

Methods

A retrospective analysis of HCC-PM patients treated with CRS + HIPEC at Beijing Shijitan Hospital from March 2017 to December 2023 was conducted, assessing clinical features, severe adverse events (SAEs), and overall survival (OS) rates.

Results

The study population comprised 10 HCC-PM patients who underwent CRS + HIPEC. The median peritoneal cancer index (PCI) was 25, and complete cytoreduction (CC0 ~ 1) was achieved in half of the patients. Three patients experienced SAEs within 30 days postoperatively. The 1-year, 3-year, and 5-year OS rates were recorded as 89.0%, 89.0%, and 21.0% respectively, with a median OS1 of 107.8 months and OS2 of 49.9 months. The median progression-free survival (PFS) was 5.0 months.

Conclusion

The application of CRS + HIPEC offers significant benefits to patients with HCC-PM. A selected group of patients may achieve prolonged PFS. Incorporating CRS + HIPEC into the treatment paradigm can thus be considered a strategic therapeutic option for patients with HCC-PM.
A comprehensive review of in planta stable transformation strategies
Authors: Bélanger Jérôme Gélinas , Copley Tanya Rose , Hoyos-Villegas Valerio , Charron Jean-Benoit , O’Donoughue Louise
Published: May 2024

Plant transformation remains a major bottleneck to the improvement of plant science, both on fundamental and practical levels. The recalcitrant nature of most commercial and minor crops to genetic transformation slows scientific progress for a large range of crops that are essential for food security on a global scale. Over the years, novel stable transformation strategies loosely grouped under the term “in planta” have been proposed and validated in a large number of model (e.g. Arabidopsis and rice), major (e.g. wheat and soybean) and minor (e.g. chickpea and lablab bean) species. The in planta approach is revolutionary as it is considered genotype-independent, technically simple (i.e. devoid of or with minimal tissue culture steps), affordable, and easy to implement in a broad range of experimental settings. In this article, we reviewed and categorized over 300 research articles, patents, theses, and videos demonstrating the applicability of different in planta transformation strategies in 105 different genera across 139 plant species. To support this review process, we propose a classification system for the in planta techniques based on five categories and a new nomenclature for more than 30 different in planta techniques. In complement to this, we clarified some grey areas regarding the in planta conceptual framework and provided insights regarding the past, current, and future scientific impacts of these techniques. To support the diffusion of this concept across the community, this review article will serve as an introductory point for an online compendium about in planta transformation strategies that will be available to all scientists. By expanding our knowledge about in planta transformation, we can find innovative approaches to unlock the full potential of plants, support the growth of scientific knowledge, and stimulate an equitable development of plant research in all countries and institutions.
Surgical removal of a peripheral venous catheter fragment in the heart in a preterm infant
Authors: Wang Gang , Zhao Zhe , Zhou Gengxu , Feng Zhichun
Published: May 2024

Peripheral venous catheter fracture with cardiovascular embolization is a rare but potentially serious complication. Herein, we report a case of peripheral venous catheter fracture with embolization in right ventricle in a preterm infant. The catheter fragment was successfully removed by surgical procedure via median sternotomy under cardiopulmonary bypass(CPB).We hope this case will increase awareness of this rare complication and improve cannulation safety.
CRISPR/Cas-based CAR-T cells: production and application
Authors: Song Ping , Zhang Qiqi , Xu Zhiyong , Shi Yueli , Jing Ruirui , Luo Dingcun
Published: May 2024

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.
La Poesia Come Traduzione
Authors: Agamben Giorgio
Published: May 2024

Questo saggio riflette sul costitutivo bilinguismo che caratterizza l’autotraduzione in italiano dei poeti dialettali del Novecento. Qui, propone Agamben, la poesia non abita più nell’identità di una lingua, ma trova una vera casa nello spazio bianco che unisce e divide i due testi, spesso stampati su pagine contrapposte. Agamben fa risalire questo bilinguismo poetico a Dante, che contrappone la lingua volgare, “che i bambini acquisiscono da chi li circonda”, alla lingua che chiama “grammaticale”, che dobbiamo imparare attraverso un lungo percorso di studi. Questa tensione traduttiva tra due lingue non riguarda solo la poesia dialettale, ma, come dimostrano chiaramente le traduzioni di Hölderlin da Pindaro e Sofocle, definisce ogni autentica intenzione poetica. Assumere questo bilinguismo intrinseco è, secondo Agamben, il compito del traduttore e del poeta.
The Mediator Serving Two Mistresses
Authors: Tengour Habib , Villa-Ignacio Teresa
Published: May 2024

This essay is an Algerian-French poet-translator’s personal reflection on the indispensable role that translation has played in his poetic creativity. Emphasizing in particular his bilingual education in the colonial Algerian context, he observes that his translation of poets from English, Arabic, and German into French is thus “doubly foreign” because his French is steeped in his Arabic culture and language. The essay advocates for the peaceful coexistence of any two languages, and especially the postcolonial coexistence of Arabic and French, as one of mutual enrichment. Tengour shows how this inclusive translational approach to Algerian bilinguality informs not only his creative process but also his editorial work, including Diwân ifriqiya, volume 4 of the Poems for the Millennium series from the University of California Press, and Poèmes du monde, a series of poetry in translation from Éditions Apic in Algeria, which has published over twenty poets from at least a dozen countries.
Precarious Petroleum
Authors: Movahedi-Lankarani Ciruce
Published: May 2024

As a major source of energy and revenue, “oil” has been rightly seen as a driver of the world's far-reaching twentieth-century social, political, and cultural transformations. But this conceptual abstraction of petroleum as a homogenous substance—lifted to the surface from static reservoirs and shipped around the world—is belied by the compositional heterogeneity of its deposits and the unpredictable dynamism of the buried geographies that hold them. Such factors have had important consequences within the histories of hydrocarbon-rich states like Iran. In the 1960s and 1970s, Iranian officials sought to build a new industry via the Shahpur Petrochemical Complex, a choice enabled by the unexpected availability of high-sulfur natural gas within the existing spaces of Iran's oil industry, and one that faced opposition from British Petroleum, which operated and largely controlled Iran's oil industry. Using archival and published materials, this article delves beneath the earth to focus on petroleum's sulfur impurities, the uncontrolled transformations of underground petroleum geographies, and the subterranean migrations of natural gas that resulted. It argues that centering notions of uncontrollability and petroleum's multiplicity opens new avenues for studying the histories of developing states like Iran, showing how the spaces opened by uncertainty were politically productive.
“They're Formidable, They're Beautiful, They're Hiding”: Filipina Migrant Domestic Workers in London and Dreams of a Global Union
Authors: Orleck Annelise
Published: May 2024

Throughout the twenty-first century the Philippines has sent more people abroad to work than almost any other country. Among them have been millions of women hired in New York, Los Angeles, London, Dubai, Hong Kong, Singapore, and other locales as domestic workers. Building on organizing experience and political knowledge they acquired as activists while still in the Philippines, overseas Filipina domestic workers have organized for better working conditions and fairer immigration policies in countries around the world. Among those are Waling Waling, a UK movement named after a Philippine orchid that grows in the dark. Some of the women of Waling Waling have been active since the 1980s. They are now seeking to organize a movement together with other Filipina domestic worker groups in countries around the world.
El Análisis del uso de la inteligencia artificial en la educación universitaria: una revisión sistemática (Analysis of the use of artificial intelligence in university education: a systematic review)
Authors: López Regalado Oscar , Núñez-Rojas Nemecio , Rafael López Gil Oscar , Sánchez-Rodríguez José
Published: May 2024

Los cambios frecuentes en la educación universitaria han sido trastocados estructuralmente por la incorporación de la inteligencia artificial (IA), mediante la utilización y aplicación por parte de los estudiantes y profesores en el proceso de enseñanza aprendizaje. El objetivo fue analizar e interpretar los resultados de la inteligencia artificial en la educación universitaria y valorar sus contribuciones en el periodo de 2019 a 2023. El método se aplicó la revisión sistemática y bibliométrica para responder a las preguntas específicas de la investigación, mediante métodos de búsqueda claros, sistemáticos y replicables; se accedió a un universo de 917 publicaciones indexadas en Scopus, WoS y PubMed y se seleccionó una muestra de 59 artículos científicos. Los resultados indican que la mayoría de las publicaciones se han realizado en la China, seguido de España y Estados Unidos, también se evidencia escasa colaboración entre investigadores, dispersión en las temáticas específicas y el aislamiento en redes pequeñas. En las universidades, se evidencia la aplicación de las herramientas de inteligencia artificial, en su uso correcto para el desarrollo del aprendizaje profundo con la activación de procesos cognitivos superiores en los estudiantes, quienes requieren de la orientación pedagógica de los docentes capacitados en esta temática.
An Enhanced Alternating Direction Method of Multipliers-Based Interior Point Method for Linear and Conic Optimization
Authors: Deng Qi , Feng Qing , Gao Wenzhi , Ge Dongdong , Jiang Bo , Jiang Yuntian , Liu Jingsong , Liu Tianhao , Xue Chenyu , Ye Yinyu , Zhang Chuwen
Published: May 2024

The alternating-direction-method-of-multipliers-based (ADMM-based) interior point method, or ABIP method, is a hybrid algorithm that effectively combines interior point method (IPM) and first-order methods to achieve a performance boost in large-scale linear optimization. Different from traditional IPM that relies on computationally intensive Newton steps, the ABIP method applies ADMM to approximately solve the barrier penalized problem. However, similar to other first-order methods, this technique remains sensitive to condition number and inverse precision. In this paper, we provide an enhanced ABIP method with multiple improvements. First, we develop an ABIP method to solve the general linear conic optimization and establish the associated iteration complexity. Second, inspired by some existing methods, we develop different implementation strategies for the ABIP method, which substantially improve its performance in linear optimization. Finally, we conduct extensive numerical experiments in both synthetic and real-world data sets to demonstrate the empirical advantage of our developments. In particular, the enhanced ABIP method achieves a 5.8× reduction in the geometric mean of run time on 105 selected linear optimization instances from Netlib, and it exhibits advantages in certain structured problems, such as support vector machine and PageRank. However, the enhanced ABIP method still falls behind commercial solvers in many benchmarks, especially when high accuracy is desired. We posit that it can serve as a complementary tool alongside well-established solvers.

History: Accepted by Antonio Frangioni, Area Editor for Design & Analysis of Algorithms—Continuous.

Funding: This research was supported by the National Natural Science Foundation of China [Grants 72394360, 72394364, 72394365, 72225009, 72171141, and 72150001] and by the Program for Innovative Research Team of Shanghai University of Finance and Economics.

Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2023.0017 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2023.0017 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Land-use change and habitat fragmentation of Leopardus pardalis in Highlands of Puebla, Mexico
Authors: Hernández-Pérez Ezequiel , Lemos Rincón Sergio Gilmar , Ayala-Hernández María M. , Aleman-Sancheschúlz Gilberto
Published: May 2024

Ocelots are relatively tolerant to habitat modification.  However, it has been observed that they may be sensitive to habitat loss and fragmentation as a result of human development.  The Sierra Norte de Puebla is considered a potential habitat for ocelots and other tropical felines.  However, it has suffered heavy loss and fragmentation of its natural ecosystems, which considerably affects habitat availability and quality.  This study analyzed the land-use changes and habitat fragmentation in the distribution range of the ocelot in the Sierra Norte de Puebla, Mexico, from 1993 to 2020.  Habitat suitability was determined using potential distribution models and vegetation and land-use maps from 1993, 2003, and 2020, obtained using supervised classification of Landsat images.  The resulting maps were reclassified in terms of the habitat suitability for Leopardus pardalis according to their quality.  Land-use changes and habitat loss were quantified with a transition matrix, and fragmentation was assessed using the Morphological Spatial Pattern Analysis tool of the program GUIDOS.  These habitat fragments were quantified using the integral index of connectivity with the CONEFOR Sensinode program.  We estimated that 22.2 % of the study area has suitable conditions for ocelots.  From 1993 to 2020, the area covered by natural vegetation decreased 16 % at an annual rate of -2.4 %.  During this period, the mean fragment size and shape index decreased; on the other hand, the number of fragments and the Euclidean distance between fragments increased.  The percentages of edge, branch, and islet vegetation dropped from 1993 to 2003 but increased in 2020.  The connectivity analysis indicated that two habitat fragments showed high values of the integral index of connectivity.  The increase in anthropogenic cover and the habitat loss for L. pardalis between 1993 and 2020 affected mainly vegetation fragments considered optimal for the persistence of this species.  In these ecosystems, agricultural and livestock practices are expanding vigorously, increasing edge habitats and decreasing the core area of habitat fragments.  The areas that recorded the presence of ocelots have optimum conditions to serve as biological corridors in the Sierra Madre Oriental, particularly in the portion of the Sierra Norte de Puebla.  The fragmentation of the ocelot habitat is of particular concern and should be addressed strategically for the long-term conservation of the ocelot and regional biodiversity.
HIV and Cryptococcal Meningitis: A Case Report
Authors: Djaputra Edith maria
Published: May 2024

Cryptococcal Meningitis (CM) has caused high morbidity and mortality rate among people living with HIV infection (PLWH). This case report showed a 32 years old female with HIV infection who came with chief complaint headache since 1 month before hospital admission (SMRS). Her headache had become worse in the past 2 days SMRS. Had been taking antiretroviral (ARV) therapy for 2 weeks and anti-toxoplasmic therapy for 3 weeks SMRS could not alleviate her complaints. Although the cerebrospinal fluid (LCS) examination has shown high probable Tuberculosis and Cryptococcal meningitis, specific examination for these infections only showed a positive result for CM. Few days after hospital admission, the patient experienced generalized seizures, monoplegia and sixth nerve palsy. Two months after high dose fluconazole therapy, the specific examination for Cryptococcal infection in CSF showed a negative result. This case report will show the difficulties in diagnosing and managing CNS opportunistic infections. Diagnosing CNS opportunistic infections, such as CM, has been a great challenge because of the low sensitivity and positive prediction value of the tests available, especially among PLWH. Managing these infections also poses some limitations, especially for the availability of their medications. Time to start ARVs has also been a big issue since ARVs were being given before 1definite diagnosis was established. This case study also showed that fluconazole alone can be used as an alternative therapy to amphotericin B and flucytosine for C.M. Therefore, this case report has shown the difficulty in diagnosing and managing CM in Indonesia.
Strength Assessment of Prosthetic Pylon Considering the Geometric of Raw Material
Authors: Syaifudin Achmad , Suryandari Dika Andini , Agustin Helena Carolina Kis
Published: May 2024

Prosthetic limbs are crucial as assistive devices for individuals with lower limb amputations. This study focuses on designing and analysing prosthetic feet, specifically the telescopic tube component, to achieve optimal material strength and aesthetic appeal. Numerical simulations using ANSYS Workbench 19 are conducted to assess the total deformation and von Mises stress. Design iterations adjust the pylon tube thickness and material selection. Prototypes are developed using aluminium 6061 tube and rod materials for further testing. Various tests, including scanning electron microscopy, metallography, axial tensile testing, and tangential tensile testing (according to ASTM B 557M), are performed to evaluate the material properties. Results indicated that the axial and yield strengths of the aluminium 6061 rod are superior to the tube type. Conversely, the aluminium 6061 tube exhibits higher ultimate and yield stability in tangential testing. Ultimately, the study concludes that the aluminium 6061 tube material is more robust and suitable for prosthetic feet.
The making of Maria Montessori
Authors: Cummins Sarah
Published: May 2024

In the first article in a new series all about Maria Montessori, Sarah Cummins, senior lecturer in the School of Education at Leeds Trinity University, shares more about Montessori's background, her history and the origin of her pioneering ideas.
Formação do Doutor em Administração no Brasil
Authors: Costa Francisco José da , Adamoglu de Oliveira Samir
Published: May 2024

Nosso ensaio teórico debate o processo de formação doutoral em Administração no Brasil e os desafios identificados neste cenário a partir de meados de 2010. Discutimos evidências da necessidade de aprimoramento desse processo formativo, considerando as perspectivas profissionais dos egressos, e a alternativa de ampliação das competências de formação nesse nível, apresentando a concepção de 'doutor em sentido pleno'. De modo a viabilizar essa concepção apresentada, propomos um modelo estruturado em seis competências, entrelaçadas em sua natureza: (i) conhecimentos teóricos; (ii) conhecimentos metodológicos; (iii) prática docente; (iv) prática de pesquisa; (v) produção escrita; e, (vi) competência técnica e profissional. Contribuímos refletindo sobre a qualidade da formação doutoral em Administração, tanto profissional quanto acadêmico, no Brasil.
Trauma and orthopaedic higher specialty trainee operating during the COVID-19 pandemic
Authors: Akehurst H , Thomas S
Published: May 2024

INTRODUCTION

The COVID-19 pandemic has had a significant impact on training in trauma and orthopaedic surgery owing to redeployment and reductions in both trauma referrals and elective service provision. While trainee surveys have reported reduced operative experience during this period, the case deficit has not previously been quantified.

METHODS

An analysis was undertaken of surgical logbooks from trauma and orthopaedic registrars in the Severn Deanery. A predictive model of pre-COVID monthly cases was fitted using trainee grade, hospital, subspecialty, clinical commitment and time of the year. This model was used to predict expected monthly cases for trainees’ post-COVID rotations, which were compared with the cases actually performed. A similar analysis was undertaken to assess primary surgeon operating.

RESULTS

A total of 28,998 cases performed by 34 registrars between 2015 and 2021 were analysed. The COVID-19 pandemic led to an immediate and profound reduction in trainee operating, which had not fully recovered by September 2021. The average deficit accumulated over the 18 months following the onset of the pandemic was 87 cases. The accumulated deficit in trainee operating corresponds to 3–4 months of work at 300 cases per year. Deficits were accrued unequally between hospitals and subspecialties, indicating that recovery efforts will need to be individualised according to trainee experience during the pandemic.

CONCLUSIONS

Action is urgently required not only to restore operative training in trauma and orthopaedic surgery but also to compensate for the deficit during the current training cycle.
Il cimbro
Authors: Bidese Ermenegildo
Published: May 2024

The aim of this contribution is to present the long history of linguistic research on Cimbrian, an alloglotte variety of Germanic origin, spoken historically in the mountains of the present provinces of Verona and Vicenza and in southern Trentino, and still used in the municipality of Lusèrn/Luserna. Moreover, the main linguistic features of Cimbrian, in particular the variety of Lusèrn/Luserna, will be presented. Finally, I will discuss some initiatives for the preservation and promotion of the Cimbrian language and culture.
L’occitano
Authors: Rivoira Matteo
Published: May 2024

This paper provides an overview of the varieties of Cisalpine Occitan. From a sociolinguistic perspective, these varieties may be regarded as both second-degree and endangered languages, though they have been involved into promotion policies for several decades. From a linguistic standpoint, the varieties of Cisalpine Occitan display features that can be traced back to an Alpine Occitan diasystem, though showing some structural similarities with Francoprovençal and Piedmontese. Some selected features of Cisalpine Occitan, belonging to different linguistic levels (phonetics and phonology, morphology, syntax and vocabulary), are presented and discussed.