bluuebunny/crossref_metadata_2025 huggingface dataset:
The area-based management tools coordination between IMO and BBNJ agreement regimes and its implications on vessel pollution control
Authors: Wang Jinpeng , Zhang Yiwei
Published: March 2024

The International Maritime Organization (IMO), as a specialized agency of the United Nations responsible for the safety and security of international shipping and the prevention of pollution from ships, has applied two main area-based management tools (ABMTs): the “Special Areas” established under the MARPOL 73/78; and the “Particularly Sensitive Sea Areas” (PSSAs) established under the IMO resolutions. The new Agreement under the United Nations Convention on the Law of the Sea on the Conservation and Sustainable Use of Marine Biological Diversity of Areas beyond National Jurisdiction (BBNJ agreement) stipulates the establishment of a comprehensive system of ABMTs to conserve and sustainably use areas beyond national jurisdiction. Strengthening coordination in the use of ABMTs established by the IMO and the BBNJ Agreement is important for vessel pollution control in the high seas. The IMO is a stakeholder for relevant proposals and consultations on proposals regarding the establishment of ABMTs in the BBNJ Agreements, and can provide information on the implementation of them. The Conference of the Parties (COPs) to the BBNJ Agreement can also make recommendations to the IMO and its parties to promote the adoption of special areas and PSSAs. This article respectively elaborates on the practices and effect of ABMTs of the IMO and explores the relevant rules of the BBNJ agreement and their enforcement. Then this article discusses the possible approaches for the ABMTs coordination between the IMO and the BBNJ agreement regimes and their implications on vessel pollution Control in the high seas. Overall, relevant rules of the BBNJ agreement shall be interpreted and applied in a manner that does not undermine relevant legal instruments of the IMO. Meanwhile, it is necessary to promote cooperation and coordination between the COPs to the BBNJ Agreement and the IMO under the idea of conserving ecosystem integrity, gradually forming a normal cooperation and information exchange mechanism.
Electron conduction mechanism in indium oxide and its implications for amorphous transport
Authors: Hu Yaoqiao , Cho Kyeongjae
Published: March 2024

The electron conduction mechanism in indium oxide (In2O3) and its implications for amorphous transport have been investigated from an orbital overlap perspective. Combined density functional theory and empirical tight binding modeling reveal that the electron transport is facilitated by the neighboring metal atomic s orbital overlap “without” oxygen’s p-orbital involvement. In other words, the electron transport pathway in oxides is only due to the metal-metal medium range connection. This electron conduction mechanism is extended to amorphous In2O3 which unveils that the amorphous disorder influences the electron transport through impacting the metal-metal medium range order including metal-metal coordination number and metal-metal separation. Our results provide an insight into the current theoretical understanding of electron transport in amorphous oxide semiconductors.
Predicted risk factors associated with secondary infertility in women: univariate and multivariate logistic regression analyses
Authors: Fatima Wafa , Akhtar Abdul Majeed , Hanif Asif , Gilani Aima , Farooq Syed Muhammad Yousaf
Published: March 2024

Introduction

Infertile women are those who regularly engage in unprotected intercourse for a period of at least 1 year and are unable to become clinically pregnant. Primary infertility means the inability of couples to conceive, without any previous successful pregnancies. Secondary Infertility refers to the inability to get pregnant for 12 months, after having a previous pregnancy for one time at least. The objectives of the current study were to analyze risk factors for secondary infertility and compare the predictive accuracy of artificial neural network (ANN) and multiple logistic regression models.

Methods

The study was conducted at The University Institute of Public Health collecting data from Gilani Ultrasound Center 18 months after approval of synopsis. A total of 690 women (345 cases and 345 controls) were selected. The women selected for the case group had to be 20–45 years of age, had any parity, and had a confirmed diagnosis of secondary infertility.

Results

Multiple logistic regression (MLR) and ANN were used. The chance of secondary infertility was 2.91 times higher in women living in a joint family [odds ratio (OR) = 2.91; 95% confidence interval (CI) (1.91, 4.44)] and was also 2.35 times higher for those women who had relationship difficulties with their husband [OR = 2.35; 95% CI (1.18, 4.70)]. Marriage at an earlier age was associated with secondary infertility with β being negative and OR being < 1 [OR = 0.94; 95% CI (0.88, 0.99)]. For the logistic regression model, the area under the receiver operative characteristic curve (ROC) was 0.852 and the artificial neural network was 0.87, which was better than logistic regression.

Discussion

Identified risk factors of secondary infertility are mostly modifiable and can be prevented by managing these risk factors.
Exploring primary care physicians’ challenges in using home blood pressure monitoring to manage hypertension in Singapore: a qualitative study
Authors: Moosa Aminath Shiwaza , Oka Prawira , Ng Chirk Jenn
Published: March 2024

Objective

Hypertension guidelines recommend using home blood pressure (HBP) to diagnose, treat and monitor hypertension. This study aimed to explore the challenges primary care physicians (PCPs) face in using HBP to manage patients with hypertension.

Method

A qualitative study was conducted in 2022 at five primary care clinics in Singapore. An experienced qualitative researcher conducted individual in-depth interviews with 17 PCPs using a semi-structured interview guide. PCPs were purposively recruited based on their clinical roles and seniority until data saturation. The interviews were audio-recorded, transcribed verbatim and managed using NVivo qualitative data management software. Analysis was performed using thematic analysis.

Results

PCPs identified variations in patients’ HBP monitoring practices and inconsistencies in recording them. Access to HBP records relied on patients bringing their records to the clinic visit. A lack of seamless transfer of HBP records to the EMR resulted in an inconsistency in documentation and additional workload for PCPs. PCPs struggled to interpret the HBP readings, especially when there were BP fluctuations; this made treatment decisions difficult.

Conclusion

Despite strong recommendations to use HBP to inform hypertension management, PCPs still faced challenges accessing and interpreting HBP readings; this makes clinical decision-making difficult. Future research should explore effective ways to enhance patient self-efficacy in HBP monitoring and support healthcare providers in documenting and interpreting HBP.
Uncovering the burden of hidradenitis suppurativa misdiagnosis and underdiagnosis: a machine learning approach
Authors: Kirby Joslyn , Kim Katherine , Zivkovic Marko , Wang Siwei , Garg Vishvas , Danavar Akash , Li Chao , Chen Naijun , Garg Amit
Published: March 2024

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular skin condition that is associated with significant psychosocial and economic burden and a diminished quality of life and work productivity. Accurate diagnosis of HS is challenging due to its unknown etiology, which can lead to underdiagnosis or misdiagnosis that results in increased patient and healthcare system burden. We applied machine learning (ML) to a medical and pharmacy claims database using data from 2000 through 2018 to develop a novel model to better understand HS underdiagnosis on a healthcare system level. The primary results demonstrated that high-performing models for predicting HS diagnosis can be constructed using claims data, with an area under the curve (AUC) of 81%–82% observed among the top-performing models. The results of the models developed in this study could be input into the development of an impact of inaction model that determines the cost implications of HS diagnosis and treatment delay to the healthcare system.
The PII protein interacts with the Amt ammonium transport and modulates nitrate/nitrite assimilation in mycobacteria
Authors: Ensinck Delfina , Gerhardt Edileusa C. M. , Rollan Lara , Huergo Luciano F. , Gramajo Hugo , Diacovich Lautaro
Published: March 2024

PII proteins are signal transduction proteins that belong to a widely distributed family of proteins involved in the modulation of different metabolisms in bacteria. These proteins are homotrimers carrying a flexible loop, named T-loop, which changes its conformation due to the recognition of diverse key metabolites, ADP, ATP, and 2-oxoglutarate. PII proteins interact with different partners to primarily regulate a set of nitrogen pathways. In some organisms, PII proteins can also control carbon metabolism by interacting with the biotin carboxyl carrier protein (BCCP), a key component of the acetyl-CoA carboxylase (ACC) enzyme complex, inhibiting its activity with the consequent reduction of fatty acid biosynthesis. Most bacteria contain at least two PII proteins, named GlnB and GlnK, with different regulatory roles. In mycobacteria, only one PII protein was identified, and the three-dimensional structure was solved, however, its physiological role is unknown. In this study we purified the Mycobacterium tuberculosis (M. tb) PII protein, named GlnB, and showed that it weakly interacts with the AccA3 protein, the α subunit shared by the three different, and essential, Acyl-CoA carboxylase complexes (ACCase 4, 5, and 6) present in M. tb. A M. smegmatis deletion mutant, ∆MsPII, exhibited a growth deficiency on nitrate and nitrite as unique nitrogen sources, and accumulated nitrite in the culture supernatant. In addition, M. tb PII protein was able to interact with the C-terminal domain of the ammonium transporter Amt establishing the ancestral role for this PII protein as a GlnK functioning protein.
Screening and performance optimization of fungi for heavy metal adsorption in electrolytes
Authors: Yang Yuhui , Liu Rui , Zhou Yizhou , Tang Yingnan , Zhang Jing , Wang Yu , Dai Tingting , Zou Ping , Bi Xiaoyi , Li Shuibing
Published: March 2024

The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25–30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43–), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.
Vesicular translocation of PARP-1 to cytoplasm causes ADP-ribosylation and disassembly of vimentin filaments during microglia activation induced by LPS
Authors: Chen Ruiqi , Xie Lirui , Fan Yang , Hua Xiangmei , Chung Chang Y.
Published: March 2024

ADP-ribosylation plays a significant role in various biological processes including genomic stability maintenance, transcriptional regulation, energy metabolism, and cell death. Using macrodomain pull-down assay with microglia lysates and MALDI-TOF-MS analysis, we identified vimentin as a major protein highly ADP-ribosylated by the poly(ADP-ribose) polymerases-1 (PARP-1) in response to LPS. ABT-888, a potent inhibitor of PARP-1/2 blocks the disassembly and ADP-ribosylation of vimentin. PARP-1 is a highly abundant nuclear protein. Its nuclear functions in repairing DNA damages induced by various stress signals, such as inflammatory stresses, have been well studied. In contrast, limited studies have been done on the cytoplasmic role(s) of PARP-1. Our study focuses on the cytoplasmic role of PARP-1 during microglia activation. Using immunofluorescence microscopy and Western blotting, we showed that a significant amount of PARP-1 is present in the cytosol of microglia cells stimulated and activated by LPS. Live cell imaging showed the translocation of nuclear PARP-1-EGFP to the cytoplasm in vesicular structures upon LPS stimulation. ABT-888 and U0126 can block this translocation. Immunofluorescence staining with various organelle marker antibodies revealed that PARP-1 vesicles show colocalization with Lamin A/C, suggesting they might be derived from the nuclear envelope through nuclear envelope budding. In conclusion, we demonstrated that PARP-1 is translocated from the nucleus to cytoplasm via vesicles upon LPS stimulation and that cytoplasmic PARP-1 causes ADP-ribosylation and disassembly of vimentin filaments during microglia activation induced by LPS.
Gender disparity in maintenance hemodialysis units in South India: a cross-sectional observational study
Authors: Shankar Mythri , Satheesh Gouri , A. Kishan , C. G. Sreedhara , Reddy Gireesh G
Published: March 2024

Background

Diseases manifest differently according to gender in many medical specialties. However, sex differences in kidney diseases have not been well explored worldwide, especially in India. These differences could also be attributed to sociocultural factors. Although CKD is more prevalent in women worldwide, most men are initiated on kidney replacement therapy (KRT). This study aimed to examine sex disparities in patients on maintenance hemodialysis.

Materials and methods

A cross-sectional observational study was conducted in two maintenance hemodialysis units at the Institute of Nephrourology, a tertiary care referral government center in Bengaluru, India. Demographic characteristics and laboratory parameters were also recorded.

Results

In total, 374 adult patients (aged >18 years) were included in the study. Most patients (72.7%) were men. Mean age in men was 46.95 ± 12.65 years, and women was 46.63 ± 13.66 years. There was no significant difference in marital status and the availability of caretakers between the groups. Spouses were the predominant caretakers for both sexes (64% men and 51% women, P = 0.14). Sons cared more for patients with mother than fathers (19.6% vs 8.8%, P = 0.074). Diabetic nephropathy was the most common cause of ESKD in both groups (33.1% vs 31.3%, P = 0.92). Men had a significantly longer duration of HTN and received more HD sessions per week than women. Mean hemoglobin (9.9 ± 1.79 vs 9.46 ± 1.47 g%) and mean serum creatinine (7.76 ± 2.65 vs 6.41 ± 2.27 mg/dl) were higher in men compared to women (P <0.002). Intradialytic complications, such as hypotension and cramps, were significantly more common in women than in men (P = 0.004). Most men (47.1%) were planning a kidney transplant (and were waitlisted) compared with fewer women (43%). There was no significant difference in the average number of hospitalizations per month or HD vintage.

Conclusion

Women tend to initiate dialysis later, and a lesser number are waitlisted for kidney transplantation, which might be partly related to varying access to or delivery of health care services. Factors such as lack of education, insufficient identification of and strategies to address cultural obstacles to healthcare, and a shortage of financial means to afford medical care are potentially correctable elements that might explain this discrepancy.
Turbulent dynamics and whole-brain modeling: toward new clinical applications for traumatic brain injury
Authors: Martínez-Molina Noelia , Sanz-Perl Yonatan , Escrichs Anira , Kringelbach Morten L. , Deco Gustavo
Published: March 2024

Traumatic Brain Injury (TBI) is a prevalent disorder mostly characterized by persistent impairments in cognitive function that poses a substantial burden on caregivers and the healthcare system worldwide. Crucially, severity classification is primarily based on clinical evaluations, which are non-specific and poorly predictive of long-term disability. In this Mini Review, we first provide a description of our model-free and model-based approaches within the turbulent dynamics framework as well as our vision on how they can potentially contribute to provide new neuroimaging biomarkers for TBI. In addition, we report the main findings of our recent study examining longitudinal changes in moderate-severe TBI (msTBI) patients during a one year spontaneous recovery by applying the turbulent dynamics framework (model-free approach) and the Hopf whole-brain computational model (model-based approach) combined with in silico perturbations. Given the neuroinflammatory response and heightened risk for neurodegeneration after TBI, we also offer future directions to explore the association with genomic information. Moreover, we discuss how whole-brain computational modeling may advance our understanding of the impact of structural disconnection on whole-brain dynamics after msTBI in light of our recent findings. Lastly, we suggest future avenues whereby whole-brain computational modeling may assist the identification of optimal brain targets for deep brain stimulation to promote TBI recovery.
Multi-consensus formation control by artificial potential field based on velocity threshold
Authors: Chang Xiaofei , Jiao Jiayue , Li Yuenan , Hong Bei
Published: March 2024

This study proposes a multi-consensus formation control algorithm by artificial potential field (APF) method based on velocity threshold. The algorithm improves the multi-consensus technique. This algorithm can split a group of agents into multiple agent groups. Note that the algorithm can easily complete the queue transformation as long as the entire proxy group is connected initially and no specific edges need to be removed. Furthermore, collision avoidance and maintenance of existing communication connectivity should be considered during the movement of all agents. Therefore, we design a new swarm motion potential function. The stability of multi-consensus formation control has proven to be effective in avoiding collisions, maintaining connectivity, and generating formations. The final numerical simulation results show the role of the controller we designed.
Modulations in neural pathways excitability post transcutaneous spinal cord stimulation among individuals with spinal cord injury: a systematic review
Authors: Tajali Shirin , Balbinot Gustavo , Pakosh Maureen , Sayenko Dimitry G. , Zariffa Jose , Masani Kei
Published: March 2024

Introduction

Transcutaneous spinal cord stimulation (TSCS), a non-invasive form of spinal cord stimulation, has been shown to improve motor function in individuals living with spinal cord injury (SCI). However, the effects of different types of TSCS currents including direct current (DC-TSCS), alternating current (AC-TSCS), and spinal paired stimulation on the excitability of neural pathways have not been systematically investigated. The objective of this systematic review was to determine the effects of TSCS on the excitability of neural pathways in adults with non-progressive SCI at any level.

Methods

The following databases were searched from their inception until June 2022: MEDLINE ALL, Embase, Web of Science, Cochrane Library, and clinical trials. A total of 4,431 abstracts were screened, and 23 articles were included.

Results

Nineteen studies used TSCS at the thoracolumbar enlargement for lower limb rehabilitation (gait & balance) and four studies used cervical TSCS for upper limb rehabilitation. Sixteen studies measured spinal excitability by reporting different outcomes including Hoffmann reflex (H-reflex), flexion reflex excitability, spinal motor evoked potentials (SMEPs), cervicomedullay evoked potentials (CMEPs), and cutaneous-input-evoked muscle response. Seven studies measured corticospinal excitability using motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS), and one study measured somatosensory evoked potentials (SSEPs) following TSCS. Our findings indicated a decrease in the amplitude of H-reflex and long latency flexion reflex following AC-TSCS, alongside an increase in the amplitudes of SMEPs and CMEPs. Moreover, the application of the TSCS-TMS paired associative technique resulted in spinal reflex inhibition, manifested by reduced amplitudes in both the H-reflex and flexion reflex arc. In terms of corticospinal excitability, findings from 5 studies demonstrated an increase in the amplitude of MEPs linked to lower limb muscles following DC-TSCS, in addition to paired associative stimulation involving repetitive TMS on the brain and DC-TSCS on the spine. There was an observed improvement in the latency of SSEPs in a single study. Notably, the overall quality of evidence, assessed by the modified Downs and Black Quality assessment, was deemed poor.

Discussion

This review unveils the systematic evidence supporting the potential of TSCS in reshaping both spinal and supraspinal neuronal circuitries post-SCI. Yet, it underscores the critical necessity for more rigorous, high-quality investigations.
TSC2 nonsense mutation in angiomyolipoma with epithelial cysts: a case report and literature review
Authors: Song Hong , Mao Guoliang , Jiao Nanlin , Li Jiajia , Gao Wanwan , Liu Yinhua , Lu Linming
Published: March 2024

Background

Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored.

Case report

A 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months.

Conclusion

To the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.
Case report: A case of high grade serous carcinoma of peritoneal origin
Authors: Liu Yiming , Wang Sixian , Wu Yingchao , Chen Guowei , Zhang Junling , Wang Xin
Published: March 2024

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.
Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features
Authors: Li Hui , Hu Xin , Ning Matthew S. , Fuller Gregory N. , Stewart John M. , Gilliam Jared C. , Wu Jia , Le Xiuning , Vaporciyan Ara A. , Lee J. Jack , Gibbons Don L. , Heymach John V. , Futreal Andrew , Zhang Jianjun
Published: March 2024

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as “metastatic choriocarcinoma” (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of “adenocarcinoma with aberrant expression of β-hCG” and finally pathologists at our hospital, who gave the diagnosis of “poorly differentiated carcinoma with choriocarcinoma features”. Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.
A case report of atypical chronic myeloid leukemia with complete hematological and major molecular response to Venetoclax/Azacitidine treatment
Authors: Chen Hongxia , Wang Ning , Li Yin , Xie Xiaohong , Yang Yi
Published: March 2024

Atypical Chronic Myeloid Leukemia (aCML), a myeloproliferative neoplasm with poor prognosis, was reclassified as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the WHO 2022 classification. Due to the heterogeneity of its clinical features and the lack of unique biomarkers, as well as limited treatment options, aCML currently lacks a standardized treatment protocol. In this case report, we reviewed a young man diagnosed with aCML who achieved complete clinical and hematologic remission subsequent to receiving a therapeutic regimen combining Venetoclax and Azacitidine.
Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention
Authors: Kelson Courtney O. , Zaytseva Yekaterina Y.
Published: March 2024

Altered lipid metabolism is a well-recognized feature of solid cancers, including colorectal cancer. In colorectal cancer, upregulation of lipid metabolism contributes to initiation, progression, and metastasis; thus, aberrant lipid metabolism contributes to a poor patient outcome. The inactivating mutation of APC, a vital tumor suppressor in the Wnt signaling pathway, is a key event that occurs early in the majority of colorectal cancer cases. The potential crosstalk between lipid metabolism and APC-driven colorectal cancer is poorly understood. This review collectively highlights and summarizes the limited understanding between mutations in APC and the upregulation of Wnt/beta-catenin signaling and lipid metabolism. The interconnection between APC inactivation and aberrant lipid metabolism activates Wnt/beta-catenin signaling which causes transcriptome, epigenetic, and microbiome changes to promote colorectal cancer initiation and progression. Furthermore, the downstream effects of this collaborative effort between aberrant Wnt/beta-catenin signaling and lipid metabolism are enhanced stemness, cellular proliferation, prooncogenic signaling, and survival. Understanding the mechanistic link between APC inactivation and alterations in lipid metabolism may foster identification of new therapeutic targets to enable development of more efficacious strategies for prevention and/or treatment of colorectal cancer.
Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice
Authors: Li Hui , Xu Mei , Chen Danlei , Wen Wen , Luo Jia
Published: March 2024

Purpose

Alcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer.

Methods

Female adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined.

Results

Alcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population.

Conclusion

PFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.
Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial
Authors: Hardy-Abeloos Camille , Gorovets Daniel , Lewis Aurora , Ji Wenyan , Lozano Alicia , Tung Chih Chun , Yu Francis , Hanlon Alexandra , Lin Haibo , Kha Anh , Yamada Yoshiya , Kabarriti Rafi , Lazarev Stanislav , Hasan Shaakir , Chhabra Arpit M. , Simone Charles B. , Choi J. Isabelle
Published: March 2024

Introduction

Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation.

Methods and materials

In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests.

Results

Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively).

Discussion

In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.
Nomogram to predict prognosis of head and neck rhabdomyosarcoma patients in children and adolescents
Authors: Wu Jinwen , Zeng Qi
Published: March 2024

Purpose

This study aims to explore the prognostic factors of head and neck rhabdomyosarcoma (HNRMS) in children and adolescents and construct a simple but reliable nomogram model for estimating overall survival (OS) of patients.

Methods

Data of all HNRMS patients during 2004–2018 were identified from the Surveillance, Epidemiology, and End Result database. Kaplan–Meier method was performed to calculate OS stratified by subgroups and comparison between subgroups was completed by log-rank test. Univariate and multivariate Cox regressions analysis were employed for identifying independent predictors, which subsequently were used for a predictive model by R software, and the efficacy of the model was evaluated by applying receiver operating curve (ROC), calibration and decision curve analysis (DCA).

Results

A total of 446 patients were included in the study. The 1-, 3-, and 5-year OS rate of the whole cohort was 90.6%, 80.0%, and 75.5%, respectively. The results of univariate and multivariate Cox regression analysis indicated that the primary site in parameningeal region, alveolar RMS histology, M1 stage, IRS stage 4, surgery, and chemotherapy were significant prognostic factors (all P<0.05). The performance of nomogram model was validated by discrimination and calibration, with AUC values of 1, 3, and 5 years OS of 0.843, 0.851, and 0.890, respectively.

Conclusion

We constructed a prognostic nomogram model for predicting the OS in HNRMS patients in children and adolescents and this model presented practical and applicable clinical value to predict survival when choosing treatment strategies.
Effects of total glucosides of paeony on serum inflammatory cytokines in animal models of rheumatoid arthritis: a systematic review and meta-analysis
Authors: He Mengdi , Hu Zhipeng , Yang Maoyi
Published: March 2024

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis of the affected joints. Total glucosides of paeony (TGP) capsules have been widely used clinically for the treatment of RA with good efficacy and safety. However, its effect on inflammatory cytokines remains unclear.

Objectives: This study aimed to summarize the effect of TGP on the expression level of serum inflammatory cytokines in RA animal models and its potential mechanisms.

Methods: Six databases were searched up to 14 August 2023, relevant animal experiment studies were screened, data were extracted, and the SYRCLE animal experiment bias risk assessment tool was used for risk assessment.

Results: A total of 24 studies were included, including 581 animals. Results showed that compared with the model control group, TGP decreased the levels of TNF-α, IL-1β, IL-6, and PGE2 and increased the levels of TGF-β1 after 1–2 weeks of intervention, decreased the levels of TNF-α, IL-1β, IL-6, IL-2, IL-17, IL-17α, IL-21, VEGF, IFN-γ and PGE2 and increased the levels of IL-10 and IL-4 after 3–4 weeks of intervention, decreased the levels of TNF-α, IL-6, IL-17α and increased the level of IL-10 after 8 weeks of intervention. There was no significant difference in the effects of TGP on the levels of IL-10, IL-17, and IFN-γ after 1–2 weeks of intervention and IL-1 and TGF-β1 after 3–4 weeks of intervention.

Conclusion: In summary, based on the existing studies, this study found that compared with the control group of the RA animal model, TGP can reduce the levels of serum pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and increase the levels of serum anti-inflammatory cytokines such as IL-10, exerting an anti-inflammatory effect by regulating and improving the levels of inflammatory cytokines, and thus alleviating the disease. Given the low quality of the included studies and the lack of sufficient evidence, more high-quality studies are still needed to validate the results of this study.
Paucatalinone A from Paulownia Catalpifolia Gong Tong Elicits mitochondrial-mediated cancer cell death to combat osteosarcoma
Authors: Wang Ganyu , Cui Zhiwei , Tian Jinqiu , Li Xinyuan , Tang Wenzhao , Jing Weiqiang , Li Aiwu , Zhang Yuankai
Published: March 2024

As the global cancer burden escalates, the search for alternative therapies becomes increasingly vital. Natural products, particularly plant-derived compounds, have emerged as promising alternatives to conventional cancer treatments due to their diverse bioactivities and favorable biosafety profiles. Here, we investigate Paucatalinone A, a newly discovered geranylated flavanone derived from the fruit of Paulownia Catalpifolia Gong Tong, notable for its significant anti-cancer properties. We revealed the capability of Paucatalinone A to induce apoptosis in osteosarcoma cells and deciphered its underlying mechanisms. Our findings demonstrate that Paucatalinone A substantially augments apoptosis, inhibits cell proliferation, and demonstrates a pronounced anti-tumor effect in a murine model of osteosarcoma. Mechanistically, Paucatalinone A disrupts calcium homeostasis and exacerbates intracellular reactive oxygen species accumulation, leading to mitochondrial impairment, cytoskeletal collapse, and caspase-dependent apoptotic cell death. This study underscores the potential of Paucatalinone A in initiating apoptosis in cancer cells and highlights the therapeutic efficacy of plant-derived agents in treating osteosarcoma, offering a viable approach for managing other intractable cancers.
Proteomics reveals the significance of vacuole Pi transporter in the adaptability of Brassica napus to Pi deprivation
Authors: Han Bei , Yan Junjun , Wu Tao , Yang Xinyu , Wang Yajie , Ding Guangda , Hammond John , Wang Chuang , Xu Fangsen , Wang Sheliang , Shi Lei
Published: March 2024

Vacuolar Pi transporters (VPTs) have recently been identified as important regulators of cellular Pi status in Arabidopsis thaliana and Oryza sativa. In the oil crop Brassica napus, BnA09PHT5;1a and BnC09PHT5;1a are two homologs of AtPHT5;1, the vacuolar Pi influx transporter in Arabidopsis. Here, we show that Pi deficiency induces the transcription of both homologs of PHT5;1a genes in B. napus leaves. Brassica PHT5;1a double mutants (DM) had smaller shoots and higher cellular Pi concentrations than wild-type (WT, Westar 10), suggesting the potential role of BnPHT5;1a in modulating cellular Pi status in B. napus. A proteomic analysis was performed to estimate the role of BnPHT5;1a in Pi fluctuation. Results show that Pi deprivation disturbs the abundance of proteins in the physiological processes involved in carbohydrate metabolism, response to stimulus and stress in B. napus, while disruption of BnPHT5;1a genes may exacerbate these processes. Besides, the processes of cell redox homeostasis, lipid metabolic and proton transmembrane transport are supposed to be unbalanced in BnPHT5;1a DM under the -Pi condition. Noteworthy, disruption of BnPHT5;1a genes severely alters the abundance of proteins related to ATP biosynthesis, and proton/inorganic cation transmembrane under normal Pi condition, which might contribute to B. napus growth limitations. Additionally, seven new protein markers of Pi homeostasis are identified in B. napus. Taken together, this study characterizes the important regulatory role of BnPHT5;1a genes as vacuolar Pi influx transporters in Pi homeostasis in B. napus.
Endophytic non-pathogenic Fusarium oxysporum reorganizes the cell wall in flax seedlings
Authors: Wojtasik Wioleta , Dymińska Lucyna , Hanuza Jerzy , Burgberger Marta , Boba Aleksandra , Szopa Jan , Kulma Anna , Mierziak Justyna
Published: March 2024

Introduction

Flax (Linum usitatissimum) is a crop producing valuable products like seeds and fiber. However, its cultivation faces challenges from environmental stress factors and significant yield losses due to fungal infections. The major threat is Fusarium oxysporum f.sp lini, causing fusarium wilt of flax. Interestingly, within the Fusarium family, there are non-pathogenic strains known as biocontrols, which protect plants from infections caused by pathogenic strains. When exposed to a non-pathogenic strain, flax exhibits defense responses similar to those seen during pathogenic infections. This sensitization process activates immune reactions, preparing the plant to better combat potential pathogenic strains. The plant cell wall is crucial for defending against pathogens. It serves as the primary barrier, blocking pathogen entry into plant cells

Methods

The aim of the study was to investigate the effects of treating flax with a non-pathogenic Fusarium oxysporum strain, focusing on cell wall remodeling. The infection’s progress was monitored by determining the fungal DNA content and microscopic observation. The plant defense response was confirmed by an increase in the level of Pathogenesis-Related (PR) genes transcripts. The reorganization of flax cell wall during non-pathogenic Fusarium oxysporum strain infection was examined using Infrared spectroscopy (IR), determination of cell wall polymer content, and analysis of mRNA level of genes involved in their metabolism.

Results and discussion

IR analysis revealed reduced cellulose content in flax seedlings after treatment with Fo47 and that the cellulose chains were shorter and more loosely bound. Hemicellulose content was also reduced but only after 12h and 36h. The total pectin content remained unchanged, while the relative share of simple sugars and uronic acids in the pectin fractions changed over time. In addition, a dynamic change in the level of methylesterification of carboxyl groups of pectin was observed in flax seedlings treated with Fo47 compared to untreated seedlings. The increase in lignin content was observed only 48 hours after the treatment with non-pathogenic Fusarium oxysporum. Analysis of mRNA levels of cell wall polymer metabolism genes showed significant changes over time in all analyzed genes. In conclusion, the research suggests that the rearrangement of the cell wall is likely one of the mechanisms behind flax sensitization by the non-pathogenic Fusarium oxysporum strain. Understanding these processes could help in developing strategies to enhance flax’s resistance to fusarium wilt and improve its overall yield and quality.
Is metaphor a natural kind?
Authors: Garello Stefana , Carapezza Marco
Published: March 2024

In Metaphor Studies, metaphor is considered as a “form of understanding one thing in terms of something else.” It is assumed that, despite their differences, metaphors share many properties and that a theory of metaphor should capture these essential properties. In short, it is assumed that metaphor is a natural kind. We call this view the Natural Kind Assumption. In this paper, we will challenge it and show that metaphor is not a natural kind. Finally, we will discuss the main philosophical consequences of this view.
Sustaining efforts to improve family well-being with parents with mental ill health and substance (mis)use
Authors: Allchin Becca , Albermann Kurt , Blake-Holmes Kate , Gatsou Lina , Hine Rochelle , van Doesum Karin , Nicholson Joanne
Published: March 2024

Research conducted over the past 30 years has developed an extensive body of knowledge on families where parents experience mental ill health and/or substance (mis)use, and interventions that are effective in improving their outcomes. A more recent focus has also explored the importance and nuance of implementation. This perspective article reflects on the concept and practice of sustainability within this body of work and considers underlying assumptions in the field about the goal and direction of interventions that make clarity about sustainability difficult. We identify challenges for understanding sustainability, relating to how and who defines it, what is measured and the impact of context. We conclude by considering how we might be better able to plan and design for sustainability within this field.
Validity and reliability of the Difficulties in Emotion Regulation Scale Short Form in Indonesian non-clinical population
Authors: Danasasmita Febrianti Santiardi , Pandia Veranita , Fitriana Efi , Afriandi Irvan , Purba Fredrick Dermawan , Ichsan Abdullah , Pradana Kent , Santoso Alfonso Haris Setia , Mardhiyah Fithriani Salma , Engellia Rita
Published: March 2024

Introduction

Emotion dysregulation is a transdiagnostic marker for vulnerability and has high comorbidity rates across various range of disorders among adolescents and young adults, highlighting the crucial need for precise assessment tools to recognize its significant impact on well-being. The Difficulties in Emotion Regulation Scale Short Form (DERS-SF) is a comprehensive instrument designed to measure the ability to regulate emotion. This study aimed to investigate the psychometric properties of DERS-SF among the non-clinical population, particularly high school and university students in Indonesia.

Methods

A total of 738 senior high school and university students completed the Indonesian version of DERS-SF and standard questionnaires to assess its validity, consisting of the Depression Anxiety Stress Scale (DASS), the Beck Depression Inventory-II (BDI-II) for young adults and the Children Depression Inventory (CDI) for adolescents. Three models were examined in factorial validity tests using confirmatory factor analysis.

Results

The results showed that DERS-SF had an overall good internal consistency with Cronbach’s alpha coefficient of.89 for the 18-item version,.90 for the 17-item version, and.91 for the 15-item version. Test-retest reliability was moderate with a value of.67. In addition, it had good satisfactory content as shown by item content validity index (I-CVI) = .96 and scale content validity index (S-CVI) = .83, as well as convergent validity. All subscales scores showed a positive and strong correlation with DASS, BDI-II, and CDI except awareness. Based on confirmatory factor analysis (CFA), the correlated 6-factor model excluding item number 6, and the 5-factor model excluding awareness were suitable to use in non-clinical populations.

Conclusion

This study established the removal of the awareness subscale in the DERS-SF Indonesian version, resulting in better reliability and validity than the original version with complete subscales.