bluuebunny/crossref_metadata_2025 huggingface dataset:
Agricultural waste-based modified biochars differentially affected the soil properties, growth, and nutrient accumulation by maize (Zea mays L.) plants
Authors: Qayyum Muhammad Farooq , Khan Dur-e-Sameen , Alghanem Suliman Mohammed Suliman , Sakit Alhaithloul Haifa Abdulaziz , Alsudays Ibtisam Mohammed , Rizwan Muhammad , Hong Yong Jean Wan
Published: June 2024

Biochar (BC) is an organic compound formed by the pyrolysis of organic wastes. Application of BCs as soil amendments has many benefits including carbon sequestration, enhanced soil fertility and sustainable agriculture production. In the present study, we acidified the different BCs prepared from rice straw, rice husk, wheat straw, cotton stalk, poultry manure, sugarcane press mud and vegetable waste; following which, we applied them in a series of pot experiments. Comparisons were made between acidified and non- acidified BCs for their effects on seed germination, soil properties (EC, pH) nutrient contents (P, K, Na) and organic matter. The treatments comprised of a control, and all above-described BCs (acidified as well as non-acidified) applied to soil at the rate of 1% (w/w). The maize crop was selected as a test crop. The results showed that acidified poultry manure BC significantly improved germination percentage, shoot length, and biomass of maize seedlings as compared to other BCs and their respective control plants. However, acidified BCs caused a significant decrease in nutrient contents (P, K, Na) of soil,maize seedlings, and the soil organic matter contents as compared to non- acidified BCs. But when compared with control treatments, all BCs treatments (acidified and non-acidified) delivered higher levels of nutrients and organic matter contents. It was concluded that none of the BCs (acidified and non-acidified) had caused negative effect on soil conditions and growth of maize. In addition, the acidification of BC prior to its application to alkaline soils might had altered soil chemistry and delivered better maize growth. Moving forward, more research is needed to understand the long-term effects of modified BCs on nutrient dynamics in different soils. In addition, the possible effects of BC application timings, application rates, particle size, and crop species have to be evaluated systemtically.
A novel score for predicting falls in community-dwelling older people: a derivation and validation study
Authors: Zhou Ming , Zhang Gongzi , Wang Na , Zhao Tianshu , Liu Yangxiaoxue , Geng Yuhan , Zhang Jiali , Wang Ning , Peng Nan , Huang Liping
Published: June 2024

Background

Early detection of patients at risk of falling is crucial. This study was designed to develop and internally validate a novel risk score to classify patients at risk of falls.

Methods

A total of 334 older people from a fall clinic in a medical center were selected. Least absolute shrinkage and selection operator (LASSO) regression was used to minimize the potential concatenation of variables measured from the same patient and the overfitting of variables. A logistic regression model for 1-year fall prediction was developed for the entire dataset using newly identified relevant variables. Model performance was evaluated using the bootstrap method, which included measures of overall predictive performance, discrimination, and calibration. To streamline the assessment process, a scoring system for predicting 1-year fall risk was created.

Results

We developed a new model for predicting 1-year falls, which included the FRQ-Q1, FRQ-Q3, and single-leg standing time (left foot). After internal validation, the model showed good discrimination (C statistic, 0.803 [95% CI 0.749–0.857]) and overall accuracy (Brier score, 0.146). Compared to another model that used the total FRQ score instead, the new model showed better continuous net reclassification improvement (NRI) [0.468 (0.314–0.622), P < 0.01], categorical NRI [0.507 (0.291–0.724), P < 0.01; cutoff: 0.200–0.800], and integrated discrimination [0.205 (0.147–0.262), P < 0.01]. The variables in the new model were subsequently incorporated into a risk score. The discriminatory ability of the scoring system was similar (C statistic, 0.809; 95% CI, 0.756–0.861; optimism-corrected C statistic, 0.808) to that of the logistic regression model at internal bootstrap validation.

Conclusions

This study resulted in the development and internal verification of a scoring system to classify 334 patients at risk for falls. The newly developed score demonstrated greater accuracy in predicting falls in elderly people than did the Timed Up and Go test and the 30-Second Chair Sit-Stand test. Additionally, the scale demonstrated superior clinical validity for identifying fall risk.
Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study
Authors: Guedes Murilo , Dias Paulo Telles , Réa Rosângela R. , Calice-Silva Viviane , Lopes Marcelo , Brandão Andrea Araujo , Bauer Andrea Carla , Senerchia Andreza Almeida , de Castro e Abreu Rocha Pedro Túlio Monteiro , Rosa Bruno Bezerra , Teixeira Cinthia Montenegro , Pecoits-Filho Roberto
Published: June 2024

Background

Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries.

Methods

A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months.

Results

Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing.

Conclusion

Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.
The relationship between fear of cancer recurrence and death anxiety among Chinese cancer patients: the serial mediation model
Authors: Chen Furong , Ou Meijun , Xiao Zhirui , Xu Xianghua
Published: June 2024

Aims

This study aims to investigate the association between fear of cancer recurrence (FCR) and death anxiety (DA) among Chinese cancer patients, while considering the mediating effects of experiential avoidance (EA) and meaning in life (MIL).

Methods

From February to June 2023, convenience sampling was used to select newly diagnosed cancer patients in a tertiary Cancer Hospital in Chinese Hunan Province as the survey objects. A total of 436 cancer patients completed the Fear of Cancer Recurrence Inventory, the Meaning in Life Questionnaire, the Acceptance and Action Questionnaire-II, and the Templer’s death anxiety scale. Descriptive analysis and Pearson correlation analysis were conducted using SPSS 28.0 software. Serial mediation analysis was performed by Hayes’ PROCESS macro.

Results

Gender, age, educational level, marital status, residence, occupation, per capita monthly household income, tumor type, and cancer stage were controlled in the model. The results revealed that fear of cancer recurrence had a significant direct effect on death anxiety (Effect = 0.075, 95% CI: 0.064 to 0.087). Additionally, three indirect pathways were identified: (1) through experiential avoidance (Effect = 0.037, 95% CI: 0.026 to 0.049), (2) through meaning in life (Effect = 0.022, 95% CI: 0.014 to 0.031), and (3) through the serial mediators involving meaning in life and experiential avoidance (Effect = 0.016, 95% CI: 0.010 to 0.023). The total indirect effect of the three mediation paths was 63.56%.

Conclusion

Fear of cancer recurrence is a significant psychological distress experienced by cancer patients, which not only directly contributes to death anxiety but also may triggers changes, such as experiential avoidance and meaning in life. Ultimately, this comprehensive psychological distress leads to death anxiety.
Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China
Authors: Yang Ruchang , Li Zhe , Zhu Yingzhao , Wu Yuxuan , Lu Xinchuan , Zhao Xueli , Liu Junjun , Du Xiangdong , Zhang Xiangyang
Published: June 2024

Introduction

Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD.

Methods

A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt.

Results

Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32).

Conclusion

Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.
Mediating effect of depression and acute stress between exposure to Israel-Gaza war media coverage and insomnia: a multinational study from five arab countries
Authors: Fekih-Romdhane Feten , Helmy Mai , Alhuwailah Amthal , Shuwiekh Hanaa Ahmed Mohamed , Naser Abdallah Y. , Maalej Emna , Obeid Sahar , Cheour Majda , Hallit Souheil
Published: June 2024

Background

In the context of persistent wars and conflicts worldwide, the impact of acute, excessive and constant exposure to media coverage of such events on mental health outcomes becomes a serious problem for public health, and requires therefore urgent investigation to inform an effective prevention and management response. The objective of the present study was to test the hypothesis that war-related media exposure is directly and indirectly associated with insomnia through depression and perceived stress among adults from the general population of different Arab countries.

Methods

A cross-sectional study was carried-out two weeks after the beginning of Israel-Gaza war on the 7th of October 2023. An anonymous online survey and a snowball sampling method were adopted to collect data. A sample of 2635 general population adults (mean age of 23.98 ± 7.55 years, 73.1% females) took part of this study.

Results

The results of the mediation analysis showed that, after adjusting over potential confounders, depression and perceived stress fully mediated the association between war media exposure and insomnia; higher war media exposure was significantly associated with higher depression (Beta = 0.13; p < .001) and perceived stress (Beta = 0.07; p < .001), whereas higher depression (Beta = 0.43; p < .001) and perceived stress (Beta = 0.31; p < .001) were significantly associated with higher insomnia. It is of note that war media exposure was not significantly and directly associated with insomnia (Beta = − 0.01; p = .178 and Beta = 0.02; p = .098 respectively).

Conclusion

The present study is the first to provide evidence that more time spent viewing the horrors of war is significantly associated with insomnia. In addition, symptoms of stress and depression were present as early as two weeks following the beginning of the war, and played a significant role in mediating the association between war media coverage and insomnia. These findings suggest that timely screening for, and management of depression and stress symptoms in clinical and preventive programs might be beneficial for community adults who have been heavily and indirectly exposed to war through media, and present with insomnia.
MyBack - effectiveness and implementation of a behavior change informed exercise programme to prevent low back pain recurrences: a hybrid effectiveness-implementation randomized controlled study protocol
Authors: Pires Diogo , Duarte Susana , Rodrigues Ana Maria , Caeiro Carmen , Canhão Helena , Branco Jaime , Alves Joana , Marques Marta , Aguiar Pedro , Fernandes Rita , Sousa Rute Dinis , Cruz Eduardo B.
Published: June 2024

Background

Low back pain (LBP) is a common health condition and the leading cause of years lived with disability worldwide. Most LBP episodes have a favourable prognosis, but recurrences within a year are common. Despite the individual and societal impact related to LBP recurrences, there is limited evidence on effective strategies for secondary prevention of LBP and successful implementation of intervention programmes in a real-world context. The aim of this study is to analyse the effectiveness of a tailored exercise and behavioural change programme (MyBack programme) in the secondary prevention of LBP; and evaluate acceptability, feasibility and determinants of implementation by the different stakeholders, as well as the implementation strategy of the MyBack programme in real context.

Methods

This protocol describes a hybrid type I, randomized controlled trial to evaluate the effectiveness and implementation of MyBack programme in the context of primary health care. The Behaviour Change Wheel framework and FITT-VP principles will inform the development of the behaviour change and exercise component of MyBack programme, respectively. Patients who have recently recovered from an episode of non-specific LBP will be randomly assigned to MyBack and usual care group or usual care group. The primary outcome will be the risk of LBP recurrence. The secondary outcomes will include disability, pain intensity, musculoskeletal health, and health-related quality of life. Participants will be followed monthly for 1 year. Costs data related to health care use and the MyBack programme will be also collected. Implementation outcomes will be assessed in parallel with the effectiveness study using qualitative methods (focus groups with participants and health providers) and quantitative data (study enrolment and participation data; participants adherence).

Discussion

To our knowledge, this is the first study assessing the effectiveness and implementation of a tailored exercise and behaviour change programme for prevention of LBP recurrences. Despite challenges related to hybrid design, it is expected that data on the effectiveness, cost-effectiveness, and implementation of the MyBack programme may contribute to improve health care in patients at risk of LBP recurrences, contributing to direct and indirect costs reduction for patients and the health system.

Trial registration number

NCT05841732.
Relationship between jejunum ATPase activity and antioxidant function on the growth performance, feed conversion efficiency, and jejunum microbiota in Hu sheep (Ovis aries)
Authors: Chen Zhanyu , Wang Guoxiu , Wang Weimin , Wang Xiaojuan , Huang Yongliang , Jia Jiale , Gao Qihao , Xu Haoyu , He Lijuan , Xu Yunfei , Liu Zhen , Sun Jinlin , Li Chong
Published: June 2024

Background

ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear.

Results

This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities.

Conclusions

The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.
YTHDF1’s grip on CRC vasculature: insights into LINC01106 and miR-449b-5p-VEGFA axis
Authors: Ma Rui-ting , Wang Yuanyuan , Ji Feng , Chen Jian-nan , Wang Tian-jun , Liu Yan , Hou Ming-xing , Guo Zhi-gang
Published: June 2024

Background

Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1.

Methods

Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway.

Results

YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1’s inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP.

Conclusions

This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.
Enhancing the production of PHA in Scenedesmus sp. by the addition of green synthesized nitrogen, phosphorus, and nitrogen–phosphorus-doped carbon dots
Authors: Sánchez-Pineda Pablo Alfredo , López-Pacheco Itzel Y. , Villalba-Rodríguez Angel M. , Godínez-Alemán José Alfonso , González-González Reyna Berenice , Parra-Saldívar Roberto , Iqbal Hafiz M. N.
Published: June 2024

Plastic consumption has increased globally, and environmental issues associated with it have only gotten more severe; as a result, the search for environmentally friendly alternatives has intensified. Polyhydroxyalkanoates (PHA), as biopolymers produced by microalgae, might be an excellent option; however, large-scale production is a relevant barrier that hinders their application. Recently, innovative materials such as carbon dots (CDs) have been explored to enhance PHA production sustainably. This study added green synthesized multi-doped CDs to Scenedesmus sp. microalgae cultures to improve PHA production. Prickly pear was selected as the carbon precursor for the hydrothermally synthesized CDs doped with nitrogen, phosphorous, and nitrogen–phosphorous elements. CDs were characterized by different techniques, such as FTIR, SEM, ζ potential, UV–Vis, and XRD. They exhibited a semi-crystalline structure with high concentrations of carboxylic groups on their surface and other elements, such as copper and phosphorus. A medium without nitrogen and phosphorous was used as a control to compare CDs-enriched mediums. Cultures regarding biomass growth, carbohydrates, lipids, proteins, and PHA content were analyzed. The obtained results demonstrated that CDs-enriched cultures produced higher content of biomass and PHA; CDs-enriched cultures presented an increase of 26.9% in PHA concentration and an increase of 32% in terms of cell growth compared to the standard cultures.
Detection of novel PPP1R1B::STARD3 fusion transcript in acute myeloid leukemia: a case report
Authors: Firouzabadi Elahe Dehghani , Allami Mohammed , Mohammed Eman Jassim , Barzegar Hossein , Dastpak Mahtab , Alemohammad Reza , Moghimi Vahid , Mahmoudian Reihaneh Alsadat , Nasrabadi Fatemeh , Arghiani Nahid , Kitamura Yohei , Hosseini Seyed Abolfazl , Ghasemi Ali , Farshchian Moein
Published: June 2024

Background

Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq).

Case presentation

A Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13).

Conclusions

Single-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression.
Developing a core outcome set for acetabular fractures: a systematic review protocol
Authors: Schulz Denise , Deichsel Adrian , Jordan Martin C. , Windolf Joachim , Raschke Michael J. , Neubert Anne
Published: June 2024

Background

Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies.

Methods

Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative.

Discussion

It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes.

Systematic review registration

PROSPERO CRD42022357644
Abolished clustering of MeCP2T158M can be partially reverted with small molecules
Authors: Lata Rodrigo , Steegmans Liesbeth , Kellens Ranie , Nijs Marnik , Klaassen Hugo , Versele Matthias , Christ Frauke , Debyser Zeger
Published: June 2024

Rett syndrome (OMIM 312750) is a rare neurodevelopmental disorder caused by de novo mutations in the Methyl-CpG Binding Protein 2 (MeCP2) gene located on the X-chromosome, typically affecting girls. Rett syndrome symptoms, characterized by microcephaly and lack of motor coordination, first appear between 6 to 18 months of age. The disease continues to progress until adulthood at which point it reaches a stationary phase. Currently, available therapy for Rett Syndrome is only symptomatic. More than 800 mutations causing Rett syndrome have been described, the most common being T158M (9% prevalence) located in the Methyl-Binding Domain (MBD) of MeCP2. Due to its importance for DNA binding through recognition of methylated CpG, mutations in the MBD have a significant impact on the stability and function of MeCP2. MeCP2 is a nuclear protein and accumulates in liquid–liquid phase condensates visualized as speckles in NIH3T3 cells by microscopy. This speckled pattern is lost with MeCP2 mutations in the MBD such as T158M. We developed a high content phenotypic assay, detecting fluorescent MeCP2 speckles in NIH3T3 cells. The assay allows the identification of small molecules that stabilize MeCP2-T158M and phenotypically rescue speckle formation. To validate the assay, a collection of 3572 drugs was screened, including FDA-approved drugs, compounds in clinical trials and biologically annotated tool compounds. 18 hits showed at least 25% rescue of speckles in the mutant cell line while not affecting wild-type MeCP2 speckles. Primary hits were confirmed in a dose response assay, a thermal shift assay with recombinant MeCP2 and by testing the MeCP2 expression levels. One class of identified hits represents histone deacetylase inhibitors (HDACis) showing 25% speckle rescue of mutant MeCP2 without toxicity. This screening strategy can be expanded to additional compound libraries and will support novel drug discovery.
Transforming adolescent menstrual health through policy: the role of value added tax exemptions in improving access to sanitary products
Authors: Shomuyiwa Deborah Oluwaseun , Odey Goodness Ogeyi , Ndep Antor Odu , Ekerin Olabode , Amesho Josephine Ndapewoshali , Luvindao Esperance , Manirambona Emery , Lucero-Prisno III Don Eliseo
Published: June 2024

In Namibia, the Value Added Tax (VAT) Amendment Act 2022, which reclassified the supply of sanitary pads as zero-rated, has significant implications for adolescent girls’ menstrual health and education. The policy change responds to the need to address period poverty by making essential menstrual products more accessible and affordable. Menstruation is a normal biological process, and access to sanitary products is a human right. Taxing menstrual products reinforces gender inequalities and raises concerns about the basic rights and dignity of women and girls. The VAT-free policy creates a system to reduce the financial burden on girls and women, making it easier for them to manage their periods safely and with dignity. It has the potential to reduce absenteeism from school, ultimately improving educational outcomes for adolescent girls. However, VAT exemptions alone are insufficient to address the broader accessibility issues that impact menstrual hygiene. Evidence-based policies that focus on the availability and affordability of a full range of sanitary products, in conjunction with regulatory mechanisms for price and quality control, are necessary to ensure that menstrual products are safe, affordable, and accessible for all.
Time-efficient combined morphologic and quantitative joint MRI: an in situ study of standardized knee cartilage defects in human cadaveric specimens
Authors: Lemainque Teresa , Pridöhl Nicola , Zhang Shuo , Huppertz Marc , Post Manuel , Yüksel Can , Yoneyama Masami , Prescher Andreas , Kuhl Christiane , Truhn Daniel , Nebelung Sven
Published: June 2024

Background

Quantitative techniques such as T2 and T1ρ mapping allow evaluating the cartilage and meniscus. We evaluated multi-interleaved X-prepared turbo-spin echo with intuitive relaxometry (MIXTURE) sequences with turbo spin-echo (TSE) contrast and additional parameter maps versus reference TSE sequences in an in situ model of human cartilage defects.

Methods

Standardized cartilage defects of 8, 5, and 3 mm in diameter were created in the lateral femora of ten human cadaveric knee specimens (81 ± 10 years old; nine males, one female). MIXTURE sequences providing proton density-weighted fat-saturated images and T2 maps or T1-weighted images and T1ρ maps as well as the corresponding two- and three-dimensional TSE reference sequences were acquired before and after defect creation (3-T scanner; knee coil). Defect delineability, bone texture, and cartilage relaxation times were quantified. Appropriate parametric or non-parametric tests were used.

Results

Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences (p ≤ 0.47). After defect creation, relaxation times significantly increased in the central femur (T2pre = 51 ± 4 ms [mean ± standard deviation] versus T2post = 56 ± 4 ms; p = 0.002) and all regions combined (T1ρpre = 40 ± 4 ms versus T1ρpost = 43 ± 4 ms; p = 0.004).

Conclusions

MIXTURE permitted time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1ρ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defects and bone texture, were comparable between MIXTURE and reference sequences.

Relevance statement

Equally time-efficient and versatile, the MIXTURE sequence platform combines morphologic imaging using familiar contrasts, excellent image correspondence versus corresponding reference sequences and quantitative mapping information, thereby increasing the diagnostic value beyond mere morphology.

Key points

• Combined morphologic and quantitative MIXTURE sequences are based on three-dimensional TSE contrasts.

• MIXTURE sequences were studied in an in situ human cartilage defect model.

• Morphologic image features, i.e., defect delineabilty and bone texture, were investigated.

• Morphologic image features were similar between MIXTURE and reference sequences.

• MIXTURE allowed time-efficient simultaneous morphologic and quantitative knee joint assessment.

Graphical Abstract
A simple method for the determination of acyclovir concentrations in human plasma using high-performance liquid chromatography
Authors: Aboelezz Asma , Kharouba Maged , Mahmoud Sherif Hanafy
Published: June 2024

Background

Acyclovir is an anti-viral medication given to treat herpes simplex and herpes zoster infection. In some severe conditions such as herpes encephalitis, acyclovir is administered intravenously. However, high acyclovir doses may cause acute kidney injury and low acyclovir dose may predispose the patient to inadequate exposure to acyclovir which could be fatal in some conditions. In such cases, the acyclovir plasma concentrations will potentially guide the diagnosis and management of the kidney injury. In this study, we provide a simple and time-efficient method for analyzing acyclovir in human plasma using high-performance liquid chromatography (HPLC).

Results

The process starts with a single protein precipitation step by adding acetonitrile to deproteinize 300 µL of plasma. The chromatographic separation conditions consist of a mobile phase of water: methanol (97:3, v/v), a flow rate of 1 mL/min, a run time of 17 min, and a detection wavelength of 254 nm. The calibration curve was linear over the range of (0.70–60 mg/L) (r2 ˃ 0.99). The retention times of acyclovir and the internal standard were around 15 and 12 min, respectively. The intra-day and inter-day analysis of acyclovir in plasma using this method exhibited accuracy and precision of less than 7%, which lies within the acceptable range. Different greenness assessment tools confirmed that the proposed method is eco-friendly.

Conclusion

The proposed method of analysis of acyclovir in the plasma using HPLC is simple, green and accurate method. This method could be applied in clinical settings where monitoring acyclovir concentrations is essential as it has wide range of the concentrations that could be detected.
From acidity to sweetness: a comprehensive review of carbon accumulation in grape berries
Authors: Lu Lizhen , Delrot Serge , Liang Zhenchang
Published: June 2024

Most of the carbon found in fruits at harvest is imported by the phloem. Imported carbon provide the material needed for the accumulation of sugars, organic acids, secondary compounds, in addition to the material needed for the synthesis of cell walls. The accumulation of sugars during fruit development influences not only sweetness but also various parameters controlling fruit composition (fruit “quality”). The accumulation of organic acids and sugar in grape berry flesh cells is a key process for berry development and ripening. The present review presents an update of the research on grape berry development, anatomical structure, sugar and acid metabolism, sugar transporters, and regulatory factors.
Preliminary safety and efficacy of TQB2930, a HER2-targeted bispecific antibody in patients with advanced breast cancer: Results from a phase 1b study.
Authors: Zhang Qingyuan , Wang Jingxuan , Li Liru , Zeng Xiaohua , Zhang Han , Song Ying , Tang Dabei , Niu Xingjian , Ma Wenjie , Tu Lifan , Fu Shuang , Pan Zoucheng
Published: June 2024

1026

Background: TQB2930 is a HER2-targeted bispecific antibody, binding to two distinct HER2 epitopes, the same domain as trastuzumab (ECD4) and pertuzumab (ECD2). This study aims to evaluate the safety and efficacy of TQB2930 for patients with advanced breast cancer after failure of standard therapy. Methods: This phase 1b, dose-escalation and expansion trial included patients preferred HER2-expressing or HER2-amplified breast cancer who had received standard therapy. In the dose-escalation phase, TQB2930 was given weekly (10mg/kg, QW), biweekly (20mg/kg, Q2W), or triweekly (30mg/kg, Q3W). After the dose-escalation phase, eligible patients were enrolled and dosed biweekly or triweekly in the expansion cohort. The primary endpoints were safety, maximum tolerated or maximum administered dose, and the secondary endpoints were immunogenicity, pharmacokinetics, and tumor response per RECIST v1.1. Results: As of Dec 20, 2023, 34 patients(pts) have received TQB2930 weekly (n=3), biweekly (n=16), and triweekly (n=15). All pts were female, the median age was 59. 22 pts had HER2 expression of ICH3+ or ICH2+ with FISH+, and the others had ICH2+ with FISH- or ICH1+. The median prior lines of therapies were 3 (range: 0-8), with one pt intolerance to first-line treatment enrolled, and the median prior lines of HER2-targeted therapies were 2 (range: 0-8). No dose-limited toxicity was observed. The main treatment-related adverse events (TRAEs) were infusion reaction, occult blood of urine, leukopenia, and neutropenia. 3 pts were reported grade≥3 TRAEs, including neutropenia, anemia, and hypokalemia. Of 31 response-evaluable pts, the objective response rate (ORR) was 25.8% with 8 partial responses (PRs) were observed (including 5 confirmed PRs and 3 PRs awaiting confirmation). The disease control rate was 80.6%. Moreover, 5 pts achieved PR at 30mg/kg (ORR 41.7%), including one with prior exposure to trastuzumab, pyrotinib, tucatinib, ARX788, and the other one prior to trastuzumab, pertuzumab, lapatinib, MRG002. The median progression-free survival for all pts was 5.5 months (95%CI 3.58-NE). Additionally, Pharmacokinetic analysis showed exposure (Cmax and AUC0-t) of TQB2930 increased linearly with doses within 10~30mg/kg. After dosing, the mean peak concentration reached at 2.5-4.3 h, and the elimination half-life of TQB2930 was 109-161 h. Conclusions: TQB2930 is well tolerated and has demonstrated promising single-agent anti-tumor activity in HER2-positive breast cancer who have failed standard anti-HER2 therapies, including multiple lines of prior HER2 targeted agents. These early signs of activity support the further exploration of combination therapy of TQB2930 and the study is ongoing. Clinical trial information: NCT06202261 .
Comprehensive analysis of TROP2, PD-L1, stromal (s)TILs, and HER2 expression patterns in patients (pts) with metastatic HR+HER2- breast cancer.
Authors: Corti Chiara , Heiling Hillary , Hughes Melissa E. , Binboğa Kurt Busem , DiLullo Molly , Li Tianyu , Tayob Nabihah , Curigliano Giuseppe , Mittendorf Elizabeth A. , Lin Nancy U. , Tolaney Sara M. , Garrido-Castro Ana Christina
Published: June 2024

1062

Background: Immune checkpoint inhibitors (ICI) have shown limited efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC) and the optimal ICI-based combination is unknown. The TROP2 antibody-drug conjugate sacituzumab govitecan (SG) demonstrated antitumor activity with a 5.5-month median PFS in endocrine refractory HR+ mBC. Given SG's potential for anticancer immunity, we sought to evaluate expression patterns of biomarkers of interest in HR+ mBC. Methods: This retrospective study included pts with HR+HER2- mBC identified at DFCI between 10/2020 and 12/2021 who received 0-1 prior lines of chemotherapy in the metastatic setting and consented to analysis of archival FFPE tissue samples. We aimed to 1) characterize expression patterns of TROP2 (SP295 H-score), PD-L1 (22C3 CPS), sTILs and HER2 (per central pathology review) in the most recent available sample; 2) assess the prognostic value of selected biomarker combinations for overall survival (OS) defined as the time from consent to either death due to any cause or last follow-up (Cox proportional hazard models; p-value <0.05 considered significant). Results: Among 142 pts included, median age at diagnosis was 46 yrs (IQR: 40–56). Baseline characteristics are shown (Table). At least one biomarker was available for 123 subjects (86.6%). TROP2 expression (n=61) was Medium/High (M-H: 101-300) in 43 pts (70.5%) and Low (L: 0-100) in 18 (29.5%). PD-L1 central assessment (n=120) revealed CPS ≥1 (PD-L1+) in 32 pts (26.7%) and <1 (PD-L1-) in 88 (73.3%); only 7 (5.8%) pts had CPS ≥10. sTILs (n=87) were ≥10% in 14 pts (16.1%) and <10% in 73 (83.9%). When analyzing TROP2 and PD-L1 (n=61), 15 pts (24.6%) were TROP2-M-H/PD-L1+, 28 (45.9%) were TROP2-M-H/PD-L1-, 5 (8.2%) were TROP2-L/PD-L1+, and 13 (21.3%) were TROP2-L/PD-L1-. When analyzing TROP2 and sTILs (n=54), 6 pts (11.1%) were TROP2-M-H/sTILs ≥10%, 32 (59.3%) were TROP2-M-H/sTILs <10%, 2 (3.7%) were TROP2-L/sTILs ≥10% and 14 (25.9%) were TROP2-L/sTILs <10%. For TROP2 and HER2 (n=46), 26 pts (56.5%) had TROP2-M-H/HER2-low tumors, 7 (15.2%) TROP2-M-H/HER2-0, 3 (6.5%) TROP2-L/HER2-low, and 10 (21.7%) TROP2-Low/HER2-0. Median OS (n=138) was 43.8 months; stratification for selected biomarker combinations will be presented although no statistical significance was found. Correlations with NGS data and HER2DX are ongoing and will be presented. Conclusions: Analyzing biomarkers of interest in pts with HR+ mBC unveiled diverse patterns, without associations with OS. Patient characteristics. [Table: see text]
Real-world treatment outcomes in patients with HR+ HER2- advanced breast cancer treated with CDK4/6 inhibitors and endocrine therapy.
Authors: Duchnowska Renata , Soter Katarzyna , Smok-Kalwat Jolanta , Grela-Wojewoda Aleksandra , Winsko-Szczęsnowicz Karolina , Pogoda Katarzyna , Kade Grzegorz , Danielewicz Iwona , Szymanowski Bartosz , Kiszka Joanna , Streb Joanna , Kalinka Ewa , Łacko Aleksandra , Żubrowska Justyna , Ziobro Marek , Czartoryska-Arlukowicz Bogumila , Jurczyk Michał , Lewandowski Tomasz , Jassem Jacek , Bieńkowski Michał
Published: June 2024

1067

Background: The addition of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) to endocrine therapy (ET) improves progression-free (PFS) and overall survival (OS) in hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- ABC) in 1st and 2nd line setting. The international guidelines advise using 1st line CDK4/6i; however, its superiority over 2nd line use is debatable. Methods: We retrospectively analyzed clinical data of HR+/HER2- ABC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) added to either 1st or 2nd line ET. Results: A total of 1511 pts (PAL=507; RIB=724; ABM=280) from 11 cancer Polish centers treated between Sep 2017 and Dec 2023. Median follow-up was 29.6 (95%CI 28.2 to 30.9) months (m). Mean age was 62.6±11.9, 58.9±12.2 and 61.4±10.8 years in PAL, RIB and ABM, respectively. 815 patients (53.9%) had visceral and 1109 (73.4%) bone metastases. 1254 pts (83%) received 1st line CDK4/6i, in 841 (67%) combined with aromatase inhibitor (AI) and in 413 (33%) with fulvestrant (FUL). Second-line CDK4/6i was used in 257 pts (17%); 59 (23%) and 198 (67%) with AI and FUL, respectively. There was no difference in PFS, PFS2, and OS between three CDK4/6i in combination with AIs in 1st and 2nd line setting. Median PFS (95%CI) for 1st line AI with PAL, RIB, ABM were 29.0 (21.6-37.0), 32.0 (24.5-36.9), not reached (N/R) (21.9-N/R) m; PFS2: 37.0 (28.8-N/R), 33.0 (29.5-40.2), N/R (28.9-N/R); OS: 48.9 (42.9-N/R), 48.6 (41.9-N/R), N/R (36.7-N/R). Median PFS (95%CI) for 2nd line AI with PAL, RIB, ABM were 11.9 (9.49-N/R), 10.8 (8.27-N/R), 11.0 (6.43-N/R); PFS2: 22.7 (16.8-N/R), 32.3 (24.9-N/R), 31.0 (13.2-N/R); OS: 27.4 (24.4-N/R), 36.7 (30.1-N/R), 45.5 (29.0-N/R) (no statistical significance). In contrast, RIB+FUL was superior to PAL+FUL and ABM+FUL in both lines (Table). The safety profile was concordant with the reported data for ET + CDK4/6i. Conclusions: Identifying predictive factors of response is essential for the rational use of CDK4/6i and ET in HR+/HER2- ABC. [Table: see text]
Economic impact of longer treatment duration in first-line for HR+/HER2- metastatic breast cancer: A retrospective analysis.
Authors: Abbass Ibrahim M. , Ng Carmen , Dillon Allison , Cheng Anna , Du Toit Yolande , Basho Reva K
Published: June 2024

1072

Background: Real-world treatment duration (TD) in the first line of therapy (1LOT) has demonstrated a strong correlation with progression-free survival (PFS). Increased TD for cancer patients (pts) in earlier lines has been linked to reduced healthcare costs by mitigating the need for costly therapies in subsequent lines, but the extent to which 1LOT costs vary based on the duration pts stay on treatment in 1LOT remains largely unknown. This study investigates the relationship between the TD of endocrine therapy (ET) plus CDK4/6 inhibition (CDKi) in 1LOT (serving as a proxy for PFS) and various healthcare cost measures incurred in 1LOT among newly diagnosed pts with HR+/HER2- metastatic breast cancer (mBC). Methods: Using the IQVIA PharMetrics Plus database, we identified adult women with newly diagnosed HR+/HER2- mBC whose 1LOT within 90 days of metastatic diagnosis (met dx) was ET + CDKi between 10/01/2016 - 06/30/2022. Pts with at least 6 months of follow-up post-met dx were included. The study followed pts from ET+ CDKi initiation until a switch, discontinuation, or a gap exceeding 90 days. Baseline characteristics were assessed 12 months before met dx. Healthcare costs (adjusted to 2022 USD) during the follow-up period were measured per patient per month (PPPM). TD was categorized based on percentile (p) distribution into six groups (<10p; ≥10p to <25p; ≥25p to <50p; ≥50p to <75p; ≥75p to <90p; and ≥90p). Cost measures included total, inpatient (inp), outpatient (outp), ER, and pharmacy (rx) costs. Generalized linear and two-part models examined the relationship between various cost measures and TD, adjusting for age, region, payer type, and Elixhauser comorbidity index (ECI). Results: The study included 1,536 pts receiving ET+ CDKi in 1LOT, with a median age of 59. The median ET + CDKi TD in 1LOT was 23.7 months. PPPM costs were $18,716; $1,044; $2,899; $63; and $14,711 for total, inp, outp, ER, and rx services, respectively. Models results indicate lower PPPM total, inp, outp and ER costs as TD increases (Table). PPPM costs were higher for the bottom 10th p (shortest TD group) compared to the top 10th p (longest TD group)(difference $6,411; $2,735; $3,297; and $205 higher for total, inp, outp, and ER visits respectively). PPPM rx costs did not vary with TD. Conclusions: Real-world TD of ET+ CDKi closely aligns with PFS reported in ET + CDKi trials, further demonstrating a strong correlation with PFS. Prolonging TD in 1LOT yields significant cost savings, primarily driven by reductions in inp, outp, and ER costs. The results underscore the need for ongoing optimization of pts selection for 1LOT for HR+ mBC. The study findings also suggest that the economic evaluation of investigated treatments should take into account treatment duration. [Table: see text]