bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of ESG Scores with Firm Performance: A Study of Indian Listed Companies
Authors: Devi Priyanka , y Sapna
Published: May 2024

This study seeks to explore whether there is a substantial correlation between corporations’ ESG (Environmental, Social and Governance) ratings and their profitability, specifically return on assets (ROA). It aims to determine whether this correlation is positive, negative or neutral in nature. The research methodology involved an investigation of companies listed on the BSE500 stock index, analysing their ESG ratings for the years 2020 and 2021. The final dataset encompassed 148 companies, resulting in 296 observations for the two years, sourced from the Ace equity database. Panel regression analysis was employed to assess the link between ESG ratings (the independent variable) and ROA (the dependent variable), while also considering financial leverage and firm size as control factors. The results revealed a statistically significant negative linkage between ESG ratings and firm performance, as indicated by ROA, at a 5% significance level. The negative relation between ESG scores and firm performance (ROA) could be attributed to several factors. Organisations that prefer ESG initiatives often incur additional costs in areas like environmental compliance and employee welfare, which can temporarily reduce profitability. Moreover, ESG-conscious firms may make long-term investments that take time to generate returns, impacting short-term ROA. Additionally, stringent ESG standards may deter certain investors or customers, affecting revenue. However, over the long run, robust ESG practices can enhance sustainability and resilience, potentially leading to improved performance and risk mitigation.
BPO Ecosystem in North East India: Reclaiming the Missed Opportunity
Authors: Bhattacharjee Biplab , Sharma Simi , Roychoudhury Basav
Published: May 2024

North Eastern Region (NER) of India is largely looked upon as a provider of cheaper and amenable workforce for the business process outsourcing (BPO) industry, with neutral accent, dedication and hospitable behaviour. All these factors make NER a potential BPO destination, further enhanced by different government (central/states) policy initiatives. However, the industry in the regions exhibited an almost flat growth curve over the years, and thus there is a need for understanding the reasons behind the failure of the undertaken policies. This study is largely based on qualitative research on the large information technology and business process management (IT-BPM) industry of India in general and (still) nascent BPO industry of NER in particular. The authors’ understanding and findings are inferred from review of policy documents, numerous data sources and discussions, focus group interviews with national BPO experts, and local BPO entrepreneurs of the region. The impact of coronavirus disease-2019 on the business process management (BPM) industry and the opportunities arising from it, particularly for this region has also been examined. The study presents a set of factors paralysing the industry in NER, and outlines some affirmative measures to rectify the failures. This analysis, though specific to the NER, highlights the issues involved in BPO operations which can be generalised and provide guidelines to other destinations.
Clinical evaluation and determinants of response to HBI0101 (BCMA CART) therapy in relapsed/refractory multiple myeloma
Authors: Kfir-Erenfeld Shlomit , Asherie Nathalie , Lebel Eyal , Vainstein Vladimir , Assayag Miri , Dubnikov Sharon Tatyana , Grisariu Sigal , Avni Batia , Elias Shlomo , Alexander-Shani Rivka , Bessig Nomi , Shehadeh Alaa , Ishtay Aseel , Zelmanovich Veronica , Zimran Eran , Pick Marjorie , Roziner Ilan , Kenett Ron S. , Cohen Yael , Avivi Irit , Cohen Cyrille J. , Gatt Moshe E. , Stepensky Polina
Published: May 2024

HBI0101 is an academic chimeric antigen receptor T-cell (CART)–targeted to B-cell maturation antigen (BCMA) for the treatment of relapsed and refractory multiple myeloma (R/RMM) and light chain amyloidosis. Herein, we present the phase 1b/2 results of 50 heavily pretreated patients with R/RMM dosed with 800 × 106 CART cells. Inclusion criteria were relatively permissive (i.e., performance status and baseline organ function) and consequently, approximately half of the enrolled patients would have been ineligible for pivotal clinical trials. The median time elapsed from patient enrollment until CART delivery was 25 days (range, 14-65). HBI0101-related toxicities included grade 1 to 3 cytokine release syndrome, grade 3 to 4 hematologic toxicities, and grade 1 to 2 immune effector cell–associated neurotoxicity syndrome. Responses were achieved in 90% of the patients, 56% achieved stringent and complete response, and 70% reached a minimal residual disease negativity. Within a median follow-up of 12.3 months, the median progression-free survival (PFS) was 11.0 months (95% confidence interval [CI], 6.2-14.6), and the overall survival was not reached (95% CI, 13.3 to not reached). Multivariable analysis on patient/disease and CART-related characteristics revealed that high-risk cytogenetic, extramedullary disease, and increased number of effector-memory T cells in CART products were independently associated with inferior PFS. In conclusion, comprehensive analyses of the parameters affecting the response to CART therapy are essential for improving patients’ outcome. This trial was registered at www.ClinicalTrials.gov as #NCT04720313.
Experimental Study on the Electrochemical Performance of PEMFC under Different Assembly Forces
Authors: Su Tongze , Liu Jiaran , Wei Yanqiang , Li Yihuizi , Luo Weichao , Tan Jinzhu
Published: May 2024

Proton exchange membrane fuel cell (PEMFC) is of paramount significance to the development of clean energy. The components of PEMFC are assembled using many pairs of nuts and bolts. The assembly champing bolt torque is critical to the electrochemical performance and mechanical stability of PEMFC. In this paper, a PEMFC with the three-channel serpentine flow field was used and studied. The different assembly clamping bolt torques were applied to the PEMFC in three uniform assembly bolt torque and six non-uniform assembly bolt torque conditions, respectively. And then, the electrochemical performance experiments were performed to study the effect of the assembly bolt torque on the electrochemical performance. The test results show that the assembly bolt torque significantly affected the electrochemical performance of the PEMFC. In uniform assembly bolt torque conditions, the maximal power density increased initially as the assembly bolt torque increased, and then decreased on further increasing the assembly torque. It existed the optimum assembly torque which was found to be 3.0 N·m in this work. In non-uniform assembly clamping bolt torque conditions, the optimum electrochemical performance appeared in the condition where the assembly torque of each bolt was closer to be 3.0 N·m. This could be due to the change of the contact resistance between the gas diffusion layer and bipolar plate and mass transport resistance for the hydrogen and oxygen towards the catalyst layers. This work could optimize the assembly force conditions and provide useful information for the practical PEMFC stack assembly.
The quality of reporting in case reports of permanent neonatal diabetes mellitus: a cross-sectional study
Authors: Jia Pengli , Wang Ling , Yang Xi , Pei WenTing , Xu Chang , Feng Jinglin , Han Ying
Published: May 2024

Background

Although randomized trials and systematic reviews provide the best evidence to guide medical practice, many permanent neonatal diabetes mellitus (PNDM) studies have been published as case reports. However, the quality of these studies has not been assessed. The purpose of this study was to assess the extent to which the current case reports for PNDM comply with the Case Report (CARE) guidelines and to explore variables associated with the reporting.

Method

Six English and four Chinese databases were searched from their inception to December 2022 for PNDM case reports. The 23 items CARE checklist was used to measure reporting quality. Primary outcome was the adherence rate of each CARE item and second outcome was total reporting score for each included PNDM case report. Linear and logistic regression analyses were used to examine the connection between five pre-specified predictor variables and the reporting quality. The predictor variables were impact factor of the published journal (<3.4 vs. ≥3.4, categorized according to the median), funding (yes vs. no), language (English vs. other language), published journal type (general vs. special) and year of publication (>2013 vs. ≤ 2013).

Result

In total, 105 PNDM case reports were included in this study. None of the 105 PNDM case reports fulfilled all 23 items of the CARE checklist. The response rate of 11 items were under 50%, including prognostic characteristics presentation (0%), patient perspective interpretation (0%), diagnostic challenges statement (2.9%), clinical course summary (21.0%), diagnostic reasoning statement (22.9%), title identification (24.8%), case presentation (33.3%), disease history description (34.3%), strengths and limitations explanation (41.0%), informed consent statement (45.7%), and lesson elucidation (47.6%). This study identified that the PNDM case reports published in higher impact factor journals were statistically associated with a higher reporting quality.

Conclusion

The reporting of case reports for PNDM is generally poor. As a result, this information may be misleading to providers, and the clinical applications may be detrimental to patient care. To improve reporting quality, journals should encourage strict adherence to the CARE guidelines.
Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma
Authors: Yamada Reiko , Kuriyama Naohisa , Tanaka Takamitsu , Nose Kenji , Nakamura Yoshifumi , Miwata Tetsuro , Tsuboi Junya , Mizuno Shugo , Nakagawa Hayato
Published: May 2024

Background/Purpose

Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC.

Methods

EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups.

Results

Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0–3) vs. 1.88 (0–8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016).　 Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively).

Conclusion

Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.
Dietary nutrient intake study among older adults: baseline Malaysian pure study
Authors: Ja’afar Mohd Hasni , Mat Nasir Nafiza , Md Isa Zaleha , Ismail Rosnah , Mohd Tamil Azmi , Ismail Noor Hassim , Ariffin Farnaza , Ab Razak Nurul Hafiza , Zainol Abidin Najihah , Yusof Khairul Hazdi
Published: May 2024

Introduction

The older adults (OA) is vulnerable to malnutrition, which may affect their health and quality of life. This study assesses the prevalence of deficiencies in dietary nutrients among the Malaysian OA stratified by residency, genders, socioeconomic status (SES) and body mass index (BMI).

Methodology

A cross-sectional study was conducted, utilizing purposive sampling, recruiting 2,299 Malaysian people aged 60 years old and above who agreed to be interviewed via a comprehensive semi-quantitative food frequency questionnaire. The nutrients intake was calculated based on the Malaysian food composition and US Department of Agriculture food composition databases. Then, the nutrients intake was compared with the Malaysian Recommended Nutrients Intake guidelines, and the prevalence of deficiencies in dietary nutrients were calculated. The median (interquartile ranges) intakes of nutrients were compared between residency (urban and rural), genders (male and female), and SES (low and middle-high) using the Mann-Whitney U test. The differences in nutrient intake between BMI categories (underweight, normal, and overweight) were identified using the Kruskal-Wallis test followed by Dunn’s post hoc test.

Results

The response rate was 70.3% (n = 2,299), predominantly were females (50.8%), received primary education (76.6%), were currently married (84.3%), were middle–high SES (57.7%), and had a normal BMI (59.8%). There was a notable inadequate intake prevalence of magnesium (100.0%), manganese (97.9%), zinc (95.6%), vitamin B6 (98.4%), potassium (91.0%), calcium (89.3%), vitamin B12 (80.2%), vitamin E (91.2%), and vitamin K (81.5%) among Malaysian OA. Additionally, significant differences were observed in nutrients intake levels across gender, residency, SES, and BMI within this population.

Conclusions

This study shows a high prevalence of dietary nutrients deficiency (> 80%) among the Malaysian OA, particularly for magnesium, manganese, potassium, zinc, vitamin B6, vitamin E, calcium, vitamin B12, and vitamin K. To improve the nutritional status of OA and safeguard against adverse health effects, it is necessary to formulate and execute strategies to enhance their dietary nutrient intakes. The strategies may involve intervention such as nutrient supplementation and promotion of consuming nutrient-rich foods.
Bioelectrical impedance analysis—derived phase angle (PhA) in lung cancer patients: a systematic review
Authors: Prete Melania , Ballarin Giada , Porciello Giuseppe , Arianna Aniello , Luongo Assunta , Belli Valentina , Scalfi Luca , Celentano Egidio
Published: May 2024

Background

Lung cancer is the second most diagnosed cancer in the world. Up to 84% of diagnosed patients have malnutrition, which can negatively affect quality of life and survival and may worsen with neoadjuvant treatment. Bioelectrical Impedance Analysis-Derived Phase Angle (PhA) in these patients could be a valid tool to assess the nutritional status in order to improve their condition.

Methods

This review provides an update on PhA assessment in lung cancer patients over the past twenty years. We searched PubMed, Embase, Scopus, Web of Science, and Cochrane, for articles regarding the PhA obtained from Bioelectrical Impedance Analysis in lung cancer patients. The authors independently performed a literature search: sample size, patient population, study type, study dates, survival and interventions were evaluated. The final review included 11 studies from different countries.

Results

Eight studies only considered patients with lung cancer, while three studies considered patients with different kind of cancer, including lung. Correlation data between PhA and age are conflicting. In patients undergoing clinical treatment and patients undergoing surgical treatment lower PhA was observed. A lower PhA is associated with a shorter survival. In three studies emerged a relationship between Karnofski Performance Status and Handgrip Strenght with PhA. From one study, univariate logistic regression analysis showed that higher PhA values represent a protective factor for sarcopenia.

Conclusion

Our research underlined interesting, but not conclusive, results on this topic; however more researches are needed to understand the clinical meaning of PhA.
Identification of neurological complications in childhood influenza: a random forest model
Authors: Li Suyun , Xiao Weiqiang , Li Huixian , Hu Dandan , Li Kuanrong , Chen Qinglian , Liu Guangming , Yang Haomei , Song Yongling , Peng Qiuyan , Wang Qiang , Ning Shuyao , Xiong Yumei , Ma Wencheng , Shen Jun , Zheng Kelu , Hong Yan , Yang Sida , Li Peiqing
Published: May 2024

Background

Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1–2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE).

Objective

To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza.

Methods

This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model.

Results

Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions.

Conclusion

This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.
Disease burden of mental disorders among children and adolescents considering both co-morbidities and suicide in Northeastern China
Authors: Li Yanxia , Chen Qian , Liu Li , Yang Xing , Mu Huijuan , Wang Qihao , Lian Jian , Chen Huijie , Gao Yuan , Yan Lingjun , Sun Wei , Pan Guowei
Published: May 2024

Background

Few studies have assessed the burden of mental disorders among children and adolescents considering the impact of co-morbidities and suicide on disability adjusted life years (DALYs).

Methods

This was a multicenter cross-sectional study. Our survey data in Liaoning Province (LN) were used to estimate the burden of six mental disorders, supplemented with data from other investigative studies conducted in China to assess four other disorders. DALYs were derived from the sum of years lived with a disability (YLDs) adjusted for co-morbidities, and the years of life lost (YLLs) adjusted for suicide. The changes in DALYs, YLDs, and YLLs were compared with and without adjustment for co-morbidities and suicide.

Results

The DALYs rate of mental disorders among children and adolescents in LN decreased from 1579.6/105 to 1391.4/105, after adjusting for both co-morbidities and suicide (-11.9%). The DALYs rate for major depression, anxiety disorder, and conduct disorder (-80.8/105, -75.0/105 and  -30.2/105, respectively) were the top three contributors to the DALYs reduction (-188.2/105). The YLDs decreased from 72724.8 to 62478.5 after co-morbidity adjustment (-17.8%), mainly due to the reduction by major depression (-35.3%) and attention deficit/hyperactivity disorder [ADHD] (-34.2%). The YLLs increased from 130 to 1697.8 after adjusting for suicides (+ 56.9% of all suicide YLLs), mainly due to the contribution of major depression (+ 32.4%) and anxiety disorder (+ 10.4%). Compared to GBD 2010, the estimated DALY rate for mental disorders in LN was to be about 80%, with the proportion of DALYs and DALY rates explained by major depressive disorder accounted for only approximately one-third (14.6% vs. 41.9% and 202.6 vs. 759.9, respectively). But the proportion and absolute level of DALY rates explained by anxiety disorders were approximately 2-fold higher (39.7% vs. 19.6% and 552.2 vs. 323.3, respectively).

Conclusions

The DALYs of mental disorders among Chinese children and adolescents were approximately 80% of the global level, with anxiety disorders imposing about 2 times the global level. Co-morbidity and suicide must be adjusted when calculating DALYs.
Smokeless tobacco consumption among women of reproductive age: a systematic review and meta-analysis
Authors: Itumalla Ramaiah , Khatib Mahalaqua Nazli , Gaidhane Shilpa , Zahiruddin Quazi Syed , Gaidhane Abhay M , Neyazi Ahmad , Hassam Ahmad Farshid , Satapathy Prakasini , Rustagi Sarvesh , Kukreti Neelima , Padhi Bijaya Kumar
Published: May 2024

Smokeless tobacco (SLT) poses many negative health impacts. Despite its longstanding presence in societies across the world, the health implications of SLT have only been rigorously studied in recent decades. This systematic review and meta-analysis aimed to consolidate existing research to provide a comprehensive understanding of the global prevalence of SLT use among women of reproductive age. Relevant articles were extracted from databases such as PubMed, EMBASE, Web of Science, and Scopus from their inception until November 11, 2023. Observational studies reporting the number of SLT users among women of reproductive age were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) tool. The meta-analysis used a random-effects model to determine SLT prevalence, supported by statistical tools like forest plots, I2 statistics, and sensitivity analyses to ensure the accuracy and comprehensiveness of the results. All statistical analyses were performed in R version 4.3. From 10 studies involving 2,053,667 participants, a pooled prevalence for SLT use among women of reproductive age was found to be 9.3% (95% CI: 0.038 to 0.21), with significant heterogeneity among studies (I2 = 100%). Publication bias was suspected among the studies. Sensitivity analysis and subgroup analysis couldn’t resolve the heterogeneity. Our analysis shows a significant prevalence of SLT use in women of reproductive age, especially in low socioeconomic and developing countries like India, Pakistan, and Nepal. For women of reproductive age, the use of smokeless tobacco (SLT) can lead to infertility, pregnancy complications, and adverse fetal outcomes, including low birth weight and preterm birth. The results highlight the necessity for specific public health measures and policy changes to decrease SLT consumption among reproductive-age women. Further studies are needed to investigate the reasons behind SLT usage in this group and to assess the impact of intervention strategies, to guide more effective public health initiatives and policies.
A meta-analysis of efficacy on dexamethasone and clomiphene in the treatment of polycystic ovary syndrome patients
Authors: Sha Ying , Zhu Jianfen , Shen Fangrong
Published: May 2024

Objective

Polycystic ovary syndrome (PCOS) is an endocrine gynecological disease affecting many women of reproductive age. Clomiphene is the first-line treatment for PCOS patients, but most individuals may be resistant to it. This study aims to assess the efficacy of dexamethasone and clomiphene in the treatment of PCOS patients, and to provide a theoretical basis for clinicians to study and treat PCOS.

Methods

Chinese and English databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Medical Network, and VIP Information Chinese Journal Service Platform (VIP) were searched from the inception to January 2023. Review Manager and Stata software were used for meta- analysis. The risk of bias of eligible studies were assessed using Cochrane’s risk of bias tool. Publication bias was assessed by funnel plots, Begg’s and Egger’s tests.

Results

A total of 12 literatures were finally included, with a total of 1270 PCOS patients. Compared with the control group, dexamethasone combined with clomiphene could significantly improve pregnancy (RR = 1.71, P < 0.00001), ovulation (RR = 1.30, P < 0.00001), luteinizing hormone level (SMD = -0.94, P < 0.00001), estradiol level (SMD = 0.99, P = 0.05), progesterone level (SMD = 5.08, P = 0.002) and testosterone level (SMD = -1.59, P < 0.00001). However, there were no significant effects on ovulation-stimulating hormone level (SMD = 0.15, P = 0.37), adverse reactions (RR = 1.30, P = 0.30), dizziness (RR = 1.50, P = 0.45), and vomiting (RR = 1.67, P = 0.48).

Conclusion

The treatment of dexamethasone combined with clomiphene is helpful to improve the ovulation and pregnancy rate in patients with PCOS, and improve the hormone levels of patients.
Proteomic characterization and cytotoxic potential of proteins from Cuscuta (Cuscuta epithymum (L.) crude herbal product against MCF-7 human breast cancer cell line
Authors: Akhtar Umaima , Khurshid Yamna , El-Aarag Bishoy , Syed Basir , Khan Ishtiaq A. , Parang Keykavous , Ahmed Aftab
Published: May 2024

Background

The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa.

Methods

The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun proteomics was subsequently performed for protein characterization. The viability assay using MTT was applied to deduce the cytotoxic potential of proteins against MCF-7 breast cancer cells, with further exploration of the effect of treatment on the expression of the apoptotic mediator BCL2-associated X protein (BAX) and B-cell lymphoma protein 2 (BCL-2) proteins, using western blotting to strengthen the findings from the in vitro viability assay.

Results

The crude proteins (CP) of CE were separated into four protein peaks (P1, P2, P3, and P4) by gel filtration chromatography. The evaluation of potency showed a dose-dependent decline in the MCF-7 cell line after CP, P1, P2, and P3 treatment with the respective IC50 values of 33.8, 43.1, 34.5, and 28.6 µg/ml. The percent viability of the cells decreased significantly upon treatment with 50 µg/ml CP, P1, P2, and P3 (P < 0.001). Western-blot analysis revealed upregulation of proapoptotic protein BAX in the cells treated with CP, P3 (P < 0.01), and P2 (P < 0.05); however, the antiapoptotic protein, BCL-2 was downregulated in the cells treated with CP and P3 (P < 0.01), but no significant change was detected in P2 treated cells. The observed cytotoxic effects of proteins in the CP, P1, P2, and P3 from the in vitro viability assay and western blot depicted the bioactivity potential of CE proteins. The database search revealed the identities of functionally important proteins, including nonspecific lipid transfer protein, superoxide dismutase, carboxypeptidase, RNase H domain containing protein, and polyribonucleotide nucleotidyltransferase, which have been previously reported from other plants to exhibit anticancer activity.

Conclusion

This study indicated the cytotoxic activity of Cuscuta proteins against breast cancer MCF-7 cells and will be utilized for future investigations on the mechanistic effect of active proteins. The survey of CE proteins provided substantial data to encourage further exploration of biological activities exhibited by proteins in Cuscuta.
IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer
Authors: Guo Jing , Wang Chunyan , Luo Ning , Wu Yuliang , Huang Wei , Zhu Jihui , Shi Weihui , Ding Jinye , Ge Yao , Liu Chunhong , Lu Zhen , Bast Robert C. , Ai Guihai , Yang Weihong , Wang Rui , Li Caixia , Chen Rong , Liu Shupeng , Jin Huajun , Zhao Binghui , Cheng Zhongping
Published: May 2024

Background

Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.

Methods

Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence.

Results

In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010).

Conclusions

Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer.

Trial registration

NCT04766320, Jan 04, 2021.
IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood
Authors: Gbaguidi Mahugnon L. Erasme , Adamou Rafiou , Edslev Sofie , Hansen Anita , Domingo Nadia D. , Dechavanne Celia , Massougbodji Achille , Garcia André , Theisen Michael , Milet Jacqueline , Donadi Eduardo A. , Courtin David
Published: May 2024

Background

Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection.

Methods

A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role.

Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure.

Results

The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1.

Conclusion

The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.
Enhancing iron content and growth of cucumber seedlings with MgFe-LDHs under low-temperature stress
Authors: Wu Hongyang , Wan Xiaoyang , Niu Jiefei , Cao Yidan , Wang Shufang , Zhang Yu , Guo Yayu , Xu Huimin , Xue Xian , Yao Jun , Zhu Cuifang , Li Yang , Li Qiang , Lu Tao , Yu Hongjun , Jiang Weijie
Published: May 2024

The development of cost-effective and eco-friendly fertilizers is crucial for enhancing iron (Fe) uptake in crops and can help alleviate dietary Fe deficiencies, especially in populations with limited access to meat. This study focused on the application of MgFe-layered double hydroxide nanoparticles (MgFe-LDHs) as a potential solution. We successfully synthesized and characterized MgFe-LDHs and observed that 1–10 mg/L MgFe-LDHs improved cucumber seed germination and water uptake. Notably, the application of 10 mg/L MgFe-LDHs to roots significantly increased the seedling emergence rate and growth under low-temperature stress. The application of 10 mg/L MgFe-LDHs during sowing increased the root length, lateral root number, root fresh weight, aboveground fresh weight, and hypocotyl length under low-temperature stress. A comprehensive analysis integrating plant physiology, nutrition, and transcriptomics suggested that MgFe-LDHs improve cold tolerance by upregulating SA to stimulate CsFAD3 expression, elevating GA3 levels for enhanced nitrogen metabolism and protein synthesis, and reducing levels of ABA and JA to support seedling emergence rate and growth, along with increasing the expression and activity of peroxidase genes. SEM and FTIR further confirmed the adsorption of MgFe-LDHs onto the root hairs in the mature zone of the root apex. Remarkably, MgFe-LDHs application led to a 46% increase (p < 0.05) in the Fe content within cucumber seedlings, a phenomenon not observed with comparable iron salt solutions, suggesting that the nanocrystalline nature of MgFe-LDHs enhances their absorption efficiency in plants. Additionally, MgFe-LDHs significantly increased the nitrogen (N) content of the seedlings by 12% (p < 0.05), promoting nitrogen fixation in the cucumber seedlings. These results pave the way for the development and use of LDH-based Fe fertilizers.

Graphical Abstract
Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness
Authors: Rajkumar Nalinikanta , Khumukcham Lokeshwar Singh , Thangjam Dhabali , Singh Surender , Khwairakpam Giten , Shilton Sonjelle , Goel Amit
Published: May 2024

Background

Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres.

Methods

Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment.

Results

Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23–32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min–8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses.

Conclusion

Community-led hepatitis care incorporating same day “test and treat” for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.
Fibroblast growth factor pathway promotes glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in prostate cancer
Authors: Ye Yongkang , Yang Fukan , Gu Zhanhao , Li Wenxuan , Yuan Yinjiao , Liu Shaoqian , Zhou Le , Han Bo , Zheng Ruinian , Cao Zhengguo
Published: May 2024

Background

The initiation of fibroblast growth factor 1 (FGF1) expression coincident with the decrease of FGF2 expression is a well-documented event in prostate cancer (PCa) progression. Lactate dehydrogenase A (LDHA) and LDHB are essential metabolic products that promote tumor growth. However, the relationship between FGF1/FGF2 and LDHA/B-mediated glycolysis in PCa progression is not reported. Thus, we aimed to explore whether FGF1/2 could regulate LDHA and LDHB to promote glycolysis and explored the involved signaling pathway in PCa progression.

Methods

In vitro studies used RT‒qPCR, Western blot, CCK-8 assays, and flow cytometry to analyze gene and protein expression, cell viability, apoptosis, and cell cycle in PCa cell lines. Glycolysis was assessed by measuring glucose consumption, lactate production, and extracellular acidification rate (ECAR). For in vivo studies, a xenograft mouse model of PCa was established and treated with an FGF pathway inhibitor, and tumor growth was monitored.

Results

FGF1, FGF2, and LDHA were expressed at high levels in PCa cells, while LDHB expression was low. FGF1/2 positively modulated LDHA and negatively modulated LDHB in PCa cells. The depletion of FGF1, FGF2, or LDHA reduced cell proliferation, induced cell cycle arrest, and inhibited glycolysis. LDHB overexpression showed similar inhibitory effect on PCa cells. Mechanistically, we found that FGF1/2 positively regulated STAT1 and STAT1 transcriptionally activated LDHA expression while suppressed LDHB expression. Furthermore, the treatment of an FGF pathway inhibitor suppressed PCa tumor growth in mice.

Conclusion

The FGF pathway facilitates glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in PCa.
NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation
Authors: Wang Runze , Xue Wei , Kan Feifei , Zhang Huiying , Wang Di , Wang Lei , Wang Jianwen
Published: May 2024

Background

Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR.

Method

Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2.

Results

The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing.

Conclusions

NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.
Systematic review of the economic evaluation model of assisted reproductive technology
Authors: Si Yuxin , Tan Tao , Pu Kexue
Published: May 2024

Background

With the increasing demand for fertility services, it is urgent to select the most cost-effective assisted reproductive technology (ART) treatment plan and include it in medical insurance. Economic evaluation reports are an important reference for medical insurance negotiation. The aim of this study is to systematically evaluate the economic evaluation research of ART, analyze the existing shortcomings, and provide a reference for the economic evaluation of ART.

Methods

PubMed, EMbase, Web of Science, Cochrane Library and ScienceDirect databases were searched for relevant articles on the economic evaluation of ART. These articles were screened, and their quality was evaluated based on the Comprehensive Health Economics Evaluation Report Standard (CHEERS 2022), and the data on the basic characteristics, model characteristics and other aspects of the included studies were summarized.

Results

One hundred and two related articles were obtained in the preliminary search, but based on the inclusion criteria, 12 studies were used for the analysis, of which nine used the decision tree model. The model parameters were mainly derived from published literature and included retrospective clinical data of patients. Only two studies included direct non-medical and indirect costs in the cost measurement. Live birth rate was used as an outcome indicator in half of the studies.

Conclusion

Suggesting the setting of the threshold range in the field of fertility should be actively discussed, and the monetary value of each live birth is assumed to be in a certain range when the WTP threshold for fertility is uncertain. The range of the parameter sources should be expanded. Direct non-medical and indirect costs should be included in the calculation of costs, and the analysis should be carried out from the perspective of the whole society. In the evaluation of clinical effect, the effectiveness and safety indexes should be selected for a comprehensive evaluation, thereby making the evaluation more comprehensive and reliable. At least subgroup analysis based on age stratification should be considered in the relevant economic evaluation.
Experimental and Numerical Evaluation for Hybrid Reinforced T-Beam with Different Ratios of Recycled Rubberized Concrete
Authors: El-Salakawy Tarik S. , Gamal Amr A. , Sayed Mohamed Essam
Published: May 2024

The use of hybrid GFRP and steel bars as main reinforcement increases the flexural capacity of T-section concrete beams and reduces ductility. Adding recycled rubber to the concrete mix would further enhance the ductility of the hybrid system. Evaluation of the concrete's flexural capacity and ductility is the main goal of the current investigation using normal concrete (NC) and rubberized recycled concrete (RRC). Eight T-beams have been experimentally investigated in this research, two beams were reinforced with steel bars and GFRP bars with zero percentage of crumb rubber (C.R). The remaining beams were reinforced with different combinations of GFRP and steel bars with rubberized concrete mixes with partial substitution of sand with recycled crumb rubber by (0%, 7.5%, 10%, and 12.5% replacements by volume) particle size 1.0 to 2.0 mm. The ductility index for the tested hybrid rubberized T-beams (HRTB) BRH1, BRH3a, BRH5, BRH2, BRH4, and BRH6, were higher than BH1 and BH2 by 28.2%, 35.47%, 65.38%, 23.76%, 30.04%, and 56.95% indicating that increasing the percentage of C.R. has a direct effect on increasing the ductility index. The ultimate failure load for the tested HRTB BRH1, BRH3a, and BRH5, decreased by 11.68%, 14.29%, and 17.47% compared to the hybrid T-beam BH1. The energy dissipation decreased for HRTB BRH1, BRH3a, BRH5, BRH2, BRH4 and BRH6 by 7.88%, 12.36%, 17.17%, 8.12%, 12.96%, and 18.28 compared to hybrid T-beams BH1 and BH2. This indicates that the existence of the very weak C.R. was not able to dissipate the energy properly within the concrete matrix. Good agreement was found between the numerical model and experimental results in terms of crack pattern, ultimate loads and deflections.