bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights in Şanlıurfa, Turkey
Authors: Yalçin Sıddika Songül , Güneş Bülent , Arikan Kalender , Balçik Orhan , Kara Özcan , Yalçin Suzan 
Published: July 2024

Abstract
Background
Controversy surrounds the impact of persistent organic pollutants (POPs) on fetal development. This study aimed to investigate levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in umbilical cord blood from Şanlıurfa mothers in Turkey, exploring associations with gestational age and birth weight.

Methods
Participants included voluntary mothers pregnant with a single fetus, providing details on maternal factors. Cord blood samples were collected immediately after delivery. Samples were extracted with a modified QuEChERS method, and OCPs (17 pesticides) and PCBs (11 congeners) compound levels were analyzed with a gas chromatograph/mass spectrometry. Detection frequencies and levels of POPs by single pollutant type and pollutant groups were calculated and compared according to gestational duration and birth weight. We used partial least squares discriminant analysis to identify the key chemicals and distinguish their respective statuses.

Results
Among 120 infants, 35 were preterm but appropriate for gestational age, 35 were term but small for gestational age (SGA), and 50 were term and appropriate for gestational age (AGA). Beta HCH, Oxy-Chlordan, and PCB 28, were not detected in cord blood samples. Half of the samples contained at least 4 types of OCPs, with a median OCP level of 38.44 ng/g. Among the DDT, 2,4’-DDE was found at the highest concentration in cord plasma samples. The PCB congeners with a frequency exceeding 50% were ranked in the following order: 151, 149, 138, 146. The median level of ∑PCBs was 5.93 ng/g. Male infants born at term with SGA status exhibited lower levels of ∑DDTs, ∑OCPs compared to male infants born preterm or at term with AGA status. Di-ortho-substituted PCBs and hexachlorinated PCBs were higher in male infants born at term with SGA status than male infants born preterm with AGA status.

Conclusion
Overall, exposure to DDT and PCBs demonstrates varying effects depending on gestational duration and birth weight, with exposure levels also differing by gender. This underscores the necessity for studies across diverse populations that investigate the combined effects of multiple pollutant exposures on gestational age, birth weight, and gender simultaneously.
Prevalence of anxiety and depression and their associated risk factors throughout pregnancy and postpartum: a prospective cross-sectional descriptive multicentred study
Authors: Jimènez-Barragan Marta , Falguera-Puig Gemma , Curto-Garcia Jorge Juan , Monistrol Olga , Coll-Navarro Engracia , Tarragó-Grima Mercè , Ezquerro-Rodriguez Olga , Ruiz Anna Carmona , Codina-Capella Laura , Urquizu Xavier , Pino Gutierrez Amparo del 
Published: July 2024

Abstract
Objective
To assess the prevalence of anxiety and depression and their associated risk factors throughout the pregnancy and postpartum process using a new screening for the early detection of mental health problems.

Design
A prospective cross-sectional descriptive multicentred study. Participants were consecutively enrolled at ≥ 12 weeks’ gestation and followed at three different time points: at 12–14 weeks of pregnancy, at 29–30 weeks of pregnancy, and 4–6 weeks postpartum. All women completed a mental screening at week 12–14 of pregnancy consisting of two questions from the Generalised Anxiety Disorder Scale (GAD-2) and the two Whooley questions. If this screening was positive, the woman completed the Edinburgh Postnatal Depression Scale (EPDS).

Setting
Seven primary care centres coordinated by a Gynaecology and Obstetrics Department in the city of Terrassa (Barcelona) in northern Spain.

Participants
Pregnant women (N = 335, age 18–45 years), in their first trimester of pregnancy, and receiving prenatal care in the public health system between July 2018 and July 2020.

Findings
The most relevant factors associated with positive screening for antenatal depression or anxiety during pregnancy, that appear after the first trimester of pregnancy, are systematically repeated throughout the pregnancy, and are maintained in the postpartum period were: a history of previous depression, previous anxiety, abuse, and marital problems. In weeks 12–14 early risk factors for positive depression and anxiety screening and positive EPDS were: age, smoking, educational level, employment status, previous psychological/psychiatric history and treatment, suicide in the family environment, voluntary termination of pregnancy and current planned pregnancy, living with a partner and partner’s income. In weeks 29–30 risk factors were: being a skilled worker, a history of previous depression or anxiety, and marital problems. In weeks 4–6 postpartum, risk factors were: age, a history of previous depression or anxiety or psychological/psychiatric treatment, type of treatment, having been mistreated, and marital problems.

Conclusions
Early screening for anxiety and depression in pregnancy may enable the creation of more effective healthcare pathways, by acting long before mental health problems in pregnant women worsen or by preventing their onset. Assessment of anxiety and depression symptoms before and after childbirth and emotional support needs to be incorporated into routine practice.
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study
Authors: Cicin Irfan , Plimack Elizabeth R. , Gurney Howard , Leibowitz Raya , Alekseev Boris Y. , Parnis Francis X. , Peer Avivit , Necchi Andrea , Bellmunt Joaquim , Nishiyama Hiroyuki , Clark Jason , Munteanu Mihaela , Kataria Ritesh , Jia Calvin , Powles Thomas , Sternberg Cora N. 
Published: July 2024

Abstract
Background
Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%.

Methods
ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1.

Results
Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35–48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67–29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent.

Conclusions
Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted.

Trial registration
ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.
Determinants of wealth-related inequalities in full vaccination coverage among children in Nepal: a decomposition analysis of nationally representative household survey data
Authors: Singh Barun Kumar , Khatri Resham B. 
Published: July 2024

Abstract
Background
Over the past two decades, child health indicators in Nepal have improved significantly at the national level. Yet, this progress hasn’t been uniform across various population subsets. This study identified the determinants associated with childhood full vaccination, assessed wealth-related inequalities, and delved into the key factors driving this inequality.

Methods
Data for this study were taken from the most recent nationally representative Nepal Demographic and Health Survey 2022. A total of 959 children aged 12–23 months who had received routine childhood basic antigens as per the national immunisation program were considered for analysis. Binary logistic regression models were conducted to identify the associated factors with outcome variable (uptake of full vaccination). The concentration curve and Erreygers normalized concentration index were used to assess inequality in full vaccination. Household wealth quintile index scores were used to measure wealth-related inequality and decomposition analysis was conducted to identify determinants explaining wealth-related inequality in the uptake of childhood vaccination.

Results
The coverage of full vaccination among children was 79.8% at national level. Several factors, including maternal health service utilisation variables (e.g., antenatal care, institutional delivery), financial challenges related to visiting health facilities, and mothers’ awareness of health mother group meetings within their ward, were associated with the uptake of full vaccination coverage among children. The concentration curve was below the line of equality, and the relative Erreygers normalized concentration index was 0.090, indicating that full vaccination was disproportionately higher among children from wealthy groups. The decomposition analysis identified institutional delivery (20.21%), the money needed to visit health facilities (14.25%), maternal education (16.79%), maternal age (8.53%), and caste (3.03%) were important contributors to wealth related inequalities in childhood full vaccination uptake.

Conclusions
There was notable wealth-related inequality in full vaccine uptake among children in Nepal. Multisectoral actions involving responsible stakeholders are pivotal in reducing the inequalities, including promoting access to maternal health services and improving educational attainment among mothers from socioeconomically disadvantaged communities.
Antioxidant activity of polysaccharide from Garcinia mangostana rind and their derivatives
Authors: Tang Zhenjie , Huang Gangliang 
Published: July 2024

Abstract
Background
Polysaccharide from Garcinia mangostana rind has many biological activities and deserves further research.

Methods
The antioxidant properties of UAEE-GMRP, UAEE-GMRP-1 A, CM-30, and Ac-30 were evaluated through two different antioxidant activity experimental systems.

Results
The four polysaccharides had a better scavenging effect on hydroxyl radicals, while their inhibitory effect on lipid peroxidation was relatively weak. However, overall, the four polysaccharides showed a certain degree of potential application in the two antioxidant experiments mentioned above, especially the chemically modified polysaccharides from Garcinia mangostana rind, which effectively improved their antioxidant activity. This also indicates that chemical modification is a better method to improve polysaccharide activity. In addition, in these two antioxidant exploration experiments, carboxymethylated polysaccharide showed stronger activity compared to the other three polysaccharides.

Conclusion
The carboxymethylation modification may have great potential for application.
Humanization of the antigen-recognition domain does not impinge on the antigen-binding, cytokine secretion, and antitumor reactivity of humanized nanobody-based CD19-redirected CAR-T cells
Authors: Safarzadeh Kozani Pooria , Safarzadeh Kozani Pouya , Rahbarizadeh Fatemeh 
Published: July 2024

Abstract
Background
The immunogenicity of the antigen-recognition domains of chimeric antigen receptor (CAR)-T cells leads to immune responses that may compromise the antitumor effects of the adoptively transferred T cells. Herein, we attempt to humanize a CD19-specific VHH (named H85) using in silico techniques and investigate the impact of antigen-recognition domain humanization on CAR expression and density, cytokine secretion, and cytolytic reactivity of CAR-T cells based on the humanized VHH.

Methods
H85 was humanized (named HuH85), and then HuH85 was compared with H85 in terms of conformational structure, physicochemical properties, antigenicity and immunogenicity, solubility, flexibility, stability, and CD19-binding capacity using in silico techniques. Next, H85CAR-T cells and HuH85CAR-T cells were developed and CAR expression and surface density were assessed via flow cytometry. Ultimately, the antitumor reactivity and secreted levels of IFN-γ, IL-2, and TNF-α were assessed following the co-cultivation of the CAR-T cells with Ramos, Namalwa, and K562 cells.

Results
In silico findings demonstrated no negative impacts on HuH85 as a result of humanization. Ultimately, H85CAR and HuH85CAR could be surface-expressed on transduced T cells at comparable levels as assessed via mean fluorescence intensity. Moreover, H85CAR-T cells and HuH85CAR-T cells mediated comparable antitumor effects against Ramos and Namalwa cells and secreted comparable levels of IFN-γ, IL-2, and TNF-α following co-cultivation.

Conclusion
HuH85 can be used to develop immunotherapeutics against CD19-associated hematologic malignancies. Moreover, HuH85CAR-T cells must be further investigated in vitro and in preclinical xenograft models of CD19+ leukemias and lymphomas before advancing into clinical trials.
The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review
Authors: Pechmann L. M. , Pinheiro F. I. , Andrade V. F. C. , Moreira C. A. 
Published: July 2024

Abstract
Background
Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures.

Main body
The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y—both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals.

Conclusion
The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
Exploring genetic association of systemic iron status and risk with incidence of diabetic neuropathy
Authors: Yu Xinyue , Jin Tianyu , Zhu Luyi , Guo Shunyuan , Deng Binbin , Cheng Yifan 
Published: July 2024

Abstract
Background
Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association.

Methods
We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran’s Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings.

Results
No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892–0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888–0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy.

Conclusion
While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.
Effect of exercise on cluneal nerve entrapment neuropathy: a case report
Authors: Özüberk Burcu , Deniz Mine Argalı , Soyupek Feray Cinevre 
Published: July 2024

Abstract
Background
Low back pain is an important disability problem frequently encountered in the clinic. In the literature, it has been shown that neuropathic pain in chronic low back pain is quite common in patients. Although superior cluneal nerve entrapment syndrome is an underdiagnosed cause of low back and leg pain, differential diagnosis is very important anatomically and clinically. The superior cluneal nerves are pure sensory nerves that innervate the skin of the upper part of the buttocks. In the literature, methods such as surgery, nerve blockade, prolotherapy, and acupuncture have been used in the treatment of cluneal nerve entrapment syndrome, but there are no studies on exercise. In this case report, our aim is to explain the importance of differential diagnosis in cluneal nerve entrapment syndrome, which is one of the common causes of low back pain in the clinic, and the effects of exercise in this disease.

Case presentation
A 22-year-old, Turkish-ethnicity, male patient with complaints of low back pain, neck–back pain, and weakness did not use alcohol or cigarettes. In his family history, there was a history of diabetes in the mother and diabetes and heart failure in the father. He had a history of osteoporosis, epilepsy, asthma, sarcoidosis, and cardiac arrhythmia. The patient reported that he suffered from constipation three to four times a month. As a result of the detailed evaluation, the planned exercise prescription was taught to the patient, and after it was confirmed that the patient did the exercises correctly for 3 days, the exercise brochure was given and followed as a home exercise program for 8 weeks.

Conclusions
Lumbar stabilization exercises, gluteal muscle strengthening exercises, thoracolumbar fascia mobilization, and stretching exercises, which will be given in accordance with the clinical anatomy of the disease after the correct diagnosis in cluneal nerve entrapment syndrome, have been beneficial for the patient. However, we think that randomized controlled studies with a large sample will contribute to the literature.