bluuebunny/crossref_metadata_2025 huggingface dataset:
Onsite and laboratory assessment of repair mortars for reinforced concrete floor slabs in heritage buildings
Authors: Franzoni Elisa , Pizzigatti Cesare
Published: March 2024

The conservation and repair of XX century architectural heritage built with reinforced concrete is becoming more and more important and requires suitable materials and technical solutions. In particular, effectiveness, compatibility and durability must be ensured, in spite of the limited extent of demolition allowed by the local authorities, and the literature in this field is still limited. In this paper, an experimental campaign was carried out in an historic reinforced concrete floor slab, where different repair mortars were used. After some on-site testing on the corrosion potential, the concrete beams of the slab were integrally cut and transported to the laboratory for a series of systematic tests, aimed at investigating the performance and compatibility of the repair materials, as well as any possible issues hindering the success of this structural intervention. The filling ability, physical compatibility, chemical compatibility and mechanical compatibility of the repair mortars and the corrosion behavior of the steel reinforcement were investigated, deriving some results of general interest, which may contribute to a better insight about the repair of heritage concrete floor slabs.
Poly(lactic acid)/ poly(ε-caprolactone) blends: the effect of nanocalcium carbonate and glycidyl methacrylate on interfacial characteristics
Authors: Negaresh Mohammadmahdi , Javadi Azizeh , Garmabi Hamid
Published: March 2024

To expand the potential applications of polylactic acid (PLA), it is essential to incorporate a highly flexible polymer into the blend. Polycaprolactone (PCL) is an ideal choice due to its ductility and biodegradability. However, blending PLA with PCL resulted in weak mechanical properties. To address this issue, glycidyl methacrylate (GMA) and nano calcium carbonate (NCC) were introduced to enhance the adhesion at the interface between PLA and PCL. SEM images provided clear visual evidence of the impact of GMA and NCC on the morphology of the blend. Both components were effective in reducing the size of the dispersed PCL phase, shrinking it to approximately half the size of the original blend. Spectroscopic analysis revealed that GMA caused a reaction between its epoxy group and the hydroxyl and carboxyl groups of PLA and PCL. This reaction led to the formation of strong peaks in the 6.5 to 7.5 range in 1H NMR, as well as peaks at 76 and 139 ppm in 13C NMR. These findings were further corroborated by FT-IR, which demonstrated that NCC, despite its surface coating, did not create any new bonds. Rheological studies further demonstrated the positive effects of GMA and NCC. Both the storage modulus (G′) and complex viscosity (η*) of the blends increased, showing improved post-processing performance. Investigation into the shear-thinning behavior of the uncompatibilized blends revealed that NCC caused a significant decrease in complex viscosity at higher frequencies, indicating the disruption of the nanoparticle network. The power-law slope was measured to be 0.62. In contrast, the blend containing the compatibilizer demonstrated a moderate decrease in viscosity, with a power-law slope of 0.36. To analyze the behavior of the PLA/PCL blends in the presence of compatibilizers and nanoparticles at intermediate frequencies, the Palirene model was utilized. The superior integrity of the compatibilized blend was effectively demonstrated by the model, which showed enhanced stress transfer and phase relaxation.
Genetic correlation between circulating metabolites and chalazion: a two-sample Mendelian randomization study
Authors: Zhang Xin , Cai Yuying , Jiang Yaping , Du Wei , An Weishu , Fu Qiangqiang , Chen Yihui
Published: March 2024

Background: Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis.

Methods: For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses.

Results: Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507–0.912; p = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439–0.759; p = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH4 = 1.95%; secondary analysis: PPH4 = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055–1.401; p = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054–1.377; p = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735–0.982; p = 0.027).

Conclusion: This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.
Case report: Simultaneous measurement of intracranial pressure and lumbar intrathecal pressure during epidural patch therapy for treating spontaneous intracranial hypotension syndrome. Spontaneous intracranial hypotension or spontaneous intraspinal hypovolume?
Authors: Engrand Nicolas , Salardaine Quentin , Desilles Jean-Philippe , Echard Cécile , Bourdillon Pierre , Williams Marc , Baille Guillaume
Published: March 2024

Objectives

Spontaneous intracranial hypotension (SIH) is frequently complicated by subacute subdural hematoma (SDH) and more rarely by bilateral thalamic ischemia. Here, we report a case of SIH-related SDH treated with three epidural patches (EPs), with follow-up of the intracranial pressure and lumbar intrathecal pressure.

Methods

A 46-year-old man presented bilateral thalamic ischemia, then a growing SDH. After failure of urgent surgical evacuation, he underwent three saline EPs, two dynamic myelography examinations and one digital subtraction angiography–phlebography examination. However, because of no dural tear and no obstacle to the venous drainage of the vein of Galen, no therapeutic procedure was available, and the patient died.

Results

The case exhibited a progressive increase in the transmission of lumbar intrathecal pressure to intracranial pressure during the three EPs. The EPs may have successfully treated the SIH, but the patient did not recover consciousness because of irreversible damage to both thalami.

Conclusion

Clinicians should be aware of the bilateral thalamic ischemia picture that may be the presenting sign of SIH. Moreover, the key problem in the pathophysiology of SIH seems to be intraspinal and intracranial volumes rather than pressures. Therefore, intracranial hypotension syndrome might actually be an intraspinal hypovolume syndrome.
Autosomal recessive primary microcephaly type 2 associated with a novel WDR62 splicing variant that disrupts the expression of the functional transcript
Authors: Chen Haizhu , Zheng Ying , Wu Hua , Cai Naiqing , Xu Guorong , Lin Yi , Li Jin-Jing
Published: March 2024

Background

Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized primarily by congenital microcephaly and intellectual disability but without extra-central nervous system malformations. This investigation aimed to elucidate the genetic underpinnings of microcephaly in a patient from a Chinese consanguineous family.

Methods

A comprehensive clinical assessment, including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic analyses, was conducted to evaluate the patient’s condition. Whole-exome sequencing (WES) was employed to identify the causative gene, followed by Sanger sequencing, to confirm the mutation and its segregation within the family. Reverse transcript polymerase chain reaction (RT-PCR) was utilized to detect changes in splicing. Western blot was employed to reveal the difference of protein expression level between the wild-type and mutant WDR62 in vitro.

Results

The patient exhibited classic MCPH symptoms, including microcephaly, recurrent epilepsy, delayed psychomotor development, and intellectual disability. Additionally, asymmetrical limb length was noted as a prominent feature. MRI findings indicated reduced brain volume with cortical malformations, while EEG demonstrated heightened sharp wave activity. A molecular analysis uncovered a novel homozygous variant c.4154–6 C > G in the WDR62 intron, and a functional analysis confirmed the pathogenicity of this mutation, resulting in the formation of an abnormal transcript with premature termination codons.

Conclusion

This study enhances our understanding of the genetic heterogeneity associated with MCPH and highlights the pivotal role of genetic testing in the diagnosing and managing of rare neurodevelopmental disorders. Furthermore, it highlights the potential of emerging genetic therapies in treating conditions such as MCPH2.
Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures
Authors: Ye Xin , Ghosh Shubhamoy , Shin Bo-Chul , Ganguly Amit , Maggiotto Liesbeth , Jacobs Jonathan P. , Devaskar Sherin U.
Published: March 2024

Introduction

Serotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut-brain axis dependent mechanism responsible for such ultimate phenotypes.

Methods

Employing maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed.

Results

At early postnatal (P) day 2 no changes in the IUGR, but a ~24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/HFhf, (n = 4) diet revealed increased serotonin by ~53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a ~40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera.

Discussion

We conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise.
The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients
Authors: Feng Lin , Gao Ling
Published: March 2024

Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply to active neurons in the brain. NVC damage can lead to chronic impairment of neuronal function. Diabetes is characterized by high blood sugar and is considered an important risk factor for cognitive impairment. In this review, we provide fMRI evidence of NVC damage in diabetic patients with cognitive decline. Combined with the exploration of the major mechanisms and signaling pathways of NVC, we discuss the effects of chronic hyperglycemia on the cellular structure of NVC signaling, including key receptors, ion channels, and intercellular connections. Studying these diabetes-related changes in cell structure will help us understand the underlying causes behind diabetes-induced NVC damage and early cognitive decline, ultimately helping to identify the most effective drug targets for treatment.
Contributions of narrow- and broad-spiking prefrontal and parietal neurons on working memory tasks
Authors: Mozumder Rana , Chung Sophia , Li Sihai , Constantinidis Christos
Published: March 2024

Neurons that generate persistent activity in the primate dorsolateral prefrontal and posterior parietal cortex have been shown to be predictive of behavior in working memory tasks, though subtle differences between them have been observed in how information is represented. The role of different neuron types in each of these areas has not been investigated at depth. We thus compared the activity of neurons classified as narrow-spiking, putative interneurons, and broad-spiking, putative pyramidal neurons, recorded from the dorsolateral prefrontal and posterior parietal cortex of male monkeys, to analyze their role in the maintenance of working memory. Our results demonstrate that narrow-spiking neurons are active during a range of tasks and generate persistent activity during the delay period over which stimuli need to be maintained in memory. Furthermore, the activity of narrow-spiking neurons was predictive of the subject’s recall no less than that of broad-spiking neurons, which are exclusively projection neurons in the cortex. Our results show that putative interneurons play an active role during the maintenance of working memory and shed light onto the fundamental neural circuits that determine subjects’ memories and judgments.
Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure
Authors: Spreafico Anna , Couselo Eva Muñoz , Irmisch Anja , Bessa Juliana , Au-Yeung George , Bechter Oliver , Svane Inge Marie , Sanmamed Miguel F. , Gambardella Valentina , McKean Meredith , Callahan Margaret , Dummer Reinhard , Klein Christian , Umaña Pablo , Justies Nicole , Heil Florian , Fahrni Linda , Opolka-Hoffmann Eugenia , Waldhauer Inja , Bleul Conrad , Staack Roland F. , Karanikas Vaios , Fowler Stephen
Published: March 2024

Introduction

Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy.

Methods

TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352).

Results

Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant samples, but showed no drug activity in vitro.

Discussion

This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed.
Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review
Authors: Yan Yuanzhuo , Zhuo Huixian , Li Tengfei , Zhang Jintao , Tan Min , Chen Yue
Published: March 2024

Prostate cancer(PCa), a leading global health concern, profoundly impacts millions of men worldwide. Progressing through two stages, it initially develops within the prostate and subsequently extends to vital organs such as lymph nodes, bones, lungs, and the liver. In the early phases, castration therapy is often employed to mitigate androgen effects. However, when prostate cancer becomes resistant to this treatment, alternative strategies become imperative. As diagnostic and treatment methodologies for prostate cancer continually advance, radioligand therapy (RLT) has emerged as a promising avenue, yielding noteworthy outcomes. The fundamental principle of RLT involves delivering radionuclide drugs to cancerous lesions through specific carriers or technologies. Subsequently, these radionuclide drugs release radioactive energy, facilitating the destruction of cancer cell tissues. At present, the positron emission tomography (PET) targeting PSMA has been widely developed for the use of diagnosis and staging of PCa. Notably, FDA-approved prostate-specific membrane antigen (PSMA) targeting agents, such as 68Ga-PSMA-11 and 177Lu-PSMA-617, represent significant milestones in enhancing diagnostic precision and therapeutic efficacy. This review emphasizes the current research status and outcomes of various radionuclide-labeled PSMA ligands. The objective is to provide valuable insights for the continued advancement of diagnostic and therapeutic approaches in the realm of prostate cancer.
Pharmacological inhibition of Src family kinases attenuates hyperuricemic nephropathy
Authors: Xiong Chongxiang , Deng Jin , Wang Xin , Hou Qidi , Zhuang Shougang
Published: March 2024

Hyperuricemia is an independent risk factor for chronic kidney disease and contributes to renal fibrosis. This study aims to investigate the effect of Src family kinase (SFK) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN, feeding rats a mixture of adenine and potassium oxonate increased Src phosphorylation, severe glomerular sclerosis, and renal interstitial fibrosis, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of PP1, a highly selective SFK inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. PP1 treatment also inhibited hyperuricemia-induced activation of the TGF-β1/Smad3, STAT3, ERK1/2, and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, PP1 treatment significantly reduced serum uric acid levels and xanthine oxidase activity. Thus, blocking Src can attenuate development of HN via a mechanism associated with the suppression of TGF-β1 signaling, inflammation, and uric acid production. The results suggest that Src inhibition might be a promising therapeutic strategy for HN.
Exploring HMMR as a therapeutic frontier in breast cancer treatment, its interaction with various cell cycle genes, and targeting its overexpression through specific inhibitors
Authors: Shabir Aisha , Qayoom Hina , Haq Burhan Ul , Abo Mansoor Adel , Abdelrahim Adil , Ahmad Irshad , Almilabairy Abdullah , Ahmad Fuzail , Mir Manzoor Ahmad
Published: March 2024

Among women, breast carcinoma is one of the most complex cancers, with one of the highest death rates worldwide. There have been significant improvements in treatment methods, but its early detection still remains an issue to be resolved. This study explores the multifaceted function of hyaluronan-mediated motility receptor (HMMR) in breast cancer progression. HMMR’s association with key cell cycle regulators (AURKA, TPX2, and CDK1) underscores its pivotal role in cancer initiation and advancement. HMMR’s involvement in microtubule assembly and cellular interactions, both extracellularly and intracellularly, provides critical insights into its contribution to cancer cell processes. Elevated HMMR expression triggered by inflammatory signals correlates with unfavorable prognosis in breast cancer and various other malignancies. Therefore, recognizing HMMR as a promising therapeutic target, the study validates the overexpression of HMMR in breast cancer and various pan cancers and its correlation with certain proteins such as AURKA, TPX2, and CDK1 through online databases. Furthermore, the pathways associated with HMMR were explored using pathway enrichment analysis, such as Gene Ontology, offering a foundation for the development of effective strategies in breast cancer treatment. The study further highlights compounds capable of inhibiting certain pathways, which, in turn, would inhibit the upregulation of HMMR in breast cancer. The results were further validated via MD simulations in addition to molecular docking to explore protein–protein/ligand interaction. Consequently, these findings imply that HMMR could play a pivotal role as a crucial oncogenic regulator, highlighting its potential as a promising target for the therapeutic intervention of breast carcinoma.
The synergistic antibacterial activity and mechanism of colistin-oxethazaine combination against gram-negative pathogens
Authors: Li Jie , Han Ning , Li Yangyang , Zhao Feifei , Xiong Wenguang , Zeng Zhenling
Published: March 2024

Background:

The rapid spread of bacteria with plasmid-mediated resistance to antibiotics poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue.

Methods:

Synergistic activity of the FDA-approved agent oxethazine combined with colistin was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of their combination of oxethazine and colistin was explored by fluorescent dye, scanning electron microscopy (SEM) and LC-MS/MS. The synergistic efficacy was evaluated in vivo by the Galleria mellonella and mouse sepsis models.

Results:

In this study, we found that oxethazine could effectively enhance the antibacterial activity of colistin against both mcr-positive and -negative pathogens, and mechanistic assays revealed that oxethazine could improve the ability of colistin to destruct bacterial outer membrane and cytoplasmic membrane permeability. In addition, their combination triggered the accumulation of reactive oxygen species causing additional damage to the membrane structure resulting in cell death. Furthermore, oxethazine significantly enhanced the therapeutic efficacy of colistin in two animal models.

Conclusion:

These results suggested that oxethazine, as a promising antibiotic adjuvant, can effectively enhance colistin activity, providing a potential strategy for treating multidrug-resistant bacteria.
The ethnomedicine, phytochemistry, and pharmacological properties of the genus Bersama: current review and future perspectives
Authors: Nigussie Gashaw , Ashenef Sintayehu , Meresa Asfaw
Published: March 2024

Bersama (Melianthaceae) has been used in traditional medicine for a wide range of ailments, including blood purifier, immune booster, psychotropic medication, and treatment for malaria, hepatitis, infertility, diabetes, impotency, meningitis, and stroke. This review gathers fragmented information from the literature on ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of the Bersama genus. It also explores the therapeutic potential of the Bersama genus in ethnophytopharmacology, allowing for further investigation. All the available information published in the English language on Bersama genus was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search using the following keywords: “Bersama genus,” “traditional use,” “phytochemistry,” “pharmacological effects,” and “toxicology”. The ethnomedical applications of the Bersama genus have been recorded, and it has been used traditionally for more than 30 different types of ailments. Thus far, more than 50 compounds have been isolated from the genus. Cardiac glycosides and terpenoids are the main compounds isolated from the Bersama genus. Different plant parts of Bersama genus extracts demonstrated a wide range of pharmacological properties, including antioxidant, antimalarial, antidiabetic, antiviral, anti-inflammatory, and cytotoxic activity. Exemplary drug leads from the genus include mangiferin and quercetin-3-O-arabinopyranoside, both of which have antioxidant activities. Bersama genus has long been used to cure a wide range of ailments. Bersama genus extracts and phytochemicals have been found to have promising pharmacological activities. Further study on promising crude extracts and compounds is required to develop innovative therapeutic candidates.
Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma
Authors: Wang Run-Jie , Ke Rui-Quan , Yu Yi-Feng , Lu Guan-Zhong , Wu San-Gang
Published: March 2024

Purpose:

To investigate the survival outcomes and toxicities associated with the addition of nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC).

Methods:

Patients with stage III-IVA nasopharyngeal carcinoma who received IC and CCRT between January 2017 and October 2021 were retrospectively included. We aimed to compare the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) between patients treated with CCRT+nimotuzumab and CCRT alone.

Results:

We included 411 patients in the analysis. Of these patients, 267 (65.0%) and 144 (35.0%) had CCRT+nimotuzumab and CCRT alone, respectively. Similar LRFS was found between those with and without nimotuzumab (92.9% vs. 92.6%, p = 0.855). The 3-year DMFS was 88.2% and 76.2% in those with and without nimotuzumab (p = 0.002). The 3-year DFS was 83.4% and 70.6% in those with and without nimotuzumab treatment (p = 0.003). The 3-year OS was 92.1% and 81.1% in those with and without nimotuzumab (p = 0.003). The multivariate Cox regression analysis indicated that the addition of nimotuzumab was independently associated with better DMFS (hazard ratio [HR] 0.606, p = 0.049), DFS (HR 0.613, p = 0.028), and OS (HR 0.497, p = 0.019). No significant differences in major toxicities were found between the two treatment arms, including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (all p > 0.05).

Conclusion:

The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in improving treatment outcomes and acceptable toxicities.
Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus
Authors: Wen-Jing Zhao , Rui-Zhi Tan , Si-Yuan He , Xiao-Mei Du , Qiong-Dan Hu , Xiao-Qian Zhang , Wen-Hua Huang , Hong-Wei Su , Jian Liu , Qiong Zhang , Li Wang
Published: March 2024

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers.

Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation.

Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF).

Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.
Changes of uterocervical angle and cervical length in early and mid-pregnancy and their value in predicting spontaneous preterm birth
Authors: Zhang Miaomiao , Li Shuilan , Tian Chao , Li Min , Zhang Baofang , Yu Hongkui
Published: March 2024

Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies.

Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15–23+6 weeks); in 75 among them, CL also had been measured in early-pregnancy (<14 weeks). These 274 pregnant women were further divided into a preterm group (n = 149, <37 weeks gestation) and a control group (n = 125, >37 weeks gestation) according to delivery before or after 37 weeks, respectively. In the preterm group, 35 patients delivered before 34 weeks and the remaining 114 delivered between 34 and 37 weeks.

Results: The optimal threshold of CL to predict preterm birth risk in women with <37 weeks gestation was 3.38 cm, and the optimal threshold of the UCA to predict preterm birth risk in the same group of women was 96°. The optimal threshold of CL to predict preterm birth risk in women with <34 weeks gestation was 2.54 cm, while that of the UCA in the same group of patients was 106°. The area under the curve for predicting preterm birth by combining the UCA and CL measurements was greater than that by using the UCA or CL alone (p < 0.01). The sensitivity and specificity for predicting preterm birth at <34 weeks gestation was 71.7% and 86.4%, respectively; and the sensitivity and specificity for predicting preterm birth at <37 weeks gestation was 87.6% and 80.6%, respectively. The difference between the two groups in CL and UCA were not significant in early pregnancy (p > 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = −0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at <34 weeks was highest when the UCA was >105°, and the proportion of deliveries between 35 and 37 weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at <34 weeks was highest when the CL was <2.5 cm.

Conclusion: The combination of UCA and CL has a better ability to predict preterm birth than either measurement alone. A more obtuse UCA or a shorter CL is associated with an earlier spontaneous preterm birth. The UCA increases from early to mid-pregnancy, while the CL decreases from early to mid-pregnancy.
Measuring the menu, not the food: “psychometric” data may instead measure “lingometrics” (and miss its greatest potential)
Authors: Arnulf Jan Ketil , Olsson Ulf Henning , Nimon Kim
Published: March 2024

This is a review of a range of empirical studies that use digital text algorithms to predict and model response patterns from humans to Likert-scale items, using texts only as inputs. The studies show that statistics used in construct validation is predictable on sample and individual levels, that this happens across languages and cultures, and that the relationship between variables are often semantic instead of empirical. That is, the relationships among variables are given a priori and evidently computable as such. We explain this by replacing the idea of “nomological networks” with “semantic networks” to designate computable relationships between abstract concepts. Understanding constructs as nodes in semantic networks makes it clear why psychological research has produced constant average explained variance at 42% since 1956. Together, these findings shed new light on the formidable capability of human minds to operate with fast and intersubjectively similar semantic processing. Our review identifies a categorical error present in much psychological research, measuring representations instead of the purportedly represented. We discuss how this has grave consequences for the empirical truth in research using traditional psychometric methods.
Inner speech in the daily lives of people with aphasia
Authors: Alexander Julianne M. , Hedrick Tessa , Stark Brielle C.
Published: March 2024

Introduction

This exploratory, preliminary, feasibility study evaluated the extent to which adults with chronic aphasia (N = 23) report experiencing inner speech in their daily lives by leveraging experience sampling and survey methodology.

Methods

The presence of inner speech was assessed at 30 time-points and themes of inner speech at three time-points, over the course of three weeks. The relationship of inner speech to aphasia severity, demographic information (age, sex, years post-stroke), and insight into language impairment was evaluated.

Results

There was low attrition (<8%) and high compliance (>94%) for the study procedures, and inner speech was experienced in most sampled instances (>78%). The most common themes of inner speech experience across the weeks were ‘when remembering’, ‘to plan’, and ‘to motivate oneself’. There was no significant relationship identified between inner speech and aphasia severity, insight into language impairment, or demographic information. In conclusion, adults with aphasia tend to report experiencing inner speech often, with some shared themes (e.g., remembering, planning), and use inner speech to explore themes that are uncommon in young adults in other studies (e.g., to talk to themselves about health).

Discussion

High compliance and low attrition suggest design feasibility, and results emphasize the importance of collecting data in age-similar, non-brain-damaged peers as well as in adults with other neurogenic communication disorders to fully understand the experience and use of inner speech in daily life. Clinical implications and future directions are discussed.
Inner speech and the body error theory
Authors: Endicott Ronald P.
Published: March 2024

Inner speech is commonly understood as the conscious experience of a voice within the mind. One recurrent theme in the scientific literature is that the phenomenon involves a representation of overt speech, for example, a representation of phonetic properties that result from a copy of speech instructions that were ultimately suppressed. I propose a larger picture that involves some embodied objects and their misperception. I call it “the Body Error Theory,” or BET for short. BET is a form of illusionism, but the particular version I favor is a cross-modal illusion. Newly described here, my hypothesis is that the experience of inner speech arises from a mix of interoception and audition. Specifically, there is the detection of slight but well-confirmed activities in the speech musculature that occur during inner speech, which helps to transform representations of normal but quiet nonverbal sounds that inevitably occur during inner speech, from breathing to background noise, into a mistaken perception of inner speech. Simply put, activities in the speech musculature mix with sounds to create the appearance of speech sounds, which thus explains the “voice within the mind.” I also show how BET’s cross-modal system fits with standard information processing accounts for speech monitoring and how it accommodates the central insights of leading theories of inner speech. In addition, I show how BET is supported by data from experience-sampling surveys and how it can be empirically tested against its rivals.
Process evaluation of PsyCovidApp, a digital tool for mobile devices aimed at protecting the mental health of healthcare professionals during the COVID-19 pandemic: a mixed method study
Authors: Fiol-deRoque Maria A. , Serrano-Ripoll Maria J. , Mira-Martínez Sofia , Pastor-Moreno Guadalupe , Sitges Carolina , García-Buades M. Esther , Gervilla Elena , Garcia-Toro Mauro , Zamanillo-Campos Rocío , Ricci-Cabello Ignacio
Published: March 2024

Introduction

PsyCovidApp, a digital intervention aimed at safeguarding the mental health of healthcare workers during the COVID-19 pandemic, demonstrated in a randomized clinical trial to yield significant improvements solely among healthcare workers undergoing psychotherapy or receiving psychotropic medication.

Objectives

(1) To identify contextual factors and mechanisms of action that influenced the impact of PsyCovidApp during the aforementioned trial; (2) To pinpoint enhancements for optimizing its efficacy.

Materials and methods

For the first objective, a process evaluation was conducted, amalgamating quantitative techniques (surveying 216 healthcare professionals who had utilized PsyCovidApp during the trial) and qualitative methods (in-depth interviews with 16 healthcare workers). The second objective involved a panel of seven experts, utilizing the RAND-UCLA methodology.

Results

The quantitative study (response rate = 40%) revealed that 22% of respondents had not fully accessed the content of PsyCovidApp. The average usage time was 22.7 min/day, being higher (p < 0.05) among consumers of psychotropic medications. Contents related to relaxation and mindfulness were most highly rated. Acceptability and usefulness scores ranged between 7.3–7.5/10 points, with higher ratings (p < 0.05) among women and older healthcare workers. The qualitative study uncovered that the primary barriers to using PsyCovidApp were workload, lack of time, and exhaustion. Its primary mechanisms of action included emotion identification, mental health regulation (e.g., insomnia, intense emotions), and learning of techniques and skills. The expert panel reached a consensus on 29 proposals to optimize PsyCovidApp.

Conclusion

The knowledge derived from this study could inform the design and implementation of future similar digital tools.
Consanguineous marriages, premarital screening, and genetic testing: a survey among Saudi university students
Authors: Jameel Tahir , Baig Mukhtiar , Murad Manal Abdulaziz , Gazzaz Zohair Jamil , Mal Youssof , Alyoubi Wedyan Eid , Alyoubi Ghadi Hamed , Alaslani Shoug Tawfiq , Alshuaibi Hanan Abdullah , Nawaz Ayesha , Alkaabi Turki
Published: March 2024

Background

Marriage among cousins or close relatives, i.e., consanguinity, is prevalent in many parts of the world, especially the Muslim world. Across civilizations, cultural norms, religious beliefs, and economic factors affect consanguineous marriages (CMs); however, such marriages have social, genetic, and health repercussions. The present study investigated the university students’ attitudes regarding CMs and factors influencing their attitudes at King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia (KSA).

Methods

This cross-sectional prospective study was conducted at KAU Jeddah in 2023. The questionnaire was distributed via electronic media (Emails, Facebook Messenger & WhatsApp). The convenience sampling technique was used to select participants, and descriptive and inferential statistics were used to analyze the data on SPSS-26.

Results

A total of 1707 university students were part of the study (females, 1,198, 70.2%; males, 509, 29.8%). Almost half of the participants, 819 (48.0%), had parents with CMs. Most of the participants, 1,391 (81.5%), had CMs in the family. Half of the participants disagreed that parents consider marriage stable due to high compatibility and the same social relationship before and after marriage. About one-third of respondents said parents believe family marriage transmits cultural values and continuity and keeps wealth in the family. More than three-fourths of the participants stated that if marriage is arranged with first cousins, they will opt for genetic analysis (82.5%) and premarital counseling (85.2%). The personal attitudes of females (p < 0.001), undergraduate (p = 0.02), and health sciences students (p = 0.02) were more positive than their counterparts. Males (OR = 0.41; p < 0.001) and non-health sciences students (OR = 0.68; p = 0.01) were less likely to have significant positive attitudes than their counterparts. Among participants who had CM parents, males (OR = 0.397; p < 0.001) and non-health sciences students (OR = 0.60; p = 0.01) and urban residents (OR = 0.59; p = 0.01) had significantly lower odds of having a positive attitude than their counterparts.

Conclusion

The practice of CMs is still prevalent in Saudi culture, with almost half of the participants having CM parents and the majority reporting these marriages in their families. Personal attitudes toward CMs were extremely positive. Most students prefer genetic testing and premarital counseling if marrying first cousins. Gender, faculty, parental income, and educational background influenced participants’ attitudes.
A comprehensive analysis concerning eating behavior associated with chronic diseases among Romanian community nurses
Authors: Onofrei Lidia-Manuela , Puiu Maria , Chirita-Emandi Adela , Serban Costela Lacrimioara
Published: March 2024

Introduction

Lifestyle factors, including inadequate eating patterns, emerge as a critical determinant of chronic disease. Apart from caring for patients, nurses should also take an active role in monitoring and managing their own health. Understanding the intricate relationship between nurses’ eating behavior and managing their own health is crucial for fostering a holistic approach to healthcare, therefore our study aimed to evaluate eating behavior and demographic factors influencing chronic disease prevalence in a sample of community nurses from Romania.

Methods

Between October–November 2023, 1920 community nurses were invited to answer an online survey, using an advertisement in their professional network. Of them, 788 responded. In the survey, which included a semi-quantitative food frequency questionnaire with 53 food items, the Intuitive Eating Survey 2 (IES-2), and demographic items were used.

Results

A multivariate model was built for the prediction of the association between eating behavior and other factors associated with chronic diseases. The majority of participants were females (95.1%), with the largest age group falling between 40 and 49.9 years (48.2%). Regarding the EFSA criteria for adequate carbohydrate and fat intake, 20.2% of the group have a high intake of carbohydrates, respectively, 43.4% of the group have a high intake of fat. Analysis of chronic diseases indicated that 24.9% of individuals reported at least one diagnosis by a physician. The presence of chronic disease was associated with a low level of perceived health status, with an OR = 3.388, 95%CI (1.684–6.814), compared to those reporting excellent or very good perceived health status. High stress had an OR = 1.483, 95%CI (1.033–2.129). BMI had an OR = 1.069, 95%CI (1.032–1.108), while low carbohydrate diet score had an OR = 0.956, 95%CI (0.920–0.992). Gender and IES-2 did not significantly contribute to the model, but their effect was controlled.

Discussion

By unraveling the intricate interplay between nutrition, lifestyle, and health outcomes in this healthcare cohort, our findings contribute valuable insights for the development of targeted interventions and support programs tailored to enhance the well-being of community nurses and, by extension, the patients they support.
Unsupervised learning and natural language processing highlight research trends in a superbug
Authors: Méndez-Cruz Carlos-Francisco , Rodríguez-Herrera Joel , Varela-Vega Alfredo , Mateo-Estrada Valeria , Castillo-Ramírez Santiago
Published: March 2024

Introduction

Antibiotic-resistant Acinetobacter baumannii is a very important nosocomial pathogen worldwide. Thousands of studies have been conducted about this pathogen. However, there has not been any attempt to use all this information to highlight the research trends concerning this pathogen.

Methods

Here we use unsupervised learning and natural language processing (NLP), two areas of Artificial Intelligence, to analyse the most extensive database of articles created (5,500+ articles, from 851 different journals, published over 3 decades).

Results

K-means clustering found 113 theme clusters and these were defined with representative terms automatically obtained with topic modelling, summarising different research areas. The biggest clusters, all with over 100 articles, are biased toward multidrug resistance, carbapenem resistance, clinical treatment, and nosocomial infections. However, we also found that some research areas, such as ecology and non-human infections, have received very little attention. This approach allowed us to study research themes over time unveiling those of recent interest, such as the use of Cefiderocol (a recently approved antibiotic) against A. baumannii.

Discussion

In a broader context, our results show that unsupervised learning, NLP and topic modelling can be used to describe and analyse the research themes for important infectious diseases. This strategy should be very useful to analyse other ESKAPE pathogens or any other pathogens relevant to Public Health.