bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical nanomaterial-based detection of biomarkers in liquid biopsy
Authors: Kim Young Jun , Rho Won-Yeop , Park Seung-min , Jun Bong-Hyun
Published: March 2024

Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques. Optical biosensors based on nanomaterials open an important opportunity in liquid biopsy because of their enhanced sensing performance with simple and practical properties. In this review article, we summarized recent innovations in optical nanomaterials to demonstrate the sensitive detection of protein, peptide, ctDNA, miRNA, exosome, and CTCs. Each study prepares the optical nanomaterials with a tailored design to enhance the sensing performance and to meet the requirements of each biomarker. The unique optical characteristics of metallic nanoparticles (NPs), quantum dots, upconversion NPs, silica NPs, polymeric NPs, and carbon nanomaterials are exploited for sensitive detection mechanisms. These recent advances in liquid biopsy using optical nanomaterials give us an opportunity to overcome challenging issues and provide a resource for understanding the unknown characteristics of the biomarkers as well as the mechanism of the disease.

Graphical abstract
Efficacy and safety of follitropin delta for ovarian stimulation in vitro fertilization/ intracytoplasmic sperm injection cycles: a systematic review with meta-analysis
Authors: Palomba Stefano , Caserta Donatella , Levi-Setti Paolo Emanuele , Busnelli Andrea
Published: March 2024

Background

Follitropin delta is a novel recombinant follicle stimulating hormone preparation uniquely expressed in a human fetal retinal cell line by recombinant DNA technology. To date, no systematic review was available about the safety and the efficacy of the follitropin delta. The objective of this study was systematically reviewing the available literature and to provide updated evidence regarding the efficacy-safety profile of follitropin delta when compared to other gonadotropin formulations for ovarian stimulation in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles.

Methods

An extensive search was performed to identify phase 1, phase 2 and phase 3 RCTs in humans focused on follitropin delta use for ovarian stimulation in IVF/ICSI cycles. The risk of bias and the overall quality of the evidence was analyzed. All data were extracted and analyzed using the intention-to-treat principle and expressed per woman randomized.

Results

A total of 7 RCTs (1 phase 1 RCT, 2 phase 2 RCTs and 4 phase 3 RCTs) were included in the qualitative analysis, whereas data of three phase 3 RCTs were meta-analyzed. All trials compared personalized recombinant follitropin delta treatment versus conventional recombinant follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. No difference between two regimens was detected for clinical pregnancy rate [odds ratio (OR) 1.06; 95% confidence intervals (CI): 0.90, 1.24; P = 0.49; I2 = 26%], ongoing pregnancy rate (OR 1.15; 95%CI: 0.90, 1.46; P = 0.27; I2 = 40%), and live birth rate (OR 1.18; 95%CI: 0.89, 1.55; P = 0.25; I2 = 55%). No data were available regarding cumulative success rates. The rate of adoption of strategies to prevent ovarian hyperstimulation syndrome (OHSS) development (OR 0.45; 95%CI: 0.30, 0.66; P < 0.0001; I2 = 0%), and the rate of both early OHSS (OR 0.62; 95%CI: 0.43, 0.88; P = 0.008; I2 = 0%) and all forms of OHSS (OR 0.61; 95%CI: 0.44, 0.84; P = 0.003; I2 = 0%) were significantly lower in the group of patients treated with personalized follitropin delta treatment compared to those treated with conventional follitropin alfa/beta administration.

Conclusion

Personalized follitropin delta treatment is associated with a lower risk of OHSS compared to conventional follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. The absence of cumulative data does not allow definitive conclusions to be drawn regarding the comparison of the effectiveness of the two treatments.

Protocol study registration

CRD42023470352 (available at http://www.crd.york.ac.uk/PROSPERO).
Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine
Authors: Li Yaqi , Bai Baoling , Wang Hui , Wu Haojie , Deng Yanjun , Shen Chen , Zhang Qin , Shi Lin
Published: March 2024

Background

Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.

Methods

Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis.

Results

A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05).

Conclusions

The levels of choline-related metabolites and glutamate–related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.
Italian guidelines for the management of irritable bowel syndrome in children and adolescents
Authors: Di Nardo Giovanni , Barbara Giovanni , Borrelli Osvaldo , Cremon Cesare , Giorgio Valentina , Greco Luigi , La Pietra Michele , Marasco Giovanni , Pensabene Licia , Piccirillo Marisa , Romano Claudio , Salvatore Silvia , Saviano Michele , Stanghellini Vincenzo , Strisciuglio Caterina , Tambucci Renato , Turco Rossella , Zenzeri Letizia , Staiano Annamaria
Published: March 2024

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms’ exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.
Prognostic value of near-infrared spectroscopy regional oxygen saturation and cerebrovascular reactivity index in acute traumatic neural injury: a CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Cohort Study
Authors: Gomez Alwyn , Froese Logan , Griesdale Donald , Thelin Eric P. , Raj Rahul , van Iperenburg Levi , Tas Jeanette , Aries Marcel , Stein Kevin Y. , Gallagher Clare , Bernard Francis , Kramer Andreas H. , Zeiler Frederick A.
Published: March 2024

Background

Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR) due to its noninvasive nature and high spatial resolution. However, the prognostic utility of these parameters has not yet been determined. This study aimed to identify threshold values of rSO2 and rSO2-based CVR at which outcomes worsened following traumatic brain injury (TBI).

Methods

A retrospective multi-institutional cohort study was performed. The cohort included TBI patients treated in four adult intensive care units (ICU). The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. Grand mean thresholds along with exposure-based thresholds were determined utilizing sequential chi-squared analysis and univariate logistic regression, respectively.

Results

In the cohort of 129 patients, there was no identifiable threshold for raw rSO2 at which outcomes were found to worsen. For both COx and COx_a, an optimal grand mean threshold value of 0.2 was identified for both survival and favorable outcomes, while percent time above − 0.05 was uniformly found to have the best discriminative value.

Conclusions

In this multi-institutional cohort study, raw rSO2was found to contain no significant prognostic information. However, rSO2-based indices of CVR, COx and COx_a, were found to have a uniform grand mean threshold of 0.2 and exposure-based threshold of − 0.05, above which clinical outcomes markedly worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.
Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism
Authors: Gu Chao , Pei Mao-Song , Guo Zhi-Hua , Wu Lei , Qi Kai-Jie , Wang Xue-Ping , Liu Hong , Liu Zhongchi , Lang Zhaobo , Zhang Shaoling
Published: March 2024

Background

Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here, we systematically investigate the metabolic landscape and regulatory network involved.

Results

We generate an association database consisting of 439 metabolites and 14,399 genes to elucidate the gene regulatory network of pear flesh metabolism. Interestingly, we detect increased DNA methylation in the promoters of most genes within the database during pear flesh development. Application of a DNA methylation inhibitor to the developing fruit represses chlorophyll degradation in the pericarp and promotes xanthophyll, β-carotene, and abscisic acid (ABA) accumulation in the flesh. We find the gradual increase in ABA production during pear flesh development is correlated with the expression of several carotenoid pathway genes and multiple transcription factors. Of these transcription factors, the zinc finger protein PbZFP1 is identified as a positive mediator of ABA biosynthesis in pear flesh. Most ABA pathway genes and transcription factors are modified by DNA methylation in the promoters, although some are induced by the DNA methylation inhibitor. These results suggest that DNA methylation inhibits ABA accumulation, which may delay fruit ripening.

Conclusion

Our findings provide insights into epigenetic regulation of metabolic regulatory networks during pear flesh development, particularly with regard to DNA methylation.
Comparison between postcontrast thin-slice T1-weighted 2D spin echo and 3D T1-weighted SPACE sequences in the detection of brain metastases at 1.5 and 3 T
Authors: Vymazal Josef , Ryznarova Zuzana , Rulseh Aaron M.
Published: March 2024

Objectives

Accurate detection of metastatic brain lesions (MBL) is critical due to advances in radiosurgery. We compared the results of three readers in detecting MBL using T1-weighted 2D spin echo (SE) and sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences with whole-brain coverage at both 1.5 T and 3 T.

Methods

Fifty-six patients evaluated for MBL were included and underwent a standard protocol (1.5 T, n = 37; 3 T, n = 19), including postcontrast T1-weighted SE and SPACE. The rating was performed by three raters in two sessions > six weeks apart. The true number of MBL was determined using all available imaging including follow-up. Intraclass correlations for intra-rater and inter-rater agreement were calculated. Signal intensity ratios (SIR; enhancing lesion, white matter) were determined on a subset of 46 MBL > 4 mm. A paired t-test was used to evaluate postcontrast sequence order and SIR. Reader accuracy was evaluated by the coefficient of determination.

Results

A total of 135 MBL were identified (mean/subject 2.41, SD 6.4). The intra-rater agreement was excellent for all 3 raters (ICC = 0.97–0.992), as was the inter-rater agreement (ICC = 0.995 SE, 0.99 SPACE). Subjective qualitative ratings were lower for SE images; however, signal intensity ratios were higher in SE sequences. Accuracy was high in all readers for both SE (R2 0.95–0.96) and SPACE (R2 0.91–0.96) sequences.

Conclusions

Although SE sequences are superior to gradient echo sequences in the detection of small MBL, they have long acquisition times and frequent artifacts. We show that T1-weighted SPACE is not inferior to standard thin-slice SE sequences in the detection of MBL at both imaging fields.

Critical relevance statement

Our results show the suitability of 3D T1-weighted turbo spin echo (TSE) sequences (SPACE, CUBE, VISTA) in the detection of brain metastases at both 1.5 T and 3 T.

Key points

• Accurate detection of brain metastases is critical due to advances in radiosurgery.

• T1-weighted SE sequences are superior to gradient echo in detecting small metastases.

• T1-weighted 3D-TSE sequences may achieve high resolution and relative insensitivity to artifacts.

• T1-weighted 3D-TSE sequences have been recommended in imaging brain metastases at 3 T.

• We found T1-weighted 3D-TSE equivalent to thin-slice SE at 1.5 T and 3 T.

Graphical Abstract
Edible microbial cellulose-based antimicrobial coatings and films containing clove extract
Authors: Ahmed Mazia , Saini Pinki , Iqbal Unaiza , Sahu Khushbu
Published: March 2024

Recently, microbial cellulose-based coatings and films have attracted substantial attention because of their promising uses in numerous fields, such as food packaging. The present work was designed to synthesize active microbial cellulose-based coatings and films with a comprehensive investigation of their antimicrobial and structural properties. Microbial cellulose was synthesized by using a gram-negative bacterium called Acetobacter aceti. The produced microbial cellulose was mixed with sodium alginate, chitosan and starch to obtain two different composite solutions, i.e., microbial cellulose + starch + chitosan (MSC) and microbial cellulose + starch + sodium alginate (MSS). The antimicrobial properties were achieved by incorporating four different concentrations of clove extract into the composite solutions. The resulting composite solutions were tested against S. aureus, Shigella, Salmonella, and E. coli through the agar diffusion assay method. The clove extract was found to be effective in inhibiting the growth of these pathogens, as a clear zone of inhibition was observed at all clove extract concentrations, with a maximum zone of inhibition of 4.0 ± 0.05 cm on E. coli for the MSC solution incorporated with 4% clove extract. The best antimicrobial solutions found were then casted into films by pouring the solutions into petri dishes and drying at 50 °C in a tray drier. The antimicrobial activity was again evaluated for the films. The results indicated that MSC 3% showed a greater zone of inhibition against all pathogens (1.7 ± 0.18 cm). Furthermore, structural and thermal analyses of the formed films were conducted. The results indicated distinctive antimicrobial and structural characteristics of the films.

Graphical Abstract
Correlation between Doppler sonography and diuretic renogram in the diagnosis and follow-up of infants with unilateral pelvi-ureteric junction obstruction
Authors: Patil Neehar , Shubha A. M. , Das Kanishka , Pavan K. V. , Prashanth G. R.
Published: March 2024

Background

Conventionally, diuretic isotope renogram is used to establish and quantify severity of the obstruction in pelvi-ureteric junction obstruction. Doppler ultrasonography too assesses obstruction by evaluating the resistive index (RI) and resistive index ratio (RIR) in the intrarenal vasculature of the kidneys. This study aimed to note correlation between RI, RIR on Doppler ultrasonography and perfusion index (PI) on diuretic isotope renogram in suspect unilateral pelvi-ureteric junction obstruction in infants. A prospective study (2016–2019) in infants with suspect unilateral hydronephrosis, i.e. anteroposterior pelvic diameter (APPD) > 15 mm, divided into Group A (0–6 months) and Group B (6–12 months) based on the age at diagnosis. The RI, RIR and PI were noted at diagnosis, at 3 and 6 months, post-interventions and the correlation assessed.

Results

37/94 with hydronephrosis were included in the study. 30 among these underwent surgical intervention. A decrease in RI and RIR and increase in PI following surgery were documented at follow-up. Also, the improvement was statistically more significant in the first 3 months following intervention.

Conclusions

An increased RI and RIR and a decreased PI are good indicators of obstruction in unilateral hydronephrosis in infants. The decline in RI with increase in PI following relief of obstruction shows a positive correlation between the two. Doppler sonography may be effective in monitoring unilateral hydronephrosis with unobstructed or equivocal renogram curves and consequently negate the need for repeated nuclear scans.
Effect of gender identity on the association between gender dysphoria and suicidality via appearance anxiety among transgender and gender-diverse young people: moderated mediation study
Authors: Li Jiaqi , Feng Yi , Yu Yi , Xu Shicun , Wang Yuanyuan
Published: March 2024

Background

Gender dysphoria is associated with suicidality among transgender and gender-diverse (TGD) people. Gender dysphoria also results in a stress on appearance.

Aims

The objectives of this study were to examine: (a) whether appearance anxiety mediates the effect of gender dysphoria on suicidality; and (b) whether gender identity moderates the mediating effect of appearance anxiety.

Method

A total of 117 769 college and university students were recruited in this cross-sectional study from Jilin Province, China. After screening based on participants’ gender identity, 2352 TGD young people (aged from 15 to 25 years) were divided into three subgroups: female to male (FTM), male to female (MTF) and non-binary. Self-report inventories measured gender dysphoria, suicidality and appearance anxiety. A structural equation model was run to examine the relationships among TGD gender identity, gender dysphoria, appearance anxiety and suicidality.

Results

Among TGD young people, gender dysphoria was significantly positively associated with suicidality (β = 0.15, 95% CI = 0.11–0.18, P < 0.001). Appearance anxiety partially mediated the association between gender dysphoria and suicidality (β = 0.07, 95% CI = 0.05–0.08, P < 0.001). Gender identity moderated the mediating effects: compared with individuals with FTM identity, among those with MTF and non-binary identities, gender dysphoria showed stronger positive effects on appearance anxiety, and appearance anxiety showed greater effects in mediating the association between gender dysphoria and suicidality.

Conclusions

Among TGD young people, gender dysphoria is significantly associated with suicidality via appearance anxiety, with gender identity moderating the mediating effects. Diverse treatments should consider the heterogeneity of TGD subgroups, with the aim of limiting the tendency of gender dysphoria to trigger appearance anxiety, thus further buffering against the risk of suicide.
Presentation of Breast Cancer and Impact of Patient Navigation on Timeliness of Diagnosis and Treatment and on Adherence to Treatment Recommendations in a Multicenter Network in Malaysia
Authors: Jaganathan Maheswari , Ang Boon Hong , Ali Adibah , Sharif Siti Zubaidah , Mohamad Mazwela , Mohd Khairy Azuddin , Muniandy Kavitha , Zainal Hani , Sabtu Fizati , Sapiee Norija , Zainal Nur Hidayati , Zaipudin Nur Fazilah Hanisah , Muniandi Mallika , Ghazali Aini Fatimah , Roimin France Olovia , Chong Clara Ching Ling , Rajaram Nadia , Jaafar Nurshuhadah , Julaihi Rokayah , Rahim Norlia , Zakaria Nor Aniza , Menon Isabella , Tajudeen Nurul Ain , Ho Kah Yee , Md Yusof Suryani , Abdul Wahab Mohamed Yusof , Ab Hadi Imi Sairi , Teo Soo-Hwang
Published: March 2024

PURPOSE

Breast cancer deaths disproportionately affect women living in low- and middle-income countries (LMICs). Patient navigation has emerged as a cost-effective and impactful approach to enable women with symptoms or suspicious mammogram findings to access timely diagnosis and patients with breast cancer to access timely and appropriate multimodality treatment. However, few studies have systematically evaluated the impact of patient navigation on timeliness of diagnosis and treatment in LMICs.

METHODS

We established a nurse- and community-navigator-led navigation program in breast clinics of four public hospitals located in Peninsular and East Malaysia and evaluated the impact of navigation on timeliness of diagnosis and treatment.

RESULTS

Patients with breast cancer treated at public hospitals reported facing barriers to accessing care, including having a poor recognition of breast cancer symptoms and low awareness of screening methods, and facing financial and logistics challenges. Compared with patients diagnosed in the previous year, patients receiving navigation experienced timely ultrasound (84.0% v 65.0%; P < .001), biopsy (84.0% v 78.0%; P = .012), communication of news (63.0% v 40.0%; P < .001), surgery (46% v 36%; P = .008), and neoadjuvant therapy (59% v 42%, P = .030). Treatment adherence improved significantly (98.0% v 87.0%, P < .001), and this was consistent across the network of four breast clinics.

CONCLUSION

Patient navigation improves access to timely diagnosis and treatment for women presenting at secondary and tertiary hospitals in Malaysia.
Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study
Authors: Bazarbashi Shouki , Alkhatib Radwan , Aseafan Mohamed , Tuleimat Yasmin , Abdel-Aziz Nashwa , Mahrous Mervat , Elsamany Sherif , Elhassan Tusneem , Alghamdi Mohammed
Published: March 2024

PURPOSE

Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment.

MATERIALS AND METHODS

We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches.

RESULTS

Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS.

CONCLUSION

This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.
Effects of Supplemental Vitamin D3, Omega-3 Fatty Acids on Physical Performance Measures in the VITamin D and OmegA-3 TriaL
Authors: Chou Sharon H , Cook Nancy R , Kotler Gregory , Kim Eunjung , Copeland Trisha , Lee I Min , Cawthon Peggy M , Buring Julie E , Manson JoAnn E , LeBoff Meryl S
Published: March 2024

Context

Declining muscle strength and performance in older adults are associated with falls, fractures, and premature death.

Objective

This work aimed to determine whether supplementation with vitamin D3 or omega-3 fatty acids vs placebo for 2 years improves physical performance measures.

Methods

VITamin D and OmegA-3 TriaL (VITAL) was a double-blinded, placebo-controlled randomized trial of supplemental vitamin D3 and/or omega-3 fatty acids vs placebo in the prevention of cancer and cardiovascular disease in 25 871 US adults. This ancillary study was completed in a New England subcohort that had in-person evaluations at baseline and 2-year follow-up. This study was conducted with 1054 participants (age: men ≥50 and women ≥55 years) at the Center for Clinical Investigations in Boston. Interventions included a 2 × 2 factorial design of supplemental vitamin D3 (cholecalciferol, 2000 IU/day) and/or marine omega-3 fatty acids (1 g/day). Main outcome measures included 2-year changes in physical performance measures of grip strength, walking speed, standing balance, repeated chair stands, and Timed-up and Go (TUG).

Results

At 2 years, all randomized groups showed worsening walking speeds and TUG. There were no differences in changes in grip strength, walking speeds, Short Physical Performance Battery (composite of walking speed, balance, and chair stands), and TUG between the vitamin D3-treated and the placebo-treated groups and between the omega-3-treated and the placebo-treated groups. Effects overall did not vary by sex, age, body mass index, or baseline measures of total or free 25-hydroxyvitamin D (25[OH]D) or plasma omega-3 index; TUG slightly worsened with vitamin D supplementation, compared to placebo, in participants with baseline total 25(OH)D levels above the median (P = .01; P for interaction = .04).

Conclusion

Neither supplemental vitamin D3 nor marine omega-3 fatty acids for 2 years improved physical performance in this generally healthy adult population.
Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism
Authors: Shahidzadeh Yazdi Zhinous , Streeten Elizabeth A , Whitlatch Hilary B , Montasser May E , Beitelshees Amber L , Taylor Simeon I
Published: March 2024

Context

The body has evolved homeostatic mechanisms to maintain free levels of Ca+2 and 1,25-dihydroxyvitamin D (1,25(OH)2D) within narrow physiological ranges. Clinical guidelines emphasize important contributions of parathyroid hormone (PTH) in maintaining this homeostasis.

Objective

This work aimed to investigate mechanisms of homeostatic regulation of vitamin D (VitD) metabolism and to apply mechanistic insights to improve clinical assessment of VitD status.

Methods

This crossover clinical trial studied community participants before and after VitD3 supplementation. Participants included 11 otherwise healthy individuals with VitD deficiency (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL). VitD3 supplements (50 000 IU once or twice a week depending on body mass index, for 4-6 weeks) were administered to achieve 25(OH)D of 30 ng/mL or greater.

Results

VitD3 supplementation significantly increased mean 25(OH)D by 2.7-fold and 24,25-dihydroxyvitamin D (24,25(OH)2D) by 4.3-fold. In contrast, mean levels of PTH, fibroblast growth factor-23, and 1,25(OH)2D did not change. Mathematical modeling suggested that 24-hydroxylase activity was maximal for 25(OH)D 50 ng/mL or greater and achieved a minimum (∼90% suppression) with 25(OH)D less than 10 to 20 ng/mL. The 1,25(OH)2D/24,25(OH)2D ratio better predicted modeled 24-hydroxylase activity (h) (ρ = −0.85; P = .001) compared to total plasma 25(OH)D (ρ = 0.51; P = .01) and the 24,25(OH)2D/25(OH)D ratio (ρ = 0.37; P = .3).

Conclusion

Suppression of 24-hydroxylase provides a first line of defense against symptomatic VitD deficiency by decreasing metabolic clearance of 1,25(OH)2D. The 1,25(OH)2D/24,25(OH)2D ratio provides a useful index of VitD status since it incorporates 24,25(OH)2D levels, and therefore provides insight into 24-hydroxylase activity. When VitD availability is limited, this suppresses 24-hydroxylase activity—thereby decreasing the level of 24,25(OH)2D and increasing the 1,25(OH)2D/24,25(OH)2D ratio. Thus, an increased 1,25(OH)2D/24,25(OH)2D ratio signifies triggering of homeostatic regulation, which occurs at early stages of VitD deficiency.
Moderate-intensity Combined Training Induces Lipidomic Changes in Individuals With Obesity and Type 2 Diabetes
Authors: Duft Renata Garbellini , Bonfante Ivan Luiz Padilha , Palma-Duran Susana Alejandra , Chacon-Mikahil Mara Patrícia Traina , Griffin Julian Leether , Cavaglieri Cláudia Regina
Published: March 2024

Context

Alterations in the lipid metabolism are linked to metabolic disorders such as insulin resistance (IR), obesity and type 2 diabetes (T2D). Regular exercise, particularly combined training (CT), is a well-known nonpharmacological treatment that combines aerobic (AT) and resistance (RT) training benefits. However, it is unclear whether moderate-intensity exercise without dietary intervention induces changes in lipid metabolism to promote a “healthy lipidome.”

Objective

The study aimed to investigate the effect of 16 weeks of CT on plasma and white adipose tissue in both sexes, middle-aged individuals with normal weight, obesity (OB), and T2D using an ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) untargeted lipidomics approach.

Methods

Body composition, maximum oxygen consumption (VO2max), strength, and biochemical markers were evaluated before and after the control/training period and correlated with lipid changes. CT consisted of 8 to 10 RT exercises, followed by 35 minutes of AT (45%-70% VO2max), 3 times a week for 16 weeks.

Results

The CT significantly reduced the levels of saturated and monounsaturated fatty acid side-chains (SFA/MUFA) in sphingolipids, glycerolipids (GL) and glycerophospholipids (GP) as well as reducing fat mass, circumferences and IR. Increased levels of polyunsaturated fatty acids in GPs and GLs were also observed, along with increased fat-free mass, VO2 max, and strength (all P < .05) after training.

Conclusion

Our study revealed that 16 weeks of moderate-intensity CT remodeled the lipid metabolism in OB, and T2D individuals, even without dietary intervention, establishing a link between exercise-modulated lipid markers and mechanisms that reduce IR and obesity-related comorbidities.
Critical importance of DNA binding for CSL protein functions in fission yeast
Authors: Marešová Anna , Oravcová Martina , Rodríguez-López María , Hradilová Miluše , Zemlianski Viacheslav , Häsler Robert , Hernández Pablo , Bähler Jürg , Převorovský Martin
Published: March 2024

CSL proteins [named after the homologs CBF1 (RBP-Jκ in mice), Suppressor of Hairless and LAG-1] are conserved transcription factors found in animals and fungi. In the fission yeast Schizosaccharomyces pombe, they regulate various cellular processes, including cell cycle progression, lipid metabolism and cell adhesion. CSL proteins bind to DNA through their N-terminal Rel-like domain and central β-trefoil domain. Here, we investigated the importance of DNA binding for CSL protein functions in fission yeast. We created CSL protein mutants with disrupted DNA binding and found that the vast majority of CSL protein functions depend on intact DNA binding. Specifically, DNA binding is crucial for the regulation of cell adhesion, lipid metabolism, cell cycle progression, long non-coding RNA expression and genome integrity maintenance. Interestingly, perturbed lipid metabolism leads to chromatin structure changes, potentially linking lipid metabolism to the diverse phenotypes associated with CSL protein functions. Our study highlights the critical role of DNA binding for CSL protein functions in fission yeast.
A Study on Utilization and Improvement through the Investigation of the Status of Preserved Remains in Jeollabuk Area
Authors: Wi Koang-Chul
Published: March 2024

The decision on conservation measures for buried cultural properties is made by the Administrator of the Cultural Heritage Administration based on academic and historical value, but there are areas that need to be reexamined in terms of systematic preservation management, accessibility, and utilization after relocation and restoration. Accordingly, this study attempted to suggest ways to preserve and utilize, and areas that need to be improved, through a survey and inspection of the current status of 29 preserved ruins in the Jeollabuk-do region. As a result of the investigation, it was confirmed that there were technical problems with the previous restoration method, problems with accessibility and usability, and the absence of a systematic management system. In order to improve this, new engineering studies on materials and protective angles used in restoration must be conducted, and accessibility and usability must be increased by relocating the variously distributed preserved remains to urban heritage exhibition halls or museums. There is. In addition, a country-centered conservation management system must be established, and a scientific and systematic conservation management system must be based on institutional improvements equivalent to designated and registered cultural properties. This can provide an opportunity to increase the value of preserved ruins and historical awareness.
COMO ANDA A INOVAÇÃO?
Authors: Macário Natanael da Silva , Felix Júnior Luiz Antonio , Costa Wênyka Preston Leite Batista da , Mesquita Rafael Fernandes de , Cruz Vera Lúcia
Published: March 2024

O objetivo deste estudo é analisar os aspectos da cultura de inovação de uma empresa de saneamento básico, por meio da percepção dos seus funcionários. A pesquisa teve natureza quantitativa e descritiva, utilizando como instrumento uma escala de cultura da inovação adaptada a partir do modelo desenvolvido por Dobni (2008), traduzido e validado no idioma português por Ladeira e Lund (2010), e teve como amostra considerada 171 respondentes, com coleta de dados realizada entre março e outubro de 2022. Foram realizados procedimentos estatísticos para validação do instrumento e posterior análise dos dados coletados. Os resultados indicam que os funcionários têm boa percepção da cultura da inovação na empresa, principalmente no que tange ao espaço para exposição de ideias e sugestões, além de uma autoanálise de criatividade positiva, e entendimento do objetivo fim da companhia; entretanto, ainda é preciso fortalecer uma sistemática de avaliação, validação e implementação dessas ideias, além de desenvolver melhor os processos de comunicação inovativa.
PROTAGONISMO DE GESTORES DE EMPRESAS FITNESS DE OURO PRETO E MARIANA
Authors: Baldi Bruna Soares , Ungheri Bruno Ocelli , De Oliveira Géssyca Tolomeu , Ferreira Renato Melo , Soares Everton Rocha
Published: March 2024

Com o contínuo crescimento do mercado fitness e a ampliação das áreas de atuação nesse campo, o desempenho administrativo de um gestor depende de competências que vão além dos saberes técnicos, envolvendo habilidades conceituais e humanas que auxiliam na definição de objetivos e os tornam capaz de alcançá-los. Sob essa premissa, o objetivo foi analisar o perfil dos gestores de empreendimentos fitness de Ouro Preto e Mariana-MG, a fim de entender como eles lidam com a gestão de suas empresas. Para isso, realizou-se uma pesquisa exploratória, de abordagem qualitativa e amostragem por conveniência. De modo geral, constatou-se que os gestores reconhecem algumas limitações em sua atuação, advindas, majoritariamente, pela falta de capacitação/ formação continuada. Por fim, sugestiona-se a inclusão de conteúdos sobre gestão no currículo dos cursos de bacharelado em Educação Física, bem como a promoção de cursos de formação continuada e de discussões sobre temas da gestão administrativa.
Ο πολιτισμός του καρκίνου
Authors: Βαρελάκη Γαρυφαλιά
Published: March 2024

Η παρούσα διδακτορική διατριβή αποτελεί την περιγραφή ενός κόσμου που συνιστά αυτό που η Susan Sontag αποκαλεί το «βασίλειο των αρρώστων», ενός κόσμου καθημερινού για όσους ζουν σε αυτόν ή τον επισκέπτονται τακτικά, ενός κόσμου κοινωνικού ο οποίος καταναλώνει τον πολιτισμό που ο ίδιος παράγει. Βασισμένη σε μία «πολύ-τοπική» εθνογραφία, η οποία έλαβε χώρα στην Αθήνα, η έρευνα εξετάζει τις συνδέσεις ανάμεσα στους ανθρώπους, τους τόπους, τις πρακτικές, τους θεσμούς και τα αντικείμενα. Η ανάλυση του εθνογραφικού υλικού επεξεργάζεται τις διαδικασίες εκείνες που διαμορφώνουν και επηρεάζουν τον τρόπο με τον οποίο συγκροτείται η εμπειρία της ασθένειας και αποτυπώνουν τα στοιχεία που δομούν τον πολιτισμό του καρκίνου. Ο καρκίνος ερμηνεύεται ως μία σχέση και εξετάζονται οι έννοιες, οι πρακτικές και οι πολιτικές της φροντίδας μέσα στο πλαίσιο της ογκολογικής κλινικής. Η εθνογραφική ανάλυση φωτίζει τα κενά που δημιουργούνται στο πλαίσιο των πολιτικών που διέπουν το Συστήμα Υγείας στη θεραπεία και στη φροντίδα του καρκίνου. Η ανάλυση των εθνικών και ευρωπαϊκών πολιτικών της φροντίδας του καρκίνου αναδεικνύει τους τρόπους με τους οποίους η έννοια της «υγείας» κατασκευάζεται μέσω των πολιτικών της πρόληψης και του ελέγχου καθώς τα όρια της «υγείας» ρευστοποιούνται μέσα από διαδικασίες ηθικοποίησης του τρόπου ζωής. Επιπλέον, εξετάζονται κριτικά οι τρόποι πρόσβασης στην εξατομικευμένη ιατρική και στις μοριακές εξετάσεις που παρέχει το Δημόσιο Σύστημα Υγείας στην Ελλάδα και περιγράφονται οι τρόποι με τους οποίους οι άξονες διαστρωμάτωσης που αποτυπώνονται, αρθρώνονται και συνδέονται μεταξύ τους, έχουν ως αποτέλεσμα την ανάδυση νέων μορφών υποκειμενικότητας και τον μετασχηματισμό της εμπειρίας του καρκίνου. Ο καρκίνος, ως μία σχέση ανάμεσα στην ασθενή και το ευρύτερο οικογενειακό περιβάλλον, προβάλλει την έννοια της «γενετικής ευθύνης», και το αίσθημα αυτής, το οποίο διαμορφώνει και ανακατασκευάζει συμπεριφορές, ενώ παράλληλα, η γενετικοποίηση της ασθένειας μετουσιώνει την ίδια της την υπόσταση από ατομική σε οικογενειακή. Τέλος, η ιδέα του εθνογραφικού εαυτού και ο τρόπος με τον οποίο τα συναισθήματα του/της ερευνητή/τριας μπορούν να αποτελέσουν υλικό της έρευνας -στο συγκεκριμένο εθνογραφικό πεδίο- αναδεικνύουν τον αναστοχαστικό «εαυτό» ως μέρος της εθνογραφικής πραγματικότητας.
Islam et démocratie
Authors: Waardenburg Jacques
Published: March 2024

Die Bezeichnungen, welche der Westen zu den islamischen Ländern pflegen kann, ist unter anderem geprägt von den politischen Systemen in diesen Ländern. Der Autor zeigt auf, wie in vielen islamischen Ländern - ausgehend von europäischen Vorbildern - versucht wurde, demokratische Systeme aufzubauen und stellt dar, warum sie oftmals scheitern.
Mortality among non-severely under nourished children with pneumonia globally: protocol for a systematic review and meta-analysis
Authors: Nalwanga Damalie , Bakker Caitlin , Kiggwe Andrew , Negash Abel Abera , Ocan Moses , Briend Andre , Maitland Kathryn , Musiiime Victor , Karamagi Charles
Published: March 2024

Background Pneumonia remains the commonest cause of ill health and mortality among children worldwide. Severe undernutrition increases the mortality risk among children with pneumonia. While children with pneumonia are at increased risk of developing malnutrition, the impact of pneumonia on mortality and nutritional status of non-severely undernourished children is not well described. The impact of nutritional supplementation on mortality and nutritional status in this population is not well understood. This review will collate available evidence on the all-cause mortality and anthropometric indices outcomes following pneumonia, as well as the impact of nutritional supplementation on mortality and anthropometry among non-severely malnourished children with pneumonia. Methods The review will be done using a priori criteria developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data will be obtained from data bases, grey literature, and bibliographies. An experienced librarian will conduct article search in PUBMED, MEDLINE, EMBASE, Web of Science, Google scholar, and Scopus. Retrieved articles will be entered in Endnote ver 9.0, duplicates removed, and transferred to Epi-reviewer for screening and data abstraction. Risk of bias in the included articles will be assessed using standard criteria. Heterogeneity will be assessed using I2-statistic and sub-group analysis will be done. Data will be analysed using both narrative and quantitative synthesis. Quantitative synthesis will be done using DeSimonian and Laird Random-effects model in STATA ver 15.0. Conclusions The results will provide baseline information about the mortality and anthropometric outcomes of pneumonia among non-severely malnourished children as well as the potential effect of nutritional supplementation on these outcomes. This will provide a basis to explore the potential for nutritional supplementation improving clinical outcomes like mortality and occurrence of severe acute malnutrition among children with severe pneumonia worldwide. Registration The review has been registered in PROSPERO (CRD42021257272; 15 July 2021).
Features of gelotophobia (fear of ridicule) in neurotic mental disorders
Authors: Shunenkov Denis , Hudyakov Aleksey , Ivanova Elena
Published: March 2024

The monograph provides a theoretical analysis of the currently available information about the peculiarities of the fear of ridicule (gelotophobia) and associated phenomena: the tendency to expose oneself as an object of humor and laughter (gelotophilia) and the tendency to ridicule others (catagelasticism). The article describes the clinical and psychological features of the fear of ridicule in patients with neurotic disorders of organic and functional origin. The necessity of developing and implementing psychocorrective and psychotherapeutic programs in the complex therapy of neurotic mental disorders aimed at correcting the fear of ridicule in order to form an internally consistent picture of the disease and increase the level of adherence to therapy is demonstrated.
It is intended for clinical psychologists, psychiatrists, psychotherapists, psychologists, educational psychologists, as well as to be used in the educational process of universities providing training and postgraduate additional education for clinical psychologists and medical doctors.
Latin language and the basics of professional terminology
Authors: Grudeva Elena
Published: March 2024

Latin veterinary terminology is the basis for the training of future specialists in the field of veterinary medicine and veterinary and sanitary expertise. The purpose of the textbook is to lay the foundations of the terminological competence of a specialist who is able to competently use veterinary medical terminology both in the study of specialized disciplines and in further practical and scientific activities.
It is intended for first-year students of veterinary universities and faculties.
Carbon neutralization of steelmaking, energy and cement industries. Silhouettes of the carbon-neutral industry.
Authors: Lasankin Serey
Published: March 2024

The monograph examines the ROLL technology that allows solving the climate problem in the steelmaking, energy and cement industries. We are not talking about the exclusion of carbon from the technological process, but about the neutralization of the resulting carbon dioxide.
ROLL technology is based on the idea of producing several products from a single heating of raw materials, and the main tools are universal ROLL chambers that bring allied productions closer together in time and space. This reduces the energy intensity of the total product and directs the saved and produced energy to neutralize carbon dioxide.
It is intended for scientific and engineering workers, teachers, graduate students and students interested in this problem.
Flotation models and hydrodynamic modes of operation of combined flotation equipment
Authors: Ksenofontov Boris
Published: March 2024

For the first time in the world literature, the monograph examines both the theoretical beginnings of the flotation process using multistage and generalized flotation models, as well as practical recommendations based on the principles of biosimilarity. Diagrams of various types of combined flotation equipment and their operating modes are presented.
New aeration systems for use in various flotation devices, including flotation combines, are considered. Examples of the use of new flotation technology using ejectors for both aeration and mixing of reagents with purified water are described.
It is offered to a wide range of readers, including researchers, university professors, graduate students, masters, bachelors and undergraduates.