bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing the transmission of carbapenem-resistant Enterobacterales at the patient: ward environmental nexus
Authors: Elton Linzy , Williams Alan , Ali Shanom , Heaphy Jelena , Pang Vicky , Commins Liam , O’Brien Conor , Yetiş Özge , Caine Estelle , Ward Imogen , Muzslay Monika , Yui Samuel , Karia Kush , Shore Ellinor , Rofael Sylvia , Mack Damien J. F. , McHugh Timothy D. , Wey Emmanuel Q.
Published: December 2024

Introduction

Colonisation and infection with Carbapenem-resistant Enterobacterales (CRE) in healthcare settings poses significant risks, especially for vulnerable patients. Genomic analysis can be used to trace transmission routes, supporting antimicrobial stewardship and informing infection control strategies. Here we used genomic analysis to track the movement and transmission of CREs within clinical and environmental samples.

Methods

25 isolates were cultured from clinical patient samples or swabs, that tested positive for OXA-48-like variants using the NG-Test® CARBA-5 test and whole genome sequenced (WGS) using Oxford Nanopore Technologies (ONT). 158 swabs and 52 wastewater samples were collected from the ward environment. 60 isolates (matching clinical isolate genera; Klebsiella, Enterobacter, Citrobacter and Escherichia) were isolated from the environmental samples using selective agar. Metagenomic sequencing was undertaken on 36 environmental wastewater and swab samples.

Results

21/25 (84%) clinical isolates had > 1 blaOXA gene and 19/25 (76%) harboured > 1 blaNDM gene. Enterobacterales were most commonly isolated from environmental wastewater samples 27/52 (51.9%), then stick swabs 5/43 (11.6%) and sponge swabs 5/115 (4.3%). 11/60 (18%) environmental isolates harboured > 1 blaOXA gene and 1.9% (1/60) harboured blaNDM-1. blaOXA genes were found in 2/36 (5.5%) metagenomic environmental samples.

Conclusions

Potential for putative patient-patient and patient-ward transmission was shown. Metagenomic sampling needs optimization to improve sensitivity.
Disutility associated with social isolation and loneliness in Germany: results of a population survey using the EQ-5D-5L instrument
Authors: König Hans-Helmut , Hajek André
Published: December 2024

Background

Social isolation and loneliness are highly prevalent and may have a negative impact on health-related quality of life (HRQL). The EQ-5D-5L is a widely used questionnaire from which an index value for HRQL based on societal preferences (utility) can be derived. The purpose of this study was to estimate the loss in utility (i.e. disutility) associated with loneliness and social isolation in the German adult population.

Methods

Data came from a quota sample of individuals aged 18–74 years residing in Germany (n = 5,000) and representing the adult population in terms of age groups, gender and geographic locations. Data collection was conducted online in August and September 2023 by a certified market research firm. The EQ-5D-5L index score based on the German value set was used as outcome. Moreover, the established Lubben Social Network Scale was used to measure social isolation. The De Jong Gierveld tool was used to quantify loneliness. Groups affected by social isolation or loneliness were compared to non-affected groups, respectively. Differences in covariates between affected and non-affected groups were balanced using entropy balancing. Linear regressions were conducted afterwards (using the weights derived from the entropy balancing). Subgroup analyses by sex and age groups as well as various robustness checks were conducted.

Results

The EQ-5D-5L index score was lower among individuals with social isolation compared to individuals without social isolation (β=-0.04, p < 0.001). Moreover, the EQ-5D-5L index score was lower among individuals with loneliness compared to individuals without loneliness (β=-0.07, p < 0.001). Several robustness checks produced similar results. The findings were almost the same for both women and men and varied only slightly between age groups.

Conclusions

We found a statistically significant and relevant disutility associated with social isolation and, even more pronounced, with loneliness. The magnitude of disutilities is similar to those reported for various chronic diseases. Taking into account the high prevalence of social isolation and, in particular, loneliness, the associated burden in terms of quality-adjusted life years (QALY) lost is likely to be tremendous. The results underline the need to take action against the high prevalence of loneliness and social isolation.
A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma
Authors: Cheng Chao , Xu Min , Pan Jinhua , Chen Qiang , Li Kai , Xu Dong , Jing Xiang , Lu Qiang , Yang Hong , Zhao Qiyu , Deng Zhuang , Jiang Tian’an
Published: December 2024

Background

At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors. By high-frequency pulse, the tumor cell membrane can be irretrievably perforated, resulting in the destruction of the intracellular environment, which can preserve important structures in the treatment area. However, there are no randomized controlled clinical trials comparing the efficacy of IRE with traditional local ablation in the treatment of liver cancer.

Aims

This study aims to conduct a randomized controlled clinical trial comparing the efficacy of IRE with RFA in the treatment of liver cancer.

Methods

We will conduct a multicenter, randomized, parallel-controlled non-inferiority clinical trial to compare the efficacy and safety of IRE and RFA for hepatocellular carcinoma (HCC). One hundred and ninety patients with HCC from five academic medical centers will be enrolled. The patients will be randomized into treatment arm (IRE) and control arm (RFA). The primary outcome is the progress -free survival (PFS) and the key secondary outcome is the Overall survival (OS).

Results

Forty-eight patients had been recruited from 5 centers, of which, 33 patients (median age, 59.1 years) with 38 tumors had completed the 1-month follow-up and 21 patients have complete the 3-month follow up, with 2.3 months median follow up period. The mean largest tumor diameter is 3.9 cm. No end point was observed for PFS or OS in both groups, and the complete ablation rate was 100% in both groups. The lesions in the IRE group showed obvious shrinkage 1 month after procedure. One major adverse event (AE) was occurred in the control group.

Conclusion

This is the first randomized controlled clinical trial to compare the clinical effects of IRE and RFA. The preliminary results suggest that both RFA and IRE are effective in the treatment of HCC, which can provide strong evidence for the use of IRE in HCC and provide more options for the treatment of patients with HCC.

Clinical Trial Registration

ClinicalTrials. gov, identifier NCT05451160.
Review of a specialist Rett syndrome clinic from 2003 to the COVID pandemic: clinic experience and carer perspectives
Authors: Sloper Emily , Hunt Megan , Clarke Angus John
Published: December 2024

Background

We have held a ‘trouble-shooting’ clinic for Rett syndrome patients from 2003 until the COVID pandemic in 2020. The clinic was multidisciplinary, including clinical genetics, paediatric neurology, adult learning disability psychiatry and physiotherapy. Access to specialist communication support and eye-gaze equipment was also often available. We have reviewed the files of patients seen in the clinic and conducted a survey of parents’ and carers’ satisfaction with the clinic and their experiences during COVID.

Results

Of the 117 patients seen in the clinic, records were reviewed of 103 (97 female, six male) who attended a total of 123 appointments. The records were unavailable for 14 patients. The most common reasons for referral were assessment of ‘episodes’ of uncertain nature (possibly epileptic, possibly autonomic), the wish for a general review by an experienced team, and questions about the diagnosis. We discuss the nature of the advice we were able to provide and offer some brief case vignettes. We wrote to the parents or carers of all patients seen and 63 respondents were willing to be interviewed about the clinic and their experiences during COVID. Respondents were generally complimentary about the clinic team, emphasising the value of a specialist clinic for those affected by a rare condition. Respondents gave insight into the range of problems experienced during COVID, especially the isolation resulting from the withdrawal of services, demonstrating the value of community support. Some respondents mentioned the shift to remote consultations, which they hoped would continue after COVID for its convenience. However, others talked about how difficult it is in a remote consultation to explain the problems of the affected family member to professionals who do not know the patient or know about Rett syndrome.

Conclusions

Our findings demonstrate the value of a disease-specific clinic provided by staff experienced with the particular rare condition. Meeting the needs of patients with ultra-rare conditions presents additional challenges. We have also found that the shift to holding a virtual clinic during COVID brought the benefit of convenience but was unsatisfactory in other ways, as it makes clinical assessment more difficult and fails to overcome the sense of isolation during a pandemic.
The impact of obesity on sleep, pulmonary and chest wall restriction in Osteogenesis Imperfecta: a pilot study
Authors: De Amicis Ramona , Landoni Vittorio , Bertoli Simona , Sartorio Alessandro , Aliverti Andrea , LoMauro Antonella
Published: December 2024

Introduction

Osteogenesis Imperfecta (OI) is characterised by brittle bones, severe skeletal deformities, low sleep quality, and restricted breathing. We aimed to distinguish how disease and obesity affect these results.

Methods

According to BMI, we considered four groups of peer adults (median age: 35.0 years): 13 subjects affected by moderate or severe OI without obesity (OIno), 14 affected by moderate or severe OI with obesity (OIob), 10 without obesity not affected by OI (OB) and 10 without obesity not affected by OI.

Results

Obstructive Sleep Apnoea Syndrome was diagnosed in 4 OIno (30%) and 9 OIob (64%). Restricted lung pattern (z-score of total lung capacity < − 1.64) was diagnosed in 10 OIno (77%); 9 OIob (65%), and 1 OB (10%) subjects. In the seated position, OIob breathed with reduced tidal volume and higher respiratory rate, resulting in hypoventilation. Both OIno and OIob were characterised by rapid and shallow breathing and lower ribcage expansion (negative in 3 (23%) OIno and 3 (21%) OIob). In the supine position, the ventilatory pattern was similar among the four groups, while both OIno and OIob were characterised by reduced ribcage contribution, which was negative in 6 (46%) OIno, 11 (78%) OIob and 1 (10%) OB.

Conclusions

This is a pilot study on a small sample, the findings and conclusions apply only to this study population. The preliminary results suggest that in subjects with moderate or severe OI per se implies (1) a 30% prevalence of obstructive sleep apnoea syndrome, (2) a restricted lung pattern, (3) a lower ribcage expansion, and (4) rapid and shallow breathing in the seated position. The additional impacts of obesity on OI seem to determine (1) a higher incidence of obstructive sleep apnoea syndrome, (2) hypoventilation in the seated position, and (3) a higher incidence of paradoxical breathing lying supine. Reversing obesity in OI is even more challenging as knowledge of the diet and the physical activity suited for these patients is still scarce.
Myasthenia gravis: understanding treatment patterns and direct medical costs in the Czech Republic
Authors: Donin Gleb , Mothejlová Karla , Horáková Magda , Vohanka Stanislav
Published: December 2024

Background

Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery.

Methods

We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients. Data were analysed for healthcare resource utilization, medication costs, and hospitalization rates related to MG and its complications.

Results

Acetylcholine inhibitors and corticosteroids were widely prescribed, with 91.1% and 75.2% of patients receiving them at least once, respectively. Immunosuppressive therapy was given to 45.2% of patients. Myasthenic crises occurred in 2% of patients, with a mean hospitalization cost of 21,020 EUR, while exacerbations occurred in 9.2% of patients, with lower costs (5,951 EUR per hospitalization). Outpatient intravenous immunoglobulin and plasma exchange therapies incurred additional costs of 20,700 EUR and 18,206 EUR per person-year, respectively. The mean total cost per patient-year was 1,271 EUR, with significant cost differences among patients with different treatment patterns.

Conclusion

This study offers real-world insights into the treatment patterns and associated direct medical costs of MG in the Czech Republic. Myasthenic crises and exacerbations pose considerable cost burdens, while outpatient therapies and common pharmacotherapies are less costly. These findings are vital for healthcare planning, economic evaluation, and resource allocation, potentially leading to enhanced patient care and outcomes.
Cilengitide sensitivity is predicted by overall integrin expression in breast cancer
Authors: Girnius Nomeda , Henstridge Aylin Z. , Marks Benjamin , Yu Jeffrey K. , Gray G. Kenneth , Sander Chris , Zervantonakis Ioannis K. , Luna Augustin
Published: December 2024

Background

Treatment options for triple-negative breast cancer (TNBC) are limited and patients face a poor prognosis. Here, we sought to identify drugs that target TNBC vulnerabilities and understand the biology underlying these responses. We analyzed the Broad Institute DepMap to identify recurrent TNBC vulnerabilities and performed a 45-compound screen on vulnerability-related pathways on a set of up to 8 TNBC cell lines. We identified a subset of cell lines with an ITGAV vulnerability and a differential sensitivity to cilengitide, an integrin inhibitor targeting ITGAV:ITGB3 and ITGAV:ITGB5. Next, we sought to understand cilengitide resistance and response biomarkers. Clinical trials targeting integrins continue enrolling patients, necessitating an understanding of how these drugs affect tumors.

Methods

We combined in vitro assays with computational approaches to systematically explore the differential sensitivity to cilengitide and resistance mechanisms. We tested an additional pan-ITGAV inhibitor (GLPG0187) to determine how generalizable our findings on cilengitide sensitivity might be to integrin inhibition. ITGB4, ITGA3, and ITGA6 knockdown experiments assessed the importance of integrin monomers in cell attachment during cilengitide treatment. Additionally, we explored the role of extracellular matrix (ECM) proteins in cilengitide response by performing cell replating experiments and by culturing on collagen, fibronectin, or laminin coated plates.

Results

We discovered that cell-derived ECM modulates cilengitide sensitivity and exogenous fibronectin addition conferred resistance to all sensitive TNBC cell lines, though fibronectin expression did not correlate with sensitivity. Instead, elevated overall integrin protein levels, not specific integrins, in TNBC cells positively correlated with resistance. This suggested that high pan-integrin expression promotes cilengitide resistance. Thus, we tested cilengitide in six luminal breast cancer cell lines (which have low integrin levels); all were sensitive. Also, pan-ITGAV inhibitor, GLPG0187, showed the same sensitivity profile across our TNBC cell lines, suggesting our findings apply to other integrin inhibitors.

Conclusions

Integrin inhibitors are appealing candidates to pursue as anti-cancer drugs because they are generally well-tolerated, but their efficacy is mixed, possibly due to the absence of predictive markers. Cilengitide induces death in breast cancer cells with low integrin abundance, where complementary ECM promotes survival. Thus, integrin inhibition in breast cancer warrants further study.
Integrative in-silico and in-vitro analysis of taurine and vitamin B12 in modulating PPARγ and Wnt signaling in hyperhomocysteinemia-induced osteoporosis
Authors: Adhish Mazumder , Manjubala I.
Published: December 2024

Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ’s key helices H3, H4/5, H11, and H12. In-vitro experiments further supported these results, demonstrating that taurine protects against oxidative damage, enhances bone mineralization, and reduces the expression levels of PPARγ, while also downregulating negative regulators of the Wnt signaling pathway, such as SOST and DKK1. Homocysteine, on the other hand, was observed to increase the expression of these regulators and impair bone formation. Vitamin B12 was included in the study due to its known role in mitigating hyperhomocysteinemia, a condition linked to impaired bone health and reduced taurine levels. While vitamin B12 alone demonstrated some beneficial effects, it did not achieve the same level of efficacy as taurine. However, a combination of taurine and vitamin B12 showed greater efficacy in ameliorating hyperhomocysteinemia-induced osteoporosis. Overall, this study highlights taurine’s therapeutic potential in counteracting the adverse effects of hyperhomocysteinemia on bone health and underscores the need for further research into taurine’s mechanisms in osteoporosis treatment.

Graphical abstract
Leucinostatins target Plasmodium mitochondria to block malaria transmission
Authors: Niu Guodong , Wang Xiaohong , Li Jun
Published: December 2024

Background

Malaria remains a critical disease. Leucinostatins from the fungus Purpureocillium lilacinum inhibited the transmission of Plasmodium falciparum to mosquitoes via contact.

Methods

Here, we modified the leucinostatin B (LB) C-terminus to make derivatives and examined their inhibition against malaria transmission to mosquitoes. Fluorescence-labeled leucinostatins were incubated with intact gametocytes and were examined under microscopy to detect the targets of leucinostatins. We also analyzed leucinostatins’ general cytotoxicity and hemolysis.

Results

The results showed that the derivatives with –H, –CH3, –Atto495, and –Biotin at C-terminus had EC50 of 1.5 nM, 0.2 nM, 4.2 nM, and 42 nM, respectively. Atto495 and biotin are similar in size and much bigger than -CH3 and -H. Based on reverse-phase HPLC elution time, we found that LB-Biotin had much higher hydrophobicity than the others, consistent with its lowest malaria transmission-blocking activity. Fluorescence microscopy showed that LB-Atto495 colocalized with mitochondria inside intact P. falciparum gametocytes. We found that leucinostatin A significantly inhibited the proliferation of human nucleated cells with IC50 around 47 nM and it did not lyse erythrocytes at 100 μM.

Conclusions

We conclude that the leucinostatins pass through the cytoplasmic membrane without lysing cells and interact with molecules specifically in mitochondria. Therefore, leucinostatins should be ideal inhibitors against mobile parasites, such as ookinetes and sporozoites, during malaria transmission.

Graphical Abstract
Task-aware image quality estimators for face detection
Authors: Singh Praneet , Reibman Amy R.
Published: December 2024

Understanding the quality of face images plays a critical role in enhancing the efficiency of end-to-end face analytics systems, which perform tasks such as face detection, alignment, and recognition in a sequential manner. Recently, the development of face quality estimators (QEs) specifically for face recognition has received significant attention. However, in end-to-end face analytics systems, the performance of the face detector directly affects the face recognizer. Thus, assessing the suitability of an image for face detection before passing it on to face recognition can improve the resource utilization in such systems. In this research, we first introduce the detectability (DET) score of an image, a novel quality metric that links image quality to face detection performance. We use this DET score to design two novel QEs for face detection: supervised face detection quality estimator (SFDQE) and unsupervised face detection quality estimator (UFDQE). We also propose the mAP vs. reject protocol (mvR), a systematic evaluation protocol for assessing QEs in the context of face detection. In our experiments, we illustrate the effectiveness of SFDQE and UFDQE in determining the suitability of an image for face detection. Furthermore, we show the ability of our QEs to generalize; each is a powerful tool for image quality estimation in general object detection scenarios.
Response of circulating fatty acid binding protein 4 concentration to low-intensity acute aerobic exercise is amplified in an exercise duration-dependent manner in healthy men
Authors: Numao Shigeharu , Uchida Ryota , Nakagaichi Masaki
Published: December 2024

Background

Circulating fatty acid-binding protein 4 (FABP4) influences cardiovascular disease and glucose metabolism. Acute aerobic exercise increases circulating FABP4 concentrations, but the factors underlying this effect in humans are unclear. We investigated the effect of exercise duration on circulating FABP4 concentrations in healthy men.

Methods

This randomized crossover study enrolled healthy young men randomly assigned to two trials, short-duration (SE) and long-duration (LE) aerobic exercises trials. Both involved acute aerobic exercise followed by 60 min of bed rest. The exercise intensity was the same (40% peak oxygen uptake); however, the duration was 40 and 70 min for the SE and LE trials, respectively. Venous blood samples were collected to measure hormones, metabolites, and FABP4 concentrations.

Results

Twelve healthy young men completed both trials. Changes in hormone levels did not differ significantly between the SE and LE trials (p > 0.05). However, the circulating FABP4 concentration increased significantly only in the LE trial immediately after exercise (p = 0.018). It increased significantly 30–60 min post-exercise in both the SE and LE trials (p < 0.018), with the extent of the increase being significantly higher in the LE trial than in the SE trial (p < 0.001). In each trial, the total incremental area under the curve of circulating FABP4 concentration was significantly positively correlated with body fat percentage (SE trial: rs = 0.699, p = 0.019; LE trial: rs = 0.643, p = 0.024).

Conclusion

Our findings suggest that exercise duration is associated with the magnitude of increased FABP4 secretion into the blood circulation. Body fat accumulation may also be involved in the magnitude of FABP4 secretion induced by acute aerobic exercise.

Trial registration

The study was pre-registered with the University Hospital Medical Information Network Center (UMIN), a clinical trial registration system (ID: UMIN000051068).
In vivo evaluation of selenium-tellurium based nanoparticles as a novel treatment for bovine mastitis
Authors: Kosaristanova Ludmila , Bytesnikova Zuzana , Fialova Tatiana , Pekarkova Jana , Svec Pavel , Ondreas Frantisek , Jemelikova Vendula , Ridoskova Andrea , Makovicky Peter , Sivak Ladislav , Dolejska Monika , Zouharova Monika , Slama Petr , Adam Vojtech , Smerkova Kristyna
Published: December 2024

Background

Bovine mastitis is one of the main causes of reduced production in dairy cows. The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus, whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses. Therefore, it is important to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains. In this study, novel selenium-tellurium based nanoparticles (SeTeNPs) were synthesized and characterized. Their antibacterial activity and biocompatibility were evaluated both in vitro and in vivo using a bovine model. A total of 10 heifers were divided into experimental and control groups (5 animals each). After intramammary infection with methicillin resistant S. aureus (MRSA) and the development of clinical signs of mastitis, a dose of SeTeNPs was administered to all quarters in the experimental group.

Results

Based on in vitro tests, the concentration of 149.70 mg/L and 263.95 mg/L of Se and Te, respectively, was used for application into the mammary gland. Three days after SeTeNPs administration, MRSA counts in the experimental group showed a significant reduction (P < 0.01) compared to the control group. The inhibitory effect observed within the in vitro experiments was thus confirmed, resulting in the suppression of infection in animals. Moreover, the superior biocompatibility of SeTeNPs in the organism was demonstrated, as the nanoparticles did not significantly alter the inflammatory response or histopathology at the site of application, i.e., mammary gland, compared to the control group (P > 0.05). Additionally, the metabolic profile of the blood plasma as well as the histology of the main organs remained unaffected, indicating that the nanoparticles had no adverse effects on the organism.

Conclusions

Our findings suggest that SeTeNPs can be used as a promising treatment for bovine mastitis in the presence of resistant bacteria. However, the current study is limited by its small sample size, making it primarily a proof of the concept for the efficacy of intramammary-applied SeTeNPs. Therefore, further research with a larger sample size is needed to validate these results.
Limbic system synaptic dysfunctions associated with prion disease onset
Authors: Foliaki Simote T. , Groveman Bradley R. , Dews Emmett A. , Williams Katie , El Soufi Hadil , Schwarz Benjamin , Leung Jacqueline M. , Schneider Christine A. , Schwartz Cindi L. , Bohrnsen Eric , Kimzey Cole D. , Race Brent , Haigh Cathryn L.
Published: December 2024

Misfolding of normal prion protein (PrPC) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes. Cognition and mood are linked to the neurophysiology of the limbic system. Little is known about how the disease affects the synaptic activity in brain parts associated with this system. We hypothesize that the dysfunction of synaptic transmission in the limbic regions correlates with the onset of reduced cognition and behavioral deficits. Here, we studied how prion infection in mice disrupts the synaptic function in three limbic regions, the hippocampus, hypothalamus, and amygdala, at a pre-clinical stage (mid-incubation period) and early clinical onset. PrD caused calcium flux dysregulation associated with lesser spontaneous synchronous neuronal firing and slowing neural oscillation at the pre-clinical stage in the hippocampal CA1, ventral medial hypothalamus, and basolateral amygdala (BLA). At clinical onset, synaptic transmission and synaptic plasticity became significantly disrupted. This correlated with a substantial depletion of the soluble prion protein, loss of total synapses, abnormal neurotransmitter levels and synaptic release, decline in synaptic vesicle recycling, and cytoskeletal damage. Further, the amygdala exhibited distinct disease-related changes in synaptic morphology and physiology compared with the other regions, but generally to a lesser degree, demonstrating how different rates of damage in the limbic system influence the evolution of clinical disease. Overall, PrD causes synaptic damage in three essential limbic regions starting at a preclinical stage and resulting in synaptic plasticity dysfunction correlated with early disease signs. Therapeutic drugs that alleviate these early neuronal dysfunctions may significantly delay clinical onset.
Dietary 5-hydroxytryptophan supplementation improves growth performance and intestinal health of weaned piglets
Authors: Xia Yinzhao , Peng Xie , Mao Jiani , Luo Ju , Li Huifeng , Ma Dengjun , Yang Zhenguo
Published: December 2024

This study investigated the effects of dietary 5-hydroxytryptophan (5-HTP) supplementation on growth performance, apparent total tract digestibility (ATTD), blood profile, intestinal morphology, transcriptomics, and microbial composition in weaned piglets. A total of twenty-four 28-day-old weaned piglets (Landrace × Large Yorkshire, 8.28 ± 1.09 kg) were randomly divided into 3 dietary treatments with 8 replicates. The dietary treatments include basal diet (CON), CON diet containing 250 or 500 mg/kg 5-HTP. The results revealed that supplementation with 250 mg/kg 5-HTP significantly increased (P < 0.05) the average daily gain (ADG) and resulted in a lower (P < 0.05) feed conversion ratio (FCR), while also decreased (P < 0.05) the diarrhea rate compared to the CON group. The ATTD of crude protein (CP) was lower in the 500 mg/kg group (P < 0.05) compared with the 250 mg/kg group. Furthermore, supplementation with 5-HTP led to significantly increased (P < 0.05) plasma albumin (ALB) and total protein (TP). In addition, supplementation with 5-HTP, particularly in the 250 mg/kg group, significantly increased (P < 0.05) serum serotonin (5-HT), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, and improved the ratio of villus height to crypt depth in the jejunum and ileum. The transcriptomic analysis revealed that the majority of differentially expressed genes (DEGs) induced by 5-HTP were related to digestion and immunity in the ileum, and 5-HTP enhanced (P < 0.05) intestinal glucose transporter 2 (GLUT2), solute carrier family 1 member 1 (SLC1A1) and solute carrier family 7 member 7 (SLC7A7) mRNA expression in weaned piglets. Furthermore, supplementation with 250 mg/kg 5-HTP increased (P < 0.05) abundance of Firmicutes, Actinobacteriota, Lachnospiracea, Ruminococcaceae and Megasphaera and decreased (P < 0.05) abundance of Spirochaetes and Treponema. Collectively, the study demonstrated that 5-HTP supplementation, particularly at 250 mg/kg, positively impacted growth performance, gut health, and microbiome composition in weaned piglets. These findings suggest the potential of using 5-HTP as a dietary supplement to enhance the health and productivity of weaned piglets.
Causal association between metabolites and age-related macular degeneration: a bidirectional two-sample mendelian randomization study
Authors: Liu Zhen-Yu , Zhang Hang , Sun Xiu-Li , Liu Jian-Ying
Published: December 2024

Background

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly population. Accumulating evidence has revealed the possible association between metabolites and AMD. This study aimed to assess the effect of plasma metabolites on AMD and its two subtypes using a bidirectional two-sample Mendelian randomization approach.

Methods

The causality between plasma metabolites and AMD was assessed by a bidirectional two-sample Mendelian randomization (MR) analysis using the genome-wide association studies (GWAS) summary statistics of 1400 genetically determined metabolites (GDMs) and AMD. For this MR analysis, inverse variance weighted (IVW) was used as the primary method, with weighted median, MR-Egger, weighted mode, and simple mode as supplementary methods to examine the causality. MR-Egger intercept, Cochran’s Q, and MR-PRESSO test were employed to evaluate possible pleiotropy and heterogeneity.

Results

The results of IVW showed significant causal associations between 13 GDMs and AMD. 1-stearoyl-GPE (18:0), androstenediol (3β,17β) monosulfate, stearoyl sphingomyelin (d18:1/18:0), xylose, and X-11,850 exhibited a protective effect on AMD, while gulonate and mannonate increased the risk of AMD. 1-stearoyl-GPE (18:0) and X-11,850 exhibited protective effects on dry AMD. DHEAS, 1-stearoyl-GPE (18:0), 5α-androstan-3β,17β-diol disulfate, xylose, androstenediol (3β,17β) monosulfate, and N2-acetyl, N6, N6-dimethyllysine exhibited a protective effect on wet AMD, while succinimide, 16a-hydroxy DHEA 3-sulfate, and X-13,553 increased the risk of wet AMD. Horizontal pleiotropy and heterogeneity did not distort the causal estimates. In the reverse MR analysis, AMD reduced the androstenediol (3β,17β) monosulfate level, and increased the stearoyl sphingomyelin(d18:1/18:0) level.

Conclusion

This study supported the effect of plasma metabolites on AMD, providing novel insights for clinical diagnosis and prevention strategy.
Surrogate model-driven multi-parameter optimization of four distinct combustion chambers in a four-stroke diesel engine
Authors: Punukollu Raviteja , Pasham Nithish Reddy , Baliga Navya
Published: December 2024

The reduction of emissions from compression ignition (CI) engines is a major area of research in response to increasing environmental regulations and the need for cleaner energy solutions. This study presents a comprehensive computational fluid dynamics (CFD) study on a sector combustor of a CI engine, focusing on the effects of injection parameters and combustion chamber design on emissions. Four distinct combustion chamber designs—rectangular, shallow depth combustion chamber (SCC), hemispherical combustion chamber (HCC), and toroidal combustion chamber (TCC)—were analyzed. Key parameters such as tumble ratio, swirl ratio, cross-tumble ratio, soot formation, and NOx emissions were observed and compared. This study uniquely combines a comparative analysis of these combustion chamber designs with an advanced optimization of injection parameters using a Multi-Objective Genetic Algorithm (MOGA), an approach not widely explored in previous CI engine research. Additionally, response surface methodology (RSM) and design of experiments (DOE) were employed to gain further insights into the influence of individual variables, providing a thorough understanding of their impact on emissions and combustion performance. The results show that SCC chambers are most effective at reducing soot emissions, while TCC designs are better at lowering NOx emissions. Later injection timings showed a 450% decrease in soot rate compared to earlier timings, whereas NOx has significantly benefited from earlier injections, which presented about a 1600% difference in the NOx production when compared to late injections. These findings offer valuable contributions to the design of cleaner and more efficient CI engines, with the potential to significantly impact future engine development.
Cisnormative Language and Erasure of Trans* and Genderqueer Student Representation in Biology Education Research
Authors: Coburn Kaitlyn , Troy Kris , Busch Carly A. , Barber-Choi Naomi , Bonney Kevin M. , Couch Brock , García-Ojeda Marcos E. , Hutto Rachel , Famble Lauryn , Flagg Matt , Gladding Tracy , Kowalkowski Anna , Landaverde Carlos , Lo Stanley M. , MacLeod Kimberly , Mbogo Blessed , Misheva Taya , Trinh Andy , Vides Rebecca , Wieboldt Erik , Gormally Cara , Maloy Jeffrey
Published: December 2024

This study characterizes how sex and gender data have been collected, analyzed, and described in papers published in CBE-LSE over a five year period. Findings demonstrate the prevalence of cisnormative language and methodologies in biology education research. Suggestions are given for being more inclusive of trans* identities in future work.
Real-World Safety and Health Care Resource Utilization of Teclistamab Under an Outpatient Model for Step-Up Dosing Administration
Authors: Sandahl Tyler B. , Soefje Scott A. , Fonseca Rafael , Ailawadhi Sikander , Parrondo Ricardo , Lin Dee , Wu Bingcao , Calay Ediz S. , Silvert Eli , Kim Nina , Carpenter Corinne , Wagner Tyler E. , Fowler Jessica , Hester Laura , Rangarajan Nivedita , Murugadoss Karthik , Marshall Alexander , Stoy Patrick , Gifkins Dina , Lin Yi , Kumar Shaji
Published: December 2024

PURPOSE

Teclistamab is initiated with a step-up dosing (SUD) schedule to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Early teclistamab users commonly received SUD in a hospital setting. This study aimed to evaluate safety and health care resource utilization (HRU) in real-world patients with multiple myeloma who initiated teclistamab SUD in an outpatient setting.

METHODS

This was a retrospective study using Mayo Clinic's electronic medical records from October 26, 2022, to October 31, 2023. Patient characteristics were summarized for all patients treated with teclistamab and separately for patients who started SUD outpatient. SUD pattern, safety, HRU, and post-SUD dosing schedule were described in patients with complete SUD.

RESULTS

At data cutoff, 65 patients received ≥1 teclistamab dose, including 58 patients who initiated SUD outpatient (median age, 69.2 years; male, 63.8%; White, 89.7%). Among 57 patients who completed SUD in an outpatient setting, all received premedications on the days of teclistamab administrations per label recommendation; 18 (31.6%) developed CRS (13 grade 1, four grade 2, and one grade 4) and two developed ICANS (one each with grade 2 and 4). All CRS and ICANS resolved with supportive care and all patients continued treatment. Eighteen patients were admitted to the hospital for CRS treatment, with a median CRS-related hospital stay of 2 days per admission. Most (60%) doses during SUD required <1 hour clinic time between administration and checkout. Post-SUD, clinic time for treatment doses decreased to <30 minutes for most doses (82%).

CONCLUSION

Outcomes of this study support outpatient administration as a safe and feasible option for teclistamab SUD to potentially reduce HRU and improve patient experiences.
“This Hyeh Is a Mighty Cruel Country”: Owen Wister's The Virginian, the Western Genre, and the Question of Animal Cruelty
Authors: Evron Nir
Published: December 2024

Owen Wister's 1902 The Virginian is often described as the first proper Western, yet in stark contrast to the popular genre it helped establish, Wister's novel is continuously preoccupied with the question of animal cruelty. To explain the novel's solicitous concern with animal suffering, as well as the later Western's blanket indifference to this theme, the essay sets The Virginian in the context of a profound late nineteenth-century transformation in the way Americans experienced and understood animals. This transformation, it argues, was occasioned by three important cultural-economic developments: the removal of livestock from the American city, the postbellum incorporation of America's food industry, and the rapid expansion of middle-class pet ownership. Wister's novel, the essay concludes, anticipates this cultural realignment with respect to animals and offers (even if only intermittently) an alternative moral horizon, one that the midcentury Western and the society it catered to would largely ignore.
Automated computational analysis and modeling for the operational improvement of air quality sensor networks in real time
Authors: Μπαγκής Ευάγγελος
Published: December 2024

Η παρούσα διατριβή προάγει την ανάπτυξη και τη διαχείριση των δικτύων αισθητήρων χαμηλού κόστους για την παρακολούθηση της ποιότητας του αέρα μέσω νέων τεχνικών βαθμονόμησης που βασίζονται στη μηχανική μάθηση. Συνδυάζοντας υπολογιστικά πειράματα και μια ολοκληρωμένη ανασκόπηση των τεχνικών και τεχνολογιών αιχμής, η έρευνα εντοπίζει και αντιμετωπίζει κρίσιμους παράγοντες που επηρεάζουν τη λειτουργικότητα, την ακρίβεια και την επεκτασιμότητα του δικτύου. Αξιοποιήθηκαν πολυαισθητήριες συσκευές, ενσωματώνοντας αισθητήρες θερμοκρασίας και υγρασίας παράλληλα με μετρήσεις ποιότητας αέρα, βελτιώνοντας την ακρίβεια μέτρησης. Οι βασικές καινοτομίες περιλαμβάνουν τη μέθοδο “στατιστικά καθοδηγούμενος νευρωνικός καταμερισμός”, η οποία βελτιώνει τη χρονική ανάλυση μέσω του διαχωρισμού δεδομένων ποιότητας αέρα μεικτής πηγής, τη μέθοδο της “χωρικά συνεχούς μάθησης”, μια προσέγγιση βαθμονόμησης σε πραγματικό χρόνο που προσαρμόζεται στα μεταβαλλόμενα περιβαλλοντικά μοτίβα σε διαφορετικά σημεία του χώρου και το “καθολικό σχήμα βαθμονόμησης” (σε όλο το δίκτυο) για ταχύτερη εκμάθηση, προσαρμοστική εισαγωγή κόμβων στο δίκτυο και αυξημένη ακρίβεια βαθμονόμησης. Επιπλέον, διευκολύνει την επεκτασιμότητα, επιτρέποντας τη γενίκευση των μοντέλων βαθμονόμησης σε πολλαπλές τοποθεσίες, μειώνοντας την ανάγκη για συχνή επαναβαθμονόμηση. Ένα ισχυρό επιχειρησιακό σύστημα εκτίμησης της ποιότητας του αέρα θα πρέπει να υποστηρίζεται από αυτές τις καινοτομίες, δίνοντας έμφαση στη στρατηγική τοποθέτηση αισθητήρων και στην προσαρμοστική βαθμονόμηση. Χρησιμοποιώντας προηγμένα υπολογιστικά συστήματα όπως το υβρική στοίβαξη γενετικού αλγορίθμου για την ενοποίηση μοντέλων και τη χωρο-χρονική διασταυρούμενη επικύρωση αυτή η έρευνα επιτρέπει τη ρεαλιστική αξιολόγηση του μοντέλου υπό δυναμικές χωροχρονικές συνθήκες. Με έμφαση στην ευρωστία του μοντέλου, η μελέτη διερευνά τεχνικές για το χειρισμό μοτίβων στα δεδομένα ποιότητας αέρα, συμπεριλαμβανομένης της αλλαγής της στατιστικής συμπεριφοράς των μεταβλητών, της χωροχρονικής αυτοσυσχέτισης και την καθυστέρηση στην λήψη δεδομένων αναφοράς, επιτρέποντας βιώσιμη μακροχρόνια λειτουργία δικτύων παρακολούθησης της ποιότητας του αέρα. Ενσωματώνοντας τον καταλογισμό με νευρωνικά δίκτυα γράφων για την ανακατασκευή των ελλειπουσών τιμών και την πρόγνωση της συγκέντρωσης των ρύπων σε πολλαπλές τοποθεσίες ταυτόχρονα, η έρευνα γεφυρώνει τις μεθοδολογίες μηχανικής μάθησης με την πρακτική ανάπτυξη δικτύων παρακολούθησης της ποιότητας του αέρα. Τα αποτελέσματα παρουσιάζουν ένα θεμελιώδες πλαίσιο για τη διαχείριση της ποιότητας του αέρα σε αστικά περιβάλλοντα, καθιερώνοντας τα δίκτυα χαμηλού κόστους ως μια επεκτάσιμη, οικονομικά αποδοτική εναλλακτική λύση στα παραδοσιακά δίκτυα παρακολούθησης. Οι βασικές συνεισφορές περιλαμβάνουν βελτίωση της χρονικής ανάλυσης, προσαρμοστική βαθμονόμηση και επιχειρησιακά εργαλεία που ενισχύουν τη μακροζωία και την ακρίβεια των μοντέλων βαθμονόμησης σε ετερογενή, ως προς τις τεχνολογίες μέτρησης, δίκτυα αισθητήρων.
Case Report: Atypical post-COVID Cogan's syndrome
Authors: Mezri Sameh , Zitouni Chaima , Sleimi Wafa , Bouzidi Mayssa , Sameh Sayhi
Published: December 2024

Background Cogan’s syndrome is a rare autoimmune disorder characterized by ocular inflammation, vestibulocochlear dysfunction, and systemic vasculitis. Case Presentation We report a 28-year-old female who experienced decreased visual acuity and ocular redness one month after a COVID-19 infection, with ophthalmological signs linked to keratitis, uveitis and retinal vasculitis. Two weeks later, she developed vertigo, tinnitus, and sudden hearing loss, leading to a diagnosis of Cogan’s disease. The patient received corticosteroid therapy, resulting in regression of ophthalmological signs, but progressed to complete deafness. One month later, she presented with lymphocytic meningitis and high intracranial pressure, which improved under treatment. The patient later received cochlear implants. Objective This case report aims to highlight an atypical presentation of Cogan’s syndrome with neurological involvement following a COVID-19 infection. This case contributes to the limited literature on such presentations. Conclusion Our case is one of only two reported instances of Cogan’s syndrome presenting with neurological signs post-COVID-19 infection, underscoring the rarity and complexity of this condition.
Virtual game-based learning environments to promote self-regulated learning skills in foreign language learners
Authors: Noriega Cortes Maira Alejandra , Carreño-Bolivar Laura
Published: December 2024

Background This mixed-method action research study explores the impact of a gamified virtual learning tool on elementary students’ self-regulated learning (SRL) skills in English language acquisition. Despite the acknowledged importance of SRL in educational contexts, limited research exists on its development among young learners. The present study is one of the products of the academic unit project “Key Factors and Essential Elements for a Comprehensive Model of Bilingual Education: A Multidimensional Approach for Diverse Contexts and Areas of Knowledge” sponsored by the School of Education at Universidad de La Sabana, institution where the first author conducted her master’s studies, and the corresponding author is a professor and main researcher of the of the academic unit project. Method Six students aged 8-10 participated in the study. Data were collected through semi-structured observations and pre- and post-questionnaires. The tool was designed based on Zimmerman’s SRL model and included tasks structured through gamification elements. For the purpose of quantitative data analysis, descriptive statistics were used; as for qualitative data, thematic analysis was the chosen approach. Results The results revealed that guided use of the gamified tool significantly enhanced students’ use of SRL strategies, particularly in goal setting, monitoring progress, and reflecting on learning outcomes. Students demonstrated increased motivation, engagement, and confidence, although explicit instruction was required to maximize the tool’s benefits. The usability of the tool was rated positively, with participants highlighting its effectiveness for language learning and SRL skill development. Conclusions The study concludes that gamified virtual environments can effectively promote SRL skills in young language learners by fostering motivation and engagement. However, for optimal outcomes, such tools should be supplemented with explicit instruction in SRL strategies. This research contributes to understanding the integration of gamified tools in elementary education, highlighting their potential to develop foundational skills essential for lifelong learning.
EAST-WEST AND MUSLIM PHILOSOPHY CULTURE OF N.K. ROERICH
Authors: Salmorbekova R. B.
Published: December 2024

This article examines East-West philosophy and the influence of Muslim culture on the thinking and ideas of Nicholas Roerich. The author explores the connection between the philosophical ideas of N.K. Roerich and his knowledge of Muslim culture, especially in the context of his travels and participation in Islamic cultural traditions. The article draws attention to Roerich's research on the East, in particular to his study of the specifics and fundamental concepts of Islamic culture. The author analyzes how Roerich interacted with the philosophical and spiritual teachings of the Islamic world and how this influenced his thinking and key ideas. In conclusion, the article draws conclusions about the significance of the influence of Muslim culture on the philosophy and thinking of Nicholas Roerich. It establishes a connection between his ideas about Eastern wisdom and the importance of mutual understanding between East and West. The abstract of this article provides an overview of its content and main thematic areas, providing readers with a summary of key arguments supported by historical research and documentary sources.