bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis
Authors: Jiang Yuxiong , Huang Dawei , Chen Qianyu , Yu Yingyuan , Hu Yifan , Wang Yu , Chen Rongfen , Yao Lingling , Zhong Xiaoyuan , Kong Luyang , Yu Qian , Lu Jiajing , Li Ying , Shi Yuling
Published: January 2024

Background

Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement.

Objective

This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response.

Methods

A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively.

Results

The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670–0.773) and validation cohort (AUC, 0.715; 95% CI 0.665–0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications.

Conclusions

This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility.

Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256.
The occurrence and development mechanisms of esophageal stricture: state of the art review
Authors: Yang Fang , Hu Yiwei , Shi Zewen , Liu Mujie , Hu Kefeng , Ye Guoliang , Pang Qian , Hou Ruixia , Tang Keqi , Zhu Yabin
Published: January 2024

Background

Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention.

Methods

A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles.

Results

Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures.

Conclusion

The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.
Outcomes of antiretroviral treatment for 0-14-year-old children living with HIV in Ganzhou, China, 2006–2023
Authors: Zeng Ting , Chen Xin , Zhang Xiao-Yi , Lian Chao-Xian , Yang Rong-Rong , Yu Li-Ling , Liao Xiao-Kang , Huang Dan-Dan , Zhang Yu-Ning , Cao Hong-Min
Published: January 2024

Background

Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART.

Methods

All 0-14-year-old CLHIV admitted to the Ganzhou Center for Disease Control and Prevention from January 2006 to June 2023 were included retrospectively. The information of treatment regimens, disease progression, and laboratory tests of the patients under ART were used to explore the outcomes and impacts of long-term ART. The normality of all the data was tested by the Shapiro-Wilk test.

Results

From 2006 to 2023, 18 CLHIV were reported in Ganzhou. Among them, 11 received ART and were followed up for 60.0 ± 48.4 months. After receiving ART, the median viral load of them decreased from 89,600 copies/ml to 22 copies/ml (P = 0.007), the median CD4+ T cell count increased from 380.7 cells/µL to 661.9 cells/µL (P = 0.028), and the median CD8+ T cell count decreased from 1065.8 cells/µL to 983.3 cells/µL (P = 0.584). The laboratory test results regarding liver function, renal function, blood cell count, and glucolipid metabolism tended to be within normal reference ranges, and the mean height-for-age z-score and weight-for-age z-score increased. However, all the three CLHIV who received cotrimoxazole developed pneumocystis carinii pneumonia, upper respiratory infection, skin lesions, bacterial pneumonia and/or thrush; the mean body-mass-index-for-age z-score decreased from 0.52 to -0.63.

Conclusion

For CLHIV, ART could effectively inhibit the replication of HIV and improve the immune function of patients. More studies that focus on ART in CLHIV are urgently needed.
Experiences of people living with HIV in low- and middle-income countries and their perspectives in self-management: a meta-synthesis
Authors: Dadi Tegene Legese , Wiemers Anja M. C. , Tegene Yadessa , Medhin Girmay , Spigt Mark
Published: January 2024

Introduction

Availability of anti-retroviral treatment has changed HIV in to a manageable chronic disease, making effective self-management essential. However, only a few studies in low- and middle-income countries (LMICs) reported experiences of people living with HIV (PLWH) on self-management.

Methods

This meta-synthesis of qualitative studies investigated perspectives of PLWH in LMICs on self-management. Various databases, including PubMed, EMBASE, EBSCO, and CINHAL, were searched through June 2022. Relevant additional articles were also included using cross-referencing of the identified papers. We used a thematic synthesis guided by the "Model of the Individual and Family Self-Management Theory" (IFSMT).

Result

PLWH in LIMICs experience a variety of challenges that restrict their options for effective self-management and compromises their quality of life. The main ones include: misconceptions about the disease, poor self-efficacy and self-management skills, negative social perceptions, and a non-patient-centered model of care that reduces the role of patients. The experiences that influenced the ability to practice self-management are summarized in context (the condition itself, physical and environmental factors, individual and family factors) and process factors (knowledge and beliefs, relationship with the health care worker, self-regulation skills and abilities, and social facilitation). Context and process greatly impacted quality of life through the self-management practices of the patients.

Conclusion and recommendation

PLWH encounter multiple challenges, are not empowered enough to manage their own chronic condition, and their needs beyond medical care are not addressed by service providers. Self-management practice of these patients is poor, and service providers do not follow service delivery approaches that empower patients to be at the center of their own care and to achieve an effective and sustainable outcome from treatment. These findings call for a comprehensive well thought self-management interventions.
ZNF148 inhibits HBV replication by downregulating RXRα transcription
Authors: Yao Xinyan , Xu Kexin , Tao Nana , Cheng Shengtao , Chen Huajian , Zhang Dapeng , Yang Minli , Tan Ming , Yu Haibo , Chen Peng , Zhan Zongzhu , He Siyi , Li Ranran , Wang Chunduo , Wu Daiqing , Ren Jihua
Published: January 2024

Background

Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study.

Methods

HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148’s impact on HBV in vivo was investigated using an established rcccDNA mouse model.

Results

ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model.

Conclusions

ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.
Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression
Authors: Meng Qingfei , Sun Huihui , Zhang Yanghe , Yang Xiangzhe , Hao Shiming , Liu Bin , Zhou Honglan , Xu Zhi-Xiang , Wang Yishu
Published: January 2024

Background

Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) is identified as an oncogene involved in multiple regulation of tumor progression, but specific mechanisms remain unclear in cervical cancer. Lactate-mediated lactylation modulates protein function. Whether DCBLD1 can be modified by lactylation and the function of DCBLD1 lactylation are unknown. Therefore, this study aims to investigate the lactylation of DCBLD1 and identify its specific lactylation sites. Herein, we elucidated the mechanism by which lactylation modification stabilizes the DCBLD1 protein. Furthermore, we investigated DCBLD1 overexpression activating pentose phosphate pathway (PPP) to promote the progression of cervical cancer.

Methods

DCBLD1 expression was examined in human cervical cancer cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of DCBLD1 on the progression of cervical cancer. Untargeted liquid chromatography-tandem mass spectrometry (LC–MS/MS) metabolomics studies were used to characterize DCBLD1-induced metabolite alterations. Western blot, immunofuorescence and transmission electron microscopy were performed to detect DCBLD1 degradation of G6PD by activating autophagy. Chromatin immunoprecipitation, dual luciferase reporter assay for detecting the mechanism by which lactate increases DCBLD1 transcription. LC–MS/MS was employed to verify specific modification sites within the DCBLD1 protein.

Results

We found that lactate increased DCBLD1 expression, activating the PPP to facilitate the proliferation and metastasis of cervical cancer cells. DCBLD1 primarily stimulated PPP by upregulating glucose-6-phosphate dehydrogenase (G6PD) expression and enzyme activity. The mechanism involved the increased enrichment of HIF-1α in the DCBLD1 promoter region, enhancing the DCBLD1 mRNA expression. Additionally, lactate-induced DCBLD1 lactylation stabilized DCBLD1 expression. We identified DCBLD1 as a lactylation substrate, with a predominant lactylation site at K172. DCBLD1 overexpression inhibited G6PD autophagic degradation, activating PPP to promote cervical cancer progression. In vivo, 6-An mediated inhibition of G6PD enzyme activity, inhibiting tumor proliferation.

Conclusions

Our findings revealed a novel post-translational modification type of DCBDL1, emphasizing the significance of lactylation-driven DCBDL1-mediated PPP in promoting the progression of cervical cancer.

Graphical Abstract

Schematic illustration of DCBLD1-induced G6PD-mediated reprogramming of PPP metabolism in promoting cervical cancer progression.
Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc
Authors: Antonello Alice , Bergamin Riccardo , Calonaci Nicola , Househam Jacob , Milite Salvatore , Williams Marc J. , Anselmi Fabio , d’Onofrio Alberto , Sundaram Vasavi , Sosinsky Alona , Cross William C. H. , Caravagna Giulio
Published: January 2024

Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated using single-cell data and simulations, is applied to over 4000 TCGA and PCAWG samples, and is incorporated into the validation process for the clinically accredited bioinformatics pipeline at Genomics England. CNAqc is designed to support automated quality control procedures for tumor somatic data validation.
RExPRT: a machine learning tool to predict pathogenicity of tandem repeat loci
Authors: Fazal Sarah , Danzi Matt C. , Xu Isaac , Kobren Shilpa Nadimpalli , Sunyaev Shamil , Reuter Chloe , Marwaha Shruti , Wheeler Matthew , Dolzhenko Egor , Lucas Francesca , Wuchty Stefan , Tekin Mustafa , Züchner Stephan , Aguiar-Pulido Vanessa
Published: January 2024

Expansions of tandem repeats (TRs) cause approximately 60 monogenic diseases. We expect that the discovery of additional pathogenic repeat expansions will narrow the diagnostic gap in many diseases. A growing number of TR expansions are being identified, and interpreting them is a challenge. We present RExPRT (Repeat EXpansion Pathogenicity pRediction Tool), a machine learning tool for distinguishing pathogenic from benign TR expansions. Our results demonstrate that an ensemble approach classifies TRs with an average precision of 93% and recall of 83%. RExPRT’s high precision will be valuable in large-scale discovery studies, which require prioritization of candidate loci for follow-up studies.
A cell atlas of the larval Aedes aegypti ventral nerve cord
Authors: Yin Chang , Morita Takeshi , Parrish Jay Z.
Published: January 2024

Mosquito-borne diseases account for nearly 1 million human deaths annually, yet we have a limited understanding of developmental events that influence host-seeking behavior and pathogen transmission in mosquitoes. Mosquito-borne pathogens are transmitted during blood meals, hence adult mosquito behavior and physiology have been intensely studied. However, events during larval development shape adult traits, larvae respond to many of the same sensory cues as adults, and larvae are susceptible to infection by many of the same disease-causing agents as adults. Hence, a better understanding of larval physiology will directly inform our understanding of physiological processes in adults. Here, we use single cell RNA sequencing (scRNA-seq) to provide a comprehensive view of cellular composition in the Aedes aegypti larval ventral nerve cord (VNC), a central hub of sensory inputs and motor outputs which additionally controls multiple aspects of larval physiology. We identify more than 35 VNC cell types defined in part by neurotransmitter and neuropeptide expression. We also explore diversity among monoaminergic and peptidergic neurons that likely control key elements of larval physiology and developmental timing, and identify neuroblasts and immature neurons, providing a view of neuronal differentiation in the VNC. Finally, we find that larval cell composition, number, and position are preserved in the adult abdominal VNC, suggesting studies of larval VNC form and function will likely directly inform our understanding adult mosquito physiology. Altogether, these studies provide a framework for targeted analysis of VNC development and neuronal function in Aedes aegypti larvae.
Ixodid ticks and zoonotic tick-borne pathogens of the Western Balkans
Authors: Kapo Naida , Zuber Bogdanović Ivana , Gagović Ema , Žekić Marina , Veinović Gorana , Sukara Ratko , Mihaljica Darko , Adžić Bojan , Kadriaj Përparim , Cvetkovikj Aleksandar , Djadjovski Igor , Potkonjak Aleksandar , Velo Enkelejda , Savić Sara , Tomanović Snežana , Omeragić Jasmin , Beck Relja , Hodžić Adnan
Published: January 2024

Ixodid ticks are distributed across all countries of the Western Balkans, with a high diversity of species. Many of these species serve as vectors of pathogens of veterinary and medical importance. Given the scattered data from Western Balkan countries, we have conducted a comprehensive review of available literature, including some historical data, with the aim to compile information about all recorded tick species and associated zoonotic pathogens in this region. Based on the collected data, the tick fauna of the Western Balkans encompasses 32 tick species belonging to five genera: Ixodes, Haemaphysalis, Dermacentor, Rhipicephalus and Hyalomma. A range of pathogens responsible for human diseases has also been documented, including viruses, bacteria and parasites. In this review, we emphasize the necessity for integrated surveillance and reporting, urging authorities to foster research by providing financial support. Additionally, international and interdisciplinary collaborations should be encouraged that include the exchange of expertise, experiences and resources. The present collaborative effort can effectively address gaps in our knowledge of ticks and tick-borne diseases.

Graphical Abstract
Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis
Authors: Kim Seongryong , Leem Galam , Choi Junjeong , Koh Yongjun , Lee Suho , Nam Sang-Hee , Kim Jin Su , Park Chan Hee , Hwang Ho Kyoung , Min Kyoung Il , Jo Jung Hyun , Lee Hee Seung , Chung Moon Jae , Park Jeong Youp , Park Seung Woo , Song Si Young , Shin Eui-Cheol , Kang Chang Moo , Bang Seungmin , Park Jong-Eun
Published: January 2024

Background

Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity.

Methods

We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples.

Results

We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data.

Conclusions

This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.

Graphical Abstract
Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil
Authors: Gomes Marilia Brito , Braga Fernanda Oliveira , Drummond Karla Guerra , Pinheiro André , Leal Franz , Porto Luís Cristóvão , Ferreira Livia Leite , Pinheiro Geraldo da Rocha Castelar , Negrato Carlos Antonio
Published: January 2024

Background/objectives

The primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC).

Methods

This cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism).

Results

The prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml).

Conclusions

In conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC.
Monitoring modifiable injury risk factors over an in-season mesocycle in semi-professional female field hockey players
Authors: Sánchez-Migallón Violeta , Moreno-Pérez Víctor , Terrón-Manrique Pablo , Fernández-Ruiz Vicente , Blake Catherine , Navandar Archit , Samanes Álvaro López
Published: January 2024

Objective

This study aimed to determine changes of modifiable injury risk factors and fatigue parameters during a mesocycle (4 months of the competitive season) in semi-professional female field hockey players (Spanish 2nd Division).

Methods

Fourteen female field hockey players (age: 22.6 ± 4.9 years) participated in the study over 4 months of the competitive season (September–December 2019). The players were tested each month for their: maximal isometric knee flexion, hip adduction, and abduction muscle strength; passive straight leg raise and ankle dorsiflexion range of motion (ROM); countermovement jump height; and perceptual fatigue (through a perceived well-being questionnaire).

Results

Statistical differences were reported in isometric knee flexion torque in the dominant and non-dominant limb (p = < 0.001, ηp2 = 0.629,0.786 respectively), non-dominant isometric hip abductors torque (p = 0.016, ηp2 = 0.266) and isometric hip adductors torque in dominant and non-dominant limbs (p = < 0.001, ηp2 = 0.441–546). Also, significant differences were reported in the straight leg raise test (p = < 0.001, ηp2 = 0–523, 0.556) and ankle dorsiflexion (p = 0.001, ηp2 = 0.376, 0.377) for the dominant and non-dominant limb respectively. Finally, the jump height measured showed significant differences (p = <.001, ηp2 = 0.490), while no differences were reported in perceived well-being parameters (p = 0.089–0.459).

Conclusion

Increments in isometric muscle strength and fluctuations in ROM values and vertical jumping capacity are reported over an in-season mesocycle (i.e., 4 months of the competitive season). This information can be used to target recovery strategies to make them more efficient.
Differential effects of cholesterol levels on cognition according to body mass index in Parkinson’s disease
Authors: Jeong Seong Ho , Chung Seok Jong , Yoo Han Soo , Jung Jin Ho , Baik Jong Sam , Sohn Young H. , Lee Phil Hyu
Published: January 2024

Background

Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson’s disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD.

Methods

This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion.

Results

TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (β = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (β =  − 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014).

Conclusions

This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.
Faber polynomial coefficient inequalities for bi-Bazilevič functions associated with the Fibonacci-number series and the square-root functions
Authors: Srivastava H. M. , Khan Shahid , Malik Sarfraz Nawaz , Tchier Fairouz , Saliu Afis , Xin Qin
Published: January 2024

Two new subclasses of the class of bi-Bazilevič functions, which are related to the Fibonacci-number series and the square-root functions, are introduced and studied in this article. Under a special choice of the parameter involved, these two classes of Bazilevič functions reduce to two new subclasses of star-like biunivalent functions related with the Fibonacci-number series and the square-root functions. Using the Faber polynomial expansion (FPE) technique, we find the general coefficient bounds for the functions belonging to each of these classes. We also find bounds for the initial coefficients for bi-Bazilevič functions and demonstrate how unexpectedly these initial coefficients behave in relation to the square-root functions and the Fibonacci-number series.
High-iron consumption decreases copper accumulation and colon length, and alters serum lipids
Authors: Lee Jisu , Lee Hyun-Joo , Jang Hyunsoo , Lee Jae-Joon , Ha Jung-Heun
Published: January 2024

In this study, we aimed to demonstrate that a significant increase in dietary iron intake disrupts the regulation of copper availability, ultimately leading to systemic copper deficiency. To investigate this, we conducted experiments using five-week-old male weanling Sprague–Dawley rats fed diets based on AIN-93G with some modifications. These diets featured varying iron content, offering choices of adequate iron (~ 120 μg/g, near the upper limit [UL]) or high iron (~ 7544 μg/g), along with low (~ 0.3 μg/g), adequate (~ 6 μg/g), or high (~ 153 μg/g) levels of dietary copper over a 5-week period. Rats consuming the high-iron diets displayed anemia, reduced copper levels in their organs and feces, and shortened colon lengths. Increased dietary iron intake resulted in an overall reduction in copper distribution within the body, likely leading to severe copper deficiency-related disorders in the experimental rats. However, the physiological disturbances caused by a high-iron diet were prevented when additional copper was included in the rodent diet. Furthermore, high iron intake led to copper deprivation, and high iron consumption resulted in elevated serum cholesterol levels. However, increasing dietary copper consumption led to a decrease in overall serum cholesterol levels. Additionally, serum alkaline phosphate and aspartate aminotransferase levels were increased by high-iron feeding, regardless of dietary copper concentration, while alanine aminotransferase levels decreased.
SGLT2 inhibitors in peritoneal dialysis: a promising frontier toward improved patient outcomes
Authors: Stepanova Natalia
Published: January 2024

Peritoneal dialysis (PD) stands as an important modality among kidney replacement therapies for end-stage kidney disease, offering patients remarkable flexibility and autonomy. Despite its widespread use, challenges such as glucose-related complications, peritoneal membrane fibrosis, declining renal function, and cardiovascular risks persist, necessitating innovative therapeutic approaches. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, originally developed for treating type 2 diabetes mellitus, have recently shown promise as add-on therapy for patients with diabetic and non-diabetic chronic kidney disease (CKD), even in advanced stages. This review describes the potential role of SGLT2 inhibitors as a breakthrough therapeutic option in PD, emphasizing their ability to address unmet clinical needs and improve patient outcomes. The multiple effects of SGLT2 inhibitors in CKD, including metabolic modulation, antihypertensive, diuretic, anemia-reducing, antioxidant, and antiinflammatory properties, are reviewed in the context of PD challenges. Additionally, the potentially protective influence of SGLT2 inhibitors on the integrity of the peritoneal membrane and the transport of solutes and water in the peritoneum are emphasized. Despite these encouraging results, the paper highlights the potential risks associated with SGLT2 inhibitors in PD and emphasizes the need for cautious and thorough investigation of dosing, long-term safety considerations, and patient-specific factors through comprehensive clinical trials. Looking forward, the review argues for well-designed studies to evaluate the expanded safety profile of SGLT2 inhibitors in PD, with particular attention paid to peritoneal membrane integrity and overall patient outcomes.
A Computational Approach: The Functional Effects of Thyroid Peroxidase Variants in Thyroid Cancer and Genetic Disorders
Authors: Sobitan Adebiyi , Gebremedhin Brhan , Yao Qiaobin , Xie Guiqin , Gu Xinbin , Li Jiang , Teng Shaolei
Published: January 2024

PURPOSE

Thyroid peroxidase (TPO) is essential for the synthesis of thyroid hormones. However, specific mutations render TPO antigenic and prone to autoimmune attacks leading to thyroid cancer, TPO deficiency, and congenital hypothyroidism (CH). Despite technological advancement, most experimental procedures cannot quickly identify the genetic causes of CH nor detect thyroid cancer in the early stages.

METHODS

We performed saturated computational mutagenesis to calculate the folding energy changes (∆∆G) caused by missense mutations and analyzed the mutations involved in post-translational modifications (PTMs).

RESULTS

Our results showed that the functional important missense mutations occurred in the heme peroxidase domain. Through computational saturation mutagenesis, we identified the TPO mutations in G393 and G348 affecting protein stability and PTMs. Our folding energy calculations revealed that seven of nine somatic thyroid cancer mutations destabilized TPO.

CONCLUSION

These findings highlight the impact of these specific mutations on TPO stability, linking them to thyroid cancer and other genetic thyroid-related disorders. Our results show that computational mutagenesis of proteins provides a quick insight into rare mutations causing Mendelian disorders and cancers in humans.
Restoring core-periphery structure of networks
Authors: Yang Bo , Li Anqi , Li Nuohan , Pei Zhiyong , Zuo Youcheng
Published: January 2024

Core-periphery structure is commonly observed in diverse real-world networks, where nodes are categorized as core or peripheral nodes by connection patterns. It plays an important role in ensuring potential functionality and intrinsic order in networks. Networks are inevitably suffering from the malicious attacks and random errors, which could lead to the collapse of core-periphery structure, and in turn the performance degradation and even the total instability of network behaviors. Therefore, it is of great significance to rapidly recover such structure after destruction. However, few of the existing works about networks have put emphasis on core-periphery restoration. Here we propose a novel recovery index to characterize and measure the quality for the core-periphery restoration when a disaster happens. Several efficient algorithms guided by our index are devised to provide optimal or near-optimal restoration plans considering both the mesoscale core-periphery structure and global network connectivity. Numerical results are provided to demonstrate the efficacy of our framework that remarkably enhances core-periphery restoration.
“Let Genius Still This Glorious Object Own”: Naming, Signing, Authoring, and Owning in the Manuscript Verse Miscellany
Authors: Schellenberg Betty A.
Published: January 2024

This essay covers what it meant to “own” a manuscript verse miscellany in the eighteenth century. Manuscript miscellanies offer palpable, if enigmatic, evidence that the often-obscure individuals who made such books understood themselves to be, simultaneously, readers, copyists, makers, editors, and authors. As a result, when they took ownership of their books by signing their names on elaborate title-pages, such gestures signified something more complex and variable than a claim to “authorship.” Rejecting a post-Romantic oppositional hierarchy of writer over reader and original author over copyist, I examine acts of selection, adaptation, and copying, indicated by naming and signing, in a representative selection of miscellanies from the database Manuscript Verse Miscellanies, 1700–1820. I also consider such patterns of selection in four miscellanies extending across seventy years: five-and-a-half-year-old Melesinda Munbee's “Collection of Several Poems” (1749); Eleanor Peart's “Collection of Poems by Several Hands” (1768); Elizabeth Frances Amherst's “The Whims of E. A. afterwards Mrs. Thomas” (1798); and Lady Charlotte Campbell Bury's untitled miscellany (ca. 1815–20). Finally, I discuss “A Selection of Modern Poems” by Azarias Williams (1785), in which highly decorative, and often dated signatures, rather than claiming authorship, establish Williams's literary taste and highly developed scribal skills, while also creating a meaningful structure for his life as a transatlantic emigré. In exhibiting the many ways in which a poem might be “owned,” manuscript verse miscellanies invite us to recalibrate the relative values of composition, copying, and adaptation in the practice of literary creativity in the eighteenth century.
Real-Time Intraoperative Ultrasound Using a Minimally Invasive Transducer During Anterior Cervical Spine Surgery
Authors: Chryssikos Timothy , Tawil Michael E. , Ambati Vardhaan S. , Macki Mohamed , DiGiorgio Anthony M. , Mummaneni Praveen V. , Tan Lee
Published: January 2024

BACKGROUND AND OBJECTIVES:

Intraoperative ultrasound (IOUS) during anterior cervical surgery is hindered by large transducer size and small operative corridor. We hypothesized that a linear (minimally invasive) transducer designed for transsphenoidal surgery can visualize the spinal cord, nerve roots, and surrounding structures during anterior cervical approaches, facilitating intraoperative assessment of central and foraminal decompression.

METHODS:

IOUS was used to evaluate 26 levels in 17 patients (15 anterior cervical discectomy and fusion, 1 corpectomy, 1 arthroplasty) with a linear probe (7 × 6-mm end-fire transducer, 150-mm length, 12–15 MHz). After pin-based distraction, discectomy, and posterior longitudinal ligament resection, IOUS assessed adequacy of cord decompression and, following proximal foraminotomy or uncinectomy, nerve root decompression. If indicated, additional decompression was completed. Criteria for adequate central and foraminal decompression were visualization of subarachnoid space around the cord and cerebrospinal fluid pulsatility along the root sleeve/absence of nerve root compression distal to the root sleeve, respectively.

RESULTS:

IOUS successfully visualized the cord, nerve roots, and surrounding structures in all 26 levels and influenced management in 11 levels (42.3%). IOUS indicated persistent cord and nerve root compression in 2 and 7 levels, respectively. Planned uncinectomy was aborted in 2 levels after IOUS demonstrated adequate nerve root decompression with intervertebral distraction/proximal foraminotomy alone. IOUS identified persistent nerve root compression after initial proximal foraminotomy in 4 levels and uncinectomy in 2 levels. An unplanned uncinectomy was performed in 1 level after IOUS showed persistent nerve root compression after multiple iterations of proximal foraminotomy. At follow-up (mean 3.1 months), the mean improvement in Numeric Rating Scale neck and arm pain, Neck Disability Index, and modified Japanese Orthopedic Association was 4.0%, 3.2%, 3.7%, and 0.7%, respectively.

CONCLUSION:

The neural elements and their relationships to surrounding bone/soft tissue can be visualized using a minimally invasive IOUS transducer during anterior cervical surgery without having to remove pin-based distraction. This allows surgeons to intraoperatively verify the extent of central and foraminal decompression.
The MEK-ERK signaling pathway promotes maintenance of cardiac chamber identity
Authors: Yao Yao , Gupta Deepam , Yelon Deborah
Published: January 2024

Ventricular and atrial cardiac chambers have unique structural and contractile characteristics that underlie their distinct functions. The maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Previous studies in zebrafish have shown that sustained FGF signaling acts upstream of Nkx factors to maintain ventricular identity, but the rest of this maintenance pathway remains unclear. Here, we show that MEK1/2-ERK1/2 signaling acts downstream of FGF and upstream of Nkx factors to promote ventricular maintenance. Inhibition of MEK signaling, like inhibition of FGF signaling, results in ectopic atrial gene expression and reduced ventricular gene expression in ventricular cardiomyocytes. FGF and MEK signaling both influence ventricular maintenance over a similar timeframe, when phosphorylated ERK (pERK) is present in the myocardium. However, the role of FGF-MEK activity appears to be context-dependent: some ventricular regions are more sensitive than others to inhibition of FGF-MEK signaling. Additionally, in the atrium, although endogenous pERK does not induce ventricular traits, heightened MEK signaling can provoke ectopic ventricular gene expression. Together, our data reveal chamber-specific roles of MEK-ERK signaling in the maintenance of ventricular and atrial identities.
Maximum velocity and leg-specific ground reaction force production change with radius during flat curve sprinting
Authors: Diaz Gabriela B. , Alcantara Ryan S. , Grabowski Alena M.
Published: January 2024

Humans attain slower maximum velocity (vmax) on curves versus straight paths, potentially due to centripetal ground reaction force (GRF) production, and this depends on curve radius. Previous studies found GRF production differences between an athlete's inside versus outside leg relative to the center of the curve. Further, sprinting clockwise (CW) versus counterclockwise (CCW) slows vmax. We determined vmax, step kinematics and individual leg GRF on a straight path and on curves with 17.2 and 36.5 m radii for nine (8 male, 1 female) competitive sprinters running CW and CCW and compared vmax with three predictive models. We combined CW and CCW directions and found that vmax slowed by 10.0±2.4% and 4.1±1.6% (P<0.001) for the 17.2 and 36.5 m radius curves versus the straight path, respectively. vmax values from the predictive models were up to 3.5% faster than the experimental data. Contact length was 0.02 m shorter and stance average resultant GRF was 0.10 body weights (BW) greater for the 36.5 versus 17.2 m radius curves (P<0.001). Stance average centripetal GRF was 0.10 BW greater for the inside versus outside leg (P<0.001) on the 36.5 m radius curve. Stance average vertical GRF was 0.21 BW (P<0.001) and 0.10 BW (P=0.001) lower for the inside versus outside leg for the 17.2 and 36.5 m radius curves, respectively. For a given curve radius, vmax was 1.6% faster in the CCW compared with CW direction (P=0.003). Overall, we found that sprinters change contact length and modulate GRFs produced by their inside and outside legs as curve radius decreases, potentially limiting vmax.
Does Health-Care Consolidation Harm Patients? Evidence from Maternity Ward Closures
Authors: Avdic Daniel , Lundborg Petter , Vikström Johan
Published: January 2024

We study how closures of maternity wards affect maternal and neonatal health. Using data on all hospital births in Sweden between 1990 and 2004, we compare changes in birth-related outcomes across hospital catchment areas that were differently exposed to ward closures. Our findings show that the closures increased maternal obstetric trauma but also decreased fetal stress and infant trauma among newborns. Adverse maternal outcomes are mainly driven by ward overcrowding, whereas increases in travel distance have no distinguishable effects. Positive effects on infant health reflect a shift of births from smaller to larger wards of higher quality. (JEL D24, G34, I11, I12, I18, J13, J16)
Experimental Evidence on the Effectiveness of Nonexperts for Improving Vaccine Demand
Authors: Alsan Marcella , Eichmeyer Sarah
Published: January 2024

We experimentally vary signals and senders to identify which combination will increase vaccine demand among a disadvantaged population in the United States—Black and White men without a college education. Our main finding is that laypeople (nonexpert concordant senders) are most effective at promoting vaccination, particularly among those least willing to become vaccinated. This finding points to a trade-off between the higher qualifications of experts on the one hand and the lower social proximity to low-socioeconomic-status populations on the other hand, which may undermine credibility in settings of low trust. (JEL D82, H51, I11, I12, I14, J15)
Mandatory Retirement for Judges Improved the Performance of US State Supreme Courts
Authors: Ash Elliott , MacLeod W. Bentley
Published: January 2024

This paper provides evidence on how mandatory retirement influences judge performance using reforms in US state supreme courts as a natural experiment. We find that introducing mandatory retirement improves court performance as measured by output (number of opinions) and legal influence (number of citations to opinions). While older judges are cited less than younger judges, the effect of mandatory retirement is larger than what is expected from a change in the age distribution. We find some evidence that the additional effect is due to selective attrition and that the presence of older judges reduces the performance of younger judges. (JEL H76, J14, J24, J26, K40)
Comparative Study on Tourist Preference for Homestay Destinations among Darjeeling, Kalimpong and Sikkim
Authors: Dutta Shomnath , Mukhopadhyay Debabrata
Published: January 2024

In the hill bound nature based tourism, popularity of Homestays has been growing very fast in the Hilly regions of India and same trend has been witnessed in the two hilly districts of West Bengal, Darjeeling & Kalimpong and in Sikkim too. This present study was an attempt to investigate the competitive tourist pulling capability of such homestay based tourist destinations from the perspective of tourist’s preference upon destination attractiveness. In this study the multi-criteria decision-making tool TOPSIS has been used to assess the present competitive position of these destinations and finally paired sample t-test was applied for identifying any difference in tourist’s preferences among these three destinations. Interestingly the result portrayed a tight neck to neck competition with marginal difference in TOPSIS score and paired t-test confirmed the presence of significant statistical difference in homestay tourist’s preference for these hotspots of this region. Though Darjeeling is found slightly ahead marginally of others but facing a fierce competition indicating serious concern for tourism policy-makers, infrastructure upgradation etc. in order to give an edge over the other two rivals.