bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer
Authors: Blyth Rhianna Rachael Romany , Birts Charles N. , Beers Stephen A. 
Published: September 2023

AbstractObesity is an established risk factor for breast cancer in postmenopausal women. However, the underlying biological mechanisms of how obesity contributes to breast cancer remains unclear. The inflammatory adipose microenvironment is central to breast cancer progression and has been shown to favour breast cancer cell growth and to reduce efficacy of anti-cancer treatments. Thus, it is imperative to further our understanding of the inflammatory microenvironment seen in breast cancer patients with obesity. Three-dimensional (3D) in vitro models offer a key tool in increasing our understanding of such complex interactions within the adipose microenvironment. This review discusses some of the approaches utilised to recapitulate the breast tumour microenvironment, including various co-culture and 3D in vitro models. We consider how these model systems contribute to the understanding of breast cancer research, with particular focus on the inflammatory tumour microenvironment. This review aims to provide insight and prospective future directions on the utility of such model systems for breast cancer research.
The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees
Authors: Barr Kenneth A. , Rhodes Katherine L. , Gilad Yoav 
Published: September 2023

AbstractBackgroundComparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues. Here, we used single-cell RNA sequencing of embryoid bodies to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees.ResultsWe find hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Using embryoid bodies from a human-chimpanzee fused cell line, we also infer the proportion of inter-species regulatory differences due to changes incisandtranselements between the species. Using thecis/transinference and an analysis of transcription factor binding sites, we identify dozens of transcription factors whose inter-species differences in expression are affecting expression differences between humans and chimpanzees in hundreds of target genes.ConclusionsHere, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences.
ZINBMM: a general mixture model for simultaneous clustering and gene selection using single-cell transcriptomic data
Authors: Li Yang , Wu Mingcong , Ma Shuangge , Wu Mengyun 
Published: September 2023

AbstractClustering is a critical component of single-cell RNA sequencing (scRNA-seq) data analysis and can help reveal cell types and infer cell lineages. Despite considerable successes, there are few methods tailored to investigating cluster-specific genes contributing to cell heterogeneity, which can promote biological understanding of cell heterogeneity. In this study, we propose a zero-inflated negative binomial mixture model (ZINBMM) that simultaneously achieves effective scRNA-seq data clustering and gene selection. ZINBMM conducts a systemic analysis on raw counts, accommodating both batch effects and dropout events. Simulations and the analysis of five scRNA-seq datasets demonstrate the practical applicability of ZINBMM.
Genetic diversity and wing geometric morphometrics among four populations of Aedes aegypti (Diptera: Culicidae) from Benin
Authors: Hounkanrin Gildas , Tchibozo Carine , Sauer Felix Gregor , Agboli Eric , Schmidt-Chanasit Jonas , Yadouleton Anges , Lühken Renke , Jöst Hanna 
Published: September 2023

Abstract
Background
The impact of the arbovirus vector Aedes aegypti is of major concern for global public health as the viruses that it transmits affect millions of people each year worldwide. Originating in Africa, Ae. aegypti has now spread throughout much of the world. While the genetic makeup of Ae. aegypti in the New World has been extensively studied, there is limited knowledge on its genetic diversity in Africa, particularly at a microgeographical level.

Methods
We investigated mitochondrial cytochrome oxidase I of four Ae. aegypti populations from Benin and employed wing morphometric analyses as a cost-effective and reliable tool to explore population structure. Our sampling encompassed various areas of Benin, from the southern to the northern borders of the country, and included urban, semi-urban, and sylvatic sites.

Results
We observed a notable level of genetic diversity (haplotype diversity of 0.8333) and nucleotide diversity (0.00421986), and identified seven distinct haplotypes. Sylvatic and semi-urban sites exhibited a greater number of haplotypes compared to urban sites. Utilizing 18 wing landmarks, we calculated the centroid size, which revealed significant variation among the three landscape types. However, principal component analysis, employed to assess wing shape variation, did not demonstrate significant differences between populations based on landscape type.

Conclusions
Our findings indicate substantial genetic and morphological diversity among Ae. aegypti populations in Benin, and provide insight into important biological characteristics of these populations with respect to their potential to transmit viruses. To the best of our knowledge, this is the first study undertaken in Africa to integrate genetics with morphology to analyse the population structure of the major arbovirus vector Ae. aegypti.

Graphical Abstract
Treatment patterns and clinical outcomes in patients with rheumatoid arthritis initiating etanercept, adalimumab, or Janus kinase inhibitor as first-line therapy: results from the real-world CorEvitas RA Registry
Authors: Pappas Dimitrios A. , O’Brien Jacqueline , Guo Lin , Shan Ying , Baker Joshua F. , Kricorian Gregory , Stryker Scott , Collier David H. 
Published: September 2023

Abstract
Background
Real-world studies assessing the comparative effectiveness of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) as first-line targeted therapy are scarce. We analyzed the real-world persistence and effectiveness of etanercept (ETN), adalimumab (ADA), and Janus kinase inhibitors (JAKis) as first-line therapy in b/tsDMARD-naïve patients with rheumatoid arthritis (RA).

Methods
Adults (≥ 18 years) enrolled in the CorEvitas RA Registry and initiating ETN, ADA, or a JAKi (alone or in combination with csDMARDs) between November 2012 and June 2021 were included if they had 6 and/or 12 months’ follow-up. Treatment persistence and effectiveness outcomes including the change in Clinical Disease Activity Index (CDAI) and patient-reported outcomes (PROs) were evaluated at follow-up, adjusting for covariates using linear and logistic regression models. An exploratory analysis for patients on monotherapy was also conducted.

Results
Of 1059 ETN, 1327 ADA, and 581 JAKi initiators; 803 ETN, 984 ADA, and 361 JAKi initiators had 6 months’ follow-up. JAKi initiators were older and had a relatively longer disease duration than ETN or ADA initiators (mean age: 61.3 vs 54.5 and 55.5 years; mean duration of RA: 8.1 vs 5.7 and 5.6 years). Unadjusted mean improvements in CDAI and PROs were similar between the groups at 6 months, except the proportion achieving LDA, remission, and MCID in CDAI, which were numerically higher in the ETN and ADA groups vs JAKi group (LDA: 43.4% and 41.9% vs 32.5%; remission: 18.2% and 15.1% vs 11.5%; MCID: 46.5% and 47.8% vs 38.0%). Adjusted effectiveness results did not reveal statistically significant differences between treatment groups at 6 months, with an exception in MCID (odds ratio [95% CI] for JAKi vs ETN: 0.65 [0.43–0.98]). At 6 months, 68.2% of ETN, 68.5% of ADA, and 66.5% of JAKi initiators remained on therapy. The findings at 12 months’ follow-up and sensitivity analysis among monotherapy initiators also showed no differences in effectiveness outcomes between the groups.

Conclusions
This analysis of real-world data from the CorEvitas RA Registry did not show differences in clinical effectiveness and treatment persistence rates in b/tsDMARD-naïve patients initiating ETN, ADA, or JAKi as first-line targeted therapy either alone or in combination with csDMARDs.
Association between inpatient glycemic variability and COVID-19 mortality: a prospective study
Authors: Ali El Chab Parolin Salma , Benicio Stocco Rebecca , Kneipp Lopes Julia do Carmo , Curcio Pereira Marcos Roberto , Massae Yamashita Milena , Domareski Goulart Maria Eduarda , Demeneck Henrique , Olandoski Marcia , Hermann de Souza Nunes Larissa , Keniche Morisawa Victor , Fanhani Cracco Luiz Augusto , Busto Silva Isabela , Silva Motta Júnior Jarbas , Veit Barreto Daniela , Lenci Marques Gustavo , Proença de Moraes Thyago , Pellegrino Baena Cristina 
Published: September 2023

Abstract
Background
This study aimed to determine the association between glycemic variability (GV) and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19).

Methods
We prospectively analyzed data from inpatients (> 18 years old) with RT-PCR confirmed COVID-19 admitted between March 2020 and July 2021. All patients were hospitalized for more than 48 h and had at least six point-of-care capillary glucose tests obtained three times daily in the pre-prandial period during hospitalization. GV was measured using the glucose standard deviation (SD) and coefficient of variation (CV). ROC curve was adjusted to determine the SD and CV cutoff values associated with mortality (44.7 mg/dL and 27.5%, respectively); values above these were considered indicative of high GV. Logistic regression models were fitted to explore the association between GV and mortality in patients with and without diabetes.

Results
A total of 628 patients were stratified into SD < 44.7 mg/dL (n = 357) versus ≥ 44.7 mg/dL (n = 271) and CV < 27.5% (n = 318) versus ≥ 27.5% (n = 310) groups. After controlling for age, sex, presence of diabetes mellitus (DM) and cardiovascular disease, we found a significant association between high GV and mortality (odds ratio 2.99 [1.88–4.77] for SD and 2.43 [1.54–3.85] for CV; p values < 0.001). The mortality rate was higher with SD ≥ 44.7 mg/dL and CV ≥ 27.5% compared to that with SD < 44.7 mg/dL and CV < 27.5%, regardless of DM (p < 0.001 for all).

Conclusion
High glycemic variability was independently associated with mortality in patients with and without DM, who were hospitalized with COVID-19.
Vitamin D improves the antidiabetic effectiveness of aerobic training via modulation of Akt, PEPCK, and G6Pase expression
Authors: Hoseini Zahra , Behpour Nasser , Hoseini Rastegar 
Published: September 2023

Abstract
Background
Although the effect of Vitamin D Supplementation (Vit D) on several chronic diseases has been well conceded, its role in diabetes remains ambiguous. The present study investigated the interactive effects of Aerobic Training (AT) and different Vit D doses on Protein Kinase B (Akt), Phosphoenolpyruvate Carboxylase (PEPCK), and Glucose-6-Phosphatase (G6Pase) protein expressions in hepatocytes of type-2 diabetic rats.

Methods
Fifty-six male Wistar rats were divided into 2 groups SHAM (non-diabetic control; n = 8), and diabetic (n = 48). Then, diabetic rats were divided into six groups: AT with high doses of Vit D (D + AT + HD), AT with moderate doses of Vit D (D + AT + MD), high doses of Vit D (D + HD), moderate doses of Vit D (D + MD), AT receiving vehicle (sesame oil; D + AT + oil), and control (oil-receiving). D + AT + HD and D + HD groups received 10,000 IU of Vit D; while D + AT + MD and D + MD groups receive 5000 IU of Vit D once a week by injection; D + AT + oil and SHAM groups received sesame oil. Diabetes was induced via intraperitoneal (IP) injection of streptozotocin (50 mg/kg body weight). After 2 months of intervention, serum insulin, glucose, and visceral fat were measured; protein expressions of Akt, PEPCK, and G6Pase were assessed by western blotting. The paired t-test, one-way analysis of variance (One-Way ANOVA), and the Tukey post hoc test were used at the signification level of P < 0.05.

Results
Our data indicate that the diabeticization of rats increased the level of insulin, glucose, and PEPCK and G6Pase protein expressions and decreased the expression of the Akt (P < 0.05 for all variables). Combined AT and moderate or high Vit D significantly reduced body weight (P = 0.001; P = 0.001), body mass index (P = 0.001; P = 0.002), food intake (P = 0.001; P = 0.001) comparing the pre-test with the post-test, respectively. Also, AT and either high or moderate Vit D alone therapies lead to the improvement of the metabolic state, however, their combination had a more significant effect on the treatment of type 2 diabetes.

Conclusions
Findings from the present study suggested that combined Vit D supplementation and AT successfully improve liver function and attenuate insulin resistance via upregulating Akt and downregulating PEPCK and G6Pase expressions, compared with monotherapy.
Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism
Authors: Li Xue , Hao Shishuai , Zou Shimin , Tu Xiaomeng , Kong Weixi , Jiang Tian , Chen Jie-Guang 
Published: September 2023

Abstract
Background
Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood.

Methods
We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence.

Results
Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses.

Limitations
It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism.

Conclusions
Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.
Small airway disease in post-acute COVID-19 syndrome, a non-conventional approach in three years follow-up of a patient with long COVID: a case report
Authors: Cherrez-Ojeda Ivan , Osorio Maria F. , Robles-Velasco Karla , Calderón Juan C. , Cortés-Télles Arturo , Zambrano Jorge , Guarderas Cristian , Intriago Belen , Gochicoa-Rangel Laura 
Published: September 2023

Abstract
Background
Small airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways.

Case presentation
We discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease.

Conclusions
The necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients.
Reconstruction of isolated hypoplasia of the patella by a modified Galeazzi procedure: a case report
Authors: Toumia Mohamed Laroussi , Mohseni Ahmed Amine , Bennour Souha , Nessib Mohamed Nabil , Boussetta Rim , Bouchoucha Sami 
Published: September 2023

Abstract
Background
Isolated Patellar Aplasia Hypoplasia is a very rare autosomal dominant disorder. Its treatment depends on the clinical manifestations that can vary widely. The lack of active extension, which can be responsible for frequent falls due to a knee instability, is the most frequent and disabling manifestation. We report an original technique that is a modification of the Galeazzi technique for recurrent dislocation of the patella to gain active extension in case of PTLAH.

Case report
A 7-year-old Caucasian boy with isolated Patellar Aplasia Hypoplasia and an extension lag of the right knee has been treated by a modified Galeazzi technique. The tendons of the semi-tendinous and gracilis muscles have been harvested and their distal insertion was kept intact. Both tendons were fixed over the top of the patella to restore knee active extension. After 6 years of follow up the patient is symptom free with a strong active extension of the operated knee.

Conclusion
Reconstruction of isolated hypoplasia of the patella by a modified Galeazzi procedure is a safe and reliable technique for skeletally immature patients offering satisfying long-term outcomes.
Acoustic object canceller: removing a known signal from monaural recording using blind synchronization
Authors: Kawamura Takao , Yamaoka Kouei , Wakabayashi Yukoh , Ono Nobutaka , Miyazaki Ryoichi 
Published: September 2023

AbstractIn this paper, we propose a technique for removing a specific type of interference from a monaural recording. Nonstationary interferences are generally challenging to eliminate from such recordings. However, if the interference is a known sound like a cell phone ringtone, music from a CD or streaming service, or a radio or TV broadcast, its source signal can be easily obtained. In our method, we define such interference as an acoustic object. Even if the sampling frequencies of the recording and the acoustic object do not match, we compensate for the mismatch and use the maximum likelihood estimation technique with the auxiliary function to remove the interference from the recording. We compare several probabilistic models for representing the object-canceled signal. Experimental evaluations confirm the effectiveness of our proposed method.
On stability of almost surjective functional equations of uniformly convex Banach spaces
Authors: Sun Yuqi , Zhang Wen 
Published: September 2023

AbstractLet Y be a uniformly convex space with power type p, and let $(G,+)$
(
G
,
+
)
be an abelian group, $\delta ,\varepsilon \geq 0$
δ
,
ε
≥
0
, $0< r<1$
0
<
r
<
1
. We first show a stability result for approximate isometries from an arbitrary Banach space into Y. This is a generalization of Dolinar’ results for $(\delta ,r)$
(
δ
,
r
)
-isometries of Hilbert spaces and $L_{p}$

L
p

($1< p<\infty $
1
<
p
<
∞
) spaces. As a result, we prove that if a standard mapping $F:G\rightarrow Y$
F
:
G
→
Y
satisfies $d(u,F(G))\leq \delta \|u\|^{r}$
d
(
u
,
F
(
G
)
)
≤
δ

∥
u
∥

r

for every $u\in Y$
u
∈
Y
and $$ \bigl\vert \bigl\Vert F(x)-F(y) \bigr\Vert - \bigl\Vert F(x-y) \bigr\Vert \bigr\vert \leq \varepsilon , \quad x,y \in G, $$
|

∥
F
(
x
)
−
F
(
y
)
∥

−

∥
F
(
x
−
y
)
∥

|
≤
ε
,

x
,
y
∈
G
,
then there is an additive operator $A:G\rightarrow Y$
A
:
G
→
Y
such that $$ \bigl\Vert F(x)-Ax \bigr\Vert =o\bigl( \bigl\Vert F(x) \bigr\Vert \bigr) \quad \text{as } \bigl\Vert F(x) \bigr\Vert \rightarrow \infty . $$

∥
F
(
x
)
−
A
x
∥

=
o

(

∥
F
(
x
)
∥

)

as

∥
F
(
x
)
∥

→
∞
.
Identification of molecular subgroups and establishment of risk model based on the response to oxidative stress to predict overall survival of patients with lung adenocarcinoma
Authors: Liu Linzhuang , Hou Qinghua , Chen Baorong , Lai Xiyi , Wang Hanwen , Liu Haozhen , Wu Liusheng , Liu Sheng , Luo Kelin , Liu Jixian 
Published: September 2023

AbstractObjectiveOxidative stress is associated with the occurrence and development of lung cancer. However, the specific association between lung cancer and oxidative stress is unclear. This study aimed to investigate the role of oxidative stress in the progression and prognosis of lung adenocarcinoma (LUAD).MethodsThe gene expression profiles and corresponding clinical information were collected from GEO and TCGA databases. Differentially expressed oxidative stress-related genes (OSRGs) were identified between normal and tumor samples. Consensus clustering was applied to identify oxidative stress-related molecular subgroups. Functional enrichment analysis, GSEA, and GSVA were performed to investigate the potential mechanisms. xCell was used to assess the immune status of the subgroups. A risk model was developed by the LASSO algorithm and validated using TCGA-LUAD, GSE13213, and GSE30219 datasets.ResultsA total of 40 differentially expressed OSRGs and two oxidative stress-associated subgroups were identified. Enrichment analysis revealed that cell cycle-, inflammation- and oxidative stress-related pathways varied significantly in the two subgroups. Furthermore, a risk model was developed and validated based on the OSRGs, and findings indicated that the risk model exhibits good prediction and diagnosis values for LUAD patients.ConclusionThe risk model based on the oxidative stress could act as an effective prognostic tool for LUAD patients. Our findings provided novel genetic biomarkers for prognosis prediction and personalized clinical treatment for LUAD patients.