bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined neurokinin-1 receptor antagonist and sorafenib is a promising approach for hepatocellular carcinoma therapy
Authors: Sedky Heba E. , Elwany Yasmine N. , Alfy Eman S. El , Elwany Mona N. , Nabil Yasmin M. , Manna Hazem F. , Abdelaziz Mohamed A. , Hadidy Wessam F. El 
Published: July 2024

Abstract
Background
HCC (Hepatocellular carcinoma) is the most common primary malignant cancer in the liver. Treatment options to incurable HCC such as sorafenib, an oral multikinase inhibitor, had numerous side effects and questionable effectiveness. Neurokinin-1 receptor (NK1R) have a major role in inflammation and tumour environment including the resistance to cell death, the induction of angiogenesis and the promotion of cell migration and proliferation. Additionally, NK-1R is over-expressed in human tumour cells including HCC. Moreover, Aprepitant, one of the NK-1R antagonists exerts multiple antitumor activities (antiproliferative, apoptotic, antimigration, and antiangiogenesis) in vivo and in vitro.

Study aim
To analyze the effectiveness of combining sorafenib with aprepitant in the management of HCC (experimental).

Patients and methods
In this retrospective experimental study, the human HCC cell line, HepG2, cells were exposed to increasing concentrations of sorafenib alone, aprepitant alone and combination of both sorafenib and aprepitant evaluation of cytotoxicity, apoptosis, MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK were done. Moreover, The extent of the NK-1 receptor expression was assessed by immunocytochemistry on 50 HCC paraffin blocks of Egyptian HCC patients and another 50 paraffin blocks of liver cirrhosis only as a control.

Results
Decreased levels of MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK was more substantial in the combination therapy compared to sorafenib alone and aprepitant alone. Moreover, the rate of apoptosis and cytotoxicity were significantly higher in the combination treatment group than the monotherapy groups with more anti inflammatory, anti angiogentic and anti metastatic effects. Also, among the 50 HCC paraffin blocks, the majority (60%) showed a strong NK-1 expression; which significantly (p < 0.05) correlated with the progression free survival (PFS) but not the overall survival (OS) of the patients when applying multivariate analysis.

Conclusion
HCC had strong expression and immunostaining for NK1R.Therefore, combined aprepitant and sorafenib may be a promising approach in HCC treatment compared to each one alone.
The utility of various predictive equations in patients with severe Obstructive Sleep Apnea: a clinical practice viewpoint in settings with limited resources
Authors: Gharib Ahmed , Elsheikh Mai S. , Galal Iman 
Published: July 2024

Abstract
Background
The continuous positive airway pressure (CPAP) needed for the treatment of obstructive sleep apnea (OSA) can be determined after a manual titration study which is often expensive and time consuming. Hence, different predictive equations were suggested to simplify the treatment of OSA. The purpose of this work was to compare the CPAP identified with manual titration with that calculated using various equations in a cohort of patients with severe OSA.

Methods
This work was conducted on patients diagnosed with severe OSA. Data collected included full medical history, demographic and anthropometric measures, polysomnography results, and the CPAP pressure obtained after manual titration which was further compared to 15 predictive equations retrieved from the literature.

Results
A total of 166 patients [137 (82.5%) males and 29 (17.5%) females] with severe OSA were recruited in the study. Their mean age was 55.91 ± 12.64, and their baseline diagnostic apnea hypopnea index was 71.75 ± 23.70. The mean CPAP manual titration pressure was 11.31 ± 2.9 cmH2O. Non-significant statistical difference was found (p > 0.05) when the mean titration pressure was calculated by Eqs. 2 (11.36 ± 2), 3 (11.55 ± 1.68), 10 (11.51 ± 2.29), 11 (11.14 ± 2.04), and 14 (11.71 ± 2.06), whereas the mean titration pressure calculated by Eqs. 1, 4, 5, 6, 7, 8, 9, 12, 13, and 15 differed significantly from the manual titration pressure (p < 0.05).

Conclusion
Predictive equations suggested to calculate CPAP pressure, albeit simple and easy to apply, yielded variable results and should be investigated carefully before their use into clinical practice.
Magnetic-free chiral eigenmode spectroscopy for simultaneous sensitive measurement of optical rotary dispersion and circular dichroism
Authors: Zhou Wenpeng , Ruan Ya-Ping , Wu Haodong , Zhang Han , Tang Jiang-Shan , Xie Zhenda , Tang Lei , Wang Yu , Ji Yue-E , Jia Kunpeng , Qiu Cheng-Wei , Lu Yan-Qing , Xia Keyu 
Published: July 2024

AbstractChirality, defined by Lord Kelvin, refers to the geometric symmetry property of an object that cannot be superposed onto its mirror image using rotations and translations. The material’s chirality can be probed with light as the optical activity: optical rotary dispersion (ORD) and circular dichroism (CD). It is still challenging to yield extremely sensitive ORD and CD for very weak chirality and measure both simultaneously. Cavity ringdown polarimetry has been reported to improve ORD detection sensitivity with the absence of equally important CD signature, at the price of high cavity finesse near 400, frequency-locking sophistication, and large magnetic field. Here, we report a unique recipe to demonstrate the simultaneous measurement of ORD and the CD by separately observing the chiral eigenmode spectra from a bowtie optical cavity with a finesse about 30, without resorting to frequency locking or magnetic field. We obtain a sensitivity of $$\sim 2.7\times 10^{-3} \text {deg}/\sqrt{\text {Hz}}$$

∼
2.7
×

10

-
3

deg
/

Hz

for ORD, $$\sim 8.1 \times 10^{-6} /\sqrt{\text {Hz}}$$

∼
8.1
×

10

-
6

/

Hz

for CD, and a spectral resolution of $$0.04~\text {pm}$$

0.04

pm

within a millisecond-scale measurement. We present a cost-effective yet ultrasensitive account for chiral chromatography, the conformational dynamics and chiroptical analysis of biological samples which particularly exhibit weak and narrow spectral signals.
A Longitudinal Study of Glucose Tolerance in Cystic Fibrosis: The Central Role of Beta Cell Functional Mass
Authors: Piona Claudia , Mozzillo Enza , Tosco Antonella , Zusi Chiara , Emiliani Federica , Volpi Sonia , Di Candia Francesca , Raia Valeria , Boselli Maria Linda , Trombetta Maddalena , Cipolli Marco , Bonadonna Riccardo C , Maffeis Claudio 
Published: July 2024

Abstract

Context
The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear.

Objective
To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in subjects with CF.

Methods
Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 subjects with CF, aged 10-25 years, who underwent 2 oral glucose tolerance tests over an at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) vs OGIS.

Results
OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (P &lt; .02, R2 Nagelkerke = 0.55), whereas age, gender, z body mass index, CF genotypes, and baseline adjusted proportional control were not.

Conclusion
In subjects with CF, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.
Primary Cilia are Required for Cell-Type Determination and Angiogenesis in Pituitary Development
Authors: Yoshida Saishu , Tsuneoka Yousuke , Tsukada Takehiro , Nakakura Takashi , Kawamura Akira , Kai Wataru , Yoshida Kiyotsugu 
Published: July 2024

Abstract
The functional maturation of the pituitary gland requires adequate cell differentiation and vascular network formation. Although spatiotemporal signaling and transcription factors are known to govern pituitary development, the involvement of primary cilia, nonmoving hair-like organelles, remains unclear. In this study, we uncovered the contribution of primary cilia to cell-type determination and vascular network formation during pituitary development. Homozygous knockout mice lacking a ciliary kinase, Dyrk2−/−, exhibit abnormalities in ciliary structure and pituitary hypoplasia, accompanied by varying degrees of failure in differentiation among all types of hormone-producing cells in the anterior lobe. Aberrations in cell differentiation in Dyrk2−/− mice arise from a decrease in the expression of crucial transcription factors, Lhx4, Lhx3, and Prop1, resulting from the inactivity of Hedgehog (Hh) signaling during the early stages of development. Furthermore, the loss of Dyrk2 results in vascular system abnormalities during the middle to late stages of development. Mechanistically, transcriptome analyses revealed the downregulation of vitronectin-integrin αvβ3-VEGFR2 signaling, essential for orchestrating vascular development. Collectively, our findings demonstrate that primary cilia play a pivotal role as critical regulators of cell survival, cell determination, and angiogenesis during pituitary gland development through the activation of Hh signaling. These findings expand our understanding of the potential link between pituitary dysfunction in human disorders and ciliopathies.
Effect and Safety of Apatinib as Neoadjuvant Therapy in Locally Advanced Differentiated Thyroid Cancer: A Phase 2 Trial
Authors: Qian Kai , Wang Yunjun , An Ning , Liu Chunhao , Guo Kai , Yang Lingyi , Wang Jun , Li Xiaoyi , Wang Zhuoying 
Published: July 2024

Abstract

Context
Presently, there is a paucity of prospective clinical trials investigating neoadjuvant therapy for locally advanced thyroid cancer.

Objective
This study was a multicenter, open-label, single-arm, phase II trial evaluating the efficacy and safety of apatinib as neoadjuvant therapy in patients with local advanced differentiated thyroid cancer (DTC).

Methods
Patients were treated with preoperative apatinib over a course of 2 to 4 cycles, culminating in surgical resection. The primary endpoints were objective response rate (ORR) and disease control rate (DCR); the secondary endpoints were the rate of R0 surgery, alterations in serum thyroglobulin levels, disease-free survival, and adverse events (AEs).

Results
A total of 14 patients who met the inclusion criteria were administered neoadjuvant apatinib. Among these, 13 patients underwent surgical procedures following apatinib treatment and were enrolled in the ITT population. The ORR was 53.8% and the DCR was 100%. Of the patients, 84.6% received R0 surgery, while the remaining 15.4% underwent R1 resection. Predominant among the observed AEs were hypertension, hand–foot syndrome, hepatic dysfunction, proteinuria, and hypothyroidism, with no instances of grade 4 or 5 AEs reported. Subsequent to surgery, patients were followed up for a median period of 34 months, during which disease progression occurred in 5 individuals (35.7%), encompassing 3 cases of locoregional recurrences and 2 cases of distant metastases.

Conclusion
Apatinib may be an effective agent in the use of neoadjuvant therapy for locally advanced DTC. Patients may therefore benefit from surgical outcomes and their long-term prognosis.
Navigating the Intersection Between the Orbit and the Skull Base: The “Mirror” McCarty Keyhole During Transorbital Approach: An Anatomic Study With Surgical Implications
Authors: Corvino Sergio , Kassam Amin , Piazza Amedeo , Corrivetti Francesco , Esposito Felice , Iaconetta Giorgio , de Notaris Matteo 
Published: July 2024

BACKGROUND AND OBJECTIVES:
McCarty keyhole (MCK) is the most important entry point during orbitocranial and cranio-orbital approaches; nevertheless, its anatomic coordinates have never been detailedly described from transorbital perspective. To provide the spatial coordinates for intraorbital projection of the “mirror” MCK by using the well-established main anatomic-surgical bony landmarks met along transorbital corridor.

METHODS:
MCK was identified in 15 adult dry skulls (30 sides) on exocranial surface of pterional region based on the well-defined external bony landmarks: on the frontosphenoid suture, 5 to 6 mm behind the joining point (JP) of frontozygomatic suture (FZS), frontosphenoid suture (FSS), and sphenozygomatic suture (SZS). A 1-mm burr hole was performed and progressively enlarged to identify the intracranial and intraorbital compartments. Exit site of the intraorbital part of burr hole was referenced to the FZS on the orbital rim, the superior orbital fissure, and the inferior orbital fissure and to the JP of FZS, FSS, and SZS. To electronically validate the results, 3-dimensional photorealistic and interactive models were reconstructed with photogrammetry. Finally, for a further validation, McCarty mirror keyhole was also exposed, based on results achieved, through endoscopic transorbital approach in 10 head specimens (20 sides).

RESULTS:
Intraorbital projection of MCK was identified on the FSS on intraorbital surface, 1.5 ± 0.5 mm posterior to JP, 11.5 ± 1.1 mm posterior to the FZS on orbital rim following the suture, 13.0 ± 1.2 mm from most anterior end of superior orbital fissure, 15.5 ± 1.4 mm from the most anterior end of the inferior orbital fissure in vertical line, on measurements under direct macroscopic visualization (mean ± SD). These values were electronically confirmed on the photogrammetric models with mean difference within 1 mm.

CONCLUSION:
To be aware of exact position of intraorbital projection of MCK during an early stage of transorbital approaches provides several surgical, clinical, and aesthetic advantages.
Hemifacial Spasm Associated With the Specific Offending Vein
Authors: Cao Chenglong , Li Mingwu , Wu Min , Jiang Xiaofeng 
Published: July 2024

BACKGROUND AND OBJECTIVES:
Hemifacial spasm (HFS) caused by venous compression is a rare occurrence. Currently, there is no relevant research on the venous characteristics and potential pathogenic mechanisms causing venous HFS. Exploring the venous characteristics in venous-type HFS may reduce the likelihood of repeated surgery.

METHODS:
The authors presented 4 cases of HFS caused by veins of middle cerebellar peduncle (V. of Mid.Cer.Ped) successfully treated with microvascular decompression.

RESULTS:
Based on intraoperative observations and abnormal muscle response (AMR) monitoring, it was determined that V. of Mid.Cer.Ped were offending vessels in these patients. Moreover, veins crossed between the facial and vestibulocochlear nerves, and then surrounded the ventral aspect of the facial nerve root. Microvascular decompression for the offending vessel was successfully performed, and AMR disappeared for each patient. These patients were discharged without any complications and involuntary contractions or twitching of facial muscles.

CONCLUSION:
The study demonstrated that veins can indeed induce HFS. The characteristic of the V. of Mid.Cer.Ped that leads to HFS is that these veins traverse between the facial nerve and the vestibulocochlear nerve, and then surround the ventral aspect of the facial nerve root. The dynamic influence of cerebrospinal fluid leads to pulsatile impingement of the facial nerve on the vein, resulting in facial nerve bending and deformation at the location of the vein. Significantly, in the context of surgery, if it is noticed that the V. of Mid.Cer.Ped surrounds the ventral aspect of the facial nerve root and the facial nerve is compressed and deformed, when AMR disappears after decompression of the artery, it may be necessary to perform vein decompression.
Evolutionary conservation of VSX2 super-enhancer modules in retinal development
Authors: Honnell Victoria , Sweeney Shannon , Norrie Jackie , Parks Madison , Ramirez Cody , Jannu Asha Jacob , Xu Beisi , Teubner Brett , Lee Ah Young , Bell Claire , Dyer Michael A. 
Published: July 2024

ABSTRACT
Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. We recently identified developmental stage- and cell type-specific modules within the murine Vsx2 SE. Here, we show that the human VSX2 SE modules have similar developmental stage- and cell type-specific activity in reporter gene assays. By inserting the human sequence of one VSX2 SE module into a mouse with microphthalmia, eye size was rescued. To understand the function of these SE modules during human retinal development, we deleted individual modules in human embryonic stem cells and generated retinal organoids. Deleting one module results in small organoids, recapitulating the small-eyed phenotype of mice with microphthalmia, while deletion of the other module led to disruptions in bipolar neuron development. This prototypical SE serves as a model for understanding developmental stage- and cell type-specific effects of neurogenic transcription factors with complex expression patterns. Moreover, by elucidating the gene regulatory mechanisms, we can begin to examine how dysregulation of these mechanisms contributes to phenotypic diversity and disease.
Mechanical regulation of lymphocyte activation and function
Authors: Pathni Aashli , Wagh Kaustubh , Rey-Suarez Ivan , Upadhyaya Arpita 
Published: July 2024

ABSTRACT
Mechanosensing, or how cells sense and respond to the physical environment, is crucial for many aspects of biological function, ranging from cell movement during development to cancer metastasis, the immune response and gene expression driving cell fate determination. Relevant physical stimuli include the stiffness of the extracellular matrix, contractile forces, shear flows in blood vessels, complex topography of the cellular microenvironment and membrane protein mobility. Although mechanosensing has been more widely studied in non-immune cells, it has become increasingly clear that physical cues profoundly affect the signaling function of cells of the immune system. In this Review, we summarize recent studies on mechanical regulation of immune cells, specifically lymphocytes, and explore how the force-generating cytoskeletal machinery might mediate mechanosensing. We discuss general principles governing mechanical regulation of lymphocyte function, spanning from the molecular scale of receptor activation to cellular responses to mechanical stimuli.
Clipping the Positive Lymph Node in Patients with Clinically Node Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: Impact on Axillary Surgery in the ISPY-2 Clinical Trial
Authors: Switalla Kayla M. , Boughey Judy C. , Dimitroff Katrina , Yau Christina , Ladores Velle , Yu Hongmei , Tchou Julia , Golshan Mehra , Ahrendt Gretchen , Postlewait Lauren M. , Piltin Mara , Reyna Chantal R. , Matsen Cindy B. , Tuttle Todd M. , Wallace Anne M. , Arciero Cletus A. , Lee Marie Catherine , Tseng Jennifer , Son Jennifer , Rao Roshni , Sauder Candice , Naik Arpana , Howard-McNatt Marissa , Lancaster Rachael , Norwood Peter , Esserman Laura J. , Mukhtar Rita A. 
Published: July 2024

Abstract
Background
For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain.

Patients and Methods
We retrospectively analyzed cN+ ISPY-2 patients (2011–2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial.

Results
Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8–6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4–1.7, p = 0.7; HR 1.8, 95% CI 0.5–6.0, p = 0.3, respectively].

Conclusion
Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC.
Dor Crônica e Possibilidades de Intervenção no Contexto da Psicologia: Revisão Integrativa
Authors: Paludo Isadora Cristina Putti , Moré Carmen Leontina Ojeda Ocampo , Inácio Amábille das Neves 
Published: July 2024

O objetivo da presente revisão integrativa foi caracterizar o estado da arte sobre a relação entre dor crônica e possibilidades de intervenção no campo da psicologia. Buscaram-se artigos publicados entre 2018 e 2022 nas bases de dados LILACS, Scopus, Web of Science, Pubmed, PsycINFO e Scielo. Os descritores utilizados foram: "Chronic pain", "Psychology", "Psychosocial Intervention" e "Psychological Intervention". Após a seleção, com base nos critérios estabelecidos, de um total de 825, foram incluídos 11 artigos que constituem o corpus do presente trabalho, os quais foram analisados com o auxílio do sotfware Atlas.ti. Os resultados apontaram para um conjunto de intervenções psicológicas baseadas na psicoeducação para o manejo da dor crônica. Observou-se diferentes abordagens de programas de controle e educação em dor e modalidades de intervenção grupal e individual. A psicologia apareceu vinculada ao trabalho multiprofissional e à proposta da integralidade do cuidado, com destaque às estratégias alternativas e não farmacológicas para o enfrentamento da dor. Os estudos analisados evidenciaram que as experiências de dor são impactadas pelos aspectos psicológicos, tensionando decisivamente a dimensão biológica de compreensão da dor.