bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx2 Deficiency in Osteoblasts Promotes Myeloma Resistance to Bortezomib by Increasing TSP-1–Dependent TGFβ1 Activation and Suppressing Immunity in Bone Marrow
Authors: Zhang Chao , Xu Xiaoxuan , Trotter Timothy N. , Gowda Pramod S. , Lu Yun , Suto Mark J. , Javed Amjad , Murphy-Ullrich Joanne E. , Li Juan , Yang Yang 
Published: December 2021

Abstract
Multiple myeloma is a plasma cell malignancy that thrives in the bone marrow (BM). The proteasome inhibitor bortezomib is one of the most effective first-line chemotherapeutic drugs for multiple myeloma; however, 15% to 20% of high-risk patients do not respond to or become resistant to this drug and the mechanisms of chemoresistance remain unclear. We previously demonstrated that multiple myeloma cells inhibit Runt-related transcription factor 2 (Runx2) in pre- and immature osteoblasts (OB), and that this OB-Runx2 deficiency induces a cytokine-rich and immunosuppressive microenvironment in the BM. In the current study, we assessed the impact of OB-Runx2 deficiency on the outcome of bortezomib treatment using OB-Runx2+/+ and OB-Runx2−/− mouse models of multiple myeloma. In vitro and in vivo experiments revealed that OB-Runx2 deficiency induces multiple myeloma cell resistance to bortezomib via the upregulation of immunosuppressive myeloid-derived suppressor cells (MDSCs), downregulation of cytotoxic T cells, and activation of TGFβ1 in the BM. In multiple myeloma tumor-bearing OB-Runx2−/− mice, treatment with SRI31277, an antagonist of thrombospondin-1 (TSP-1)–mediated TGFβ1 activation, reversed the BM immunosuppression and significantly reduced tumor burden. Furthermore, treatment with SRI31277 combined with bortezomib alleviated multiple myeloma cell resistance to bortezomib-induced apoptosis caused by OB-Runx2 deficiency in cocultured cells and produced a synergistic effect on tumor burden in OB-Runx2−/− mice. Depletion of MDSCs by 5-fluorouracil or gemcitabine similarly reversed the immunosuppressive effects and bortezomib resistance induced by OB-Runx2 deficiency in tumor-bearing mice, indicating the importance of the immune environment for drug resistance and suggesting new strategies to overcome bortezomib resistance in the treatment of multiple myeloma.
O-GlcNAcylation of Blimp-1 in Lymphocytes Inhibits Its Transcriptional Function and Is Associated with Migration and Invasion of Breast Cancer Cells
Authors: Chen Yan-Fang , Shao Guang-Can , Li Jie , Yang An-Qi , Li Jing , Ye Xin-Shan 
Published: December 2021

AbstractLymphocyte infiltration is an important feature of cancer. There is a complex network of chemokines that influence the degree and phenotype of lymphocyte infiltration, as well as the growth, survival, migration, and angiogenesis of tumor cells. High heterogeneity metastasis is a major obstacle to the treatment of breast cancer. Herein, we showed that O-GlcNAcylation of B lymphocyte–induced maturation protein-1 (Blimp-1) in lymphocytes inhibited the migration and invasion of breast cancer cells. It was found that Blimp-1 O-GlcNAcylation at Ser448 and Ser472 in lymphocytes promoted its nuclear localization, and blocked the bindings to three regions upstream of the ccl3l1 promoter to inhibit its expression. Decreased expression of CCL3L1 in lymphocytes not only decreased CCR5 expression in breast cancer cells, but also inhibited the membrane localization and activation of CCR5, thus blocking the migration and invasion of breast cancer cells in vitro. Therefore, O-GlcNAcylation of Blimp-1 in lymphocytes may serve as a new target for the treatment of metastatic breast cancer.Implications:This study reveals a new mechanism by which the lymphatic system promotes breast cancer cell metastasis.
Preparation of a Beverage Containing Freeze-Dried Watercress for a Clinical Trial of Carcinogen and Toxicant Detoxification
Authors: Bonorden Melissa J.L. , Carmella Steven G. , Ballinger Oliver T. , Williams Jessica , Dorn Irv , Vanderloo Hanna , Fujioka Naomi , Hatsukami Dorothy K. , Hecht Stephen S. 
Published: December 2021

AbstractWatercress is an excellent source of phenethyl isothiocyanate (PEITC), shown in many studies to enhance carcinogen and toxicant detoxification and to inhibit carcinogenesis. Based on a previous observation that PEITC can enhance the detoxification of common environmental pollutants such as acrolein, crotonaldehyde, benzene, and 1,3-butadiene, we designed a clinical trial testing the hypothesis that daily consumption of a drink containing freeze-dried watercress, an abundant source of PEITC, would have a similar effect, particularly observed in subjects who were null in certain glutathione S-transferase genes. This manuscript describes the preparation of nearly 100 pounds of freeze-dried watercress for this trial, starting with laboratory-scale pilot studies and proceeding to industrial-scale production of the fully validated product in compliance with all food safety requirements. Initial results validating subject compliance in the clinical trial are also presented.Prevention Relevance:This study describes the preparation of a beverage containing freeze-dried watercress suitable for consumption in a clinical trial to determine whether a constituent of this beverage–PEITC, which has cancer prevention properties–can enhance detoxification of common environmental carcinogens and toxicants such as benzene, which may have a role in environmentally induced cancer.See related Spotlight, p. 139
ANALYSIS OF IMMEDIATE AND LONG-TERM RESULTS OF SUBLAY AND TAPP TECHNIQUES IN THE TREATMENT OF VENTRAL HERNIAS
Authors: Dubchenko V. S. 
Published: December 2021

The accumulated clinical experience has proven that the “sublay” technique allows to achieve greater functional activity of the anterior abdominal wall and is the method of choice in the treatment of ventral hernia. The use of self-adhesive nets during laparoscopic transabdominal preperitoneal plasty (TAPP- Transabdominal Preperitoneal Plastic) in the treatment of small and medium ventral hernia is safe and effective, with low values of postoperative pain syndrome and rapid functional recovery after surgery, without increasing the recurrence in the short term.
The aim – was to analyze the immediate and long-term results of “sublay” and TAPP techniques in the treatment of ventral hernias of lower and median localization. The author noted that the search for technical methods aimed to reduce the intra-abdominal pressure in this hernioplasty technique was relevant and practically significant.
Material and Methods. The work was performed on the basis of the surgical department of the State Institution “Specialized Multi-Purpose Hospital №1 of Ministry of Health of Ukraine”, Department of General Surgery of the State Institution “Dnipro State Medical University of Ministry of Health of Ukraine”.
Results. Comparison of immediate and long-term results of peritoneal-prosthetic-aponeurosis thickness studies showed a statistically significant difference (p < 0.001) using different techniques. When analyzing the separated results, reliable differences (p <0.001) depending on the gender of patients were recorded. Thus, in males, when using the “sublay” technique the peritoneal-prosthetic-aponeurosis thickness was greater by 1.15 mm (by 42.43 %) in comparison with the Tapptechnique, and in females, by 1.16 mm (by 42.09 %), respectively.
Conclusions. The analysis of the immediate and long-term results of the “sublay” and TAPP techniques in the treatment of ventral hernias of lower and median localization showed that the “sublay” technique was characterized by traumatic surgical intervention, shift of the prosthesis to one side, as a consequence of its deformation. When using this technique, peritoneum-prosthetic-aponeurosis thickness values were significantly higher – by 13.16 % and 42.40 % in the early and distant postoperative periods, respectively. Also, when using the Tapp technique in the distant period the thickness was significantly reduced (p <0,0001) by 49,47 % in comparison with the immediate results.
КОНСЕРВАТИВНЕ ЛІКУВАННЯ СТРЕСОВОГО НЕТРИМАННЯ СЕЧІ У ЖІНОК ЗА ДОПОМОГОЮ ЕЛЕКТРОСТИМУЛЯЦІЇ З ОЦІНКОЮ ОТРИМАНИХ РЕЗУЛЬТАТІВ
Authors: Возіанов С. О. , Захараш М. П. , Чабанов П. В. , Захараш Ю. М. , Севастьянова Н. А. , Угаров В. Ю. , Репринцева А. С. 
Published: December 2021

Мета дослідження – підвищення ефективності лікування жінок із стресовим нетриманням сечі.
Матеріал і методи. Обстежено 87 жінок зі стресовим нетриманням сечі. Для визначення функціонального стану нервово-м'язового апарату нижніх сечовивідних шляхів використовували електроміографію сечового міхура і його сфінктерного апарату та урофлоуметрію.
Результати. При лікуванні жінок зі зниженим тонусом нервово-м'язових структур нижніх сечових шляхів за допомогою електростимуляції отримано позитивний ефект в 79,2 % хворих, що підтверджується поліпшенням клінічної картини і результатами електроміографії та урофлоуметрії.
Висновки. Лікування пацієнтів зі стресовим нетриманням сечі за допомогою електростимуляції є ефективним.
МАСОМЕТРИЧНА ХАРАКТЕРИСТИКА КАМЕР СЕРЦЯ ПРИ ПОСТРЕЗЕКЦІЙНІЙ ПОРТАЛЬНІЙ ГІПЕРТЕНЗІЇ
Authors: Гданська Н. М. , Татарчук Л. В. , Гнатюк М. С. , Коноваленко С. О. , Цицюра Р. І. 
Published: December 2021

Видалення значних об’ємів паренхіми печінки нерідко призводить до пострезекційної портальної гіпертензії, яка ускладнюється кровотечами з варикозно розширених вен стравохода і шлунка, прямої кишки, асцитом, спленомегалією, вторинним гіперспленізмом, паренхіматозною жовтяницею, портосистемною енцефалопатією, поліорганною недостатністю.
Мета – встановити особливості масометричних змін камер серця в умовах пострезекційної портальної гіпертензії.
Матеріал і методи. Масометрично досліджені камери серця 34 лабораторних статевозрілих білих щурів-самців, які були поділені на 2 групи. 1-а група нараховувала 15 інтактних практично здорових експериментальних тварин, 2-а – 19 щурів зі змодельованою пострезекційною портальною гіпертензією. Евтаназію щурів здійснювали кровопусканням в умовах тіопенталового наркозу. Проводили окреме зважування частин серцевого м’яза, при якому враховували: чисту масу серця, абсолютну масу лівого і правого шлуночків, шлуночковий індекс, індекс Фултона, масу лівого і правого передсердь, відсотки мас шлуночків і передсердь, індекс передсердь, індекс передсердно-шлуночковий правий і лівий. Частини серця досліджували гістологічно. Масометричні параметри камер серця обробляли статистично.
Результати. Встановлено, що резекція лівої та правої бокових часток печінки у щурів призводила до розвитку пострезекційної портальної гіпертензії, яка характеризувалася розширенням та венозним повнокров’ям ворітної печінкової вени, брижових вен, вен стравоходу та шлунка, передньої черевної стінки, спленомегалією, асцитом. Масометричні параметри камер серця при цьому змінювалися. Так, чиста маса серця в умовах змодельованого експерименту збільшилася на 19,5 %, абсолютна маса лівого шлуночка – на 24,1 %. правого – на 11,4 % (р<0,001), лівого передсердя – на 21,0 %, правого – на 8,4 % (р<0,01). Шлуночковий індекс при цьому зменшився на 10,3 %, індекс передсердно-шлуночковий лівий – на 3,7 %, правий – на 2,5 %, індекс Фултона зріс на 17,7 %, індекс передсердь – на 9,8 %, серцевий індекс – на 11,6 %, що свідчило при диспропорційність гіпертрофії камер серця в умовах пострезекційної портальної гіпертензії і підтверджувалося відсотками їх масометричних параметрів.
Висновки. Проведеним масометричним вивченням особливостей ремоделювання камер серця в умовах пострезекційної портальної гіпертензії встановлено нерівномірне, диспропорційне збільшення мас камер серця з домінуючою гіпертрофією лівого шлуночка та лівого передсердя.
Anatomical Classification and Posttreatment Remodeling Characteristics to Guide Management and Follow-Up of Neonates and Infants With Coronary Artery Fistula: A Multicenter Study From the Coronary Artery Fistula Registry
Authors: Gowda Srinath T. , Latson Larry , Sivakumar Kothandam , Hiremath Gurumurthy , Crystal Matthew , Law Mark , Shahanavaz Shabana , Asnes Jeremy , Veeram Reddy Surendranath , Kobayashi Daisuke , Alwi Mazeni , Ichida Fukiko , Hirono Keiichi , Tahara Masahiro , Takeda Atsuhito , Minami Takaomi , Kutty Shelby , Nugent Alan W. , Forbes Thomas , Prieto Lourdes R. , Qureshi Athar M. 
Published: December 2021

Background:
Coronary artery fistulas (CAFs) presenting in infancy are rare, and data regarding postclosure sequelae and follow-up are limited.

Methods:
A retrospective review of all the neonates and infants (<1 year) was conducted from the CAF registry for CAF treatment. The CAF type (proximal or distal), size, treatment method, and follow-up angiography were reviewed to assess outcomes and coronary remodeling.

Results:
Forty-eight patients were included from 20 centers. Of these, 30 were proximal and 18 had distal CAF; 39 were large, 7 medium, and 2 had small CAF. The median age and weight was 0.16 years (0.01–1) and 4.2 kg (1.7–10.6). Heart failure was noted in 28 of 48 (58%) patients. Transcatheter closure was performed in 24, surgical closure in 18, and 6 were observed medically. Procedural success was 92% and 94 % for transcatheter closure and surgical closure, respectively. Follow-up data were obtained in 34 of 48 (70%) at a median of 2.9 (0.1–18) years. Angiography to assess remodeling was available in 20 of 48 (41%). I. Optimal remodeling (n=10, 7 proximal and 3 distal CAF). II. Suboptimal remodeling (n=7) included (A) symptomatic coronary thrombosis (n=2, distal CAF), (B) asymptomatic coronary thrombosis (n=3, 1 proximal and 2 distal CAF), and (C) partial thrombosis with residual cul-de-sac (n=1, proximal CAF) and vessel irregularity with stenosis (n=1, distal CAF). Finally, (III) persistent coronary artery dilation (n=4). Antiplatelets and anticoagulation were used in 31 and 7 patients post-closure, respectively. Overall, 7 of 10 (70%) with proximal CAF had optimal remodeling, but 5 of 11 (45%) with distal CAF had suboptimal remodeling. Only 1 of 7 patients with suboptimal remodeling were on anticoagulation.

Conclusions:
Neonates/infants with hemodynamically significant CAF can be treated by transcatheter or surgical closure with excellent procedural success. Patients with distal CAF are at higher risk for suboptimal remodeling. Postclosure anticoagulation and follow-up coronary anatomic evaluation are warranted.
Mechanisms of Sinoatrial Node Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Mesquita Thassio , Zhang Rui , Cho Jae Hyung , Zhang Rui , Lin Yen-Nien , Sanchez Lizbeth , Goldhaber Joshua I. , Yu Joseph K. , Liang Jialiu A. , Liu Weixin , Trayanova Natalia A. , Cingolani Eugenio 
Published: December 2021

Background:
The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown.

Methods:
Dahl salt-sensitive rats fed a high-salt diet and C57Bl6 mice fed a high-fat diet and an inhibitor of constitutive nitric oxide synthase (Nω-nitro-L-arginine methyl ester [L-NAME]; 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction. Rats and mice fed with a normal diet or those that had a sham surgery served as respective controls. A comprehensive characterization of SAN function and chronotropic response was conducted by in vivo, ex vivo, and single-cell electrophysiologic studies. RNA sequencing of SAN was performed to identify transcriptomic changes. Computational modeling of biophysically-detailed human HFpEF SAN was created.

Results:

Rats with phenotypically-verified HFpEF exhibited limited chronotropic response associated with intrinsic SAN dysfunction, including impaired β-adrenergic responsiveness and an alternating leading pacemaker within the SAN. Prolonged SAN recovery time and reduced SAN sensitivity to isoproterenol were confirmed in the 2-hit mouse model. Adenosine challenge unmasked conduction blocks within the SAN, which were associated with structural remodeling. Chronotropic incompetence and SAN dysfunction were also found in rats with HF with reduced ejection fraction. Single-cell studies and transcriptomic profiling revealed HFpEF-related alterations in both the “membrane clock” (ion channels) and the “Ca
2+
clock” (spontaneous Ca
2+
release events). The physiologic impairments were reproduced in silico by empirically-constrained quantitative modeling of human SAN function.

Conclusions:
Chronotropic incompetence and SAN dysfunction were seen in both models of HF. We identified that intrinsic abnormalities of SAN structure and function underlie the chronotropic response in HFpEF.
Structure supports function: Informing directed and dynamic functional connectivity with anatomical priors
Authors: Pascucci David , Rubega Maria , Rué-Queralt Joan , Tourbier Sebastien , Hagmann Patric , Plomp Gijs 
Published: December 2021

Abstract
The dynamic repertoire of functional brain networks is constrained by the underlying topology of structural connections. Despite this intrinsic relationship between structural connectivity (SC) and functional connectivity (FC), integrative and multimodal approaches to combine the two remain limited. Here, we propose a new adaptive filter for estimating dynamic and directed FC using structural connectivity information as priors. We tested the filter in rat epicranial recordings and human event-related EEG data, using SC priors from a meta-analysis of tracer studies and diffusion tensor imaging metrics, respectively. We show that, particularly under conditions of low signal-to-noise ratio, SC priors can help to refine estimates of directed FC, promoting sparse functional networks that combine information from structure and function. In addition, the proposed filter provides intrinsic protection against SC-related false negatives, as well as robustness against false positives, representing a valuable new tool for multimodal imaging in the context of dynamic and directed FC analysis.
Bridging physiological and perceptual views of autism by means of
sampling-based Bayesian inference
Authors: Echeveste Rodrigo , Ferrante Enzo , Milone Diego H. , Samengo Inés 
Published: December 2021

Abstract
Theories for autism spectrum disorder (ASD) have been formulated at different levels, ranging from physiological observations to perceptual and behavioral descriptions. Understanding the physiological underpinnings of perceptual traits in ASD remains a significant challenge in the field. Here we show how a recurrent neural circuit model that was optimized to perform sampling-based inference and displays characteristic features of cortical dynamics can help bridge this gap. The model was able to establish a mechanistic link between two descriptive levels for ASD: a physiological level, in terms of inhibitory dysfunction, neural variability, and oscillations, and a perceptual level, in terms of hypopriors in Bayesian computations. We took two parallel paths—inducing hypopriors in the probabilistic model, and an inhibitory dysfunction in the network model—which lead to consistent results in terms of the represented posteriors, providing support for the view that both descriptions might constitute two sides of the same coin.
Inferring excitation-inhibition dynamics using a maximum entropy
model unifying brain structure and function
Authors: Fortel Igor , Butler Mitchell , Korthauer Laura E. , Zhan Liang , Ajilore Olusola , Sidiropoulos Anastasios , Wu Yichao , Driscoll Ira , Schonfeld Dan , Leow Alex 
Published: December 2021

Abstract
Neural activity coordinated across different scales from neuronal circuits to large-scale brain networks gives rise to complex cognitive functions. Bridging the gap between micro- and macroscale processes, we present a novel framework based on the maximum entropy model to infer a hybrid resting-state structural connectome, representing functional interactions constrained by structural connectivity. We demonstrate that the structurally informed network outperforms the unconstrained model in simulating brain dynamics, wherein by constraining the inference model with the network structure we may improve the estimation of pairwise BOLD signal interactions. Further, we simulate brain network dynamics using Monte Carlo simulations with the new hybrid connectome to probe connectome-level differences in excitation-inhibition balance between apolipoprotein E (APOE)-ε4 carriers and noncarriers. Our results reveal sex differences among APOE-ε4 carriers in functional dynamics at criticality; specifically, female carriers appear to exhibit a lower tolerance to network disruptions resulting from increased excitatory interactions. In sum, the new multimodal network explored here enables analysis of brain dynamics through the integration of structure and function, providing insight into the complex interactions underlying neural activity such as the balance of excitation and inhibition.
The Spirit in Daniel and The Twelve
Authors: Wadholm Rick 
Published: December 2021

Abstract
The Spirit moves through the books of Daniel and The Twelve (Minor Prophets). In this article, the relevant texts of these books are examined in brief and summarized with regard to the Spirit’s person and work by means of engagement with those passages making use of ‮רוח‬‎. These summaries that follow the canonical order of the Old Testament are then pointedly summarized by a brief constructive theology of the Spirit in four points: the Spirit testifies, the Spirit judges, the Spirit is life, the Spirit is gift.
The Spirit in the Gospel according to John, 1 John, and 2 John
Authors: Thomas John Christopher 
Published: December 2021

Abstract
This study seeks to trace the role and significance of pneumatology within the Gospel according to John and 1–2 John using a narrative, literary approach that has emerged with an amazing amount of consistency among a variety of biblical scholars who have sought to discern an approach to the interpretation of Scripture worthy of the Pentecostal tradition. This exploration draws heavily from and builds upon my previous studies on this theme within the broader Johannine literature.
The Spirit in 1 and 2 Thessalonians
Authors: George Roji Thomas 
Published: December 2021

Abstract
In the Thessalonian correspondence, Paul, through his occasional yet repeated references to the Spirit’s role in the life of a believer, individual and corporate, teaches that the Spirit is active in a person’s life from the time faith in the gospel is kindled in them. The Spirit regenerates a sinner through deep conviction and power and continues to sanctify a person to live in holiness according to the will of God. Paul reminds them that even their joy amid suffering is the work of the Spirit in them. It enables them not only to imitate Christ and the other believing communities in suffering but also to become a model for other persecuted communities. Paul firmly encourages them to embrace the charismatic gifts of the Spirit among them, but he warns them to be cautious so as to avoid their possible misuse.