bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Stem Cells, not Bulk Tumor Cells, Determine Mechanisms of Resistance to SMO Inhibitors
Authors: George Joshy , Chen Yaohui , Abdelfattah Nourhan , Yamamoto Keiko , Gallup Thomas D. , Adamson Scott I. , Rybinski Brad , Srivastava Anuj , Kumar Parveen , Lee Min Gyu , Baskin David S. , Jiang Wen , Choi Jong Min , Flavahan William , Chuang Jeffrey H. , Kim Betty Y.S. , Xu Jiaqiong , Jung Sung Yun , Yun Kyuson 
Published: May 2022

The emergence of treatment resistance significantly reduces the clinical utility of many effective targeted therapies. Although both genetic and epigenetic mechanisms of drug resistance have been reported, whether these mechanisms are stochastically selected in individual tumors or governed by a predictable underlying principle is unknown. Here, we report that the dependence of cancer stem cells (CSC), not bulk tumor cells, on the targeted pathway determines the molecular mechanism of resistance in individual tumors. Using both spontaneous and transplantable mouse models of sonic hedgehog (SHH) medulloblastoma treated with a SHH/Smoothened inhibitor (SMOi), sonidegib/LDE225, we show that genetic-based resistance occurs only in tumors that contain SHH-dependent CSCs. In contrast, SHH medulloblastomas containing SHH-dependent bulk tumor cells but SHH-independent CSCs (SI-CSC) acquire resistance through epigenetic reprogramming. Mechanistically, elevated proteasome activity in SMOi-resistant SI-CSC medulloblastomas alters the tumor cell maturation trajectory through enhanced degradation of specific epigenetic regulators, including histone acetylation machinery components, resulting in global reductions in H3K9Ac, H3K14Ac, H3K56Ac, H4K5Ac, and H4K8Ac marks and gene expression changes. These results provide new insights into how selective pressure on distinct tumor cell populations contributes to different mechanisms of resistance to targeted therapies. This insight provides a new conceptual framework to understand responses and resistance to SMOis and other targeted therapies.Significance:The mechanism by which individual tumors become resistant to targeted therapies is thought to be unpredictable. This study provides novel insights into how selective pressure on cancer stem versus bulk tumor cells drives distinct and predictable mechanisms of resistance to targeted therapies. This finding paves a way for future treatment strategies that incorporate anticipated resistance mechanisms in devising second-line therapies in a personalized manner.
Understanding Baseline Physical Activity in Cardiac Rehabilitation Enrollees Using Mobile Health Technologies
Authors: Golbus Jessica R. , Gupta Kashvi , Stevens Rachel , Jeganathan V. Swetha , Luff Evan , Boyden Thomas , Mukherjee Bhramar , Klasnja Predrag , Kheterpal Sachin , Kohnstamm Sarah , Nallamothu Brahmajee K. 
Published: May 2022

Background:
Baseline physical activity in patients when they initiate cardiac rehabilitation is poorly understood. We used mobile health technology to understand baseline physical activity of patients initiating cardiac rehabilitation within a clinical trial to potentially inform personalized care.

Methods:

The VALENTINE (Virtual Application-Supported Environment to Increase Exercise During Cardiac Rehabilitation Study) is a prospective, randomized-controlled, remotely administered trial designed to evaluate a mobile health intervention to supplement cardiac rehabilitation for low- and moderate-risk patients. All participants receive a smartwatch and usual care. Baseline physical activity was assessed remotely after enrollment and included (1) 6-minute walk distance, (2) daily step count, and (3) daily exercise minutes, both over 7 days and for compliant days, defined by
>
8 hours of watch wear time. Multivariable linear regression identified patient-level features associated with these 3 measures of baseline physical activity.

Results:

From October 2020 to March 2022, 220 participants enrolled in the study. Participants are mostly White (184 [83.6%]); 67 (30.5%) are female and 84 (38.2%) are
>
65 years old. Most participants enrolled in cardiac rehabilitation after percutaneous coronary intervention (105 [47.7%]) or coronary artery bypass surgery (39 [17.7 %]). Clinical diagnoses include coronary artery disease (78.6%), heart failure (17.3%), and valve repair or replacement (26.4%). Baseline mean 6-minute walk distance was 489.6 (SD, 143.4) meters, daily step count was 6845 (SD, 3353), and exercise minutes was 37.5 (SD, 33.5). In a multivariable model, 6-minute walk distance was significantly associated with age and sex, but not cardiac rehabilitation indication. Sex but not age or cardiac rehabilitation indication was significantly associated with daily step count and exercise minutes.

Conclusions:
Baseline physical activity varies substantially in low- and moderate-risk patients enrolled in cardiac rehabilitation. Future studies are warranted to explore whether personalizing cardiac rehabilitation programs using mobile health technologies could optimize recovery.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04587882
Comment on Paolo Euron’s “Uncanny Beauty: Aesthetics of Companionship, Love, and Sex Robots”
Authors: Arnold Thomas 
Published: May 2022

Abstract
Paolo Euron’s “Uncanny Beauty: Aesthetics of Companionship, Love, and Sex Robots” lays out a vision for appreciating sex robots in aesthetic terms, centering the concept of “beauty” as a measure of what they can inspire culturally and existentially. In these comments I turn toward the field of human-robot interaction and the ethical challenges that inhabit the core of such an aesthetic turn.
Neural Patterns in Parietal Cortex and Hippocampus Distinguish Retrieval of Start versus End Positions in Working Memory
Authors: Cristoforetti Giulia , Majerus Steve , Sahan Muhammet Ikbal , van Dijck Jean-Philippe , Fias Wim 
Published: May 2022

Abstract
Coding serial order of information is a fundamental ability of our cognitive system, and still, little is known about its neural substrate. This study examined the neural substrates involved in the retrieval of information that is serially stored in verbal working memory task using a sensitive multivariate analysis approach. We compared neural activity for memorized items stemming from the beginning versus the end of a memory list assessing the degree of neural pattern discordance between order positions (beginning vs. end). The present results confirmed and refined the role of the intraparietal sulcus in the processing of serial order information in working memory. An important finding is that the hippocampus showed sensitivity to serial order information. Our results indicate that the representation of serial order information relies on a broader set of neural areas and highlight the role of the intraparietal sulcus and the hippocampus, in addition to the supramarginal gyrus and the SMA. The contribution of different neural regions might reflect the involvement of distinct levels of serial order coding (i.e., spatial, attentional, temporal) that support the representation of serial order information.
What Happened When? Cerebral Processing of Modified Structure and Content in Episodic Cueing
Authors: Siestrup Sophie , Jainta Benjamin , El-Sourani Nadiya , Trempler Ima , Wurm Moritz F. , Wolf Oliver T. , Cheng Sen , Schubotz Ricarda I. 
Published: May 2022

Abstract
Episodic memories are not static but can change on the basis of new experiences, potentially allowing us to make valid predictions in the face of an ever-changing environment. Recent research has identified prediction errors during memory retrieval as a possible trigger for such changes. In this study, we used modified episodic cues to investigate whether different types of mnemonic prediction errors modulate brain activity and subsequent memory performance. Participants encoded episodes that consisted of short toy stories. During a subsequent fMRI session, participants were presented videos showing the original episodes, or slightly modified versions thereof. In modified videos, either the order of two subsequent action steps was changed or an object was exchanged for another. Content modifications recruited parietal, temporo-occipital, and parahippocampal areas reflecting the processing of the new object information. In contrast, structure modifications elicited activation in right dorsal premotor, posterior temporal, and parietal areas, reflecting the processing of new sequence information. In a post-fMRI memory test, the participants' tendency to accept modified episodes as originally encoded increased significantly when they had been presented modified versions already during the fMRI session. After experiencing modifications, especially those of the episodes' structure, the recognition of originally encoded episodes was impaired as well. Our study sheds light onto the neural processing of different types of episodic prediction errors and their influence on subsequent memory recall.
Effect of injection pain and withdrawal movement of propofol and rocuronium in the induction of anaesthesia on postoperative pain outcomes in gynaecological laparoscopic surgery: a prospective observational study
Authors: Lee Cheol , Yim Hyeonbin , Ham Hyangdo 
Published: May 2022

Abstract

Introduction:
The experience and perception of pain may vary among individuals.This prospective cohort study aimed to determine the impact of injection pain/withdrawal movement of propofol and rocuronium in the induction of anaesthesia on postoperative pain outcomes in gynaecological laparoscopic surgery.

Methods:
A total of 100 patients aged 19–60 years received propofol and rocuronium injections for the induction of anaesthesia. The incidence of propofol injection pain (PIP) and rocuronium-induced withdrawal movement (RIWM), postoperative pain scores and total opioid consumption were evaluated, and the associations between PIP/RIWM and postoperative pain outcomes were determined.

Results:
Visual analogue scale (VAS) for pain after surgery and total opioid consumption after surgery were significantly higher in patients with PIP or RIWM than in patients without PIP or RIWM. The correlations of PIP/RIWM with VAS at 1 h, VAS at 24 h and total opioid consumption were significant and weakly positive (r = 0.249, r = 0.234, r = 0.22 and r = 0.234, respectively). The RIWM correlated more positively with pain score compared to PIP at 1 h (r = 0.408 vs. r = 0.234), PIP at 24 h (r = 0.398 vs. r = 0.227) and with total opioid consumption for 48 h after surgery (r = 0.457 vs. r = 0.234).

Conclusion:
During anaesthesia induction, the occurrence of PIP and RIWM may predict the severity of postoperative pain and total opioid consumption, with RIWM emerging as a stronger predictor than PIP.
Evaluation of the relationship between cardiac calcification and cardiovascular disease using the echocardiographic calcium score in patients undergoing peritoneal dialysis: a cross-sectional study
Authors: Sin Ho-Kwan , Wong Ping-Nam , Lo Kin-Yee , Lo Man-Wai , Chan Shuk-Fan , Lo Kwok-Chi , Wong Yuk-Yi , Ho Lo-Yi , Kwok Wing-Tung , Chan Kai-Chun , Wong Andrew Kui-Man , Mak Siu-Ka 
Published: May 2022

Introduction:
An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown.

Methods:
This cross-sectional study assessed 125 patients on PD. The ECS (range 0–8) was compared between subjects with CVD and those without.

Results:
Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD.

Conclusion:
The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.
Improved population coverage of the human papillomavirus vaccine after implementation of a school-based vaccination programme: the Singapore experience
Authors: Vijayalakshmi Karuppiah , Goei Anne Hui Yi 
Published: May 2022

Introduction:
Cervical cancer has a high disease burden in Singapore, and it is strongly associated with human papillomavirus (HPV) infections. Despite constant efforts to encourage vaccination, local HPV vaccine uptake remains low. Universal mass vaccination is a proven cost-effective method to reduce the cervical cancer disease burden. This paper reviews the newly implemented school-based HPV vaccination programme in Singapore and the factors that led to its success.

Methods:
Fully subsidised HPV vaccinations were offered to all Secondary 1 female students on an opt-in basis, starting as a rollout dose in 2019. One-time catchup vaccination was also offered to female students in Secondary 2–5. Eligible recipients were identified using enrolment data provided by Ministry of Education schools. A total of 19,144 students across 139 schools were offered the rollout dose, and 20,854 students across 140 schools were offered the catchup doses.

Results:
High vaccine uptake rates of 80.6%–87.3% were noted with the introduction of the school-based programme, translating to high vaccine coverage of 90.3%–93.4%. Only a small proportion of students (1.5%–1.9% per cohort) opted out. The rate of reported side effects, which were commonly known effects, was low at one in 1000. Among the students who reported side effects, those who received the second vaccine dose did so uneventfully.

Conclusion:
High HPV vaccine coverage was achieved after implementation of the school-based immunisation programme. Timely assessment of knowledge lapses and targeted intervention, strong partnerships with stakeholders, constant on-site adaptation and positive social influence contributed to its success. This model can be applied to future school health programmes.
Evaluation of IMERG Satellite Precipitation over the Land–Coast–Ocean Continuum. Part II: Quantification
Authors: Derin Yagmur , Kirstetter Pierre-Emmanuel , Brauer Noah , Gourley Jonathan J. , Wang Jianxin 
Published: May 2022

Abstract
To understand and manage water systems under a changing climate and meet an increasing demand for water, a quantitative understanding of precipitation is most important in coastal regions. The capabilities of the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) V06B product for precipitation quantification are examined over three coastal regions of the United States: the West Coast, the Gulf of Mexico, and the East Coast, all of which are characterized by different topographies and precipitation climatologies. A novel uncertainty analysis of IMERG is proposed that considers environmental and physical parameters such as elevation and distance to the coastline. The IMERG performance is traced back to its components, i.e., passive microwave (PMW), infrared (IR), and morphing-based estimates. The analysis is performed using high-resolution, high-quality Ground Validation Multi-Radar/Multi-Sensor (GV-MRMS) rainfall estimates as ground reference at the native resolution of IMERG of 30 min and 0.1°. IMERG Final (IM-F) quantification performance heavily depends on the respective contribution of PMW, IR, and morph components. IM-F and its components overestimate the contribution of light rainfall (<1 mm h−1) and underestimate the contribution of high rainfall rates (>10 mm h−1) to the total rainfall volume. Strong regional dependencies are highlighted, especially over the West Coast, where the proximity of complex terrain to the coastline challenges precipitation estimates. Other major drivers are the distance from the coastline, elevation, and precipitation types, especially over the land and coast surface types, that highlight the impact of precipitation regimes.
Goldhillite, Cu5Zn(AsO4)2(OH)6⋅H2O, a new mineral species, and redefinition of philipsburgite, Cu5Zn[(AsO4)(PO4)](OH)6⋅H2O, as an As–P ordered species
Authors: Ismagilova Rezeda M. , Rieck Branko , Kampf Anthony R. , Giester Gerald , Zhitova Elena S. , Lengauer Christian L. , Krivovichev Sergey V. , Zolotarev Andrey A. , Ciesielczuk Justyna , Mikhailova Julia A. , Belakovsky Dmitry I. , Bocharov Vladimir N. , Shilovskikh Vladimir V. , Vlasenko Natalia S. , Nash Barbara P. , Adams Paul M. 
Published: May 2022

AbstractPhilipsburgite has been redefined as the intermediate member of the goldhillite–philipsburgite–kipushite isomorphous series with the ideal formula Cu5Zn[(AsO4)(PO4)](OH)6⋅H2O due to the site-selective As–P substitution. The new mineral goldhillite, ideally Cu5Zn(AsO4)2(OH)6⋅H2O [or Cu5Zn(AsO4)(AsO4)(OH)6⋅H2O], is the arsenate end-member of this series. Goldhillite occurs on fracture surfaces in a rock comprised mostly of quartz with iron hydroxides in association with mixite, cornwallite and conichalcite. Goldhillite forms transparent, bright emerald-green, tabular crystals with vitreous lustre, flattened on {100}, up to 1 mm across and in rosettes up to 1.5 mm. The mineral is brittle with uneven fracture and perfect cleavage on {100}; the Mohs hardness is 3.5. The calculated density for the holotype is 4.199 g cm–3. The Raman spectrum is consistent with the presence of H2O-molecules, OH-groups, AsO4 tetrahedra and traces of PO4. Electron microprobe analyses of goldhillite (H2O content based on the crystal structure) provided: CuO 48.91, ZnO 13.18, As2O5 26.06, P2O5 3.25, H2O 8.97, total 100.37 wt.%. The empirical formula for goldhillite based on O = 15 apfu is (Cu4.69Zn1.23)Σ5.92(As0.86P0.18O4)2(OH)5.61⋅H2O. The crystal structures of goldhillite and philipsburgite were determined using single-crystal X-ray diffraction data and refined to R1 = 0.054 (for 2365 I > 2σI reflections) and 0.052 (for 2308 I > 2σI reflections), respectively. Goldhillite is monoclinic, P21/c, a = 12.3573(5), b = 9.2325(3), c = 10.7163(4) Å, β = 97.346(4)°, V = 1212.59(8) Å3 and Z = 4. Philipsburgite is monoclinic, P21/c, a = 12.3095(9), b = 9.2276(3), c = 10.7195(3) Å, β = 97.137(7)°, V = 1208.16(10) Å3 and Z = 4. The strongest lines of the powder X-ray diffraction pattern of goldhillite [d, Å (I, %)(hkl)] are: 4.09 (28)(300), 3.41 (23)(12$\bar{2}$, 221, 311), 2.57 (100)(132, 11$\bar{4}$, 20$\bar{4}$), 2.17 (18)(42$\bar{3}$, 332), 1.95 (22)(432) and 1.54 (20)(13$\bar{6}$, 060). Goldhillite is named after its type locality, the Gold Hill mine, Tooele County, Utah, USA.
Medvedevite, KMn2+V5+2O6Cl⋅2H2O, a new fumarolic mineral from the Tolbachik fissure eruption 2012–2013, Kamchatka Peninsula, Russia
Authors: Shablinskii Andrey P. , Avdontceva Margarita S. , Vergasova Lidiya P. , Filatov Stanislav K. , Avdontseva Evgenia Yu. , Povolotskiy Alexey V. , Moskaleva Svetlana V. , Kargopoltsev Anatoly A. , Britvin Sergey N. , Shorets Olga U. 
Published: May 2022

AbstractMedvedevite, KMn2+V5+2O6Cl⋅2H2O, is a new mineral discovered in the Toludskoe lava field, formed during the 2012–2013 Tolbachik fissure eruption. The mineral occurs as thin acicular transparent bright red crystals up to 0.15 mm. Medvedevite is associated with thénardite, halite, aphthitalite, leonite, kieserite, eugsterite and syngenite. The empirical formula calculated on the basis of 13+ positive charge units for the anhydrous part and 2H2O is (K1.02Na0.03)Σ1.05Mn2+0.95(V5+1.92S6+0.05Si0.04)Σ2.01O6.02Cl0.96⋅2H2O. The crystal structure of medvedevite was determined using single-crystal X-ray diffraction data: monoclinic crystal system, the space group is P21/c, a = 7.1863(2), b = 10.1147(3), c = 12.7252(4) Å, β = 106.243(3)°, V = 888.04(5) Å3, Z = 4 and R1 = 0.029. The concept of ‘structural unit’ and ‘interstitial complex’ could be applied to the crystal structure of medvedevite. The structural units in medvedevite are based on the high bond-valence V5+O5 polyhedra which share edges and link into [V2O6] chains elongated along the a axis. The interstitial complexes consist of Mn2+, K+ cations and H2O groups and occupy the interstices between structural units. The mineral is optically biaxial (+), with α =1.782(2), β = 1.786(2), γ = 1.792(2), 2V(calc) = 41° (λ = 589 nm). The seven strongest lines of the powder XRD pattern are [d, Å (I, %) (hkl)]: 7.79(100)(011); 5.70(11)(110); 4.75(14)(11$\bar{2}$); 3.89(29)(022); 3.25(53)(031); 2.958(79)(21$\bar{3}$); and 2.850(33)(220). The mineral has been named in honour of the Russian geologist and chemist Robert Alexandrovich Medvedev (1939–2005).
Mutational landscape of nasopharyngeal carcinoma based on targeted next-generation sequencing: implications for predicting clinical outcomes
Authors: Zhou Zihan , Li Peifeng , Zhang Xianbin , Xu Juan , Xu Jin , Yu Shui , Wang Dongqing , Dong Wei , Cao Xiujuan , Yan Hongjiang , Sun Mingping , Ding Xiuping , Xing Jun , Zhang Peng , Zhai Limin , Fan Tingyong , Tian Shiyu , Yang Xinhua , Hu Man 
Published: May 2022

Abstract
Background
The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS).

Methods
A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell’s concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan–Meier curves and log-rank tests.

Results
The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts.

Conclusions
In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.