bluuebunny/crossref_metadata_2025_split huggingface dataset:
MonkeyDB: effectively testing correctness under weak isolation levels
Authors: Biswas Ranadeep , Kakwani Diptanshu , Vedurada Jyothi , Enea Constantin , Lal Akash 
Published: October 2021

Modern applications, such as social networking systems and e-commerce platforms are centered around using large-scale storage systems for storing and retrieving data. In the presence of concurrent accesses, these storage systems trade off isolation for performance. The weaker the isolation level, the more behaviors a storage system is allowed to exhibit and it is up to the developer to ensure that their application can tolerate those behaviors. However, these weak behaviors only occur rarely in practice and outside the control of the application, making it difficult for developers to test the robustness of their code against weak isolation levels.
This paper presents MonkeyDB, a mock storage system for testing storage-backed applications. MonkeyDB supports a key-value interface as well as SQL queries under multiple isolation levels. It uses a logical specification of the isolation level to compute, on a read operation, the set of all possible return values. MonkeyDB then returns a value randomly from this set. We show that MonkeyDB provides good coverage of weak behaviors, which is complete in the limit. We test a variety of applications for assertions that fail only under weak isolation. MonkeyDB is able to break each of those assertions in a small number of attempts.
Compacting points-to sets through object clustering
Authors: Barbar Mohamad , Sui Yulei 
Published: October 2021

Inclusion-based set constraint solving is the most popular technique for whole-program points-to analysis whereby an analysis is typically formulated as repeatedly resolving constraints between points-to sets of program variables. The set union operation is central to this process. The number of points-to sets can grow as analyses become more precise and input programs become larger, resulting in more time spent performing unions and more space used storing these points-to sets. Most existing approaches focus on improving scalability of precise points-to analyses from an algorithmic perspective and there has been less research into improving the data structures behind the analyses.
Bit-vectors as one of the more popular data structures have been used in several mainstream analysis frameworks to represent points-to sets. To store memory objects in bit-vectors, objects need to mapped to integral identifiers. We observe that this object-to-identifier mapping is critical for a compact points-to set representation and the set union operation. If objects in the same points-to sets (co-pointees) are not given numerically close identifiers, points-to resolution can cost significantly more space and time. Without data on the unpredictable points-to relations which would be discovered by the analysis, an ideal mapping is extremely challenging.
In this paper, we present a new approach to inclusion-based analysis by compacting points-to sets through object clustering. Inspired by recent staged analysis where an auxiliary analysis produces results approximating a more precise main analysis, we formulate points-to set compaction as an optimisation problem solved by integer programming using constraints generated from the auxiliary analysis’s results in order to produce an effective mapping. We then develop a more approximate mapping, yet much more efficiently, using hierarchical clustering to compact bit-vectors. We also develop an improved representation of bit-vectors (called core bit-vectors) to fully take advantage of the newly produced mapping. Our approach requires no algorithmic change to the points-to analysis. We evaluate our object clustering on flow sensitive points-to analysis using 8 open-source programs (>3.1 million lines of LLVM instructions) and our results show that our approach can successfully improve the analysis with an up to 1.83× speed up and an up to 4.05× reduction in memory usage.
Effect of Lower Limb Muscle Fatigue on Fall Risk for Transfemoral Amputee: A Pilot Study
Authors: Mohd Safee Mohd Khairuddin , Abu Osman Noor Azuan 
Published: October 2021

Muscle fatigue is a decline in muscle maximum force during contraction and can influence the fall risk among people. This study is aimed at identifying the effect of fatigue on prospective fall risk in transfemoral amputees (TFA). Fourteen subjects were involved in this study with TFA (

34.7
±
8.1

yrs,

n
=
7

) and normal subjects (

31.1
±
7.4

yrs,

n
=
7

). Fatigue of lower limb muscles was induced with the fatigue protocol. Subjects were tested prefatigue and postfatigue using the standardized fall risk assessment. All results were calculated and compared between pre- and postfatigue to identify fatigue’s effect on both groups of subjects. The results showed that the fall risk increased significantly during pre- and postfatigue for TFA (

p
=
0.018

), while there were no significant differences in normal subjects (

p
=
0.149

). Meanwhile, the fall risk between TFA and normal subjects for prefatigue (

p
=
0.082

) and postfatigue (

p
=
0.084

) also showed no significant differences. The percentage (%) of increased fall risk for TFA was 19.2% compared to normal subjects only 16.7%. However, 61.4% increased of % fall risk in TFA after fatigue by using the baseline of the normal subject as the normalized % of fall risk. The increasing fall risks for TFA after fatigue are three times higher than the potential fall risk in normal subjects. The result indicates that they need to perform more precautions while prolonging lower limb activities. These results showed the implications of fatigue that can increase the fall risk due to muscle fatigue from repetitive and prolonged activities. Therefore, rehabilitation programs can be done very safely and precisely so that therapists can pursue fitness without aggravating existing injuries.
The HNF4α-BC200-FMR1–Positive Feedback Loop Promotes Growth and Metastasis in Invasive Mucinous Lung Adenocarcinoma
Authors: Chen Xiong , Zhao Yujie , Wang Daxuan , Lin Ying , Hou Jihuan , Xu Xiaolin , Wu Jianben , Zhong Linhai , Zhou Yitong , Shen Jinying , Zhang Wenqing , Cao Hanwei , Hong Xiaoting , Hu Tianhui , Zhan Yan-yan 
Published: October 2021

Abstract

Invasive mucinous lung adenocarcinoma (IMA) is a subtype of lung adenocarcinoma with a strong invasive ability. IMA frequently carries "undruggable" KRAS mutations, highlighting the need for new molecular targets and therapies. Nuclear receptor HNF4α is abnormally enriched in IMA, but the potential of HNF4α to be a therapeutic target for IMA remains unknown. Here, we report that P2 promoter-driven HNF4α expression promotes IMA growth and metastasis. Mechanistically, HNF4α transactivated lncRNA BC200, which acted as a scaffold for mRNA binding protein FMR1. BC200 promoted the ability of FMR1 to bind and regulate stability of cancer-related mRNAs and HNF4α mRNA, forming a positive feedback circuit. Mycophenolic acid, the active metabolite of FDA-approved drug mycophenolate mofetil, was identified as an HNF4α antagonist exhibiting anti-IMA activities in vitro and in vivo. This study reveals the role of a HNF4α-BC200-FMR1–positive feedback loop in promoting mRNA stability during IMA progression and metastasis, providing a targeted therapeutic strategy for IMA.

Significance:
Growth and metastatic progression of invasive mucinous lung adenocarcinoma can be restricted by targeting HNF4α, a critical regulator of a BC200-FMR1-mRNA stability axis.
Catecholamines Mediate Psychologic Stress–Induced Cancer Progression
Authors: Bernabé Daniel G. 
Published: October 2021

Abstract
Catecholamines, which are involved in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and cancer progression. The study in this issue of Cancer Research by Liu and colleagues reveals a new mechanism by which psychologic stress stimulates cancer progression through the D2 dopamine receptor and activation of the oxygen-independent HIF1α pathway. Although most investigations so far have focused on the action of the stress-related catecholamines norepinephrine and epinephrine on tumor cells, this study shows that dopamine and its receptor can be a potential therapeutic target. The findings broaden the understanding of the interaction of catecholamines with the tumor microenvironment and reinforces the need to look at psychologic stress as a modulator of cancer progression.
See related article by Liu et al., p. 5353
SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1
Authors: Pennington Katie L. , McEwan Colten M. , Woods James , Muir Colin M. , Pramoda Sahankumari A.G. , Eastmond Riley , Balasooriya Eranga R. , Egbert Christina M. , Kaur Sandeep , Heaton Tyler , McCormack Katherine K. , Piccolo Stephen R. , Kurokawa Manabu , Andersen Joshua L. 
Published: October 2021

Abstract

PTOV1 is an oncogenic protein, initially identified in prostate cancer, that promotes proliferation, cell motility, and invasiveness. However, the mechanisms that regulate PTOV1 remain unclear. Here, we identify 14-3-3 as a PTOV1 interactor and show that high levels of 14-3-3 expression, like PTOV1, correlate with prostate cancer progression. We discover an SGK2-mediated phosphorylation of PTOV1 at S36, which is required for 14-3-3 binding. Disruption of the PTOV1–14–3-3 interaction results in an accumulation of PTOV1 in the nucleus and a proteasome-dependent reduction in PTOV1 protein levels. We find that loss of 14-3-3 binding leads to an increase in PTOV1 binding to the E3 ubiquitin ligase HUWE1, which promotes proteasomal degradation of PTOV1. Conversely, our data suggest that 14-3-3 stabilizes PTOV1 protein by sequestering PTOV1 in the cytosol and inhibiting its interaction with HUWE1. Finally, our data suggest that stabilization of the 14-3-3–bound form of PTOV1 promotes PTOV1-mediated expression of cJun, which drives cell-cycle progression in cancer. Together, these data provide a mechanism to understand the regulation of the oncoprotein PTOV1.

Implications:
These findings identify a potentially targetable mechanism that regulates the oncoprotein PTOV1.
Glioblastoma–Astrocyte Connexin 43 Gap Junctions Promote Tumor Invasion
Authors: McCutcheon Sean , Spray David C. 
Published: October 2021

Abstract

Glioblastoma multiforme (GBM), classified as World Health Organization grade IV astrocytoma, is the deadliest adult cancer of the central nervous system. An important contributing factor to poor survival rates in GBM is extensive invasion, which decreases the efficacy of resection and subsequent adjuvant therapies. These treatments could be markedly improved with increased resolution of the genetic and molecular initiators and effectors of invasion. Connexin 43 (Cx43) is the principal astrocytic gap junction (GJ) protein. Despite the heterogeneity of GBM, a subpopulation of cells in almost all GBM tumors express Cx43. Functional GJs between GBM cells and astrocytes at the tumor edge are of critical interest for understanding invasion. In this study, we find that both in vitro and in ex vivo slice cultures, GBM is substantially less invasive when placed in a Cx43-deficient astrocyte environment. Furthermore, when Cx43 is deleted in GBM, the invasive phenotype is recovered. These data strongly suggest that there are opposing roles for Cx43 in GBM migration. We find that Cx43 is localized to the tumor edge in our ex vivo model, suggesting that GBM–astrocyte GJ communication at the tumor border is a driving force for invasion. Finally, we find that by a Cx43-dependent mechanism, but likely not direct channel-mediated diffusion, miRNAs associated with cell–matrix adhesion are transferred from GBM to astrocytes and miR-19b promotes invasion, revealing a role for post-transcriptional manipulation of astrocytes in fostering an invasion-permissive peritumoral niche.

Implications:
Cx43-mediated communication, specifically miRNA transfer, profoundly impacts glioblastoma invasion and may enable further therapeutic insight.
Electrostatic Discharge (ESD) as a Cause of Facial Nerve Stimulation After Cochlear Implantation: A Case Report
Authors: Rath Smruti , Glaun Mica , Emery Claudia , Liu Yi-Chun Carol 
Published: October 2021

Objective: To discuss persistent facial nerve stimulation (FNS) related to repeated electrostatic discharge (ESD) shock following cochlear implantation. Methods: Single case report with literature review. Results: FNS is a feared complication after cochlear implantation, occurring in approximately 7% of cases, with most patients having anatomic abnormalities. The presented case has no anatomical abnormalities but reported frequent environmental static shock. FNS during the first 1 to 3 seconds of processor attachment caused a significant decrease in the patient’s quality of life, requiring subsequent re-implantation with full resolution. Conclusions: FNS is a complication of cochlear implantation that can cause a great deal of distress and discomfort. Frequent electrostatic discharge (ESD) contributed to device malfunctioning and FNS in a patient with otherwise normal anatomy and should be avoided if possible.
The Influence of Depressive Symptoms on Parenting: Examining Longitudinal Dyadic Spillover and Crossover Processes During the Transition to Parenthood
Authors: Fentz Hanne N. , Nygaard Kenneth , Simonsen Marianne , Trillingsgaard Tea 
Published: October 2021

Limited research exists on dyadic spillover and crossover processes in parenting when depressive symptoms occur. This study examined both direct actor and partner effects from parents’ prenatal depressive symptoms to parenting 19 months postpartum and effects mediated via the parent’s own depressive symptoms 10 months postpartum. The Actor–Partner Interdependence Mediation Model was applied to a sample of 534 couples participating in a randomized controlled trial of a universal parenting support program. For both parents, direct and mediated actor effects were found from depressive symptoms to own parental stress and attachment at 19 months postpartum. For fathers, but not mothers, direct and mediated actor effects were also seen for own postnatal childcare involvement although in mixed directions. Direct partner effects were not indicated across gender, however mediated partner effects appeared from mothers’ depressive symptoms to fathers’ later parental stress and attachment-related feelings, but not vice versa. Findings highlight the importance of a dyadic approach to examine depressive symptoms and parenting processes during the transition to parenthood .
Comparative analysis of the quantitative parameter method and elasticity color mode method for real-time shear wave elastography in the diagnosis of benign and malignant solid breast lesions
Authors: Xue Shan-Shan , Zhao Qiao-Ling , Ruan Li-Tao , Wang Fei-Qian , Zhou Can , Sheng Wei 
Published: October 2021

Objective: To examine the performance of real-time shear wave elastography (RT-SWE) in routine clinical practice. Methods: This was a prospective study of 500 patients. The elasticity color mode method was judged by a four-mode system. The quantitative parameter method was used to measure the modulus of elasticity of the lesions. Pathologic reports were used as a gold standard to comparatively analyze the diagnostic performance of the two methods. Results: A total of 553 tumors were detected. The average mode value and the modulus of elasticity (Emax) of the benign breast masses was lower than that of malignant masses ( p < 0.05). With Emax = 67.4 as the diagnostic threshold value, the sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of the two methods were not statistically significant different ( p > 0.05). Conclusions: The shear wave quantitative parameter method and the elasticity color mode method showed similar performances in the diagnosis of benign and malignant breast masses. The elasticity color mode method is convenient and intuitive, whereas the quantitative parameter method can be used to objectively assess the lesions when it is difficult to score the elasticity of an image, but could not be relied on alone.
Return to Sports and Minimum 2-Year Outcomes of Bilateral Hip Arthroscopy in High-Level Athletes With a Propensity-Matched Benchmarking Against a Unilateral Control Group
Authors: Owens Jade S. , Jimenez Andrew E. , Monahan Peter F. , Maldonado David R. , Kyin Cynthia , Saks Benjamin R. , Ankem Hari K. , Sabetian Payam W. , Lall Ajay C. , Domb Benjamin G. 
Published: October 2021

Background: Return to sports (RTS) and patient-reported outcomes (PROs) for high-level athletes after bilateral hip arthroscopy have not been well established. Purpose: (1) To report minimum 2-year PROs and RTS rates in high-level athletes who underwent staged bilateral primary hip arthroscopies and (2) to compare clinical results against a propensity-matched control group of high-level athletes who underwent unilateral primary hip arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed for high-level athletes (professional, college, or high school) who underwent staged bilateral hip arthroscopy for femoroacetabular impingement syndrome between September 2009 and October 2018. Inclusion criteria were preoperative and minimum 2-year follow-up for modified Harris Hip Score, Non-arthritic Hip Score, Hip Outcome Score–Sports Specific Subscale (HOS-SSS), and visual analog scale for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia (lateral center-edge angle <18°), and previous ipsilateral hip surgery/conditions. Rates of achieving the minimal clinically important difference (MCID), patient acceptable symptomatic state (PASS), and maximum outcome improvement satisfaction threshold were recorded in addition to RTS. These athletes were then propensity matched in a 1:3 ratio to high-level athletes who underwent unilateral arthroscopy for comparison. Outcomes were compared among the first hip of the study group, the second hip of the study group, and the control group. Results: A total of 74 high-level athletes who underwent bilateral hip arthroscopy met the inclusion criteria, and follow-up was available for 68 (91.9%) at 58.9 ± 24.5 months (mean ± SD). Athletes undergoing bilateral hip arthroscopy returned to sports at a high rate (81.7%), demonstrated significant improvements in all recorded PROs, and achieved the MCID and PASS for the HOS-SSS at rates of 80.9% and 64.7%, respectively. PROs, RTS rate, and rates of achieving the MCID and PASS for the HOS-SSS were similar when the bilateral study group was compared with the unilateral control group ( P > .05). Conclusion: High-level athletes who undergo staged bilateral primary hip arthroscopy for femoroacetabular impingement syndrome may expect favorable PROs and RTS rates at minimum 2-year follow-up. These results were comparable with those of a propensity-matched control group of high-level athletes who underwent unilateral primary hip arthroscopy.
Labral Tear Management in Patients Aged 40 Years and Older Undergoing Primary Hip Arthroscopy: A Propensity-Matched Case-Control Study With Minimum 2-Year Follow-up
Authors: Maldonado David R. , Ouyang Vivian W. , Owens Jade S. , Jimenez Andrew E. , Saks Benjamin R. , Sabetian Payam W. , Lall Ajay C. , Domb Benjamin G. 
Published: October 2021

Background: Previous literature has suggested that primary acetabular labral reconstruction leads to lower secondary surgery rates than does labral repair for patients aged ≥40 years. Purpose: To report minimum 2-year patient-reported outcome (PRO) scores, survivorship, and secondary surgeries in patients aged ≥40 years who underwent primary hip arthroscopy with labral reconstruction compared with a propensity-matched primary labral repair group. Study Design: Case-control study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed for patients who underwent a primary hip arthroscopy for femoroacetabular impingement syndrome between January 2014 and June 2018. Patients aged ≥40 years who underwent a labral reconstruction or a labral repair and had preoperative and minimum 2-year PROs for the modified Harris Hip Score, Nonarthritic Hip Score, and visual analog scale (VAS) for pain were included. Patients with previous ipsilateral hip conditions and surgery, Tönnis grade >1, hip dysplasia, or workers’ compensation status were excluded. Patients in the reconstruction group were propensity matched 1:2 to patients in the repair group based on age, sex, and body mass index. Secondary surgeries and achievement of the minimal clinically important difference (MCID), patient acceptable symptom state (PASS), and maximum outcome improvement (MOI) were recorded. Results: A total of 53 and 106 hips were included in the labral reconstruction and repair groups, respectively. The average follow-up time was 37.6 months. The average ages for the reconstruction and repair groups were 48.01 ± 5.4 years and 48.61 ± 6.0 years, respectively. Both groups achieved significant improvements in all PROs at a minimum of 2 years, with similar achievements of MCID, PASS, and MOI, and comparable secondary surgery rates. Conclusion: Patients aged ≥40 years who received primary labral repair and primary labral reconstruction achieved similar significant improvements in all PROs, VAS pain, and patient satisfaction at the minimum 2-year follow-up, with comparable rates of secondary surgeries and achieving MCID, PASS, and MOI. Based on these findings, labral repair remains the gold standard treatment for viable labrum in this population group, while reconstruction is a useful alternative for irreparable labrum.