bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome
Authors: Xu Xia , Guan Rui , Gong Ke , Xie Huaibing , Shi Lei 
Published: February 2022

Abstract
Background
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism.

Methods
PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays.

Results
Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p.

Conclusion
Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.
Assessing inertial measurement unit locations for freezing of gait detection and patient preference
Authors: O’Day Johanna , Lee Marissa , Seagers Kirsten , Hoffman Shannon , Jih-Schiff Ava , Kidziński Łukasz , Delp Scott , Bronte-Stewart Helen 
Published: February 2022

Abstract
Background
Freezing of gait, a common symptom of Parkinson’s disease, presents as sporadic episodes in which an individual’s feet suddenly feel stuck to the ground. Inertial measurement units (IMUs) promise to enable at-home monitoring and personalization of therapy, but there is a lack of consensus on the number and location of IMUs for detecting freezing of gait. The purpose of this study was to assess IMU sets in the context of both freezing of gait detection performance and patient preference.

Methods
Sixteen people with Parkinson’s disease were surveyed about sensor preferences. Raw IMU data from seven people with Parkinson’s disease, wearing up to eleven sensors, were used to train convolutional neural networks to detect freezing of gait. Models trained with data from different sensor sets were assessed for technical performance; a best technical set and minimal IMU set were identified. Clinical utility was assessed by comparing model- and human-rater-determined percent time freezing and number of freezing events.

Results
The best technical set consisted of three IMUs (lumbar and both ankles, AUROC = 0.83), all of which were rated highly wearable. The minimal IMU set consisted of a single ankle IMU (AUROC = 0.80). Correlations between these models and human raters were good to excellent for percent time freezing (ICC = 0.93, 0.89) and number of freezing events (ICC = 0.95, 0.86) for the best technical set and minimal IMU set, respectively.

Conclusions
Several IMU sets consisting of three IMUs or fewer were highly rated for both technical performance and wearability, and more IMUs did not necessarily perform better in FOG detection. We openly share our data and software to further the development and adoption of a general, open-source model that uses raw signals and a standard sensor set for at-home monitoring of freezing of gait.
Towards functional robotic training: motor learning of dynamic tasks is enhanced by haptic rendering but hampered by arm weight support
Authors: Özen Özhan , Buetler Karin A. , Marchal-Crespo Laura 
Published: February 2022

Abstract
Background
Current robot-aided training allows for high-intensity training but might hamper the transfer of learned skills to real daily tasks. Many of these tasks, e.g., carrying a cup of coffee, require manipulating objects with complex dynamics. Thus, the absence of somatosensory information regarding the interaction with virtual objects during robot-aided training might be limiting the potential benefits of robotic training on motor (re)learning. We hypothesize that providing somatosensory information through the haptic rendering of virtual environments might enhance motor learning and skill transfer. Furthermore, the inclusion of haptic rendering might increase the task realism, enhancing participants’ agency and motivation. Providing arm weight support during training might also enhance learning by limiting participants’ fatigue.

Methods
We conducted a study with 40 healthy participants to evaluate how haptic rendering and arm weight support affect motor learning and skill transfer of a dynamic task. The task consisted of inverting a virtual pendulum whose dynamics were haptically rendered on an exoskeleton robot designed for upper limb neurorehabilitation. Participants trained with or without haptic rendering and with or without weight support. Participants’ task performance, movement strategy, effort, motivation, and agency were evaluated during baseline, short- and long-term retention. We also evaluated if the skills acquired during training transferred to a similar task with a shorter pendulum.

Results
We found that haptic rendering significantly increases participants’ movement variability during training and the ability to synchronize their movements with the pendulum, which is correlated with better performance. Weight support also enhances participants’ movement variability during training and reduces participants’ physical effort. Importantly, we found that training with haptic rendering enhances motor learning and skill transfer, while training with weight support hampers learning compared to training without weight support. We did not observe any significant differences between training modalities regarding agency and motivation during training and retention tests.

Conclusion
Haptic rendering is a promising tool to boost robot-aided motor learning and skill transfer to tasks with similar dynamics. However, further work is needed to find how to simultaneously provide robotic assistance and haptic rendering without hampering motor learning, especially in brain-injured patients.
Trial registrationhttps://clinicaltrials.gov/show/NCT04759976
Statistical analysis plan for an international, double-blind, randomized controlled clinical trial on the use of phantom motor execution as a treatment for phantom limb pain
Authors: Lendaro Eva , Earley Eric J. , Ortiz-Catalan Max 
Published: February 2022

Abstract
Background
Phantom limb pain (PLP) is a detrimental condition that can greatly diminish the quality of life. Purposeful control over the phantom limb activates the affected neural circuitry and leads to dissolution of the pathological relationship linking sensorimotor and pain processing (which gives rise to PLP). An international, double-blind, randomized controlled clinical trial (RCT) on the use of phantom motor execution (PME) as a treatment for PLP is currently undertaken, where PME is compared to an active placebo treatment, namely phantom motor imagery (PMI).

Methods and design
Sixty-seven subjects suffering from PLP in upper or lower limbs are randomly assigned in 2:1 ratio to PME or PMI interventions respectively. Subjects allocated to either treatment receive 15 interventions where they are exposed to the same VR-AR environments using the same device. The only difference between interventions is whether phantom movements are performed (PME) or imagined (PMI).

Results
The primary outcome of the study is to examine whether 15 sessions of PME can induce a greater PLP relief, compared to PMI. The secondary objectives are to examine whether 15 sessions of PME provide a greater improvement in different aspects related to PLP compared to PMI, such as pain duration, pain intensity as measured by other metrics, and the patient’s own impression about the effect of treatment. Long-term retention of treatment benefits will be assessed as change in all the variables (both primary and secondary) between baseline and follow-up timepoints (at 1, 3, and 6 months post-treatment).

Conclusion
This manuscript serves as the formal statistical analysis plan (version 1.0) for the international, double-blind, randomized controlled clinical trial on the use of PME as a treatment for PLP. The statistical analysis plan was completed on 3 August 2021.

Trial registration
ClinicalTrials.govNCT03112928. Registered on April 13, 2017
SAP version: version: 1.0, date: 2021/08/03
Protocol version: This document has been written based on information contained in the study protocol published in Lendaro et al. (BMJ Open 8:e021039, 2018), in July 2018.
SAP revisions: Not applicable
Novel gene mutations in three Japanese patients with ARC syndrome associated mild phenotypes: a case series
Authors: Satomura Yoshinori , Bessho Kazuhiko , Nawa Nobutoshi , Kondo Hidehito , Ito Shogo , Togawa Takao , Yano Masanao , Yamano Yuki , Inoue Taisuke , Fukui Miho , Onuma Shinsuke , Fukuoka Tomoya , Yasuda Kie , Kimura Takeshi , Tachibana Makiko , Kitaoka Taichi , Nabatame Shin , Ozono Keiichi 
Published: February 2022

Abstract
Background
Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing.

Case presentation
Case 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother’s VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39.

Conclusions
The first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.
Comparison of soil chemical and microbial properties in monoculture larch and mixed plantations in a temperate forest ecosystem in Northeast China
Authors: Yang Kai , Zhu Jiaojun , Zhang Weiwei , Gu Jiacun , Wang Zhengquan , Xu Shuang 
Published: February 2022

Abstract
Background
The introduction of broadleaved tree species in monoculture larch plantations to establish mixed plantations is a feasible way to improve soil properties. However, our understanding of how mixed plantations of larch and broadleaved tree species affect soil properties, particularly microbial community structures and functions, remains limited. We compared three paired monoculture larch (Larix gmelinii) and mixed [L. gmelinii–Fraxinus mandshurica (a dominant broadleaved species)] plantations to investigate the effect of a larch–broadleaved tree species combination on the carbon (C) and nitrogen (N) content, abundance and composition of microbial communities, and enzyme activities associated with litter and soil.

Results
The bacterial abundance in the litter, soil N availability, pH and electronic conductivity were significantly higher in the mixed-species plantation in comparison with those of the monoculture plantation. However, in the litter of mixed-species plantation, the relative levels of Agaricomycetes fungi were lower than those of the monoculture plantation, indicating that soil fungal communities were affected more than bacterial communities. In contrast, soil in the mixed-species plantation showed increased exoglucanase and N-acetyl-β-glucosaminidase activities. However, the C and N levels, δ13C and δ15N values, and fungal abundance in litter and soil were not significantly different between the monoculture and mixed-species plantations.

Conclusions
Our findings suggest that fungal community compositions and enzyme activities are sensitive to the introduction of broadleaved tree species into larch plantations. Thus, these parameters can be used as important indicators to evaluate the effects of tree species selection on soil restoration.
Aptness of entomogenus fungi with diatomaceous earth against various stored grain insect pests
Authors: Hanif Ch. Muhammad Shahid , Mansha Muhammad Zeeshan , Aatif Hafiz Muhammad , Zaman Qamar uz , Ijaz Muhammad , Ikram Kamran , Khan Azhar Abbas , Ismail Muhammad , Ashir Muhammad 
Published: February 2022

Abstract
Background
Numerous biotic and abiotic factors are responsible for losses of grains quality and quantity during storage. Insecticides used to control stored grain insect pests are not only hazardous to mammals and environment but also induce resistance in insect pests towards these synthetic chemicals. A current trial was conducted, during 2020, in a stored grain laboratory at the College of Agriculture, BZU, Bahadur Sub Campus, Layyah, Punjab, Pakistan. A diatomaceous earth (DE) formulation enhanced with bitterbarkomycin (DEBBM) and combined with Beauveria bassiana (Balsamo) Vuillemin was evaluated against Cryptolestes ferrugineus, (Stephens) (Coleoptera: Laemophloeidae), Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) and Tribolium castaneum (Coleoptera: Tenebrionidae) under laboratory conditions.

Results
DEBBM was applied at the rate of 50 mg/kg, DE (150 mg/kg) and Beauveria bassiana (1.5 × 108 and 1.5 × 1010 conidia/kg) alone as well as in combination with wheat, rice and maize. Treated adult mortality was recorded at 7, 14 and 21 days after exposure. Results of the current study showed that insect pest mortality was maximum in the case of combined application of DEBBM with B. bassiana (high concentration) at prolonged exposure time as compared to their alone application. Mortality of C. ferrugineus was maximum in wheat and rice (100%) over maize (97%), while, R. dominica exhibited high mortality in wheat (100%) followed by rice (97%) and maize (94%) at combined application of DEBBM with B. bassiana (high concentration) after 21 days. Regarding T. castaneum mortality was high in wheat (100%) followed by rice (93%) and maize (88%) in case of combined application of DEBBM with B. bassiana (high concentration) at prolonged exposure time (21 days).

Conclusion
In crux, the current trial showed that a mixture of DEBBM and B. bassiana is helpful in controlling tested insect pests.
Corticosteroid-Binding Globulin Deficiency Independently Predicts Mortality in Septic Shock
Authors: Meyer Emily Jane , Nenke Marni Anne , Davies Michael Laurence , Chapman Marianne , Rankin Wayne , Rushworth R Louise , Torpy David James 
Published: February 2022

Abstract

Context
Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock.

Objective
To determine whether severely deficient serum CBG &lt; 200 nmol/L (reference range 269-641 nmol/L) independently predicts septic shock mortality.

Methods
A prospective observational study in patients with septic shock. Patients were categorized into 2 groups: mean plasma CBG concentrations &lt;200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorization by nadir CBG. Primary outcome was intensive care unit (ICU) mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal replacement therapy, and clinician-instituted hydrocortisone.

Results
135 patients were included. Mortality rates in ICU were higher in the CBG &lt; 200 nmol/L vs the CBG ≥ 200 nmol/L group: 32.4% vs 13.9% [odds ratio (OR) 2.97 (95% CI 1.19, 7.41); P = 0.02] with 28-day mortality OR 2.25 (95% CI 0.99, 5.11) and 90-day mortality OR 2.21 (95% CI 0.99, 4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG &lt; 200 nmol/L (adjusted OR 3.23, 95% CI 1.06, 9.88), Acute Physiology and Chronic Health Evaluation II &gt; 25 (adjusted OR 3.58, 95% CI 1.20, 10.68), Sequential Organ Failure Assessment (SOFA) liver score (adjusted OR 1.98, 95% CI 1.04, 3.72), and renal replacement therapy (adjusted OR 6.59, 95% CI 2.17, 20.01). Nadir CBG levels were associated with higher SOFA cardiovascular scores and norepinephrine total dose (μg; P &lt; 0.01) and duration (days; P &lt; 0.01). Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality.

Conclusion
Septic shock patients with CBG &lt; 200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor.
Logic-Based Benders Decomposition for Integrated Process Configuration and Production Planning Problems
Authors: Martínez Karim Pérez , Adulyasak Yossiri , Jans Raf 
Published: February 2022

We propose a general logic-based Benders decomposition (LBBD) for production planning problems with process configuration decisions. This family of problems appears in contexts where the machines are set up according to specific patterns, templates, or, in general, process configurations that allow for simultaneously producing products of different types. The problem requires determining feasible configurations for the machines and their corresponding production levels to fulfill the demand at the minimum total cost. The structure of this problem contains nonlinear constraints that link the number of units produced of each product with the used configurations and their production levels. We decompose the original problem into a master problem, where the configurations are determined, and a subproblem, where the production amounts are determined. This allows us to apply the LBBD technique to solve the problem using a standard LBBD implementation and a branch-and-check algorithm. LBBD enhancements through logic-based inequalities generated for subsets of products with common characteristics are proposed. Such inequalities represent a form of the subproblem relaxation added to the master problem during its resolution. In our computational experiments, we apply the proposed LBBD approaches to two different applications from the literature: cutting stock problems in the steel industry and a printing problem. Results show that the LBBD methods find optimal solutions much faster than the solution approaches in the literature and have a superior performance with respect to the number of instances solved to optimality and the solution quality. Summary of Contribution: In this work, we introduce a unified exact solution algorithm based on logic-based Benders decomposition to solve a class of integrated production planning problems that include process configuration decisions. We propose a general mathematical representation of the original integrated planning problem and logic-based Benders reformulations that can be applied to solve several problems within the studied class. Our implementation frameworks provide guidelines to practitioners in the field. The solution approaches in this paper together with the proposed methodological enhancements can be adapted to solve other integrated planning problems in a similar context, including the case when the original problem has a complex combinatorial and nonlinear structure.
Metastasis patterns and prognosis of octogenarians with metastatic breast cancer: A large-cohort retrospective study
Authors: Lv Zhenye , Zhang Wendan , Zhang Yingjiao , Zhong Guansheng , Zhang Xiaofei , Yang Qiong , Li Ying 
Published: February 2022

Background
Breast cancer may differ biologically in patients aged over 80 years. The objective of the current study was to analyze the metastasis patterns and prognosis of elderly patients with metastatic breast cancer (MBC) and compare it to patients of other ages.

Methods
The Surveillance, Epidemiology, and End Results (SEER) database was utilized to select MBC patients from 2010 to 2015. Chi-squared test was used to compare clinicopathological characteristics among different aged groups. The Kaplan-Meier method and multivariate Cox model were utilized for survival analysis.

Results
A total of 10479 MBC patients were included, among which 1036 (9.9%) patients were aged over 80 years. Compared with other aged group, the elderly patients tended to have a higher proportion of HR+/Her2- subtype, white race, lower tumor differentiation, and receive less treatment, including surgery, chemotherapy and radiotherapy (P< 0.001). MBC patients with different age presented with distinctive metastatic patterns. The older patients were more likely to have lung metastasis, but less likely to have bone, brain, liver and multiple sites metastasis than the younger group (P <0.001). The proportion of TNBC subtype increased substantially in the older patients with brain metastasis, compared to the younger and middle-aged group. The old age was demonstrated to significantly associate with worse prognosis of MBC patients. Additionally, our findings also showed that older MBC patients could achieve dramatical overall survival benefit from surgery (HR = 0.58; P <0.001) and chemotherapy (HR = 0.59; P <0.001), but not the radiotherapy (HR = 0.96; P = 0.097).

Conclusion
The elderly MBC patients presented with distinctive metastatic patterns, clinical characteristics, and prognostic outcomes compared with younger patients. Our findings could assist clinicians in making appropriate therapeutic decision.