bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective assessment of porcine circovirus 3 (PCV-3) in formalin-fixed, paraffin-embedded tissues from pigs affected by different clinical-pathological conditions
Authors: Cobos Àlex , Sibila Marina , Alomar Jaume , Pérez Mónica , Huerta Eva , Segalés Joaquim 
Published: December 2022

Abstract
Background
Porcine circovirus 3 (PCV-3) is a recently discovered pathogen of swine that has been associated with several conditions. However, many questions remain unanswered regarding its infection, especially in terms of pathogenesis and disease impact. The aim of the present study was to retrospectively investigate the presence of PCV-3 genome by real time quantitative PCR (qPCR) and in situ hybridization (ISH) on selected formalin-fixed paraffin-embedded tissues of pigs affected by different clinical conditions and histological lesions.

Materials and methods
Conditions investigated included porcine dermatitis and nephropathy syndrome (PDNS), periweaning failure-to-thrive syndrome (PFTS), congenital tremors type AII, reproductive disorders, and pigs affected by systemic periarteritis/arteritis, myocarditis, or encephalitis. Studied cases (n = 587) were investigated from a diagnostic database (n = 4162) that comprised samples collected within the period 1998–2021. From each condition/lesion, 10 to 12 cases were subsequently selected and tested by qPCR and ISH (72 cases total).

Results
A total of 587 cases fulfilled inclusion criteria of the different studied conditions and were distributed among the seven groups. For the further selected cases, PCV-3 genome was found by qPCR in 12/12 periarteritis, 5/10 reproductive disease, 5/10 PFTS, 3/10 myocarditis, 1/10 encephalitis and 1/10 congenital tremor cases. PCV-3 was not found in any of the PDNS cases assessed. In periarteritis cases, tissues more commonly affected were mesenteric arteries and kidney. Reproductive disease cases associated to PCV-3 genome consistently displayed myocarditis. The lesions and labelling distribution of PFTS cases with presence of PCV-3 genome were comparable to those of the periarteritis group. qPCR and ISH yielded similar results within each studied case and were statistically comparable.

Conclusion
Our results suggest that periarteritis is the hallmark lesion of PCV-3-SD, and that mesenteric lymph node and kidney appeared to be the most reliable organs to confirm the presence of PCV-3 genome in cases with periarteritis.
Spatial and temporal drivers of post-fire tree establishment and height growth in a managed forest landscape
Authors: Andrus Robert A. , Droske Christine A. , Franz Madeline C. , Hudak Andrew T. , Lentile Leigh B. , Lewis Sarah A. , Morgan Penelope , Robichaud Peter R. , Meddens Arjan J. H. 
Published: December 2022

AbstractBackgroundIn seed-obligate conifer forests of the western US, land managers need a better understanding of the spatiotemporal variability in post-fire recovery to develop adaptation strategies. Successful establishment of post-fire seedlings requires the arrival of seeds and favorable environmental conditions for germination, survival, and growth. We investigated the spatiotemporal limitations to post-fire seedling establishment and height growth in dry to moist mixed conifer forests with and without post-fire forest management treatments (salvage logging, grass seeding) in areas burned from low to high severity. In 2011, we measured post-fire seedling establishment year, juvenile density (seedlings and saplings), and height growth (annual and total) in 50 plots with six conifer species in the School Fire (2005), Blue Mountains, WA, USA. In 2021, we remeasured the plots for post-fire juvenile density and height growth.ResultsPost-fire juvenile tree densities appeared sufficient for self-replacement of forest (> 60 stems ha−1) in 96% of plots in 2021 (median 3130 stems ha−1), but densities were highly variable (range 33–100,501 stems ha−1). Annual seedling establishment was positively correlated with cooler, wetter climate conditions during the summer of germination (July–September) and the growing season of the subsequent year (April–September) for multiple tree species. We found lower juvenile densities at greater distances to seed sources and with higher grass cover, while salvage logging had no effect. Annual height growth was shorter on warmer, drier topographic positions for three species, whereas annual height growth was associated with climate variability for one species. Shifts in height class structure from 2011 to 2021 were, in part, explained by differences among species in annual height growth.ConclusionsAbundant and widespread tree seedling establishment for multiple conifer species after fire was strong evidence that most burned sites in the present study are currently on a trajectory to return to forest. However, post-fire establishment may be constrained to brief periods of cooler, wetter climate conditions following future fires. Long-term monitoring of post-fire recovery dynamics is needed to inform management activities designed to adapt forests to climate change and future disturbances, which will collectively shape future forest structure and composition.
MUTYH and KLF6 gene expression fluctuations in tumor tissue and tumor margins tissues of colorectal cancer
Authors: Naebi Hoora , Bandegi Ahmadreza , Talebinasab Fereshteh , Samidoust Pirouz , Norollahi Seyedeh Elham , Vahidi Sogand , Samadani Ali Akbar 
Published: December 2022

Abstract
Background
Colorectal cancer (CRC) is one of the most important cancers in the world, and its prevalence varies depending on the geographical area. Genetically, tumor regeneration in CRC as a multi-step process involves activating mutations in protocogenes and losing the function of tumor suppressor genes as well as DNA repair and recovery genes. Occur in this way, our goal was to investigate the expression of KLF6 genes as a tumor suppressor and MUTYH involved in the DNA repair process in colorectal cancer.

Methods
This research was conducted during the years 2019–2018 in Razi Hospital, Rasht. The subjects included 30 tumoral and 30 non-tumoral tissues of colorectal cancer and 20 healthy controls. The real-time PCR method was used to investigate the gene expression. For data analysis by SPSS, parametric statistical tests ANOVA and T test and regression analysis were used and p value values less than 0.05 were considered significant.

Results
The expression of KLF6 gene in tumoral tissues showed a significant decrease compared to non-tumoral tissues (P = 0.04). Also, the expression of MUTYH gene in tumor tissue showed a significant decrease compared to non-tumoral (P = 0.02) and this decrease in MUTYH gene expression had a significant relationship with increasing tumor stage (P = 0.01).

Conclusion
These findings suggest that decreased expression of KLF6 and MUTYH genes in the study population has a significant relationship with colorectal cancer and can be considered as tumor marker in diagnostic purpose.
Survey on Cairene primary school teachers’ knowledge and attitude about stuttering
Authors: Elrefaie Dina Ahmed , Ella Mahmoud Youssef Abou El , Halim Amal Saeed Abd El , Gobran Randa Reda 
Published: December 2022

Abstract

Background
Behavior of teachers towards stutterers could have an impact on stutterers’ self-image and the way they are viewed and treated by their peers. Assessment of the amount of knowledge of primary school teachers is essential to include awareness about stuttering in teachers’ education to enable early identification and proper management for these children.

Aim
This study aimed to feature the primary school teachers’ knowledge and attitude towards stuttering students.

Method
This study included 100 primary school teachers selected from 4 primary governmental schools in Cairo. Our subjects were subjected to a questionnaire field study to measure their assumptions, attitudes, and knowledge of stuttering and persons who stutter.

Results
There was some good teachers’ attitude like talk as if the stutterer is talking normally. In addition, tell the student to slow down the rate of speech, and tell the student to think before he/she speaks, allowing stutters to take a deep breath, praising the student when he/she speaks well. While there were undesirable reactions in the form of teachers feel inpatient and the stutterer is nervous, shy and has difficulty in making friends.

Conclusion
The results of this study showed some good knowledge of teachers about stuttering with some favorable attitude about stuttering which can help people who stutter (PWS) to overcome their difficulty, but still it is not enough. More efforts should be made to improve teachers’ behavior to insure giving the best possible help to PWS.
The Impact of Inflammation and General Anesthesia on Memory and Executive Function in Mice
Authors: Khodaei Shahin , Wang Dian-Shi , Ariza Anthony , Syed Raza M. , Orser Beverley A. 
Published: December 2022

BACKGROUND:
Perioperative neurocognitive disorders (PNDs) are complex, multifactorial conditions that are associated with poor long-term outcomes. Inflammation and exposure to general anesthetic drugs are likely contributing factors; however, the relative impact of each factor alone versus the combination of these factors remains poorly understood. The goal of this study was to compare the relative impact of inflammation, general anesthesia, and the combination of both factors on memory and executive function.

METHODS:
To induce neuroinflammation at the time of exposure to an anesthetic drug, adult male mice were treated with lipopolysaccharide (LPS) or vehicle. One day later, they were anesthetized with etomidate (or vehicle). Levels of proinflammatory cytokines were measured in the hippocampus and cortex 24 hours after LPS treatment. Recognition memory and executive function were assessed starting 24 hours after anesthesia using the novel object recognition assay and the puzzle box, respectively. Data are expressed as mean (or median) differences (95% confidence interval).

RESULTS:
LPS induced neuroinflammation, as indicated by elevated levels of proinflammatory cytokines, including interleukin-1β (LPS versus control, hippocampus: 3.49 pg/mg [2.06–4.92], P < .001; cortex: 2.60 pg/mg [0.83–4.40], P = .010) and tumor necrosis factor-α (hippocampus: 3.50 pg/mg [0.83–11.82], P = .002; cortex: 2.38 pg/mg [0.44–4.31], P = .021). Recognition memory was impaired in mice treated with LPS, as evinced by a lack of preference for the novel object (novel versus familiar: 1.03 seconds [−1.25 to 3.30], P = .689), but not in mice treated with etomidate alone (novel versus familiar: 2.38 seconds [0.15–4.60], P = .031). Mice cotreated with both LPS and etomidate also exhibited memory deficits (novel versus familiar: 1.40 seconds [−0.83 to 3.62], P = .383). In the puzzle box, mice treated with either LPS or etomidate alone showed no deficits. However, the combination of LPS and etomidate caused deficits in problem-solving tasks (door open task: −0.21 seconds [−0.40 to −0.01], P = .037; plug task: −0.30 seconds [−0.50 to −0.10], P < .001; log values versus control), indicating impaired executive function.

CONCLUSIONS:
Impairments in recognition memory were driven by inflammation. Deficits in executive function were only observed in mice cotreated with LPS and etomidate. Thus, an interplay between inflammation and etomidate anesthesia led to cognitive deficits that were not observed with either factor alone. These findings suggest that inflammation and anesthetic drugs may interact synergistically, or their combination may unmask covert or latent deficits induced by each factor alone, leading to PNDs.
High-Flow Nasal Cannula for Apneic Oxygenation in Obese Patients for Elective Surgery: A Systematic Review and Meta-Analysis
Authors: Bright Matthew R. , Harley William A. , Velli Gina , Zahir Syeda Farah , Eley Victoria 
Published: December 2022

BACKGROUND:
Obese patients desaturate rapidly during the apneic period after induction of anesthesia for elective surgery. Administration of oxygen using high-flow nasal cannulae (HFNCs) may prevent desaturation in nonobese patients compared to facemask (FM) preoxygenation. The aim of this meta-analysis was to compare the effectiveness of HFNC to FM preoxygenation techniques in reducing preintubation desaturation in obese patients undergoing elective surgery.

METHODS:
This study protocol was registered on PROSPERO (CRD42022309391). Adult studies that compared HFNC and FM preoxygenation in obese patients requiring general anesthesia for elective surgery were included. The primary outcome was desaturation resulting in oxygen saturation of <92% from induction of anesthesia until intubation. Secondary outcomes included the lowest arterial oxygen content before intubation expressed in mm Hg, safe apnea time expressed in seconds, the lowest oxygen saturation before intubation expressed as a percentage, patient-reported discomfort, the need for rescue ventilation, and the incidence of aspiration of gastric contents during intubation. Risk of bias was assessed using the Cochrane Collaboration tool. Certainty was assessed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

RESULTS:
Six studies including 351 participants were eligible for analysis. There was no difference in odds of oxygen desaturation <92% between HFNC and FM (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.15–1.63; P = .24). The HFNC group had a significantly longer safe apnea time (mean difference [MD], –124.20 with 95% CI, –200.47 to −47.93; P = .001). There was no difference between HFNC and FM in the lowest arterial oxygen content (MD, −23.90; 95% CI, −88.64 to 40.85; P = .47) and the lowest peripheral oxygenation saturation (MD, −0.47 with 95% CI, –5.07 to 4.12; P = .84). HFNC had a lower odd of discomfort than FM (OR, 0.13; 95% CI, 0.03–0.52; P = .004). There was no difference in the odds of aspiration of gastric contents between HFNC and FM (OR, 0.33; 95% CI, 0.01–8.21; P = .50). The risk of bias for our primary and secondary outcomes was low. The GRADE assessment for our primary outcome indicated a low level of certainty. For secondary outcomes, the GRADE assessment indicated a very low certainty for all outcomes except for patient discomfort, which was indicated as a moderate level of certainty.

CONCLUSIONS:
There may be no difference between HFNC and FM preoxygenation in preventing oxygen desaturation <92% or the lowest oxygen saturation before intubation. Preparation remains important to prevent and manage desaturation during induction of obese patients.
N-WASP-Arp2/3 signaling controls multiple steps of dendrite maturation in Purkinje cells in vivo
Authors: Hasegawa Koichi , Matsui Takeshi K. , Kondo Junpei , Kuwako Ken-ichiro 
Published: December 2022

ABSTRACT
During neural development, the actin filament network must be precisely regulated to form elaborate neurite structures. N-WASP tightly controls actin polymerization dynamics by activating an actin nucleator Arp2/3. However, the importance of N-WASP-Arp2/3 signaling in the assembly of neurite architecture in vivo has not been clarified. Here, we demonstrate that N-WASP-Arp2/3 signaling plays a crucial role in the maturation of cerebellar Purkinje cell (PC) dendrites in vivo in mice. N-WASP was expressed and activated in developing PCs. Inhibition of Arp2/3 and N-WASP from the beginning of dendrite formation severely disrupted the establishment of a single stem dendrite, which is a characteristic basic structure of PC dendrites. Inhibition of Arp2/3 after stem dendrite formation resulted in hypoplasia of the PC dendritic tree. Cdc42, an upstream activator of N-WASP, is required for N-WASP-Arp2/3 signaling-mediated PC dendrite maturation. In addition, overactivation of N-WASP is also detrimental to dendrite formation in PCs. These findings reveal that proper activation of N-WASP-Arp2/3 signaling is crucial for multiple steps of PC dendrite maturation in vivo.
A comparison of simultaneous multislice and conventional diffusion tensor imaging techniques for ischemic stroke evaluation at 1.5T
Authors: Culleton Sinéad , Hashemizadeh Kolowori Seyyed Kazem , Roberts John , de Havenon Adam , DiBella Edward , McNally J Scott 
Published: December 2022

Objective:
Diffusion tensor imaging (DTI) is a promising technique for ischemic stroke evaluation; however, acquisition time is longer than DWI. Simultaneous multislice (SMS) imaging acquires multiple slices together and reduces scan time. This study compared conventional and SMS DTI for ischemic stroke workup.

Methods:
Following IRB approval, the departmental stroke protocol was supplemented with SMS DTI on a clinical 1.5T MRI. Cases suspicious for ischemic stroke outside the treatment window were included. Standard DTI (STD-DTI, 20-direction, b = 2000 s/mm2), was followed by SMS-2-DTI (two slices simultaneously imaged). Two blinded neuroradiologists independently assessed image quality and DTI-trace status (positive/negative = stroke/other). Average image quality, interrater reliability (κ), receiver operating characteristic area under the curve (AUC), signal-to-noise ratio (SNR = DTI-source min/max/average), coefficient of variation (CV), mean diffusivity (MD), and fractional anisotropy (FA, of DTI-trace) were compared using two-tailed t-tests and a p &lt; .05.

Results:
41 patients were evaluated. SMS-2-DTI decreased DTI time by 132.17 ± 15.33 s, a 45% reduction. SMS-2-DTI reduced image quality (STD-DTI 4.7 ± 0.5 vs SMS-2-DTI 3.8 ± 0.6, p &lt; .001). Diagnostic accuracy persisted, AUC was high for observer 1 (STD-DTI 0.95, 95%CI = 0.88–1.00 vs SMS-2-DTI 0.94, 95%CI = 0.87–1.00, p = .86) and observer 2 (STD-DTI 0.89, 95%CI = 0.79–0.99 vs SMS-2-DTI 0.86, 95%CI = 0.76–0.97, p = .66). Interrater reliability was high for STD-DTI (κ = 0.80, 95%CI = 0.61–0.98) and SMS-2-DTI (κ = 0.84, 95%CI = 0.67–1.00). SMS-2-DTI significantly decreased average SNR (STD-DTI 42.85 ± 4.44 vs SMS-2-DTI 32.58 ± 4.30, p &lt; .001), and CV MD (STD-DTI 0.23 ± 0.03 vs 0.20 ± 0.04, p &lt; .001). CV FA and CV DTI-trace were not statistically different.

Conclusions:
This study supports using SMS to accelerate DTI for ischemic stroke workup at 1.5T in the non-hyper-acute setting.

Advances in knowledge:
This study highlights the feasibility of accelerated multislice DTI for faster diagnostic DTI-trace images capable of ischemic stroke detection.
A Splicing Approach to Best Subset of Groups Selection
Authors: Zhang Yanhang , Zhu Junxian , Zhu Jin , Wang Xueqin 
Published: December 2022

Best subset of groups selection (BSGS) is the process of selecting a small part of nonoverlapping groups to achieve the best interpretability on the response variable. It has attracted increasing attention and has far-reaching applications in practice. However, due to the computational intractability of BSGS in high-dimensional settings, developing efficient algorithms for solving BSGS remains a research hotspot. In this paper, we propose a group-splicing algorithm that iteratively detects the relevant groups and excludes the irrelevant ones. Moreover, coupled with a novel group information criterion, we develop an adaptive algorithm to determine the optimal model size. Under certain conditions, it is certifiable that our algorithm can identify the optimal subset of groups in polynomial time with high probability. Finally, we demonstrate the efficiency and accuracy of our methods by comparing them with several state-of-the-art algorithms on both synthetic and real-world data sets. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms-Discrete. Funding: This work was supported by National Natural Science Foundation of China [Grants 72171216, 71921001, and 71991474], the Key Research and Development Program of Guangdong [Grant 2019B020228001], the Science and Technology Program of Guangzhou, China [Grant 202002030129], The Fundamental Research Funds for the Central Universities and the Research Funds of Renmin University of China [Grant 22XNH161], and the Outstanding Graduate Student Innovation and Development Program of Sun Yat-Sen University [Grant 19lgyjs64]. Supplemental Material: The online appendix and video are available at https://doi.org/10.1287/ijoc.2022.1241 .
Optimal Enrollment in Late-Stage New Drug Development with Learning of Drug’s Efficacy for Group-Sequential Clinical Trials
Authors: Tian Zhili , Hazen Gordon B. , Li Hong 
Published: December 2022

Problem definition: The cost for developing a new drug ranged from $1 billion to more than $2 billion between 2010 and 2019. In addition to high development costs, the efficacy of the candidate drug, patient enrollment, the market exclusivity period (MEP), and the planning horizon are uncertain. Moreover, slow enrollment leads to increased costs, canceled clinical trials, and lost potential revenue. Many firms, hoping to detect efficacy versus futility of the candidate drug early to save development costs, plan interim analyses of patient-response data in their clinical trials. Academic/practical relevance: The problem for optimizing patient-enrollment rates has an uncertain planning horizon. We developed a continuous-time dynamic programming (DP) model with learning of a drug’s efficacy and MEP to assist firms in developing optimal enrollment policies in their clinical trials. We also established the optimality equation for this DP model. Through a clinical trial for testing a cancer drug developed by a leading pharmaceutical firm, we demonstrate that our DP model can help firms effectively manage their trials with a sizable profit gain (as large as $270 million per drug). Firms can also use our model in simulation to select their trial design parameters (e.g., the sample sizes of interim analyses). Methodology: We update a drug’s efficacy by Bayes’ rules. Using the stochastic order and the likelihood-ratio order of distribution functions, we prove the monotonic properties of the value function and an optimal policy. Results: We established that the value of the drug-development project increases as the average response from patients using the candidate drug increases. For drugs having low annual revenue or a strong market brand or treating rare diseases, we also established that the optimal enrollment policy is monotonic in the average patient response. Moreover, the optimal enrollment rate increases as the variance of the MEP decreases. Managerial implications: Firms can use the properties of the value function to select late-stage clinical trials for their drug-development project portfolios. Firms can also use our optimal policy to guide patient recruitment in their clinical trials considering competition from other drugs in the marketplace. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.1162 .