bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA1/ATF1-Mediated Transactivation is Involved in Resistance to PARP Inhibitors and Cisplatin
Authors: Endo Shino , Yoshino Yuki , Shirota Matsuyuki , Watanabe Gou , Chiba Natsuko 
Published: November 2021

Homologous recombination (HR)-deficient cells are sensitive to PARP inhibitors through a synthetic lethal effect. We previously developed an HR activity assay named Assay of Site-Specific HR Activity (ASHRA). Here, we evaluated the HR activity of 30 missense variants of BRCA1 by ASHRA and found that several BRCA1 variants showed intermediate HR activity, which was not clearly discerned by our previous analyses using a conventional method. HR activity measured by ASHRA was significantly correlated with sensitivity to olaparib. However, cells expressing the severely HR-deficient BRCA1-C61G variant were resistant to olaparib, and resistance was dependent on high expression of activating transcription factor 1 (ATF1), which binds to BRCA1 and activates the transcription of target genes to regulate cell proliferation. The BRCA1-C61G variant bound to ATF1 and stimulated ATF1-mediated transactivation similar to wild-type BRCA1. High expression of ATF1 conferred resistance to olaparib and cisplatin activating BRCA1/ATF1-mediated transcription without affecting HR activity in BRCA2-knockdown or RAD51-knockdown cells, but not in BRCA1-knockdown cells. These results suggest that ASHRA is a useful method to evaluate HR activity in cells and to predict the sensitivity to PARP inhibitors. The expression level of ATF1 might be an important biomarker of the effect of PARP inhibitors and platinum agents on HR-deficient tumors with the BRCA1-C61G variant or alteration of non-BRCA1 HR factors such as BRCA2 and RAD51.

Significance:
ASHRA could evaluate HR activity in cells and predict the sensitivity to PARP inhibitors. High expression level of ATF1 may predict the resistance of BRCAness tumors with alterations of non-BRCA1 HR factors to PARP inhibitors and platinum agents.
Traveling Waves in Quasi-One-Dimensional Neuronal Minicolumns
Authors: Baker Vincent , Cruz Luis 
Published: November 2021

Abstract
Traveling waves of neuronal activity in the cortex have been observed in vivo. These traveling waves have been correlated to various features of observed cortical dynamics, including spike timing variability and correlated fluctuations in neuron membrane potential. Although traveling waves are typically studied as either strictly one-dimensional or two-dimensional excitations, here we investigate the conditions for the existence of quasi-one-dimensional traveling waves that could be sustainable in parts of the brain containing cortical minicolumns. For that, we explore a quasi-one-dimensional network of heterogeneous neurons with a biologically influenced computational model of neuron dynamics and connectivity. We find that background stimulus reliably evokes traveling waves in networks with local connectivity between neurons. We also observe traveling waves in fully connected networks when a model for action potential propagation speed is incorporated. The biological properties of the neurons influence the generation and propagation of the traveling waves. Our quasi-one-dimensional model is not only useful for studying the basic properties of traveling waves in neuronal networks; it also provides a simplified representation of possible wave propagation in columnar or minicolumnar networks found in the cortex.
A Normative Account of Confirmation Bias During Reinforcement Learning
Authors: Lefebvre Germain , Summerfield Christopher , Bogacz Rafal 
Published: November 2021

Abstract
Reinforcement learning involves updating estimates of the value of states and actions on the basis of experience. Previous work has shown that in humans, reinforcement learning exhibits a confirmatory bias: when the value of a chosen option is being updated, estimates are revised more radically following positive than negative reward prediction errors, but the converse is observed when updating the unchosen option value estimate. Here, we simulate performance on a multi-arm bandit task to examine the consequences of a confirmatory bias for reward harvesting. We report a paradoxical finding: that confirmatory biases allow the agent to maximize reward relative to an unbiased updating rule. This principle holds over a wide range of experimental settings and is most influential when decisions are corrupted by noise. We show that this occurs because on average, confirmatory biases lead to overestimating the value of more valuable bandits and underestimating the value of less valuable bandits, rendering decisions overall more robust in the face of noise. Our results show how apparently suboptimal learning rules can in fact be reward maximizing if decisions are made with finite computational precision.
Sensitivity of Forecast Uncertainty to Different Microphysics Schemes within a Convection-Allowing Ensemble during SoWMEX-IOP8
Authors: Chen Chin-Hung , Chung Kao-Shen , Yang Shu-Chih , Chen Li-Hsin , Lin Pay-Liam , Torn Ryan D. 
Published: November 2021

Abstract
A mesoscale convective system that occurred in southwestern Taiwan on 15 June 2008 is simulated using convection-allowing ensemble forecasts to investigate the forecast uncertainty associated with four microphysics schemes—the Goddard Cumulus Ensemble (GCE), Morrison (MOR), WRF single-moment 6-class (WSM6), and WRF double-moment 6-class (WDM6) schemes. First, the essential features of the convective structure, hydrometeor distribution, and microphysical tendencies for the different microphysics schemes are presented through deterministic forecasts. Second, ensemble forecasts with the same initial conditions are employed to estimate the forecast uncertainty produced by the different ensembles with the fixed microphysics scheme. GCE has the largest spread in most state variables due to its most efficient phase conversion between water species. By contrast, MOR results in the least spread. WSM6 and WDM6 have similar vertical spread structures due to their similar ice-phase formulas. However, WDM6 produces more ensemble spread than WSM6 does below the melting layer, resulting from its double-moment treatment of warm rain processes. The model simulations with the four microphysics schemes demonstrate upscale error growth through spectrum analysis of the root-mean difference total energy (RMDTE). The RMDTE results reveal that the GCE and WDM6 schemes are more sensitive to initial condition uncertainty, whereas the MOR and WSM6 schemes are relatively less sensitive to that for this event. Overall, the diabatic heating–cooling processes connect the convective-scale cloud microphysical processes to the large-scale dynamical and thermodynamical fields, and they significantly affect the forecast error signatures in the multiscale weather system.
Do Oncologic Outcomes From Head and Neck Versus Truncal and Extremity Melanoma Differ? A Single-Institution Single-Subspecialty Experience
Authors: Baecher Kirsten M , Turgeon Michael K , Medin Caroline R , Mahendran Geetha , Flakes Terrill M , Delman Keith A , Lowe Michael C 
Published: November 2021

Background Outcomes are thought to be worse in head and neck (H&N) melanoma patients. However, definitive evidence of inferior outcomes in H&N melanoma in the modern era is lacking. We sought to ascertain whether H&N melanomas carry a worse prognosis than melanomas of other sites. Methods All patients who underwent excision for primary melanoma by fellowship-trained surgical oncologists at a single institution from 2014 to 2020 were queried from the electronic medical record. Patients who had AJCC eighth edition stage I-III disease were included. Results Of 1127 patients, 28.7% had primary H&N melanoma. H&N patients were more likely to be male, older, and present with more advanced AJCC stage. Median follow-up was 20.0 months (IQR 26.4). On multivariable analyses controlling for other variables, H&N melanoma was associated with worse RFS. Notably, H&N melanoma was not associated with worse MSS, DMFS, or OS on univariate or multivariable analyses. Among patients who recurred, H&N patients were significantly more likely to recur locally compared to non-H&N patients. On subgroup analysis, scalp melanoma was also associated with worse RFS compared to patients with melanoma in locations other than the scalp. When patients with scalp melanoma were excluded from analysis, non-scalp H&N RFS was not significantly different from the non-H&N group on univariate or multivariable analyses. Discussion In this series from a high-volume tertiary referral center, the differences in rates and sites of recurrence between H&N and non-H&N melanoma do not impact melanoma-specific or overall survival, suggesting that H&N melanoma patients should be treated similarly with respect to regional and systemic therapies.
Clinical heterogeneity and reduced penetrance in DICER1 syndrome: a report of three families
Authors: Azzollini Jacopo , Ferrari Andrea , Stracuzzi Alessandra , Chiaravalli Stefano , Terenziani Monica , Spreafico Filippo , Grasso Maurizia , Collini Paola , Pensotti Valeria , Massimino Maura , Arbustini Eloisa , Manoukian Siranoush 
Published: November 2021

Introduction: DICER1 syndrome is characterized by increased susceptibility to malignancies, mostly occurring in childhood. The range of phenotypic effects of DICER1 variants is under investigation, and the syndrome’s phenotypic spectrum is steadily widening. We report on three Italian families showing heterogeneous clinical presentation and reduced penetrance in family members. Case descriptions: Patient 1 is a 10-year-old girl with a Sertoli-Leydig cell tumor. Although family history was unremarkable, genetic testing identified a DICER1 germline variant, inherited from her healthy father. Benign thyroid nodules were subsequently diagnosed in both the proband and her father. Patient 2 is an 8-month-old boy with type 1 pleuropulmonary blastoma. His sister developed a nephroblastoma at age 2 years. A DICER1 novel variant was identified in both siblings and their healthy father. Patient 3 is a 22-year-old man who developed a spinal extramedullary intradural mass diagnosed as rhabdomyosarcoma with a peculiar tubular, gland-like component. Tumor testing revealed two pathogenic DICER1 variants, one of which was confirmed to be germline and identified in his 17-year-old healthy brother and in his father, who showed multiple thyroid nodules. Conclusions: Among our patients, three developed tumors most frequently associated with DICER1 syndrome (i.e. pleuropulmonary blastoma, nephroblastoma, and Sertoli-Leydig cell tumor). One developed a peculiar sarcoma of the spinal cord not previously described in DICER1 syndrome. Genetic testing in relatives highlighted the paternal origin and reduced penetrance in all families, with thyroid benign lesions as the most common features in otherwise unaffected individuals.
Representativeness of the PDOPPS cohort compared to the Australian PD population
Authors: Ethier Isabelle , Boudville Neil , McDonald Stephen , Brown Fiona , Kerr Peter G , Walker Rowan , Holt Stephen Geoffroy , Badve Sunil V , Cho Yeoungjee , Hawley Carmel , Robison Laura , Reidlinger Donna , Milanzi Elasma , Bieber Brian , McCullough Keith , Johnson David W 
Published: November 2021

Background: The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) is an international, prospective study following persons treated by peritoneal dialysis (PD) to identify modifiable practices associated with improvements in PD technique and person survival. The aim of this study was to assess the representativeness of the Australian cohort included in PDOPPS compared to the complete Australian PD population, as reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Methods: Adults with at least one PD treatment reported to ANZDATA Registry during the census period of PDOPPS Phase I (November 2014 to April 2018) were compared to the Australian PDOPPS cohort. The primary outcomes were the representativeness of centres and persons. Secondary outcomes explored the association of person characteristics with consent to study participation. Results: After data linkage, 511 PDOPPS participants were compared to 5616 Australians treated with PD. Within centres eligible for PDOPPS, selected centres were similar to other Australian centres. The PDOPPS participants’ cohort tended to include older persons, more males, a higher proportion of Caucasians and more persons with higher socioeconomic advantage compared to the Australian PD population. Differences in distribution across sex and ethnicities between the PDOPPS cohort and the overall PD population were in part due to the selection and consent processes, during which females and non-Caucasians were more likely to not consent to PDOPPS participation. Conclusion: Sampling methods used in PDOPPS allowed for good national representativeness of the included centres. However, representativeness of the unweighted PDOPPS sample was suboptimal in regard to some participant characteristics.
Comparative effect of dense-and-disperse versus non-repetitive and non-sequential frequencies in electroacupuncture-induced analgesia in a rodent model of peripheral neuropathic pain
Authors: Chao Liaw , Gonçalves Alexandre SR , Campos Ana Carolina P , Assis Daniele V , Jerônimo Rodrigo , Kuroki Mayra A , Sant’Anna Fernando M , Meas Yunsan , Rouxeville Yves , Hsing Wu , Pagano Rosana L 
Published: November 2021

Background: Neuropathic pain (NP) is a complex disease that remains challenging to treat. Low-frequency dense-and-disperse (DD) electroacupuncture (EA) has been used as adjuvant therapy for neuropathic pain; however, its analgesic effect decreases as stimulation time increases, or when it is repeatedly used. We hypothesized that a new frequency parameter could improve the effectiveness of EA, and aimed to compare the efficacy and duration of the analgesic effect between classic DD-EA and non-repetitive and non-sequential frequency (random frequency (RF)-EA) in neuropathic rats. Furthermore, the effect of RF-EA at local traditional acupuncture point locations versus auricular vagus nerve stimulation (aVNS) was evaluated. Methods: Male Wistar rats with peripheral neuropathy were subjected to a single session of DD-EA or RF-EA for 20 or 40 min at ST36 + GB34. An additional group of rats was treated with RF-EA for 20 min using aVNS at the appropriate ear point locations. Paw pressure test, von Frey filaments and spontaneous pain scores were evaluated. Sham-operated rats were used as controls. Results: In all, 20 min of RF-EA reversed hyperalgesia (for 24 h) and allodynia (for 8 h), showing a longer analgesic effect than DD-EA. Both RF-EA and DD-EA induced partial inhibition of spontaneous pain for 8 h. Forty minutes of DD-EA did not interfere with the NP phenomena; however, RF-EA induced significant long-term analgesia. aVNS induced an analgesic effect similar to local stimulation. Conclusion: This pilot study shows that RF-EA at both local traditional acupuncture point and auriculotherapy point locations induces long-lasting analgesia in neuropathic rats, and more effectively so than classical DD-EA.
The Service-Profit Chain: Reflections, Revisions, and Reimaginations
Authors: Hogreve Jens , Iseke Anja , Derfuss Klaus 
Published: November 2021

Over the past 25 years, the service–profit chain (SPC) has become a prominent guidepost for service managers and researchers. In this article, we reflect on and synthesize published research to clarify what researchers have learned about the SPC and what remains less well understood. Based on an in-depth discussion of the field, we present a revised SPC and propose multiple areas in which further research would be worthwhile, such as internal service quality as specific systems of human resource management practices, both employee and customer well-being as additional mediators, different targets of employee and customer loyalty, contingencies, and non-linear and feedback effects. We conclude by reimagining the SPC, and we discuss digital and artificial-intelligence–driven changes to the SPC’s structure. Finally, based on the insights we discuss, we inform scholars of the current state of SPC research and provide a detailed agenda for future research.
Comparison between the change in total corneal astigmatism and actual change in refractive astigmatism in transepithelial photorefractive keratectomy (tPRK), laser in situ keratomileusis (LASIK) and femtosecond laser assisted laser in situ keratomileusis (FsLASIK)
Authors: Bohac Maja , Biscevic Alma , Shijakova Violeta , Gabric Ivan , Gabric Kresimir , Patel Sudi 
Published: November 2021

Purpose To compare changes in astigmatism by refraction and total corneal astigmatism after tPRK, LASIK and FsLASIK. Setting Specialty Eye Hospital Svjetlost, Zagreb, Croatia. Design Partially masked, semi-randomized, prospective, case-by-case, interventional, clinical study. Methods Patients with a stable refraction (-0.75DS to −8.00DS, astigmatism ≤1.00DC) underwent tPRK, LASIK or FsLASIK without complication. Astigmatism was measured at both corneal surfaces over the central 3.2 mm zone (approximately using Pentacam HRTM) preoperatively and 3 months postoperatively. Pentacam and refraction data were subjected to vector analysis to calculate the surgically induced changes in i) total corneal astigmatism (SIATCA) ii) any astigmatism by refraction (SIAR) and the vectorial difference (DV) between SIATCA and SIAR. Results Reporting key findings (p < .01), there was a significant difference between mean SIATCA and SIAR powers after tPRK (75eyes) but not after LASIK (100eyes) or FsLASIK (100eyes). Mean (±sd,95% CIs) values for DV powers were, tPRK −1.13DC(±0.71, −1.29 to −0.97), LASIK −0.39DC(±0.23,-0.44 to −0.34), FsLASIK −0.55DC(±0.38,-0.62 to −0.47). The differences were significant. For the tPRK and FsLASIK cases, linear regression revealed significant associations between I) SIATCA (x) &DV (z) powers (tPRK z = 1.586x-0.179, r  =  0.767, p < .01; FsLASIK z  =  0.442x-0.303, r  =  .484,p < .01), II) sines of SIATCA (x1) &DV (z1) axes (tPRK, z1 = 0.523 × 1 + 0.394, r = .650,p < .01; FsLASIK z1 = 0.460 × 1-0.308, r = .465,p < .01). Conclusions tPRK is more prone to unintended changes in astigmatism. The difference between SIATCA & SIAR after tPRK or FsLASIK is mediated by SIATCA. Photoablating deeper regions of the cornea reduces the gap between SIATCA & SIAR.
A painful red eye in an intravenous drug abuser: When not everything is what it seems
Authors: Leuzinger-Dias Mariana , Godinho Gonçalo , Lima-Fontes Mário , Oliveira-Ferreira Cláudia , Camisa Elisa , Falcão-Reis Fernando , Silva Marta , Figueira Luís 
Published: November 2021

Introduction Endogenous endophthalmitis is a rare but devastating ocular infection, resulting from microbial seeding of the eye during bacteremia or fungemia. Among other sources of septicemia, intravenous drug abuse is a significant risk factor, and endogenous endophthalmitis should always be thought of in any patient with a history of injectable drug use, presenting with a painful vision loss and a red inflamed eye. Case Description We report the case of a 47-year-old male, with a history of injectable drug consumption, who presented to our emergency department complaining of a painful red eye and recent deterioration of visual acuity. After the first clinical hypothesis of endogenous endophthalmitis being considered, the final diagnosis of Human Leukocyte Antigen (HLA) B27-associated acute anterior uveitis was established. Conclusion Ocular inflammation is one of the most challenging fields in all ophthalmology. Several inflammatory disorders, ranging from a wide variety of infectious and non-infectious conditions, can present themselves with the same clinical signs and symptoms, making their diagnosis extremely defiant.
The association between an oral glucose tolerance test performed at term pregnancy and obstetric outcomes
Authors: Barak Oren , Yoles Israel , Wainstock Tamar , Gadassi Noa , Schiller Tal , Vaisbuch Edi 
Published: November 2021

Aims Assessing the value of oral glucose tolerance test performed at term pregnancy in identifying obstetric complications. Methods Retrospective cohort study of women with a normal 50 g glucose challenge test who also had an oral glucose tolerance test at term (defined as at or after 37 weeks of gestation). Comparison between the pathological and normal oral glucose tolerance test groups was performed. Results The mean glucose in the glucose challenge test of women in the normal oral glucose tolerance test ( n = 256) group was lower than that in the pathological oral glucose tolerance test ( N = 16) group (105 ± 17 mg/dl (5.8 ± 0.9 mmol/l) vs 117 ± 13 mg/dl (6.5 ± 0.7 mmol/l), p = 0.007). Relevant obstetrical complications did not differ significantly between the groups. Of note, in the pathological oral glucose tolerance test group only one woman delivered a macrosomic infant. Conclusions A pathological oral glucose tolerance test performed at term was unable to identify women at risk for impaired glucose metabolism-related obstetric complications and is therefore of limited clinical value and seems to be unjustified.
Association of Elmiron (pentosanpolysulphate sodium) with pigmented maculopathy: An update for urologists and patients
Authors: Kailavasan Mithun , Goddard Jonathan Charles 
Published: November 2021

Introduction: Bladder pain syndrome (BPS) is a difficult disorder to diagnose and manage with a limited number of treatment options that have a good evidence base. Elmiron (pentosanpolysulphate sodium (PPS)) is recognised as a main second-line treatment option in many international guidelines. Recently published retrospective studies suggest that there is an association between Elmiron and pigmented maculopathy, a rare disease associated with visual impairment. Objectives: To review the known literature on Elmiron and pigmented maculopathy and alternative oral pharmacotherapy options for BPS. To promote awareness on this topic and aid urologists in managing Elmiron prescription. Methods: We reviewed the most commonly used oral treatments for BPS, in particular Elmiron, the current evidence to support this association with eye disease and its position in the management pathway of this complex condition. Conclusions: Recent retrospective longitudinal studies have demonstrated an association of Elmiron with pigmented maculopathy. However, as yet the exact nature of this relationship is unknown. Nevertheless, Elmiron remains an important part of the treatment pathway for BPS. We suggest clinicians should fully inform patients of this association, including patients who have been previously comenced on Elmiron. There should be ongoing and continuing reviews of all treatments to review its efficacy in indiviual patients. Level of evidence: Not applicable