bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual differences in causal structures inferred during feature negative learning
Authors: Lee Jessica C , Lovibond Peter F
Published: September 2020

Traditional associative learning theories predict that training with feature negative (A+/AB-) contingencies leads to the feature B acquiring negative associative strength and becoming a conditioned inhibitor (i.e., prevention learning). However, feature negative training can sometimes result in negative occasion setting, where B modulates the effect of A. Other studies suggest that participants learn about configurations of cues rather than their individual elements. In this study, we administered simultaneous feature negative training to participants in an allergist causal learning task and tested whether evidence for these three types of learning (prevention, modulation, configural) could be captured via self-report in the absence of any procedural manipulation. Across two experiments, we show that only a small subset of participants endorse the prevention option, suggesting that traditional associative models that predict conditioned inhibition do not completely capture how humans learn about negative contingencies. We also show that the degree of transfer in a summation test corresponds to the implied causal structure underlying conditioned inhibition, occasion-setting, and configural learning, and that participants are only partially sensitive to explicit hints about causal structure. We conclude that feature negative training is an ambiguous causal scenario that reveals individual differences in the representation of inhibitory associations, potentially explaining the modest group-level inhibitory effects often found in humans.
Bottom-up perceptual salience and top-down retro-cues concurrently determine state in visual working memory
Authors: Fan Lingxia , Zhang Lin , Diao Liuting , Xu Mengsi , Chen Ruiyang , Zhang Xuemin
Published: September 2020

Recent studies have demonstrated that in visual working memory (VWM), only items in an active state can guide attention. Further evidence has revealed that items with higher perceptual salience or items prioritised by a valid retro-cue in VWM tend to be in an active state. However, it is unclear which factor (perceptual salience or retro-cues) is more important for influencing the item state in VWM or whether the factors can act concurrently. Experiment 1 examined the role of perceptual salience by asking participants to hold two features with relatively different perceptual salience (colour vs. shape) in VWM while completing a visual search task. Guidance effects were found when either colour or both colour and shape in VWM matched one of the search distractors but not when shape matched. This demonstrated that the more salient feature in VWM can actively guide attention, while the less salient feature cannot. However, when shape in VWM was cued to be more relevant (prioritised) in Experiment 2, we found guidance effects in both colour-match and shape-match conditions. That is, both more salient but non-cued colour and less salient but cued shape could be active in VWM, such that attentional selection was affected by the matching colour or shape in the visual search task. This suggests that bottom-up perceptual salience and top-down retro-cues can jointly determine the active state in VWM.
A prospective study on transfer of pronator teres to extensor carpi radialis brevis for forearm and wrist deformity in children with cerebral palsy
Authors: Singh Gobinder , Singh Vivek , Ahmad Sabeel , Kalia R. B. , Arora Shobha S. , Dubey Siddharth
Published: September 2020

We prospectively evaluated the clinical and functional outcomes of pronator teres to extensor carpi radialis brevis transfer in children with cerebral palsy. Patients were followed-up at 6 months postoperatively, and functionally assessed using the House classification, Manual Ability Classification System (MACS) and Upper Extremity Functional Index (UEFI). Fifteen children with a mean age of 8.1 years underwent tendon transfers. All patients were of Gschwind and Tonkin Grade 2 for pronation deformity; eight patients were of Zancolli’s classification Group 1 and seven, Group 2 for wrist flexion deformity. The average gain in active supination was 67°, and wrist extension 15°. An increase of 7.0 in the UEFI score was recorded, although no significant improvement in MACS and House classification was observed. We conclude that the pronator teres to extensor carpi radialis brevis transfer improves upper limb function through effective correction of forearm pronation and wrist flexion deformities.

Level of evidence: II
Prognostic role of a new index (multi inflammatory index) in patients with metastatic colorectal cancer: results from the randomized ITACa trial
Authors: Casadei Gardini Andrea , Scarpi Emanuela , Valgiusti Martina , Monti Manlio , Ruscelli Silvia , Matteucci Laura , Bartolini Giulia , Vertogen Bernadette , Pagan Flavia , Rovesti Giulia , Frassineti Giovanni Luca , Passardi Alessandro
Published: September 2020

Aims:

We created a new index (Multi Inflammatory Index, MII) composed of an inflammatory index [neutrophil-to lymphocyte-ratio (NLR): MII-1; platelet-to-lymphocyte ratio (PLR): MII-2; or systemic immune-inflammation index (SII): MII-3] and C-reactive protein (CRP). Our aim was to evaluate the prognostic and/or predictive capacity of the MII in the randomized ITACa (Italian Trial in Advanced Colorectal Cancer) study on patients with metastatic colorectal cancer undergoing first-line chemotherapy.

Methods:

Between November 2007 and March 2012, baseline NLR, PLR; SII and CRP were available for 131 patients, 66 receiving chemotherapy plus bevacizumab and 65 receiving chemotherapy alone.

Results:

Patients with low (<25) MII-1 levels had a better outcome than those with high (⩾25) levels: median progression-free survival (PFS) was 12.4 versus 8.9 months [hazard ratio (HR) = 1.74, 95% confidence interval (CI) 1.21–2.51, p = 0.003] and median overall survival (OS) was 30.9 months versus 15.0 months (HR = 2.05, 95% CI 1.40–3.02, p = 0.0002), respectively. Similar results were obtained for patients with low (<1424) MII-2 levels compared with those with high (⩾1424) levels: median PFS was 12.6 versus 8.9 months (HR = 1.95, 95% CI 1.35–2.82, p = 0.0004) and median OS was 32.4 versus 14.6 months, respectively (HR = 2.42, 95% CI 1.64–3.57, p < 0.0001). Patients with low (<6068) MII-3 levels had a longer median PFS and OS than those with high (⩾6068) levels: 12.6 versus 8.9 months (HR = 1.91, 95% CI 1.33–2.76, p = 0.005) and 30.9 versus15.0 months (HR = 2.10, 95% CI 1.43–3.09, p = 0.0002), respectively. Following adjustment for clinical covariates, multivariate analysis confirmed all MII indexes as independent prognostic factors for predicting PFS and OS.

Conclusion:

All MII indexes appear to be useful as prognostic markers.

Trial registration

ClinicalTrials.gov identifier: NCT01878422 (registration date: 07/06/2013) https://clinicaltrials.gov/ct2/show/NCT01878422
Brain metastases from Truncal and extremity bone and soft tissue sarcoma: Single institution study of oncologic outcomes
Authors: Chan Chung Ming , Lindsay Adam D , Spiguel Andre RV , Scarborough Mark T , Gibbs C Parker
Published: September 2020

Brain metastases are a rare occurrence in patients with sarcoma. The prognosis for patients is poor, and treatment can contribute to considerable morbidity. We sought to examine the experience of our institution in managing these patients over a period of 17 years. We performed a retrospective cohort study of patients managed for sarcoma of the extremity or trunk who developed brain metastases from 2000 to 2017. Clinical data were analyzed and we assessed survival outcomes. 14 patients presenting at a mean age of 46.7 years were included. All patients were treated with radiotherapy for their brain metastases. 3 patients underwent surgical excision of their intracranial metastases. Two patients were treated with radium-223 dichloride. Kaplan–Meier survival analysis and the log rank test were used to calculate the survival probability, and to compare patient subgroups. All patients in this study developed lung or bone metastases at a mean interval of 13.3 months prior to the development of brain metastasis. The median interval from diagnosis of a brain metastasis to death was 3.6 months. The Kaplan–Meier survival probability at 6 months was 28.6%, and 14.3% at 1 year. Surgery was not found to be associated with increased survival. Patients with cerebellar metastasis had increased survival probability as compared to those with cerebral metastasis. Patients with extremity or trunk sarcoma who develop brain metastases frequently develop lung or bone metastases in the year preceding their diagnosis of brain metastasis. Patients with cerebellar metastasis may have better survival than those with cerebral metastasis, and an aggressive treatment approach should be considered. Despite aggressive treatment, the prognosis is grim.
Acquired left-to-right shunting through a valve-incompetent foramen ovale in a cat with hypertrophic cardiomyopathy and congestive heart failure
Authors: Winter Randolph L , Jennings Ryan N , Cronin James P , Rhinehart Jaylyn D , Schober Karsten E
Published: September 2020

Case summary

An 8-year-old spayed female domestic shorthair cat was presented for a recheck evaluation of hypertrophic cardiomyopathy and chronic kidney disease. Three years prior to presentation, the patient was diagnosed with obstructive hypertrophic cardiomyopathy and started on atenolol. The left ventricular outflow tract obstruction subsequently resolved. Biochemical analysis a week prior to presentation demonstrated severe azotemia. Transthoracic echocardiograph revealed pericardial effusion, pleural effusion, severe left ventricular concentric hypertrophy, severe left atrial enlargement and continuous left-to-right flow through the interatrial septum near the fossa ovalis. The patient was euthanized owing to poor prognosis, and gross examination at necropsy revealed a valve-incompetent patent foramen ovale secondary to severe left atrial dilation.

Relevance and novel information

To our knowledge, this is the first report of an acquired left-to-right shunt through a valve-incompetent foramen ovale in a cat with hypertrophic cardiomyopathy. Severe left atrial dilation was suspected to cause interatrial shunting through the valve-incompetent foramen ovale, and this finding may be relevant to echocardiographic evaluations in other cats.
Reluctant to Share: How Third Person Perceptions of Fake News Discourage News Readers From Sharing “Real News” on Social Media
Authors: Yang Fan , Horning Michael
Published: September 2020

Rampant fake news on social media has drawn significant attention. Yet, much remains unknown as to how such imbalanced evaluations of self versus others could shape social media users’ perceptions and their subsequent attitudes and behavioral intentions regarding social media news. An online survey ( N = 335) was conducted to examine the third person effect (TPE) in fake news on social media and suggested that users perceived a greater influence of fake news on others than on themselves. However, although users evaluated fake news as socially undesirable, they were still unsupportive of government censorship as a remedy. In addition, the perceived prevalence of fake news leads audiences to reported significantly less willingness to share all news on social media either online or offline.
Clinician-Patient Dialogue About Preventive Chronic Migraine Treatment
Authors: Blumenfeld Andrew M.
Published: September 2020

Many new medications for the treatment of migraine are now available on the market. In the current evolving migraine treatment landscape, an individualized treatment approach is needed. This review provides practical recommendations on how to obtain a correct diagnosis and then engage in a long-term partnership with patients with the most severe form of migraine: chronic migraine (CM). Given the need to effectively treat this complex neurological disease, clinicians in primary care, general neurologists, and headache specialists are at the forefront to ease the burden of this disease for their patients. This manuscript will review how to discuss the currently available treatment options to help control migraine attacks, manage expectations, and, together with the patient, determine the most effective and appropriate treatment. The goal is to create an environment where the clinician partners with the patient in shared decision-making to choose the most effective appropriate treatment for the individual patient.
Poor Associations Between Radiographic Tibiofemoral Osteoarthritis and Patient-Reported Outcomes at 16 Years After Anterior Cruciate Ligament Reconstruction
Authors: Identeg Fredrik , Senorski Eric Hamrin , Svantesson Eleonor , Samuelsson Kristian , Sernert Ninni , Kartus Jüri-Toomas , Sundemo David
Published: September 2020

Background:

Radiographic tibiofemoral (TF) osteoarthritis (OA) is common in patients after anterior cruciate ligament (ACL) reconstruction at long-term follow-up. The association between radiographic OA and patient-reported outcomes has not been thoroughly investigated.

Purpose:

To determine the association between radiographic TF OA and patient-reported outcome measure (PROM) scores at 16 years after ACL reconstruction.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

This study was based on 2 randomized controlled studies comprising 193 patients who underwent unilateral ACL reconstruction. A long-term follow-up was carried out at 16.4 ± 1.7 years after surgery and included a radiographic examination of the knee and recording of PROM scores. Correlation analyses were performed between radiographic OA (Kellgren-Lawrence [K-L], Ahlbäck, and cumulative Fairbank grades) and the PROMs of the International Knee Documentation Committee (IKDC) subjective knee form, Lysholm score, and Tegner activity scale. A linear univariable regression model was used to assess how the IKDC score differed with each grade of radiographic OA.

Results:

Of 193 patients at baseline, 147 attended the long-term follow-up. At long-term follow-up, 44.2% of the patients had a K-L grade of ≥2 in the injured leg, compared with 6.8% in the uninjured leg. The mean IKDC score at follow-up was 71.2 ± 19.9. Higher grades of radiographic OA were significantly correlated with lower IKDC and Lysholm scores ( r = –0.36 to –0.22). Patients with a K-L grade of 3 to 4 had significantly lower IKDC scores compared with patients without radiographic OA (K-L grade 0-1). Adjusted beta values were –15.7 (95% CI, –27.5 to –4.0; P = .0093; R 2 = 0.09) for K-L grade 3 and –25.2 (95% CI, –41.7 to –8.6; P = .0033; R 2 = 0.09) for K-L grade 4.

Conclusion:

There was a poor but significant correlation between radiographic TF OA and more knee-related limitations, as measured by the IKDC form and the Lysholm score. Patients with high grades of radiographic TF OA (K-L grade 3-4) had a statistically significant decrease in IKDC scores compared with patients without radiographic TF OA at 16 years after ACL reconstruction. No associations were found between radiographic TF OA and the Tegner activity level.
Revision ACL Reconstruction in Adolescent Patients
Authors: Rugg Caitlin M. , Pitcher Austin A. , Allen Christina , Pandya Nirav K.
Published: September 2020

Background:

High failure rates have been documented after anterior cruciate ligament reconstruction (ACLR) in pediatric patients, and revision surgery is indicated due to high activity levels of children and adolescents.

Purpose:

To define trends in revision ACLR in patients who underwent initial ACLR at younger than 18 years.

Study Design:

Case series; Level of evidence, 4.

Methods:

An electronic medical record was used to retrospectively identify revision ACLR procedures performed by 2 surgeons between the years 2010 and 2016 in patients younger than 18 years at initial reconstruction. Descriptive information, intraoperative findings, surgical techniques, and rehabilitation data were recorded from initial and revision surgeries. Descriptive statistics were used.

Results:

A total of 32 patients (17 girls, 15 boys) met the inclusion criteria, with a mean age of 15.8 years at initial reconstruction. For initial reconstructions, 15 patients underwent transphyseal procedures, 3 patients underwent adult-type procedures using an anatomic reconstruction technique that did not take into account the physis, and 2 patients underwent partial intraepiphyseal procedures. Graft types included hamstring autograft (n = 17), allograft (n = 5), hybrid (n = 4), and bone–patellar tendon–bone autograft (BTB; n = 3). Average primary reconstruction graft diameter was 8.0 mm (girls, 7.72 mm; boys, 8.36 mm; P = .045). After initial reconstruction, 10 patients had postoperative protocol noncompliance, and 8 patients reported delayed recovery. Mean time to retear was 565 days (range, 25-1539 days). At revision, BTB autograft was used in 50% (n = 16), followed by hamstring autograph (31.3%; n = 10) and allograft (12.5%; n = 4); mean graft diameter was 9.05 mm. Chondral surgery was more common during revision (25% for revision vs 0% for index; P = .031). There were 4 patients who required staged reconstruction with bone grafting. At mean final follow-up of 29.5 months (SD, 22.2 months), there were 3 graft failures (9.4%) and 5 contralateral ACL ruptures (15.6%).

Conclusion:

Most patients with ACL graft failure were adequately treated with a single revision. Conversion from a soft tissue graft to a BTB autograft was the most common procedure. Infrequently, patients required staged reconstructions. Providers should have a high index of suspicion for associated intra-articular injuries resulting from graft failure in adolescent patients.
Medical Care-Related Decisions among Patients Diagnosed with Early Stage Malignant Brain Tumor: A Qualitative Study
Authors: Numata Hanako , Noguchi-Watanabe Maiko , Mukasa Akitake , Tanaka Shota , Takayanagi Shunsaku , Saito Nobuhito , Yamamoto-Mitani Noriko
Published: September 2020

Medical care-related decision-making among patients with malignant brain tumors has not been sufficiently discussed. This study aimed to develop a framework for understanding patients’ experiences in the decision-making process. Semi-structured interviews with 14 patients were analyzed using a grounded theory approach, focusing on their 48 decision-making points. Additionally, interviews with two family members and seven healthcare providers, and participant observations were used to gain contextual insight into patients’ experiences. Patients faced decisions while they struggled in vulnerability under shock, fear, and anxiety while hoping. Under this context, they showed four decision-making patterns: (1) led by the situation, (2) controlled by others, (3) entrusted someone with the decision, and (4) myself as a decision-making agent. Across these patterns, the patients were generally satisfied with their decisions even when they did not actively participate in the process. Healthcare providers need to understand patients’ contexts and their attitudes toward yielding decision-making to others.
Breast lobular carcinoma in situ associated podocytopathy
Authors: Muzib Abdulrahman , Wanchoo Rimda , Jhaveri Kenar D
Published: September 2020

Paraneoplastic glomerular diseases are rare. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies. Other podocytopathies such as focal segmental glomerulosclerosis have not been classically associated with solid malignancy. In this case report, we present a case of a 52-year-old female with a diagnosis of focal segmental glomerulosclerosis associated with breast lobular carcinoma in situ. The focal segmental glomerulosclerosis diagnosis preceded the diagnosis of the breast cancer. While the proteinuria came into partial remission with conservative management, a dramatic resolution of focal segmental glomerulosclerosis was noted post-surgery and hormonal therapy for the breast cancer.
Granulomata in Clear Cell Renal Cell Carcinoma: An Uncommon Presentation of a Common Cancer, Not Two Separate Entities
Authors: Russell Daniel Hugh
Published: September 2020

Sarcoidal-like granulomata (SLG) are known to occur as a response to a variety of tumor types, including lymphomas, prominently seminoma, other miscellaneous carcinomas, and rarely in renal cell carcinoma. There have been a handful of previously reported cases in the literature of SLG occurring in association with RCC. Of those previously reported, none were associated with infection and only 3 patients had a history of sarcoidosis. The prognostic significance of SLG in RCC is unsettled and somewhat complicated by the relative rarity of its occurrence and the paucity of data therein. A case is presented of an otherwise histologically typical clear cell renal cell carcinoma with peri-tumoral and intra-tumoral SLG. Special stains were negative for organisms and past medical history was negative for sarcoidosis and connective tissue disease.
Gaps in end-of-life care and lack of support for family carers in Poland and Central Eastern Europe
Authors: Krakowiak Piotr
Published: September 2020

The growth of life expectancy in Central Eastern Europe and increase in the number of older people in that region are the consequences of changes in the 1990s period, connected to transition from the communism into a market economy. Central Eastern Europe is already facing consequences of fast ageing and insufficient development of state health care and social services. Those result in gaps in the provision of end-of-life care and overburden of family caregivers. This essay addresses gaps in end-of-life care, showing the development of hospice-palliative care on one side, and highlighting main problems with long-term care on the other. There is scarce support for informal caregivers and lack of cooperation between health and social care. End-of-life care is over medicalized in hospice-palliative care and hardly existing in long-term care. Dying is more a social than medical event, and as such, it should be cared for by compassionate communities, encouraging cooperation of professionals with family caregivers and society. Unfortunately, to date, there is no adequate cooperation in social dimension of end-of-life care in most of Central Eastern Europe. The social dimension of end-of-life care has to be recognized and empowered with the health promoting palliative care and introduction of compassionate communities in Central Eastern Europe.
VAV1 mutations contribute to development of T-cell neoplasms in mice
Authors: Fukumoto Kota , Sakata-Yanagimoto Mamiko , Fujisawa Manabu , Sakamoto Tatsuhiro , Miyoshi Hiroaki , Suehara Yasuhito , Nguyen Tran B. , Suma Sakurako , Yanagimoto Shintaro , Shiraishi Yuichi , Chiba Kenichi , Bouska Alyssa , Kataoka Keisuke , Ogawa Seishi , Iqbal Javeed , Ohshima Koichi , Chiba Shigeru
Published: September 2020

Activating mutations in the Vav guanine nucleotide exchange factor 1 (VAV1) gene are reported in various subtypes of mature T-cell neoplasms (TCNs). However, oncogenic activities associated with VAV1 mutations in TCNs remain unclear. To define them, we established transgenic mice expressing VAV1 mutants cloned from human TCNs. Although we observed no tumors in these mice for up to a year, tumors did develop in comparably aged mice on a p53-null background (p53−/−VAV1-Tg), and p53−/−VAV1-Tg mice died with shorter latencies than did p53-null (p53−/−) mice. Notably, various TCNs with tendency of maturation developed in p53−/−VAV1-Tg mice, whereas p53−/− mice exhibited only immature TCNs. Mature TCNs in p53−/−VAV1-Tg mice mimicked a subtype of human peripheral T-cell lymphoma (PTCL-GATA3) and exhibited features of type 2 T helper (Th2) cells. Phenotypes seen following transplantation of either p53−/−VAV1 or p53−/− tumor cells into nude mice were comparable, indicating cell-autonomous tumor-initiating capacity. Whole-transcriptome analysis showed enrichment of multiple Myc-related pathways in TCNs from p53−/−VAV1-Tg mice relative to p53−/− or wild-type T cells. Remarkably, amplification of the Myc locus was found recurrently in TCNs of p53−/−VAV1-Tg mice. Finally, treatment of nude mice transplanted with p53−/−VAV1-Tg tumor cells with JQ1, a bromodomain inhibitor that targets the Myc pathway, prolonged survival of mice. We conclude that VAV1 mutations function in malignant transformation of T cells in vivo and that VAV1-mutant–expressing mice could provide an efficient tool for screening new therapeutic targets in TCNs harboring these mutations.
Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma
Authors: Allen Pamela B. , Savas Hatice , Evens Andrew M. , Advani Ranjana H. , Palmer Brett , Pro Barbara , Karmali Reem , Mou Eric , Bearden Jeffrey , Dillehay Gary , Bayer Robert A. , Eisner Robert M. , Chmiel Joan S. , O’Shea Kaitlyn , Gordon Leo I. , Winter Jane N.
Published: September 2020

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell’s palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.
Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series
Authors: Weber Andrew G. , Chau Alice S. , Egeblad Mikala , Barnes Betsy J. , Janowitz Tobias
Published: September 2020

Background

Mechanically ventilated patients with COVID-19 have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system.

Methods

Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation—treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed.

Results

The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified.

Conclusions

Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
Selection for feed efficiency using the social effects animal model in growing Duroc pigs: evaluation by simulation
Authors: Herrera-Cáceres William , Sánchez Juan Pablo
Published: September 2020

Background

Traits recorded on animals that are raised in groups can be analysed with the social effects animal model (SAM). For multiple traits, this model specifies the genetic correlation structure more completely than the animal model (AM). Our hypothesis was that by using the SAM for genetic evaluation of average daily gain (ADG) and backfat thickness (BF), a high rate of improvement in feed conversion ratio (FCR) might be achieved, since unfavourable genetic correlations between ADG and BF reported in a Duroc pig line could be partially avoided. We estimated genetic and non-genetic correlations between BF, ADG and FCR on 1144 pigs using Bayesian methods considering the SAM; and responses to selection indexes that combine estimates of indirect (IGE) and direct (DGE) genetic effects for ADG and BF by stochastic simulation.

Results

Estimates of the ratio of the variance of DGE to the phenotypic variance were 0.31, 0.39 and 0.25 and those of the total genetic variance to the phenotypic variance were 0.63, 0.74 and 0.93 for ADG, BF and FCR, respectively. In spite of this, when the SAM was used to generate data and for the genetic evaluations, the average economic response was worse than that obtained when BV predictions from the AM were considered. The achieved economic response was due to a direct reduction in BF and not to an improvement in FCR.

Conclusions

Our results show that although social genetic effects play an important role in the traits studied, their proper consideration in pig breeding programs to improve FCR indirectly is still difficult. The correlations between IGE and DGE that could help to overcome the unfavourable genetic correlations between DGE did not reach sufficiently high magnitudes; also, the genetic parameters estimates from the SAM have large errors. These two factors penalize the average response under the SAM compared to the AM.
Hypercluster: a flexible tool for parallelized unsupervised clustering optimization
Authors: Blumenberg Lili , Ruggles Kelly V.
Published: September 2020

Background

Unsupervised clustering is a common and exceptionally useful tool for large biological datasets. However, clustering requires upfront algorithm and hyperparameter selection, which can introduce bias into the final clustering labels. It is therefore advisable to obtain a range of clustering results from multiple models and hyperparameters, which can be cumbersome and slow.

Results

We present hypercluster, a python package and SnakeMake pipeline for flexible and parallelized clustering evaluation and selection. Users can efficiently evaluate a huge range of clustering results from multiple models and hyperparameters to identify an optimal model.

Conclusions

Hypercluster improves ease of use, robustness and reproducibility for unsupervised clustering application for high throughput biology. Hypercluster is available on pip and bioconda; installation, documentation and example workflows can be found at: https://github.com/ruggleslab/hypercluster.
Transcriptome characterization of BPG axis and expression profiles of ovarian steroidogenesis-related genes in the Japanese sardine
Authors: Nyuji Mitsuo , Hongo Yuki , Yoneda Michio , Nakamura Masahiro
Published: September 2020

Background

The clupeoid fishes are ecologically and commercially important fish species worldwide that exhibit a high level of population fluctuation, accompanied by alteration of reproductive traits. However, knowledge about their reproductive physiology in order to understand mechanisms underlying such population dynamics is limited. The endocrine system along with the brain–pituitary–gonadal (BPG) axis is critical for regulating reproduction. The aims of this study were to provide transcript data and genes related to the BPG axis, and to characterize the expression profiles of ovarian steroidogenesis-related genes in the Japanese sardine (Sardinops melanostictus, Clupeidae).

Results

RNA sequencing was performed using the sardine brain, pituitary, and gonad in both sexes. A total of 290,119 contigs were obtained and 115,173 non-redundant ORFs were annotated. The genes differentially expressed between ovary and testis were strongly associated with GO terms related to gamete production. The tissue-specific profile of the abundance of transcripts was characterized for the major regulators in the BPG axis, such as gonadotropin-releasing hormone, gonadotropin, and steroidogenic enzyme. By comparing between ovary and testis, out of eight different 17β-hydroxysteroid dehydrogenase (Hsd17b) genes identified, higherhsd17b7expression was found in testis, whereas higher expression ofhsd17b8,hsd17b10,hsd17b12a, andhsd17b12bwas found in ovary. The cDNAs encoding key endocrine factors in the ovarian steroidogenic pathway were cloned, sequenced, and quantitatively assayed. In the pituitary,follicle-stimulating hormone betapeaked during vitellogenesis, whileluteinizing hormone betapeaked at the completion of vitellogenesis. In the ovary,follicle-stimulating hormone receptorandluteinizing hormone receptorwere upregulated from mid- to late phase of vitellogenesis. Furthermore, three steroidogenic enzyme genes (cyp11a1,cyp17a1, andcyp19a1a) gradually increased their expression during ovarian development, accompanying a rise in serum estradiol-17β, while3β-hydroxysteroid dehydrogenaseandsteroidogenic acute regulatory proteindid not change significantly.

Conclusions

This is the first report of deep RNA sequencing analysis of Japanese sardine, in which many key genes involved in the BPG axis were identified. Expression profiles of ovarian steroidogenesis-related genes provide a molecular basis of the physiological processes underlying ovarian development in the sardine. Our study will be a valuable resource for clarifying the molecular biology of clupeoid fishes.
Differential expression in leaves of Saccharum genotypes contrasting in biomass production provides evidence of genes involved in carbon partitioning
Authors: Correr Fernando Henrique , Hosaka Guilherme Kenichi , Barreto Fernanda Zatti , Valadão Isabella Barros , Balsalobre Thiago Willian Almeida , Furtado Agnelo , Henry Robert James , Carneiro Monalisa Sampaio , Margarido Gabriel Rodrigues Alves
Published: September 2020

Background

The development of biomass crops aims to meet industrial yield demands, in order to optimize profitability and sustainability. Achieving these goals in an energy crop like sugarcane relies on breeding for sucrose accumulation, fiber content and stalk number. To expand the understanding of the biological pathways related to these traits, we evaluated gene expression of two groups of genotypes contrasting in biomass composition.

Results

First visible dewlap leaves were collected from 12 genotypes, six per group, to perform RNA-Seq. We found a high number of differentially expressed genes, showing how hybridization in a complex polyploid system caused extensive modifications in genome functioning. We found evidence that differences in transposition and defense related genes may arise due to the complex nature of the polyploidSaccharumgenomes. Genotypes within both biomass groups showed substantial variability in genes involved in photosynthesis. However, most genes coding for photosystem components or those coding forphosphoenolpyruvate carboxylases(PEPCs) were upregulated in the high biomass group.Sucrose synthase(SuSy) coding genes were upregulated in the low biomass group, showing that this enzyme class can be involved with sucrose synthesis in leaves, similarly tosucrose phosphate synthase(SPS) andsucrose phosphate phosphatase(SPP). Genes in pathways related to biosynthesis of cell wall components andexpansinscoding genes showed low average expression levels and were mostly upregulated in the high biomass group.

Conclusions

Together, these results show differences in carbohydrate synthesis and carbon partitioning in the source tissue of distinct phenotypic groups. Our data from sugarcane leaves revealed how hybridization in a complex polyploid system resulted in noticeably different transcriptomic profiles between contrasting genotypes.
Oral microbial profile variation during canine ligature-induced peri-implantitis development
Authors: Qiao Shichong , Wu Dongle , Wang Mengge , Qian Shujiao , Zhu Yu , Shi Junyu , Wei Yongjun , Lai Hongchang
Published: September 2020

Background

Dental implants have become well-established in oral rehabilitation for fully or partially edentulous patients. However, peri-implantitis often leads to the failure of dental implants. The aim of this study was to understand the core microbiome associated with peri-implantitis and evaluate potential peri-implantitis pathogens based on canine peri-implantitis model.

Results

In this study, three beagle dogs were used to build peri-implantitis models with ligature-induced strategy. The peri-implant sulcular fluids were collected at four different phases based on disease severity during the peri-implantitis development. Microbial compositions during peri-implantitis development were monitored and evaluated. The microbes were presented with operational taxonomic unit (OTU) classified at 97% identity of the high-throughput 16S rRNA gene fragments. Microbial diversity and richness varied during peri-implantitis. At the phylum-level, Firmicutes decreased and Bacteroides increased during peri-implantitis development. At the genus-level, Peptostreptococcus decreased and Porphyromonas increased, suggesting peri-implantitis pathogens might be assigned to these two genera. Further species-level and co-occurrence network analyses identified several potential keystone species during peri-implantitis development, and some OTUs were potential peri-implantitis pathogens.

Conclusion

In summary, canine peri-implantitis models help to identify several potential keystone peri-implantitis associated species. The canine model can give insight into human peri-implantitis associated microbiota.
C-reactive protein for prediction of atrial fibrillation recurrence after catheter ablation
Authors: Meyre Pascal B. , Sticherling Christian , Spies Florian , Aeschbacher Stefanie , Blum Steffen , Voellmin Gian , Madaffari Antonio , Conen David , Osswald Stefan , Kühne Michael , Knecht Sven
Published: September 2020

Background

Inflammation plays an important role in the initiation and progression of atrial fibrillation (AF), but data about the relationship between subclinical inflammation and recurrence of AF after catheter ablation remains poorly studied. We aimed to assess whether plasma levels of C-reactive protein (CRP) are associated with long-term AF recurrence following catheter ablation.

Methods

Prior to the intervention, plasma CRP concentrations were measured in patients who underwent first catheter ablation for AF. AF recurrence was evaluated after 12 months and defined as any AF episode longer than 30 s recorded on either 12-lead electrocardiogram, 24-h Holter or 7-day Holter monitoring. Multivariable adjusted Cox models were constructed to examine the association of CRP levels and AF recurrence.

Results

Of the 711 patients (mean age: 61 years, 25% women) included in this study, 247 patients (35%) experienced AF recurrence after ablation. Patients who were in the highest CRP quartile had a higher rate of recurrent AF compared to those who were in the lowest quartile (53.4 vs. 33.1% at 1 year of follow-up; P = 0.004). The adjusted hazard ratios (aHR) of recurrent AF across increasing quartiles of CRP were 1.0 (reference), 1.26 (95% confidence interval [CI], 0.86–1.84), 1.15 (95% CI, 0.78–1.70) and 1.60 (95% CI, 1.10–2.34) (P trend = 0.015). A similar effect was observed when CRP was analyzed as continuous variable (aHR per unit increase, 1.21; 95% CI, 1.05–1.39; P = 0.009). When a predefined CRP cut-off of 3 mg/l was applied, patients with CRP levels of 3 mg/l or above had a higher risk of AF recurrence than those with levels below (aHR, 1.44; 95% CI, 1.06–1.95; P = 0.019).

Conclusions

Increasing pre-interventional CRP levels are associated with a higher risk of AF recurrence in patients undergoing catheter ablation for AF.

Trail registration

ClinicalTrials.gov identifier, NCT03718364.
Value of the platelet-to-lymphocyte ratio in the prediction of left ventricular thrombus in anterior ST-elevation myocardial infarction with left ventricular dysfunction
Authors: Zhang Qian , Si Daoyuan , Zhang Zhongfan , Wang Chengbing , Zheng Haikuo , Li Shouping , Huang Shijian , Zhang Wenqi
Published: September 2020

Background

The predictors of left ventricular thrombus (LVT) formation are not well defined in the contemporary era, especially in those patients at high risk. We aimed to evaluate whether the platelet/lymphocyte ratio (PLR) is valuable in the determination of LVT formation in patients with anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction.

Methods

The LVT group (n = 46) was identified from anterior STEMI patients with LV dysfunction who were treated with primary percutaneous coronary intervention (PCI) from January 2017 to December 2019 at the China-Japan Union Hospital of Jilin University. The no-LVT group (n = 92) were also selected from the same batch of patients and were age- and sex-matched to the patients with LVT. The PLR was determined at admission and was calculated as the ratio of the platelet count to the lymphocyte count using the complete blood count. The presence of LVT was determined by echocardiography.

Results

The PLR were significantly higher in patients with LVT than in no-LVT group (p = 0.001). In a receiver operator characteristic curve (ROC) analysis, using a cut-off value of 118.07 (AUC 0.673, 95% CI: 0.574–0.771, P = 0.001), the PLR could independently predict the occurrence of LVT. Multivariate analysis showed that an increased PLR (OR = 1.011, 95% CI: 1.004–1.018, P = 0.002), the presence of a left ventricular aneurysm (OR = 46.350, 95% CI: 5.659–379.615, P < 0.001) and increased DTBT (OR = 1.005, 95% CI: 1.001–1.009, P = 0.012) were independent predictors of LVT formation.

Conclusions

In acute anterior STEMI patients with LV dysfunction, an increased PLR and DTBT and the presence of an LV aneurysm were independent predictors of LVT formation. A larger prospective study is warranted to evaluate this result.

Trial registration

This study was registered (May 4, 2019) on Chinese Clinical Trial Registry (ChiCTR-DDD-17011214).
Contrasting cumulative risk and multiple individual risk models of the relationship between Adverse Childhood Experiences (ACEs) and adult health outcomes
Authors: LaNoue Marianna D. , George Brandon J. , Helitzer Deborah L. , Keith Scott W.
Published: September 2020

Background

A very large body of research documents relationships between self-reported Adverse Childhood Experiences (srACEs) and adult health outcomes. Despite multiple assessment tools that use the same or similar questions, there is a great deal of inconsistency in the operationalization of self-reported childhood adversity for use as a predictor variable. Alternative conceptual models are rarely used and very limited evidence directly contrasts conceptual models to each other. Also, while a cumulative numeric ‘ACE Score’ is normative, there are differences in the way it is calculated and used in statistical models. We investigated differences in model fit and performance between the cumulative ACE Score and a ‘multiple individual risk’ (MIR) model that enters individual ACE events together into prediction models. We also investigated differences that arise from the use of different strategies for coding and calculating the ACE Score.

Methods

We merged the 2011–2012 BRFSS data (N = 56,640) and analyzed 3 outcomes. We compared descriptive model fit metrics and used Vuong’s test for model selection to arrive at best fit models using the cumulative ACE Score (as both a continuous or categorical variable) and the MIR model, and then statistically compared the best fit models to each other.

Results

The multiple individual risk model was a better fit than the categorical ACE Score for the ‘lifetime history of depression’ outcome. For the outcomes of obesity and cardiac disease, the cumulative risk and multiple individual risks models were of comparable fit, but yield different and complementary inferences.

Conclusions

Additional information-rich inferences about ACE-health relationships can be obtained from including a multiple individual risk modeling strategy. Results suggest that investigators working with large srACEs data sources could empirically derive the number of items, as well as the exposure coding strategy, that are a best fit for the outcome under study. A multiple individual risk model could also be considered in addition to the cumulative risk model, potentially in place of estimation of unadjusted ACE-outcome relationships.
Performance of unanchored matching-adjusted indirect comparison (MAIC) for the evidence synthesis of single-arm trials with time-to-event outcomes
Authors: Jiang Yawen , Ni Weiyi
Published: September 2020

Background

The objectives of the present study were to evaluate the performance of a time-to-event data reconstruction method, to assess the bias and efficiency of unanchored matching-adjusted indirect comparison (MAIC) methods for the analysis of time-to-event outcomes, and to propose an approach to adjust the bias of unanchored MAIC when omitted confounders across trials may exist.

Methods

To evaluate the methods using a Monte Carlo approach, a thousand repetitions of simulated data sets were generated for two single-arm trials. In each repetition, researchers were assumed to have access to individual-level patient data (IPD) for one of the trials and the published Kaplan-Meier curve of another. First, we compared the raw data and the reconstructed IPD using Cox regressions to determine the performance of the data reconstruction method. Then, we evaluated alternative unanchored MAIC strategies with varying completeness of covariates for matching in terms of bias, efficiency, and confidence interval coverage. Finally, we proposed a bias factor-adjusted approach to gauge the true effects when unanchored MAIC estimates might be biased due to omitted variables.

Results

Reconstructed data sufficiently represented raw data in the sense that the difference between the raw and reconstructed data was not statistically significant over the one thousand repetitions. Also, the bias of unanchored MAIC estimates ranged from minimal to substantial as the set of covariates became less complete. More, the confidence interval estimates of unanchored MAIC were suboptimal even using the complete set of covariates. Finally, the bias factor-adjusted method we proposed substantially reduced omitted variable bias.

Conclusions

Unanchored MAIC should be used to analyze time-to-event outcomes with caution. The bias factor may be used to gauge the true treatment effect.