bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expansion and re-classification of the extracytoplasmic function (ECF) σ factor family
Authors: Casas-Pastor Delia , Müller Raphael R , Jaenicke Sebastian , Brinkrolf Karina , Becker Anke , Buttner Mark J , Gross Carol A , Mascher Thorsten , Goesmann Alexander , Fritz Georg 
Published: December 2020

AbstractExtracytoplasmic function σ factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As a result, we identified an average of ∼10 ECFs per bacterial genome and 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands previous classification efforts ∼50-fold, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences and an openly accessible data repository called ‘ECF Hub’ (https://www.computational.bio.uni-giessen.de/ecfhub), will serve as a powerful hypothesis-generator to guide future research in the field.
Extremely low gestational age infants: Developing a multidisciplinary care bundle
Authors: Ferretti Emanuela , Daboval Thierry , Rouvinez-Bouali Nicole , Lawrence Sarah L , Lemyre Brigitte 
Published: December 2020

AbstractBackgroundClinical experience in managing extremely low gestational age infants, particularly those born &lt;24 weeks’ gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born &lt;26 weeks’ gestation, with special considerations for infants of &lt;24 weeks, to harmonize and improve quality of care.MethodsWe created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology.ResultsA care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants &lt;26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%).ConclusionIt will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.
The Whack-a-Mole Game: Tobin Taxes and Trading Frenzy
Authors: Cai Jinghan , He Jibao , Jiang Wenxi , Xiong Wei 
Published: December 2020

Abstract
To dampen trading frenzy in the stock market, the Chinese government tripled the stamp tax for stock trading on May 30, 2007. The greatly increased trading cost triggered a migration of the trading frenzy from the stock market to the warrant market, which was not subject to the stamp tax. This migration exacerbated a price bubble in the warrant market. Our analysis of investor account data uncovers not only large inflows of new investors to the warrant market but also greatly intensified trading by existing warrant investors. This episode exemplifies the so-called “whack-a-mole” game in financial regulations.
Treatment of Chronic Hematogenous Osteomyelitis in Children With Antibiotic Impregnated Calcium Sulphate
Authors: Ellur Vikas , Kumar Girish , Sampath Jayanth S. 
Published: December 2020

Background:
The purpose of this study was to evaluate the clinical and radiologic outcome of chronic hematogenous osteomyelitis (CHOM) in children, treated with single-stage debridement and dead space management using antibiotic impregnated calcium sulphate pellets.

Methods:
The authors retrospectively evaluated a consecutive series of 34 patients who presented with CHOM from 2011 to 2017. In each case, CHOM was classified according to the Beit CURE classification. Following thorough surgical debridement, the resulting dead space in the bone was filled with the antibiotic impregnated beads before primary closure.

Results:
Of the 31 patients available for follow up, effective regeneration of bone was confirmed in all cases, with radiographic bone healing typically observed at around 12 weeks. None of the children required reoperation for infection and none had recurrence of infection at the time of final review. The beads were completely absorbed within 3 months. No systemic adverse reactions to the local delivery of antibiotics were observed in this study.

Conclusions:
The authors found that single-stage debridement in conjunction with antibiotic impregnated calcium sulphate was an effective means of treating CHOM in children, with effective eradication of infection in every case.

Level of Evidence:
Level IV—Retrospective case series. See instructions for authors for a complete description of levels of evidence.
Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma
Authors: Elinzano Heinrich , Toms Steven , Robison Jordan , Mohler Alex , Carcieri Arieana , Cielo Deus , Donnelly Jennifer , Disano Dylan , Vatketich John , Baekey John , Sturtevant Ashlee , MacKinnon Kelsey , Wood Roxanne , Safran Howard 
Published: December 2020

Background:
Liposomal formulations may improve the solubility and bioavailability of drugs potentially increasing their ability to cross the blood-brain barrier. We performed a phase I study to determine the maximum tolerated dose and preliminary efficacy of pegylated nanoliposomal irinotecan (nal-IRI)+metronomic temozolomide (TMZ) in patients with recurrent glioblastoma.

Patients and Methods:
Patients with glioblastoma who progressed after at least 1 line of therapy were eligible. All patients received TMZ 50 mg/m2/d until disease progression. Three dose levels of nal-IRI were planned, 50, 70, and 80 mg/m2, intravenously every 2 weeks. Patients were accrued in a 3+3 design. The study included a preliminary assessment after the first 13 evaluable patients. The trial would be terminated early if 0 or 1 responses were observed in these patients.

Results:
Twelve patients were treated over 2 dose levels (nal-IRI 50 and 70 mg/m2). At dose level 2, nal-IRI 70 mg/m2, 2 of 3 patients developed dose-limiting toxicities including 1 patient who developed grade 4 neutropenia and grade 3 diarrhea and anorexia and 1 patient with grade 3 diarrhea, hypokalemia fatigue, and anorexia. Accrual to dose level 1 was expanded to 9 patients. The Drug Safety Monitoring Board (DSMB) reviewed the data of the initial 12 patients—there were 0/12 responses (0%) and the median progression-free survival was 2 months and accrual was halted.

Conclusions:
The maximum tolerated dose of nal-IRI was 50 mg/m2 every 2 weeks with TMZ 50 mg/m2/d. The dose-limiting toxicities were diarrhea and neutropenia. No activity was seen at interim analysis and the study was terminated.
Clinical Trial Emulation by Matching Time-dependent Propensity Scores
Authors: Lenain Rémi , Boucquemont Julie , Leffondré Karen , Couchoud Cécile , Lassalle Mathilde , Hazzan Marc , Foucher Yohann 
Published: December 2020

Background:
No study to our knowledge has examined the use of observational data to emulate a clinical trial whereby patients at the time of kidney transplant proposal are randomly assigned to an awaiting transplantation or transplantation group. The main methodologic issue is definition of the baseline for dialyzed patients assigned to awaiting transplantation, resulting in the inability to use common propensity score-based approaches. We aimed to use time-dependent propensity score to better appraise the benefit of transplantation.

Methods:
We studied 23,231 patients included in the French registry and on a transplant waiting list from 2005 to 2016. The main outcome was time to death. By matching on time-dependent propensity score, we obtained 10,646 pairs of recipients (transplantation group) versus comparable patients remaining on dialysis (awaiting transplantation group).

Results:
The baseline exposure, that is, pseudo-randomization, was matching time. Median follow-up time was 3.5 years. At 10 years’ follow-up, the restricted mean survival time was 8.8 years [95% confidence interval (CI) = 8.7, 8.9] in the transplantation group versus 8.2 years (95% CI = 8.1, 8.3) in the awaiting transplantation group. The corresponding life expectancy gain was 6.8 months (95% CI = 5.5, 8.2), and this corresponded to one prevented death at 10 years for 13 transplantations.

Conclusions:
Our study has estimated the life expectancy gain due to kidney transplantation. It confirms transplantation as the best treatment for end-stage renal disease. Furthermore, we demonstrated that this simple method should also be considered for estimating marginal effects of time-dependent exposures.
Optical Coherence Tomography for the Investigation of Skin Adaptation in Lower-Limb Prosthesis Users
Authors: Swanson Eric C. , Friedly Janna L. , Wang Ruikang K. , Sanders Joan E. 
Published: December 2020

ABSTRACT

Introduction
Mechanically induced skin breakdown is a significant problem for many lower-limb prosthesis users. It is known that skin can adapt to the mechanical stresses of prosthesis use thereby reducing the risk of breakdown, yet little is understood about the biology behind skin adaptation. This is a proof-of-concept study for the use of novel, noninvasive optical coherence tomography (OCT) imaging techniques to investigate skin adaptation.

Methods
Two OCT imaging-based tests were used to evaluate features of the skin that may be involved in adaptation to limb-socket interface stresses. The tests were used to assess the function and structure of the cutaneous microvasculature, respectively. Epidermal thickness was also quantified. Tests were run on three lower-limb prosthesis users in a region of the residual limb believed to be highly stressed within the prosthetic socket. The measurements were compared with measurements taken at a location-matched site on the contralateral limb.

Results
Two of three participants demonstrated a faster time-to-peak and larger peak magnitude reactive hyperemia response in their residual limb compared with their contralateral limb. Two of three participants also demonstrated a larger magnitude vessel density at maximum dilation in their residual limb versus contralateral limb. The epidermal thickness was greater in the residual limb versus contralateral limb for all participants.

Conclusions
This study demonstrated the utility of two novel OCT imaging techniques for investigating skin adaptation in users of lower-limb prostheses. If we are able to confirm these findings on a larger subject population, we will better understand the biology behind mechanically induced skin adaptation. These findings, along with the noninvasive OCT imaging methods introduced here, would have the potential to improve clinical practice by enabling the development of rehabilitation techniques and therapeutics to better strengthen skin, thereby reducing the incidence of harmful skin breakdown.
Characteristics Among Premenarchal Girls With Lichen Sclerosus
Authors: Wang Melinda , Arlen Angela M. , Vash-Margita Alla 
Published: December 2020

Objectives
Lichen sclerosus (LS), a chronic inflammatory dermatosis localized in the anogenital region, is known to be associated with lower urinary tract symptoms (LUTS) in postmenopausal women; however, there is a paucity of data on prepubertal girls. We sought to characterize the relationship between LS, LUTS, and constipation among premenarchal girls.

Materials and Methods
We conducted a retrospective chart review of premenarchal girls presenting at the pediatric adolescent gynecology and pediatric urology clinics at our institution diagnosed with vulvar LS during a 4-year period. Demographics, clinical presentation, time from onset of urinary and/or bowel symptoms to LS diagnosis, and treatment response were assessed. Analysis was completed using median, range, and nonparametric statistical analysis where appropriate.

Results
Nineteen premenarchal girls with LS met inclusion criteria. The median age at LS diagnosis was 6.2 years (range = 3.3–13.3 yrs). Most girls (12/19, 63.2%) presented with LUTS during LS evaluation, and 11 (57.9%) of 19 patients had constipation. Pruritus and hypopigmentation were the most frequently encountered LS symptom and sign, respectively. Fourteen (73.7%) of the 19 girls had resolution/improvement of LS symptoms after LS treatment. Of the 12 patients with LUTS, 7 (58.3%) had resolution/improvement of LUTS symptoms, 3 (25.0%) had unchanged voiding symptoms, and 2 (16.7%) had unknown changes.

Conclusions
Although further studies are needed to better characterize the relationship between LUTS, constipation, and LS, our findings suggest that premenarchal subjects presenting with LUTS should be assessed for LS. Likewise, patients presenting with LS should be assessed for LUTS and constipation.
Are Nursing Interventions Effective in Improving Quality of Life in Cancer Survivors? A Systematic Review
Authors: Rodríguez-Matesanz Irati , Ambrosio Leire , Domingo-Oslé Marta , Elizondo-Rodríguez Nerea , La Rosa-Salas Virginia , Garcia-Vivar Cristina 
Published: December 2020

Background
Cancer survivors (CSs) have needs that can negatively impact their quality of life (QoL). Oncology nurses play a key role in providing comprehensive care in cancer survivorship, although little is known about their impact on health outcomes.

Objective
The aim of this study was to determine the effectiveness of nursing interventions to improve QoL and satisfaction with care of CSs.

Methods
A systematic review was conducted. PubMed, CINAHL, PsycINFO, and Cochrane databases were searched for experimental studies. The Joanna Briggs Institute Checklist for Randomized Controlled Trials was used to verify the quality of the studies (Prospero reference: CRD42020148294).

Results
Of the 8 clinical trials eligible for inclusion, 5 demonstrated that interventions conducted by nurses improved the overall QoL or some of its domains in CSs. The included studies focused on short-term survival; no studies in long-term CSs were identified. Two studies assessed satisfaction with care of survivors, obtaining positive results.

Conclusions
Nursing interventions seem to improve the QoL of short-term CSs. However, because of the low number of studies identified, the findings of this systematic review should be interpreted with caution.

Implications for practice
Further studies are necessary to strengthen the implementation of effective nursing intervention in cancer practice. Research should particularly be conducted with long-term CSs as there is lack of data on this specific stage of cancer.
What Is on the Horizon for Novel Immunotherapies in Lung Cancer?
Authors: Garon Edward B. , Li Debory Yi 
Published: December 2020

Abstract
Programmed death (ligand) 1 checkpoint inhibitors have become standard treatment in patients with non–small cell lung cancer. Recently, combinations of nivolumab and ipilimumab have entered the clinic based on regulatory approval. Oftentimes, these checkpoint inhibitors are given in conjunction with chemotherapy. Through increased understanding of checkpoint evasion by cancer cells, many promising studies using combination therapies have continued to develop that aim to attack cancer cells by eliciting immunogenic responses through different modalities. Novel approaches include (1) using vaccines to trigger immune response, (2) combining multiple checkpoint inhibitors, (3) targeting inflammatory responses, (4) utilizing multitargeted tyrosine kinase inhibitors, (5) employing agonists of T-cell stimulators, and (6) applying specific biomarker antagonists to treat lung cancer patients. Herein, we discuss several studies that aim to answer what lies ahead in lung cancer treatment.
What Is the Standard First-Line Treatment for Advanced Non–Small Cell Lung Cancer?
Authors: Ricciuti Biagio , Awad Mark M. 
Published: December 2020

Abstract
The initial treatment regimens for advanced non–small cell lung cancer (NSCLC) have drastically evolved over the last 15 years with the rapid development of improved genomic sequencing technologies and the emergence of immune checkpoint inhibitors. Highly active oral kinase inhibitors are now approved for several molecularly defined subsets of NSCLC, including those harboring alterations in the EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK genes, although acquired resistance to these targeted therapies remains a significant clinical challenge. In lung cancers lacking targetable mutations, programmed death 1/programmed death ligand 1 immune checkpoint inhibitors, used alone or in combination with cytotoxic T-lymphocyte-associated protein 4 inhibitors and/or cytotoxic chemotherapy, have led to meaningful improvements in overall survival. With many therapeutic options available to patients, here we review the recommended frontline treatment regimens for advanced NSCLC with and without targetable genomic drivers.
Harnessing the Immune System to Tackle Small Cell Lung Cancer
Authors: Newton Benjamin Robert , Chiang Anne C. 
Published: December 2020

Abstract
Immunotherapy has improved first-line therapy for small cell lung cancer and has activity in the relapsed setting as well. The immunobiology of small cell lung cancer poses challenges for immunotherapy, and efforts are underway to unlock to the potential of immunotherapy through the identification of meaningful disease subsets and the development of novel combination therapies.
Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the rostral ventromedial medulla in mice
Authors: Sluka Kathleen A. , Danielson Jessica , Rasmussen Lynn , Kolker Sandra J. 
Published: December 2020

Abstract

Introduction:
Regular physical activity/exercise is an effective nonpharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The rostral ventromedial medulla (RVM) sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia.

Objective:
The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry.

Methods:
Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the RVM and the nucleus raphe obscurus/nucleus raphe pallidus, dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-d-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated. Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by 2 intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2).

Results:
Physically active animals had less mu-opioid-expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the nucleus raphe obscurus/nucleus raphe pallidus. No changes were observed for TPH.

Conclusions:
These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition.
New Insights on Long-Term Hepatitis B Virus Responses in HIV–Hepatitis B virus Co-infected Patients: Implications for Antiretroviral Management in Hepatitis B virus-Endemic Settings
Authors: Dunn David , Price Huw , Vudriko Tobias , Kityo Cissy , Musoro Godfrey , Hakim James , Gilks Charles , Kaleebu Pontiano , Pillay Deenan , Gilson Richard ,   DART Virology Group
Published: December 2020

Background:
WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting.

Setting:
Clinical centers in Uganda and Zimbabwe.

Methods:
DART was a randomized trial of monitoring practices in HIV-infected adults starting antiretroviral therapy. Baseline samples were tested retrospectively for HBV serological markers and HBV DNA. Longitudinal HBV DNA testing at 48 weeks and the last available sample before HBV-relevant modification of antiretroviral therapy was performed on patients with detectable HBV DNA at baseline.

Results:
Two hundred twenty-four hepatitis B surface antigen-positive patients were followed for up to 4.8 years. Of the drugs with anti-HBV activity, 166 were prescribed lamivudine–tenofovir and 58 lamivudine alone. Ninety-eight percent (96/98) patients with baseline HBV DNA <6 log10 IU/mL achieved viral suppression at 48 weeks (HBV DNA <48 IU/mL), regardless of regimen, compared with 50%(26/52) for HBV DNA >6 log10 IU/mL. Of the 83 patients suppressed at 48 weeks and with follow-up data, only 7(8%) experienced viral rebound (range 200–3460 IU/mL). Of the 20 patients not suppressed at 48 weeks and with follow-up data, HBV DNA levels generally declined with lamivudine–tenofovir, but increased with lamivudine alone. Alanine transaminase flares were not observed in any patient who experienced viral rebound.

Conclusions:
The suppressive effect of lamivudine alone was highly durable (up to 5 years) in HIV–HBV co-infected patients with baseline HBV DNA <6 log10 IU/mL. It may be feasible to develop stratified approaches using lamivudine as the only drug with anti-HBV activity.