bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target serum concentration of vancomycin may be reached earlier with a loading dose
Authors: Huang Yanxia , He Le , Deng Yunxin , Zhang Renjing , Meng Mei , Liu Jiao , Chen Dechang 
Published: January 2022

Abstract

Background:
Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit (ICU). One of the reasons for this is the substandard drug trough concentration. We aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of vancomycin.

Methods:
This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having, or confirmed to have, gram-positive cocci infection and treated with vancomycin. One group of the patients was administered a loading dose of vancomycin (loading group) and compared with the group that did not receive a loading dose (control group). The baseline characteristics, vancomycin serum concentrations, and clinical outcomes were collected and analyzed.

Results:
Fifty-five patients were finally included, of which 29 received a loading dose of vancomycin. The serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group (10.3 ± 6.1 mg/L vs. 5.7 ± 4.4 mg/L, P = 0.002). The results for both groups were similar before the fifth dose (12.4 ± 7.3 mg/L vs. 10.3 ± 6.3 mg/L in the loading and the control groups, respectively; P = 0.251). The 28-day mortality was lower for the loading group than for the control group (6.7% vs. 34.6% in the loading and control groups, respectively; P = 0.026). No significant differences were observed in serum creatinine (Cr) concentrations of the two groups.

Conclusion:
With the loading dose of vancomycin, the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.

Trial registration:

https://www.chictr.org.cn; ChiCTR2000035369
Interleukins in the treatment of melanoma
Authors: Xu Xinyuan , Dai Wei , Li Chunying 
Published: January 2022

Abstract
Interleukins (ILs) and associated cytokines serve as the means of communication for immune cells and non-immune cells. The use of ILs in harnessing the immune system to cancer treatment has been a promising approach. ILs not only nurture an environment enabling cancer growth but also simultaneously trigger a productive tumor-directed immune response. These properties of ILs are increasingly being explored as a strategy to improve the outcomes of cancer. Here, we describe recently innovative technological approaches that have been developed to improve the pharmacokinetics, safety, and efficacies of IL-2, 15, 10, and 18 in the treatment of melanoma. Furthermore, the combination of ILs and immune checkpoint inhibition may synergize to reshape the tumor environment, thus yielding better clinical benefits in the future.
Biplanar Lipoabdominoplasty: Introducing the Subscarpal Lipo Aponeurotic System
Authors: Wolf Yoram , Weissman Oren , Dima Helena , Sandbank Judith , Fainzilber-Goldman Yifat 
Published: January 2022

Background:
Preservation of Scarpa’s fascia in abdominoplasty has been previously presented. Herein we introduce the subscarpal lipo aponeurotic system (SLAS) and the technique of preserving the SLAS and its tightening in lipoabdominoplasty.

Methods:
A retrospective cohort study of patients who underwent lipoabdominoplasty performed by a single plastic surgeon (YW) between 2014 and 2019 was conducted. We compared postoperative complications, aesthetic outcomes, and procedure lengths between standard and biplanar lipoabdominoplasty with SLAS tightening. Supra-scarpal fat and SLAS tissue specimens were obtained for histological analysis.

Results:
In total, 179 patients underwent biplanar lipoabdominoplasty with SLAS tightening and were compared with a control group of 65 patients who underwent standard lipoabdominoplasty. Fifty-four patients (29.9%) underwent concomitant umbilical, epigastric, or postoperative ventral hernia (POVH) repair. No major complications were encountered other than one skin necrosis in a standard lipoabdominoplasty. Moderate complication rate was 10.05% in the biplanar group, compared with 16.92% in the standard lipoabdominoplasty. The average length of the procedure and overall aesthetic results were equivalent.

Conclusions:
The SLAS can be individually dissected and used during abdominoplasty. No statistically significant differences were found in complication rates, length of procedure, or aesthetic outcomes between standard and biplanar lipoabdominoplasty with SLAS tightening. Further investigation is needed. Nonetheless, we postulate that patients who would benefit the most from this procedure are those with weakening of the abdominal wall, and with some fullness of the hip line, as this technique adds reinforcement to the lower abdomen and “pulls in” the flanks.
Iliocostalis Muscle Rotational Flap: A Novel Flap for Esophagopleural Fistula Repair
Authors: Nam Arthur J. , Yoon Joshua , Krause Eric M. , Elegbede Adekunle I. , Carr Shamus R. 
Published: January 2022

Summary:
Intrathoracic fistulas present major challenges to reconstructive surgeons. Reconstruction with muscle flaps have been shown to improve patient outcomes; however, there are patients for whom one or more of the commonly used muscle flaps is not available for several reasons. We describe the use of an iliocostalis muscle rotational flap for the repair of a caudally located esophagopleural fistula in the setting of definitive chemoradiotherapy for treatment of nonsmall-cell lung cancer and reirradiation with photons for local recurrence 5 years later. Our repair remained intact through the nearly 12-month follow-up period during which the patient tolerated a regular diet. This report demonstrates that the iliocostalis lumborum muscle is a viable option for repair of intrathoracic fistulas that are located in the distal esophagus, even in the setting of previous thoracotomy and radiation, and should be part of the reconstructive surgeon’s armamentarium in the management of intrathoracic fistulas.
The Shadow Pandemic: A Qualitative Exploration of the Impacts of COVID-19 on Service Providers and Women Survivors of Intimate Partner Violence and Brain Injury
Authors: Haag Halina (Lin) , Toccalino Danielle , Estrella Maria Jennifer , Moore Amy , Colantonio Angela 
Published: January 2022

Background:
Intimate partner violence (IPV) affects up to 1 in 3 women over their lifetime and has intensified during the COVID-19 pandemic. Although most injuries are to the head, face, and neck, the intersection of IPV and brain injury (BI) remains largely unrecognized. This article reports on unexplored COVID-19–related impacts on service providers and women survivors of IPV/BI.

Objectives:
To explore the impact of the COVID-19 pandemic on survivors and service providers.

Participants:
Purposeful sampling through the team's national Knowledge-to-Practice (K2P) network and snowball sampling were used to recruit 24 participants across 4 categories: survivors, executive directors/managers of organizations serving survivors, direct service providers, and employer/union representatives.

Design:
This project used a qualitative, participatory approach using semistructured individual or group interviews. Interviews were conducted via videoconferencing, audio-recorded, and transcribed. Transcripts were thematically analyzed by the research team to identify themes.

Findings:
COVID-19 has increased rates and severity of IPV and barriers to services in terms of both provision and uptake. Three main themes emerged: (1) implications for women survivors of IPV/BI; (2) implications for service delivery and service providers supporting women survivors of IPV/BI; and (3) key priorities. Increased risk, complex challenges to mental health, and the impact on employment were discussed. Adaptability and flexibility of service delivery were identified as significant issues, and increased outreach and adaptation of technology-based services were noted as key priorities.

Conclusions:
The COVID-19 pandemic has intensified IPV/BI, increased challenges for women survivors and service providers, and accentuated the continued lack of IPV/BI awareness. Recommendations for service delivery and uptake are discussed.
Bridging the Acute-to-Outpatient Care Gap in Mental Health
Authors: Kantaria Tina , Talag Germiniano , Fan Jia , Navarro Filda , Sonza Patrick , Fears Scott , Yang Calvin , Balsam Jeffrey , Birman Sharon , Lam Mona , Guze Barry , Raja Pushpa 
Published: January 2022

Background:
A national Department of Veterans Affairs (VA) mental health (MH) quality metric tracks engagement in outpatient MH care after discharge from residential and inpatient settings, with recommendations for 2 or more visits 30 days postdischarge.

Local Problem:
A gap in transitioning patients from residential to outpatient MH care was identified at this site.

Methods:
A transition management process was developed and piloted, including a new MH Discharge Consult and an RN Transition Care Managers team.

Interventions:
Transition Care Managers triaged Discharge Consults, communicated with schedulers and patients pre- and postdischarge, and tracked MH engagement for 30 days postdischarge. Process, outcome, and balancing measures were developed and iteratively adjusted using Plan-Do-Study-Act (PDSA) cycles.

Results:
Over 55 weeks, 443 Discharge Consults were placed. There was an average 89% success rate in connecting patients with 2 or more MH visits versus 53% preintervention.

Conclusions:
This pilot showed promising results in improving postdischarge MH engagement with the use of PDSA cycles to collect data and refine processes.
The Association Between Patterns of Social Engagement and Conversion From Mild Cognitive Impairment to Dementia
Authors: Amano Takashi , Park Sojung , Morrow-Howell Nancy , Carpenter Brian 
Published: January 2022

Objectives:
This study examined the association between patterns of social engagement and conversion from cognitive impairment, no dementia (CIND) to dementia. It also tested whether social engagement is associated with conversion independently from physical and cognitive engagements.

Method:
Data from 2 waves (2010 and 2014) of the Health and Retirement Study (HRS) were used. The sample consisted of 1227 people who had CIND in 2010. To identify the heterogeneity of social engagement, latent class analysis was utilized. Multinomial logistic regression analysis was utilized to investigate the association between patterns of social engagement and probability of conversion to dementia and death or dropout.

Results:
The result showed that patterns of social engagement that represent higher level and more variety of social engagement were associated with lower probabilities of conversion to dementia in 4 years but not with probabilities of death or dropout. The relationship held after controlling for physical and cognitive engagements.

Discussion:
Findings implied that promoting social engagement may be protective against developing dementia even for the high-risk group of people with CIND. Future studies should investigate the mechanism behind the relationship between patterns of social engagement and lower probabilities of conversion to dementia.
Single-cell multi-omics analyses reveal EZH2 as a main driver of retinoic acid resistance in PLZF-RARA leukemia
Authors: Poplineau M. , Platet N. , Mazuel A. , Hérault L. , Koide S. , Kuribayashi W. , Carbuccia N. , N’Guyen L. , Vernerey J. , Oshima M. , Birnbaum D. , Iwama A. , Duprez E. 
Published: January 2022

ABSTRACTCancer relapse is caused by a subset of malignant cells that are resistant to treatment. To characterize resistant cells and their vulnerabilities, we studied the retinoic acid (RA)-resistant PLZF-RARA acute promyelocytic leukemia (APL) using single-cell multi-omics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells and identified a subset of cells resistant to RA that depend on a fine-tuned transcriptional network targeting the epigenetic regulator Enhancer of Zeste Homolog 2 (EZH2). Epigenomic and functional analyses validated EZH2 selective dependency of PLZF-RARA leukemia and its driver role in RA resistance. Targeting pan-EZH2 activities (canonical/non-canonical) was necessary to eliminate leukemia relapse initiating cells, which underlies a dependency of resistant cells on an EZH2 non-canonical activity and the necessity to degrade EZH2 to overcome resistance.Our study provides critical insights into the mechanisms of RA resistance that allow us to eliminate treatment-resistant leukemia cells by targeting EZH2, thus highlighting a potential targeted therapy approach.HIGHLIGHTS- sc-RNAseq identifies PLZF-RARA leukemia heterogeneity and retinoic acid resistant cells- sc-ATACseq refines leukemic cell identity and resolves retinoic acid resistant networks- EZH2 is a selective dependency of PLZF-RARA leukemia and drives retinoic acid resistance- Targeting pan-EZH2 activities (canonical/non-canonical) is necessary to overcome leukemia onset
Lack of evidence for functional luteinising hormone chorionic gonadotropin receptors in non-pregnant human endometrial stromal cells
Authors: Mann ON , Kong C-S , Lucas ES , Brosens JJ , Hanyaloglu AC , Brighton PJ 
Published: January 2022

AbstractThe human luteinising hormone chorionic gonadotropin receptor (LHCGR) is a G-protein coupled receptor activated by both human chorionic gonadotropin (hCG) and luteinizing hormone (LH), two structurally related gonadotropins with essential roles in ovulation and maintenance of the corpus luteum. LHCGR expression predominates in ovarian tissues where it elicits functional responses through cyclic adenosine mononucleotide (cAMP), Ca2+ and extracellular signal-regulated kinase (ERK) signalling. LHCGR has also been localized to the human endometrium, with purported roles in decidualization and implantation. However, these observations are contentious. In this investigation, transcripts encoding LHCGR were undetectable in bulk RNA sequencing datasets from whole cycling endometrial tissue and cultured human endometrial stromal cells (EnSC). However, analysis of single-cell RNA sequencing data revealed cell-to-cell transcriptional heterogeneity and identified a small subpopulation of stromal cells with discernible LHCGR transcripts. In HEK-293 cells expressing recombinant LHCGR, both hCG and LH elicited robust cAMP, Ca2+ and ERK signals that were absent in wild type HEK-293 cells. However, none of these responses were recapitulated in primary EnSC cultures. In addition, proliferation, viability and decidual transformation of EnSC were refractory to both hCG and LH, irrespective of treatment to induce differentiation. Although we challenge the assertion that LHCGR is expressed at a functionally active level in the human endometrium, the discovery of a discrete subpopulation of EnSC that express LHCGR transcripts may plausibly account for the conflicting evidence in the literature.
Discovery of novel compounds as potent activators of Sirt3
Authors: Reverdy Célina , Gitton Gaetan , Guan Xiangying , Adhya Indranil , Dumpati Rama Krishna , Roy Samir , Chall Santu , Errasti Gauthier , Delacroix Thomas , Chakrabarti Raj 
Published: January 2022

ABSTRACTAmong the sirtuin enzymes, Sirt3 is one of the most important deacetylases as it regulates acetylation levels in mitochondria, which are linked to the metabolism of multiple organs and therefore involved in many types of age-related human diseases such as cancer, heart diseases and metabolic diseases. Given the dearth of direct activators of Sirt3, the identification of new modulators could be a key step in the development of new therapeutics. Here we report the discovery of Sirt3 modulators, including activators, through the use of DNA encoded library technology (DEL). The most enriched compounds after DEL selection against SIRT3 were evaluated according to their activity and affinity. Our best activator seems at least as potent as Honokiol (HKL) while the docking studies suggest that our modulators interact with Sirt3 at an atypical site. Our results establish the attractiveness of the DEL technology in identifying novel and potent Sirt3 activators and, therefore, in associated therapeutic applications.
Genomic dissection of the microevolution of Australian epidemic Bordetella pertussis
Authors: Xu Zheng , Hu Dalong , Wai Luu Laurence Don , Octavia Sophie , Keil Anthony D , Sintchenko Vitali , Tanaka Mark M. , Mooi Frits R. , Robson Jenny , Lan Ruiting 
Published: January 2022

AbstractWhooping cough (pertussis) is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, pertussis has re-emerged in many countries and caused two large epidemics in Australia since 2007. Here, we undertook a genomic and phylogeographic study of 385 Australian B. pertussis isolates collected from 2008 to 2017. The Australian B. pertussis population was found to be composed of mostly ptxP3 strains carrying different fim3 alleles, with ptxP3-fim3A genotype expanded far more than ptxP3-fim3B. Within the former, there were six co-circulating epidemic lineages (EL1 to EL6). The multiple ELs emerged, expanded, and then declined at different time points over the two epidemics, likely driven by immune selection from pertussis vaccination and natural infection in addition to local and global transmission events. Both hard and soft selective sweeps through vaccine selection pressures determined the current B. pertussis population dynamics. Relative risk analysis found that once a new B. pertussis lineage emerged, it was more likely to spread locally within the first 1.5 years. However, after 1.5 years, any new lineage was likely to expand to a wider region and became no longer spatially structured across the country. Phylogenetic analysis revealed the expansion of ptxP3 strains was also associated with replacement of the type III secretion system allele bscI1 with bscI3. This study advanced our understanding of the epidemic population structure and spatial and temporal dynamics of B. pertussis in a highly immunised population.
Differential serotonergic modulation of principal neurons and interneurons in the anterior piriform cortex
Authors: Piszár Ildikó , Lőrincz Magor L. 
Published: January 2022

ABSTRACTOriginating from the brainstem raphe nuclei, serotonin is an important neuromodulator involved in a variety of physiological and pathological functions. Specific optogenetic stimulation of serotonergic neurons results in the divisive suppression of spontaneous, but not sensory evoked activity in the majority of neurons in the primary olfactory cortex and an increase in firing in a minority of neurons. To reveal the mechanisms involved in this dual serotonergic control of cortical activity we used a combination of in vitro electrophysiological recordings from identified neurons in the primary olfactory cortex, optogenetics and pharmacology and found that serotonin suppressed the activity of principal neurons, but excited local interneurons. The results have important implications in sensory information processing and other functions of the olfactory cortex and related brain areas.
Staphylococcus aureus activates the Aryl Hydrocarbon Receptor in Human Keratinocytes
Authors: Stange Eva-Lena , Rademacher Franziska , Drerup Katharina Antonia , Heinemann Nina , Möbus Lena , Gläser Regine , Harder Jürgen 
Published: January 2022

AbstractStaphylococcus (S.) aureus is an important pathogen causing various infections including - as most frequently isolated bacterium - cutaneous infections. Keratinocytes as the first barrier cells of the skin respond to S. aureus by the release of defense molecules such as cytokines and antimicrobial peptides. Although several pattern recognition receptors expressed in keratinocytes such as Toll-like and NOD-like receptors have been reported to detect the presence of S. aureus, the mechanisms underlying the interplay between S. aureus and keratinocytes are still emerging. Here we report that S. aureus induced gene expression of CYP1A1 and CYP1B1, responsive genes of the aryl hydrocarbon receptor (AhR). AhR activation by S. aureus was further confirmed by AhR gene reporter assays. AhR activation was mediated by factor(s) < 2 kDa secreted by S. aureus. Whole transcriptome analyses and real-time PCR analyses identified IL-24, IL-6 and IL-1beta as cytokines induced in an AhR-dependent manner in S. aureus-treated keratinocytes. AhR inhibition in a 3D organotypic skin equivalent confirmed the crucial role of the AhR in mediating the induction of IL-24, IL-6 and IL-1beta upon stimulation with living S. aureus. Taken together, we further highlight the important role of the AhR in cutaneous innate defense and identified the AhR as a novel receptor mediating the sensing of the important skin pathogen S. aureus in keratinocytes.
Retrospective analysis of long‐term survival factors in patients with advanced non‐small cell lung cancer treated with nivolumab
Authors: Murakami Yusuke , Tamiya Akihiro , Taniguchi Yoshihiko , Adachi Yuichi , Enomoto Takatoshi , Azuma Koji , Inagaki Yuji , Kouno Shunichi , Matsuda Yoshinobu , Okishio Kyoichi , Atagi Shinji 
Published: January 2022

AbstractBackgroundNivolumab, an immune checkpoint inhibitor (ICI), has changed the treatment paradigm for advanced non‐small cell lung cancer (NSCLC). However, factors associated with long‐term survival in NSCLC patients treated with ICIs remain unknown. This study aimed to evaluate patient characteristics and clinical laboratory changes related to long‐term survival in NSCLC patients treated with nivolumab, using real‐world data.MethodsWe retrospectively reviewed the medical records of consecutive patients with advanced NSCLC with Eastern Cooperative Oncology Group performance status (ECOG‐PS) ≤1 treated with nivolumab. We defined patients with overall survival (OS) ≥3 years as long‐term survivors. We evaluated the differences in patient characteristics and tumor response between nonlong‐term survivors and long‐term survivors and performed univariate and multivariate analyses of factors associated with long‐term survival.ResultsOut of 213 patients with advanced NSCLC treated with nivolumab, 162 patients with ECOG‐PS ≤1 were included in the study. Young age, ECOG‐PS 0, absolute neutrophil count decrease, lymphocyte percentage increase, and neutrophil‐to‐lymphocyte ratio (NLR) change (ΔNLR) <1 were significantly associated with long‐term survival. Long‐term survivors had significantly higher response and disease control rates than nonlong‐term survivors. Multivariate analysis showed that ΔNLR <1 was significantly associated with long‐term survival. Further, OS was significantly different between the PS 0 and PS 1 groups (median OS: 32.0 months vs. 10.6 months) and the nonincreasing NLR and increasing NLR groups (median OS: 20.8 months vs. 5.7 months).ConclusionsΔNLR <1 was a significant long‐term survival factor compared to ΔNLR ≥1 in advanced NSCLC patients treated with nivolumab.