bluuebunny/crossref_metadata_2025 huggingface dataset:
IRONMAN peptide interacts with OsHRZ1 and OsHRZ2 to maintain Fe homeostasis in rice
Authors: Peng Feng , Li Chenyang , Lu Chengkai , Li Yang , Xu Peng , Liang Gang
Published: July 2022

IRONMAN (IMA) is a family of small peptides which positively regulate plant responses under Fe deficiency. However, the molecular mechanism by which OsIMA1 and OsIMA2 regulate Fe homeostasis in rice is unclear. Here, we reveal that OsIMA1 and OsIMA2 interact with the potential Fe sensors, OsHRZ1 (HAEMERYTHRIN MOTIF-CONTAINING REALLY INTERESTING NEW GENE (RING) AND ZINC-FINGER PROTEIN 1) and OsHRZ2. OsIMA1 and OsIMA2 contain a conserved 17 amino acid C-terminal region which is responsible for the interactions with OsHRZ1 and OsHRZ2. Plants overexpressing OsIMA1 (OsIMA1ox) show increased Fe concentration in seeds and reduced fertility, as observed in the hrz1-2 loss-of-function mutant plants. Moreover, the expression patterns of Fe deficiency inducible genes in the OsIMA1ox plants are the same as those in hrz1-2. Co-expression assays suggest that OsHRZ1 and OsHRZ2 promote the degradation of OsIMA1 proteins. As the interaction partners of OsHRZ1, the OsPRI (POSITIVE REGULATOR OF IRON HOMEOSTASIS) proteins also interact with OsHRZ2. The conserved C-terminal region of four OsPRIs contributes to the interactions with OsHRZ1 and OsHRZ2. An artificial IMA (aIMA) derived from the C-terminal of OsPRI1 can be also degraded by OsHRZ1. Moreover, aIMA overexpressing rice plants accumulate more Fe without reduction of fertility. This work establishes the link between OsIMAs and OsHRZs, and develops a new strategy for Fe fortification in rice.
Eating Disorders in U.S. Active Duty Military Members and Veterans: A Systematic Review
Authors: Touma Danielle A , Quinn Meghan E , Freeman Vanessa E , Meyer Eric G
Published: July 2022

Introduction

Feeding and eating disorders can be difficult to treat and frequently co-occur with other mental health conditions. The last systematic review of eating disorders in a military and veteran population was published in 2015. An updated review is warranted to re-examine the current literature on eating disorders in the active duty and veteran populations.

Materials and Methods

A systematic review that described the prevalence, co-occurrence of other disorders and/or events, and health care utilization of U.S. active duty members and veterans was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases and Medical Subject Headings (MeSH) terms used are listed in Appendix A. Each category of the literature was extracted and graded using the Oxford Centre for Evidence-Based Medicine Levels of Evidence.

Results

Twenty-one studies revealed prevalence estimates with varying rates based on demographic information. Trauma exposure is consistently associated with eating disorder development. Individuals diagnosed with eating disorders had greater health care utilization.

Conclusions

Research on eating disorders in the military and veteran populations has expanded in recent years. Limitations of the evidence included in this review stem from the use of self-reported questionnaires, changes to medical record systems, and limited generalizability to the overall population of patients with eating disorders. Further research should investigate the impact of demographic factors and trauma exposure on the development of an eating disorder within the military and veteran populations.
SDSS-IV MaNGA – gas rotation velocity lags in the final sample of MaNGA galaxies
Authors: Bizyaev Dmitry , Walterbos Rene A M , Chen Yan-Mei , Drory Niv , Lane Richard R , Brownstein Joel R , Riffel Rogemar A
Published: July 2022

We consider the largest sample of 561 edge-on galaxies observed with integral field units by the MaNGA survey and find 300 galaxies where the ionized gas shows a negative vertical gradient (lag) in its rotational speed. We introduce the stop altitude as the distance to the galactic mid-plane at which the gas rotation should stop in the linear approximation. We find correlations between the lags, stop altitude and galactic mass, stellar velocity dispersion, and overall Sersic index. We do not find any correlation of the lags or stop altitude with the star formation activity in the galaxies. We conclude that low-mass galaxies (log(M*/M⊙) < 10) with low-Sersic index and with low-stellar velocity dispersion possess a wider ‘zone of influence’ in the extragalactic gas surrounding them with respect to higher mass galaxies that have a significant spherical component. We estimated the trend of the vertical rotational gradient with radius and find it flat for most of the galaxies in our sample. A small subsample of galaxies with negative radial gradients of lag has an enhanced fraction of objects with aged low-surface brightness structures around them (e.g. faint shells), which indicates that noticeable accretion events in the past affected the extraplanar gas kinematics and might have contributed to negative radial lag gradients. We conclude that an isotropic accretion of gas from the circumgalactic medium plays a significant role in the formation of rotation velocity lags.
Constraining the reionization and thermal history of the Universe using a seminumerical photon-conserving code script
Authors: Maity Barun , Choudhury Tirthankar Roy
Published: July 2022

Given that the reionization history of cosmic hydrogen is yet to be stringently constrained, it is worth checking the prospects of doing so using physically motivated models and available observational data. For this purpose, we use an extended version of the explicitly photon-conserving seminumerical model of reionization, script, which also includes thermal evolution of the intergalactic medium (IGM). The model incorporates the effects of inhomogeneous recombination and radiative feedback self-consistently and is characterized by five free parameters (two for the redshift-dependent ionization efficiency, two for the ionizing escape fraction, and another for reionization temperature increment). We constrain these free parameters by simultaneously matching with various observational probes, e.g. estimates of the ionized hydrogen fraction, the CMB scattering optical depth and the galaxy UV luminosity function. In addition, we include the low-density IGM temperature measurements obtained from Lyman-α absorption spectra at z∼5.5, a probe not commonly used for Bayesian analysis of reionization parameters. We find that the interplay of the various data sets, particularly inclusion of the temperature data, leads to tightening of the parameter constraints. Our default models prefer a late end of reionization (at z ≲ 6), in agreement with other recent studies. We can also derive constraints on the duration of reionization, $\Delta z=1.81^{+0.51}_{-0.67}$ and the mid-point of reionization, $z_{\mathrm{mid}}=7.0^{+0.30}_{-0.40}$. The constraints can be further tightened by including other available and upcoming data sets.
Molecular survey of Cryptoplax japonica (Polyplacophora: Cryptoplacidae) reveals cryptic lineages in the northwestern Pacific
Authors: Park Jina , Lee Yucheol , Kim Taeho , Kern Elizabeth , Kil Hyun-Jong , Eernisse Douglas J , Saito Hiroshi , Park Joong-Ki
Published: July 2022

The chiton genus Cryptoplax is widely distributed in the Indo-Pacific, extending to southern Australia and the northwestern Pacific (NWP), with 17 recognized species. Among these species, Cryptoplax japonica is commonly found on rocky intertidal and subtidal substrates in the NWP, whereas another species, C. propior, is rarely seen because of its cryptic subtidal habitat and limited distribution. In this study, we surveyed the genetic diversity of C. japonica populations based on 93 individuals from 24 sampling sites along the Korean and Japanese coastlines, including the type locality, using DNA sequences of the mitochondrial gene cytochrome c oxidase subunit I (COI). Haplotype network and phylogenetic analyses of COI sequences revealed two highly divergent genetic lineages of C. japonica separated by a large pairwise genetic distance (10.62%), which was comparable to the genetic difference when either of these two lineages (A or B) is compared with the co-occurring C. propior. In addition to COI sequences, average sequence divergence in 16S rDNA between these three lineages ranged from 2.0 to 3.3%. In contrast to this deep sequence divergence, both morphological examination of radula, girdle and articulamentum colouring, and morphometric analyses of shell measurements using principal component analysis and linear discriminant analysis revealed no diagnostic differences between the two C. japonica lineages. The co-occurrence of these two divergent lineages within most of our studied area, with no morphological differences, indicates cryptic divergence. More extensive sampling from the entire distributional ranges of these cryptic species, in combination with the use of additional molecular markers could shed light on the mechanisms underlying their divergence.
Smoking Cessation in People With and Without Diabetes After Acute Coronary Syndrome
Authors: Clement Ludivine , Gencer Baris , Muller Olivier , Klingenberg Roland , Räber Lorenz , Matter Christian M , Lüscher Thomas F , Windecker Stephan , Mach François , Rodondi Nicolas , Nanchen David , Clair Carole
Published: July 2022

Introduction

People with diabetes smoke at similar rates as those without diabetes, with cardiovascular consequences. Smoking cessation rates were compared between people with and without diabetes 1 year after an acute coronary syndrome (ACS).

Aims and Methods

People with ACS who smoked and were part of an observational prospective multicenter study in Switzerland were included from 2007 to 2017 and followed for 12 months. Seven-day point prevalence abstinence was assessed at 12 months follow-up. Association between diabetes and smoking cessation was assessed using multivariable-adjusted logistical regression model.

Results

2457 people with ACS who smoked were included, the mean age of 57 years old, 81.9% were men and 13.3% had diabetes. At 1 year, smoking cessation was 35.1% for people with diabetes and 42.6% for people without diabetes (P-value .01). After adjustment for age, sex, and educational level, people with diabetes who smoked were less likely to quit smoking compared with people without diabetes who smoked (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59–0.98, P-value = .037). The multivariable-adjusted model, with further adjustments for personal history of previous cardiovascular disease and cardiac rehabilitation attendance, attenuated this association (OR 0.85, 95% CI 0.65–1.12, P-value = .255). Among people with diabetes, cardiac rehabilitation attendance was a positive predictor of smoking cessation, and personal history of cardiovascular disease was a negative predictor of smoking cessation.

Conclusions

People with diabetes who smoke are less likely to quit smoking after an ACS and need tailored secondary prevention programs. In this population, cardiac rehabilitation is associated with increased smoking cessation.

Implications

This study provides new information on smoking cessation following ACSs comparing people with and without diabetes. After an ACS, people with diabetes who smoked were less likely to quit smoking than people without diabetes. Our findings highlight the importance of tailoring secondary prevention to people with diabetes.
Proteomics reveals differential adsorption of angiogenic platelet lysate proteins on calcium phosphate bone substitute materials
Authors: da Costa Marques Richard , Simon Johanna , d’Arros Cyril , Landfester Katharina , Jurk Kerstin , Mailänder Volker
Published: July 2022

Protein adsorption on biomaterials for bone substitution, such as calcium phosphates (CaP), evokes biological responses and shapes the interactions of biomaterials with the surrounding biological environment. Proteins adsorb when CaP materials are combined with growth factor-rich hemoderivatives prior to implantation to achieve enhanced angiogenesis and stimulate new bone formation. However, the identification of the adsorbed proteins and their angiogenic effect on bone homeostasis remain incompletely investigated. In this study, we analyzed the adsorbed complex protein composition on CaP surfaces when using the hemoderivatives plasma, platelet lysate in plasma (PL), and washed platelet lysate proteins (wPL). We detected highly abundant, non-regenerative proteins and anti-angiogenic proteins adsorbed on CaP surfaces after incubation with PL and wPL by liquid chromatography and mass spectrometry (LC–MS) proteomics. Additionally, we measured a decreased amount of adsorbed pro-angiogenic growth factors. Tube formation assays with human umbilical endothelial cells demonstrated that the CaP surfaces only stimulate an angiogenic response when kept in the hemoderivative medium but not after washing with PBS. Our results highlight the necessity to correlate biomaterial surfaces with complex adsorbed protein compositions to tailor the biomaterial surface toward an enrichment of pro-angiogenic factors.
Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy
Authors: Tao Weiyong , Tuo Zhan , Wu Feige , Mu Ketao , Xu Cunjing , Shi Yuxiao , Sun Zeyu , Wang Yifan , Li Yan , Zhong Zhenyu , Zhou Lei , Wang Jianglin , Liu Jie , Du Yingying , Zhang Shengmin
Published: July 2022

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.
Understanding Loneliness and Social Exclusion in Residential Centers for Social Inclusion
Authors: Arnoso Martínez Ainara , Pizarro Pacheco Maribel , Arnoso Martínez Maitane , Asla Alcibar Nagore , Elgorriaga Astondoa Edurne
Published: July 2022

Loneliness and social isolation are widely recognized as one of the most important and deep-rooted problems facing society, with special impact on people who are immersed in processes of social exclusion. The study examined the relationship between loneliness and social exclusion in residential centers. It used phenomenological interviews (N = 11) to explore the subjective experiences of loneliness among people in residential centers for social inclusion to determine the variables associated with their emergence and development, as well as the factors aggravating or alleviating the influence of loneliness on their lives. The results yielded five themes associated with the loneliness of residents, with an interweaving of different axes of exclusion: (1) loneliness and unfulfilled need for meaningful relationships; (2) family losses and conflicts; (3) the experiences of homelessness and residential centers; (4) the economic dependence, contribution, and social inclusion; and (5) the loneliness associated with marginalization and social stigma. Authors present the implications of these findings on social work and some lines of psychosocial intervention.
A Systematic Review and Quantitative Synthesis of the Efficacy of Quaternary Ammonium Disinfestants Against Fungal Plant Pathogens
Authors: Copes Warren E. , Ojiambo Peter S.
Published: July 2022

Quaternary ammonium compounds (QACs) have been used as disinfestants in plant production systems since the late 20th century. In studies on the control of fungal pathogens in agricultural and horticultural crop production systems, the efficacy of QAC disinfestants is variable, ranging from very high to ineffective. A systematic review and meta-analysis were performed to establish and understand how pathogen- and application-related factors influenced product efficacy. The meta-analysis was based on 124 studies involving 14 fungal plant pathogen genera, eight target materials, and four generations of QAC products that contained different mixtures of active ingredients. A significant (P < 0.0001) reduction in either disease intensity or propagule viability resulted following disinfestation using QAC products. Hedges’ g standardized mean difference (g̅+) across the studies was 2.16, indicating that QACs, on average, were highly effective against fungal pathogens. Heterogeneity was significant (P < 0.0001), indicating that effect sizes (g) were not representative of a common mean effect size and supported selection of a random effects model. In all, 78.5% of the observed variance consisted of variance in true effects with a high estimate of between-study variability (τ2 = 2.15). For fungal genus, subgroup g̅+ for genera Pseudonectria and Calonectria was significantly (P < 0.0038) higher than for all other genus subgroups, except Fusarium. For target materials, subgroup g̅+ for solution, cloth, plant, and metal were significantly (P > 0.0071) higher than for inorganic material or wood. For product generation, subgroup g̅+ for fifth-generation products was significantly (P > 0.0071) higher than for fourth-, third-, and second-generation products. Dose and time accounted for only 8 and 4%, respectively, of the true variance in effect sizes in the regression model dose, time, and dose–time (P = 0.0004). Genus accounted for 40 and 51% of the true variance in effect sizes in the regression models dose and genus (P = 0.0008) and time and genus (P = 0.0007), respectively. Target material accounted for 18 and 19% of the true variance in effect sizes in the regression models dose and target (P = 0.0001) and time and target (P = 0.0001), respectively. QAC product generation accounted for 24 and 21% of the true variance in effect sizes in the regression models dose and QAC generation (P = 0.0034) and time and QAC generation (P = 0.0189), respectively. These results show that the current recommended rates for dose and contact time are generally expected to result in effective disinfestation for commercial QAC products. However, the efficacy against fungal plant pathogens is likely to be influenced by the fungal genus and target being treated and the generation of the QAC product that is used for disinfestation.
Trauma-Informed Pedagogy to Foster Resilience in Graduate Nursing Education
Authors: Thompson Christina N. , Otts Jo Ann A. , Stuart Wilma P. , McMullan Taralyn W. , Williams David S.
Published: July 2022

The experiences of graduate nursing students during the COVID-19 pandemic necessitate a trauma-informed approach to education. Three hundred graduate nursing students responded to a discussion assignment in a doctoral-level health care policy course. Thematic analysis identified common themes of fear, anxiety, frustration, and exhaustion (n = 93). Conflict and strain were identified in relation to all major roles (provider, student, and family member), ultimately creating physical and mental barriers to fulfilling each of the roles. Curricular standards must maintain rigor while incorporating flexibility into design standards to assist students when faced with trauma or crisis.
Pandemic Adaptations to an Honors Program Inaugural Capstone Projects
Authors: Crespo-Fierro Michele
Published: July 2022

The COVID-19 pandemic and public health response of the US health care system and government provided unique opportunities for nursing education as it disrupted the usual mode of operation. An honors program at a private university at the epicenter of the pandemic pivoted multiple times to avoid failing to support the capstone projects of its inaugural cohort. Collaborative outreach with mentors and instructional technologists created opportunities for virtual delivery of patient and nursing student education and program evaluation. The lessons learned became part of the roster of resources for future cohorts to sustainably design and deliver their capstone projects.
The Effects of Disaster Nursing Education Program on Beliefs in General Disaster Preparedness, Disaster Response Self-Efficacy, and Psychological Resilience in Nursing Students
Authors: Çiriş Yildiz Cennet , Yildirim Dilek
Published: July 2022

AIM

This study was conducted to evaluate the effects of a disaster nursing and management education program on beliefs in general disaster preparedness, disaster response self-efficacy, and psychological resilience in nursing students.

METHOD

The sample consisted of nursing students receiving undergraduate education in Istanbul, Turkey. Participants were randomly divided into the intervention (n = 65) and control (n = 66) groups. The intervention group was given an eight-module education program with theoretical and applied components. Data were collected using the Belief in General Disaster Preparedness Scale, the Disaster Response Self-Efficacy Scale, and the Brief Resilience Scale.

RESULTS

The mean Belief in General Disaster Preparedness Scale, Disaster Response Self-Efficacy Scale, and Brief Resilience Scale scores of the intervention group were higher than those of the control group.

CONCLUSION

The disaster nursing and management education program provided to nursing students was determined to increase beliefs in general disaster preparedness, disaster response self-efficacy, and psychological resilience.
Not all benign: disease course, complications, and sequalae of chronic recurrent multifocal osteomyelitis in children
Authors: Yasin Shima , Sato T. Shawn , Ferguson Polly
Published: July 2022

Purpose of review

Advances in pathogenesis of chronic recurrent multifocal osteomyelitis in children (CRMO) have shaped therapeutic strategies. The use of whole-body MRI (WBMRI) and improved awareness of CRMO has increased rates and timeliness of CRMO diagnoses. In this review, we highlight the findings from recently published CRMO cohorts and describe the course, complications, and long-term sequalae of CRMO. It is important for clinicians to be aware of the potential for long-term sequelae in order to optimize therapy and avoid complications.

Recent findings

Despite recent advances in defining disease pathogenesis, children with CRMO continue to suffer from complications and deformities. Involvement of the spine can be asymptomatic and is not as rare as previously suggested. This can result in damaging outcomes, such as vertebral fractures and permanent deformities. A subset of patients has polycyclic disease course and some continue to have active disease for years and well into adulthood, with significant impacts on quality of life.

These recent findings have considerable implication on clinical practice regarding diagnosis, treatment, and monitoring of the disease. Collectively, they support the need for continued monitoring of the disease and screening using comprehensive imaging, such as WBMRI.
Complications of severe acute respiratory syndrome coronavirus 2 infection in children
Authors: Caorsi Roberta , Civino Adele , Ravelli Angelo
Published: July 2022

Purpose of review

Although during the initial stages of COVID-19 pandemic, the pediatric population seemed to be less affected, a number of SARS-CoV-2-related manifestations emerged over time, the principal of which is the multisystem inflammatory syndrome in children (MIS-C). Here we provide an update on the main pediatric disorders associated with SARS-CoV-2 infection.

Recent findings

MIS-C is novel postinfectious manifestation with clinical features similar to Kawasaki disease and characterized by intense systemic inflammation affecting multiple organs. Many children required intensive care therapy because of circulatory shock, usually of myocardial origin. Appropriate treatment with immunomodulatory therapies led to favorable outcomes in most patients, with recovery of overall health and cardiac dysfunction. In addition to MIS-C, a variety of other complications of COVID-19 in children have been described, including thrombotic events, neurologic manifestations, and chilblain-like lesions. There is still uncertainty about the true prevalence of long COVID in children and its distinction from pandemic-related complaints.

The experience gained so far with MIS-C and the other SARS-CoV-2-related complications in children and adolescents will facilitate accurate diagnosis and appropriate treatment. Further studies are needed to elucidate the pathophysiology of MIS-C and to determine the real impact of long-COVID in the pediatric age group.
Health inequities in the rheumatic diseases of childhood
Authors: Jarvis Jim , Falkenstein Danielle K.
Published: July 2022

Purpose of review

To describe differences in disease manifestations and outcomes in pediatric rheumatic diseases as they occur in non-European-descended populations in North America.

Recent findings

Differences in disease prevalence, clinical phenotypes, disease course, and outcomes have been described across the spectrum of pediatric-onset rheumatic diseases. Although these differences are commonly explained by differences in genetic risk or access to tertiary healthcare facilities, our emerging understanding of the immunobiology of historical/ongoing trauma suggest a more complex explanation for these observed differences.

Health inequities as observed in pediatric rheumatic diseases are likely to emerge from a complex interplay between social and biological factors. The important contribution of historical and repetitive trauma deserves further exploration.
Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis
Authors: Nie Dingrui , Chen Cunte , Li Yangqiu , Zeng Chengwu
Published: July 2022

Regulated cell death (RCD) is essential for maintaining cell homeostasis and preventing diseases. Besides classical apoptosis, several novel nonapoptotic forms of RCD including NETosis, pyroptosis, ferroptosis, and cuproptosis have been reported and are increasingly being implicated in various cancers and inflammation. Disulfiram (DSF), an aldehyde dehydrogenase inhibitor, has been used clinically for decades as an anti-alcoholic drug. New studies have shown that DSF possesses potent anti-inflammatory and anti-cancer effects by regulating these new types of RCD. Here, we summarize the mechanisms and discuss the potential application of DSF in the treatment of cancers and inflammatory diseases.
KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation
Authors: Xu Jiayue , Wang Dongsheng , Ma Hongliu , Zhai Xueying , Huo Yue , Ren Yue , Li Weiqian , Chang Le , Lu Dongxu , Guo Yuehong , Si Yanmin , Gao Yufeng , Wang Xiaoshuang , Ma Yanni , Wang Fang , Yu Jia
Published: July 2022

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.
β-Lactam Therapeutic Drug Monitoring in Critically Ill Patients: Weighing the Challenges and Opportunities to Assess Clinical Value
Authors: Dilworth Thomas J. , Schulz Lucas T. , Micek Scott T. , Kollef Marin H. , Rose Warren E.
Published: July 2022

OBJECTIVE:

β-lactams are the cornerstone of empiric and targeted antibiotic therapy for critically ill patients. Recently, there have been calls to use β-lactam therapeutic drug monitoring (TDM) within 24–48 hours after the initiation of therapy in critically ill patients. In this article, we review the dynamic physiology of critically ill patients, β-lactam dose response in critically ill patients, the impact of pathogen minimum inhibitory concentration (MIC) on β-lactam TDM, and pharmacokinetics in critically ill patients. Additionally, we highlight available clinical data to better inform β-lactam TDM for critically ill patients.

DATA SOURCES:

We retrospectively analyzed patients admitted for sepsis or septic shock at a single academic medical center who were treated with β-lactam antibiotics.

STUDY SELECTION:

Indexed studies in PubMed in English language were selected for review on topics relative to critical care physiology, β-lactams, pharmacokinetics/pharmacodynamics, TDM, and antibiotic susceptibility.

DATA EXTRACTION:

We reviewed potentially related studies on β-lactams and TDM and summarized their design, patients, and results. This is a synthetic, nonsystematic, review.

DATA SYNTHESIS:

In the retrospective analysis of patients treated with β-lactam antibiotics, approximately one-third of patients received less than 48 hours of β-lactam therapy. Of those who continued beyond 48 hours, only 13.7% had patient-specific factors (augmented renal clearance, fluid overload, morbid obesity, and/or surgical drain), suggesting a potential benefit of β-lactam TDM.

CONCLUSIONS:

These data indicate that a strategy of comprehensive β-lactam TDM for critically ill patients is unwarranted as it has not been shown yet to improve patient-oriented outcomes. This review demonstrates that β-lactam TDM in the ICU, while laudable, layers ambiguous β-lactam exposure thresholds upon uncertain/unknown MIC data within a dynamic, unpredictable patient population for whom TDM results will not be available fast enough to significantly affect care. Judicious, targeted TDM for those with risk factors for β-lactam over- or underexposure is a better approach but requires further study. Clinically, choosing the correct antibiotic and dosing β-lactams aggressively, which have a wide therapeutic index, to overcome critical illness factors appears to give critically ill patients the best likelihood of survival.
Mind the target: programmed death ligand 1 in oesophagogastric cancers
Authors: Wylie Luke A. , Baker Harriet C. , Smyth Elizabeth C.
Published: July 2022

Purpose of review

Metastatic oesophagogastric cancers carry a prognosis of generally less than 2 years despite current treatment. There has been recent excitement in the field focused on immune checkpoint inhibition though anti-PD-1 antibodies. In this article, we review recent phase 3 clinical trials evaluating first line PD-L1 inhibition in metastatic HER-2-negative oesophagogastric cancers and discuss future questions and challenges in the field.

Recent findings

Prior studies have shown promise using PD-L1 inhibition as third and fourth line treatment but recent phase 3 clinical trials have shown clear benefit to overall survival as first line treatment. PD-L1 inhibition as monotherapy demonstrated earlier death rates but there are a subset of patients with a long-term durable benefit when compared with chemotherapy. PD-L1 inhibition when combined with chemotherapy showed benefit in overall survival and progression-free survival and is enhanced in subsets of patients with increased PD-L1 expression.

Although there are still open questions how best to assess PD-L1 status, these studies provide clear evidence for use of PD-L1 inhibition combined with cytotoxic chemotherapy as first-line treatment in metastatic or unresectable oesophagogastric cancers that express PD-L1. In addition, they lay the groundwork for future studies evaluating PD-1 inhibition in earlier stages of disease.
Vascular complications in patients with brain tumors
Authors: Diaz Maria , Schiff David
Published: July 2022

Purpose of review

Venous thromboembolism (VTE) and other vascular events are common in patients with brain tumors, but their optimal management is not firmly established, in large part due to the competing risk of intracranial hemorrhage (ICH) in this population.

Recent findings

There is conflicting evidence on whether therapeutic anticoagulation increases the risk of ICH in patients with brain tumors, with several metanalysis and retrospective cohort studies showing an increased risk and others showing no differences. Current guidelines recommend anticoagulating brain tumors patients with VTE with either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), and several retrospective studies have shown the risk of ICH with DOACs is similar or smaller than with LMWH.

An increased risk of VTE exists in a variety of brain tumor types. Most patients with brain tumors and VTE should receive therapeutic anticoagulation, and recent retrospective evidence supports the use of both LMWH and DOACs as effective and relatively safe in this setting. Patients with brain tumors are also at increased risk of other vascular tumor- or treatment-related complications whose optimal management is unclear.
Precision medicine in chronic obstructive pulmonary disease
Authors: Halpin David M.G.
Published: July 2022

Over the last 20 years, it has become possible to use a precision medicine approach to the management of chronic obstructive pulmonary disease (COPD). Clinical and physiological features as well as a blood biomarker can be used to target treatments to patients most likely to benefit and avoid treatment in patients less likely to benefit. Future advances in a precision medicine approach to COPD will depend on more precise characterization of individual patients, possibly using quantitative imaging, new physiological techniques, novel biomarkers and genetic profiling. Precision medicine has led to significant improvements in the management of COPD and clinicians should use all available information to optimize the treatment of individual patients.
Retinol-binding protein-4 and nonalcoholic fatty liver disease
Authors: Huang Hangkai , Xu Chengfu
Published: July 2022

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common as the global economy grows and living standards improve. Timely and effective preventions and treatments for NAFLD are urgently needed. Retinol-binding protein-4 (RBP4), the protein that transports retinol through the circulation, was found to be positively related to diabetes, obesity, cardiovascular disease, and other metabolic diseases. Observational studies on the association between serum RBP4 level and the prevalence of NAFLD found contradictory results. Some of the underlying mechanisms responsible for this association have been revealed, and the possible clinical implications of treating NAFLD by targeting RBP4 have been demonstrated. Future studies should focus on the predictive value of RBP4 on NAFLD development and its potential as a therapeutic target in NAFLD.
Zygomatic Muscle Neurotization with Nerve Grafts and End-to-Side Neurorrhaphies: A New Technique for Facial Palsy
Authors: Viterbo Fausto , Magnani Lucas Vannuchi , Nunes Helga Caputo
Published: July 2022

Moebius syndrome is a rare congenital facial palsy that can generate serious emotional repercussions, mainly due to the inability to smile. Currently, no treatment is available; however, surgery can restore muscle function. This case report introduces a new technique for the treatment of Moebius syndrome with zygomatic muscle neurotization using nerve grafts and end-to-side neurorrhaphies, in a 3-year-old girl diagnosed with bilateral Moebius syndrome who was unable to smile on the left side. After 4 years, the patient presented with full smile restoration on the left side, with right and left independent movements and complete symmetry.
Breaking Barriers to Breast Reconstruction among Socioeconomically Disadvantaged Patients at a Large Safety-net Hospital
Authors: Meade Anna E. , Cummins Samantha M. , Farewell Jordyn T. , Duque Sofia , Mulqueen Sydney K. , Chuah Ashleigh , Zhang Andrew Y.
Published: July 2022

Background:

Socioeconomic disparities remain prevalent among those who undergo breast reconstruction. At our institution, patients must meet certain criteria to become eligible for breast reconstruction. The purpose of this study was to determine the impact of socioeconomic factors on breast reconstruction eligibility, enrollment, choice, and completion at our large safety-net institution.

Methods:

A retrospective chart review of patients who underwent partial or total mastectomy at a large safety-net hospital from 2016 to 2019 was completed. Surgical and demographic data were compared across varying socioeconomic factors.

Results:

A total of 645 patients were included in the study. More patients of a racial minority had government-based insurance than White patients (89% versus 81%; P = 0.01). Those with government-based insurance had higher average hemoglobin A1c values (6.26 versus 6.0; P = 0.03), proportion of American Society of Anesthesiologists scores greater than III (46% versus 40%; P = 0.01), and smokers (23% versus 9%; P = 0.02) than those with private insurance. Diabetic patients, patients with an American Society of Anesthesiologists greater than III, and active smokers were significantly less likely to receive a plastic surgery consult. Patients with government-based insurance underwent immediate tissue expander placement at mastectomy at rates lower than those with private insurance (57% versus 69%; P = 0.01).

Conclusions:

Barriers remain for socioeconomically disadvantaged patients to be eligible for, undergo, and complete breast reconstruction. Obesity, diabetes, smoking, and poor overall health were identified as the main barriers and were associated with racial minorities, government-based insurance, and lower incomes. Concerted effort through multidisciplinary teams is needed to maximize eligibility of socioeconomically disadvantaged breast cancer patients for reconstruction.
Examination of a Modified Graft Preparation Technique to Induce Double-Scroll Formation and Promote the Use of Younger Descemet Membrane Endothelial Keratoplasty Donor Tissue
Authors: Odell Kelly , Hikes Matthew T. , Can Kaden , Veldman Peter B. , Terry Mark A. , Tran Khoa D. , Straiko Megan M. W.
Published: July 2022

Purpose:

The purpose of this study was to determine whether controlled balanced salt solution (BSS) bursts during graft preparation can safely promote formation of a double-scrolled Descemet membrane endothelial keratoplasty (DMEK) graft in younger donor tissue.

Methods:

DMEK grafts prepared from young donor tissue (average age, 55 years; range, 39–66 years) were floated in BSS to spontaneously form scrolls (N = 10 pairs). Controlled BSS bursts were used to promote double-scroll (DS) formation in 1 member of each pair. Grafts were stained, preloaded, and shipped before cell viability analysis. After appropriate training, a less experienced technician performed this technique on 10 additional corneas. Outcomes measured for both technicians include the success rate for obtaining a DS, scroll conformation after shipping, and endothelial cell loss (ECL).

Results:

There was no difference in ECL between grafts subjected to additional manipulation compared with unmanipulated mate grafts (observer 1: 15.2% ± 3.3% vs. 15.2% ± 4.4%, P = 0.99; observer 2: 16.3% ± 2.9% vs. 15.9% ± 4.5%, P = 0.8). A technician experienced with this technique had a 90% success rate, whereas a less experienced technician had a 70% success rate. The mean ECL of the 10 grafts manipulated by the less experienced technician was not significantly different from results obtained from the experienced technician (observer 1: 18.5% ± 6.0% vs. 15.2% ± 3.3%, P = 0.15; observer 2: 18.1% ± 5.6% vs. 16.3% ± 2.9%, P = 0.34). Scrolls maintained their conformation during shipping events.

Conclusions:

Double-scroll graft formation using controlled BSS bursts is a reliable technique that can be performed without causing additional damage to DMEK grafts. This technique may make graft unscrolling easier and can promote the use of younger donor tissue for DMEK.
Case Series of Patients With Hereditary Benign Intraepithelial Dyskeratosis
Authors: Seely Mason , Jackson Kevin , Meeker Austin , Daluvoy Melissa
Published: July 2022

Purpose:

The purpose of this retrospective case series was to compare the outcomes of different treatment options for patients diagnosed with hereditary benign intraepithelial dyskeratosis (HBID).

Methods:

The study is designed as a single-institution retrospective chart review of patients who were clinically diagnosed with HBID during their care at the Duke Eye Center. Patient demographics were obtained, and disease course after different therapies was analyzed.

Results:

Seventeen patients were diagnosed with HBID. 52.9% (9/17) of patients identified with HBID reported Native American ancestry. Medical therapy alone failed to reduce the size or number of corneal lesions in any patient identified in this study. Ten of the 17 patients required surgical intervention. Two eyes received corneal biopsies, 3 eyes received a full conjunctival lesion excision with amniotic membrane grafting, 12 eyes received superficial keratectomy with amniotic membrane grafting, and 1 eye received keratoprosthesis. Lesion recurrence was seen in 9 of the 10 patients treated with surgical excision with an average time to recurrence of 1.5 and 2 months for conjunctival excisions and superficial keratectomy, respectively, when excluding patients who missed scheduled postoperative follow-up appointments.

Conclusions:

Hereditary benign intraepithelial dyskeratosis is a rare and poorly understood disorder that predominantly affects people with Native American ancestry. Medical therapy only provides symptomatic relief, and patients who receive surgical excision almost always develop recurrence. As a result, we recommend future investigations focus on identifying the optimal surgical technique and timing to limit the morbidity of HBID and improve outcomes.
Keratoplasty Registries: Lessons Learned
Authors: Chu Hsiao-Sang , Hu Fung-Rong , Liu Hsin-Yu , Srikumaran Divya
Published: July 2022

Clinical registries have been developed for decades in the field of ophthalmology, and they are especially well-suited to the study of keratoplasty practices. A comprehensive donor/recipient registry system can provide insight into donor, recipient, and surgical factors associated with immediate and long-term outcomes and adverse reactions. Furthermore, linkage with demographic databases can elucidate relationships with social determinants of health and potentially shape public policy. The vast sample size and multicenter nature of registries enable researchers to conduct sophisticated multivariate or multilayered analyses. In this review, we aim to emphasize the importance of registry data for keratoplasty practice and 1) summarize the structure of current keratoplasty registries; 2) examine the features and scientific contributions of the registries from Australia, the United Kingdom, Singapore, the Netherlands, Sweden, Eye Bank Association of America, and European Cornea and Cell Transplant registries; 3) compare registry-based studies with large single-site clinical studies; 4) compare registry-based studies with randomized control studies; and 5) make recommendations for future development of keratoplasty registries. Keratoplasty registries have increased our knowledge of corneal transplant practices and their outcomes. Future keratoplasty registry-based studies may be further strengthened by record linkage, data sharing, and international collaboration.
Meta-analysis of the Risk Factors for Urinary Tract Infection in Children
Authors: Renko Marjo , Salo Jarmo , Ekstrand Milka , Pokka Tytti , Pieviläinen Oskari , Uhari Matti , Tapiainen Terhi
Published: July 2022

Context:

The incidence of urinary tract infection (UTI) varies with age, but there is limited evidence on the role of other risk factors.

Objective:

The aim of this meta-analysis was to investigate the risk factors for UTIs in children.

Data sources:

PubMed from 1966 to May 2019.

Study selection:

All studies assessing at least 1 possible risk factor for occurrence or recurrence of UTI with a clear definition of symptomatic UTI in children were eligible. We excluded studies with UTIs related to hospital treatment or severe congenital renal abnormalities.

Data extraction:

After the quality assessment we extracted data on the given risk factor in children with and without UTI. The data were extracted separately for the occurrence and recurrence of UTIs.

Results:

We included 24 studies in the meta-analysis. Circumcision decreased the occurrence of UTIs with an odds ratio (OR) of 0.1 [95% confidence interval (CI): 0.06–0.17) and breast-feeding with an OR of 0.4 (CI: 0.19–0.86), both with low heterogeneity. Being overweight or obese increased the risk of UTI (OR: 2.23; CI: 1.37–3.63). Both poor fluid intake (OR: 6.39; CI: 3.07–13.39) and infrequent voiding (OR: 3.54; CI: 1.68–7.46) were associated with recurrent UTIs.

Limitations:

The design, populations and definitions varied between the studies.

Conclusions:

Being overweight or obese and having poor fluid intake are modifiable risk factors that increase the risk for UTIs in children. Breast-feeding and circumcision are associated with a decreased occurrence of UTIs.
Advances in the Treatment of Rosacea-Associated Facial Erythema
Authors: Wang Yun , Guo Shu-Ping , Cao Jun , Ren Ling
Published: July 2022

Facial erythema is the main characteristic of rosacea. It has a negative impact on quality of life. The two forms of rosacea-associated erythema are inflammatory erythema and non-inflammatory erythema. There are numerous therapeutic options available that achieve satisfactory responses. This review summarizes the latest advances in the treatment of rosacea-related erythema and concludes the treatment of two forms of them.